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.
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.
Loading comments…
More from this week
Newsletters
Subscribe to the InSight+ newsletter
Immediate and free access to the latest articles
No spam, you can unsubscribe anytime you want.
By providing your information, you agree to our Access Terms and our Privacy Policy. This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.