Zinc Absorption from Micronutrient Powders Is Low in Bangladeshi Toddlers at Risk of Environmental Enteric Dysfunction and May Increase Dietary Zinc Requirements

Abstract

Background: Environmental enteric dysfunction (EED), a chronic inflammatory disorder of the small bowel, is suspected to impair absorption of micronutrients, including zinc.

Objective: The objective of this study was to compare zinc absorption from micronutrient powder (MNP) over a range of zinc doses in young children screened for EED with use of the lactulose:mannitol ratio (L:M).

Methods: Bangladeshi children aged 18-24 mo, grouped according to high and low L:M (≥0.09 and <0.09, respectively), were randomly assigned to MNP with 0, 5, 10, or 15 mg Zn/sachet (10 subjects per dose per L:M group). Over a day, fractional absorption of zinc was measured from an MNP-fortified meal and from unfortified meals with stable isotope tracers; total daily absorbed zinc (TAZ, milligrams per day) was determined as the primary outcome. Secondary outcomes included investigation of relations of TAZ to intake, to physiologic requirement, and to other variables, including biomarkers of systemic and intestinal inflammation, using nonlinear models. TAZ was also compared with published data on child zinc absorption.

Results: In 74 subjects who completed the study, zinc absorption did not differ by L:M grouping. Most biomarkers of intestinal inflammation were elevated in both L:M groups. For combined L:M groups, mean ± SD TAZ for each MNP dose (0, 5, 10, and 15 mg/sachet) was 0.57 ± 0.30, 0.68 ± 0.31, 0.90 ± 0.43, and 1.0 ± 0.39 mg/d, respectively (P = 0.002), and exceeded the estimated physiologic requirement only for the 10- and 15-mg MNP doses. Zinc absorption was notably lower at all intake levels compared with published data (P < 0.0001) and was inversely related to serum α-1 acid glycoprotein and to fecal Entamoeba histolytica (P = 0.02).

Conclusion: Results indicate impaired absorption of zinc, which may predispose to zinc deficiency in young children with evidence of enteropathy. These findings suggest that current doses of zinc in MNP may be insufficient to yield zinc-related preventative benefits in similar settings. This study is registered at clinicaltrials.gov as NCT02758444.

FIGURE 1

The relation of total absorbed zinc to total dietary zinc intake in Bangladeshi toddlers (A) grouped by high (≥0.09) and low (<0.09) L:M and (B) compared with reference data. (A) The curves show the similar fits of a saturation response model to each L:M group. The parameter data for the curves are presented in Table 4. (B) Comparison of the combined data from (A) to similar modeling of data from a study of breastfed infants in Denver (28) (highest curve) and from the analysis of data compiled from multiple studies of zinc absorption in infants and children (38). The curve representing the latter model shows the prediction for infants of age 19 mo, the mean age of the subjects of this study. For both curves from published analyses, the dashed portion of the curve shows the ranges of the data that were modeled in each case and the dotted portion represents the extrapolation of the curve to cover the range of the current data. L:M, lactulose:mannitol ratio.

FIGURE 2

Relations of absorbed zinc to dietary zinc and (A) phytate intake, (B) AGP, and (C) E. histolytica in Bangladeshi toddlers. (A) The relation of total absorbed zinc to total dietary zinc and dietary phytate intakes for the combined L:M groups. The surface shows the fit of a saturation response model (38) to the data. The absence of a phytate effect on absorption is apparent from the lack of a slope in the phytate axis. The vertical lines from data symbols to the model surface represent the deviations between data and the model. The parameter data for the models are presented in Table 4. (B) The relation of total absorbed zinc to total dietary zinc intake and serum concentration of AGP, a marker of systemic inflammation, showing decreasing absorption with increasing AGP concentration. (C) The relation of total absorbed zinc to total dietary zinc intake and the presence of E. histolytica, an intestinal parasite, showing decreasing absorption with greater infection. AGP, α-1 acid glycoprotein; E. histolytica, Entamoeba histolitica; L:M, lactulose:mannitol ratio.