Metabolome and microbiome alterations related to short-term feeding of a micronutrient-fortified, high-quality legume protein-based food product to stunted school age children: A randomized controlled pilot trial.

BACKGROUND & AIMS: Stunting in children is a comorbid condition in undernutrition that may be ameliorated by the provision of high-quality foods that provide protein and micronutrients. Addressing this problem in lower social economic environments requires, in part, affordable and scalable food-based solutions with efficacious food products. Towards this end, biochemical/metabolic indicators for fast-throughput screening of foods and their components are desired. A highly acceptable and economical micronutrient-fortified food product with different levels of legume protein was provided to stunted Indian children for one month, to determine change in their linear growth and explore associated biochemical, metabolomic and microbiome indicators. METHODS: A randomized controlled pilot trial was conducted with 100 stunted children (6-10 years of age) to elucidate metabolic and microbiome-based biomarkers associated with linear growth. They were randomized into 4 groups receiving 6, 8, 10 or 12 g of legume-based protein for one month. Anthropometry, blood biochemistry, aminoacidomics, acylcarnitomics and fecal microbiome were measured before and after feeding. RESULTS: No significant differences were observed between groups in height, height-for-age Z-score (HAZ) or BMI-for-age Z-score (BAZ); however, 38 serum metabolites were altered significantly (Bonferroni adjusted P < 0.1) in response to the interventions. IGF-1 (Insulin like Growth Factor-1) was positively (ρ > 0.2, P = 0.02), while serine and ornithine (ρ < -0.2, P = 0.08) were negatively associated with change in height. Leucine, isoleucine and valine positively correlated (P = 0.011, 0.023 and 0.007 respectively) with change in BAZ. Three Operational Taxonomic Units belonging to Bacteroidetes and Firmicutes (VIP score > 1.5) were significantly correlated with change in height. CONCLUSIONS: In this pilot trial, a number of fasting serum metabolomic and fecal microbiome signatures were associated with linear growth after a short-term dietary intervention. The alterations of these markers should be validated in long-term dietary intervention trials as potential screening indicators towards the development of food products that favor growth. This trial was registered at www.ctri.nic.in as CTRI/2016/12/007564.

Effect of ascorbic acid rich, micro-nutrient fortified supplement on the iron bioavailability of ferric pyrophosphate from a milk based beverage in Indian school children.

BACKGROUND AND OBJECTIVES: Nutritional anemia is a significant public health issue with 50-80% prevalence in Indian children. Fortification of food, specifically milk, with iron is a potential approach to increase dietary iron intake. Ferric pyrophosphate [Fe4(P2O7)3] is organoleptically neutral and is less soluble in acid medium and, further, has low bioavailability in milk. However, since ascorbic acid is a potent enhancer of iron absorption, the coadministration of ascorbic acid with Fe4(P2O7)3 might enhance the absorption of iron. We evaluated the effect of ascorbic acid on iron absorption from a Fe4(P2O7)3 and an ascorbic acid fortified milk beverage with respect to milk fortified with Fe4(P2O7)3 alone. METHODS AND STUDY DESIGN: A double-blind, two-way crossover, randomized study was conducted in 25 mildly anemic children. The test group received milk fortified with beverage powder containing 7 mg isotopically labeled iron (57Fe/58Fe) as Fe4(P2O7)3, equimolar proportions of ascorbic acid and 200 mg of calcium whereas control group received milk fortified with energy, calcium and iron equivalent beverage powder. Fractional iron absorption was measured by erythrocyte incorporation of stable isotopes of iron (57Fe/58Fe) in both the groups. RESULTS: The fractional iron absorption from the control drink was 0.80% (95% CI: 0.57, 1.12). Fortifying the milk with an equimolar amount of ascorbic acid increased the fractional iron absorption almost 2-fold to 1.58% (95% CI: 1.13, 2.22). CONCLUSIONS: The presence of ascorbic acid in an equimolar ratio with that of iron from Fe4(P2O7)3 salt in milk as a fortificant enhanced iron absorption when compared to milk fortified with only Fe4(P2O7)3.

The effects of regular consumption of a multiple micronutrient fortified milk beverage on the micronutrient status of school children and on their mental and physical performance.

Multiple micronutrient deficiencies exist in school going children in India and bridging the gap between nutrient intake and requirements is an effective way to combat the deficiencies. This study aimed to test the effect of a multi-micronutrient fortified malt and cocoa based milk beverage on the micronutrient status, cognition, physical performance and nutritional deficiencies of 7-10 years old south Indian children. A randomized, double blind placebo controlled study design was used with normal healthy children from low to middle income families, aged 7-10 years randomly assigned to receive either a multi-micronutrient fortified or an unfortified milk based control drink. The drinks were provided 6 days/week for 5 months. Assessments included anthropometry, blood biochemistry, physical performance and cognition at baseline and endline. The baseline characteristics of the study groups were similar. The changes in body weight and height were similar between the groups at the end of the study. Levels of vitamin B12, red cell folate and vitamin B2 significantly improved in the intervention group, while vitamin D, selenium and body iron showed no difference. The Hemoglobin (Hb) and serum ferritin levels of the control group decreased at endline, while those in the intervention group maintained their levels. The serum transferrin receptor levels increased in both the groups. The prevalence of iron deficiency and Vitamin B2 deficiency were significantly lower in the intervention group at endline. Overall improvement in cognitive and physical performance was seen in both the groups at endline, with no significant differences between the groups. The micronutrient fortified milk based drink was efficacious in improving the micronutrient status of Vitamin B2, Vitamin B12 and red cell folate and in preventing a decline in Hb level compared to an unfortified milk based drink. It also reduced anemia and the risk of deficiencies of iron, and B12, in apparently healthy children. ClinicalTrials.gov IdentifierNCT01415557. Clinical Trial RegistryIndia - REF/2012/12/004332.

Micronutrient supplementation improves physical performance measures in Asian Indian school-age children.

Micronutrients are important in physical work capacity and therefore performance. The impact of a multi-micronutrient-fortified nutritional beverage on physical performance measures among clinically healthy school-age children was assessed in a double-blind (for test and placebo groups), placebo-controlled, randomized trial in children aged between 7 and 10.5 y (n = 300). The participants with height- and weight-for-age Z-scores between 0 and ≥ -3 were randomized to 1 of 3 study arms: fortified choco-malt beverage powder (F), matched energy equivalent unfortified placebo (U), and untreated control (C). Participants in the F and C groups were given 40 g fortified (19 key vitamins and minerals) and unfortified choco-malt beverage, respectively, daily for 120 d. Primary efficacy outcomes included endurance and aerobic capacity using a 20-m shuttle test and step test. Other physical performance measures included speed (40-m sprint), visual reaction time, maximal hand grip, and forearm static endurance. Micronutrient status included thiamin, riboflavin, folate, niacin, iron, pyridoxal phosphate, and vitamins B-12 and C. All measurements were made at baseline and the end of the intervention. There was a within-subject increase in aerobic capacity and whole body endurance (P < 0.05) accompanied by a significant improvement in the status of iron thiamin, riboflavin, pyridoxal phosphate, folate, and vitamins C and B-12 in the F group compared to the within-subject changes in the other 2 groups (P < 0.05). The study suggests that multiple micronutrient supplementation in similar populations may be beneficial in improving micronutrient status and enhancing aerobic capacity and endurance in children.