Effects of lipid-based nutrient supplements on gut markers in stunted children: Secondary analysis of a randomised trial

Objectives: To examine the effects of lipid-based nutrient supplements (LNS) containing milk protein (MP) and/or whey permeate (WP) on markers of intestinal inflammation and enterocyte mass among stunted children. Furthermore, to explore whether gut status modifies effects of LNS on growth and micronutrient status. Methods: In a 2 × 2 factorial trial 12–59 months-old Ugandan children with stunting were randomized to four LNS formulations (100 g/day for 12 weeks) containing MP or soy protein and WP or maltodextrin, or to no supplementation. Linear mixed-effects models were used to explore faecal myeloperoxidase (f-MPO) and plasma citrulline (p-cit) as outcomes and modifiers of the intervention effects (ISRCTN13093195). Results: Of 750 children, mean ± SD age was 32.0 ± 11.7 months and height-for-age Z-score was −3.02 ± 0.74. Neither MP nor WP had effects on p-cit or f-MPO. f-MPO decreased over time among controls (ratio of change 0.54, 95% confidence interval [CI]: 0.35, 0.84), but not among those given LNS (0.99, 95% CI: 0.79, 1.23) (p = 0.016). In contrast, LNS had no effect on p-cit (p = 0.27). The effect of LNS on cobalamin (B12) status was reduced in children with p-cit <20 µmol/L; whereby there was 20% (95% CI: 2, 35) lower increase in plasma cobalamin and 59% (95% CI: 13, 125) smaller decrease in plasma methylmalonic acid. p-cit or f-MPO did not modify the effects of LNS on growth or other micronutrient markers. Conclusion: LNS had no effect on enterocyte mass and possibly increased intestinal inflammation. The effect of LNS on cobalamin status was reduced in those with low enterocyte mass.