How some populations adapt to vitamin D scarcity

 

Vitamin D metabolism varies from one human population to another, as do most heritable traits. This is the subject of a review article I’ve recently published in the journal Nutrients. Here is the abstract:

 

 

Vitamin D metabolism differs among human populations because our species has adapted to different natural and cultural environments. Two environments are particularly difficult for the production of vitamin D by the skin: the Arctic, where the skin receives little solar UVB over the year; and the Tropics, where the skin is highly melanized and blocks UVB. In both cases, natural selection has favored the survival of those individuals who use vitamin D more efficiently or have some kind of workaround that ensures sufficient uptake of calcium and other essential minerals from food passing through the intestines. Vitamin D scarcity has either cultural or genetic solutions. Cultural solutions include consumption of meat in a raw or boiled state and extended breastfeeding of children. Genetic solutions include higher uptake of calcium from the intestines, higher rate of conversion of vitamin D to its most active form, stronger binding of vitamin D to carrier proteins in the bloodstream, and greater use of alternative metabolic pathways for calcium uptake. Because their bodies use vitamin D more sparingly, indigenous Arctic and Tropical peoples can be misdiagnosed with vitamin D deficiency and wrongly prescribed dietary supplements that may push their vitamin D level over the threshold of toxicity.

 

 

Reference

 

Frost P. (2022) The Problem of Vitamin D Scarcity: Cultural and Genetic Solutions by Indigenous Arctic and Tropical Peoples. Nutrients 14(19):4071. https://doi.org/10.3390/nu14194071

 

Vitamin D scarcity and natural selection

 

In humans who are dark-skinned or who live above the Arctic Circle, natural selection has favored those who use vitamin D more efficiently or have workarounds of one sort or another for vitamin D scarcity. Yakut family, Wikicommons (Uyban)

 

 

Vitamin D is less easily obtained by some people than by others. It is less available to those who are dark-skinned or who live above the Arctic Circle. Because less UV light enters the skin for biosynthesis, natural selection has favored individuals who use this vitamin more efficiently or have workarounds of one sort or another (Frost 2009; Frost 2012; Frost 2018).

 

Vitamin D levels are thus naturally lower in Arctic and dark-skinned humans. Some variation exists even among Europeans, with levels being lower in darker-skinned southern Europeans than in lighter-skinned northern Europeans (Snellman et al. 2009; van der Wielen et al. 1995).

 

Unfortunately, vitamin D deficiency is diagnosed on the basis of norms developed for light-skinned people from temperate latitudes. Inuit and African Americans are thus diagnosed as “deficient” and offered vitamin supplementation, which has the effect of bathing their body tissues in concentrations of vitamin D that they and their ancestors have not experienced for tens of thousands of years, if not longer.

 

If  Arctic and darker-skinned humans naturally have lower levels of vitamin D, their optimal range of levels will likewise be lower, and toxic effects may occur at levels that lie within the optimal range of Europeans. You may have been told that this cannot happen because toxicity occurs only if you ingest huge amounts of this vitamin. Actually, toxicity begins at relatively low levels. In light-skinned humans from the temperate zone, the optimal range seems to extend only from 40 nmol/L to 100 nmol/L:

 

·         The total mortality rate is about 50% greater in men whose vitamin D levels are either below 46 nmol/L or above 98 nmol/L (Michaelsson et al. 2010).

·         The risk of prostate cancer is significantly greater below 40 nmol/L and above 60 nmol/L (Tuohimaa 2008; Tuohimaa et al. 2009).

·         Mortality for 7 types of cancer (endometrial, esophageal, gastric, kidney, non-Hodgkin's lymphoma, pancreatic, ovarian) is significantly greater below 45 nmol/L and above 124 nmol/L (Helzlsouer et al. 2010).

·         The risk of pancreatic cancer is significantly greater above 100 nmol/L (Stolzenberg-Solomon et al. 2010).

·         The risk of cardiovascular disease is significantly greater below 50 nmol/L and above 62.5 nmol/L, and mortality from all causes is significantly greater above 122.5 nmol/L (Davis 2009).

 

Perhaps most worrisome, studies on mice indicate a U-shaped response curve for the aging process, with premature aging associated with both too little and too much vitamin D (Tuohimaa 2009; Tuohimaa et al. 2009).

 

Vitamin D metabolism and gene-culture coevolution among the Inuit

 

To what extent has the safe range of vitamin D been shifted downward in Arctic and dark-skinned humans? To answer that question, we need to understand gene-culture coevolution. When humans enter a new environment, they adapt by pushing the bounds of phenotypic plasticity—they do the most with what they have already. There is then natural selection for genetic variants that can stabilize this new pattern of adaptation and make it more innate. A new phenotype thus ends up becoming a new genotype.

 

Traditionally, Inuit coped with vitamin D scarcity through a high-meat/low-cereal diet and through extended breastfeeding of children for two years or longer. This diet not only provided vitamin D but also helped the body use this vitamin more efficiently, specifically by means of β-casein in breast milk, unknown substances in meat, and absence of phytic acid (Frost 2018). 

 

Those cultural adaptations were followed by physiological adaptations: receptors that bind more tightly to the vitamin D molecule; a lower set-point for calcium-regulated release of parathyroid hormone; and conversion of vitamin D at a higher rate from its common form to its most active form. Inuit breast milk might also be richer in β-casein (Frost 2018).

 

That gene-culture coevolution has been notably demonstrated by a genome study of the Greenland Inuit, whose marine diet has apparently selected for genetic variants that help their bodies digest and use polyunsaturated fatty acids (Fumagalli et al. 2015).

 

Research on indigenous northern Eurasian peoples

 

Before 2020, the Inuit were the only non-European population for whom we had research on cultural and physiological adaptations to vitamin D scarcity (Frost 2012; Frost 2018). Two studies have since been published on this subject with regard to indigenous peoples in northern Eurasia.

 

Research by Khrunin et al. (2020)

 

This research team looked for signals of natural selection in the genomes of eight northern populations: Russians from the Archangelsk and Vologda regions; Izhemski Komi; Priluzski Komi; Veps; Khanty; Mansi; and Nenets. The strongest signal came from two genes: SLC37A2 and PKNOX2. The first gene is expressed when vitamin D₃ is present in peripheral blood cells. The authors go on to note:

 

Deficit of vitamin D is often observed in northern populations, where exposure to sunlight is limited for many months. Hypothetically, mutations in the VDR-controlled SLC37A2 gene may help northern populations adjust to vitamin D levels. At the same time, the same mutations could have effects on alcohol tolerance in these populations through the PKNOX2 gene, located on the opposite strand of DNA in the same locus. 

 

The second gene, PKNOX2, is associated with alcohol addiction in mice and humans. The authors add that this finding “is of special interest in the context of the well-known alcohol addiction that occurs widely in indigenous populations of Northern Eurasia.”

 

Could vulnerability to alcoholism be a side-effect of adaptation to vitamin D scarcity? The hypothesis is interesting, although I lean more toward another explanation. Some populations, like those around the Mediterranean, have had a long history of drinking fermented beverages instead of water, which might be contaminated with bacteria that cause dysentery and other diseases. Consequently, natural selection has favored individuals who have higher levels of alcohol dehydrogenase and other physiological adaptations that make alcohol less toxic. Conversely, other populations, like northern Eurasians, have consumed fermented beverages for a shorter time, and their bodies are less adapted to alcohol (Nabhan 2004, pp. 27-30; Ridley 2000).

 

Research by Malyarchuk (2020)

 

This is a study of a single polymorphic gene, GC, in several indigenous peoples of northeastern Siberia (Eskimos, Chukchi, Koryaks), central Siberia (Evens, Evenks, Yakuts), southern Siberia (Tuvinians, Shorts, Altaians, Buryats), and western Siberia (Kets, Khanty, Mansi, Selkups, Nenets, Nganasans). The GC gene produces a protein that is the main carrier of vitamin D in the body.

 

One GC variant, specifically the T variant at rs4588, is much less frequent in northeast and central Siberians (5.4%, 3.1%) than in southern and western Siberians (28.6%, 27.5%). Conversely, the G variant is much more frequent in the northeast and center (32.1%, 46.9%) than in the south and west (16.1%, 12.5%). I initially thought the reason was a higher level of European admixture in southern and western Siberia. But there is little European admixture in East Asians, and they resemble southern and western Siberians in having the same high frequency of the T variant (26.1%).

 

The G variant may have become more frequent in northeast and central Siberians as an adaptation to vitamin D scarcity. As one goes farther north, the skin produces less vitamin D because less UV light enters the skin. More research is needed, however, on two other factors: (1) amount of vitamin D from dietary sources; and (2) skin pigmentation. It may be that southern Siberians are somewhat darker-skinned than northern Siberians, although that isn’t my impression. These points are made by Malyarchuk (2020) in the Results and Discussion section. Researchers should study:

 

… the gene-environment interactions by taking into account the vitamin D status of the indigenous population, ethnicity, influence of environmental conditions (the level of natural ambient light and seasonal patterns), and specifics of nutrition. The influence of such factors on the distribution of GC polymorphism variants is evidenced by the data obtained in this work on the high prevalence of haplotypes encoding the Gc1F isoform in northeast Asia under condition of low intensity of solar radiation. In addition, an important factor contributing to vitamin D deficiency may be a relatively high level of melanin in the skin of representatives of the Arctic peoples, which prevents the penetration of ultraviolet rays into the skin and thereby hinders the synthesis of vitamin D₃

 

References

 

Davis, C.D. (2009). Vitamin D and health: can too much be harmful? American Journal of Lifestyle Medicine 3(5): 407-408. https://doi.org/10.1177/1559827609338154

 

Frost, P. (2009). Black-White differences in cancer risk and the vitamin-D hypothesis. Journal of the National Medical Association 101: 1310-1313.

https://doi.org/10.1016/s0027-9684(15)31151-2

 

Frost, P. (2012). Vitamin D deficiency among northern Native Peoples: a real or apparent problem? International Journal of Circumpolar Health 71(S2): 18001

https://doi.org/10.3402/IJCH.v71i0.18001

 

Frost, P. (2018). To supplement or not to supplement: are Inuit getting enough vitamin D? Études Inuit Studies 40(2): 271-291.

https://doi.org/10.7202/1055442ar

 

Frost, P. (2020). Ethnic differences in vitamin-D metabolism. E Scholarly Community Encyclopedia.

https://encyclopedia.pub/3033

 

Fumagalli, M., I. Moltke, N. Grarup, F. Racimo, P. Bjerregaard, M.E. Jørgensen et al. (2015). Greenlandic Inuit show genetic signatures of diet and climate adaptation. Science 349(6254): 1343-1347. https://doi.org/10.1126/science.aab2319

 

Helzlsouer, K.J. and Steering Committee of Vitamin D Pooling Project of Rarer Cancers (2010).  Abstract PL04-05: Vitamin D: panacea or a Pandora’s box for prevention? Cancer Prevention Research 3(1 Suppl 1): PL04-05. https://doi.org/10.1158/1940-6207.PREV-09-PL04-05

 

Khrunin, A.V., G.V. Khvorykh, A.N. Fedorov, and S.A. Limborska (2020). Genomic landscape of the signals of positive natural selection in populations of Northern Eurasia: A view from Northern Russia. PLoS ONE 15(2): e0228778. https://doi.org/10.1371/journal.pone.0228778

 

Malyarchuk, B.A. (2020). Polymorphism of GC gene, encoding vitamin D binding protein, in aboriginal populations of Siberia. Ecological Genetics 18(2): 243-250.

https://doi.org/10.17816/ecogen18634

 

Michaëlsson, K., J.A. Baron, G. Snellman, R. Gedeborg, L. Byberg, J. Sundström et al. (2010). Plasma vitamin D and mortality in older men: a community-based prospective cohort study. American Journal of Clinical Nutrition 92(4): 841-848. https://doi.org/10.3945/ajcn.2010.29749 

 

Nabhan, G.P. (2004). Why Some Like It Hot. Food, Genes, and Cultural Diversity. Washington: Island Press/Shearwater Books.

 

Ridley, M. (2000).Genome: The Autobiography of a Species in 23 Chapters. New York: HarperCollins.

 

Snellman, G., H. Melhus, R. Gedeborg, et al. (2009). Seasonal genetic influence on serum 25-hydroxyvitamin D levels: a twin study. PLoS ONE 4(11): e7747. https://doi.org/10.1371/journal.pone.0007747

 

Stolzenberg-Solomon, R.Z., E.J. Jacobs, A.A. Arslan, D. Qi, A.V. Patel, K.J. Helzlsouer et al.

(2010). Circulating 25-hydroxyvitamin D and risk of pancreatic cancer, Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. American Journal of Epidemiology 172(1): 81-93.

https://doi.org/10.1093/aje/kwq120

 

Tuohimaa, P. (2009). Vitamin D and aging. The Journal of Steroid Biochemistry and Molecular Biology 114(1-2): 78-84. https://doi.org/10.1016/j.jsbmb.2008.12.020 

 

Tuohimaa, P., T. Keisala, A. Minasyan, J. Cachat, and A Kalueff (2009). Vitamin D, nervous system and aging. Psychoneuroendocrinology 34S: S278-286. https://doi.org/10.1016/j.psyneuen.2009.07.003

 

van der Wielen R.P., M.R. Lowik, H. van den Berg, L.C. de Groot, J. Haller J, et al. (1995). Serum vitamin D concentrations among elderly people in Europe. Lancet 346: 207–210. https://doi.org/10.1016/S0140-6736(95)91266-5

Inuit and vitamin D

Inuit mothers (Wikicommons - Ansgar Walk) - Inuit have low levels of vitamin D. Does this mean they're not getting enough? Or have their bodies adapted to an environment where it cannot easily be made in the skin or obtained from the diet?

Inuit people have "insufficient" vitamin D, even among those who eat a traditional diet and live a traditional lifestyle. There are consequently moves afoot to remedy this insufficiency by providing vitamin D supplements. In my opinion, this is a response to a largely nonexistent problem and will probably have adverse consequences.

My arguments are explained in an article I have just published in Inuit Studies. Here is the abstract:

Inuit have vitamin D blood levels that generally fall within the range of insufficiency, even when they live on a traditional diet of fish and game meat. Without this vitamin, bones soften and become deformed, a condition called rickets in children and osteomalacia in adults. Until recent times, however, this condition was much rarer among Inuit than among non-Inuit, even when the latter included people living near Inuit communities under similar conditions of climate and housing. This rarity was attributed to extended breastfeeding and a high-meat/low-cereal diet. The situation subsequently reversed, with Inuit becoming more at risk of developing rickets, first in Labrador during the 1920s and later elsewhere. To reduce this excess risk, researchers have recommended vitamin D supplementation, arguing that breast milk has too little vitamin D and that even a traditional diet cannot provide the recommended daily intake. We should ask, however, whether the problem is definitional. Inuit may have lower levels of vitamin D because they need less, having adapted culturally and physiologically to an environment where this vitamin is less easily synthesized in the skin. These adaptations include a diet that enhances calcium bioavailability (by means of ß-casein in breast milk, certain unknown substances in meat, and absence of phytic acid), as well as genetic changes that enable vitamin D to be used more efficiently. Although Inuit are today more at risk of developing rickets than are non-Inuit, this excess risk is nonetheless small and seems to have a dietary cause-namely, early weaning and abandonment of a high-meat/low-cereal diet.

Please feel free to offer comments or criticisms.

Reference

Frost, P. (2018). To supplement or not to supplement: are Inuit getting enough vitamin D? Études Inuit Studies 40(2): 271-291.

https://www.researchgate.net/publication/329450593_To_Supplement_or_Not_to_Supplement_Are_Inuit_Getting_Enough_Vitamin_D

When Europeans turned white

No, that’s not a climatic adaptation

(actress Lily Cole - source)


“European skin turned pale only recently”—such was the headline in Science five years ago. 

[…] a new report on the evolution of a gene for skin color suggests that Europeans lightened up quite recently […]  the implication is that our European ancestors were brown-skinned for tens of thousands of years (Gibbons, 2007)

The report had been presented by a postdoc, Heather Norton, at the annual meeting of the American Association of Physical Anthropologists (Norton & Hammer, 2007). Over the following years, I e-mailed periodically to ask her when the study would be published. To make a long story short, she landed a faculty position and found herself overwhelmed by new responsibilities. There were still problems with the dating of this genetic change, and time couldn’t be found to work them out. So the study stayed “on the back burner.”

Five years later, the study has finally been published … by another research team. Beleza et al. (2012) generally confirmed Norton’s preliminary finding but found evidence that Europeans had lightened through a 2-stage process. Around 30,000 years ago, not long after entering Europe, the ancestors of today’s Europeans and East Asians lightened in skin color through a new allele at the KITLG gene. But the real whitening came much later, between 19,000 and 11,000 years ago among ancestral Europeans only, through new alleles at TYRP1, SLC24A5, and SLC45A2. This finding strikes down the two leading explanations for the whiteness of European skin:

1.     As modern humans spread north from Africa and into higher latitudes with less solar UV, their skin had to lose pigmentation to maintain the same level of vitamin-D synthesis. Europeans therefore began to turn white once their ancestors entered European latitudes some 40,000 years ago (Loomis, 1970; Murray, 1934).

This explanation might account for the initial loss of pigmentation circa 30,000 BP, when ancestral Europeans probably became as light-skinned as Amerindians. But it cannot explain the much greater loss of pigmentation more than twenty thousand years later.

2.     Some writers, like Sweet (2002), have suggested that the transition from hunting and gathering to farming increased the body’s need for vitamin D (because cereals contain phytic acids that immobilize calcium and phosphorus within the body and because a high-meat diet seems to reduce vitamin-D requirements). In Europe, however, this transition began only 8,000 years ago and did not reach northern Europe until 7,000-3,000 BP.

Beleza et al. (2012) suggest that a colder climate forced Ice Age Europeans to wear more clothing and spend more time in shelters, thus reducing their exposure to solar UV. It was thus at that time, and not when modern humans first entered Europe, that European skin turned white in order to maintain the same level of vitamin-D synthesis.

But then why didn’t Europeans revert after the Ice Age to their original brown color? And why do we see brown skin in humans who have long lived with weaker solar UV and even colder weather in northern Asia and North America? This is notably the case with Amerindian groups in Canada and Alaska who derive very little vitamin D from either the sun or their diet (Frost, 2012a, 2012b).

In any case, it is only during the summer that solar UV is intense enough for the skin to synthesize vitamin D. Yet European summers were not much cooler during the last ice age than they are today. The Central Russian Plain, for instance, had a July mean temperature of 16° back then, versus 18° now (Hoffecker, 2002, p. 23). So Ice Age Europeans had little reason to be less exposed to solar UV. Indeed, the open steppe-tundra was much more exposed to the sun than the forested environments before and after the Ice Age.

Sexual selection?

There remains of course my explanation (Frost, 2006; Frost, 2008). White skin was not climatically advantageous. It was visually advantageous, as were two other unique color traits. Within this same geographic area, centered on northern and eastern Europe, hair is not only black but also brown, flaxen, golden, or red. Eyes are not only brown but also blue, gray, hazel, or green.

Yet, in each case, the genes are different. European skin lightened mainly through replacement of alleles at three genes: SLC45A2, SLC24A5, and TYRP1. European hair color diversified through a proliferation of new alleles at the MC1R gene. European eye color diversified through a proliferation of new alleles in the HERC2-OCA2 region and elsewhere.

These European color traits have evolved along separate trajectories, yet the goal seems similar—a shift toward brighter and more visible colors. But visible to whom?

To the opposite sex? Sexual selection favors visual qualities that catch the attention of potential mates. In the case of skin color, a pre-existing sexual dimorphism has made lighter skin a visible female characteristic. Women are the “fair sex.” They’re paler than men from puberty onward (Edwards & Duntley, 1939).

Skin color is, in fact, a key visual cue for sex recognition, being even more crucial than face shape (Bruce & Langton, 1994; Hill, Bruce, & Akamatsu, 1995; Russell & Sinha, 2007; Russell et al., 2006; Tarr et al., 2001; Tarr, Rossion, & Doerschner, 2002). When shown a human face, subjects can recognize its sex even if the image is blurred and differs only in color (Tarr et al., 2001).

The specific cues are hue and luminosity. A man is browner and ruddier in hue than a woman because melanin and blood are more present in his skin’s outer tissues (Edwards & Duntley, 1939). A woman has higher luminous contrast between her facial skin and her lips or eyes (Dupuis-Roy et al., 2009; Russell, 2003). These cues may explain the similar evolution of cosmetics in a wide range of culture areas, i.e., women generally seek to lighten their facial color and to increase its contrast with their lip and eye color (Russell, 2003; Russell, 2009; Russell, 2010).

Thus, the more a woman is lighter-skinned, the more she is recognizably female. This is not just a matter of conscious sex recognition. It’s also a matter of men acting on half-conscious feelings. Even when a woman is recognized as such, her mating success may be influenced by subtle differences in the way men perceive her femininity.

Extreme sexual selection on the European steppe-tundra

But if sexual selection were the cause, why did it occur only 19,000 to 11,000 years ago and only in Europe? What was so special about that time and place?

That time frame coincides with the last ice age (25,000-10,000 BP), particularly the glacial maximum (20,000-15,000 BP). In Europe, especially on the northern and eastern plains, there were now vast expanses of steppe-tundra that supported herds of wandering reindeer and other herbivores, which in turn supported a large human population. Bioproductivity was in fact much higher there than on today’s arctic barrens. Steppe-tundra also existed in Asia, but it was colder and drier, being farther north and farther from the moderating influence of the Atlantic Ocean. Its human population was not only smaller but also more vulnerable to periodic extinctions, particularly at the height of the last ice age.

Europe’s steppe-tundra was a singularity among the many environments that modern humans encountered as they spread out from Africa during the Paleolithic. It offered an abundance of food, but almost all of the food was in the form of meat. Since hunting was primarily a male activity, men had to bear almost the entire burden of food provisioning. Women either processed the food that men supplied or did activities unrelated to food, such as garment making or shelter building.

There were also demographic consequences. First, polygyny became less common, being limited to those able hunters who could support more than one family. Second, the death rate among young males increased. In hunter-gatherer societies, the male death rate increases with hunting distance, reaching a maximum in environments where hunters pursue migratory herds over long distances. As a result, women greatly outnumbered men on the mate market. Women had to compete for the attention of potential mates, and sexual selection favored the mating success of those who could.

In other species, sexual selection changes physical appearance from a dull, cryptic coloration to a brighter, more eye-catching one. This is especially true for traits on or near the face—the focus of visual attention. Since most genes for human skin, hair, and eye color are not sex-linked, any selection for new color traits in one sex would spill over onto the other sex. As European women whitened, so did Europeans of both sexes.

In time, sexual selection also leads to sexual dimorphism. Sex-linked alleles would appear through random mutation and gradually replace similar alleles that are not sex-linked. Some sexual dimorphism is indeed evident in European color traits. A twin study has shown that hair is lighter-colored in women than in men, with red hair being especially more frequent, and that women show greater variation in hair color (Shekar et al., 2008). Skin color, however, is actually less dimorphic in light-skinned humans than in those of medium skin color, probably because of a “ceiling effect,” i.e., girls cannot become much lighter-skinned after puberty if the population is already close to the limit of maximum paleness (Frost, 2007).

 

Conclusion

White European skin evolved relatively fast during the last ice age, specifically from 19,000 to 11,000 years ago. This was also probably the same time frame for the evolution of European hair and eye colors. Anyway, that’s my bet.

These color traits—white skin and a diverse palette of hair and eye colors— are not adaptations to a cooler, less sunny climate. They are adaptations by early European women to intense mate competition, specifically a shortage of potential mates due to a low polygyny rate and a high death rate among young men.

This situation was created by the steppe-tundra that covered most of Europe as late as 10,000 years ago. Early Europeans were able to colonize this environment but only at the price of a severe imbalance between men and women on the mate market.

References

Beleza, S., A. Murias dos Santos, B. McEvoy, I. Alves, C. Martinho, E. Cameron, M.D. Shriver, E.J. Parra & J. Rocha.(2012).The timing of pigmentation lightening in Europeans, Molecular Biology and Evolution, 20, online

Bruce,V., & S. Langton. (1994). The use of pigmentation and shading information in recognising the sex and identities of faces, Perception, 23(7), 803–822.

Dupuis-Roy, N., I. Fortin, D. Fiset, & F. Gosselin. (2009). Uncovering gender discrimination cues in a realistic setting, Journal of Vision, 9(2), 10, 1–8. http://journalofvision.org/9/2/10/, doi:10.1167/9.2.10.

Edwards, E.A. & S.Q. Duntley. (1939). The pigments and color of living human skin, American Journal of Anatomy, 65, 1-33.

Frost, P. (2012a). Vitamin D deficiency among northern Native Peoples: a real or apparent problem? International Journal of Circumpolar Health, 71, 18001 - DOI: 10.3402/IJCH.v71i0. http://www.circumpolarhealthjournal.net/index.php/ijch/article/view/18001

Frost, P. (2012b). Reply to W.B. Grant ‘Re: Vitamin D deficiency among northern Native Peoples’ International Journal of Circumpolar Health, 71, 18435 - DOI: 10.3402/ijch.v71i0.18435 http://www.circumpolarhealthjournal.net/index.php/ijch/article/view/18435/pdf_1

Frost, P. (2008). Sexual selection and human geographic variation, Special Issue: Proceedings of the 2^nd Annual Meeting of the NorthEastern Evolutionary Psychology Society. Journal of Social, Evolutionary, and Cultural Psychology, 2(4),169-191. http://137.140.1.71/jsec/articles/volume2/issue4/NEEPSfrost.pdf

Frost, P. (2007). Comment on Human skin-color sexual dimorphism: A test of the sexual selection hypothesis, American Journal of Physical Anthropology,133, 779-781.
http://onlinelibrary.wiley.com/doi/10.1002/ajpa.20555/abstract

Frost, P. (2006). European hair and eye color - A case of frequency-dependent sexual selection? Evolution and Human Behavior, 27, 85-103 http://www.sciencedirect.com/science/journal/10905138

Gibbons, A. (2007). American Association Of Physical Anthropologists Meeting: European Skin Turned Pale Only Recently, Gene Suggests. Science 20 April 2007:Vol. 316. no. 5823, p. 364 DOI: 10.1126/science.316.5823.364a
http://www.sciencemag.org/cgi/content/summary/316/5823/364a

Hill, H., V. Bruce, & S. Akamatsu. (1995). Perceiving the sex and race of faces: The role of shape and colour, Proceedings of the Royal Society B: Biological Sciences, 261, 367–373.

Hoffecker, J.F. (2002). Desolate Landscapes. Ice-Age Settlement in Eastern Europe, Rutgers University Press.

Loomis, W.F. (1970). Rickets. Scientific American, 223, 77-91.

Murray, F.G. (1934). Pigmentation, sunlight, and nutritional disease. American Anthropologist, 36, 438-445.

Norton, H.L. & M.F. Hammer (2007). Sequence variation in the pigmentation candidate gene SLC24A5 and evidence for independent evolution of light skin in European and East Asian populations, Program of the 77th Annual Meeting of the American Association of Physical Anthropologists, p. 179.

Russell, R. (2010). Why cosmetics work. In Adams, R., Ambady, N., Nakayama, K., & Shimojo, S. (eds.) The Science of Social Vision. New York: Oxford.

Russell, R. (2009). A sex difference in facial pigmentation and its exaggeration by cosmetics. Perception, 38, 1211-1219.

Russell, R. (2003). Sex, beauty, and the relative luminance of facial features, Perception, 32, 1093-1107.

Russell, R. & P. Sinha. (2007). Real-world face recognition: The importance of surface reflectance properties, Perception, 36, 1368-1374.

Russell, R., P. Sinha, I. Biederman, & M. Nederhouser. (2006). Is pigmentation important for face recognition? Evidence from contrast negation, Perception, 35, 749-759.

Shekar, S.N., D.L. Duffy, T. Frudakis, G.W. Montgomery, M.R. James, R.A. Sturm, & N.G. Martin. (2008). Spectrophotometric methods for quantifying pigmentation in human hair—Influence of MC1R genotype and environment. Photochemistry and Photobiology, 84, 719–726.

Sweet, F.W. (2002). The paleo-etiology of human skin tone. http://backintyme.com/essays/?p=4

Tarr, M.J., D. Kersten, Y. Cheng, & B. Rossion. (2001). It’s Pat! Sexing faces using only red and green, Journal of Vision, 1(3), 337, 337a, http://journalofvision.org/1/3/337/, doi:10.1167/1.3.337.

Tarr, M.J., B. Rossion, & K. Doerschner. (2002). Men are from Mars, women are from Venus: Behavioral and neural correlates of face sexing using color, Journal of Vision, 2(7), 598, 598a, http://journalofvision.org/2/7/598/, doi:10.1167/2.7.598.

Vitamin D and Northern Natives

Annual average exposure to erythema-inducing UV radiation at ground level. Source: Jablonski & Chaplin, 2000. At high northern latitudes, vitamin D can be obtained only from one’s diet, notably fatty fish. Yet many northern native peoples consume little fish. Have they evolved a different vitamin D metabolism?

I’ve just published an article on population differences in vitamin D metabolism, specifically about northern native peoples. Comments are welcome.

Abstract

Vitamin-D deficiency seems to be common among northern native peoples, notably Inuit and Amerindians. It has usually been attributed to: 1) higher latitudes that prevent vitamin-D synthesis most of the year; 2) darker skin that blocks solar UVB; and 3) fewer dietary sources of vitamin D. Although vitamin-D levels are clearly lower among northern natives, it is less clear that these lower levels indicate a deficiency. The above factors predate European contact, yet pre-Columbian skeletons show few signs of rickets—the most visible sign of vitamin-D deficiency. Furthermore, because northern natives have long inhabited high latitudes, natural selection should have progressively reduced their vitamin-D requirements. There is in fact evidence that the Inuit have compensated for decreased production of vitamin D through increased conversion to its most active form and through receptors that bind more effectively. Thus, when diagnosing vitamin-D deficiency in these populations, we should not use norms that were originally developed for European-descended populations who produce this vitamin more easily and have adapted accordingly.


References

Frost, P. (2011). Vitamin D deficiency among northern Native Peoples: A real or apparent problem? International Journal of Circumpolar Health, early view
http://www.ijch.fi/aheadofprint.php

Jablonski, N.G. and G. Chaplin (2000). The evolution of human skin coloration, Journal of Human Evolution, 39, 57-106.

Review of 2010

Drinking from the wrong chalice? By his mid-40s, Michael Jackson had skin like parchment.

The end of 2010 is drawing nigh, and the time has come to review my predictions from last year.

Brain growth genes

Back in 2005, it was found that human populations vary considerably at two genes, ASPM and microcephalin, that control the growth of brain tissue. The finding seemed to be ‘huge’ in its implications. Then, it all fizzled out. No correlation could be found between variation at either gene and differences in mental ability or head circumference (Mekel-Bobrov et al., 2007; Rushton et al., 2007).

A recent study has now shown that ASPM and several other genes (MCPH1, CDK5RAP2, CENPJ) do in fact influence growth of brain tissue, specifically cortical tissue.

… In 2010, we’ll probably see further developments in this area. Stay tuned.

This year did see further developments. Interestingly, these gene loci seem to interact with sex and ethnicity in their effects:

[In a Norwegian study by Rimol et al.] for each of the 15 positive SNPs, the association was sex-specific with all significant results for CDK5RAP2 SNPs being found only in males, whilst the significant results for MCPH1 and ASPM were only found in females.

The second study, by Wang et al., only considered variation in the coding sequence of MCPH1 but found that one non-synonymous SNP is associated with male cranial volume but not female cranial volume in a Chinese population of nearly 900 individuals, supporting a role for sex in the action of microcephaly genes. Intriguingly, it also suggests that SNPs in the same locus can have opposite effects in males and females, as for MCPH1 an exonic SNP contributes to Chinese male cranial volume whilst intronic SNPs and SNPs downstream of the coding sequence are associated with Norwegian female brain size. As the authors discuss, these results strongly suggest some microcephaly variants may influence brain development dependent on hormonal background or through interactions with genes which are differentially expressed between the sexes, potentially contributing to sex specific differences in brain structure. (Montgomery & Mundy 2010)

But why did earlier studies find nothing?

First, many of the previous studies only tested for associations with the few, recently derived ASPM and MCPH1 haplotypes which were the focus of claims of recent positive selection, while both Rimol et al. and Wang et al. consider a larger number of SNPs for which there is no a priori evidence for selection. Second, despite the possibility of deriving clear hypotheses of what phenotypes these loci should affect, many previous studies examined traits that are, at best, not directly relevant (e.g. IQ or altruism) or quite distantly removed (e.g. adult head circumference). (Montgomery & Mundy 2010)

Many people had thought that all variation in mental capacity shows up on IQ tests. So they threw in the towel once it became apparent that IQ does not vary with genetic variation at these loci.

So how do these loci affect mental capacity? I’ve argued that the most recent ASPM variant seems to be associated with the spread of alphabetical writing. It may thus assist the visual cortex in recognizing, storing, and processing strings of alphabetical script (Frost 2008).

Alternatively, Dediu and Ladd (2007) have argued that ASPM and microcephalin variants correlate with use or non-use of tone languages. This hypothesis has been tested with Chinese, Korean, Hmong, and American Caucasians who had little training in tone recognition, i.e., they were not musicians and did not engage in singing or instrument playing. The Chinese and Koreans consistently outperformed the other participants when asked to identify the relative distance between two tones. The Hmong showed no such advantage, even though they shared the ASPM and microcephalin characteristics of the Chinese and Koreans (Hove et al., 2010). Thus, while some East Asian populations apparently are better at processing differences in pitch, this aptitude seems to be unrelated to ASPM or microcephalin.

Early modern human genome

Scientists have retrieved mtDNA from a 30,000 year-old hunter-gatherer from Kostenki, Russia. This seems to be part of a trend to study the genome of early modern humans.

The Kostenki mtDNA genome was entirely sequenced, despite problems that seemed intractable (difficulties in distinguishing between early modern human DNA and contamination from present-day human DNA). The authors concluded: “With this approach, it may even become possible to analyze the nuclear genomes of early modern humans” (Krause et al., 2010).

This development is indeed promising. If we can compare early modern DNA with present-day nuclear DNA, we’ll find out the exact genetic changes, especially those in neural wiring, that led to the ‘big bang’ of modern human evolution some 80,000 to 60,000 years ago. Unfortunately, this ‘big bang’ almost certainly took place in Africa, where the climate is much less conducive to DNA preservation.

Ethnic differences in vitamin D metabolism

This year will see further evidence that natural selection has caused differences in metabolism among different human populations, including vitamin D metabolism.

For instance, many populations have long been established at latitudes where vitamin-D synthesis is impossible for most of the year. Some of these populations can get vitamin D from dietary sources (e.g., fatty fish) but most cannot. In these circumstances, natural selection seems to have adjusted their metabolism to reduce their vitamin-D requirements. We know that the Inuit have compensated for lower production of vitamin D by converting more of this vitamin to its most active form (Rejnmark et al., 2004). They also seem to absorb calcium more efficiently, perhaps because of a different vitamin-D receptor genotype (Sellers et al., 2003). Even outside the Arctic zone, there seem to be differences in vitamin-D metabolism from one population to another. In particular, vitamin-D levels seem to be generally lower in darker-skinned populations (Frost, 2009).

… Unfortunately, our norms for adequate vitamin intake are based on subjects or populations of European origin. We are thus diagnosing vitamin-D deficiency in non-European individuals who are, in fact, perfectly normal. This is particularly true for African Americans, nearly half of whom are classified as vitamin-D deficient, even though few show signs of calcium deficiency—which would be a logical outcome. Indeed, this population has less osteoporosis, fewer fractures, and a higher bone mineral density than do Euro-Americans, who generally produce and ingest more vitamin D (Frost, 2009).

… What will be the outcome of raising vitamin-D levels in these populations? Keep in mind that we are really talking about a hormone, not a vitamin. This hormone interacts with the chromosomes and gradually shortens their telomeres if concentrations are either too low or too high. Tuohimaa (2009) argues that optimal levels may lie in the range of 40-60 nmol/L. In non-European populations the range is probably lower. It may also be narrower in those of tropical origin, since their bodies have not adapted to the wide seasonal variation of non-tropical humans.

If this optimal range is continually exceeded, the long-term effects may look like those of aging …

I hope that people of African or Native origin will resist the vitamin-D siren song. Otherwise, many of them will become shriveled-up husks by their mid-40s … just like Michael Jackson.

Evidence continued to mount this year that vitamin-D metabolism differs by ethnicity. For risk of atherosclerosis, the optimal range is lower among African Americans than among European Americans. A sample of African Americans showed a positive correlation between calcified plaque formation and blood levels of vitamin D (25(OH)D), despite a negative correlation among European Americans over the same range (Freedman et al., 2010).

Another study of African Americans found that blood levels of 25(OH)D decreased linearly with increasing African ancestry, the decrease being 2.5-2.75 nmol/L per 10% increase in African ancestry. Sunlight and diet were 46% less effective in raising these levels among subjects with high African ancestry than among those with low/medium African ancestry (Signorello et al. 2010).

The New York Times has recently covered the growing unease with vitamin D supplements:

The very high levels of vitamin D that are often recommended by doctors and testing laboratories — and can be achieved only by taking supplements — are unnecessary and could be harmful, an expert committee says.

… The 14-member expert committee was convened by the Institute of Medicine, an independent nonprofit scientific body, at the request of the United States and Canadian governments. It was asked to examine the available data — nearly 1,000 publications — to determine how much vitamin D and calcium people were getting, how much was needed for optimal health and how much was too much.

… Some labs have started reporting levels of less than 30 nanograms of vitamin D per milliliter of blood as a deficiency. With that as a standard, 80 percent of the population would be deemed deficient of vitamin D, Dr. Rosen said. Most people need to take supplements to reach levels above 30 nanograms per milliliter, he added.

But, the committee concluded, a level of 20 to 30 nanograms [50 to 75 nmol/L] is all that is needed for bone health, and nearly everyone is in that range.

… It is not clear how or why the claims for high vitamin D levels started, medical experts say. First there were two studies, which turned out to be incorrect, that said people needed 30 nanograms of vitamin D per milliliter of blood, the upper end of what the committee says is a normal range. They were followed by articles and claims and books saying much higher levels — 40 to 50 nanograms or even higher — were needed.

After reviewing the data, the committee concluded that the evidence for the benefits of high levels of vitamin D was “inconsistent and/or conflicting and did not demonstrate causality.”

Evidence also suggests that high levels of vitamin D can increase the risks for fractures and the overall death rate and can raise the risk for other diseases. (Kolata 2010)

H/T to Tod

References

Dediu, D., and D.R. Ladd (2007). Linguistic tone is related to the population frequency of the adaptive haplogroups of two brain size genes, ASPM and Microcephalin. Proceedings of the National Academy of Sciences, 104, 10944-10949.

Freedman B.I., L.E. Wagenknecht, K.G. Hairston KG et al. (2010). Vitamin D, adiposity, and calcified atherosclerotic plaque in African-Americans. Journal of Clinical Endocrinology & Metabolism, 95, 1076-1083.

Frost, P. (2009). Black-White differences in cancer risk and the vitamin-D hypothesis, Journal of the National Medical Association, 101, 1310-1313.

Frost, P. (2008). The spread of alphabetical writing may have favored the latest variant of the ASPM gene, Medical Hypotheses, 70, 17-20.

Hove, M.J., M.E. Sutherland, and C.L. Krumhansl. (2010). Ethnicity effects in relative pitch, Psychonomic Bulletin & Review, 17, 310-316.

Kolata, G. (2010). Report Questions Need for 2 Diet Supplements, The New York Times, November 29, 2010
http://www.nytimes.com/2010/11/30/health/30vitamin.html?_r=2&hp

Krause, J., A.W. Briggs, M. Kircher, T. Maricic, N. Zwyns, A. Derevianko, and S. Pääbo. (2010). A Complete mtDNA genome of an early modern human from Kostenki, Russia, Current Biology 20, 231–236.

Mekel-Bobrov, N., Posthuma D., Gilbert S.L., et al. (2007). The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence. Hum Mole Genet, 16, 600–8.

Montgomery, S.H. and N.I. Mundy. (2010). Brain Evolution : Microcephaly genes weigh in, Current Biology, 20(5), R244

Rejnmark L, Jørgensen ME, Pedersen MB, et al. (2004). Vitamin D insufficiency in Greenlanders on a Westernized fare: ethnic differences in calcitropic hormones between Greenlanders and Danes, Calcif Tissue Int, 74, 255-263.

Rimol, L.M., I. Agartz, S. Djurovic, A.A. Brown, J.C. Roddey, A.K. Kähler, M. Mattingsdal, L. Athanasiu, A.H. Joyner, N.J. Schork, et al. for the Alzheimer’s Disease Neuroimaging Initiative (2010). Sex-dependent association of common variants of microcephaly genes with brain structure. Proceedings of the National Academy of Science. USA, 107, 384–388.

Rushton, J.P., Vernon, PA.., Bons, T.A. (2007). No evidence that polymorphisms of brain regulator genes Microcephalin and ASPM are associated with general mental ability, head circumference or altruism. Biology Letters-UK, 3, 157–60.

Sellers EAC, Sharma A, Rodd C. (2003). Adaptation of Inuit children to a low-calcium diet, CMAJ, 168, 1141-1143.

Signorello, L.B., S.M. Williams, W. Zheng, J.R. Smith, J. Long, Q. Cai, M.K, Hargeaves, B.W. Hollis, and W.J. Blot. (2010). Blood vitamin D levels in relation to genetic estimation of African ancestry, Cancer Epidemiology, Biomarkers & Prevention, 19(9), 2325–2331.

Tuohimaa, P. (2009). Vitamin D and aging, Journal of Steroid Biochemistry and Molecular Biology, 114, 78-84.

Wang, J.K., Li, Y., and Su, B. (2008). A common SNP of MCPH1 is associated with cranial volume variation in Chinese population. Human Molecular Genetics, 17, 1329–1335.