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

item SMITH, HANNAH - Washington University
item RYAN, KELSEY - Washington University
item STEPHENSON, KEVIN - Washington University
item WESTCOTT, CLAIRE - Washington University
item THAKWALAKWA, CHRISSIE - University Of Malawi
item MALETA, KEN - University Of Malawi
item CHENG, JACQUELINE - Cornell University
item BRENNA, J - Cornell University
item SHULMAN, ROBERT - Children'S Nutrition Research Center (CNRC)
item TREHAN, INDI - Washington University
item MANARY, MARK - Children'S Nutrition Research Center (CNRC)

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/10/2014
Publication Date: 10/1/2014
Citation: Smith, H.E., Ryan, K.N., Stephenson, K.B., Westcott, C., Thakwalakwa, C., Maleta, K., Cheng, J.Y., Brenna, J.T., Shulman, R.J., Trehan, I., Manary, M.J. 2014. Multiple micronutrient supplementation transiently ameliorates environmental enteropathy in Malawian children aged 12-35 months in a randomized controlled clinical trial. Journal of Nutrition. 144:2059-2065. doi:10.3945/jn.114.201673.

Interpretive Summary: Children living in poor sanitary conditions can develop inflammation in their intestines which leads to poor growth. In this study we tested whether providing a supplement with the recommended daily intake of 26 vitamins, minerals, and specific fats could reduce the intestinal inflammation. Our results showed that supplementation can improve the gastrointestinal inflammation. Future work should consider including such supplements in vunerable populations.

Technical Abstract: 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 '-3 (n-3) polyunsaturated fatty acids reduce mucosal inflammation in Crohn disease. 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. 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 ('L:M) after 12 and 24 wk of supplementation. Comparisons were made for 'L: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. 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 'L:M [mean (95% CI)] of -0.10 (-0.04, -0.15; P = 0.001), and children receiving only MNs had 'L:M of -0.12 (-0.03, -0.21; P = 0.002). After 24 wk, children who received MNs + FO had a 'L:M of -0.09 (-0.03, -0.15; P = 0.001); children receiving only MNs had a 'L:M of -0.11 (-0.02, -0.20; P = 0.001), and the C group had 'L:M of -0.07 (0.02, -0.16); P = 0.002). Linear growth was similar in all groups, ~4.3 cm over 24 wk. Although the effect was modest, these data suggest MNs can transiently ameliorate EE in rural African children.