Antioxidant dietary supplements: Rationale and current status as chemopreventive agents for prostate cancer

Epidemiologic data suggest that the environment is responsible for most prostate cancers (PCA). One major mechanism by which the environment can influence carcinogenesis is oxidative damage. This refers to the generation of reactive oxygen species (ROS) that then damage important biomolecules, including DNA, protein, and lipids. Experimental observations suggest that oxidative damage is associated with PCA. These include: a) the association of PCA and dietary fat consumption (a major substrate for oxidative stress), b) oxidative biomarker data (suggesting increased oxidative stress among patients with PCA), c) ubiquitous defects in the glutathione-s-transferase pi pathway (a major endogenous antioxidant mechanism), and d) evidence that androgens (an important promoter of PCA growth) work in part via generation of ROS. Perhaps the best indirect evidence for oxidative stress comes from randomized double-blind prevention trials of antioxidants. Vitamin E and selenium have both been shown to reduce prostate cancer incidence. Although PCA prevention was not the primary endpoint of these studies, the statistical likelihood that both would prove beneficial by chance alone is 1 in 400. These data suggest that antioxidants may be beneficial in preventing PCA. Further research including randomized trials is warranted.