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CAN vitamin D supplementation reduce the risk of COVID-19 infection and reduce mortality? It’s a question that has received media attention and one which deserves exploration, given recent evidence. This article aims to explore that evidence.
We know that vitamin D is important for bone and muscle health and regulates calcium levels in the blood. An adequate 25-hydroxyvitamin D (25(OH)D) level greater than 50 nmol/L is recommended at the end of winter or in early spring (when levels are the lowest) to develop and maintain healthy bones and muscles and in the prevention of osteoporosis and osteomalacia.
We know vitamin D also plays an important role in regulating the body’s immune response to respiratory viruses and has antiviral effects. Vitamin D is also important for pulmonary function in young adults, inhibits pulmonary inflammatory responses, and modulates innate defence responses to respiratory viral pathogens.
Prevalence of vitamin D deficiency in Australia
The Australian Bureau of Statistics National Health Surveys demonstrate that about 23% of Australian adults have vitamin D deficiency, 17% have mild deficiency, 6% moderate and less than 1% severe deficiency. Vitamin D levels vary considerably by season, with the highest prevalence of vitamin D deficiency in winter (36%), especially in the lower latitudes of Australia. In winter, rates of vitamin D deficiency were highest in the south-eastern states of Victoria (49%), the Australian Capital Territory (49%) and Tasmania (43%) compared with the northern states of Queensland (15%) and the Northern Territory (17%).
According to Vitamin D and health in adults in Australia and New Zealand, vulnerable groups with greatest risk of vitamin D deficiency include the housebound, community-dwelling older and/or disabled people, those in residential care, dark-skinned people (particularly those modestly dressed), and other people who regularly avoid sun exposure or work indoors. Only 5–10% of vitamin D requirements are sourced from dietary sources. Sunshine is the main source of vitamin D production by the body.
Sun exposure for vitamin D production
Vitamin D is produced in the skin during exposure to sunlight (ultraviolet B [UVB] radiation at 290–315 nm) ultraviolet light on 7-dehydrocholesterol in the skin to form provitamin D3, which is then converted to cholecalciferol.
Sunlight ultraviolet radiation intensity is highest in regions situated nearest the equator. In the current pandemic, COVID-19 has been associated with a lower mortality in populations closer to the equator compared with those populations further away from the equator where vitamin D deficiency is more likely. A recent article published in the American Journal of Infection Control found a highly significant, positive correlation between lower death rates and a country’s proximity to the equator. The evidence suggests a direct correlation between sunlight exposure and reduced mortality. COVID-19 mortality may also increase with northerly latitude after adjustment for age suggesting a link with ultraviolet and vitamin D according to an article published in BMJ Nutrition, Prevention and Health.
Vitamin D supplements and risk of acute respiratory infections
Vitamin D supplements are available in Australia primarily as cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) for the prevention and treatment of vitamin D deficiency. Cholecalciferol 1000IU is widely available over the counter.
A recent systematic review and meta-analysis of 25 randomised control trials with over 10 000 participants found that vitamin D (D3 or D2) supplementation was safe and reduced the incidence of viral acute respiratory tract infections (ARTIs). The risk of infections reduced among those who received daily or weekly vitamin D supplements, especially in individuals with severe deficiency (25(OH)D concentration < 25 nmol/L) at baseline. Patients with severe deficiency experienced the greatest benefits from supplementation of vitamin D; their risk of respiratory infections went down by up to 70%. Individuals with 25(OH)D concentrations greater than or equal to 25 nmol/L at baseline reduced the risk of ARTIs by up to 25% with vitamin D supplementation. However, there was much heterogeneity and confounders in the study and more research is required.
Vitamin D supplements and risk of COVID-19 infection
Explosive media attention has focused on vitamin D status, supplements, and its impact on COVID-19 infection following the publication of several studies. Let’s explore a few of these studies:
Recent research suggests Vitamin D status may play a role in the prevention, risk and mortality associated with COVID-19. The researchers identified a potential crude association between the mean vitamin D levels in various European countries with COVID-19 cases and COVID-19 mortality warranting further research.
Another study of 489 patients who had a vitamin D level measured in the year before COVID-19 testing found the relative risk of testing positive for COVID-19 was 1.77 times greater for patients with vitamin D deficiency compared with patients with likely sufficient levels, a difference that was statistically significant.
A recent review article found vitamin D supplements may reduce influenza- and COVID-19-related infections and death.
Possible mechanisms by which vitamin D may influence COVID-19 infection is when the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells in the respiratory system via ACE2 receptors, vitamin D may activate these receptors thereby inhibiting SARS-CoV-2 entering the cells and inhibit one of the specific proteins that is important in the viral replication of SARS-CoV-2. It may also play a role by reducing the risk of inflammation and producing a cytokine storm, although more research is required.
An Israeli population-based study found vitamin D deficiency may be an independent risk factor for COVID-19 infection, severity and hospitalisation.
A recent study published in the The Journal of Clinical Endocrinology and Metabolism of 216 patients with COVID-19 and 197 population-based controls found vitamin D deficiency was present in 82.2% of COVID-19 cases and 47.2% of population-based controls but there was no causal relationship found between vitamin D deficiency and COVID-19 severity. Vitamin D-deficient patients with COVID-19 had a greater prevalence of hypertension and cardiovascular diseases, as well as a longer length of hospital stay compared with population-based controls and than those with serum 25(OH)D levels greater than or equal to 20 ng/mL.
A recent randomised open label, pilot trial performed with patients with COVID-19 admitted to hospital, and with a clinical picture of ARTI confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR, explored the potential role of calcifediol (25(OH)D) supplement for the treatment of COVID-19. The study demonstrated that the patients treated early with calcifediol, combined with routine care of a combination of oral hydroxychloroquine and azithromycin, significantly reduced intensive care unit admission and severity of the disease compared with those who did not receive supplements. However, the study had many confounders, such as diabetes and hypertension, and no placebo was used in the control group. So the study should be viewed with caution; larger trials with groups properly matched are required to verify these results.
Key public health messages
Increasing appropriate sun exposure for vitamin D, especially over autumn and winter, and/or taking vitamin D supplements in high risk individuals are major key public health messages that may help individuals improve immune system and deal with viral infections better, whether that may be for COVID-19, influenza or other respiratory viruses, although more research is required. The daily requirement for vitamin D is 600–800IU. Diet usually accounts for 110IU a day with the balance being made up by UVB exposure. Daily or weekly supplementation with vitamin D has a low cost and can be safely recommended at doses of 1000IU per day. Severe deficiency and people with obesity warrant higher doses for supplementation. Vitamin D is a fat-soluble vitamin and is better absorbed if taken with a fatty meal.
At present, there is no strong evidence to support taking vitamin D supplements to specifically prevent or treat COVID-19. However, new trials are currently underway and may assist in providing advice for 2021 should COVID-19 infection rates increase next autumn and winter. It is essential that public health advice and measures are evidence-based, accurate and timely.
Overall, what we can safely advise our patients is the role of adequate sun exposure, vitamin D in high risk patients, good nutrition and eating well to address nutritional status, and positive behavioral and lifestyle approaches to support the immune system. Hand hygiene, physical distancing, and wearing masks, including eye protection, are important to help prevent viral spread. Smoking avoidance; breathing clean air; addressing obesity and chronic diseases, such as hypertension and diabetes; and exercise all play an important role in supporting the immune system.
Conclusion
The research for vitamin D supplementation and reduction of COVID-19 risk and severity of infection is not robust at this stage, despite wide community interest, until more randomised control trials are available. It is encouraging that there are a number of clinical trials underway to determine if intervention with vitamin D supplementation affects COVID-19 infection and severity. The CORONAVIT trial aims to assess vitamin D risk and severity of COVID-19 and other ARTIs.
While yet to be proven, it would be prudent to consider vitamin D supplementation, particularly in the southern states of Australia where vitamin D deficiency is more prevalent. For Australians living in the lower latitudes of Australia and for the high risk groups of vitamin D deficiency, vitamin D supplements may play an important role in the COVID-19 pandemic environment, especially over the winter period should we have another wave in 2021. The good news is we are entering summer and COVID-19 clusters are very low throughout Australia as a result of stringent lockdown and measures implemented by health authorities.
Associate Professor Vicki Kotsirilos AM is a GP in Melbourne. She holds adjunct associate professorial positions with NICM Health Research Institute and La Trobe University’s, Department of Dietetics and Human Nutrition, Faculty of Health Sciences.
The statements or opinions expressed in this article reflect the views of the authors and do not represent the official policy of the AMA, the MJA or InSight+ unless so stated.
This recently published systematic review and meta-analysis may add to the weight of evidence that low vitamin D status may be associated with an increased risk of COVID-19 infection. Further studies are needed to evaluate the impact of vitamin D supplementation on the clinical severity and prognosis in patients with COVID-19.
Click here for study:
https://www.ijidonline.com/article/S1201-9712(20)32600-X/abstract
When I lay broken in rehab after a terrible bicycle accident Dr. Jelbart encouraged me to take my supplements. I do not recall her recommending vit.D. However after weeks of i.v. ketamine and fentanyl it is a miracle I remember anything.
D is good. Thanks for your article Prof. K; and some insightful comments above.
Talking to an immunology Prof. we need levels > 100. We know south of 75 does not cut the mustard.
D supplementation must include K.
Any comments on the idea that pulsed large doses of D (e.g. 100,000 i.u. once per month, or 7,500 i.u. once weekly) increase fracture risk?
Because in many patients 1000 i.u daily has a paltry effect on serum levels, anecdotally 2000 i.u. daily gives more bang for buck.
D’s ant-endarteritis effect is cardio-protective, useful in IHD.
Our cytokine response to Covid is likely responsible for the arteritis amongst those 6% of known cases unfortunately severely affected in Australia (vide Worldometer).
Looking at any single variable is always difficult in the complex human organic chemistry equation. These at-risk groups typically have a variety of deficiencies. Ideally, folks should test for and treat all nutrient deficiencies.
Natural D serum levels in community dwelling natives at the equator are 40-60 ng/ml. Life Guards might have 100 ng/ml at summer’s end.
There are strong vit D intervention studies with other conditions. See Dr. Wagner’s work with birth complications and breastfeeding. Dr. Lappe reduced stress fractures in Navy BT by 20% with extra D and calcium.
The real methodological challenge is recommendations for “blind dosing” (a fixed dose everyone should take). D requirements vary by body size, age, lifestyle, initial serum level, race, etc. Dr. Heaney, MD, a D researcher, suggests 35 IU D3/pound of body weight as a maintenance dose starting point. The only thing that counts is serum level. Dosing protocols to raise low serum D vary, but daily dosing yields more stable serum levels across time.
Can use natural sunlight at solar noon at a UVB sufficient latitude and season, exposing at least 40% of skin (ideally shorts and bras as appropriate). A Sperti UVB lamp (the body control D production) works well (night shift workers, miners, sub crews, etc.). Some types of tanning beds. Supplements are the easiest. There are BTW other sun products, so solar exposure vs supplements isn’t a fully apples-apples comparison.
Finally, D functions along with co-factors (magnesium, boron, zinc and vitamin A). If a subject seems treatment resistant, the first suspect is a magnesium deficiency. Every country is unique, but nutrient deficiencies in the US are fairly common. The mythical “healthy diet” is more urban legend than fact (apparently pizza isn’t fully nourishing).
Remember, ONLY serum levels count. Blind doing has blind effects.
I have long been an advocate of Vit D and interestingly there is good data in the sepsis literature showing that supplemetary Vit D, Vit C and Thiamin (B1) improves survival. My observation is that our sunsafe public health message has inadvertantly led to widespread Vit D deficiency. I personally do not wear sunscreen unless I am going to be sun exposed for more than 20 mins in summer. I do not wear sunscreen in spring, autumn or winter (except skiing). The cancer council has some useful guidelines.
https://wiki.cancer.org.au/policy/Position_statement_-_Risks_and_benefits_of_sun_exposure
A wonderful article Vicki! A Clear, concise summary of the research on Vitamin D to date. I am especially appreciative of the information of its anti inflammatory effects on the respiratory system and cytokine storm prevention. While the research of Vitamin D to protect against Covid 19 is in the early stages, nevertheless with so much albeit low level evidence of efficacy as Vicki has clearly detailed, it appears prudent to recommend widespread appropriate supplementation, especially during the winter months in southern Australia. Thanks!
Great article Vicki with a clear assessment of the role of Vit D in management of Covid and prevention of Covid. But, I suspect everyone will just go for the vaccines ( just assuming that they have no other consequences) and also hoping the immunity works and lasts.
So sad how little regard there is for these Integrative Medicine approaches. It seems like the Pharmaceutical Industries have us all in the palms of their hands. Thanks for having a go Vicki opening the question of the role of Vit D.
Thanks Vicky.
A very good article.
The role of Vitamin D in building immunity to viruses and respiratory illnesses is widely accepted. When the COVID-19 pandemic hit our shores early this year it was too early to show definitively that the vitamin would have a useful impact, although many experts in nutritional medicine expected that it would. Nearly a year into the pandemic, however, we have dozens of research papers from quality institutions around the world – including from the US, Spain, Israel and the United Kingdom. These demonstrate that optimal blood levels of 90-130 nmol/L not only enhance immunity to COVID-19 but also reduce the severity of outcomes should infection occur. Some jurisdictions are already encouraging and supporting supplementation, with the UK the most recent to announce plans to supply four months of Vitamin D supplements to vulnerable residents as a tool to enhance COVID-19 defences. Australia should do the same – notwithstanding our current low case numbers, we know how quickly a resurgence of the virus can occur, and we have a window of opportunity to prepare our population for that. Unfortunately, our Government is yet to act, citing the need for “more evidence”. Such a conservative approach, when the risks associated with appropriate Vitamin D supplementation are negligible, is foolish and frustrating. As a profession, however, we are in a position to influence even without the backing of Government policy. We must advocate and inform not just at the political level, but importantly at the patient level. The elderly and those with darker skin are at particular risk of Vitamin D deficiency, while certain cohorts of our community, including those with co-morbidities such as diabetes and obesity, are most vulnerable to the virus. We should be testing their Vitamin D levels and ensuring they are at optimum levels to provide protection. Given an estimated 50% of Australians are deficient in Vitamin D, most adults can benefit from a daily dose of 1000-4000iu with no adverse risk, while some need substantially more. It is one thing for the Government to say it is not ready to make a recommendation, and quite another for medical professionals not to do everything in their power to support the health of their patients.
Please remember that vitamin D is no longer regarded as a vitamin; it has been reclassified as a hormone. Routine testing should be a part of best medical practice.
Thank you Vicki. Yours is clearest exposition of the subject I have found and devoid of waffle. It fortifies the cautious affair with supplements of this high latitude, octogenarian,, non-medical microbioologist!
Is there any resistance from drug companies to influence doctors away from using vitamin D. There is no money in it for them.
Absorption of Vitamin D with Sun exposure may change with age. Vitamin D is an oil soluble vitamin and as humans age their skin becomes drier. Are there any studies exploring this
Should be a simple study to determine if there is a difference in supplementation and diet and access to sunshine in state managed aged care homes where there were very few deaths as opposed to federally managed homes in Victoria where most of the deaths occurred.
Thank you for your input on the Cordoba trial Paul Beaumont, kindly Vicki
I am very pleased to see the vit D trial discussed. The colleagues in Spain are to be congratulated. Overworked, under the strain of a tsunami of cases with inadequate resources, they managed to do a randomized pilot trial. They gave what was the standard of care to all patients. Who dares to call them unethical?
This trial should not be denigrated by alluding to a mismatch in risk factors such as hypertension. The authors used a multivariate analysis to control for hypertension and the difference was still enormously significant. P = 0.003.
The 25-fold reduction in admission to ICU with a Fisher exact p value of 0.0001 creates a major ethical problem. The numbers who died were too small to be significant. (p = 0.1)
The only trial that can be done in this instance is one with a comparison to historical controls. The known death rate is around 3%. If 200 cases were treated with the high dose calcifediol and there were no deaths, a comparison to historical controls would be statistically significant. This is should have been completed yesterday.
3 weeks ago I advised 13 people of the results of the trial and they chose to take vit D. They all had a short illness and no complications
thanks for the clarification with the Cordoba trial Anthony, kindly, Vicki
The startling reality is Vitamin-D deficiency is most evident in older people, obese people, poor diet, darker skinned people AND those with restricted access to plentiful strong sunshine. My VIT-d test showed I was under 25nmol, I worked in an office long hours in Canberra and over 60yo and had an excellent diet and went outdoors on the weekend.
Generally I appreciated the article, which was well written and researched, and interesting to read. But there were a few mistakes. Latitude numbers being one of them. Contrary to what was written, the calcifediol trial in Cordoba in Spain did actually have a placebo. There were approx 75 patients. 50 given calcifediol, 25 not given it. So the 25 not given it were the placebo. Deaths occurred in the placebo group. Not in the calcifediol group. Attendance at an ICU was much higher in the placebo group. A larger trial is now underway involving 15 Spanish hospitals and thousands of patients. The 75 patient Cordoba trial was however unethical. Clinical trials only occur when there is a hypothesis of efficacy. Which is presumably why there were twice as many in the calcifediol group.
So those researchers allowed people in the placebo group to die, by denying them a treatment hypothesized to be efficacious. Calcifediol is a safe treatment. Like vitamin d tablets. Very safe.
And people died in that study. Not good.
Also the cytokine storm is caused by the host’s unregulated immune response to viral debrus not by the virus. This can be regulated with vitamin D or corticosteroids such as dexamethosone or methylprednisolone. And it can be regulated by vitamin C. For good information about covid-19 and it’s treatment please refer to Paul Marik at EVMS in Norfolk, Virginia. FLCCC.net
Very timely and stimulating article. Adds to the protean articles demonstrating the likely value of adequate repletion with Vitamin D for many other human systems and functions beyond bone including immune system and protection against cognitive decline in older males.
I wonder if Prof Kotsirilos meant “For Australians living in the lower latitudes of Australia…vitamin D supplements may play an important role ” or rather: adults living in the higher latitudes… as latitude numbers get higher, further away from equator, though visually lower on the usual maps….