Vitamin D Hypothesis
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Vitamin D Hypothesis
The vitamin D hypothesis is an evolutionary explanation for part of the worldwide variation in human skin pigmentation. It proposes that as human populations moved into environments with different levels of ultraviolet radiation, natural selection favored pigmentation that helped balance two competing biological requirements: protection from excessive ultraviolet radiation and the production of adequate vitamin D in the skin.
In regions with intense ultraviolet radiation, high concentrations of melanin provide substantial protection against ultraviolet damage. In regions where ultraviolet B (UVB) radiation is weaker or strongly seasonal, however, very dark pigmentation can reduce the penetration of UVB into the skin. Because UVB is required for cutaneous vitamin D production, lighter pigmentation may have increased the efficiency of vitamin D synthesis among populations living in low-UV environments.
The hypothesis therefore views much of human pigmentation as an evolutionary compromise rather than as a simple progression from darker to lighter skin. Dark pigmentation can be advantageous under strong ultraviolet exposure, while reduced pigmentation can become advantageous where insufficient UVB creates a risk of vitamin D deficiency.
Modern research generally treats this process as more complex than vitamin D alone. Pigmentation evolved through interactions among ultraviolet radiation, vitamin D, folate, genetics, migration, diet, climate, cultural practices, and demographic history.
Ultraviolet Radiation, Melanin, and Vitamin D
Vitamin D can be synthesized in human skin when UVB radiation initiates photochemical reactions involving vitamin D precursors. The amount that can be produced depends on numerous environmental and behavioral factors, including latitude, season, time of day, atmospheric conditions, altitude, clothing, the amount of exposed skin, lifestyle, and pigmentation.
Latitude is particularly important because the amount of UVB reaching Earth's surface declines substantially at higher latitudes and during winter. At some northern latitudes, solar UVB becomes too weak during parts of the year to support substantial cutaneous vitamin D production.
Melanin absorbs and disperses ultraviolet radiation. This provides important photoprotection, reducing ultraviolet penetration and damage to cellular structures. At the same time, increased pigmentation can reduce the amount of UVB available for vitamin D synthesis under some exposure conditions.
Experimental research has repeatedly examined whether people with different pigmentation levels produce different amounts of vitamin D when exposed to comparable UVB doses. Several studies have reported slower or smaller vitamin D responses in more deeply pigmented skin. Other experiments have found that sufficiently large ultraviolet doses can substantially reduce or eliminate these differences, and some controlled studies have concluded that factors such as baseline vitamin D status, cholesterol, UVB dose, and exposed body surface area can be as important as pigmentation.
The evidence therefore supports an interaction rather than a simple rule. Pigmentation can influence vitamin D production, but it operates alongside environmental exposure, behavior, physiology, diet, and inherited variation in vitamin D metabolism.
The Evolutionary Trade-Off
The vitamin D hypothesis developed from the striking geographical relationship between indigenous human pigmentation and ultraviolet radiation. Populations whose ancestors lived for long periods in regions of intense UV radiation generally evolved greater pigmentation, while many populations living in regions with substantially lower UV radiation evolved lighter pigmentation.
One influential evolutionary model proposes two opposing selective pressures.
Under intense ultraviolet radiation, darker skin provides greater photoprotection. In lower-UV environments, reduced pigmentation allows UVB to penetrate the skin more efficiently and may increase vitamin D production.
Vitamin D is important for calcium metabolism, skeletal development, and many other physiological processes. Severe deficiency can cause rickets in children and osteomalacia in adults. Historically, severe rickets could deform the pelvis and skeleton, potentially impairing mobility and childbirth. Such consequences provide a plausible route through which inadequate vitamin D could have reduced reproductive fitness.
The evolutionary importance of vitamin D may also extend beyond bone health. Vitamin D receptors occur in many tissues, and vitamin D signaling is involved in immune function, cell proliferation, differentiation, reproductive physiology, skin biology, vascular processes, and other regulatory systems.
For this reason, the evolutionary consequences of chronic vitamin D deficiency may have involved multiple biological systems rather than skeletal disease alone.
Folate and the Vitamin D-Folate Hypothesis
A broader version of the model is often called the vitamin D-folate hypothesis. It proposes that human pigmentation evolved partly through a balance between the need to produce vitamin D and the need to protect folate and other sensitive biological molecules from excessive ultraviolet radiation.
Laboratory research shows that folic acid and biologically important forms of folate can undergo photodegradation. Folate is essential to DNA synthesis and repair, cell division, fertility, pregnancy, and fetal development.
Adequate folate is particularly important during pregnancy because folate deficiency increases the risk of neural tube defects. Folate also contributes to male reproductive biology, and low folate concentrations have been associated with increased sperm DNA damage.
These reproductive functions make folate preservation potentially relevant to natural selection.
Under this model, intense ultraviolet radiation favored increased melanin because pigmentation helped shield the body from UV-related damage and possibly reduced the degradation of folate. At lower latitudes of UV exposure, this photoprotective advantage diminished while the need to maintain sufficient vitamin D production became relatively more important.
Human pigmentation may therefore represent a balance between photoprotection in high-UV environments and photosynthesis of vitamin D in lower-UV environments.
Migration and the Evolutionary Mismatch
Human migration provides some of the clearest modern examples of the relationship among pigmentation, ultraviolet radiation, and vitamin D.
When populations move rapidly between regions, their inherited pigmentation may no longer correspond closely to the ultraviolet environment in which they live. Cultural change occurs far faster than genetic adaptation.
Darkly pigmented populations whose ancestors lived in high-UV regions can therefore experience increased vitamin D deficiency after migration to northern environments with weak or strongly seasonal UVB. Studies of immigrants in Britain, Denmark, Canada, and other high-latitude countries have repeatedly documented low vitamin D concentrations and, in some populations, increased rates of nutritional rickets and osteomalacia.
Research involving South Asian populations in northern Europe has found that ordinary summer sunlight exposure recommendations developed for lighter-skinned populations may not always be sufficient to produce comparable vitamin D concentrations.
Pigmentation is not the only cause of these disparities. Clothing, indoor living, limited sun exposure, diet, age, supplementation, socioeconomic conditions, and cultural practices can substantially modify vitamin D status.
Conversely, rickets can occur even in tropical environments with abundant sunlight. Research from Kenya and other regions shows that malnutrition, calcium deficiency, living conditions, limited exposure, and other factors can override the theoretical advantage of high ambient UV radiation.
Migration studies therefore illustrate both the strength and the limitations of a purely pigmentation-based explanation.
Genetics and the Evolution of Pigmentation
Skin pigmentation is a highly polygenic trait. Numerous genes contribute to the production, distribution, type, and regulation of melanin.
Population-genetic research has identified strong evidence of natural selection on pigmentation-associated genes. Important loci include genes such as SLC24A5, SLC45A2, OCA2, TYR, TYRP1, KITLG, and others.
A major insight from genetic research is that lighter skin did not evolve through a single genetic pathway. European and East Asian populations developed lighter pigmentation partly through different sets of genetic changes, providing evidence for convergent evolution.
This indicates that similar environmental pressures can produce broadly similar phenotypes through different genetic routes.
Genetics also affects vitamin D physiology directly. Variation in vitamin D receptors, vitamin D-binding proteins, synthesis pathways, transport mechanisms, and metabolic enzymes contributes to differences in circulating vitamin D concentrations and responses to ultraviolet exposure.
The evolutionary response to low UVB therefore may not have been limited to changes in pigmentation. Populations could also adapt through changes in vitamin D metabolism, diet, physiology, or other biological systems.
Ancient DNA and the Timing of Depigmentation
Ancient DNA has substantially complicated earlier models of European pigmentation evolution.
Genomic evidence indicates that some Mesolithic Europeans living at relatively high latitudes retained ancestral pigmentation variants. Major alleles associated with lighter pigmentation did not necessarily become widespread immediately after modern humans entered Europe.
Some pigmentation variants underwent strong selection only thousands of years later.
Ancient genomes also show that changes in pigmentation frequencies can reflect both natural selection and population migration. New pigmentation alleles could spread because populations carrying them expanded or replaced earlier populations, while subsequent selection altered their frequencies further.
This delayed and uneven history suggests that low UVB alone cannot explain every change in pigmentation.
Diet may have altered selective pressure as well. Populations consuming vitamin-D-rich foods could potentially maintain adequate vitamin D without requiring equally strong selection for depigmentation. Changes associated with agriculture, food production, and population movement may consequently have altered the balance of selective pressures.
The ancient-DNA record therefore supports a role for natural selection while showing that the evolutionary history was neither immediate nor uniform.
Pregnancy, Reproduction, and Fitness
Pregnancy increases the biological importance of vitamin D and folate because both nutrients participate in maternal and fetal physiology.
Studies have documented substantial vitamin D deficiency among some pregnant immigrant and darkly pigmented populations living at northern latitudes. Maternal deficiency can also result in low vitamin D concentrations in newborns.
Vitamin D receptors and metabolic pathways are present in reproductive tissues, and experimental and clinical research has connected vitamin D signaling with fertility, estrogen biosynthesis, skeletal development, and other reproductive processes.
Folate provides the opposing side of the evolutionary model. It is essential to fetal neural development, DNA synthesis, sperm quality, and other reproductive functions.
Because natural selection operates most strongly on traits affecting reproductive success, the consequences of both vitamin D deficiency and folate depletion provide plausible mechanisms linking ultraviolet environments to the evolution of pigmentation.
Alternative Hypotheses and Competing Selective Pressures
The vitamin D hypothesis is influential, but the uploaded research does not support treating it as the only explanation for human pigmentation.
Some researchers argue that the physiology of the epidermal permeability barrier may have contributed to the evolution of pigmentation. Experimental research indicates differences in barrier function associated with pigmentation and shows that ultraviolet exposure can impair the epidermal barrier.
Climate may have contributed additional selective pressures. Hypotheses involving cold injury, thermoregulation, and energy conservation have been proposed as partial explanations for geographical pigmentation differences.
Sexual selection has also been investigated. Models based on mate choice and sexual dimorphism propose that cultural preferences and reproductive competition could have modified pigmentation frequencies after geographic variation had already developed.
Skin cancer has been proposed as another selective force favoring dark pigmentation in early humans. Other researchers argue that most skin cancers historically would have occurred too late in life to exert selection as strongly as reproductive-age effects such as folate protection.
Several pigmentation genes also have functions beyond pigmentation. Selection acting on a gene for another physiological trait can indirectly alter skin color through pleiotropy.
These alternatives need not be mutually exclusive. Human pigmentation may reflect multiple selective forces operating simultaneously or at different times and places.
Culture, Diet, and Behavior
Human biological evolution increasingly occurred in interaction with culture.
Clothing reduces ultraviolet exposure. Architecture and indoor living change the amount of sunlight reaching the skin. Diet can provide vitamin D independently of ultraviolet radiation. Agriculture can change nutrient availability. Migration can move populations into radically different ultraviolet environments within a few generations.
These factors weaken any simple relationship between latitude and pigmentation.
Modern vitamin D status therefore cannot be predicted from skin color alone. Two people with similar pigmentation may experience very different vitamin D environments because of occupation, clothing, diet, supplementation, outdoor activity, geographic location, and season.
Likewise, low circulating vitamin D measurements do not necessarily have identical biological implications among all populations. Variation in vitamin D-binding proteins, receptors, metabolism, and other inherited physiological characteristics can influence vitamin D biology.
The evolution of pigmentation is best understood as a gene-environment-culture interaction rather than a response to ultraviolet radiation in isolation.
Modern Significance
Rapid global migration has created many combinations of ancestry, pigmentation, diet, lifestyle, and ultraviolet environment that were uncommon during most of human evolution.
People with deeply pigmented skin living at northern latitudes may have a higher probability of inadequate cutaneous vitamin D production, particularly when sunlight exposure is limited. Conversely, lightly pigmented individuals living in intense ultraviolet environments may experience greater UV-related skin damage without protective behavior.
These patterns represent examples of evolutionary mismatch: traits that evolved under one set of environmental conditions are expressed in another.
The research also cautions against interpreting pigmentation as a simple biological classification of human populations. Human skin color is a continuously varying, polygenic trait shaped repeatedly by natural selection, migration, ancestry, environmental conditions, and cultural behavior.
Conclusion
The vitamin D hypothesis provides an important framework for explaining the evolution of human skin pigmentation. Its central idea is that natural selection helped balance the protective value of melanin under intense ultraviolet radiation against the need for sufficient UVB penetration to produce vitamin D in environments where ultraviolet radiation was weaker.
Geographic patterns of pigmentation, experimental research on UVB and vitamin D synthesis, the prevalence of vitamin D deficiency following migration to low-UV environments, and genetic evidence of selection on pigmentation genes all provide support for important components of the hypothesis.
The evidence also shows that the evolutionary history is more complicated than a single vitamin D mechanism. Folate protection, diet, ancient population movements, cultural practices, vitamin D metabolism, epidermal barrier biology, climate, sexual selection, pleiotropy, and other selective pressures may all have contributed.
Ancient DNA is especially important because it demonstrates that lighter pigmentation did not simply appear as soon as humans entered northern latitudes. Pigmentation alleles changed in frequency over thousands of years through both natural selection and population movement.
The most comprehensive interpretation is therefore not that vitamin D alone determined human skin color, but that pigmentation represents an evolving compromise among ultraviolet radiation, nutrient biology, genetics, culture, migration, and reproduction. Human skin pigmentation is one of the clearest examples of the complex interaction between biological evolution and changing environments.
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Core Evolutionary Framework and the Vitamin D Hypothesis
| Prashiela Manga; Stacie Loftus | Annals of Human Genetics | 2025
Genetics of Skin, Hair, and Eye Color in Human Pigmentation Disorders. Reviews the genetic machinery controlling pigmentation and places modern variation in the context of environmental and evolutionary pressures.
| Kyra Diehl et al. | Cutis | 2024
Exploring Skin Pigmentation Adaptation: A Systematic Review on the Vitamin D Adaptation Hypothesis. Systematically evaluates evidence that lighter pigmentation was favored at higher latitudes because it improved cutaneous vitamin D synthesis.
| Nina G. Jablonski | Feldman and Pike's Vitamin D | 2024
Evolution of Human Skin Pigmentation and Vitamin D. Reviews pigmentation evolution using UV geography, paleontology, genomics, migration history, and the need to maintain vitamin D production.
| Mark D. Lucock | American Journal of Biological Anthropology | 2023
The Evolution of Human Skin Pigmentation: A Changing Medley of Vitamins, Genetic Variability, and UV Radiation During Human Expansion. Integrates vitamin D, folate, pigmentation genes, diet, antioxidants, migration, and cultural adaptations.
| Mark D. Lucock et al. | American Journal of Human Biology | 2022
Biophysical Evidence to Support and Extend the Vitamin D-Folate Hypothesis. Tests relationships among UV exposure, pigmentation variants, vitamin D, folate, and nutrient-related genes in humans.
| Nina G. Jablonski | Pigment Cell & Melanoma Research | 2021
The Evolution of Human Skin Pigmentation Involved the Interactions of Genetic, Environmental, and Cultural Variables. Emphasizes that pigmentation evolution reflects UV radiation, diet, migration, cultural practices, and genetic history rather than one selective pressure alone.
| Andrea Hanel; Carsten Carlberg | Experimental Dermatology | 2020
Skin Colour and Vitamin D: An Update. Reviews evidence for vitamin-D-driven depigmentation but argues that ancient-genomic population movements and vitamin D pathway adaptations complicate the classical hypothesis.
The Vitamin D-Folate Hypothesis in Human Vascular Health. Extends the evolutionary model by examining how vitamin D, folate, UV exposure, pigmentation, and vascular physiology interact.
| Patrice Jones; Mark Lucock; Martin Veysey; Emma Beckett | Nutrients | 2018
The Vitamin D-Folate Hypothesis as an Evolutionary Model for Skin Pigmentation. Reviews evidence that pigmentation evolved partly to balance vitamin D photosynthesis against UV-related folate loss.
| Nina G. Jablonski; George Chaplin | International Journal of Paleopathology | 2018
The Roles of Vitamin D and Cutaneous Vitamin D Production in Human Evolution and Health. Explains how skin pigmentation could balance photoprotection with sufficient vitamin D production across different UV environments.
| Nina G. Jablonski | Vitamin D, Fourth Edition | 2018
Evolution of Human Skin Color and Vitamin D. Synthesizes evidence that depigmentation evolved repeatedly in low-UVB environments and discusses modern mismatches between ancestry, pigmentation, and UV exposure.
| Nina G. Jablonski | Journal of the Royal College of Physicians of Edinburgh | 2012
The Evolution of Human Skin Colouration and Its Relevance to Health in the Modern World. Connects dark pigmentation with folate protection and lighter pigmentation with vitamin D production after dispersal from tropical Africa.
| Nina G. Jablonski; George Chaplin | Philosophical Transactions of the Royal Society B | 2012
Human Skin Pigmentation, Migration and Disease Susceptibility. Describes pigmentation as a compromise between UV protection and vitamin D synthesis and examines consequences of recent migrations.
| Nina G. Jablonski; George Chaplin | Proceedings of the National Academy of Sciences | 2010
Human Skin Pigmentation as an Adaptation to UV Radiation. Presents the influential two-cline model: dark pigmentation favored under intense UV and depigmentation favored where UVB was insufficient for efficient vitamin D synthesis.
| A.W.C. Yuen; Nina G. Jablonski | Medical Hypotheses | 2010
Vitamin D: In the Evolution of Human Skin Colour. Argues that skeletal, reproductive, and other consequences of vitamin D deficiency were severe enough to create substantial selection for lighter pigmentation.
| George Chaplin; Nina G. Jablonski | American Journal of Physical Anthropology | 2009
Vitamin D and the Evolution of Human Depigmentation. Examines the geographical and evolutionary case for natural selection favoring depigmentation as humans entered low-UVB environments.
| Nina G. Jablonski | Annual Review of Anthropology | 2004
The Evolution of Human Skin and Skin Color. Reviews the evolutionary history of naked skin, melanization, UV radiation, folate protection, and vitamin D production.
| George Chaplin | American Journal of Physical Anthropology | 2004
Geographic Distribution of Environmental Factors Influencing Human Skin Coloration. Maps environmental variables influencing pigmentation and shows the close relationship between indigenous skin color and UV radiation.
| Nina G. Jablonski; George Chaplin | Journal of Human Evolution | 2000
The Evolution of Human Skin Coloration. Provides a foundational quantitative analysis relating global skin pigmentation to UV radiation and opposing requirements for photoprotection and vitamin D synthesis.
| W.F. Loomis | Science | 1967
Skin-Pigment Regulation of Vitamin-D Biosynthesis in Man. One of the earliest explicit formulations proposing that lighter skin was favored at low latitudes of UVB availability to permit adequate vitamin D production.
UVB, Skin Pigmentation, and Cutaneous Vitamin D Production
| Ken Batai et al. | PLOS Genetics | 2021
Genetic Loci Associated With Skin Pigmentation in African Americans and Their Effects on Vitamin D Deficiency. Links pigmentation variants including SLC24A5, SLC45A2, and OCA2 with pigmentation and severe vitamin D deficiency risk.
| Pernille Datta et al. | Photochemical & Photobiological Sciences | 2021
Low Vitamin D in Dark-Skinned Immigrants Is Mainly Due to Clothing Habits and Low UVR Exposure: A Danish Observational Study. Finds that reduced exposed skin and lower actual UV exposure accounted for much of the difference between immigrant and Danish participants.
| Reinhold Vieth | Osteoporosis International | 2020
Weaker Bones and White Skin as Adaptions to Improve Anthropological Fitness for Northern Environments. Explores vitamin D, skeletal mineralization, pelvic deformation, childbirth, and natural selection in northern environments.
| John L.M. Hawk | Photodermatology, Photoimmunology & Photomedicine | 2020
Safe, Mild Ultraviolet-B Exposure: An Essential Human Requirement for Vitamin D and Other Vital Bodily Parameter Adequacy. Reviews the physiological importance of low-level UVB exposure while discussing the balance between beneficial vitamin D production and photodamage.
| Ze'ev Hochberg; Irit Hochberg | Frontiers in Endocrinology | 2019
Evolutionary Perspective in Rickets and Vitamin D. Reviews rickets from evolutionary, dietary, cultural, genetic, and pigmentation perspectives.
| Suma Uday; Wolfgang Högler | Archives of Disease in Childhood | 2018
Prevention of Rickets and Osteomalacia in the UK: Political Action Overdue. Describes the continuing interaction among northern latitude, dark pigmentation, migration, vitamin D deficiency, and rickets.
| Elio Kechichian; Khaled Ezzedine | American Journal of Clinical Dermatology | 2018
Vitamin D and the Skin: An Update for Dermatologists. Reviews cutaneous vitamin D production, metabolism, pigmentation, photoprotection, and dermatological implications.
| Wolfgang Rossberg et al. | Anticancer Research | 2016
Human Pigmentation, Cutaneous Vitamin D Synthesis and Evolution: Variants of Genes Involved in Skin Pigmentation Are Associated With 25(OH)D Serum Concentration. Links inherited pigmentation variants with vitamin D concentrations and discusses their evolutionary implications.
| Wafaa Z. Mostafa; Rehab A. Hegazy | Journal of Advanced Research | 2015
Vitamin D and the Skin: Focus on a Complex Relationship. Reviews UVB synthesis, pigmentation, vitamin D metabolism, skin disease, and the benefits and risks of sunlight exposure.
| Janniche Nissen et al. | American Journal of Clinical Nutrition | 2015
Common Variants in CYP2R1 and GC Genes Are Determinants of Serum 25-Hydroxyvitamin D After UVB Irradiation. Shows that genetic variation modifies vitamin D responses to both UVB and dietary intake.
| Feng Xiang et al. | Photochemical & Photobiological Sciences | 2015
A Systematic Review of the Influence of Skin Pigmentation on Changes in Concentrations of Vitamin D and 25-Hydroxyvitamin D Following Experimental UV Irradiation. Reviews controlled studies testing whether pigmentation changes vitamin D production after standardized ultraviolet exposure.
| Richard Saternus et al. | Endocrinology | 2015
A Closer Look at Evolution: Variants of Genes Involved in Skin Pigmentation, Including EXOC2, TYR, TYRP1, and DCT, Are Associated With 25(OH)D Serum Concentration. Provides genetic evidence connecting pigmentation pathways with contemporary vitamin D status.
| Carolina Bonilla et al. | BMC Public Health | 2014
Skin Pigmentation, Sun Exposure and Vitamin D Levels in Children of the Avon Longitudinal Study of Parents and Children. Examines how pigmentation, ancestry, season, and sunlight behavior jointly influence childhood vitamin D status.
| F. Libon; E. Cavalier; A.F. Nikkels | Dermatology | 2013
Skin Color Is Relevant to Vitamin D Synthesis. Reports a stronger vitamin D response to standardized UVB exposure in fair-skinned participants than in deeply pigmented participants.
| Camille E. Powe et al. | New England Journal of Medicine | 2013
Vitamin D-Binding Protein and Vitamin D Status of Black Americans and White Americans. Demonstrates that ancestry-associated differences in vitamin D-binding protein complicate interpretation of total circulating vitamin D.
| Robert Kift et al. | British Journal of Dermatology | 2013
Lifestyle Factors Including Less Cutaneous Sun Exposure Contribute to Starkly Lower Vitamin D Levels in U.K. South Asians Compared With the White Population. Shows that pigmentation interacts strongly with behavior, clothing, outdoor exposure, and lifestyle.
| Mark D. Farrar et al. | American Journal of Clinical Nutrition | 2013
Efficacy of a Dose Range of Simulated Sunlight Exposures in Raising Vitamin D Status in South Asian Adults. Quantifies the greater UV exposure required to substantially improve vitamin D status among South Asian adults living at northern latitude.
| Daniel D. Bikle | Molecular and Cellular Endocrinology | 2011
Vitamin D Metabolism and Function in the Skin. Reviews the skin's ability to synthesize and metabolize vitamin D and the biological roles of vitamin D signaling in epidermal tissues.
| Morten K.B. Bogh et al. | Experimental Dermatology | 2011
Vitamin D Production Depends on Ultraviolet-B Dose but Not on Dose Rate: A Randomized Controlled Trial. Demonstrates that total UVB dose, rather than how rapidly the dose is delivered, is the major determinant of vitamin D response.
| Morten K.B. Bogh et al. | British Journal of Dermatology | 2011
Interdependence Between Body Surface Area and Ultraviolet B Dose in Vitamin D Production: A Randomized Controlled Trial. Shows that both UVB dose and the amount of exposed skin influence vitamin D production.
| Mark D. Farrar et al. | American Journal of Clinical Nutrition | 2011
Recommended Summer Sunlight Exposure Amounts Fail to Produce Sufficient Vitamin D Status in UK Adults of South Asian Origin. Finds that sunlight recommendations developed for lighter-skinned populations may not produce equivalent vitamin D levels in darker-skinned people.
| Morten K.B. Bogh et al. | Journal of Investigative Dermatology | 2010
Vitamin D Production After UVB Exposure Depends on Baseline Vitamin D and Total Cholesterol but Not on Skin Pigmentation. A controlled study found baseline vitamin D and cholesterol more predictive of UVB-induced increases than measured pigmentation, providing an important challenge to simple pigmentation models.
| Ivan Camacho; Jennifer Tzu; Robert S. Kirsner | Journal of Investigative Dermatology | 2010
Regulation of Vitamin D Production Is Independent of Skin Color. Discusses evidence questioning whether pigmentation alone adequately explains differences in vitamin D production.
| Michael G. Kimlin | Molecular Aspects of Medicine | 2008
Geographic Location and Vitamin D Synthesis. Examines geographic variation in UVB and its implications for populations living at different latitudes.
| Laura A.G. Armas et al. | Journal of the American Academy of Dermatology | 2007
Ultraviolet-B Radiation Increases Serum 25-Hydroxyvitamin D Levels: The Effect of UVB Dose and Skin Color. Experimental UVB exposures showed that both radiation dose and skin pigmentation influence increases in circulating vitamin D.
| Michael F. Holick | New England Journal of Medicine | 2007
Vitamin D Deficiency. Reviews sunlight-dependent vitamin D synthesis, latitude, pigmentation, diet, bone health, and the global prevalence of deficiency.
| Ann R. Webb | Progress in Biophysics and Molecular Biology | 2006
Who, What, Where and When—Influences on Cutaneous Vitamin D Synthesis. Explains how geographic location, season, atmospheric conditions, skin exposure, pigmentation, and behavior determine vitamin D photosynthesis.
| Ola Engelsen et al. | Photochemistry and Photobiology | 2005
Daily Duration of Vitamin D Synthesis in Human Skin With Relation to Latitude, Ozone, Altitude, Ground Cover, Aerosols and Clouds. Models where and when solar UVB exceeds the threshold needed for vitamin D production.
| Hector F. DeLuca | American Journal of Clinical Nutrition | 2004
Overview of General Physiologic Features and Functions of Vitamin D. Summarizes vitamin D production and physiology relevant to understanding why deficiency could exert evolutionary selection.
| John M. Pettifor et al. | South African Medical Journal | 1996
The Effect of Season and Latitude on In Vitro Vitamin D Formation by Sunlight in South Africa. Demonstrates marked geographic and seasonal differences in the capacity of natural sunlight to generate vitamin D.
| Michael F. Holick | American Journal of Clinical Nutrition | 1995
Environmental Factors That Influence the Cutaneous Production of Vitamin D. Reviews how latitude, season, time of day, atmospheric conditions, clothing, sunscreen, age, and pigmentation alter the amount of vitamin D produced in human skin.
| L.Y. Matsuoka et al. | Archives of Dermatology | 1991
Racial Pigmentation and the Cutaneous Synthesis of Vitamin D. Demonstrates differences in vitamin D production following a standardized UVB exposure among people with different pigmentation levels.
| A.R. Webb; B.R. DeCosta; M.F. Holick | Journal of Clinical Endocrinology & Metabolism | 1989
Sunlight Regulates the Cutaneous Production of Vitamin D3 by Causing Its Photodegradation. Shows that sunlight both produces and limits vitamin D through photochemical reactions, preventing unlimited accumulation.
| A.R. Webb; L. Kline; M.F. Holick | Journal of Clinical Endocrinology & Metabolism | 1988
Influence of Season and Latitude on the Cutaneous Synthesis of Vitamin D3. Demonstrates a winter period at northern latitudes during which sunlight cannot produce meaningful cutaneous vitamin D.
| Michael F. Holick | Federation Proceedings | 1987
Photosynthesis of Vitamin D in the Skin: Effect of Environmental and Life-Style Variables. Reviews how UVB, latitude, season, clothing, pigmentation, and lifestyle affect vitamin D synthesis.
| C.W. Lo; P.W. Paris; M.F. Holick | American Journal of Clinical Nutrition | 1986
Indian and Pakistani Immigrants Have the Same Capacity as Caucasians to Produce Vitamin D in Response to Ultraviolet Irradiation. Provides an important counterpoint suggesting sufficiently large UV doses can overcome pigmentation-related differences.
| T.L. Clemens et al. | The Lancet | 1982
Increased Skin Pigment Reduces the Capacity of Skin to Synthesise Vitamin D3. Experimental work showing that greater pigmentation can reduce vitamin D production under comparable UV exposure.
| M.F. Holick; J.A. MacLaughlin; S.H. Doppelt | Science | 1981
Regulation of Cutaneous Previtamin D3 Photosynthesis in Man: Skin Pigment Is Not an Essential Regulator. An early experimental challenge to simple models in which melanin alone determines vitamin D production.
| J.A. Ford | Nursing Mirror | 1979
Rickets and Osteomalacia: High Risk for Asian Immigrants in Britain. Documents vitamin D-related bone disease among migrants living in a lower-UV environment.
| R.M. Neer | American Journal of Physical Anthropology | 1975
The Evolutionary Significance of Vitamin D, Skin Pigment, and Ultraviolet Light. Argues that rickets, pelvic deformation, impaired childbirth, and other deficiency effects could have influenced evolutionary fitness.
Folate, Reproduction, and Evolutionary Fitness
| Patrice Jones et al. | American Journal of Human Biology | 2018
Frequency of Folate-Related Polymorphisms Varies by Skin Pigmentation. Finds associations between global pigmentation patterns and frequencies of variants involved in folate metabolism.
| Patrice Jones et al. | Exploratory Research and Hypothesis in Medicine | 2016
Converging Evolutionary, Environmental and Clinical Ideas on Folate Metabolism. Connects geographic UV variation with folate-related polymorphisms and evolutionary adaptation.
| Wang Yafei et al. | Journal of Human Genetics | 2012
Is the Prevalence of MTHFR C677T Polymorphism Associated With Ultraviolet Radiation in Eurasia? Examines geographic evidence that UV exposure may have influenced natural selection on folate metabolism.
| J.D. Williams et al. | Subcellular Biochemistry | 2012
Folate in Skin Cancer Prevention. Reviews folate-dependent DNA synthesis and repair mechanisms relevant to UV-exposed skin.
| Elisabeth Lerchbaum; Barbara Obermayer-Pietsch | European Journal of Endocrinology | 2012
Vitamin D and Fertility: A Systematic Review. Reviews evidence linking vitamin D receptors and metabolism with reproductive function in males and females.
| J.D. Williams; M.K. Jacobson | Journal of Photochemistry and Photobiology B | 2010
Photobiological Implications of Folate Depletion and Repletion in Cultured Human Keratinocytes. Examines how folate status changes the response of skin cells to photochemical stress.
| Susan J. Duthie et al. | Journal of Proteome Research | 2010
Blood Folate Status and Expression of Proteins Involved in Immune Function, Inflammation, and Coagulation. Shows systemic biological effects of changing folate status.
| Asta Juzeniene et al. | Free Radical Biology and Medicine | 2009
5-Methyltetrahydrofolate Can Be Photodegraded by Endogenous Photosensitizers. Shows that biologically important reduced folate can be damaged through light-driven reactions involving endogenous molecules.
| T.T.T. Tam et al. | Journal of Photochemistry and Photobiology B | 2009
Photodegradation of 5-Methyltetrahydrofolate in the Presence of Uroporphyrin. Adds evidence that endogenous photosensitizers can accelerate folate degradation during light exposure.
| Jesse T. Fox et al. | Journal of Biological Chemistry | 2009
A UV-Responsive Internal Ribosome Entry Site Enhances Serine Hydroxymethyltransferase 1 Expression for DNA Damage Repair. Links ultraviolet exposure with regulation of a major folate-dependent metabolic enzyme.
| J.C. Boxmeer et al. | Fertility and Sterility | 2009
Low Folate in Seminal Plasma Is Associated With Increased Sperm DNA Damage. Provides evidence that inadequate folate may adversely affect male reproductive biology.
| Arnfinn H. Steindal et al. | Photochemical & Photobiological Sciences | 2008
5-Methyltetrahydrofolate Is Photosensitive in the Presence of Riboflavin. Investigates mechanisms through which light exposure may reduce biologically active folate.
| Roy M. Pitkin | American Journal of Clinical Nutrition | 2007
Folate and Neural Tube Defects. Reviews the strong relationship between folate status and neural-tube development, illustrating a major route through which folate deficiency affects reproductive fitness.
| Tsunenobu Tamura; Mary Frances Picciano | American Journal of Clinical Nutrition | 2006
Folate and Human Reproduction. Reviews folate's importance in fertility, pregnancy, fetal development, and reproductive success.
| Charalambos Antoniades et al. | Circulation | 2006
5-Methyltetrahydrofolate Rapidly Improves Endothelial Function and Decreases Superoxide Production. Demonstrates physiological functions of reduced folate relevant to proposed UV-folate trade-offs.
| Morten Kristian Off et al. | Journal of Photochemistry and Photobiology B | 2005
Ultraviolet Photodegradation of Folic Acid. Characterizes the chemical breakdown of folic acid under UV radiation and provides mechanistic evidence relevant to folate-protection hypotheses.
| C. Courtemanche et al. | Journal of Immunology | 2004
Folate Deficiency Inhibits the Proliferation of Primary Human CD8+ T Lymphocytes. Demonstrates broader physiological costs of low folate beyond fetal development.
| K. Kinuta et al. | Endocrinology | 2000
Vitamin D Is an Important Factor in Estrogen Biosynthesis of Both Female and Male Gonads. Provides experimental evidence connecting vitamin D signaling directly with reproductive physiology.
| T. Yoshizawa et al. | Nature Genetics | 1997
Mice Lacking the Vitamin D Receptor Exhibit Impaired Bone Formation, Uterine Hypoplasia and Growth Retardation. Demonstrates reproductive and skeletal effects of disrupted vitamin D signaling.
| R.F. Branda; J.W. Eaton | Science | 1978
Skin Color and Nutrient Photolysis: An Evolutionary Hypothesis. Shows UV exposure can destroy folate and proposes that dark pigmentation evolved partly to protect essential nutrients from photolysis.
Pigmentation Genetics, Vitamin D Genetics, Ancient DNA, and Genomic Adaptation
| Tina Lasisi et al. | Proceedings of the National Academy of Sciences | 2021
The Evolution of Skin Pigmentation-Associated Variation in West Eurasia. Uses ancient genomes to separate migration from natural selection in the rise of light-pigmentation alleles.
| Joana A. Revez et al. | Nature Communications | 2020
Genome-Wide Association Study Identifies 143 Loci Associated With 25-Hydroxyvitamin D Concentration. Shows that vitamin D status has a highly polygenic genetic architecture beyond pigmentation alone.
| William J. Pavan; Richard A. Sturm | Annual Review of Genomics and Human Genetics | 2019
The Genetics of Human Skin and Hair Pigmentation. Reviews pigmentation loci and evolutionary pressures responsible for population differences.
| Zhaohui Yang et al. | Molecular Biology and Evolution | 2018
Darwinian Positive Selection on the Pleiotropic Effects of KITLG Explain Skin Pigmentation and Winter Temperature Adaptation in Eurasians. Suggests pigmentation genes may have been selected for multiple environmental functions, not vitamin D alone.
| Leslea J. Hlusko et al. | Proceedings of the National Academy of Sciences | 2018
Environmental Selection During the Last Ice Age on the Mother-to-Infant Transmission of Vitamin D and Fatty Acids Through Breast Milk. Proposes that EDAR selection in Beringia may have improved nutrient transmission to infants under severe vitamin D constraints.
| Xia Jiang et al. | Nature Communications | 2018
Genome-Wide Association Study in 79,366 European-Ancestry Individuals Informs the Genetic Architecture of 25-Hydroxyvitamin D Levels. Expands the number of genetic loci known to influence vitamin D status.
| Nicholas G. Crawford et al. | Science | 2017
Loci Associated With Skin Pigmentation Identified in African Populations. Reveals the deep evolutionary history and global distribution of several pigmentation alleles.
| Dov Tiosano et al. | G3: Genes, Genomes, Genetics | 2016
Latitudinal Clines of the Human Vitamin D Receptor and Skin Color Genes. Finds geographic patterns in VDR and pigmentation variation consistent with adaptation to differences in ultraviolet radiation.
| Mark Lucock et al. | Journal of Evidence-Based Complementary & Alternative Medicine | 2015
Vitamin D: Beyond Metabolism. Reviews wide-ranging physiological effects of vitamin D that could potentially influence natural selection beyond skeletal health.
| Sandra Wilde et al. | Proceedings of the National Academy of Sciences | 2014
Direct Evidence for Positive Selection of Skin, Hair, and Eye Pigmentation in Europeans During the Last 5,000 Years. Ancient DNA shows strong recent selection on several European pigmentation alleles.
| Iñigo Olalde et al. | Nature | 2014
Derived Immune and Ancestral Pigmentation Alleles in a 7,000-Year-Old Mesolithic European. Shows that some Mesolithic Europeans retained ancestral pigmentation variants despite living at high latitude.
| Sandra Beleza et al. | Molecular Biology and Evolution | 2013
The Timing of Pigmentation Lightening in Europeans. Estimates that several major European depigmentation sweeps began thousands of years after modern humans first entered Europe.
| Adam E. Handel et al. | BMC Medicine | 2013
Vitamin D Receptor ChIP-seq in Primary CD4+ Cells: Relationship to Serum 25-Hydroxyvitamin D Levels and Autoimmune Disease. Maps vitamin-D-receptor activity and shows that vitamin D status influences genomic regulation in immune cells.
| Barbara Prietl et al. | Nutrients | 2013
Vitamin D and Immune Function. Reviews vitamin D's influence on innate and adaptive immunity, suggesting additional biological consequences of chronic deficiency.
| Jonathan L. Rees; Rosalind M. Harding | Journal of Investigative Dermatology | 2012
Understanding the Evolution of Human Pigmentation: Recent Contributions From Population Genetics. Reviews genetic evidence that natural selection produced pigmentation diversity in different populations.
| Mark B. Meyer; Paul D. Goetsch; J. Wesley Pike | Molecular Endocrinology | 2012
VDR/RXR and TCF4/β-Catenin Cistromes in Colonic Cells of Colorectal Tumor Origin. Demonstrates extensive vitamin-D-receptor interactions with gene-regulatory networks.
| James C. Fleet et al. | Biochemical Journal | 2012
Vitamin D and Cancer: A Review of Molecular Mechanisms. Reviews vitamin D control of proliferation, differentiation, apoptosis, and other pathways affecting cellular fitness.
| Diane Berry; Elina Hyppönen | Current Opinion in Nephrology and Hypertension | 2011
Determinants of Vitamin D Status: Focus on Genetic Variations. Reviews inherited differences in vitamin D synthesis, transport, and metabolism that may modify environmental effects.
| Satu Heikkinen et al. | Nucleic Acids Research | 2011
Nuclear Hormone 1α,25-Dihydroxyvitamin D3 Elicits a Genome-Wide Shift in the Locations of VDR Chromatin Occupancy. Demonstrates that vitamin D alters gene regulation across the genome, illustrating potential pathways through which vitamin D availability could affect fitness.
| Sreeram V. Ramagopalan et al. | Genome Research | 2010
A ChIP-seq Defined Genome-Wide Map of Vitamin D Receptor Binding: Associations With Disease and Evolution. Maps VDR-regulated genomic regions and identifies signals relevant to human evolution.
| Dominique Prié; Gérard Friedlander | Clinical Journal of the American Society of Nephrology | 2010
Reciprocal Control of 1,25-Dihydroxyvitamin D and FGF23 Formation Involving the FGF23/Klotho System. Describes physiological feedback systems that regulate active vitamin D and mineral metabolism.
| Thomas J. Wang et al. | The Lancet | 2010
Common Genetic Determinants of Vitamin D Insufficiency: A Genome-Wide Association Study. Identifies inherited variants in vitamin D synthesis, metabolism, and transport that strongly influence circulating vitamin D.
| Jiyoung Ahn et al. | Human Molecular Genetics | 2010
Genome-Wide Association Study of Circulating Vitamin D Levels. Identifies common genetic variants contributing to differences in vitamin D status between individuals.
| Rebecca S. Mason et al. | Journal of Steroid Biochemistry and Molecular Biology | 2010
Photoprotection by 1α,25-Dihydroxyvitamin D and Analogs: Further Studies on Mechanisms and Implications for UV-Damage. Examines mechanisms through which vitamin D can limit ultraviolet-induced cellular injury.
| Akira Shimada et al. | Journal of Autoimmunity | 2008
Evidence for Association Between Vitamin D Receptor BsmI Polymorphism and Type 1 Diabetes in Japanese. Demonstrates functional population variation in the vitamin D receptor pathway.
| Jürgen Schauber; Richard L. Gallo | Experimental Dermatology | 2008
The Vitamin D Pathway: A New Target for Control of the Skin's Immune Response? Reviews the role of vitamin D in cutaneous innate immunity and antimicrobial defense.
| Sushil Samuel; Marvin D. Sitrin | Nutrition Reviews | 2008
Vitamin D's Role in Cell Proliferation and Differentiation. Summarizes evidence that vitamin D acts far beyond calcium metabolism by regulating cell growth and differentiation.
| Esteban J. Parra | American Journal of Physical Anthropology | 2007
Human Pigmentation Variation: Evolution, Genetic Basis, and Implications for Public Health. Reviews the unusual strength of natural selection on pigmentation and its relevance to vitamin D and photoprotection.
| O. Lao et al. | Annals of Human Genetics | 2007
Signatures of Positive Selection in Genes Associated With Human Skin Pigmentation. Finds evidence of population-specific selection in several pigmentation genes.
| Heather L. Norton et al. | Molecular Biology and Evolution | 2007
Genetic Evidence for the Convergent Evolution of Light Skin in Europeans and East Asians. Shows that lighter pigmentation arose partly through different genetic pathways in western and eastern Eurasia.
| Katie M. Dixon et al. | Journal of Steroid Biochemistry and Molecular Biology | 2007
In Vivo Relevance for Photoprotection by the Vitamin D Rapid Response Pathway. Provides evidence that vitamin D signaling may protect skin against ultraviolet-induced cellular damage.
| Rajesh Gupta et al. | Journal of Investigative Dermatology | 2007
Photoprotection by 1,25-Dihydroxyvitamin D3 Is Associated With an Increase in p53 and a Decrease in Nitric Oxide Products. Identifies molecular mechanisms that may make vitamin D advantageous in UV-exposed tissues.
| Brian McEvoy; Sandra Beleza; Mark D. Shriver | Human Molecular Genetics | 2006
The Genetic Architecture of Normal Variation in Human Pigmentation. Describes different histories of pigmentation selection in African, European, and East Asian populations.
| Yue Fang et al. | American Journal of Human Genetics | 2005
Promoter and 3′-Untranslated-Region Haplotypes in the Vitamin D Receptor Gene Predispose to Osteoporotic Fracture. Demonstrates functional health consequences of inherited VDR variation.
| Rebecca L. Lamason et al. | Science | 2005
SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans. Identifies one of the major variants contributing to lighter pigmentation in European populations.
| André G. Uitterlinden et al. | Gene | 2004
Genetics and Biology of Vitamin D Receptor Polymorphisms. Reviews functional variation in VDR and its potential consequences for vitamin D physiology.
| Gary Wong et al. | Journal of Steroid Biochemistry and Molecular Biology | 2004
1,25-Dihydroxyvitamin D and Three Low-Calcemic Analogs Decrease UV-Induced DNA Damage Via the Rapid Response Pathway. Demonstrates reduced UV-related DNA damage after vitamin D receptor pathway activation.
| Arie Ravid et al. | Journal of Endocrinology | 2002
Vitamin D Inhibits the Activation of Stress-Activated Protein Kinases by Physiological and Environmental Stresses in Keratinocytes. Shows a protective role for vitamin D signaling in skin cells exposed to environmental stress.
| Joseph M. Zmuda; Jane A. Cauley; Robert E. Ferrell | Epidemiologic Reviews | 2000
Molecular Epidemiology of Vitamin D Receptor Gene Variants. Reviews geographic and population variation in VDR polymorphisms relevant to alternative vitamin D adaptations.
| J. Lee; J.I. Youn | Journal of Dermatological Science | 1998
The Photoprotective Effect of 1,25-Dihydroxyvitamin D3 on Ultraviolet Light B-Induced Damage in Keratinocytes and Its Mechanism of Action. Demonstrates direct vitamin-D-mediated protection against UVB damage in skin cells.
Migration, Latitude, Rickets, Pregnancy, and Population Health
| İrem Dündar; Mehmet Ali Büyükavcı | Turkish Journal of Pediatrics | 2023
Nutritional Rickets in Turkish and Refugee Children Aged 0–2: An Increasing Problem Despite Vitamin D Prophylaxis. Shows that rickets remains a concern where migration, infancy, nutrition, and vitamin D deficiency intersect.
| William B. Grant et al. | Nutrients | 2021
Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities? Reviews the interaction of pigmentation, latitude, UVB exposure, circulating vitamin D, and population health differences.
| Genevieve Lane et al. | Applied Physiology, Nutrition, and Metabolism | 2019
Canadian Newcomer Children's Bone Health and Vitamin D Status. Examines vitamin D and skeletal health among immigrant and refugee children after settlement at high northern latitude.
| Paul Lips; R.T. de Jongh | Bone Reports | 2018
Vitamin D Deficiency in Immigrants. Reviews the exceptionally high prevalence of deficiency among immigrant populations living in Europe and other high-latitude regions.
| Kerry D.J. Jones et al. | Maternal & Child Nutrition | 2018
Vitamin D Deficiency Causes Rickets in an Urban Informal Settlement in Kenya and Is Associated With Malnutrition. Demonstrates that rickets can occur even at tropical latitude, emphasizing that nutrition and living conditions can override geographic UV advantage.
| Karen M. O'Callaghan; Mairead E. Kiely | Proceedings of the Nutrition Society | 2018
Ethnic Disparities in the Dietary Requirement for Vitamin D During Pregnancy. Reviews evidence that ancestry, skin pigmentation, diet, and UV exposure influence vitamin D requirements during pregnancy.
| Suma Uday; Wolfgang Högler | Current Osteoporosis Reports | 2017
Nutritional Rickets and Osteomalacia in the Twenty-First Century: Revised Concepts, Public Health, and Prevention Strategies. Reviews modern rickets epidemiology and its continuing concentration among dark-skinned and migrant populations.
| Caroline A. Martin; Udaya Gowda; Andre M.N. Renzaho | Nutrition | 2016
The Prevalence of Vitamin D Deficiency Among Dark-Skinned Populations According to Their Stage of Migration and Region of Birth: A Meta-Analysis. Shows that migration from high-UV to lower-UV environments is strongly associated with vitamin D deficiency in dark-skinned populations.
| Tom D. Thacher et al. | Public Health Reviews | 2016
Nutritional Rickets in Immigrant and Refugee Children. Documents the concentration of nutritional rickets among dark-skinned migrant children living in regions with lower UVB availability.
| Åse R. Eggemoen et al. | BMC Pregnancy and Childbirth | 2016
Vitamin D Deficiency and Supplementation in Pregnancy in a Multiethnic Population-Based Cohort. Shows that immigrant origin, skin pigmentation, diet, supplementation, and sun exposure contribute to large differences in maternal vitamin D.
| Spyridon Karras et al. | European Journal of Clinical Nutrition | 2016
Hypovitaminosis D in Pregnancy in the Mediterranean Region: A Systematic Review. Finds high deficiency even in sunny environments, with skin color, clothing, season, and supplementation strongly influencing vitamin D status.
| Naweed S. Alzaman et al. | American Journal of Clinical Nutrition | 2016
Vitamin D Status of Black and White Americans and Changes in Vitamin D Metabolites After Varied Doses of Vitamin D Supplementation. Finds lower total and directly measured free vitamin D in Black participants but similar supplementation responses between groups.
| Anders H. Berg et al. | Clinical Chemistry | 2015
24,25-Dihydroxyvitamin D3 and Vitamin D Status of Community-Dwelling Black and White Americans. Uses vitamin D metabolites to investigate whether conventional measurements indicate equivalent biological deficiency across populations.
| Thilini Ruwanpathirana et al. | BMC Cardiovascular Disorders | 2014
Assessment of Vitamin D and Its Association With Cardiovascular Disease Risk Factors in an Adult Migrant Population. Provides evidence of widespread low vitamin D status in migrant adults living in Melbourne.
| Monique Aucoin et al. | Canadian Family Physician | 2013
Vitamin D Status of Refugees Arriving in Canada: Findings From the Calgary Refugee Health Program. Documents widespread deficiency among refugees arriving from diverse geographic regions.
| Francesco Cadario et al. | Italian Journal of Pediatrics | 2013
Vitamin D Status in Cord Blood and Newborns: Ethnic Differences. Finds substantial ethnic variation in neonatal vitamin D concentrations, reflecting differences in maternal vitamin D status.
| J.C. Gallagher et al. | Journal of Clinical Endocrinology & Metabolism | 2013
Effects of Vitamin D Supplementation in Older African American Women. Examines dose-response relationships and vitamin D requirements in an African American population.
| F. Schreuder; R.M.D. Bernsen; J.C. van der Wouden | Annals of Family Medicine | 2012
Vitamin D Supplementation for Nonspecific Musculoskeletal Pain in Non-Western Immigrants: A Randomized Controlled Trial. Tests a clinical consequence of vitamin D deficiency common among migrants to northern Europe.
| Mohammed Sheikh et al. | Journal of Immigrant and Minority Health | 2011
Vitamin D Deficiency in Refugee Children From Conflict Zones. Finds high vitamin D deficiency among recently arrived refugee children and highlights migration-related environmental mismatch.
| Tom D. Thacher; Bart L. Clarke | Mayo Clinic Proceedings | 2011
Vitamin D Insufficiency. Reviews the causes, physiology, skeletal consequences, diagnosis, and treatment of inadequate vitamin D.
| Bruce W. Hollis et al. | Journal of Bone and Mineral Research | 2011
Vitamin D Supplementation During Pregnancy: Double-Blind, Randomized Clinical Trial of Safety and Effectiveness. Demonstrates the substantial vitamin D requirements of pregnancy and provides evidence relevant to reproductive selection pressures.
| Jesper Brok; Lene Huusom; Dina Cortes | Ugeskrift for Laeger | 2011
Severe Vitamin D Deficiency in Children Born in Denmark of Dark-Skinned Women. Reports deficiency among children whose ancestry and pigmentation were poorly matched to northern European UV conditions.
| Lisa B. Signorello et al. | Cancer Epidemiology, Biomarkers & Prevention | 2010
Blood Vitamin D Levels in Relation to Genetic Estimation of African Ancestry. Finds an inverse relationship between African genetic ancestry and circulating vitamin D concentrations.
| Ann Prentice et al. | Clinical Reviews in Bone and Mineral Metabolism | 2009
Vitamin D Deficiency and Its Health Consequences in Africa. Examines vitamin D physiology and bone disease in African populations, helping distinguish pigmentation effects from diet, calcium intake, and lifestyle.
| Signe Sparre Beck-Nielsen et al. | European Journal of Pediatrics | 2009
Nutritional Rickets in Denmark: A Retrospective Review of Children's Medical Records From 1985 to 2005. Finds nutritional rickets disproportionately concentrated among immigrant children.
| Adit A. Ginde; Jonathan M. Liu; Carlos A. Camargo Jr. | Archives of Internal Medicine | 2009
Demographic Differences and Trends of Vitamin D Insufficiency in the US Population, 1988–2004. Demonstrates strong differences in vitamin D status by race, age, and other demographic characteristics.
| Rikke Andersen et al. | European Journal of Clinical Nutrition | 2008
Pakistani Immigrant Children and Adults in Denmark Have Severely Low Vitamin D Status. Demonstrates marked deficiency in a dark-skinned migrant population living at northern latitude.
| R.J. Clifton-Bligh et al. | Diabetic Medicine | 2008
Maternal Vitamin D Deficiency, Ethnicity and Gestational Diabetes. Examines associations among ethnicity, maternal vitamin D status, and pregnancy outcomes.
| Lisa M. Bodnar et al. | Journal of Nutrition | 2007
High Prevalence of Vitamin D Insufficiency in Black and White Pregnant Women Residing in the Northern United States and Their Neonates. Shows particularly high rates of deficiency among Black pregnant women and their newborns at northern latitude.
| I.M. van der Meer et al. | American Journal of Clinical Nutrition | 2006
High Prevalence of Vitamin D Deficiency in Pregnant Non-Western Women in The Hague, Netherlands. Finds severe deficiency particularly among pregnant women from darker-skinned immigrant populations.
| Susan S. Harris | Journal of Nutrition | 2006
Vitamin D and African Americans. Reviews the low average 25-hydroxyvitamin D concentrations observed in African Americans and examines pigmentation, diet, bone physiology, and possible adaptive responses.
| John M. Pettifor | American Journal of Clinical Nutrition | 2004
Nutritional Rickets: Deficiency of Vitamin D, Calcium, or Both? Explains why rickets cannot always be attributed solely to low vitamin D and highlights the importance of dietary calcium.
| Susan Nesby-O'Dell et al. | American Journal of Clinical Nutrition | 2002
Hypovitaminosis D Prevalence and Determinants Among African American and White Women of Reproductive Age. Shows major population differences in vitamin D status among women during reproductive years.
| Paul Lips | Osteoporosis International | 2001
Vitamin D Deficiency and Secondary Hyperparathyroidism in the Elderly: Consequences for Bone Loss and Fractures and Therapeutic Implications. Explains skeletal mechanisms through which persistent vitamin D deficiency could reduce survival and physical fitness.
| Margaret Lawson; Michael Thomas | BMJ | 1999
Vitamin D Concentrations in Asian Children Aged 2 Years Living in England: Population Survey. Reports low vitamin D concentrations among young Asian children born and raised in Britain.
| Margaret Lawson; Michael Thomas; Anthony Hardiman | European Journal of Clinical Nutrition | 1999
Dietary and Lifestyle Factors Affecting Plasma Vitamin D Levels in Asian Children Living in England. Identifies diet, sunlight exposure, clothing, and lifestyle as important contributors to deficiency.
| T. Solanki et al. | Age and Ageing | 1995
Are Elderly Asians in Britain at a High Risk of Vitamin D Deficiency and Osteomalacia? Examines the combined effects of pigmentation, age, diet, limited sunlight exposure, and northern latitude.
| J.E. Jensen | Ugeskrift for Laeger | 1995
Severe Vitamin D Deficiency in an Immigrant Family. Provides a clinical example of severe deficiency following migration to a low-UV environment.
| P.J. Finch et al. | Quarterly Journal of Medicine | 1992
Clinical and Histological Spectrum of Osteomalacia Among Asians in South London. Documents vitamin D-related skeletal disease in a migrant population living under lower-UV conditions.
| M.A. Preece et al. | The Lancet | 1973
Vitamin-D Deficiency Among Asian Immigrants to Britain. Classic evidence of widespread deficiency following migration from sunnier South Asian environments to Britain.
Alternative Hypotheses, Skin Biology, Selective Pressures, and Broader Mechanisms
| Eunyoung Chang; Youngju Kim | Nutrients | 2017
Vitamin D Insufficiency Exacerbates Adipose Tissue Macrophage Infiltration and Decreases AMPK/SIRT1 Activity in Obese Rats. Adds evidence that vitamin D status affects metabolism and inflammatory physiology.
| Zoe Apalla et al. | Dermatology Practical & Conceptual | 2017
Epidemiological Trends in Skin Cancer. Reviews skin-cancer patterns useful for evaluating whether cancer mortality could have acted as a major historical selection pressure.
| Philippe Autier et al. | Lancet Diabetes & Endocrinology | 2017
Effect of Vitamin D Supplementation on Non-Skeletal Disorders: A Systematic Review of Meta-Analyses and Randomised Trials. Finds that many observational associations between vitamin D and disease are not strongly reproduced by supplementation trials, cautioning against overly broad evolutionary assumptions.
| Peter M. Elias; Mary L. Williams | American Journal of Physical Anthropology | 2016
Basis for the Gain and Subsequent Dilution of Epidermal Pigmentation During Human Evolution. Develops skin-barrier and metabolic-conservation alternatives to a vitamin-D-centered model.
| S.A.N. D'Mello et al. | International Journal of Molecular Sciences | 2016
Signaling Pathways in Melanogenesis. Reviews molecular pathways controlling melanin production and the genes through which selection can modify pigmentation.
| Shaun F. Morrison | F1000Research | 2016
Central Control of Body Temperature. Reviews thermoregulation mechanisms relevant to alternative hypotheses involving pigmentation, temperature, and energy conservation.
The Vitamin D Hypothesis: Dead or Alive? Critiques the argument that vitamin D was the principal evolutionary driver of human depigmentation and emphasizes alternative skin-barrier and climatic mechanisms.
| Karel Chalupsky et al. | Antioxidants & Redox Signaling | 2015
Folic Acid Promotes Recycling of Tetrahydrobiopterin and Protects Against Hypoxia-Induced Pulmonary Hypertension by Recoupling Endothelial Nitric Oxide Synthase. Provides another mechanism through which adequate folate could affect cardiovascular and reproductive fitness.
| Mel Greaves | Proceedings of the Royal Society B | 2014
Was Skin Cancer a Selective Force for Black Pigmentation in Early Hominin Evolution? Argues that lethal skin cancers may have contributed to selection for strong pigmentation in early humans.
| Nina G. Jablonski; George Chaplin | Proceedings of the Royal Society B | 2014
Skin Cancer Was Not a Potent Selective Force in the Evolution of Protective Pigmentation in Early Hominins. Challenges the skin-cancer hypothesis and emphasizes reproductive-age selective pressures such as folate protection.
| Matthew J. Maley et al. | European Journal of Applied Physiology | 2014
The Effect of Ethnicity on the Vascular Responses to Cold Exposure of the Extremities. Examines population differences in cold-response physiology relevant to non-UV explanations for pigmentation evolution.
| Min Zhang et al. | Molecular Medicine Reports | 2014
High-Dose Folic Acid Improves Endothelial Function by Increasing Tetrahydrobiopterin and Decreasing Homocysteine Levels. Demonstrates important vascular functions of folate relevant to the opposing folate side of the vitamin D–folate hypothesis.
| Olena Andrukhova et al. | Molecular Endocrinology | 2014
Vitamin D Is a Regulator of Endothelial Nitric Oxide Synthase and Arterial Stiffness in Mice. Demonstrates a direct role for vitamin D in vascular physiology.
| Sana Ajabshir; Anam Asif; Ali Nayer | Journal of Nephropathology | 2014
The Effects of Vitamin D on the Renin-Angiotensin System. Reviews another physiological pathway through which vitamin D status could influence health and fitness.
| Philippe Autier et al. | Lancet Diabetes & Endocrinology | 2014
Vitamin D Status and Ill Health: A Systematic Review. Critically examines whether low vitamin D causes numerous diseases or is often a consequence or marker of poor health.
| Helena Marti-Soler et al. | PLOS ONE | 2014
Seasonal Variation of Overall and Cardiovascular Mortality: A Study in 19 Countries From Different Geographic Locations. Documents geographic and seasonal health variation potentially related to multiple environmental factors including UV exposure.
Solar UV Radiation Reduces the Barrier Function of Human Skin. Demonstrates that UV exposure can directly impair epidermal barrier properties.
| Andrzej Slominski; Michal Zmijewski; Janusz Pawelek | Pigment Cell & Melanoma Research | 2012
L-Tyrosine and L-DOPA as Hormone-Like Regulators of Melanocyte Functions. Explores biochemical regulation of melanocytes and mechanisms influencing pigmentation phenotypes.
| Kun Li et al. | British Journal of Dermatology | 2012
Association of Vitamin D Receptor Gene Polymorphisms and Serum 25-Hydroxyvitamin D Levels With Generalized Vitiligo. Links vitamin D pathway genetics with pigmentation-related biology and circulating vitamin D.
| K.E. Wong et al. | Journal of Biological Chemistry | 2011
Targeted Expression of Human Vitamin D Receptor in Adipocytes Decreases Energy Expenditure and Induces Obesity in Mice. Suggests vitamin D signaling may influence energy metabolism as well as skeletal and reproductive physiology.
| Cristina Agliardi et al. | Brain, Behavior, and Immunity | 2011
Vitamin D Receptor Gene SNPs Influence VDR Expression and Modulate Protection From Multiple Sclerosis. Shows functional consequences of VDR genetic variation that may contribute to latitude-related adaptation.
| Peter M. Elias; Mary L. Williams | Journal of Human Evolution | 2011
Barrier Requirements as the Evolutionary “Driver” of Epidermal Pigmentation in Humans. Argues that epidermal permeability-barrier requirements may have played an important role in pigmentation evolution independent of vitamin D.
| Peter M. Elias et al. | American Journal of Human Biology | 2010
Evidence That Stress to the Epidermal Barrier Influenced the Development of Pigmentation in Humans. Presents physiological evidence for a skin-barrier explanation of pigmentation differences.
| R. Gunathilake et al. | Journal of Investigative Dermatology | 2009
pH-Regulated Mechanisms Account for Pigment-Type Differences in Epidermal Barrier Function. Provides physiological evidence that pigmentation is associated with differences in skin-barrier performance.
| Yuko Oda et al. | Journal of Investigative Dermatology | 2009
Vitamin D Receptor and Coactivators SRC2 and 3 Regulate Epidermis-Specific Sphingolipid Production and Permeability Barrier Formation. Shows that vitamin D signaling itself contributes to skin-barrier biology.
| K.E. Wong et al. | American Journal of Physiology-Endocrinology and Metabolism | 2009
Involvement of the Vitamin D Receptor in Energy Metabolism: Regulation of Uncoupling Proteins. Provides evidence for VDR involvement in thermogenesis and energy balance.
| J.E. Burgess; F. Macfarlane | Journal of the Royal Army Medical Corps | 2009
Retrospective Analysis of the Ethnic Origins of Male British Army Soldiers With Peripheral Cold Weather Injury. Finds ancestry-related differences in cold injury risk that are relevant to alternative climate-adaptation hypotheses.
| Michaela Brenner; Vincent J. Hearing | Photochemistry and Photobiology | 2008
The Protective Role of Melanin Against UV Damage in Human Skin. Explains how melanin absorbs and disperses UV radiation and protects cellular DNA.
| E. Mata-Greenwood; D.B. Chen | Reproductive Sciences | 2008
Racial Differences in Nitric Oxide-Dependent Vasorelaxation. Examines population differences in vascular physiology relevant to hypotheses connecting UV, folate, pigmentation, and circulation.
| Sharif B. Mohr et al. | Diabetologia | 2008
The Association Between Ultraviolet B Irradiance, Vitamin D Status and Incidence Rates of Type 1 Diabetes in 51 Regions Worldwide. Finds geographic correlations between UVB availability and disease incidence, illustrating possible physiological consequences of latitude-related vitamin D differences.
| Evelyne van Etten et al. | European Journal of Immunology | 2007
The Vitamin D Receptor Gene FokI Polymorphism: Functional Impact on the Immune System. Demonstrates that VDR variants can alter biological responses, supporting metabolic adaptation as an additional evolutionary pathway.
| Peter Frost | American Journal of Physical Anthropology | 2007
Human Skin-Color Sexual Dimorphism: A Test of the Sexual Selection Hypothesis. Examines whether systematic sex differences in pigmentation support a role for mate choice in skin-color evolution.
| Jared Diamond | Nature | 2005
Geography and Skin Colour. Discusses the geographic patterning of human pigmentation and the competing environmental pressures proposed to explain it.
| Karel Chalupsky; Hua Cai | Proceedings of the National Academy of Sciences | 2005
Endothelial Dihydrofolate Reductase: Critical for Nitric Oxide Bioavailability and Role in Angiotensin II Uncoupling of Endothelial Nitric Oxide Synthase. Links folate metabolism directly to vascular function.
| Patrick J. Stover | Nutrition Reviews | 2004
Physiology of Folate and Vitamin B12 in Health and Disease. Reviews folate-dependent DNA synthesis, methylation, cell division, and reproduction, explaining why UV-related folate protection could have strong evolutionary consequences.
| Kenichi Aoki | Journal of Theoretical Biology | 2002
Sexual Selection as a Cause of Human Skin Colour Variation: Darwin's Hypothesis Revisited. Models sexual selection as a possible contributor to geographic pigmentation differences.
| John M. Diamond | Nature | 2001
Evolutionary Biology: Skin Color in the Tropics. Discusses evolutionary explanations for pigmentation and the complex relationship between UV radiation, natural selection, and human biology.
| Nikiforos Kollias et al. | Journal of Photochemistry and Photobiology B | 1991
Photoprotection by Melanin. Reviews the physical and chemical mechanisms through which melanin reduces penetration and damage from ultraviolet radiation.
| Pierre L. van den Berghe; Peter Frost | Ethnic and Racial Studies | 1986
Skin Color Preference, Sexual Dimorphism and Sexual Selection: A Case of Gene-Culture Co-Evolution? Proposes an interaction between cultural preferences and biological selection in pigmentation evolution.
| P.W. Post; F. Daniels Jr.; R.T. Binford Jr. | Human Biology | 1975
Cold Injury and the Evolution of “White” Skin. Proposes that depigmentation may partly reflect adaptation to cold environments rather than vitamin D alone.
