Vitamin C supplementation lowers urinary levels of 4-hydroperoxy-2-nonenal metabolites in humans

The lack of suitable biomarkers of oxidative stress is a common problem for antioxidant intervention studies in humans. We evaluated the efficacy of vitamin C supplementation in decreasing biomarkers of lipid peroxidation in nonsmokers and in cigarette smokers, a commonly studied, free-living human model of chronic oxidative stress. Participants received ascorbic acid (500 mg twice per day) or placebo for 17 days in a double-blind, placebo-controlled, randomized crossover design study. The urinary biomarkers assessed and reported herein are derived from 4-hydroperoxy-2-nonenal (HPNE) and include the mercapturic acid (MA) conjugates of 4-hydroxy-2(E)-nonenal (HNE), 1,4-dihydroxy-2(E)-nonene (DHN), and 4-oxo-2(E)-nonenol(ONO). Vitamin C supplementation decreased the urinary concentrations of both ONO-MA (p = 0.0013) and HNE-MA (p = 0.0213) by ~ 30%; however, neither cigarette smoking nor sex affected these biomarkers. In contrast, vitamin C supplementation decreased urinary concentrations of DHN-MA (three-way interaction p = 0.0304) in nonsmoking men compared with nonsmoking women (p < 0.05), as well as in nonsmoking men compared with smoking men (p < 0.05). Vitamin C supplementation also decreased (p = 0.0092) urinary total of metabolites by ~ 20%. Thus, HPNE metabolites can be reduced favorably in response to improved plasma ascorbic acid concentrations, an effect due to ascorbic acid antioxidant function.