L-isoleucine-supplemented oral rehydration solution in the treatment of acute diarrhoea in children: a randomized controlled trial

N H Alam, R Raqib, H Ashraf, F Qadri, S Ahmed, M Zasloff, B Agerberth, M A Salam, N Gyr, R Meier, N H Alam, R Raqib, H Ashraf, F Qadri, S Ahmed, M Zasloff, B Agerberth, M A Salam, N Gyr, R Meier

Abstract

Antimicrobial peptides represent an important component of the innate immune defenses of living organisms, including humans. They are broad-spectrum surface-acting agents secreted by the epithelial cells of the body in response to infection. Recently, L-isoleucine and its analogues have been found to induce antimicrobial peptides. The objectives of the study were to examine if addition of L-isoleucine to oral rehydration salts (ORS) solution would reduce stool output and/or duration of acute diarrhoea in children and induce antimicrobial peptides in intestine. This double-blind randomized controlled trial was conducted at the Dhaka Hospital of ICDDR,B. Fifty male children, aged 6-36 months, with acute diarrhoea and some dehydration, attending the hospital, were included in the study. Twenty-five children received L-isoleucine (2 g/L)-added ORS (study), and 25 received ORS without L-isoleucine (control). Stool weight, ORS intake, and duration of diarrhoea were the primary outcomes. There was a trend in reduction in mean +/- standard deviation (SD) daily stool output (g) of children in the L-isoleucine group from day 2 but it was significant on day 3 (388 +/- 261 vs. 653 +/- 446; the difference between mean [95% confidence interval (CI) (-)265 (-509, -20); p = 0.035]. Although the cumulative stool output from day 1 to day 3 reduced by 26% in the isoleucine group, it was not significant. Also, there was a trend in reduction in the mean +/- SD intake of ORS solution (mL) in the L-isoleucine group but it was significant only on day 1 (410 +/- 169 vs. 564 +/- 301), the difference between mean (95% CI) (-)154 (-288, -18); p = 0.04. The duration (hours) of diarrhoea was similar in both the groups. A gradual increase in stool concentrations of beta-defensin 2 and 3 was noted but they were not significantly different between the groups. L-isoleucine-supplemented ORS might be beneficial in reducing stool output and ORS intake in children with acute watery diarrhoea. A further study is warranted to substantiate the therapeutic effect of L-isoleucine.

Trial registration: ClinicalTrials.gov NCT01034228.

Figures

Fig.
Fig.
Kaplan-Meir survival curve for duration of diarrhoea

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