The Vitamin D–Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas

Jones, Patrice; Lucock, Mark; Veysey, Martin; Beckett, Emma L.

doi:10.3390/nu10050554

Cited by 49 publications

(65 citation statements)

References 98 publications

(135 reference statements)

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“…The only significant (and relatively strong) negative correlation with folic acid concentrations was found with respect to the frequency of visiting tanning salons. This pattern is in agreement with current theories (Jones, Lucock, Veysey, & Beckett, 2018) according to which in human populations there exist two mutually independent skin darkness latitudinal gradients, the results of two distinct selection pressures. The first gradient is found in populations which originated between subtropical and subpolar latitudes, that is, in the temperate climate.…”

Section: Discussionsupporting

confidence: 92%

Increased calcidiol level in redhaired people: Could redheadedness be an adaptation to temperate climate?

Flegr

Sýkorová

Fiala

et al. 2019

Preprint

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About 1-2% of European population are redhaired, meaning they synthesize more 19 pheomelanin than eumelanin, the main melanin pigment. Several mutations could be 20 responsible for this phenotype. It has been suggested that corresponding mutations spread in 21 Europe due to a founder effect shaped either by a relaxation of selection for dark, UV-22 protective phenotypes or by sexual selection in favor of rare phenotypes. In our study, we 23 investigated the levels of vitamin D precursor calcidiol and folic acid in the blood serum of 24 73 redhaired and 130 non-redhaired individuals. In redhaired individuals, we found higher 25 calcidiol concentrations and approximately the same folic acid concentrations as in non-26 redhaired subjects. Calcidiol concentrations correlated with the intensity of hair redness 27 measured by two spectrophotometric methods and estimated by participants themselves and 28 by independent observers. In non-redhaired individuals, calcidiol levels covaried with the 29 amount of sun exposure and intensity of suntan while in redhaired individuals, this was not 30the case. It suggests that increased calcidiol levels in redhaired individuals are due to 31 differences in physiology rather than in behavior. We also found that folic acid levels 32 increased with age and the intensity of baldness and decreased with the frequency of visiting 33 tanning salons. Our results suggest that the redhaired phenotype could be an evolutionary 34 adaptation for sufficient photosynthesis of provitamin D in conditions of low intensity of UV-35 B radiation in central and northern parts of Europe.36

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Section: Discussionsupporting

confidence: 92%

Increased calcidiol level in redhaired people: Could redheadedness be an adaptation to temperate climate?

Flegr

Sýkorová

Fiala

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…The relationship between vitamin D-associated SNPs and skin pigmentation is an important consideration regarding differences between geographically defined populations. Skin pigmentation is an apparent adaptation to differing UVB environments, with darker-pigmented populations originating in areas of high UVB, and lighter-pigmented populations in lower UVB areas [11][12][13]. However, the genetic architecture underlying skin pigmentation differs even between populations exposed to similar UVB regimes.…”

Section: Introductionmentioning

confidence: 99%

Distribution of variants in multiple vitamin D-related loci (DHCR7/NADSYN1, GC, CYP2R1, CYP11A1, CYP24A1, VDR, RXRα and RXRγ) vary between European, East-Asian and Sub-Saharan African-ancestry populations

et al. 2020

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Background: The frequency of vitamin D-associated gene variants appear to reflect changes in long-term ultraviolet B radiation (UVB) environment, indicating interactions exist between the primary determinant of vitamin D status, UVB exposure and genetic disposition. Such interactions could have health implications, where UVB could modulate the impact of vitamin D genetic variants identified as disease risk factors. However, the current understanding of how vitamin D variants differ between populations from disparate UVB environments is limited, with previous work examining a small pool of variants and restricted populations only. Methods: Genotypic data for 46 variants within multiple vitamin D-related loci (DHCR7/NADSYN1, GC, CYP2R1, CYP11A1, CYP27A1, CYP24A1, VDR, RXRα and RXRγ) was collated from 60 sample sets (2633 subjects) with European, East Asian and Sub-Saharan African origin via the NCBI 1000 Genomes Browser and ALFRED (Allele Frequency Database), with the aim to examine for patterns in the distribution of vitamin D-associated variants across these geographic areas. Results: The frequency of all examined genetic variants differed between populations of European, East Asian and Sub-Saharan African ancestry. Changes in the distribution of variants in CYP2R1, CYP11A1, CYP24A1, RXRα and RXRγ genes between these populations are novel findings which have not been previously reported. The distribution of several variants reflected changes in the UVB environment of the population's ancestry. However, multiple variants displayed population-specific patterns in frequency that appears not to relate to UVB changes. Conclusions: The reported population differences in vitamin D-related variants provides insight into the extent by which activity of the vitamin D system can differ between cohorts due to genetic variance, with potential consequences for future dietary recommendations and disease outcomes.

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“…It remains unclear how lower folate concentrations may improve outcomes in early pregnancy but contribute to complications seen later in gestation; perhaps a subtlety in folate metabolism that has yet to be elucidated may explain this phenomenon. One possibility may align with a current theory proposing that darker melanin prevents UV-mediated folate degradation in the circulation at the dermal layer [34]; given African American women with darker melanin are less susceptible to folate oxidation, they may need lower levels of folates to promote proper embryo development and pregnancy health compared to lighter-skinned mothers.…”

Section: Discussionmentioning

confidence: 85%

The effect of race and supplementation on maternal and umbilical cord plasma folates

Maulik

Haandel

Allsworth

et al. 2019

The Journal of Maternal-Fetal & Neonatal Medicine

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Objective: The purpose of this study is to test the hypothesis that race and supplementation affect the concentration and correlation of various folate species in maternal and umbilical cord blood. Methods: This is a single-center, prospective, cross-sectional cohort of cord blood samples obtained from 40 uncomplicated term pregnancies as a pilot study, following a protocol approved by the Institutional Review Board. High performance liquid chromatography mass spectrometry quantitated the following concentrations in extracted plasma samples: 5-methyltetrahydrofolate (5MTHF), 5,10-methenyl-tetrahydrofolate (5,10-MeTHF), tetrahydrofolate (THF), and unmetabolized folic acid. Results: Folate concentrations in the umbilical cord plasma were consistently higher than maternal samples for 5MTHF (p < .001), 5,10-MeTHF (p < .001), and THF (p < .001); cord blood folic acid levels, however, were lower than maternal samples (p < .03). While 5MTHF was the most prevalent folate, ratios comparing cord blood to maternal blood folates suggests a fourfold preponderance of THF in cord blood folate signature, a trend unchanged by supplementation. Prenatal supplementation increased the concentrations of 5MTHF, for both maternal (p < .01) and cord blood samples (p < .005). In comparison to the other two racial groups, African American 5MTHF concentration demonstrated a lower total folate concentration in both maternal samples and cord blood samples, in addition to a relatively blunted response to supplementation. A significantly positive correlation between maternal and cord blood 5MTHF concentration was noted in all three racial groups. Supplementation resulted in a positive correlation between maternal and cord blood 5MTHF concentrations (r ¼ 0.85, p < .0001). Conclusions: 5MTHF is the most prevalent folate in both cord and maternal plasma, and race and supplementation primarily affect variations in maternal and fetal 5MTHF concentrations and their correlation with each other. However, the greater concentration of THF in cord blood relative to maternal blood offers preliminary insight into the importance of how folate metabolism differs in the specific context of fetal development and physiology, with greater emphasis on DNA synthesis and stability. Furthermore, supplementation appeared to not have as great an impact on African American maternal or cord blood folates, suggesting a variable benefit of current repletion strategies to certain subsets of the population. Future studies that further elucidate these differences and their impact on birth outcomes may help inform supplementation protocols that are more personalized, with greater efficacy in promoting positive perinatal outcomes. ARTICLE HISTORY

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The Vitamin D–Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas

Cited by 49 publications

References 98 publications

Increased calcidiol level in redhaired people: Could redheadedness be an adaptation to temperate climate?

Increased calcidiol level in redhaired people: Could redheadedness be an adaptation to temperate climate?

Distribution of variants in multiple vitamin D-related loci (DHCR7/NADSYN1, GC, CYP2R1, CYP11A1, CYP24A1, VDR, RXRα and RXRγ) vary between European, East-Asian and Sub-Saharan African-ancestry populations

The effect of race and supplementation on maternal and umbilical cord plasma folates

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