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Antioxidant Supplementation Decreases Lipid Peroxidation Biomarker F₂-isoprostanes in Plasma of Smokers¹

School of Public Health [M. D., G. B.] and Department of Nutritional Sciences [M. H.], University of California, Berkeley, California 94720-7360; Vanderbilt University, Division of Clinical Pharmacology, Nashville, Tennessee 37232-6602 [J. D. M.]; Department of Biomedical Research, Our Lady of Mercy Medical Center, Bronx, New York 10466-2697 [E. P. N.]; University of California Davis School of Medicine, Sacramento, California 95817 [M. G. T., C. E. C.]; Department of Nutrition and Food Management, Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331-6512 [M. G. T.]; and Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, California 90089-9121 [L. P.]

Free radicals in cigarette smoke (CS) cause oxidative damage to proteins, DNA, and lipids, contributing to the pathobiology of atherosclerosis, heart disease, and cancer. In vitro studies have shown that antioxidants quench free radicals and ameliorate certain aspects of biomolecular damage caused by CS. It is hypothesized that a combination of antioxidants is more effective than a single antioxidant, due to their interactions. To investigate whether supplemental antioxidants reduce CS-related lipid peroxidation in vivo and whether they are more effective in combination, we conducted an intervention study in smokers. In a randomized double-blind placebo-controlled trial, we investigated whether vitamin C or an antioxidant mixture containing vitamin C, -lipoic acid, and vitamin E decreases plasma F₂-isoprostane levels, an index of oxidant stress, in smokers. Plasma of 126 smokers (mean age, 46 years; age range, 20–78 years) was analyzed for F₂-isoprostanes at baseline and after intervention with antioxidants and placebo. In smokers with a body mass index (BMI) above the median, 2 months of daily supplementation with 500 mg of vitamin C decreased plasma F₂-isoprostane levels by 28.8 pmol/liter when compared with the placebo group (P = 0.001); levels in the mixture group were 7.45 pmol/liter lower after treatment, but this difference was not statistically significant (P = 0.14). There was no treatment effect in smokers with a low BMI. BMI was significantly positively associated with plasma F₂-isoprostane levels (trend P = 0.001). Antioxidants decrease smoking-related lipid peroxidation markers of oxidative stress in humans with high BMI. Our results do not indicate that an antioxidant combination is more effective than vitamin C alone. The intake of antioxidants may help prevent smoking-related diseases. Smoking cessation should still be considered the most effective way to prevent smoking-related diseases.

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