Why I don’t take vitamin D supplements

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 hydroxylated 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?

December 7, 2013 update:  A comprehensive review of 290 vitamin D interventional studies and 172 randomized trials, published in this month’s Lancet, adds further support my thesis that vitamin D levels are a consequence, not a cause, of health status

http://www.thelancet.com/journals/landia/article/PIIS2213-8587(13)70165-7/abstract

Low serum concentrations of 25-hydroxyvitamin D (25[OH]D) have been associated with many non-skeletal disorders. However, whether low 25(OH)D is the cause or result of ill health is not known. We did a systematic search of prospective and intervention studies that assessed the effect of 25(OH)D concentrations on non-skeletal health outcomes in individuals aged 18 years or older. We identified 290 prospective cohort studies (279 on disease occurrence or mortality, and 11 on cancer characteristics or survival), and 172 randomised trials of major health outcomes and of physiological parameters related to disease risk or inflammatory status. Investigators of most prospective studies reported moderate to strong inverse associations between 25(OH)D concentrations and cardiovascular diseases, serum lipid concentrations, inflammation, glucose metabolism disorders, weight gain, infectious diseases, multiple sclerosis, mood disorders, declining cognitive function, impaired physical functioning, and all-cause mortality. High 25(OH)D concentrations were not associated with a lower risk of cancer, except colorectal cancer. Results from intervention studies did not show an effect of vitamin D supplementation on disease occurrence, including colorectal cancer. In 34 intervention studies including 2805 individuals with mean 25(OH)D concentration lower than 50 nmol/L at baseline supplementation with 50 μg per day or more did not show better results. Supplementation in elderly people (mainly women) with 20 μg vitamin D per day seemed to slightly reduce all-cause mortality. The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status is reported in a wide range of disorders. In elderly people, restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival.

 

 

 

 

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26 Comments

  1. Michael

    This is a terribly unscientific post—there is no mechanistic evidence (ie. mouse studies) to support their claim. To address their clinical data, you cannot use randomized controlled trials to investigate the effects of vitamin (including vitamin D) and mineral supplementation. When you begin with a population of people, these individuals have varying concentrations of vitamins D due to varying degrees of sun exposure and diet. You cannot just randomly assign these individuals into two groups and give them a vitamin/mineral supplement without measuring the concentrations of these vitamin D at baseline (before the trial). You want to make sure that the individuals both groups start with similar levels of whatever particular micronutrient you are investigating or multiple micronutrients if you are interested in a specific effect of vitamin D.

    One of the studies that was used to show that vitamins have no effect on cancer incidence was vitamin D. Postmenopausal women were given only 400 IU of vitamin D and 1,000 mg of calcium a day for 6 years and colon cancer incidence was determined. After two years of supplementation the women talking the vitamin D/calcium were still deficient in D they had levels of 23ng/ml compared to the placebo which was 12ng/ml. You need vitamin D levels of 30 ng/ml just to maintain normal bone homeostasis. Neither of these groups even met that requirment and you are going to make a conclusion that vitamin D has no effect on colon cancer incidence just because your treatment group had slightly high D levels than your placebo, even though they were still deficient? Why not make the conclusion, 400 IU per day after 2 years was not an adequate dose to raise vitamin D levels to an adequate status. Therefore, no conclusion can be made on the effect of vitamin D supplementation on colon cancer incidence…because we did not give these women an adequate dose! It has been shown that supplementing with 400 IU per day on average only raises serum vitamin D levels by 5ng/ml. That is not very much particularly for a person that is vitamin D deficient. If you want to determine the potential benefits of vitamin D supplementation on different disease outcomes, don’t you think it would be more effective to give people a dose of vitamin D that will ensure they have adequate levels?

    If we look at other studies with higher vitamin D supplementation we see that a daily dose of 1500 IU of vitamin D resulted in a 17% reduction in total cancer incidence, a 29% reduction in total cancer mortality, a 43% decrease in cancer of the digestive system (including colon cancer) as well as a 45% decrease in cancer mortality associated with digestive system cancers. Research from UCSD found that women supplementing with 2000 IU/day and had serum levels of 52ng/ml was associated with a 50% reduction in breast cancer incidence.

    This article repeatedly and emphatically states: “correlation does not equal causation.”This is true and is WHY WE TURN TO MOUSE MODELS TO INVESTIGATE THE MECHANISMS BY WHICH VITAMIN D HORMONE PREVENTS DISEASES OF AGING. They do not cite one paper using mouse models. There are thousands of well-done mechanistic studies that have been done on mice demonstrating the protective effect of vitamin D hormone on inflammation, DNA damage, mitochondrial function, metabolism, bone homeostasis, brain function and behavior, lipid metabolism, immune function and more

    Reply
  2. ser

    wow. interesting thoughts.

    my doc just told me I MUST TAKE D IMMEDIATELY for she thought my d levels were really low (a 38), but taking d turns my skin a funny colour. she said for me to take sublingual, but after a few weeks and my skin (i am very fair) is again becoming an odd brownish colour that looks very unhealthy, so i am going to take way less but i would really like to stop altogether…i have hormone problems and have asked to see an endocrinologist and now i knnow it’s a kind of hormone…it’s all very confusing and i do have a bunch of chronic health challenges. i did ask to have a calcium test so in three months she wants to test my d again and has added that, for apparently parathyroid problems cause low d and high calcium, and i have other thyroid problems already.

    in any of your reseach have you come across that odd skin colour experience and if so what the heck it means?

    i’m really confused and don’t want to make my other health problems worse since as the research you found suggests artificially pumping up the d might wreck natural mechanisms. i do take many supplements but they all noticabley improve some or many health challenges and make my skin look very healthy. being so pale my skin is a great litmus test of what is and isn’t working. i have digestive issues and don’t process food properly, especially fruits and veggies, so it’s just an necessary evil. i did best with supplements intravenously but i really can’t afford it.

    thanks so much for sharing your research and findings

    Reply
    • Todd

      Ser,

      So your doctor thinks that your vitamin D (25-D) level of 38 is “low”. And just why does your doctor think so? What is her evidence that this is a problem?

      My doctor measured my 25-D levels in 2009 at 24 ng/mL. Despite absolutely no health problems or symptoms, he was concerned that this was low and had me start supplementing daily. A year later, my 25-D levels had increased to 52 ng/mL. This is supposedly consistent with improved health. But I noticed absolutely nothing, and there was no objective or subjective change in my health. Just a raised level of 25-D. I subsequently stopped taking vitamin D because I found no reason to do so, and my levels dropped back down to about the original level. Again, with no noticeable effects.

      As you mention, the low vitamin D could be a result of parathyroid problems. If that is the case, why treat the symptoms? Why not treat the cause?

      I can’t explain your brownish skin color. There could be many reasons, such as excess vitamin A or beta-carotene, eating a lot of carrots, jaundice, or medication side effects.

      http://www.rightdiagnosis.com/sym/orange_skin.htm

      You mention that you have a lot of chronic health challenges and hormone problems — so your situation may be complex to sort out. I’m not a doctor and I can’t diagnose or prescribe. I think you should consult with several doctors to find one that has insight into your problem, not just a general practitioner who looks at printouts of blood tests.

      Reply
  3. Great article! Another thing that high levels of vitamin D does is “lock” calcium in the blood so that it is unusable in the soft tissue where it belongs playing a role in immune function. Vitamin D helps “transport” calcium from our diet into the blood, but it is Vitamin F that helps transport it from the blood into the soft tissues where it is required for proper immune function!

    Furthermore, I’m working on the world’s most advanced “Nutritional Hormetic” database and BioSuvey for the world’s most efficient decision-making software to help determine the EXACT nutritional supplements a person’s body prefers as well as the EXACT (minimum) dosage of those supplments. http://www.ML-Ei.com

    Reply
  4. Glad to have found you and your community. Will enjoy exploring these pages.
    This article is very instructive. It raises a couple of questions.
    I’ve supplemented Vit D for ten years. Approx. 2000 iu daily, average level of 60 ng/ml. Nothing extreme, but very consistent and long-term. Recently, scans showed uncharacteristic arterial thickening, which has apparently been reversed by adding Vitamin K, A, and magnesium. I suspect imbalance triggered soft tissue calcification.
    At the same time, breast scans showed microcalcifications, which biopsy identified as neoplastic (DCIS). Were they related? Could micros in the breast be due to the same imbalance?
    This lesion was low grade, non-necrotic and non-comedo. We are learning that this type of neoplasia is distinctly different from high grade, necrotic, comedo type and far less likely to progress to cancer.
    Evolving screening technology has skyrocketed detection of both conditions (and other similar conditions) beyond our ability for accurate prognosis and individual treatment. We’ve got to figure this out.
    There was obvious cellular stress here, but a lifelong health-conscious patient like me wonders often if anything was really wrong, or if this lesion was something that ebbs and flows in the body and I just got “pulled over” during the flow. I can’t help but wonder if there’s not a lot of overdiagnosis (and overtreatment) going on out there and this particular imbalance may play a large part.

    Because I suspect calcium imbalance due to isolated supplementation, supplementing no longer seems as wise as once it did. Your philosophy of a balanced, varied diet, fresh air, exercise, water and fun sounds like a plan to me.
    I’d love any thoughts you’d have on these questions. Many thanks in advance.
    K

    Reply
    • Todd

      I have little to add to your thoughtful comment, K. I think you well appreciate that everything is a balance and that we go astray by focusing too much on isolated supplements and disconnected diagnostic measures, failing to see the forest for the trees.

      Todd

      Reply
  5. John

    This is a weightless and subjective article. The author is obviously just looking for attention by trying to persuade people that vitamin d isn’t worth supplementatikn

    Reply
    • Todd

      Exactly, just subjective opinion. I was just looking for attention. Unlike your comment, which contained highly specific objections, citations and incisive analysis.

      Reply
  6. Thanks for taking the time to present alternative ideas.

    “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”

    I would REALLY appreciate a study backing the claim up that 25,D inhibits VDR. I’m not doubting you, I just want to see the evidence for that statement.

    According to this study 25 has an affinity for VDR of 1% that of 1,25…It also claims there’s a .49 correlation between 25 and 1,25 – which isn’t “little”…good review article:
    http://onlinelibrary.wiley.com/store/10.1359/jbmr.070716/asset/5650221105_ftp.pdf?v=1&t=i4lus57j&s=7d39cec8da1c108fdb6843a9053f3567ee1cb859

    Another study has it as .564
    http://www.direct-ms.org/sites/default/files/25D%20levels%20PwMS%20Ireland%2007.pdf

    Reply
    • Todd

      Joe,

      Thanks for sending the links. The first link seems to be broken. The paper from the second link is interesting. Though it examines the correlations between 25-D and 1,25-D, it doesn’t directly address the question of inhibition or competitive binding. Tangentially, I did find it interesting that they found that there was no significant difference in vitamin D status between MS patients and normal controls:

      There were no significant differences in plasma PTH, 25(OH)D and 1,25(OH)2D3 concentrations between individuals with MS and control volunteers…At the group level, vitamin D status was adequate in both groups (25(OH)D concentrations >50 nmol/L).

      Now to answer your question: Evidence for the inhibitory effect of Vitamin D3 (25-D) on the VDR can be found in Albert et al, “Vitamin D: The alternative hypothesis”. Autoimmunity Reviews, Volume 8, Issue 8, July 2009, Pages 639–644:

      Full text pre-print: http://autoimmunityresearch.org/transcripts/AR-Albert-VitD.pdf
      Published abstract: http://www.sciencedirect.com/science/article/pii/S1568997209000457

      Of particular relevance is the caption to Figure 1 which shows the similarity of the two forms of Vitamin D. The nearly identical binding constants and molecular homology provide convincing evidence that 25-D competitively inhibits 1,25-D binding to the VDR:

      The secosteroids 25-hydroxyvitamin D (yellow) and 1,25- dihydroxyvitamin D (purple). Note that although the secosteroids have nearly identical structures, 25-D lacks the extra hydroxyl group, serving to stabilize the helices of the VDR and activate it[40]. The two metabolites have nearly identical affinities for the VDR: 1,25-D has an estimated Kd of 8.48 while that of 25-D is 8.36.

      Hope that addresses your question.

      Todd

      Reply
      • Thanks! Very interesting study. I’ve read it before but rereading some of the ideas were interesting.

        You might like this study that I found that vitamin d supplementation decreases klotho, which is implicated in IQ and longevity:
        http://www.ncbi.nlm.nih.gov/pubmed/23673970

        Vitamin D needs a sweet spot – the question is where that is. For myself, I’d still like to maintain it at 40-50ng/ml, but to each their own.

        Reply
      • Hi Todd,
        I’ve written an article that mostly agrees with your position.

        Hope you like http://selfhacked.com/2014/12/22/experiment-megadosing-vitamin-d3/

        Reply
        • Todd

          Hi Joe,

          Great article. Balanced and well-researched, like the rest of your site.

          I agree with your statement:

          Ignore the Science If Your Experience is Different. I’m a big proponent of paying attention to your body and less to the background noise i.e. the clinical ‘scientific evidence’. I’ve found better health outcomes for myself when I ignore it and turn to self-experimentation that is based on the fundamentals of science. This means I look at how the body functions and experiment based on that. I tweak accordingly.

          As I’ve mentioned in previous comments, my 25-D levels when last tested were 24 ng/ml, considered “deficient” by medical orthodoxy. Years ago, at the urging of my physician, I took supplements to raise my levels, and they reached 52 ng/l at the next test. Yet noticed absolutely no objective or subjective effect on my actual health. I had my bone mineral density tested this last year and my T-score of 2.0 is in the 99th percentile for men my age. So no problems with my skeletal health! I also almost never get colds, flus, infections and have no autoimmune or respiratory conditions. I’m perennially in a good mood. So I must be doing something right.

          This makes me question whether there is a definable fixed requirement for vitamin D for all people. Perhaps some need more, some need less, depending on their expression of VDR and other hormone receptors.

          Perhaps I just use vitamin D more efficiently than others? :-)

          Todd

          Reply
  7. Michael

    Dear Todd,

    Thank You so much for your great article. I’m a 30 year old male and a few years ago I made the mistake of taking vitamin d as a supplement. I trusted guys like Dr. Mercola about the claims that vitamin d whould do wonders for my health and that not taking high amounts is almost irresponsible for a health conscious person. So I (stupidly) took a few 100.000 units for days and high amounts (up to 10.000 I. U.) per day for months. What I got from this is, was facial flushing which was later diagnosed as rosacea (with ocular rosacea as well). On top of that nightmare, I got symptoms like constipation, high blood pressure, insomnia, heart palpitations and some other symptoms. I got a blood test of course. No increased calcium and a vitamin d level of “only” 55ng. And after I discontinued the vitamin d the symptoms are partially getting better. But they are not gone and that after over a half year of no supplements whatsoever. I will maybe try a low calcium diet and also tell my doctor what a moron I was. I totally agree with you on vitamin d and supplements in general and whould like to see people taking this as a warning and my case as an example of what can go wrong, when you take unnatural amounts of a vitamin (which is actually a hormone). I wish you all the best.

    Reply
    • Todd

      Thanks for sharing your personal odyssey, Michael. Let it stand as a warning to others who are on the fence about vitamin D supplementation.

      Regarding calcium: Our bodies are pretty smart about how much calcium we need, and about where to put it. Calcium is helpful in skeletal tissues, and in regulating metabolic processes, but can be harmful when deposited in the arteries. Similarly, vitamin D in the right form and the right tissues at the right time is crucial to regulating numerous metabolic processes, particularly immune function. It is naive and misguided to think that we should correct “deficits” of either vitamin D or calcium by flooding the system with exogenous sources. To use an analogy from Valter Longo, it’s like trying to improve a Mozart symphony by having the cello section play very loud through the entire piece. Our metabolisms are intricately regulated complex networks of cascading biochemical pathways with positive and negative feedback loops. Change one input and the systems adjust homeostatically. The adjustments take place over different time scales, and the effects are not always immediately apparent. This is particularly true in the case of regulatory compounds such as hormones, vitamins, and enzymes.

      The longer I live, the more I appreciate and am amazed by the ability of organisms to heal and stengthen themselves in response to the imposed demands and stimulation provided by normal every day factors we encounter in our environment — food, exercise, social interaction, mental challenges. The factors we evolved to handle quite well, with a bit of wisdom, insight and luck.

      Reply
      • Michael

        Thanks for your reply :-) I totally agree with you. The human body is a remarkable machine. And I just hope that my body will be able to find the homeostatic balance on it’s own. The best strategy is probably a healthy lifestyle and the further exclusion of all supplements. When I realized the vitamin d was to blame (took me way too long), I thought another supplement (vitamin k2, the next “miracle” vitamin) whould help me. But it didn’t. Go figure! Anyway, it could be worse and I’m just thankful for people like you, who provide useful information for free. So keep up the good work 😉

        Reply
      • Logan

        So if my endocrinologist keeps telling me that my Vitamin D level is much too low….I should try natural measures instead? I get stomach upset from taking Vit D. I worry when she says my D is so low. Don’t know what to do! I have hashimotos disease and find it hard to take any vitamins. My regular general practitioner said he does another test to see what the “true” vitamin D level is. He said I run high! My endo has no idea what he is testing. What do you think?

        Reply
      • M.James

        “Thanks for sharing your personal odyssey, Michael. Let it stand as a warning to others who are on the fence about vitamin D supplementation”…

        Honestly…let it stand as a warning that you shouldn’t megadose something beneficial, just because it’s good for you. There’s no medical basis to the consumption of hundreds of thousands of IUs of vitamin D a day (except in extreme cases under physician management), and this is not what people like Mercola have recommended as implied by the comment.

        Vitamin A is another example of something that is beneficial in the right dosage range, but dangerous when taken to extremes. An adequate amount of the vitamin promotes a healthy immune system, skin, endocrine system, and proper eye function; whilst an overdose causes joint and muscle pain, liver damage, and a host of other problems.

        The fact that taking an outrageous excess of a vitamin causes negative side effects doesn’t mean that supplementation is dangerous, nor does it mean that the vitamin itself is dangerous. A disregard of caution and common sense is dangerous.

        Reply
  8. Anna

    Hi Todd,
    If vitamin d level is a marker of health as you say, then is someone with a completely natural(without supplementing) high D level healthier then you with your 24ng/ml? Vitamin d levels are most of all related to sun exposure and dietary intake.

    Reply
    • Todd

      Hi Anna,

      I’m not asserting that vitamin D (as 25-D) is or is not a marker of health. I’m only suggesting that this is one possibility. If so, then it is a consequence, not a cause of good health. And that would mean that raising vitamin D by supplementation would not thereby reverse a health condition that leads to low vitamin D.

      A separate question is whether or not 24 ng/ml is “low”. Even if we accept that statistically speaking the probability of good health is associated with higher measured levels of 25-D, the graph in my post above shows extremely low correlation between measured 25-D levels and the more biologically relevant 1,25-D levels. And similarly, the correlation of vitamin D levels with measures of health is very approximate and shows high variation.

      Since I don’t show any clinical symptoms related to immunity, infection, fatigue, etc. that are often claimed to be associated with low(er) vitamin D levels, I’m not worried.

      Todd

      Reply
  9. Erich

    Yeah, but since I started supplementing with vitamin D about a year and a half ago I never get sick anymore.

    Reply
  10. pks

    Agreed.I was started on Vitamin D 10,000 IU a week and within a month, My TSH went to 20 even though the T4 and T3 were normal.

    Reply
  11. Tabetha

    Hi. I enjoyed reading this and another article of yours regarding vitamin D. My situation is that I had a recent blood test to check my vitamin D levels which came in at 17.1 and is considered low. I am now 29 weeks pregnant. Ehen I began seeing a midwife for prenatal care at around 14 weeks, she suggested that I supplement. I explained that I don’t like to supplement anything without quite a bit of research and being able to find a quality supply source that I can afford. So then she suggested I get my levels checked so I would have more information to work from, but my parallel care provider doing my labwork didn’t think that I needed my vitamin D checked. After switching care providers, I was recommended to het my level checked, which is how I now know my level…months after I could have been building up my levels in the sun – my husband and I arefarming and so I felt like I was getting enough regularly even though I wasn’t getting a tan (fair skin and freckles with previous precancerous skin cells that were surgically removed in office while I was in high school). So anyway, my question then has to do with the importance of vitamin D as it supports a growing fetis and whether food-based sources of vitamin D like oily fish (and of course, I have to limit fish as well for the safety of the baby) would be a good idea? You also mentioned that VD gets stored as fat and is unusable, but what if your body is in a state of ketosis? Will burning fat cause VD to become accessible? Sorry for long paragraph and typos. I am on a phone. Thanks, Tabethatrogdon.trogdon@

    Reply
    • Todd

      Tabetha,

      Lot’s of good questions. I can’t really give you any clinical advice about your own situation and your pregnancy. Certainly you want to be sure your baby is getting adequate nutrition. The best way to get enough vitamin D is through your whole food diet — and there are many good sources other than fish. If your practitioner feels the levels are low, you could consider supplementing. I’m not against short term supplementation to address specific needs, e.g. clinical symptoms or pregnancy. My caution is more about long term supplementation and the homeostatic effects that it could have on the VDR. But supplementation for 9 months should not be an issue if it is helpful to you.

      Todd

      Reply
  12. Kristy

    Very interesting article! I have been searching for info regarding low 25-D and elevated 1,25-D. I have this issue and the docs are telling me that they are seeing it in people with Lyme. My sister also has Lyme. We both have Babesia WA-1 and she has been on several different antibiotics and antiparasitics, while I have not gone that route. The last blood test showed that the Babesia could no longer be detected in her blood and her Vit D has normalized, each around 40 ng/ml-pg/ml. I believe she was prescribed a supplement, not sure how regularly she was taking it. My docs are telling me to absolutely not take Vit D. I am ok with that, it does not make me feel good at all, even being out in the sun makes me feel yucky.

    Reply

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