Methionine loading seems to be accompanied by increased oxidative stress and damage. However, it is not known how this oxidative stress is generated. We performed the present crossover study to further elucidate the effects of methionine loading on oxidative stress in the blood of healthy volunteers, and to examine possible preventative effects of N-acetylcysteine (NAC) administration. A total of 18 healthy subjects were given two oral methionine loads of 100 mg/kg body weight, 4 weeks apart, one without NAC (Met group), and one in combination with supplementation with 2×900 mg doses of NAC (Met+NAC group). Blood samples were collected before and 2, 4, 8 and 24 h after methionine loading for measurements of thiol levels, protein carbonyls, lipid peroxidation, cellular fibronectin and ferric reducing ability of plasma (FRAP; i.e. antioxidant capacity). After methionine loading, whole-blood levels of free and oxidized cysteine and homocysteine were increased in both groups. Furthermore, the total plasma levels of homocysteine were higher, whereas those of cysteine were lower, after methionine loading in both groups. Lower levels of oxidized homocysteine and a higher free/oxidized ratio were found in the Met+NAC group compared with the Met group. Although the antioxidant capacity decreased after methionine loading, no major changes over time were found for protein carbonyls or cellular fibronectin in either group. Our results suggest that methionine loading may initiate the generation of reactive oxygen species by the (auto)-oxidation of homocysteine. In addition, supplementation with NAC seems to be able to partially prevent excessive increases in the levels of homocysteine in plasma and of oxidized homocysteine in whole blood, and might thereby contribute to the prevention of oxidative stress.

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