VITAL: Does supplemental vitamin D affect bone health?

2022-08-31
Alexandra Papaioannou, James Douketis

Dr Alexandra Papaioannou, Director in the Division of Geriatric Medicine at McMaster University studying pharmacology and quality of life in the elderly, as well as author of the McMaster Textbook chapter on frailty, joins Dr James Douketis to discuss vitamin D supplementation in healthy midlife and elderly individuals.

For a Publications of the Week article discussing vitamin D supplementation and fractures in midlife and older adults, click here.

James Douketis, MD: Hello everyone. My name is Jim Douketis and I’m pleased to join you with another [episode of the McMaster Perspective series accompanying Publications of the Week]. This time we’re joined by Dr Alexandra Papaioannou, who is a professor of medicine and holder of the Eli Lilly Chair in osteoporosis research. We’ll be talking about VITAL (VITamin D and OmegA-3 TriaL), which looks at vitamin D supplementation and its potential benefits in a broad population.

First of all, welcome, Alex, and thank you for joining us today. Why don’t you tell us a little bit about the background, about vitamin D supplementation in the general community? I’m talking about middle-age to elderly people, [as] we know that it’s been widely recommended, and then we’ll go into the discussion of this trial.

Alexandra Papaioannou, MD, MSc: Thank you very much, Jim, for inviting me to speak on this really important trial that we’ve been waiting for for many years. Why it’s important is [because] over a third of adults are taking vitamin D for a variety of reasons in North America. Interest around vitamin D first started when the Institute of Medicine... and in Canada, there was a recommendation that all adults achieve 600 to 800 international units (IUs) per day. A lot of my patients will ask me, “Well, where do you get vitamin D from?” Unfortunately, it’s not really that available naturally in many foods. It’s only really available in fatty livers of fish.

So, as a result, because of these recommendations and because of the history of rickets in children, the government started adding vitamin D to fortified cereals, to milk, to bread. If you think about it, that’s when you’ll see “fortified with vitamin D.” The other really common place we find vitamin D in is from the sun. And we’re always concerned because of our latitude in the north that we may not be absorbing vitamin D.

The next question is, why is vitamin D so topical? The recommendations around vitamin D were, number one, we needed vitamin D to absorb calcium, to keep in the gut, to keep bones healthy. That’s the main role. But interestingly, [as shown by] other trials, vitamin D has receptors practically in every tissue in the body. That’s why, as you’ve seen with other trials, there’s interest around vitamin D and cancer, vitamin D and mood, vitamin D and stroke: because vitamin D receptors are ubiquitous in the body. So [there’s] lots of interest around vitamin D, and that’s what informed the VITAL trial that we’re talking about today.

James Douketis: Thanks for that very lucid background. The VITAL trial was a very large, very ambitious randomized trial of over 20,000 patients. And, as you say, it looked at vitamin D, but it also looked at n-3 fatty acids to prevent major diseases like cancer and cardiovascular disease.

This ancillary component of the trial looked at fracture risk. And I have to say that when I saw the results, I was a bit surprised. So maybe you can give us your broad take on the trial, Dr Papaioannou, in terms of what the strengths were, maybe what its weaknesses were... What do you think of the trial results overall?

Alexandra Papaioannou: The trial was a very strong, large trial in 25,000 individuals. It was a factorial design, so a group of individuals received vitamin D, another group received vitamin D and placebo, and there was a group that also took calcium with vitamin D. And there were the other groups also with the omega-3 [acids] in the factorial design. The bottom line in the trial is, despite taking vitamin D in the general population... I think this trial has definitively said we don’t need to take vitamin D by pill to prevent fractures in the general population. This trial didn’t really look at those who have a strong family history of osteoporosis, who may have diseases that put them at risk for osteoporosis and fractures. This trial did not address that.

Also, another strength is they did do vitamin D levels. And low vitamin D levels, even in that group, when they did subgroup analysis, that didn’t change the outcome. So this trial is, again, really supporting [the approach that] in the prevention phase supplements don’t seem to be impacting on disease long term.

James Douketis: Okay. Obviously [VITAL is] a very important study that informs a lot of questions. Does this mean that we don’t need to routinely check vitamin D levels in patients who are 50 or ≥55, and that we should only be considering vitamin D supplementation in an at-risk population? How does it change… what do you think our current practice and approach should be in this clinical domain?

Alexandra Papaioannou: Really important questions, Jim. It does change. We’ve been spending a tremendous amount of health-care dollars and dollars in North America doing vitamin D levels in the well individuals. So yes, this trial is saying, “Don’t do vitamin D levels on everybody. Only those who are at high risk.”

James Douketis: Can you maybe drill down a little bit about that? What’s a typical patient that if I saw in my internal medicine practice, maybe I should be measuring vitamin D levels and maybe I should be supplementing? What’s a typical phenotype in your mind in terms of that at-risk individual?

Alexandra Papaioannou: People who may be at high risk for vitamin D deficiency or osteoporosis, especially maybe people with underlying liver disease, where vitamin D is converted in the liver to the more active form and then finally in the kidney. Those individuals are a different risk group.

People who are taking steroids or prednisone are also a very different group. They’re at much higher risk because steroids affect vitamin D at the gut level and calcium absorption. So certainly those with malabsorption, and those with fractures or who are at high risk for osteoporosis. This trial was not really used to address that group.

James Douketis: Yeah. Do you think that—just as a final question—this trial will lead to other trials in those selected patients? And do you know of any research that’s looking at these patient subgroups?

Alexandra Papaioannou: Certainly there are trials underway internationally looking at those subgroups. And we also know right now in those subgroups—say, those on steroids or prednisone—that they’re very high risk for fractures and that those individuals do need vitamin D supplementation and do need careful monitoring. And certainly those groups who have malabsorption syndromes also need to be assessed. In all the clinical trials with osteoporosis therapeutic drugs, they did include adequate vitamin D and calcium supplementation.

James Douketis: My take is that this is really a paradigm-changing, eye-opening trial. But, as any good trials, it asks some more questions than it answers. So I think the book is not closed on this.

Dr Papaioannou, I’d like to thank you very much for your insights and for joining us for this iteration of McMaster Perspective. Thank you very much.

Alexandra Papaioannou: Thanks.

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