A systematic review of the impacts of post-harvest handling on provitamin A, iron and zinc retention in seven biofortified crops.

Post-harvest handling can affect micronutrient retention in biofortified crops through to the point of consumption. Here we conduct a systematic review identifying 67 articles examining the retention of micronutrients in conventionally bred biofortified maize, orange sweet potato, cassava, pearl millet, rice, beans and wheat. Provitamin A crops maintain high amounts compared with non-biofortified counterparts. Iron and zinc crops have more variability in micronutrient retention dependent on processing method; for maximum iron and zinc content, whole grain product consumption such as whole wheat flour or only slightly milled brown rice is beneficial. We offer preliminary suggestions for households, regulatory bodies and programme implementers to increase consumer awareness on best practices for preparing crops to maximize micronutrient content, while highlighting gaps in the literature. Our online, interactive Micronutrient Retention Dashboard ( https://www.cpnh.cornell.edu/mn-retention-db ) offers an at-a-glance view of the compiled minimum and maximum retention found, organized by processing method.

A randomized trial of iron- and zinc-biofortified pearl millet-based complementary feeding in children aged 12 to 18 months living in urban slums.

BACKGROUND & AIMS: Biofortification of staple crops with higher levels of micronutrients via traditional breeding methods is a sustainable strategy and can possibly complement fortification and other interventions to target micronutrient deficiencies in low resource settings, particularly among vulnerable populations such as children. We aimed to determine if iron- and zinc-biofortified pearl millet (FeZnPM, Dhanashakti, ICTP-8203Fe)-based complementary feeding improves nutritional status, including iron biomarkers and growth, in children living in urban slums of Mumbai. METHODS: We conducted a randomized controlled trial of FeZnPM among 223 children aged 12-18 months who were not severely anemic at baseline (hemoglobin ≥9.0 g/dL). Children were randomized to receive either FeZnPM or conventional non-biofortified pearl millet (CPM) daily for 9 months. Iron status (hemoglobin, serum ferritin), plasma zinc, and anthropometric indicators (length, weight, mid-upper arm circumference, triceps and subscapular skinfolds) were evaluated at enrollment and throughout the trial. World Health Organization (WHO) anthropometric z-scores were calculated using WHO growth standards. Primary outcomes were hemoglobin and serum ferritin concentrations, and growth, defined as WHO z-scores. An intent to treat approach was used for analyses. We used the Hodges-Lehmann-Sen test to assess the change in primary outcomes between baseline and the last visit and report corresponding 95% confidence intervals. RESULTS: At baseline, 67.7% of children were anemic (hemoglobin <11.0 g/dL) and 59.6% were iron deficient (serum ferritin <12.0 µg/L). FeZnPM did not significantly increase iron biomarkers or improve growth, compared to CPM. In subgroup analyses, FeZnPM improved hemoglobin concentrations in male children, and in children with iron deficiency or iron depletion (serum ferritin <25.0 µg/L) at baseline, relative to CPM. CONCLUSIONS: Daily consumption of FeZnPM-based complementary foods did not significantly impact iron and zinc status or growth in children living in Mumbai's urban slums. However, the intervention significantly improved hemoglobin concentrations among male children and among individuals who were iron-deficient or iron-depleted at baseline. TRIAL REGISTRATION: This trial is registered with Clinicaltrials.gov (ID: NCT02233764), and Clinical Trials Registry of India (ID: REF/2014/10/007731).

Review of the Impact Pathways of Biofortified Foods and Food Products.

Biofortification is the process of increasing the concentrations and/or bioavailability of micronutrients in staple crops and has the potential to mitigate micronutrient deficiencies globally. Efficacy trials have demonstrated benefits of consuming biofortified crops (BFCs); and in this paper, we report on the results of a systematic review of biofortified crops effectiveness in real-world settings. We synthesized the evidence on biofortified crops consumption through four Impact Pathways: (1) purchased directly; (2) in informal settings; (3) in formal settings; or (4) in farmer households, from their own production. Twenty-five studies, covering Impact Pathway 1 (five studies), Impact Pathway 2 (three), Impact Pathway 3 (three), Impact Pathway 4 (21) were included. The review found evidence of an improvement in micronutrient status via Impact Pathway 4 (mainly in terms of vitamin A from orange sweet potato) in controlled interventions that involved the creation of demand, the extension of agriculture and promotion of marketing. In summary, evidence supports that biofortified crops can be part of food systems interventions to reduce micronutrient deficiencies in farmer households; ongoing and future research will help fully inform their potential along the other three Impact Pathways for scaling up.

Vitamin B-12 and the Gastrointestinal Microbiome: A Systematic Review.

Vitamin B-12 deficiency is a major public health problem affecting individuals across the lifespan, with known hematological, neurological, and obstetric consequences. Emerging evidence suggests that vitamin B-12 may have an important role in other aspects of human health, including the composition and function of the gastrointestinal (gut) microbiome. Vitamin B-12 is synthesized and utilized by bacteria in the human gut microbiome and is required for over a dozen enzymes in bacteria, compared to only 2 in humans. However, the impact of vitamin B-12 on the gut microbiome has not been established. This systematic review was conducted to examine the evidence that links vitamin B-12 and the gut microbiome. A structured search strategy was used to identify in vitro, animal, and human studies that assessed vitamin B-12 status, dietary intake, or supplementation, and the gut microbiome using culture-independent techniques. A total of 22 studies (3 in vitro, 8 animal, 11 human observational studies) were included. Nineteen studies reported that vitamin B-12 intake, status, or supplementation was associated with gut microbiome outcomes, including beta-diversity, alpha-diversity, relative abundance of bacteria, functional capacity, or short-chain fatty acids (SCFA) production. Evidence suggests that vitamin B-12 may be associated with changes in bacterial abundance. While results from in vitro studies suggest that vitamin B-12 may increase alpha-diversity and shift gut microbiome composition (beta-diversity), findings from animal studies and observational human studies were heterogeneous. Based on evidence from in vitro and animal studies, microbiome outcomes may differ by cobalamin form and co-intervention. To date, few prospective observational studies and no randomized trials have been conducted to examine the effects of vitamin B-12 on the human gut microbiome. The impact of vitamin B-12 on the gut microbiome needs to be elucidated to inform screening and public health interventions.

Effects of oral vitamin D supplementation on linear growth and other health outcomes among children under five years of age.

BACKGROUND: Vitamin D is a secosteroid hormone that is important for its role in calcium homeostasis to maintain skeletal health. Linear growth faltering and stunting remain pervasive indicators of poor nutrition status among infants and children under five years of age around the world, and low vitamin D status has been linked to poor growth. However, existing evidence on the effects of vitamin D supplementation on linear growth and other health outcomes among infants and children under five years of age has not been systematically reviewed. OBJECTIVES: To assess effects of oral vitamin D supplementation on linear growth and other health outcomes among infants and children under five years of age. SEARCH METHODS: In December 2019, we searched CENTRAL, PubMed, Embase, 14 other electronic databases, and two trials registries. We also searched the reference lists of relevant publications for any relevant trials, and we contacted key organisations and authors to obtain information on relevant ongoing and unpublished trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs assessing the effects of oral vitamin D supplementation, with or without other micronutrients, compared to no intervention, placebo, a lower dose of vitamin D, or the same micronutrients alone (and not vitamin D) in infants and children under five years of age who lived in any country. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: Out of 75 studies (187 reports; 12,122 participants) included in the qualitative analysis, 64 studies (169 reports; 10,854 participants) contributed data on our outcomes of interest for meta-analysis. A majority of included studies were conducted in India, USA, and Canada. Two studies reported for-profit funding, two were categorised as receiving mixed funding (non-profit and for-profit), five reported that they received no funding, 26 did not disclose funding sources, and the remaining studies were funded by non-profit funding. Certainty of evidence varied between high and very low across outcomes (all measured at endpoint) for each comparison. Vitamin D supplementation versus placebo or no intervention (31 studies) Compared to placebo or no intervention, vitamin D supplementation (at doses 200 to 2000 IU daily; or up to 300,000 IU bolus at enrolment) may make little to no difference in linear growth (measured length/height in cm) among children under five years of age (mean difference (MD) 0.66, 95% confidence interval (CI) -0.37 to 1.68; 3 studies, 240 participants; low-certainty evidence); probably improves length/height-for-age z-score (L/HAZ) (MD 0.11, 95% CI 0.001 to 0.22; 1 study, 1258 participants; moderate-certainty evidence); and probably makes little to no difference in stunting (risk ratio (RR) 0.90, 95% CI 0.80 to 1.01; 1 study, 1247 participants; moderate-certainty evidence). In terms of adverse events, vitamin D supplementation results in little to no difference in developing hypercalciuria compared to placebo (RR 2.03, 95% CI 0.28 to 14.67; 2 studies, 68 participants; high-certainty evidence). It is uncertain whether vitamin D supplementation impacts the development of hypercalcaemia as the certainty of evidence was very low (RR 0.82, 95% CI 0.35 to 1.90; 2 studies, 367 participants). Vitamin D supplementation (higher dose) versus vitamin D (lower dose) (34 studies) Compared to a lower dose of vitamin D (100 to 1000 IU daily; or up to 300,000 IU bolus at enrolment), higher-dose vitamin D supplementation (200 to 6000 IU daily; or up to 600,000 IU bolus at enrolment) may have little to no effect on linear growth, but we are uncertain about this result (MD 1.00, 95% CI -2.22 to 0.21; 5 studies, 283 participants), and it may make little to no difference in L/HAZ (MD 0.40, 95% CI -0.06 to 0.86; 2 studies, 105 participants; low-certainty evidence). No studies evaluated stunting. As regards adverse events, higher-dose vitamin D supplementation may make little to no difference in developing hypercalciuria (RR 1.16, 95% CI 1.00 to 1.35; 6 studies, 554 participants; low-certainty evidence) or in hypercalcaemia (RR 1.39, 95% CI 0.89 to 2.18; 5 studies, 986 participants; low-certainty evidence) compared to lower-dose vitamin D supplementation. Vitamin D supplementation (higher dose) + micronutrient(s) versus vitamin D (lower dose) + micronutrient(s) (9 studies) Supplementation with a higher dose of vitamin D (400 to 2000 IU daily, or up to 300,000 IU bolus at enrolment) plus micronutrients, compared to a lower dose (200 to 2000 IU daily, or up to 90,000 IU bolus at enrolment) of vitamin D with the same micronutrients, probably makes little to no difference in linear growth (MD 0.60, 95% CI -3.33 to 4.53; 1 study, 25 participants; moderate-certainty evidence). No studies evaluated L/HAZ or stunting. In terms of adverse events, higher-dose vitamin D supplementation with micronutrients, compared to lower-dose vitamin D with the same micronutrients, may make little to no difference in developing hypercalciuria (RR 1.00, 95% CI 0.06 to 15.48; 1 study, 86 participants; low-certainty evidence) and probably makes little to no difference in developing hypercalcaemia (RR 1.00, 95% CI 0.90, 1.11; 2 studies, 126 participants; moderate-certainty evidence). Four studies measured hyperphosphataemia and three studies measured kidney stones, but they reported no occurrences and therefore were not included in the comparison for these outcomes. AUTHORS' CONCLUSIONS: Evidence suggests that oral vitamin D supplementation may result in little to no difference in linear growth, stunting, hypercalciuria, or hypercalcaemia, compared to placebo or no intervention, but may result in a slight increase in length/height-for-age z-score (L/HAZ). Additionally, evidence suggests that compared to lower doses of vitamin D, with or without micronutrients, vitamin D supplementation may result in little to no difference in linear growth, L/HAZ, stunting, hypercalciuria, or hypercalcaemia. Small sample sizes, substantial heterogeneity in terms of population and intervention parameters, and high risk of bias across many of the included studies limit our ability to confirm with any certainty the effects of vitamin D on our outcomes. Larger, well-designed studies of long duration (several months to years) are recommended to confirm whether or not oral vitamin D supplementation may impact linear growth in children under five years of age, among both those who are healthy and those with underlying infectious or non-communicable health conditions.

Nutrition and the Gut Microbiota in 10- to 18-Month-Old Children Living in Urban Slums of Mumbai, India.

In this cross-sectional study, we describe the composition and diversity of the gut microbiota among undernourished children living in urban slums of Mumbai, India, and determine how nutritional status, including anthropometric measurements, dietary intakes from complementary foods, feeding practices, and micronutrient concentrations, is associated with their gut microbiota. We collected rectal swabs from children aged 10 to 18 months living in urban slums of Mumbai participating in a randomized controlled feeding trial and conducted 16S rRNA sequencing to determine the composition of the gut microbiota. Across the study cohort, Proteobacteria dominated the gut microbiota at over 80% relative abundance, with Actinobacteria representation at <4%, suggesting immaturity of the gut. Increased microbial α-diversity was associated with current breastfeeding, greater head circumference, higher fat intake, and lower hemoglobin concentration and weight-for-length Z-score. In redundancy analyses, 47% of the variation in Faith's phylogenetic diversity (Faith's PD) could be accounted for by age and by iron and polyunsaturated fatty acid intakes. Differences in community structure (ß-diversity) of the microbiota were observed among those consuming fats and oils the previous day compared to those not consuming fats and oils the previous day. Our findings suggest that growth, diet, and feeding practices are associated with gut microbiota metrics in undernourished children, whose gut microbiota were comprised mainly of Proteobacteria, a phylum containing many potentially pathogenic taxa.IMPORTANCE The impact of comprehensive nutritional status, defined as growth, nutritional blood biomarkers, dietary intakes, and feeding practices, on the gut microbiome in children living in low-resource settings has remained underreported in microbiome research. Among undernourished children living in urban slums of Mumbai, India, we observed a high relative abundance of Proteobacteria, a phylum including many potentially pathogenic species similar to the composition in preterm infants, suggesting immaturity of the gut, or potentially a high inflammatory burden. We found head circumference, fat and iron intake, and current breastfeeding were positively associated with microbial diversity, while hemoglobin and weight for length were associated with lower diversity. Findings suggest that examining comprehensive nutrition is critical to gain more understanding of how nutrition and the gut microbiota are linked, particularly in vulnerable populations such as children in urban slum settings.

Effect of iron and zinc-biofortified pearl millet consumption on growth and immune competence in children aged 12-18 months in India: study protocol for a randomised controlled trial.

INTRODUCTION: Biofortified crops represent a sustainable agricultural solution for the widespread micronutrient malnutrition in India and other resource-limited settings. This study aims to investigate the effect of the consumption of foods prepared with iron- and zinc-biofortified pearl millet (FeZn-PM) by children on biomarkers of iron and zinc status, growth, and immune function. METHODS AND ANALYSIS: We will conduct a randomised controlled feeding trial in identified slums of Mumbai, India among 200 children aged between 12 and 18 months. Children will be randomised to receive foods prepared with the biofortified PM (FeZn-PM, ICTP8203-Fe) or non-biofortified PM. Anthropometric and morbidity data will be gathered every month for 9 months. Biological samples will be collected at baseline, midline and endline to assess iron and zinc status, including haemoglobin, serum ferritin, serum transferrin receptor, serum zinc, C-reactive protein and alpha-1 acid glycoprotein. Biological samples will be archived for future analyses. The midline measurement will be a random serial sample between baseline and endline. Immune function will be assessed at each time point by the measurement of T cell counts and vaccine responses in a subset, respectively. ETHICS AND DISSEMINATION: This study has obtained clearance from the Health Ministry Screening Committee of the Indian Council of Medical Research. Ethical clearance has been obtained from Cornell University's Institutional Review Board, the Inter System Biomedica Ethics Committee and St John's Research Institute's Institutional Ethics Review Board. The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Clinical trial registration number NCT02233764. CTRI registration number REF/2014/10/007731.