Randomized, placebo-controlled pilot trial of the effects of alpha-tocopherol supplementation on levels of autoantibodies against 5-hydroxymethyl-2-deoxyuridine in melanoma patients.

Abstract

We conducted a randomized, placebo-controlled pilot trial to assess whether supplementation of 1000 mg/day alpha-tocopherol for 3 months offered protection against DNA base damage in melanoma outpatients (n=46). Plasma autoantibodies (aAbs) against 5-hydroxymethyl-2-deoxyuridine (HMdU) were measured as an immune marker of DNA base damage. After 3 months of supplementation (final level), plasma levels of alpha-tocopherol increased significantly (P<0.0005) in the alpha-tocopherol compared with the placebo treatment group. Supplementation with alpha-tocopherol also resulted in a significant (P=0.04) decrease in plasma gamma-tocopherol levels among males. Overall, we did not find any significant differences in the plasma anti-HMdU aAb levels between the two treatment groups. However, when the patients were stratified by the clinical characteristics of the melanoma, we found that alpha-tocopherol supplementation resulted in a borderline significant (P=0.06) 48% decrease in plasma anti-HMdU aAb levels in patients with less aggressive melanomas (Breslow thickness </=1 mm) only. Within-group analysis showed that women had significantly (P<0.05) higher baseline levels of anti-HMdU aAbs compared with men in each treatment group. However, the final levels of anti-HMdU aAbs were significantly (P<0.05) higher in women in the alpha-tocopherol supplemented group only. Although reliable conclusions cannot be drawn from this pilot study, which is limited by the small sample size, the results suggest that short-term alpha-tocopherol supplementation may offer some protection against less aggressive melanomas. Further studies using much larger sample sizes are required to confirm this finding.