Markers of Systemic Inflammation and Environmental Enteric Dysfunction Are Not Reduced by Zinc or Multivitamins in Tanzanian Infants: A Randomized, Placebo-Controlled Trial

Jacqueline M Lauer, Christine M McDonald, Rodrick Kisenge, Said Aboud, Wafaie W Fawzi, Enju Liu, Hao Q Tran, Andrew T Gewirtz, Karim P Manji, Christopher P Duggan, Jacqueline M Lauer, Christine M McDonald, Rodrick Kisenge, Said Aboud, Wafaie W Fawzi, Enju Liu, Hao Q Tran, Andrew T Gewirtz, Karim P Manji, Christopher P Duggan

Abstract

Objective: To examine whether daily zinc and/or multivitamin supplementation reduce biomarkers of environmental enteric dysfunction (EED), systemic inflammation, or markers of growth in a sample of infants from Dar es Salaam, Tanzania.

Study design: Subgroup analysis of infants participating in a randomized, double-blind, placebo-controlled trial received daily oral supplementation of zinc, multivitamins, zinc + multivitamins, or placebo for 18 months starting at 6 weeks of age. EED (anti-flagellin and anti-lipopolysaccharide immunoglobulins), systemic inflammation (C-reactive protein and alpha-1-acid glycoprotein), and growth biomarkers (insulin-like growth factor-1 and insulin-like growth factor binding protein-3) were measured via enzyme-linked immunosorbent assay in a subsample of 590 infants at 6 weeks and 6 months of age. EED biomarkers also were measured in 162 infants at 12 months of age.

Results: With the exception of anti-lipopolysaccharide IgG concentrations, which were significantly greater in infants who received multivitamins compared with those who did not (1.41 ± 0.61 vs 1.26 ± 0.65, P = .006), and insulin-like growth factor binding protein-3 concentrations, which were significantly lower in children who received zinc compared with those who did not (981.13 ± 297.59 vs 1019.10 ± 333.01, P = .03), at 6 months of age, we did not observe any significant treatment effects of zinc or multivitamins on EED, systemic inflammation, or growth biomarkers.

Conclusions: Neither zinc nor multivitamin supplementation ameliorated markers of EED or systemic inflammation during infancy. Other interventions should be prioritized for future trials.

Trial registration: Clinicaltrials.gov: NCT00421668.

Keywords: C-reactive protein; alpha-1-acid glycoprotein; anti-LPS; anti-flagellin; insulin-like growth factor binding protein-3; insulin-like growth factor-1.

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Figures

Figure
Figure
Flowchart of study enrollment and follow-up evaluation. LAZ, length-for-age z score.

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