Vitamin D has been associated with numerous health benefits, including cardiovascular and immune health, bone strength, and prevention of cancer. However, studies claim that most of us are deficient in vitamin D, and thereby unnecessarily vulnerable to increased heart disease, stroke, cancer, diabetes, osteoporosis, infection and autoimmune disorders. According to a review of recent studies in Natural News, there is a woldwide epidemic of vitamin D deficiency: 59% of the population is “vitamin D deficient”. The article goes onto to speculate that “What’s becoming increasingly clear from all the new research is that vitamin D deficiency may be the common denominator behind our most devastating modern degenerative diseases.”
Supplementation with vitamin D capsules is advocated even by “primal” advocate Mark Sisson, normally one to take inspiration from our paleolithic ancestors, shunning medication and embracing a lifestyle of eating whole foods and engaging in moderately stressful, playful exercise:
We can’t all bask in the midday sun.. For those of us unable to run shirtless and shoeless through a sun kissed meadow…our option is oral intake… food will help, but it won’t suffice. You need something stronger. ..take a good D3 supplement if you can’t get real sunlight. As long as you don’t go overboard on the dosage, you’re good to go. If it’s not in an oil-based capsule, just take it with a bit of fatty food (not a stretch for an Primal eater). It travels the same pathway and results in the same benefits. It’s always easier to just let nature take its course, but it’s not always realistic. A good general rule is 4000 IU per day.
Therefore, we should supplement with vitamin D. Right?
Not so fast. A closer examination shows that low vitamin D levels may be a consequence, not a cause, of poor health. And that supplementation with Vitamin D may actually be counterproductive. Let me explain.
Homeostatic regulation. First, I’d like to return briefly to a previous post I wrote. In The case against antioxidants, I presented evidence that supplementation with antioxidants is not only unhelpful, but may actually be counterproductive. In my article, I surveyed several meta-analyses of the antioxidant vitamins A, C, and E — demonstrating a lack of benefit from supplementation, and in some cases positive harm. At first, this result surprised me. How can one explain it? After all, we know that vitamin-rich fruits, vegetables and herbs are good for us. Extracts from these anti-oxidant-rich foods have been shown to neutralize reactive oxygen species (ROS) in the lab. Hence, it must be the case that fruits, vegetables and herbs are good for us because of their antioxidant content – right?
Wrong. As we all know, correlation does not always imply causation. And it turns out that fruits, vegetables and nuts may improve our resistance to oxidative damage for reasons other than their antioxidant content. A more likely reason is that these foods are rich in polyphenolic phytochemicals–such as bioflavanoids– that stimulate the cells in our bodies to turn on a transcription factor called Nrf2, which activates our “xenobiotic” defense system. This xenobiotic defense system or Antioxdiant Response Element turns on the production of a number of endogenous anti-oxidant enzymes–such as superoxide dismutase and glutathione peroxidase–that inactivate ROS species catalytically. That means that unlike the antioxidant chemicals in foods–which quickly get used up one-for-one when neutralizating oxidant molecules–the anti-oxidant enzymes turn over thousands of times, and are thus far more potent and sustainable defenses. In addition, these enzymes are produced in cells throughout the body, localized where they are needed most.
In short, empowering our in-born antioxidant defense system is much more effective than supplementing with chemical antioxidants.
But what is even more startling is that supplementing with endogenous antioxidants can actually suppress your body’s endogenous ARE defense system. Startling, but not too surprising once you realize that the ARE system is homeostatically regulated. That means that your metabolism compensates for external changes by making the appropriate internal changes in order to restore a rough balance. Just as body temperature, blood glucose, and countless other internal variables are regulated, our defenses against oxidative stress are regulated.
Homeostatic regulation, ubiquitous in biology, evolved to help us adjust to changing circumstances, and to conserve resources. If antioxidants are supplied from the outside, there is less need to spend energy and internal resources making our own anti-oxidant enzymes, so the organism turns town their production. In my earlier article, I surveyed studies showing that this is just what happens, concluding:
So it appears that, by consuming more antioxidants, we become dependent upon them and perversely reduce our innate ability to detoxify. With any let-up in the constant supply of external defenses, we become more vulnerable to oxidative and inflammatory attack. And the externally supplied antioxidants themselves are in any case much less effective than the endogenous ones.
I ended by recommending that we select foods and herbs not for their anti-oxidant content, but rather for their hormetic ability to stimulate our native ability to produce’s its own detoxifying antioxidant enzymes. At the top of that list are brightly colored and bitter foods and herbs, such as broccoli, blueberries, red peppers, curcumin, green tea and even chocolate.
The moral of the story: When possible, build your own capacity rather than relying on external supplies.
Now on to vitamin D. Not everyone realizes that this “vitamin” is actually a hormone — a secosteroid in the same family as other steroid hormones like testosterone and cortisol. As a hormone, the primary function of vitamin D is to regulate levels of calcium and phosphorus in the bloodstream, thereby promoting healthy bone formation. But vitamin D also regulates a number of other important processes in the body, such as activation of both the innate immune system and the adaptive immune system.
The diet can supply vitamin D as either D2 (ergocalciferol, from plants) or D3 (cholescalciferol, from animals), but it is most effectively synthesized in the skin by the action of UV-B rays in sunlight acting on 7-dehydroxycholesterol. (Yes, it all starts with cholesterol!). But neither D2 nor D3 — the molecules present in supplements or food — are biologically active forms of the vitamin. The diagram at right shows how vitamin D must first be converted by hydroxylation to calcidiol (usually designated as 25 (OH) D, or just “25-D”) in the liver and then further hydroxyulated to calcitriol (1,25 (OH)2 D or just “1,25-D”) in the kidney. It is the 1,25-D form that is biologically active, binding to the vitamin D receptor (VDR) and activating a cascade of important biological functions, such as calcium absorption in the intestines. So a well-functioning liver and kidney are required in order for vitamin D to be effective.
Vitamin D studies. Nobody doubts the important role of vitamin D in the body. But are higher levels of a hormone like vitamin D–whether or not provided as a supplement– always a good thing? Well, that is far from clear. In a review of vitamin D studies in The End of Illness, David Agus, professor of medicine at University of Southern California, cites both positive and negative consequences of increased vitamin D levels. On the positive side, a 2009 study presented by the Intermountain Medical Center in Utah, following 27,686 men older than 50 years over the course of a decade, found that those with the lowest levels of vitamin D had:
- 90% higher incidence of heart failure
- 81% higher incidence of heart attack
- 51% higher incidence of stroke
Pretty impressive association! And yet Agus also cites two negative studies worthy of comment:
- A 2010 double-blind, placebo-controlled study, published in the Journal of the American Medical Association, found that older women who received annual oral high-dose vitamin D had an increased risk for falls and fractures.
- A 2008 study, published in the Journal of the National Cancer Institute, found that vitamin D does not reduce the risk of prostate cancer, and furthermore that higher circulating levels of 25-hydroxyvitamin D may be associated with an increased risk of more aggressive forms of prostate cancer.
Correlation vs. causation. Agus points out that most of the vitamin D studies are “observational studies” that show associations. They uncover a correlation bertween vitamin D levels and some other condition. But they don’t show cause and effect. The few mechanistic studies of vitamin D action were mostly carried out in cell culture, for example adding vitamin D to breast cancer cell cultures suppressed their growth. But in real humans, vitamin D is part of a homeostatic regulation system. Vitamin D doesn’t just do one thing, like promote bone growth. It is involved in as the regulation of as many as 2000 genes, turning up the expression of some, turning down the expression of others.
So how do we interpret these associations? As Agus points out, in regard to the Utah study:
An association, however, does not prove cause and effect. Another way of looking at this study is to say it’s quite possible that a heart condition lowers vitamin D levels, directly or indirectly— by keeping people with health challenges indoors and out of the sun. Also, obesity throws another wrench into the problem because excess fat absorbs and holds on to vitamin D so that it cannot be properly used in the body. Hence, is low vitamin D in this study just a marker for those who were obese? It’s the old chicken-and-egg conundrum. The same can be said for hundreds of other such studies that link the health (or lack thereof) of an individual to levels of vitamin D.
This is the key point: Low vitamin D levels may be a biomarker for other problems. It may be the consequence, rather than the cause, of certain conditions such as heart disease or obesity. For the same reason, high vitamin D levels may be a biomarker for good health. Agus quotes Dr. JoAn Manson, chief of preventive medicine at Brigham and Women’s Hospital:
People may have high vitamin D levels because they exercise a lot and are getting ultraviolet-light exposure from exercising outdoors. Or they may have high vitamin D because they are health conscious and take supplements. But they also have a healthy diet, don’t smoke, and do a lot of the other things that keep you healthy.
If vitamin D level in the blood is merely a biomarker, a consequence of good or bad health, then adding vitamin D to the diet will not necessarily improve your health. To really know whether vitamin D supplementation is beneficial, we need to look at interventional studies, where supplements are provided, and the outcomes are compared with those of control subjects who don’t get the supplement. In fact the two above-cited studies on the effects of supplementation on bone fractures in older women, and prostrate cancer in older men are two such interventional studies. And they showed that vitamin D supplementation was harmful in both cases. And note that the positive Utah study I cited above–showing a correlation between low vitamin D levels and elevated incidence of cardiovascular disease and stroke–was an observational study, not an interventional one. The men in that study with the higher vitamin D blood levels and lower incidence of heart disease were not given supplements.
Vitamin D levels are homeostatically regulated in our bodies, and this process varies with your genetics and health. As one examlple of this, people with lighter skin color and less melanin in the skin evolved to make higher vitamin D levels even with reduced sun exposure; the converse is true of those with darker skin. (This may explain why African Americans are at much higher risk for vitamin D “deficiency”, particularly if they live in higher latitudes and work indoors). People vary widely in the level at which they regulate vitamin D levels in their blood — it tends to be homeostatically controlled in a given individual, but the “normal” level may vary between 8 and 80 ng/ml, or even more widely than that. Vitamin D levels are are genetically controlled by 3 or 4 genes, and are under control of the vitamin D receptor. (This homeostatic regulation of vitamin D levels will sound familiar to those who read my previous post, “Change your receptors, change your set point“). As Agus notes,
When your cells are deluged with vitamin D…they will pull back on their sensitivity to vitamin D by reducing their number of receptors for vitamin D. But if there’s a perceived shortfall of vitamin D in the bloodstream, your cells will up-regulate— create more receptors for vitamin D— to become more sensitive to every vitamin D molecule that passes by. What happens, then, when we consume lots of vitamin D from unnatural sources such as supplements? (I use the term unnatural to imply that it’s not coming from the sun, which is a source of vitamin D that has built-in regulatory mechanisms.) No doubt our bodies are adept at adjusting using their feedback loops as I just described, and the constant surplus of vitamin D means our cells are constantly down-regulating. If we took the supplemental vitamin D away, our cells would up-regulate to make up the difference. Vitamin D has multiple downstream signaling molecules, for the vitamin D receptor signals several reactions.
So if you take vitamin D supplements, and vitamin D is regulated homeostatically, your body will turn down its endogenous production of vitamin D. If you believe that vitamin D is a “biomarker” of good health, do you really want to turn down the upstream processes that synthesize vitamin D? Think about that before you pop a vitamin D capsule.
Unintended consequences. Even worse, taking vitamin D supplements may actually suppress the immune system. This “alternative hypothesis” of vitamin D has been put forward by Trevor Marshall and Paul Albert. Supplementation with vitamin D will tend to increase levels of the inactive form of vitamin D–that is, 25-D. Conversion of inactive 25-D to active 1,25-D in the kidneys is not immediate, and may not be efficient, particular if kidney function is less than optimal. Now here is the problem: While both the inactive 25-D and active 1,25 bind to the vitamin D receptor (VDR), only the 1,25-D turns on the VDR, allowing it to perform its beneficial functions; the inactive 25-D actually inhibits the VDR. This is a problem because the VDR is the “gate-keeper” of the innate immune system, regulating over a thousand genes. So elevated levels of 25-D can result in immunosuppressive effects. As Albert writes in Vitamin D: The alternative hypothesis:
Indeed, the secosteroid 25-D may exert palliation on the innate immune system not unlike the way corticosteroids exert palliation on the adaptive immune system. So is it possible then that supplemental vitamin D is now perceived as a wonder substance simply because it effectively palliates the inflammation associated with diseases across the board? If so, this would certainly explain why its effects are most noticeable in the short-term and why efficacy often diminishes in the long-term.
And we need to also take into account the regulation of vitamin D levels through homeostatic feedback processes. Consider that it is typically the 25-D form of vitamin D–not the biologically active 1,25-D– that is measured in blood tests. And there is very little correlation between the active and inactive forms, as shown in the the figure below, from a 2009 study by Blaney et al., published in the Annals of the New York Academy of Sciences in a sample of 100 Canadian patients. As the authors note, while many of the subjects had very low levels of 25-D–the type reported in most blood tests–most of them had levels of 1,25-D elevated above the normal range. Can those subjects with low levels of 25-D but elevated levels of the biologically active 1,25-D truly be considered vitamin D deficient?
Because low levels of 25-D are often associated with inflammatory conditions such as cardiovascular disease and autoimmune disease, people jump to the conclusion that low 25-D levels are a cause of the inflammatory condition. On this point, listen again to Albert:
Yet, the alternative hypothesis must be considered – that the low levels of 25-D observed in patients with chronic disease could just as easily be a result rather than a cause of the inflammatory disease process. Our research suggests that this is the case. Indeed we have found that 1,25-D tends to rise in patients with chronic disease and that these high levels of 1,25-D are able to downregulate through the PXR nuclear receptor the amount of pre-vitamin D converted into 25-D, leading to lower levels of 25-D. I describe this finding further in my paper. So are we really facing an epidemic of vitamin D “deficiencey” or are we simply beginning to note more signs of an imminent epidemic of chronic disease – an epidenmic which would be exacerbated by increasing the amount of vitamin D added to our food supply?
So the body is making enough active vitamin D to deal with inflammation–maybe even too much, leading to downregulation of the inactive 25-D precursor. Trevor Marshall has also pointed out that elevated levels of 1,25-D may result from impaired activity of the VDR, which is essential for innate immunity. The excess 1,25-D can cause problems with other secosteroid receptors in the body, such as the thyroid receptor. But adding more 25-D, beyond what is needed, will tend to only further inhibit the VDR, interfering with its beneficial anti-inflammatory actions, and impairing innate immunity. In other words, well-intended supplementation with Vitamin D3 may actual backfire. Something to think about!
Marshall is currently conducting studies with a protocol involving restriction of vitamin D and use of an agonist drug that binds to the VDR receptor, upregulating it, and acting as an immuno-stimulant to treat immune disorders like arthritis and multiple sclerosis. Marshall’s protocol is controversial, because it flies in the face of the orthodoxy about Vitamin D. He acknowledges that vitamin D supplementation can indeed deliver some short term benefits because it acts as an immuno-suppressant–in much the same was as corticosteroids like prednisone. But just as prednisone is useful for acute treatments, yet is harmful if taken chronically, the immune-suppresant effects of vitamin D on the VDR may be detrimental.
One need not go to the extent of restricting or avoiding vitamin D to exercise some caution about actively supplementing it. If supplementation has risks, is there anything you can do to ensure adequate levels of the active form of vitamin D? Certainly, it is important to have at least an adequate level of D3 entering the liver, by eating foods rich in vitamin D, and through biosynthesis from adequate exposure to sunlight. But you also want to make sure that the conversion processes to 25-D in the liver and 1,25-D in the kidneys are functioning well. Which means eating a low-inflammatory diet — that is, one that is low in sugars, processed omega-6 vegetable oils and other pro-inflammatory compounds.
Here is the takeaway from this vitamin D story, together with my earlier post about antioxidants: Inflammatory conditions, such as heart disease, infection or autoimmune disease are often associated with reduced levels of certain biomarkers in the blood, such as antioxidant vitamins or hormones. Our natural instinct is to conclude that these are “deficiencies” that need to be corrected. While that may sometimes be the case, particularly in extreme cases, you should keep in mind the direct supplementation with additional vitamin or hormone may actually be counterproductive–by shutting down or impairing your body’s own ability to mount it’s own defense against oxidative stress and inflammation.
Rather than taking hormone and vitamin supplements, it is more effective to stimulate your body to strengthen its own defense and detoxification systems. I’m not against all supplementation — for example, I believe that ingestion of phytochemical-rich vegetables and herbs is useful as a hormetic stimulus. But I think we have to overcome the simplistic notion that if X is a good thing, we should consume more of X.
The body is more than a repository for chemicals — it is a self-regulating organism with hundreds of complex and dynamic feedback loops, evolved to enable us to adapt to changing circumstances and meet many challenges. We should take care that what we ingest is used to build up our natural capacities, not subvert them.
February 11, 2013 update: For suggestions on how you might be able to get the benefits of vitamin D supplementation without the possible downsides, see the more recent post: An alternative to vitamin D supplements?
Excellent, thought-provoking post. Extrapolating your point, I guess for every nutrient we need to evaluate the optimal dose, and how to get it (this is something Paul Jaminet also often talks about). We can add to that also how often, and whether to adjust according to diurnal and annual cycles.
E.g., intermittent fasting, or going low-carb in the winter, and higher carb in the summer through seasonal eating. That accounts for the fuel nutrients, fats and carbs.
Then we have amino acids, which is obviously a quite complicated story. My thinking so far is that it’s best to vary it up as much as possible, aiming for complete sources, but of widely different amino acid profiles. Basically, nose-to-tail eating.
For minerals and elements, I feel supplementation might be necessary, dependent on where you live (obviously, there’s no endogenous production of these). Some have to be carefully balanced, e.g., potassium vs sodium, and copper vs zink, etc.
For “Vitamins” like vitamin D, it’s more dicey, and it’s great that you’ve dug through the research. I look forward to your thoughts about other micronutrients.
Ulrik,
I think we tend to obsess too much about carefully balancing or cycling nutrients. Let’s keep it simple: avoid inflammation and get adequate intake of natural fats, proteins, and phytonutrient-rich vegetables and fruits containing adequate soluble fiber. While it is obviously true that we can’t synthesize essential minerals, most of us–unless severely malnourished–get sufficient amounts of these in a balanced diet. If you remain healthy, your metabolism can likely take care of absorbing, utilizing and balancing the minerals it needs. Where there are mineral deficiencies, it is often due to malabsorption (stemming from diet-induced inflammation, high-phytate grains, hyperinsulinemia, and impaired gut health) rather than a true lack of minerals in food.
WOW, I just took my very first D-3 supplement yesterday! I’ve done so because of performing my own [limited?] research and following the NuSi team who, not only outwardly support the supplement, but take it themselves. No, haven’t gotten my D levels checked recently, but with the winter rapidly approaching and less and less time being spent outside, I thought it to be a fairly reasonable health decision…
I respect all of the reading/opinions/research on these subjects, but who or what should I believe anymore? That’s MY conundrum!
Interesting perspective.
But in the case of Vitamin D, which is practically impossible to get adequate levels from food, wouldn’t a low level simply be a result of inadequate sunlight exposure? And if so, wouldn’t supplementation be the best solution?
I read on one of the paleo blogs like Chris Kresser or Michael Eades that some people (genetic) can’t synthesize vitamin D through the skin via sunlight very well and need supplementation.
Ron, Leonardo and Ben,
Who to believe? I respect Attia, Taubes, Kresser and Eades. But go back and read their evidence and arguments for supplementing with vitamin D. As I emphasize in my article, nobody doubts the correlation between low levels of measured 25-D and higher incidence of inflammatory conditions like heart disease, cancer, infection, and autoimmune disease. But do those guys provide any research showing that low vitamin D (25-D) actually causes these health problems? Or is it mere association–in which case cause and effect may be reversed? Are there any interventional studies showing that supplementing with vitamin D has any long term benefits? (Short term reduction in infections may be due to immunosuppression, not a desireable long term strategy).
A very small part of the population may indeed be genetically incapable of synthesizing vitamin D from sunlight, or may consume foods totally lacking in vitamin D (although that would be rare, given the prevalence of government-mandated vitamin D enrichment into dairy and other foods). But for the rest of us: the Minimum Daily Requirement of vitamin D was established based upon correlations, before the science understood the regulation of 1,25-D and the role of the Vitamin D Receptor. The whole point of my article is that the conventional understanding of what constitutes an “adequate” level of vitamin D may be flawed and in need of being revisited. I think it may be more productive to focus on what dietary and lifestyle factors favor the proper utilization and regulation of vitamin D, and the function of the vitamin D receptor.
I welcome evidence and arguments that challenge my thesis.
http://www.ncbi.nlm.nih.gov/pubmed/21135266
This was a study that showed Vitamin D supplementation for a year in overweight men increased their Testosterone levels. They went from in the deficient range (where many doctors would start hormone replacement treatment) to the low end of the normal range.
Testosterone has been shown to improve Metabolic syndrome, and aid weight loss & waist circumference reduction.
Thanks for the very well written post. Vitamin D has become a very hot topic. There are hundreds-if not thousands- of correlation studies showing beneficial effects of vitamin D. Of course, as you so rightly point out, correlation is not causation. The largest flaw in the logic of the vitamin d proponents is that obesity has been shown to cause vitamin d deficiency (through sequestration in fat tissue)-but obesity itself it correlated with many different poor health outcomes.
While by no means an expert, here is my take on the vitamin D issue. As I understand it, there are three mechanisms of action of Vit. D: endocrine, paracrine, and autocrine. Endocrine activity is well established, causing bone mineralization, and its deficiency causes rickets (osteomalacia in adults). 1, 25 vit. D is the endocrine (active) form of vit D. Symptoms of rickets do not appear until the vitamin d level is very low. No doubt about it, the treatment for rickets is supplementation with vit. D.
The controversy comes in the paracrine and autocrine activity of Vit. D. Paracrine activity refers to hormonal activity that occurs in tissue close by-while autocrine activity refers to to a cell taking up 25 vit D, converting it to 1,25 vit D, secreting the vitamin d-which then acts on the same cell.
One of the reasons autocrine and paracrine activity are controversial is that it is usually claimed that they reduce the incidence of other diseases-for instance, colds, cancer, multiple sclerosis, depression, asthma, etc. The list of diseases claimed is very long. But rather than causing a single, distinct disease, such as rickets, deficiency here causes an increase in the incidence of a variety of other diseases-with other causes.
The vitamin D advocates claim that a “normal” level of vitamin d-in order to have good functioning of autocrine and paracrine effects-is higher than that needed for endocrine effects.
In the past, health benefits have been claimed for other vitamins by trying to obtain a “supranormal” level of the vitamin-such as antioxidants, vitamin E, vitamin C. Under scrutiny, these claims have failed.
The vitamin D advocates, however, make a different claim-that the “normal” level is higher than what we see in order to induce rickets. If they are correct, and the normal level is higher, then supplementation is probably healthful.
The last comment was getting a little long, so I split it in 2.
There is evidence for an autocrine effect in cancer prevention. Apoptosis is “programmed cell death”, by which a cancerous cell “commits suicide”. Apoptosis is a vitamin D mediated, autocrine effect:
http://www.immunerecoverywellness.com/pdfs/cancer/Vitamin%20D.pdf
There are also randomized controlled trials showing decreased cancer incidence in people supplemented with vitamin D:
http://www.ncbi.nlm.nih.gov/pubmed/17556697
Another autocrine effect of vitamin D is the secretion of Cathelicidin-an antimicrobial peptide:
http://en.wikipedia.org/wiki/Cathelicidin
There have been RCTs showing decreased infections in people supplemented with vit d, and other RCTs showing no effect.
It’s all very difficult. What really is the “normal” level for vitamin D? If the lower level is correct, trying to supplement to a “supranormal” level will probably not help, and may harm. On the other hand, if the higher level is correct, supplementation will probably help.
I’ll tell you what we do in our family. I take-and give my kids-supplements for half the year-winter. That way, there is a period of no supplements-but plenty of sunshine.
Its completely anecdotal, but since we started supplementing with vitamin D, no one has got cancer! More to the point, my kids are remarkably healthy. They are the ones who always get the award at the end of the year for perfect attendance-no school days missed for illness.
Hi Nate,
Many thanks for bringing to my attention to the studies you linked. A few thoughts:
1. I wonder about the significance of the cell culture studies. Since they consider only the direct action of the 1,25-D on hormone signaling and apoptosis, they leave out the regulatory effects on the Vitamin D receptor (VDR) upon over a thousand genes in other cell types, and other secondary effects such as feedback downregulation of 25-D levels.
2. Regarding the 2008 cancer intervention study by Lappe et al. I don’t have access to the full study, just the abstract you linked. But, as one reviewer noted, the reduction in cancer incidence appears to be statistically insignificant. Out of about 1200 women, there were 4 cancers in the supplementation group, versus 7 in the placebo group. Four years is also a fairly short time to be able to draw conclusions about cancer mortality. So I’m still looking for interventional studies that show statistically significant long term benefits of vitamin D supplementation.
3. You are certainly right to point out a possible beneficial effect of vitamin D’s induction of cathlecidin as a result of VDR activation. This may in part explain the reduced rates of infection that have been noted following vitamin D supplementation. (http://news.harvard.edu/gazette/story/2012/08/vitamin-ds-impact-on-infection/), although the effect is not consistent (http://www.sciencedaily.com/releases/2012/10/121002161751.htm), and suppression of infection or immune response is what I would consider to be a short term response. We can of course also suppress infections with antibiotics and apply steroids to dampen immune response. I wouldn’t hesitate to do this on an acute basis in an emergency. But my general approach to health is to use hormesis and other methods to stimulate and strengthen the body’s defense and repair mechanisms, rather than resorting to palliative approaches which could weaken us in the long term.
Regards,
Todd
Let’s be quite clear that D3 synthesis via UV action on the skin, can raise levels of 25(OH)D substantially. I’m wondering whether there exists in correlation with elevated incidence of autoimmune diseases and cancer in Mediterranean regions as a consequence of VDR inhibition?
It’s also clear that sunlight synthesis appears to be no different in effect to supplementation.
I honestly doubt hormesis is relevant in this case 25(OH)D is stored in the liver, released and converted as required. Homeostatis is the ruling process, not hormesis.
Bill,
No disagreement about the effectiveness of sunlight in vitamin D synthesis, and the equivalence of supplemented vs. synthesized 25-D. Quoting from what I wrote in my post
I’m also not sure where you get the idea that I’m confusing hormesis with homeostasis. I’m clear on the difference between these two processes. Hormesis is a biological phenomenon whereby a beneficial effect (improved health, stress tolerance, growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses. It has its roots in a set of defense and repair processes which act to resist damage and restore function. That is the connection between hormesis and homeostasis — a set of regulatory processes by which an organism acts to maintain a relatively constant internal environment. The connection is that the stresses of hormesis activate homeostatic processes to result in what Mark Sisson has termed “supercompensation” — a strengthening of defensive capabilities. So the hormesis of weight lifting induces muscle trauma and supercompensating muscle repair. Cold showers, intermittent fasting, and Stoicism all work by similar processes of super compensation. None of these processes would work without homeostasis. So homeostasis is a necessary condition for hormesis.
But the action of homeostasis is not always a response to hormesis. Sometimes it just involves a response to a minor disturbance, like the physiological responses to acidifcation of the blood or a drop in body temperature, so as to return the organism to the starting point. So in the case of the vitamin D (25-D) storage or synthesis, there is homeostasis, because these levels are regulated. No hormesis is involved. And I never said it was involved.
Why does my article have to do with hormesis, you may ask? Well, not all of my articles are directly about hormesis, even though that’s the main theme of my blog. But the connection is spelled out very clearly in the last 3 paragraphs of my blog post above — easy enough to scroll up and read them.
Hmmm – still implicit, Todd.
I think the crux of it is more a question of just how much D we thrive on. The arguments that we adapted to have less melanin as we migrated northwards are compelling, and it would seem that this pre-hormone is critical to optimum health.
Since your article is speculative, I can also speculate..
The Inuit obtain D from diet, and are likely replete, despite virtually nil by UV synthesis. In effect, this could be seen to be a kind of “supplementation”.
I think the data from Grassroots Health are the most interesting, and no-one is making a fortune out of promoting supplementation – it’s way too cheap. So we can rule out “conflict of interest” from those promoting supplementation – er, but not in the case of those promoting sun lamps (!)
It seems to be the case, though, that there is a wide variation in individual requirements.
What I find most “challenging” is the assertion that 25(OH)D can actually cause VDR inhibition – unless we entertain the concept of liver saturation. But then, surely, we would be at the toxicity threshold?
My main point remains – is there any epidemiological evidence to support abundant sunlight exposure with VDR inhibition, as might be expected in Mediterranean climates? (Presumably elevated incidence of the cancer and autoimmune disease, as reported by Grassroots Health)
I wonder if supplementation from more complete food sources, like cod liver oil with no synthetic vitamins added, would have a different effect due to the “synergy” (Weston Price’s term) between vits. A and D.
Over on Seth Roberts’ blog there has been a steady stream of posts relating to D supplementation with the general theme that it seems to matter *when* you take D. If you take 4000 or so first thing early in the morning, it helps you sleep better and thus feel more alert when awake. If you take D later in the day, it does not have this beneficial effect.
The working hypothesis is that our bodies expect to see sunlight in the morning and getting an early pulse of D simulates that, helping set our circadian clock better. Sleeping better in turn promotes health in all sorts of ways – if D helps you sleep better, that boosts the immune system.
Most existing studies of D supplementation do not instruct people to take it at a particular time, so they might be missing out on this benefit.
I don’t “buy” this at all.
25(OH)D is not released into the bloodstream until hours after UV exposure, and is then stored in the liver, being released “as required” and converted to the active form in various sites, but primarily the kidneys.
In supplementation, it seems to be irrelevant whether you take 42,000iu weekly, or 6,000iu daily, let alone what time of day you take it.
Everything I’ve seen on this topic is subjective, and has not been studied.
This came at a great time since I just finished my bottle of Vitamin D pills. I think I’ll hold off on buying another bottle for the time being.
I was convinced that vitamin D really helped me with depression. After supplementing, I’d never feel as low and hopeless as I did before. Maybe this improvement in my mood was caused by something else. I’ll stop taking the D supplements and see how I feel.
Thanks for the insightful post.
Trevor Marshall doesn’t strike a chord for me – here he gets a sound rebuttal:
http://www.cmaj.ca/content/167/8/849.1.full.pdf+html
Bill,
I followed your link to the letter by Marshall and the response by Hanley. Not sure I would call Hanley’s response a “rebuttal”. Hanley doesn’t really address Marshall’s main challenges to the consensus view about vitamin D “deficiency”, nor does he discuss the Marshall protocol. Hanley’s letter in fact acknowledges errors that Marshall pointed out an article that Hanley co-authored, and he agrees with Marshall that the 1,25-D is the most biologically active form of vitamin D. He then goes on to make some rather minor points regarding malabsorption syndromes and osteomalacia, where low vitamin D levels result in poor bone mineralization. I don’t think anyone (myself, David Agus or Trevor Marshall included) doubts the reality of true vitamin D deficiencies in cases such as these, or rickets. But that is tangential to the main question regarding whether “vitamin D deficiency” should be re-defined as broadly as it has been in recent years, and whether we should supplement at levels far higher than those need to prevent rickets or bone demineralization.
Let me be clear here that I don’t follow everything that Trevor Marshall advocates. For example, I’m far from convinced about the soundness of his “Marshall protocol” that actually attempts to drive down levels levels of 25-D, including avoidance of sunlight, in order to treat certain chronic inflammatory and autoimmune disorders. However, I do believe that he and David Agus have at least raised valid reasons to be skeptical that active vitamin D supplementation is an unalloyed good thing. In that respect, they have done us a service by pointing to the lack of well-controlled positive interventional studies, the existence of studies showing deleterious effects, and the reality that vitamin D, as with any hormone, is subject to feedback regulation. The fact that vitamin D’s interaction with the VDR has widespread effects on regulation of hundreds of immune modulating genes, many of which are poorly understood, should give anyone pause. Vitamin D may indeed provide many people with short term benefits, e.g. reports of controlling asthma or depression. But what of the long term effects? Cortisone, predisone, and human growth hormone also have amazing short term benefits — but I wouldn’t advise use them chronically.
I’m not anti-vitamin D. I just don’t think the case has been made for routine and long-term supplementation, except in cases of severe deficiency.
Thanks for your note!
Todd
Todd,
This may be a personal question, and delete this if it is
, but do you take any supplements at all? Mere curiosity.
Ron,
It’s a fair question. I do not take any vitamin or mineral supplements, or any hormones — not because I fear them, but because I believe I get the nutrients I need in adequate amounts from wholesome meats, vegetables and other foods, and I don’t have any apparent problems with absorption. But I also don’t necessarily trust published “standards” of how much is enough.
I do not have a fully developed theory of whether and when supplementation is beneficial or not. I’m still doing a lot of reading on this. There is one pill I take every day, which I won’t reveal at this point, other than to say it is not a supplement, but a mixture of “hormetic” compounds which induce a beneficial endogenous antioxidant response and significantly shortens my recovery time after workouts.
Todd
“But I also don’t necessarily trust published “standards” of how much is enough.”
Totally agree!
“…which I won’t reveal at this point”
Thanks for the cliffhanger!
Thank you for this post. A few thoughts and questions:
Would you think that the health benefits of Vit D, if they are hormetic in nature, would have a U-shaped curve, with a ‘sweet spot’ for optimal health, much like exercise?
You mentioned Mark Sisson and evolutionary reasoning, so wouldn’t you think that comparing vit D levels from people living most of the time inside with levels from ‘outside living people’. Do you have any data on this?
Thanks again.
Pieter,
While I sometimes take inspiration from the observations of “paleo” authors like Mark Sisson and Robb Wolf, I’m not convinced that so-called “evolutionary reasoning” is a sound methodology. The evidence for what our ancestors ate and how they lived is sparse and often speculative. There is great variety in human dietary practices and even genetics. And of course, our more primitive forebears did not necessarily live longer or exhibit great health. It’s wise to balance these anthropological or evolutionary studies and speculations with modern physiology and biochemistry. Of greatest interest and importance, in my view, is a sound understanding of homeostatic regulation — how our body and metabolism responds to and compensates for what we ingest and what we do.
I think that it is too simplistic and reductionistic to posit a single optimum or sweet spot for individual nutrients or biomarkers — whether they be macronutrients like fats, or hormones, vitamins or minerals. Certainly at the extremes, very low vitamin D is associated with rickets, and very high levels with toxicity. But there is no single optimum level for all individuals in all health conditions. These chemistries need to be considered as parts of a complex, dynamic system that is in constant flux. A level that represents “deficiency” for one person may be adequate or excessive for another. In certain cases it is the balance, not the absolute level that is important. For example, Vitamin D exists as part of a regulatory system that includes Vitamin A, calcium and zinc.
Furthermore, as my article indicates, Vitamin D levels – when measured as vitamin D3 or 25-D — may be more of a consequence than a cause of health, and do not correlate well with the biologically active form, the 1,25-D. I have no doubt that people who spend more time outdoors have higher 25-D levels — because they are synthesizing the precursor in their skin. And they are healthier. But so what? Are they healthier BECAUSE they synthesize more Vitamin D? And should we replicate this by supplementing with Vitamin D? That is not proven.
Wealthy people own more sports cars, but they are not wealthy BECAUSE they buy sports cars. And buying a sports car will not make you rich.
Todd,
A little off topic, but did you see this article on the mechanisms of action for omega-3 PFA’s?
http://www.the-scientist.com/?articles.view/articleNo/32901/title/Omega-3s–Fishing-for-a-Mechanism/
Hormesis makes another appearance!
Nate
Nate,
Thanks for the excellent article. It potentially resolves a mystery I had always wondered about: How can such easily oxidized n-3 PUFAs, which go rancid and become harmful when oxidized, exert such beneficial biological effects? The hormesis explanation is not only appealing, but also has good experimental support from the article. I think this rationale also supports another line of thinking that I’ve been intrigued by: namely, that while chronic exposure to elevated levels of reactive oxygen species (ROS) is generally detrimental, we in fact benefit from intermittent, more selective exposure to oxidative “stress”. Chris Masterjohn likes to frame oxidation as a means of cellular “communication”. Stamping out this communication is not desireable. Rather, what we want is a well-regulated system of oxidative communication.
Todd
Very interesting post.
A nice and now well documented example of low 25 D as a consequence rather than a cause of illness is primary hyperparathyroidism. Removing the tumor(s) spontanenously restores “normal” 25 D levels in blood.
Supplementing vit D in these patients before bad glands parathyroidectomy is quite dangerous.
http://parathyroid.com/low-vitamin-d.htm
Todd,
Dr Joseph Mercola claims that in winter, the best way to get D3 is from his tanning beds. http://tanningbeds.mercola.com/
I see some support for this idea at:
http://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
http://www.dnva.no/geomed/solarpdf/Nr_12_Holick.pdf
What do you think of Mercola’s claim?
An advantage of tanning (or direct sun exposure) over supplements is that vitamin D synthesis in the skin is self-limiting, so toxic build up is unlikely. I’m a bit skeptical of tanning beds, because even though brief, the rate of UV exposure is much higher than normal, more of the body is exposed, and the risk of skin cancer is elevated (http://www.cancer.gov/newscenter/entertainment/tipsheet/tanning-booths). If you are going to use tanning beds or spend a lot of time in the sun, the sane approach is to build up a base slowly. If you are pale and suddenly increase your exposure, your risk of burning (and cancer) are elevated than if you build up a base level of melanin in the skin.
The bottom line, however, is that claims that most of us are “deficient” of Vitamin D are overblown — even in the winter. Rickets may have been a problem during the Great Depression, but not today. Many other factors besides vitamin D affect calcium absorption, so we can’t blame osteoporosis on vitamin D deficiency. Getting moderate sun exposure and eating a diet with a good source of animal and fish fat in the diet provides enough vitamin D for most of us.
A bit off-topic, but…
What is your opinion on supplementing turmeric or standardized circumin?
Tumeric is one of the few things I “supplement” — though I’m not sure it technically should be considered a supplement, since it is not a matter of correcting a dietary deficiency, as much as it is one of stimulating natural defenses. It is a Nrf2 activator, known to upregulate endogenous antioxidant enzymes. I have found it personally effective in reducing muscle soreness and improving post-workout recovery. I’ll be posting more on that at some point. For now, you might check out my post, “The case against antioxidants“.
Thanks, Todd. Turmeric is one of the few things I take. I was not aware of the NRF2 connection, but I know turmeric seems to be very good. I love your work. Keep it up!
Robb,
I’m preparing for pregnancy in the next 6 months. I’m reading a lot of support for the Green Pastures fermented cod liver oil/butter blend because it carries with it the vitamins needed to metabolize D. Is this something you’d recommend at this point. I hear/read so much conflicting information that it’s hard to decipher what’s best. Do you have any other recommendations for pre-natal supplements? I know Chris Kresser speaks about supplements quite often but I don’t want to break the bank! Any thoughts on pre-natal supplementation would be much appreciated. Love your info!
Todd,
Thank your the great article.
Would you through fish oil in this as well? In other words, most primal/paleo folks say don’t worry about supplements EXCEPT vitamin D and fish oil. With your article pointing to the fact that perhaps supplemental vitamin D is not as beneficial as we think, should we be supplemental fish oil either?
Unfortunately, writings like this tend to do more harm than good. Sure, it’s good to question things. It seems by the logic of this article that I should perhaps limit my water intake and keep my hydration at a low level to upregulate the hormones that signal my body to store water, since of course that is controlled homeostatically.
Seems like this article is full of a lot of “could be’s” and very little good science. In light of all the good info currently on vit d supplementation, I’ll wait for some better info before jumping ship.
Conrad, what harm is being done? Todd is raising important questions. Your analogy is not accurate. Is water a supplement or a required nutrient?
My analogy is correct. Vit D3 is not merely a supplement, it also is a required nutrient. If it wasn’t then we wouldn’t even be talking about it. If we put water in a capsule and market it, is it no longer a required nutrient? No, that doesn’t change, supplements aren’t inherently inferior. Chemicals are chemicals, your body doesn’t necessarily know the difference. Ever heard of molecular mimicry?
I’m not against healthy skepticism. I’m against skepticism that doesn’t understand the facts. I’m against stirring the pot to create drama.
The harm I see is in taking a substance that is showing great promise in good solid research. A substance that more and more people are taking and improving their health with and throwing confusion in to the mix.
This article lacks scientific substance and depth in comparison to others who are finding objective data to support maintaining optimal levels. As an example, the author apparently doesn’t understand the immune MODULATING effects of this substance as he didn’t give any acknowledgement to it when addressing suppression of the immune system. This is often a good thing and Vit D doesn’t just keep suppressing the immune system more and more the longer you take it.
Conad,
You suggest that I am trying to “stir the pot to create drama.” That’s not my intent. I’m just trying to get at the truth, and present the results of what I found. I”m open to any new information that would warrant changing my mind.
You say that the article lacks scientific substance. In the above article I cited a substantive studies, published in reputable journals, that found negative outcomes (increased bone fractures and higher incidence of prostrate cancer) from vitamin D supplementation. I would like to hear your specific objections to those studies.
You and I agree that both water and vitamin D are essential for human life. Beyond that, I think the analogy breaks down:
1. We need to consume water because we can’t manufacture it in our bodies. By contrast, we can manufacture our own vitamin D–starting from a cholesterol derivative–by the action of UV-B in the skin.
2. You are correct that both Vitamin D3 and water levels in the body are “regulated”. In the case of water, excretion and perspiration are “regulated” by salinity sensors in the kidneys. But this is very different that the feedback regulation of vitamin D, which is essentially a hormone. You would have to ingest extreme amounts of water — more than about 15 liters — to cause health problems such as hyponatremia. By contrast, vitamin D has hormonal action via ligand-receptor binding that initiate a cascade of genetic and physiological effects. 25-D levels are subject to feedback regulation by the biologically active 1,25-D form of the vitamin, via receptor binding to the VDR. (http://ajprenal.physiology.org/content/289/1/F8.full) Supplementing with high levels of D3 will not only downregulate vitamin D synthesis in the skin and liver; but by binding to the VDR, which in turn regulates more than 200 genes, many of which are associated with the innate immune system and cancer.
Drinking a lot of water can cause little more than temporary discomfort.
You are correct that vitamin is properly considered an immunomodulator, with both immunostimulatory and immunosuppressive effects, depending on the individual’s health status. However, as the authors of this review of vitamin D’s role in autoimmunity conclude, “On the whole, vitamin D confers an immunosuppressive effect.”:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955167/
Thanks for adding to the discussion.
Todd
Todd,
This is exactly why Conrad said, “Articles like these do more harm than good.” You are not accurately capturing the current scientific opinion of vitamin D. While it’s fine and good to be skeptical, you need to be evidence-based, and this review is not evidence-based. Here’s where you can learn more about evidence-based medicine: http://www.cebm.net/index.aspx?o=5653
The increase in fractures is because they used a 500,000 IU mega-dose. We now know that mega-doses 300,000 IU and over superficially increase bone turnover, thus leading to an increase in fractures. Daily dosing does not negatively affect bone turnover, and in fact, meta-analyses show that vitamin D decreases fracture incidence.
Researchers actually believe vitamin D can help in prostate cancer. Several trials have been completed demonstrating its safety in use for patients with prostate cancer and several trials are underway to see if it helps in treatment. There have been some randomized controlled trials that have shown vitamin D may prevent prostate cancer, too.
Vitamin D supplementation does not down-regulate synthesis in the skin or decrease conversion of vitamin D to 25(OH)D in the liver (in fact for the latter, it does the opposite).
Also, it seems like you don’t understand autoimmune diseases very well.
#39
Hi Todd,
“This is the key point: Low vitamin D levels MAY be a biomarker for other problems. It may be the consequence, rather than the cause…
IF vitamin D level in the blood is merely a biomarker, a consequence of good or bad health, then adding vitamin D to the diet will not necessarily improve your health.”
Vitamin D levels do not APPEAR to fall in the biomarker category of being a consequence such as C-Reactive Protein levels.
We both agree that vitamin D is essential for optimal health. I think we can both agree that there is a difference between major deficiency leading to rickets and lesser prolonged deficiency that may promote long-latency diseases. Essentially we have to get sunlight of an adequate UV intensity for our body to make this. Many people get very little sun exposure and many more cover themselves in UV blocking sunscreen and D is not present in adequate quantitiy in food. So what happens when we don’t get enough? Does our body down-regulate its need for this substance? This sounds like a big MAYBE.
There are many nutrients that our body can’t make that we have to get from outside sources; various vitamins and minerals, cofactors for creating ATP, essential amino acids, etc. If we don’t get them then we WILL NOT express optimum health. Since many people are not getting adequate UV exposure, supplementation makes sense as the next best thing.
Research/studies are not all created equal. In fact there are a lot of crap studies out there. Just because it’s in a journal doesn’t mean it’s good science. Here’s a link to a paper that discusses some of the common errors in Vit D research. (Page 6/7) http://www.chineseherbacademy.org/Vitamin_D.pdf
This is my specific objection to those studies. I didn’t find links to see for myself but it doesn’t even make sense that Vit D would CAUSE and increase in falls nor an increase in fractures considering it’ role in calcium utilization amongst other elements of bone health. http://www.mayoclinicproceedings.org/article/S0025-6196%2811%2962740-7/fulltext
I respect your time in putting together a lengthy blog post and addressing/citing various research and discussion on this topic. I know that these take a long time.
So what do you say about people who are dealing with known autoimmune diseases, ( for me it’s Chronic Lyme disease and under active thyroid). I’m currently under the care of a Naturopathic Physician who monitors my vitamin D levels among many other things. She has me on 4,000 IU’s currently to bring up low Vitamin D levels. Any other suggestions on how to get those levels up without supplementation in the dead of winter.
Sheilla,
I acknowledge that Vitamin D can “help” moderate the effects of autoimmune diseases. No doubt this translates to feeling better in the short term. But it is likely that this is due to an immuno-suppressive effect. You would also feel better by taking a steroid like Prednisone. Just because vitamin D is “natural”, people seem to forget that it is basically a hormone.
My main point is not to focus so much on achieving a target level of some biomarker like Vitamin D, but to address the root cause of what is causing the autoimmune disorder in the first place. I have some ideas on how to approach that which I hope to address after some additional research.
Todd
my understanding is that vitamin D supplementation is ineffective and perhaps harmful if it is not balanced with vitamin A, K2 and magnesium (and I’m sure we’ll find even more co-factors that are involved in Vitamin D metabolism in the near future since all this vitamin D research has only come out in the past decade) so it does make sense that supplementation is not necessary.
and yes, correlation does not equal cause…
thank you for this article.
JM,
Good points.
I find it interesting that contemporary nutritionists think they have figured out the precise ratios at which vitamins and minerals must be balanced for perfect health, and to avoid harm — as if our metabolisms had not evolved to compensate for the ever-varying ratios that come to us through the food supply, and as modulated by our genetic and environmental variability. It’s like economists who try to micromanage a complex economy.
Certainly we should be aware of gross deficiencies that endanger our health and bring us close to verifiable health problems such as rickets. I’m aware that vitamin D and other supplements can be helpful. But even if you feel better or address a short term problem by supplementing, that doesn’t mean long term supplementation is advisable. If you are generally healthy, it seems prudent to trust the biology of our bodies over the latest nutritional research and guidelines that seem to change every few years. For how many years exactly have people been supplementing with megadoses of vitamins. How many long term studies are there? And even if we have good data on single nutrients, do we understand the interactions and ratio effects?
I’m quite healthy, thank you, without taking these supplements. Until I see longer term studies, I trust evolution more than the last 2 decades of nutritional research.
Todd
This is a common argument that supplements =/= nutrients from food sources. While I can’t speak on evidence of other nutrients, I can speak that current evidence to date says vitamin D3 is vitamin D3, whether it’s coming from your skin, supplement or a pound of salmon.
The general idea in supplementing with vitamin D is that few 21st century humans get enough sunlight to make adequate amounts of vitamin D. In fact, studies out of Africa found that Hadzabe and Masaai tribes have 25OHD levels around 45 ng/ml. The average indoor-lifestyle American would need to supplement with 4,000 IU+/day to achieve this level. To me, this is not blindly feeding the body a nutrient. This is a goal oriented practice with a target in mind: to achieve ancestral vitamin D levels.
While we certainly need more evidence for vitamin D supplementation, for the time being, choosing not to supplement is choosing not to get as much vitamin D as sun-dwellers do. It’s a choice for the individual.
There are actually quite a few randomized controlled trials showing that vitamin D supplementation is effective for a multitude of things:
-1,000 IU/day for infants with heart failure improved their heart fraction.
-Mega-dosing with vitamin D reduced risk of death fivefold for patients with cystic fibrosis vs placebo.
-Mega-dosing with vitamin D reduced risk of death by two-fold patients admitted to the hospital for traumatic brain injury vs placebo.
-50,000 IU/week prevented or delayed onset of multiple sclerosis vs placebo.
These are all serious conditions with patients with serious needs. In these instances, choosing to administer a supplement to them is vital and evidence-based. I implore you to read more about some randomized controlled trials published last year here: http://blog.vitamindcouncil.org/2012/12/18/rct-vitamin-d-levels-and-traumatic-brain-injury/
Lastly, sun exposure may be choice, for other reasons (it likely regulates a lot of things in the body), but in regards to vitamin D, again, there is poor evidence that sun exposure is better practice than supplementing.
Cheers,
Brant
Brant,
Thank you for your post. You may be surprised to know that I agree with you on a key point: that supplements like vitamin D can be helpful in acute treatment of people who are very ill. But I haven’t seen evidence that supplementation with vitamin D provides any long term benefits for those of us who are generally in good health.
Furthermore, why should we care whether or not our measured vitamin D blood levels are lower than those of “ancestral” African tribesmen? By itself, the observation that the Hadzabe and Masaai have higher 25-D levels than do you or me proves nothing. For this to be a meaningful fact, we would need to establish that (a) these tribesmen live longer or are healthier than we are in some important respect; and (b) this is more than a mere association, that is, we would need proof that their higher vitamin D levels causes their good health or is somehow essential for it. It could also be the case that their good health is the cause, not the consequence of their higher vitamin D levels. Correlation does not establish causation, or the direction of causation.
The randomized controlled studies you cite concern people with major illnesses: infants with heart failure, cystic fibrosis patients, and those with traumatic brain injury. Even assuming some of these ill people benefit, the traumatic brain injury study you linked is not so easy to interpret. The brain injury patients were divided into 3 groups and treated for 3 months:
Placebo: 15% had “good recovery” (however that is defined)
Progesterone: 25% had good recovery
Progesterone + vitamin D: 35% had good recovery
So vitamin D enhanced the benefits of progesterone. But since there was no “vitamin D only” leg to the study, we don’t know whether vitamin D by itself would have helped. In fact, the study report speculates that vitamin D helped progesterone due to “complementary mechanisms”. And this study was apparently designed to follow up on the observation that “Recent studies have suggested that vitamin D deficiency may worsen traumatic brain injury and reduce the effects of current treatment.” So we are left with a mixed picture about how effective vitamin D is for trauma patients. Sometimes it helps, sometimes it hurts.
The other thing to point out here is that this study, like the others, was a short term study. You can find numerous studies showing that treatment of conditions with hormones and steroids provide significant benefits in the short term — weeks to months. But we know that the body responds to hormones and steroids by homeostatic compensations, and that sustained administration of these powerful agents can have significant side effects, including elevated risks of cancer and cardiovascular disease. We also know that megadosing vitamin C is very useful in treating acute infection. But long term studies show problems with megadosing vitamin C and other antioxidants. I’ve listed a number of such studies in my article, “The case against antioxidants”
I come back to my main point: For healthy individuals — not those with major illnesses — the case has not been made that long term supplementation is helpful. In fact, I’ve cited several studies in my article indication that vitamin D can be harmful in some cases. It’s not so black and white as advocates of vitamin D supplementation suggest.
Todd
I wouldn’t say there isn’t any evidence that supplementation helps long-term health, it’s just the highest standard of evidence – randomized controlled trials – have not been done yet for a large scale population. These kinds of trials cost millions of dollars and are just now underway:
• In the United States, they’re administering 2000 IU/day or placebo to 20,000 participants.
• In Finland, 1600 IU/day or 3200 IU/day to 18,000 participants.
• In New Zealand, 3300 IU/day or placebo to 5,100 participants.
• In Europe, 2000 IU/day or placebo to 2,150 participants.
• In the UK, 2000 IU/day or placebo in 20,000 participants.
Results are coming in 2020. While waiting for the results before you start supplementing is always an option, I’ll offer a hint: they’re studying these doses because they think there is benefit.
I think you should care about ancestral vitamin D levels because it places the burden of proof on the argument that we don’t need those vitamin D levels. Right now, people calling for higher vitamin D levels/supplementation are asked for proof, when based on what we know, the burden of proof should be placed on the argument that lower levels are fine, when there is poor evidence this is the case.
Thanks for the breakdown of the randomized controlled trial I posted.
I actually meant to link to this blog here which flies through the results of 21 randomized controlled trials published in 2012: http://blog.vitamindcouncil.org/2012/12/31/a-look-back-at-2012-a-few-key-randomized-controlled-trials/
Evidence and arguments that challenge your thesis:
1. Adapted from http://www.vitamindcouncil.org/news-archive/2008/professor-marshalls-recent-discovery/:
If low vitamin D levels are the result of disease, then cancer would cause low vitamin D levels, not the other way around. Professor Joanne Lappe directly disproved that theory in a randomized controlled trial when she found that baseline vitamin D levels were strong and independent predictors of who would get cancer in the future. The lower your levels, the higher the risk. Furthermore, increasing baseline levels from 31 to 38 ng/ml (77.5 to 95 nmol/L) reduced incident cancers by more than 60% over a four year period.
Therefore, remaining vitamin D deficient (below 40 ng/ml) will cause some who are otherwise generally in good health to die from cancer.
2. For people living outside (sub)tropial regions we know that vitamin D levels follow a seasonal pattern: highest during the end of the summer and lowest towards the end of the winter. Which makes perfect sense as on these latitudes there is no UVB available for the skin to produce vitamin D during fall and winter.
We also know the flu and common cold bottom in the summer and peak in the winter.
So whenever vitamin D levels peak -overtly caused by the UVB of the sun- infectious diseases like the flu and common cold bottom. If vitamin D would be mainly immunosuppressive it would be the other way around; causing less resistance during the summer thus more harmful infections.
David,
Thanks for engaging in the debate. (And for doing so in a straightforward, respectful manner). Let me try to respond to your specific points:
1. You say “If low vitamin D levels are the result of disease, then cancer would cause low vitamin D levels, not the other way around.” I don’t see how the conclusion here follows from the premise. Low vitamin D might result from diseases that have nothing to do with cancer — say, compromised immunity, infection or other causes. That leaves open the question of whether or not cancer is causally related to vitamin D levels.
2. I already commented on the Lappe study in my above comment #10 in reply to Nate:
http://gettingstronger.org/2012/11/why-i-dont-take-vitamin-d-supplements/comment-page-1/#comment-21000
Critical analysis of Lappe’s data suggest the study was flawed because the control group was not properly randomized, the duration of the study was too short, and the incidence of cancer too low to establish statistical significance:
http://ajcn.nutrition.org/content/87/3/792.1.long
http://ajcn.nutrition.org/content/86/6/1804.long
3. As you indicate, the increase of vitamin D levels in the summer and in the tropics is exactly what we should expect, since UVB catalyzes vitamin D synthesis in the skin. But the fact that colds and flus are ALSO less frequent in the summer does not by itself prove that this has anything to do with vitamin D levels. It is merely a correlation. There could be countless other seasonal factors (e.g. ability of infectious organisms to spread or thrive) that influence the incidence of respiratory infections. In general, if the incidences of A and B go up and down together, then it is possible that A causes B, that B causes A, that both are separately caused by C, or that it is mere temporal coincidence. June is the most popular month for weddings and graduations, but June graduations don’t (usually) cause June weddings
4. Let’s suppose that Vitamin D does in fact reduce colds, as you suggest. If so, we cannot rule out that Vitamin D does so by SUPPRESSING immune symptoms in the short term. (Odd as it may seem, immune suppressants like corticosteroids do control infectious symptoms in the short term). But even if naturally elevated vitamin D levels positively stimulates the immune system, that doesn’t mean it is wise to supplement daily and continuously for the long term. Vitamin D is an immunomodulatory compound. Even if it is an effective immunostimulant when moderately elevated for weeks or month, there are examples of other compounds (vitamin C, Echinacea) that become immunosuppresive at elevated doses or when ingested chronically:
http://jabfm.org/content/15/5/417.full.pdf
http://www.ncbi.nlm.nih.gov/pubmed/3642207
5. Finally, even if chronic vitamin D supplementation is helpful in combatting colds and flus, that doesn’t establishing its advisability as a daily supplement. We would want to look at many possible effects beyond the prevention of cancers and respiratory infections.
I’m all for using drugs and supplements, even experimentally, to treat short term conditions. But I’m chastened by examples of drugs and even “natural” supplements that demonstrated initially beneficial effects for weeks or even years — but where the downsides took years to show up. Supplementation by estrogen and growth hormone are only two examples of this.
In my view, the evidence we should demand for long term supplementation by healthy people should meet a much higher standard than what we require for acute treatments of sick people. At the end of the day, this risk threshold is as much a personal judgement as it is a matter of pure science.
Todd
Hello,
I read your post on the CASE AGAINST ANTIOXIDANTS. Happy to have read a thorough analysis representing the “other side” to this debate/issue.
I agree to what you have said… and the following question popped up:
What would be the efficacy of taking supplements, antioxidants etc on a sporadic and random basis … As to not disrupt the ARE … and make your body rely on the crutches…
Would you consider it a waste of money or is there a certain logic to this idea?
Kevin,
There is something to your suggestion. If you are going to experiment with supplementation, a case can be made to vary the dose and frequency and avoid getting into a pattern of “dependency” that weakens endogenous defenses. But in general, I would avoid supplements except when you have a known health risk or acute issue that needs addressing — for example an infection or allergy that responds to the supplement. And I would take it only as long as you need to.
If you are healthy, why supplement?
The exception I would make to this would be foods or compounds that actively stimulate or build immunity or other defenses, e.g. curcumin. These are not “supplements” to address a “deciency”, but rather positive stimuli to defense and repair systems. I’ll have more to say about that shortly.
Todd
Thank you Todd, I appreciate the individualized responses.
I guess that the rationale would be to hedge potential risks (like they say in finance)…
I feel healthy but the following question looms: what if my diet lacks in certain minerals and antioxidants…
I can eliminate the risks by not supplementing on a constant basis but try to gain the benefits of supplementation if my body needs it… If my body doesn’t need it, it will probably flush it out…
I realize that the preceding logic is not very thorough and scientific… (on a side note, I follow a paleo/primal/upgraded paleo and realize that diet is the building block to good health…)
“”If you are healthy, why supplement?”"
This is the problem. I consider myself quite healthy for my age – remember, this is usually an opinion and is very subjective if you think about it; I mean, what IS healthy?.
A few members of my family swear by taking vitamin c in the winter months to stave off colds/flu. In the not so distant past, I thought it was poppycock – not sure why, just a self-proclaimed belief (ie, no cure for the common cold, blah, blah).
But then I caught a massive upper respiratory infection, or at least a cold that led to it, about 5 or so years ago. Lingered for a few weeks as I remember. I told myself that I didn’t want to go through that again and ever since then, have been taking the extra C during the depths of winter and haven’t had a cold or flu since. I know, could be coincidence, but it also may not be. This is my problem. How does one really know if taking a supplement is advantageous or not? If I didn’t take it, would I have caught a cold or virus? Who knows; it’s possible. Or… is it possible that I actually caught a virus somewhere in there and the extra supplementation helped my immune system and eradicated it before any symptoms could surface? Or… is it possible that I never even came in contact with a virus in the first place? Again, no way to really know.
I’m erring towards (what I feel is) the safe side and thinking that the supplementation (including D) is preventing sickness, only during the winter months for now (am in the northeast US). I’ve nothing else to go by for this trial and error study on myself
I have to believe it’s working.
Obviously, one could go back and forth on this and have strong arguments on both sides. I don’t necessarily agree with your [theories], Todd, but I don’t disagree either, if that makes any sense.
Thanks for your quick and long response, Todd!
Some remarks:
1. Just read ‘cancer’ where I wrote ‘disease’. Point at issue is whether there is a causal relation between disease and observed low vitamin D levels, not what disease caused it.
2. ‘But, as one reviewer noted, the reduction in cancer incidence appears to be statistically insignificant. Out of about 1200 women, there were 4 cancers in the supplementation group, versus 7 in the placebo group.‘ Unfortunately, The New York Times article you cited here in reply to Nate was completely mistaken about the numbers. There were 13 cancers in the supplementation group, versus 37 in the placebo group. Here’s the original paper: http://www.grc.com/health/pdf/Vitamin_D_and_calcium_supplementation_reduces_cancer_risk.pdf.
And here the rebuttals of the researchers to your 2 other cited critical responses to their research:
http://ajcn.nutrition.org/content/87/3/793.short
http://ajcn.nutrition.org/content/86/6/1805.short
They conclude: ‘The concerns of Ojha et al about the validity of our study have no sound basis. The design of our study (population-based, random assignment, double-blind, and placebo-controlled), the low dropout rate, and the excellent compliance with treatment provide confidence that the findings are valid. Furthermore, our findings are supported by a large body of epidemiologic, observational, and case-control evidence that vitamin D decreases cancer risk. Finally, vitamin D supplementation is safe and inexpensive. We argue that it is in the public interest to strongly support optimal vitamin D nutritional status.’
3. There are many other examples like the winter flu season. Bottom line: there’s a strong trend that whenever there’s plenty of UVB from the sun available, vitamin D levels are up and diseases are down.
4. To my knowledge this effect has not been reported with vitamin D. As long as you don’t go beyond 50.000 iU a day for many months and keep your level under 100 ng/ml all seems to be completely safe. It’s really hard to poison yourself with vitamin D. Some guy had been poisoned with vitamin D by his girlfriend and got more than 1,6 million iU per day on average. He only got toxic after several months. And survived.
5. A critical distinction between vitamin D and supplements like estrogen and growth hormone is the natural occurrence. Our ancestors used to live in East Africa near the equator for tens of thousands of years. They likely got between 5.000 to 20.000 iU on average per day resulting in D levels of 40 to 80 ng/ml. That’s how we survived as a species for over 100.000 years; hard to argue with that. Experts agree that vitamin D through the sun is the same as from a supplement. So whenever I can’t get my daily D from the sun I take it from a pill. “Primal” practice facilitated by modern technology.
Nature is so complex so that we don’t have to be. “magic miracle pills” to think that we can recreate the power of the sun in a pill is ignorant. We understand less than 5% of plant wholefoods yet we try and isolate parts of them and think “more is better”. there’s a reason why pharmaceutical isolated vitamins cause chaos at a cellular level and why a carrot doesn’t. There’s a reason why the carrot looks and tastes like a carrot and not like a tablet. The entire structure is necessary to deliver the messages to the cells
Great article!! I have had a DNA test due to having autoimmune thyroid disease. My doctor was suspicious & his suspicions were confirmed, I have a polymorphism of my vit D receptor gene. Yes my D levels were low, but after about 6 or so months of taking vit D, it started to raise my cortisol too high & to either suppress my thyroid hormones or sending me extremely hyperthyroid. It makes me very tired too. My dr has quite a few patients with this genetic issue. The problem is majority of dr’s are unaware this condition exists & people are self dosing without being tested & if they have a reaction, their dr would never suspect vit D could be the culprit. I also have the MTHFR gene mutation which means regular folic acid, normally found in vit B’s, is a no no as my system doesn’t know how to convert it. I believe a lot of the popullation have this issue, but wouldn’t know it. Sometimes vitamins are just bad news for some of us sadly.