Researchers Aim to Clarify Vitamin D Supplementation


Should you prescribe Vitamin D to your patient to prevent fractures? If so, how much?

Should you prescribe Vitamin D to your patient to prevent fractures? If so, how much?

Such questions are becoming increasingly confusing for many clinicians as studies with conflicting results pop up in the literature.

“The data in terms of fracture reduction has been questioned from very large systematic reviews and meta-analyses,” says Meryl LeBoff, chief of the Calcium and Bone Section in the Endocrinology, Diabetes and Hypertension Division at Brigham and Women’s Hospital in Boston.

As a result, some clinicians are probably not prescribing enough vitamin D supplementation, while others prescribe too much, says Dr. LeBoff. “A lot of doctors may not prescribe it at all,” she says. “And then there would be a concern about very, very high supplemental doses.”

The U.S. Preventive Services Task Force is undertaking a review of the literature in hopes of providing some answers. Its primary question: “Does supplementation with vitamin D or calcium alone or vitamin D combined with calcium prevent fractures or reduce fracture-related morbidity and mortality?”

It also hopes to determine information about the risks of such supplementation, and about dosing intervals, fracture types and subpopulations.

Though most doctors’ associations and governments recommend vitamin D, they don’t all recommend the same amounts.

“There’s some controversy about how much vitamin D you should be taking,” says Dr. LeBoff.

For most people the Institute of Medicine recommends 600 international units per day (IU/d) up to age 70 years, and 800 IU after that. But some other major societies recommend around 800 to 1000 IU/d to maintain bone health.

The question of vitamin D deficiency is becoming more pressing as the population ages and the risk of bone fractures increases. Already 53.6 million Americans have osteoporosis and/or low bone mass that increases their risk of fracture, according to analyses of National Health and Nutrition Examination Surveys data.

There is good reason to think vitamin D can help prevent fractures. Muscles have vitamin D receptors. People with low serum levels of the nutrient have weaker muscles and less dense bones. They run an increased risk of falls.

Modern populations spend more time indoors, and often use sunscreen when outdoors, reducing the amount of vitamin D they synthesize in their skin.

And the typical diet in most countries doesn’t include adequate amounts of vitamin D especially in the late fall and winter months so bone loss may occur during these seasons. Vitamin D is present in oily fishes, fish liver oils, and vitamin-supplemented milk. “But there is not  sufficient amounts of vitamin D in most  diets, particularly in winter, and that’s why people need to take supplements,” says Dr. LeBoff.

However there are few randomized clinical trials and the evidence is conflicting for an effect of supplement vitamin D in the prevention of fractures.

Most randomized controlled trials of vitamin D supplementation have studied the nutrient in combination with calcium. One meta-analysis of such trials by an expert panel of the National Osteoporosis Foundation found that taking the 2 types of supplement together cut the risk of total fractures by 15%.

But researchers have wondered whether higher doses of supplemental vitamin D might prove more effective, and whether vitamin D might prevent fractures when not combined with calcium. There are fewer randomized clinical trials of these approaches to supplementation.

And there do seem to be some risks. In one recent trial, investigators randomly assigned 200 men and women aged 70 or older who had fallen in the prior year to 3 groups: 24,000 IU of vitamin D3 per month (the equivalent of 800 IU per day), or 24,000 IU of D3 per month with calcifediol, or 60,000 IU of vitamin D3.

Those who took the 60,000 IU per month of D3 and the D3 plus calcifediol did achieve a higher serum vitamin D levels, but they were more likely to fall again over the following year than those taking the lower dose.  Dr. LeBoff speculates that the high monthly doses of vitamin D instead of daily vitamin D doses may have contributed to these findings.

On the other hand, lower doses have not proven effective. A trial in which 2,578 people 70 years or older were divided in two, one group given 400 IU/d of D3, the other a placebo, showed no difference between the two groups.

The prescription for one group may not suit another. Not only older people, but people living in northern latitudes have lower serum vitamin D levels on average, as do African Americans. Celiac disease, inflammatory bowel disease and rheumatoid arthritis are also associated with low serum levels of vitamin D.

“You don’t need to measure vitamin D in everybody,” says Dr. LeBoff. “But in patients that we see for evaluation of osteoporosis, we do check the [serum] 25 hydroxy vitamin D. There is a lot of vitamin D deficiency.”

Dr. LeBoff is heading up a study sponsored by the National Institute of Health of the effects of  supplemental vitamin D on bone fractures: the Vitamin D and Omega-3 fatty acid trial (VITAL).  In this study 25,874 adults in the US were randomly assigned to either 2000 IU per day of vitamin Dand/or omega-3 fatty acids or placebo. Participants will also be permitted to take up to 800 IU of additional vitamin D supplements.

Over the course of five years, the investigators will measure their fractures. In a sub-study  that includes in person visits, many other health outcomes are being evaluated. “I think it will be a really important study in terms of advancing science on the effects of vitamin D effects on bone,” she says.

While awaiting the results of this trial, as well as the USPSTF review, clinicians should continue to use the Institute of Medicine or National Osteoporosis Foundation recommendations, says Dr. LeBoff.




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  • JAMA Intern Med. 2016;176(2)
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