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High and low vitamin D levels cause mortality?

Today’s news brings a U-shaped curve from a cod liver oil country. The Danish authors found that both too low and too high vitamin D levels are associated with excessive mortality. In particular, they found people with levels above 56 ng/ml (140 nmol/L) had a 40% increased chance of dying compared to those with a level of 30 ng/ml (75 nmol/L), while people with low levels had more than a 200% increased risk of dying over the three years of the study.

Durup D, Jørgensen HL, Christensen J, Schwarz P, Heegaard AM, Lind B. A Reverse J-Shaped Association of All-Cause Mortality with Serum 25-Hydroxyvitamin D in General Practice, the CopD Study. J Clin Endocrinol Metab. 2012 May 9.

Several problems immediately come to mind after reading the study. First, according to a Cochrane review, the preformed vitamin A, as in cod liver oil, is associated with excess mortality. How do I know they were taking cod liver oil to get higher vitamin D levels? Because, consumption of cod liver oil in Norway is about 44% by females, and females tended to have the highest 25(OH)D levels in the above study.

Brustad M, Braaten T, Lund E. Predictors for cod-liver oil supplements use–the Norwegian Women and Cancer Study. Eur J Clin Nutr. 2004 Jan;58(1):128-36.

Second, another far northern cod liver oil country, Sweden, also found a U shaped risk.

Michaëlsson K, Baron JA, Snellman G, Gedeborg R, Byberg L, Sundström J, Berglund L, Arnlöv J, Hellman P, Blomhoff R, Wolk A, Garmo H, Holmberg L, Melhus H. Plasma vitamin D and mortality in older men: a community-based prospective cohort study. Am J Clin Nutr. 2010 Oct;92(4):841-8. Epub 2010 Aug 18.

However, eight studies, mostly from non-cod liver oil countries, have found no such association with high levels, but a clear risk of dying with low levels (referenced in first paper), although the number of high levels in many of these eight papers was modest.

Third, the man who started the vitamin D revolution, Professor Reinhold Vieth, questions these far northern studies because he has a theory that intracellular vitamin D enzyme systems harmfully reset when under significant seasonal variations. If the authors of the paper in question sorted their results by season, I cannot find it. We know death rates are lowest in the summer when vitamin D levels are the highest, so without seasonal data, Vieth’s explanation cannot be tested.

Vieth R. Enzyme kinetics hypothesis to explain the U-shaped risk curve for prostate cancer vs. 25-hydroxyvitamin D in nordic countries. Int J Cancer. 2004 Sep 1;111(3):468; author reply 469. No abstract available.

Fourth, the study in question implies that vitamin D levels that the hunter-gatherers in Tanzania easily achieve with sun exposure are dangerous.

I doubt it. I doubt Mother Nature is that dumb.

Further reading:

About John Cannell, MD

Dr. John Cannell is founder of the Vitamin D Council. He has written many peer-reviewed papers on vitamin D and speaks frequently across the United States on the subject. Dr. Cannell holds an M.D. and has served the medical field as a general practitioner, emergency physician, and psychiatrist.
u-shaped curve

2 Responses to High and low vitamin D levels cause mortality?

  1. Karsten says:

    I haven’t read the paper, but I’m wondering if they controlled for pre-existing conditions at the beginning of the study. People have been aware of the possible beneficial effects of vitamin D in e.g. cancer and CVD for quite a few years, so it’s entirely likely that those with prior diagnoses were taking higher doses. I.e. the disease was the cause, rather than the result of the elevated vitamin D levels.

  2. Brant Cebulla says:

    Karsten. Had a read-through of the study. They attempted to somewhat control for pre-existing conditions by excluding anyone who died within a year of getting their blood drawn, which is not very thorough.

    I echo your thoughts and so does Dr. Grant in his blog. Here are some things I’d point out:

    Blood samples were from 2004-2010, a time period (in addition to today) where vitamin D got a lot of interest from the media, researchers and medical field; a lot of interest in its potential or known benefit for a wide array of diseases. Since a slight majority of the population fell under 50 nmol/l, the natural question is, who are these people who have levels above 50 nmol/l? Probably people who took vitamin D supplements, and probably took the supplements as part of treatment of diseases X, Y or Z

    A few more things about Denmark: They don’t supplement as many foods as the United States does. Also, people who self-perceive that they have poor health are also much more likely to supplement/self-medicate. My guess is that this is different than in the United States, where people believe they are “boosting” their already good health with supplements.

    These observational studies will become less and less reliable the closer blood samples were drawn to present time. People with high vitamin D levels in 1970s and 80s had high levels because they got a lot of sun exposure. People in the 2000s with high vitamin D levels are already facing some adverse condition. Some Vitamin D Council followers are ahead of the curve, but still, many take vitamin D because they’re coping with multiple sclerosis, type II diabetes, cancers, etc…

    This is why we need randomized controlled trials, and they’re on their way! In a true randomized study, both people with and without pre-existing health problems will be taking vitamin D or placebo.

    And I still think there is better evidence in support of high vitamin D levels today. Let’s not forget a meta-analysis of randomized controlled trials that found that vitamin D3 supplementation reduced all cause mortality by 6%.