Environmental enteric dysfunction (EED) is a common problem in developing countries and is caused by inflammation leading to reduced intestinal absorption and diminished barrier function causing diarrhea and poor growth. Preventative treatments for large populations can be problematic, and this study evaluated the effectiveness of zinc as well as multi-vitamin supplementation to prevent complications of EED.
This double-blind, placebo-controlled study involved 6-week old infants in Tanzania born to mothers without HIV infection. Subjects were divided into 4 groups: infants receiving zinc supplementation, infants receiving multivitamin supplementation (consisting of vitamin C, vitamin E, vitamin B6, vitamin B12, thiamine, riboflavin, niacin, and folate), infants receiving both zinc and multivitamin supplementation, and infants receiving placebo. Compliance was monitored by medication count, and blood work was obtained at 6 weeks, 6 months, and 12 months of age to monitor serum anti-flagellin antibodies (IgA / IgG) and anti-lipopolysaccharide (anti-LPS) antibodies (IgA / IgG) to assess for EED; C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP) to assess for inflammation; and insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels to assess for growth.
In total, 2400 infants were enrolled in the study for which 590 infants with a history of EED had completed the study at 6 months and 162 infants with a history EED completed the study at 12 months. No statistical difference was seen in maternal, child, and socioeconomic factors between the 4 study groups except for the category of maternal mid-upper arm circumference. There was a significant increase in EED biomarker levels as children became older. However, no changes in biomarker concentration for EED, inflammation, and growth were noted between groups except for IGGBP-3 levels which were significantly lower at 6 months of age in children who received zinc supplementation and anti-LPS IgG levels which were significantly higher at 6 months of age in children who received multivitamin supplementation.
This study suggests that zinc and multivitamin supplementation does not improve EED in children, and such supplementation may not be helpful in reducing downstream effects of diarrhea and poor growth for children living in developing countries. Further studies are needed to validate these findings so that appropriate use of nutritional resources can serve such populations.
Lauer J, McDonald C, Kisenge R, Aboud S, Fawzi W, Liu E, Tran H, Gerwirtz A, Manji K, Duggan C. Markers of systemic inflammation and environmental enteric dysfunction are not reduced by zinc or multivitamins in Tanzanian infants: a randomized, placebo-controlled trial. Journal of Pediatrics 2019; 210: 34-40.