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

Hannah E. Smith, Kelsey N. Ryan, Kevin B. Stephenson, Claire Westcott, Chrissie Thakwalakwa, Ken Maleta, Jacqueline Y. Cheng, J. Thomas Brenna, Robert J. Shulman, Indi Trehan, Mark J. Manary

Research output: Contribution to journalArticle

30 Scopus citations

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.

Original languageEnglish
Pages (from-to)2059-2065
Number of pages7
JournalJournal of Nutrition
Volume144
Issue number12
DOIs
StatePublished - Jan 1 2014

Keywords

  • Enteropathy
  • Environmental enteropathy
  • Fish oil
  • Malawi
  • Micronutrients

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