An ongoing dialogue on HIV/AIDS, infectious diseases,
February 7th, 2021
Does Taking Vitamin D Prevent or Treat COVID-19?
Vitamin D supplementation — critical in prevention and treatment of COVID-19?
Or does it do nothing — except further enrich the vitamin and supplements industry, which is worth more than 100 billion dollars?
The challenge is figuring out which of these is the truth, and after several weeks of thinking about the issue, I find it’s far from straightforward — with many strong (and conflicting) opinions held by lots of smart people.
I waded into these choppy waters a couple of months ago with this post after seeing a pre-print of a negative vitamin D study:
Low vitamin D levels may correlate with worse outcomes in many diseases.
But supplementing does not necessarily improve outcomes. In fact, it almost never does.
(Still waiting for a truly convincing study in any infection.)
Lather, rince, repeat.https://t.co/RlqpSCPlRC
— Paul Sax (@PaulSaxMD) December 8, 2020
You can tell what my “priors” were on this research question. Most studies of vitamin supplementation in all diseases have ended with negative results — it’s really quite remarkable the sheer number — and in some medical problems the vitamin treatment arm actually does worse.
For vitamin D specifically, here’s a list of the negative randomized clinical trials done just in the past couple of years summarized by NEJM Journal Watch:
- Prenatal supplementation and neurodevelopmental outcomes in children
- Falls in older adults
- A range of physical and cognitive outcomes in adults older than 70
- Macular degeneration
- Bone density (this one surprised me)
- Childhood asthma
- Preventing depression in adults 50 and older
- Preventing TB in children
- Outcomes in critical illness
- Diabetes-related kidney function
- Bone density (again!)
For each of these disease areas, observational studies found an association between low vitamin D levels and poor outcomes, with a mechanistic explanation of why that might be, and how such adverse outcomes could be reversed with supplements.
But alas, all of the randomized trials were negative — no significant benefit. Not only that, the study on falls in older adults and one of the bone density studies actually showed worse outcomes with higher doses — never a good trend.
But I quickly learned that despite these negative studies, my skeptical view about vitamin D and COVID-19 is far from universal.
Indeed, the response to the post was surprisingly brisk, and quite polarized — some agreeing with the post that “association is not causation — basic principles.”
Others criticized the study design, in particular the eligibility criteria (too sick) and dosing strategy (daily dosing would be better). Someone sent me this hour-long video, a tour-de-force graphical explanation of how vitamin D is critical for prevention and treatment of COVID-19; another person sent this “Roll Call” of credible experts calling for vitamin D treatment.
Then a physician I know well from teaching together (a primary care doctor) sent me a 2017 meta-analysis of randomized trials on vitamin D supplementation to prevent viral respiratory tract infections. The studies included are mostly of good quality, and the aggregate results suggest a substantial benefit.
Perhaps this is why Tony Fauci says he takes a vitamin D supplement?
Now motivated to learn more, I reached out to Dr. David Meltzer from the University of Chicago. He’s the first-author on a nicely done study finding a strong association between low vitamin D levels and testing positive for COVID-19, and he kindly agreed to be interviewed in this OFID podcast about this paper and his ongoing studies. Highly recommended — he’s a smart, experienced clinical researcher, doing community-based randomized trials of various vitamin D interventions.
And there’s quite a bit of other research going on right now, as summarized nicely here in this review by Rita Rubin in JAMA. She also cites some inconsistencies in the research to date, along with a discussion of the funders of some of the trials — not surprisingly, companies from the supplements industry and labs that offer vitamin D tests.
So where do I stand on this vitamin D issue?
It seems highly likely that low vitamin D levels are associated with worse outcomes in COVID-19. Levels are a marker for various components of ill health — inactivity, poor nutrition, lack of fresh air and sunshine.
Conversely, taking vitamin supplements in observational studies often is associated with better outcomes. Whether this is because such people are more health-seeking, or whether the supplement is doing anything, isn’t possible to disentangle. For a perfect example, here’s a recent study showing that regular supplement takers of vitamin D were less likely to get diagnosed with COVID-19. But the benefit didn’t appear to be mediated by higher vitamin D levels.
As to whether taking a vitamin D supplement causally helps to prevent or treat COVID-19, many questions remain. Would it work in everyone? Or just those with low levels? (Essentially every citizen in Boston this time of year, I write, as the snow briskly continues to fall.) Or would it provide benefits only to those at high risk of severe disease? And if one recommends it for patients, friends, and family, what’s the right dose? And the best formulation?
Fortunately, my hospital colleague Dr. JoAnn Manson is leading one of the many studies evaluating vitamin D, both as COVID-19 prevention and treatment. She has extensive experience running large clinical trials, all done by mail/remotely, so if we’re going to get an answer, she’s the right person to do it.
My prediction? Odds are it won’t do anything. But I hope I’m wrong.
That’s why we do the studies!
And here’s the David Meltzer podcast stream, in case you want to stay on this page and look at our cute dog.