COVID-19: Scientists raise the vitamin D alarm

By Nikki Hancocks

- Last updated on GMT

Getty | solarseven
Getty | solarseven

Related tags Vitamin d COVID-19

A group of researchers and doctors have formed an international alliance aiming to encourage governments to increase recommendations for vitamin D intake to 4,000 IU daily as they believe this would reduce COVID-19 hospitalisations.

The group action involves a public awareness campaign, petitions and calls to MPs. They also plan to write an international open letter to the world’s governments.

Dr Gareth Davies, (PhD Medical Physics, Imperial College, London), says the UK government’s recommendation of 400 IU daily of vitamin D is 10 times smaller than the group believes is necessary during this global pandemic. Those in the alliance believe that 4,000 IUs daily should be sufficient to ensure a healthy immune response in most people, with some in the group advocating a short course of up to 10,000 IU in cases of severe deficiency.

Between March to July 2020, Dr Davies has been working full time as an independent coronavirus research scientist, and has continued part-time thereafter. Much of his research has been around this vitamin. He says much of the confusion around vitamin D stems from the fact it is so poorly understood, firstly due to the fact it isn’t actually a ‘vitamin’ but a steroid pre-hormone produced in the skin in strong sunlight which is then converted into an active hormone by the liver and kidneys.

“For most people, the idea that a simple over-the-counter vitamin can actually help fight a pandemic is so preposterous and I think this is largely due to the fact it is referred to as a ‘vitamin’ when it’s not; it is an essential hormone which the immune system requires in order to function adequately.”

Dr Davies explains that whilst research around this hormone first centred around the avoidance of rickets, our knowledge of the health benefits of this hormone are now far more far ranging and we now understand that it is a key component to the function of our immune system.

Scepticism and confusion

Dr Davies argues that much of the confusion and scepticism around the research into vitamin D, immunity and COVID-19 is due to the fact that research will often show a correlation and this is not seen to be causation. But Dr Davies disagrees with this conclusion.

“Correlation isn’t always causation but that word ‘always’ is critical because sometimes – and often – correlation is causation. Most doctors wrongly think clinical trials are the only way to infer cause, but we can actually do this more effectively by analysing large data sets using modern techniques.”

He and two collaborating doctors, published a preprint of their research in May, drawing on methods from Physics, Data Science and Artificial Intelligence in which they conclude that vitamin D deficiency causes severe COVID19 disease in response to the Sars-Cov-2 virus. Their two part analysis looked at 1.6 million data points of deaths and recoveries from 240 global reporting locations. 

In June, the UK government ordered an evidence review into vitamin D and COVID-19​ but Dr Davies says the scientific community was up in arms’ following the NICE report​. 

Our paper​ was one of just 13 preprints acknowledged by the NICE evidence review - but was listed in an appendix of preprints excluded due not yet being peer-reviewed. Peer-review takes up to a year in normal conditions and though hundreds of studies had been published, very few had been peer-reviewed. 

“NICE reviewed only five papers, four for the hypothesis and one against, ignoring the hundreds of other pre-print studies on SARS-CoV-2 and vitamin D, and thousands of studies published on prior coronaviruses and vitamin D. 

“In a fast moving global pandemic such as this when so much new research is being carried out, surely they should look at the newest research?”

Speaking about concerns around overdosing, Dr Davies says he can’t understand why that concern would outweigh the urgent concern of the pandemic. 

“People make this hormone when their skin is exposed to the sun. If there is danger of people overdosing on this hormone then where are those people and why aren’t we overdosing when we spend too much time in the sun? Coronavirus has killed one million people and governments are concerned about vitamin D overdosing!"

Vitamin D and the immune system 

“If vitamin D levels are high, the innate immune system is strong,” explains Dr Davies. “This is the first line of defence the body employs when a pathogen first invades. In many cases, the innate immune response can entirely deal with an invasion before it takes hold. 

“It’s also involved a health adaptive immune response. This is a slower response where the body begins to make antibodies that specifically target the invading pathogen if it fails to control it via innate immune response.” 

Dr Davies points out there’s a very specific reason this hormone is important with the COVID-19 virus, due to the mechanism by which it enters our cells. 

“It targets a protein spike on cell surfaces called ACE2 which is part of something called the renin-angiotensin system or RAS. Among other things, the RAS regulates blood pressure and inflammatory response. To use a metaphor, it’s like an engine with an accelerator and a brake. To tackle an infection the accelerator is pressed to ramp up inflammatory response to deal with the invading pathogen, but the brake also is depressed to keep things under control. 

“When the invasion is dealt with, the accelerator comes off and the brake brings everything down to an idling state again. The ACE2 protein is the brake, but ACE2 is depleted as the virus replicates which effectively breaks the brake. With only an accelerator, the RAS quickly runs out of control leading to cytokine storm, out-of-control inflammation and the lungs fill up causing pneumonia. This is what kills people. Vitamin D helps here by keeping the accelerator under control by suppressing a mechanism further upstream that activates it. 

“We also know that the ACE2 receptors are normally ‘invisible’ when the RAS is in its idle state, as they ACE2 receptors form a bound complex with another cell receptor. This complex comes apart during the inflammatory response when ACE2 is needed, but this also makes it visible to the virus. Vitamin D helps to keep the RAS calm so that ACE2 remains hidden.” 

NHS advice

The government says it has issued new vitamin D recommendations "to ensure that the majority of the UK population has satisfactory vitamin D blood levels throughout the year, in order to protect musculoskeletal health".

On it's NHS website​, it states: "Recommendations refer to average intake over a period of time, such as one week, and take account of day-to-day variations in vitamin D intake.

"SACN also looked at possible links between vitamin D and non-musculoskeletal conditions, including cancer, multiple sclerosis and cardiovascular disease. They didn't find enough evidence to draw any firm conclusions.

"In spring and summer, most of us get enough vitamin D from sunlight on our skin and a healthy, balanced diet.

"However, SACN couldn't make any recommendations about how much sunlight people would need to get enough vitamin D because there are a number of factors that can affect how much vitamin D is produced in the skin. So the recommendations assume "minimal sunshine exposure".

"During autumn and winter (from October until the end of March) the sun isn't strong enough in the UK to produce vitamin D. That means we have to rely on getting it just from the food we eat. 

"Because it's difficult to get enough vitamin D from food alone, many of us risk not getting enough. Taking a supplement helps to keep levels of the vitamin topped up during the colder months."

The NHS also advises people do not take more than 100 micrograms (4,000 IU) of vitamin D a day as it says this could be harmful.

Independent Opinion

Martin Hewison, PhD, Professor of Molecular Endocrinology and Director of Education at the Institute of Metabolism and Systems Research, The University of Birmingham, is an expert on the subject of vitamin D who isn't part of the alliance.

He agrees the current UK recommendations for vitamin D intake are "extremely conservative" and provides further explanation around the confusion.

"400 IU/day (10 micrograms/day) is not meant to optimise vitamin D but it is simply a level that SACN estimated that most UK people can reach to avoid severe vitamin D-deficiency (serum 25-hydroxyvitamin D < 10ng/ml).

"However, we do not know what the optimal level of vitamin D is for good immune function because these studies have simply not been carried out."

He is currently working with UK researchers to explore a different, UK-focused, approach based on supplementation with 1,000 IU/day vitamin D. He admits this will be seen as a compromise by North Americans but suggests it is a realistic step forward for the UK.

That being said, he says he does understand the position of those recommending 4,000 IU daily.

There are two important questions yet to be answered, he says. "Is vitamin D protecting against actual COVID-19 infection in the general population? Does vitamin D improve prognosis once you are infected? 

"The answer may be both but I am guessing that the requirements for vitamin D are different for these two facets of COVID-19. Possibly you need higher levels to protect once you are infected." 

Alliance ongoing action

Four of the doctors and scientists involved in this campaign have created a webinar​ on the subject of vitamin D and immunity which they have shared with the public, press and government advisors. 

This open letter's current signatory list includes:

Dr Gareth Davies PhD (Medical Physics), Imperial College, London, UK; Codex World Top 50 Innovator 2019.

Professor Barbara Boucher Medical Doctor (retired), Honorary Professor, Centre for Diabetes, Bart's & The London School of Medicine and Dentistry, Queen Mary University of London, UK.

Dr Attila R Garami MD, PhD Multidisciplinary Medical Sciences, Senior Biomarker Consultant, BL, Switzerland

Dr David Grimes Medical Doctor (retired), University of Manchester, UK.

Dr Helga Rhein Medical Doctor (retired), Sighthill Health Centre, Edinburgh, UK.

Professor Peter Cobbold Emeritus Professor, Cell Biology, University of Liverpool, UK.

Dr Joanna Byers Medical Doctor (MBChB, Birmingham), Dip Global and Remote Healthcare (Plymouth), MSc Occupational Therapy (Essex), UK.

Dr Linda Benskin PhD, RN, SRN; Independent Researcher/Educator for VHWs and Clinical Research, Education, & Charity Liaison for Ferris Mfg. Corp, Austin/Ft. Worth TX, USA.

Dr William B Grant PhD (Physics) University of California, Berkeley; Sunlight, Director at Nutrition, and Health Research Center​, San Francisco, CA, USA.

Dr Ute-Christiane Meier Dr. Med. Habil., PhD (Oxon), Kings College, Institute of Psychiatry, London, UK.

Dr Ased Ali B.Sc.(Hons), MBChB, PhD, FRCS (Urol); Consultant Urological Surgeon and Honorary Clinical Lecturer, Mid Yorkshire Hospitals NHS Trust.

Dr Jaimin Bhatt MBChB, MMed(Surg), FRCSEd(Urol), FEBU; Consultant Urological Surgeon, Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde.

Dr David Carman BSc (Microbiology & Biochemistry) MBChB, University of Cape Town, South Africa.

Dr Karl Pfleger PhD (AI/Machine Learning) Stanford; Biotechnology investor, San Francisco, CA, USA.

Professor Michael F. Holick PhD, MD; Professor of Medicine, Physiology and Biophysics; Director of the General Clinical Research Unit; and Director of the Bone Health Care Clinic and the Director of the Heliotherapy, Light, and Skin Research Center at Boston University Medical Center.

Professor Bruce W. Hollis PhD, Professor of Pediatrics, Biochemistry and Molecular Biology, Director of Pediatric Nutritional Sciences, Medical University of South Carolina, USA.

Professor Richard B Mazess Emeritus Professor, Medical Physics, University of Wisconsin, Madison, USA; Founder of Bone Care Intl who developed a vitamin D analog for the treatment of end-stage renal patients.

Dr Henriette Coetzer MBChB, Medical doctor, healthcare risk consultant and NHS Trust CSO, Somerset., MBChB, Medical doctor, healthcare risk consultant and NHS Trust CSO, Somerset.

Carole Baggerly Founder Director of GrassrootsHealth​, a nonprofit vitamin D research organization with 48 senior international vitamin D researchers​contributing to its operations.

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