The Vitamin D-folate hypothesis as an evolutionary model for skin pigmentation: an update and integration of current ideas

Vitamin D is unique in being generated in our skin following ultraviolet radiation (UVR) exposure. Ongoing research into vitamin D must therefore always consider the influence of UVR on vitamin D processes. The close relationship between vitamin D and UVR forms the basis of the “vitamin D–folate hypothesis”, a popular theory for why human skin colour has evolved as an apparent adaption to UVR environments. Vitamin D and folate have disparate sensitivities to UVR; whilst vitamin D may be synthesised following UVR exposure, folate may be degraded. The vitamin D–folate hypothesis proposes that skin pigmentation has evolved as a balancing mechanism, maintaining levels of these vitamins. There are several alternative theories that counter the vitamin D–folate hypothesis. However, there is significant overlap between these theories and the now known actions of vitamin D and folate in the skin. The focus of this review is to present an update on the vitamin D–folate hypothesis by integrating these current theories and discussing new evidence that supports associations between vitamin D and folate genetics, UVR, and skin pigmentation. In light of recent human migrations and seasonality in disease, the need for ongoing research into potential UVR-responsive processes within the body is also discussed.