Methionine-adequate cysteine-free diet does not limit erythrocyte glutathione synthesis in young healthy adult men.

The Journal of nutrition. 2008;138(11):2172-8

Plain language summary

The amino acid cysteine is believed to be a rate-limiting substrate for synthesis of the antioxidant glutathione. The aim of this study was to determine whether cysteine supplementation increased glutathione synthesis in healthy men. Four healthy men of average age 20 years were each given five levels of cysteine intake ranging from 0 to 40mg per kg body weight per day. Each level of intake was given for a period of 3 days, with glutathione levels in red blood cells measured on the 3rd day of each period. Subjects were also provided with a standardised diet, an amino acid mixture equivalent to that found in egg protein, a daily multivitamin supplement, a choline supplement and methionine throughout the study. In this study, increasing cysteine intake did not result in increased glutathione synthesis. The authors concluded that a diet with adequate protein intake is sufficient for glutathione synthesis in healthy adults.

Abstract

Most methods of determining amino acid (AA) requirements are based on endpoints that determine adequacy for protein synthesis. However, the sulfur AA (SAA) cysteine is believed to be the rate-limiting substrate for synthesis of the most abundant intracellular antioxidant, glutathione (GSH). Our objectives were to determine whether supplementation of cysteine in a diet containing adequate SAA for protein synthesis, as methionine, increased GSH synthesis by measuring the fractional and absolute synthesis rates, and if concentration of GSH changed in response to feeding 5 graded intakes of cysteine (0, 10, 20, 30, and 40 mg x kg(-1) x d(-1)) in a random order with a fixed methionine intake of 14 mg x kg(-1) x d(-1) and a protein intake of 1 g x kg(-1) x d(-1). Each subject received a multivitamin and choline supplement during the study. Four healthy adult men each underwent 5 isotope infusion studies of 7-h duration after a 2-d adaptation to the level of cysteine intake being studied on the isotope infusion day. The isotope used was [U-(13)C(2)-(15)N]glycine. Analyses included erythrocyte GSH synthesis rates and concentration and urinary sulfate excretion. The GSH synthesis rates and concentration, measured at a methionine intake of 14 mg x kg(-1) x d(-1), did not change with increasing intakes of cysteine. Urinary sulfate excretion showed a significant positive relationship with cysteine intake (r = 0.92; P < 0.01). In conclusion, this study provides preliminary evidence that consumption of SAA adequate to meet the requirement for protein synthesis does not limit GSH synthesis in healthy adult men receiving an otherwise adequate diet.

Lifestyle medicine

Fundamental Clinical Imbalances : Immune and inflammation
Patient Centred Factors : Mediators/Cysteine
Environmental Inputs : Diet ; Nutrients
Personal Lifestyle Factors : Nutrition
Functional Laboratory Testing : Blood ; Urine
Bioactive Substances : Amino acids ; Protein ; Sulphur amino acids

Methodological quality

Jadad score : 1
Allocation concealment : No

Metadata

Nutrition Evidence keywords : Amino acids ; Protein ; Sulphur amino acids