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.

Zinc Absorption From Agronomically Biofortified Wheat Is Similar to Post-Harvest Fortified Wheat and Is a Substantial Source of Bioavailable Zinc in Humans.

BACKGROUND: Limited data exist on human zinc absorption from wheat biofortified via foliar (FBW) or root (hydroponically fortified wheat, HBW) zinc application. Stable isotope labels added at point of consumption (extrinsic labeling) might not reflect absorption from native zinc obtained by intrinsic labeling. OBJECTIVES: We measured fractional and total zinc absorption (FAZ, TAZ) in FBW and HBW wheat, compared with control wheat (CW) and fortified wheat (FW). The effect of labeling method was assessed in HBW (study 1), and the effect of milling extraction rate (EXR, 80% and 100%) in FBW (studies 2 and 3). METHODS: Generally healthy adults (n = 71, age: 18-45 y, body mass index: 18.5-25 kg/m2) were allocated to 1 of the studies, in which they served as their own controls. In study 1, men and women consumed wheat porridges colabeled intrinsically and extrinsically with 67Zn and 70Zn. In studies 2 and 3, women consumed wheat flatbreads (chapatis) labeled extrinsically. Zinc absorption was measured with the oral to intravenous tracer ratio method with a 4-wk wash-out period between meals. Data were analyzed with linear mixed models. RESULTS: In study 1 there were no differences in zinc absorption from extrinsic versus intrinsic labels in either FW or HBW. Similarly, FAZ and TAZ from FW and HBW did not differ. TAZ was 70-76% higher in FW and HBW compared with CW (P < 0.01). In studies 2 and 3, TAZ from FW and FBW did not differ but was 20-48% higher compared with CW (P < 0.001). Extraction rate had no effect on TAZ. CONCLUSIONS: Colabeling demonstrates that extrinsic zinc isotopic labels can be used to accurately quantify zinc absorption from wheat in humans. Biofortification through foliar zinc application, root zinc application, or fortification provides higher TAZ compared with unfortified wheat. In biofortified wheat, extraction rate (100-80%) has a limited impact on total zinc absorption. These studies were registered on clinicaltrials.gov (NCT01775319).

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.

Iron bioavailability from fresh cheese fortified with iron-enriched yeast.

PURPOSE: An iron-enriched yeast able to lyse at body temperature was developed for iron fortification of chilled dairy products. The aim was to evaluate iron (Fe) absorption from iron-enriched yeast or ferrous sulfate added to fresh cheese. METHODS: Two stable isotope studies with a crossover design were conducted in 32 young women. Fe absorption from fresh cheese fortified with iron-enriched yeast (2.5 mg 58Fe) was compared to that from ferrous sulfate (2.5 mg 57Fe) when ingested with fresh cheese alone or with fresh cheese consumed with bread and butter. Iron absorption was determined based on erythrocyte incorporation of isotopic labels 14 days after consumption of the last test meal. RESULTS: Geometric mean fractional iron absorption from fresh cheese fortified with iron-enriched yeast consumed alone was significantly lower than from the cheese fortified with FeSO4 (20.5 vs. 28.7 %; p = 0.0007). When the fresh cheese was consumed with bread and butter, iron absorption from both fortificants decreased to 6.9 % from the iron-enriched yeast compared to 8.4 % from ferrous sulfate. The relative bioavailability of the iron-enriched yeast compared to ferrous sulfate was 0.72 for the cheese consumed alone and 0.82 for cheese consumed with bread and butter (p = 0.157). CONCLUSIONS: Iron from iron-enriched yeast was 72-82 % as well absorbed as ferrous sulfate indicating that the yeast lysed during digestion and released its iron.

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.

Modeling Zinc Intake for Intervention and Scenario Analysis.

BACKGROUND: A large number of illnesses, afflicting one-third of the world's population, have been attributed to zinc deficiency. Inadequate dietary intake of bioavailable forms of zinc is considered the most frequent cause of zinc deficiency, which is most common in arid regions of developing countries. OBJECTIVE: To employ a modeling approach in a test population to analyze how best to eliminate zinc deficiency using different plausible dietary scenarios. METHODS: A comprehensive database was built upon food consumption patterns of two population groups residing in a village and a suburb in semiarid central Iran near Isfahan city. A database was created on zinc and phytic acid concentrations of different foods and ingredients consumed by the study populations. A zinc intake model was constructed and parameterized accounting for bioavailability and model input uncertainties. RESULTS: The zinc intake of about one-third of both study populations, which did not differ significantly in their rates of zinc deficiency, was below the Estimated Average Requirement (EAR) for zinc. Scenario analyses predicted that at the current rate of food consumption, it would take up to 60 years for 97.5% of the population to meet their zinc EARs. Fortification of wheat flour and biofortification of wheat grains would result in 93% and 88% of the population, respectively, achieving their EARs in 15 years. CONCLUSIONS: The modeled results suggest that fortification and biofortification are the most effective and sustainable strategies to combat zinc deficiency. The methodology developed in this study is general and is shown to be a useful tool for the analysis of possible future trends and intervention scenarios.

Iron bioavailability in 8-24-month-old Thai children from a micronutrient-fortified quick-cooking rice containing ferric ammonium citrate or a mixture of ferrous sulphate and ferric sodium ethylenediaminetetraacetic acid.

A quick-cooking rice, produced from broken rice, is a convenient ingredient for complementary foods in Thailand. The rice is fortified with micronutrients including iron during the processing procedure, which can cause unacceptable sensory changes. A quick-cooking rice fortified with ferric ammonium citrate (FAC) or a mixture of ferrous sulphate (FeSO4 ) and ferric sodium ethylenediaminetetraacetic acid (NaFeEDTA), with a 2:1 molar ratio of iron from FeSO4 : iron from NaFeEDTA (FeSO4 + NaFeEDTA), gave a product that was organoleptically acceptable. The study compared iron absorption by infants and young children fed with micronutrient-fortified quick-cooking rice containing the test iron compounds or FeSO4 . Micronutrient-fortified quick-cooking rice prepared as a traditional Thai dessert was fed to two groups of 15 8-24-month healthy Thai children. The iron fortificants were isotopically labelled with (57) Fe for the reference FeSO4 or (58) Fe for the tested fortificants, and iron absorption was quantified based on erythrocyte incorporation of the iron isotopes 14 days after feeding. The relative bioavailability of FAC and of the FeSO4 + NaFeEDTA was obtained by comparing their iron absorption with that of FeSO4 . Mean fractional iron absorption was 5.8% [±standard error (SE) 1.9] from FAC and 10.3% (±SE 1.9) from FeSO4 + NaFeEDTA. The relative bioavailability of FAC was 83% (P = 0.02). The relative bioavailability of FeSO4 + NaFeEDTA was 145% (P = 0.001). Iron absorption from the rice containing FAC or FeSO4 + NaFeEDTA was sufficiently high to be used in its formulation, although iron absorption from FeSO4 + NaFeEDTA was significantly higher (P < 0.00001).

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.

Phytic acid concentration influences iron bioavailability from biofortified beans in Rwandese women with low iron status.

BACKGROUND: The common bean is a staple crop in many African and Latin American countries and is the focus of biofortification initiatives. Bean iron concentration has been doubled by selective plant breeding, but the additional iron is reported to be of low bioavailability, most likely due to high phytic acid (PA) concentrations. OBJECTIVE: The present study evaluated the impact of PA on iron bioavailability from iron-biofortified beans. METHODS: Iron absorption, based on erythrocyte incorporation of stable iron isotopes, was measured in 22 Rwandese women who consumed multiple, composite bean meals with potatoes or rice in a crossover design. Iron absorption from meals containing biofortified beans (8.8 mg Fe, 1320 mg PA/100 g) and control beans (5.4 mg Fe, 980 mg PA/100 g) was measured with beans containing either their native PA concentration or with beans that were ∼50% dephytinized or >95% dephytinized. RESULTS: The iron concentration of the cooked composite meals with biofortified beans was 54% higher than in the same meals with control beans. With native PA concentrations, fractional iron absorption from the control bean meals was 9.2%, 30% higher than that from the biofortified bean meals (P < 0.001). The quantity of iron absorbed from the biofortified bean meals (406 µg) was 19% higher (P < 0.05) than that from the control bean meals. With ∼50% and >95% dephytinization, the quantity of iron absorbed from the biofortified bean meals increased to 599 and 746 µg, respectively, which was 37% (P < 0.005) and 51% (P < 0.0001) higher than from the control bean meals. CONCLUSIONS: PA strongly decreases iron bioavailability from iron-biofortified beans, and a high PA concentration is an important impediment to the optimal effectiveness of bean iron biofortification. Plant breeders should focus on lowering the PA concentration of high-iron beans. This trial was registered at clinicaltrials.gov as NCT01521273.

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.