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

Background: We previously reported that daily supplementation with alpha-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 alpha-tocopherol inhibited tumor angiogenesis, an effect demonstrated in animal models.

Patients And Methods: We evaluated whether long-term supplementation with alpha-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 alpha-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 alpha-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 alpha-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 alpha-tocopherol in the ATBC Study may have been through reduced VEGF concentrations and the suppression of tumor angiogenesis and therefore growth.