Multiple micronutrient supplementation transiently ameliorates environmental enteropathy in Malawian children aged 12-35 months in a randomized controlled clinical trial

J Nutr. 2014 Dec;144(12):2059-65. doi: 10.3945/jn.114.201673. Epub 2014 Oct 1.

Abstract

Background: Environmental enteropathy (EE) is subclinical, diffuse villous atrophy characterized by T cell infiltration of the small intestinal mucosa associated with nutrient malabsorption and stunting. EE is assessed by the lactulose:mannitol (L:M) test, whereby nonmetabolized sugars are ingested and quantified in the urine. Multiple micronutrient (MN) deficiency morphologically mimics EE, and ω-3 (n-3) polyunsaturated fatty acids reduce mucosal inflammation in Crohn disease.

Objective: We tested the hypothesis that supplementary MNs, with or without fish oil (FO), would improve L:M in rural Malawian children aged 1-3 y compared with a control (C) group receiving a placebo.

Methods: The MNs and FO provided the Recommended Dietary Intake for 26 vitamins, minerals, eicosapentaenoic acid, and docosahexaenoic acid. This was a 3-arm, randomized, double-blind, placebo-controlled clinical trial, with the primary outcomes being the change in L:M (ΔL:M) after 12 and 24 wk of supplementation. Comparisons were made for ΔL:M after 12 and 24 wk within each group by using a Wilcoxon matched pairs signed rank test, because the data are not normally distributed.

Results: A total of 230 children had specimens adequate for analysis; all had an abnormal baseline L:M, defined as >0.10. After 12 wk, children who received MNs + FO had a ΔL:M [mean (95% CI)] of -0.10 (-0.04, -0.15; P = 0.001), and children receiving only MNs had ΔL:M of -0.12 (-0.03, -0.21; P = 0.002). After 24 wk, children who received MNs + FO had a ΔL:M of -0.09 (-0.03, -0.15; P = 0.001); children receiving only MNs had a ΔL:M of -0.11 (-0.02, -0.20; P = 0.001), and the C group had ΔL:M of -0.07 (0.02, -0.16); P = 0.002). Linear growth was similar in all groups, ∼4.3 cm over 24 wk.

Conclusion: Although the effect was modest, these data suggest MNs can transiently ameliorate EE in rural African children. The trial was registered at clinicaltrials.gov as NCT01593033.

Keywords: Malawi; enteropathy; environmental enteropathy; fish oil; micronutrients.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Cluster Analysis
  • Dietary Supplements*
  • Docosahexaenoic Acids / administration & dosage
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Eicosapentaenoic Acid / administration & dosage
  • Energy Intake
  • Fatty Acids, Unsaturated / blood
  • Female
  • Fish Oils / administration & dosage
  • Follow-Up Studies
  • Humans
  • Infant
  • Intestinal Diseases / drug therapy*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Lactulose / urine
  • Malawi
  • Male
  • Mannitol / urine
  • Micronutrients / administration & dosage*
  • Micronutrients / deficiency
  • Nutrition Assessment
  • Patient Compliance
  • Recommended Dietary Allowances
  • Vitamin A / administration & dosage

Substances

  • Fatty Acids, Unsaturated
  • Fish Oils
  • Micronutrients
  • Vitamin A
  • Docosahexaenoic Acids
  • Mannitol
  • Lactulose
  • Eicosapentaenoic Acid

Associated data

  • ClinicalTrials.gov/NCT01593033