The vitamin D-folate hypothesis in human vascular health

The vitamin D-folate hypothesis has been proposed as an explanation for the evolution of human skin pigmentation. According to this hypothesis, a darkened skin pigment was adapted by early human populations living in equatorial Africa to protect against photodegradation of bioavailable folate by ultraviolet radiation (UVR). As humans moved away from the equator to more northern latitudes and occupied regions of lower UVR exposure and greater seasonal variation, however, depigmentation occurred to allow for adequate biosynthesis of vitamin D. Vitamin D and folate are both recognized for their evolutionary importance in healthy pregnancy and early childhood development. More recently, evidence has emerged demonstrating the importance of both vitamin D and folate in vascular health via their effects in reducing oxidative stress and improving nitric oxide (NO) bioavailability. Thus, populations with darkened skin pigmentation may be at elevated risk of vascular dysfunction and cardiovascular disease in low UVR environments due to hypovitaminosis D; particularly important as darkly-pigmented African-Americans represent an at-risk population for cardiovascular disease. Conversely, lightly pigmented populations in high UVR environments may be at risk of deleterious vascular effects of UVR-induced folate degradation. The focus of this review is to explore the currently available literature regarding the potential role of UVR in vascular health via its differential effects on vitamin D and folate metabolism, as well as the interaction between skin pigmentation, genetics, and environment in modulating the vascular influence of UVR exposure.