Vitamin D not so good for health?

By Razib Khan | January 27, 2008 11:30 am

Long time readers of this weblog will know I have an interest in Vitamin D. It has been hypothesized to be one of the major causal factors in generating human skin color variation, and we know from evolutionary genomics that the genes which underly skin color have been under very recent & powerful selection pressures. There is also data that Vitamin D levels may have a relationship to endemic diseases such as flu, and chronic ones such as arthritis. And then we find out nuggets such as the fact that most non-whites in Canada are Vitamin D deficient.
But what if we’re putting the cart before the horse? Vitamin D Deficiency Study Raises New Questions About Disease And Supplements:

“Our disease model has shown us why low levels of vitamin D are observed in association with major and chronic illness,” Marshall added. “Vitamin D is a secosteroid hormone, and the body regulates the production of all it needs. In fact, the use of supplements can be harmful, because they suppress the immune system so that the body cannot fight disease and infection effectively.”
Marshall’s research has demonstrated how ingested vitamin D can actually block VDR activation, the opposite effect to that of Sunshine….

Vitamin D deficiency, long interpreted as a cause of disease, is more likely the result of the disease process, and increasing intake of vitamin D often makes the disease worse. “Dysregulation of vitamin D has been observed in many chronic diseases, including many thought to be autoimmune,” said J.C. Waterhouse, Ph.D., lead author of a book chapter on vitamin D and chronic disease.
“We have found that vitamin D supplementation, even at levels many consider desirable, interferes with recovery in these patients.”
“We need to discard the notion that vitamin D affects a disease state in a simple way,” Marshall said. “Vitamin D affects the expression of over 1,000 genes, so we should not expect a simplistic cause and effect between vitamin D supplementation and disease. The comprehensive studies are just not showing that supplementary vitamin D makes people healthier.”

The original paper is Vitamin D discovery outpaces FDA decision making. You can find a preprint here. The article actually states “Vitamin D activates the VDR [Vitamin D receptor] to transcribe (or repress) 913 genes, and the possibility that it might affect expression of as many as 27,091….” It is interesting to me, from an evolutionary perspective, that Vitamin D production might be interrelated with numerous biochemical processes. That being said, I can’t but help feel throwing out “27,091” genes affected is an attempt to interject a large number into the argument to puff up the case. Modeling evolutionary genetics as a system where alleles operate independently and additively is an ideal, and it only is truly relevant in the case of loci where extant genetic variation is related to the normal range of phenotypic variation. Molecular biology and biochemistry make clear that as a matter of mechanism our physiology is characterized by an incredibly complex network of interdependent processes mediated by a bewildering array of biomolecules. The key is not that Vitamin D (through VDR) modulates thousands of genes, but whether this is atypical for a major biomolecule. My impression is that it’s not, so the authors impress me more when they stick to their molecular bread & butter, as opposed to placing their work in a systematic perspective. We’re modulating so many inputs simultaneously that arguments about “thousands and thousands” don’t sound convincing in the bigger picture.
The paper also delves into a pretty controversial area:

It has been assumed that the obesity epidemic is due to unhealthy lifestyle choices. Surprisingly, however, several carefully controlled studies have failed to confirm that assumed causal link between lifestyle and childhood obesity…Additionally, other studies are showing an association between lowered levels of 25-D and obesity…indicating the alternative hypothesis of metabolic homeostasis should be considered alongside the customary assumption of deficiency.
The VDR is responsible for expression of key antimicrobial peptides. Both cathelicidin and defensin antimicrobial peptides are active in the GI tract, and are known to regulate the composition of bacterial flora…in addition to their role of responding to known pathogens. The activity of, particularly, cathelicidin, is important in the neonatal gut…Cathelicidin and defB2 are both expressed…by the VDR when it is activated by 1,25-D.
Is it possible that the chronic addition of immunomodulatory ‘Vitamin D’ to the diet of Homo sapiens has disturbed the historic composition of gut microbiota, and thus is at least partly responsible for the current epidemic of obesity? Physicians know that chronic administration of corticosteroids encourages obesity. More research is needed to better define the immunomodulatory activities of this secosteroid, before encouraging even more of it to be added to the food chain.

I’m open to the idea of pathogens having a greater phenotypic affect on us than we’re aware of, but this seems a bit extreme. Like the earlier assertion about 27,000 genes it seems like the author is trying to go for broke and make a really grand hypothesis when the molecular talking points are good enough to capture interest. It would have been nice if they tried to correlate obesity rates internationally with the level of Vitamin D supplementation; or run some multiple regression on American ethnic groups and regions, who do vary a fair amount in between population obesity. And just as there are tens of thousands of genes potentially affected by VDR, there are hundreds of dietary and lifestyle shifts which might account for the obesity epidemic.
All that being said, this paper has made me think. I’ve been reading up about the biochemical complexities of this pathway lately, and it’s too easy to just pretend it’s a black-box and play evolutionary games. Details matter. I think that the paper points out some molecular processes which need to be accounted for, but it would have been nice if they left it at that instead of trying to throw out a bunch of wild conjectures which seem superfluous to their main argument.


Comments (14)

  1. Kind of cranky if you ask me. Lots of claims way out of proportion to the evidence. No one knows the full answer to this story yet, and these claims are pretty fantastical.

  2. John Emerson

    D toxicity in high doses is well known. Years ago a research scientist told me that Vitamin D is a steroid hormone and that he would use it only with extreme care. I suspect that the natural-health people who would normally be very suspicious of a steroid hormone are the most likely to use D supplements.
    I recently saw the definition of “vitamin” in Wiki. It’s purely functional — a compound (not a mineral element) necessary for health that the body doesn’t produce itself. Vitamin D is only a vitamin in certain circumstances (low sunlight) since the body can produce it in many conditions.

  3. I agree that the link between Vitamin D supplementation and the rise in obesity is tenuous at best, and that’s probably being generous. Although I find it hard to believe that this particular supplement is a statistically meaningful cause of obesity, supplements in general might have their part to play. We are tending more and more to eat low-quality food and get our vitamins and minerals from supplements, which are far less efficient than food at actually delivering those compounds to our tissues. In that way, I can certainly see a link between supplements and obesity.

  4. Lassi Hippeläinen

    The obesity problem isn’t limited to the USA alone. There have been several cases where introduction to “western” lifestyle has lead to increase in obesity. A good example: the Polynesians. They don’t use supplements – they don’t have the money. They don’t even eat as much fish as they used to. Their growing girth seems to correlate with import of cheap canned pork.

  5. If what he says about supplementation actually being immunosuppressive is true, then that’s very interesting, though it’s annoying that I can’t seem to find any of his relevant citations online.
    Beyond that, my bogometer is redlining. If he’s not a crank he’s trying hard to sound like one. Especially when I read something like “the body regulates the production of all it needs” — how can you regulate the production of something you don’t have the raw materials to make? If someone simply isn’t getting enough sun and his diet isn’t making up for it then his body can’t just duct tape some vitamin D together from spare carbons lying around. There’s no magic to it.
    The attempt to pin the increase in obesity on dietary vitamin D is weak — sometimes I wonder if people realize just how easy it is to get fat simply by being sedentary. Obviously genetics and gut flora are major players in determining an individual’s tendencies, but when we’re trying to explain a shift in the population mean then it need not be anything more complicated than a shift toward less physical activity combined with an overabundance of simple carbs in the diet. He’s hearing hoofbeats and looking for emus.
    There are two things said here which are true and important: 1) Vitamin D is important for a whole lot of biochemical pathways, and 2) these pathways interact in multifarious ways that are complicated and not always obvious. To which my immediate reaction is no shit.

  6. There are two things said here which are true and important: 1) Vitamin D is important for a whole lot of biochemical pathways, and 2) these pathways interact in multifarious ways that are complicated and not always obvious. To which my immediate reaction is no shit.
    yeah. like i said, they should have stuck to elucidating molecular pathways, not ‘explaining’ the obesity epidemic….

  7. Anon reader

    well dang. as a middle aged woman i’m concerned about my bones and i take vitamin D to help my body absorb calcium. now i’m nervous about the 800 units of D i take today.
    i do know that weight bearing exercise increases bone density so i walk and use hand weights for arm exercises while i’m watching tv in the evenings.

  8. Anonymous

    Great Blog!
    I think that the claim seems a bit far-fetched, just based on the level of dietary Vitamin D found in our foods. If most of Canada is deficient in Vitamin D, I wouldn’t expect to see an increase in obesity. But in fact, we are seeing an obesity explosing in “civilized” societies. It seems to me that these societies are forgetting about Vitamin D, not over-ingesting it.

  9. Caledonian

    People are willing to grasp for any straw to save them from confronting the obvious fact: we’re fat because we eat too much and don’t exercise enough.
    Since that would mean that we’re ‘lazy’, and being lazy is bad, we’ll fall for any alternative explanation.

  10. Sandgroper

    I’ve got this mental image of all my fellow Australians sitting on the couch watching the cricket for weeks on end, guzzling beer and scoffing cheeseburgers, and this guy saying “You’re all fat because you take Vitamin D supplements.”
    No, don’t think so.

  11. Sandgroper

    Actually, I think I’m right in saying that there has never been Vitamin D supplementation of milk or bread in Australia, because no one dreamed that Vitamin D deficiency would be a major problem in that sunburnt country.
    But it turns out that it is. A substantial proportion of the white population is Vitamin D deficient. It would be really interesting if that were caused by disease processes rather than dietery deficiency or too little UV in winter (which is actually on the cards in winter in southern Australia, even for whiteys) or due to increased use of sunscreen (the observed incidence of Vit D deficiency has increased since the advent of public education about skin cancer).
    But to attribute the growing incidence of obesity and associated diseases to Vitamin D supplementation rather than much more obvious lifestyle and dietary causes is a joke. Unless they’re secretly putting the Vitamin D in the beer.

  12. Vitamin D supplementation couldn’t possibly be responsible for the obesity epidemic because the amount found in supplemented foods has been shown to be too little to measurably raise blood levels. Stronger vitamin D supplementation is to recent to have had an effect.

  13. I found your article to be most interesting.
    Here is something you might also find interesting:
    Beta carotene supplementation may increase mortality risk:

  14. Andreas Bringedal

    Nobody here mentions that there are two types of vitamin D. You have the 25D, the one that is commonly measured and found lacking, and you have 1,25D. Many of those that has low 25D has an abnormally high amount of 1,25D yet this usually isn’t tested(because it’s much more difficult, timeconsuming and costly I guess) and they are then labeled as having too low levels of vit D even when they actually have abnormally high levels of the active form. Also what is seen as normal range of 1,25D is too high because it’s so common to have much of it.
    25d and 1,25 regulate the actiavtion of the innate immune system. 25D turn it down and 1,25 turn it up. High 1,25 levels indicate that the body is trying to turn on the innate immune system but are failing because ligands from bacteria is competing with it to turn it off. It’s a self preservating mechanism on the part of the bacteria.
    A great many people think D vit works the other way around, that it is important to fend of infections like flu or cold. If that had been the case then there wouldn’t be such a thing as a summer cold that last the whole summer(a norwegian summer anyway). The D vit actually prevent the immune system to fight of the cold which is why it lasts so long. So just because D vit prevent the body from producing a proper fever and other symptoms of a working immune system, doesn’t mean that it has fought off the infection, it has just slowed down the fight against the infection.


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About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at


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