Sixty seconds on . . . vitamin DBMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m3872 (Published 05 October 2020) Cite this as: BMJ 2020;371:m3872
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Vitamin D and Corona virus infection
Dr Holick has noted that Vitamin D deficiency is a global health issue that afflicts more than one billion children and adults worldwide. He also observed an association of vitamin D deficiency with many acute and chronic diseases and Vitamin D deficiency is pandemic (1). Ilie and colleagues observed relationships between vitamin D levels and the number COVID-19 cases and also the mortality caused by this infection. Elderly people have a low vitamin D level (2).
Recently an Israeli study done by Dr Merzon and colleagues shows that suboptimal plasma vitamin D levels may be a potential risk factor for COVID-19 infection (3). This study is helpful for healthcare systems in identifying people at risk, and to reduce the risk of the COVID-19 infection. (3). Low plasma 25(OH)D level appears to be an important risk factor for COVID-19 infection (3).
To reduce the risk of infection, Dr Grant and colleagues recommended that people at risk of influenza and/or COVID-19 should consider taking 10,000 IU/day of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/day. The world is in the grip of the COVID-19 and pandemic, and public health measures can reduce the risk of infection. Vitamin D may act by inducing cathelicidins and defensins that can lower viral replication rates (4).
Hence vitamin D is likely to be very useful in reducing the the spread of corona virus infection.
Dr Mahantayya V Math
Honorary Associate Professor in Physiology
Dr Rita M khadkikar
Associate Professor in Physiology
Dr Yashoda R Kattimani
Associate Professor in Physiology
MGM Medical College, Navi Mumai 410209, Maharashtra State ,India
1. Holick, M.F. (2017) The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord, 18, 153 -165.
2 Ilie, P.C., Stefanescu, S. and Smith, L. (2020) The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging Clin Exp Res .
3. Merzon E, Tworowski D, Gomany rohovski A, et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study [published online ahead of print, 2020 Jul 23]. FEBS J. 2020;10.1111/febs.15495. doi:10.1111/febs.15495
4. Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, Bhattoa HP. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients. 2020 Apr 2;12(4):988. doi: 10.3390/nu12040988. PMID: 32252338; PMCID: PMC7231123.
Competing interests: No competing interests
Vitamin D Mitigates COVID-19, Say 40+ Patient Studies (listed below) – Yet BAME, Elderly, Care-homers, and Obese are still ‘D’ deficient, thus at greater COVID-19 risk - WHY?
Vitamin D reduces COVID-19; infection; severity; ICU admission and mortality: as clearly evidenced by; immune biology, observational and interventional studies, and wider considerations of; latitude, seasonal UVB exposure, and national supplementation policies: the uncertainty is the quantum: but studies suggest ‘D’ effects are likely large - 50% less infectivity – multiples lower ICU and mortality rate.
Vitamin D is a steroid hormone, also present in limited dietary sources. For most, the major ‘D’ source is skin exposure to UVB in sunlight, which waxes and wanes seasonally. Supplementation is the only other option. ‘D’ with 50 metabolites is more bio-actively influential than appreciated. Sensible ‘D’ supplementation has a 100-year track-record. Side-effects are minimal.
Dexamethasone in the same structural steroid family as ‘D’, shares common VDR (vitamin-D-receptor) and related gene pathways, is artificial, and in some circumstances mitigates against COVID-19, albeit with variable side-effects. Dexamethasone is clearly a useful adjunct.
‘D’ deficiencies are widespread globally, and particularly in; BAME, African Americans, Elderly, Carehomers,[6, 7] (Reality-check ref.) and Obese Persons; groups also at high-risk of COVID-19. Regions with proactive Vitamin-D-policies, education, nutritional supplementation, and/or greater UVB exposure, have much lower COVID-19 infection and mortality; e.g. Finland, Norway, New Zealand and, Equatorial-Africa (despite poverty / high urban-multi-person-dwelling-occupation).
Appropriate vitamin D supplementation risks are small: rewards huge. Public policy application of Bradford-Hill risk / harm criteria, used for smoking, social-distancing and masks, would support ‘D’ supplementation of at-risk groups, and ‘D’ testing of all COVID-19 hospital patients.
Parachute RCTs studies (Smith & Pell. J CBE ) [10, 11] ; analogies for research situations of observable risk reduction, but limited viable ethical alternatives; incisively, with wry humour, highlight risks of overly focusing on para-RCT-centric research.
Patient-based-studies; four interventions [12-14, 85]; a retrospective examination of clinical practice; and thirty-nine observationals,[16-50, 86] three more are questioned;[51-53] some are preprints. All consider, mixed-size pre-and -or-post-infection ‘D’ samples, and COVID-19 positive patients. All studies variously evidence mitigation of COVID-19 infectivity and/or severity, by ‘D’.
Additionally, Biobank-study ‘D’ data (all over 10-years-old),[54-56] showed positive associations before adjustment. Comorbidities adjusted for, are impacted by vitamin D levels, making evaluation complex. EPIC vitamin D data had no date-limits.
Latitudinal, COVID-19 seasonality, and wider, studies, including of polymorphisms, grow in number; including those referencing historic pandemics and influenzas: Juzeniene is a stand-out. Latitudinal studies[63, 64] are helpful, but limited by availability of current accurate population ‘D’ data.
An in-vitro study, observes; “Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2.”
Numerous studies, explain vitamin D’s central genetic evolutionary,[67, 68] and wider role, in immune modulation, through multiple various and diverse  pathways, including via peroxisomes and mitochondria. More generally, studies link low ‘D’ with negative wider health effects including increased mortality.
Early 2020 hypotheses linking COVID-19 infectivity / severity, to vitamin D, include; Grant, Brown, and Davies. Helpful summaries include Benskin.
The urgent need for major studies, has been raised in several BMJ Rapid Responses.[76-82]
Collectively, studies strongly suggest essential prohormone-and-nutrient vitamin D, is a far more effective potential basal COVID-19 treatment, than any additive pharmaceutical available to date. Pharmaceuticals and vaccines are ultimately appreciated adjuncts, to meeting essential evolutionary biological nutrient intake imperatives.
Immediately testing of all COVID-19 hospital patient admissions for vitamin D, and supplementing where necessary, according to established NICE guidelines, would provide time for new protocol, RCT-clinical-trials.
Thus, there is every reason to ‘D’ test hospitalised COVID-19 patients. Arguably, not to do so, in light of study outcomes to date, risks negligence. Judges, if asked, may take a broad-view in weighing evidence.
Since late January 2020, a loose group, have requested major clinical studies of sufficient power, including in care-homes, and hospitals. I thank Cooper, Grant, Grimes, Lahore, Pfleger, Rhein, Shotwell, Sarkar, and others, for sharing.
However, high-level drive and funding, have been lacking, exacerbated by the Wellcome-Gates-Accelerator exclusion from funding of ‘D’. Consequentially, research establishments excluded ‘D’ trials, focusing instead on repurposing, and new drugs, including in care-home settings. ‘D’ studies would reduce the study patient pool: further, successful ‘D’ outcomes may reduce funding for long-shot studies.
‘D’ is a non-patentable product family, produced by evolution, for which humans can garner no credit, with limited financial drivers to satisfy eternal human-yearning for golden but elusive bonanzas.
Overall, if the depth of information, and number of studies on ‘D’, consistently pointing in the same direction, related to a new COVID-19 ‘drug’, with minimal side-effects, it would have been front-page-news. Additional clinical research would have been prioritised with determination and alacrity, and ‘D’ by now, licensed as a standard-treatment-protocol.
In terms of saving lives, mental health and economies, it is inconsequential whether deficiency is due to pre-existing low-levels at infection, or infection driven catabolism. IF the issue was dehydration, nobody would dream of saying, ‘withhold treatment until determination if dehydration was due to; fever, or low historic water intake pre-infection’.
Surely the simple steps, of ‘D’ supplementing, and/or testing-and-supplementing, of at least all COVID-19 patients, and high-risk-persons, should be implemented as a matter of urgency. Thought-provokingly hospital ‘D’ supplementation was standard practice in Daniel Drake Center for Post-Acute Care in Cincinnati for many years.
Absent: authorities; redirecting resources and research-focus; changing public health and hospital testing and supplementation policies, to ones that fully recognise the often-discriminatory impact and extent of ‘D’ deficiency disease, particularly in high risk groups; and funding and driving of urgent further ‘D’ research; human-frailties dictate ‘D’ will be shuffled into the pending-tray; notwithstanding observed 50% ‘D’ related reductions in infection (Kaufman 190,000 patient-base),[27, 39, 41] and reductions in ICU patients by multiples (Castillo, Tan et al).[12, 17, 31, 45, 48]
Pragmatic recognition of the need to: supplement ‘D’ in; high risk groups, COVID-19 hospital patients, and more widely; eliminate the ‘social-injustice’[6, 7] of vitamin ‘D’ discrimination against; BAME, the Elderly, Carehomers and Obese; reduce infection, ICU pressures and mortality, so public fear: could provide a cheap resource-and-cost-saving basal treatment protocol, added to by vaccines, a ‘paradigm-shift’ enlightening bleak COVID-19 outlooks, empowering people, thus possible exit from D-deficient COVID-19 pandemic shadow-lands, steering a ‘D’ course to a brighter pastures.
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Competing interests: No competing interests
The government have just announced a six month trial to see whether Vitamin D can protect against Covid . The first Rapid Response on this topic was from Peter Cobbold on 2 March  more than seven months ago since when there has been a steady stream of correspondence. The government seem to have kicked the matter into touch for many months more, perhaps beyond the point when they hope to somehow be distributing vaccines against the virus. But arguably they could have just endeavoured to make sure everyone’s Vitamin D levels were up to scratch in the first place all those months ago, which would have protected the population against all infectious diseases and not done any harm. This was something seemingly they never wanted to do, and for which they should still be answerable.
 Vanessa Chalmers and Luke Andrews, ‘ UK doctors will finally trial whether vitamin D can protect people from Covid-19 after months of mounting evidence the cheap supplement could be a life-saver’, Daily Mail 13 October 2020, https://www.dailymail.co.uk/news/article-8834307/Doctors-trial-vitamin-D...
 Peter H Cobbold, ‘ Re: Preventing a covid-19 pandemic‘, 2 March 2020, https://www.bmj.com/content/368/bmj.m810/rr-1
Competing interests: AgeofAutism.com, an on-line daily journal, concerns itself with the potential environmental sources for the proliferation of autism, neurological impairment, immune dysfunction and chronic disease. I receive no payment as UK Editor
It is natural to experience fatigue at another imperfect trial prematurely heralding the efficacy of Vitamin D, but I was disappointed the recent Spanish pilot RCT trial was not referenced in the article:
Unfortunately it was small (26 in control arm) so the 2 deaths in the control arm did not achieve statistical significance.
The ICU admission rate of 50% was suspiciously high in the control group, especially as ICU admission criteria were partially dependent on presence of co-morbidities, given that hypertension and diabetes (and being male) were over-represented in control group despite non-placebo randomisation. BMI information was also not collected nor was baseline vit D status.
However, the patients randomised (at 2:1) to the calcifediol 25(OH)D arm registered only 1 patient (2%) admitted to ICU and no deaths.
Given that vitamin D replacement/supplementation is well tolerated and deficiency is common, if I were in a high risk group or advising a high risk patient/group, I would be tempted to use standard vit D prophylactically or a fast acting analogue if treatment was needed, especially with winter coming, until further RCT evidence refutes these preliminary findings.
Competing interests: No competing interests
Drs Lewis and Rhein, and many other clinicians, regard supplementation with D3 as a preventive therapy for Covid19. And I agree..
But D3 is far more than an alternative therapy to, say, dexamethasone, et cetera. When we ask: why is SARS-CoV-2 so sucessful as a virus when SARS-CoV and MERS failed to go pandemic, we see yet more reason why having a physiological level of D3 is so important. Unlike SARS and MERS, SARS-CoV-2 expresses spike proteins with a far higher affinity for ACE2 that acts as the receptor giving the virus entry into cells (https://www.nature.com/articles/s41423-020-0400-4#Sec2) ACE-2 presentation on cell surfaces is heightened in D3-deficiency as a result of sub-optimal renin production. This pathway explains the link between hypertension and low D3 and arguably the higher mortality from Covid-19 of hypertensives.
A fuller analysis deserves longer than 60 seconds (there is a chicken and egg conundrum to explain). D3 deficiency as judged by physiological level (25(OH)D 100 to 150 nmol//L) is widespread, indeed the norm, in developed nations, allowing this virus to proliferate. The virus is not clever, it's us who have been dumb to D3 for decades.
Competing interests: No competing interests
I couldn’t agree more with my Australian GP colleague, Dr. Peter Lewis.
We have well reported widespread vitamin D deficiency in the UK. Vitamin D, however, is undisputedly an important actor in the immune system. Why, therefore, do we have to prove that it is beneficial not to be D-deficient, especially now, during a pandemic, when our immune systems should be in perfect condition to battle viruses?
But we tolerate that half the population is grossly deficient, the other half less so, but still deficient. And call it 'genetic' when far too many people of BAME back ground died of covid19.
Why would we only be told about this vitamin deficiency when a link to covid19 can be proven?
Why do our public health departments hesitate? Why not think of a practical solution, as suggested by 7 professors and consultants of the UK and Ireland in a letter to The Times today (6/10/20)? Why not give vitamin D the benefit of the doubt? Why not look to our neighbouring countries? For instance, Norway, Sweden, Finland, who have similar latitude, genetics, climate, but all have a much higher awareness of the need to take sufficient supplements, as well as public implementation of effective food fortification. In spite of the latest NICE review, ample evidence does exist, if one cares to look.
Competing interests: No competing interests
There are now close to 30 or so studies demonstrating that having optimal blood levels of 25(OH)-vitamin D (75-150 nmol/L) reduces covid-19 risks: reduced risk of infection; reduced risk of severe disease; reduced risk of dying. Many researchers now regard the evidence as ‘overwhelming’. Despite this, there still will be those who say that we need ‘more research’, but in the meantime, there is little to be lost (vitamin D supplements are inexpensive and have low risk of toxicity) and a huge amount to gain by recommending a decent daily dose of vitamin D3 (say 1-2,000 IU for children and 4-5,000 IU for adults).
Competing interests: No competing interests