Effects of randomized supplementation of methionine or alanine on cysteine and glutathione production during the early phase of treatment of children with edematous malnutrition.

BACKGROUND: We have shown that a low glutathione concentration and synthesis rate in erythrocytes are associated with a shortage of protein-derived cysteine in children with edematous severe acute malnutrition (SAM). OBJECTIVE: We tested the hypothesis that methionine supplementation may increase protein-derived cysteine and upregulate cysteine synthesis, thereby improving glutathione synthesis during the early treatment of edematous SAM. DESIGN: The cysteine flux, its de novo synthesis and release from protein breakdown, and erythrocyte glutathione synthesis rate were measured in 12 children with edematous SAM in the fed state by using stable isotope tracers at 3 clinical phases as follows: 3 ± 1 d (±SE) [clinical phase 1 (CP1)], 8 ± 1 d [clinical phase 2 (CP2)], and 14 ± 2 d (clinical phase 3) after admission. Subjects were randomly assigned to receive equimolar supplements (0.5 mmol ⋠kg(-1) ⋠d(-1)) of methionine or alanine (control) immediately after CP1. RESULTS: In the methionine compared with the alanine group, cysteine flux derived from protein breakdown was faster at CP2 than CP1 (P < 0.05), and the change in plasma cysteine concentration from CP1 to CP2 was greater (P < 0.05). However, there was no evidence of a difference in cysteine de novo synthesis and its total flux or erythrocyte glutathione synthesis rate and concentration between groups. CONCLUSIONS: Methionine supplementation increased cysteine flux from body protein but had no significant effect on glutathione synthesis rates. Although cysteine is made from methionine, increased dietary cysteine may be necessary to partially fulfill its demand in edematous SAM because glutathione synthesis rates and concentrations were less than previous values shown at full recovery. This study was registered at clinicaltrials.gov as NCT00473031.