Biophysical evidence to support and extend the vitamin D-folate hypothesis as a paradigm for the evolution of human skin pigmentation

Mark D Lucock; Patrice R Jones; Martin Veysey; Rohith Thota; Manohar Garg; John Furst; Charlotte Martin; Zoe Yates; Christopher J Scarlett; Nina G Jablonski; George Chaplin; Emma L Beckett

doi:10.1002/ajhb.23667

Biophysical evidence to support and extend the vitamin D-folate hypothesis as a paradigm for the evolution of human skin pigmentation

Am J Hum Biol. 2022 Apr;34(4):e23667. doi: 10.1002/ajhb.23667. Epub 2021 Aug 21.

Authors

Affiliations

¹ School of Environmental and Life Sciences, University of Newcastle, Ourimbah, New South Wales, Australia.
² Medicine, Hull York Medical School, Heslington, UK.
³ Nutraceuticals Research Group, University of Newcastle, Callaghan, New South Wales, Australia.
⁴ Metabolism and Nutrition, Riddet Institute, Massey University, Palmerston North, New Zealand.
⁵ Maths and Physical Sciences, University of Newcastle, Ourimbah, New South Wales, Australia.
⁶ Biomedical Sciences and Pharmacy, University of Newcastle, Ourimbah, New South Wales, Australia.
⁷ Anthropology Department, The Pennsylvania State University, University Park, Pennsylvania, USA.

PMID: 34418235
DOI: 10.1002/ajhb.23667

Abstract

Objective: To test the "vitamin D-folate hypothesis for the evolution of human skin pigmentation."

Methods: Total ozone mapping spectrometer (TOMS) satellite data were used to examine surface UV-irradiance in a large (n = 649) Australian cross-sectional study population. Genetic analysis was used to score vitamin D- and folate-related gene polymorphisms (n = 22), along with two pigmentation gene variants (IRF4-rs12203592/HERC2-rs12913832). Red cell folate and vitamin D₃ were measured by immunoassay and HPLC, respectively.

Results: Ultraviolet radiation (UVR) and pigmentation genes interact to modify blood vitamin levels; Light skin IRF4-TT genotype has greatest folate loss while light skin HERC2-GG genotype has greatest vitamin D₃ synthesis (reflected in both TOMS and seasonal data). UV-wavelength exhibits a dose-response relationship in folate loss within light skin IRF4-TT genotype (305 > 310 > 324 > 380 nm). Significant vitamin D₃ photosynthesis only occurs within light skin HERC2-GG genotype, and is maximal at 305 nm. Three dietary antioxidants (vitamins C, E, and β-carotene) interact with UVR and pigmentation genes preventing oxidative loss of labile reduced folate vitamers, with greatest benefit in light skin IRF4-TT subjects. The putative photosensitiser, riboflavin, did not sensitize red cell folate to UVR and actually afforded protection. Four genes (5xSNPs) influenced blood vitamin levels when stratified by pigmentation genotype; MTHFR-rs1801133/rs1801131, TS-rs34489327, CYP24A-rs17216707, and VDR-ApaI-rs7975232. Lightest IRF4-TT/darkest HERC2-AA genotype combination (greatest folate loss/lowest vitamin D₃ synthesis) has 0% occurrence. The opposing, commonest (39%) compound genotype (darkest IRF4-CC/lightest HERC2-GG) permits least folate loss and greatest synthesis of vitamin D₃ .

Conclusion: New biophysical evidence supports the vitamin D-folate hypothesis for evolution of skin pigmentation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Australia
Cross-Sectional Studies
Folic Acid
Genotype
Humans
Skin Pigmentation* / genetics
Ultraviolet Rays / adverse effects
Vitamin D*
Vitamins

Substances

Vitamins
Vitamin D
Folic Acid