title: Vitamin C supplementation lowers urinary levels of 4-hydroperoxy-2-nonenal metabolites in humans.
abstract: 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 (500mg 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.
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Heather C
authors.initials: HC
authors.lastname: Kuiper
authors.forename: Richard S
authors.initials: RS
authors.lastname: Bruno
authors.forename: Maret G
authors.initials: MG
authors.lastname: Traber
authors.forename: Jan F
authors.initials: JF
authors.lastname: Stevens
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry / Q000652:urine; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000447:Aldehydes / Q000737:chemistry / Q000652:urine*; D000475:Alkenes / Q000737:chemistry / Q000652:urine; D000975:Antioxidants / Q000008:administration & dosage* / Q000032:analysis; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D012737:Sex Factors; D012907:Smoking / Q000097:blood / Q000652:urine; D055815:Young Adult
chemical_list: C091765:1,4-dihydroxy-2-nonene; D000447:Aldehydes; D000475:Alkenes; D000975:Antioxidants; D015415:Biomarkers; C547259:4-hydroperoxy-2-nonenal; D001205:Ascorbic Acid; D000111:Acetylcysteine