title: Multiple micronutrient supplementation transiently ameliorates environmental enteropathy in Malawian children aged 12-35 months in a randomized controlled clinical trial.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Washington University, St. Louis, MO;
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Smith
authors.affiliation: Department of Pediatrics, Washington University, St. Louis, MO;
authors.forename: Kelsey N
authors.initials: KN
authors.lastname: Ryan
authors.affiliation: Department of Pediatrics, Washington University, St. Louis, MO;
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Stephenson
authors.affiliation: Department of Pediatrics, Washington University, St. Louis, MO;
authors.forename: Claire
authors.initials: C
authors.lastname: Westcott
authors.affiliation: College of Medicine, University of Malawi, Blantyre, Malawi;
authors.forename: Chrissie
authors.initials: C
authors.lastname: Thakwalakwa
authors.affiliation: College of Medicine, University of Malawi, Blantyre, Malawi;
authors.forename: Ken
authors.initials: K
authors.lastname: Maleta
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY; and.
authors.forename: Jacqueline Y
authors.initials: JY
authors.lastname: Cheng
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY; and.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Brenna
authors.affiliation: Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Shulman
authors.affiliation: Department of Pediatrics, Washington University, St. Louis, MO; College of Medicine, University of Malawi, Blantyre, Malawi;
authors.forename: Indi
authors.initials: I
authors.lastname: Trehan
authors.affiliation: Department of Pediatrics, Washington University, St. Louis, MO; College of Medicine, University of Malawi, Blantyre, Malawi; Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX manary@kids.wustl.edu.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Manary
mesh_terms: D002675:Child, Preschool; D016000:Cluster Analysis; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage; D002149:Energy Intake; D005231:Fatty Acids, Unsaturated / Q000097:blood; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007410:Intestinal Diseases / Q000188:drug therapy*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007792:Lactulose / Q000652:urine; D008295:Malawi; D008297:Male; D008353:Mannitol / Q000652:urine; D018977:Micronutrients / Q000008:administration & dosage* / Q000172:deficiency; D015596:Nutrition Assessment; D010349:Patient Compliance; D064167:Recommended Dietary Allowances; D014801:Vitamin A / Q000008:administration & dosage
chemical_list: D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D018977:Micronutrients; D014801:Vitamin A; D004281:Docosahexaenoic Acids; D008353:Mannitol; D007792:Lactulose; D015118:Eicosapentaenoic Acid
keywords: Malawi; enteropathy; environmental enteropathy; fish oil; micronutrients