Non-haem Iron Absorption Research Articles

A Comparative Review on Iron Deficiency Anemia among Children and Long-Term Strategy

Background: One of the most prevalent dietary disorders in the world is iron deficiency anemia (IDA) which impacts people of all ages, genders, and physiological categories. In the current situation, iron fortification in food is seen as a long-term, cost-effective, and sustainable technique.Scope and approach: The ideal mix of iron form and food carrier, as wellas the food circumstances in which it is consumed, are critical. Combining iron with a bioavailability booster and avoiding interactions with iron inhibitors are suggested. As a result, this paper provides a thorough examination of the high prevalence of IDA, its various causes, absorption of haem and non-haem iron, and bioavailability,in addition to iron fortification strategies.Results: Ascorbic acid and meat components in animal tissue are the most prominent enhancers of iron absorption in diets. Polyphenols, phytates, and calcium are the utmost potentinhibitors of iron absorption. Additional approaches to minimize iron uptake from diets may include changes in diet that lower iron consumption and reduce iron bioavailability.Conclusion: Food fortification is a viable technique for lowering anemia prevalence. The combination of iron fortificants and food vehicles should be harmless, agreeable, and ingested by the target population for an effective fortification program.It should also have no negative impact on the ultimate product’s acceptance and stability. Novel food fortification techniques may lead to the development of new approaches to treating iron deficiency and anemia.International Journal of Human and Health Sciences Vol. 07 No. 02 April’23 Page: 106-116

Quercetin inhibits intestinal non-haem iron absorption by regulating iron metabolism genes in the tissues

PurposeThere 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 amounts, 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 metabolism.MethodsRats were subject to gastric gavage and systemic quercetin administration. Treatments were followed with uptake studies using radiolabeled iron, serum iron and transferrin saturation measurements, LC-MS/MS analysis of quercetin metabolites in serum, determination of tissue non-haem iron content and analysis of gene expression of iron-related proteins.ResultsBoth oral and intraperitoneal (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. Additionally, IP quercetin induced highly significant increased liver expression of hepcidin, a hormone known to inhibit intestinal iron uptake.ConclusionsOral 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 anaemia, the most widespread nutritional disorder in the world.

Protein Hydrolysates as Promoters of Non-Haem Iron Absorption.

Iron (Fe) is an essential micronutrient for human growth and health. Organic iron is an excellent iron supplement due to its bioavailability. Both amino acids and peptides improve iron bioavailability and absorption and are therefore valuable components of iron supplements. This review focuses on protein hydrolysates as potential promoters of iron absorption. The ability of protein hydrolysates to chelate iron is thought to be a key attribute for the promotion of iron absorption. Iron-chelatable protein hydrolysates are categorized by their absorption forms: amino acids, di- and tri-peptides and polypeptides. Their structural characteristics, including their size and amino acid sequence, as well as the presence of special amino acids, influence their iron chelation abilities and bioavailabilities. Protein hydrolysates promote iron absorption by keeping iron soluble, reducing ferric iron to ferrous iron, and promoting transport across cell membranes into the gut. We also discuss the use and relative merits of protein hydrolysates as iron supplements.

Lactobacillus plantarum 299v and an increase of non‐haem iron absorption: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006

Following an application from Probi AB submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Sweden, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Lactobacillus plantarum 299v and an increase of non-haem iron absorption. The food that is the subject of the health claim is ‘Lactobacillus plantarum 299v (Lp299v)’. The Panel considers that Lp299v is sufficiently characterised. The claimed effect proposed by the applicant is ‘increase of non-haem iron absorption’. The target population proposed by the applicant is ‘healthy adults who want to increase their iron uptake’. The Panel considers that increasing non-haem iron absorption is a beneficial physiological effect. In weighing the evidence, the Panel took into account that the results of two double-blind, placebo-controlled, cross-over studies are inconsistent, as one study with some methodological limitations showed a positive effect of Lp299v on non-haem absorption, whereas the other did not show an effect. The Panel noted that among four single-blind, placebo-controlled, sequential studies at risk of systematic bias, three studies showed a positive effect of Lp299v on non-haem absorption and one did not show an effect. The Panel also took into account that there is no evidence for a plausible mechanism by which Lp299v could increase non-haem iron absorption in vivo in humans. The Panel concludes that the scientific evidence is insufficient to establish a cause and effect relationship between the consumption of Lp299v and an increase of non-haem iron absorption.

Outcome of a public consultation on the draft guidance of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the scientific requirements for health claims related to the immune system, the gastrointestinal tract and defence against pathogenic microorganisms

Outcome of a public consultation on the draft guidance of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the scientific requirements for health claims related to the immune system, the gastrointestinal tract and defence against pathogenic microorganisms

Probiotic strainLactobacillus plantarum299v increases iron absorption from an iron-supplemented fruit drink: a double-isotope cross-over single-blind study in women of reproductive age

Iron deficiency is common, especially among young women. Adding probiotics to foods could be one way to increase iron absorption. The aim of this study was to test the hypothesis that non-haem iron absorption from a fruit drink is improved by adding Lactobacillus plantarum 299v (Lp299v). Iron absorption was studied in healthy women of reproductive age using a single-blind cross-over design in two trials applying the double-isotope (55Fe and 59Fe) technique. In Trial 1, iron absorption from a fruit drink containing 109 colony-forming units (CFU) Lp299v was compared with that from a control drink without Lp299v. Trial 2 had the same design but 1010 CFU were used. The test and control drinks contained approximately 5 mg of iron as ferrous lactate and were labelled with 59Fe (B) and 55Fe (A), respectively, and consumed on 4 consecutive days in the order AABB. Retention of the isotopes was measured with whole-body counting and in blood. Mean iron absorption from the drink containing 109 CFU Lp299v (28·6(sd 12·5) %) was significantly higher than from the control drink (18·5(sd 5·8) %), n 10, P<0·028). The fruit drink with 1010 CFU Lp299v gave a mean iron absorption of 29·1(sd 17·0) %, whereas the control drink gave an absorption of (20·1(sd 6·4) %) (n 11, P<0·080). The difference in iron absorption between the 109 CFU Lp299v and the 1010 CFU Lp299v drinks was not significant (P=0·941). In conclusion, intake of probiotics can increase iron absorption by approximately 50 % from a fruit drink having an already relatively high iron bioavailability.

Iron and vegetarian diets.

Vegetarians who eat a varied and well balanced diet are not at any greater risk of iron deficiency anaemia than non-vegetarians. A diet rich in wholegrains, legumes, nuts, seeds, dried fruits, iron-fortified cereals and green leafy vegetables provides an adequate iron intake. Vitamin C and other organic acids enhance non-haem iron absorption, a process that is carefully regulated by the gut. People with low iron stores or higher physiological need for iron will tend to absorb more iron and excrete less. Research to date on iron absorption has not been designed to accurately measure absorption rates in typical Western vegetarians with low ferritin levels.

Oxalic acid does not influence nonhaem iron absorption in humans: a comparison of kale and spinach meals

To evaluate the influence of oxalic acid (OA) on nonhaem iron absorption in humans. Two randomized crossover stable iron isotope absorption studies. Zurich, Switzerland. Sixteen apparently healthy women (18-45 years, <60 kg body weight), recruited by poster advertizing 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 (57)Fe or (58)Fe 14 days after the administration of labelled 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 (reference 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 reference 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.

The G277S transferrin mutation does not affect iron absorption in iron deficient women

Iron deficiency anaemia is one of the most important nutritional diseases, with high prevalence worldwide. The G277S transferrin mutation has been implicated as a risk factor for iron deficiency in menstruating women. However, the subject is controversial and there are no data concerning the possible influence of this polymorphism on iron absorption. To undertake a pilot study to investigate the effect of carrying the G277S transferrin mutation on non-haem iron absorption from a meal in young menstruating women compared to wild-type controls. Menstruating women with low iron stores (serum ferritin < 30 microg/l) or who had suffered from iron deficiency anaemia or had a family history of anaemia were recruited (n = 162). Haematological parameters were analysed, including haemoglobin, ferritin, total-iron binding capacity and transferrin saturation. Non-haem iron absorption from a meal was measured in 25 non-anaemic women either with the G277S/G277G (n = 10) or the wild type G277G/G277G (n = 15) genotype. The incorporation of stable isotopes of iron into erythrocytes was used to measure absorption. There were no significant differences in iron status indices or non-haem iron absorption between genotypes. However, G277S carriers did not show the usual inverse association between iron stores and non-haem iron absorption. Further studies should focus on the effects of a combination of polymorphisms in iron metabolism genes on iron absorption.

A lactic acid-fermented oat gruel increases non-haem iron absorption from a phytate-rich meal in healthy women of childbearing age

Lactic acid-fermented foods have been shown to increase Fe absorption in human subjects, possibly by lowering pH, activation of phytases, and formation of soluble complexes of Fe and organic acids. We tested the effect of an oat gruel fermented with Lactobacillus plantarum 299v on non-haem Fe absorption from a low-Fe bioavailability meal compared with a pasteurised, fermented oat gruel and non-fermented oat gruels. In a cross-over trial twenty-four healthy women with a mean age of 25 (sd 4) years were served (A) fermented gruel, (B) pasteurised fermented gruel, (C) pH-adjusted non-fermented gruel, and (D) non-fermented gruel with added organic acids. The meals were extrinsically labelled with 55Fe or 59Fe and consumed on 4 consecutive days, for example, in the order ABBA or BAAB followed by CDDC or DCCD in a second period. Fe absorption was determined from isotope activities in blood samples. The fermented gruel with live L. plantarum 299v increased Fe absorption significantly (P < 0.0001) compared with the pasteurised and non-fermented gruels. The lactic acid concentration in the fermented gruel was 19 % higher than in the pasteurised gruel, but the Fe absorption was increased by 50 %. In the gruel with organic acids, the lactic acid concentration was 52 % lower than in the pasteurised gruel, with no difference in Fe absorption. The fermented gruel increased non-haem Fe absorption from a phytate-rich meal in young women, indicating a specific effect of live L. plantarum 299v and not only an effect of the organic acids.

Mechanisms of Haem and Non-Haem Iron Absorption: Lessons from Inherited Disorders of Iron Metabolism

Our current state of knowledge of the mechanism and regulation of intestinal iron absorption has been critically dependent on the analysis of inherited disorders of iron homeostasis in both humans and other animal species. Mutations in DMT1 and Ireg1 have revealed that these molecules are major mediators of iron transport across the brush border and basolateral membranes of the enterocyte, respectively. Similarly, the iron oxidase hephaestin has been shown to play an important role in basolateral iron efflux. The analysis of a range of human iron loading disorders has provided very strong evidence that the products of the HFE, TfR2, hepcidin and hemojuvelin genes comprise integral components of the machinery that regulates iron absorption and iron traffic around the body. Engineered mouse strains have already proved very effective in helping to dissect pathways of iron homeostasis, and in the future they will continue to provide important insights into the absorption of both inorganic and haem iron by the gut.

Pork meat increases iron absorption from a 5-day fully controlled diet when compared to a vegetarian diet with similar vitamin C and phytic acid content

Meat increases absorption of non-haem iron in single-meal studies. The aim of the present study was to investigate, over a 5 d period, the potential increasing effect of consumption of pork meat in a whole diet on the fractional absorption of non-haem iron and the total absorption of iron, when compared to a vegetarian diet. A randomised cross-over design with 3 x 5 d whole-diet periods with diets containing Danish-produced meat, Polish-produced meat or a vegetarian diet was conducted. Nineteen healthy female subjects completed the study. All main meals in the meat diets contained 60 g of pork meat and all diets had high phytic acid content (1250 mumol/d). All main meals were extrinsically labelled with the radioactive isotope (59)Fe and absorption of iron was measured in a whole body counter. The non-haem iron absorption from the Danish meat diet was significantly higher compared to the vegetarian diet (P=0.031). The mean fractional absorption of non-haem iron was 7.9 (se1.1), 6.8 (se 1.0) and 5.3 (se 0.6) % for the Danish and Polish meat diets and vegetarian diet, respectively. Total absorption of iron was higher for both meat diets compared to the vegetarian diet (Danish meat diet: P=0.006, Polish meat diet: P=0.003). The absorption ratios of the present study were well in accordance with absorption ratios estimated using algorithms on iron bioavailability. Neither the meat diets nor the vegetarian diets fulfilled the estimated daily requirements of absorbed iron in spite of a meat intake of 180 g/d in the meat diets.

Epigallocatechin gallate (EGCG) (TEAVIGO™) does not impair nonhaem-iron absorption in man

A number of studies have shown that tea catechins can inhibit intestinal iron absorption, mostly iron in the nonhaem form. This randomized, double-blind, placebo-controlled, 3-periods cross-over study examined the degree of inhibition of nonhaem iron absorption by pure crystalline epigallocatechin gallate (EGCG). The study was designed to show the maximum inhibitory action of EGCG by selecting 30 healthy women with low iron stores. Treatments were 150 mg, 300 mg EGCG and placebo each for 8 consecutive study days with a wash-out period of 14 days between treatments. Iron incorporation was assessed by supplying 57Fe orally and 58Fe intravenously. Differences in fractional nonhaem iron absorption between the treatments were evaluated by using two-sided ANOVA. Results showed a relative nonhaem iron absorption reduction of 14% with 150mg EGCG and 27% for 300mg EGCG treatment compared to placebo. Differences were statistically significant (p < or = 0.05) between the placebo and the 300mg EGCG treatments and between the 150 and 300 mg EGCG treatments. The inverse relation between EGCG dose and fractional nonhaem iron absorption was linear (p = 0.0002). In this study the magnitude of the inhibitory action of EGCG on nonhaem iron absorption was found to be much lower than that reported in the literature for black tea and similar compounds. The doses of EGCG in supplements, which will be lower than those used in this study, are not expected to have any health relevant effects on iron absorption in subjects with normal iron stores.

Impact of tea drinking on iron status in the UK: a review.

The aims of this review are (1) to evaluate the literature on the likely impact of tea drinking on the iron status of different groups within the UK population and (2) to formulate targeted and evidence based advice on tea drinking in the context of iron nutrition in different groups of people. A literature search identified 35 references specific to the effects of black tea on iron absorption and iron nutrition plus one recent review article. Each study was assessed in terms of methodogical quality and relevance to the tea drinking patterns of the UK population. There is clear evidence to show that tea drinking limits the absorption of nonhaem iron. However, there are few studies which have assessed the influence of tea drinking on indicators of iron status. There are no intervention studies and the conclusions reported in this review are based on 12 observational studies mostly from other countries. These studies have reported either significant negative correlations between tea drinking and blood indicators of iron status or more cases of anemia in tea drinkers compared with nontea drinkers. Many of the studies reviewed report additional relationships between iron status indices and other factors (both dietary and nondietary), highlighting the complexity of influences on iron absorption and iron status. From the available evidence there is no need to advise any restriction on tea drinking in healthy people with no risk of iron deficiency. In groups at risk of iron deficiency the advice should be to drink tea between meals and to wait at least 1 h after eating before drinking tea.

Quantification of unlabelled non-haem iron absorption in human subjects: a pilot study.

A method for measuring unlabelled Fe absorption has been investigated in a pilot study using a simple mathematical model. The metabolism of newly absorbed Fe can be approximated as a single-compartment model with the sampled compartment being the plasma pool. Five female volunteers (aged 30-55 years) were recruited to participate in the pilot study. After a 10 mg oral dose of unlabelled ferrous sulfate, the change in plasma Fe concentration over the following 6 h was used to estimate the quantity of absorbed Fe from the mathematical model. To assess the accuracy of the new technique, a 1 mg oral dose of (57)Fe-labelled iron sulfate was given simultaneously with a 225 microg intravenous dose of (58)Fe as iron citrate. The plasma appearance of the labelled Fe was used to estimate the absorption of the oral label from the traditional area under the curve method. There was no significant difference (P=0.61) between the geometric mean absorption of the unlabelled (19 (-1 sd 12, +1 sd 28) %) and the labelled Fe (17 (-1 sd 10, +1 sd 29) %). These initial results are encouraging, but further work needs to be undertaken with smaller doses, as typically found in meals. The effect of diurnal variation in serum Fe concentration on the estimation of unlabelled Fe absorption needs further assessment.

Risk factors for low iron intake and poor iron status in a national sample of British young people aged 4-18 years.

To examine the prevalence and dietary, sociodemographic and lifestyle risk factors of low iron intake and poor iron status in British young people. National Diet and Nutrition Survey of young people aged 4-18 years. Great Britain, 1997. In total, 1699 young people provided 7-day weighed dietary records, of which 11% were excluded because the participant reported being unwell with eating habits affected. Blood was obtained from 1193 participants, with iron status indicated by haemoglobin, serum ferritin and transferrin saturation. Iron intakes were generally adequate in most young people aged 4-18 years. However, low iron intakes (below the Lower Reference Nutrient Intake) occurred in 44% of adolescent girls (11-18 years), being less prevalent with high consumption of breakfast cereals. Low haemoglobin concentration (<115 g l-1, 4-12 years; <120 or <130 g l-1, 13+ years for girls and boys, respectively) was observed in 9% of children aged 4-6 years, pubertal boys (11-14 years) and older girls (15-18 years). Adolescent girls who were non-Caucasians or vegetarians had significantly poorer iron status than Caucasians or meat eaters, independent of other risk factors. The three iron status indices were correlated significantly with haem, but not non-haem, iron intake. Adolescent girls showed the highest prevalence of low iron intake and poor iron status, with the latter independently associated with non-Caucasian ethnicity and vegetarianism. Risk of poor iron status may be reduced by consuming (particularly lean red) meat or enhancers of non-haem iron absorption (e.g. fruit or fruit juice) in vegetarians.

Rapid regulation of divalent metal transporter (DMT1) protein but not mRNA expression by non-haem iron in human intestinal Caco-2 cells

A divalent metal transporter, DMT1, located on the apical membrane of intestinal enterocytes is the major pathway for the absorption of dietary non-haem iron. Using human intestinal Caco-2 TC7 cells, we have shown that iron uptake and DMT1 protein in the plasma membrane were significantly decreased by exposure to high iron for 24 h, in a concentration-dependent manner, whereas whole cell DMT1 protein abundance was unaltered. This suggests that part of the response to high iron involved redistribution of DMT1 between the cytosol and cell membrane. These events preceded changes in DMT1 mRNA, which was only decreased following 72 h exposure to high iron.

Iron status and dietary levels of iron affect the bioavailability of haem and nonhaem iron in Atlantic salmonSalmo salar

The absorption of haem iron and nonhaem iron in 155-g Atlantic salmon Salmo salar was studied by simultaneous labelling of the two forms of iron with 59Fe or 55Fe, respectively. Iron absorption was measured after incorporation of this element into blood and tissue 2 days after oral administration. Fish with a low iron status showed a significantly greater absorption of both haem and nonhaem iron than iron-loaded fish. The low-iron group distributed a larger proportion of the iron to kidney and spleen than the iron-loaded or control fish. Absorption of both forms of iron increased with higher doses administered, but absorption relative to dose administered decreased. There was a trend suggesting that increased levels of dietary haem iron resulted in the reduced uptake of nonhaem iron, but not vice versa. The results of the present study suggest that factors affecting bioavailability of haem and nonhaem iron in Atlantic salmon are similar to those of other vertebrates.

Iron deficiency in children: detection and prevention.

Iron deficiency in children: detection and prevention.

Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages

The effects of different polyphenol-containing beverages on Fe absorption from a bread meal were estimated in adult human subjects from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in either phenolic acids (chlorogenic acid in coffee), monomeric flavonoids (herb teas, camomile (Matricaria recutita L.), vervain (Verbena officinalis L.), lime flower (Tilia cordata Mill.), pennyroyal (Mentha pulegium L.) and peppermint (Mentha piperita L.), or complex polyphenol polymerization products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and reduced absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages containing 20-50 mg total polyphenols/serving reduced Fe absorption from the bread meal by 50-70%, whereas beverages containing 100-400 mg total polyphenols/serving reduced 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 camomile 47%. At an identical concentration of total polyphenols, black tea was more inhibitory than cocoa, and more inhibitory than herb teas camomile, vervain, lime flower and pennyroyal, but was of equal inhibition to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Our findings demonstrate that herb teas, as well as black tea, coffee and coca can be potent inhibitors of Fe absorption. This property should be considered when giving dietary advice in relation to Fe nutrition.