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Intervention and Mechanisms of Alanyl-glutamine for Inflammation, Nutrition, and Enteropathy: A Randomized Controlled
Sean R Moore1, Laura A Quinn1, Elizabeth A Maier2
1Division of Pediatric Gastroenterology, Hepatology, & Nutrition, Department of Pediatrics, University of Virginia, Charlottesville, VA.
Insights
Alanyl-glutamine (Ala-Gln) supplementation improved gut integrity and growth in children at risk of environmental enteropathy (EE). An intermediate dose showed the most promising short-term results for gut health and ponderal growth.
Area of Science:
- Pediatric Nutrition
- Gastroenterology
- Clinical Trials
Background:
- Environmental enteropathy (EE) is a public health concern in low-income communities, affecting gut integrity and child growth.
- Alanyl-glutamine (Ala-Gln) is a dipeptide with potential to support gut health and nutrient absorption.
Purpose of the Study:
- To determine the minimum effective dosage of alanyl-glutamine (Ala-Gln) for improving gut integrity and growth in children at risk of environmental enteropathy (EE).
Main Methods:
- A double-blinded, randomized, placebo-controlled dose-response trial was conducted with 140 children (2-60 months) at risk of EE.
- Participants received 10 days of nutritional supplementation with varying doses of Ala-Gln or a glycine placebo.
- Primary outcome was urinary lactulose-mannitol excretion; secondary outcomes included anthropometry and fecal markers.
Main Results:
- A modest improvement in gut integrity (urinary lactulose excretion) was observed with the highest Ala-Gln dose.
- Transient improvements in weight-for-height z-scores (WHZ) and weight-for-age z-scores (WAZ) were noted in Ala-Gln groups.
- No significant effects on fecal inflammatory markers or urine metabolic profiles were detected, but modest reductions in fecal energy and lactoferrin were observed.
Conclusions:
- An intermediate dose of Ala-Gln demonstrated short-term benefits for gut integrity and ponderal growth in children at risk of EE.
- Lower Ala-Gln doses improved ponderal growth without significantly enhancing gut integrity.
Objective:
Determine the minimum dosage of alanyl-glutamine (Ala-Gln) required to improve gut integrity and growth in children at risk of environmental enteropathy (EE).
Methods:
This was a double-blinded randomized placebo-controlled dose-response trial. We enrolled 140 children residing in a low-income community in Fortaleza, Brazil. Participants were 2 to 60 months old and had weight-for-age (WAZ), height-for-age (HAZ), or weight-for-height (WHZ) z-scores less than -1. We randomized children to 10 days of nutritional supplementation: Ala-Gln at 3 g/day, Ala-Gln at 6 g/day, Ala-Gln at 12 g/day, or an isonitrogenous dose of glycine (Gly) placebo at 12.5 g/day. Our primary outcome was urinary lactulose-mannitol excretion testing. Secondary outcomes were anthropometry, fecal markers of inflammation, urine metabolic profiles, and malabsorption (spot fecal energy).
Results:
Of 140 children, 103 completed 120 days of follow-up (24% dropout). In the group receiving the highest dose of Ala-Gln, we detected a modest improvement in urinary lactulose excretion from 0.19% on day 1 to 0.17% on day 10 (P = 0.05). We observed significant but transient improvements in WHZ at day 10 in 2 Ala-Gln groups, and in WHZ and WAZ in all Ala-Gln groups at day 30. We detected no effects on fecal inflammatory markers, diarrheal morbidity, or urine metabolic profiles; but did observe modest reductions in fecal energy and fecal lactoferrin in participants receiving Ala-Gln.
Conclusions:
Intermediate dose Ala-Gln promotes short-term improvement in gut integrity and ponderal growth in children at risk of EE. Lower doses produced improvements in ponderal growth in the absence of enhanced gut integrity.
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