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The expected rise in glutathione levels would likely be somewhat lower than the initial rise in synthesis rate, as glutathione acts as a feedback competitive inhibitor of glutamate cysteine ligase.10 In animal studies, glycine supplementation has been reported to increase tissue glutathione levels in milk-fed piglets and in rats subjected to burn injury, alcohol-induced liver injury, or fructose-induced metabolic syndrome.11-14 Clinical studies evaluating urinary excretion of 5-L-oxoproline provide evidence that dietary glycine is indeed limiting for glutathione synthesis in humans consuming their typical diets (as opposed to experimental diets depleted of glycine).15-17 When glycine availability is too low to sustain normal rates of glutathione synthesis, the consequent rise in tissue levels of gamma-glutamylcysteine results in increased conversion of this compound to 5-L-oxoproline that is then excreted in the urine.15,16 In a study comparing daily urinary excretion of this metabolite in omnivores and vegetarians, vegetarian males excreted 86% more 5-L-oxoproline than omnivore males, and vegetarian females excreted 37% more than omnivore females.17 These researchers also found that urinary excretion of 5-L-oxoproline rose significantly when subjects were switched from a diet providing 6.2 g of nitrogen per day to one providing 4 g of nitrogen per day

Cancer Epidemiology and Prevention Biomarkers , 14 (2), 467475

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