Associations between intestinal mucosal function and changes in plasma zinc concentration following zinc supplementation

Abstract

Objectives: Subclinical environmental enteropathy is associated with malabsorption of fats, carbohydrates, and vitamins A, B12, and folate; however, little information is available on mineral absorption. We therefore investigated the relation between intestinal mucosal function (measured by the lactulose:mannitol permeability test and plasma citrulline concentration), and zinc (Zn) absorption, as estimated by the change in plasma Zn concentration (PZC) following short-term Zn or placebo supplementation.

Methods: We conducted a randomized, partially masked, placebo-controlled trial among 282 apparently healthy children 6 to 23 months of age in Burkina Faso. After completing baseline intestinal function tests, participants received either 5 mg Zn, as zinc sulfate, or placebo, daily for 21 days.

Results: At baseline, mean ± standard deviation PZC was 62.9 ± 11.9 μg/dL; median (interquartile range) urinary lactulose:mannitol (L:M) recovery ratio and plasma citrulline concentrations were 0.04 (0.03-0.07) and 11.4 (9.0-15.6) μmol/L, respectively. Change in PZC was significantly greater in the Zn-supplemented versus placebo group (15.6 ± 13.3 vs 0.02 ± 10.9 μg/dL; P < 0.0001), and was negatively associated with initial urinary L:M recovery ratio (-1.1 μg/dL per 50% increase in urinary L:M recovery ratio; P = 0.014); this latter relation did not differ between supplementation groups (P = 0.26). Baseline plasma citrulline concentration was not associated with change in PZC.

Conclusions: Although altered intestinal permeability may reduce dietary Zn absorption, it likely does not undermine the efficacy of Zn supplementation, given the large increases in PZC following short-term Zn supplementation observed in this study, even among those with increased urinary L:M recovery ratios.

Trial registration: ClinicalTrials.gov NCT00944853.

Conflict of interest statement

Conflicts of interest: All authors declare: no support from any institution for the submitted work, no financial relationships with any institutions that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work. K. Ryan Wessells drafted the manuscript. No honorarium, grant, or other form of payment was given to anyone to produce the manuscript.

Figures

Figure 1

Consort flow diagram detailing the number of children who were enrolled and completed the study, by treatment group.

Figure 2

Relationship between change in plasma zinc concentration from baseline to post-supplementation and urinary L:M recovery ratio (natural log scale), by study group. The partial correlation coefficient is adjusted for differences in mean change in plasma zinc concentrations among groups, initial plasma zinc concentration, child age, height-for-age Z score, change in weight-for-age Z score (baseline to final), baseline and final AGP ≥ 1 g/L, final HRP2 > 0.75 ng/mL, time of day (final) and elapsed time since last breastfeed (final). Urinary L:M recovery ratio and change in plasma zinc concentration were correlated (r = −0.14, P = 0.014); the relationship did not differ between study groups (ANCOVA, P for interaction = 0.26). Number of participants by study group: Zn, N = 168, Placebo, N= 86.

Figure 3

Relationship between change in plasma citrulline concentration and change in weight-for-age Z score from baseline to post- supplementation. The partial correlation coefficient is adjusted for initial plasma citrulline concentration (r = 0.34, P=0.0035). N=75.