Future Trials Unlikely to Support Vitamin D Supplementation

Marlene Busko

January 24, 2014

A new meta-analysis of trials of vitamin D supplements for the prevention of myocardial infarction (MI), stroke, cancer, or hip fracture in seniors finds that, in general, taking vitamin D does not lower the incidence of these outcomes. Moreover, in a sequential meta-analysis, the researchers showed that any future clinical trials would also likely find that vitamin D supplements would not reduce the incidence of these outcomes by 15% or more.

It was unclear whether taking vitamin D supplements with or without calcium might reduce the risk for death by 5%, however.

"The take-away message is that there is little justification currently for prescribing vitamin D to prevent heart attack, stroke, cancer, or fractures in otherwise-healthy people living in the community," lead author Mark Bolland, PhD, from the University of Auckland, New Zealand, told Medscape Medical News in an email.

"In our paper, the only benefit from vitamin D was in reducing hip-fracture risk in elderly women living in residential care; in those 2 studies, the vitamin D supplements were given with calcium, at a dose of 800 IU/day, and higher doses are probably not necessary… In terms of harm, there was uncertainty as to whether vitamin D without calcium might increase the risk of hip fracture," he noted.

One possible exception is people who truly have very low levels of vitamin D, who may benefit from supplements, he said. "For people at risk of osteomalacia because of very low vitamin D levels — frail elderly people living in residential care, people who actively avoid the sun, and people with deeply pigmented skin — it is worth considering taking vitamin D supplements." However, "For other people, vitamin D supplements are unnecessary," he stressed.

The study was published online January 24 in Lancet Diabetes & Endocrinology.

In an accompanying editorial, Karl Michaëlsson, MD, from Uppsala University, Sweden, says the finding by Dr. Bolland and colleagues that future studies are not likely to change the recommendation that most people will not benefit from vitamin D supplements is "of particular interest."

Do Vitamin-D Supplements Help, Harm, or Have Null Effects?

A deficiency in vitamin D has been linked to fractures, ischemic heart disease, cerebrovascular disease, and cancer, yet taking vitamin D supplements remains controversial, "probably because the evidence from randomized clinical trials has been fairly weak," Dr. Bolland surmised. "A few trials have showed positive effects of vitamin D supplements on various outcomes, but most show no effect, and a few have shown increased risk of fracture."

In the new paper, the researchers examined meta-analyses of studies looking at vitamin D supplements and MI, stroke, cancer, fractures, and mortality. Then they did a sequential analysis to see whether the risk estimates would be altered by future trials.

They obtained data from 44 reports of 40 individual randomized controlled trials. The vitamin D doses in the supplements ranged from 200 to 1100 IU/day, or 100,000 to 150,000 IU every 3 months.

In 23 of the 32 trials (73%) that reported baseline 25-hydroxyvitamin-D levels, the average baseline level was less than 50 nmol/L, "which is widely considered to be normal, although some people think higher levels, eg, from higher than 75 to 80 nmol/L, are normal," Dr. Bolland explained. In most studies, among participants who took the supplements, 25-hydroxyvitamin-D levels increased to normal levels.

The study participants were typically women in their 70s or 80s, and most trials lasted longer than a year.

"The findings [of no benefit] will probably come as no surprise to people who have held skeptical views about the effectiveness of vitamin D supplementation," Dr. Bolland speculated. "On the other hand, people who have endorsed calls for widespread vitamin D supplementation will probably view these results as surprising."

In a review published in the Lancet by the same New Zealand research group last October ( Lancet. 2014;383:146-155) , vitamin D supplements had no meaningful effect on bone density, "and this taken together with the current findings that vitamin D supplements do not prevent fracture suggests that they don't have a role in preventing osteoporosis," Dr. Bolland added.

Use Supplements for True Insufficiency

In his accompanying editorial, Dr. Michaëlsson says a massive demand now exists for the measurement of blood concentrations of 25-hydroxyvitamin D, and supplemental use of vitamin D in the past decade has soared. For example, in the United States during the period from 2002 to 2011, sales of vitamin D supplements increased more than 10-fold, from $42 million to $605 million.

But he cautions that while several researchers have claimed that higher doses of vitamin D are needed to have a positive effect on health, high annual doses of vitamin D increase the risk for fractures and falls. "Without stringent indications — ie, supplementing those without true insufficiency — there is a legitimate fear that vitamin D supplementation might actually cause net harm."

The finding by Dr. Bolland and team that the "the body of evidence is already sufficiently large" so that future trials will not change the conclusion that vitamin D is not of use in most people is the most pertinent, Dr. Michaëlsson stresses.

For his part, Dr. Bolland concludes, "Until more information is available, it would be prudent to choose a cautious approach to vitamin D supplementation and to put more emphasis on the development of evidence-based cutoff points for vitamin D inadequacy."

The study was funded by the Health Research Council of New Zealand. The authors have reported no relevant financial relationships.

Lancet Diabetes Endocrinol 2014. Published online January 24, 2014. Abstract Editorial


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