Pendulum Swings Further Away From Vitamin D Supplements

A new randomized controlled trial offers no support for the use of increasingly popular vitamin D supplements to prevent cardiovascular disease or reduce mortality.

But the trial, published in JAMA Cardiology, is also not the last word on the subject and leaves open the possibility that vitamin D may be found beneficial in the future for cardiovascular disease or other indications.

Family physician doctors in New Zealand randomized more than 5,100 adults between 50 and 84 years of age to vitamin D or placebo. Vitamin D was administered as an initial dose of 200,000 IU, followed by monthly doses of 100,000 IU. There was no hint of any effect on the primary outcome between the groups.

After 3.3 years of follow-up, cardiovascular disease occurred in 11.8% of participants in the vitamin D group and in 11.5% in the placebo group. The results were similar in the important subgroups of participants with vitamin D deficiency at baseline and in those with previous cardiovascular disease.

The study used higher overall doses than used in many previous studies, which had been criticized for this potential weakness. A random sample of 438 participants in the study showed that 25(OH)D levels were 20 ng/mL higher in the treatment group, reaching optimal levels as suggested by observational studies. The authors acknowledged that there are questions whether the monthly dosing of vitamin D results in persistent increases in vitamin D levels.

It is well-established that people with low vitamin D levels are at increased risk for cardiovascular disease but unknown whether this is a cause-and-effect relationship or, if so, whether supplements would be effective. “Our results do not support the findings from observational studies that report an inverse association between 25 (OH)D and CVD, which could be explained by residual confounding from other lifestyle risk factors,” the authors concluded. “It is possible that 25 (OH)D concentrations are a surrogate marker of sun exposure, which may have other health effects entirely separate from vitamin D.”

Erin Michos (Johns Hopkins) commented that “the evidence supports that generally healthy people should not take vitamin and mineral supplementation for CVD prevention, and that includes Vitamin D.” She said the large on-going VITAL study, with more than 25,000 participants, will provide much more clarity on the effects of vitamin D supplements on heart disease, cancer, and other endpoints. But Michos said she suspects that VITAL will also be a negative trial, “especially since vitamin D deficiency was not an enrollment criteria. That likely will be the end of the era of enthusiasm for use of vitamin D for preventing all chronic ills.”

“I am a strong believer that IF supplementation might help anyone (and that is a big if), it likely would be only among individuals with deficiency,” said Michos. “MORE IS NOT BETTER, and people with adequate vitamin D stores do not need supplementation.” She pointed out that, although there was no signal of benefit in the group with low vitamin D levels at baseline, the trial was not powered to detect differences. She speculated that supplements might also be found helpful in people with severe vitamin D deficiencies, such as below 15 ng/mL.

JoAnn Manson (Brigham and Women’s Hospital) is the principal investigator of VITAL. She said it’s important to wait for the results of VITAL and other ongoing studies looking at cardiovascular disease, cancer, and many other areas of potential interest. “No single trial is going to provide a conclusive result.” We need to consider “the totality of the evidence, but so far the RCTs [randomized controlled trials] have been disappointing,” she acknowledged. “The pendulum tends to swing very widely.”

“It does move the needle toward more skepticism,” Manson said, despite “the bandwagon” of support in favor of vitamin D supplements.

One major problem of the vitamin D enthusiasm is that it “threatens to compromise the validity of the ongoing RCTs because a lot of people are taking vitamin D on their own and their clinicians are routinely screening for vitamin D blood levels.”

Michos also expressed concern about the popularity of vitamin D supplements. “Many patients love their supplements and don’t want to take prescription medications because they want to be ‘healthy’ and ‘natural’ instead. But there is nothing natural about getting your nutrients in a pill form. I tell my patients that their best bets for CVD prevention are to eat a healthy diet rich in fruits and veggies, get regular physical activity, and maintain a normal weight. (And perhaps a modest dose of sunshine would be good too for the body and soul, but that is just personal opinion.)”


  1. James Stein says

    For CVD, vitamin D’s effectiveness is some where between vitamin C and vitamin E!

  2. Please edit your simple mistake it is not 20.000 iu but 200.000 iu the initial dose, as well I love this kind of research where they do not define many things like what they considered Severe Deficient, Deficient, Insufficient, Adequate, Optimum, High & Toxic

  3. Interesting article! I have personally been told my D levels were low. That seems to be a common problem, but it is interesting that achieving optimal levels seems to have no bearing on preventing cardiovascular disease. I look forward to the results of further research. Thanks for your post.

  4. The way we humans are structured to achieve sufficient levels of D is to go out in the sun, more-or-less daily, and allow our skin to synthesize a few thousand IU.
    To dose at such enormous levels with a month between is so far beyond normal as to make it clear that this research anything but the final answer.

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