Long-term alpha-tocopherol supplementation is associated with lower serum vascular endothelial growth factor levels

Background: We previously reported that daily supplementation with a-tocopherol reduced prostate cancer risk in a large, randomized trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. One potential mechanism explaining this is that a-tocopherol inhibited tumor angiogenesis, an effect demonstrated in animal models. Patients and Methods: We evaluated whether long-term supplementation with a-tocopherol modified serum vascular endothelial growth factor (VEGF) levels, a cytokine integrally involved in angiogenesis, in men who were not diagnosed with cancer and had baseline and follow-up blood available. One hundred of these men who received a-tocopherol (50 mg daily) were randomly selected and matched on age, study center and time between blood draws to 100 men who received placebo (median follow-up 3.7 years). VEGF levels were measured by enzyme-linked immunosorbent assay. The effect of α-tocopherol supplementation on serum VEGF was evaluated using a matched-paired t-test for differences in the change in VEGF over the intervention period between groups. Results: There was an 11% reduction in VEGF levels in the α-tocopherol group as compared with a 10% increase in the placebo group (p = 0.03). Conclusion: Our findings suggest that one of the mechanisms behind the inhibition of prostate carcinogenesis by a-tocopherol in the ATBC Study may have been through reduced VEGF concentrations and the suppression of tumor angiogenesis and therefore growth.