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New study suggests that both high and low vitamin D levels may increase fracture risk

Posted on: September 18, 2014   by  Amber Tovey


A new longitudinal study published in Journal of Bone and Mineral Research found a U-shaped curve for the association between vitamin D levels and fracture risk in older men. In other words, men with both low vitamin D levels and high vitamin D levels had an increased fracture risk.

Vitamin D is traditionally known for its effects on bone health. Vitamin D works in the body to increase the absorption of calcium from the diet. Calcium helps make bones denser and stronger. Vitamin D has independent genetic effects on bone development. Because of this, researchers believe that vitamin D helps prevent as well as heal fractures.

A meta-analysis of four randomized controlled trials by the same group found that vitamin D supplementation results in a 28% reduction in the number of falls per person, per year.

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12 Responses to New study suggests that both high and low vitamin D levels may increase fracture risk

  1. Rita and Misty

    Hi Amber,

    I wonder the source of the vitamin D supplementation for the folks studied, in particular for those with a higher 25(OH)D level.

    You may ask why does source matter?

    Well if those with a higher 25(OH)D level were consuming Cod Liver Oil as a source of vitamin D supplementation, then they would have vitamin A levels at perhaps either plainly toxic or sub-clinically (perhaps not the right term) toxic levels.

    And, there has been research that indicates too much vitamin A will weaken bones and leave folks more prone to fractures.

    So just maybe it is not having a natural 25(OH)D level of 46 ng/ml that makes you more prone to fractures, but rather having way too high a vitamin A level that weakens your bones, and leaves you open to fractures…. Correct?

    I would welcome the thoughts of others here in our VDC community.

    Be well,


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  2. Magic


    Maybe we are prejudiced but I suspect “foul play” every time I read stuff like this. Seems like “experts” are trying too hard to discredit vitamin D3. Our son has been taking 20,000 for years. He is a FIT 49 year old and received his information from the health club. I know you and I have been taking numbers of D3 that make many doctors gasp. I wouldn’t ingest large amount if I hadn’t really checked it out for years………….


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  3. Rita and Misty


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  4. Ted

    Magic – I don’t think it is necessary to suspect “foul play.” Here are a couple of possibilities. I am willing to bet that many older people with higher (40 ng/ml) 25(OH)D levels probably don’t get it from the sun – they take supplements, as do I. And further I suspect people who take supplemental vitamin D are more likely to take other supplements, including multivitamins. Even taking two or three multivitamins a day, on the theory that more is better, may result in Vitamin A overdose. Dr. Cannell addresses this in a blog post titled “Vitamin D Toxicity.” So one possibility is that people who are attentive to their Vitamin D status may also be more prone to overdosing on Vitamin A.

    Another possibility is simply that older people who have high levels of serum vitamin D are, as a consequence, healthier and more likely to engage in physical activity, and, therefore, more prone to accidents and broken bones. Older people with low serum D are more fragile, while those with high serum D are more active. Looking just at serum vitamin D, you get a U-shaped relationship with fracture rates.


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  5. danrab

    How do I REDUCE my calcitriol levels, which are 2x the upper limit, when I am not supplementing?

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  6. bdelia9934

    I wonder if the individuals with the highest vitamin D levels were failing to get adequate levels of magnesium and Vitamin K in their diet along with calcium and Vitamin D, all four of which are necessary for good bone health.

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  7. PeterVermont

    It is plausible that very high vitamin D levels can end up pulling calcium from the bone. Unfortunately I cannot find the reference (lame!). Basically, vitamin D (not speaking of non-calcium related functions) increases calcium absorption but does not have a huge role in building bone per se – that is primarily the function of the vitamin K dependent proteins that vitamin D up-regulates. If you take high dose vitamin D it is prudent to also take vitamin K2 to ensure that all that extra calcium you are absorbing is deposited in your bones rather than increasing vascular calcification.

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  8. PeterVermont

    I found a reference to vitamin D possibly causing bone resorption. See “Vitamin D endocrine system and osteoclasts” http://www.nature.com/bonekeyreports/2014/140205/bonekey2013229/full/bonekey2013229.html

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  9. Amber Tovey

    You all make great points.

    Like Rita said, the source of vitamin D is very important. Dr. Cannell discussed the relationship between fracture risk and vitamin D in a previous blog. He mentioned a study that found people with vitamin D status around 22 ng/ml and above 90 ng/ml had the lowest fracture rate. He, like Rita, predicted that the “complicated” relationship with high levels was due to taking both vitamin A and vitamin D.

    As I pointed out in the blog, I believe the largest limitation was that they only measured their vitamin D levels once. Not only could their levels have easily changed by the end of the study, but their levels could have been much lower or higher throughout life, such as during peak bone mass development. Bone mass progressively declines after age 30. Some people may have compensated for low bone mass by supplementing with vitamin D later in life.

    Two randomized controlled trials found similar results to this study. Both RCTs found that those who supplemented had higher rates of fracture. However, the participants were given annual doses of 300,000 IU of vitamin D2 in one study, and annual doses of 500,000 IU of vitamin D3. These dosages are not ideal, seeing as they are annual rather than daily. Also, as most of you know, vitamin D2 has been proven to be less effective than vitamin D3.

    Sanders KM, Stuart AL, Williamson EJ, et al. Annual high‐dose oral vitamin D and falls and fractures in older women: a randomised controlled trial. JAMA. 2010;303(18):1815.

    SmithH, AndersonF,RaphaelH,Maslin P, CrozierS,CooperC.Effect of annual intramuscular vitamin D on fracture risk in elderly men and women—a population‐based, randomized, double‐blind, placebo‐controlled trial. Rheumatology (Oxford). 2007;46(12):1852

    With the limitations considered, I do believe this study elicits more research to provide clarity.

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  10. Rita and Misty

    Hi Amber TY for all your great work. Dr Cannell is so smart regarding the difficult vitamin D relationship…along with vitamin A. I wonder also about other nutrients that play masquerade with respect to vitamin D. Like for example curcumin. Very interesting. Ok and TY again.

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  11. mbuck

    Co-factors are vital whether one gets D3 from the sun, supplements, UVB lights or any combination. This bears repeating often because folks think just upping the D3 alone is all they need. The D3Plus from BioTech has the co-factors in the proportions needed for proper metabolism. This product is recommended by Dr. Cannell.

    The best source of vitamin A is beta-carotene containing plants such as colorful vegetables. There are two reasons for this. One, the body will take what it needs and flush out any excess. Two, the vitamin A found in most supplements are retinoids, or retinoic acid, an oil-based preparation that conflicts with D3 absorption and takes a long time for the body to dispose of excess. Dr. Cannell has written about this before, so do a search on this site for a much better, detailed and comprehensive treatment of this subject.

    (Personal opinion, theory and conjecture follows, and no, I am not a med professional:)

    However because of the 40 to 60% absorption rate of Mg (magnesium) in the gut, I also take 2 heaping tablespoons of powdered (using a food processor) organic almonds and one heaping tablespoon powdered brazil nuts for Se (selenium) daily. Taking these in water is easier than than chewing through several handfuls of nuts and dramatically increases the surface area of the nutrients, enabling a higher rate of absorption of these more bio-available forms of Mg and Se. I have convinced myself that natural sources of nutrients if prepared in a more bio-available manner increases my chances of maintaining adequate levels.


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  12. pheppel

    Inadequate Vitamin K2 is another issue that might increase the risk for fracture with higher levels of Vitamin D. Higher levels of Vitamin D increase the production of calcium binding proteins like MGP and Osteocalcin. These proteins need to be activated through carboxylation to function properly. Osteocalcin is responsible for mineralizing the bone matrix. Vitamin K2 activates osteocalcin by facilitating carboxylation. Osteocalcin needs two site carboxylation to be activated. It is clear that if you start with a perfect match between levels of Osteocalcin and Vitamin K2 such that all Osteocalcin is activated then you will be able to mineralize as much bone as you have Osteocalcin available to conduct the mineralization. Now if you double Osteocalcin but maintain the same levels of Vitamin K2 and you get random carboxylation of the two Osteocalcin sites, ¼ of Osteocalcin will be carboxylated at both sites and fully activated, ½ of Osteocalcin will be partially carboxylated and not functional and ¼ will not be carboxylated at either site and also not functional. The result of this set-up is that you have half the functioning Osteocalcin that you had before increasing Osteocalcin through Vitamin D supplementation. The moral here is that you need to be careful when increasing blood levels of Vitamin D to also increase Vitamin K2.

    Osteocalcin is the protein responsible for moving calcium into bone, MPG is responsible for removing calcium from soft tissue like arteries. The same reasoning applies to MPG. If you increase MPG production through Vitamin D supplementation but do not increase Vitamin K2 availability, you can end up with less functional MPG. So you could envision a study where higher levels of vitamin D might be found to increase the risk of heart disease through increased calcification of the arteries.

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