Effect of cysteine and glycine on oxidative stress.

Sekhar R, Patel S, Guthikonda A, Reid M, Balasubramanyam A, Taffet G, Jahoor F. 2011. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am J Clin Nutr 94:3;847-53.

Elevated oxidative stress has been linked to several age related illnesses including the development of cataracts, macular degeneration, immune deficiencies, neurodegenerative diseases and increased DNA damage. Glutathione is the most abundant endogenous intracellular antioxidant synthesised from the amino acids glutamate, cysteine and glycine. Glutathione plays a central role in antioxidant defences and preventing irreversible cell damage. Cellular levels of this antioxidant decline with ageing.

In this study researchers tested whether glutathione deficiency occurs because of diminished synthesis and contributes to oxidative stress in ageing; they examined whether stimulating glutathione synthesis with its precursors cysteine and glycine could alleviate oxidative stress. Eight healthy elderly individuals (60-75 yrs) and 8 younger subjects (30-40 yrs) were recruited for this study (5 men and 3 women in each group).

At baseline researchers measured the subjects blood count, glucose concentration and liver and renal profile. Both groups received infusions of stable isotopes to measure glutathione synthesis in the fasted state. Only the elderly subjects received intervention: oral treatment of 14 days with 0.81 mmol cysteine x [kg.sup.-1] x [d.sup.-1] (as n-acetyl cysteine) and 1.33 mmol glycine x [kg.sup.-1] x [d.sup.-1]. The younger subjects were kept as controls.

The younger subjects had a lower body mass index (BMI) than the elderly subjects. Younger subjects were euglycemic, while the elderly subjects had impaired glucose tolerance and higher concentrations of fasting glucose and glycated hemoglobin. No differences in hematologic variables, renal function or liver enzymes were found between the two groups or before and after glutathione precursor supplementation in the elderly.

Compared with younger control subjects, elderly subjects had 55.2% lower concentrations of glycine and 24.4% lower concentrations of cysteine in RBCs. After the elderly subjects received cysteine and glycine supplementation, RBC glycine concentrations increased by 117.6%, and RBC cysteine concentrations increased by 55.1%.

Prior to supplementation the elderly subjects had 46.2% lower RBC glutathione concentrations than the control (2.08 [+ or -] 0.12 compared with 1.12 [+ or -] 0.18 mmol glutathione/L RBC; P < 0.05). They also had a 44.9% slower glutathione fractional synthesis rate (FSR) and a 68.2% slower absolute synthesis rate (ASR) at baseline.

After treatment with cysteine and glycine for 14 days, the elderly subjects had 94.6% higher RBC glutathione concentration (from 1.12 [+ or -] 0.18 to 2.18 [+ or -] 0.35 mmol glutathione/L RBC; P < 0.05) and a 78.8% higher FSR resulting in a 230.9% higher ASR (from 0.55 [+ or -] 0.12 to 1.82 [+ or -] 0.39 mmol glutathione/L RBC per day; P < 0.01).

The slower rates of glutathione synthesis in the elderly subjects at baseline were associated with significantly higher concentrations of markers of oxidative damage (plasma reactive oxygen metabolites, plasma F2-isoprostanes and lipid peroxides). After 14 days of treatment with dietary cysteine and glycine supplements, a significant decrease in these variables was observed which resulted in post supplementation values that were similar to those of the young control subjects.

Although a very small sample size, this study indicates that a deficiency of glutathione precursors in the elderly predisposes not only to glutathione deficiency but also to oxidative stress and subsequent damage.

Kathleen Murphy MNHAA

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