Clinical studies of GSH/GSSG redox variation. We made the surprising finding that substantial oxidation (approximately 25 mV) was apparent in individuals >60 compared to <43 y old (30). We also found that diabetic individuals were about 20 mV more oxidized than similarly aged individuals without known disease. In a follow-up study, we found that GSH/GSSG redox as a function of age was biphasic, with no apparent association with age below 45 y and a linear oxidation with age after 50 y. Preliminary data from our study of diurnal variation in GSH/GSSG redox status show that there was an increase in GSH during the evening and nighttime hours and that the redox state was more reduced during this time period. These results are consistent with rodent studies showing that hepatic GSH undergoes a diurnal variation linked to sulfur amino acid intake (31-32). These results support our central hypothesis that sulfur amino acid intake is a determinant of plasma GSH/GSSG redox state in humans.