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Supplementation With Lactoferrin and Lysozyme Ameliorates Environmental Enteric Dysfunction

A Double-Blind, Randomized, Placebo-Controlled Trial

Cheng, William D., MD, MA1,2; Wold, Karl J., BS1; Bollinger, Lucy B., MD, MA1,3; Ordiz, M. Isabel, PhD1; Shulman, Robert J., MD4; Maleta, Kenneth M., MBBS, PhD5; Manary, Mark J., MD1,4,5; Trehan, Indi, MD, MPH, DTM&H1,6,7

American Journal of Gastroenterology: April 2019 - Volume 114 - Issue 4 - p 671–678
doi: 10.14309/ajg.0000000000000170

INTRODUCTION: Environmental enteric dysfunction (EED) predisposes children throughout the developing world to high rates of systemic exposure to enteric pathogens and stunting. Effective interventions that treat or prevent EED may help children achieve their full physical and cognitive potential. The objective of this study is to test whether 2 components of breast milk would improve a biomarker of EED and linear growth during the second year of life.

METHODS: A prospective, randomized, double-blind, placebo-controlled clinical trial among children aged 12–23 months was conducted in rural Malawi. The experimental group received a daily supplement of 1.5 g of lactoferrin and 0.2 g of lysozyme for 16 weeks. The primary outcome was an improvement in EED, as measured by the change in the percentage of ingested lactulose excreted into the urine (Δ%L).

RESULTS: Among 214 children who completed the study, there was a significant difference in Δ%L between the control and experimental groups over 8 weeks (an increase of 0.23% vs 0.14%, respectively; P = 0.04). However, this relative improvement was not as strongly sustained over the full 16 weeks of the study (an increase of 0.16% vs 0.11%, respectively; P = 0.17). No difference in linear growth over this short period was observed. The experimental intervention group had significantly lower rates of hospitalization and the development of acute malnutrition during the course of the study (2.5% vs 10.3%, relative risk 0.25; P < 0.02).

DISCUSSION: Supplementation with lactoferrin and lysozyme in a population of agrarian children during the second year of life has a beneficial effect on gut health. This intervention also protected against hospitalization and the development of acute malnutrition, a finding with a significant clinical and public health importance. This finding should be pursued in larger studies with longer follow-up and optimized dosing.

1Department of Pediatrics, Washington University, St. Louis, Missouri, USA;

2Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA;

3Department of Pediatrics, University of Washington, Seattle, Washington, USA;

4Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA;

5School of Public Health and Family Medicine, University of Malawi, Blantyre, Malawi;

6Department of Paediatrics and Child Health, University of Malawi, Blantyre, Malawi;

7Lao Friends Hospital for Children, Luang Prabang, Lao PDR.

Correspondence: Indi Trehan. E-mail:

SUPPLEMENTARY MATERIAL accompanies this paper at

Received October 16, 2018

Accepted January 16, 2019

© The American College of Gastroenterology 2019. All Rights Reserved.
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