The following data were extracted from each included study: reference citation, affiliated institutions of authors, author specialties, journal name, year of publication, study period, type of article, type of study, mechanism of adaptation, data concluding or supporting vitamin D as the driver, and data concluding or suggesting against vitamin D as the driver. Data concluding or supporting vitamin D as the driver were recorded from statistically significant results, study conclusions, and direct quotations. Data concluding or suggesting against vitamin D as the driver also were recorded from significant results, study conclusions, and direct quotes. The mechanism of adaptation was based on vitamin D synthesis modulation, melanin upregulation, genetic selections, genetic drift, mating patterns, increased vitamin D sensitivity, interbreeding, and diet.
Studies included in the analysis were placed into 1 of 3 categories: supporting, neutral, and against. Strength of Recommendation Taxonomy (SORT) criteria were used to classify the level of evidence of each article.4 Each article’s level of evidence was then graded (Table 1). The SORT grading levels were based on quality and evidence type: level 1 signified good-quality, patient-oriented evidence; level 2 signified limited-quality, patient-oriented evidence; and level 3 signified other evidence.4
Results
Article Selection—A total of 229 articles were identified for screening, and 39 studies met inclusion criteria.1-3,5-40 Systematic and retrospective reviews were the most common types of studies. Genomic analysis/sequencing/genome-wide association studies (GWAS) were the most common methods of analysis. Of these 39 articles, 26 were classified as supporting the evolutionary vitamin D adaptation hypothesis, 10 were classified as neutral, and 3 were classified as against (Table 1).
Of the articles classified as supporting the vitamin D hypothesis, 13 articles were level 1 evidence, 9 were level 2, and 4 were level 3. Key findings supporting the vitamin D hypothesis included genetic natural selection favoring vitamin D synthesis genes at higher latitudes with lower UVR and the skin lightening that occurred to protect against vitamin D deficiency (Table 1). Specific genes supporting these findings included 7-dehydrocholesterol reductase (DHCR7), vitamin D receptor (VDR), tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), oculocutaneous albinism type 2 melanosomal transmembrane protein (OCA2), solute carrier family 45 member 2 (SLC45A2), solute carrier family 4 member 5 (SLC24A5), Kit ligand (KITLG), melanocortin 1 receptor (MC1R), and HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2)(Table 2).
A search of PubMed, Embase, and the Cochrane Reviews database was conducted to generate research articles published from 2010 to 2022 evaluating the influence of UV radiation–dependent production of vitamin D on skin pigmentation through historical migration patterns.
Of the articles classified as being against the vitamin D hypothesis, 1 article was level 1 evidence, 1 was level 2, and 1 was level 3. Key findings refuting the vitamin D hypothesis included similar amounts of vitamin D synthesis in contemporary dark- and light-pigmented individuals, vitamin D–rich diets in the late Paleolithic period and in early agriculturalists, and metabolic conservation being the primary driver (Table 1).
Of the articles classified as neutral to the hypothesis, 7 articles were level 1 evidence and 3 were level 2. Key findings of these articles included genetic selection favoring vitamin D synthesis only for populations at extremely northern latitudes, skin lightening that was sustained in northern latitudes from the neighboring human ancestor the chimpanzee, and evidence for long-term evolutionary pressures and short-term plastic adaptations in vitamin D genes (Table 1).