THE EFFECTS OF VITAMIN-C SUPPLEMENTATION ON BIOMARKERS OF OXYGEN RADICAL GENERATED DAMAGE IN HUMAN VOLUNTEERS WITH LOW OR HIGH CHOLESTEROL LEVELS

A human volunteer study was conducted to test the effect of vitamin C supplementation on biomarkers of oxygen radical-mediated damage in ind ividuals with a range of serum cholesterol levels. A group of 48 non-s mokers, 24 men and 24 women, was selected from a panel of over 100 vol unteers to give as wide a range of serum cholesterol levels as possibl e. None of the volunteers was taking medication to control cholesterol levels and they maintained their normal dietary habits so as not to c ompromise their cholesterol status. Volunteers were allocated to three groups of 16, each consisting of four males with low cholesterol leve ls (<6 mmol/L) matched for age and build with four males with high cho lesterol levels (>6 mmol/L) and eight females matched in the some way. A three-treatment, three-treatment period, cross-over design was adop ted to take account of any temporal differences in response. The three treatments given were placebo, 60 mg vitamin C/day (the recommended d aily allowance) and 6 g vitamin C/day. Each treatment was given for 14 days with 6 weeks between the treatment periods. All procedures were performed to the standards of Good Clinical Practice. Blood samples we re taken at the end of each treatment period. Serum was assayed for ch olesterol whilst vitamin C, total antioxidant capacity, lipid peroxida tion breakdown products and ras p21 protein levels were measured in pl asma. lymphocytes were examined for DNA damage using the Comet assay a nd chromosome aberration test. The Comet assay was conducted with and without challenge with hydrogen peroxide and the chromosome aberration test with and without challenge with bleomycin. Vitamin C supplementa tion caused a statistically significant increase in plasma vitamin C c oncentrations and total antioxidant capacity but did not affect choles terol levels or ras p21 protein levels. There was a non-significant do se-related decrease in lipid peroxidation breakdown products with vita min C supplementation. No effect on DNA damage was observed in the Com et assay, either with or without hydrogen peroxide challenge, or in th e chromosome aberration test without bleomycin. However, a statistical ly significant increase in bleomycin-induced aberrations was Found aft er vitamin C supplementation. This may be due to effects of vitamin C on iron status. Comparison of male and female subjects showed statisti cally significant differences in plasma vitamin C levels, the antioxid ant capacity of the plasma and the number of chromosome aberrations in duced by bleomycin challenge of lymphocytes in vitro. The results were the same for both low and high cholesterol subjects. This study provi des no evidence of a beneficial effect on any of the biomarkers studie d of vitamin C supplementation over a short-term supplementation perio d of 2 weeks in a population of healthy, non-smoking individuals eatin g a nutritionally adequate diet. (C) 1997 Wiley-Liss, Inc.