Vitamin D and folate: A reciprocal environmental association based on seasonality and genetic disposition

The purpose of this study was (1) to elucidate any reciprocal seasonal relationship that might exist between red cell folate (RCF) and serum vitamin D3 Levels; (2) to explore whether folate-related gene variants that influence/alter DNA-thymidylate and methyl group biosynthesis modify any associations detected in objective 1; and (3) to consider whether these processes might influence reproductive success consistent with the "folate-vitamin D-UV hypothesis of skin pigmentation" evolutionary model.

A large (n = 649) Australian cross-sectional study population was examined. Polymerase chain reaction (PCR)/Restriction fragment length polymorphism (RFLP) analysis was used to genotype C677T-MTHFR, C1420T-SHMT, T401C-MTHFD and 2R > 3R-TS. RCF was measured by chemiluminescent immunoassay and vitamin D2 and D3 by HPLC.

RCF and photosynthesized vitamin D3 , but not RCF and dietary vitamin D2 , exhibit a significant reciprocal association in spring and summer. Three folate genes (C677T-MTHFR, C1420T-SHMT, and 2R > 3R-TS) strengthen this effect in spring, and another (T401C-MTHFD) in summer. Effects are seasonal, and do not occur over the whole year.

Findings are consistent with what might be required for the "folate-vitamin D-UV hypothesis of skin pigmentation" model. It suggests genetic influence in provision of one-carbon units by 5,10-methylene-H4 folate, may be an important factor in what appears to be a clear seasonal relationship between vitamin D3 and folate status.