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HomeA Practitioner's Must ReadScientists adamant vitamin D pills generally ineffective – US study

Scientists adamant vitamin D pills generally ineffective – US study

The long accepted theory that vitamin D pills can prevent bone fractures appears to have been blown out of the water, according to US researchers, who say not only do the the pills not prevent bone fractures but they also don’t protect against many other diseases either, contrary to common belief.

Their findings add to questions about medical guidance many now take for granted.

The New York Times reports that the idea made so much sense it was almost unquestioningly accepted: vitamin D pills can protect bones from fractures. After all, the body needs the vitamin for the gut to absorb calcium, which bones need to grow and stay healthy.

But now, in the first large randomised controlled study in the US, funded by the federal government, researchers report that vitamin D pills taken with or without calcium have no effect on bone fracture rates.

The results, published in The New England Journal of Medicine, hold for people with osteoporosis and even those whose blood tests deemed them vitamin D deficient.

These results followed other conclusions from the same study that found no support for a long list of purported benefits of vitamin D supplements.

So, for the millions of people who take vitamin D supplements and the labs that do more than 10m vitamin D tests each year, an editorial published along with the paper has some advice: Stop.

“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,” wrote Dr Steven Cummings, a research scientist at the California Pacific Medical Centre Research Institute, and Dr Clifford Rosen, a senior scientist at the the Maine Health Institute for Research.

Rosen is an editor at The New England Journal of Medicine.

There are exceptions, they say. People with conditions like celiac or Crohn’s disease need vitamin D supplements, as do those who live in conditions where they are sunshine-deprived and may not eat enough foods routinely supplemented with vitamin D, such as cereals and dairy products, to help them absorb calcium.

Getting into such a severe vitamin D-deprived state is “very hard to do in the general population”, Cummings said.

The two scientists know that in making such strong statements they are taking on vitamin sellers, testing labs and advocates who have claimed that taking vitamin D, often in huge amounts, can cure or prevent a wide variety of ailments and even help people live longer.

Doctors often check for vitamin D levels as part of routine blood tests. The study involved 25,871 participants – men aged 50 and older and women 55 and older – who were assigned to take 2,000 international units of vitamin D each day or a placebo.

The research was part of a comprehensive vitamin D study called VITAL. It was funded by the National Institutes of Health and began after an expert group convened by the National Academy of Medicine, a non-profit organisation, examined the health effects of vitamin D supplements and found little evidence.

The expert group’s members were supposed to come up with a minimum daily requirement for the vitamin but found most clinical trials that had studied the subject were inadequate, making them ask if there were any truth to the claims that vitamin D improved health.

The prevailing opinion at the time was that vitamin D was likely to prevent bone fractures. Researchers thought that as vitamin D levels fell, parathyroid hormone levels would increase at a detriment to bones.

Rosen said those concerns led him and the other members of the National Academy of Medicine’s expert group to set what he called an “arbitrary value” of 20 nanograms per millilitre of blood as the goal for vitamin D levels and to advise people to get 600 to 800 international units of vitamin D supplements to achieve that goal.

Labs in the United States then arbitrarily set 30 nanograms per millilitre as the cut-off point for normal vitamin D levels, a reading so high that almost everyone in the population would be considered vitamin D-deficient.

The presumed relationship between vitamin D and parathyroid levels has not held up in subsequent research, Rosen said. But uncertainty continued, so the National Institutes of Health funded the VITAL trial to get some solid answers about vitamin D’s relationship to health.

The first part of VITAL, previously published, found that vitamin D did not prevent cancer or cardiovascular disease in trial participants. Nor did it prevent falls, improve cognitive functioning, reduce atrial fibrillation, change body composition, reduce migraine frequency, improve stroke outcomes, protect against macular degeneration or reduce knee pain.

Another large study, in Australia, found that people taking the vitamin did not live longer.

Dr JoAnn Manson, chief of preventive medicine at Brigham and Women’s Hospital in Harvard Medical School and the leader of the main VITAL trial, said the study was so large it included thousands of people with osteoporosis or with vitamin D levels in a range considered low or “insufficient”.

That allowed the investigators to determine that they also received no benefit for fracture reduction from the supplement.

“That will surprise many,” Manson said. “But we seem to need only small-to-moderate amounts of the vitamin for bone health. Larger amounts do not confer greater benefits.”

The bone study’s first author and principal investigator, Dr Meryl LeBoff, an osteoporosis expert at Brigham and Women’s Hospital, said she was surprised. She had expected a benefit.

But she cautioned that the study did not address the question of whether people with osteoporosis or low bone mass just short of the condition should be taking vitamin D and calcium, along with osteoporosis medications. Professional guidelines say they should take vitamin D and calcium, and she will continue to adhere to them in her own practice.

Dr Dolores Shoback, an osteoporosis expert at the University of California, San Francisco, also will continue to advise patients with osteoporosis and low bone mass to take vitamin D and calcium.

It is “a simple intervention and I will continue to prescribe it”, she said. Others go a bit further.

Dr Sundeep Khosla, a professor of medicine and physiology at the Mayo Clinic, said that since vitamin D “will do little or no harm and may have benefits”, he would continue to advise his patients with osteoporosis to take it, recommending the 600 to 800 units a day in the National Academy of Medicine report.

“I will still tell my family and friends who don’t have osteoporosis to take a multivitamin a day to make sure they don’t get vitamin D deficient,” he said.

Khosla follows that advice himself. Many multivitamin tablets now contain 1,000 units of vitamin D, he added.

But Cummings and Rosen remain firm, even questioning the very idea of a vitamin D deficiency for healthy people.

“If vitamin D doesn’t help, what is a vitamin D deficiency?” Cummings asked. “That implies you should take vitamin D.”

Rosen, who signed off on the National Academy of Medicine report, has become a vitamin D therapeutic nihilist.

“I don’t believe any more in 600 units,” he said. “I don’t believe you should do anything.”

Study details

Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults

Meryl LeBoff, Sharon Chou, Kristin Ratliff, Nancy Cook, Bharti Khurana,
Eunjung Kim, Peggy Cawthon, Douglas Bauer, Dennis Black, Chris Gallagher, I-Min Lee, Julie Buring et al.

Published in The New England Journal of Medicine on 28 July

Abstract

Background
Vitamin D supplements are widely recommended for bone health in the general population, but data on whether they prevent fractures have been inconsistent.

Methods
In an ancillary study of the Vitamin D and Omega-3 Trial (VITAL), we tested whether supplemental vitamin D3 would result in a lower risk of fractures than placebo. VITAL was a two-by-two factorial, randomised, controlled trial that investigated whether supplemental vitamin D3 (2000 IU per day), n−3 fatty acids (1 g per day), or both would prevent cancer and cardiovascular disease in men 50 years of age or older and women 55 years of age or older in the United States. Participants were not recruited on the basis of vitamin D deficiency, low bone mass, or osteoporosis. Incident fractures were reported by participants on annual questionnaires and adjudicated by centralised medical-record review. The primary end points were incident total, nonvertebral, and hip fractures. Proportional-hazards models were used to estimate the treatment effect in intention-to-treat analyses.

Results
Among 25,871 participants (50.6% women [13,085 of 25,871] and 20.2% Black [5106 of 25,304]), we confirmed 1991 incident fractures in 1551 participants over a median follow-up of 5.3 years. Supplemental vitamin D3, as compared with placebo, did not have a significant effect on total fractures (which occurred in 769 of 12,927 participants in the vitamin D group and in 782 of 12,944 participants in the placebo group; hazard ratio, 0.98; 95% confidence interval [CI], 0.89 to 1.08; P=0.70), nonvertebral fractures (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P=0.50), or hip fractures (hazard ratio, 1.01; 95% CI, 0.70 to 1.47; P=0.96). There was no modification of the treatment effect according to baseline characteristics, including age, sex, race or ethnic group, body-mass index, or serum 25-hydroxyvitamin D levels. There were no substantial between-group differences in adverse events as assessed in the parent trial.

Conclusions
Vitamin D3 supplementation did not result in a significantly lower risk of fractures than placebo among generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass, or osteoporosis

 

The New York Times article – Study Finds Another Condition That Vitamin D Pills Do Not Help (Restricted access)

 

NEJM article – Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults (Open access)

 

See more from MedicalBrief archives:

 

Doctors warn about dangers of vitamin D overdose after man hospitalised

 

Vitamin D and Omega-3 supplementation reduced autoimmune disease – VITAL trial

 

Vitamin D deficiency from inadequate sunlight may increase colorectal cancer risk

 

Lancet removes hyped preprint on efficacy of vitamin D for COVID-19

 

 

 

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