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
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