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

Am J Hum Biol. 2018 Sep;30(5):e23166. doi: 10.1002/ajhb.23166. Epub 2018 Sep 9.

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Australia
  • Cholecalciferol / blood
  • Cholecalciferol / chemistry
  • Cross-Sectional Studies
  • Ergocalciferols / blood
  • Ergocalciferols / chemistry
  • Erythrocytes / chemistry
  • Female
  • Folic Acid / blood*
  • Folic Acid / genetics
  • Humans
  • Male
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Seasons
  • Serum / chemistry
  • Vitamin D / blood*
  • Vitamin D / genetics
  • Vitamins / blood*
  • Vitamins / genetics

Substances

  • Ergocalciferols
  • Vitamins
  • Vitamin D
  • Cholecalciferol
  • Folic Acid