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 (500 mg twice per day) or placebos for 17 d 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 (3-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 bỹ 20%. Thus, HPNE metabolites can be reduced favorably in response to improved plasma ascorbic acid concentrations, an effect due to ascorbic acid antioxidant function.

Evaluation of the effect of vitamin C on caspase 9 and oxidative stress in rheumatoid arthritis patients

“…In agreement with these results, Meki et al (2009) and Kuiper et al (2011) found significant reduction in lipid peroxidation in response to vitamin C administration. Also, Al-Jassabi and Khalil (2006) found that vitamin C markedly inhibited oxidative DNA damage (as indicated by measurement of 8 OHdG).…”

Vitamins C and E: Beneficial effects from a mechanistic perspective

“…Our research group has investigated the effect of vitamin C supplementation (500 mg twice daily for 17 days) on urinary levels of metabolites of 4-hydroperoxy-2( E )-nonenal, as an indicator of oxidative stress [82, 83], in a double-blind, placebo-controlled, randomized crossover study in 22 young adults. Vitamin C supplementation was found to decrease the urinary concentrations of these LPO product metabolites by 20-30% [84], in support of the notion that vitamin C supplementation exerts antioxidant effects and reduces oxidative stress in vivo.…”

Lung cancer biomarkers for the assessment of modified risk tobacco products: an oxidative stress perspective

“…Recently, a urinary assay for the mercapturic acid conjugate of 4-HNE has been developed and reductions following 12-weeks of smoking cessation reported (Kuiper et al, 2010). In other studies, these authors reported that vitamin C supplementation reduced the urinary 4-HNE secretion (Kuiper et al, 2011). Thus, biomarkers of 4-HNE show promise as biomarkers of biological effect in smokers but, clearly, further work is required to understand the differences observed between detection methods and to estimate the possibility of dietary confounding in non-clinical studies.…”