title: 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.
authors.affiliation: Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Insitute, Bethesda, Maryland 20892-8314, USA. mahabirs@mail.nih.gov
authors.forename: Somdat
authors.initials: S
authors.lastname: Mahabir
authors.forename: Krystyna
authors.initials: K
authors.lastname: Frenkel
authors.forename: Mary Sue
authors.initials: MS
authors.lastname: Brady
authors.forename: Daniel
authors.initials: D
authors.lastname: Coit
authors.forename: Leonard
authors.initials: L
authors.lastname: Leibes
authors.forename: Jerzy
authors.initials: J
authors.lastname: Karkoszka
authors.forename: Marianne
authors.initials: M
authors.lastname: Berwick
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D001323:Autoantibodies / Q000032:analysis*; D004249:DNA Damage; D004260:DNA Repair; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D010865:Pilot Projects; D010919:Placebos; D012878:Skin Neoplasms / Q000188:drug therapy / Q000276:immunology; D013936:Thymidine / Q000031:analogs & derivatives* / Q000276:immunology*; D014810:Vitamin E / Q000627:therapeutic use; D024502:alpha-Tocopherol / Q000627:therapeutic use*; D024504:gamma-Tocopherol / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D001323:Autoantibodies; D010919:Placebos; D014810:Vitamin E; C018080:5-hydroxymethyl-2'-deoxyuridine; D024504:gamma-Tocopherol; D024502:alpha-Tocopherol; D013936:Thymidine