Total Iron Absorbed from Iron-Biofortified Potatoes Is Higher than that from Nonbiofortified Potatoes: A Randomized Trial Using Stable Iron Isotopes in Women from the Peruvian Highlands.

BACKGROUND: Yellow-fleshed potatoes biofortified with iron have been developed through conventional breeding, but the bioavailability of iron is unknown. OBJECTIVES: Our objective was to measure iron absorption from an iron-biofortified yellow-fleshed potato clone in comparison with a nonbiofortified yellow-fleshed potato variety. METHODS: We conducted a single-blinded, randomized, crossover, multiple-meal intervention study. Women (n = 28; mean ± SD plasma ferritin 21.3 ± 3.3 µg/L) consumed 10 meals (460 g) of both potatoes, each meal extrinsically labeled with either 58Fe sulfate (biofortified) or 57Fe sulfate (nonfortified), on consecutive days. Iron absorption was estimated from iron isotopic composition in erythrocytes 14 d after administration of the final meal. RESULTS: Mean ± SD iron, phytic acid, and ascorbic acid concentrations in iron-biofortified and the nonfortified potato meals (mg/per 100 mg) were 0.63 ± 0.01 and 0.31 ± 0.01, 39.34 ± 3.04 and 3.10 ± 1.72, and 7.65 ± 0.34 and 3.74 ± 0.39, respectively (P < 0.01), whereas chlorogenic acid concentrations were 15.14 ± 1.72 and 22.52 ± 3.98, respectively (P < 0.05). Geometric mean (95% CI) fractional iron absorption from the iron-biofortified clone and the nonbiofortified variety were 12.1% (10.3%-14.2%) and 16.6% (14.0%-19.6%), respectively (P < 0.001). Total iron absorption from the iron-biofortified clone and the nonbiofortified variety were 0.35 mg (0.30-0.41 mg) and 0.24 mg (0.20-0.28 mg) per 460 g meal, respectively (P < 0.001). CONCLUSIONS: TIA from iron-biofortified potato meals was 45.8% higher than that from nonbiofortified potato meals, suggesting that iron biofortification of potatoes through conventional breeding is a promising approach to improve iron intake in iron-deficient women. The study was registered at www. CLINICALTRIALS: gov as Identifier number NCT05154500.

Iron Fortification Practices and Implications for Iron Addition to Salt.

This introductory article provides an in-depth technical background for iron fortification, and thus introduces a series of articles in this supplement designed to present the current evidence on the fortification of salt with both iodine and iron, that is, double-fortified salt (DFS). This article reviews our current knowledge of the causes and consequences of iron deficiency and anemia and then, with the aim of assisting the comparison between DFS and other common iron-fortified staple foods, discusses the factors influencing the efficacy of iron-fortified foods. This includes the dietary and physiological factors influencing iron absorption; the choice of an iron compound and the fortification technology that will ensure the necessary iron absorption with no sensory changes; encapsulation of iron fortification compounds to prevent unacceptable sensory changes; the addition of iron absorption enhancers; the estimation of the iron fortification level for each vehicle based on iron requirements and consumption patterns; and the iron status biomarkers that are needed to demonstrate improved iron status in populations regularly consuming the iron-fortified food. The supplement is designed to provide a summary of evidence to date that can help advise policy makers considering DFS as an intervention to address the difficult public health issue of iron deficiency anemia, while at the same time using DFS to target iodine deficiency.

The Potential of Iodine and Iron Double-Fortified Salt Compared with Iron-Fortified Staple Foods to Increase Population Iron Status.

The potential of double-fortified salt (DFS) to improve population iron status is compared with the potential of iron-fortified wheat flour, maize flour, rice grains, and milk products. The potential for a positive impact on iron status is based on reported efficacy studies, consumption patterns, the extent of industrialization, and whether there are remaining technical issues with the fortification technologies. Efficacy studies with DFS, and with iron-fortified wheat flour, maize flour, and rice, have all reported good potential to improve population iron status. Iron-fortified milk powder has shown good impact in young children. When these foods are industrially fortified in modern, automated facilities, with high-level quality control and assurance practices, high-quality raw materials, and a wide population coverage, all vehicles have good potential to improve iron status. Relative to other fortification vehicles, fortification practices with wheat flour are the most advanced and iron-fortified wheat flour has the highest potential for impact in the short- to medium-term in countries where wheat flour is consumed as a staple. Liquid milk has the least potential, mainly because an acceptable iron fortification technology has not yet been developed. Maize is still predominantly milled in small-scale local mills and, although the extruded rice premix technology holds great promise, it is still under development. Salt has a proven record as an excellent vehicle for iodine fortification and has demonstrated good potential for iron fortification. However, technical issues remain with DFS and further studies are needed to better understand and avoid color formation and iron-catalyzed iodine losses in both high- and low-quality salts under different storage conditions. There is currently a risk that the introduction of DFS may jeopardize the success of existing salt iodization programs because the addition of iron may increase iodine losses and cause unacceptable color formation.

Iron Absorption from Bouillon Fortified with Iron-Enriched Aspergillus oryzae Is Higher Than That Fortified with Ferric Pyrophosphate in Young Women.

BACKGROUND: Bouillon cubes are a potential vehicle for iron fortification. They are currently fortified with ferric pyrophosphate (FePP), which is known to be poorly absorbed. The objective of this study was to assess the iron absorption of Aspergillus oryzae grown in FePP (ASP-p) and compare it with FePP and ferrous sulfate (FeSO4)-fortified bouillon cubes. METHODS: In 2 single-blinded, crossover studies, healthy women with serum ferritin concentrations <40 µg/L were randomly assigned to consume a rice-vegetable meal with iron-fortified chicken bouillon. Subjects in study I (n = 17, 18-26 y) consumed iron from both iron sources as 57FePP and 58ASP-p (intrinsically labeled with 58FePP) with a meal containing 4.2 mg of total iron provided for 3 d. Study II (n = 18, 18-29 y) was similar except that subjects consumed 57FeSO4 and 58ASP-p. Whole-blood stable isotope enrichment after 14 d was used to measure fractional iron absorption. Hemoglobin, hematocrit, serum ferritin, hepcidin, and serum C-reactive protein were analyzed at baseline and at 14 d. A t test was used to compare the mean differences in fractional absorptions within each study and baseline characteristics between studies. RESULTS: Geometric mean (95% CI) fractional iron absorption of FePP [0.94% (0.63%, 1.40%)] was lower than ASP-p [2.20% (1.47%, 3.30%)] (P < 0.0001) in study I. In study II, ASP-p fractional absorption [2.98% (2.03%, 4.38%)] was lower than that of FeSO4 [9.88% (6.70%, 14.59%)] (P < 0.0001). Both ferritin (r = -0.41, P = 0.014) and hepcidin (r = -0.42, P = 0.01) concentrations were inversely correlated with ASP-p iron absorption. Fractional absorption of ASP-p was also positively correlated with FePP (r = 0.92, P < 0.0001) and FeSO4 (r = 0.52, P < 0.02) absorption. CONCLUSIONS: ASP-p-fortified bouillon provided 2.3-fold higher absorbable iron than the currently used FePP. Bouillon fortified with ASP-p may contribute sufficient bioavailable iron to meet the daily iron requirements in young women only if consumed with other iron-fortified staple foods. This trial was registered at clinicaltrials.gov as NCT03586245.

Addition of Whole Wheat Flour During Injera Fermentation Degrades Phytic Acid and Triples Iron Absorption from Fortified Tef in Young Women.

BACKGROUND: Iron deficiency is a major public health concern in Ethiopia, where the traditional diet is based on tef injera. Iron absorption from injera is low due to its high phytic acid (PA) content. OBJECTIVES: We investigated ways to increase iron absorption from FeSO4-fortified tef injera in normal-weight healthy women (aged 21-29 y). METHODS: Study A (n = 22) investigated the influence on fractional iron absorption (FIA) from FeSO4-fortified injera of 1) replacing 10% tef flour with whole wheat flour (a source of wheat phytase), or 2) adding an isolated phytase from Aspergillus niger. Study B (n = 18) investigated the influence on FIA of replacing FeSO4 in tef injera with different amounts of NaFeEDTA. In both studies, the iron fortificants were labeled with stable isotopes and FIA was calculated from erythrocyte incorporation of stable iron isotopes 14 d after administration. RESULTS: In study A, the median (IQR) FIA from the 100% tef injera meal was 1.5% (0.7-2.8%). This increased significantly (P < 0.05) to 5.3% (2.4-7.1%) on addition of 10% whole wheat flour, and to 3.6% (1.6-6.2%) on addition of A. niger phytase. PA content of the 3 meals was 0.62, 0.20, and 0.02 g/meal, respectively. In study B, the median (IQR) FIA from the 100% tef injera meal was 3.3% (1.1-4.4%) and did not change significantly (P > 0.05) on replacing 50% or 75% of FeSO4 with NaFeEDTA. CONCLUSIONS: FIA from tef injera by young women was very low. NaFeEDTA was ineffective at increasing iron absorption, presumably due to the relatively low EDTA:Fe molar ratios. Phytate degradation, however, greatly increased during tef fermentation on addition of native or isolated phytases. Replacing 10% tef with whole wheat flour during injera fermentation tripled FIA in young women and should be considered as a potential strategy to improve iron status in Ethiopia.

Biomarkers of Nutrition for Development (BOND)-Iron Review.

This is the fifth in the series of reviews developed as part of the Biomarkers of Nutrition for Development (BOND) program. The BOND Iron Expert Panel (I-EP) reviewed the extant knowledge regarding iron biology, public health implications, and the relative usefulness of currently available biomarkers of iron status from deficiency to overload. Approaches to assessing intake, including bioavailability, are also covered. The report also covers technical and laboratory considerations for the use of available biomarkers of iron status, and concludes with a description of research priorities along with a brief discussion of new biomarkers with potential for use across the spectrum of activities related to the study of iron in human health.The I-EP concluded that current iron biomarkers are reliable for accurately assessing many aspects of iron nutrition. However, a clear distinction is made between the relative strengths of biomarkers to assess hematological consequences of iron deficiency versus other putative functional outcomes, particularly the relationship between maternal and fetal iron status during pregnancy, birth outcomes, and infant cognitive, motor and emotional development. The I-EP also highlighted the importance of considering the confounding effects of inflammation and infection on the interpretation of iron biomarker results, as well as the impact of life stage. Finally, alternative approaches to the evaluation of the risk for nutritional iron overload at the population level are presented, because the currently designated upper limits for the biomarker generally employed (serum ferritin) may not differentiate between true iron overload and the effects of subclinical inflammation.

Iron Bioavailability from Ferric Pyrophosphate in Extruded Rice Cofortified with Zinc Sulfate Is Greater than When Cofortified with Zinc Oxide in a Human Stable Isotope Study.

Background: Extruded rice grains are often cofortified with iron and zinc. However, it is uncertain if the addition of zinc to iron-fortified rice affects iron absorption and whether this is zinc-compound specific.Objective: We investigated whether zinc, added as zinc oxide (ZnO) or zinc sulfate (ZnSO4), affects human iron absorption from extruded rice fortified with ferric pyrophosphate (FePP).Methods: In 19 iron-depleted Swiss women (plasma ferritin ≤16.5 µ/L) aged between 20 and 39 y with a normal body mass index (in kg/m2; 18.7-24.8), we compared iron absorption from 4 meals containing fortified extruded rice with 4 mg Fe and 3 mg Zn. Three of the meals contained extruded rice labeled with FePP (57FePP): 1) 1 meal without added zinc (57FePP-Zn), 2) 1 cofortified with ZnO (57FePP+ZnO), and 3) 1 cofortified with ZnSO4 (57FePP+ZnSO4). The fourth meal contained extruded rice without iron or zinc, extrinsically labeled with ferrous sulfate (58FeSO4) added as a solution after cooking. All 4 meals contained citric acid. Iron bioavailability was measured by isotopic iron ratios in red blood cells. We also measured relative in vitro iron solubility from 57FePP-Zn, 57FePP+ZnO, and 57FePP+ZnSO4 expressed as a fraction of FeSO4 solubility.Results: Geometric mean fractional iron absorption (95% CI) from 57FePP+ZnSO4 was 4.5% (3.4%, 5.8%) and differed from 57FePP+ZnO (2.7%; 1.8%, 4.1%) (P < 0.03); both did not differ from 57FePP-Zn: 4.0% (2.8%, 5.6%). Relative iron bioavailabilities compared with 58FeSO4 were 62%, 57%, and 38% from 57FePP+ZnSO4, 57FePP-Zn, and 57FePP+ZnO, respectively. In vitro solubility from 57FePP+ZnSO4 differed from that of 57FePP-Zn (14.3%; P < 0.02) but not from that of 57FePP+ZnO (10.2% compared with 13.1%; P = 0.08).Conclusions: In iron-depleted women, iron absorption from FePP-fortified extruded rice cofortified with ZnSO4 was 1.6-fold (95% CI: 1.4-, 1.9-fold) that of rice cofortified with ZnO. These findings suggest that ZnSO4 may be the preferable zinc cofortificant for optimal iron bioavailability of iron-fortified extruded rice. This trial was registered at clinicaltrials.gov as NCT02255942.

The Potential of Fermentation and Contamination of Teff by Soil to Influence Iron Intake and Bioavailability from Injera Flatbread.

The high phytic acid (PA) concentration in the diet based on teff injera is a likely contributing cause of iron deficiency in Ethiopia. We monitored PA during teff injera fermentation in 30 households in Debre Zeyit, Ethiopia and evaluated its influence on iron bioavailability, considering contaminant soil iron in teff flour. After fermentation (48h), mean PA concentration in injera batter decreased from 0.87 to 0.58 g/100 g dm (P < 0.001). Low phytase activity in teff flour (0.44 µmol phosphate/min/g) and a rapid drop in pH, indicated that PA degradation was driven by microbial phytases. The iron concentration in injera batter among the households ranged widely from 14.5-160.4 mg/100 g dm (mean: 34.7 mg/100 g dm) principally due to contamination with soil. Estimated intrinsic iron concentration of teff based on the strong correlation between total iron and aluminium concentrations (P < 0.001; aluminium concentrations in injera batter: 28.7-184.9 mg/100 g dm) was 4.4 mg/100 g dm, indicating that 86-97 % is extrinsic iron from soil. The median daily iron intakes from 3-day weighed food records in 10 young children were 18.9 mg/day including soil iron vs. 4.9 mg/day without soil iron (P < 0.01). The PA:iron molar ratios indicated low iron bioavailability from teff injera, particularly when soil iron was excluded. Traditional fermentation thus has a modest influence on PA levels and more complete degradation is needed to improve iron bioavailability. There is an urgent need to better understand the bioavailability of contamination iron from soil before considering national fortification or biofortification strategies in Ethiopia.

Zinc Absorption by Adults Is Similar from Intrinsically Labeled Zinc-Biofortified Rice and from Rice Fortified with Labeled Zinc Sulfate.

BACKGROUND: Biofortification of staple food crops is a promising strategy to combat zinc deficiency, and it is of particular interest for rice and crops that are not consumed as flours and therefore not suitable for postharvest fortification. Because zinc absorption is decreased by phytic acid (PA) and perhaps other dietary components, it is important to measure the absorption of zinc from a biofortified crop before determining its efficacy. OBJECTIVE: In this study, we compared the zinc absorption from zinc-biofortified rice (hydroponically enriched with (70)Zn) with that from a control rice of the same variety fortified with (70)ZnSO4 at point of use to reach the same total zinc content of 1.1 mg/meal. Both rice meals had a PA:Zn molar ratio of 12. METHODS: Fractional absorption of zinc (FAZ) was measured with the use of the double-isotope tracer ratio method in 16 apparently healthy adults [18-45 y old; BMI (in kg/m(2)) 19-25] who consumed 2 single meals at 4-wk intervals in random order in a crossover design. RESULTS: The FAZ from the biofortified rice (mean ± SD: 25.1 ± 8.7%) did not differ significantly from that of the point-of-use fortified rice (mean ± SD: 20.8 ± 7.1%) (P = 0.08). CONCLUSIONS: These results suggest that the native zinc accumulated in the biofortified rice was readily released from the rice matrix and that its absorption by adults was influenced by PA and other food components in a similar way to the inorganic zinc compound added to the rice at point of use. Moreover, rice biofortification is likely to be as good as postharvest zinc fortification as an intervention strategy to combat zinc deficiency. This trial was registered at clinicaltrials.gov as NCT01633450.

Mode of oral iron administration and the amount of iron habitually consumed do not affect iron absorption, systemic iron utilisation or zinc absorption in iron-sufficient infants: a randomised trial.

Different metabolic pathways of supplemental and fortification Fe, or inhibition of Zn absorption by Fe, may explain adverse effects of supplemental Fe in Fe-sufficient infants. We determined whether the mode of oral Fe administration or the amount habitually consumed affects Fe absorption and systemic Fe utilisation in infants, and assessed the effects of these interventions on Zn absorption, Fe and Zn status, and growth. Fe-sufficient 6-month-old infants (n 72) were randomly assigned to receive 6·6 mg Fe/d from a high-Fe formula, 1·3 mg Fe/d from a low-Fe formula or 6·6 mg Fe/d from Fe drops and a formula with no added Fe for 45 d. Fractional Fe absorption, Fe utilisation and fractional Zn absorption were measured with oral (57Fe and 67Zn) and intravenous (58Fe and 70Zn) isotopes. Fe and Zn status, infection and growth were measured. At 45 d, Hb was 6·3 g/l higher in the high-Fe formula group compared with the Fe drops group, whereas serum ferritin was 34 and 35 % higher, respectively, and serum transferrin 0·1 g/l lower in the high-Fe formula and Fe drops groups compared with the low-Fe formula group (all P<0·05). No intervention effects were observed on Fe absorption, Fe utilisation, Zn absorption, other Fe status indices, plasma Zn or growth. We concluded that neither supplemental or fortification Fe nor the amount of Fe habitually consumed altered Fe absorption, Fe utilisation, Zn absorption, Zn status or growth in Fe-sufficient infants. Consumption of low-Fe formula as the only source of Fe was insufficient to maintain Fe stores.

The effect of iron-fortified complementary food and intermittent preventive treatment of malaria on anaemia in 12- to 36-month-old children: a cluster-randomised controlled trial.

BACKGROUND: Iron deficiency (ID) and malaria co-exist in tropical regions and both contribute to high rates of anaemia in young children. It is unclear whether iron fortification combined with intermittent preventive treatment (IPT) of malaria would be an efficacious strategy for reducing anaemia in young children. METHODS: A 9-month cluster-randomised, single-blinded, placebo-controlled intervention trial was carried out in children aged 12-36 months in south-central Côte d'Ivoire, an area of intense and perennial malaria transmission. The study groups were: group 1: normal diet and IPT-placebo (n = 125); group 2: consumption of porridge, an iron-fortified complementary food (CF) with optimised composition providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferrous fumarate 6 days per week (CF-FeFum) and IPT-placebo (n = 126); group 3: IPT of malaria at 3-month intervals, using sulfadoxine-pyrimethamine and amodiaquine and no dietary intervention (n = 127); group 4: both CF-FeFum and IPT (n = 124); and group 5: consumption of porridge, an iron-fortified CF with the composition currently on the Ivorian market providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferric pyrophosphate 6 days per week (CF-FePP) and IPT-placebo (n = 127). The primary outcome was haemoglobin (Hb) concentration. Linear and logistic regression mixed-effect models were used for the comparison of the five study groups, and a 2 × 2 factorial analysis was used to assess treatment interactions of CF-FeFum and IPT (study groups 1-4). RESULTS: After 9 months, the Hb concentration increased in all groups to a similar extent with no statistically significant difference between groups. In the 2 × 2 factorial analysis after 9 months, no treatment interaction was found on Hb (P = 0.89). The adjusted differences in Hb were 0.24 g/dl (95 % CI -0.10 to 0.59; P = 0.16) in children receiving IPT and -0.08 g/dl (95 % CI -0.42 to 0.26; P = 0.65) in children receiving CF-FeFum. At baseline, anaemia (Hb <11.0 g/dl) was 82.1 %. After 9 months, IPT decreased the odds of anaemia (odds ratio [OR], 0.46 [95 % CI 0.23-0.91]; P = 0.023), whereas iron-fortified CF did not (OR, 0.85 [95 % CI 0.43-1.68]; P = 0.68), although ID (plasma ferritin <30 µg/l) was decreased markedly in children receiving iron fortified CF (OR, 0.19 [95 % CI 0.09-0.40]; P < 0.001). CONCLUSIONS: IPT alone only modestly decreased anaemia, but neither IPT nor iron fortified CF significantly improved Hb concentration after 9 months. Additionally, IPT did not augment the effect of the iron fortified CF. CF fortified with highly bioavailable iron improved iron status but not Hb concentration, despite three-monthly IPT of malaria. Thus, further research is necessary to develop effective combination strategies to prevent and treat anaemia in malaria endemic regions. TRIAL REGISTRATION: http://www.clinicaltrials.gov ; identifier NCT01634945; registered on July 3, 2012.

Zinc absorption by young adults from supplemental zinc citrate is comparable with that from zinc gluconate and higher than from zinc oxide.

The water-soluble zinc salts gluconate, sulfate, and acetate are commonly used as supplements in tablet or syrup form to prevent zinc deficiency and to treat diarrhea in children in combination with oral rehydration. Zinc citrate is an alternative compound with high zinc content, slightly soluble in water, which has better sensory properties in syrups but no absorption data in humans. We used the double-isotope tracer method with (67)Zn and (70)Zn to measure zinc absorption from zinc citrate given as supplements containing 10 mg of zinc to 15 healthy adults without food and compared absorption with that from zinc gluconate and zinc oxide (insoluble in water) using a randomized, double-masked, 3-way crossover design. Median (IQR) fractional absorption of zinc from zinc citrate was 61.3% (56.6-71.0) and was not different from that from zinc gluconate with 60.9% (50.6-71.7). Absorption from zinc oxide at 49.9% (40.9-57.7) was significantly lower than from both other supplements (P < 0.01). Three participants had little or no absorption from zinc oxide. We conclude that zinc citrate, given as a supplement without food, is as well absorbed by healthy adults as zinc gluconate and may thus be a useful alternative for preventing zinc deficiency and treating diarrhea. The more insoluble zinc oxide is less well absorbed when given as a supplement without food and may be minimally absorbed by some individuals. This trial was registered at clinicaltrials.gov as NCT01576627.

Influence of phytase, EDTA, and polyphenols on zinc absorption in adults from porridges fortified with zinc sulfate or zinc oxide.

Fortification of cereal staples with zinc is recommended to combat zinc deficiency. To optimize zinc absorption, strategies are needed to overcome the inhibitory effect of phytic acid (PA) and perhaps polyphenols. Five zinc absorption studies were conducted in young adults consuming maize or sorghum porridges fortified with 2 mg zinc as zinc sulfate (ZnSO4) or zinc oxide (ZnO) and containing combinations of PA or polyphenols as potential inhibitors and EDTA and phytase as potential enhancers. Fractional absorption of zinc (FAZ) was measured by using the double isotopic tracer ratio method. Adding phytase to the maize porridge immediately before consumption or using phytase for dephytinization during meal preparation both increased FAZ by >80% (both P < 0.001). Adding Na2EDTA at an EDTA:zinc molar ratio of 1:1 increased FAZ from maize porridge fortified with ZnSO4 by 30% (P = 0.01) but had no influence at higher EDTA ratios or on absorption from ZnO. FAZ was slightly higher from ZnSO4 than from ZnO (P = 0.02). Sorghum polyphenols had no effect on FAZ from dephytinized sorghum porridges but decreased FAZ by 20% from PA-rich sorghum porridges (P < 0.02). The combined inhibitory effect of polyphenols and PA was overcome by EDTA. In conclusion, ZnSO4 was better absorbed than ZnO, phytase used to degrade PA during digestion or during food preparation substantially increased zinc absorption from zinc-fortified cereals, EDTA at a 1:1 molar ratio modestly enhanced zinc absorption from ZnSO4-fortified cereals but not ZnO-fortified cereals, and sorghum polyphenols inhibited zinc absorption in the presence, but not absence, of PA. This trial was registered at clinicaltrials.gov as NCT01210794.

Triple-fortified rice containing vitamin A reduced marginal vitamin A deficiency and increased vitamin A liver stores in school-aged Thai children.

Vitamin A (VA)-fortified rice is a potential intervention strategy to prevent VA deficiency in at-risk populations. Hot-extruded, triple-fortified rice grains with added VA, zinc, and iron were produced by hot extrusion technology and their ability to improve VA status was tested in Thai schoolchildren. The fortification levels were 10 mg of iron, 9 mg of zinc, and 1.05 mg of VA/g extruded rice. A paired stable isotope dilution technique with labeled ¹³C2-retinyl acetate (¹³C-RID) was used to quantify VA pool size at the beginning and end of the feeding period. Fifty healthy schoolchildren with a serum retinol (SR) concentration of >0.7 µmol/L were randomly assigned to 2 groups to receive either triple-fortified rice (n = 25) or natural rice (n = 25) for 2 mo as part of the daily school meal. The fortified grains, mixed 1:50 with regular rice, were estimated to provide an extra 890 µg of VA/d, 5 d/wk. ¹³C2-retinyl acetate (1.0 µmol) was administered orally to each child before and at the end of the feeding period to estimate total body reserves (TBRs) of VA, which increased significantly (P < 0.05) in the intervention group from 153 ± 66 µmol retinol at baseline to 269 ± 148 µmol retinol after 2 mo of feeding. There was no change in the TBRs of VA in the control group (108 ± 67 vs. 124 ± 89 µmol retinol) (P = 0.22). Serum retinol remained unchanged in both groups. We conclude that VA-fortified, hot-extruded rice is an efficacious vehicle to provide additional VA to at-risk populations, and that the efficacy of VA-fortified foods can be usefully monitored by the ¹³C-RID measurement of TBRs of VA but not by changes in SR concentration.

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.

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 schoolchildren 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 addition 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.

A higher proportion of iron-rich leafy vegetables in a typical Burkinabe maize meal does not increase the amount of iron absorbed in young women.

Food-to-food fortification can be a promising approach to improve the low dietary iron intake and bioavailability from monotonous diets based on a small number of staple plant foods. In Burkina Faso, the common diet consists of a thick, cereal-based paste consumed with sauces composed of mainly green leaves, such as amaranth and jute leaves. Increasing the quantity of leaves in the sauces substantially increases their iron concentration. To evaluate whether increasing the quantity of leaves in sauces would provide additional bioavailable iron, an iron absorption study in 18 young women was conducted in Zurich, Switzerland. Burkinabe composite test meals consisting of the maize paste tô accompanied by an iron-improved amaranth sauce, an iron-improved jute sauce, or a traditional amaranth sauce were provided as multiple meals twice a day for 2 consecutive days. Iron absorption was measured as erythrocyte incorporation of stable iron isotopes. Mean fractional iron absorption from maize paste consumed with an iron-improved amaranth sauce (4.9%) did not differ from the same meal consumed with an iron-improved jute sauce (4.9%; P = 0.9), resulting in a similar quantity of total iron absorbed (679 vs. 578 µg; P = 0.3). Mean fractional iron absorption from maize paste accompanied by a traditional amaranth sauce (7.4%) was significantly higher than that from the other 2 meal types (P < 0.05), but the quantity of total iron absorbed was similar (591 µg; P = 0.4 and 0.7, respectively). A food-to-food fortification approach based on an increase in leafy vegetables does not provide additional bioavailable iron, presumably due to the high phenolic compound concentration of the leaves tested. Alternative measures, such as adding iron absorption enhancers to the sauces, need to be investigated to improve iron nutrition from Burkinabe maize meals.

The effect of timing of iron supplementation on iron absorption and haemoglobin in post-malaria anaemia: a longitudinal stable isotope study in Malawian toddlers.

BACKGROUND: In sub-Saharan Africa, children with Plasmodium falciparum malaria and anaemia are often given iron supplementation at the time of malaria treatment. Inflammation during and after malaria may decrease iron absorption, thus, absorption might be improved if the start of supplementation is delayed. The study objective was to measure iron absorption from iron supplements started immediately or delayed by two weeks after completion of therapy against uncomplicated P. falciparum malaria. METHODS: Malawian toddlers (n=48; age 12-24 months) were alternatively assigned to two groups according to their appearance at the health centre: group A was provided iron supplements (30 mg Fe daily) as a FeSO4-containing syrup for eight weeks starting immediately after malarial treatment; group B was given the iron after a two-week delay. Iron absorption from the syrup was measured on the first day of iron supplementation, and after two and eight weeks in both groups. Haemoglobin (Hb), iron status and inflammation were assessed every two weeks. Fractional iron absorption at each time point and cumulative absorption was quantified by measuring erythrocyte incorporation of 57Fe and compared using mixed models. RESULTS: Comparing group A and B, geometric mean iron absorption did not differ on the first day of supplementation (9.0% vs. 11.4%, P=0.213) and cumulative iron absorption from the three time points did not differ (6.0% vs. 7.2%, P=0.124). Hb concentration increased in both groups two weeks after malaria treatment (P<0.001) and did not differ after eight weeks of supplementation (P=0.542). CONCLUSIONS: In anaemic toddlers after uncomplicated malaria, a two-week delay in starting iron supplementation did not significantly increase iron absorption or Hb concentration. Iron absorption is sufficiently high in the immediate post-malaria period to warrant supplementation. These findings suggest there is no need to change the current practice of immediate iron supplementation in this setting. TRIAL REGISTRATION: This trial was registered at Pan African Clinical Trials Registry (pactr.org) as PACTR2010050002141682.

Sodium iron EDTA and ascorbic acid, but not polyphenol oxidase treatment, counteract the strong inhibitory effect of polyphenols from brown sorghum on the absorption of fortification iron in young women.

In addition to phytate, polyphenols (PP) might contribute to low Fe bioavailability from sorghum-based foods. To investigate the inhibitory effects of sorghum PP on Fe absorption and the potential enhancing effects of ascorbic acid (AA), NaFeEDTA and the PP oxidase enzyme laccase, we carried out three Fe absorption studies in fifty young women consuming dephytinised Fe-fortified test meals based on white and brown sorghum varieties with different PP concentrations. Fe absorption was measured as the incorporation of stable Fe isotopes into erythrocytes. In study 1, Fe absorption from meals with 17 mg PP (8·5%) was higher than that from meals with 73 mg PP (3·2%) and 167 mg PP (2·7%; P< 0·001). Fe absorption from meals containing 73 and 167 mg PP did not differ (P= 0·9). In study 2, Fe absorption from NaFeEDTA-fortified meals (167 mg PP) was higher than that from the same meals fortified with FeSO4 (4·6 v. 2·7%; P< 0·001), but still it was lower than that from FeSO4-fortified meals with 17 mg PP (10·7%; P< 0·001). In study 3, laccase treatment decreased the levels of PP from 167 to 42 mg, but it did not improve absorption compared with that from meals with 167 mg PP (4·8 v. 4·6%; P= 0·4), whereas adding AA increased absorption to 13·6% (P< 0·001). These findings suggest that PP from brown sorghum contribute to low Fe bioavailability from sorghum foods and that AA and, to a lesser extent, NaFeEDTA, but not laccase, have the potential to overcome the inhibitory effect of PP and improve Fe absorption from sorghum foods.

Dynamics of anemia in relation to parasitic infections, micronutrient status, and increasing age in South-Central Côte d'Ivoire.

BACKGROUND: Parasitic diseases (eg, malaria and helminthiases) exert enormous burdens on public health and social well-being. Moreover, parasitic infections are important causes of anemia in tropical Africa, exacerbated by lack of a diversified diet and inflammatory and genetic diseases. There is a paucity of longitudinal studies monitoring the dynamics of anemia in relation to the aforementioned parameters. METHODS: We designed a 14-month prospective longitudinal study in 3 cohorts (ie, infants aged 6-23 months, children aged 6-8 years, and women aged 15-25 years) in the Taabo health demographic surveillance system located in south-central Côte d'Ivoire. Parasitological, hematological, and micronutrient data were obtained from repeated cross-sectional surveys, utilizing standardized, quality-controlled methods. RESULTS: We found that young age, Plasmodium and Schistosoma infections, cellular iron deficiency, and stunting were significantly negatively associated with hemoglobin concentration. Moreover, iron status biomarkers (ie, ferritin and soluble transferrin receptor) were significantly associated with inflammatory parameters. CONCLUSIONS: Based on our results, effective prevention and control measures that target parasitic diseases and iron deficiency are needed. These measures might include the distribution of long-lasting insecticidal nets, intermittent preventive treatment for malaria, regular anthelmintic drug administration, and improved intake of bioavailable iron, coupled with health and nutritional education and improved hygiene, water, and sanitation.