Vitamin D and cardiovascular disease.

It has long been known from case series that vitamin D excess can lead to atherosclerosis and vascular calcification in humans. In the 1980s, ecological studies provided data that deficient human vitamin D status may also increase the risk of developing cardiovascular disease (CVD). The assumption of a biphasic vitamin D effect on CVD is supported by experimental studies: Numerous studies have demonstrated positive effects of the vitamin D hormone (1,25-dihydroxyviramin D) on the cardiovascular system. However, the effects and mechanisms that lead to vascular calcification by vitamin D excess could also be confirmed. Large prospective observational studies support the hypothesis of a U-shaped association between vitamin D and CVD. These studies indicate that deficient circulating 25-hydroxyvitamin D levels (<30 nmol/l) are independently-associated with increased CVD morbidity and mortality. They also suggest that those circulating 25-hydroxyvitamin D levels, which have long been considered to be safe (100-150 nmol/l), are associated with an increased CVD risk. Meanwhile, numerous randomized controlled trials have investigated the effects of vitamin D supplements or ultraviolet B radiation on biochemical cardiovascular risk markers, cardiovascular physiology, and cardiovascular outcomes. Overall, results are mixed with the majority of studies reporting neither beneficial nor adverse vitamin D effects. Several limitations in the study design, which may have prevented beneficial vitamin D effects, are discussed. In conclusion, it must be stated that the role of vitamin D in the prevention and management of CVD as well as the dose-response relationship of potentially harmful effects still remain to be established.