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.

Ensuring the Efficacious Iron Fortification of Foods: A Tale of Two Barriers.

Iron fortification of foods has always been a challenge. This is because iron fortification compounds vary widely in relative absorption; because many foods undergo unacceptable changes in color or flavor from the addition of iron; and because many of the iron-fortified foods contain potent inhibitors of iron absorption. These technical barriers have largely been overcome, and efficacious iron-fortified foods, that maintain or improve the iron status of women or children in long-term feeding studies, can be designed. Commercially fortified infant foods are efficacious, and other commercial iron-fortified foods targeted at women and children will provide a useful amount of iron provided the fortification level is adjusted according to the relative absorption of the iron compound. Technologies for the large-scale fortification of wheat and maize flour are also well established, and iron fortification of rice, using the recently developed extruded premix technique, is showing great promise. However, some important knowledge gaps still remain, and further research and development is needed in relation to iron (and iodine)-fortified salt and iron-fortified liquid milk. The usefulness of less-soluble iron compounds, such as ferrous fumarate, to fortify foods for infants and young children in low- and middle-income countries (LMICs) also needs further investigation. A more formidable barrier to efficacious iron-fortified food has been reported in recent years. This is the infection-initiated inflammation barrier, which inhibits iron absorption in response to infection. This barrier is particularly important in LMICs where infections such as malaria and HIV are widespread, and gastrointestinal infections are common due to poor quality water supplies and sanitation. Another source of inflammation in such countries is the high prevalence of obesity in women. Most countries in sub-Saharan Africa have high inflammation which not only decreases the efficacy of iron-fortified and iron-biofortified foods but complicates the monitoring of large-scale iron fortification programs. This is because iron deficiency anemia cannot be differentiated from the more prominent anemia of inflammation and because inflammation confounds the measurement of iron status. There is an urgent need to better quantify the impact of inflammation on the efficacy of iron-fortified foods. However, at present, in LMICs with high inflammation exposure, infection control, cleaner water, improved sanitation, and a decrease in obesity prevalence will undoubtedly have a greater impact on iron status and anemia than the iron fortification of foods.

Iron Bioavailability from Ferrous Ammonium Phosphate, Ferrous Sulfate, and Ferric Pyrophosphate in an Instant Milk Drink-A Stable Isotope Study in Children.

Ferrous ammonium phosphate (FAP) is an iron salt that has been developed for the fortification of food matrices sensitive to color and flavor changes. The objective of the study was to measure iron absorption from FAP in young children and compare it to a previous evaluation of FAP in young women. A double-blind randomized crossover study with two parallel arms was used to evaluate the iron absorption from FAP added to reconstituted milk powder in comparison to that from ferrous sulfate (FeSO4) and ferric pyrophosphate (FePP). Iron absorption was measured in 39 children aged 3- to 6-years-old using erythrocyte incorporation of stable Fe isotopes (57Fe, 58Fe). The geometric mean iron absorption in iron replete children from FAP, FeSO4 and FePP from milk was 8.3%, 7.6% and 2.1%, respectively. Iron absorption from FAP and FeSO4 fortified milk was not significantly different (p = 0.199); however, it was significantly higher than from FePP fortified milk (p < 0.001). Iron bioavailability from FAP and FePP relative to FeSO4 (relative bioavailability (RBV)) was 110% and 33%, respectively. The RBV of FAP (110%) in iron replete children was higher than previously reported RBV (71%) in mainly iron deficient women. The difference in iron status between the children and women in the respective studies may explain the different RBV values and is discussed.

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.

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.

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.

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.

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.

Iron Fortified Complementary Foods Containing a Mixture of Sodium Iron EDTA with Either Ferrous Fumarate or Ferric Pyrophosphate Reduce Iron Deficiency Anemia in 12- to 36-Month-Old Children in a Malaria Endemic Setting: A Secondary Analysis of a Cluster-Randomized Controlled Trial.

Iron deficiency anemia (IDA) is a major public health problem in sub-Saharan Africa. The efficacy of iron fortification against IDA is uncertain in malaria-endemic settings. The objective of this study was to evaluate the efficacy of a complementary food (CF) fortified with sodium iron EDTA (NaFeEDTA) plus either ferrous fumarate (FeFum) or ferric pyrophosphate (FePP) to combat IDA in preschool-age children in a highly malaria endemic region. This is a secondary analysis of a nine-month cluster-randomized controlled trial conducted in south-central Côte d'Ivoire. 378 children aged 12-36 months were randomly assigned to no food intervention (n = 125; control group), CF fortified with 2 mg NaFeEDTA plus 3.8 mg FeFum for six days/week (n = 126; FeFum group), and CF fortified with 2 mg NaFeEDTA and 3.8 mg FePP for six days/week (n = 127; FePP group). The outcome measures were hemoglobin (Hb), plasma ferritin (PF), iron deficiency (PF < 30 µg/L), and anemia (Hb < 11.0 g/dL). Data were analyzed with random-effect models and PF was adjusted for inflammation. The prevalence of Plasmodium falciparum infection and inflammation during the study were 44-66%, and 57-76%, respectively. There was a significant time by treatment interaction on IDA (p = 0.028) and a borderline significant time by treatment interaction on iron deficiency with or without anemia (p = 0.068). IDA prevalence sharply decreased in the FeFum (32.8% to 1.2%, p < 0.001) and FePP group (23.6% to 3.4%, p < 0.001). However, there was no significant time by treatment interaction on Hb or total anemia. These data indicate that, despite the high endemicity of malaria and elevated inflammation biomarkers (C-reactive protein or α-1-acid-glycoprotein), IDA was markedly reduced by provision of iron fortified CF to preschool-age children for 9 months, with no significant differences between a combination of NaFeEDTA with FeFum or NaFeEDTA with FePP. However, there was no overall effect on anemia, suggesting most of the anemia in this setting is not due to ID. This trial is registered at clinicaltrials.gov (NCT01634945).

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 Proportion of Anemia Associated with Iron Deficiency in Low, Medium, and High Human Development Index Countries: A Systematic Analysis of National Surveys.

Iron deficiency is commonly assumed to cause half of all cases of anemias, with hereditary blood disorders and infections such as hookworm and malaria being the other major causes. In countries ranked as low, medium, and high by the Human Development Index, we conducted a systematic review of nationally representative surveys that reported the prevalence of iron deficiency, iron deficiency anemia, and anemia among pre-school children and non-pregnant women of reproductive age. Using random effects meta-analyses techniques, data from 23 countries for pre-school children and non-pregnant women of reproductive age was pooled, and the proportion of anemia attributable to iron deficiency was estimated by region, inflammation exposure, anemia prevalence, and urban/rural setting. For pre-school children and non-pregnant women of reproductive age, the proportion of anemia associated with iron deficiency was 25.0% (95% CI: 18.0, 32.0) and 37.0% (95% CI: 28.0, 46.0), respectively. The proportion of anemia associated with iron deficiency was lower in countries where anemia prevalence was >40%, especially in rural populations (14% for pre-school children; 16% for non-pregnant women of reproductive age), and in countries with very high inflammation exposure (20% for pre-school children; 25% for non-pregnant women of reproductive age). Despite large heterogeneity, our analyses suggest that the proportion of anemia associated with iron deficiency is lower than the previously assumed 50% in countries with low, medium, or high Human Development Index ranking. Anemia-reduction strategies and programs should be based on an analysis of country-specific data, as iron deficiency may not always be the key determinant of anemia.

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.

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.

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.

In Ivorian school-age children, infection with hookworm does not reduce dietary iron absorption or systemic iron utilization, whereas afebrile Plasmodium falciparum infection reduces iron absorption by half.

BACKGROUND: In sub-Saharan Africa, parasitic diseases and low bioavailable iron intake are major causes of anemia. Anemia results from inflammation, preventing iron recycling and decreasing dietary iron absorption. Hookworm, Plasmodium, and Schistosoma infections contribute to anemia, but their influence on dietary iron absorption and recycling is unknown. OBJECTIVE: The objective was to measure inflammation biomarkers, hepcidin, iron absorption, and utilization pre- and posttreatment in children with afebrile malaria, hookworm, and Schistosoma haematobium infection. DESIGN: Ivorian children aged 11-17 y with afebrile Plasmodium falciparum (n = 17), hookworm (n = 16), or S. haematobium infection (n = 8) consumed a syrup containing 3 mg 57Fe as ferrous sulfate and received an intravenous infusion of 50 µg 58Fe as ferrous citrate. Children were treated for their respective infection, and the iron studies were repeated 4 wk later. Iron and inflammation biomarkers and hepcidin were measured. RESULTS: Geometric mean iron absorptions in the afebrile malaria and hookworm groups were 12.9% and 32.2% (P < 0.001) before treatment and 23.6% and 30.0% (P = 0.113) after treatment, respectively. Treatment of afebrile malaria reduced inflammation (P < 0.001) and serum hepcidin (P = 0.004) and improved iron absorption (P = 0.003). Treatment of hookworm infection neither affected inflammation biomarkers nor altered iron absorption. Similarly, there was a lack of treatment effects in the S. haematobium-infected group; however, the small sample size limits conclusions. Geometric mean iron utilization ranged between 79.1% and 88.0% in the afebrile malaria and hookworm groups with no significant differences pre- and posttreatment. CONCLUSIONS: In school-age children, hookworm infection does not produce inflammation or increase serum hepcidin, and it does not influence iron absorption or utilization. In contrast, afebrile malaria causes inflammation, increases hepcidin, and reduces iron absorption but not utilization. These findings provide insights into the iron metabolism and the etiology of anemia in parasitic infections.