According to a November 28 press release from the Department of Health & Social Care, the UK government is planning to distribute free Vitamin D supplements to 2.7 million of the most vulnerable people in Britain this winter, a move already taken by the Scottish parliament. This is welcome news to the hundreds of researchers and medical professionals who have been urging governments and healthcare bodies since the beginning of the pandemic to pay more attention to the growing body of evidence that Vitamin D reduces the incidence, severity and mortality of Covid 19.
In September, the evidence was amplified when David Meltzer, an internist and economist at the University of Chicago, and his colleagues, published the results of the first analysis of Vitamin D deficiency with testing positive for Covid-19. The results found people low in Vitamin D to be “at substantially higher risk of testing positive for Covid-19”. In study after study (40+ at the last count) researchers the world over have been discovering significant correlations between Vitamin D supplementation and reduced severity of Covid-19 symptoms, including fewer deaths.
So why did it take the UK government so long to begin talking seriously about Vitamin D? And why is the messaging still so muted?
Although the supplement distribution is a welcome move, with all the evidence now amassed and health professionals in such vigorous agreement as to its significance, what we should be seeing is a massive public health campaign around Vitamin D, with state funding of large-scale clinical trials. Hopefully, this is just around the corner since the government has announced a reviewal of the evidence. And yet, disappointingly, the media is not holding the government to account. In their article announcing the planned free distribution of supplements, the BBC claimed that ‘there is limited evidence that vitamin D protects against or treats Covid-19’. This echoes the statement of Health Secretary, Matt Hancock, who said in a parliamentary session in September that government-led research did not ‘appear to have any impact’ on the virus, when in fact, officials admitted that no such trials have been conducted. Whether this was a genuine mistake on the part of the Health Secretary or an intentional obfuscation is anyone’s guess.
Some of the confusion about what constitutes reliable evidence lies in the difference between observational studies and controlled clinical trials. Clinical trials are the gold standard for medical research, and include a control group (or placebo group) and an experimental group; the one that receives the intervention. However, when the resources are not available for control studies, well-designed observational studies, particularly of larger populations, can be extremely valuable in determining associations between specific exposures and results. Whereas it is true that a few of the studies have not demonstrated a statistically significant link between Vitamin D supplementation and improved Covid-19 patient outcomes, the findings of dozens of peer-reviewed, randomized, double-blind, observational studies suggest otherwise.
As far back as May, Joanne. E. Manson, Prof. of Medicine at Harvard Medical School described the evidence as being “quite compelling” that Vitamin D offers protection against infection and complications from Covid 19, ”particularly against the severe reaction cytokine storm.” Rose Anne Kenney, from Trinity College Dublin called the evidence, “very strong.” And in his letter to the British Medical Journal on October 5, Australian GP, Peter J. Lewis echoed these and other voices, when he referred to the evidence from research studies as “overwhelming”.
Large scale controlled clinical trials require serious funding, organization and human resources, which is why, especially when there is no drug company behind the intervention, they more often require governmental support. For the past several months, doctors, scientists and healthcare professionals have been calling for such trials to be conducted into Vitamin D and Covid-19 on the strength of the results of the numerous observational studies. This issue has been raised in several BMJ Rapid Responses and can be read in the conclusions of many of the researchers themselves, often in quite urgent terms.
Thankfully, (although apparently unbeknownst to the Health Secretary or the BBC) we now have two, albeit quite small, controlled clinical studies on Vitamin D and Vitamin D analogues in the treatment of Covid-19. The most recent was carried out in India and was published in Nature on 19 November 2020. This study concluded that Vitamin D deficiency not only markedly increases the chance of having severe disease after infection with SARS Cov-2, but that Vitamin D deficiency translates to increased mortality.
The first randomized clinical trial in the world on Vitamin D and Covid-19 was conducted at the Reina Sofía University Hospital in Spain and the results were published August 29 in The Journal of Steroid Biochemistry and Molecular Biology. The results were clear. Vitamin D supplementation improved outcomes for Covid-19 patients, reduced the chances for ending up in intensive care, and reduced mortality. The researchers are now extending the study throughout hospitals in Spain.
These two clinical studies support a number of the findings of the other 40 or so observational studies on Covid-19 and Vitamin D:
- There is a greater incidence of Covid-19 in Vitamin D deficient patients and Vitamin D deficient people are more likely to test positive for the virus.
- Covid-19 patients with low Vitamin D levels are more likely to be hospitalized.
- Vitamin D supplementation reduces the likelihood of a Covid-19 patient going to intensive care.
- Vitamin D offers a protective effect both in terms of symptoms and survival in those who take it as a regular supplement before contracting the virus.
- Supplementing with Vitamin D, or exposure to UVB radiation that forms Vitamin D through the skin, reduces Covid-19 fatalities.
- The most gains are experienced in patients who are more severely Vitamin D deficient.
- Moderate doses are more effective than high doses.
Vitamin D deficiency is a global problem but its safety and usage is well-established and understood. Vitamin D toxicity is extremely rare and there are no nasty side effects at the doses being recommended. We can source it from fatty fish, cheese, eggs, and beef liver, but we get most of it from sunshine. Healthcare professionals have long advised supplementation of Vitamin D in the Winter, since the the lack of sun leads many, particularly the elderly, to become deficient. Vitamin D has been found to enhance innate immunity and suppress the expression of pro-inflammatory cytokines. The link between strong Vitamin D levels and resistance to respiratory infections has also long been known. And now we have persuasive evidence that Vitamin D can play an important part in any treatment program for the coronavirus.
You would think that in light of this, international and government health agencies would be lining up to conduct the kind of clinical trials that would remove doubt once and for all. Yet there have been none so far, neither by the World Health Organization as evidenced by their International Clinical Trials Registry Platform (WHO ICTRP), the CDC, nor the National Institutes of Health. In fact there are currently no federally funded clinical trials of the effects of Vitamin D on Covid-19 at all. One can’t help but wonder, if we were we talking about a new or redeveloped drug that could be marketed to giant profits and reputational acclaim, whether the enthusiasm would be greater. After all, the discovery that hundreds of others have already made that an ordinary Vitamin (actually a hormone, but let’s not nit pick) that anyone can get reading the newspaper in their back garden on a sunny day and costs pennies to produce commercially can help Covid-19 patients is not exciting to those driven by such motivations.
As Robert A. Brown, Chair and researcher at the McCarrison Society, a nutrition-based think tank, writes in the BMJ, ‘…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.’
Fortunately, institutions are now taking it upon themselves to forge ahead with clinical trials of Vitamin D and Covid-19. There are currently 59 such trials either planned or already underway around the world, including several in the United States and a large trial in planning by Queen Mary University of London funded by Barts Charity.
Such large scale clinical trials could easily have been supported by the likes of the Gates Foundation that has made Covid-19 a central focus of their current work. In May, the Gates Foundation joined forces with Wellcome and Mastercard to the tune of 125 million dollars to ‘identify potential treatments for COVID-19, accelerate their development, and prepare for the manufacture of millions of doses for use worldwide.’ This initiative is being coordinated by the Covid-19 Therapeutics Accelerator which is seeking international investment of ‘at least’ 11.6 billion USD over the next year. Back in March, the Therapeutics Accelerator donors announced grants of $20 million to three institutions—the University of Washington, University of Oxford, and La Jolla Institute for Immunology—to fund clinical trials in order to identify highly potent immunotherapies for the current pandemic. None of these institutions are engaging in clinical trials of Vitamin D in treatment of the disease.
Currently, the only FDA-approved Covid treatment drug is remdesivir, produced by the biopharma giant Gilead Sciences and sold under the brand name Veklury. Remdesivir was also the first Covid treatment drug to receive a conditional marketing authorization in Europe. Surprisingly, the WHO recommends against its use, having stated that there is no evidence that it improves survival or helps people stay off ventilators. Last month, Therapeutics Accelerator, granted 500,000 USD to Almac to develop production of a drug for the treatment of Covid-19. That drug was remdesivir.
From a business point of view, remdesivir kicks Vitamin D out of the park. While remdesivir costs over 3000 dollars for a 5-day course, a one month supply of Vitamin D3 will set you back around 4 dollars. Vitamin D is not and cannot be patented. It can be made very cheaply in huge amounts with production not confined to a single country or region.
The reluctance to invest in clinical trials or to promote the robust body of evidence for a cheap and easily scalable intervention for Covid-19, raises many questions about the influence of the pharmaceutical industry and their backers and lobbyists on government health ministries and public health policy. How these relationships might be impacting the interests of public health should be cause for concern. Hopefully, the full force of scientific inquiry and the integrity of thousands of researchers and health professionals who genuinely seek to improve the outcomes for people affected by this disease will prevail. Fortunately in this case, if our institutions fail us, we need go no further than our local chemist, or – weather permitting – our own back yard.