Precision Nutrition Opportunities to Help Mitigate Nutrition and Health Challenges in Low- and Middle-Income Countries: An Expert Opinion Survey.

Precision nutrition involves several data collection methods and tools that aim to better inform nutritional recommendations and improve dietary intake, nutritional status, and health outcomes. While the benefits of collecting precise data and designing well-informed interventions are vast, it is presently unclear whether precision nutrition is a relevant approach for tackling nutrition challenges facing populations in low- and middle-income countries (LMIC), considering infrastructure, affordability, and accessibility of approaches. The Swiss Food & Nutrition Valley (SFNV) Precision Nutrition for LMIC project working group assessed the relevance of precision nutrition for LMIC by first conducting an expert opinion survey and then hosting a workshop with nutrition leaders who live or work in LMIC. The experts were interviewed to discuss four topics: nutritional problems, current solutions, precision nutrition, and collaboration. Furthermore, the SFNV Precision Nutrition for LMIC Virtual Workshop gathered a wider group of nutrition leaders to further discuss precision nutrition relevance and opportunities. Our study revealed that precision public health nutrition, which has a clear focus on the stratification of at-risk groups, may offer relevant support for nutrition and health issues in LMIC. However, funding, affordability, resources, awareness, training, suitable tools, and safety are essential prerequisites for implementation and to equitably address nutrition challenges in low-resource communities.

Knowledge, Attitudes and Practices of Pregnant Women and Healthcare Providers in Bangladesh regarding Multivitamin Supplements during Pregnancy.

Micronutrient deficiencies are widespread among pregnant women in low- and middle-income countries (LMIC) and lead to potentially adverse effects for mother and baby. In Bangladesh, maternal malnutrition remains a severe problem, with high rates of anemia (49.6% of pregnant women and 47.8% of lactating women are anemic) and other nutritional deficiencies. A Knowledge, Attitudes, and Practices (KAP) study was conducted to assess Bangladeshi pregnant women's perceptions and related behaviors, as well as awareness and knowledge among pharmacists and healthcare professionals concerning prenatal multivitamin supplements. This was done in both rural and urban areas across Bangladesh. A total of 732 quantitative interviews were conducted (330 with providers and 402 with pregnant women, with an equal split between urban and rural areas for both sets of audiences; 200 women were users of prenatal multivitamin supplements, while 202 women were aware non-users). The study identified a few findings that can guide further research or market-based interventions to reduce micronutrient deficiencies. These include most pregnant women not knowing the right time to start multivitamin supplements (56.0%, [n = 225], stating that a woman should start taking supplements 'after the first trimester'), not knowing their benefits, and how they help both the mother and baby-only 29.5% [n = 59] stated that they believed the supplements helped their baby to grow well). Further, barriers to taking the supplements include women believing a nutritious diet is a substitute (88.7% [n = 293]), and a perceived lack of support from other family members (21.8%, [n = 72]). This suggests that there is a need for further awareness-raising among all pregnant women, their family members, and providers.

Evaluation of spray-dried eggs as a micronutrient-rich nutritional supplement.

Regular consumption of hen eggs can help to prevent deficiencies of essential nutrients, such as essential amino acids, vitamin A and E or trace elements zinc and selenium, for vulnerable populations. This study focused on assessing the nutritional value of spray-dried eggs, favored by their manufacturability, storability and ease of addition to (complementary) foods. Using a wide range of analytical techniques, we recorded and compared the nutrient profiles of commercially produced pasteurized whole eggs and their respective powder samples spray-dried at 160°C. Important nutrients that were not significantly affected by spray-drying include total fat content, several amino acids, α- and δ-tocopherol, lutein, zeaxanthin, essential trace elements and cobalamin. The most notable mean losses were found for unsaturated fatty acids, e.g., linoleic (by -38.7%, from 4.11 ± 0.45 to 2.52 ± 0.75 g/100 g DM) and linolenic acid (by -60.8%, from 0.76 ± 0.05 to 0.30 ± 0.04 g/100 g DM). Despite recording significant retinol losses in two out of three batches, the overall low reduction of -14% recommend spray-dried eggs as a valuable source of vitamin A. A daily intake of spray-dried egg powder corresponding to one medium sized egg meets dietary reference values for children, e.g., by 100% for vitamin E, by 24% for retinol, by 61% for selenium and by 22% for zinc. In conclusion, even though a dry weight comparison favors supplementation with pasteurized whole eggs, our results demonstrate a high potential for spray-dried eggs as nutritional supplement. However, the spray-drying process should be optimized toward higher retentions of unsaturated fatty acids and retinol.

Small and Medium Enterprises' Perspectives on Food Fortification Amid the Growing Burden of Malnutrition.

The need for a profound food system transformation has never been greater. The growing burden of malnutrition has become the new normal, with two billion people who are overweight, over 140 million children under five who are stunted and over two billion people affected by hidden hunger. Food fortification has been recognized as a cost-effective strategy to address micronutrient deficiencies. Small and medium enterprises (SMEs) play a strategic role in the food supply chain in low- and middle-income countries, accounting for over 80% of food sales. It is therefore critical to create an enabling environment to facilitate SMEs' involvement in food fortification practices as a potential solution to tackle all forms of malnutrition. This review highlights SMEs' relevance as agents of change in the food system through food fortification practices and their indirect yet key role in producing nutritious, tasty and affordable foods. It discusses their challenges (e.g., access to long-term finance, sustainable technical assistance, limited capacity), presents solutions and discusses how different actors can help SMEs to overcome these challenges. Furthermore, it presents a relevant public-private partnership case study to demonstrate how SMEs can address the growing burden of malnutrition through food fortification practices, nutrient profiling schemes and demand generation.

Effect of multiple micronutrient supplements vs iron and folic acid supplements on neonatal mortality: a reanalysis by iron dose.

OBJECTIVE: Antenatal multiple micronutrient supplements (MMS) are a cost-effective intervention to reduce adverse pregnancy and birth outcomes. However, the current WHO recommendation on the use of antenatal MMS is conditional, partly due to concerns about the effect on neonatal mortality in a subgroup of studies comparing MMS with iron and folic acid supplements (IFA) containing 60 mg of iron. We aimed to assess the effect of MMS vs IFA on neonatal mortality stratified by iron dose in each supplement. METHODS: We updated the neonatal mortality analysis of the 2020 WHO guidelines using the generic inverse variance method and applied the random effects model to calculate the effect estimates of MMS vs. IFA on neonatal mortality in subgroups of trials (n=13) providing the same or different amounts of iron, i.e. MMS with 60 mg of iron vs IFA with 60 mg of iron; MMS with 30 mg of iron vs IFA with 30 mg of iron; MMS with 30 mg of iron vs IFA with 60 mg of iron; and MMS with 20 mg of iron vs IFA with 60 mg of iron. RESULTS: There were no statistically significant differences in neonatal mortality between MMS and IFA within any of the subgroups of trials. Analysis of MMS with 30 mg vs IFA with 60 mg of iron (7 trials, 14,114 participants), yielded a nonsignificant Risk Ratio (RR) of 1.12 (95% CI 0.83 to 1.50). CONCLUSION: Neonatal mortality did not differ between MMS and IFA regardless of iron dose in either supplement.

Multiple micronutrient supplements versus iron-folic acid supplements and maternal anemia outcomes: an iron dose analysis.

Antenatal multiple micronutrient supplements (MMS) are more effective than iron and folic acid (IFA) supplements in reducing adverse pregnancy outcomes. Questions remain, however, about the ability of MMS to prevent anemia as effectively as IFA, especially at a lower dose of daily iron and in areas of high anemia prevalence. Analyzing data from 11 trials from a recent Cochrane review, we compared MMS to IFA, delivering either 30 or 60 mg of iron, in sustaining hemoglobin and preventing third trimester anemia and iron deficiency anemia (IDA), accounting for daily iron dose, total supplemental iron intake, and baseline prevalence of anemia. There were no differences between MMS and IFA in third trimester hemoglobin concentration or risks of anemia or IDA by iron dose or total supplemental iron consumed. MMS providing 30 mg of iron was comparable to IFA with 60 mg of iron: mean hemoglobin difference of -0.26 g/L (95% CI: -1.41 to 0.89), risk ratios of 0.99 (95% CI: 0.92-1.07) for anemia, and 1.31 (95% CI: 0.66-2.60) for IDA. Baseline prevalence of anemia did not explain heterogeneity in findings. Compared to IFA, MMS results in comparable hemoglobin concentration and protection against anemia during pregnancy, independently of iron dose.

Interventions to improve calcium intake through foods in populations with low intake.

Calcium intake remains inadequate in many low- and middle-income countries, especially in Africa and South Asia, where average intakes can be below 400 mg/day. Given the vital role of calcium in bone health, metabolism, and cell signaling, countries with low calcium intake may want to consider food-based approaches to improve calcium consumption and bioavailability within their population. This is especially true for those with low calcium intake who would benefit the most, including pregnant women (by reducing the risk of preeclampsia) and children (by reducing calcium-deficiency rickets). Specifically, some animal-source foods that are naturally high in bioavailable calcium and plant foods that can contribute to calcium intake could be promoted either through policies or educational materials. Some food processing techniques can improve the calcium content in food or increase calcium bioavailability. Staple-food fortification with calcium can also be a cost-effective method to increase intake with minimal behavior change required. Lastly, biofortification is currently being investigated to improve calcium content, either through genetic screening and breeding of high-calcium varieties or through the application of calcium-rich fertilizers. These mechanisms can be used alone or in combination based on the local context to improve calcium intake within a population.

The Potential Impact of Climate Change on the Micronutrient-Rich Food Supply.

Micronutrient deficiencies are a major cause of morbidity and mortality in low- and middle-income countries worldwide. Climate change, characterized by increasing global surface temperatures and alterations in rainfall, has the capacity to affect the quality and accessibility of micronutrient-rich foods. The goals of this review are to summarize the potential effects of climate change and its consequences on agricultural yield and micronutrient quality, primarily zinc, iron, and vitamin A, of plant foods and upon the availability of animal foods, to discuss the implications for micronutrient deficiencies in the future, and to present possible mitigation and adaptive strategies. In general, the combination of increasing atmospheric carbon dioxide and rising temperature is predicted to reduce the overall yield of major staple crops, fruits, vegetables, and nuts, more than altering their micronutrient content. Crop yield is also reduced by elevated ground-level ozone and increased extreme weather events. Pollinator loss is expected to reduce the yield of many pollinator-dependent crops such as fruits, vegetables, and nuts. Sea-level rise resulting from melting of ice sheets and glaciers is predicted to result in coastal inundation, salt intrusion, and loss of coral reefs and mangrove forests, with an adverse impact upon coastal rice production and coastal fisheries. Global ocean fisheries catch is predicted to decline because of ocean warming and declining oxygen. Freshwater warming is also expected to alter ecosystems and reduce inland fisheries catch. In addition to limiting greenhouse gas production, adaptive strategies include postharvest fortification of foods; micronutrient supplementation; biofortification of staple crops with zinc and iron; plant breeding or genetic approaches to increase zinc, iron, and provitamin A carotenoid content of plant foods; and developing staple crops that are tolerant of abiotic stressors such as elevated carbon dioxide, elevated temperature, and increased soil salinity.

The Future of Moringa Foods: A Food Chemistry Perspective.

The tree Moringa oleifera Lam. provides its leaves, pods, flowers and seeds for human nutrition. The chemical profile of all these Moringa products varies substantially, not only among the different parts of the plants used. Cultivating, processing as well as storage conditions chiefly determine the contents of nutrients and anti-nutritive constituents. Anti-nutrients, e.g., phytic acid or tannins, are present in notable amounts and may affect micronutrient bioavailability. Although Moringa oleifera products have been promoted for several health benefits and are discussed as an alternative treatment in various diseases, risk assessment studies evaluating contamination levels are scarce. Recent investigations have demonstrated alarming contents of heavy metals, polycyclic aromatic hydrocarbons and mycotoxins in Moringa oleifera products, indicating the need for a comprehensive risk assessment and contingent legal regulation of these products. In this mini review, we briefly outline pivotal, food chemistry and nutrition related data on Moringa preparations in order to stimulate in-depth research to close the presented knowledge gaps.

Food Fortification: The Advantages, Disadvantages and Lessons from Sight and Life Programs.

Deficiencies in one or more micronutrients such as iron, zinc, and vitamin A are widespread in low- and middle-income countries and compromise the physical and cognitive capacity of millions of people. Food fortification is a cost-effective strategy with demonstrated health, economic and social benefits. Despite ongoing debates globally and in some countries regarding the performance and safety of food fortification, the practice offers significant benefits across each of the main vehicles for food fortification (large-scale food fortification, biofortification and point-of-use or home fortification) ranging from reducing the prevalence of nutritional deficiencies and economic benefits to societies and economies. Using Sight and Life's global and national experiences in implementing food fortification efforts, we demonstrate how different programs in LMICs have successfully addressed challenges with food fortification and in doing so, find that these efforts are most successful when partnerships are formed that include the public and private sector as well as other parties that can provide support in key areas such as advocacy, management, capacity building, implementation and regulatory monitoring.

The True Value of Spirulina.

Algae products are attracting growing interest due to their pleasant taste and their high contents in protein, essential amino acids, vitamins, and minerals. Specifically, spirulina products are widely promoted for their high vitamin B12 content. So far, knowledge regarding the contamination with cyanotoxins, heavy metals, pesticides, or polycyclic aromatic hydrocarbons (PAHs) is scarce, although some studies reported high contaminant levels in spirulina products. The regular intake of spirulina, and very likely other algae products as well, as a dietary supplement in the gram range demands a closer monitoring of potentially harmful constituents.

Inadequacy of nutrients and contaminants found in porridge-type complementary foods in Rwanda.

Child malnutrition remains persistently high in Rwanda. Complementary foods play a key role in young child nutrition. This study explores the quality and safety of complementary food products available in the Rwandan market. Ten of the most consumed porridge-type complementary food products in Rwanda have been analysed. Mean values of macronutrient and micronutrient contents were compared against three international standards and evaluated against label claims. Mean mycotoxin, microbiological, and pesticide contamination were compared with maximum tolerable limits. Mean energy density (385 kcal/100 g) and total fat content (7.9 g/100 g) were lower than all three international benchmarks. The mean fibre content of 8.5 g/100 g was above the maximum recommended amount of Codex Alimentarius and more than double the amount claimed on labels. Mean levels of vitamin A (retinyl palmitate, 0.54 mg/100 g) and vitamin E (α-tocopherol, 3.7 mg/100 g) fell significantly short of all three standards, whereas calcium and zinc requirements were only partially met. Average iron content was 12.1 mg/100 g. The analysis revealed a mean aflatoxin contamination of 61 µg/kg, and high mold and yeast infestation. Escherichia coli and pesticide residues were found, whereas no heavy metals could be quantitated. Overall, complementary food products in Rwanda show inadequate nutrient contents and high aflatoxin and microbial contamination levels. Improved regulation and monitoring of both local and imported products are needed to improve the quality and safety of complementary foods in Rwanda.

Perspective: Integration to Implementation (I-to-I) and the Micronutrient Forum-Addressing the Safety and Effectiveness of Vitamin A Supplementation.

An ongoing challenge to our ability to address the role of food and nutrition in health promotion and disease prevention is how to design and implement context-specific interventions and guidance that are safe, efficacious, and avoid unintended consequences. The integration to effective implementation (I-to-I) concept is intended to address the complexities of the global health context through engagement of the continuum of stakeholders involved in the generation, translation, and implementation of evidence to public health guidance/programs. The I-to-I approach was developed under the auspices of the Micronutrient Forum and has been previously applied to the question of safety and effectiveness of interventions to prevent and treat nutritional iron deficiency. The present article applies the I-to-I approach to questions regarding the safety and utility of large-dose vitamin A supplementation programs, and presents the authors' perspective on key aspects of the topic, including coverage of the basic and applied biology of vitamin A nutrition and assessment, clinical implications, and an overview of the extant data with regard to both the justification for and utility of available intervention strategies. The article includes some practical considerations based on specific country experiences regarding the challenges of implementing vitamin A-related programs. This is followed by an overview of some challenges associated with engagement of the enabling communities that play a critical role in the implementation of these types of public health interventions. The article concludes with suggestions for potential approaches to move this important agenda forward.

Including 60 mg Elemental Iron in a Multiple Micronutrient Supplement Blunts the Increase in Serum Zinc after 12 Weeks of Daily Supplementation in Predominantly Anemic, Nonpregnant Cambodian Women of Reproductive Age.

BACKGROUND: Multiple micronutrient (MMN) supplementation may result in interaction effects due to competing absorptive pathways of trace elements. OBJECTIVES: The aim of this study was to investigate the effect of MMN supplementation with or without iron on serum zinc, selenium, and copper concentrations in Cambodian women. METHODS: In a 2 × 2 factorial double-blind randomized 12-wk trial, predominantly anemic, nonpregnant women (aged 18-45 y) received daily 60 mg of iron (Fe; n = 201); 14 other micronutrients including zinc (15 mg), selenium (65 µg), and copper (2 mg), but no iron (MMN; n = 202); 60 mg iron plus MMN (Fe + MMN; n = 206); or a placebo (n = 200). Fasting morning blood was collected at baseline and 12 wk from women in 26 villages in Kampong Chhnang province. Serum zinc, selenium, and copper concentrations (secondary outcomes of the randomized controlled trial) were measured using inductively coupled plasma mass spectrometry. Generalized linear regression was used to estimate intervention effects [ß coefficient (95% CI)] for Fe (with or without MMN) and MMN (with or without Fe) after testing for the presence of an Fe × MMN interaction. RESULTS: A total of 760 women completed the trial. Zinc deficiency prevalence at baseline was 45% (inflammation-adjusted serum zinc <10.7 µmol/L). A significant Fe × MMN interaction (P = 0.02) was detected in the 2 × 2 analysis with serum zinc concentration as the outcome: the MMN group had a higher mean serum zinc concentration at 12 wk (12.3 µmol/L; 95% CI: 12.2, 12.4 µmol/L) compared with all other groups, and the Fe + MMN group had a higher mean serum zinc concentration (11.6 µmol/L; 95% CI: 11.5, 11.7 µmol/L) compared with the Fe group (11.0 µmol/L; 95% CI: 10.9, 11.0 µmol/L) and the placebo group (11.2 µmol/L; 95% CI: 11.1, 11.4 µmol/L). CONCLUSIONS: The inclusion of 60 mg iron in the daily MMN formulation may be interfering with the absorption and/or metabolism of supplemental zinc in Cambodian women. This is of particular concern when MMN supplementation is implemented in populations with risk of zinc deficiency. This trial was registered at clinicaltrials.gov as NCT-02481375.

Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low- and middle-income countries.

Inadequate micronutrient intakes are relatively common in low- and middle-income countries (LMICs), especially among pregnant women, who have increased micronutrient requirements. This can lead to an increase in adverse pregnancy and birth outcomes. This review presents the conclusions of a task force that set out to assess the prevalence of inadequate micronutrient intakes and adverse birth outcomes in LMICs; the data from trials comparing multiple micronutrient supplements (MMS) that contain iron and folic acid (IFA) with IFA supplements alone; the risks of reaching the upper intake levels with MMS; and the cost-effectiveness of MMS compared with IFA. Recent meta-analyses demonstrate that MMS can reduce the risks of preterm birth, low birth weight, and small for gestational age in comparison with IFA alone. An individual-participant data meta-analysis also revealed even greater benefits for anemic and underweight women and female infants. Importantly, there was no increased risk of harm for the pregnant women or their infants with MMS. These data suggest that countries with inadequate micronutrient intakes should consider supplementing pregnant women with MMS as a cost-effective method to reduce the risk of adverse birth outcomes.

Situation analysis of procurement and production of multiple micronutrient supplements in 12 lower and upper middle-income countries.

Globally, there are few vitamin and mineral ingredient manufacturers. To support local, in-country or regional procurement and production of multiple micronutrient supplements (MMS), the following production scenarios are possible: (a) straight ingredients of vitamins and minerals forms imported or locally produced that are mixed, tableted, or encapsulated and packaged by a local manufacturer; (b) import or local production of a vitamin and minerals premix that is tableted or encapsulated and packaged locally; (c) import of a bulk, finished product (tablets or capsules) that is packaged and branded; and (d) or import of a branded packaged product. This paper is a situation analysis of the market, manufacturing, and policy factors that are driving the production of MMS in 12 lower and upper middle-income countries. Key informants completed a self-administered structured questionnaire, which examined the local context of products available in the market and their cost, regulations and policies, in Brazil, Colombia, Guatemala, Mexico, Peru, Bangladesh, India, Vietnam, Ghana, Kenya, Nigeria, and South Africa. Our study found that although most countries have the capacity to produce locally MMS, the major barriers observed for sustainable and affordable production include (a) poor technical capacity and policies for ensuring quality along the value chain and (b) lack of policy coherence to incentivize local production and lower the manufacture and retail price of MMS. Also, better guidelines and government oversight will be required because not one country had an MMS formulation that matched the globally recommended formulation of the United Nations Multiple Micronutrient Preparation (UNIMMAP).

Low serum ω-3 and ω-6 polyunsaturated fatty acids and other metabolites are associated with poor linear growth in young children from rural Malawi.

Background: Stunting affects ∼25% of children <5 y of age and is associated with impaired cognitive and motor development and increased morbidity and mortality. The pathogenesis of stunting is poorly understood.Objective: The purpose of this study was to identify altered metabolic pathways associated with child stunting.Design: We measured 677 serum metabolites using liquid chromatography-tandem mass spectrometry in a cross-sectional study of 400 Malawian children aged 12-59 mo, of whom 62% were stunted.Results: A low height-for-age z score (HAZ) was associated with lower serum concentrations of 1) ω-3 (n-3) and ω-6 (n-6) polyunsaturated fatty acids (PUFAs), 2) sulfated neurosteroids, which play a role in brain development, 3) carnitine, a conditionally essential nutrient with an important role in the carnitine shuttle for the metabolism of fatty acids and energy production, and 4) γ-glutamyl amino acids, which represent an altered γ-glutamyl cycle of glutathione metabolism. A low HAZ was associated with significantly higher serum concentrations of 5 biomarkers related to cigarette smoke exposure.Conclusions: This metabolomics study shows a cross-sectional association between stunting and low serum ω-3 and ω-6 long-chain PUFAs, which are essential for growth and development; low sulfated neurosteroids, which play a role in brain development; low carnitine, which is essential for ß-oxidation of fatty acids; alterations in glutathione metabolism; and increased serum metabolites that are associated with secondhand tobacco smoke exposure. This trial was registered at www.controlled-trials.com as ISRCTN14597012.

The effect of oral iron with or without multiple micronutrients on hemoglobin concentration and hemoglobin response among nonpregnant Cambodian women of reproductive age: a 2 x 2 factorial, double-blind, randomized controlled supplementation trial.

Background: Despite a high prevalence of anemia among nonpregnant Cambodian women, current reports suggest that iron deficiency (ID) prevalence is low. If true, iron supplementation will not be an effective anemia reduction strategy.Objective: We measured the effect of daily oral iron with or without multiple micronutrients (MMNs) on hemoglobin concentration in nonpregnant Cambodian women screened as anemic.Design: In this 2 × 2 factorial, double-blind, randomized trial, nonpregnant women (aged 18-45 y) with hemoglobin concentrations ≤117 g/L (capillary blood) were recruited from 26 villages in Kampong Chhnang province and randomly assigned to receive 12 wk of iron (60 mg; Fe group), MMNs (14 other micronutrients; MMN group), iron plus MMNs (Fe+MMN group), or placebo capsules. A 2 × 2 factorial intention-to-treat analysis with the use of a generalized mixed-effects model was used to assess the effects of iron and MMNs and the interaction between these factors. Results: In July 2015, 809 women were recruited and 760 (94%) completed the trial. Baseline anemia prevalence was 58% (venous blood). Mean (95% CI) hemoglobin concentrations at 12 wk in the Fe, MMN, Fe+MMN, and placebo groups were 121 (120, 121), 116 (116, 117), 123 (122, 123), and 116 (116, 117) g/L, with no iron × MMN interaction (P = 0.66). Mean (95% CI) increases in hemoglobin were 5.6 g/L (3.8, 7.4 g/L) (P < 0.001) among women who received iron (n = 407) and 1.2 g/L (-0.6, 3.0 g/L) (P = 0.18) among women who received MMNs (n = 407). The predicted proportions (95% CIs) of women with a hemoglobin response (≥10 g/L at 12 wk) were 19% (14%, 24%), 9% (5%, 12%), 30% (24%, 35%), and 5% (2%, 9%) in the Fe, MMN, Fe+MMN, and placebo groups, respectively.Conclusions: Daily iron supplementation for 12 wk increased hemoglobin in nonpregnant Cambodian women; however, MMNs did not confer additional significant benefit. Overall, ∼24% of women who received iron responded after 12 wk; even fewer would be likely to respond in the wider population. This trial was registered at clinicaltrials.gov as NCT02481375.