HIV and ID Observations

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February 7th, 2021

Does Taking Vitamin D Prevent or Treat COVID-19?

Louie wonders whether the “D” in vitamin D stands for “Dog.”

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:

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:

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.

 

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41 Responses to “Does Taking Vitamin D Prevent or Treat COVID-19?”

  1. Deborah A ONan says:
    February 7, 2021 at 9:20 pm

    so is the covid variant infection prevented with the current vaccine?

    • Arturo Azpiroz says:
      February 8, 2021 at 6:12 am

      the efficacy of the Pfizer-BioNTech COVID-19 vaccine may be only slightly reduced against B.1.351, according to anindustry-supported, in vitro study posted on the preprint server bioRxiv.

      For the study, researchers engineered three SARS-CoV-2 viruses that had spike protein mutations seen in B.1.351 and B.1.1.7, the variant first detected in the U.K. They then tested sera from 20 vaccinated people for neutralization against these viruses and wild-type SARS-CoV-2.

      Neutralization titers were roughly comparable for the three experimental viruses and wild-type virus. Of note, for one third of the serum samples, neutralization titers were half as high for the virus with B.1.351 mutations than for wild-type virus.
      AstraZeneca-Oxford vaccine halted in South Africa: South Africa on Sunday halted use of the AstraZeneca-Oxford vaccine after clinical trial evidence indicated that it did not protect against mild-to-moderate COVID-19 caused by B.1.351 — the highly contagious SARS-CoV-2 variant that first emerged there — the New York Times reports. Whether the vaccine protects against severe disease caused by B.1.351 is unclear.
      This information I have done through some cut and paste of recent news. I think we do not need to be aware of the efficacy or not of the different vaccines for the different variants of SARS-Cov 2. Simply put the vaccine that is available, protect people at risk and the rest that are infected as soon as possible to achieve herd immunity. Otherwise the story will be endless.
      Regarding vitamin D, I share what was said by Dr Sax. Only as a suggestion to those who wish to supplement with this vitamin, it seems better to use softgel of 400 IU SUCKS (for a direct action on the pharynx … etc) until reaching a daily dose of 1200IU, for example (that is, 400IU three times a day).

      • Arturo Azpiroz says:
        February 8, 2021 at 9:21 am

        I apologize for introducing, inadvertently, the word sucks which is somewhat ambiguous. I have wanted to refer to sucking the capsule like a candy, for a direct action of vitamin D on the oropharyngeal mucosa. I take this opportunity to indicate that the passage from international units to micrograms is easy, just divide by 40; so 400IU is 10 micrograms and 1200IU is 30 micrograms.

  2. David says:
    February 7, 2021 at 11:07 pm

    You note that people who take D3 as a dietary supplement have lower rates of COVID but you don’t know why? You conjecture that it may be because they are health conscious. This is meaningless

  3. Merlin D Bruna says:
    February 7, 2021 at 11:12 pm

    I have watched reports on the use of vitamin D3 in other countries that have done studies on it.
    From the information I saw the vitamin does help. The majority of our country is below normal levels for the vitamin. So yes I am taking a supplement.

  4. Loretta S says:
    February 7, 2021 at 11:56 pm

    I recently had a new patient who noted on her intake paperwork that she takes 10,000 IU of Vitamin D3 daily. I asked her why she takes such a large dose and she responded that she had heard that Vitamin D might help her avoid a COVID-19 infection.

  5. Jen Barkley says:
    February 7, 2021 at 11:57 pm

    Another factor to consider are the racial differences in both vitamin D levels (lower in Black people and anyone with dark skin tone) and COVID infection and severity risks (Black and Latinx overrepresented), which could be an explanation for the correlation that is probably not causation.

  6. Randall Hart says:
    February 8, 2021 at 12:22 am

    Here’s my take on it . Can we really wait for testing to be done. I say take it as a precautionary until a final verdict is completed.
    It may very well save thousands of lives by the time any results are actually finalized.If it doesn’t help there is no real harm in taking vit d.

  7. John Ellis says:
    February 8, 2021 at 12:22 am

    So sad that in the United States we cannot stand up large, relatively simple, national trials like RECOVERY in the UK that documented dexamethasone protection in covid-19 hospitalization. I think they will soon also report on aspirin in covid-19. There is enough reason to justify a large RCT of vitamin D, one would think.

  8. Josep M Llibre says:
    February 8, 2021 at 6:53 am

    Vitamin D is a surrogate marker of many underlying (sometimes severe) diseases. Most of them end up with cachexia, malnutrition, and lack of exercise. These underlying diseases are indeed associated with a worse prognosis in most infectious diseases. Obviously, treating with Vit D does not correct these diseases are is therefore unlikely that it would impact positively the outcome.
    So, yes, the association is not causation.

  9. Carol Vassar, MD says:
    February 8, 2021 at 7:14 am

    With so many studies done on Vitamin D, it may be a great opportunity to display the merits of observational studies and meta-analyses compared to randomized controlled trials ( or case controlled and cohort studies if there are enough of them about Vitamin D). Because we do the weaker studies and publish them people think that they can be trusted. The public needs to better understand that even the best research does not provide certainty when applied to a specific situation but provides a relative chance of benefit or harm .

  10. Chuck says:
    February 8, 2021 at 8:50 am

    I don,t know about the real motivation and reasoning behind the studies done on vitamin d3. I do know that those paying for the study inevitably have a vested interest in the outcome.
    What I personally do know is this: From childhood I have had nearly every flu and cold, bronchitis, and pneumonia. I fully expected to be dead long ago because I thought I had some genetic weakness in my respiratory system and would naturally succumb to it early in life.
    Then in 2010 a nurse practitioner told me that I needed to take 10,000 IU of D3 daily.
    I started and have not quit. In fact I upped that to 15,000 daily as winter 2019 started. My wife has been taking 10,000 also.
    Since then, due to necessity, we have been
    in contact with family, two of whom have had Covid-19 confirmed.
    Neither of us have had any issues or symptoms. We both turned 70 in 2020.
    I think I will keep taking my D3!

  11. Jarrod says:
    February 8, 2021 at 8:56 am

    Paul Sax said so. Therefore it MUST be true.

  12. Jarrod says:
    February 8, 2021 at 9:15 am

    There is a problem with everyone of those tests. The last one cited. Bone density, says towards the end that they chose HEALTHY men and women 55 to 70, who already had a “normal” blood serum level to begin with. Now take all those healthy men and women, keep all things the same, and put them up against people of color, who are poor, with comorbidities and let’s see what happens. There is a bias and a trick to everyone of those studies, such that I could drive a Mac truck through it. Another study used the elderly and only gave them all an amount of d that wouldn’t help a mouse. The findings all point to, stay unhealthy and keep the dollars rolling in so we can treat you with chemicals and pretend we care.

  13. Mark Penzel says:
    February 8, 2021 at 9:34 am

    With that adoring look on his face, I think Louie is wondering whether the “D” is for Dad.

  14. Ales Ambrozic says:
    February 8, 2021 at 11:45 am

    Vitamin D is only one chain link and strengthening one link in the chain makes the chain stronger (i.e. positive effect) only if this link is the weakest in the chain (the reason for many negative trials). In covid-19 there is an oxidative stress driving most inflammatory processes. The chain might be: vitamin D acting as transcription factor of Nrf2, which is, when activated (activators of Nrf2 are many phytochemicals, physical activity, etc.) transcription factor of numerous antioxidant enzymes (which are in diabetes, obesity, cardiovascular diseases, … deficient); further glutathione (role of N-acetyl cysteine in covid-19?) is one of the most important substrates in antioxidant processes.
    This is only a small part of the story, but the take home message is: Don’t test only one chain link; activate the whole path (or more paths), increase the strength of the whole chain and results will be measurable.

  15. Franko Ku says:
    February 8, 2021 at 12:24 pm

    UK is pushing more studies as well
    https://amp.theguardian.com/world/2021/feb/05/matt-hancock-orders-third-review-on-link-between-vitamin-d-and-covid

  16. Franko Ku says:
    February 8, 2021 at 12:36 pm

    D3 is a hormone and notice that advanced cancers recently shown to be a benefit is not on your list.
    Careful that double blind study isn’t like the bogus one funded by drug companies years ago for Vitamin C for immunity, then dissed by the NIH.
    Or the one for Niacin to reduce LDL but had the anti-flushing compound as well. Pure niacin pennies per pill works.
    Or the $1000 Remdesivir studies now shown to be in question for Covid.

  17. jorge bravo says:
    February 8, 2021 at 12:48 pm

    En mi humilde opinión un pequeño trabajo realizado en una de las provincias mas pobres de mi país Argentina , pude reunir 275 casos , de los cuales 100 personas con covid tenían dosaje de colecalciferol bajo, y covid positivo , no se les repuso vit D, y al resto también con colecalciferol bajo y covid positivo se les repuso colecalciferol. ( a las 72 hs de pcr +) , en forma observacional, se observo mejor y mas acortando el tiempo recuperación que el otro grupo, es obvio que no fue el único medicamento usado, me llamo la atención que NO requirieron hospitalización. el grupo de 175 persona. respetuosamente os saludo.

  18. D says:
    February 8, 2021 at 1:48 pm

    Sometimes it’s shoot the engineers and full speed ahead.

  19. Chasd says:
    February 8, 2021 at 8:00 pm

    Most of the studies I have seen are trying to treat a Covid case with high dose Vitamin D. That would be like treating a sunburn with sunscreen, a little too late. Studies that show treatment after getting the virus doesn’t prove it won’t work as a prevention prior to getting the virus..

  20. John Westerdale says:
    February 9, 2021 at 12:27 am

    If I get a full dose with 20 minutes in the sun, what happens after 40 minutes? Is there some regulation mechanism, or resource depletion that regulates VitD levels? Just eating more d3 never lifts my levels over 20.

    • Arturo Azpiroz says:
      February 10, 2021 at 9:40 am

      The fully active form of vit. D is 1-25 (OH) 2 D3 that is synthesized in the kidney from 25 (OH) D3 from the liver. This step is crucial and well controlled to avoid toxicity. Hypocalcemia (through increased PTH), hypophosphatemia (eg, increased FGF23) increase renal 1-hydroxylase activity. Also, conversely, the increase in 1-25 (OH) 2 D3 blocks renal synthesis and shifts it to an underactive 24-25 (OH) 2 D3.
      The cause of low levels of VIT D despite taking supplements can be diverse: for example intestinal problems of fat malabsorption, poor handling by the laboratory of the sample, low levels of 25 (OH) D3 with normal / high levels of 1-25 (OH) D3 in cases of high PTH or granulomatous inflammation or even (as seems to happen more in the black race) low levels of vitamin D transporter protein with normal levels of free vitamin D.

  21. Roberta says:
    February 9, 2021 at 2:53 am

    It is misleading saying vitamin d, because vitamin d is synthetic and therefore toxic to your system, however vitamin d3 is what is required to help build up your immune system. D3 will protect your lungs plus 25mg of zinc daily will stop the proliferation of any virus that enters your system, all this is well known by all medical personnel, you can google it for yourself, i can’t believe it’s being withheld from us

  22. Eric A Davis says:
    February 9, 2021 at 11:21 am

    I had covid-19 in June of 2021. I currently take D3, vitamin C, vitamin E, turmeric and elderberry EVERDAY. I had a covid test February 6 and got my results back February 8th. I was negative. I am 74 years old and I have been feeling better since I had covid in June that I felt before I had covid-19. Plus, I black.

  23. JJ Jingleheimer Smith says:
    February 9, 2021 at 12:31 pm

    I am a 65-year old Uber driver. Since March, I have had about 4,000 people in my car through 3 COVID spikes in my city. I take 5,000 IU/day of D3, 40mg Zinc, and 1200 mg of Quercitin. I’ve never been sick through this whole mess. Of course I wear a mask and blast the AC in the car which blows from front to back. Have I been exposed? Have I had an asymptomatic case? Who knows.

  24. Ching-Lung Cheung says:
    February 9, 2021 at 12:40 pm

    Agree with the viewpoints, actually I wrote an editorial about the same topic too.

    https://pmj.bmj.com/content/early/2021/01/14/postgradmedj-2020-139388

  25. Mary Ann says:
    February 9, 2021 at 1:23 pm

    Let us not forget about the synergistic effect between Vitamin D3 and K2. It is best to take both of them not just D3 by itself.

  26. Darcy Wooten says:
    February 9, 2021 at 6:27 pm

    Louie is the cutest!!!!

    Thanks for a great discussion.

  27. Dr Tag says:
    February 10, 2021 at 11:46 pm

    The sheer amount of contradictive garbage that is published every day is obviously a sign that it’s not a panacea, because if it was there would be agreement.
    We have a lot of QUANTITY of data but NO QUALITY on data.

  28. Alan King says:
    February 11, 2021 at 7:41 am

    Also, it is reasonable to think that vitamin D may act as a Negative acute phase reactants are those whose concentrations decrease in an acute phase response. These include: Serum albumin. Transferrin and some suggestion of vitamin D. Most studies on vitamin D are case control or retrospective. So a COVID patient in the ICU with a vitamin D level of 22 doesn’t have much relevance.

    Of course Mr. Louie is adorable COVID stress reliever. I am currently relying on Ziggy and Zara my standard poodle editors as I read every morning with their flanking me. Thankful for the big things in life!

  29. David Fitzgerald says:
    February 11, 2021 at 8:47 pm

    Really tired of the decades of controversy regarding micronutrient supplementation in citizens of the first world who are more often over nourished then undernourished. About 10 years ago, at the last lecture I heard on Vitamin D, I jokingly commented that the most recent convicting data on the benefits of micronutrient supplementation was from 1747 when James Lind showed that citrus fruit consumption prevented scurvy.

    Lets stop believing in magic pills and potions and instead focus on encouraging a healthy diet and lifestyle, stress reduction and exercise and maintaining a normal body mass index. We are scientists and clinicians – not snake oil salesmen.

  30. Roy Ilan says:
    February 13, 2021 at 8:01 am

    Encouraging all to review the following analysis:
    https://blog.rootclaim.com/vitamin-d-can-likely-end-the-covid-19-pandemic/
    While clear-cut evidence for or against the role of vitamin D in preventing/ameliorating severe illness due to COVID-19 infection is lacking, evaluating the risk-benefit ratio might make sense.
    Risks: close to none
    Benefits: inexpensive and safe intervention, huge potential fir saving lives, resources, burnout, whatever else this pandemic has brought on us.

  31. Fernando says:
    February 13, 2021 at 9:15 am

    I always wonder how can the ignorance about Vitamin D prevail in the 21st century. Most doctors still don’t understand simple things about it, like the fact that it’s slow to absorb, and the fact that prescribing the doses widely recommended (600iu/day) will not have any effect at all in most people, and fact that the focus should be your serum level and not the dose you take. And this is basic stuff! Anyone familiar with the work of the Coimbra Protocol that has been achieving amazing results in treating auto immune diseases only with high doses of vitamin D for many years, is convinced about the strong modulation role of vitamina D in the immune system, so by now their should be no question about this. When I see so many studies still making basic mistakes like the ones above I wonder if it’s just ignorance or something else. For those still questioning vitamin D take a look at the study from Barcelona (under peer review) and wait a little bit until the new Cordoba study is released (both show the important effects of calcifediol in avoiding ICU and death).

    • Arturo Azpiroz says:
      February 16, 2021 at 11:15 am

      A few days ago I answered, in this blog, a question about the mechanisms of control of vitamin D toxicity, however, the high daily doses (of up to 10,000 IU) taken for years by other blog colleagues without adverse events never cease to amaze me. Could you give me a guide in this regard?
      Thank you

  32. Clyde Meckel says:
    February 13, 2021 at 11:41 am

    Randomized trial of cacifediol on hospital admit associated with decreased ICU admission and death. Preprint in Lancet.

    https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3771318

  33. Louis Tsarouhas, MD says:
    February 13, 2021 at 12:03 pm

    As a 59 yo primary care doctor I read with zeal daily 3 medical newsletters to stay abreast the “ literature.” After about 160,000 intimate patient encounters, review of the science published and the art of medicine as I experience it, my take….
    Yes, Dr Fitzgerald is correct….exercise, diet, more exercise, lifestyle and stress management are the cornerstones of Health. Period full stop.
    However most studies fail to understand “normal vs. normative”…….healthy vitamin D levels need to be above 70 ng/dL. Latitude on Mother Earth determines supplement dosing needs along with skin pigment and personal biology.
    Bottom line : all humans above 10 degrees latitude need at least 2,000 and most in Princeton, NJ area need 5-10,000 IU daily taken with Food to achieve NORMAL healthy vitamin D levels.

  34. Dr. A says:
    February 13, 2021 at 12:54 pm

    I’m disheartened to see you misrepresent the most recent RCT literature on Vitamin D. I wouldn’t expect you to stop after the title when you reference a paper in your posts.

    Just one example: BMD. You say the 2 studies listed do not show benefit on BMD from supplementation. One study was not an RCT for vitamin D supplementation vs placebo, but instead comparing usual supplementation with high-dose. It does NOT answer the question about the efficacy of usual dose supplementation on BMD. The second study on BMD has terribly high p-values, again, NOT proving that supplementation is ineffective.

    It’s this kind of superficial thinking that confuses the public when the source is deemed “trusted.” I’d expect this from a guru.

  35. ken osborn says:
    February 13, 2021 at 1:22 pm

    In 2008 an acupuncturist I was seeing recommended taking vitamin D at 5000 IU/day to reverse some moderate bone loss. I have a background in chemistry/toxicology and I thought this was crazy. I almost considered cancelling further appointments. Together with a research chemist we did some calculations: my days of swimming and all day full-body exposure to the sun (not recommended these days) gave me the equivalent of 100,000 IU/day! Of course not all of that makes it thru the liver and kidneys to the calcitriol form.

    On the basis of those calculations I started taking 3000 IU/day. It did nothing to rebuild my bones to their former glory but I did notice an almost immediate benefit: prior to taking supplemental vitamin D the annual cold/flu season was continuous for me with multiple infections. In the 2009 season I had no colds and have only had 3 since then. And those have not put me in bed as previous bouts had.

    Later my personal doctor was livid at my taking 3000 IU/day. We agreed I should get a blood test. The results were within the accepted range and my doctor added 3000 IU vitamin D to the list of recommended medications should I get hospitalized. (Which did happen and when I asked a nurse to bring me 3000 IU of vitamin D she initially refused. I asked her to take a look at my prescribed list and she returned with the 3000 IU vitamin D.)

    I know this is a study of N=1, but my personal take is to continue taking supplemental vitamin D along with periodic blood tests to make sure I neither take too much or too little.

    Thank you.

  36. Sharri Hoople says:
    April 1, 2021 at 8:49 pm

    Damn tough!

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

Biography | Disclosures | Summaries

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