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

Abstract

BackgroundEnvironmental enteric dysfunction (EED), a chronic inflammatory disorder of the small bowel, is suspected to impair absorption of micronutrients, including zinc.ObjectiveThe 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).MethodsBangladeshi 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.ResultsIn 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).ConclusionResults 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.

Zinc Absorption and Endogenous Fecal Zinc Losses in Bangladeshi Toddlers at Risk for Environmental Enteric Dysfunction

“…The mean (±SD) ingested aqueous doses approximated the planned quantity and did not differ between the groups (3.2 ± 0.2 mg for both, P = 0.39). Average FAZs were similar to the predicted values (Table 1), but the variability of the FAZ data was 3 to 4 times larger than that observed for absorption of zinc consumed in meals in other children studied from this same community (9) (Fig. 1).…”

“…Although data are limited, studies in adults suggest that the site of reabsorption of endogenous zinc is the distal small bowel, and thus may be less impacted by EED compared with absorption of dietary zinc, which occurs primarily in the proximal small bowel where the characteristic pathology of EED is most prominent (3,4,38). The habitual dietary intake of the participants was well below recommended intakes (39), and our findings of impaired zinc absorption from virtually the same diets in similar aged children from the same community resulted in daily absorbed zinc well below estimated physiologic requirements (9). Survey data for children in the communities from which the participants were recruited also indicate high rates of zinc deficiency (10).…”

“…●—FAZ from aqueous zinc dose (high L:M, present study); ○ —FAZ from aqueous zinc dose (low L:M, present study); x —FAZ from single meal supplemented with zinc. Data from (9). FAZ = fractional absorption of ingested zinc.…”

“…Reduced zinc absorption and zinc deficiency have frequently been cited as potential links between EED and the growth failure commonly associated with this condition (1,3,35). Indeed, in a companion study, we reported markedly reduced absorption of zinc from meals in toddlers with evidence of EED (9). The positive association of FAZ with markers of systemic inflammation and intestinal permeability (L:R) observed here appears to contradict the earlier findings, but this is likely a consequence of the different study design.…”

“…Values are presented as median (interquartile values). * High L:M ≥ 0.09, low L:M < 0.09. † References for normal ranges provided in previous publication (9). ‡ Mann-Whitney nonparametric test.…”