Effect of serum folate status on total folate and 5-methyltetrahydrofolate in human skin123

It has been suggested that human skin color adapts to balance the need for vitamin D synthesis in comparison with the protection of DNA and folate from photodegradation. However, the folate content of human skin is unknown and may affect the effectiveness of the antifolate methotrexate for the treatment of psoriasis. We examined whether total folate and 5-methyl-(6S)-tetrahydrofolate (5-MTHF) in human skin can be predicted by serum concentrations and whether there are differences in the proportion of 5-MTHF in dermis compared with epidermis. Total folate (by using a microbiological assay) and 5-MTHF (by using high-pressure liquid chromatography) were measured in fasting serum and fresh skin obtained at surgery by using a recovery validated extraction method. Total folate in human epidermis was shown to be low compared with in many other tissues, and dermal folate was an order-of-magnitude even lower. These concentrations were directly and linearly linked to serum folate status. Although the percentage of 5-MTHF of the total in the dermis was similar to that in other organs, it was especially high in the epidermis and increased to >65% as serum folate decreased. The high proportion of 5-MTHF in the epidermis, which is further emphasized in subjects with a lower (10–20-nmol/L) serum folate status, points to a special role for this form of folate in skin, perhaps as a protectant from ultraviolet-induced photosensitization reactions. 5-MTHF may also maintain methylation reactions that influence the proliferative activity. These results may help to individualize the treatment of psoriasis patients with methotrexate and folate.