MD, PhD, FMedSci, FRSB, FRCP, FRCPEd.

There is some encouraging evidence regarding the positive influence of vitamin D on COVID-19. But is it convincing? Is it causal? As always, it is worth looking at the totality of the reliable evidence.

In this systematic review and meta-analysis, the researchers analyze the association between vitamin D deficiency and COVID-19 severity. They conducted an analysis of the prevalence of vitamin D deficiency and insufficiency in people with the disease. Five online databases—Embase, PubMed, Scopus, Web of Science, ScienceDirect and pre-print Medrevix were searched. The inclusion criteria were observational studies measuring serum vitamin D in adult and elderly subjects with COVID-19. The main outcome was the prevalence of vitamin D deficiency in severe cases of COVID-19.

The researchers identified 1542 articles and 27 met their inclusion criteria. The results show that

  • vitamin D deficiency was not associated with a higher chance of infection by COVID-19,
  • severe cases of COVID-19 present 64% more vitamin D deficiency compared with mild cases,
  • vitamin D concentration insufficiency increased hospitalization and mortality rates,
  • There was a positive association between vitamin D deficiency and the severity of the disease.

The authors concluded that the results of the meta-analysis confirm the high prevalence of vitamin D deficiency in people with COVID-19, especially the elderly. We should add that vitamin D deficiency was not associated with COVID-19 infection. However, we observed a positive association between vitamin D deficiency and the severity of the disease. From this perspective, evaluating blood vitamin D levels could be considered in the clinical practice of health professionals. Moreover, vitamin D supplementation could be considered in patients with vitamin D deficiency and insufficiency, if they have COVID-19. However, there is no support for supplementation among groups with normal blood vitamin D values with the aim of prevention, prophylaxis or reducing the severity of the disease.

These are interesting findings, no doubt. They relate to associations, as the authors repeatedly stress in the text of the paper. They do not, however, signify cause and effect relationships. The principal outcome of this research should be a hypothesis that subsequently needs testing in clinical trials.

So, why on earth did the authors chose that seriously misleading title of their paper? It clearly implies a causal effect; and this can only be verified by conducting clinical trials. One such study has been published (as discussed here) and it concluded that administration of calcifediol may improve the clinical outcome of subjects requiring hospitalization for COVID-19.

My conclusion: it seems well worth conducting more and more rigorous clinical trials.

41 Responses to “Vitamin D deficiency aggravates COVID-19” … ??? … really? … perhaps!

  • Yes, this is a debated topic.
    The excellent German science communicator Mai Thi Nguyen-Kim dedicated her latest video to this topic. As all of her videos, well worth watching!
    https://www.youtube.com/watch?v=ud9d5cMDP_0
    (automatic subtitle translation is available)

    Quick, related question:
    According to your “Lectures & Talks” calendar, you were scheduled to give a talk about “Trust and truth in health research” a couple of days ago. Did this conference take place and will your talk be available online?

    • you were scheduled to give a talk about “Trust and truth in health research” a couple of days ago. Did this conference take place and will your talk be available online?
      YES +YES

  • Confused About Vitamin D? …
    Matt Hancock (the current UK Minister For Health) stood up in the House Of Commons recently and claimed that a ‘trial’ investigating vitamin D had taken place, and that it ‘did not appear to have any impact on the effects of Covid-19’. But officials have since admitted that no clinical trials on the vitamin have been carried out at all. So the Minister ‘mis-spoke’ it seems.
    The Public are rightly confused about the importance of this multi-tasking, immunomodulatory steroidal hormone when British GP’s refuse to provide a test for serum 25(OH)D unless a risk of rickets or serious bone disease is suspected – quite unbelievable.

    While certain academics and pompous professors continue to insist on yet more Vitamin D trials, people are dying. Do they care? We know that Vitamin D at sufficient levels in the blood can help to counter the so called ‘cytokine storm’. Strange that very few mainstream medics disclose what their last Vitamin D blood test result was – wonder why that is?

    I am not embarrassed to tell the world I maintain a consistent level of around 150 nmol/L serum 25(OH)D. My own GP considers this level to be ‘toxic’, but they are unable to produce one shred of evidence to back-up their claim.

    And for your further consideration this latest paper concludes:
    Low 25(OH)D levels on admission are associated with COVID-19 disease stage and mortality.
    https://pubmed.ncbi.nlm.nih.gov/33236114/

    • “We know that Vitamin D at sufficient levels in the blood can help to counter the so called ‘cytokine storm’”
      evidence please!
      “While certain academics and pompous professors continue to insist on yet more Vitamin D trials, people are dying. Do they care?”
      to suggest to act without good evidence is just plain stupid [said the pompous professor].

      • Top Vitamin D and COVID-19 recent updates

        Clinical trials are proving that Vitamin D fights COVID-19 in hospitals by VitaminDWiki
        Vitamin D should fight COVID-19 (but Irish Consortium recommends only 1,000 IU) – Nov 21, 2020
        Hospital COVID-19 observation: 7X more likely to live if more than 20 ng of vitamin D– Nov 19, 2020
        Severe COVID-19 not fought by vitamin D when given too late – RCT Nov 18, 2020
        Higher vitamin D associated with fewer cases and deaths in India Nov 2020
        Image
        COVID-19 defeated 3x faster by 420,000 IU Vitamin D nanoemulsion – RCT Nov 12, 2020
        2X fewer COVID-19 deaths observed if infrequent vitamin D (2X more deaths if daily dose) – ClinicalTrial Oct 20, 2020
        Vitamin D fighting COVID-19 meets all Bradford Hill Criteria – Nov 2020
        French National Academy recommended 100,000 IU of Vitamin D to elderly to fight COVID-19 – May 2020
        Chinese COVID-19 study – 80 pct of severe cases had low Vitamin D, all asymptomatic cases had OK Vit D – Oct 13, 2020
        Vitamin D and COVID-19 – observational studies found it helps, never hurts – Campbell Oct 31, 2020
        Low Vitamin D associated 1.8X increased risk of COVID-19 death in hosptial – meta-analysis Nov 4, 2020
        COVID-19 lung death 4X more likely in Iran if less than 25 ng of vitamin D – Oct 30, 2020
        Evidence Regarding Vitamin D and Risk of COVID-19 and its Severity – Oct 27, 2020
        COVID-19 patients who happened to be taking Vitamin D did much better – Oct 27,2020
        9X COVID-19 survival in nursing home if had 80,000 IU dose of vitamin D in previous month – Oct 2020
        COVID-19 fought by Vitamin D in 43 studies – Oct 15, 2020
        15 studies indicating that Vitamin D fights COVID-19 – Dr. Grimes Oct 9, 2020
        32X more likely to have severe-critical COVID-19 in Turkish hospital if Vitamin D deficient – Oct 5, 2020
        Image
        Vitamin D Cuts SARS-CoV-2 Infection Rate by Half Mercola Sept 28
        47% lower SARS-CoV-2 positivity rate if > 50 ng vs 30 ng vs < 30 ng
        2X higher risk of hospitialization if <30 ng
        ICU patients got semi-activated Vitamin D – death rate dropped to 2% from 50%
        Virtually no COVID-19 cases in countries having more than 30 ng of Vitamin D – Sept 17, 2020

      • Edzard, I was certainly not inferring you might be a ‘pompous professor’… heaven forbid! My idea of such a person is someone like Prof Sir Rory Collins, a highly respected voice (allegedly) in the medical community. He has often stated in public that ALL adults should take Statins for life as a preventative against cardiovascular disease … that is a voice of someone dancing to the tune of Big Pharma me thinks. As a fit and healthy 74 year old I will continue to respectfully ignore his thoughtful advice.

        • someone like Prof Sir Rory Collins, a highly respected voice (allegedly) in the medical community. He has often stated in public that ALL adults should take Statins for life as a preventative against cardiovascular disease …

          Most of the cardiologists I know seem to believe that everybody should not only take statins, but also aspirin and beta blockers. There was a fourth drug, too, but I can’t remember what (maybe it was clopidogrel, another anti-platelet agent).

          On the other hand, gastroenterologists, and most surgeons, would prefer it if nobody ever took aspirin.

          that is a voice of someone dancing to the tune of Big Pharma me thinks

          No, it is the voice of someone who pays attention to the results of very large prospective randomised trials. Gastroenterologists see the stomach bleeds, and surgeons curse when their view is obscured by blood oozing everywhere, but the prevented cardiac deaths are only visible to epidemiologists.

          As a fit and healthy 74 year old I will continue to respectfully ignore his thoughtful advice.

          I am tempted to wonder what you mean by fit and healthy. Do you know the state of your coronary arteries, for instance? They tend to work quite well until the point where they suddenly occlude and cause a myocardial infarction. Has your family doctor assessed your risk of a cardiovascular event, which would be based primarily on your family history, your previous medical history, your blood pressure, your serum lipid levels and whether you have ever smoked, and to a lesser extent on your weight and exercise habits?

          • @Dr. JMK

            “No, it is the voice of someone who pays attention to the results of very large prospective randomised trials. Gastroenterologists see the stomach bleeds, and surgeons curse when their view is obscured by blood oozing everywhere, but the prevented cardiac deaths are only visible to epidemiologists.”

            Doc, this reminds me of the many oncologist that pat themselves on the back that their cancer patient didn’t die from their specific cancer. However, the effects of the cancer treatment killed them in the end. The oncologist is quite satisfied with this, after all, they didn’t kill the poor chap… DIRECTLY. Proven SCIENCE ! ….everybody cheer. The MD did his job ? …. YES he did, if more patients coming through the door is the goal.
            The psychologist treats the schizophrenic patient with anti-psychotic drugs, makes a small amount of progress treating the ills of the patients mind. However in the end kills the patient from obesity, diabetes, kidney disease, brain shrinkage, or a plethora of other deadly outcomes. Proven SCIENCE …BRAVO !

          • Dr Julian, with respect, your comments are quite ridiculous. You know nothing about my state of health. My medical history is well known to at least two highly qualified Harley Street/Upper Wimpole Street physicians that you would probably know of. I work alongside a number of conventional medics and the other lot you despise (CAM) or SCAM as you prefer – so I receive a balanced overall picture. You may disagree.
            I have also undertaken an aortic pulse wave velocity test that indicated my main arteries are similar to a man appx. 30 years old and my blood pressure is a steady 120/75. … I am happy with that. My exercise includes regular rebounding to maintain good lymph and cardiovascular health and I don’t smoke.
            So how about you Julian?
            Did you know that some Statin drugs can and do cross the blood-brain barrier? Is it just coincidence therefore that some Statin users complain of memory loss and lack of concentration etc? And just out of interest, do YOU take Statins?

          • why does that remind me of an old joke?:
            Alll those health freaks will one day feel very stupid lying in hospital dying of nothing.

          • Mike Grant,

            You know nothing about my state of health.

            Of course not. I only know what you have reported, which isn’t much, and specifically I know nothing about what risk factors you might have for coronary heart disease. However, since you have chosen not to take statins I was curious to know whether or not you might be considered to be somebody who would benefit from them.

            My medical history is well known to at least two highly qualified Harley Street/Upper Wimpole Street physicians that you would probably know of.

            That may be so, though I wouldn’t have thought that this was particularly relevant. For that matter I have been a Harley Street physician myself, though not for very long as I found it rather impractical to practise there. I found it was much easier to keep my private practice close by my NHS one, and safer, too.

            I work alongside a number of conventional medics and the other lot you despise (CAM) or SCAM as you prefer – so I receive a balanced overall picture. You may disagree.

            I despise charlatans and frauds who know very well that their treatments are useless but are happy to prey on people at their most vulnerable. I don’t despise the many alternative practitioners who are well-meaning and hold genuine beliefs, but I don’t share those beliefs when the evidence does not support them.

            I am not sure what you mean by a balanced picture. You must have access to a range of views, but I hope you don’t give them all equal weight

            My exercise includes regular rebounding to maintain good lymph and cardiovascular health

            What is rebounding? Something to do with intermittent short bursts of exercise, or something else entirely? What do you mean by lymphatic health – I suppose something to do with maintaining lymphatic draingage, which in any case shouldn’t be a problem unless you have had lymph node surgery, radiotherapy or filariasis? I can’t envisage any specific type of exercise that might affect lymphocyte function.

            I don’t smoke

            Good. As I am sure you know, smoking is the biggest risk factor of all when it comes to cardiovascular health as well as many other aspects of health in general. It completely swamps the effect of any other lifestyle changes, though people still manage to find all kinds of spurious arguments to justify it to themselves.

            Is it just coincidence therefore that some Statin users complain of memory loss and lack of concentration etc?

            I am not sufficiently familiar with the fine details of statin trials to be able to answer this question. If prospective randomised double-blinded trials found these symptoms to be more prevalent in the treated group then it is not coincidence. If they looked for them and did not find them then it is. If they weren’t designed to show such toxicity then the question remains open.

            These are rather vague symptoms that everybody experiences at various times, particularly if they are looking out for them, and people tend to latch on to any suggested cause which seems plausible to them. On that basis I would expect that for most people taking statins any association probably is coincidental.

            What I do know is that large-scale trials have shown that for those at risk, statins have been overwhelmingly shown to confirm a benefit.

            just out of interest, do YOU take Statins?

            Yes I do, on the advice of my GP. I have never been aware of any toxicity from them.

            When it comes to my own health, I prefer to find doctors who I trust, and let them get on with their job. Outside my own area of specialisation no amount of reading the literature is going to give me the expertise that comes with specialist training, accesss to multidisciplinary meetings and years of experience.

    • Actually, research is finding cytokine storm is only present in a small number of severe COVID cases.

      • seems that Mike, the cherry-picker, reads research highly selectively

        • Edzard, if I am cherry picking these studies ‘selectively’ as you say, then you are welcome to counter them with studies that show otherwise… look forward to reading them.

      • How “small” is “small” Kathryn, don’t those ‘few’ lies matter to you?

      • Kathryn, please provide your evidence as Edzard requires; how do you define a “small number of cases”? I have seen many studies describing the levels of serum 25(OH)D present in a broad range of hospitalised covid patients around the world, indicating that the severity (and number of fatalities) relating to covid-19 are directly linked to
        patient levels of 25(OH)D on admission to hospital. If you provide your evidence on this forum I will then reply with published studies to counter your claim.
        However, apart from each of us trying to score points, you seem to have a wider agenda – implying that Vitamin D
        has no significant ability to support the human immune system – why would that be I wonder?

      • Hello again Kathryn, I’m keen to avoid some possibly misleading reporting in the media. Please let me know exactly what you mean by your claim: “research is finding cytokine storm is only present in a small number of severe COVID cases”. I look forward to reading any evidence supporting your assertion.

  • I don’t think it would be possible to investigate this ethically in a clinical trial, since the question being asked here is what effect vitamin D deficiency has on the risk and severity of Covid-19. A trial would necessitate a control group consisting of people who have been diagnosed with vitamin D deficiency, which we know can have serious adverse consequences, and then leaving them untreated. It would also require a large number of subjects since only a small proportion of them would (hopefully) be expected to contract Covid-19 at all.

    For this kind of question, observational studies, with all their shortcomings, are the best we are going to get. It is very often the case that doctors are faced with the need to make a clinical decision when the evidence upon which they would like to base it simply isn’t there, or (more likely) is there but is not very good evidence.

    • And your real point is?….

      • The observational studies that have been summarised show a correlation between low vitamin D levels and worse outcomes, but as we know, correlation does not imply causation, and this type of study does not correct for confounding factors.

        My real point is that, while it would be interesting to know whether vitamin D deficiency has an adverse effect on the outcome of Covid-19, if somebody has been found to be deficient then we already know that they require treatment regardless (this follows, more-or-less, from the very definition of a vitamin), and it is not ethical to withhold that treatment for the purpose of a randomised controlled trial to investigate whether such deficiency causes additional problems over and above those that are already known.

        A different question, which still needs answering, is whether there is any beneficial effect, either on the risk of becoming infected or on the severity of illness, from giving supplements to those whose baseline vitamin D levels are in the normal range. Another way of looking at this is whether what is currently considered to be normal might actually be sub-optimal.

        In the meantime, as usual, doctors faced with sick patients are not in a position to wait for the outcomes of trials that have not yet been completed (or started) and have to use their judgement.

  • Is it me or do good ol’ vitamins A B C D continue to kill all life ills, seems every 10 yrs one of aforementioned will kill current disease. Well, according to our scientific research at chiro, homeopath, and naturopathy world lab. Where is this research facility, what country?

    • try to make some sense, please.

    • Jim, seems you should get yourself educated – with the greatest respect naturally! Vitamin D is NOT simply a “good ol’ vitamin” as you describe it. Vitamin D ends up as Calcitriol thanks to a complex set of pathways in your body. This is described by scientists and medics who know their subject as an ‘immonumodulating steroidal hormone’ and our immune cells have receptors designed to accept those immunomodulating Calcitriol molecules. If you disagree with that claim, then let’s see your evidence. And your thinking is severely muddled when you make references to chiro, homeopath and naturopothy… where on earth are you getting your knowledge from I wonder?

      • Mike,

        This is described by scientists and medics who know their subject as an ‘immonumodulating steroidal hormone’

        They appear to be using the worlds “steroidal” and “hormone” to mean something different from the definitions I was taught at medical school.

        • … and you real point is?

        • When did you leave medical school out of interest?

        • So what that you were taught something different at medical school ….there are many examples of differing words and phrases in medical language that in effect mean the same thing.

          • there are many examples of differing words and phrases in medical language that in effect mean the same thing.

            That is true. You can refer to an infarct resulting from a middle cerebral artery occlusion as a cerebrovascular accident, a stroke or apoplexy, and often eponyms, descriptive English names and Latin terms can all refer to the same thing.

            However, technical terms such as hormone have a precise definition to avoid ambiguity. You never hear doctors talking about heart attacks, for instance, as this is medically meaningless. Sometimes a medical term might suggest something completely different to the layman, such as heart failure, which properly does not refer to cardiac arrest.

            Occasionally workers in different branches of medicine will use the same term in different ways, which can be confusing and is best avoided. PND, for instance, can be post-natal depression, post-nasal drip or (most commonly) paroxysmal nocturnal dyspnoea.

  • https://khn.org/news/how-michael-holick-sold-america-on-vitamin-d-and-profited/
    Here is an interesting read on the debate on what levels of vit D are low enough to be deficient and how recommendations have been skewed by special interests.

  • Since you requested ‘evidence’, here are the summaries and links to just two of dozens of examples that associate calcitriol to the effects of covid-19. People are dying, and the majority of those fatalities are deficient in circulating 25(OH)D… but you already know that, yes?

    “We show FOR THE FIRST TIME that the active form of Vitamin D, CALCITRIOL, exhibits significant potent activity against SARS-CoV-2 … this is the first report of a DIRECT INHIBITORY EFFECT of CALCITRIOL on SARS-CoV-2”.

    “….Vitamin D deficiency markedly increases the chance of having severe disease after infection with SARS Cov-2. The intensity of inflammatory response is also higher in vitamin D deficient COVID-19 patients. This all translates to increased morbidity and mortality in COVID-19 patients who are deficient in vitamin D”.

    https://www.nature.com/articles/s41598-020-77093-z

    https://www.biorxiv.org/content/10.1101/2020.06.21.162396v1.full

  • I am complying with requests for EVIDENCE relating to Vitamin D and look forward to receiving a charge of ‘cherry picking’. Here is the link to yet another paper for your perusal:
    “CONCLUSIONS:
    Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.
    https://www.bmj.com/content/356/bmj.i6583

    • why would anyone say this is cherry-picking.
      it just has little to do with COVUS-19, that’s all.

      • Oh Edzard, how many more papers are you gong to dismiss? If this study doesn’t give us all some relevance to Vitamin D and viral pathogens, then I must question your judgement. Read on;

        “…The present study demonstrates an association between VitD deficiency and severity of COVID-19. VitD-deficient patients had a higher hospitalization rate and required more (intensive) oxygen therapy and IMV. In our patients, when adjusted for age, gender, and comorbidities, VitD deficiency was associated with a 6-fold higher hazard of severe course of disease and a ~15-fold higher risk of death”.

        https://www.mdpi.com/2072-6643/12/9/2757/htm

  • Those who dismiss Vitamin D (Calcitriol the active form) as not having any significant relevance or benefit for our immune system only highlights the blinkered thinking of a certain section of mainstream medicine who for their own reasons choose to remain in denial. I will continue to publicise valid papers, observational studies and informed opinion so the medical profession might one day agree on this subject:

    Another paper (link below) offers these key recommendations:
    There seems nothing to lose and potentially much to gain by recommending vitamin D supplementation for all, e.g. at 800–1000 IU/day, making it clear that this is to help ensure immune health and not solely for bone and muscle health.

    This should be mandated for prescription in care homes, prisons and other institutions where people are likely to have been indoors for much of the time during the summer.

    People likely to be currently deficient should consider taking a higher dose, e.g. 4000 IU/day for the first four weeks before reducing to 800 IU–1000 IU/day

    People admitted to hospital with COVID-19 should have their vitamin D status checked and/or supplemented and consideration should be given to testing high-dose calcifediol in the RECOVERY trial.

    We feel this matter should be pursued with GREAT URGENCY. Vitamin D levels in the UK will be falling from October onwards as we head into winter.

    https://royalsocietypublishing.org/doi/10.1098/rsos.201912

    • Bravo Mike Grant! Thanks SO MUCH for standing up and speaking for the many, many average citizens who have the interest and taken the time to educate ourselves on the significant benefits of having adequate Vitamin D levels. COVID-19 has only brought this issue into sharper focus. It’s nothing short of bewildering that virtually all medical authorities and “experts” remain silent on this (or worse — make statements that sow fear, uncertainty and doubt), while at the same time giving tacit approval to the current disastrous practice of forbidding people from living normal lives and working to support themselves. Anyone with more than two functioning brain cells knows there’s absolutely zero proven health risk and considerable upside to moderate Vitamin D supplementation, but significant danger to mental and physical health (amongst numerous other negatives) and very little demonstrated benefit from these never-ending lockdowns. It’s so painfully obvious that Vitamin D should be vigorously promoted, at the very least as part of the effort to contain the coronavirus and prevent illness and death.

      I often wonder if any of our health authorities ever consider that their credibility and that of the entire public-facing medical profession is seriously at stake — and won’t be there at all when they need it perhaps even more if/when the next pandemic hits.

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