Iron Absorption: Factors, Limitations, and Improvement Methods
- Elif PiskinElif PiskinFaculty of Engineering and Natural Sciences, Food Engineering Department, Istanbul Sabahattin Zaim University, Halkali, 34303 Istanbul, TurkeyMore by Elif Piskin
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- Danila CianciosiDanila CianciosiFaculty of Medicine, Department of Clinical Sciences, Polytechnic University of Marche, via Pietro Ranieri, 60131 Ancona, ItalyMore by Danila Cianciosi
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- Sukru Gulec*Sukru Gulec*Email: [email protected]Molecular Nutrition and Human Physiology Laboratory, Department of Food Engineering, İzmir Institute of Technology, 35430 Urla, İzmirMore by Sukru Gulec
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- Merve Tomas*Merve Tomas*Email: [email protected]Faculty of Engineering and Natural Sciences, Food Engineering Department, Istanbul Sabahattin Zaim University, Halkali, 34303 Istanbul, TurkeyMore by Merve Tomas
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- Esra Capanoglu*Esra Capanoglu*Email: [email protected]Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, Maslak, 34469 Istanbul, TurkeyMore by Esra Capanoglu
Copyright © 2022 The Authors. Published by American Chemical Society
Abstract
Iron is an essential element for human life since it participates in many functions in the human body, including oxygen transport, immunity, cell division and differentiation, and energy metabolism. Iron homeostasis is mainly controlled by intestinal absorption because iron does not have active excretory mechanisms for humans. Thus, efficient intestinal iron bioavailability is essential to reduce the risk of iron deficiency anemia. There are two forms of iron, heme and nonheme, found in foods. The average daily dietary iron intake is 10 to 15 mg in humans since only 1 to 2 mg is absorbed through the intestinal system. Nutrient–nutrient interactions may play a role in dietary intestinal iron absorption. Dietary inhibitors such as calcium, phytates, polyphenols and enhancers such as ascorbic acid and proteins mainly influence iron bioavailability. Numerous studies have been carried out for years to enhance iron bioavailability and combat iron deficiency. In addition to traditional methods, innovative techniques are being developed day by day to enhance iron bioavailability. This review will provide information about iron bioavailability, factors affecting absorption, iron deficiency, and recent studies on improving iron bioavailability.
1. Introduction
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Iron is one of the essential heavy metals for human nutrition, and it is a vital element for human life. (1) It plays critical roles in oxygen and electron transport, cell division, differentiation, and regulation of gene expression. (2) 70% of the iron in the human body binds to the hemoglobin, the pigment of red blood cells (RBCs) that gives the blood its red color, and the rest binds to other proteins, such as myoglobin, transferrin, and ferritin, or is stored in the cells. The reticuloendothelial system, which clears damaged RBCs by macrophages of the spleen, liver, and bone marrow, plays a role in systemic iron homeostasis. (3)
Two types of iron can be found in foods, including heme and nonheme. Heme iron is present only in animal products such as meat, fish, and poultry, whereas nonheme iron is found in fruits, vegetables, dried beans, nuts, grain products, and meat. (4) Heme iron is absorbed with better efficiency from the intestine than nonheme iron. (5) Tight control of dietary iron absorption is essential to maintain an iron level within the normal range to reduce the risk of iron deficiency.
The standard definition of intestinal nutrient bioavailability is the portion of the absorbed and utilized nutrients from digested foods through enterocyte cells of the intestine. The absorption rate of iron has been reported as 25–30% in the consumption of organ meats, 7–9% in green leafy vegetables, 4% in grains, and 2% in dried legumes, indicating that food types or other dietary factors might influence iron bioavailability. (6) For instance, ascorbic acid is a well-known dietary factor improving iron bioavailability; (7) however, calcium, polyphenols, and phytates reduce intestinal iron absorption. (8,9) Thus, we need to consider the type of foods in our diet to maintain an iron balance in the body. Inadequate iron absorption leads to iron deficiency anemia. Iron deficiency is the most common nutritional deficiency worldwide. It negatively affects the cognitive development in infants, children, and adolescents. Maternal iron deficiency anemia may cause low birth weight and preterm delivery. (10) The report from the World Health Organization indicated that more than 27% of the world’s population experiences iron deficiency anemia. Therefore, the prevention of iron deficiency is crucial for these groups.
In this review, iron bioavailability, iron deficiency and anemia, dietary factors affecting iron bioavailability, and recent studies on increasing iron bioavailability were determined using the search terms “iron, iron bioavailability, iron absorption, iron deficiency and anemia, iron bioavailability enhancers/inhibitors, iron bioavailability improvement, encapsulation of iron, and nanoparticulation of iron” via PubMed, Web of Science, and Google Scholar databases. While papers and reports having a scientific quality are included in the study, articles written in languages other than English and the ones for which full text could not be reached formed the exclusion criteria of the study. In addition, under the title “iron bioavailability improvement methods” only the studies published after the year 2014 are included. As a result of the search, a total of 1254 studies were found, and the article was created by referring to 178 sources at the end of the eliminations made in line with the inclusion/exclusion criteria.
2. Iron Absorption
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Dietary iron absorption is primarily performed through enterocyte cells on the duodenum and upper jejunum of the small intestine. Because humans do not have an active iron excretion system, intestinal iron absorption is critical for maintaining iron balance in the body. (11) A typical Western diet contains 7 mg of iron per 1000 kcal; however, only 1–2 mg is absorbed daily. (12) Nonheme iron accounts for up to 90% of the iron consumed through food. It is in the form of Fe+3 complexes in foods, and its absorption is affected by dietary factors and iron status in the human body. Contrary to nonheme iron, heme iron has a high absorption rate and is less affected by dietary factors. Heme iron accounts for 10% of dietary iron. (13,14) Two different molecular mechanisms are involved in absorbing heme and nonheme iron in the intestines; however, iron enters the same intracellular pool as newly absorbed heme or nonheme iron and can be stored in iron storage protein. (11) Body iron status and dietary food types may influence intestinal iron absorption. Furthermore, cast iron pots and cookware can also be a source of significant quantities of dietary iron and, most importantly, the form of iron in food as heme or nonheme. In addition, the diet consumption patterns of nonheme iron absorption are affected by the diet. (15) Getting enough iron is one of the requirements for a healthy life. (16) Reference Dietary (Daily) Allowance (RDA) values, the average daily nutrient intake level for healthy people to meet the adequate nutrient needs of the body, have been established by the Food and Nutrition Board, Institute of Medicine (IOM). (17,18) In addition, for infants from birth to 6 months, an average intake (AI) for iron equivalent to the mean intake of iron in healthy, breastfed infants are established. According to the IOM, the AI value for infants aged 0–6 months and the RDA value for those aged 7–13 months are 0.27 mg/day and 11 mg/day, respectively. For children aged 1–3 years, 4–8 years, and 9–13 years; these values are 7 mg/day, 10 mg/day, and 8 mg/day, respectively. In adolescence (14–18 years), the RDA value changes between men and females. While the RDA for male adolescents is 11 mg/day, the RDA value is 15 mg/day for female adolescents. For adults over 19, the RDA value is 8 mg/day and 18 mg/day for males and females, respectively. In addition, the RDA value for lactating women younger than 18 years old is 10 mg/day, and it is 9 mg/day for those over 18 years of age. Furthermore, RDA changes for vegetarians. The RDA for a vegetarian man is 14 mg/day, and for vegetarian females aged between 14 and 18 years, 19 and 50 years, and over 51 years, it is 26 mg/day, 14 mg/day, and 33 mg/day, respectively. Iron deficiency occurs when the body’s iron requirement is unmet, which may cause health problems. (18)
3. Iron Deficiency and Anemia (IDA)
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Iron deficiency and iron deficiency anemia are global health problems and common medical conditions seen in daily clinical practice. (19) Iron deficiency is when the amount of iron needed by the body cannot be met due to some physiological consequences, including blood loss and limited dietary supply. (19,20) The World Health Organization (WHO) defines iron deficiency anemia as a hemoglobin (Hb) level of less than 13 g/dl in men and 12 g/dl in women. (21) Iron deficiency is the most common nutritional deficiency worldwide. It is a significant health problem for children, adolescents, pregnant women, and those with low socioeconomic status, especially in developing countries. Furthermore, IDA also affects many people around the industrialized world. (22) However, the prevalence of iron deficiency in developing countries is approximately four times higher than in developed countries. (23) Recently, up to one-third of the world’s population is suffering from iron deficiency. Infants, the elderly, and women, especially during menstruation and pregnancy, are at high risk for IDA. (24)
IDA is a severe problem that negatively affects growth, cognitive function, and behaviors in infants. (25−28) It induces some health problems in adults, including restless legs syndrome (RLS), (29) diminished quality of life, (30) fatigue and weakness, (31) trouble concentrating, and lack of work productivity. (32) In pregnant women, low iron levels may affect the birth weight and cause prematurity (33,34) and even mortality in the mother and child. (35) In addition, a link between preoperative anemia and increased risk of 30-day morbidity and mortality in patients undergoing major noncardiac surgery was demonstrated. (36) A schematic summary of the cause and symptoms of iron deficiency anemia is provided in Figure 1.
Figure 1
Figure 1. Iron deficiency anemia causes and symptoms.
4. Bioavailability of Iron from Dietary Sources
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Heme iron contributes 10–15% of the total iron intake. However, since heme iron is absorbed better than nonheme iron, with an approximate 15–35% of absorption, it can account for more than 40% of total intestinal iron absorption. (37) In contrast to heme iron, nonheme iron is found in animal and plant sources (i.e., cereals, beans, and herbs) and iron-enriched or fortified foods such as iron-fortified cereal. (38,39)
The iron content of foods does not indicate its bioavailability because iron absorption depends on some factors, mainly the form of iron. Because plants mainly contain nonheme iron, even if its iron content is high, absorption of iron is low due to plant-based molecule–iron interactions. (40) Red meat is the most significant source of iron since it is rich in heme iron, which is highly bioavailable. (41,42) Since 30–70% of the iron in meat is in the form of heme, the iron requirement for humans is mainly met by red meat in developed countries. In contrast, in underdeveloped and developing countries, iron intake depends on plant-based diets that contain mostly nonheme iron, often absorbed less than 10%. (42,43) Therefore, the consumption of iron-containing food is one of the main factors determining the body iron status.
5. Dietary Factors Affecting Iron Bioavailability
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The absorption of iron heavily depends on the physical state of iron as ferrous and ferric. (44) Nonheme iron in the diet is primarily in an oxidized or ferric form, although ferrous iron is more likely to be carried into enterocytes. (11) Ferric iron is precipitated in solutions with a pH higher than 3, whereas most ferrous iron remains soluble at a neutral pH. Therefore, ferric iron must first be solubilized and chelated in the stomach to be absorbed in the less acidic proximal small intestine. (45) The chelation happens rapidly by the other components in food as iron is released in the intestinal lumen. These chelators may be enhancers and inhibitors influencing iron absorption via iron solubility. (6) Therefore, diet composition is one of the main factors influencing the absorption of nonheme iron. (46)Figure 2 shows the main enhancers and inhibitors of iron bioavailability, and Table 1 shows the relevant studies.
Figure 2
Figure 2. Main enhancers and inhibitors of iron bioavailability.
Table 1. Main Enhancers and Inhibitors of Iron Absorption
| type of study | component/dose | experimental model | main results | reference |
|---|---|---|---|---|
| in vivo | ascorbic acid/25 to 1000 mg | 63 male subjects | As vitamin C dose was increased from 25 to 1000 mg, absorption of iron showed an increase from 0.8% to 7.1% in male subjects who were fed with a liquid formula meal containing 4.1 mg of iron. | (56) |
| in vitro | ascorbic acid/- | caco-2 cell | Ascorbic acid enhanced the absorption only when it was added along with the digests to Caco-2 cells during the iron uptake study. | (50) |
| in vitro | ascorbic acid/- | caco-2 cells | While phytic acid, sodium oxalate, and sodium silicate decrease iron absorption, ascorbic acid has the ability to counteract their inhibitory effects. | (51) |
| in vivo | animal tissue/25 g | 8 healthy infants 43–49 weeks of age | Inclusion of meat to the vegetable puree significantly increased the nonheme iron absorption. | (64) |
| in vivo | animal tissue/25, 50, or 75 g | 45 healthy women with a mean age of 24 ± 3 years | Dose–response increase was observed when pork meat was added to a high-phytate, low-ascorbic-acid meal. | (65) |
| While 25 g of meat did not influence the nonheme iron absorption, inclusion of 50 and 75 g of meat increased the absorption significantly (44% and 57%, respectively). | ||||
| in vivo | animal tissue/- | randomized crossover trial in 21 young women with low iron stores | Addition of fish to high-phytate bean meal enhanced the iron bioavailability. | (66) |
| in vitro | animal tissue/- | caco-2 cell | Caco-2 cells’ response to nonheme iron from infant rice was significantly increased by bovine coproducts (kidney, lung, and heart). | (67) |
| For the kidney, lung, and heart, relative uptake of iron was found to be 207.13%, 171.21%, and 265.28%, respectively. | ||||
| in vivo | phytate/- | 58 men and 60 women, aged 19–58 years | Iron absorption was significantly increased by the removal of phytates in bran. | (74) |
| The addition of potassium and magnesium phytates in amounts present in bran showed an inhibition of iron absorption. | ||||
| in vivo | phytate/seven dose levels from 2 to 250 mg | 34 men and 90 women, aged 19–47 years | Inhibitory effect of phytate was dose dependent. | (76) |
| Ascorbic acid may reduce the inhibitory impact of phytate. | ||||
| in vivo | phytate/718 to 1190 mg/d in the high-phyate group and 623 to 385 mg/d in the low phytate group | 32 nonanemic females, 18–35 years of age, with suboptimal iron stores | Inhibitory effects of phytate on nonheme iron absorption were lessened by eating a high-phytate diet on a regular basis in young women with low iron status. | (79) |
| in vivo | phytate/- | 720 pregnant women | Bioavailability of iron and calcium in the diets of pregnant women was inhibited by phytate intake. | (78) |
| in vivo | phytate/77 ± 11 mg | 102 females aged between 20 and 30 years | 12 weeks of high-phytate wholegrain bread consumption had no effect on iron status in women at reproductive age. | (80) |
| in vivo | phytate/817 ± 21 mg | 14 women aged 19–42 years who were not habitually consuming iron-containing nutritional supplements | A significant effect of phytate content on iron absorption was not found when porridge was fortified with iron in the form of either sodium iron EDTA or ferrous sulfate. | (81) |
| in vivo | polyphenols/from 52 to 396 mg | 23 males and 54 females aged 19–40 years | Black tea was more inhibitory than cocoa and more inhibitory than herbal teas camomile, vervain, lime flower, and pennyroyal but equivalent to peppermint tea at the same total polyphenol content. | (82) |
| in vivo | polyphenols/20, 50, and 200 mg | 97 apparently nonpregnant, nonlactating women aged between 18 and 45 years and weighing below 60 kg | Red bean polyphenols inhibited iron bioavailability dose-dependently. While 20 mg of bean polyphenols had no effect on iron absorption, 50 mg and 200 mg lowered iron bioavailability by 18% and 45%, respectively. | (83) |
| in vitro | polyphenols/- | caco-2 cell | Polyphenolic compounds inhibited the heme iron absorption in a dose-dependent manner. | (121) |
| In small amounts of polyphenols (≤4.6 mg/L) ascorbic acid counteracted the inhibitory effect; however, in higher levels (46 mg/L), it could not modulate the inhibition. | ||||
| in vivo | polyphenols/- | 17 mother–child pairs | Polyphenol-rich tea reduced iron absorption from wheat bread fortified with ferrous sulfate or ferrous fumarate by 56–72%. | (89) |
| in vivo | polyphenols/492 mg | 50 women aged 21–30 years | In both IDA and nonanemic women, tea consumption decreased iron absorption from NaFeEDTA by more than 85%. | (90) |
| in vitro | polyphenols/- | caco-2 cell | Catechin, 3,4-dihydroxybenzoic acid, kaempferol, and kaempferol 3-glucoside promoted iron uptake, while myricetin, myricetin 3-glucoside, quercetin, and quercetin 3-glucoside showed an inhibitory effect. | (84) |
| in vivo | calcium/100 and 200 mg | 788 children aged 6–11 years | As the ascorbic acid and calcium did not exist, iron absorption from the casein/whey-based drink was 20% lower in iron-repleted children than the ones with IDA. | (97) |
| Calcium addition decreased the mean iron absorption by 18–27%. | ||||
| in vivo | calcium/500 mg | 13 premenopausal women with pre-existing marginal Fe status aged 28–35 years | Iron absorption from a single meal was reduced from 10.2% to 4.8%. | (95) |
| The extent of the calcium impact differed significantly across subjects having similar iron stores. | ||||
| in vitro | proteins/30 g | simulated gastrointestinal digestion | Iron absorption decreased by the substitution of casein or whey protein for egg white. Mean absorption values fell from 6.67 to 3.65% and 2.53 to 0.98%, respectively. | (122) |
| in vivo | proteins/30 g | 15 men and 19 women ranging in age from 18 to 45 years | Iron absorption of completely dephytinized glycinin was found to be 124% compared to egg white; however, relative absorption of completely dephytinized conglycinin was only 44%. Conglycinin fraction of soybean proteins was reported to be an inhibitor of iron absorption. | (105) |
| in vivo | prebiotic/4% of the diet | 40 female albino rats (ten-week-old) | Yogurt containing long-chain inulin was more effective for iron absorption than yogurt containing short-chain inulin. | (111) |
| Fe2(SO4)3 and long-chain inulin fortified yogurt increased the iron bioavailability. In addition, liver function and the antioxidant capacity were improved. | ||||
| in vivo | prebiotic/- | 24 healthy women aged 35–45 years | No significant differences were observed in heme and nonheme iron bioavailability in the control group. | (109) |
| Bioavailability of heme iron from the prebiotic group increased significantly by 56% after prebiotic intake. | ||||
| No significant differences were observed in nonheme iron bioavailability. | ||||
| in vivo | prebiotic/∼20 g | 36 nonpregnant, nonlactating women with low iron status, aged between 18 and 40 years and with a body weight <65 kg | Inulin enhanced the iron absorption by 14% which was statistically insignificant. | (110) |
The presence of ascorbic acid in the diet increases the absorption of nonheme iron. (47) Ascorbic acid aids iron absorption by creating a chelate with ferric iron Fe3+ at a stomach acid pH that stays soluble at the alkaline pH of the duodenum, the first section of the small intestine. (48) In addition, ascorbate, ascorbic acid salt, donates an electron, acting as a free radical scavenger and reducing iron oxidation states to Fe2+, which is the only bioavailable form for enterocyte cells. (49) Fe2+ is the only iron that can be absorbed through iron transporters of intestinal enterocyte cells. (11) To date, numerous in vivo and in vitro cell culture studies on the effect of ascorbic acid on iron absorption have been reported. Recently, Khoja et al. reported that when ascorbic acid was added into the digesta of plant products (fenugreek sprouts, fenugreek seeds, baobab fruit pulp, and moringa leaves) ascorbic acid enhanced iron absorption in the Caco-2 cell culture model. (50) He et al. used an in vitro digestion/Caco-2 cell model to investigate the effects of phytic acid, sodium oxalate, and sodium silicate on nonheme iron bioavailability in the presence and absence of ascorbic acid. The findings revealed that phytic acid, sodium oxalate, and sodium silicate restrict ferrous iron absorption, but ascorbic acid can counteract this inhibitory impact and enhance ferrous iron uptake. (51) Similar results were obtained by Villano et al. (52) who showed that ascorbic acid can resist to the inhibitory effect of polyphenols.
The effect of vitamin C has been proven to be dose dependent (53,54) and can increase the absorption of iron only when both nutrients are consumed together. (55) It has been reported that iron absorption gradually increases from 0.8% to 7.1% when increasing amounts of ascorbic acid, ranging from 25 to 1000 mg, are added to a liquid formula meal containing 4.1 mg of nonheme iron. Moreover, it also has been reported that although 500 mg of ascorbic acid taken with food increases the absorption of iron six times ascorbic acid taken 4–8 h before is less effective. (56) In this sense, incorporation of ascorbic acid into the diet may seem effective for higher intake of iron; however, besides the technical difficulties during the preparation and storage due to the instability of ascorbic acid, (47) studies have proven that the addition of ascorbic acid to the whole diet has a more negligible effect on increasing iron absorption. (57−60) In this sense, the impact of meal composition and the whole food matrix in the diet may influence ascorbic acid and may explain the dramatic improvements in iron absorption.
Animal tissues, such as beef, chicken, fish, pork, and lamb, have a positive effect on dietary nonheme iron absorption. (61) The enhancing effect of animal tissues on nonheme iron absorption was first reported by Layrisse et al. Veal muscle, veal liver, and fish were demonstrated to enhance nonheme iron absorption by 150% in human subjects consuming meals of maize and black beans. (62) Later, Bjorn-Rasmussen and Hallberg reported that adding chicken, beef, fish, or calf thymus to a maize meal enhanced nonheme iron absorption. As a result of the study, it was concluded that meat increases absorption by inactivating the luminal factors that prevent iron absorption. The authors stated that the most likely mechanism for this effect is the formation of a luminal transporter that transports iron to the mucosal cell membrane. (63) Engelmann et al. added 25 g of lean beef to the 80 g of vegetable puree, and as a result, an increase in absorption of nonheme iron in infants was observed. (64) Bech et al. added pork meat to a meal presumed to have low iron bioavailability. In consequence, they observed that the addition of a small amount of pork (>50 g) to a meal that has high inhibitory and low enhancer components (7.4 mg of vitamin C and 220 mg of phytate) increases the bioavailability of iron in a dose-dependent manner. (65) Navas-Carretero et al. studied the effect of consuming fish (salmon) on nonheme iron bioavailability from a phytate-rich bean meal. They reported that adding fish to the bean meal significantly enhanced iron absorption in iron-deficient women. (66) A more recent study by O’Flaherty et al. showed that fortification of kidney, heart, and lung meats into infant rice cereals improved nonheme iron absorption to 207.13%, 265.28%, and 171.21%, respectively. (67) The mechanism of enhancing the effect of animal tissues known as the meat factor has not been identified. (68) Hurrell et al. attempted to classify the meat factor in this sense. Nonheme iron absorption was improved by 180% and 100%, respectively, when freeze-dried beef and chicken muscle were compared to egg albumin. Muscle tissue has been reported to have a protein- and/or peptide-related influence on iron absorption. However, it was also reported that other variables such as glycosaminoglycans might have played a role as well. (69)
Phytate and polyphenols are the major iron absorption inhibitors in plant-based foods because they make a complex with dietary iron in the gastrointestinal tract. (9) Phytate is a naturally occurring component found in plants, and it has an inhibitory effect on the bioavailability of most minerals. (70,71) Phytate cannot be digested by the human body and cannot be absorbed in the small intestine due to the lack of endophytases. (72) As a result, minerals chelated in phytic acid are not bioavailable. (73) Hallberg et al. removed phytates in bran by endogenous phytase to observe how its removal impacts absorption and reported that iron absorption is significantly increased in the absence of phytate. (74) Troesch et al. reviewed the evidence from human studies investigating the impact of phytase on iron and zinc bioavailability. They concluded that phytase promotes the absorption of iron and zinc from phytate-rich meals and can potentially improve magnesium, calcium, and phosphorus absorption. (75) The dose-dependent inhibitory impact of sodium phytate on iron absorption was investigated by Hallberg et al. Wheat rolls with no phytates and including seven dose levels from 2 and 250 mg were served to humans. It was reported that phytate’s inhibitory impact was significantly dependent on the phytate amount. While 2 mg inhibited the iron absorption by 18%, this value reached up to 82% by 250 mg. Moreover, the impact of ascorbic acid was also evaluated in the study, and the addition of ascorbic acid was observed to counteract the inhibitory effect of phytates. (76)
The inhibitory effect of phytate is considered to be exaggerated for iron in single test meal studies compared with that achieved in whole diets. (77) For instance, in a single meal study by Al Hasan et al., it has been reported that phytate intake inhibits the bioavailability of iron and calcium from the diets of pregnant women. (78) On the contrary, Armah et al. demonstrated that eating a high-phytate diet regularly can lessen the inhibitory effects of phytate on nonheme-iron absorption in young women with low iron status. (79) Similarly, Hoppe et al. reported that consuming low-phytate whole grain bread on a whole diet had no significant effect on iron status compared to consuming high-phytate wholegrain bread. (80) Previously, Mendoza et al. investigated iron absorption from porridges prepared from genetically modified strains of low-phytate maize and unmodified wild-type maize, both of which were fortified with either ferrous sulfate or sodium iron EDTA. They revealed no significant impacts of modified low phytate on improving iron absorption. (81)
Polyphenols are found in the human diet mainly due to their presence in vegetables, cereals, spices, tea, coffee, red wine, and cocoa. (82,83) Polyphenols are known iron bioavailability inhibitors and are assumed to work similarly to phytate by forming a complex with iron. (84) The inhibitory impact of polyphenols on iron absorption has been reported in numerous studies. (82,85−87) Petry et al. investigated the effect of bean polyphenols on iron absorption in humans. To determine the effect of bean polyphenols on iron absorption in the absence of phytic acid, increasing quantities of red bean hulls were introduced as a source of bean polyphenols to noninhibitory bread meals where phytic acid had been destroyed during dough fermentation. Twenty mg of bean polyphenols did not affect iron absorption. In comparison, 50 mg and 200 mg of bean polyphenols lowered iron bioavailability by 18% and 45%, respectively, demonstrating that red bean polyphenols inhibited iron bioavailability in a dose-dependent manner. (83) Polyphenols have even been reported to inhibit heme iron absorption depending on the dose. It has been proven that ascorbic acid counteracts the inhibitory effect at low polyphenol doses. However, it cannot show this effect at high doses. (88) A recent study by Ndiaye et al. showed that polyphenol-rich tea reduced iron absorption from wheat bread fortified with ferrous sulfate or ferrous fumarate by 56–72% in Senegalese mother-child pairs. (89) Lazrak et al. studied the bioavailability of iron from NaFeEDTA when added to wheat flour-based meals in both nonanemic women and women with IDA when consumed with and without traditional Moroccan green tea, which had 492 mg GA/ml polyphenols per meal portion serving size/day. The results showed that tea consumption reduced iron absorption from NaFeEDTA by more than 85% in both IDA and nonanemic women. (90) The precise mechanism by which polyphenols reduce the bioavailability of nonheme iron is not fully understood. (91) Interestingly, using Caco-2 cells demonstrated that some polyphenols such as catechin and kaempferol promote iron absorption. In addition, these studies have reported myricetin, myricetin 3-glucoside, quercetin, and quercetin 3-glucosides as inhibitors. (84,92)
Calcium is also known to inhibit iron absorption, but it differentiates from other inhibitors since it affects nonheme iron and heme iron. (93) The studies suggested that calcium influenced iron absorption by regulating enterocyte iron transporter proteins. (8) The action of the mechanism has not been fully clarified yet; however, studies trying to ascertain the mechanism are available in the literature. Previously, it has been suggested that calcium inhibition may occur in the final steps of mucosal cell-to-plasma transport after the two forms of iron had entered a common cellular iron pool, possibly because these two forms of iron have different apical mucosal receptors. (93) However, an opposing view has argued that although there are differences in the apical receptors for heme and nonheme iron, calcium inhibition may occur during the initial entry of iron into the mucosal cell via inhibition of iron transport. (94) Although the mechanism has not been fully understood, the inhibition effect of calcium on iron bioavailability has been proved. Benkhedda et al. demonstrated that calcium reduced iron absorption from a single meal from 10.2% to 4.8%; however, the calcium impact differed significantly across subjects having similar iron stores. Authors concluded that aside from the levels of iron stored in the body and the kind of diet, physiologic or genetic variables significantly impact iron absorption in people with similar body iron stores. (95) In this context, factors other than iron status may influence the expression of iron transporters which are responsible for intestinal iron absorption and their cellular location. (8) Consumption of an iron-fortified milk product that supplied 100% of the required daily iron intake did not improve iron status in iron-deficient women over four months in a randomized controlled study. The results revealed that consumption of iron-fortified milk does not improve the iron status in iron-deficient menstruating women. The authors concluded that the presence of calcium and casein in the product is the reason for the impact. (96) Walczyk et al. investigated the effect of calcium (0, 100, and 200 mg/test meal) on iron absorption from a casein/whey-based drink fortified with ferrous sulfate in the absence and presence of ascorbic acid (0, 42.5, and 85 mg/test meal) in a series of randomized crossover studies in both iron-replete (IR) schoolchildren and schoolchildren with IDA. Iron absorption from the casein/whey-based drink was 20% lower in IR children than in IDA children without calcium and ascorbic acid. The lowered addition of calcium means iron absorption by 18–27%, with the impact being more significant with higher calcium levels. Calcium salts (used as supplements) and milk/dairy products had similar effects. (97) Separating calcium and iron intakes would be a solution to this nutritional challenge. However, evidence shows that long-term calcium supplementation taken simultaneously or separately from meals does not affect iron status. (98−101) These variations in short- and long-term impacts of calcium are most likely due to adaptation to a high calcium intake as an iron absorption regulation mechanism to maintain iron homeostasis (8)
Proteins have been reported to be inhibitors or enhancers of iron absorption depending on their source. While proteins from meat were reported to be enhancers, (63,69,102) other proteins such as eggs were indicated to be inhibitory. (103) Kim et al. conducted a comprehensive study comparing the effect of proteins (from pork, egg albumin, egg yolk, soybean, and casein) on iron absorption and intestinal solubility. They reported that adding pork protein enhanced the iron bioavailability and solubility in the intestine, while they were lowest in the presence of egg yolk. (102) Cook et al. studied the effect of different semipurified proteins, including casein, egg albumen, and isolated soy protein. When egg albumen and casein were replaced in protein equivalent quantities in a semisynthetic meal, close mean absorptions (2.5% and 2.7%) were observed. However, isolated soybean protein decreased the absorption to 0.5%. (104) Lynch et al. determined the contribution of soybean protein isolate components to the iron absorption inhibitory property of soybean. They concluded that the two main inhibitors of iron absorption in soybean protein isolates were the protein-related part found in the phytic acid and conglycine (7S) fraction. (105)
Dietary fiber is one of the main components of edible plant parts that is resistant to digestion and absorption in the small intestine of humans and undergoes complete or partial fermentation in the large intestine. (106) Studies investigating the correlation between iron bioavailability and dietary fibers have not demonstrated results that agree with each other. (107) Insoluble dietary fibers are known to inhibit mineral bioavailability. However, soluble dietary fibers have a smaller effect on intestinal iron absorption. (108) Weinborn et al. conducted a human study on the effect of a prebiotic mixture composed of soluble fibers (inulin, polidextrose, arabic gum, and guar gum) on heme nonheme iron. They found that while the prebiotic mix improved the heme iron absorption, nonheme iron absorption was unaffected. (109) Another human study on enhancing the effects of inulin was performed by Petry et al. However, they reported that inulin did not affect iron absorption in adult women. (110) A recent in vivo study on rats was published in 2021 by Mohammed et al. on the bioavailability of yogurt fortified with iron and supplemented by long- and short-chain inulin. Results showed that fortified yogurt with inulin, particularly the long-chain inulin and iron, has a promising impact on treating iron deficiency by enhancing iron absorption. (111) One possible mechanism for enhancing the impact of prebiotics may be that prebiotics promote iron absorption through prebiotic fermentation by beneficial microorganisms found in the colon producing short-chain fatty acids (SCFAs). SCFAs can contribute to lowering the pH of the luminal content, enhancing iron solubility by increasing the reduction of Fe(III) to Fe(II), and can increase the absorbent surface area by stimulating the proliferation of epithelial cells. (112)
Oxalic acid and oxalates are considered undesirable components in human and animal nutrition. The excessive consumption of plants high in oxalates may cause hyperoxaluria, which might result in kidney and bladder stones and renal edema and calcification in the worst-case scenario. (113) Oxalic acid was previously reported to inhibit calcium (114,115) and zinc (116) absorption. However, its impact on iron absorption is debatable. Rat studies have shown that the effect of adding purified oxalic acid to the diet is neutral. (117,118) Similarly, a human study reported that the effect of oxalic acid on iron absorption is insignificant. The authors presumed that most of the iron found in the meal is in the ferric form in the gastric and duodenal phases of digestion. When iron is in the ferrous form, such as in ascorbic-acid-rich foods, oxalic acid may limit iron absorption by producing insoluble ferrous oxalate. (119) On the contrary, Gupta et al. reported oxalic acid as the most significant inhibitory factor for iron and calcium absorption from green leafy vegetables. (120)
In short, nonheme iron absorption is affected by the presence of various nutrients. Polyphenols, phytates, calcium, and specific proteins are known to decrease iron absorption, while ascorbic acid, animal tissues, and some other proteins may improve the absorption. For dietary fibers, discussions are still under debate. Calcium differs from all these nutrients as it decreases the absorption of both nonheme and heme iron. The mechanism of action for this condition has not been fully elucidated. Looking at all these, dietary factors for iron absorption carry crucial importance, especially for individuals experiencing iron deficiency and anemia, which are intensely studied subjects with promising developments.
6. Recent Studies on Improving Iron Bioavailability
ARTICLE SECTIONS
Various strategies are known and applied to reduce the prevalence of iron deficiency anemia. (123) In addition, numerous studies have been carried out for years to enhance iron absorption in humans. General estimates of iron bioavailability include in vitro studies, animal bioassays, and human trials. In vitro methods have been used as an alternative to in vivo techniques for estimating mineral bioavailability. Most of the in vitro methods have been developed to mimic physiological conditions of the intestine system. Human and animal studies on iron absorption are time consuming and expensive and offer a limited capacity to assess luminal interactions of iron and food ingredients. These factors directed scientists to develop fast and efficient in vitro methods that help analyze food–iron interactions and estimate iron bioavailability.
In consequence, a simulation of in vitro digestion combined with caco-2 cell monolayers (human epithelial cell line) was developed. (124) The caco-2 model is considered helpful because it is of human origin, has many characteristics analogous to the intestinal epithelium, takes up nonheme iron, and exhibits uptake properties consistent with in vivo observations in humans and animals. (125) Therefore, this section covers in vitro digestion/caco-2 cell culture model studies and in vivo human and animal studies. Recent in vivo studies to improve iron bioavailability are shown in Table 2 and in vitro/caco-2 cell culture model studies in Table 3.
Table 2. Recent in Vivo Studies on Improving Iron Bioavailability
| technique | compound | study system | food | results | reference |
|---|---|---|---|---|---|
| encapsulation | iron encapsulated in banana peel matrix | animal bioassay (rat) | tempeh | A significant (p < 0.05) increase was observed in serum hemoglobin and iron levels in all groups with the highest value found in an iron matrix dose of 20 ppm. | (137) |
| iron and folic acid (FA) bovine serum albumin nanoparticles | animal bioassay (rat) | stirred functional yogurt | Enhancement in the levels of hemoglobin, iron, ferritin, and total protein was observed. | (138) | |
| microencapsulated liposomal iron pyrophosphate | human trial | iron pyrophosphate sachets | Microencapsulated liposomal iron pyrophosphate sachets showed higher palatability and bioavailability. | (145) | |
| Serum hemoglobin levels in nonpregnant women of reproductive age were significantly increased. | |||||
| lipoosomal iron | human trial | oral liposomal iron | 62% of the patients who completed the treatment responded to oral liposomal iron therapy (mean increases of hemoglobin from 11.4 to 12.6 g/dL). | (146) | |
| Number of patients with mild iron deficiency was decreased. | |||||
| chelation | tripeptide iron complex, ferrous glycinate | animal bioassay (rat) | - | Blood parameters such as hemoglobin, serum ferritin, and transferrin levels as well as growth parameters and mRNA expression which is a marker of iron deficiency showed that the tripeptide iron complex was more efficient than FeSO4 or the ferrous glycinate complex in alleviating IDA. | (154) |
| desalted duck egg white peptides-ferrous chelate | animal bioassay (rat) | - | In iron-deficient rats, 3 weeks of treatment caused red blood cells, serum ferritin, hemoglobin, and serum iron levels to reach the normal levels. | (152) | |
| The effects of IDA were reduced more efficiently by desalted duck egg white peptide-ferrous chelate compared to FeSO4. | |||||
| whey protein concentrate–iron complex | animal bioassay (rat) | - | In regular weaning and anemic conditions, the WPC–Fe complex supplementation improves iron bioavailability, hemoglobin level, percent apparent digestibility coefficient, and percent retention/intake. | (161) | |
| In iron-deficient animals, a spray-dried WPC–Fe complex supplementation significantly increased iron digestion and metabolism. | |||||
| nanoparticulation | ferric hydroxide-polyphosphate nanoparticles | animal bioassay (rat) | - | Relative iron bioavailability from polyP-FeO NPs was greater by ∼170% relative to FeSO4. | (168) |
| bio iron(II) nanoparticles | animal bioassay (rat) | yogurt | Bioiron nanoparticles were good sources of bioavailable iron. | (169) | |
| Bioiron nanoparticles in 200 and 400 μg/mL were safe and enhanced yogurt quality and shelf life. | |||||
| β-lactoglobulin fibril iron nanoparticles | animal bioassay (rat) | - | β-Lactoglobulin fibril iron nanoparticles were digestible and bioavailable without altering the organoleptic features of the food carriers. | (170) | |
| β-Lactoglobulin fibril nanocomposites showed no toxicity in a rat assay. |
Table 3. Recent in Vitro Studies on Improving Iron Bioavailability
| technique | compound | food | results | reference |
|---|---|---|---|---|
| encapsulation | iron encapsulated in thermo-resistant modified starch with or without vitamin C | conventionally and sourdough fermented breads | The bioavailability and bioaccessibility of iron from conventially fermented bread were higher in general. | (136) |
| Iron transport efficiency represented a wide range (1.16–13.78%). | ||||
| Fortified breads showed bioaccessibility values changing from 41.45 to 99.31%. | ||||
| Type of fermentation affected the degree of iron oxidation during digestion. | ||||
| Iron source, either ferrous sulfate or ferrous lactate, showed an effect on tested parameters but not statistically significant. | ||||
| microencapsulated iron coated by whey protein isolate and a starch-based aqueous coating | tea | Cellular absorption or iron from microcapsules was increased by 73%. | (140) | |
| Within 30 min of tea brewing, microcapsules reduced the formation of the iron–polyphenol complex in the tea by 60%. | ||||
| chelation | iron–casein complex with ascorbic acid | water and milk | Ascorbic acid addition at the molar ratio of 2:1 improved the iron absorption from ICCs and FeSO4 to close levels, and absorption levels were significantly higher than ferric pyrophosphate (FePP) with and without ascorbic acid. | (153) |
| lentil-derived hydrolyzed protein–iron complex | - | A significant decrease in the anemic condition in caco-2 cells was observed by looking at the mRNA levels of marker genes (divalent metal transporter-1 (DMT1), transferrin receptor (TFR), and ankyrin repeat domain 37 (ANKRD37)) that were induced by iron deficiency anemia. | (157) | |
| iron–red tilapia viscera hydrolysate complex | - | The highest iron binding ability was obtained by hydrolysate with 42.5% of hydrolyzation degree. | (158) | |
| 4.7 times higher bioavailability compared to free iron salts was obtained in the complex of red tilapia viscera hydrolysate with 42.5% of hydrolyzation degree and iron. | ||||
| whey protein–iron complex | - | Both mineral uptake and ferritin synthesis were better in the case of WP–mineral complexes. | (160) | |
| Minerals (iron and zinc) complexed with whey protein showed a significantly lower pro-oxidant activity but had higher bioaccessibility (76%) compared to iron salts alone (68%). | ||||
| whey protein–iron FeCl2 and FeSO4) complex | - | Complexes prepared with low molecular mass peptides and FeCl2 enhanced the iron bioavailability by approximately 70% compared to FeSO4. | (159) | |
| Complexes except for those synthesized with low molecular mass peptides (<5 kDa) increased bioaccessibility value to a level higher than 85%. |
Different approaches, including encapsulation and chelation, are applied to improve iron bioavailability. (15) Encapsulation is a way of entrapping active agents within a carrier medium and is an effective technique for enhancing the delivery of bioactive molecules and living cells into food. (126) Encapsulation can be made either in nano or micro forms. The main target of this process is to create a thermodynamically and physically strong barrier against environmental conditions, essentially enzymes, pH, oxygen, and water vapor. (127) Various studies are available in the literature that encapsulate iron in microstructured emulsion particles, (128) double emulsions, (129−131) maltodextrin microparticles, (132) liposomes, (133,134) and hydrolyzed glucomannan. (135) Bryszewska et al. conducted a study in which ferrous sulfate or ferrous fumarate was encapsulated with or without vitamin C, and bread was fortified. The study used both in vitro bioavailability cell culture systems (human epithelial adenocarcinoma cell line caco-2) and test tube bioaccessibility approaches.
Both bioaccessibility and bioavailability of iron were higher in encapsulated forms. In addition, the type of iron source, ferrous lactate or sulfate, did not show a significant difference in those parameters. The reason for enhancement was that capsules created a barrier between the iron and food matrix, preventing the interaction between bioavailability inhibitors. (136) Kusuma and Ermamilia generated microbeads from banana peels to encapsulate the iron, and they assessed the bioavailability of iron-fortified food using the microbeads to fortify tempeh, an Indonesian food. The study applied in vivo conditions in 35 male Sprague–Dawley rats of age 2 weeks. A standard diet-fed rat (37 mg of elemental iron) or standard diet plus tempeh with elemental iron dose (10 and 20 ppm), encapsulated iron-fortified tempeh with elemental iron dose (10 ppm 20 ppm), and encapsulated iron-fortified tempeh with elemental iron dose + probiotic (10 ppm probiotic and 20 ppm probiotic). After 4 weeks of treatment, a significant (p < 0.05) increase was observed in serum hemoglobin and the iron levels in all groups. The hemoglobin and serum iron levels were the highest in iron-fortified tempeh with elemental iron dose + probiotic group (11.01 6 0.15 g/dl and 340.556 1.55 mg/dl, respectively) followed by encapsulated iron-fortified tempeh with an elemental iron dose group (10.71 6 0.15 g/dl and 338.07 6 4.17 mg/dl). The authors indicated that fortification of tempeh with encapsulated iron enhanced the iron status in iron deficiency anemia. (137) Darwish et al. formed iron and folic acid (FA) in bovine serum albumin nanoparticles as antianemic pharmacological agents that fortify stirred functional yogurt (SFY). They compared these with a plain control and SFY fortified with iron in free forms. Bioavailability, as well as viscosity, oxidative interactions, and microstructural properties of IDA-induced Albino rats were examined. At the end of the 4-week feeding period, Fe + FA nanocapsule-fortified SFY restored hemoglobin (16.53 gdL1), iron (109.25 gdL1), ferritin (33.25 gdL1), and total protein (8.6 gdL1), with considerable competition demonstrated in calcium and zinc absorbance. This repair in blood values was based on the targeted site-specific delivery of nanocapsules to cells in the digestive tract, which increases bioavailability and solubility. Based on the findings, the authors added that iron (Fe) and folic acid (FA) bovine serum albumin nanoparticles (BSA-NPs) could be suggested as an antianemia supplement in a variety of functional food applications. (138) Filiponi et al. obtained iron–peptide complexes by reacting small whey peptides (<5 kDa) with ferrous sulfate and encapsulating them by using maltodextrin and polydextrose as wall materials. The results revealed that iron bioavailability from caco-2 cells was significantly higher than their free forms. (139) Leiva Arrieta, (140) Bryszewska, (141) and Cian et al. (142) studied encapsulated iron absorption as in vitro bioaccessibility, and they also observed the enhancement impact of encapsulated iron.
Liposomes having high biodegradability and biocompatibility and being less toxic are used as drug carriers. Liposomal iron is prepared by the microencapsulation method by entrapping micronized iron inside the liposomal layer. (143) It is a relatively new development with high absorption and lower side effects. (144) In a study by Hussain et al., the efficacy of microencapsulated liposomal iron pyrophosphate on nonpregnant women at reproductive age with iron deficiency anemia was investigated. The study was carried out with 558 women for 12 weeks. It was observed that the hemoglobin levels in those women significantly increased from 8.71 ± 2.24 to 10.47 ± 1.69. (145) In a more recent study, de Alvarenga Antunes et al. designed a study on patients who had inactive or mildly active inflammatory bowel disease (IBD) and IDA. The patients took oral liposomal iron for 8 weeks. At the end of the 8 weeks, it was found that oral liposomal iron is effective in improving mild iron deficiency anemia in patients with IBD. Additionally, the quality of life of the patients was increased, and a decrease in fatigue was seen in some patients. Moreover, no adverse effects were observed in the patients. (146) Liposomal iron confers stability to the molecule and the ability to release the content gradually. In addition, the gradual release aids in better absorption. (145) Since it leads to a more rapid increase in Hb levels, it may be a potential treatment method for IDA.
Emulsions are one of the promising encapsulation and delivery technologies used mainly in the food and pharmaceutical industries, with advantages such as controlled release and chemical stability of encapsulated nutrients. (147) Two types of emulsions are available for food grades: water in oil and oil in water emulsions and double ones. (126) In the literature, several recent studies encapsulate iron in emulsions efficiently. (130,131,148,149) Looking at a bioaccessibility study, Buyukkestelli and El prepared a double (W1/O/W2) emulsion to encapsulate ferric chloride and measured the bioaccessibility. It was observed that the bioaccessibility of iron was higher in emulsions, and it was directly proportional to the W2 phase. (129) The complex of iron and iron-chelating peptides has been proposed as a much better enhancer of iron bioavailability and iron absorption than ionized iron. (150) Chelation protects minerals from inhibitors and increases bioavailability by 2–3 times. It overcomes encapsulation instability and the unproven safety of nanoparticles. However, although chelated mineral complexes are promising, their cost limits their use. (151) Recently, iron-chelating modes of peptides are gaining attention, and numerous studies have been done to clarify their capability to improve iron bioavailability. (150) Li et al. desalted the salted duck egg white and then formed desalted duck egg white peptide (DPs-Fe) and iron chelate to examine the bioavailability of this complex in vivo. While a standard diet was applied to the control group, the positive control group was fed with ferrous sulfate (FeSO4), and iron-deficient rats were fed with DPs-Fe. After 3 weeks of treatment, hemoglobin (Hb), red blood cells (RBCs), serum iron (SI), and serum ferritin (SF) levels reached the normal levels in iron-deficient rats. In addition, the DPs-Fe had no adverse effects on the healthy state of rats. In conclusion, the authors declared that DPs-Fe is more effective than FeSO4 in alleviating the impacts of iron deficiency. Thus, it was added by the authors that it could be a potential iron supplement for iron-deficient people. (152)
Sabatier et al. developed an iron–casein complex (ICC) with the aim of dairy fortification with iron. However, the study’s main objective was to state the ascorbic acid effect on the in vitro bioavailability of ICC compared to ferrous sulfate (FeSO4) and ferric pyrophosphate (FePP). Typically, in acidic environments, the solubility of ICC and FeSO4 was similar. However, only part of the iron dissociated from caseins. The authors declared that this case indicates that ICC is an iron chelate. Ascorbic acid addition in the molar ratio of 2:1 improved the iron absorption from ICCs and FeSO4 to close levels. However, the absorption levels were significantly higher than FePP. The absorption levels were translated into relative in vitro bioavailability to FeSO4 of 36% for FePP and 114 and 104% for the two ICCs. The authors declared that ICCs with better organoleptic characteristics compared to iron salts could be a good alternative for fortifying dairy products. (153) Xiao et al. studied the impacts of a tripeptide iron complex (REE-Fe) on iron-deficiency anemia rats. Sprague–Dawley rats were randomized into seven groups at random: a control group, an iron-deficiency control group, and iron-deficiency groups treated with ferrous sulfate (FeSO4), ferrous glycinate (Fe-Gly), or REE-Fe at low, medium, or high doses. The rats were given various iron supplements intragastrically once a day for 21 days. As a consequence, by looking at the blood parameters such as hemoglobin, serum ferritin, and transferrin levels, as well as growth parameters and mRNA expression which is a marker of iron deficiency, it was observed that REE-Fe was more efficient than FeSO4 or Fe-Gly to alleviate IDA. (154) Peptide–iron complexes can be absorbed as a whole in the form of soluble chelates and kept in the ferrous state in the digestive system. Chelates increase iron bioavailability by allowing ferrous metals to pass through the apical membrane of the intestinal epithelium. (155) Therefore, the chelation method can regulate iron bioavailability, as proven in studies.
In the past decades, the hydrolysates obtained from proteolytic digestion of various food sources have gained attention since they can bind metal ions and enhance their stability, solubility, and bioavailability due to their spatial structure and diverse residues with chains that can donate electrons. (156) Evcan and Gulec formed a lentil-derived hydrolyzed protein–iron complex and observed the bioavailability in vitro in an anemic caco-2 cell line. The hydrolyzed protein–iron complex showed a significant decrease in the anemic condition in caco-2 cells by reducing the mRNA levels of marker genes (divalent metal transporter-1 (DMT1), transferrin receptor (TFR), and ankyrin repeat domain 37 (ANKRD37)) that were induced by iron deficiency anemia. (157) Gómez et al. hydrolyzed red tilapia viscera to obtain protein hydrolysate having iron-chelating activity. The iron content of hydrolysate with 42.5% of hydrolyzation degree (RTVH_B) and its fraction was evaluated. Additionally, iron bioavailability was measured indirectly as ferritin synthesis in a caco-2 cell model. The RTVH-B showed the maximum iron binding ability. In addition, the Fe2+–RTVH-B complex showed 4.7 times higher iron bioavailability than free iron salts. The authors suggested a potential application of RTVH-B as dietary supplements to improve iron absorption. (158)
Iron is a susceptible element for forming new complexes that can inhibit or enhance its bioavailability. Whey protein has been discussed to enhance iron absorption depending on the complexation. (159) Shilpashree et al. prepared whey protein–iron and whey protein–zinc complexes to evaluate their oxidative stability, in vitro bioavailability in the caco-2 model, and bioaccessibility. It was observed that iron and zinc complexed with whey protein have significantly lower pro-oxidant activity while having higher bioaccessibility (76%) than iron salts alone (68%). Furthermore, the bioavailability of whey protein-bound minerals in caco-2 cells was reported to be significantly higher as compared to free minerals. In conclusion, the authors additionally indicated that inhibition of iron catalytic activity by complexing with whey protein is possible, and both whey protein iron and zinc complexes have the potential to be used as organic fortificants in several foods. (160) Caetano-Silva et al. prepared whey protein–iron complexes with different ligands, including whey protein hydrolysate having a higher and lower fraction than 5 kDa and whey protein isolate. FeCl2 and FeSO4 were used as iron sources. The study was carried out at in vitro conditions. The bioavailability was measured indirectly as ferritin synthesis in a caco-2 cell model, and bioaccessibility was evaluated after in vitro gastrointestinal digestion. Results indicated that complexes prepared with low molecular mass peptides and FeCl2 enhanced the iron bioavailability by approximately 70% compared to FeSO4. Moreover, except for those synthesized with low molecular mass peptides (<5 kDa), all complexes increased the bioaccessibility value to a level higher than 85%. (159) Gandhi et al. conducted a study on rats. They assessed iron bioavailability from a spray-dried whey protein concentrate–iron (WPC–Fe) complex in weaning and anemic rats. Ferrous sulfate heptahydrate was used as an iron source. The normal-diet fed rats were subgrouped into control, WPC, FeSO4 (as positive standard), and WPC-Fe. Results showed that supplementation of the WPC–Fe complex increased the bioavailability, hemoglobin level, % apparent digestibility coefficient, and % retention. Furthermore, the WPC–Fe complex enhanced HDL cholesterol, catalyzed activity, and reduced LDL/VLDL and total cholesterol levels. The authors declared that the use of the WPC–Fe complex decreases the anemia prevalence in rats to combat anemia and iron-deficiency-related disorders. (161) Similar findings have also been obtained from studies conducted on a succinylated sodium caseinate–iron complex (Shilpashree et al.) (162) and lactose–iron complex (Sharma et al.). (163)
Nanotechnology is emerging as a viable technique for effective iron food fortification and drug delivery for the treatment of anemia, and food technologists and researchers are increasingly active in using it. (164) Nanoparticles have been previously proven to improve the bioavailability of the material. (165,166) However, even though these nanosized particles have better bioavailability, the mechanism and function of produced ferritin mimetic nanoparticles are unclear. (15) Besides their positive effects, oral nanoparticles causing adverse effects are still a concern, especially for their application in the food industry. (167) Most recently, Li et al. prepared highly negatively charged ferric hydroxide-polyphosphate nanoparticles (PolyP-FeONPs) and investigated the iron bioavailability in rat-polarized human intestinal epithelial caco-2 cells. They observed in rats that the relative iron bioavailability from PolyP-FeONPs was more significant (∼170% relative to FeSO4). (168) El-Saadony et al. formed bio iron(II) nanoparticles by using the Bacillus subtilis ML6 supernatant that reduces FeCl3 and produces biological ferrous nanoparticles (bio-Fe(II) NPs), and they supplemented yogurt with bio-Fe(II) NPs. They concluded that bio-Fe(II) NPs were good and safe sources of bioavailable iron with improved sensory properties. (169) Shen et al. developed a novel β-lactoglobulin fibril–iron nanoparticle hybrid material for iron supplementation. Biodegradable amyloid fibril and iron nanoparticles were combined to form a hybrid material. The new iron nanoparticles were stable in foods and beverages and did not cluster together. In vivo testing revealed that the novel supplement was easily digestible and bioavailable without altering the organoleptic features of the food carriers. Furthermore, in rat toxicological investigations, iron β-lactoglobulin fibril nanocomposites showed no toxicity. (170)
7. Conclusion
ARTICLE SECTIONS
Iron is an essential element for human life, and due to its electron exchange features, it takes part in oxygen transport, energy production, DNA, RNA, and protein synthesis. It is involved in the structure of many enzymes and/or is necessary for their function. Sufficient iron intake, especially from meat, poultry, and seafood, is necessary to prevent iron deficiency and anemia since these foods are rich in the bioavailable form of heme iron. In underdeveloped and developing countries, mainly meat and fish products fall into the category of expensive products, and people may have limited access to these products. On the other hand, there are people who avoid the consumption of these products in line with their own sensitivities and preferences. These people may be at higher risk for iron deficiency and anemia. In this context, the importance of studies to increase iron bioavailability is indisputable. Encapsulation, emulsification, chelation, and fortification play an important role in increasing the bioavailability and absorption rate of iron. Commercial iron supplements are available for humans suffering from IDA or wishing to get iron as a supplement. However, because of the free iron-dependent radical generation, some of the commercial iron supplements may produce adverse effects in the gut lumen and mucosal area of the intestine. Therefore, preventing iron deficiency through the widespread consumption of iron supplements requires continuous innovation in products and processes and also requires a high level of public awareness.
Author Information
ARTICLE SECTIONS
- Esra Capanoglu - Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, Maslak, 34469 Istanbul, Turkey;
https://orcid.org/0000-0003-0335-9433;
References
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- 2BOLDT, D. H. New Perspectives on Iron: An Introduction. Am. J. Med. Sci. 1999, 318 (4), 207, DOI: 10.1097/00000441-199910000-00001[Crossref], [PubMed], [CAS], Google Scholar2https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK1MvltVertg%253D%253D&md5=fe646caf722550bc8f1a9c43c1a209e8New perspectives on iron: an introductionBoldt D HThe American journal of the medical sciences (1999), 318 (4), 207-12 ISSN:0002-9629.Iron is an essential nutritional element for all life forms. Iron plays critical roles in electron transport and cellular respiration, cell proliferation and differentiation, and regulation of gene expression. Two emerging new functions for iron are its necessary role in supporting transcription of certain key genes required for cell growth and function [eg, nitric oxide synthase, protein kinase C-beta, p21 (CIP1/WAF1)] and its complex role in hematopoietic cell differentiation. However, iron is also potentially deleterious. Reactive oxygen species generated by Fenton chemistry may contribute to major pathological processes such as cancer, atherosclerosis, and neurodegenerative diseases. Iron-generated reactive oxygen species may also function in normal intracellular signaling. Therefore, roles of iron are both essential and extraordinarily diverse. This symposium explores this diversity by covering topics of iron absorption and transport, the regulation of gene expression by iron responsive proteins, the cellular biology of heme, hereditary hemochromatosis, and clinical use of serum transferrin receptor measurements.
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- 4Hurrell, R. F. Preventing Iron Deficiency Through Food Fortification. Nutr. Rev. 1997, 55 (6), 210– 222, DOI: 10.1111/j.1753-4887.1997.tb01608.x[Crossref], [PubMed], [CAS], Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK2svisV2ksw%253D%253D&md5=8363e47b78421a2e966c684681962a13Preventing iron deficiency through food fortificationHurrell R FNutrition reviews (1997), 55 (6), 210-22 ISSN:0029-6643.One way to prevent iron deficiency anemia in developing countries is through the fortification of food products with iron. In addition to avoiding undesirable color and flavor changes, the main challenge is to protect the fortification iron from potential inhibitors of iron absorption present in commonly fortified foods.
- 5Roughead, Z. K.; Zito, C. A.; Hunt, J. R. Initial Uptake and Absorption of Nonheme Iron and Absorption of Heme Iron in Humans Are Unaffected by the Addition of Calcium as Cheese to a Meal with High Iron Bioavailability. Am. J. Clin. Nutr. 2002, 76 (2), 419– 425, DOI: 10.1093/ajcn/76.2.419[Crossref], [PubMed], [CAS], Google Scholar5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XlslOlt7o%253D&md5=76b5dfe41f083f5ed519a53afa72e85dInitial uptake and absorption of nonheme iron and absorption of heme iron in humans are unaffected by the addition of calcium as cheese to a meal with high iron bioavailabilityRoughead, Zamzam K.; Zito, Carol A.; Hunt, Janet R.American Journal of Clinical Nutrition (2002), 76 (2), 419-425CODEN: AJCNAC; ISSN:0002-9165. (American Society for Clinical Nutrition)Quant. data on the mucosal uptake and serosal transfer of nonheme iron in humans and the effects of calcium on these processes are limited. The initial mucosal uptake, the subsequent serosal transfer of nonheme iron, and the effects of adding calcium to meals on both heme and nonheme iron retention were examd. in 17 humans (9 women, 8 men) with normal Hb and ferritin levels. Whole-gut lavage and whole-body scintillation counting methods were used to det. the 8-h uptake of nonheme iron and the 2-wk retention (absorption) of heme and nonheme iron after consumption of radiolabeled foods. The initial uptake and absorption of nonheme iron were 11 and 7%, resp., and the absorption of heme iron was 15%. Two-thirds of the nonheme iron taken up by the mucosa within 8 h was retained by the body after 2 wk (serosal transfer index 0.63). Blood serum ferritin levels correlated inversely with the initial uptake and absorption of nonheme iron, but not with the nonheme serosal transfer index or the absorption of heme iron. Adding calcium (127 mg in cheese) to the meal did not affect the iron absorption. Thus, the initial mucosal uptake was the primary control point for nonheme iron absorption. An apparent decrease in heme iron absorption assocd. with the lavage procedure suggested that the uptake of heme iron may take longer and proceed further through the intestine than that of nonheme iron. The absorption of both forms of iron was not affected by the addn. of cheese to the meals with high iron bioavailability.
- 6Zijp, I. M.; Korver, O.; Tijburg, L. B. M. Effect of Tea and Other Dietary Factors on Iron Absorption. Crit. Rev. Food Sci. Nutr. 2000, 40 (5), 371– 398, DOI: 10.1080/10408690091189194[Crossref], [PubMed], [CAS], Google Scholar6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXnsFCis7k%253D&md5=4e8461e34169d1f66c605c7997a57887Effect of tea and other dietary factors on iron absorptionZijp, Itske M.; Korver, Onno; Tijburg, Lilian B. M.Critical Reviews in Food Science and Nutrition (2000), 40 (5), 371-398CODEN: CRFND6; ISSN:1040-8398. (CRC Press LLC)Iron deficiency is a major world health problem, i.e., to a great extent, caused by poor iron absorption from the diet. Several dietary factors can influence this absorption. Absorption enhancing factors are ascorbic acid and meat, fish and poultry; inhibiting factors are plant components in vegetables, tea and coffee (e.g., polyphenols, phytates), and calcium. After identifying these factors their individual impact on iron absorption is described. Specific attention was paid to the effects of tea on iron absorption. We propose a calcn. model that predicts iron absorption from a meal. Using this model we calcd. the iron absorption from daily menus with varying amts. of enhancers and inhibitors. From these calcns. we conclude that the presence of sufficient amts. of iron absorption enhancers (ascorbic acid, meat, fish, poultry, as present in most industrialized countries) overcomes inhibition of iron absorption from even large amts. of tea. In individuals with low intakes of heme iron, low intakes of enhancing factors and/or high intakes of inhibitors, iron absorption may be an issue. Depletion of iron stores enhances iron absorption, but this effect is not adequate to compensate for the inhibition of iron absorption in such an inadequate dietary situation. For subjects at risk of iron deficiency, the following recommendations are made. Increase heme-iron intake (this form of dietary iron present in meat fish and poultry is hardly influenced by other dietary factors with respect to its absorption); increase meal-time ascorbic acid intake; fortify foods with iron. Recommendations with respect to tea consumption (when in a crit. group) include: consume tea between meals instead of during the meal; simultaneously consume ascorbic acid and/or meat, fish and poultry.
- 7Cepeda-Lopez, A. C.; Melse-Boonstra, A.; Zimmermann, M. B.; Herter-Aeberli, I. In Overweight and Obese Women, Dietary Iron Absorption Is Reduced and the Enhancement of Iron Absorption by Ascorbic Acid Is One-half That in Normal-Weight Women. Am. J. Clin. Nutr. 2015, 102 (6), 1389– 1397, DOI: 10.3945/ajcn.114.099218[Crossref], [PubMed], [CAS], Google Scholar7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XntlWrsro%253D&md5=77944293b662169dec201b929dc43636In overweight and obese women, dietary iron absorption is reduced and the enhancement of iron absorption by ascorbic acid is one-half that in normal-weight womenCepeda-Lopez, Ana C.; Melse-Boonstra, Alida; Zimmermann, Michael B.; Herter-Aeberli, IsabelleAmerican Journal of Clinical Nutrition (2015), 102 (6), 1389-1397CODEN: AJCNAC; ISSN:0002-9165. (American Society for Nutrition)Background: Iron deficiency is common in overweight and obese individuals. This deficiency may be due to adiposity-related inflammation that increases serum hepcidin and decreases dietary iron absorption. Because hepcidin reduces iron efflux from the basolateral enterocyte, it is uncertain whether luminal enhancers of dietary iron absorption such as ascorbic acid can be effective in overweight and obese individuals. Objective: In this study, we compared iron absorption from a meal with ascorbic acid (+AA) and a meal without ascorbic acid (-AA) in women in a normal-wt. group (NW) with those in overweight and obese groups combined (OW/OB). Design: Healthy, nonanemic women [n = 62; BMI (in kg/m2): 18.5-39.9] consumed a stable-isotope-labeled wheat-based test meal -AA and a wheat-based test meal +AA (31.4 mg ascorbic acid). We measured iron absorption and body compn. with the use of dual-energy X-ray absorptiometry, blood vol. with the use of a carbon monoxide (CO)-rebreathing method, iron status, inflammation, and serum hepcidin. Results: Inflammatory biomarkers (all P < 0.05) and hepcidin (P = 0.08) were lower in the NW than in the OW/OB. Geometric mean (95% CI) iron absorptions in the NW and OW/OB were 19.0% (15.2%, 23.5%) and 12.9% (9.7%, 16.9%) (P = 0.049), resp., from -AA meals and 29.5% (23.3%, 38.2%) and 16.6% (12.8%, 21.7%) (P = 0.004), resp., from +AA meals. Median percentage increases in iron absorption for -AA to +AA meals were 56% in the NW (P < 0.001) and 28% in OW/OB (P = 0.006). Serum ferritin [R2 = 0.22; β = -0.17 (95% CI: -0.25, -0.09)], transferrin receptor [R2 = 0.23; β = 2.79 (95% CI: 1.47, 4.11)], and hepcidin [R2 = 0.13; β = -0.85 (95% CI: -1.41, -0.28)] were significant predictors of iron absorption. Conclusions: In overweight and obese women, iron absorption is two-thirds that in normal-wt. women, and the enhancing effect of ascorbic acid on iron absorption is one-half of that in normal-wt. women. Recommending higher intakes of ascorbic acid (or other luminal enhancers of iron absorption) in obese individuals to improve iron status may have a limited effect.
- 8Lönnerdal, B. Calcium and Iron Absorption - Mechanisms and Public Health Relevance. Int. J. Vitam. Nutr. Res. 2010, 80 (4–5), 293– 299, DOI: 10.1024/0300-9831/a000036[Crossref], [PubMed], [CAS], Google Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXlsFWis7Y%253D&md5=453bf41a58f51c5b501e0a16afdcf320Calcium and iron absorption - mechanisms and public health relevanceLonnerdal, BoInternational Journal for Vitamin and Nutrition Research (2010), 80 (4-5), 293-299CODEN: IJVNAP; ISSN:0300-9831. (Hogrefe & Huber Publishers)A review. Studies on human subjects have shown that calcium (Ca) can inhibit iron (Fe) absorption, regardless of whether it is given as Ca salts or in dairy products. This has caused concern as increased Ca intake commonly is recommended for children and women, the same populations that are at risk of Fe deficiency. However, a thorough review of studies on humans in which Ca intake was substantially increased for long periods shows no changes in hematol. measures or indicators of iron status. Thus, the inhibitory effect may be of short duration and there also may be compensatory mechanisms. The interaction between Ca and Fe may be a lumenal event, affecting Fe uptake through DMT1 (divalent metal transporter 1) at the apical membrane. However, it is also possible that inhibition occurs during Fe transfer into circulation, suggesting roles for the serosal exporter ferroportin (FPN) and hephaestin. We explored these possibilities in human intestinal Caco-2 cells cultured in monolayers. Iron transport (59Fe) and expression of DMT1, FPN, and hephaestin were assessed after 1.5 and 4 h with 0 or 100 μM CaCl2. Although Ca did not affect Fe uptake or DMT1 expression at 1.5 h, FPN abundance at the basolateral membrane decreased, resulting in increased cellular Fe retention and decreased Fe efflux. After 4 h, DMT1 and FPN expression increased and there was increased FPN at the membrane, suggesting a rebound effect. Thus, the effect of Ca on Fe absorption may be of short duration and adaptation may occur with time. This may explain why studies on long-term Ca supplementation of different groups fail to show any adverse effects on Fe status.
- 9Schönfeldt, H. C.; Pretorius, B.; Hall, N. Bioavailability of Nutrients. Encycl. Food Heal. 2016, 401– 406, DOI: 10.1016/B978-0-12-384947-2.00068-4
- 10Sifakis, S.; Pharmakides, G. Anemia in Pregnancy. Ann. N.Y. Acad. Sci. 2000, 900, 125– 136, DOI: 10.1111/j.1749-6632.2000.tb06223.x[Crossref], [PubMed], [CAS], Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXjsFChtro%253D&md5=1db3cfd0afb7c4ebc27672b610bac9f9Anemia in pregnancySifakis, S.; Pharmakides, G.Annals of the New York Academy of Sciences (2000), 900 (Young Woman at the Rise of the 21st Century: Gynecological and Reproductive Issues in Health and Disease), 125-136CODEN: ANYAA9; ISSN:0077-8923. (New York Academy of Sciences)A review, with 52 refs. Anemia is one of the most frequent complications related to pregnancy. Normal physiol. changes in pregnancy affect the Hb, and there is a relative or abs. redn. in Hb concn. The most common true anemias during pregnancy are iron deficiency anemia (approx. 75%) and folate deficiency megaloblastic anemia, which are more common in women who have inadequate diets and who are not receiving prenatal iron and folate supplements. Severe anemia may have adverse effects on the mother and the fetus. Anemia with Hb levels less than 6 gr/dL is assocd. with poor pregnancy outcome. Prematurity, spontaneous abortions, low birth wt., and fetal deaths are complications of severe maternal anemia. Nevertheless, a mild to moderate iron deficiency does not appear to cause a significant effect on fetal Hb concn. An Hb level of 11 gr/dL in the late first trimester and also of 10 gr/dL in the second and third trimesters are suggested as lower limits for Hb concn. In an iron-deficient state, iron supplementation must be given and follow-up is indicated to diagnose iron-unresponsive anemias.
- 11Gulec, S.; Anderson, G. J.; Collins, J. F. Mechanistic and Regulatory Aspects of Intestinal Iron Absorption. Am. J. Physiol. - Gastrointest. Liver Physiol. 2014, 307 (4), 397– 409, DOI: 10.1152/ajpgi.00348.2013
- 12Johnson-Wimbley, T. D.; Graham, D. Y. Diagnosis and Management of Iron Deficiency Anemia in the 21st Century. Therap. Adv. Gastroenterol. 2011, 4 (3), 177– 184, DOI: 10.1177/1756283X11398736[Crossref], [PubMed], [CAS], Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3MnisFGktg%253D%253D&md5=27e353206a99730bf146b44635e042cfDiagnosis and management of iron deficiency anemia in the 21st centuryJohnson-Wimbley Terri D; Graham David YTherapeutic advances in gastroenterology (2011), 4 (3), 177-84 ISSN:.Iron deficiency is the single most prevalent nutritional deficiency worldwide. It accounts for anemia in 5% of American women and 2% of American men. The goal of this review article is to assist practitioners in understanding the physiology of iron metabolism and to aid in accurately diagnosing iron deficiency anemia. The current first line of therapy for patients with iron deficiency anemia is oral iron supplementation. Oral supplementation is cheap, safe, and effective at correcting iron deficiency anemia; however, it is not tolerated by some patients and in a subset of patients it is insufficient. Patients in whom the gastrointestinal blood loss exceeds the intestinal ability to absorb iron (e.g. intestinal angiodysplasia) may develop iron deficiency anemia refractory to oral iron supplementation. This population of patients proves to be the most challenging to manage. Historically, these patients have required numerous and frequent blood transfusions and suffer end-organ damage resultant from their refractory anemia. Intravenous iron supplementation fell out of favor secondary to the presence of infrequent but serious side effects. Newer and safer intravenous iron preparations are now available and are likely currently underutilized. This article discusses the possible use of intravenous iron supplementation in the management of patients with severe iron deficiency anemia and those who have failed oral iron supplementation.
- 13Fleming, R. E.; Bacon, B. R. Orchestration of Iron Homeostasis. N. Engl. J. Med. 2005, 352 (17), 1741– 1744, DOI: 10.1056/NEJMp048363[Crossref], [PubMed], [CAS], Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXjsFyiurY%253D&md5=5351184f232d8291008534abbfc1e1a2Orchestration of iron homeostasisFleming, Robert E.; Bacon, Bruce R.New England Journal of Medicine (2005), 352 (17), 1741-1744CODEN: NEJMAG; ISSN:0028-4793. (Massachusetts Medical Society)There is no expanded citation for this reference.
- 14Mackenzie, B.; Garrick, M. D. Iron Imports. II. Iron Uptake at the Apical Membrane in the Intestine. Am. J. Physiol. - Gastrointest. Liver Physiol. 2005, 289 (6), 981– 986, DOI: 10.1152/ajpgi.00363.2005
- 15Shubham, K.; Anukiruthika, T.; Dutta, S.; Kashyap, A. V.; Moses, J. A.; Anandharamakrishnan, C. Iron Deficiency Anemia: A Comprehensive Review on Iron Absorption, Bioavailability and Emerging Food Fortification Approaches. Trends Food Sci. Technol. 2020, 99, 58– 75, DOI: 10.1016/j.tifs.2020.02.021[Crossref], [CAS], Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXkslamtLo%253D&md5=df75d56f56243cf43e3fa8d112be877bIron deficiency anemia: A comprehensive review on iron absorption, bioavailability and emerging food fortification approachesShubham, Kumar; Anukiruthika, T.; Dutta, Sayantani; Kashyap, A. V.; Moses, Jeyan A.; Anandharamakrishnan, C.Trends in Food Science & Technology (2020), 99 (), 58-75CODEN: TFTEEH; ISSN:0924-2244. (Elsevier Ltd.)Anemia, a morbid condition, is a global concern that affects people of all age groups. This scenario has attracted the attention of several government organizations for implementing strict regulations to provide nutritional security. Iron fortification and supplementation has been in practice from the past decades. However, there is a need for detg. an effective strategy to address this rising concern among the vulnerable population. Among the existing approaches, iron fortification of foods remains to be cheaper and effective in targeting large-scale population without the intervention of pharmaceutical drugs. The key challenge is the bioavailability of iron from fortified foods. Thus, this work presents a comprehensive review of morbidities of anemia, causes, the significance of haem and non-haem iron, absorption, and bioavailability, in context with different iron fortification approaches. Apart from the nutritional deficit, anemia is also assocd. with a sedentary lifestyle linked with obesity and diabetes. The complex interaction of elemental iron and its physiol. have been highlighted in consideration with potential iron enhancers and inhibitors. It was found that the incorporation of haem iron would complement the effectiveness of non-haem iron through fortification. Several iron fortification techniques focused on combating iron deficiency have been described. Food fortification is a promising strategy for reducing the prevalence of anemia. Food vehicles must be designed considering its synergistic effects with iron complexes for effective absorption and bioavailability. However, the scalability, cost economics, safety concerns and acceptability of the iron-fortified foods remain as constraints that have to be addressed. Further, the application of novel food processing techniques with food fortification can result in the emergence of novel approaches for addressing iron deficiency and anemia.
- 16Kanayama, Y.; Tsuji, T.; Enomoto, S.; Amano, R. Multitracer Screening: Brain Delivery of Trace Elements by Eight Different Administration Methods. Biometals 2005, 18 (6), 553– 565, DOI: 10.1007/s10534-005-4775-6[Crossref], [PubMed], [CAS], Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XlsVei&md5=a8081deae7e762111703b69a271075e4Multitracer Screening: Brain Delivery of Trace Elements by Eight Different Administration MethodsKanayama, Yousuke; Tsuji, Takae; Enomoto, Shuichi; Amano, RyoheiBioMetals (2005), 18 (6), 553-565CODEN: BOMEEH; ISSN:0966-0844. (Springer)Trace elements are closely assocd. with the normal functioning of the brain. Therefore, it is important to det. how trace elements enter, accumulate, and are retained in the brain. Using the multitracer technique, which allows simultaneous tracing of many elements and comparison of their behavior under identical exptl. conditions, we examd. the influence of different administration methods, i.e., i.v. (IV), i.p. (IP), i.m. (IM), s.c. (SC), intracutaneous (IC), intranasal (IN), peroral (PO), and percutaneous (PC) administration, on the uptake of trace elements. A multitracer soln. contg. 16 radionuclides (i.e., 7Be, 46Sc, 48V, 51Cr, 54Mn, 59Fe, 56Co, 65Zn, 74As, 75Se, 83Rb, 85Sr, 88Y, 88Zr, 95mTc, and 103Ru) was used. The results indicated that the 83Rb brain uptake rate with intranasal administration was approx. twice those obtained with the other administration methods. This result indicated that a portion of Rb was delivered into the brain circumventing the blood circulation and that delivery could be accomplished mainly by olfactory transport. Multitracer screening of trace element delivery revealed differences in brain uptake pathways among administration methods.
- 17Swanson, C. A. Iron Intake and Regulation: Implications for Iron Deficiency and Iron Overload. Alcohol 2003, 30 (2), 99– 102, DOI: 10.1016/S0741-8329(03)00103-4[Crossref], [PubMed], [CAS], Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXmvVygsb4%253D&md5=51e8fc48ea03c052c7710ce3bcf03290Iron intake and regulation: implications for iron deficiency and iron overloadSwanson, Christine A.Alcohol (New York, NY, United States) (2003), 30 (2), 99-102CODEN: ALCOEX; ISSN:0741-8329. (Elsevier Science Inc.)A review. Although Fe deficiency anemia is the most common nutritional deficiency worldwide and in the United States, the health effects of Fe overload merit increased attention. In the United States, public health interventions such as fortification and enrichment of foods with Fe were undertaken to reduce the prevalence of Fe deficiency anemia and improve health. These measures, along with Fe supplementation, remain controversial, because addnl. exposure to dietary Fe places some segments of the population at increased risk of Fe excess. The health consequences of unmistakable Fe excess are exemplified by hemochromatosis, an Fe storage disease assocd. with liver damage further exacerbated by alc. consumption. Progressive liver damage assocd. with this condition is generally attributed to increased oxidative stress. In otherwise healthy individuals, more modest levels of Fe storage may occur if Fe is provided by supplements or otherwise added to the food supply. Increased Fe intake and storage were linked to a variety of chronic diseases. The assocns. are not firmly established but are of considerable public health importance.
- 18Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc; National Academies Press (US): Washington (DC), 2001. DOI: 10.17226/10026 .
- 19Camaschella, C. Iron Deficiency. Blood 2019, 133 (1), 30– 39, DOI: 10.1182/blood-2018-05-815944[Crossref], [PubMed], [CAS], Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXnt1Ohs7k%253D&md5=3cda9d081c09e6285152f5d28756e9afIron deficiencyCamaschella, ClaraBlood (2019), 133 (1), 30-39CODEN: BLOOAW; ISSN:1528-0020. (American Society of Hematology)A review. Iron deficiency anemia affects >1.2 billions individuals worldwide, and iron deficiency in the absence of anemia is even more frequent. Total-body (abs.) iron deficiency is caused by physiol. increased iron requirements in children, adolescents, young and pregnant women, by reduced iron intake, or by pathol. defective absorption or chronic blood loss. Adaptation to iron deficiency at the tissue level is controlled by iron regulatory proteins to increase iron uptake and retention; at the systemic level, suppression of the iron hormone hepcidin increases iron release to plasma by absorptive enterocytes and recycling macrophages. The diagnosis of abs. iron deficiency is easy unless the condition is masked by inflammatory conditions. Special attention is needed in areas endemic for malaria and other infections to avoid worsening of infection by iron treatment. Ongoing efforts aim at optimizing iron salts-based therapy by protocols of administration based on the physiol. of hepcidin control and reducing the common adverse effects of oral iron. IV iron, esp. last-generation compds. administered at high doses in single infusions, is becoming an effective alternative in an increasing no. of conditions because of a more rapid and persistent hematol. response and acceptable safety profile. Risks/benefits of the different treatments should be weighed in a personalized therapeutic approach to iron deficiency.
- 20Muñoz, M.; Antonio García-Erce, J.; Ngel, A.; Remacha, F. Disorders of Iron Metabolism. Part II: Iron Deficiency and Iron Overload. J. Clin. Pathol. 2011, 64 (4), 287– 296, DOI: 10.1136/jcp.2010.086991[Crossref], [PubMed], [CAS], Google Scholar20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXlvFGqt7k%253D&md5=3efafcb0f1552daab900b1b4f239478aDisorders of iron metabolism. part II: iron deficiency and iron overloadMunoz, Manuel; Garcia-Erce, Jose Antonio; Remacha, Angel FranciscoJournal of Clinical Pathology (2011), 64 (4), 287-296CODEN: JCPAAK; ISSN:0021-9746. (BMJ Publishing Group)A review. Main disorders of iron metab. Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron deficiency anemia. In chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, resulting in hypoferremia and iron restricted erythropoiesis, despite normal iron stores (functional iron deficiency), and finally anemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD + ID). In contrast, low hepcidin expression may lead to hereditary haemochromatosis (HH type I, mutations of the HFE gene) and type II (mutations of the hemojuvelin and hepcidin genes). Mutations of transferrin receptor 2 lead to HH type III, whereas those of the ferroportin gene lead to HH type IV. All these syndromes are characterised by iron overload. As transferrin becomes satd. in iron overload states, non-transferrin bound iron appears. Part of this iron is highly reactive (labile plasma iron), inducing free radical formation. Free radicals are responsible for the parenchymal cell injury assocd. with iron overload syndromes. Role of lab. testing in diagnosis In iron deficiency status, lab. tests may provide evidence of iron depletion in the body or reflect iron deficient red cell prodn. Increased transferrin satn. and/or ferritin levels are the main cues for further investigation of iron overload. The appropriate combination of different lab. tests with an integrated algorithm will help to establish a correct diagnosis of iron overload, iron deficiency and anemia. Review of treatment options Indications, advantages and side effects of the different options for treating iron overload (phlebotomy and iron chelators) and iron deficiency (oral or i.v. iron formulations) will be discussed.
- 21BLANC, B. Nutritional Anemias. Report of a WHO Scientific Group. WHO Tech Rep. Ser. 1968, 405, 1– 40Google ScholarThere is no corresponding record for this reference.
- 22Hercberg, S.; Preziosi, P.; Galan, P. Iron Deficiency in Europe. Public Health Nutr. 2001, 4 (2b), 537– 545, DOI: 10.1079/PHN2001139[Crossref], [PubMed], [CAS], Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3MngvVaisQ%253D%253D&md5=1c20047c7770459de83140f122c903a6Iron deficiency in EuropeHercberg S; Preziosi P; Galan PPublic health nutrition (2001), 4 (2B), 537-45 ISSN:1368-9800.In Europe, iron deficiency is considered to be one of the main nutritional deficiency disorders affecting large fractions of the population, particularly such physiological groups as children, menstruating women and pregnant women. Some factors such as type of contraception in women, blood donation or minor pathological blood loss (haemorrhoids, gynaecological bleeding...) considerably increase the difficulty of covering iron needs. Moreover, women, especially adolescents consuming low-energy diets, vegetarians and vegans are at high risk of iron deficiency. Although there is no evidence that an absence of iron stores has any adverse consequences, it does indicate that iron nutrition is borderline, since any further reduction in body iron is associated with a decrease in the level of functional compounds such as haemoglobin. The prevalence of iron-deficient anaemia has slightly decreased in infants and menstruating women. Some positive factors may have contributed to reducing the prevalence of iron-deficiency anaemia in some groups of population: the use of iron-fortified formulas and iron-fortified cereals; the use of oral contraceptives and increased enrichment of iron in several countries; and the use of iron supplements during pregnancy in some European countries. It is possible to prevent and control iron deficiency by counseling individuals and families about sound iron nutrition during infancy and beyond, and about iron supplementation during pregnancy, by screening persons on the basis of their risk for iron deficiency, and by treating and following up persons with presumptive iron deficiency. This may help to reduce manifestations of iron deficiency and thus improve public health. Evidence linking iron status with risk of cardiovascular disease or cancer is unconvincing and does not justify changes in food fortification or medical practice, particularly because the benefits of assuring adequate iron intake during growth and development are well established. But stronger evidence is needed before rejecting the hypothesis that greater iron stores increase the incidence of CVD or cancer. At present, currently available data do not support radical changes in dietary recommendations. They include all means for increasing the content of dietary factors enhancing iron absorption or reducing the content of factors inhibiting iron absorption. Increased knowledge and increased information about factors may be important tools in the prevention of iron deficiency in Europe.
- 23Osungbade, K. O.; Oladunjoye, A. O. Anaemia in Developing Countries: Burden and Prospects of Prevention and Control. Anemia 2012, 3, 116– 129, DOI: 10.5772/29148
- 24von Haehling, S.; Ebner, N.; Evertz, R.; Ponikowski, P.; Anker, S. D. Iron Deficiency in Heart Failure: An Overview. JACC Hear. Fail. 2019, 7 (1), 36– 46, DOI: 10.1016/j.jchf.2018.07.015
- 25Palti, H.; Pevsner, B.; Adler, B. Does Anemia in Infancy Affect Achievement on Developmental and Intelligence Tests?. Hum. Biol. 1983, 55 (1), 183– 194[PubMed], [CAS], Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaL3s7osVWmtQ%253D%253D&md5=7bf8ea224777122b4d08eba9b3fdc9e5Does anemia in infancy affect achievement on developmental and intelligence tests?Palti H; Pevsner B; Adler BHuman biology (1983), 55 (1), 183-94 ISSN:0018-7143.There is no expanded citation for this reference.
- 26Lozoff, B.; Jimenez, E.; Wolf, A. W. Long-Term Developmental Outcome of Infants with Iron Deficiency. N. Engl. J. Med. 1991, 325 (10), 687– 694, DOI: 10.1056/NEJM199109053251004[Crossref], [PubMed], [CAS], Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK3MzjtlKktA%253D%253D&md5=7ba1c393cd370ec123e4b625ffb6903eLong-term developmental outcome of infants with iron deficiencyLozoff B; Jimenez E; Wolf A WThe New England journal of medicine (1991), 325 (10), 687-94 ISSN:0028-4793.BACKGROUND: Iron-deficiency anemia has been associated with lowered scores on tests of mental and motor development in infancy. However, the long-term developmental outcome of infants with iron deficiency is unknown, because developmental tests in infancy do not predict later intellectual functioning. METHODS: This study is a follow-up evaluation of a group of Costa Rican children whose iron status and treatment were documented in infancy. Eighty-five percent (163) of the 191 children in the original group underwent comprehensive clinical, nutritional, and psychoeducational assessments at five years of age. The developmental test battery consisted of the Wechsler Preschool and Primary Scale of Intelligence, the Spanish version of the Woodcock-Johnson Psycho-Educational Battery, the Beery Developmental Test of Visual-Motor Integration, the Goodenough-Harris Draw-a-Man Test, and the Bruininks-Oseretsky Test of Motor Proficiency. RESULTS: All the children had excellent hematologic status and growth at five years of age. However, children who had moderately severe iron-deficiency anemia as infants, with hemoglobin levels less than or equal to 100 g per liter, had lower scores on tests of mental and motor functioning at school entry than the rest of the children. Although these children also came from less socioeconomically advantaged homes, their test scores remained significantly lower than those of the other children after we controlled for a comprehensive set of background factors. For example, the mean (+/- SD) adjusted Woodcock-Johnson preschool cluster score for the children who had moderate anemia in infancy (n = 30) was 448.6 +/- 9.7, as compared with 452.9 +/- 9.2 for the rest of the children (n = 133) (P less than 0.01); the adjusted visual-motor integration score was 5.9 +/- 2.1, as compared with 6.7 +/- 2.3 (P less than 0.05). CONCLUSIONS: Children who have iron-deficiency anemia in infancy are at risk for long-lasting developmental disadvantage as compared with their peers with better iron status.
- 27Walter, T. Effect of Iron-Deficiency Anemia on Cognitive Skills and Neuromaturation in Infancy and Childhood. Food Nutr. Bull. 2003, 24, S104– S110, DOI: 10.1177/15648265030244S207
- 28Carter, R. C.; Jacobson, J. L.; Burden, M. J.; Armony-Sivan, R.; Dodge, N. C.; Angelilli, M. L.; Lozoff, B.; Jacobson, S. W. Iron Deficiency Anemia and Cognitive Function in Infancy. Pediatrics 2010, 126 (2), e427– e434, DOI: 10.1542/peds.2009-2097
- 29Daubian-Nose, P.; Frank, M. K.; Esteves, A. M. Sleep Disorders: A Review of the Interface between Restless Legs Syndrome and Iron Metabolism. Sleep Sci. 2014, 7 (4), 234– 237, DOI: 10.1016/j.slsci.2014.10.002[Crossref], [PubMed], [CAS], Google Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28zjs1yrsA%253D%253D&md5=175047fe79f897941d1c61584c96f493Sleep disorders: A review of the interface between restless legs syndrome and iron metabolismDaubian-Nose Paulo; Frank Miriam K; Esteves Andrea MaculanoSleep science (Sao Paulo, Brazil) (2014), 7 (4), 234-7 ISSN:1984-0659.Restless legs syndrome (RLS) is characterized by unpleasant sensations mainly in the legs. 43% of RLS-associated conditions have also been associated with systemic iron deficiency. The objective of this study was to review in the literature the relationship between iron metabolism and RLS. With an initial search using the keywords combination "Iron Metabolism OR Iron Deficiency AND Restless Legs Syndrome," 145 articles were screened, and 20 articles were selected. Few studies were found for this review in the period of 2001-2014, however, the correlation between RLS and iron was evident.
- 30Sîrbu, O.; Floria, M.; Dascalita, P.; Stoica, A.; Adascalitei, P.; Sorodoc, V.; Sorodoc, L. Anemia in Heart Failure - from Guidelines to Controversies and Challenges. Anatol. J. Cardiol. 2018, 20 (1), 52, DOI: 10.14744/ANATOLJCARDIOL.2018.08634[Crossref], [PubMed], [CAS], Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c%252FislOmtQ%253D%253D&md5=b38e637b094470d30e551744efe7cbd3Anemia in heart failure - from guidelines to controversies and challengesSirbu Oana; Dascalita Petru; Stoica Alexandra; Adascalitei Paula; Sorodoc Victorita; Sorodoc Laurentiu; Floria MarianaAnatolian journal of cardiology (2018), 20 (1), 52-59 ISSN:.Anemia associated with heart failure is a frequent condition, which may lead to heart function deterioration by the activation of neuro-hormonal mechanisms. Therefore, a vicious circle is present in the relationship of heart failure and anemia. The consequence is reflected upon the patients' survival, quality of life, and hospital readmissions. Anemia and iron deficiency should be correctly diagnosed and treated in patients with heart failure. The etiology is multifactorial but certainly not fully understood. There is data suggesting that the following factors can cause anemia alone or in combination: iron deficiency, inflammation, erythropoietin levels, prescribed medication, hemodilution, and medullar dysfunction. There is data suggesting the association among iron deficiency, inflammation, erythropoietin levels, prescribed medication, hemodilution, and medullar dysfunction. The main pathophysiologic mechanisms, with the strongest evidence-based medicine data, are iron deficiency and inflammation. In clinical practice, the etiology of anemia needs thorough evaluation for determining the best possible therapeutic course. In this context, we must correctly treat the patients' diseases; according with the current guidelines we have now only one intravenous iron drug. This paper is focused on data about anemia in heart failure, from prevalence to optimal treatment, controversies, and challenges.
- 31Barragán-Ibañez, G.; Santoyo-Sánchez, A.; Ramos-Peñafiel, C. O. Iron Deficiency Anaemia. Rev. Médica del Hosp. Gen. México 2016, 79 (2), 88– 97, DOI: 10.1016/J.HGMX.2015.06.008
- 32Camaschella, C. Iron-Deficiency Anemia. new Engl. J. o f Med. 2015, 372 (19), 1832– 1843, DOI: 10.1056/NEJMra1401038
- 33Rasmussen, K. M. Is There a Causal Relationship between Iron Deficiency or Iron-Deficiency Anemia and Weight at Birth, Length of Gestation and Perinatal Mortality?. J. Nutr. 2001, 131 (2), 590S– 603S, DOI: 10.1093/jn/131.2.590S[Crossref], [PubMed], [CAS], Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXht1Kjt78%253D&md5=5258dd20847f71232c59097ed0cedfcdIs there a causal relationship between iron deficiency or iron-deficiency anemia and weight at birth, length of gestation and perinatal mortality?Rasmussen, Kathleen M.Journal of Nutrition (2001), 131 (2S-2), 590S-603SCODEN: JONUAI; ISSN:0022-3166. (American Society for Nutritional Sciences)A review with 61 refs. An extensive literature review was conducted to identify whether iron deficiency, iron-deficiency anemia and anemia from other causes are related to low birth wt., preterm birth, or perinatal mortality. Strong evidence exists for an assocn. between maternal Hb concns. and birth wt. and between maternal Hb concns. and preterm birth. It was not possible to det. how much of this assocn. is attributable to iron-deficiency anemia in particular. Minimal values for both low birth wt. and preterm birth occurred at maternal Hb concns. below the current cut-off value for anemia during pregnancy (110 g/L) in a no. of studies, particularly those in which maternal Hb values were not controlled for during gestation. Supplementation of anemic or nonanemic pregnant women with iron, folic acid, or both does not appear to improve the birth wt. or the duration of gestation. These studies must be interpreted cautiously because most are subject to a bias toward false-neg. findings. Although there may be other reasons to offer women supplemental iron during pregnancy, the currently available evidence from studies with designs appropriate to establish a causal relationship is insufficient to support or reject this practice for the specific purposes of raising birth wt. or lowering the rate of preterm birth.
- 34Scholl, T. O. Maternal Iron Status: Relation to Fetal Growth, Length of Gestation, and Iron Endowment of the Neonate. Nutr. Rev. 2011, 69, S23– S29, DOI: 10.1111/j.1753-4887.2011.00429.x
- 35Brabin, B. J.; Hakimi, M.; Pelletier, D. An Analysis of Anemia and Pregnancy-Related Maternal Mortality. J. Nutr. 2001, 131 (2S-2), 604S– 614S, DOI: 10.1093/jn/131.2.604S[Crossref], [PubMed], [CAS], Google Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXht1Kjt7w%253D&md5=6dd47a55e469973053b3db1fbd3632beAn analysis of anemia and pregnancy-related maternal mortalityBrabin, Bernard J.; Hakimi, Mohammad; Pelletier, DavidJournal of Nutrition (2001), 131 (2S-2), 604S-615SCODEN: JONUAI; ISSN:0022-3166. (American Society for Nutritional Sciences)A review with 62 refs. The published data on the relationship of anemia as a risk factor for maternal mortality were analyzed from cross-sectional, longitudinal, and case-control studies; no randomized trial data were not available for anal. The following 6 methods of estn. of mortality risk were used: the correlation of maternal mortality rates with maternal anemia prevalence derived from national statistics, the proportion of maternal deaths attributable to anemia, the proportion of anemic women who die, population-attributable risk of maternal mortality due to anemia, adolescence as a risk factor for anemia-related mortality, and causes of anemia assocd. with maternal mortality. The av. ests. for all-cause anemia-attributable mortality (both direct and indirect) were 6.37, 7.26, and 3.0% for Africa, Asia, and Latin America, resp. The case fatality rates, based mainly on hospital studies, varied from <1 to >50%. The relative risk of mortality assocd. with moderate anemia (Hb 40-80 g/L) was 1.35 (95% CI 0.92-2.00) and for severe anemia (<47 g/L) was 3.51 (95% CI 2.05-6.00). The population-attributable risk ests. can be defended on the basis of the strong assocn. between severe anemia and maternal mortality, but not for mild or moderate anemia. In holoendemic malarious areas with a 5% severe anemia prevalence (Hb <70 g/L), it was estd. that in primigravidae there would be 9 severe-malaria anemia-related deaths and 41 nonmalarial anemia-related deaths (mostly nutritional) per 100,000 live births. The iron deficiency component in these ests. is unknown.
- 36Musallam, K. M.; Tamim, H. M.; Richards, T.; Spahn, D. R.; Rosendaal, F. R.; Habbal, A.; Khreiss, M.; Dahdaleh, F. S.; Khavandi, K.; Sfeir, P. M.; Soweid, A.; Hoballah, J. J.; Taher, A. T.; Jamali, F. R. Preoperative Anaemia and Postoperative Outcomes in Non-Cardiac Surgery: A Retrospective Cohort Study. Lancet 2011, 378 (9800), 1396– 1407, DOI: 10.1016/S0140-6736(11)61381-0[Crossref], [PubMed], [CAS], Google Scholar36https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3MbhsFWnuw%253D%253D&md5=fd39cee2a09f91e15e42d1333090b42dPreoperative anaemia and postoperative outcomes in non-cardiac surgery: a retrospective cohort studyMusallam Khaled M; Tamim Hani M; Richards Toby; Spahn Donat R; Rosendaal Frits R; Habbal Aida; Khreiss Mohammad; Dahdaleh Fadi S; Khavandi Kaivan; Sfeir Pierre M; Soweid Assaad; Hoballah Jamal J; Taher Ali T; Jamali Faek RLancet (London, England) (2011), 378 (9800), 1396-407 ISSN:.BACKGROUND: Preoperative anaemia is associated with adverse outcomes after cardiac surgery but outcomes after non-cardiac surgery are not well established. We aimed to assess the effect of preoperative anaemia on 30-day postoperative morbidity and mortality in patients undergoing major non-cardiac surgery. METHODS: We analysed data for patients undergoing major non-cardiac surgery in 2008 from The American College of Surgeons' National Surgical Quality Improvement Program database (a prospective validated outcomes registry from 211 hospitals worldwide in 2008). We obtained anonymised data for 30-day mortality and morbidity (cardiac, respiratory, CNS, urinary tract, wound, sepsis, and venous thromboembolism outcomes), demographics, and preoperative and perioperative risk factors. We used multivariate logistic regression to assess the adjusted and modified (nine predefined risk factor subgroups) effect of anaemia, which was defined as mild (haematocrit concentration >29-<39% in men and >29-<36% in women) or moderate-to-severe (≤29% in men and women) on postoperative outcomes. FINDINGS: We obtained data for 227,425 patients, of whom 69,229 (30·44%) had preoperative anaemia. After adjustment, postoperative mortality at 30 days was higher in patients with anaemia than in those without anaemia (odds ratio [OR] 1·42, 95% CI 1·31-1·54); this difference was consistent in mild anaemia (1·41, 1·30-1·53) and moderate-to-severe anaemia (1·44, 1·29-1·60). Composite postoperative morbidity at 30 days was also higher in patients with anaemia than in those without anaemia (adjusted OR 1·35, 1·30-1·40), again consistent in patients with mild anaemia (1·31, 1·26-1·36) and moderate-to-severe anaemia (1·56, 1·47-1·66). When compared with patients without anaemia or a defined risk factor, patients with anaemia and most risk factors had a higher adjusted OR for 30-day mortality and morbidity than did patients with either anaemia or the risk factor alone. INTERPRETATION: Preoperative anaemia, even to a mild degree, is independently associated with an increased risk of 30-day morbidity and mortality in patients undergoing major non-cardiac surgery. FUNDING: Vifor Pharma.
- 37Hurrell, R.; Egli, I. Iron Bioavailability and Dietary Reference Values. Am. J. Clin. Nutr. 2010, 91 (5), 1461S– 1467S, DOI: 10.3945/ajcn.2010.28674F[Crossref], [PubMed], [CAS], Google Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXlsVWru7g%253D&md5=512facdc0d5ba0ca7f37c98c3e6039a5Iron bioavailability and dietary reference valuesHurrell, Richard; Egli, InesAmerican Journal of Clinical Nutrition (2010), 91 (5S), 1461S-1467SCODEN: AJCNAC; ISSN:0002-9165. (American Society for Nutrition)A review. Iron differs from other minerals because iron balance in the human body is regulated by absorption only because there is no physiol. mechanism for excretion. On the basis of intake data and isotope studies, iron bioavailability has been estd. to be in the range of 14-18% for mixed diets and 5-12% for vegetarian diets in subjects with no iron stores, and these values have been used to generate dietary ref. values for all population groups. Dietary factors that influence iron absorption, such as phytate, polyphenols, calcium, ascorbic acid, and muscle tissue, have been shown repeatedly to influence iron absorption in single-meal isotope studies, whereas in multimeal studies with a varied diet and multiple inhibitors and enhancers, the effect of single components has been, as expected, more modest. The importance of fortification iron and food additives such as erythorbic acid on iron bioavailability from a mixed diet needs clarification. The influence of vitamin A, carotenoids, and non-digestible carbohydrates on iron absorption and the nature of the "meat factor" remain unresolved. The iron status of the individual and other host factors, such as obesity, play a key role in iron bioavailability, and iron status generally has a greater effect than diet compn. It would therefore be timely to develop a range of iron bioavailability factors based not only on diet compn. but also on subject characteristics, such as iron status and prevalence of obesity.
- 38Blanco-Rojo, R.; Vaquero, M. P. Iron Bioavailability from Food Fortification to Precision Nutrition. A Review. Innov. Food Sci. Emerg. Technol. 2019, 51, 126– 138, DOI: 10.1016/j.ifset.2018.04.015
- 39McDermid, J. M.; Lönnerdal, B. Iron. Adv. Nutr. 2012, 3 (4), 532– 533, DOI: 10.3945/an.112.002261[Crossref], [PubMed], [CAS], Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38fgtFKqsg%253D%253D&md5=4914c9d0761aa9a64e1db3245d4a08afIronMcDermid Joann M; Lonnerdal BoAdvances in nutrition (Bethesda, Md.) (2012), 3 (4), 532-3 ISSN:.There is no expanded citation for this reference.
- 40Rutzke, C. J.; Glahn, R. P.; Rutzke, M. A.; Welch, R. M.; Langhans, R. W.; Albright, L. D.; Combs, G. F.; Wheeler, R. M. Bioavailability of Iron from Spinach Using an in Vitro/Human Caco-2 Cell Bioassay Model. Habitation (Elmsford). 2004, 10 (1), 7– 14, DOI: 10.3727/154296604774808900[Crossref], [PubMed], [CAS], Google Scholar40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2M3kt1Kmsw%253D%253D&md5=8732d0364810f151f231757281cbcd1dBioavailability of iron from spinach using an in vitro/human Caco-2 cell bioassay modelRutzke Corinne J; Glahn Raymond P; Rutzke Michael A; Welch Ross M; Langhans Robert W; Albright Louis D; Combs Gerald F Jr; Wheeler Raymond MHabitation (Elmsford, N.Y.) (2004), 10 (1), 7-14 ISSN:1542-9660.Spinach (Spinacia oleracea) cv Whitney was tested for iron bioavailabilty using an in vitro human intestinal cell culture ferritin bioassay technique previously developed. Spinach was cultured in a growth chamber for 33 days, harvested, and freeze-dried. Total iron in the samples was an average of 71 micrograms/g dry weight. Spinach was digested in vitro (pepsin and 0.1 M HCl followed by pancreatin and 0.1 M NaHCO3) with and without the addition of supplemental ascorbic acid. Caco-2 cell cultures were used to determine iron bioavailability from the spinach mixtures. Production of the iron-binding protein ferritin in the Caco-2 cells showed the supplemental ascorbic acid doubled bioavailability of iron from spinach. The data show fresh spinach is a poor source of iron, and emphasize the importance of evaluation of whole meals rather than single food items. The data support the usefulness of the in vitro/Caco-2 cell ferritin bioassay model for prescreening of space flight diets for bioavailable iron.
- 41Tamburrano, A.; Tavazzi, B.; Anna, C.; Callà, M.; Amorini, A. M.; Lazzarino, G.; Vincenti, S.; Zottola, T.; Campagna, M. C.; Moscato, U.; Laurenti, P. Biochemical and Nutritional Characteristics of Buffalo Meat and Potential Implications on Human Health for a Personalized Nutrition. Ital. J. Food Saf. 2019, 8, 8317, DOI: 10.4081/ijfs.2019.8317[Crossref], [PubMed], [CAS], Google Scholar41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXosFentbw%253D&md5=0c84cdc67185d08143ab6ce320ee0e47Biochemical and nutritional characteristics of buffalo meat and potential implications on human health for a personalized nutritionTamburrano, Andrea; Tavazzi, Barbara; Calla, Cinzia Anna Maria; Amorini, Angela Maria; Lazzarino, Giacomo; Vincenti, Sara; Zottola, Tiziana; Campagna, Maria Concetta; Moscato, Umberto; Laurenti, PatriziaItalian Journal of Food Safety (2019), 8 (3), 8317CODEN: IJFSGY; ISSN:2239-7132. (PAGEPress Publications)The human consumption of food animal products is the main topic of an important debate among professionals in this sector: dietologists, dietitians and nutritional biologists. The red meat provides all the essential amino acids, bioavailable iron, zinc, calcium, lipids and B-group vitamins. A valid alternative to beef could be the buffalo meat. Italy is the largest European producer of buffalo meat and derivs. The high nutritional characteristics of buffalo meat make it suitable to be included in the Mediterranean diet to customize it in relation to the needs and conditions of the population. Polyunsatd./satd. fatty acids ratio can be influenced by diet, breed and type of breeding, but muscle tissue fat percentage is the main factor in detg. a favorable fatty acid compn. This review focuses on the biochem. and nutritional characteristics of the buffalo meat (content of fats, cholesterol, amino acids, vitamins and minerals), explaining their variability depending on the different breeds, and the favorable implications on the human health. These results suggest that buffalo meat can be a healthier alternative to beef, not only for healthy people in particular physiol. conditions (i.e. pregnancy), but also for persons at risk for cardiovascular and cerebrovascular diseases, thus achieving the goal of a personalized nutrition.
- 42Czerwonka, M.; Tokarz, A. Iron in Red Meat-Friend or Foe. Meat Sci. 2017, 123, 157– 165, DOI: 10.1016/j.meatsci.2016.09.012[Crossref], [PubMed], [CAS], Google Scholar42https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhs1yqsL3O&md5=57e612fac794a69abebe2b457e203a3aIron in red meat-friend or foeCzerwonka, Malgorzata; Tokarz, AndrzejMeat Science (2017), 123 (), 157-165CODEN: MESCDN; ISSN:0309-1740. (Elsevier Ltd.)In developed countries, due to high content and bioavailability, red and processed meats are the main sources of iron in the diet. Adequate intake of this nutrient is essential for the proper development and functioning of the human body, and its deficiencies are assocd. mainly with the occurrence of anemia, which is one of the most widespread nutritional problems in the world. However, excessive intake of iron can be detrimental to health. Studies have shown that high consumption of red meat and its products, and thereby iron, particularly in the form of heme, increases the risk of non-communicable diseases, including cancers, type II diabetes and cardiovascular disease. Due to the high nutritional value, the presence of red meat in the diet is preferable, but according to World Cancer Research Fund International its consumption should not exceed 500 g per wk. Furthermore, there are several potential ways to suppress the toxic effects of heme iron in the diet.
- 43Zimmermann, M. B.; Hurrell, R. F. Nutritional Iron Deficiency. Lancet 2007, 370, 511– 520, DOI: 10.1016/S0140-6736(07)61235-5[Crossref], [PubMed], [CAS], Google Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXovFCjsbg%253D&md5=90661953b34c68bb0b0ad44e197f0b9fNutritional iron deficiencyZimmermann, Michael B.; Hurrell, Richard F.Lancet (2007), 370 (9586), 511-520CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)A review. Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estd. 2 billion people. Nutritional iron deficiency arises when physiol. requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations consuming monotonous plant-based diets. The high prevalence of iron deficiency in the developing world has substantial health and economic costs, including poor pregnancy outcome, impaired school performance, and decreased productivity. Recent studies have reported how the body regulates iron absorption and metab. in response to changing iron status by upregulation or downregulation of key intestinal and hepatic proteins. Targeted iron supplementation, iron fortification of foods, or both, can control iron deficiency in populations. Although tech. challenges limit the amt. of bioavailable iron compds. that can be used in food fortification, studies show that iron fortification can be an effective strategy against nutritional iron deficiency. Specific lab. measures of iron status should be used to assess the need for fortification and to monitor these interventions. Selective plant breeding and genetic engineering are promising new approaches to improve dietary iron nutritional quality.
- 44Ems, T.; Huecker, M. R. Biochemistry, Iron Absorption. StatPearls 2019.Google ScholarThere is no corresponding record for this reference.
- 45Conrad, M. E.; Umbreit, J. N. Pathways of Iron Absorption. Blood Cells, Mol. Dis. 2002, 29 (3), 336– 355, DOI: 10.1006/bcmd.2002.0564[Crossref], [PubMed], [CAS], Google Scholar45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXlt1yksw%253D%253D&md5=dc13157e6ae25b0913a4a21c17dd257ePathways of iron absorptionConrad, Marcel E.; Umbreit, Jay N.Blood Cells, Molecules & Diseases (2002), 29 (3), 336-355CODEN: BCMDFX; ISSN:1079-9796. (Elsevier Science)A review. Iron is vital for all living organisms but excess iron can be lethal because it facilitates free radical formation. Thus iron absorption is carefully regulated to maintain an equil. between absorption and body loss of iron. In countries where meat is a significant part of the diet, most body iron is derived from dietary heme because heme binds few of the dietary chelators that bind inorg. iron. Uptake of heme into enterocytes occurs as a metalloporphyrin in an endosomal process. Intracellular iron is released from heme by heme oxygenase to enter plasma as inorg. iron. Ferric iron is absorbed via a β3 integrin and mobilferrin pathway (IMP) which is unshared with other nutritional metals. Ferrous iron uptake is facilitated by a DMT-1 pathway which is shared with manganese. In the iron deficient gut, large quantities of both mobilferrin and DMT-1 are found in goblet cells and intraluminal mucins suggesting that they are secreted with mucin into the intestinal lumen to bind iron to facilitate uptake by the cells. In the cytoplasm, IMP and DMT assoc. in a large protein complex called paraferritin which serves as a ferrireductase. Paraferritin solubilizes iron binding proteins and reduces iron to make iron available for prodn. of iron contg. proteins such as heme. Iron uptake by intestinal absorptive cells is regulated by the iron concn. within the cell. Except in hemochromatosis it remains in equil. with total body stores via transferrin receptors on the basolateral membrane of absorptive cells. Increased intracellular iron either up-regulates or satiates iron binding proteins on regulatory proteins to alter their location in the intestinal mucosa.
- 46Sharp, P. A. Intestinal Iron Absorption: Regulation by Dietary & Systemic Factors. Vitam. Nutr. Res. 2010, 80 (4–5), 231– 242, DOI: 10.1024/0300-9831/a000029[Crossref], [CAS], Google Scholar46https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXlsFWis78%253D&md5=db1ba22d9bdace071d28786cbf054b24Intestinal iron absorption: regulation by dietary & systemic factorsSharp, Paul A.International Journal for Vitamin and Nutrition Research (2010), 80 (4-5), 231-242CODEN: IJVNAP; ISSN:0300-9831. (Hogrefe & Huber Publishers)A review. Iron is an essential trace metal in human metab. However, imbalances in iron homeostasis are prevalent worldwide and have detrimental effects on human health. Humans do not have the ability to remove excess iron and therefore iron homeostasis is maintained by regulating the amt. of iron entering the body from the diet. Iron is present in the human diet in no. of different forms, including heme (from meat) and a variety of non-heme iron compds. While heme is absorbed intact, the bioavailability of non-heme iron varies greatly depending on dietary compn. A no. of dietary components are capable of interacting with iron to regulate its soly. and oxidn. state. Interestingly, there is an emerging body of evidence suggesting that some nutrients also have direct effects on the expression and function of enterocyte iron transporters. In addn. to dietary factors, body iron status is a major determinant of iron absorption. The roles of these important dietary and systemic factors in regulating iron absorption will be discussed in this review.
- 47Teucher, B.; Olivares, M.; Cori, H. Enhancers of Iron Absorption: Ascorbic Acid and Other Organic Acids. Vitam. Nutr. Res. 2004, 74 (6), 403– 419, DOI: 10.1024/0300-9831.74.6.403[Crossref], [CAS], Google Scholar47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhvFKgs7w%253D&md5=e0cb605164b75c917c4fe7ef4ecae81bEnhancers of iron absorption: ascorbic acid and other organic acidsTeucher, Birgit; Olivares, Manuel; Cori, HectorInternational Journal for Vitamin and Nutrition Research (2004), 74 (6), 403-419CODEN: IJVNAP; ISSN:0300-9831. (Hogrefe & Huber Publishers)A review. Ascorbic acid (AA), with its reducing and chelating properties, is the most efficient enhancer of non-heme iron absorption when its stability in the food vehicle is ensured. The no. of studies investigating the effects of AA on ferrous sulfate absorption far outweighs that of other iron fortificants. The promotion of iron absorption in the presence of AA is more pronounced in meals contg. inhibitors of iron absorption. Meals contg. low to medium levels of inhibitors require the addn. of AA at molar ratio of 2:1 (e.g., 20 mg AA: 3 mg iron). To promote absorption in the presence of high levels of inhibitors, AA needs to be added at molar ratios in excess of 4:1, which may be impractical. The effectiveness of AA in promoting iron absorption from less sol. compds., such as ferrous fumarate and elemental iron, requires further investigation. The instability of AA during food processing, storage and cooking, and the possibility of unwanted sensory changes limit the no. of suitable food vehicles for AA, whether used as vitamin fortificant or as an iron enhancer. Suitable vehicles include dry-blended foods, such as complementary precooked cereal-based infant foods, powd. milk, and other dry beverage products made for reconstitution that are packaged, stored, and prepd. in a way that maximizes retention of vitamin C. The consumption of natural sources of vitamin C in fruits and vegetables with iron-fortified dry blended foods is also recommended. Encapsulation can decrease AA losses during processing and storage, but these interventions will also add to cost. The bioavailability of encapsulated iron in the presence/absence of AA will need careful assessment in human clin. trials. Long-term effects of high AA intakes on iron status may be less than predicted from single meal studies. The hypothesis that an overall increase of dietary AA intake, or fortification of some foods commonly consumed with the main meal with AA alone, may be as effective as the fortification of the same food vehicle with AA and iron, merits further investigation. This must involve considerations of practicalities of implementation. To date, programs based on iron and AA fortification of infant formulas and cow milk provide the strongest evidence for the efficacy of AA fortification. The effects of added org. acids (acetic, propionic, lactic, citric, fumaric, malic, succinic, tartaric), as measured by in vitro and in vivo methods, is dependent on the source of iron, the type and concn. of org. acid, pH, processing methods, and the food matrix. The iron absorption-enhancing effect of AA is more potent than that of other org. acids due to its ability to reduce ferric to ferrous iron. Based on the data available, other org. acids may only be effective at molar ratios of acid to iron in excess of 100. This would translate into the min. presence/addn. of 1 g citric acid to a meal contg. 3 mg iron. Further characterization of the effectiveness of various org. acids in promoting iron absorption is required, esp. with respect to the optimal molar ratios of org. acid to iron, and assocd. feasibility for food application purposes. The suggested amt. of any org. acid required to produce nutritional benefits will result in unwanted organoleptic changes in most foods, thus limiting the application to a small no. of food vehicles (condiments, beverages). Fermented foods that already contain high levels of org. acids may be suitable iron fortification vehicles.
- 48Lynch, S. R.; Cook, J. D. INTERACTION OF VITAMIN C AND IRON. Ann. N.Y. Acad. Sci. 1980, 355 (1), 32– 44, DOI: 10.1111/j.1749-6632.1980.tb21325.x[Crossref], [PubMed], [CAS], Google Scholar48https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3MXot1GqsA%253D%253D&md5=acadf7f1ea69e2593b09d5ef8e4ed01fInteraction of vitamin C and ironLynch, Sean R.; Cook, James D.Annals of the New York Academy of Sciences (1980), 355 (Micronutr. Interact.: Vitam., Miner., Hazard. Elem.), 32-44CODEN: ANYAA9; ISSN:0077-8923.A review with 38 refs. on the enhancement of Fe absorption by dietary ascorbic acid [50-81-7].
- 49Smirnoff, N. Ascorbic Acid Metabolism and Functions: A Comparison of Plants and Mammals. Free Radic. Biol. Med. 2018, 122, 116– 129, DOI: 10.1016/j.freeradbiomed.2018.03.033[Crossref], [PubMed], [CAS], Google Scholar49https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXntVClu78%253D&md5=a8cb074b6bf244818a1b2c151e57e48bAscorbic acid metabolism and functions: A comparison of plants and mammalsSmirnoff, NicholasFree Radical Biology & Medicine (2018), 122 (), 116-129CODEN: FRBMEH; ISSN:0891-5849. (Elsevier B.V.)A review. Ascorbic acid is synthesized by eukaryotes, the known exceptions being primates and some other animal groups which have lost their functional gulonolactone oxidase. Prokaryotes do not synthesize ascorbate and do not need an ascorbate supply, so the functions that are essential for mammals and plants are not required or are substituted by other compds. The ability of ascorbate to donate electrons enables it to act as a free radical scavenger and to reduce higher Fe oxidn. states to Fe2+. These reactions are the basis of its biol. activity along with the relative stability of the resulting resonance stabilized monodehydroascorbate radical. The importance of these properties is emphasized by the evolution of at least 3 biosynthetic pathways and the prodn. of an ascorbate analog, erythroascorbate, by fungi. The Fe-reducing activity of ascorbate maintains the reactive center Fe2+ of 2-oxoglutarate-dependent dioxygenases (2-ODDs) thus preventing inactivation. These enzymes have diverse functions and, recently, the possibility that ascorbate status in mammals could influence 2-ODDs involved in histone and DNA demethylation thereby influencing stem cell differentiation and cancer has been uncovered. Ascorbate is involved in Fe uptake and transport in plants and animals. While the above biochem. functions are shared between mammals and plants, ascorbate peroxidase (APX) is an enzyme family limited to plants and photosynthetic protists. It provides these organisms with increased capacity to remove H2O2 produced by photosynthetic electron transport and photorespiration. The Fe-reducing activity of ascorbate enables hydroxyl radical prodn. (pro-oxidant effect) and the reactivity of dehydroascorbate (DHA) and reaction of its degrdn. products with proteins (dehydroascorbylation and glycation) is potentially damaging. Ascorbate status influences gene expression in plants and mammals, but at present there is little evidence that it acts as a specific signaling mol. It most likely acts indirectly by influencing the redox state of thiols and 2-ODD activity. However, the possibility that dehydroascorbylation is a regulatory post-translational protein modification could be explored.
- 50Khoja, K. K.; Aslam, M. F.; Sharp, P. A.; Latunde-Dada, G. O. In Vitro Bioaccessibility and Bioavailability of Iron from Fenugreek, Baobab and Moringa. Food Chem. 2021, 335, 127671, DOI: 10.1016/j.foodchem.2020.127671[Crossref], [PubMed], [CAS], Google Scholar50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsFSgsb7N&md5=9a278968fdca7a2a5410c65cb4900b3bIn vitro bioaccessibility and bioavailability of iron from fenugreek, baobab and moringaKhoja, Kholoud K.; Aslam, Mohamad F.; Sharp, Paul A.; Latunde-Dada, Gladys O.Food Chemistry (2021), 335 (), 127671CODEN: FOCHDJ; ISSN:0308-8146. (Elsevier Ltd.)Iron deficiency anemia (IDA) is a common nutritional disorder worldwide. Sustainable food-based approaches are being advocated to use high and bioavailable dietary iron sources to prevent iron deficiency. The study investigated the bioaccessibility and bioavailability of iron from some plant products. Total iron levels in the samples were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). Fractionation of the iron from the digested exts. was carried out by centrifugation and ultrafiltration. Iron bioavailability was detd. using an in vitro simulated peptic-pancreatic digestion, followed by measurement of ferritin in Caco-2 cells. The highest amt. of bioaccessible iron was obtained from moringa leaves (9.88% ± 0.45 and 8.44 ± 0.01 mg/100 g), but the highest percentage bioavailability was from baobab fruit pulp (99.7% ± 0.13 and 1.74 ± 0.01 mg/100 g) resp. All the plant products, except for baobab, significantly inhibited iron uptake from FeSO4 and FAC, with fenugreek sprout being the most inhibitory.
- 51He, W.; Li, X.; Ding, K.; Li, Y.; Li, W. Ascorbic Acid Can Reverse the Inhibition of Phytic Acid, Sodium Oxalate and Sodium Silicate on Iron Absorption in Caco-2 Cells. Int. J. Vitam. Nutr. Res. 2018, 88 (1–2), 65– 72, DOI: 10.1024/0300-9831/a000503[Crossref], [PubMed], [CAS], Google Scholar51https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3M7ovVOlsw%253D%253D&md5=010a13fd621c204a4974170a070c20a4Ascorbic Acid can Reverse the Inhibition of Phytic Acid, Sodium Oxalate and Sodium Silicate on Iron Absorption in Caco-2 cellsHe Wanling; Li Xiaoli; Ding Ke; Li Yuanxiao; Li WangInternational journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition (2018), 88 (1-2), 65-72 ISSN:0300-9831.The objective of the present study is to determine the effect of phytic acid (PA), sodium oxalate (SO) and sodium silicate (SS) on non-heme iron bioavailability in both the presence and absence of ascorbic acid (AA) using an in vitro digestion/Caco-2 cell model, and the levels of AA needed to promote Fe absorption from Fe complexed with PA, SO or SS were also determined. The results indicated that adding PA at 1:1, 3:1, 5:1 and 10:1 molar as compared to Fe decreased ferrous iron uptake by 55.80 %(P < 0.05), 72.33 % (P < 0.05), 73.32 % (P < 0.05), and 73.26 % (P < 0.05), respectively. Adding SS at 1:1, 3:1, 5:1 and 10:1 molar as compared to Fe also decreased ferrous iron uptake by 51.40 % (P < 0.05), 66.12 %(P < 0.05), 60.19 % (P < 0.05) and 45.11 % (P < 0.05), respectively. Adding SO at 5:1 and 10:1 molar as compared to Fe decreased ferrous iron uptake by 40.81 % (P < 0.05) and 33.14 % (P < 0.05), respectively. When adding AA to iron plus organic acid medias reached molar ratios of 5:5:1 AA:PA:Fe, 3:5:1 AA:SO:Fe and 5:5:1 AA:SS:Fe, iron absorption from FeSO4 were significantly increased (P < 0.05). However, no significant effect was observed in iron absorption from FeCl3 when adding AA to the media. The results showed that PA, SS or SO decreases iron uptake from ferrous Fe, and AA can counteract their inhibiting effect on ferrous iron absorption and thus increase ferrous iron uptake. The results may be important for elucidating factors affecting iron bioavailability in the small intestine and for the development of foods with improved iron bioavailability.
- 52Villaño, D.; Vilaplana, C.; Medina, S.; Algaba-Chueca, F.; Cejuela-Anta, R.; Miguel Martínez-Sanz, J.; Ferreres, F.; Gil-Izquierdo, A.; Mcphee, D. J.; Mena, P. Relationship between the Ingestion of a Polyphenol-Rich Drink, Hepcidin Hormone, and Long-Term Training. Molecules 2016, 21 (10), 1333, DOI: 10.3390/molecules21101333[Crossref], [CAS], Google Scholar52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvFaqsbnL&md5=8e3ba0334132e95cb51688e8aa76237cRelationship between the Ingestion of a polyphenol-rich drink, hepcidin hormone, and long-term trainingVillano, Debora; Vilaplana, Cristina; Medina, Sonia; Algaba-Chueca, Francisco; Cejuela-Anta, Roberto; Martinez-Sanz, Jose Miguel; Ferreres, Federico; Gil-Izquierdo, AngelMolecules (2016), 21 (10), 1333/1-1333/13CODEN: MOLEFW; ISSN:1420-3049. (MDPI AG)The effects of polyphenol-rich foods on the iron status of athletes, as well as the effect of phys. training on the hormone hepcidin, implicated in iron metab., are not clear. We investigated the influence on iron metab. of a long-term training intervention of 120 days, measuring the hepcidin concn. in the plasma of 16 elite triathletes, and the effect of the ingestion of 200 mL of either aronia-citrus juice or a placebo drink for 45 days, in a crossover design. The highest plasma hepcidin concns. were obsd. at the beginning of the study (116 ± 63 nM) and levels steadily decreased until the end of the intervention (final value 10 ± 7.5 nM). Long-term training might reduce inflammation and, hence, could be responsible for the decrease in hepcidin in triathletes. Polyphenols from aronia-citrus juice did not interfere in iron absorption, as we did not observe significant differences between the intake of the placebo drink or juice with regard to hepcidin levels. Further studies are required to ascertain the time and conditions necessary to restore hepcidin levels, which reflect the iron status of triathletes.
- 53Mao, X.; Yao, G. Effect of Vitamin C Supplementations on Iron Deficiency Anemia in Chinese Children. Biomed. Environ. Sci. 1992, 5 (2), 125– 129[PubMed], [CAS], Google Scholar53https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK38zlt1Kksg%253D%253D&md5=be63e72308810217d76278f410aacbbaEffect of vitamin C supplementations on iron deficiency anemia in Chinese childrenMao X; Yao GBiomedical and environmental sciences : BES (1992), 5 (2), 125-9 ISSN:0895-3988.A total of 65 children with mild iron deficiency anemia (IDA) were divided into 5 groups, and received 0, 25, 50, 100 and 150 mg/day of vitamin C (VC) respectively every day for 8 weeks. Hemoglobin, serum ferritin, free erythrocyte and hematocrit were determined every week. At a daily average intake of about 30 mg of VC and 7.5 mg of Fe, the results of the study indicate that: (1) VC supplement alone could effectively control children's IDA, and a dose-dependent relationship was observed. (2) 50 mg/day of VC is the most efficient dosage and 6 weeks is the shortest time for an effective therapy. (3) With a diet predominantly comprised of plant foods, it is suggested that appropriate dose of VC should be supplemented for the children during winter and spring in northeastern areas of China.
- 54Davidsson, L.; Walczyk, T.; Morris, A.; Hurrell, R. F. Influence of Ascorbic Acid on Iron Absorption from an Iron-Fortified, Chocolate-Flavored Milk Drink in Jamaican Children. Am. J. Clin. Nutr. 1998, 67 (5), 873– 877, DOI: 10.1093/ajcn/67.5.873[Crossref], [PubMed], [CAS], Google Scholar54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXislaju7Y%253D&md5=2f98b0189607104aa4f96806e358ece2Influence of ascorbic acid on iron absorption from an iron-fortified, chocolate-flavored milk drink in Jamaican childrenDavidsson, Lena; Walczyk, Thomas; Morris, Audrey; Hurrell, Richard F.American Journal of Clinical Nutrition (1998), 67 (5), 873-877CODEN: AJCNAC; ISSN:0002-9165. (American Society for Clinical Nutrition)The influence of ascorbic acid on Fe absorption from an Fe-fortified chocolate-flavored milk drink (6.3 mg total Fe per serving) was evaluated using a stable-isotope technique in 20 6-7-yr-old Jamaican children. Each child received 2 test meals labeled with 5.6 mg 57Fe and 3.0 mg 58Fe as ferrous sulfate on 2 consecutive days. Three different doses of ascorbic acid (0, 25, 50 mg per 25-g serving) were evaluated in 2 crossover studies. Iron isotope ratios were measured by neg. thermal ionization mass spectrometry. In the first study, iron absorption was greater after the addn. of 25 mg ascorbic acid: the geometric mean iron absorption was 1.6% (range 0.9-4.2%) and 5.1% (2.2-17.3%) for the test meals contg. 0 and 25 mg ascorbic acid, resp. In the second study, a difference in iron absorption was obsd. when the ascorbic acid content was increased from 25 to 50 mg: the geometric mean iron absorption was 5.4% (range 2.7-10.8%) compared with 7.7% (4.7-16.5%), resp. The chocolate drink contained relatively high amts. of polyphenolic compds., phytic acid, and calcium, all well-known inhibitors of iron absorption. The low iron absorption without added ascorbic acid shows that chocolate milk is a poor vehicle for iron fortification unless sufficient amts. of an iron-absorption enhancer are added. Regular consumption of iron-fortified chocolate milk drinks contg. added ascorbic acid could have a pos. effect on iron nutrition in population groups vulnerable to iron deficiency.
- 55Cook, J. D.; Reddy, M. B. Effect of Ascorbic Acid Intake on Nonheme-Iron Absorption from a Complete Diet. Am. J. Clin. Nutr. 2001, 73 (1), 93– 98, DOI: 10.1093/ajcn/73.1.93[Crossref], [PubMed], [CAS], Google Scholar55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXitVSktQ%253D%253D&md5=405667dd2c699a5d60408a7c34173fa8Effect of ascorbic acid intake on nonheme-iron absorption from a complete dietCook, James D.; Reddy, Manju B.American Journal of Clinical Nutrition (2001), 73 (1), 93-98CODEN: AJCNAC; ISSN:0002-9165. (American Society for Clinical Nutrition)Background: Ascorbic acid has a pronounced enhancing effect on the absorption of dietary nonheme iron when assessed by feeding single meals to fasting subjects. This contrasts with the negligible effect on iron balance of long-term supplementation with vitamin C. Objective: Our goal was to examine the effect of vitamin C on nonheme-iron absorption from a complete diet rather than from single meals. Design: Iron absorption from a complete diet was measured during 3 sep. dietary periods in 12 subjects by having the subjects ingest a labeled wheat roll with every meal for 5 d. The diet was freely chosen for the first dietary period and was then altered to maximally decrease or increase the dietary intake of vitamin C during the second and third periods. Results: There was no significant difference in mean iron absorption among the 3 dietary periods despite a range of mean daily intakes of dietary vitamin C of 51-247 mg/d. When absorption values were adjusted for differences in iron status and the 3 absorption periods were pooled, multiple regression anal. indicated that iron absorption correlated neg. with dietary phosphate (P = 0.0005) and pos. with ascorbic acid (P = 0.0069) and animal tissue (P = 0.0285). Conclusions: The facilitating effect of vitamin C on iron absorption from a complete diet is far less pronounced than that from single meals. These findings may explain why several prior studies did not show a significant effect on iron status of prolonged supplementation with vitamin C.
- 56Cook, J. D.; Monsen, E. R. Vitamin C, the Common Cold, and Iron Absorption. Am. J. Clin. Nutr. 1977, 30 (2), 235– 241, DOI: 10.1093/ajcn/30.2.235[Crossref], [PubMed], [CAS], Google Scholar56https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE2sXhvVyjtrw%253D&md5=9a9c599b87a3f01ba4fe6b44ae459b3dVitamin C, the common cold, and iron absorptionCook, James D.; Monsen, Elaine R.American Journal of Clinical Nutrition (1977), 30 (2), 235-41CODEN: AJCNAC; ISSN:0002-9165.A sizable segment of the population was found to be taking large quantities of vitamin C [50-81-7] to reduce the no. of severity of upper respiratory infections. To det. the effect of this supplementation on Fe balance, multiple radioiron absorption tests were performed in 63 male subjects. The increase in Fe absorption from a semisynthetic meal was directly proportional to the amt. of ascorbic acid added over the range 25-1000 mg. The ratio of Fe absorption (with/without ascorbic acid) at these 2 extremes was 1.65 and 9.57, resp. The relative increase was substantially less when the test meal contained meat. A large dose of vitamin C taken with breakfast did not effect Fe absorption from the noon or evening meal. A telephone survey of 100 individuals revealed that 67 were taking supplemental ascorbic acid in doses ranging as high as 2 g daily. The av. intake of supplemental ascorbic acid in this population was 280 mg daily. If taken only with breakfast, this level of supplementation would produce a nearly 2-fold increase in the amt. of Fe absorbed daily. If taken in divided does with each meal, the increase in Fe absorption would be more than 3-fold.
- 57Cook, J. D.; Watson, S. S.; Simpson, K. M.; Lipschitz, D. A.; Skikne, B. S. The Effect of High Ascorbic Acid Supplementation on Body Iron Stores. Blood 1984, 64 (3), 721– 726, DOI: 10.1182/blood.V64.3.721.721[Crossref], [PubMed], [CAS], Google Scholar57https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL2cXls12mtbo%253D&md5=45456506b8c76f46613970a58e09991bThe effect of high ascorbic acid supplementation on body iron storesCook, James D.; Watson, Selena S.; Simpson, Karen M.; Lipschitz, David A.; Skikne, Barry S.Blood (1984), 64 (3), 721-6CODEN: BLOOAW; ISSN:0006-4971.To examine the effects of enhancing the availability of dietary Fe on Fe balance, 17 adult volunteer subjects were given 2 g of ascorbic acid [50-81-7] daily with meals for 16 wk. Serum ferritin levels before and after the study averaged 46 and 43 μg/L, resp., indicating a negligible effect on Fe stores. When vitamin C supplementation was continued for an addnl. 20 mo in 5 Fe-replete and 4 Fe-deficient subjects, serum ferritin detns. again failed to indicate any significant effect of the vitamin C on Fe reserves. These findings were not explained by intestinal adaptation to the enhancing effect of the vitamin, because radioisotopic measurements of nonheme Fe absorption showed no redn. in the enhancing effect of 1 g of ascorbic acid after 4 mo of megadoses of vitamin C. It is concluded that altering the availability of nonheme dietary Fe has little effect on Fe status when the diet contains substantial amts. of meat.
- 58Malone, H. E.; Kevany, J. P.; Scott, J. M.; O’Broin, S. D.; O’Connor, G. Ascorbic Acid Supplementation : Its Effects on Body Iron Stores and White Blood Cells. Irish J. Med. Sci. 1986 1553 1986, 155 (3), 74– 79, DOI: 10.1007/BF02940053
- 59Hunt, J. R.; Mullen, L. M.; Lykken, G. I.; Gallagher, S. K.; Nielsen, F. H. Ascorbic Acid: Effect on Ongoing Iron Absorption and Status in Iron-Depleted Young Women. Am. J. C/in Nutr 1990, 51, 649– 655, DOI: 10.1093/ajcn/51.4.649[Crossref], [PubMed], [CAS], Google Scholar59https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3cXhvFKqurs%253D&md5=25275050ffa2736ee9e9a5fb0cc7fc2aAscorbic acid: effect on ongoing iron absorption and status in iron-depleted young womenHunt, Janet R.; Mullen, Loanne M.; Lykken, Glenn I.; Gallagher, Sandra K.; Nielsen, Forrest H.American Journal of Clinical Nutrition (1990), 51 (4), 649-55CODEN: AJCNAC; ISSN:0002-9165.The effect of ascorbic acid on Fe retention from a diet with predicted low Fe bioavailability (contg. minimal meat and ascorbic acid) was investigated in Fe-depleted premenopausal women. Women were depleted of storage Fe (indicated by serum ferritin) through a combination of diet (5.0 mg Fe/2000 kcal for 67-88 days) and phlebotomy. They then consumed a diet contg. 13.7 mg Fe/2000 kcal, supplemented with placebo or ascorbic acid 3 times daily (1500 mg total) with meals for 5.5 wk. Ascorbic acid improved apparent Fe absorption (balance method) [38 vs. 27%]. Ascorbic acid also improved Hb levels, erythrocyte protoporphyrins, and serum Fe but not hematocrit, serum ferritin, Fe-binding capacity, or transferrin satn. In Fe-depleted women consuming a diet with predicted poor Fe availability, ascorbic acid supplementation enhanced body Fe retention for 5.5 wk.
- 60Hunt, J. R.; Gallagher, S. K.; Johnson, L. K. Effect of Ascorbic Acid on Apparent Iron Absorption by Women with Low Iron Stores14. Am. J. Clin. Nutr. 1994, 59, 1381– 1385, DOI: 10.1093/ajcn/59.6.1381[Crossref], [PubMed], [CAS], Google Scholar60https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXmvF2kurc%253D&md5=84645f53294d6fa6dbc43ab4c36b192cEffect of ascorbic acid on apparent iron absorption by women with low iron storesHunt, Janet R.; Gallagher, Sandra K.; Johnson, LuAnn K.American Journal of Clinical Nutrition (1994), 59 (6), 1381-5CODEN: AJCNAC; ISSN:0002-9165.The effect of ascorbic acid supplementation on apparent iron absorption was tested in women with low iron stores. For 10 wk, 25 healthy nonpregnant women, aged 20-45 yr with low serum ferritin (3.5-17.7 μg/L), consumed either a diet with predicted poorly bioavailable iron or a typical Western diet, classified according to dietary meat and ascorbic acid contents. Meals were supplemented with ascorbic acid (500 mg, three times a day) for 5 of the 10 wk, in a double-blind, crossover design. Ascorbic acid did not affect most biochem. indexes of iron status, the biol. half-life of 59Fe, or apparent iron absorption (diet - feces) from either diet, but slightly increased serum ferritin (11.9 vs 10.7 μg/L, P<0.06) when data from both diets were combined. These results support other evidence that ascorbic acid has less effect on iron bioavailability than has been predicted from tests with single meals.
- 61Cook, J. D.; Monsen, E. R. Food Iron Absorption in Human Subjects. III. Comparison of the Effect of Animal Proteins on Nonheme Iron Absorption. Am. J. Clin. Nutr. 1976, 29 (8), 859– 867, DOI: 10.1093/ajcn/29.8.859[Crossref], [PubMed], [CAS], Google Scholar61https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE1cXlt1yiu74%253D&md5=85a04f386bea28bf1123b1b0edf746c8Food iron absorption in human subjects. III. Comparison of the effect of animal proteins on nonheme iron absorptionCook, James D.; Monsen, Elaine R.American Journal of Clinical Nutrition (1976), 29 (8), 859-67CODEN: AJCNAC; ISSN:0002-9165.The ability of various animal proteins to enhance the absorption of dietary nonheme Fe was evaluated by performing multiple radioiron absorption measurements in 70 volunteer subjects. Protein equiv. substitutions of 9 animal foods were made in 2 basic test meals. The 1st was a std. meal of high Fe availability (mean absorption, 8.3%) contg. beef muscle as the animal protein. The 2nd was a semisynthetic meal of low Fe availability (mean absorption, 1.4%) contg. ovalbumin as the protein source. Two categories of animal protein was defined. Substitution of beef, lamb, pork, liver, fish, and chicken for the egg ovalbumin in the semisynthetic meal resulted in a significant, 2-4-fold increase in Fe absorption, whereas no increase was obsd. with milk, cheese, or egg. Reciprocal findings were obtained when these foods were substituted for the beef contained in the std. meal. All sources of animal proteins are not equiv. in their effect on nonheme iron absorption.
- 62Layrisse, M.; Martínez-Torres, C.; Roche, M. Effect of Interaction of Various Foods on Iron Absorption. Am. J. Clin. Nutr. 1968, 21 (10), 1175– 1183, DOI: 10.1093/ajcn/21.10.1175[Crossref], [PubMed], [CAS], Google Scholar62https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF1cXkvFCit74%253D&md5=028862df99cb0295d0757dd519f219e8Effect of interaction of various foods on iron absorptionLayrisse, Miguel; Martinez-Torres, Carlos; Roche, MarcelAmerican Journal of Clinical Nutrition (1968), 21 (10), 1175-83CODEN: AJCNAC; ISSN:0002-9165.The absorption of Fe from food of animal origin was compared with that from a meal of vegetable origin. The absorption of Fe from veal combined with corn or black beans was less than that when veal was given alone. The decrease was less when veal was mixed with black beans. Corn did not inhibit the absorption of Fe from fish. Corn or black bean Fe was absorbed better when combined with food from animal origin than when given alone; in 2 expts. it was 3-fold greater. Amino acids in the same no. and proportions as are present in 100 g. of fish muscle enhanced Fe absorption from black beans about 3-fold. Thus, the interaction of vegetable with animal food during digestion may change the pattern of Fe absorption. A certain proportion of animal food should be given to enhance Fe absorption from vegetable food.
- 63Bjorn-Rasmussen, E.; Hallberg, L. Effect of Animal Proteins on the Absorption of Food Iron in Man. Ann. Nutr. Metab. 2004, 23 (3), 192– 202, DOI: 10.1159/000176256
- 64Engelmann, M. D. M.; Davidsson, L.; Sandström, B.; Walczyk, T.; Hurrell, R. F.; Michaelsen, K. F. The Influence of Meat on Nonheme Iron Absorption in Infants. Pediatr. Res. 1998, 43 (6), 768– 773, DOI: 10.1203/00006450-199806000-00009[Crossref], [PubMed], [CAS], Google Scholar64https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK1c3otlejtw%253D%253D&md5=0bf6bcf285eed28fcd4fca3054bec26eThe influence of meat on nonheme iron absorption in infantsEngelmann M D; Davidsson L; Sandstrom B; Walczyk T; Hurrell R F; Michaelsen K FPediatric research (1998), 43 (6), 768-73 ISSN:0031-3998.During weaning the infant has a high iron requirement, and highly available dietary iron is needed to ensure optimal iron status. Muscle tissue has been identified as an enhancer of nonheme iron absorption in adults, although the influence of meat on nonheme iron absorption in infants has not been previously reported. The effect of the addition of 25 g of meat (lean beef) on nonheme iron absorption from a home-prepared vegetable puree meal (80 g of vegetables) was investigated in infants in the present study. The meals did not differ in their contents of other known enhancers or inhibitors of nonheme iron absorption. Incorporation of stable isotopes of iron (57Fe and 58Fe) into red blood cells 14 d after intake was used to measure iron absorption, using a cross-over design in eight healthy infants 43-49 wk of age. Nonheme iron absorption was significantly increased (p = 0.002) from the vegetable puree with added meat (geometric mean 15.0%) compared with the pureed vegetables (geometric mean 9.9%). These results thus suggest that meat is also an enhancer of nonheme iron absorption in infants and that nonheme iron absorption from weaning foods can be increased by the addition of meat.
- 65Bech, S. B.; Hansen, M.; Bukhave, K.; Jensen, M.; Sørensen, S. S.; Kristensen, L.; Purslow, P. P.; Skibsted, L. H.; Sandström, B. Nonheme-Iron Absorption from a Phytate-Rich Meal Is Increased by the Addition of Small Amounts of Pork Meat. Am. J. Clin. Nutr. 2003, 77 (1), 173– 179, DOI: 10.1093/ajcn/77.1.173
- 66Navas-Carretero, S.; Pérez-Granados, A. M.; Sarriá, B.; Vaquero, M. P.; Carbajal, A.; Pedrosa, M. M.; Roe, M. A.; Fairweather-Tait, S. J. Oily Fish Increases Iron Bioavailability of a Phytate Rich Meal in Young Iron Deficient Women. J. Am. Coll. Nutr. 2008, 27 (1), 96– 101, DOI: 10.1080/07315724.2008.10719680[Crossref], [PubMed], [CAS], Google Scholar66https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXmtlOgtLo%253D&md5=55fa83cb23f4341054818b8c4fcfbd6aOily fish increases iron bioavailability of a phytate rich meal in young iron deficient womenNavas-Carretero, Santiago; Perez-Granados, Ana M.; Sarria, Beatriz; Carbajal, Angeles; Pedrosa, Mercedes; Roe, Mark A.; Fairweather-Tait, Susan J.; Vaquero, M. PilarJournal of the American College of Nutrition (2008), 27 (1), 96-101CODEN: JONUDL; ISSN:0731-5724. (American College of Nutrition)Iron deficiency is assocd. with diets of low iron bioavailability. Non-heme iron absorption is modulated by dietary constituents, one of which is the "meat factor" present in meat, fish (oily and lean) and poultry and is an important enhancer of iron absorption in humans. Food processing also affects iron bioavailability. The effects of consuming "sous vide" cooked salmon (Salmo salar) fish on non-heme iron bioavailability from bean meals rich in phytate were studied in 21 young iron-deficient women with low iron stores (blood serum ferritin <30 μg/L). Two test meals were extrinsically labeled with stable isotopes of iron (57Fe or 58Fe). Iron bioavailability was measured as the incorporation of stable isotopes into erythrocytes at 14 days after meals consumption. The addn. of fish to the bean meal increased iron absorption. Serum ferritin concns. and iron absorption were inversely correlated for both the bean meal (R2 = 0.294) and the fish + bean meal (R2 = 0.401). Thus, "sous vide" cooked salmon fish increases iron absorption from high phytate bean meals in humans.
- 67O’Flaherty, E. A. A.; Tsermoula, P.; O’Neill, E. E.; O’Brien, N. M. Co-Products of Beef Processing Enhance Non-Haem Iron Absorption in an in Vitro Digestion/Caco-2 Cell Model. Int. J. Food Sci. Technol. 2019, 54 (4), 1256– 1264, DOI: 10.1111/ijfs.14049[Crossref], [CAS], Google Scholar67https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitlyhtLvL&md5=98edbf6b2838369449c6ad081d0e8d68Co-products of beef processing enhance non-haem iron absorption in an in vitro digestion/caco-2 cell modelO'Flaherty, Elisabeth A. A.; Tsermoula, Paraskevi; O'Neill, Eileen E.; O'Brien, Nora M.International Journal of Food Science and Technology (2019), 54 (4), 1256-1264CODEN: IJFTEZ; ISSN:0950-5423. (Wiley-Blackwell)Summary : Beef processing produces high vols. of protein rich, low value, 'waste' co-products such as offal. Beef improves uptake of low bioavailable non-haem iron (found in vegetables, fortificants, supplements) and this effect is dubbed the 'meat-factor', although the underlying mechanism is not fully understood. Here, we investigate whether bovine co-products (kidney, lung, heart) not previously studied share this enhancing potential. This was detd. by coupled in vitro digestion of co-products and subsequent caco-2 cell ferritin formation (an intracellular iron storage protein). In this study we show that bovine co-products significantly increase caco-2 cells' response to non-haem iron from infant rice cereal. The presence of these co-products, (kidney, lung and heart), increased relative uptake (by 207.13%, 171.21%, 265.28%, resp.), to a greater extent than beef (30.23%). Our findings present a novel function for co-products of beef processing that may have potential as food ingredients to improve non-haem iron bioavailability, thus adding value.
- 68F, D.; T, A. Factors Affecting Iron Absorption and Mitigation Mechanisms: A Review. Int. J. Agric. Sci. Food Technol. 2018, 024– 030, DOI: 10.17352/2455-815X.000033
- 69Hurrell, R. F.; Reddy, M. B.; Juillerat, M.; Cook, J. D. Meat Protein Fractions Enhance Nonheme Iron Absorption in Humans. J. Nutr. 2006, 136 (11), 2808– 2812, DOI: 10.1093/jn/136.11.2808[Crossref], [PubMed], [CAS], Google Scholar69https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtFGqtLfO&md5=ceb08f068ac29bb02abed781ebd89272Meat protein fractions enhance nonheme iron absorption in humansHurrell, Richard F.; Reddy, Manju B.; Juillerat, Marcel; Cook, James D.Journal of Nutrition (2006), 136 (11), 2808-2812CODEN: JONUAI; ISSN:0022-3166. (American Society for Nutrition)The nature of the enhancing effect of muscle tissue on nonheme iron absorption in humans is unclear but thought to be related to muscle proteins. We conducted radioiron absorption studies to compare iron absorption from proteins isolated from beef and chicken muscle with that from freeze-dried beef and chicken muscle and from egg albumin. All meals contained an equiv. amt. of protein as part of a semisynthetic liq. formula. Freeze-dried beef and chicken muscle increased iron absorption 180% (P < 0.001) and 100% (P < 0.001), resp., relative to egg albumin. When added to the meal at an equiv. protein level (15 g), the isolated beef protein and the isolated heme-free beef protein with 94 and 98% protein content, resp., increased iron absorption to the same extent as the native beef muscle. Similarly, when added to the meal at an equiv. protein level (30 g), isolated chicken muscle protein (94% protein) increased iron absorption similarly to native chicken muscle. Iron absorption from the meal contg. the isolated hemefree chicken protein, however, was 120% (P < 0.01) greater than from the meal contg. freeze-dried chicken muscle, indicating that a nonprotein component of muscle tissue with iron-binding potential may have been removed or concd. by the protein extn. and sepn. procedures. Our results support the hypothesis that the enhancing effect of muscle tissue on iron absorption is mainly protein related but indicate that other factor may also play a role.
- 70Me, N.; Faizadatul, N.; Aw, A. Determination of Phytate, Iron, Zinc, Calcium Contents and Their Molar Ratios in Commonly Consumed Raw and Prepared Food in Malaysia. Mal. J. Nutr. 2009, 15 (2), 213– 222
- 71Harland, B. F.; Morris, E. R. Phytate: A Good or a Bad Food Component?. Nutr. Res. (N.Y.) 1995, 15 (5), 733– 754, DOI: 10.1016/0271-5317(95)00040-P[Crossref], [CAS], Google Scholar71https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXmtlGgsr4%253D&md5=fab495a652a78547c19cb2a86628965cPhytate: A good or a bad food component?Harland, Barbara F.; Morris, Eugene R.Nutrition Research (New York, NY, United States) (1995), 15 (5), 733-54CODEN: NTRSDC; ISSN:0271-5317.A review with 136 refs. of the nutritional benefits of phytate.
- 72Wilson, M. S. C.; Bulley, S. J.; Pisani, F.; Irvine, R. F.; Saiardi, A. A Novel Method for the Purification of Inositol Phosphates from Biological Samples Reveals That No Phytate Is Present in Human Plasma or Urine. Open Biol. 2015, 5 (3), 150014, DOI: 10.1098/rsob.150014[Crossref], [PubMed], [CAS], Google Scholar72https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MnotV2qtw%253D%253D&md5=8bbdcbae8b91a9726997dc77198190b5A novel method for the purification of inositol phosphates from biological samples reveals that no phytate is present in human plasma or urineWilson Miranda S C; Saiardi Adolfo; Bulley Simon J; Pisani Francesca; Irvine Robin FOpen biology (2015), 5 (3), 150014 ISSN:.Inositol phosphates are a large and diverse family of signalling molecules. While genetic studies have discovered important functions for them, the biochemistry behind these roles is often not fully characterized. A key obstacle in inositol phosphate research in mammalian cells has been the lack of straightforward techniques for their purification and analysis. Here we describe the ability of titanium dioxide (TiO2) beads to bind inositol phosphates. This discovery allowed the development of a new purification protocol that, coupled with gel analysis, permitted easy identification and quantification of InsP6 (phytate), its pyrophosphate derivatives InsP7 and InsP8, and the nucleotides ATP and GTP from cell or tissue extracts. Using this approach, InsP6, InsP7 and InsP8 were visualized in Dictyostelium extracts and a variety of mammalian cell lines and tissues, and the effects of metabolic perturbation on these were explored. TiO2 bead purification also enabled us to quantify InsP6 in human plasma and urine, which led to two distinct but related observations. Firstly, there is an active InsP6 phosphatase in human plasma, and secondly, InsP6 is undetectable in either fluid. These observations seriously question reports that InsP6 is present in human biofluids and the advisability of using InsP6 as a dietary supplement.
- 73Brouns, F. Phytic Acid and Whole Grains for Health Controversy. Nutrients 2022, 14 (1), 25, DOI: 10.3390/nu14010025[Crossref], [CAS], Google Scholar73https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhsFyjsbk%253D&md5=a35d1a510330fa034cb66deaf8cf1aa2Phytic Acid and Whole Grains for Health ControversyBrouns, FredNutrients (2022), 14 (1), 25CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)Phytate (PA) serves as a phosphate storage mol. in cereals and other plant foods. In food and in the human body, PA has a high affinity to chelate Zn2+ and Fe2+, Mg2+, Ca2+, K+, Mn2+ and Cu2+. As a consequence, minerals chelated in PA are not bio-available, which is a concern for public health in conditions of poor food availability and low mineral intakes, ultimately leading to an impaired micronutrient status, growth, development and increased mortality. For low-income countries this has resulted in communications on how to reduce the content of PA in food, by appropriate at home food processing. However, claims that a redn. in PA in food by processing per definition leads to a measurable improvement in mineral status and that the consumption of grains rich in PA impairs mineral status requires nuance. Frequently obsd. decreases of PA and increases in sol. minerals in in vitro food digestion (increased bio-accessibility) are used to promote food benefits. However, these do not necessarily translate into an increased bioavailability and mineral status in vivo. In vitro essays have limitations, such as the absence of blood flow, hormonal responses, neural regulation, gut epithelium assocd. factors and the presence of microbiota, which mutually influence the in vivo effects and should be considered. In Western countries, increased consumption of whole grain foods is assocd. with improved health outcomes, which does not justify advice to refrain from grain-based foods because they contain PA. The present commentary aims to clarify these seemingly controversial aspects.
- 74Hallberg, L.; Rossander, L.; Skaanberg, A. B. Phytates and the Inhibitory Effect of Bran on Iron Absorption in Man. Am. J. Clin. Nutr. 1987, 45 (5), 988– 996, DOI: 10.1093/ajcn/45.5.988[Crossref], [PubMed], [CAS], Google Scholar74https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL2sXksFOkt7k%253D&md5=3092d7a9c96f2207562812945940f95aPhytates and the inhibitory effect of bran on iron absorption in manHallberg, Leif; Rossander, Lena; Skaanberg, Ann BrittAmerican Journal of Clinical Nutrition (1987), 45 (5), 988-96CODEN: AJCNAC; ISSN:0002-9165.The cause of marked inhibitory effect of bran on absorption of dietary nonheme iron was studied in man by double-radioiron technique. Washing bran with hydrochloric acid but not with water removed inhibitory factor(s). Inhibition was almost restored by reconstituting phytate level. Removal of phytates in bran by endogenous phytase significantly increased absorption of iron. Removing, by washing with water, phosphates formed from phytates during enzymic dephytinization led to a bran fraction with only a small remaining inhibitory effect on iron absorption. Half the iron in bran is in the form of monoferric phytate, which is well-absorbed. When potassium and magnesium phytates were added in amts. present in bran, the same inhibitory effect on iron absorption was seen. Although there appear to be other factors in bran that partly explain the inhibition, phytates are the main cause of the inhibitory effect of bran on iron absorption.
- 75Troesch, B.; Jing, H.; Laillou, A.; Fowler, A. Absorption Studies Show That Phytase from Aspergillus Niger Significantly Increases Iron and Zinc Bioavailability from Phytate-Rich Foods. Food Nutr. Bull. 2013, 34 (2), 90– 101, DOI: 10.1177/15648265130342S111
- 76Hallberg, L.; Brune, M.; Rossander, L. Iron Absorption in Man: Ascorbic Acid and Dose-Dependent Inhibition by Phytate. Am. J. Clin. Nutr. 1989, 49 (1), 140– 144, DOI: 10.1093/ajcn/49.1.140[Crossref], [PubMed], [CAS], Google Scholar76https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL1MXptlyhsA%253D%253D&md5=f7885a7e1efd2c842a1046a203926de1Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytateHallberg, Leif; Brune, Mats; Rossander, LenaAmerican Journal of Clinical Nutrition (1989), 49 (1), 140-4CODEN: AJCNAC; ISSN:0002-9165.The dose-dependent inhibitory effect of Na phytate on Fe absorption was studied in man by serving wheat rolls contg. no phytates and rolls to which various amts. (7 dose levels ranging 2- 250 mg expressed as phytate P) were added just before serving. Fe in the 2 kinds of rolls was labeled with 2 radioisotopes of Fe (55Fe, 59Fe), and the rolls were served on alternate days. The inhibition of Fe absorption was strongly related to the amt. of phytate added; 2 mg inhibited absorption by 18%, 25 mg by 64%, and 250 mg by 82%. The addn. of ascorbic acid counteracted the inhibition, whereas the corresponding effect of meat was less well defined and only seen at the highest phytate level. The marked inhibition of Fe absorption by phytates and the counteracting effect of ascorbic acid have wide nutritional implications.
- 77Gibson, R. S.; Bailey, K. B.; Gibbs, M.; Ferguson, E. L. A Review of Phytate, Iron, Zinc, and Calcium Concentrations in Plant-Based Complementary Foods Used in Low-Income Countries and Implications for Bioavailability. Food Nutr. Bull. 2010, 31 (2), 134– 146, DOI: 10.1177/15648265100312S206
- 78Al Hasan, S. M.; Hassan, M.; Saha, S.; Islam, M.; Billah, M.; Islam, S. Dietary Phytate Intake Inhibits the Bioavailability of Iron and Calcium in the Diets of Pregnant Women in Rural Bangladesh: A Cross-Sectional Study. BMC Nutr. 2016, 2 (1), 1– 10, DOI: 10.1186/s40795-016-0064-8
- 79Armah, S. M.; Boy, E.; Chen, D.; Candal, P.; Reddy, M. B. Regular Consumption of a High-Phytate Diet Reduces the Inhibitory Effect of Phytate on Nonheme-Iron Absorption in Women with Suboptimal Iron Stores. J. Nutr. 2015, 145 (8), 1735– 1739, DOI: 10.3945/jn.114.209957[Crossref], [PubMed], [CAS], Google Scholar79https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVSrsbjP&md5=8a36305c9252c070c268aae6797d931eRegular consumption of a high-phytate diet reduces the inhibitory effect of phytate on nonheme-iron absorption in women with suboptimal iron storesArmah, Seth M.; Boy, Erick; Chen, Dan; Candal, Priscila; Reddy, Manju B.Journal of Nutrition (2015), 145 (8), 1735-1739CODEN: JONUAI; ISSN:0022-3166. (American Society for Nutrition)Background: High phytate (HP) consumption is a concern in developing countries because of the high prevalence of iron deficiency in these countries. Objective: We investigated whether habitual consumption of an HP diet reduces the inhibitory effect of phytate on nonheme-iron absorption. Methods: Thirty-two nonanemic females, 18-35 y of age, with normal body mass index but with suboptimal iron stores (serum ferritin, ≤30 μg/L), were matched for serum ferritin concn. and randomly assigned to HP and low-phytate (LP) groups, in a parallel design study. Each subject consumed HP or LP foods with at least 2 of their daily meals for 8 wk, resulting in a change in phytate intake (from 718 to 1190 mg/d in the HP group and 623 to 385 mg/d in the LP group). The serum iron response over 4 h after a test meal contg. 350 mg of phytate was measured at baseline and postintervention. Ferritin, transferrin receptor, and hepcidin concns. were measured at baseline and 8 wk. Results: Twenty-eight subjects completed the study (n = 14 per group). The serum iron response to the test meal increased in the HP group at postintervention, resulting in a 41% increase in the area under the curve (AUC; P < 0.0001). However, no effect was obsd. in the LP group (21% decrease in AUC; P = 0.76). The postintervention serum iron response was lower (P < 0.0001) in the LP group than in the HP group after controlling for the baseline serum iron response and hepcidin concn., reflecting in a 64% lower AUC. Conclusions: We found that habitual consumption of an HP diet can reduce the neg. effect of phytate on nonheme-iron absorption among young women with suboptimal iron stores. Future studies are needed to explore possible mechanisms.
- 80Hoppe, M.; Ross, A. B.; Svelander, C.; Sandberg, A.-S.; Hulthén, L. Low-Phytate Wholegrain Bread Instead of High-Phytate Wholegrain Bread in a Total Diet Context Did Not Improve Iron Status of Healthy Swedish Females: A 12-Week, Randomized, Parallel-Design Intervention Study. Eur. J. Nutr. 2019, 58, 853– 864, DOI: 10.1007/s00394-018-1722-1[Crossref], [PubMed], [CAS], Google Scholar80https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtVSgt7fI&md5=4c7724d6de8db017012fed8d241f431dLow-phytate wholegrain bread instead of high-phytate wholegrain bread in a total diet context did not improve iron status of healthy Swedish females: a 12-week, randomized, parallel-design intervention studyHoppe, Michael; Ross, Alastair B.; Svelander, Cecilia; Sandberg, Ann-Sofie; Hulthen, LenaEuropean Journal of Nutrition (2019), 58 (2), 853-864CODEN: EJNUFZ; ISSN:1436-6207. (Springer)Purpose: To investigate the effects of eating wholegrain rye bread with high or low amts. of phytate on iron status in women under free-living conditions. Methods: In this 12-wk, randomized, parallel-design intervention study, 102 females were allocated into two groups, a high-phytate-bread group or a low-phytate-bread group. These two groups were administered: 200 g of blanched wholegrain rye bread/day, or 200 g dephytinized wholegrain rye bread/day. The bread was administered in addn. to their habitual daily diet. Iron status biomarkers and plasma alkylresorcinols were analyzed at baseline and post-intervention. Results: Fifty-five females completed the study. In the high-phytate-bread group (n = 31) there was no change in any of the iron status biomarkers after 12 wk of intervention (p > 0.05). In the low-phytate bread group (n = 24) there were significant decreases in both ferritin (mean = 12%; from 32 ± 7 to 27 ± 6μg/L, geometric mean ± SEM, p < 0.018) and total body iron (mean = 12%; from 6.9 ± 1.4 to 5.4 ± 1.1 mg/kg, p < 0.035). Plasma alkylresorcinols indicated that most subjects complied with the intervention. Conclusions: In Swedish females of reproductive age, 12 wk of high-phytate wholegrain bread consumption had no effect on iron status. However, consumption of low-phytate wholegrain bread for 12 wk resulted in a redn. of markers of iron status. Although single-meal studies clearly show an increase in iron bioavailability from dephytinization of cereals, medium-term consumption of reduced phytate bread under free-living conditions suggests that this strategy does not work to improve iron status in healthy women of reproductive age.
- 81Mendoza, C.; Viteri, F. E.; Lönnerdal, B.; Raboy, V.; Young, K. A.; Brown, K. H. Absorption of Iron from Unmodified Maize and Genetically Altered, Low-Phytate Maize Fortified with Ferrous Sulfate or Sodium Iron EDTA. Am. J. Clin. Nutr. 2001, 73 (1), 80– 85, DOI: 10.1093/ajcn/73.1.80[Crossref], [PubMed], [CAS], Google Scholar81https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXitVSktw%253D%253D&md5=a1637e9dfb42646cc4b2c1d0ea82e1d3Absorption of iron from unmodified maize and genetically altered, low-phytate maize fortified with ferrous sulfate or sodium iron EDTAMendoza, Concepcion; Viteri, Fernando E.; Lonnerdal, Bo; Raboy, Victor; Young, Kevin A.; Brown, Kenneth H.American Journal of Clinical Nutrition (2001), 73 (1), 80-85CODEN: AJCNAC; ISSN:0002-9165. (American Society for Clinical Nutrition)Background: Reducing the phytate content in grains by genetic manipulation is a novel approach to increasing nonheme-iron absorption from mixed diets. Fractional iron absorption from a genetically modified strain of low-phytate maize (LPM) increased significantly, by 50%. Objective: We assessed iron absorption from porridges prepd. from the same LPM (lpa-1-1 mutant) and unmodified wild-type maize (WTM), both of which were fortified with either ferrous sulfate or sodium iron EDTA. Design: Porridges providing 3.4 mg Fe were fortified with either ferrous sulfate or sodium iron EDTA to provide an addnl. 1 mg Fe/serving. In 14 nonanemic women, iron absorption was measured as the amt. of radioiron incorporated into red blood cells (extrinsic tag method) 12 d after consumption of the study diets. Results: No significant effect of phytate content on iron absorption was found when porridge was fortified with either sodium iron EDTA or ferrous sulfate. Fractional absorption of iron from WTM porridge fortified with sodium iron EDTA (5.73%) was 3.39 times greater than that from the same porridge fortified with ferrous sulfate (1.69%). Fractional absorption of iron from the sodium iron EDTA-fortified LPM porridge (5.40%) was 2.82 times greater than that from LPM porridge fortified with ferrous sulfate (1.91%) (P < 0.0001 for both comparisons, repeated-measures anal. of variance). Thus, the previously identified benefit of LPM was no longer detectable when maize porridge was fortified with addnl. iron. Conclusion: Iron was absorbed more efficiently when the fortificant was sodium iron EDTA rather than ferrous sulfate, regard-less of the type of maize.
- 82Hurrell, R. F.; Reddy, M.; Cook, J. D. Inhibition of Non-Haem Iron Absorption in Man by Polyphenolic-Containing Beverages. Br. J. Nutr. 1999, 81 (4), 289– 295, DOI: 10.1017/S0007114599000537[Crossref], [PubMed], [CAS], Google Scholar82https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXjsVKktr4%253D&md5=fee5108582206ff5765fa233d76c5b9bInhibition of non-haem iron absorption in man by polyphenolic-containing beveragesHurrell, Richard F.; Reddy, Manju; Cook, James D.British Journal of Nutrition (1999), 81 (4), 289-295CODEN: BJNUAV; ISSN:0007-1145. (CABI Publishing)The effects of different polyphenol-contg. beverages on Fe absorption from a bread meal were estd. in 77 adult humans from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in phenolic acids (chlorogenic acid in coffee), monomeric flavonoids [herb teas from chamomile (Matricaria recutita), vervain (Verbena officinalis), lime flower (Tilia cordata), pennyroyal (Mentha pulegium), and peppermint (Mentha piperita)], or complex polyphenol polymn. products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and decreased the absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages contg. 20-50 mg total polyphenols/serving decreased the Fe absorption from the bread meal by 50-70%, whereas beverages contg. 100-400 mg total polyphenols/serving decreased the Fe absorption by 60-90%. Inhibition by black tea was 79-94%, peppermint tea 84%, pennyroyal 73%, cocoa 71%, vervain 59%, lime flower 52%, and chamomile 47 %. At identical concns. of total polyphenols, black tea was more inhibitory than cocoa, herb teas, chamomile, vervain, lime flower, and pennyroyal, but was equal to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Thus, herb teas, black tea, coffee, and cocoa can be potent inhibitors of dietary Fe absorption. This should be considered when giving dietary advice in relation to Fe nutrition.
- 83Petry, N.; Egli, I.; Zeder, C.; Walczyk, T.; Hurrell, R. The Journal of Nutrition Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions Polyphenols and Phytic Acid Contribute to the Low Iron Bioavailability from Common Beans in Young Women 1,2. J. Nutr. 2010, 140, 1977– 1982, DOI: 10.3945/jn.110.125369[Crossref], [PubMed], [CAS], Google Scholar83https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtl2nur%252FF&md5=b8adb180a47f59c0bb445b02a8cd56b9Polyphenols and phytic acid contribute to the low iron bioavailability from common beans in young womenPetry, Nicolai; Egli, Ines; Zeder, Christophe; Walczyk, Thomas; Hurrell, RichardJournal of Nutrition (2010), 140 (11), 1977-1982CODEN: JONUAI; ISSN:0022-3166. (American Society for Nutrition)Low iron absorption from common beans might contribute to iron deficiency in countries where beans are a staple food. High levels of phytic acid (PA) and polyphenols (PP) inhibit iron absorption; however, the effect of bean PP on iron absorption in humans has not been demonstrated and, with respect to variety selection, the relative importance of PP and PA is unclear. To evaluate the influence of bean PP relative to PA on iron absorption in humans, 6 stable iron isotope absorption studies were conducted in women (16 or 17 per study). Bean PP (20, 50, and 200 mg) were added in studies 1-3 as red bean hulls to a bread meal. Studies 4-6 investigated the influence on iron absorption of PP removal and dephytinization of whole red bean porridge and PP removal from dephytinized porridge. Iron absorption was lowered by 14% with 50 mg PP (P < 0.05) and by 45% with 200 mg PP (P < 0.001). The mean iron absorption from whole bean porridge was 2.5%. PP and PA removal increased absorption 2.6-fold (P < 0.001) and removal of PP from dephytinized porridge doubled absorption (P < 0.001). Between-study comparisons indicated that dephytinization did not increase iron absorption in the presence of PP, but in their absence, absorption increased 3.4-fold (P < 0.001). These data suggest that in countries where beans are a staple food, PP and PA concns. should be considered when selecting bean varieties for human consumption. Lowering only one inhibitor will have a modest influence on iron absorption.
- 84Hart, J. J.; Tako, E.; Kochian, L. V.; Glahn, R. P. Identification of Black Bean (Phaseolus Vulgaris L.) Polyphenols That Inhibit and Promote Iron Uptake by Caco-2 Cells. J. Agric. Food Chem. 2015, 63 (25), 5950– 5956, DOI: 10.1021/acs.jafc.5b00531[ACS Full Text
], [CAS], Google Scholar84https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXpsFaku7w%253D&md5=109cd1955538bb8735aa7f0ed423169fIdentification of Black Bean (Phaseolus vulgaris L.) Polyphenols That Inhibit and Promote Iron Uptake by Caco-2 CellsHart, Jonathan J.; Tako, Elad; Kochian, Leon V.; Glahn, Raymond P.Journal of Agricultural and Food Chemistry (2015), 63 (25), 5950-5956CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)In nutritional studies, polyphenolic compds. are considered to be inhibitors of Fe bioavailability. Because they are presumed to act in a similar manner, total polyphenols are commonly measured via the Folin-Ciocalteu colorimetric assay. This study measured the content of polyphenolic compds. in white and black beans and examd. the effect of individual polyphenols on iron uptake by Caco-2 cells. Anal. of seed coat exts. by LC-MS revealed the presence of a range of polyphenols in black bean, but no detectable polyphenols in white bean. Exts. from black bean seed coats strongly inhibited iron uptake. Examn. of the eight most abundant black bean seed coat, non-anthocyanin polyphenols via Caco-2 cell assays showed that four (catechin, 3,4-dihydroxybenzoic acid, kaempferol, and kaempferol 3-glucoside) clearly promoted iron uptake and four (myricetin, myricetin 3-glucoside, quercetin, and quercetin 3-glucoside) inhibited iron uptake. The four inhibitors were present in 3-fold higher total concn. than the promoters (143 ± 7.2 vs 43.6 ± 4.4 μM), consistent with the net inhibitory effect obsd. for black bean seed coats. The ability of some polyphenols to promote iron uptake and the identification of specific polyphenols that inhibit Fe uptake suggest a potential for breeding bean lines with improved iron nutritional qualities. - 85Bezwoda, W. R.; Torrance, J. D.; Bothwell, T. H.; Macphail, A. P.; Graham, B.; Mills, W. Iron Absorption from Red and White Wines. Scand. J. Haematol. 1985, 34 (2), 121– 127, DOI: 10.1111/j.1600-0609.1985.tb02243.x[Crossref], [PubMed], [CAS], Google Scholar85https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL2MXhs1GlsLs%253D&md5=339af174afeda2bd10ce0b0bbe978c14Iron absorption from red and white winesBezwoda, W. R.; Torrance, J. D.; Bothwell, T. H.; Macphail, A. P.; Graham, B.; Mills, W.Scandinavian Journal of Haematology (1985), 34 (2), 121-7CODEN: SJHAAQ; ISSN:0036-553X.Fe (3 mg) was added as FeSO4 to 2 dL red wine, white wine, and 7% alc., and its absorption was then measured in 38 fasting male subjects. The original concns. of Fe in the 2 wines were low, being 1.01-1.08 mg/L (red wine) and 0.13-0.20 (white wine). The mean absorption from red wine was only 20% of that from the alc. soln. white >4 times as much was absorbed from white wine as from the alc. Direct comparison showed greater absorption from white wine (10.4%) than from red wine (4.4%). Removal of ∼80% of the polyphenols in red wine increased the geometric mean Fe absorption from 1.9% to 3.6%. In vitro expts. indicated that Fe was less sol. and less dialyzable in red wines than in white wines. This was possibly due to the binding of Fe to polyphenols in red wines. Electrophoretic studies suggested that the Fe in white wines was complexed to hydroxycarboxylic acids.
- 86Cook, J. D.; Reddy, M. B.; Hurrell, R. F. The Effect of Red and White Wines on Nonheme-Iron Absorption in Humans. Am. J. Clin. Nutr. 1995, 61 (4), 800– 804, DOI: 10.1093/ajcn/61.4.800[Crossref], [PubMed], [CAS], Google Scholar86https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXlsVCgsrY%253D&md5=0c043c716f263eac3b67292591731f1aThe effect of red and white wines on nonheme-iron absorption in humansCook, James D.; Reddy, Manju B.; Hurrell, Richard F.American Journal of Clinical Nutrition (1995), 61 (4), 800-4CODEN: AJCNAC; ISSN:0002-9165.The effect of the phenolic compds. in wine was examd. in this study by performing radioiron-absorption measurements from extrinsically labeled test meals in 33 human subjects. In four sep. studies we obsd. that absorption was 2- to 3-fold higher from white wine contg. a low concn. of polyphenols than from two red wines contg. a 10-fold higher concn. of polyphenols. The interaction between the polyphenols and alc. in wine was evaluated by reducing the alc. content of the wines by ≈90%. When the alc. concn. was reduced, there was a significant 28% decrease in nonheme-iron absorption with red wine but no effect with white wine. The inhibitory effect of red wines with reduced alc. content was about twofold greater when they were consumed with a small bread roll than when taken without food. Our findings indicate that the inhibitory effect of phenolic compds. in red wine is unlikely to affect iron balance significantly.
- 87Kim, E. Y.; Ham, S. K.; Shigenaga, M. K.; Han, O. Bioactive Dietary Polyphenolic Compounds Reduce Nonheme Iron Transport across Human Intestinal Cell Monolayers. J. Nutr. 2008, 138 (9), 1647– 1651, DOI: 10.1093/jn/138.9.1647[Crossref], [PubMed], [CAS], Google Scholar87https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhtVylurrI&md5=3d09c488f0adda18af01cae7ff06ce63Bioactive dietary polyphenolic compounds reduce nonheme iron transport across human intestinal cell monolayersKim, Eun-Young; Ham, Soo-Kyung; Shigenaga, Mark K.; Han, OkheeJournal of Nutrition (2008), 138 (9), 1647-1651CODEN: JONUAI; ISSN:0022-3166. (American Society for Nutrition)There is persuasive epidemiol. evidence that regular intake of dietary bioactive polyphenolic compds. promotes human health. Because dietary polyphenolic compds. have a wide range of effects in vivo and vitro, including chelation of metals such as iron, it is prudent to test whether the regular consumption of bioactive polyphenolic components impair the utilization of dietary iron. We examd. the influence of the dietary polyphenols (-)-epigallocatechin-3-gallate (EGCG) and grape seed ext. (GSE) on transepithelial iron transport in Caco-2 intestinal cells. The range of EGCG and GSE concns. used in this study was within physiol. levels and did not affect the integrity of differentiated Caco-2 cell monolayers. Both EGCG and GSE decreased (P < 0.001) transepithelial iron transport. However, apical iron uptake was increased (P < 0.001) by the addn. of EGCG and GSE. The increased uptake of iron might be due in part to the reducing activity of EGCG and GSE. Both EGCG and GSE reduced ∼15% of the applied Fe3+ to Fe2+ in the uptake buffer. Despite the increased cellular levels of 55Fe, the transfer of iron across the basolateral membrane of the enterocyte was extremely low, indicating that basolateral exit via ferroportin-1 was impaired, possibly through formation of a nontransportable polyphenol-iron complex. Our data show that polyphenols inhibit nonheme iron absorption by reducing basolateral iron exit rather than by decreasing apical iron import in intestinal cells.
- 88Ma, Q.; Kim, E. Y.; Lindsay, E. A.; Han, O. Bioactive Dietary Polyphenols Inhibit Heme Iron Absorption in a Dose-Dependent Manner in Human Intestinal Caco-2 Cells. J. Food Sci. 2011, 76 (5), H143– H150, DOI: 10.1111/j.1750-3841.2011.02184.x[Crossref], [PubMed], [CAS], Google Scholar88https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXns1SrsbY%253D&md5=1fc07ed23691ec1f60913eee1c27e4bfBioactive dietary polyphenols inhibit heme iron absorption in a dose-dependent manner in human intestinal Caco-2 cellsMa, Qianyi; Kim, Eun-Young; Lindsay, Elizabeth Ann; Han, OkheeJournal of Food Science (2011), 76 (5), H143-H150CODEN: JFDSAZ; ISSN:0022-1147. (Wiley-Blackwell)Although heme iron is an important form of dietary iron, its intestinal absorption mechanism remains elusive. Our previous study revealed that (-)-epigallocatechin-3-gallate (EGCG) and grape seed ext. (GSE) markedly inhibited intestinal heme iron absorption by reducing the basolateral iron export in Caco-2 cells. The aim of this study was to examine whether small amts. of EGCG, GSE, and green tea ext. (GT) could inhibit heme iron absorption, and to test whether the inhibitory action of polyphenols could be offset by ascorbic acid. A heme-55Fe absorption study was conducted by adding various concns. of EGCG, GSE, and GT to Caco-2 cells in the absence and presence of ascorbic acid. Polyphenolic compds. significantly inhibited heme-55Fe absorption in a dose-dependent manner. The addn. of ascorbic acid did not modulate the inhibitory effect of dietary polyphenols on heme iron absorption when the cells were treated with polyphenols at a concn. of 46 mg/L. However, ascorbic acid was able to offset or reverse the inhibitory effects of polyphenolic compds. when lower concns. of polyphenols were added (≤ 4.6 mg/L). Ascorbic acid modulated the heme iron absorption without changing the apical heme uptake, the expression of the proteins involved in heme metab. and basolateral iron transport, and heme oxygenase activity, indicating that ascorbic acid may enhance heme iron absorption by modulating the intracellular distribution of 55Fe. These results imply that the regular consumption of dietary ascorbic acid can easily counteract the inhibitory effects of low concns. of dietary polyphenols on heme iron absorption but cannot counteract the inhibitory actions of high concns. of polyphenols.
- 89Ndiaye, N. F.; Idohou-Dossou, N.; Burkli, S.; Diouf, A.; Loucoubar, C.; Guiro, A. T.; Zimmermann, M. B.; Wade, S.; Moretti, D. Polyphenol-Rich Tea Decreases Iron Absorption from Fortified Wheat Bread in Senegalese Mother-Child Pairs and Bioavailability of Ferrous Fumarate Is Sharply Lower in Children. Eur. J. Clin. Nutr. 2020, 74, 1221– 1228, DOI: 10.1038/s41430-020-0601-z[Crossref], [PubMed], [CAS], Google Scholar89https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlslGhs7s%253D&md5=610b575cb0d7ec8ed92f19b45016a9d2Polyphenol-rich tea decreases iron absorption from fortified wheat bread in Senegalese mother-child pairs and bioavailability of ferrous fumarate is sharply lower in childrenNdiaye, Ndeye Fatou; Idohou-Dossou, Nicole; Burkli, Simone; Diouf, Adama; Loucoubar, Cheikh; Guiro, Amadou Tidiane; Zimmermann, Michael Bruce; Wade, Salimata; Moretti, DiegoEuropean Journal of Clinical Nutrition (2020), 74 (8), 1221-1228CODEN: EJCNEQ; ISSN:0954-3007. (Nature Research)Fractional iron absorption (FAFe) from ferrous fumarate (FeFum) and ferrous sulfate (FeSO4) in adults is generally comparable. While FeFum is commonly used to fortify infant foods, FAFe from FeFum in young children and infants may be decreased compared with FeSO4 and this effect has not been assessed in inhibitory vs noninhibitory meals. Previous studies also reported FAFe to be strongly correlated in mother-child pairs. Our objective was to measure FAFe from fortified bread labeled with 58FeSO4 and 57FeFum in mother-child pairs with and without a commonly consumed herbal tea of Combretum micranthum (Tisane Kinkeliba, TK). Senegalese mother-child pairs (n = 17) were randomly assigned to receive, in a 2 x 2 factorial design, fortified bread with 58FeSO4 or 57FeFum consumed with TK or water. FAFe was assessed by measuring erythrocyte incorporation of stable iron-isotopes 14 days after administration. In children, relative bioavailability (RBV) from FeFum was 51 and 64% compared with FeSO4 when served with TK or water (both, P < 0.05). In mothers, the presence of TK decreased FAFe by 56% (P < 0.05) and 50% (P = 0.077) and in children by 65 and 72% (both, P < 0.0001), in the meals with 58FeSO4 and 57FeFum, resp. After adjustment for plasma ferritin, there was a pos. correlation between FAFe in mothers and children (r = 0.4142, P = 0.001). In Senegalese women and children, herbal tea decreased FAFe from a wheat-based meal. The RBV of FeFum was low in children but not in their mothers. FAFe was modestly correlated in mother-child pairs, possibly due to shared genetic, epigenetic or environmental background.
- 90Lazrak, M.; El Kari, K.; Stoffel, N. U.; Elammari, L.; Al-Jawaldeh, A.; Loechl, C. U.; Yahyane, A.; Barkat, A.; Zimmermann, M. B.; Aguenaou, H. Tea Consumption Reduces Iron Bioavailability from NaFeEDTA in Nonanemic Women and Women with Iron Deficiency Anemia: Stable Iron Isotope Studies in Morocco. J. Nutr. 2021, 151 (9), 2714– 2720, DOI: 10.1093/jn/nxab159[Crossref], [PubMed], [CAS], Google Scholar90https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2c%252Fptlaguw%253D%253D&md5=041e3e742c8ba0d9154a36316f88b279Tea Consumption Reduces Iron Bioavailability from NaFeEDTA in Nonanemic Women and Women with Iron Deficiency Anemia: Stable Iron Isotope Studies in MoroccoLazrak Meryem; El Kari Khalid; Aguenaou Hassan; Stoffel Nicole U; Zimmermann Michael B; Elammari Laila; Yahyane Abdelhakim; Al-Jawaldeh Ayoub; Loechl Cornelia U; Barkat AminaThe Journal of nutrition (2021), 151 (9), 2714-2720 ISSN:.BACKGROUND: Available data suggest that polyphenols from tea can inhibit iron absorption from ferric sodium EDTA (NaFeEDTA), but previous studies were done in small groups of mostly nonanemic adults. Morocco recently introduced national wheat flour fortification with NaFeEDTA, but tea is the national beverage and is consumed with most meals. OBJECTIVES: Our objective was to quantify bioavailability of iron from NaFeEDTA when added to a wheat flour-based meal in both nonanemic women and women with iron deficiency anemia (IDA), when consumed with and without traditional Moroccan green tea. METHODS: We recruited 2 groups of healthy Moroccan women (n = 46): women with IDA (n = 25; hemoglobin <12 g/dL, serum ferritin <15 μg/L) and nonanemic women (n = 21). Each group received in random order 2 standardized test meals containing 6 mg Fe as isotopically labeled NaFeEDTA and either 300 mL of tea or water. Fractional iron absorption (FIA) was measured by the erythrocyte incorporation of stable iron isotopes after 14 d. We performed linear mixed-model analysis and post hoc sample t tests to assess the effects of group and tea on FIA. RESULTS: The polyphenol content of the tea serving was 492 mg. Tea consumption reduced iron absorption from NaFeEDTA by >85% in both IDA and nonanemic women. There were group (P < 0.001) and tea (P < 0.001) effects on FIA, but no group by tea interaction (P = 0.312). Median (IQR) FIA (%) in women with IDA from test meals consumed without and with tea was 36.7 (24.2-39.8) and 4.1 (2.8-6.1), respectively (P < 0.001). Median (IQR) FIA (%) in nonanemic women from test meals consumed without and with tea was 16.7 (9.2-24.2) and 1.4 (0.8-2.9), respectively (P < 0.001). CONCLUSIONS: FIA from wheat flour-based meals without and with tea was ∼2-fold higher in women with IDA than in nonanemic women. Providing fortificant iron as NaFeEDTA cannot overcome the inhibition of tea polyphenols on iron absorption, even in IDA, where iron absorption is strongly upregulated. This trial was registered at www.clinicaltrials.gov as NCT02175888.
- 91Lesjak, M.; Balesaria, S.; Skinner, V.; Debnam, E. S.; Srai, S. K. S. Quercetin Inhibits Intestinal Non-Haem Iron Absorption by Regulating Iron Metabolism Genes in the Tissues. Eur. J. Nutr. 2019, 58, 743– 753, DOI: 10.1007/s00394-018-1680-7[Crossref], [PubMed], [CAS], Google Scholar91https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmsVehtL8%253D&md5=b37dd8076fac2372e15b89f292e3163fQuercetin inhibits intestinal non-haem iron absorption by regulating iron metabolism genes in the tissuesLesjak, Marija; Balesaria, Sara; Skinner, Vernon; Debnam, Edward S.; Srai, Surjit Kaila S.European Journal of Nutrition (2019), 58 (2), 743-753CODEN: EJNUFZ; ISSN:1436-6207. (Springer)There is general agreement that some dietary polyphenols block non-haem iron uptake, but the mechanisms by which they achieve this action are poorly understood. Since the polyphenol quercetin is ingested daily in significant amts., we have investigated the effect of quercetin on duodenal non-haem iron absorption in vivo, as well as its effect on factors known to be involved in systemic iron metab. Rats were subject to gastric gavage and systemic quercetin administration. Treatments were followed with uptake studies using radiolabeled iron, serum iron and transferrin satn. measurements, LC-MS/MS anal. of quercetin metabolites in serum, detn. of tissue non-haem iron content and anal. of gene expression of iron-related proteins. Both oral and i.p. (IP) quercetin caused serum and tissue iron depletion by two means, first by increasing mucosal iron uptake and inhibiting iron efflux from duodenal mucosa, and second by decreasing levels of duodenal DMT1, Dcytb and FPN. Addnl., IP quercetin induced highly significant increased liver expression of hepcidin, a hormone known to inhibit intestinal iron uptake. Oral quercetin significantly inhibited iron absorption, while IP quercetin significantly affected iron-related genes. These results could lead to development of new effective ways of preventing and treating iron deficiency anemia, the most widespread nutritional disorder in the world.
- 92Hart, J. J.; Tako, E.; Glahn, R. P. Characterization of Polyphenol Effects on Inhibition and Promotion of Iron Uptake by Caco-2 Cells. J. Agric. Food Chem. 2017, 65 (16), 3285– 3294, DOI: 10.1021/acs.jafc.6b05755[ACS Full Text], [CAS], Google Scholar92https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXltlWgt7w%253D&md5=d9d5e141bb9f874b1f40471b72774e73Characterization of Polyphenol Effects on Inhibition and Promotion of Iron Uptake by Caco-2 CellsHart, Jonathan J.; Tako, Elad; Glahn, Raymond P.Journal of Agricultural and Food Chemistry (2017), 65 (16), 3285-3294CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)Polyphenolic compds. present in the seed coat of common bean (Phaseolus vulgaris L.) are known to act collectively as inhibitors of iron bioavailability. Recent research identified specific polyphenols as being potent Fe uptake inhibitors. That research also identified other polyphenols as being promoters of Fe uptake. The present study extends that work using a Caco-2 cell model to characterize the effects of 43 addnl. polyphenols on Fe uptake. In addn., this study indicates that the inhibitory compds. have a more potent effect that outweighs the ability of promoting compds. to increase Fe uptake. For example, a ratio of 100:0 epicatechin (a promoter)/myricetin (an inhibitor) produced 78.5 ± 6.7 ng ferritin/mg protein, 90:10 yielded 27.4 ± 3.0, 50:50 yielded 3.42 ± 0.54, and 0:100 yielded 2.26 ± 0.25 ng ferritin/mg protein. A simulation of the relative concns. of eight major polyphenols (four inhibitors, four promoters) present in a sample of black bean seed coats demonstrated that most of the inhibitory compds. would need to be removed to reduce the neg. effect on Fe uptake. In vivo studies are now warranted to confirm the above in vitro effects. Such work would be significant as other bean color classes exist that are likely to have polyphenolic profiles that are more favorable to Fe bioavailability.
- 93Hallberg, L.; Rossander-Hulthèn, L.; Brune, M.; Gleerup, A. Inhibition of Haem-Iron Absorption in Man by Calcium. Br. J. Nutr. 1993, 69 (2), 533– 540, DOI: 10.1079/BJN19930053[Crossref], [PubMed], [CAS], Google Scholar93https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3sXitlakurc%253D&md5=970d2d9614c788e1fd1adeaddfe831cfInhibition of heme-iron absorption in man by calciumHallberg, Leif; Rossander-Hulthen, Lena; Brune, Mats; Gleerup, AnnBritish Journal of Nutrition (1993), 69 (2), 533-40CODEN: BJNUAV; ISSN:0007-1145.The inhibiting effect of Ca on non-heme-Fe absorption is well established. Present studies showed that Ca inhibited heme-Fe absorption to the same extent when the same amt. of Ca (165 mg Ca as CaCl2) was added to a meal. Attempts were made to examine the mechanism for this inhibition in the present studies. Meat is the only known dietary factor influencing heme-Fe absorption. The present studies were designed to examine whether Ca interfered with the enhancing effect of meat on heme-Fe absorption. The inhibition was the same whether biosynthetically radio-Fe-labeled Hb was given in meals with or without meat. The heme-Fe-absorption ratio with:without added Ca was 0.59 (SE 0.07) when Ca was added to a hamburger meal and 0.52 (SE 0.03) when added to a wheat roll. These values were not significantly different. The inhibition of heme-Fe absorption by Ca is, thus, a direct effect on the absorption of heme-Fe and not an indirect counteracting effect of the well-known enhancing effect of meat on heme-Fe absorption. Control studies were conducted to ensure that heme-Fe had not been degraded to non-heme-Fe during prepn. of the foods. Since Ca inhibits the absorption of heme- and non-heme-Fe to the same extent, the present results strongly suggest that Ca interferes with the transport of Fe through the mucosal cells and is common for heme- and non-heme-Fe transport at a late stage. The observations that Ca strongly interferes with the absorption of both heme- and non-heme-Fe have important nutritional implications.
- 94Roughead, Z. K.; Zito, C. A; Hunt, J. R Inhibitory Effects of Dietary Calcium on the Initial Uptake and Subsequent Retention of Heme and Nonheme Iron in Humans: Comparisons Using an Intestinal Lavage Method. Am. J. Clin. Nutr. 2005, 82 (3), 589– 597, DOI: 10.1093/ajcn/82.3.589[Crossref], [PubMed], [CAS], Google Scholar94https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtVaksLzP&md5=ab0bb24be42c65e28c192d0b6825ee99Inhibitory effects of dietary calcium on the initial uptake and subsequent retention of heme and nonheme iron in humans: Comparisons using an intestinal lavage methodRoughead, Zamzam K.; Zito, Carol A.; Hunt, Janet R.American Journal of Clinical Nutrition (2005), 82 (3), 589-597CODEN: AJCNAC; ISSN:0002-9165. (American Society for Clinical Nutrition)Calcium is the only reported dietary inhibitor of both heme- and nonheme-iron absorption. It has been proposed that the 2 forms of iron enter a common pool in the enterocyte and that calcium inhibits the serosal transfer of iron into blood. We aimed to ascertain whether the inhibitory effect of calcium occurs during initial mucosal uptake or during serosal transfer and to compare the serosal transfer of heme and nonheme iron, which should not differ if the 2 forms have entered a common mucosal iron pool. Whole-gut lavage and whole-body counting were used to measure the initial uptake (8 h) and retention (2 wk) of heme and nonheme iron with and without a calcium supplement (450 mg). Two expts. tested basal meals with low iron bioavailability and 360 mg Ca2+ (n = 15) or with high iron bioavailability and 60 mg Ca (n = 12). Results showed that added calcium reduced the initial uptake of heme iron by 20%, from 49% to ≈40% from both meals (P = 0.02), and reduced the total iron absorbed from the low- and high-bioavailability meals by ≈25% [from 0.033 to 0.025 mg (P = 0.06) and from 0.55 to 0.40 mg (P < 0.01), resp.]. Calcium did not affect the serosal transfer of either form of iron. Thus, calcium supplementation reduced heme and total iron without significantly affecting nonheme-iron absorption, regardless of meal bioavailability. Calcium inhibited the initial mucosal uptake rather than the serosal transfer of heme iron. Differences in serosal transfer indicate that heme and nonheme iron did not enter a common absorptive pool within 8 h after a meal.
- 95Benkhedda, K.; L’abbé, M. R.; Cockell, K. A. Effect of Calcium on Iron Absorption in Women with Marginal Iron Status. Br. J. Nutr. 2010, 103 (5), 742– 748, DOI: 10.1017/S0007114509992418[Crossref], [PubMed], [CAS], Google Scholar95https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXitFCku7w%253D&md5=5aa29ccfbb6448830ee47a1aac5976acEffect of calcium on iron absorption in women with marginal iron statusBenkhedda, Karima; L'Abbe, Mary R.; Cockell, Kevin A.British Journal of Nutrition (2010), 103 (5), 742-748CODEN: BJNUAV; ISSN:0007-1145. (Cambridge University Press)We measured non-haem Fe absorption with and without added Ca in a short-term feeding study, in thirteen women with marginal Fe status, by the use of a double stable isotope technique. Supplementing 500 mg Ca as calcium carbonate significantly (P = 0·0009) reduced Fe absorption from a single meal from 10·2 % (range 2·2-40·6) to 4·8 % (range 0·7-18·9). A significant inverse correlation in the absence ( - 0·67, P = 0·010) and presence ( - 0·58, P = 0·037) of Ca, resp., was found between Fe absorption and Fe stores measured by serum ferritin (SF). Wide variation in Fe absorption was obsd. between individuals in the absence and in the presence of Ca, despite pre-selection of participants within a relatively narrow range of iron stores (SF concns.). Correction of Fe absorption data based on group mean SF was not found to be useful in reducing the inter-individual variability in iron absorption. It appears that selecting a study group with a narrow initial range of Fe stores does not necessarily reduce the inter-individual variability in Fe bioavailability measurements. These results support the hypothesis that body Fe stores, although an important determinant of dietary Fe absorption, are not the main factor that dets. Fe absorption under conditions of identical dietary intake in subjects with low Fe stores.
- 96Toxqui, L.; Pérez-Granados, A. M.; Blanco-Rojo, R.; Wright, I.; González-Vizcayno, C.; Vaquero, M. P. Effects of an Iron or Iron and Vitamin D-Fortified Flavored Skim Milk on Iron Metabolism: A Randomized Controlled Double-Blind Trial in Iron-Deficient Women. J. Am. Coll. Nutr. 2013, 32 (5), 312– 320, DOI: 10.1080/07315724.2013.826116[Crossref], [PubMed], [CAS], Google Scholar96https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhs1Sgtr8%253D&md5=592cee7c6194bbe9884743951981a874Effects of an Iron or Iron and Vitamin D-Fortified Flavored Skim Milk on Iron Metabolism: A Randomized Controlled Double-Blind Trial in Iron-Deficient WomenToxqui, Laura; Perez-Granados, Ana M.; Blanco-Rojo, Ruth; Wright, Ione; Gonzalez-Vizcayno, Carmen; Vaquero, M. PilarJournal of the American College of Nutrition (2013), 32 (5), 312-320CODEN: JONUDL; ISSN:1541-1087. (Taylor & Francis, Inc.)Iron deficiency anemia and vitamin D deficiency are considered global pandemics. The aim of this study was to det. whether the consumption of a dairy product fortified with iron and vitamin D, compared to the equiv. with only added iron, exerts an addnl. effect on iron metab. in iron-deficient menstruating women. The design was a randomized, placebo-controlled, double-blind, parallel-group trial of 16 wk' duration. Subjects were randomized into 2 groups that consumed, as part of their usual diet, 500 mL/day of an iron (n = 54) or iron- and vitamin D-fortified (n = 55) flavored skim milk. At baseline and monthly, dietary intake, body wt., and hematol. and iron metab. biomarkers were detd. Serum 25-hydroxyvitamin D was analyzed at baseline and weeks 8 and 16. Data were analyzed by anal. of variance (ANOVA) of repeated measures for time and Time×Group interaction effects. A total of 109 volunteers completed the study. Calcium and iron intakes increased during the intervention (p < 0.001 for both groups). Serum 25-hydroxyvitamin D significantly increased in Fe + D group during the assay (p < 0.001) and at week 16 it was higher compared to the Fe group (p < 0.05). Serum ferritin, serum transferrin, mean corpuscular vol., mean corpuscular Hb, and red blood cell distribution width showed significant time effects but no Time×Group interaction. Higher values of erythrocytes (p = 0.01), hematocrit (p = 0.05), and Hb (p = 0.03) at week 8 were obsd. in the Fe + D group compared to the Fe group. Iron-fortified flavored skim milk does not improve iron status in iron-deficient menstruating women. However, vitamin D fortification slightly enhances erythropoiesis and iron status.
- 97Walczyk, T.; Muthayya, S.; Wegmüller, R.; Thankachan, P.; Sierksma, A.; Frenken, L. G. J.; Thomas, T.; Kurpad, A.; Hurrell, R. F. Inhibition of Iron Absorption by Calcium Is Modest in an Iron-Fortified, Casein- and Whey-Based Drink in Indian Children and Is Easily Compensated for by Addition of Ascorbic Acid. J. Nutr. 2014, 144 (11), 1703– 1709, DOI: 10.3945/jn.114.193417[Crossref], [PubMed], [CAS], Google Scholar97https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvVygsrbI&md5=cac234bd02b2965a9b044fa931e69a01Inhibition of iron absorption by calcium is modest in an iron-fortified, casein- and whey-based drink in Indian children and is easily compensated for by addition of ascorbic acidWalczyk, Thomas; Muthayya, Sumithra; Wegmuller, Rita; Thankachan, Prashanth; Sierksma, Aafje; Frenken, Leon G. J.; Thomas, Tinku; Kurpad, Anura; Hurrell, Richard F.Journal of Nutrition (2014), 144 (11), 1703-1709CODEN: JONUAI; ISSN:0022-3166. (American Society for Nutrition)Background: Calcium inhibits and ascorbic acid (AA) enhances iron absorption from iron-fortified foods. Absorption efficiency depends on iron status, although the interaction is unclear. Objective: We investigated the ability of AA to overcome calcium-induced inhibition of iron absorption in children differing in iron status. Methods: The effect of calcium (0, 100, and 200 mg/test meal) on iron absorption in the absence and presence of AA (0, 42.5, and 85 mg/test meal) from a casein/whey-based drink fortified with ferrous sulfate was assessed in a series of randomized crossover studies both in iron-replete (IR) Indian school children and in children with iron deficiency anemia (IDA) (6-11 y; n = 14-16/group) by using stable isotopes. Results: In the absence of calcium and AA, iron absorption from the casein/whey-based drink was 20% lower in IR children than in children with IDA. The addn. of calcium reduced mean iron absorption by 18-27%, with the effect being stronger for high added calcium (P < 0.01). AA at a 2:1 or 4:1 molar ratio enhanced iron absorption by a factor of 2-4 and greatly overcompensated for the inhibitory effect of calcium on iron absorption in a dose-dependent manner (P < 0.001). The dose-response effect tended to be stronger (P < 0.1) in the IDA group, and iron status was of far less influence on iron absorption than the enhancing effect of AA. Conclusion: When adding AA to iron-fortified milk products, care should be taken not to provide absorbable iron in excess of needs.
- 98Liya Yan, B.; Prentice, A.; Dibba, B.; A Jarjou, L. M.; Stirling, D. M.; Fairweather-tait, S. The Effect of Long-Term Calcium Supplementation on Indices of Iron, Zinc and Magnesium Status in Lactating Gambian Women. Br. J. Nutr. 1996, 76, 821– 831, DOI: 10.1079/BJN19960089
- 99Abrams, S. A.; Abrams, S. A. Calcium Turnover and Nutrition through the Life Cycle. Proc. Nutr. Soc. 2001, 60 (2), 283– 289, DOI: 10.1079/PNS200082[Crossref], [PubMed], [CAS], Google Scholar99https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXksFagtrY%253D&md5=ac6bee14bc9a3728cb935ef92e81488dCalcium turnover and nutrition through the life cycleAbrams, Steven A.Proceedings of the Nutrition Society (2001), 60 (2), 283-289CODEN: PNUSA4; ISSN:0029-6651. (CABI Publishing)A review with 41 refs. is given. Ca nutritional requirements and bone Ca turnover can be assessed using numerous techniques. Among these techniques are bone mass measurements, tracer kinetic studies, bone histomorphometry and biochem. studies. Stable-isotope-based kinetic studies offer unique advantages in their ability to assess both Ca absorption and turnover. This approach is safe and readily applicable to subjects of all ages. Ca is essential for growth and maintenance of bone mineral throughout life. During pregnancy, increased intestinal absorption of Ca by the mother provides much of the Ca supplied to the fetus. During infancy, Ca supplied in human milk is primarily derived from maternal bone stores, which are quickly replenished during and after weaning. Early childhood is a time of relatively slow bone growth, with a rapid increase occurring during puberty. Recent kinetic studies demonstrate an increase in both Ca absorption and bone Ca deposition assocd. with early puberty. Bone Ca deposition reaches a max. in females shortly before menarche. At that time the bone Ca deposition rate is approx. five times that of adulthood. The decline in bone Ca deposition rate is gradual after menarche. Ca absorption from the diet shows a gradual decline in adulthood as well. Ca supplementation, in the presence of adequate vitamin D, is effective in enhancing bone mineral content in childhood and in helping to maintain bone mineral content in adults. Maintaining adequate Ca nutriture throughout life may be necessary to minimize the risk of bone-loss disorders.
- 100Mølgaard, C.; Kaestel, P.; Michaelsen, K. F. Long-Term Calcium Supplementation Does Not Affect the Iron Status of 12–14-y-Old Girls 1–3. Am. J. Clin. Nutr. 2005, 82 (1), 98– 102, DOI: 10.1093/ajcn/82.1.98[Crossref], [PubMed], [CAS], Google Scholar100https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmsVSgs74%253D&md5=ec6eeded932b211de8e58e0a1ec6d609Long-term calcium supplementation does not affect the iron status of 12-14-y-old girlsMolgaard, Christian; Koestel, Pernille; Michaelsen, Kim F.American Journal of Clinical Nutrition (2005), 82 (1), 98-102CODEN: AJCNAC; ISSN:0002-9165. (American Society for Clinical Nutrition)Background: Single-meal studies have established that calcium has an acute inhibitory effect on the absorption of iron. However, there is growing evidence that high calcium intakes do not compromise iron status. Objective: We evaluated whether long-term calcium supplementation taken with the main meal affected biomarkers of iron status in adolescent girls with high requirements of both iron and calcium. Design: The study was a randomized, double-blind, placebo-controlled trial of supplementation with 500 mg Ca/d for 1 y among 113 adolescent girls aged 13.2 ± 0.4 y at enrollment. Participants were advised to take the supplement with their evening meal, which usually contributes the majority of dietary iron. Iron status was assessed at baseline and after 1 y of supplementation by measuring Hb and serum concns. of ferritin and transferrin receptors (TfRs). Results: The mean (±SD) Hb at enrollment was 134 ± 9 g/L, geometric mean serum ferritin was 26.3 μg/L (interquartile range: 18.6-39.4 μg/L), and serum TfR was 4.19 mg/L (3.52-5.10 mg/L). Daily calcium supplementation had no effect on the least-squares mean concns. of iron-status markers adjusted for their baseline values (Hb: 136 and 134 g/L, P = 0.31; ferritin: 25.4 and 26.1 μg/L, P = 0.73; TfR: 4.1 and 4.4 mg/L, P = 0.12; and the ratio of TfR to ferritin: 160 and 161 in the calcium and placebo groups, resp.; P = 0.97). Conclusion: Although it remains to be shown in iron-deficient persons, long-term iron status does not seem to be compromised by high calcium intakes.
- 101Gaitan, D.; Flores, S.; Saavedra, P.; Miranda, C.; Olivares, M.; Arredondo, M.; Lopez de Romana, D.; Lonnerdal, B.; Pizarro, F. Calcium Does Not Inhibit the Absorption of 5 mg of Nonheme or Heme Iron at Doses Less Than 800 mg in Nonpregnant Women. J. Nutr. 2011, 141 (9), 1652– 1656, DOI: 10.3945/jn.111.138651[Crossref], [PubMed], [CAS], Google Scholar101https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFaisL7J&md5=6030c7bcef9f6642894f9179155e7fa8Calcium does not inhibit the absorption of 5 milligrams of nonheme or heme iron at doses less than 800 milligrams in nonpregnant womenGaitan, Diego; Flores, Sebastian; Saavedra, Pia; Miranda, Constanza; Olivares, Manuel; Arredondo, Miguel; Lopez de Romana, Daniel; Lonnerdal, Bo; Pizarro, FernandoJournal of Nutrition (2011), 141 (9), 1652-1656CODEN: JONUAI; ISSN:0022-3166. (American Society for Nutrition)Calcium is the only known component in the diet that may affect absorption of both nonheme and heme iron. However, the evidence for a calcium effect on iron absorption mainly comes from studies that did not isolate the effect of calcium from that of other dietary components, because it was detected in single-meal studies. Our objective was to establish potential effects of calcium on absorption of nonheme and heme iron and the dose response for this effect in the absence of a meal. Fifty-four healthy, nonpregnant women were selected to participate in 4 iron absorption studies using iron radioactive tracers. We evaluated the effects of calcium doses between 200 and 1500 mg on absorption of 5 mg nonheme iron (as ferrous sulfate). We also evaluated the effects of calcium doses between 200 and 800 mg on absorption of 5 mg heme iron [as concd. RBC (CRBC)]. Calcium was administered as calcium chloride in all studies and minerals were ingested on an empty stomach. Calcium doses ≥1000 mg diminished nonheme iron absorption by an av. of 49.6%. A calcium dose of 800 mg diminished absorption of 5 mg heme iron by 37.7%. In conclusion, we demonstrated an isolated effect of calcium (as chloride) on absorption of 5 mg of iron provided as nonheme (as sulfate) and heme (as CRBC) iron. This effect was obsd. at doses higher than previously reported from single-meal studies, starting at ∼800 mg of calcium.
- 102Kim, M.; Lee, D. T.; Lee, Y. S. Iron Absorption and Intestinal Solubility in Rats Are Influenced by Dietary Proteins. Nutr. Res. (N.Y.) 1995, 15 (11), 1705– 1716, DOI: 10.1016/0271-5317(95)02041-0[Crossref], [CAS], Google Scholar102https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XjtFKh&md5=8c503f3f623d72a9815070dfada2c386Iron absorption and intestinal solubility in rats are influenced by dietary proteinsKim, Meehye; Lee, Dong-Tae; Lee, Yeon-SookNutrition Research (New York) (1995), 15 (11), 1705-16CODEN: NTRSDC; ISSN:0271-5317. (Elsevier)The effects of different proteins (pork, egg albumin, egg yolk, soybean and casein) on iron absorption and intestinal soly. were examd. in growing rats. Rats were fed iron-adequate diets including one of the protein sources for 14 d. All the diets were adjusted to contain similar levels of protein (220 g crude protein /kg diet) and iron (51-53 mg iron /kg diet). Apparent iron absorption was detd. using conventional chem. balances. Sol. iron in the intestinal contents and plasma iron concn. in portal blood were detd. shortly after the meal. Portal blood iron and intestinal sol. iron were highly correlated (r = 0.92, p =0.042). The addn. of pork protein greatly improved the soly. (42%) and apparent absorption (42%) of iron. In contrast, in rats fed egg yolk protein, iron soly. (17%) in the small intestine significantly decreased together with apparent iron absorption (13%) and iron concn. of the portal blood when compared with other groups. The effects of proteins on intestinal soly. and apparent absorption of iron were in increasing order: egg yolk < soybean < egg albumin < casein < pork. Our results suggest that the iron enhancing/inhibiting effect of pork/egg yolk results from their protein fractions. The iron soly. in the small intestine may be responsible for the difference in iron absorption of various proteins.
- 103Ishikawa, S.-I.; Tamaki, S.; Arihara, K.; Itoh, M. Egg Yolk Protein and Egg Yolk Phosvitin Inhibit Calcium, Magnesium, and Iron Absorptions in Rats. J. Food Sci. 2007, 72 (6), 412– 419, DOI: 10.1111/j.1750-3841.2007.00417.x[Crossref], [CAS], Google Scholar103https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXptlSntbY%253D&md5=fac68d5d3f77644e083d42b7117276b9Egg yolk protein and egg yolk phosvitin inhibit calcium, magnesium, and iron absorptions in ratsIshikawa, S.-I.; Tamaki, S.; Arihara, K.; Itoh, M.Journal of Food Science (2007), 72 (6), S412-S419CODEN: JFDSAZ; ISSN:0022-1147. (Blackwell Publishing, Inc.)Egg yolk decreases the absorption of iron. The effects of egg yolk protein and egg yolk phosvitin on the absorption of Ca, Mg, P, and Fe were studied in 5 wk old male Wistar rats. They were fed purified diets contg. casein, soybean protein, or egg yolk protein for 14 days. The apparent absorptions of Ca, Mg, and Fe in the rats fed the yolk protein diet were lower than in rats fed the casein and soybean protein diets. The apparent P absorption and the apparent protein digestibility in the yolk protein group were lower than in the casein and soybean protein groups. In feces of the yolk protein-fed rats, serine comprised >30% of total amino acids. The addn. of egg yolk phosvitin to the casein diets at 1 and 2% had effects on Ca and Mg absorptions similar to those produced by the diet with yolk protein. The tricine Na dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) pattern suggested that phosphopeptide fragments with mol. wts. of 28, 22, and 15 kDa were present in the small intestine contents of rats fed phosvitin. Thus compared to casein and soybean protein, the yolk protein decreased calcium and magnesium absorption via the resistance of phosvitin to digestive tract proteolytic action.
- 104Cook, J. D.; Morck, T. A.; Lynch, S. R. The Inhibitory Effect of Soy Products on Nonheme Iron Absorption in Man. Am. J. Clin. Nutr. 1981, 34 (12), 2622– 2629, DOI: 10.1093/ajcn/34.12.2622[Crossref], [PubMed], [CAS], Google Scholar104https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL38XjtlOjsQ%253D%253D&md5=8210f3635869c53aa551546850169e9eThe inhibitory effect of soy products on nonheme iron absorption in manCook, James D.; Morck, Timothy A.; Lynch, Sean R.American Journal of Clinical Nutrition (1981), 34 (12), 2622-9CODEN: AJCNAC; ISSN:0002-9165.Radioiron absorption studies were performed in male volunteer subjects to det. the effect on nonheme Fe absorption of various semipurified proteins. When egg albumen and casein were substituted in protein-equiv. quantities in a semisynthetic meal, similar mean absorptions of 2.5 and 2.7% were obsd. In contrast, isolated soy protein reduced absorption sharply, to an av. of 0.5%. When egg albumen in the semisynthetic meal was replaced with full fat soy flour, textured soy flour, and isolated soy protein, absorption fell from 5.5 to 1.0, 1.9, and 0.4%, resp., indicating an inhibitory effect of a wide range of soy products. The effect of substituting textured soy flour for meat in a meal contg. a hamburger, french fries, and a milkshake was also evaluated. With 3:1 and 2:1 ratios of meat to unhydrated textured soy flour, absorption decreased by 61 and 53%, resp. The soy products tested in this study thus have a pronounced inhibitory effect on the absorption of nonheme iron.
- 105Lynch, S R; Dassenko, S A; Cook, J D; Juillerat, M A; Hurrell, R F Inhibitory Effect of a Soybean-Protein-Related Moiety on Iron Absorption in Humans13. Am. J. Clin. Nutr. 1994, 60 (4), 567– 572, DOI: 10.1093/ajcn/60.4.567[Crossref], [PubMed], [CAS], Google Scholar105https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXhvVGms7Y%253D&md5=8c5aa38b36ed6eac549c0f7ad11755bfInhibitory effect of a soybean-protein-related moiety on iron absorption in humansLynch, Sean R.; Dassenko, Sandra A.; Cook, James D.; Juillerat, Marcel -A; Hurrell, Richard F.American Journal of Clinical Nutrition (1994), 60 (4), 567-72CODEN: AJCNAC; ISSN:0002-9165.The inhibitory effect of soybean protein isolates on nonheme-iron absorption was studied in 34 human subjects. Iron absorption was measured by using an extrinsic radioiron label in liq.-formula meals contg. hydrolyzed corn starch, corn oil, and either egg white or a series of soybean-protein derivs. The unmodified soybean-protein isolate markedly inhibited iron absorption. Percentage absorption was 19-fold higher when an extensively enzyme-hydrolyzed prepn. with very little phytate was used as the protein source. Both the glycinin (11S) and conglycinin (7S) fractions of soybean protein were inhibitory to iron absorption. Dephytinization removed the inhibitory effect of the glycinin but not of the conglycinin fraction. We conclude that there are two major inhibitors of iron absorption in soybean-protein isolates, phytic acid and a protein-related moiety contained in the conglycinin (7S) fraction.
- 106McPherson Kay, R. Dietary Fiber. J. Lipid Res. 1982, 23 (2), 221– 242, DOI: 10.1016/S0022-2275(20)38151-7
- 107Feltrin, C.; De Morais, M. B.; De Cássia Freitas, K.; De Morais, T. B.; Neto, U. F.; Amancio, O. M. S. Effect of Soluble Fiber Pectin on Growth and Intestinal Iron Absorption in Rats During Recovery from Iron Deficiency Anemia. Biol. Trace Elem. Res. 2009 1291 2009, 129 (1), 221– 228, DOI: 10.1007/s12011-008-8307-4
- 108Bosscher, D.; Van Caillie-Bertrand, M.; Van Cauwenbergh, R.; Deelstra, H. Availabilities of Calcium, Iron, and Zinc from Dairy Infant Formulas Is Affected by Soluble Dietary Fibers and Modified Starch Fractions. Nutrition 2003, 19 (7–8), 641– 645, DOI: 10.1016/S0899-9007(03)00063-7[Crossref], [PubMed], [CAS], Google Scholar108https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXkvVKhsLg%253D&md5=64e3ec5374a3924ae64c708f81fe9228Availabilities of calcium, iron, and zinc from dairy infant formulas is affected by soluble dietary fibers and modified starch fractionsBosscher, Douwina; Van Caillie-Bertrand, Micheline; Van Cauwenbergh, Rudy; Deelstra, HendrikNutrition (New York, NY, United States) (2003), 19 (7/8), 641-645CODEN: NUTRER; ISSN:0899-9007. (Elsevier Science Inc.)Insol. dietary fiber is a known inhibitor of mineral absorption, whereas the effects of sol. dietary fibers (including prebiotics) are less known. The aim was to study Ca, Fe, and Zn availabilities from dairy infant formulas supplemented with sol. dietary fibers and modified starches in vitro. Dairy infant formulas were supplemented with sol. dietary fibers (3%, dry wt) and modified starches (16% pregelatinized rice starch and 1.9% maltodextrin, dry wt) and kept in a well-controlled and defined environment in vitro. Pooled mature human milk was used as the ref. std. Ca availability from std. formula was elevated by 30% after inulin supplementation (17.2%), whereas locust bean gum (11.9%) and high esterified pectin (11.7%) reduced availability by approx. 10%. Iron availability from std. formula was increased by pregelatinized rice starch (3.8%), whereas availability was reduced in the following order: high esterified pectin (2.3%), oligofructose (2.2%), and low esterified pectin (2.1%). Zn availability was highest after the addn. of pregelatinized rice starch (13.5%) but lowest with the addn. of locust bean gum (6.8%) and maltodextrin (5.4%). This study showed that addn. of sol. dietary fiber affects Ca, Fe, and Zn availabilities in pos. (inulin) and neg. ways, depending on the type of the dietary fiber used.
- 109Weinborn, V.; Valenzuela, C.; Olivares, M.; Arredondo, M.; Weill, R.; Pizarro, F. Prebiotics Increase Heme Iron Bioavailability and Do Not Affect Non-Heme Iron Bioavailability in Humans. Food Funct. 2017, 8 (5), 1994– 1999, DOI: 10.1039/C6FO01833E[Crossref], [PubMed], [CAS], Google Scholar109https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmtFGnt7Y%253D&md5=48c5beb4aa317436e8079da703b3e342Prebiotics increase heme iron bioavailability and do not affect non-heme iron bioavailability in humansWeinborn, Valerie; Valenzuela, Carolina; Olivares, Manuel; Arredondo, Miguel; Weill, Ricardo; Pizarro, FernandoFood & Function (2017), 8 (5), 1994-1999CODEN: FFOUAI; ISSN:2042-6496. (Royal Society of Chemistry)The aim of this study was to establish the effect of a prebiotic mix on heme and non-heme iron (Fe) bioavailability in humans. To this purpose, twenty-four healthy women were randomized into one of two study groups. One group ate one yogurt per day for 12 days with a prebiotic mix (prebiotic group) and the other group received the same yogurt but without the prebiotic mix (control group). Before and after the intake period, the subjects participated in Fe absorption studies. These studies used 55Fe and 59Fe radioactive isotopes as markers of heme Fe and non-heme Fe, resp., and Fe absorption was measured by the incorporation of radioactive Fe into erythrocytes. The results showed that there were no significant differences in heme and non-heme Fe bioavailability in the control group. Heme Fe bioavailability of the prebiotic group increased significantly by 56% post-prebiotic intake. There were no significant differences in non-heme Fe bioavailability in this group. We concluded that daily consumption of a prebiotic mix increases heme Fe bioavailability and does not affect non-heme iron bioavailability.
- 110Petry, N.; Egli, I.; Chassard, C.; Lacroix, C.; Hurrell, R. Inulin Modifies the Bifidobacteria Population, Fecal Lactate Concentration, and Fecal PH but Does Not Influence Iron Absorption in Women with Low Iron Status. Am. J. Clin. Nutr. 2012, 96 (2), 325– 331, DOI: 10.3945/ajcn.112.035717[Crossref], [PubMed], [CAS], Google Scholar110https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFarurjM&md5=de7897d00413f4ed8d7abf8a3f031486Inulin modifies the bifidobacteria population, fecal lactate concentration, and fecal pH but does not influence iron absorption in women with low iron statusPetry, Nicolai; Egli, Ines; Chassard, Christophe; Lacroix, Christophe; Hurrell, RichardAmerican Journal of Clinical Nutrition (2012), 96 (2), 325-331CODEN: AJCNAC; ISSN:0002-9165. (American Society for Nutrition)Background: Bioavailability of nonheme iron is influenced by the concn. of inhibitors and enhancers in the diet. The fructans inulin and oligofructose have been shown to improve iron absorption in animals through colonic uptake, but this has not been confirmed in humans. Objective: The aim of the intervention study was to evaluate the influence of inulin on iron absorption, bifidobacteria, total bacteria, short-chain fatty acids (SCFAs), and fecal pH in women with low iron status (plasma ferritin <25 μg/L). Design: The subjects (n = 32) consumed inulin or placebo 3 times/d (∼20 g/d) for 4 wk, sepd. by a 2-wk washout period. Iron absorption was measured after 3 wk of inulin and placebo consumption from a std. test meal by using stable-iron-isotope techniques. Fecal bacteria were measured by quant. polymerase chain reaction, and fecal acids by HPLC. Results: Mean fractional iron absorption in the inulin (15.2%; 95% CI: 8.0%, 28.9%) and placebo (13.3%; 95% CI: 8.1%, 24.3%) periods did not differ significantly (P = 0.10). Inulin decreased fecal pH (P < 0.001) and increased fecal bifidobacteria (P < 0.001) and fecal lactate (P < 0.001) but had no effect on fecal SCFAs and total bacteria. Changes in lactate and acetate concns. were pos. correlated with changes in propionate (P < 0.001) and butyrate (P < 0.02) concns., resp. Iron absorption correlated with fecal pH in the placebo period (P < 0.01) but not in the inulin period (P = 0.37). Conclusion: Although inulin showed prebiotic activity, we were unable to show an increase in iron absorption in women with low iron status.
- 111Mohammed, O.; Dyab, N.; Kheadr, E.; Dabour, N. Effectiveness of Inulin-Type on the Iron Bioavailability in Anemic Female Rats Fed Bio-Yogurt. RSC Adv. 2021, 11 (4), 1928– 1938, DOI: 10.1039/D0RA08873K[Crossref], [PubMed], [CAS], Google Scholar111https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXkvF2jug%253D%253D&md5=66f6b99e32962d3b61e2fdd56a621884Effectiveness of inulin-type on the iron bioavailability in anemic female rats fed bio-yogurtMohammed, Osama; Dyab, Noha; Kheadr, Ehab; Dabour, NassraRSC Advances (2021), 11 (4), 1928-1938CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)It is well-documented that iron deficiency leads to anemia, which is the utmost crit. problem of nutrition worldwide. Inulin, indigestible polysaccharides, or prebiotic agents may act as vehicles to enhance the iron bioavailability through the formation of the polysaccharide-iron complex. The present study was undertaken to evaluate the therapeutic effects of yogurt fortified with iron and supplemented by long- or short-chain inulin on the growth status, blood parameters, antioxidant capacity, and liver function enzymes in anemic rats. Five animal groups were assigned as the control (G1), which were fed a std. diet and there were four anemic groups, in which haemolytic anemia was induced by phenylhydrazine. The anemic rats were divided into 4 groups according to the regime of feeding as G2: control anemic group fed low-iron diet while the remaining anemic groups were fed yogurt fortified with Fe2(SO4)3 without inulin (G3) or with either long- (G4) or short-chain (G5) inulin. The results showed that the animals subjected to treatment G4 had the highest (P ≤ 0.05) wt. gain and organ coeff. compared with other anemic groups (G2, G3, and G5). Among the anemic groups, the animals that belonged to G4 showed a significant restorative effect by returning the Hb and hematocrit levels and the red blood cell count to the normal control liver. Also, the liver iron content, enzymic activities, and antioxidant capacities improved in the animals subjected to G4 and G5 treatment groups. The histol. structures of the liver tissues of the animals that belonged to G4 and G5 were extremely close to that of the normal control liver. Long-chain inulin-contg. yogurt exhibited the best effects in terms of iron supplementation, bioavailability, and antioxidant activities. This formula might be a potential new iron supplement and a good functional food candidate.
- 112Mahajan, P. B.; BS, R. K.; Kapil, U.; Ramadass, B. Supplementation of Higher Doses of Iron in Programmes to Control Anaemia Is a Double Edged Sword. Indian J. Community Heal. 2018, 30 (Supp), 04– 08
- 113Horner, H. T.; Cervantes-Martinez, T.; Healy, R.; Reddy, M. B.; Deardorff, B. L.; Bailey, T. B.; Al-Wahsh, I.; Massey, L. K.; Palmer, R. G. Oxalate and Phytate Concentrations in Seeds of Soybean Cultivars [Glycine Max (L.) Merr.]. J. Agric. Food Chem. 2005, 53 (20), 7870– 7877, DOI: 10.1021/jf051193i[ACS Full Text], [CAS], Google Scholar113https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXpslCitLY%253D&md5=960c9fe6fb29b672fc4a7a512c26f5e3Oxalate and Phytate Concentrations in Seeds of Soybean Cultivars [Glycine max (L.) Merr.]Horner, Harry T.; Cervantes-Martinez, Teresa; Healy, Rosanne; Reddy, Manju B.; Deardorff, Betsy L.; Bailey, Theodore B.; Al-Wahsh, Ismail; Massey, Linda K.; Palmer, Reid G.Journal of Agricultural and Food Chemistry (2005), 53 (20), 7870-7877CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)This study analyzed soybean seeds from 116 cultivars for total, insol., and sol. oxalate (Ox), phytate (InsP6), calcium (Ca), and magnesium (Mg) because of their potential beneficial or harmful effects on human nutrition. These cultivars were divided into four groups (A-D) on the basis of the year and geog. location where they were grown. Oxalate concn. ranged from about 82 to 285 mg/100 g of dry seed. The InsP6 concn. ranged from 0.22 to 2.22 g/100 g of dry seed. There was no correlation between Ox and InsP6 within or among the four groups of cultivars. There was a significant correlation between total Ox and Ca, but not Mg, in group D cultivars (r = 0.3705; p < 0.0005). No significant relationship was found in the group A-C cultivars. Eleven group D cultivars had InsP6 less than 500 mg/100 g, but all had total Ox of 130 mg/100 g or greater. Five cultivars from groups A-C had relatively low InsP6 (group B; ≤1.01 g/100 g) and low Ox (<140 mg/100 g). These cultivars could be useful for producing soy foods beneficial to populations at risk for kidney stones and for improved mineral bioavailability. The Ox and InsP6 concns. of the cultivars indicate that choosing specific parents could generate seeds in succeeding generations with desirable Ox and InsP6 concns.
- 114Heaney, R. P.; Weaver, C. M.; Recker, R. R. Calcium Absorbability from Spinach. Am. J. Clin. Nutr. 1988, 47 (4), 707– 709, DOI: 10.1093/ajcn/47.4.707[Crossref], [PubMed], [CAS], Google Scholar114https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL1cXktlKqsLY%253D&md5=c84b3a3881206beeb39a28b4000e9fffCalcium absorbability from spinachHeaney, Robert P.; Weaver, Connie M.; Recker, Robert R.American Journal of Clinical Nutrition (1988), 47 (4), 707-9CODEN: AJCNAC; ISSN:0002-9165.The absorbability of Ca from spinach was compared with the absorbability of Ca from milk in healthy adults in a randomized cross-over design in which the test meal of either milk or spinach had 200 mg Ca labeled with 45Ca. Absorption was measured by the std. double-isotope method in which both the test food and the miscible Ca pool are labeled with different Ca tracers. Measurement of both Ca and oxalate in test spinach revealed a very slight stoichiometric excess of oxalate; hence it is likely that all of the spinach Ca was effectively bound. Absorption was higher from milk in every case, with the mean absorption from milk averaging 27.6% and from spinach, 5.1%. The mean within-subject difference between Ca absorption from milk and from spinach was 22.5%. Thus, spinach Ca is much less readily available than is milk Ca.
- 115Heaney, R. P.; Weaver, C. M. Oxalate: Effect on Calcium Absorbability. Am. J. Clin. Nutr. 1989, 50 (4), 830– 832, DOI: 10.1093/ajcn/50.4.830[Crossref], [PubMed], [CAS], Google Scholar115https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL1MXmtFelurg%253D&md5=e03fb5c71ef421c1099f9a957a2835b4Oxalate: effect on calcium absorbabilityHeaney, Robert P.; Weaver, Connie M.American Journal of Clinical Nutrition (1989), 50 (4), 830-2CODEN: AJCNAC; ISSN:0002-9165.Absorption of Ca from intrinsically labeled Ca oxalate was measured in normal women and compared with absorption of Ca from milk in these same subjects, both when the test substances were ingested in sep. meals and when ingested together. Fractional Ca absorption from oxalate averaged 0.100 when ingested alone and 0.140 when ingested together with milk. Absorption was, as expected, substantially lower than absorption from milk (0.358). Nevertheless, Ca oxalate absorbability in these women was higher than was previously found for spinach Ca. When milk and Ca oxalate were ingested together, there was no interference of oxalate in milk Ca absorption and no evidence of tracer exchange between the 2 labeled Ca species.
- 116Kelsay, J. L.; Prather, E. S. Mineral Balances of Human Subjects Consuming Spinach in a Low-Fiber Diet and in a Diet Containing Fruits and Vegetables. Am. J. Clin. Nutr. 1983, 38 (1), 12– 19, DOI: 10.1093/ajcn/38.1.12[Crossref], [PubMed], [CAS], Google Scholar116https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaL3s3isl2msQ%253D%253D&md5=82830e86ce29a2eb8aad8ec818a3fa6fMineral balances of human subjects consuming spinach in a low-fiber diet and in a diet containing fruits and vegetablesKelsay J L; Prather E SThe American journal of clinical nutrition (1983), 38 (1), 12-9 ISSN:0002-9165.The effects of spinach in the diet on mineral balances were examined in 12 men who consumed three controlled diets for 4 wk each. Diet 1, a low-fiber diet, contained spinach, which is high in oxalic acid, every other day. Diet 2 contained fiber in fruits and vegetables, including spinach every other day. Diet 3 was the same as diet 2 except that cauliflower, which is low in oxalic acid, replaced the spinach. During wk 4, mean balances of calcium, magnesium, and zinc on diet 2 were negative and significantly lower than those on diet 1. Magnesium and zinc balances during wk 4 were also significantly lower on diet 2 than on diet 3. Mean balances of these minerals were not significantly lower on diet 2 during wk 3, nor were there any significant differences among mineral balances when wk 3 and 4 were considered together. Fecal oxalic acid was significantly greater on diet 2 than on diet 1 during both wk 3 and 4.
- 117Van Campen, D. R.; Welch, R. M. Availability to Rats of Iron from Spinach: Effects of Oxalic Acid. J. Nutr. 1980, 110 (8), 1618– 1621, DOI: 10.1093/jn/110.8.1618[Crossref], [PubMed], [CAS], Google Scholar117https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3cXltlWjsbY%253D&md5=81a264d325e0e474552b85389e502884Availability to rats of iron from spinach: effects of oxalic acidVan Campen, Darrell R.; Welch, Ross M.Journal of Nutrition (1980), 110 (8), 1618-21CODEN: JONUAI; ISSN:0022-3166.The availability to rats of Fe from 2 varieties of spinach was detd. Also, the absorption of Fe was compared between FeCl3 and Fe oxalate [15843-42-2] and the effects of adding 0.75% oxalate to the diet were detd. Absorption of Fe from both varieties of spinach was comparable to that from FeCl3 and the Fe was equally available from Fe oxalate and FeCl3. The addn. of 0.75% oxalic acid [144-62-7] to the diet did not depress Fe absorption and, if anything, appeared to enhance Fe utilization by rats.
- 118Gordon, D. T.; Chao, L. S. Relationship of Components in Wheat Bran and Spinach to Iron Bioavailability in the Anemic Rat. J. Nutr. 1984, 114 (3), 526– 535, DOI: 10.1093/jn/114.3.526[Crossref], [PubMed], [CAS], Google Scholar118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL2cXhslemsr0%253D&md5=7c30dc2f69269581c48c56b0d5189145Relationship of components in wheat bran and spinach to iron bioavailability in the anemic ratGordon, Dennis T.; Chao, Lucia S.Journal of Nutrition (1984), 114 (3), 526-35CODEN: JONUAI; ISSN:0022-3166.Components found in wheat bran and spinach were evaluated as to their affect on the bioavailability of Fe from FeSO4 by using the criteria of Hb regeneration in anemic rats. The relative biol. values (RBV) of Fe in wheat bran and spinach (FeSO4 = 100%) were 124 and 53%, resp. Control diets with graded levels of FeSO4 did not contain dietary fiber (cellulose [9004-34-6]). Adding cellulose (1.74%) or phytic acid [83-86-3] (0.66%) at levels contained in the wheat bran diet significantly increased the RBV of the Fe2+ to 126 and 124%, resp. The addn. of 2.10% oxalic acid [144-62-7], the amt. in the spinach diet, caused the highest increase in RBV, to 164%. Combining these dietary components, plus lignin [9005-53-2] (0.67%) and pectin [9000-69-5] (0.63%), in various combinations, resulted in RBVs ≥100%. The bioavailability of Fe in plant foods appears to be dependent on how this nutrient is presented to the mucosa. RBV for iron were also calcd. based on food intake and growth rate. The latter parameters are believed to have greater utility in detg. RBV when food intake and(or) growth rate may vary among animals consuming different sources of test Fe.
- 119Genannt Bonsmann, S S.; Walczyk, T; Renggli, S; Hurrell, R F Oxalic Acid Does Not Influence Nonhaem Iron Absorption in Humans: A Comparison of Kale and Spinach Meals Food Public Procurement View Project Shaping the School Environment to Promote Healthy Diet and Lifestyle Habits View Project. Eur. J. Clin. Nutr. 2008, 62 (3), 336– 341, DOI: 10.1038/sj.ejcn.1602721[Crossref], [PubMed], [CAS], Google Scholar119https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXivVOqt7o%253D&md5=da079f19d716b298a5c5219afdc6d8bbOxalic acid does not influence nonhaem iron absorption in humans: a comparison of kale and spinach mealsGenannt Bonsmann, S. Storcksdieck; Walczyk, T.; Renggli, S.; Hurrell, R. F.European Journal of Clinical Nutrition (2008), 62 (3), 336-341CODEN: EJCNEQ; ISSN:0954-3007. (Nature Publishing Group)To evaluate the influence of oxalic acid (OA) on nonheme iron absorption in humans. Two randomized crossover stable iron isotope absorption studies. Zurich, Switzerland. Sixteen apparently healthy women (18-45 years, <60 kg body wt.), recruited by poster advertising from the staff and student populations of the ETH, University and University Hospital of Zurich, Switzerland. Thirteen subjects completed both studies. Iron absorption was measured based on erythrocyte incorporation of 57Fe or 58Fe 14 days after the administration of labeled meals. In study I, test meals consisted of two wheat bread rolls (100 g) and either 150 g spinach with a native OA content of 1.27 g (ref. meal) or 150 g kale with a native OA content of 0.01 g. In study II, 150 g kale given with a potassium oxalate drink to obtain a total OA content of 1.27 g was compared to the spinach meal. After normalization for the spinach ref. meal absorption, geometric mean iron absorption from wheat bread rolls with kale (10.7%) did not differ significantly from wheat rolls with kale plus 1.26 g OA added as potassium oxalate (11.5%, P=0.86). Spinach was significantly higher in calcium and polyphenols than kale and absorption from the spinach meal was 24% lower compared to the kale meal without added OA, but the difference did not reach statistical significance (P>0.16). Potassium oxalate did not influence iron absorption in humans from a kale meal and our findings strongly suggest that OA in fruits and vegetables is of minor relevance in iron nutrition. European Journal of Clin. Nutrition (2008) 62, 336-341; doi:10.1038/sj.ejcn.1602721; published online 18 Apr. 2007.
- 120Gupta, S.; Lakshmi, J.; Prakash, J. In Vitro Bioavailability of Calcium and Iron from Selected Green Leafy Vegetables †. J. Sci. Food Agric. J. Sci. Food Agric 2006, 86, 2147– 2152, DOI: 10.1002/jsfa.2589[Crossref], [CAS], Google Scholar120https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtFajsr3K&md5=112f15d85b54adf82aea19f586843985In vitro bioavailability of calcium and iron from selected green leafy vegetablesGupta, Sheetal; Jyothi, Lakshmi A.; Prakash, JamunaJournal of the Science of Food and Agriculture (2006), 86 (13), 2147-2152CODEN: JSFAAE; ISSN:0022-5142. (John Wiley & Sons Ltd.)The objective of the present investigation was to analyze the relative influence of oxalic acid, phytic acid, tannin and dietary fiber on in vitro availability of Fe and Ca from green leafy vegetables (GLV). Thirteen GLV were selected and analyzed for Fe, Ca, oxalic acid, phytic acid, tannin and dietary fiber contents using std. methods. The bioavailability of Ca and Fe in the GLV was estd. by equil. dialysis. Oxalic acid content was less than 1 g kg-1 in four greens and ranged between 1.22 to 11.98 g kg-1 in the remaining. Dietary fiber ranged from 19.5 to 113.7 g kg-1. Tannin content ranged between 0.6138 and 2.1159 g kg-1 with the exception of two GLV that had 0.1332 and 14.8619 g kg-1. Four GLV were found to have approx. 40% bioavailable Fe, while the others were in the range of 6-30%. In vitro available Ca was less than or equal to 25% in 8 GLV and between 34% and 52% in 5 GLV. Multiple regression anal. revealed that these factors together accounted for 53% (r2 = 0.53) and 45% (r2 = 0.45) inhibition of Fe and Ca absorption, resp. These findings infer that Ca and Fe availability is influenced by the constituents present in the GLV.
- 121Ma, Q.; Kim, E.-Y.; Lindsay, E. A.; Han, O. Bioactive Dietary Polyphenols Inhibit Heme Iron Absorption in a Dose-Dependent Manner in Human Intestinal Caco-2 Cells. J. Food Sci. 2011, 76, H143, DOI: 10.1111/j.1750-3841.2011.02184.x[Crossref], [PubMed], [CAS], Google Scholar121https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXns1SrsbY%253D&md5=1fc07ed23691ec1f60913eee1c27e4bfBioactive dietary polyphenols inhibit heme iron absorption in a dose-dependent manner in human intestinal Caco-2 cellsMa, Qianyi; Kim, Eun-Young; Lindsay, Elizabeth Ann; Han, OkheeJournal of Food Science (2011), 76 (5), H143-H150CODEN: JFDSAZ; ISSN:0022-1147. (Wiley-Blackwell)Although heme iron is an important form of dietary iron, its intestinal absorption mechanism remains elusive. Our previous study revealed that (-)-epigallocatechin-3-gallate (EGCG) and grape seed ext. (GSE) markedly inhibited intestinal heme iron absorption by reducing the basolateral iron export in Caco-2 cells. The aim of this study was to examine whether small amts. of EGCG, GSE, and green tea ext. (GT) could inhibit heme iron absorption, and to test whether the inhibitory action of polyphenols could be offset by ascorbic acid. A heme-55Fe absorption study was conducted by adding various concns. of EGCG, GSE, and GT to Caco-2 cells in the absence and presence of ascorbic acid. Polyphenolic compds. significantly inhibited heme-55Fe absorption in a dose-dependent manner. The addn. of ascorbic acid did not modulate the inhibitory effect of dietary polyphenols on heme iron absorption when the cells were treated with polyphenols at a concn. of 46 mg/L. However, ascorbic acid was able to offset or reverse the inhibitory effects of polyphenolic compds. when lower concns. of polyphenols were added (≤ 4.6 mg/L). Ascorbic acid modulated the heme iron absorption without changing the apical heme uptake, the expression of the proteins involved in heme metab. and basolateral iron transport, and heme oxygenase activity, indicating that ascorbic acid may enhance heme iron absorption by modulating the intracellular distribution of 55Fe. These results imply that the regular consumption of dietary ascorbic acid can easily counteract the inhibitory effects of low concns. of dietary polyphenols on heme iron absorption but cannot counteract the inhibitory actions of high concns. of polyphenols.
- 122Hurrell, R. F.; Lynch, S. R.; Trinidad, T. P.; Dassenko, S. A.; Cook, J. D. Iron Absorption in Humans as Influenced by Bovine Milk Proteins. Am. J. Clin. Nutr. 1989, 49 (3), 546– 552, DOI: 10.1093/ajcn/49.3.546[Crossref], [PubMed], [CAS], Google Scholar122https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL1MXhslaisbo%253D&md5=0b45dc2a128b9d484788205b1bd7c105Iron absorption in humans as influenced by bovine milk proteinsHurrell, Richard F.; Lynch, Sean R.; Trinidad, Trinidad P.; Dassenko, Sandra A.; Cook, James D.American Journal of Clinical Nutrition (1989), 49 (3), 546-52CODEN: AJCNAC; ISSN:0002-9165.The effect of the 2 major bovine milk protein fractions on the dialyzability of Fe in vitro under simulated gastrointestinal conditions and on the absorption of Fe by humans was studied. Liq.-formula meals were prepd. from hydrolyzed maize starch, corn oil, and either spray-dried egg white or a milk-protein product. In meals contg. egg white, 3.32% of the Fe was dialyzable. The substitution of casein and whey protein products reduced the dialyzable fraction to 0.19-0.56% and 0.86-1.60%, resp. Percentage Fe absorption was also reduced by the substitution of casein or whey protein for egg white. Mean absorption values fell from 6.67 to 3.65% and 2.53 to 0.98%, resp. When the intact milk-protein products were replaced by enzyme- or acid-hydrolyzed prepns., the dialyzable fraction increased markedly and in proportion to the extent of hydrolysis. A similar but much smaller effect on absorption was obsd. Thus, bovine casein and whey proteins are responsible at least in part for the poor bioavailability of the Fe in some infant formulas.
- 123Liberal, Â.; Pinela, J.; Vívar-Quintana, A. M.; Ferreira, I. C. F. R.; Barros, L. Fighting Iron-Deficiency Anemia: Innovations in Food Fortificants and Biofortification Strategies. Foods 2020, 9 (12), 1871, DOI: 10.3390/foods9121871[Crossref], [CAS], Google Scholar123https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXosV2nsLw%253D&md5=9648f4bc4a86da64d1513ff25cee67e9Fighting iron-deficiency anemia: innovations in food fortificants and biofortification strategiesLiberal, Angela; Pinela, Jose; Vivar-Quintana, Ana Maria; Ferreira, Isabel C. F. R.; Barros, LillianFoods (2020), 9 (12), 1871CODEN: FOODBV; ISSN:2304-8158. (MDPI AG)Iron deficiency remains one of the main nutritional disorders worldwide and low iron intake and/or bioavailability are currently the major causes of anemia. To fight this public health problem, the scientific challenge is to find an iron form with sufficient bioavailability to increase its levels in humans through food fortification. In turn, biofortification appears as a comparatively advantageous and bearable strategy for the delivery of vitamins and other micronutrients for people without access to a healthy and diverse diet. This approach relies on plant breeding, transgenic techniques, or agronomic practices to obtain a final food product with a higher iron content. It is also known that certain food constituents are able to favor or inhibit iron absorption. The management of these compds. can thus successfully improve the absorption of dietary iron and, ultimately, contribute to fight this disorder present all over the world. This review describes the main causes/manifestations of iron-deficiency anemia, forms of disease prevention and treatment, and the importance of a balanced and preventive diet. A special focus was given to innovative food fortification and biofortification procedures used to improve the iron content in staple food crops.
- 124Kleiveland, C.; Lea, T.; Mackie, A.; Requena, T.; Swiatecka, D.; Wichers, H. The Impact of Food Bioactives on Health In Vitro and Ex Vivo Models 2015, 103– 111, DOI: 10.1007/978-3-319-16104-4
- 125Gangloff, M. B.; Glahn, R. P.; Miller, D. D.; Van Campen, D. R. Assessment of Iron Availability Using Combined in Vitro Digestion and Caco-2 Cell Culture. Nutr. Res. (N.Y.) 1996, 16 (3), 479– 487, DOI: 10.1016/0271-5317(96)00029-2[Crossref], [CAS], Google Scholar125https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28Xis1Kqu74%253D&md5=628a276414d9cf4ace3a64c2e415d3aeAssessment of iron availability using combined in vitro digestion and Caco-2 cell cultureGangloff, Mary Beth; Glahn, Raymond P.; Miller, Dennis D.; Van Campen, Darrell R.Nutrition Research (New York) (1996), 16 (3), 479-87CODEN: NTRSDC; ISSN:0271-5317. (Elsevier)A model for the rapid assessment of iron availability was developed that combines in vitro digestion with iron uptake by Caco-2 cell monolayers. In this method, samples (beef, ascorbic acid, or citric acid) were adjusted to pH 2, labeled with 59Fe, and subjected to pepsin digestion (pH 2, 37°C) for 1 h to simulate gastric digestion. Next, a dialysis bag (12,000-14,000 mol. wt. cutoff) contg. 150 mM PIPES buffer (pH 6.7) was placed in the digest and incubation continued for 30 min. Then, a pancreatin-bile mixt. was added, and incubation was continued for an addnl. 2 h. The contents of the dialysis bag were removed and an aliquot applied to Caco-2 cell monolayers. After a 60 min incubation, iron that was non-specifically bound to the surface of the monolayer was removed by rinsing with a soln. contg. bathophenanthrolinedisulfonic acid and sodium dithionite. Cells were then counted for 59Fe activity to measure uptake. Beef and ascorbic acid enhanced Caco-2 cell iron uptake, whereas citric acid had no effect. These results compare favorably with literature reports of human studies and suggest that a dialyzable factor(s) less than 14,000 daltons, released during beef digestion, was responsible for the iron absorption-enhancing properties of beef. We believe that this system will be useful for studying basic mechanisms of iron absorption and for in vitro estn. of iron bioavailability.
- 126Nedovic, V.; Kalusevic, A.; Manojlovic, V.; Levic, S.; Bugarski, B. An Overview of Encapsulation Technologies for Food Applications. Procedia Food Sci. 2011, 1, 1806– 1815, DOI: 10.1016/j.profoo.2011.09.265[Crossref], [CAS], Google Scholar126https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XjtVKntbg%253D&md5=ad3e3319cb902479624bce6ecd925784An overview of encapsulation technologies for food applicationsNedovic, Viktor; Kalusevic, Ana; Manojlovic, Verica; Levic, Steva; Bugarski, BrankoProcedia Food Science (2011), 1 (), 1806-1815CODEN: PFSRC5; ISSN:2211-601X. (Elsevier Ltd.)Encapsulation is a process to entrap active agents within a carrier material and it is a useful tool to improve delivery of bioactive mols. and living cells into foods. Materials used for design of protective shell of encapsulates must be food-grade, biodegradable and able to form a barrier between the internal phase and its surroundings. Among all materials, the most widely used for encapsulation in food applications are polysaccharides. Proteins and lipids are also appropriate for encapsulation. Spray drying is the most extensively applied encapsulation technique in the food industry because it is flexible, continuous, but more important an economical operation. Most of encapsulates are spray-dried ones, rest of them are prepd. by spray-chilling, freeze-drying, melt extrusion and melt injection. Mol. inclusion in cyclodextrins and liposomal vesicles are more expensive technologies, and therefore, less exploited. There are no. of reasons why to employ an encapsulation technol. and this paper reviews some of them. For example, this technol. may provide barriers between sensitive bioactive materials and the environment, and thus, to allow taste and aroma differentiation, mask bad tasting or smelling, stabilize food ingredients or increase their bioavailability. One of the most important reasons for encapsulation of active ingredients is to provide improved stability in final products and during processing. Another benefit of encapsulation is less evapn. and degrdn. of volatile actives, such as aroma. Furthermore, encapsulation is used to mask unpleasant feelings during eating, such as bitter taste and astringency of polyphenols. Also, another goal of employing encapsulation is to prevent reaction with other components in food products such as oxygen or water. In addn. to the above, encapsulation may be used to immobilize cells or enzymes in food processing applications, such as fermn. process and metabolite prodn. processes. There is an increasing demand to find suitable solns. that provide high productivity and, at the same time, satisfy an adequate quality of the final food products. This paper aims to provide a short overview of commonly used processes to encapsulate food actives.
- 127Soukoulis, C.; Bohn, T. A Comprehensive Overview on the Micro- and Nano-Technological Encapsulation Advances for Enhancing the Chemical Stability and Bioavailability of Carotenoids. Crit. Rev. Food Sci. Nutr. 2018, 58 (1), 1– 36, DOI: 10.1080/10408398.2014.971353[Crossref], [PubMed], [CAS], Google Scholar127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtFKhsr7K&md5=d484e80f95abb238e267ef4eccf77d69A comprehensive overview on the micro- and nano-technological encapsulation advances for enhancing the chemical stability and bioavailability of carotenoidsSoukoulis, Christos; Bohn, TorstenCritical Reviews in Food Science and Nutrition (2018), 58 (1), 1-36CODEN: CRFND6; ISSN:1040-8398. (Taylor & Francis, Inc.)Carotenoids are lipophilic secondary plant compds., and their consumption within fruits and vegetables has been pos. correlated with a decreased risk of developing several chronic diseases. However, their bioavailability is often compromised due to incomplete release from the food matrix, poor soly. and potential degrdn. during digestion. In addn., carotenoids in food products are prone to oxidative degrdn., not only lowering the nutritional value of the product but also triggering other quality deteriorative changes, such as formation of lipid pro-oxidants (free radicals), development of discolorations or off-flavor defects. Encapsulation refers to a physicochem. process, aiming to entrap an active substance in structurally engineered micro- or nano-systems, in order to develop an effective thermodynamical and phys. barrier against deteriorative environmental conditions, such as water vapor, oxygen, light, enzymes or pH. In this context, encapsulation of carotenoids has shown to be a very effective strategy to improve their chem. stability under common processing conditions including storage. In addn., encapsulation may also enhance bioavailability (via influencing bioaccessibility and absorption) of lipophilic bioactives, via modulating their release kinetics from the carrier system, soly. and interfacial properties. In the present paper, it is aimed to present the state of the art of carotenoid microencapsulation in order to enhance storability and bioavailability alike.
- 128Dubey, B. N.; Windhab, E. J. Iron Encapsulated Microstructured Emulsion-Particle Formation by Prilling Process and Its Release Kinetics. J. Food Eng. 2013, 115 (2), 198– 206, DOI: 10.1016/j.jfoodeng.2012.10.013[Crossref], [CAS], Google Scholar128https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhs1OmsLvN&md5=ad2a2fbdfc9124dc4809191176377babIron encapsulated microstructured emulsion-particle formation by prilling process and its release kineticsDubey, Bipro N.; Windhab, Erich J.Journal of Food Engineering (2013), 115 (2), 198-206CODEN: JFOEDH; ISSN:0260-8774. (Elsevier Ltd.)Encapsulation of functional components is commonly used to protect them from the environment, or to control their release. In the present study, iron is used as a model nutrient that is encapsulated in water-in-oil emulsion. Fat based emulsion particles are produced using that emulsion through prilling process using twin fluid atomizers. The particles are characterized in terms of size and size distribution, and their internal structure is investigated by cryogenic SEM (cryo-SEM). The iron release kinetics through the fat matrix of the emulsion particles in an in vitro gastric system (pH ≈ 2.0) is described by the second order kinetics. An empirical correlation of the release kinetics rate const. is proposed as a function of the viscosity ratio of dispersed to continuous phase, mean particle size, and shelf-life of the particles. It is seen that the release kinetics can be controlled by choosing particle size and thickener concn.
- 129Ilyasoglu Buyukkestelli, H.; El, S. N. Development and Characterization of Double Emulsion to Encapsulate Iron. J. Food Eng. 2019, 263, 446– 453, DOI: 10.1016/j.jfoodeng.2019.07.026[Crossref], [CAS], Google Scholar129https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsFWqsrjE&md5=6a1cecfd4fb4324911cc15ef186c8934Development and characterization of double emulsion to encapsulate ironIlyasoglu Buyukkestelli, Hulya; El, Sedef NehirJournal of Food Engineering (2019), 263 (), 446-453CODEN: JFOEDH; ISSN:0260-8774. (Elsevier Ltd.)In this study, it was aimed to prep. and characterize double (W1/O/W2) emulsions for encapsulation of ferric chloride within the internal aq. phase (W1). The primary (W1/O) emulsion to be used in double emulsion was examd. for oxidative stability and whey protein isolate was found effective in improving oxidn. stability. The double emulsions were prepd. with different primary emulsion:external water phase (W1/O:W2) ratios as 40:60, 30:70 and 20:80; the emulsions were characterized in terms of droplet size, encapsulation efficiency, rheol., creaming stability and in vitro iron bioaccessibility. The emulsion with 40:60 ratio had the highest viscosity and encapsulation efficiency whereas it had the lowest creaming index and droplet size. It was also obtained that iron bioaccessibility increased as the ratio of W2 phase increased and the double emulsion with 20:80 ratio showed the highest bioaccessibility (52.97 ± 0.89%). This study may enable the use of double emulsion encapsulation in the enrichment of food products with iron.
- 130Prichapan, N.; McClements, D. J.; Klinkesorn, U. Encapsulation of Iron within W1/O/W2 Emulsions Formulated Using a Natural Hydrophilic Surfactant (Saponin): Impact of Surfactant Level and Oil Phase Crystallization. Food Biophys. 2020, 15 (3), 346– 354, DOI: 10.1007/s11483-020-09628-w
- 131Prichapan, N.; Mcclements, D. J.; Klinkesorn, U. Iron Encapsulation in Water-in-Oil Emulsions: Effect of Ferrous Sulfate Concentration and Fat Crystal Formation on Oxidative Stability. J. Food Sci. 2018, 83 (2), 309– 317, DOI: 10.1111/1750-3841.14034[Crossref], [PubMed], [CAS], Google Scholar131https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXnt12ntw%253D%253D&md5=c22d9e2415a141e34c1bc087c57fd605Iron Encapsulation in Water-in-Oil Emulsions: Effect of Ferrous Sulfate Concentration and Fat Crystal Formation on Oxidative StabilityPrichapan, Nattapong; McClements, David Julian; Klinkesorn, UtaiJournal of Food Science (2018), 83 (2), 309-317CODEN: JFDSAZ; ISSN:0022-1147. (Wiley-Blackwell)Iron deficiency is a major global human health concern. Encapsulation of iron in functional food products may help to solve this problem. However, iron is highly reactive and may promote rapid lipid oxidn. in fatty foods. In this study, the effect of ferrous sulfate (0.1 to 0.5 wt%) and rice bran stearin (0 or 30 wt%) on the phys. properties, oxidative stability, and encapsulation efficiency of 20 wt% water-in-oil (W/O) emulsions stabilized with polyglycerol polyricinoleate was investigated. In the presence of rice bran stearin crystals in the continuous oil phase, W/O emulsions had smaller mean droplet diams. (d ∼ 250 nm) and better phys. stability than its absence (d ∼ 330 nm). An increase in the ferrous sulfate concn. in the water droplets led to a decrease in the oxidative stability of the W/O emulsions. However, the presence of rice bran stearin significantly (P ≤ 0.05) improved their oxidative stability. Moreover, addn. of rice bran stearin also significantly (P ≤ 0.05) improved the encapsulation efficiency and delayed ferrous sulfate release from the W/O emulsions. The impact of pH and ionic strength on the encapsulation efficiency of the W/O emulsion was also investigated. Ionic strength affected the encapsulation efficiency much more than pH. The W/O emulsions created in the present study may be useful for the encapsulation and delivery of iron and other water-sol. nutrients into food products. Practical Application : Water-in-oil (W/O) emulsions may be used to encapsulate, protect, and deliver water-sol. bioactive compds. or nutrients into food products. In this study, W/O emulsions stabilized using an oil-sol. surfactant (polyglycerol polyricinoleate, PGPR) and fat crystal network (rice bran stearin) were shown to be useful for encapsulation and delivery of iron into foods. This strategy may be a promising approach to reduce iron deficiency, a major nutritional deficiency for people with inadequate food supplies.
- 132Churio, O.; Valenzuela, C. Development and Characterization of Maltodextrin Microparticles to Encapsulate Heme and Non-Heme Iron. LWT 2018, 96, 568– 575, DOI: 10.1016/j.lwt.2018.05.072[Crossref], [CAS], Google Scholar132https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtFWhtr%252FM&md5=ab84caa2aae767cbfde39f3d625d71c1Development and characterization of maltodextrin microparticles to encapsulate heme and non-heme ironChurio, Osmaly; Valenzuela, CarolinaLWT--Food Science and Technology (2018), 96 (), 568-575CODEN: LSTWB3; ISSN:0023-6438. (Elsevier Ltd.)Selection of an appropriate encapsulating material and its properties are crit. issues to optimize iron encapsulation systems. Therefore, the aim of this work was to develop and characterize different types of heme and non-heme iron-maltodextrin microparticles. Different concns. of bovine erythrocytes (BE) and ferrous sulfate (FS) were encapsulated using an optimal maltodextrin concn. of 40% w/v by spray-drying. The microparticles were characterized by iron content, yield, Z potential, size, color, SEM, FTIR and iron release under simulated gastrointestinal conditions. Results indicate that FS microparticles exhibited a higher iron content (54-90 mg/g) than BE microparticles (0.28-0.77 mg/g), Z Potential for all microparticles was neg. and FS microparticles had a smaller size (918-981 nm) than BE microparticles (10,390-16,643 nm). FS microparticles had an irregular spherical shape and a shriveled surface, while BE microparticles exhibited a spherical shape and a smooth surface. The main interactions of FS microparticles were O-H bridges and C-O bonds, whereas for BE microparticles these were O-H, C-O and N-H bonds. Iron was released from both types of microparticles: high amts. under gastric conditions, and quickly under intestinal conditions.
- 133Xu, Z.; Liu, S.; Wang, H.; Gao, G.; Yu, P.; Chang, Y. Encapsulation of Iron in Liposomes Significantly Improved the Efficiency of Iron Supplementation in Strenuously Exercised Rats. Biol. Trace Elem. Res. 2014 1621 2014, 162 (1), 181– 188, DOI: 10.1007/s12011-014-0143-0
- 134Cheng, J.; Kenaan, A.; Zhao, D.; Qi, D.; Song, J. Photo-Polymerizable Ferrous Sulfate Liposomes as Vehicles for Iron Fortification of Food. Nanomedicine Nanotechnology, Biol. Med. 2020, 30, 102286, DOI: 10.1016/j.nano.2020.102286[Crossref], [PubMed], [CAS], Google Scholar134https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38fntlWmtw%253D%253D&md5=5457102e78fea282a049245cd136e88ePhoto-polymerizable ferrous sulfate liposomes as vehicles for iron fortification of foodCheng Jin; Kenaan Ahmad; Zhao Di; Qi Daizong; Song JieNanomedicine : nanotechnology, biology, and medicine (2020), 30 (), 102286 ISSN:.The development of photo-polymerizable ferrous sulfate liposomes has been perused for iron fortification of food. Iron fortification is accompanied by several limitations that reduce its quality as it provokes sensory problems due to the oxidation of Fe(2+) into Fe(3+). To overcome such undesirable effects and improve the bioavailability of iron, photo-polymerizable 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) phospholipids have been employed as iron delivery system. DC8,9PC possesses diacetylene groups that undergo intramolecular cross-linking following UV treatment, resulting in enhanced stability, high encapsulation efficiency (~91%) without inducing sensory changes during milk fortification, along with less oxidation and con-tent leakage after long term storage in ethanol. Furthermore, polymeric Fe-DC8,9PC liposomes present high in vivo iron bioavailability in hemoglobin (Hb)-repletion study in rats, with no indications of toxicity examined by hematoxylin-eosin test. This methodology offers great promise for a simple, reliable, cost-effective, and robust platform for treating iron deficiency anemia, seeking to bring its application toward market.
- 135Wardhani, D. H.; Wardana, I. N.; Ulya, H. N.; Cahyono, H.; Kumoro, A. C.; Aryanti, N. The Effect of Spray-Drying Inlet Conditions on Iron Encapsulation Using Hydrolysed Glucomannan as a Matrix. Food Bioprod. Process. 2020, 123, 72– 79, DOI: 10.1016/j.fbp.2020.05.013[Crossref], [CAS], Google Scholar135https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtFKitLvL&md5=887e4941d41017d073ceebcdd39e5038The effect of spray-drying inlet conditions on iron encapsulation using hydrolysed glucomannan as a matrixWardhani, Dyah Hesti; Wardana, Irsyadia Nindya; Ulya, Hana Nikma; Cahyono, Heri; Kumoro, Andri Cahyo; Aryanti, NitaFood and Bioproducts Processing (2020), 123 (), 72-79CODEN: FBPREO; ISSN:0960-3085. (Elsevier B.V.)Spray-drying is an encapsulation method that can be used to protect iron from oxidn. Hydrolyzed glucomannan has shown potential as an encapsulant due to its ability to form a fine, dense network upon drying. The aim of this study was to evaluate the potential of hydrolyzed glucomannan as a matrix for iron at inlet air temps. of spray-drying of 110°C, 120°C, 130°C and 140°C. The physicochem. properties and performance of the iron encapsulation powder were detd. The results indicated that the inlet air temp. influences the properties and performance of the powder. An increase in the inlet air temp. from 110°C to 140°C led to a greater loading capacity and particle size distribution but had an insignificant impact on the moisture content, soly. and swelling. Higher drying air temps. tended to produce a darker powder. The morphol. anal. revealed that higher inlet drying air temps. produced powders with rounder shapes, whereas lower temps. produced irregular shapes that tended to form deep concavities on the powder surface. The samples from all inlet temps. showed similar functional groups but in different intensities. The release of iron at pH 6.8 was higher for the lower inlet temps. Samples with the highest inlet temp. showed the highest performance in protecting iron from oxidn. Considering the performance, 130°C is recommended as the inlet air temp. for iron spray-drying encapsulation using hydrolyzed glucomannan.
- 136Bryszewska, M. A.; Tomás-Cobos, L.; Gallego, E.; Villalba, M. P.; Rivera, D.; Taneyo Saa, D. L.; Gianotti, A. In Vitro Bioaccessibility and Bioavailability of Iron from Breads Fortified with Microencapsulated Iron. LWT 2019, 99, 431– 437, DOI: 10.1016/j.lwt.2018.09.071[Crossref], [CAS], Google Scholar136https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvV2gsbrJ&md5=4169d32b176ed73ead38d3383aa62f19In vitro bioaccessibility and bioavailability of iron from breads fortified with microencapsulated ironBryszewska, Malgorzata Anita; Tomas-Cobos, Lidia; Gallego, Elisa; Villalba, MariPaz; Rivera, Daniel; Taneyo Saa, Danielle Laure; Gianotti, AndreaLWT--Food Science and Technology (2019), 99 (), 431-437CODEN: LSTWB3; ISSN:0023-6438. (Elsevier Ltd.)Iron deficiency is the most prevalent mineral deficiency in the world. Food fortification offers an alternative to std. oral iron therapy, which often causes unpleasant side effects. In this study, bread was fortified with either ferrous sulfate or ferrous fumarate. To prevent undesired organoleptic changes in color, odor and taste, iron compds. were introduced in the form of microcapsules. Eight types of bread were prepd. using conventional fermn. or sourdough and fortified with one of four types of microcapsule. The in vitro bioaccessibility and bioavailability of the iron were detd. using the human epithelial adenocarcinoma cell line Caco-2, preceded by digestion in a dynamic gastrointestinal digester, which mimics the upper gastrointestinal tract of an adult human. The bioaccessibility of the iron after digestion of the fortified breads varied from 41.45 to 99.31%. The iron transport efficiency varied widely, from 1.16 to 13.78%. Generally, both bioaccessibility and transport efficiency were higher in the samples of breads prepd. by conventional fermn. The mRNA expression of DMT1 and IREG1, cellular iron transporters which serve as mol. markers of iron movement across the intestinal border, was not statistically significant.
- 137Jati Kusuma, R.; Ermamilia, A. Fortification of Tempeh with Encapsulated Iron Improves Iron Status and Gut Microbiota Composition in Iron Deficiency Anemia Condition. Nutr. Food Sci. 2018, 48 (6), 962– 972, DOI: 10.1108/NFS-01-2018-0027
- 138Darwish, A. M. G.; Soliman, T. N.; Elhendy, H. A.; El-Kholy, W. M. Nano-Encapsulated Iron and Folic Acid-Fortified Functional Yogurt Enhance Anemia in Albino Rats. Front. Nutr. 2021, 8, 135, DOI: 10.3389/fnut.2021.654624
- 139Filiponi, M. P.; Gaigher, B.; Caetano-Silva, M. E.; Alvim, I. D.; Pacheco, M. T. B. Microencapsulation Performance of Fe-Peptide Complexes and Stability Monitoring. Food Res. Int. 2019, 125, 108505, DOI: 10.1016/j.foodres.2019.108505[Crossref], [PubMed], [CAS], Google Scholar139https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtlaht7jO&md5=1a0524c56a8a0b0c2d27045f84bb2c40Microencapsulation performance of Fe-peptide complexes and stability monitoringFiliponi, Marilia Pinheiro; Gaigher, Bruna; Caetano-Silva, Maria Elisa; Alvim, Izabela Dutra; Pacheco, Maria Teresa BertoldoFood Research International (2019), 125 (), 108505CODEN: FORIEU; ISSN:0963-9969. (Elsevier B.V.)Iron supplementation presents several challenges, such as low bioavailability, high reactivity and a metallic taste. Iron absorption is enhanced by complexing with org. compds. such as peptides, while microencapsulation is an alternative to protect the mineral and mask undesirable flavors. Fe-peptide complexes were obtained by reacting small whey peptides (< 5 kDa) with iron (from ferrous sulfate) under controlled conditions. Maltodextrin (MD) and polydextrose (PD) were used as the wall materials and spray dried to form particles contg. the active Fe-peptide. The conditions of enzymic hydrolysis with the bacterial endopeptidase produced from Bacillus licheniformis were optimized to achieve a high degree of cleavage (∼20% degree of hydrolysis). The physicochem. and structural properties of the microparticles were evaluated during storage (365 days). The encapsulation process showed high efficiency (84%) and process yield (≥90%). The iron dialyzability and uptake by Caco-2 cells from microparticles were at least 3-fold higher than the ferrous sulfate. The water content and water activity varied from 3.0 to 5.7% and from 0.29 to 0.44, resp., after 365 days. SEM revealed morphol. stability during storage and EDX showed the presence of iron ions at the surface of the microparticles, which could be free or complexed. The microparticles can be an alternative of higher bioavailable iron besides the further protection and iron stability which the microparticles may present when compared with the Fe-peptide complexes. Future studies could demonstrate the feasibility of applying these microparticles in formulation for food supplementation, concerning bioavailability and sensory aspects.
- 140Leiva Arrieta, A. Double (Iron and Zinc) Fortified Black Tea : Assessing the Bioaccessibility and Bioavailability Using Spray Drying Microencapsulation Technology. Cureus 2020, DOI: 10.14288/1.0394846
- 141Bryszewska, M. A. Comparison Study of Iron Bioaccessibility from Dietary Supplements and Microencapsulated Preparations. Nutrients 2019, 11 (2), 273, DOI: 10.3390/nu11020273[Crossref], [CAS], Google Scholar141https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtlKrtrjK&md5=d9832f928a6831f003991f11480579daArticle comparison study of iron bioaccessibility from dietary supplements and microencapsulated preparationsBryszewska, Malgorzata AnitaNutrients (2019), 11 (2), 273CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)Iron deficiency is the most common form of malnutrition. Factors responsible for this so-called "hidden hunger" include poor diet, increased micronutrient needs and health problems such as diseases and infections. Body iron status can be increased by the intake of dietary supplements and fortified food. The aim of the present study was to compare iron bioaccessibility from com. nutritional supplements and iron microcapsules. A comparison study was performed under conditions mimicking gastric and gastrointestinal digestion. A prepn. of encapsulated ferrous sulfate or lactate and vitamin C, in a formula, showed bioaccessibility factors of up to 100% when digested individually, and around 60% in the presence of a food matrix. The degree of oxidn. of the ferrous ions differed, depending on the type of prepn., the presence of vitamin C and the food matrix. The highest percentage content of ferrous ion, in the sol. fractions after gastrointestinal digestion, was shown by the prepn. contg. microencapsulated ferrous lactate or ferrous sulfate and vitamin C. Encapsulation seems to limit the interaction of iron with the food matrix and protect it against oxidn., thus making it more accessible for intestinal uptake.
- 142Cian, R. E.; Proaño, J. L.; Salgado, P. R.; Mauri, A. N.; Drago, S. R. High Iron Bioaccessibility from Co-Microencapsulated Iron/Ascorbic Acid Using Chelating Polypeptides from Brewers’ Spent Grain Protein as Wall Material. LWT 2021, 139, 110579, DOI: 10.1016/j.lwt.2020.110579[Crossref], [CAS], Google Scholar142https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXisVChtL3P&md5=379827800c221c9cf8c8ec55784bed4dHigh iron bioaccessibility from co-microencapsulated iron/ascorbic acid using chelating polypeptides from brewers 'spent grain protein as wall materialCian, Raul E.; Proano, Janina L.; Salgado, Pablo R.; Mauri, Adriana N.; Drago, Silvina R.LWT--Food Science and Technology (2021), 139 (), 110579CODEN: LSTWB3; ISSN:0023-6438. (Elsevier Ltd.)Iron fortification is an important and difficult task since most of the bioavailable iron sources are reactive against food matrix. Microencapsulation technol. can prevent iron interaction with food matrix. Co-microencapsulation of iron and ascorbic acid was carried out by spray-drying using a protein conc. obtained from brewers 'spent grain (BSG-PC) and locust bean gum as chelating wall materials. Microcapsules were formulated using a 22 factorial design. The effect of BSG-PC/wall material (8.6 and 17.2 g protein 100 g-1) and ascorbic acid/iron molar ratio (0.9:1 and 1.8:1) on iron encapsulation yield (FeE), ascorbic acid encapsulation (AAE), iron chelated by wall material (FeC), iron bioaccessibility (FeB), particle size, zeta potential, and surface hydrophobicity of the microcapsules were assessed. Higher level of BSG-PC increased FeB at low ascorbic acid/iron molar ratio due to the high iron-chelating activity of BSG proteins (IC50: 7.9 ±1.2 mg mL-1). At low levels of BSG-PC, FeB was promoted by ascorbic acid in a dose response way. A multiple response maximization of FeE, AAE, FeB, and FeC was performed and validated. Optimal microcapsule formula resulted with 29% of FeB after simulated gastrointestinal digestion. The optimization procedure allowed obtaining a fortifier with the higher iron bioaccessibility and iron content.
- 143Biniwale, P.; Pal, B.; Sundari, T.; Mandrupkar, G.; Datar, N.; Khurana, A. S.; Qamra, A.; Motlekar, S.; Jain, R. Liposomal Iron for Iron Deficiency Anemia in Women of Reproductive Age: Review of Current Evidence. Open J. Obstet. Gynecol. 2018, 08 (11), 993– 1005, DOI: 10.4236/ojog.2018.811100[Crossref], [CAS], Google Scholar143https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitVCru7%252FM&md5=e668a24d3f33d9ec8063136be01e228fLiposomal iron for iron deficiency anemia in women of reproductive age: review of current evidenceBiniwale, Parag; Pal, Bhaskar; Sundari, Tripura; Mandrupkar, Gorakh; Datar, Nikhil; Khurana, Amandeep Singh; Qamra, Amit; Motlekar, Salman; Jain, RishiOpen Journal of Obstetrics and Gynecology (2018), 8 (11Spec.Iss.), 993-1005CODEN: OJOGB2; ISSN:2160-8806. (Scientific Research Publishing, Inc.)Iron deficiency anemia is the most frequent nutritional deficiency disorder. Conventionally administered oral iron is assocd. with gastrointestinal intolerance that affects the outcomes and compliance. Liposomal iron is assocd. with increased absorption without causing significant adverse effects. In this review, we have discussed the technol. of liposomal iron prepn., mechanisms of its absorption and clin. evidence on its utility in iron deficiency states in pregnant and non-pregnant women. Based on the available evidence, we compared liposomal iron to conventional oral iron. Encapsulation of micronized iron in liposomes is assocd. with lesser exposure to gastric contents, lesser interaction with food contents, no exposure to different digestive juices, targeted delivery of iron and allows lower doses to be administered in lieu of direct absorption without need for protein carriers. The available evidence suggests that liposomal iron significantly increases Hb, ferritin levels in pregnant women as well as in women with iron deficiency.
- 144Pisani, A.; Riccio, E.; Sabbatini, M.; Andreucci, M.; Del Rio, A.; Visciano, B. Effect of Oral Liposomal Iron versus Intravenous Iron for Treatment of Iron Deficiency Anaemia in CKD Patients: A Randomized Trial. Nephrol Dial Transpl. 2015, 30, 645– 652, DOI: 10.1093/ndt/gfu357[Crossref], [PubMed], [CAS], Google Scholar144https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsF2nt7vM&md5=3f566b1366e3f157246c8f2adb21c514Effect of oral liposomal iron versus intravenous iron for treatment of iron deficiency anemia in CKD patients: a randomized trialPisani, Antonio; Riccio, Eleonora; Sabbatini, Massimo; Andreucci, Michele; Del Rio, Antonio; Visciano, BiancaNephrology, Dialysis, Transplantation (2015), 30 (4), 645-652CODEN: NDTREA; ISSN:0931-0509. (Oxford University Press)Introduction Iron deficiency is a common cause of anemia in non-dialysis chronic kidney disease (ND-CKD). Controversies exist about the optimal route of administration for iron therapy. Liposomal iron, a new generation oral iron with high gastrointestinal absorption and bioavailability and a low incidence of side effects, seems to be a promising new strategy of iron replacement. Therefore, we conducted a study to det. whether liposomal iron, compared with i.v. (IV) iron, improves anemia in ND-CKD patients. Methods In this randomized, open-label trial, 99 patients with CKD (stage 3-5, not on dialysis) and iron deficiency anemia[Hb (Hb) ≤12 g/dL, ferritin ≤100 ng/mL, transferrin satn. ≤25%] were assigned (2:1) to receive oral liposomal iron (30 mg/day, Group OS) or a total dose of 1000 mg of IV iron gluconate (125 mg infused weekly) (Group IV) for 3 mo. The patients were followed-up for the treatment period and 1 mo after drug withdrawal. The primary end point was to evaluate the effects of the two treatments on Hb levels; the iron status, compliance and adverse effects were also evaluated. Results The short-term therapy with IV iron produced a more rapid Hb increase compared with liposomal iron, although the final increase in Hb was similar with either treatment; the difference between the groups was statistically significant at the first month and such difference disappeared at the end of treatment. After iron withdrawal, Hb concns. remained stable in Group IV, while recovered to baseline in the OS group. The replenishment of iron stores was greater in the IV group. The incidence of adverse event was significantly lower in the oral group (P < 0.001), and the adherence was similar in the two groups. Conclusions Our study shows that oral liposomal iron is a safe and efficacious alternative to IV iron gluconate to correct anemia in ND-CKD patients, although its effects on repletion of iron stores and on stability of Hb after drug discontinuation are lower.
- 145Hussain, U.; Zia, K.; Iqbal, R.; Saeed, M.; Ashraf, N. Efficacy of a Novel Food Supplement (Ferfer) Containing Microencapsulated Iron in Liposomal Form in Female Iron Deficiency Anemia. Cureus 2019, DOI: 10.7759/CUREUS.4603
- 146de Alvarenga Antunes, C. V.; de Alvarenga Nascimento, C. R.; Campanha da Rocha Ribeiro, T.; de Alvarenga Antunes, P.; de Andrade Chebli, L.; Martins Gonçalves Fava, L.; Malaguti, C.; Maria Fonseca Chebli, J. Treatment of Iron Deficiency Anemia with Liposomal Iron in Inflammatory Bowel Disease: Efficacy and Impact on Quality of Life. Int. J. Clin. Pharm. 2020 423 2020, 42 (3), 895– 902, DOI: 10.1007/s11096-020-01044-x
- 147Prichapan, N.; Klinkesorn, U. Factor Affecting the Properties of Water-in-Oil-in-Water Emulsions for Encapsulation of Minerals and Vitamins. Songklanakarin J. Sci. Technol. 2014, 36 (6).Google ScholarThere is no corresponding record for this reference.
- 148Chang, Y. H.; Lee, S. Y.; Kwak, H.-S. Physicochemical and Sensory Properties of Milk Fortified with Iron Microcapsules Prepared with Water-in-Oil-in-Water Emulsion during Storage. Int. J. Dairy Technol. 2016, 69 (3), 452– 459, DOI: 10.1111/1471-0307.12282[Crossref], [CAS], Google Scholar148https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtVyitLfI&md5=f529a18e95c964e45230056ab98bd84fPhysicochemical and sensory properties of milk fortified with iron microcapsules prepared with water-in-oil-in-water emulsion during storageChang, Yoon Hyuk; Lee, Sun Young; Kwak, Hae-SooInternational Journal of Dairy Technology (2016), 69 (3), 452-459CODEN: IJDTFQ; ISSN:1364-727X. (Wiley-Blackwell)This study investigated the possibility of fortifying iron microcapsule powder into milk and the effects of the fortification on the physicochem. and sensory properties of the products during storage. The iron microcapsules were prepd. by the water-in-oil-in-water (W/O/W) emulsion technique. Fortifying the lower concns. (0.1-0.3%, w/v) of iron microcapsules into the milk samples did not significantly change thiobarbituric acid values. The L-values for the milk samples were not significantly influenced by fortifying iron microcapsules (0.1-0.7%, w/v). The overall acceptability scores were not affected when the lowest concn. of iron microcapsules (0.1%, w/v) was fortified into the milk.
- 149Hosseini, S. M. H.; Hashemi Gahruie, H.; Razmjooie, M.; Sepeidnameh, M.; Rastehmanfard, M.; Tatar, M.; Naghibalhossaini, F.; Van der Meeren, P. Effects of Novel and Conventional Thermal Treatments on the Physicochemical Properties of Iron-Loaded Double Emulsions. Food Chem. 2019, 270, 70– 77, DOI: 10.1016/j.foodchem.2018.07.044[Crossref], [PubMed], [CAS], Google Scholar149https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtlalsLrN&md5=399fd29c5f5f1a9f2054d9d04625caa3Effects of novel and conventional thermal treatments on the physicochemical properties of iron-loaded double emulsionsHosseini, Seyed Mohammad Hashem; Hashemi Gahruie, Hadi; Razmjooie, Maryam; Sepeidnameh, Marziyeh; Rastehmanfard, Mahsa; Tatar, Mohsen; Naghibalhossaini, Fakhraddin; Van der Meeren, PaulFood Chemistry (2019), 270 (), 70-77CODEN: FOCHDJ; ISSN:0308-8146. (Elsevier Ltd.)In this work, changes in different physicochem. properties of iron-loaded double emulsions (DEs) were monitored under the influence of novel (microwave and ohmic) and conventional heat treatments. Microwave heating led to destabilization and obvious phase sepn. As compared to control samples, heat treatment increased particle size, light absorbance, centrifugal instability, iron expulsion from the internal aq. phase, color difference, chem. instability of the lipid phase, release of iron in simulated gastrointestinal fluids and iron bioavailability in cell line SW742. Emulsion viscosity and whiteness index decreased after heat treatment, whereas the zeta-potential remained unchanged. There was a neg. correlation between physicochem. stability and heat treatment intensity. Conventional heating resulted in greater stability than ohmic heating. Yoghurt samples (as model systems) were fortified with either iron-loaded or iron-free DEs. Our results showed that the presence of iron in the aq. phase resulted in significant lipid oxidn. during storage.
- 150Wu, W.; Yang, Y.; Sun, N.; Bao, Z.; Lin, S. Food Protein-Derived Iron-Chelating Peptides: The Binding Mode and Promotive Effects of Iron Bioavailability. Food Res. Int. 2020, 131, 108976, DOI: 10.1016/j.foodres.2020.108976[Crossref], [PubMed], [CAS], Google Scholar150https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVOnt70%253D&md5=b6675d2e2e02509542e7857294fd0459Food protein-derived iron-chelating peptides: The binding mode and promotive effects of iron bioavailabilityWu, Wenfei; Yang, Yiying; Sun, Na; Bao, Zhijie; Lin, SongyiFood Research International (2020), 131 (), 108976CODEN: FORIEU; ISSN:0963-9969. (Elsevier B.V.)A review. Iron is known as an essential nutrient in the human body. Insufficient iron uptake is easy to result in iron deficiency anemia, which is a public health problem in both developing and developed countries. Iron, complexed by iron-chelating peptides, have been proposed as a superior candidate to ionized iron for improving iron absorption and bioavailability. Nowadays, as more and more iron-chelating peptides are identified from different food sources, the iron-peptide binding mode attracts much attention. Meanwhile, many studies have been conducted on the iron-chelating peptides to make clear their iron bioavailability enhancement potential. The aim of this review is to provide an overview of research progress in food protein-derived iron-chelating peptides. The review would be of particular value for iron-peptide complexes as functional ingredients or iron supplements.
- 151Mattar, G.; Haddarah, A.; Haddad, J.; Pujola, M.; Sepulcre, F. New Approaches, Bioavailability and the Use of Chelates as a Promising Method for Food Fortification. Food Chem. 2022, 373, 131394, DOI: 10.1016/j.foodchem.2021.131394[Crossref], [PubMed], [CAS], Google Scholar151https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitlCjtL3J&md5=88562e72173aa064ad671185ce93f2ffNew approaches, bioavailability and the use of chelates as a promising method for food fortificationMattar, Ghadeer; Haddarah, Amira; Haddad, Joseph; Pujola, Montserrat; Sepulcre, FranscescFood Chemistry (2022), 373 (Part_A), 131394CODEN: FOCHDJ; ISSN:0308-8146. (Elsevier Ltd.)A review. Food fortification has been used for many years to combat micronutrient deficiencies; the main challenge with food fortification is the combination of a bioavailable, affordable fortificant with the best (food) vehicle as a carrier to reach at-risk populations. This paper considers mineral deficiencies, esp. iron, food fortification, target populations, and the use of chelates in food fortification, as well as different types of mineral-chelate complexes, advantages and limitations of previous trials, methods used for anal. of these complexes, bioavailability of minerals, factors influencing it, and methods particularly those in vitro for predicting outcomes. Three innovative methods (encapsulation, nanoparticulation, and chelation) were explored, which aim to overcome problems assocd. with conventional fortification, esp. those affecting organoleptic properties and bioavailability; but often lead to the emergence of new limitations (for example instability, impracticality and high costs) requiring further research.
- 152Li, B.; He, H.; Shi, W.; Hou, T. Effect of Duck Egg White Peptide-Ferrous Chelate on Iron Bioavailability in Vivo and Structure Characterization. J. Sci. Food Agric. 2019, 99 (4), 1834– 1841, DOI: 10.1002/jsfa.9377[Crossref], [PubMed], [CAS], Google Scholar152https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVCiu7rL&md5=5583cafd78a1a6293209314a56f7821bEffect of duck egg white peptide-ferrous chelate on iron bioavailability in vivo and structure characterizationLi, Bo; He, Hui; Shi, Wen; Hou, TaoJournal of the Science of Food and Agriculture (2019), 99 (4), 1834-1841CODEN: JSFAAE; ISSN:0022-5142. (John Wiley & Sons Ltd.)BACKGROUND : In order to utilize the industrial byproduct 'salted duck egg white' as novel iron additives, the effects of desalted duck egg white peptides-ferrous chelate (DPs-Fe) on the promotion of iron uptake and the structure were investigated. RESULTS : Different doses of DPs-Fe were given and iron sulfate (FeSO4) was used as a pos. control. After three weeks, Hb (Hb), hematocrit (HCT), red blood cells (RBCs), mean corpuscular vol. (MCV), serum iron (SI) and serum ferritin (SF) in iron-deficiency anemia (IDA) rats could be significantly (P < 0.05) increased to the normal levels by DPs-Fe. The gene expressions of divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1) and Hepcidin could be regulated by DPs-Fe. Addnl., DPs-Fe was formed during the chelation process and the structure was characterized. Eight crucial iron-chelating peptides of duck egg white peptides (DPs) were identified by HPLC-ESI-MS/MS, such as Pro-Val-Glu-Glu and Arg-Ser-Ser. It indicated that Glu, Asp, Lys, His, Ser, Cys residues might play crucial roles in the chelating of DPs with iron. CONCLUSION : DPs-Fe could be a potential iron supplement, and the Glu, Asp, Lys, His played important roles in binding iron and promoting iron uptake. This research expands the understanding of iron uptake by DPs and provides an opportunity for recycling a discarded processing byproduct. © 2018 Society of Chem. Industry.
- 153Sabatier, M.; Rytz, A.; Husny, J.; Dubascoux, S.; Nicolas, M.; Dave, A.; Singh, H.; Bodis, M.; Glahn, R. P. Impact of Ascorbic Acid on the In Vitro Iron Bioavailability of a Casein-Based Iron Fortificant. Nutrients 2020, 12 (9), 2776, DOI: 10.3390/nu12092776[Crossref], [CAS], Google Scholar153https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitFWltL%252FF&md5=e388291d6b0d555373cadf50045377d9Impact of ascorbic acid on the in vitro iron bioavailability of a casein-based iron fortificantSabatier, Magalie; Rytz, Andreas; Husny, Joeska; Dubascoux, Stephane; Nicolas, Marine; Dave, Anant; Singh, Harjinder; Bodis, Mary; Glahn, Raymond P.Nutrients (2020), 12 (9), 2776CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)A new iron-casein complex (ICC) has been developed for iron (Fe) fortification of dairy matrixes. The objective was to assess the impact of ascorbic acid (AA) on its in vitro bioavailability in comparison with ferrous sulfate (FeSO4) and ferric pyrophosphate (FePP). A simulated digestion coupled with the Caco-2 cell culture model was used in parallel with soly. and dissocn. tests. Under dild. acidic conditions, the ICC was as sol. as FeSO4, but only part of the iron was found to dissoc. from the caseins, indicating that the ICC was an iron chelate. The Caco-2 cell results in milk showed that the addn. of AA (2:1 molar ratio) enhanced iron uptake from the ICCs and FeSO4 to a similar level (p = 0.582; p = 0.852) and to a significantly higher level than that from FePP (p < 0.01). This translated into a relative in vitro bioavailability to FeSO4 of 36% for FePP and 114 and 104% for the two ICCs. Similar results were obtained from water. Increasing the AA to iron molar ratio (4:1 molar ratio) had no addnl. effect on the ICCs and FePP. However, ICC absorption remained similar to that from FeSO4 (p = 0.666; p = 0.113), and was still significantly higher than that from FePP (p < 0.003). Therefore, even though iron from ICC does not fully dissoc. under gastric digestion, iron uptake suggested that ICCs are absorbed to a similar amt. as FeSO4 in the presence of AA and thus provide an excellent source of iron.
- 154Xiao, C.; Lei, X.; Wang, Q.; Du, Z.; Jiang, L.; Chen, S.; Zhang, M.; Zhang, H.; Ren, F. Effects of a Tripeptide Iron on Iron-Deficiency Anemia in Rats. Biol. Trace Elem. Res. 2016, 169 (2), 211– 217, DOI: 10.1007/s12011-015-0412-6[Crossref], [PubMed], [CAS], Google Scholar154https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtVygu7jO&md5=0f6099675ea5a0c2711c78364b2920caEffects of a Tripeptide Iron on Iron-Deficiency Anemia in RatsXiao, Chen; Lei, Xingen; Wang, Qingyu; Du, Zhongyao; Jiang, Lu; Chen, Silu; Zhang, Mingjie; Zhang, Hao; Ren, FazhengBiological Trace Element Research (2016), 169 (2), 211-217CODEN: BTERDG; ISSN:0163-4984. (Springer)This study aims to investigate the effects of a tripeptide iron (REE-Fe) on iron-deficiency anemia rats. Sprague-Dawley rats were randomly divided into seven groups: a normal control group, an iron-deficiency control group, and iron-deficiency groups treated with ferrous sulfate (FeSO4), ferrous glycinate (Fe-Gly), or REE-Fe at low-, medium-, or high-dose groups. The rats in the iron-deficiency groups were fed on an iron-deficient diet to establish iron-deficiency anemia (IDA) model. After the model established, different iron supplements were given to the rats once a day by intragastric administration for 21 days. The results showed that REE-Fe had effective restorative action returning body wt., organ coeffs., and hematol. parameters in IDA rats to normal level. In addn., comparing with FeSO4 or Fe-Gly, high-dose REE-Fe was more effective on improving the levels of renal coeff., total iron-binding capacity, and transferrin. Furthermore, the liver hepcidin mRNA (mRNA) expression in the high-dose group was significantly higher (p < 0.05) than that in the FeSO4 or Fe-Gly group and showed no significant difference (p > 0.05) with the normal control group. The findings suggest that REE-Fe is an effective source of iron supplement for IDA rats and might be exploited as a new iron fortifier.
- 155Tang, N.; Chen, L. Q.; Zhuang, H. Effects of Heme Iron Enriched Peptide on Iron Deficiency Anemia in Rats. Food Funct. 2014, 5 (2), 390– 399, DOI: 10.1039/C3FO60292C[Crossref], [PubMed], [CAS], Google Scholar155https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsF2rtro%253D&md5=33a0de11ed38dc65678521e9f02842f9Effects of heme iron enriched peptide on iron deficiency anemia in ratsTang, Ning; Chen, Le-qun; Zhuang, HongFood & Function (2014), 5 (2), 390-399CODEN: FFOUAI; ISSN:2042-6496. (Royal Society of Chemistry)The present study aims to investigate whether a daily intake of heme iron enriched peptide obtained from bovine Hb is effective in alleviating iron deficiency anemia (IDA). Wistar rats were randomly divided into six groups: a control group, an anemic group not treated, and anemic groups treated with FeSO4 or with the heme iron enriched peptide at low, moderate or high doses. The rats in the anemic groups were fed on a low-iron diet to establish the iron deficiency anemia model. After the model had been established, different doses of heme iron enriched peptide were given to the rats once a day via intragastric administration. After the iron supplement administration, it was obsd. that heme iron enriched peptide had effective restorative action returning the Hb, red blood cells, hematocrit, mean corpuscular vol., mean corpuscular Hb concn. and serum iron in IDA animals to normal values or better. In addn., compared with FeSO4, higher Fe bioavailability and fewer side effects were obsd. The rats in the moderate dose group had the highest apparent Fe absorption. Moreover, in vivo antioxidant activity was also obsd., enhancing the activities of antioxidant enzymes and reduced malondialdehyde levels in IDA rats. Furthermore, the heme iron enriched peptide also exhibited strong in vitro antioxidant activities. In conclusion, heme iron enriched peptide significantly alleviated iron deficiency anemia, and exhibited strong in vitro and in vivo antioxidant activities. This suggests that heme iron enriched peptide might be exploited as a safe, efficient new iron supplement.
- 156Caetano-Silva, M. E.; Netto, F. M.; Bertoldo-Pacheco, M. T.; Alegría, A.; Cilla, A. Peptide-Metal Complexes: Obtention and Role in Increasing Bioavailability and Decreasing the pro-Oxidant Effect of Minerals. Crit. Rev. Food Sci. Nutr. 2021, 61 (9), 1470– 1489, DOI: 10.1080/10408398.2020.1761770[Crossref], [PubMed], [CAS], Google Scholar156https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVShur3P&md5=4a181b156e98743abfa8e8709d365bb6Peptide-metal complexes: obtention and role in increasing bioavailability and decreasing the pro-oxidant effect of mineralsCaetano-Silva, Maria Elisa; Netto, Flavia Maria; Bertoldo-Pacheco, Maria Teresa; Alegria, Amparo; Cilla, AntonioCritical Reviews in Food Science and Nutrition (2021), 61 (9), 1470-1489CODEN: CRFND6; ISSN:1040-8398. (Taylor & Francis, Inc.)A review. Bioactive peptides derived from food protein sources have been widely studied in the last years, and scientific researchers have been proving their role in human health, beyond their nutritional value. Several bioactivities have been attributed to these peptides, such as immunomodulatory, antimicrobial, antioxidant, antihypertensive, and opioid. Among them, metal-binding capacity has gained prominence. Mineral chelating peptides have shown potential to be applied in food products so as to decrease mineral deficiencies since peptide-metal complexes could enhance their bioavailability. Furthermore, many studies have been investigating their potential to decrease the Fe pro-oxidant effect by forming a stable structure with the metal and avoiding its interaction with other food constituents. These complexes can be formed during gastrointestinal digestion or can be synthesized prior to intake, with the aim to protect the mineral through the gastrointestinal tract. This review addresses: (i) the amino acid residues for metal-binding peptides and their main protein sources, (ii) peptide-metal complexation prior to or during gastrointestinal digestion, (iii) the function of metal (esp. Fe, Ca, and Zn)-binding peptides on the metal bioavailability and (iv) their reactivity and possible pro-oxidant and side effects.
- 157Evcan, E.; Gulec, S. The Development of Lentil Derived Protein-Iron Complexes and Their Effects on Iron Deficiency Anemia in Vitro. Food Funct. 2020, 11 (5), 4185– 4192, DOI: 10.1039/D0FO00384K[Crossref], [PubMed], [CAS], Google Scholar157https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmsFOqu7o%253D&md5=80d9a8a81ff213a5ec6976a8c4844588The development of lentil derived protein-iron complexes and their effects on iron deficiency anemia in vitroEvcan, Ezgi; Gulec, SukruFood & Function (2020), 11 (5), 4185-4192CODEN: FFOUAI; ISSN:2042-6496. (Royal Society of Chemistry)Iron deficiency anemia (IDA) is the most common nutrient-dependent health problem in the world and could be reversed by com. available iron supplementation. The form of iron supplement is important due to its toxicity on the gastrointestinal system (GI), so the development of new dietary strategies might be important for the prevention of IDA. It has been shown that plant-based proteins bind to iron and might decrease the free form of iron before absorption and increase iron bioavailability. Thus, we aimed to form lentil derived protein-iron complexes and to test the functional properties of hydrolyzed protein-iron complexes in anemic Caco-2 cell line. Our main findings were that (i) lentil derived proteins had the capacity to chelate iron minerals and (ii) hydrolyzed protein-iron complexes significantly reduced the mRNA levels of iron regulated divalent metal transporter-1 (DMT1), transferrin receptor (TFR), and ankyrin repeat domain 37 (ANKRD37) marker genes that were induced by iron deficiency anemia. The current findings suggest that hydrolyzed protein-iron complexes might have functional properties in iron deficiency anemia in vitro. Further in vivo studies are necessary to show lentil derived proteins and iron might be used as supplements or food additives to reduce the risk of iron deficiency anemia.
- 158Gómez, L. J.; Gómez, N. A.; Zapata, J. E.; López-Garciá, G.; Cilla, A.; Alegriá, A. Optimization of the Red Tilapia (Oreochromis Spp.) Viscera Hydrolysis for Obtaining Iron-Binding Peptides and Evaluation of In Vitro Iron Bioavailability. Foods 2020, 9 (7), 883, DOI: 10.3390/foods9070883[Crossref], [CAS], Google Scholar158https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXisFarsrrI&md5=894c9f3cf3493b50112d24b609b2d73cOptimization of the red tilapia (Oreochromis spp.) viscera hydrolysis for obtaining iron-binding peptides and evaluation of in vitro iron bioavailabilityGomez, Leidy J.; Gomez, Nathalia A.; Zapata, Jose E.; Lopez-Garcia, Gabriel; Cilla, Antonio; Alegria, AmparoFoods (2020), 9 (7), 883CODEN: FOODBV; ISSN:2304-8158. (MDPI AG)Iron deficiencies continue to cause significant health problems in vulnerable populations. A good strategy to combat mineral deficiency includes fortification with iron-binding peptides. This research aims to det. the optimal conditions to hydrolyze red tilapia viscera (RTV) using Alcalase 2.4 L and recovery of iron-binding protein hydrolyzate. The result showed that under the optimal hydrolysis condition including pH 10, 60 °C, E/S ratio of 0.306 U/g protein, and substrate concn. of 8 g protein/L, the obtained hydrolyzate with 42.5% degree of hydrolysis (RTVH-B), displayed the maximal iron-binding capacity of 67.1 - 1.9%. Peptide fractionation was performed using ultrafiltration and the <1 kDa fraction (FRTVH-V) expressed the highest iron-binding capacity of 95.8 - 1.5%. Iron content of RTVH-B and its fraction was assessed, whereas iron uptake was measured indirectly as ferritin synthesis in a Caco-2 cell model and the result showed that bioavailability of bound minerals from protein complexes was significantly higher (p < 0.05) than iron salt in its free form, increased 4.7 times for the Fe2+-RTVH-B complex. This research suggests a potential application of RTVH-B as dietary supplements to improve iron absorption.
- 159Caetano-Silva, M. E.; Cilla, A.; Bertoldo-Pacheco, M. T.; Netto, F. M.; Alegría, A. Evaluation of in Vitro Iron Bioavailability in Free Form and as Whey Peptide-Iron Complexes. J. Food Compos. Anal. 2018, 68, 95– 100, DOI: 10.1016/j.jfca.2017.03.010[Crossref], [CAS], Google Scholar159https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXlvVGgs7s%253D&md5=e45d149bcf2dd2ec57993dca9f4e464eEvaluation of in vitro iron bioavailability in free form and as whey peptide-iron complexesCaetano-Silva, Maria Elisa; Cilla, Antonio; Bertoldo-Pacheco, Maria Teresa; Netto, Flavia Maria; Alegria, AmparoJournal of Food Composition and Analysis (2018), 68 (), 95-100CODEN: JFCAEE; ISSN:0889-1575. (Elsevier Inc.)Finding alternatives for food fortification in a bioavailable form of iron is needed because iron deficiency leads to several diseases. Iron soly. and in vitro iron absorption were evaluated in free and complexed forms, as iron salts or peptide-iron complexes. Whey peptide-iron complexes were synthesized with various ligands (whey protein hydrolyzate; its fractions >5 kDa and <5 kDa, obtained by ultrafiltration/diafiltration using a 5-kDa cut-off membrane; and whey protein isolate) and iron sources (FeCl2 and FeSO4). Iron bioaccessibility was assessed after in vitro gastrointestinal digestion, whereas iron uptake was measured indirectly as ferritin synthesis in a Caco-2 cell model. Although all complexes showed high bioaccessibility (>85%), only complexes that were synthesized with low-mol.-mass peptides (<5 kDa) and FeCl2 increased iron uptake by approx. 70% compared with FeSO4, one of the most widely used salts for fortification. Thus, this complex is an alternative for food fortification that deserves further research.
- 160Shilpashree, B. G.; Arora, S.; Kapila, S.; Sharma, V. Whey Protein-Iron or Zinc Complexation Decreases pro-Oxidant Activity of Iron and Increases Iron and Zinc Bioavailability. LWT 2020, 126, 109287, DOI: 10.1016/j.lwt.2020.109287[Crossref], [CAS], Google Scholar160https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlslKrsLs%253D&md5=3e554da61aba010af9aac15617947156Whey protein-iron or zinc complexation decreases pro-oxidant activity of iron and increases iron and zinc bioavailabilityShilpashree, B. G.; Arora, Sumit; Kapila, Suman; Sharma, VivekLWT--Food Science and Technology (2020), 126 (), 109287CODEN: LSTWB3; ISSN:0023-6438. (Elsevier Ltd.)Iron and zinc are involved in various functions and their deficiency may lead to several health issues. Fortification of these micronutrients in food is considered as the most effective approach to control deficiencies. Due to high reactivity, iron fortification involves various challenges with respect to oxidative stability and bioaccessibility. Whey protein (WP) serve as an inexpensive protein source and thus have been used in the prepn. of protein-mineral (iron or zinc) complexes. In the present study, WP-mineral complexes were prepd. and evaluated for their oxidative stability and bioavailability. Thiobarbituric acid value and induction period were measured as index for oxidative stability of lipids in linoleic acid emulsions. The pro-oxidant activity of iron when used as WP-iron complex was significantly reduced (P < 0.05) as compared to iron salt. In-vitro bioaccessibility studies revealed that bound proteins provided favorable conditions (i.e. insol. at gastric and sol. at intestinal phase) to minerals. Moreover, the bioavailability of bound minerals in Caco-2 cells was significantly higher as compared to free minerals due the presence of digested whey proteins. Finally, catalytic activity of iron can be inhibited by complexation with WP and both WP-iron or zinc complexes could be used as org. fortificants in different food formulations.
- 161Gandhi, K.; Devi, S.; Gautam, P. B.; Sharma, R.; Mann, B.; Ranvir, S.; Sao, K.; Pandey, V. Enhanced Bioavailability of Iron from Spray Dried Whey Protein Concentrate-Iron (WPC-Fe) Complex in Anaemic and Weaning Conditions. J. Funct. Foods 2019, 58, 275– 281, DOI: 10.1016/j.jff.2019.05.008[Crossref], [CAS], Google Scholar161https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXpsFWrt7Y%253D&md5=2edb7e9793c5fb9bc811ad4694df8d67Enhanced bioavailability of iron from spray dried whey protein concentrate-iron (WPC-Fe) complex in anaemic and weaning conditionsGandhi, Kamal; Devi, Savita; Gautam, Priyae Brath; Sharma, Rajan; Mann, Bimlesh; Ranvir, Suvartan; Sao, Khushbu; Pandey, VanitaJournal of Functional Foods (2019), 58 (), 275-281CODEN: JFFOAX; ISSN:1756-4646. (Elsevier Ltd.)The lower bioavailability of iron from the diet has led to iron deficiency and several ill-effects on health. The objective of this study was to assess the bioavailability of iron from spray dried whey protein conc.-iron (WPC-Fe) complex in weaning and anemic rats. Blood Hb level, bioavailability, lipid profile, antioxidant status and concn. of iron delivery mols. were analyzed under in vivo conditions. Hb level, % apparent digestibility coeff. and % retention/intake were increased in weaning and anemic rats on 7th and 28th days. Addnl., WPC-Fe supplementation reduced nitric oxide (NO) prodn., maintained serum triglycerides, total cholesterol, LDL, VLDL and HDL-cholesterol. Simultaneously, it decreased the superoxide level and lipid peroxidn. and increased the catalase activity. The level of iron delivery/transport mols. including liver and serum ferritin and transferrin concn. was enhanced. Thus, WPC-Fe complex could be a better and innovative org. iron fortificant with enhanced bioavailability of iron.
- 162Shilpashree, B. G.; Arora, S.; Kapila, S.; Sharma, V. Physicochemical Characterization of Mineral (Iron/Zinc) Bound Caseinate and Their Mineral Uptake in Caco-2 Cells. Food Chem. 2018, 257, 101– 111, DOI: 10.1016/j.foodchem.2018.02.157[Crossref], [PubMed], [CAS], Google Scholar162https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXktFahu7k%253D&md5=05b3447b5cee41e0572898037ad48d59Physicochemical characterization of mineral (iron/zinc) bound caseinate and their mineral uptake in Caco-2 cellsShilpashree, B. G.; Arora, Sumit; Kapila, Suman; Sharma, VivekFood Chemistry (2018), 257 (), 101-111CODEN: FOCHDJ; ISSN:0308-8146. (Elsevier Ltd.)Milk proteins (esp. caseins) are widely accepted as good vehicle for the delivery of various bioactive compds. including minerals. Succinylation is one of the most acceptable chem. modification techniques to enhance the mineral binding ability of caseins. Addn. of minerals to succinylated proteins may alter their physicochem. and biochem. properties. Physicochem. characteristics of succinylated sodium caseinate (S.NaCN)-mineral (iron/zinc) complexes were elucidated. Chromatog. behavior and fluorescence intensity confirmed the structural modification of S.NaCN upon binding with minerals. The bound mineral from protein complexes showed significantly higher (P < 0.05) in vitro bioavailability (mineral uptake) than mineral salts in Caco-2 cells. Also, iron bound S.NaCN showed higher cellular ferritin formation than iron in its free form. These mineral bound protein complexes with improved bioavailability could safely replace inorg. fortificants in various functional food formulations.
- 163Sharma, A.; Shilpa Shree, B. G.; Arora, S.; Kapila, S. Preparation of Lactose-Iron Complex and Its Cyto-Toxicity, in-Vitro Digestion and Bioaccessibility in Caco-2 Cell Model System. Food Biosci. 2017, 20, 125– 130, DOI: 10.1016/j.fbio.2017.10.001[Crossref], [CAS], Google Scholar163https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXivFGntLg%253D&md5=6951c86252c8044f7ea453d429beab68Preparation of lactose-iron complex and its cyto-toxicity, in-vitro digestion and bioaccessibility in Caco-2 cell model systemSharma, Apurva; Shilpa Shree, B. G.; Arora, Sumit; Kapila, SumanFood Bioscience (2017), 20 (), 125-130CODEN: FBOICO; ISSN:2212-4306. (Elsevier Ltd.)Iron deficiency disorder continues to be a severe public health concern. Presently, several iron supplements are available; however, they are generally assocd. with higher oxidn. and lower bioavailability. Iron forms a very stable and sol. complex with lactose. Therefore, the aim of the present work was to develop a lactose-iron complex with better oxidative stability, bioavailability and lower cytotoxicity. Oxidative stability of complex in linoleic acid emulsion was evaluated by TBA value and induction period. Iron bioavailability from the complex was estd. in Caco-2 cell model system. The impact of complex on cell viability was assessed using tetrazolium based colorimetric assay. It was obsd. in the present study that the ability of iron to catalyze the oxidn. of lipids reduced in the form of lactose-iron complex as compared to the free form of iron. The complex also showed significantly higher (p<0.05) iron bioavailability than free iron salt. Higher mineral uptake and higher cellular ferritin formation were obsd. from lactose-iron complex in Caco-2 cells. It also showed lower toxicity than ferrous sulfate on Caco-2 cells. Hence, it could be safely concluded that lactose-iron complex could be an innovative iron fortificant with better oxidative stability and bioavailability for use in functional dairy foods in order to combat iron deficiency disorders.
- 164Kumari, A.; Anil, A.; Chauhan, K.; Chauhan, A. K. Iron Nanoparticles as a Promising Compound for Food Fortification in Iron Deficiency Anemia: A Review. J. Food Sci. Technol. 2021, 1– 17, DOI: 10.1007/s13197-021-05184-4[Crossref], [PubMed], [CAS], Google Scholar164https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2c3nsVSqug%253D%253D&md5=a9e77bdd648e51040edb589fedfeded5Iron nanoparticles as a promising compound for food fortification in iron deficiency anemia: a reviewKumari Aparna; Chauhan Anil KumarJournal of food science and technology (2021), (), 1-17 ISSN:0022-1155.ABSTRACT: Iron deficiency anemia (IDA) is a global health concern that is affecting all age groups significantly. Among many of the existing methods, the fortification of foods with iron salts is the best and most cost-effective strategy for targeting large-scale populations to provide nutritional security. The fortification of foods with iron salts is a challenging task because most iron complexes (ferrous sulfate, ferrous chloride) used in fortification are highly water-soluble, which impart unacceptable organoleptic changes in food vehicles and also causes gastrointestinal problems. However, insoluble iron salts (ferric pyrophosphate) do not cause unacceptable taste or color in food vehicles but low bioavailable. Nanosized iron salts can overcome these concerns. The particle size of iron salts has been reported to play an important role in the absorption of iron. Reduction in the particle size of iron compounds increases its surface area, which in turn improves its solubility in the gastric juice leading to higher absorption. Nanosized iron compound produces minimal organoleptic changes in food vehicles compared to water-soluble iron complexes. Thus nanosized iron salts find potential applications in food fortification to reduce IDA. This paper focuses on providing a complete review of the various iron salts used in IDA, including their bioavailability, the challenges to food fortification, the effects of nanosized iron salts on IDA, and their applications in food fortification. GRAPHIC ABSTRACT: Fortification of foods with water-soluble Fe salts imparts unacceptable organoleptic changes in food vehicle and adverse impact on health. However, insoluble iron salts do not cause unacceptable taste or color in food vehicles but low bioavailable. Using Nano-sized iron compound produces minimal organoleptic changes in food vehicles compared to changes produced by water-soluble iron complexes, improves Fe absorption in the gastrointestinal tract and does not cause any health issues.
- 165Shafie, E. H.; Keshavarz, S. A.; Kefayati, M. E.; Taheri, F.; Sarbakhsh, P.; Vafa, M. R. The Effects of Nanoparticles Containing Iron on Blood and Inflammatory Markers in Comparison to Ferrous Sulfate in Anemic Rats. Int. J. Prev. Med. 2016, DOI: 10.4103/2008-7802.193092
- 166Foujdar, R.; Chopra, H. K.; Bera, M. B.; Chauhan, A. K.; Mahajan, P. Effect of Probe Ultrasonication, Microwave and Sunlight on Biosynthesis, Bioactivity and Structural Morphology of Punica Granatum Peel’s Polyphenols-Based Silver Nanoconjugates. Waste Biomass Valorization 2020 125 2021, 12 (5), 2283– 2302, DOI: 10.1007/s12649-020-01175-2
- 167Mattar, G.; Haddarah, A.; Haddad, J.; Pujola, M.; Sepulcre, F. New Approaches, Bioavailability and the Use of Chelates as a Promising Method for Food Fortification. Food Chem. 2022, 373, 131394, DOI: 10.1016/j.foodchem.2021.131394[Crossref], [PubMed], [CAS], Google Scholar167https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitlCjtL3J&md5=88562e72173aa064ad671185ce93f2ffNew approaches, bioavailability and the use of chelates as a promising method for food fortificationMattar, Ghadeer; Haddarah, Amira; Haddad, Joseph; Pujola, Montserrat; Sepulcre, FranscescFood Chemistry (2022), 373 (Part_A), 131394CODEN: FOCHDJ; ISSN:0308-8146. (Elsevier Ltd.)A review. Food fortification has been used for many years to combat micronutrient deficiencies; the main challenge with food fortification is the combination of a bioavailable, affordable fortificant with the best (food) vehicle as a carrier to reach at-risk populations. This paper considers mineral deficiencies, esp. iron, food fortification, target populations, and the use of chelates in food fortification, as well as different types of mineral-chelate complexes, advantages and limitations of previous trials, methods used for anal. of these complexes, bioavailability of minerals, factors influencing it, and methods particularly those in vitro for predicting outcomes. Three innovative methods (encapsulation, nanoparticulation, and chelation) were explored, which aim to overcome problems assocd. with conventional fortification, esp. those affecting organoleptic properties and bioavailability; but often lead to the emergence of new limitations (for example instability, impracticality and high costs) requiring further research.
- 168Li, S.; Guo, T.; Guo, W.; Cui, X.; Zeng, M.; Wu, H. Polyphosphates as an Effective Vehicle for Delivery of Bioavailable Nanoparticulate Iron(III). Food Chem. 2022, 373, 131477, DOI: 10.1016/j.foodchem.2021.131477[Crossref], [PubMed], [CAS], Google Scholar168https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXisVSrt7nO&md5=52c2e90bbc1899113a741e08b8c6011ePolyphosphates as an effective vehicle for delivery of bioavailable nanoparticulate iron(III)Li, Shiyang; Guo, Tengjiao; Guo, Wei; Cui, Xuan; Zeng, Mingyong; Wu, HaohaoFood Chemistry (2022), 373 (Part_B), 131477CODEN: FOCHDJ; ISSN:0308-8146. (Elsevier Ltd.)Polyphosphates are widely used food additives with the potential to increase iron bioavailability but chem. nature of their sol. complexes with iron remains largely unknown. Here, pyrophosphate, tripolyphosphate, hexametaphosphate and ∼25-chain-length polyphosphate solubilized 896, 896, 1120 and 1344 mg Fe(III) per g, resp., at neutral pH by mediating the formation of highly-neg.-charged ferric hydroxide-polyphosphate nanoparticles (PolyP-FeONPs). PolyP-FeONPs displayed fading yellow color with increasing initial dissolved P/Fe ratio ((P/Fe)init) and decreasing polyphosphate length due to rising proportion of Fe(III)-phosphate bonds, and specifically, pyrophosphate resulted colorless PolyP-FeONPs at (P/Fe)init ≥ 4. PolyP-FeONPs had weak pro-oxidant activity in glyceryl trilinoleate emulsion and good colloidal stability under spray/freeze-drying and gastrointestinal conditions. Serum iron kinetics in rats revealed sustained iron release and ∼170% iron bioavailability of oral PolyP-FeONPs relative to FeSO4. Calcein-fluorescence-quenching assay in polarized Caco-2 cells unveiled divalent-metal-transporter-1-independent and macropinocytosis-dependent iron uptake from PolyP-FeONPs. This study helps develop food-compatible, highly-bioavailable and sustained-release iron prepns.
- 169El-Saadony, M. T.; Sitohy, M. Z.; Ramadan, M. F.; Saad, A. M. Green Nanotechnology for Preserving and Enriching Yogurt with Biologically Available Iron (II). Innov. Food Sci. Emerg. Technol. 2021, 69, 102645, DOI: 10.1016/j.ifset.2021.102645
- 170Shen, Y.; Posavec, L.; Bolisetty, S.; Hilty, F. M.; Nyström, G.; Kohlbrecher, J.; Hilbe, M.; Rossi, A.; Baumgartner, J.; Zimmermann, M. B.; Mezzenga, R. Amyloid Fibril Systems Reduce, Stabilize and Deliver Bioavailable Nanosized Iron. Nat. Nanotechnol. 2017, 12 (7), 642– 647, DOI: 10.1038/nnano.2017.58[Crossref], [PubMed], [CAS], Google Scholar170https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmvVCmtrw%253D&md5=0330060acd7331ee4b51b39423f67a88Amyloid fibril systems reduce, stabilize and deliver bioavailable nanosized ironShen, Yi; Posavec, Lidija; Bolisetty, Sreenath; Hilty, Florentine M.; Nystrom, Gustav; Kohlbrecher, Joachim; Hilbe, Monika; Rossi, Antonella; Baumgartner, Jeannine; Zimmermann, Michael B.; Mezzenga, RaffaeleNature Nanotechnology (2017), 12 (7), 642-647CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)Iron-deficiency anemia (IDA) is a major global public health problem. A sustainable and cost-effective strategy to reduce IDA is iron fortification of foods, but the most bioavailable fortificants cause adverse organoleptic changes in foods. Iron nanoparticles are a promising soln. in food matrixes, although their tendency to oxidize and rapidly aggregate in soln. severely limits their use in fortification. Amyloid fibrils are protein aggregates initially known for their assocn. with neurodegenerative disorders, but recently described in the context of biol. functions in living organisms and emerging as unique biomaterial building blocks. Here, we show an original application for these protein fibrils as efficient carriers for iron fortification. We use biodegradable amyloid fibrils from β-lactoglobulin, an inexpensive milk protein with natural reducing effects, as anti-oxidizing nanocarriers and colloidal stabilizers for iron nanoparticles. The resulting hybrid material forms a stable protein-iron colloidal dispersion that undergoes rapid dissoln. and releases iron ions during acidic and enzymic in vitro digestion. Importantly, this hybrid shows high in vivo iron bioavailability, equiv. to ferrous sulfate in Hb-repletion and stable-isotope studies in rats, but with reduced organoleptic changes in foods. Feeding the rats with these hybrid materials did not result in abnormal iron accumulation in any organs, or changes in whole blood glutathione concns., inferring their primary safety. Therefore, these iron-amyloid fibril hybrids emerge as novel, highly effective delivery systems for iron in both solid and liq. matrixes.
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Abstract
Figure 1
Figure 1. Iron deficiency anemia causes and symptoms.
Figure 2
Figure 2. Main enhancers and inhibitors of iron bioavailability.
References
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- 5Roughead, Z. K.; Zito, C. A.; Hunt, J. R. Initial Uptake and Absorption of Nonheme Iron and Absorption of Heme Iron in Humans Are Unaffected by the Addition of Calcium as Cheese to a Meal with High Iron Bioavailability. Am. J. Clin. Nutr. 2002, 76 (2), 419– 425, DOI: 10.1093/ajcn/76.2.419[Crossref], [PubMed], [CAS], Google Scholar5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XlslOlt7o%253D&md5=76b5dfe41f083f5ed519a53afa72e85dInitial uptake and absorption of nonheme iron and absorption of heme iron in humans are unaffected by the addition of calcium as cheese to a meal with high iron bioavailabilityRoughead, Zamzam K.; Zito, Carol A.; Hunt, Janet R.American Journal of Clinical Nutrition (2002), 76 (2), 419-425CODEN: AJCNAC; ISSN:0002-9165. (American Society for Clinical Nutrition)Quant. data on the mucosal uptake and serosal transfer of nonheme iron in humans and the effects of calcium on these processes are limited. The initial mucosal uptake, the subsequent serosal transfer of nonheme iron, and the effects of adding calcium to meals on both heme and nonheme iron retention were examd. in 17 humans (9 women, 8 men) with normal Hb and ferritin levels. Whole-gut lavage and whole-body scintillation counting methods were used to det. the 8-h uptake of nonheme iron and the 2-wk retention (absorption) of heme and nonheme iron after consumption of radiolabeled foods. The initial uptake and absorption of nonheme iron were 11 and 7%, resp., and the absorption of heme iron was 15%. Two-thirds of the nonheme iron taken up by the mucosa within 8 h was retained by the body after 2 wk (serosal transfer index 0.63). Blood serum ferritin levels correlated inversely with the initial uptake and absorption of nonheme iron, but not with the nonheme serosal transfer index or the absorption of heme iron. Adding calcium (127 mg in cheese) to the meal did not affect the iron absorption. Thus, the initial mucosal uptake was the primary control point for nonheme iron absorption. An apparent decrease in heme iron absorption assocd. with the lavage procedure suggested that the uptake of heme iron may take longer and proceed further through the intestine than that of nonheme iron. The absorption of both forms of iron was not affected by the addn. of cheese to the meals with high iron bioavailability.
- 6Zijp, I. M.; Korver, O.; Tijburg, L. B. M. Effect of Tea and Other Dietary Factors on Iron Absorption. Crit. Rev. Food Sci. Nutr. 2000, 40 (5), 371– 398, DOI: 10.1080/10408690091189194[Crossref], [PubMed], [CAS], Google Scholar6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXnsFCis7k%253D&md5=4e8461e34169d1f66c605c7997a57887Effect of tea and other dietary factors on iron absorptionZijp, Itske M.; Korver, Onno; Tijburg, Lilian B. M.Critical Reviews in Food Science and Nutrition (2000), 40 (5), 371-398CODEN: CRFND6; ISSN:1040-8398. (CRC Press LLC)Iron deficiency is a major world health problem, i.e., to a great extent, caused by poor iron absorption from the diet. Several dietary factors can influence this absorption. Absorption enhancing factors are ascorbic acid and meat, fish and poultry; inhibiting factors are plant components in vegetables, tea and coffee (e.g., polyphenols, phytates), and calcium. After identifying these factors their individual impact on iron absorption is described. Specific attention was paid to the effects of tea on iron absorption. We propose a calcn. model that predicts iron absorption from a meal. Using this model we calcd. the iron absorption from daily menus with varying amts. of enhancers and inhibitors. From these calcns. we conclude that the presence of sufficient amts. of iron absorption enhancers (ascorbic acid, meat, fish, poultry, as present in most industrialized countries) overcomes inhibition of iron absorption from even large amts. of tea. In individuals with low intakes of heme iron, low intakes of enhancing factors and/or high intakes of inhibitors, iron absorption may be an issue. Depletion of iron stores enhances iron absorption, but this effect is not adequate to compensate for the inhibition of iron absorption in such an inadequate dietary situation. For subjects at risk of iron deficiency, the following recommendations are made. Increase heme-iron intake (this form of dietary iron present in meat fish and poultry is hardly influenced by other dietary factors with respect to its absorption); increase meal-time ascorbic acid intake; fortify foods with iron. Recommendations with respect to tea consumption (when in a crit. group) include: consume tea between meals instead of during the meal; simultaneously consume ascorbic acid and/or meat, fish and poultry.
- 7Cepeda-Lopez, A. C.; Melse-Boonstra, A.; Zimmermann, M. B.; Herter-Aeberli, I. In Overweight and Obese Women, Dietary Iron Absorption Is Reduced and the Enhancement of Iron Absorption by Ascorbic Acid Is One-half That in Normal-Weight Women. Am. J. Clin. Nutr. 2015, 102 (6), 1389– 1397, DOI: 10.3945/ajcn.114.099218[Crossref], [PubMed], [CAS], Google Scholar7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XntlWrsro%253D&md5=77944293b662169dec201b929dc43636In overweight and obese women, dietary iron absorption is reduced and the enhancement of iron absorption by ascorbic acid is one-half that in normal-weight womenCepeda-Lopez, Ana C.; Melse-Boonstra, Alida; Zimmermann, Michael B.; Herter-Aeberli, IsabelleAmerican Journal of Clinical Nutrition (2015), 102 (6), 1389-1397CODEN: AJCNAC; ISSN:0002-9165. (American Society for Nutrition)Background: Iron deficiency is common in overweight and obese individuals. This deficiency may be due to adiposity-related inflammation that increases serum hepcidin and decreases dietary iron absorption. Because hepcidin reduces iron efflux from the basolateral enterocyte, it is uncertain whether luminal enhancers of dietary iron absorption such as ascorbic acid can be effective in overweight and obese individuals. Objective: In this study, we compared iron absorption from a meal with ascorbic acid (+AA) and a meal without ascorbic acid (-AA) in women in a normal-wt. group (NW) with those in overweight and obese groups combined (OW/OB). Design: Healthy, nonanemic women [n = 62; BMI (in kg/m2): 18.5-39.9] consumed a stable-isotope-labeled wheat-based test meal -AA and a wheat-based test meal +AA (31.4 mg ascorbic acid). We measured iron absorption and body compn. with the use of dual-energy X-ray absorptiometry, blood vol. with the use of a carbon monoxide (CO)-rebreathing method, iron status, inflammation, and serum hepcidin. Results: Inflammatory biomarkers (all P < 0.05) and hepcidin (P = 0.08) were lower in the NW than in the OW/OB. Geometric mean (95% CI) iron absorptions in the NW and OW/OB were 19.0% (15.2%, 23.5%) and 12.9% (9.7%, 16.9%) (P = 0.049), resp., from -AA meals and 29.5% (23.3%, 38.2%) and 16.6% (12.8%, 21.7%) (P = 0.004), resp., from +AA meals. Median percentage increases in iron absorption for -AA to +AA meals were 56% in the NW (P < 0.001) and 28% in OW/OB (P = 0.006). Serum ferritin [R2 = 0.22; β = -0.17 (95% CI: -0.25, -0.09)], transferrin receptor [R2 = 0.23; β = 2.79 (95% CI: 1.47, 4.11)], and hepcidin [R2 = 0.13; β = -0.85 (95% CI: -1.41, -0.28)] were significant predictors of iron absorption. Conclusions: In overweight and obese women, iron absorption is two-thirds that in normal-wt. women, and the enhancing effect of ascorbic acid on iron absorption is one-half of that in normal-wt. women. Recommending higher intakes of ascorbic acid (or other luminal enhancers of iron absorption) in obese individuals to improve iron status may have a limited effect.
- 8Lönnerdal, B. Calcium and Iron Absorption - Mechanisms and Public Health Relevance. Int. J. Vitam. Nutr. Res. 2010, 80 (4–5), 293– 299, DOI: 10.1024/0300-9831/a000036[Crossref], [PubMed], [CAS], Google Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXlsFWis7Y%253D&md5=453bf41a58f51c5b501e0a16afdcf320Calcium and iron absorption - mechanisms and public health relevanceLonnerdal, BoInternational Journal for Vitamin and Nutrition Research (2010), 80 (4-5), 293-299CODEN: IJVNAP; ISSN:0300-9831. (Hogrefe & Huber Publishers)A review. Studies on human subjects have shown that calcium (Ca) can inhibit iron (Fe) absorption, regardless of whether it is given as Ca salts or in dairy products. This has caused concern as increased Ca intake commonly is recommended for children and women, the same populations that are at risk of Fe deficiency. However, a thorough review of studies on humans in which Ca intake was substantially increased for long periods shows no changes in hematol. measures or indicators of iron status. Thus, the inhibitory effect may be of short duration and there also may be compensatory mechanisms. The interaction between Ca and Fe may be a lumenal event, affecting Fe uptake through DMT1 (divalent metal transporter 1) at the apical membrane. However, it is also possible that inhibition occurs during Fe transfer into circulation, suggesting roles for the serosal exporter ferroportin (FPN) and hephaestin. We explored these possibilities in human intestinal Caco-2 cells cultured in monolayers. Iron transport (59Fe) and expression of DMT1, FPN, and hephaestin were assessed after 1.5 and 4 h with 0 or 100 μM CaCl2. Although Ca did not affect Fe uptake or DMT1 expression at 1.5 h, FPN abundance at the basolateral membrane decreased, resulting in increased cellular Fe retention and decreased Fe efflux. After 4 h, DMT1 and FPN expression increased and there was increased FPN at the membrane, suggesting a rebound effect. Thus, the effect of Ca on Fe absorption may be of short duration and adaptation may occur with time. This may explain why studies on long-term Ca supplementation of different groups fail to show any adverse effects on Fe status.
- 9Schönfeldt, H. C.; Pretorius, B.; Hall, N. Bioavailability of Nutrients. Encycl. Food Heal. 2016, 401– 406, DOI: 10.1016/B978-0-12-384947-2.00068-4
- 10Sifakis, S.; Pharmakides, G. Anemia in Pregnancy. Ann. N.Y. Acad. Sci. 2000, 900, 125– 136, DOI: 10.1111/j.1749-6632.2000.tb06223.x[Crossref], [PubMed], [CAS], Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXjsFChtro%253D&md5=1db3cfd0afb7c4ebc27672b610bac9f9Anemia in pregnancySifakis, S.; Pharmakides, G.Annals of the New York Academy of Sciences (2000), 900 (Young Woman at the Rise of the 21st Century: Gynecological and Reproductive Issues in Health and Disease), 125-136CODEN: ANYAA9; ISSN:0077-8923. (New York Academy of Sciences)A review, with 52 refs. Anemia is one of the most frequent complications related to pregnancy. Normal physiol. changes in pregnancy affect the Hb, and there is a relative or abs. redn. in Hb concn. The most common true anemias during pregnancy are iron deficiency anemia (approx. 75%) and folate deficiency megaloblastic anemia, which are more common in women who have inadequate diets and who are not receiving prenatal iron and folate supplements. Severe anemia may have adverse effects on the mother and the fetus. Anemia with Hb levels less than 6 gr/dL is assocd. with poor pregnancy outcome. Prematurity, spontaneous abortions, low birth wt., and fetal deaths are complications of severe maternal anemia. Nevertheless, a mild to moderate iron deficiency does not appear to cause a significant effect on fetal Hb concn. An Hb level of 11 gr/dL in the late first trimester and also of 10 gr/dL in the second and third trimesters are suggested as lower limits for Hb concn. In an iron-deficient state, iron supplementation must be given and follow-up is indicated to diagnose iron-unresponsive anemias.
- 11Gulec, S.; Anderson, G. J.; Collins, J. F. Mechanistic and Regulatory Aspects of Intestinal Iron Absorption. Am. J. Physiol. - Gastrointest. Liver Physiol. 2014, 307 (4), 397– 409, DOI: 10.1152/ajpgi.00348.2013
- 12Johnson-Wimbley, T. D.; Graham, D. Y. Diagnosis and Management of Iron Deficiency Anemia in the 21st Century. Therap. Adv. Gastroenterol. 2011, 4 (3), 177– 184, DOI: 10.1177/1756283X11398736[Crossref], [PubMed], [CAS], Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3MnisFGktg%253D%253D&md5=27e353206a99730bf146b44635e042cfDiagnosis and management of iron deficiency anemia in the 21st centuryJohnson-Wimbley Terri D; Graham David YTherapeutic advances in gastroenterology (2011), 4 (3), 177-84 ISSN:.Iron deficiency is the single most prevalent nutritional deficiency worldwide. It accounts for anemia in 5% of American women and 2% of American men. The goal of this review article is to assist practitioners in understanding the physiology of iron metabolism and to aid in accurately diagnosing iron deficiency anemia. The current first line of therapy for patients with iron deficiency anemia is oral iron supplementation. Oral supplementation is cheap, safe, and effective at correcting iron deficiency anemia; however, it is not tolerated by some patients and in a subset of patients it is insufficient. Patients in whom the gastrointestinal blood loss exceeds the intestinal ability to absorb iron (e.g. intestinal angiodysplasia) may develop iron deficiency anemia refractory to oral iron supplementation. This population of patients proves to be the most challenging to manage. Historically, these patients have required numerous and frequent blood transfusions and suffer end-organ damage resultant from their refractory anemia. Intravenous iron supplementation fell out of favor secondary to the presence of infrequent but serious side effects. Newer and safer intravenous iron preparations are now available and are likely currently underutilized. This article discusses the possible use of intravenous iron supplementation in the management of patients with severe iron deficiency anemia and those who have failed oral iron supplementation.
- 13Fleming, R. E.; Bacon, B. R. Orchestration of Iron Homeostasis. N. Engl. J. Med. 2005, 352 (17), 1741– 1744, DOI: 10.1056/NEJMp048363[Crossref], [PubMed], [CAS], Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXjsFyiurY%253D&md5=5351184f232d8291008534abbfc1e1a2Orchestration of iron homeostasisFleming, Robert E.; Bacon, Bruce R.New England Journal of Medicine (2005), 352 (17), 1741-1744CODEN: NEJMAG; ISSN:0028-4793. (Massachusetts Medical Society)There is no expanded citation for this reference.
- 14Mackenzie, B.; Garrick, M. D. Iron Imports. II. Iron Uptake at the Apical Membrane in the Intestine. Am. J. Physiol. - Gastrointest. Liver Physiol. 2005, 289 (6), 981– 986, DOI: 10.1152/ajpgi.00363.2005
- 15Shubham, K.; Anukiruthika, T.; Dutta, S.; Kashyap, A. V.; Moses, J. A.; Anandharamakrishnan, C. Iron Deficiency Anemia: A Comprehensive Review on Iron Absorption, Bioavailability and Emerging Food Fortification Approaches. Trends Food Sci. Technol. 2020, 99, 58– 75, DOI: 10.1016/j.tifs.2020.02.021[Crossref], [CAS], Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXkslamtLo%253D&md5=df75d56f56243cf43e3fa8d112be877bIron deficiency anemia: A comprehensive review on iron absorption, bioavailability and emerging food fortification approachesShubham, Kumar; Anukiruthika, T.; Dutta, Sayantani; Kashyap, A. V.; Moses, Jeyan A.; Anandharamakrishnan, C.Trends in Food Science & Technology (2020), 99 (), 58-75CODEN: TFTEEH; ISSN:0924-2244. (Elsevier Ltd.)Anemia, a morbid condition, is a global concern that affects people of all age groups. This scenario has attracted the attention of several government organizations for implementing strict regulations to provide nutritional security. Iron fortification and supplementation has been in practice from the past decades. However, there is a need for detg. an effective strategy to address this rising concern among the vulnerable population. Among the existing approaches, iron fortification of foods remains to be cheaper and effective in targeting large-scale population without the intervention of pharmaceutical drugs. The key challenge is the bioavailability of iron from fortified foods. Thus, this work presents a comprehensive review of morbidities of anemia, causes, the significance of haem and non-haem iron, absorption, and bioavailability, in context with different iron fortification approaches. Apart from the nutritional deficit, anemia is also assocd. with a sedentary lifestyle linked with obesity and diabetes. The complex interaction of elemental iron and its physiol. have been highlighted in consideration with potential iron enhancers and inhibitors. It was found that the incorporation of haem iron would complement the effectiveness of non-haem iron through fortification. Several iron fortification techniques focused on combating iron deficiency have been described. Food fortification is a promising strategy for reducing the prevalence of anemia. Food vehicles must be designed considering its synergistic effects with iron complexes for effective absorption and bioavailability. However, the scalability, cost economics, safety concerns and acceptability of the iron-fortified foods remain as constraints that have to be addressed. Further, the application of novel food processing techniques with food fortification can result in the emergence of novel approaches for addressing iron deficiency and anemia.
- 16Kanayama, Y.; Tsuji, T.; Enomoto, S.; Amano, R. Multitracer Screening: Brain Delivery of Trace Elements by Eight Different Administration Methods. Biometals 2005, 18 (6), 553– 565, DOI: 10.1007/s10534-005-4775-6[Crossref], [PubMed], [CAS], Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XlsVei&md5=a8081deae7e762111703b69a271075e4Multitracer Screening: Brain Delivery of Trace Elements by Eight Different Administration MethodsKanayama, Yousuke; Tsuji, Takae; Enomoto, Shuichi; Amano, RyoheiBioMetals (2005), 18 (6), 553-565CODEN: BOMEEH; ISSN:0966-0844. (Springer)Trace elements are closely assocd. with the normal functioning of the brain. Therefore, it is important to det. how trace elements enter, accumulate, and are retained in the brain. Using the multitracer technique, which allows simultaneous tracing of many elements and comparison of their behavior under identical exptl. conditions, we examd. the influence of different administration methods, i.e., i.v. (IV), i.p. (IP), i.m. (IM), s.c. (SC), intracutaneous (IC), intranasal (IN), peroral (PO), and percutaneous (PC) administration, on the uptake of trace elements. A multitracer soln. contg. 16 radionuclides (i.e., 7Be, 46Sc, 48V, 51Cr, 54Mn, 59Fe, 56Co, 65Zn, 74As, 75Se, 83Rb, 85Sr, 88Y, 88Zr, 95mTc, and 103Ru) was used. The results indicated that the 83Rb brain uptake rate with intranasal administration was approx. twice those obtained with the other administration methods. This result indicated that a portion of Rb was delivered into the brain circumventing the blood circulation and that delivery could be accomplished mainly by olfactory transport. Multitracer screening of trace element delivery revealed differences in brain uptake pathways among administration methods.
- 17Swanson, C. A. Iron Intake and Regulation: Implications for Iron Deficiency and Iron Overload. Alcohol 2003, 30 (2), 99– 102, DOI: 10.1016/S0741-8329(03)00103-4[Crossref], [PubMed], [CAS], Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXmvVygsb4%253D&md5=51e8fc48ea03c052c7710ce3bcf03290Iron intake and regulation: implications for iron deficiency and iron overloadSwanson, Christine A.Alcohol (New York, NY, United States) (2003), 30 (2), 99-102CODEN: ALCOEX; ISSN:0741-8329. (Elsevier Science Inc.)A review. Although Fe deficiency anemia is the most common nutritional deficiency worldwide and in the United States, the health effects of Fe overload merit increased attention. In the United States, public health interventions such as fortification and enrichment of foods with Fe were undertaken to reduce the prevalence of Fe deficiency anemia and improve health. These measures, along with Fe supplementation, remain controversial, because addnl. exposure to dietary Fe places some segments of the population at increased risk of Fe excess. The health consequences of unmistakable Fe excess are exemplified by hemochromatosis, an Fe storage disease assocd. with liver damage further exacerbated by alc. consumption. Progressive liver damage assocd. with this condition is generally attributed to increased oxidative stress. In otherwise healthy individuals, more modest levels of Fe storage may occur if Fe is provided by supplements or otherwise added to the food supply. Increased Fe intake and storage were linked to a variety of chronic diseases. The assocns. are not firmly established but are of considerable public health importance.
- 18Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc; National Academies Press (US): Washington (DC), 2001. DOI: 10.17226/10026 .
- 19Camaschella, C. Iron Deficiency. Blood 2019, 133 (1), 30– 39, DOI: 10.1182/blood-2018-05-815944[Crossref], [PubMed], [CAS], Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXnt1Ohs7k%253D&md5=3cda9d081c09e6285152f5d28756e9afIron deficiencyCamaschella, ClaraBlood (2019), 133 (1), 30-39CODEN: BLOOAW; ISSN:1528-0020. (American Society of Hematology)A review. Iron deficiency anemia affects >1.2 billions individuals worldwide, and iron deficiency in the absence of anemia is even more frequent. Total-body (abs.) iron deficiency is caused by physiol. increased iron requirements in children, adolescents, young and pregnant women, by reduced iron intake, or by pathol. defective absorption or chronic blood loss. Adaptation to iron deficiency at the tissue level is controlled by iron regulatory proteins to increase iron uptake and retention; at the systemic level, suppression of the iron hormone hepcidin increases iron release to plasma by absorptive enterocytes and recycling macrophages. The diagnosis of abs. iron deficiency is easy unless the condition is masked by inflammatory conditions. Special attention is needed in areas endemic for malaria and other infections to avoid worsening of infection by iron treatment. Ongoing efforts aim at optimizing iron salts-based therapy by protocols of administration based on the physiol. of hepcidin control and reducing the common adverse effects of oral iron. IV iron, esp. last-generation compds. administered at high doses in single infusions, is becoming an effective alternative in an increasing no. of conditions because of a more rapid and persistent hematol. response and acceptable safety profile. Risks/benefits of the different treatments should be weighed in a personalized therapeutic approach to iron deficiency.
- 20Muñoz, M.; Antonio García-Erce, J.; Ngel, A.; Remacha, F. Disorders of Iron Metabolism. Part II: Iron Deficiency and Iron Overload. J. Clin. Pathol. 2011, 64 (4), 287– 296, DOI: 10.1136/jcp.2010.086991[Crossref], [PubMed], [CAS], Google Scholar20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXlvFGqt7k%253D&md5=3efafcb0f1552daab900b1b4f239478aDisorders of iron metabolism. part II: iron deficiency and iron overloadMunoz, Manuel; Garcia-Erce, Jose Antonio; Remacha, Angel FranciscoJournal of Clinical Pathology (2011), 64 (4), 287-296CODEN: JCPAAK; ISSN:0021-9746. (BMJ Publishing Group)A review. Main disorders of iron metab. Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron deficiency anemia. In chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, resulting in hypoferremia and iron restricted erythropoiesis, despite normal iron stores (functional iron deficiency), and finally anemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD + ID). In contrast, low hepcidin expression may lead to hereditary haemochromatosis (HH type I, mutations of the HFE gene) and type II (mutations of the hemojuvelin and hepcidin genes). Mutations of transferrin receptor 2 lead to HH type III, whereas those of the ferroportin gene lead to HH type IV. All these syndromes are characterised by iron overload. As transferrin becomes satd. in iron overload states, non-transferrin bound iron appears. Part of this iron is highly reactive (labile plasma iron), inducing free radical formation. Free radicals are responsible for the parenchymal cell injury assocd. with iron overload syndromes. Role of lab. testing in diagnosis In iron deficiency status, lab. tests may provide evidence of iron depletion in the body or reflect iron deficient red cell prodn. Increased transferrin satn. and/or ferritin levels are the main cues for further investigation of iron overload. The appropriate combination of different lab. tests with an integrated algorithm will help to establish a correct diagnosis of iron overload, iron deficiency and anemia. Review of treatment options Indications, advantages and side effects of the different options for treating iron overload (phlebotomy and iron chelators) and iron deficiency (oral or i.v. iron formulations) will be discussed.
- 21BLANC, B. Nutritional Anemias. Report of a WHO Scientific Group. WHO Tech Rep. Ser. 1968, 405, 1– 40Google ScholarThere is no corresponding record for this reference.
- 22Hercberg, S.; Preziosi, P.; Galan, P. Iron Deficiency in Europe. Public Health Nutr. 2001, 4 (2b), 537– 545, DOI: 10.1079/PHN2001139[Crossref], [PubMed], [CAS], Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3MngvVaisQ%253D%253D&md5=1c20047c7770459de83140f122c903a6Iron deficiency in EuropeHercberg S; Preziosi P; Galan PPublic health nutrition (2001), 4 (2B), 537-45 ISSN:1368-9800.In Europe, iron deficiency is considered to be one of the main nutritional deficiency disorders affecting large fractions of the population, particularly such physiological groups as children, menstruating women and pregnant women. Some factors such as type of contraception in women, blood donation or minor pathological blood loss (haemorrhoids, gynaecological bleeding...) considerably increase the difficulty of covering iron needs. Moreover, women, especially adolescents consuming low-energy diets, vegetarians and vegans are at high risk of iron deficiency. Although there is no evidence that an absence of iron stores has any adverse consequences, it does indicate that iron nutrition is borderline, since any further reduction in body iron is associated with a decrease in the level of functional compounds such as haemoglobin. The prevalence of iron-deficient anaemia has slightly decreased in infants and menstruating women. Some positive factors may have contributed to reducing the prevalence of iron-deficiency anaemia in some groups of population: the use of iron-fortified formulas and iron-fortified cereals; the use of oral contraceptives and increased enrichment of iron in several countries; and the use of iron supplements during pregnancy in some European countries. It is possible to prevent and control iron deficiency by counseling individuals and families about sound iron nutrition during infancy and beyond, and about iron supplementation during pregnancy, by screening persons on the basis of their risk for iron deficiency, and by treating and following up persons with presumptive iron deficiency. This may help to reduce manifestations of iron deficiency and thus improve public health. Evidence linking iron status with risk of cardiovascular disease or cancer is unconvincing and does not justify changes in food fortification or medical practice, particularly because the benefits of assuring adequate iron intake during growth and development are well established. But stronger evidence is needed before rejecting the hypothesis that greater iron stores increase the incidence of CVD or cancer. At present, currently available data do not support radical changes in dietary recommendations. They include all means for increasing the content of dietary factors enhancing iron absorption or reducing the content of factors inhibiting iron absorption. Increased knowledge and increased information about factors may be important tools in the prevention of iron deficiency in Europe.
- 23Osungbade, K. O.; Oladunjoye, A. O. Anaemia in Developing Countries: Burden and Prospects of Prevention and Control. Anemia 2012, 3, 116– 129, DOI: 10.5772/29148
- 24von Haehling, S.; Ebner, N.; Evertz, R.; Ponikowski, P.; Anker, S. D. Iron Deficiency in Heart Failure: An Overview. JACC Hear. Fail. 2019, 7 (1), 36– 46, DOI: 10.1016/j.jchf.2018.07.015
- 25Palti, H.; Pevsner, B.; Adler, B. Does Anemia in Infancy Affect Achievement on Developmental and Intelligence Tests?. Hum. Biol. 1983, 55 (1), 183– 194[PubMed], [CAS], Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaL3s7osVWmtQ%253D%253D&md5=7bf8ea224777122b4d08eba9b3fdc9e5Does anemia in infancy affect achievement on developmental and intelligence tests?Palti H; Pevsner B; Adler BHuman biology (1983), 55 (1), 183-94 ISSN:0018-7143.There is no expanded citation for this reference.
- 26Lozoff, B.; Jimenez, E.; Wolf, A. W. Long-Term Developmental Outcome of Infants with Iron Deficiency. N. Engl. J. Med. 1991, 325 (10), 687– 694, DOI: 10.1056/NEJM199109053251004[Crossref], [PubMed], [CAS], Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK3MzjtlKktA%253D%253D&md5=7ba1c393cd370ec123e4b625ffb6903eLong-term developmental outcome of infants with iron deficiencyLozoff B; Jimenez E; Wolf A WThe New England journal of medicine (1991), 325 (10), 687-94 ISSN:0028-4793.BACKGROUND: Iron-deficiency anemia has been associated with lowered scores on tests of mental and motor development in infancy. However, the long-term developmental outcome of infants with iron deficiency is unknown, because developmental tests in infancy do not predict later intellectual functioning. METHODS: This study is a follow-up evaluation of a group of Costa Rican children whose iron status and treatment were documented in infancy. Eighty-five percent (163) of the 191 children in the original group underwent comprehensive clinical, nutritional, and psychoeducational assessments at five years of age. The developmental test battery consisted of the Wechsler Preschool and Primary Scale of Intelligence, the Spanish version of the Woodcock-Johnson Psycho-Educational Battery, the Beery Developmental Test of Visual-Motor Integration, the Goodenough-Harris Draw-a-Man Test, and the Bruininks-Oseretsky Test of Motor Proficiency. RESULTS: All the children had excellent hematologic status and growth at five years of age. However, children who had moderately severe iron-deficiency anemia as infants, with hemoglobin levels less than or equal to 100 g per liter, had lower scores on tests of mental and motor functioning at school entry than the rest of the children. Although these children also came from less socioeconomically advantaged homes, their test scores remained significantly lower than those of the other children after we controlled for a comprehensive set of background factors. For example, the mean (+/- SD) adjusted Woodcock-Johnson preschool cluster score for the children who had moderate anemia in infancy (n = 30) was 448.6 +/- 9.7, as compared with 452.9 +/- 9.2 for the rest of the children (n = 133) (P less than 0.01); the adjusted visual-motor integration score was 5.9 +/- 2.1, as compared with 6.7 +/- 2.3 (P less than 0.05). CONCLUSIONS: Children who have iron-deficiency anemia in infancy are at risk for long-lasting developmental disadvantage as compared with their peers with better iron status.
- 27Walter, T. Effect of Iron-Deficiency Anemia on Cognitive Skills and Neuromaturation in Infancy and Childhood. Food Nutr. Bull. 2003, 24, S104– S110, DOI: 10.1177/15648265030244S207
- 28Carter, R. C.; Jacobson, J. L.; Burden, M. J.; Armony-Sivan, R.; Dodge, N. C.; Angelilli, M. L.; Lozoff, B.; Jacobson, S. W. Iron Deficiency Anemia and Cognitive Function in Infancy. Pediatrics 2010, 126 (2), e427– e434, DOI: 10.1542/peds.2009-2097
- 29Daubian-Nose, P.; Frank, M. K.; Esteves, A. M. Sleep Disorders: A Review of the Interface between Restless Legs Syndrome and Iron Metabolism. Sleep Sci. 2014, 7 (4), 234– 237, DOI: 10.1016/j.slsci.2014.10.002[Crossref], [PubMed], [CAS], Google Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28zjs1yrsA%253D%253D&md5=175047fe79f897941d1c61584c96f493Sleep disorders: A review of the interface between restless legs syndrome and iron metabolismDaubian-Nose Paulo; Frank Miriam K; Esteves Andrea MaculanoSleep science (Sao Paulo, Brazil) (2014), 7 (4), 234-7 ISSN:1984-0659.Restless legs syndrome (RLS) is characterized by unpleasant sensations mainly in the legs. 43% of RLS-associated conditions have also been associated with systemic iron deficiency. The objective of this study was to review in the literature the relationship between iron metabolism and RLS. With an initial search using the keywords combination "Iron Metabolism OR Iron Deficiency AND Restless Legs Syndrome," 145 articles were screened, and 20 articles were selected. Few studies were found for this review in the period of 2001-2014, however, the correlation between RLS and iron was evident.
- 30Sîrbu, O.; Floria, M.; Dascalita, P.; Stoica, A.; Adascalitei, P.; Sorodoc, V.; Sorodoc, L. Anemia in Heart Failure - from Guidelines to Controversies and Challenges. Anatol. J. Cardiol. 2018, 20 (1), 52, DOI: 10.14744/ANATOLJCARDIOL.2018.08634[Crossref], [PubMed], [CAS], Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c%252FislOmtQ%253D%253D&md5=b38e637b094470d30e551744efe7cbd3Anemia in heart failure - from guidelines to controversies and challengesSirbu Oana; Dascalita Petru; Stoica Alexandra; Adascalitei Paula; Sorodoc Victorita; Sorodoc Laurentiu; Floria MarianaAnatolian journal of cardiology (2018), 20 (1), 52-59 ISSN:.Anemia associated with heart failure is a frequent condition, which may lead to heart function deterioration by the activation of neuro-hormonal mechanisms. Therefore, a vicious circle is present in the relationship of heart failure and anemia. The consequence is reflected upon the patients' survival, quality of life, and hospital readmissions. Anemia and iron deficiency should be correctly diagnosed and treated in patients with heart failure. The etiology is multifactorial but certainly not fully understood. There is data suggesting that the following factors can cause anemia alone or in combination: iron deficiency, inflammation, erythropoietin levels, prescribed medication, hemodilution, and medullar dysfunction. There is data suggesting the association among iron deficiency, inflammation, erythropoietin levels, prescribed medication, hemodilution, and medullar dysfunction. The main pathophysiologic mechanisms, with the strongest evidence-based medicine data, are iron deficiency and inflammation. In clinical practice, the etiology of anemia needs thorough evaluation for determining the best possible therapeutic course. In this context, we must correctly treat the patients' diseases; according with the current guidelines we have now only one intravenous iron drug. This paper is focused on data about anemia in heart failure, from prevalence to optimal treatment, controversies, and challenges.
- 31Barragán-Ibañez, G.; Santoyo-Sánchez, A.; Ramos-Peñafiel, C. O. Iron Deficiency Anaemia. Rev. Médica del Hosp. Gen. México 2016, 79 (2), 88– 97, DOI: 10.1016/J.HGMX.2015.06.008
- 32Camaschella, C. Iron-Deficiency Anemia. new Engl. J. o f Med. 2015, 372 (19), 1832– 1843, DOI: 10.1056/NEJMra1401038
- 33Rasmussen, K. M. Is There a Causal Relationship between Iron Deficiency or Iron-Deficiency Anemia and Weight at Birth, Length of Gestation and Perinatal Mortality?. J. Nutr. 2001, 131 (2), 590S– 603S, DOI: 10.1093/jn/131.2.590S[Crossref], [PubMed], [CAS], Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXht1Kjt78%253D&md5=5258dd20847f71232c59097ed0cedfcdIs there a causal relationship between iron deficiency or iron-deficiency anemia and weight at birth, length of gestation and perinatal mortality?Rasmussen, Kathleen M.Journal of Nutrition (2001), 131 (2S-2), 590S-603SCODEN: JONUAI; ISSN:0022-3166. (American Society for Nutritional Sciences)A review with 61 refs. An extensive literature review was conducted to identify whether iron deficiency, iron-deficiency anemia and anemia from other causes are related to low birth wt., preterm birth, or perinatal mortality. Strong evidence exists for an assocn. between maternal Hb concns. and birth wt. and between maternal Hb concns. and preterm birth. It was not possible to det. how much of this assocn. is attributable to iron-deficiency anemia in particular. Minimal values for both low birth wt. and preterm birth occurred at maternal Hb concns. below the current cut-off value for anemia during pregnancy (110 g/L) in a no. of studies, particularly those in which maternal Hb values were not controlled for during gestation. Supplementation of anemic or nonanemic pregnant women with iron, folic acid, or both does not appear to improve the birth wt. or the duration of gestation. These studies must be interpreted cautiously because most are subject to a bias toward false-neg. findings. Although there may be other reasons to offer women supplemental iron during pregnancy, the currently available evidence from studies with designs appropriate to establish a causal relationship is insufficient to support or reject this practice for the specific purposes of raising birth wt. or lowering the rate of preterm birth.
- 34Scholl, T. O. Maternal Iron Status: Relation to Fetal Growth, Length of Gestation, and Iron Endowment of the Neonate. Nutr. Rev. 2011, 69, S23– S29, DOI: 10.1111/j.1753-4887.2011.00429.x
- 35Brabin, B. J.; Hakimi, M.; Pelletier, D. An Analysis of Anemia and Pregnancy-Related Maternal Mortality. J. Nutr. 2001, 131 (2S-2), 604S– 614S, DOI: 10.1093/jn/131.2.604S[Crossref], [PubMed], [CAS], Google Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXht1Kjt7w%253D&md5=6dd47a55e469973053b3db1fbd3632beAn analysis of anemia and pregnancy-related maternal mortalityBrabin, Bernard J.; Hakimi, Mohammad; Pelletier, DavidJournal of Nutrition (2001), 131 (2S-2), 604S-615SCODEN: JONUAI; ISSN:0022-3166. (American Society for Nutritional Sciences)A review with 62 refs. The published data on the relationship of anemia as a risk factor for maternal mortality were analyzed from cross-sectional, longitudinal, and case-control studies; no randomized trial data were not available for anal. The following 6 methods of estn. of mortality risk were used: the correlation of maternal mortality rates with maternal anemia prevalence derived from national statistics, the proportion of maternal deaths attributable to anemia, the proportion of anemic women who die, population-attributable risk of maternal mortality due to anemia, adolescence as a risk factor for anemia-related mortality, and causes of anemia assocd. with maternal mortality. The av. ests. for all-cause anemia-attributable mortality (both direct and indirect) were 6.37, 7.26, and 3.0% for Africa, Asia, and Latin America, resp. The case fatality rates, based mainly on hospital studies, varied from <1 to >50%. The relative risk of mortality assocd. with moderate anemia (Hb 40-80 g/L) was 1.35 (95% CI 0.92-2.00) and for severe anemia (<47 g/L) was 3.51 (95% CI 2.05-6.00). The population-attributable risk ests. can be defended on the basis of the strong assocn. between severe anemia and maternal mortality, but not for mild or moderate anemia. In holoendemic malarious areas with a 5% severe anemia prevalence (Hb <70 g/L), it was estd. that in primigravidae there would be 9 severe-malaria anemia-related deaths and 41 nonmalarial anemia-related deaths (mostly nutritional) per 100,000 live births. The iron deficiency component in these ests. is unknown.
- 36Musallam, K. M.; Tamim, H. M.; Richards, T.; Spahn, D. R.; Rosendaal, F. R.; Habbal, A.; Khreiss, M.; Dahdaleh, F. S.; Khavandi, K.; Sfeir, P. M.; Soweid, A.; Hoballah, J. J.; Taher, A. T.; Jamali, F. R. Preoperative Anaemia and Postoperative Outcomes in Non-Cardiac Surgery: A Retrospective Cohort Study. Lancet 2011, 378 (9800), 1396– 1407, DOI: 10.1016/S0140-6736(11)61381-0[Crossref], [PubMed], [CAS], Google Scholar36https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3MbhsFWnuw%253D%253D&md5=fd39cee2a09f91e15e42d1333090b42dPreoperative anaemia and postoperative outcomes in non-cardiac surgery: a retrospective cohort studyMusallam Khaled M; Tamim Hani M; Richards Toby; Spahn Donat R; Rosendaal Frits R; Habbal Aida; Khreiss Mohammad; Dahdaleh Fadi S; Khavandi Kaivan; Sfeir Pierre M; Soweid Assaad; Hoballah Jamal J; Taher Ali T; Jamali Faek RLancet (London, England) (2011), 378 (9800), 1396-407 ISSN:.BACKGROUND: Preoperative anaemia is associated with adverse outcomes after cardiac surgery but outcomes after non-cardiac surgery are not well established. We aimed to assess the effect of preoperative anaemia on 30-day postoperative morbidity and mortality in patients undergoing major non-cardiac surgery. METHODS: We analysed data for patients undergoing major non-cardiac surgery in 2008 from The American College of Surgeons' National Surgical Quality Improvement Program database (a prospective validated outcomes registry from 211 hospitals worldwide in 2008). We obtained anonymised data for 30-day mortality and morbidity (cardiac, respiratory, CNS, urinary tract, wound, sepsis, and venous thromboembolism outcomes), demographics, and preoperative and perioperative risk factors. We used multivariate logistic regression to assess the adjusted and modified (nine predefined risk factor subgroups) effect of anaemia, which was defined as mild (haematocrit concentration >29-<39% in men and >29-<36% in women) or moderate-to-severe (≤29% in men and women) on postoperative outcomes. FINDINGS: We obtained data for 227,425 patients, of whom 69,229 (30·44%) had preoperative anaemia. After adjustment, postoperative mortality at 30 days was higher in patients with anaemia than in those without anaemia (odds ratio [OR] 1·42, 95% CI 1·31-1·54); this difference was consistent in mild anaemia (1·41, 1·30-1·53) and moderate-to-severe anaemia (1·44, 1·29-1·60). Composite postoperative morbidity at 30 days was also higher in patients with anaemia than in those without anaemia (adjusted OR 1·35, 1·30-1·40), again consistent in patients with mild anaemia (1·31, 1·26-1·36) and moderate-to-severe anaemia (1·56, 1·47-1·66). When compared with patients without anaemia or a defined risk factor, patients with anaemia and most risk factors had a higher adjusted OR for 30-day mortality and morbidity than did patients with either anaemia or the risk factor alone. INTERPRETATION: Preoperative anaemia, even to a mild degree, is independently associated with an increased risk of 30-day morbidity and mortality in patients undergoing major non-cardiac surgery. FUNDING: Vifor Pharma.
- 37Hurrell, R.; Egli, I. Iron Bioavailability and Dietary Reference Values. Am. J. Clin. Nutr. 2010, 91 (5), 1461S– 1467S, DOI: 10.3945/ajcn.2010.28674F[Crossref], [PubMed], [CAS], Google Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXlsVWru7g%253D&md5=512facdc0d5ba0ca7f37c98c3e6039a5Iron bioavailability and dietary reference valuesHurrell, Richard; Egli, InesAmerican Journal of Clinical Nutrition (2010), 91 (5S), 1461S-1467SCODEN: AJCNAC; ISSN:0002-9165. (American Society for Nutrition)A review. Iron differs from other minerals because iron balance in the human body is regulated by absorption only because there is no physiol. mechanism for excretion. On the basis of intake data and isotope studies, iron bioavailability has been estd. to be in the range of 14-18% for mixed diets and 5-12% for vegetarian diets in subjects with no iron stores, and these values have been used to generate dietary ref. values for all population groups. Dietary factors that influence iron absorption, such as phytate, polyphenols, calcium, ascorbic acid, and muscle tissue, have been shown repeatedly to influence iron absorption in single-meal isotope studies, whereas in multimeal studies with a varied diet and multiple inhibitors and enhancers, the effect of single components has been, as expected, more modest. The importance of fortification iron and food additives such as erythorbic acid on iron bioavailability from a mixed diet needs clarification. The influence of vitamin A, carotenoids, and non-digestible carbohydrates on iron absorption and the nature of the "meat factor" remain unresolved. The iron status of the individual and other host factors, such as obesity, play a key role in iron bioavailability, and iron status generally has a greater effect than diet compn. It would therefore be timely to develop a range of iron bioavailability factors based not only on diet compn. but also on subject characteristics, such as iron status and prevalence of obesity.
- 38Blanco-Rojo, R.; Vaquero, M. P. Iron Bioavailability from Food Fortification to Precision Nutrition. A Review. Innov. Food Sci. Emerg. Technol. 2019, 51, 126– 138, DOI: 10.1016/j.ifset.2018.04.015
- 39McDermid, J. M.; Lönnerdal, B. Iron. Adv. Nutr. 2012, 3 (4), 532– 533, DOI: 10.3945/an.112.002261[Crossref], [PubMed], [CAS], Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38fgtFKqsg%253D%253D&md5=4914c9d0761aa9a64e1db3245d4a08afIronMcDermid Joann M; Lonnerdal BoAdvances in nutrition (Bethesda, Md.) (2012), 3 (4), 532-3 ISSN:.There is no expanded citation for this reference.
- 40Rutzke, C. J.; Glahn, R. P.; Rutzke, M. A.; Welch, R. M.; Langhans, R. W.; Albright, L. D.; Combs, G. F.; Wheeler, R. M. Bioavailability of Iron from Spinach Using an in Vitro/Human Caco-2 Cell Bioassay Model. Habitation (Elmsford). 2004, 10 (1), 7– 14, DOI: 10.3727/154296604774808900[Crossref], [PubMed], [CAS], Google Scholar40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2M3kt1Kmsw%253D%253D&md5=8732d0364810f151f231757281cbcd1dBioavailability of iron from spinach using an in vitro/human Caco-2 cell bioassay modelRutzke Corinne J; Glahn Raymond P; Rutzke Michael A; Welch Ross M; Langhans Robert W; Albright Louis D; Combs Gerald F Jr; Wheeler Raymond MHabitation (Elmsford, N.Y.) (2004), 10 (1), 7-14 ISSN:1542-9660.Spinach (Spinacia oleracea) cv Whitney was tested for iron bioavailabilty using an in vitro human intestinal cell culture ferritin bioassay technique previously developed. Spinach was cultured in a growth chamber for 33 days, harvested, and freeze-dried. Total iron in the samples was an average of 71 micrograms/g dry weight. Spinach was digested in vitro (pepsin and 0.1 M HCl followed by pancreatin and 0.1 M NaHCO3) with and without the addition of supplemental ascorbic acid. Caco-2 cell cultures were used to determine iron bioavailability from the spinach mixtures. Production of the iron-binding protein ferritin in the Caco-2 cells showed the supplemental ascorbic acid doubled bioavailability of iron from spinach. The data show fresh spinach is a poor source of iron, and emphasize the importance of evaluation of whole meals rather than single food items. The data support the usefulness of the in vitro/Caco-2 cell ferritin bioassay model for prescreening of space flight diets for bioavailable iron.
- 41Tamburrano, A.; Tavazzi, B.; Anna, C.; Callà, M.; Amorini, A. M.; Lazzarino, G.; Vincenti, S.; Zottola, T.; Campagna, M. C.; Moscato, U.; Laurenti, P. Biochemical and Nutritional Characteristics of Buffalo Meat and Potential Implications on Human Health for a Personalized Nutrition. Ital. J. Food Saf. 2019, 8, 8317, DOI: 10.4081/ijfs.2019.8317[Crossref], [PubMed], [CAS], Google Scholar41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXosFentbw%253D&md5=0c84cdc67185d08143ab6ce320ee0e47Biochemical and nutritional characteristics of buffalo meat and potential implications on human health for a personalized nutritionTamburrano, Andrea; Tavazzi, Barbara; Calla, Cinzia Anna Maria; Amorini, Angela Maria; Lazzarino, Giacomo; Vincenti, Sara; Zottola, Tiziana; Campagna, Maria Concetta; Moscato, Umberto; Laurenti, PatriziaItalian Journal of Food Safety (2019), 8 (3), 8317CODEN: IJFSGY; ISSN:2239-7132. (PAGEPress Publications)The human consumption of food animal products is the main topic of an important debate among professionals in this sector: dietologists, dietitians and nutritional biologists. The red meat provides all the essential amino acids, bioavailable iron, zinc, calcium, lipids and B-group vitamins. A valid alternative to beef could be the buffalo meat. Italy is the largest European producer of buffalo meat and derivs. The high nutritional characteristics of buffalo meat make it suitable to be included in the Mediterranean diet to customize it in relation to the needs and conditions of the population. Polyunsatd./satd. fatty acids ratio can be influenced by diet, breed and type of breeding, but muscle tissue fat percentage is the main factor in detg. a favorable fatty acid compn. This review focuses on the biochem. and nutritional characteristics of the buffalo meat (content of fats, cholesterol, amino acids, vitamins and minerals), explaining their variability depending on the different breeds, and the favorable implications on the human health. These results suggest that buffalo meat can be a healthier alternative to beef, not only for healthy people in particular physiol. conditions (i.e. pregnancy), but also for persons at risk for cardiovascular and cerebrovascular diseases, thus achieving the goal of a personalized nutrition.
- 42Czerwonka, M.; Tokarz, A. Iron in Red Meat-Friend or Foe. Meat Sci. 2017, 123, 157– 165, DOI: 10.1016/j.meatsci.2016.09.012[Crossref], [PubMed], [CAS], Google Scholar42https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhs1yqsL3O&md5=57e612fac794a69abebe2b457e203a3aIron in red meat-friend or foeCzerwonka, Malgorzata; Tokarz, AndrzejMeat Science (2017), 123 (), 157-165CODEN: MESCDN; ISSN:0309-1740. (Elsevier Ltd.)In developed countries, due to high content and bioavailability, red and processed meats are the main sources of iron in the diet. Adequate intake of this nutrient is essential for the proper development and functioning of the human body, and its deficiencies are assocd. mainly with the occurrence of anemia, which is one of the most widespread nutritional problems in the world. However, excessive intake of iron can be detrimental to health. Studies have shown that high consumption of red meat and its products, and thereby iron, particularly in the form of heme, increases the risk of non-communicable diseases, including cancers, type II diabetes and cardiovascular disease. Due to the high nutritional value, the presence of red meat in the diet is preferable, but according to World Cancer Research Fund International its consumption should not exceed 500 g per wk. Furthermore, there are several potential ways to suppress the toxic effects of heme iron in the diet.
- 43Zimmermann, M. B.; Hurrell, R. F. Nutritional Iron Deficiency. Lancet 2007, 370, 511– 520, DOI: 10.1016/S0140-6736(07)61235-5[Crossref], [PubMed], [CAS], Google Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXovFCjsbg%253D&md5=90661953b34c68bb0b0ad44e197f0b9fNutritional iron deficiencyZimmermann, Michael B.; Hurrell, Richard F.Lancet (2007), 370 (9586), 511-520CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)A review. Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estd. 2 billion people. Nutritional iron deficiency arises when physiol. requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations consuming monotonous plant-based diets. The high prevalence of iron deficiency in the developing world has substantial health and economic costs, including poor pregnancy outcome, impaired school performance, and decreased productivity. Recent studies have reported how the body regulates iron absorption and metab. in response to changing iron status by upregulation or downregulation of key intestinal and hepatic proteins. Targeted iron supplementation, iron fortification of foods, or both, can control iron deficiency in populations. Although tech. challenges limit the amt. of bioavailable iron compds. that can be used in food fortification, studies show that iron fortification can be an effective strategy against nutritional iron deficiency. Specific lab. measures of iron status should be used to assess the need for fortification and to monitor these interventions. Selective plant breeding and genetic engineering are promising new approaches to improve dietary iron nutritional quality.
- 44Ems, T.; Huecker, M. R. Biochemistry, Iron Absorption. StatPearls 2019.Google ScholarThere is no corresponding record for this reference.
- 45Conrad, M. E.; Umbreit, J. N. Pathways of Iron Absorption. Blood Cells, Mol. Dis. 2002, 29 (3), 336– 355, DOI: 10.1006/bcmd.2002.0564[Crossref], [PubMed], [CAS], Google Scholar45Pathways of iron absorptionConrad, Marcel E.; Umbreit, Jay N.Blood Cells, Molecules & Diseases (2002), 29 (3), 336-355CODEN: BCMDFX; ISSN:1079-9796. (Elsevier Science)A review. Iron is vital for all living organisms but excess iron can be lethal because it facilitates free radical formation. Thus iron absorption is carefully regulated to maintain an equil. between absorption and body loss of iron. In countries where meat is a significant part of the diet, most body iron is derived from dietary heme because heme binds few of the dietary chelators that bind inorg. iron. Uptake of heme into enterocytes occurs as a metalloporphyrin in an endosomal process. Intracellular iron is released from heme by heme oxygenase to enter plasma as inorg. iron. Ferric iron is absorbed via a β3 integrin and mobilferrin pathway (IMP) which is unshared with other nutritional metals. Ferrous iron uptake is facilitated by a DMT-1 pathway which is shared with manganese. In the iron deficient gut, large quantities of both mobilferrin and DMT-1 are found in goblet cells and intraluminal mucins suggesting that they are secreted with mucin into the intestinal lumen to bind iron to facilitate uptake by the cells. In the cytoplasm, IMP and DMT assoc. in a large protein complex called paraferritin which serves as a ferrireductase. Paraferritin solubilizes iron binding proteins and reduces iron to make iron available for prodn. of