Taking vitamin D supplements did not significantly reduce the risk of fractures among adults in midlife and older adults, compared with placebo, according to results from an ancillary study of the Vitamin D and Omega-3 Trial (VITAL).
The data showed that taking 2000 IU of supplemental vitamin D each day without coadministered calcium did not have a significant effect on nonvertebral fractures (hazard ratio [HR], 0.97; P = .50), hip fractures (HR, 1.01; P = .96), or total fractures (HR, 0.98; P = .70), compared with taking placebo, among individuals who did not have osteoporosis, vitamin D deficiency, or low bone mass, report Meryl S. LeBoff, MD, a professor of medicine at Harvard Medical School and chief of the calcium and bone section at Brigham and Women’s Hospital in Boston, Massachusetts, and colleagues.
The findings were published online July 27 in The New England Journal of Medicine.
Prior randomized, controlled trials have presented conflicting findings. Some have shown that there is some benefit to supplemental vitamin D, whereas others have shown no effect or even harm with regard to risk of fractures, LeBoff noted.
“Because of the conflicting data at the time, we tested this hypothesis in an effort to advance science and understanding of the effects of vitamin D on bone. In a previous study, we did not see an effect of supplemental vitamin D on bone density in a subcohort from the VITAL trial,” LeBoff told Medscape Medical News.
“We previously reported that vitamin D, about 2000 units per day, did not increase bone density, nor did it affect bone structure, according to PQCT [peripheral quantitative CT]. So that was an indicator that since bone density is a surrogate marker of fractures, there may not be an effect on fractures,” she added.
These results should dispell any idea that vitamin D alone could significantly reduce fracture rates in the general population, note Steven R. Cummings, MD, of the University of California, San Francisco, and Clifford Rosen, MD, of Maine Medical Center Research Institute, Scarborough, in an accompanying editorial.
“Adding those findings to previous reports from VITAL and other trials showing the lack of an effect for preventing numerous conditions suggests that providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements, and people should stop taking vitamin D supplements to prevent major diseases or extend life,” the editorialists write.
The researchers assessed 25,871 participants from all 50 states during a median follow-up time of 5.3 years. Participants were randomly assigned in a 1:1 ratio to receive placebo or vitamin D.
The mean age of the participants was 67.1 years; 50.6% of the study cohort were women, and 20.2% of the cohort were Black. Participants did not have low bone mass, vitamin D deficiency, or osteoporosis.
Participants agreed not to supplement their dietary intake with more than 1200 mg of calcium each day and no more than 800 IU of vitamin D each day.
Participants filled out detailed surveys to evaluate baseline prescription drug use, demographic factors, medical history, and the consumption of supplements, such as fish oil, calcium, and vitamin D, during the run-in stage. Yearly surveys were used to assess side effects, adherence to the investigation protocol, falls, fractures, physical activity, osteoporosis and associated risk factors, onset of major illness, and the use of nontrial prescription drugs and supplements, such as vitamin D and calcium.
The researchers adjudicated incident fracture data using a centralized medical record review. To approximate the therapeutic effect in intention-to-treat analyses, they used proportional-hazard models.
Notably, outcomes were similar for the placebo and vitamin D groups with regard to incident kidney stones and hypercalcemia.
The effect of vitamin D supplementation was not modified by baseline parameters such as race or ethnicity, sex, body mass index, age, or blood 25-hydroxyvitamin D levels.
Cummings and Rosen point out that these findings, along with other VITAL trial data, show that no subgroups classified on the basis of baseline 25-hydroxyvitamin D levels, including those with levels <20 ng/mL, benefited from vitamin supplementation.
“There is no justification for measuring 25-hydroxyvitamin D in the general population or treating to a target serum level. A 25-hydroxyvitamin D level might be a useful diagnostic test for some patients with conditions that may be due to or that may cause severe deficiency,” the editorialists note.
Except with regard to select patients, such as individuals living in nursing homes who have limited sun exposure, the use of the terms “vitamin D deficiency” and “vitamin D “insufficiency” should now be reevaluated, Rosen and Cummings write.
The study’s limitations include its assessment of only one dosage of vitamin D supplementation and a lack of adjustment for multiplicity, exploratory, parent trial, or secondary endpoints, the researchers note.
The number of participants who had vitamin D deficiency was limited, owing to ethical and feasibility concerns regarding these patients. The data are not generalizable to individuals who are older and institutionalized or those who have osteomalacia or osteoporosis, the researchers write.
“The interpretation of this [study] to me is that vitamin D is not for everybody,” said Baha Arafah, MD, professor of medicine at Case Western Reserve University and chief of the Division of Endocrinology at University Hospital in Cleveland, Ohio, who was not involved in the study.
“This is not the final word; I would suggest that you don’t throw vitamin D at everybody. I would use markers of bone formation as a better measure to determine whether they need vitamin D or not, specifically looking at parathyroid hormone,” Arafah said in a phone interview.
Arafah pointed out that these data do not mean that clinicians should stop thinking about vitamin D altogether. “I think that would be the wrong message to read. If you read through the article, you will find that there are people who do need vitamin D; people who are deficient do need vitamin D. There’s no question that excessive or extreme vitamin D deficiency can lead to other things, specifically, osteomalacia, weak bones, [and] poor mineralization, so we are not totally out of the woods at this time.”
The ancillary study of the VITAL trial was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Pharmavite donated the vitamin D 3 supplements used in the trial. LeBoff reports that she holds stock in Amgen. Cummings reports personal fees and nonfinancial support from Amgen outside the submitted work. Rosen is associate editor of The New England Journal of Medicine. Arafah reports no relevant financial relationships.
Ashley Lyles is an award-winning medical journalist. She is a graduate of New York University’s Science, Health, and Environmental Reporting Program. Her work has appeared in outlets such as The New York Times Daily 360, PBS NewsHour, The Huffington Post, Undark, The Root, Psychology Today, Insider, and Tonic (Health by Vice), among other publications.