Vitamin supplementation and breast cancer: is homeostasis a factor?

Recent observations by several research groups on many thousands of women have yielded the disappointing view that mega-dose vitamin supplementation does not provide significant protection against breast cancer. This is a review of the pertinent literature with a goal of identifying testable hypotheses that might explain the epidemiology and be helpful in designing subsequent evaluations. In one hypothesis presented, the vitamin content of peripheral cells that protect breast epithelium is not markedly affected by supplementation. In the second hypothesis the metabolic status (redox state) of epithelial cells is more important than the absolute level (reduced plus oxidized) of each antioxidant. In either case, extremes in diet fail to alter inherent homeostatic mechanisms.