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Associations Between Intestinal Mucosal Function and Changes in Plasma Zinc Concentration Following Zinc Supplementation

Wessells, K. Ryan*; Hess, Sonja Y.*; Rouamba, Noel; Ouédraogo, Zinewendé P.; Kellogg, Mark; Goto, Rie§; Duggan, Christopher||; Ouédraogo, Jean-Bosco; Brown, Kenneth H.*

Journal of Pediatric Gastroenterology and Nutrition: September 2013 - Volume 57 - Issue 3 - p 348–355
doi: 10.1097/MPG.0b013e31829b4e9e
Original Articles: Hepatology and Nutrition

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.

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*Department of Nutrition, University of California, Davis, Davis, CA

Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso

Department of Pathology, Boston Children's Hospital, Boston, MA

§Department of Archaeology and Anthropology, Division of Biological Anthropology, University of Cambridge, Cambridge, UK

||Division of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, MA.

Address correspondence and reprint requests to Kenneth H. Brown, MD, Department of Nutrition, 1 Shields Ave, University of California, Davis, CA 95616 (e-mail:

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Funding for this study was provided by Nutriset, SAS (Malauney, France), the Henry A. Jastro Graduate Research Scholarship Award (University of CA, Davis), a Bristol-Myers Squibb Freedom to Discover Award, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD K24HD058795). The researchers were independent of funders. The study funders had no influence on the study design, collection, analysis, interpretation of data, writing of the report, or the decision to submit the article for publication. registration number: NCT00944853.

© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,