Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries.

Vitamin D inhibits the development and growth of prostate cancer cells. Epidemiologic results on serum vitamin D levels and prostate cancer risk have, however, been inconsistent. We conducted a longitudinal nested case-control study on Nordic men (Norway, Finland and Sweden) using serum banks of 200,000 samples. We studied serum 25(OH)-vitamin D levels of 622 prostate cancer cases and 1,451 matched controls and found that both low (</=19 nmol/l) and high (>/=80 nmol/l) 25(OH)-vitamin D serum concentrations are associated with higher prostate cancer risk. The normal average serum concentration of 25(OH)-vitamin D (40-60 nmol/l) comprises the lowest risk of prostate cancer. The U-shaped risk of prostate cancer might be due to similar 1,25-dihydroxyvitamin D(3) availability within the prostate: low vitamin D serum concentration apparently leads to a low tissue concentration and to weakened mitotic control of target cells, whereas a high vitamin D level might lead to vitamin D resistance through increased inactivation by enhanced expression of 24-hydroxylase. It is recommended that vitamin D deficiency be supplemented, but too high vitamin D serum level might also enhance cancer development.