Exogenous Phytase Added to Lipid Based Nutrient Supplements Increases Fractional and Total Absorption of Zinc Among Young Gambian Children: A Randomized Controlled Trial (OR07-01-19).

Objectives: Dietary phytate inhibits zinc absorption from composite meals in adults. The objective of this study was to investigate the efficacy of adding exogenous phytase to a small-quantity lipid based nutrient supplement (SQ-LNS) on zinc absorption among young children. Methods: In a double-blind randomized controlled trial, intra-individual differences in fractional and total absorption of zinc (FAZ and TAZ, respectively) from SQ-LNS with and without phytase were measured in 30 asymptomatic 18-23 month old children in the Kiang West district of The Gambia. Using a cross-over design, children received for one day each test meals of a millet-based porridge with 20 g SQ-LNS containing 8 mg zinc and either: 1) exogenous phytase (∼500 phytase units (FTU)) or 2) no exogenous phytase. The test meals were provided on consecutive days in randomized order. FAZ was measured using a dual-stable isotope tracer ratio technique with 67 Zn and 70 Zn as oral tracers, randomized independently of SQ-LNS product, and 68 Zn as the intravenous tracer. TAZ was calculated as the product of total dietary zinc (TDZ) intake from test meals (i.e., porridge, SQ-LNS and stable isotope) and FAZ. FAZ and TAZ were compared for meals with and without phytase using mixed-models ANOVA with product, study day, and oral isotope allocation as fixed effects and individual child as a random effect. Results: Twenty-six participants completed the study. The prevalence of stunting, underweight and wasting were 20%, 30% and 13%, respectively; no children had low plasma zinc concentrations (< 65 μg/dL). TDZ and phytate intakes from the test meals were 7.2 ± 2.2 mg and 182.9 ± 64.7 mg, respectively (phytate: zinc molar ratio = 2.4 ± 0.2). Mean FAZ increased from 8.6 ± 1.3% to 16.0 ± 1.3% when exogenous phytase was added to the SQ-LNS product (P = 0.0002). Mean TAZ from porridge test meals containing SQ-LNS with phytase was more than double that from test meals containing SQ-LNS without phytase (1.12 ± 0.07 mg and 0.52 ± 0.07 mg, respectively; P < 0.0001). Conclusions: The addition of exogenous phytase to a meal of millet-based porridge with SQ-LNS improved both FAZ and TAZ. These results suggest that phytate reduction may be an important strategy to improve zinc absorption among young children. Funding Sources: Nutriset, SAS

Respiratory infections drive hepcidin-mediated blockade of iron absorption leading to iron deficiency anemia in African children.

Iron deficiency anemia (IDA) is the most prevalent nutritional condition worldwide. We studied the contribution of hepcidin-mediated iron blockade to IDA in African children. We measured hepcidin and hemoglobin weekly, and hematological, inflammatory, and iron biomarkers at baseline, 7 weeks, and 12 weeks in 407 anemic (hemoglobin < 11 g/dl), otherwise healthy Gambian children (6 to 27 months). Each child maintained remarkably constant hepcidin levels (P < 0.0001 for between-child variance), with half consistently maintaining levels that indicate physiological blockade of iron absorption. Hepcidin was strongly predicted by nurse-ascribed adverse events with dominant signals from respiratory infections and fevers (all P < 0.0001). Diarrhea and fecal calprotectin were not associated with hepcidin. In multivariate analysis, C-reactive protein was the dominant predictor of hepcidin and contributed to iron blockade even at very low levels. We conclude that even low-grade inflammation, especially associated with respiratory infections, contributes to IDA in African children

Impact of fortified versus unfortified lipid-based supplements on morbidity and nutritional status: A randomised double-blind placebo-controlled trial in ill Gambian children

Multiple micronutrients (MMN) are commonly prescribed in pediatric primary healthcare in sub-Saharan Africa to improve nutritional status and appetite without evidence for their effectiveness or international clinical guidelines. Community-wide MMN supplementation has shown limited and heterogeneous impact on growth and morbidity. Short-term ready-to-use therapeutic foods in acutely sick children in a hospital setting also had limited efficacy regarding subsequent growth. The effectiveness of MMN in improving morbidity or growth in sick children presenting for primary care has not been assessed.We undertook a double-blind randomised controlled trial of small-quantity lipid-based nutrient supplements (SQ-LNS) fortified with 23 micronutrients in children aged 6 months (mo) to 5 years (y) presenting with an illness at a rural primary healthcare centre in The Gambia. Primary outcomes were repeat clinic presentations and growth over 24 wk. Participants were randomly assigned to receive 1 of 3 interventions: (1) supplementation with micronutrient-fortified SQ-LNS for 12 wk (MMN-12), (2) supplementation with micronutrient-fortified SQ-LNS for 6 wk followed by unfortified SQ-LNS for 6 wk (MMN-6), or (3) supplementation with unfortified SQ-LNS for 12 wk (MMN-0) to be consumed in daily portions. Treatment masking used 16 letters per 6-wk block in the randomisation process. Blinded intention-to-treat analysis based on a prespecified statistical analysis plan included all participants eligible and correctly enrolled. Between December 2009 and June 2011, 1,101 children (age 6-60 mo, mean 25.5 mo) were enrolled, and 1,085 were assessed (MMN-0 = 361, MMN-6 = 362, MMN-12 = 362). MMN supplementation was associated with a small increase in height-for-age z-scores 24 wk after recruitment (effect size for MMN groups combined: 0.084 SD/24 wk, 95% CI: 0.005, 0.168; p = 0.037; equivalent to 2-5 mm depending on age). No significant difference in frequency of morbidity measured by the number of visits to the clinic within 24 wk follow-up was detected with 0.09 presentations per wk for all groups (MMN-0 versus MMN-6: adjusted incidence rate ratio [IRR] 1.03, 95% CI: 0.92, 1.16; MMN-0 versus MMN-12: 1.05, 95% CI: 0.93, 1.18). In post hoc analysis, clinic visits significantly increased by 43% over the first 3 wk of fortified versus unfortified SQ-LNS (adjusted IRR 1.43; 95% CI: 1.07, 1.92; p = 0.016), with respiratory presentations increasing by 52% with fortified SQ-LNS (adjusted IRR 1.52; 95% CI: 1.01, 2.30; p = 0.046). The number of severe adverse events during supplementation were similar between groups (MMN-0 = 20 [1 death]; MMN-6 = 21 [1 death]; MMN-12 = 20 [0 death]). No participant withdrew due to adverse effects. Study limitations included the lack of supervision of daily supplementation.Prescribing micronutrient-fortified SQ-LNS to ill children presenting for primary care in rural Gambia had a very small effect on linear growth and did not reduce morbidity compared to unfortified SQ-LNS. An early increase in repeat visits indicates a need for the establishment of evidence-based guidelines and caution with systematic prescribing of MMN. Future research should be directed at understanding the mechanisms behind the lack of effect of MMN supplementation on morbidity measures and limited effect on growth.ISRCTN 73571031

A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia

Infant DNA methylation profiles are associated with their mother’s periconceptional nutritional status. DNA methylation relies on nutritional inputs for one-carbon metabolic pathways, including the efficient recycling of homocysteine. This randomised controlled trial in nonpregnant women in rural Gambia tests the efficacy of a novel nutritional supplement designed to improve one-carbon-related nutrient status by reducing plasma homocysteine, and assesses its potential future use in preconception trials

Effect of exogenous phytase added to small-quantity lipid-based nutrient supplements (SQ-LNS) on the fractional and total absorption of zinc from a millet-based porridge consumed with SQ-LNS in young Gambian children: a randomized controlled trial

Background: Dietary phytate inhibits zinc absorption from composite meals in adults. Objective: The objective of this study was to investigate the effect of adding exogenous phytase to a small-quantity lipid-based nutrient supplement (SQ-LNS) on zinc absorption among young children. Methods: In a double-blind randomized controlled trial, intraindividual differences in fractional and total absorption of zinc (FAZ and TAZ, respectively) from a millet-based porridge containing SQ-LNS with and without phytase were measured in 30 asymptomatic children 18–23 mo of age in the Kiang West district of The Gambia. Using a crossover design, children received for 1 d each porridge test meals with 20 g SQ-LNS containing 8 mg zinc and either 1) exogenous phytase or 2) no exogenous phytase. The test meals were provided on consecutive days in randomized order. FAZ was measured using a triple stable isotope tracer ratio technique with Zn-67 and Zn-70 as oral tracers and Zn-68 as the intravenous tracer. Results: Twenty-six participants completed the study. The prevalence of stunting and wasting were 20% and 13%, respectively; no children had low plasma zinc concentrations (<65 μg/dL). Total mean ± SD dietary zinc intake from the test meals was 7.3 ± 2.2 mg (phytate:zinc molar ratio = 3.1 ± 0.3, not accounting for phytase activity). Mean FAZ increased from 8.6% ± 1.3% to 16.0% ± 1.3% when exogenous phytase was added to the SQ-LNS product (P < 0.001). Mean TAZ from test meals containing SQ-LNS with phytase was more than double that from test meals containing SQ-LNS without phytase (1.1 ± 0.1 mg and 0.5 ± 0.1 mg, respectively; P < 0.001). Conclusions: The addition of exogenous phytase to SQ-LNS increased both FAZ and TAZ. These results suggest that phytate reduction may be an important strategy to increase zinc absorption among young children. This trial was registered at clinicaltrials.gov as NCT02668133.ISSN:0002-9165ISSN:1938-320

Respiratory infections drive hepcidin-mediated blockade of iron absorption leading to iron deficiency anemia in African children.

Iron deficiency anemia (IDA) is the most prevalent nutritional condition worldwide. We studied the contribution of hepcidin-mediated iron blockade to IDA in African children. We measured hepcidin and hemoglobin weekly, and hematological, inflammatory, and iron biomarkers at baseline, 7 weeks, and 12 weeks in 407 anemic (hemoglobin < 11 g/dl), otherwise healthy Gambian children (6 to 27 months). Each child maintained remarkably constant hepcidin levels (P < 0.0001 for between-child variance), with half consistently maintaining levels that indicate physiological blockade of iron absorption. Hepcidin was strongly predicted by nurse-ascribed adverse events with dominant signals from respiratory infections and fevers (all P < 0.0001). Diarrhea and fecal calprotectin were not associated with hepcidin. In multivariate analysis, C-reactive protein was the dominant predictor of hepcidin and contributed to iron blockade even at very low levels. We conclude that even low-grade inflammation, especially associated with respiratory infections, contributes to IDA in African children

Baseline characteristics according to randomised groups.

<p>Baseline characteristics according to randomised groups.</p

Compliance overall and by intervention group.

<p>Compliance overall and by intervention group.</p

CONSORT flow chart of the trial.

<p>KW, Kiang West; MMN, multiple micronutrients.</p

Anthropometric measurements at recruitment and follow-up dates by intervention group.

<p>Anthropometric measurements at recruitment and follow-up dates by intervention group.</p