FIGURE 3.

The figure shows the complex relationship between folate dependent one‐carbon transfers into dTMP (DNA), purines (GTP and hence BH₄) and methionine (methyl groups, including genomic CpG groups) and the contribution these make to melanogenesis. It also shows how anti‐oxidant vitamins interact to protect labile folates from UVR, and details the biochemistry related to the formation of the three forms of melanin (pheomelanin, DHICA‐eumelanin and DHI‐eumelanin—in order of increasing darkness). A working hypothesis is that folate is required for BH₄ and hence melanin production. Therefore, a low folate equates to lower BH₄ and hence reduced melanin biosynthesis. This reduction in melanin leads to even more UVR‐related folate loss and hence ever greater DNA damage. This propagates a progressive negative spiral in folate status since the low folate that does exist will be redirected to DNA repair, and demonstrates how dietary antioxidant status is likely relevant in this scenario for protecting reduced and highly labile folates from UV‐related oxidation. Folate gene and pigmentation gene interactions are also likely important in modulating this progressive negative spiral in folate status