Richard F. Hurrell

Nutritional iron deficiency

Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estimated 2 billion people. Nutritional iron deficiency arises when physiological 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 metabolism 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 technical challenges limit the amount of bioavailable iron compounds that can be used in food fortification, studies show that iron fortification can be an effective strategy against nutritional iron deficiency. Specific laboratory 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.

Potential for increasing the content and bioavailability of Fe, Zn and Ca in plants for human nutrition

This paper reviews the possibility and limits for increasing the content and bioavailability of iron (Fe), zinc (Zn) and calcium (Ca) in edible parts of staple crops, such as cereals, pulses, roots and tubers as a way to combat mineral deficiencies in human populations. Theoretically, this could be achieved by increasing the total level of Fe, Zn and Ca in the plant foods, while at the same time increasing the concentration of compounds which promote their uptake (ascorbic acid), and/or by decreasing the concentration of compounds which inhibit their absorption (phytic acid or phenolic compounds). The content of Zn and Ca in grains and fruits can in some cases be increased through soil and/or foliar applications of Zn and Ca fertilisers. Plant breeding and genetic engineering techniques, however, have the greatest potential to increase Fe and Zn content in grains, roots and tubers. The possibility of enhancing Ca and ascorbic acid content in plant foods by plant breeding and genetic engineering remained to be explored. The critical factor is to ensure that the extra minerals have an adequate bioavailability for man. Given the important role of phytic acid and polyphenols in plant physiology, reducing the levels of these compounds in the edible parts of plants does not appear to be wise although introduction of phytases which are active during digestion is an exciting possibility.

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.

Genetic engineering approaches to improve the bioavailability and the level of iron in rice grains

Abstract Iron deficiency is the most widespread micronutrient deficiency world-wide. A major cause is the poor absorption of iron from cereal and legume-based diets high in phytic acid. We have explored three approaches for increasing the amount of iron absorbed from rice-based meals. We first introduced a ferritin gene from Phaseolus vulgaris into rice grains, increasing their iron content up to two-fold. To increase iron bioavailability, we introduced a thermotolerant phytase from Aspergillus fumigatus into the rice endosperm. In addition, as cysteine peptides are considered a major enhancer of iron absorption, we overexpressed the endogenous cysteine-rich metallothionein-like protein. The content of cysteine residues increased about seven-fold and the phytase level in the grains about 130-fold, giving a phytase activity sufficient to completely degrade phytic acid in a simulated digestion experiment. High phytase rice, with an increased iron content and rich in cysteine-peptide, has the potential to greatly improve iron nutrition in rice-eating populations.

Fortification: Overcoming Technical and Practical Barriers

The main barriers to successful iron fortification are the following: 1) finding an iron compound that is adequately absorbed but causes no sensory changes to the food vehicle; and 2) overcoming the inhibitory effect on iron absorption of dietary components such as phytic acid, phenolic compounds and calcium. These barriers have been successfully overcome with some food vehicles but not with others. Iron-fortified fish sauce, soy sauce, curry powder, sugar, dried milk, infant formula and cereal based complementary foods have been demonstrated to improve iron status in targeted populations. The reasons for this success include the use of soluble iron such as ferrous sulfate, the addition of ascorbic acid as an absorption enhancer or the use of NaFeEDTA to overcome the negative effect of phytic acid. In contrast, at the present time, it is not possible to guarantee a similar successful fortification of cereal flours or salt. There is considerable doubt that the elemental iron powders currently used to fortify cereal flours are adequately absorbed, and there is an urgent need to investigate their potential for improving iron status. Better absorbed alternative compounds for cereal fortification include encapsulated ferrous sulfate and NaFeEDTA, which, unlike ferrous sulfate, do not provoke fat oxidation of cereals during storage. Encapsulated compounds also offer a possibility to fortify low grade salt without causing off-colors or iodine loss. Finally, a new and useful additional approach to ensuring adequate iron absorption from cereal based complementary foods is the complete degradation of phytic acid with added phytases or by activating native cereal phytases.

The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Côte d'Ivoire

BACKGROUND Iron is essential for the growth and virulence of many pathogenic enterobacteria, whereas beneficial barrier bacteria, such as lactobacilli, do not require iron. Thus, increasing colonic iron could select gut microbiota for humans that are unfavorable to the host. OBJECTIVE The objective was to determine the effect of iron fortification on gut microbiota and gut inflammation in African children. DESIGN In a 6-mo, randomized, double-blind, controlled trial, 6-14-y-old Ivorian children (n = 139) received iron-fortified biscuits, which contained 20 mg Fe/d, 4 times/wk as electrolytic iron or nonfortifoed biscuits. We measured changes in hemoglobin concentrations, inflammation, iron status, helminths, diarrhea, fecal calprotectin concentrations, and microbiota diversity and composition (n = 60) and the prevalence of selected enteropathogens. RESULTS At baseline, there were greater numbers of fecal enterobacteria than of lactobacilli and bifidobacteria (P < 0.02). Iron fortification was ineffective; there were no differences in iron status, anemia, or hookworm prevalence at 6 mo. The fecal microbiota was modified by iron fortification as shown by a significant increase in profile dissimilarity (P < 0.0001) in the iron group as compared with the control group. There was a significant increase in the number of enterobacteria (P < 0.005) and a decrease in lactobacilli (P < 0.0001) in the iron group after 6 mo. In the iron group, there was an increase in the mean fecal calprotectin concentration (P < 0.01), which is a marker of gut inflammation, that correlated with the increase in fecal enterobacteria (P < 0.05). CONCLUSIONS Anemic African children carry an unfavorable ratio of fecal enterobacteria to bifidobacteria and lactobacilli, which is increased by iron fortification. Thus, iron fortification in this population produces a potentially more pathogenic gut microbiota profile, and this profile is associated with increased gut inflammation. This trial was registered at controlled-trials.com as ISRCTN21782274.

Phytic acid degradation as a means of improving iron absorption.

Phytic acid is a potent inhibitor of native and fortification iron absorption and low absorption of iron from cereal- and/or legume-based complementary foods is a major factor in the etiology of iron deficiency in infants. Dephytinization of complementary foods or soy-based infant formulas is technically possible but, as phytic acid is strongly inhibitory at low concentrations, complete enzymatic degradation is recommended. If this is not possible, the phytic acid to iron molar ratio should be decreased to below 1:1 and preferably below 0.4:1. Complete dephytinization of cereal- and legume-based complementary foods has been shown to increase the percentage of iron absorption by as much as 12-fold (0.99% to 11.54%) in a single-meal study when the foods were reconstituted with water. The addition of milk, however, inhibits iron absorption and overcomes the enhancing effect of phytic acid degradation. Dephytinization can therefore be strongly recommended only for cereal/legume mixtures reconstituted with water, especially low-cost complementary foods destined for infants in developing countries. In countries where infant cereals are consumed with milk, ascorbic acid addition can more easily be used to overcome the negative effect of phytic acid on iron absorption. Similarly with soy-based infant formulas, especially if manufactured from low-phytate isolates, ascorbic acid can be used to ensure adequate iron absorption.

Fighting Iron Deficiency Anemia with Iron-Rich Rice

Objective: Iron deficiency is estimated to affect about 30% of the world population. Iron supplementation in the form of tablets and food fortification has not been successful in developing countries, and iron deficiency is still the most important deficiency related to malnutrition. Here we present experiments that aim to increase the iron content in rice endosperm and to improve its absorption in the human intestine by means of genetic engineering. Methods: We first introduced a ferritin gene from Phaseolus vulgaris into rice grains, increasing their iron content up to twofold. To increase iron bioavailability, we introduced a thermo-tolerant phytase from Aspergillus fumigatus into the rice endosperm. In addition, as cysteine peptides are considered major enhancers of iron absorption, we over-expressed the endogenous cysteine-rich metallothionein-like protein. Results: The content of cysteine residues increased about sevenfold and the phytase level in the grains about one hundred and thirtyfold, giving a phytase activity sufficient to completely degrade phytic acid in a simulated digestion experiment. Conclusions: This rice, with higher iron content, rich in phytase and cysteine-peptide has a great potential to substantially improve iron nutrition in those populations where iron deficiency is so widely spread.

Bioavailability of Minerals and Trace Elements

In this review a brief summary will be given of the food sources, absorptive mechanism and subsequent metabolism of the nine mineral and trace element identified as being nutritionally important (calcium, chromium, cuivre, iodine, iron, magnesium, manganese, selenium, zinc)

Interlaboratory trial on the determination of the In Vitro iron dialysability from food

An in vitro method for the estimation of iron bioavailability was subjected to an interlaboratory trial. The method involved a simulated gastrointestinal digestion using pepsin for the gastric stage followed by pancreatin and bile salts for the intestinal stage. The proportion of iron diffused through a semipermeable membrane (molecular mass cut-off 10 kDa) was used to measure the iron dialysability. An interlaboratory trial between nine laboratories was conducted to evaluate the repeatability and reproducibility of the agreed method. The reproducibility of the method among the participating laboratories was 20-30% and depended on the content of dialysable iron. Several factors contributing to the variation in the in vitro dialysability among laboratories are discussed. The pH adjustment in the intestinal digestion was identified as one of the critical parameters. The present in vitro method was used to evaluate the iron dialysability from three meals. The dialysability data were in reasonable agreement with human absorption data. The usefulness of the in vitro dialysability method is discussed.