Vitamin D and COVID-19: surviving the times

Updated 23 January 2022 (scroll down for updates)


You've probably heard or read that vitamin D deficiency might be a risk factor for getting into a lot of trouble with COVID-19. As it's winter in the northern hemisphere, ... make sure you are getting enough vitamin D: roughly 1000 IU (25 µg) per day should be fine, unless your doctor recommends something else for your particular condition (if applicable). You can give the same dose to children. The official recommendations by the National Institutes of Health (United States) are 600 IU starting from one 1 year of age. Also a good idea to give vitamin D supplemements to your parents/grandparents (But make sure they know the amount and don't take 100 tablets at once).

A new relevant analysis has just been published regarding vitamin D and COVID-19:

A systematic review and meta-analysis in the journal Criticial Reviews in Food Science and Nutrition, published online on 4 November 2020, states that ...
  • ... vitamin D deficiency was associated, but not significantly, with a 35% higher risk of getting infected with the new coronavirus. (Their wording is different, but it means the same thing.)
  • ... vitamin D insufficiency (= mild deficiency) was associated with an 81% increased risk of hospitalization in people who were infected with coronavirus.
  • ... vitamin D insufficiency was associated with an 82% increased risk of dying, in people who were infected with coronavirus.
Vitamin D deficiency was defined as 25-OH-D less than 50 nmol/L (20 ng/mL).
Vitamin D insufficiency is not defined in the text, but probably they mean 50-70 nmol/L (20-28 ng/mL). Less would be deficiency, and more would be sufficiency.

This is from the original article:
"We identified 1542 articles and selected 27. Vitamin D deficiency was not associated [this is technically incorrect wording, I would say, because yes actually associated but not significantly] with a higher chance of infection by COVID-19 (OR = 1.35; 95% CI = 0.80-1.88), but we identified that severe cases of COVID-19 present 64% (OR = 1.64; 95% CI = 1.30-2.09) more vitamin D deficiency compared with mild cases. A vitamin D concentration insufficiency increased hospitalization (OR = 1.81, 95% CI = 1.41-2.21) and mortality from COVID-19 (OR = 1.82, 95% CI = 1.06-2.58). We observed a positive association between vitamin D deficiency and the severity of the disease.
This is the first systematic review we know of that reports the relationship between vitamin D levels and COVID-19 severity. 
In conclusion, the results of the meta-analysis confirm the high prevalence of vitamin D deficiency in people with COVID-19, especially the elderly. We should add that vitamin D deficiency was not [significantly] associated with COVID-19 infection. However, we observed a positive association between vitamin D deficiency and the severity of the disease. 
Moreover, vitamin D supplementation could be considered in patients with vitamin D deficiency and insufficiency, if they have COVID-19. However, there is no support [good scientific evidence] for supplementation among groups with normal blood vitamin D values with the aim of prevention, prophylaxis or reducing the severity of the disease." (Pereira et al. 2020)

This echoes previous reports such as: "Our significant findings were that [COVID-19] patients with low concentrations of 25OH-D (≤30nmol/l) [12 ng/ml] [...] were more likely to become hypoxic and require ventilatory support." (Mandal et al. 2020)

In addition, a review article published online on 31 October 2020, in the journal Nutrients, states ... nothing that really says anything new:

"[...] the evidence seems strong enough that people and physicians can use or recommend vitamin D supplements to prevent or treat COVID-19 in light of their safety and wide therapeutic window." (Mercola et al. 2020)

In other words, vitamin D, that you should pay attentention to anyway, can be recommended because it doesn't do any harm (at the recommended dose above).

More interesting, I find, is that this article, in a quite highly-respected nutrition science journal (my opinion), was written by the famouse American "alternative health magician" (my words) Mercola. I assumed, when I saw the name, that it probably wasn't THAT Mercola, but it is. Is Mercola converting to science? Or just joining the other pseudo-scientists in science? 

The World Cancer Research Fund (WCFR), as agile as their name, have also very recently weighed in in their email newsletter, repeating the statements from April 2020: 

Your immune system can influence the risk of infection! 😼 [You wouldn't have guessed that.]

Another brilliant statement is: "No one food is recommended over another [...]."

More useful maybe: "Important nutrients for effective immune function are:


Vitamins A, B6, B12, C and D 

I have highlighted the ones you will get from healthy plants foods, without thinking about them ever, in green
  • Legumes, whole grains, nuts and seeds are excellent sources of iron and zinc.
  • Take a supplememt for B12 and (at least in winter) vitamin D.
  • If you live in areas with low soil selenium, such as Europe, consider taking a supplement such as VEG1 by the Vegan Society (which contains selenium; no, I don't sell it) or eating about a Brazil nut a day (or a few, every few days; eating too many is probably not ideal, because we shouldn't get too much selenium either).
More info here.

Update 9 November 2020:

"There is growing evidence linking vitamin D deficiency with risk of COVID-19. [...] There is considerable evidence to support the higher level for sufficiency (20 ng/ml or 50 nmol/L) recommended by the European Food Safety Authority and the American Institute of Medicine and hence greater supplementation (20 micrograms or 800 IU per day). Serum 25(OH)D concentrations in the UK typically fall by around 50% through winter. We believe that governments should urgently recommend supplementation with 20-25 micrograms (800-1,000 IU) per day." (Griffin et al. 2020)

Update 16 November 2020:
"[.] with no imminent end to the pandemic , people should be encouraged to improve their lifestyle to lessen the risks both in the current and likely subsequent waves of COVID-19." (Silvero et al. 2020)

Update 17 November 2020:
"There are now, to our knowledge, 14 studies that indicate the specific benefit in the COVID-19 pandemic of having a blood level of vitamin D greater than 30 ng/mL (75 nmol/L), and a very significant danger of death from infection if the blood level lies below 10 ng/mL (25 nmol/L).3 [...] with vitamin D deficiency at a time of a serious pandemic, the target blood level is critical, should be checked for and the dose adjusted accordingly. We suggest a target level of not less than 30 ng/mL [75 nmol/L] and not more than 60 ng/mL [150 nmol/L]. In most adults, this will be achieved by a mean D3 supplement of 4,000 IU daily. [...]
Another neglected fact is that vitamin D, acting via its VDR receptor, forms the working heterodimer not alone but paired with the vitamin A-activated retinol receptor (RXR). Yet National Institute for Health and Care Excellence (NICE) guidelines are dismissive of vitamin D's role in immunity, while generous in that of vitamin A.5 This is completely illogical as, in their joint functions, the two match each other mol for mol.
NICE is a body that is orientated towards evaluating randomised controlled trials (RCTs) of pharmaceutical products, and so largely discounts observational studies. [...]
But to help satisfy NICE skeptics, fortunately we now have an RCT from Córdoba, Spain, into the effect of vitamin D in COVID-19 pneumonia, which appeared after the paper by Weir and colleagues.7 It demonstrated that, in those treated with oral 25(OH)D, there was a subsequent need for intensive care unit transfer in only 2% (with no deaths), versus 50% and two deaths in the control group. Evidence is cumulative, and is about more than RCTs, as Sir Austin Bradford Hill expounded more than half a century ago in establishing the causative link between smoking and lung cancer.
It is to be hoped that the Royal College of Physicians will now advise the government that a universal vitamin D supplement averaging around 4,000 IU [100 µg] daily for an adult, which even NICE declares to be safe, should be taken at least during winter months. And as a long stop, the blood level of vitamin D should be checked occasionally to cover individual variation. We predict that this would make us all healthier in many ways, prevent a predicted COVID-19 ‘second wave’ [...]." (Anderson et al. 2020) [Note that I would not recommend taking 4000 IU vitamin D per day unless this has been prescribed by a physician. I would not take more than 2000 IU [50 µg] daily without the explicit advice from a physcian. However, up to 4000 IU [100 µg] is the amount that is officially still considered safe by the National Institutes of Health (NIH; United States) for humans 9 years and older.]

Update 21 November 2020:
"The fatality rate was high[er] in vitamin D deficient [patients] (21% vs 3.1%). Vitamin D level is markedly low in severe COVID-19 patients. Inflammatory response is high in vitamin D deficient COVID-19 patients. This all translates into increased mortality in vitamin D deficient COVID-19 patients. As per the flexible approach in the current COVID-19 pandemic authors recommend mass administration of vitamin D supplements to population at risk for COVID-19." (Jain et al. 2020)

"Recent studies on COVID-19 patients have shown that vitamin D and selenium deficiencies are evident in patients with acute respiratory tract infections. Vitamin D improves the physical barrier against viruses and stimulates the production of antimicrobial peptides. It may prevent cytokine storms by decreasing the production of inflammatory cytokines. Selenium enhances the function of cytotoxic effector cells. Furthermore, selenium is important for maintaining T cell maturation and functions, as well as for T cell-dependent antibody production. Vitamin C is considered an antiviral agent as it increases immunity. Administration of vitamin C increased the survival rate of COVID-19 patients by attenuating excessive activation of the immune response. Vitamin C increases antiviral cytokines and free radical formation, decreasing viral yield. It also attenuates excessive inflammatory responses and hyperactivation of immune cells. In this mini-review, the roles of vitamin C, vitamin D, and selenium in the immune system are discussed in relation to COVID-19.
Nutritional therapy should be a part of patient care for survival of this life-threatening disease (COVID-19), as well as for better and shorter recovery. Most importantly, checking malnutrition and providing optimal nutritional supplementation are critical steps for optimal functioning of the immune system in the human body. Patients with malnutrition are more likely to be from lower socioeconomic groups; thus, nutrition supplementation is important for the risk group as well as older adults who have a relatively weak immune system. [...]. Since severely ill COVID-19 patients were reported to be deficient in more than one nutrient, we suggest that nutritional deficiencies may favor the onset of COVID-19 and increase the severity of the disease. Combination of some of these micronutrients (vitamin C, vitamin D, and selenium) may help to boost the immune system, prevent virus spread, and reduce the disease progressing to severe stages." (Bae and Kim 2020)

Update 22 November 2020:
"While it would be preferable to have large-scale randomised control trial data to conclusively prove the case for vitamin D supplementation as a protectant against SARS-CoV-2 infection and Covid-19 illness, this is extremely challenging in a quickly evolving pandemic. Given the strong emerging evidence which suggests a protective role for vitamin D against Covid-19, the proposition of future randomised control trials incorporating a non-intervention arm which includes those with baseline vitamin D deficiency in whom there is an existing clinical imperative to intervene is untenable from an ethical perspective. Conducting such randomised placebo-controlled trials only in those who are vitamin D replete is futile as it cannot address the question of clinical efficacy in those who have low vitamin D levels, and who would be the target of any proposed intervention. So while data from well-designed, prospective randomised control trials would provide definitive evidence in this area, these are, and may remain, elusive. We are consequently reliant on data which are imperfect in isolation, but which in their totality, present compelling evidence for a protective effect of vitamin D against Covid-19, and which strongly support urgent intervention in this regard.
In this context, reflecting on lessons learned in managing the Ebola outbreak in Africa, Dr. Michael Ryan, Executive Director of WHO, captured the imperative to act decisively in the current Covid-19 crisis: “Be fast, have no regrets. You must be the first mover. The virus will always get you if you don’t move quickly; if you need to be right before you move, you will never win”. He went on to conclude, “Perfection is the enemy of the good when it comes to emergency management; speed trumps perfection. The problem in society we have at the moment is that everyone is afraid of making a mistake. Everyone is afraid of the consequence of error. But the greatest error is not to move. The greatest error is to be paralysed by the fear of failure.”
[...] Without vitamin D supplementation, the blood levels associated with protection against severe viral respiratory infection due to SARS-CoV-2 will not be achieved. While food fortified with vitamin D is recommended as a first-line strategy to augment intakes, for the vast majority, vitamin D supplements will also be required. The evidence linking vitamin D deficiency with increased risk of SARS-CoV-2 infection and Covid-19 disease severity has evolved significantly since March 2020, and now strongly supports the need for intervention in this area. Given this evidence and the unambiguous safety profile of daily intakes at these levels, we recommend that adults in Ireland should be supplemented with oral vitamin D3 at 20–25 μg/day (800–1000 IU/day) for the duration of this pandemic. For those who are overweight or obese, or who have dark skin pigmentation or other risk factors for vitamin D deficiency, it is likely that supplementation at daily doses higher than this will be required to achieve the serum 25(OH)D levels needed for optimal immunity against Covid-19. In these groups and in older adults, amongst whom vitamin D deficiency and severe deficiency (i.e. 25(OH)D < 25/30 nmol/l) prevail, and for whom SARS-CoV-2 infection carries significantly greater clinical risk, prescription at these higher daily doses according to baseline serum 25(OH)D should proceed as required under medical supervision. This is especially important for older adults resident in nursing homes or other long-term care settings who are particularly vulnerable; here, sufficient vitamin D supplementation to achieve a minimum serum 25(OH)D level of 50 nmol/l should be expeditiously implemented as a priority element of standard care." (McCartney et al. 2020

Update 24 November 2020:
"Whilst waiting for an effective vaccination and treatment for COVID-19, it would seem reasonable to encourage efforts to achieve reference nutritional intakes to optimise innate immune responses to infection. Vitamin D supplementation in accordance to national guidelines is a cheap intervention with a good safety profile that has multiple health benefits and should therefore be recommended to the general public." (Hosack et al. 2020)

"We fully agree that vitamin D supplementation in accordance to the existing national guidelines should be recommended to the general public. Although we would be delighted if vitamin D supplementation did lessen risk of infection or severe COVID-19, there are currently no robust trials addressing this question." (Hastie et al. 2020)

Update 25 November 2020:
"A state-by-state Mendelian randomisation analysis of excess COVID-19 mortality of African-Americans in the USA shows a greater disparity in northern states than in southern states. It is conceivable that vitamin D adequacy denies the virus easy footholds and thereby slows spreading of the contagion. This finding should drive home the message that vitamin D supplementation is particularly important for individuals with dark skin tones. Vitamin D deficiency, even for a few months during the winter and spring season, must be rigorously remedied because of its many adverse health impacts that include decreased life expectancy and increased mortality. Slowing the spread of COVID-19 would be an added bonus." (Kohlmeier 2020)

Update 19 December 2020:
"While there is insufficient evidence to recommend vitamin D for the prevention or treatment of covid-19 at this time, we encourage people to follow government advice on taking the supplement throughout the autumn and winter period. As research continues on the impact of vitamin D on covid-19, we are continuing to monitor evidence as it is published and will review and update the guidance if necessary." (Wise 2020)

Update 4 January 2021:
"We suggest that supplementation of subjects at high risk of COVID-19 with vitamin D (1.000 to 3.000 IU) to maintain its optimum serum concentrations may be of significant benefit for both in the prevention and treatment of the COVID-19." (Boulkrane et al. 2020

[Note that the effectiveness of vitamin D supplementation in regard to any benefit for COVID-19 prevention or treament is currently controversial. However, at least trying to meet general daily intake recommendations (i.e. taking a supplement of about 600-1000 IU vitamin D per day during winter) is safe and seems very reasonable.]

Update 6 January 2021:
"This systematic review and meta-analysis indicated 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." (Liu et al. 2021)

Update 13 January 2021:
"This study demonstrates the high frequency of hypocalcemia and hypovitaminosis D in severe COVID-19 patients and provides further evidence of their potential link to poor short-term prognosis. It is, therefore, possible that the correction of hypocalcemia, as well as supplementation with vitamin D, may improve the vital prognosis." (Bennouar et al. 2021)
This may indicate that a very low intake of calcium combined with a vitamin D deficiency could be even worse than just a vitamin D deficiency - also in terms of COVID-19.

Update 15 January 2021:
"NICE [National Institute for Health and Care Excellence, United Kingdom] should continue to monitor new evidence as it is peer-reviewed and published, including results from several clinical trials on vitamin D and COVID-19 outcomes that are currently underway. However, particularly in countries where the pandemic situation continues to worsen (and will continue to do so during the winter months before the effects of vaccinations become perceptible), additional evidence could come in just too late. In an ideal world, all health decisions would be made based on overwhelming evidence, but a time of crisis may call for a slightly different set of rules." (The Lancet. Diabetes & Endocrinology, 8 Jan 2021; editorial, no author name given)

Update 17 January 2021:
"Randomized controlled trials are the optimal study design for causal interpretation, but they have their challenges. At best, RCTs provide answers to very precise questions—but clinical management and public health decisions often require extrapolation beyond the tight confines of any given trial. Accordingly, we believe that all types of research (basic, clinical/translational, and population) can provide valuable information. Taken together, they can provide evidence‐based guidance for clinicians and public health leaders. As investigators design and implement RCTs of vitamin D supplementation to prevent COVID‐19, we encourage consideration of the issues raised here. Likewise, we encourage a greater tolerance for ‘mixed’ results given the likely heterogeneity of future trial designs—and the inherent challenges of RCT research on vitamin D." (Camargo and Martineau 2021)

Update 23 January 2021:
"The results indicate that a low 25(OH)D concentration is a contributing factor to COVID-19 severity, which, combined with previous studies, provides a convincing set of evidence." (Walrand 2021)

Update 25 January 2021:
"Vitamin D deficiency is common but readily preventable by supplementation that is very safe and cheap. A target blood level of at least 50 nmol[/l], as indicated by the US National Academy of Medicine and by the European Food Safety Authority, is supported by evidence. This would require supplementation with 800 IU/day (not 400 IU/day as currently recommended in UK) to bring most people up to target. Randomized placebo-controlled trials of vitamin D in the community are unlikely to complete until spring 2021-although we note the positive results from Spain of a randomized trial of 25-hydroxyvitamin D3 (25(OH)D3 or calcifediol) in hospitalized patients. We urge UK and other governments to recommend vitamin D supplementation at 800-1000 IU/day for all, making it clear that this is to help optimize immune health and not solely for bone and muscle health. This should be mandated for prescription in care homes, prisons and other institutions where people are likely to have been indoors for much of the summer. Adults likely to be deficient should consider taking a higher dose, e.g. 4000 IU/day for the first four weeks before reducing to 800 IU-1000 IU/day. People admitted to the hospital with COVID-19 should have their vitamin D status checked and/or supplemented and consideration should be given to testing high-dose calcifediol in the RECOVERY trial. We feel this should be pursued with great urgency. Vitamin D levels in the UK will be falling from October onwards as we head into winter. There seems nothing to lose and potentially much to gain." (Griffin et al. 2020)

Update 31 January 2021:
"Our findings suggest that habitual use of vitamin D supplements is related to a lower risk of COVID-19 infection, although we cannot rule out the possibility that the inverse association is due to residual confounding or selection bias. Further clinical trials are needed to verify these results." (Ma et al. 2021)

Update 17 February 2021:
"Meta-analyses of vitamin D supplementation in prevention of acute respiratory infection and trials in tuberculosis and other conditions also support efficacy of low dose daily maintenance rather than intermittent bolus dosing. This is particularly relevant during the current COVID-19 pandemic given the well-documented associations between COVID-19 risk and vitamin D deficiency. We would urge that clinicians take note of these findings and give strong support to widespread use of daily vitamin D supplementation." (Griffin et al. 2021)

Update 23 March 2021 (META-ANALYSIS):
"In conclusion, low serum 25 (OH) Vitamin-D level was significantly associated with a higher risk of COVID-19 infection. The limited currently available data suggest that sufficient Vitamin D level in serum is associated with a significantly decreased risk of COVID-19 infection." (Teshome et al. 2021)

Update 28 March 2021 (two different META-ANALYSES):
"Vitamin D deficiency was also associated with worse severity and higher mortality than in nondeficient patients (OR = 2.6; 95% CI, 1.84-3.67; P < .01 and OR = 1.22; 95% CI, 1.04-1.43; P < .01, respectively). Reduced vitamin D values resulted in a higher infection risk, mortality and severity [of] COVID-19 [SARS-CoV-2] infection." (Petrelli et al. 2021)

"While the available evidence to-date, from largely poor-quality observational studies, may be viewed as showing a trend for an association between low serum 25(OH)D levels and COVID-19 related health outcomes, this relationship was not found to be statistically significant. Calcifediol supplementation may have a protective effect on COVID-19 related ICU admissions. The current use of high doses of vitamin D in COVID-19 patients is not based on solid evidence. It awaits results from ongoing trials to determine the efficacy, desirable doses, and safety, of vitamin D supplementation to prevent and treat COVID-19 related health outcomes." (Bassatne et al. 2021)

Update 1 June 2021 (association of genetically determined vitamin D levels with COVID-19 risk)
"In this 2-sample MR [Mendelian randomization] study, we did not observe evidence to support an association between 25OHD levels and COVID-19 susceptibility, severity, or hospitalization. Hence, vitamin D supplementation as a means of protecting against worsened COVID-19 outcomes is not supported by genetic evidence. Other therapeutic or preventative avenues should be given higher priority for COVID-19 randomized controlled trials." (Butler-Laporte et al. 2021)

Update 26 July 2021 (systematic review and meta-analysis)
"Low serum vitamin D levels are statistically significantly associated with the risk of COVID-19 infection. Supplementation of vitamin D especially in the deficiency risk groups is indicated." (Szarpak et al. 2021)

Update 31 August 2021 (meta-analysis)
"In this meta-analysis, we found a potential increased risk of developing severe COVID-19 infection among patients with low vitamin D levels. There are plausible biological mechanisms supporting the role of vitamin D in COVID-19 severity. Randomized controlled trials are needed to test for potential beneficial effects of vitamin D in COVID-19 outcomes." (Ben-Eltriki et al. 2021)

Update 15 September 2021 (Mendelian randomization study)
"A growing body of evidence suggests that vitamin D deficiency has been associated with an increased susceptibility to viral and bacterial respiratory infections. [...] Ambient UVB was strongly and inversely associated with COVID-19 hospitalization and death overall and consistently after stratification by BMI and ethnicity. [...] The main MR analysis did not show that genetically-predicted vitamin D levels are causally associated with COVID-19 risk (OR = 0.77, 95% CI 0.55-1.11, P = 0.160), but MR sensitivity analyses indicated a potential causal effect (weighted mode MR: OR = 0.72, 95% CI 0.55-0.95, P = 0.021; weighted median MR: OR = 0.61, 95% CI 0.42-0.92, P = 0.016). Analysis of MR-PRESSO did not find outliers for any instrumental variables and suggested a potential causal effect (OR = 0.80, 95% CI 0.66-0.98, p-val = 0.030). In conclusion, the effect of vitamin D levels on the risk or severity of COVID-19 remains controversial, further studies are needed to validate vitamin D supplementation as a means of protecting against worsened COVID-19." (Li et al. 2021) [The analyses all point in the direction of a protective effect of sunlight/UVB radiation and vitamin D supplementation.]

Update 6 October 2021 (Systematic review and meta-analaysis)
"According to obtained result from D-CIMA, one which has low serum vitamin D are 1.64 times (95%CI=[1.32-2.04],p<0.001) more likely to get Covid-19 infection. In D-CSMA, we found that people with the serum 25(OH)D level below 20ng/mL or 50nmol/L have 2.58 times (95%CI=[1.28-5.19],p=0.008) more likely to risk having severe Covid-19. We obtained from D-CMMA that low vitamin D level has no effect on Covid-19 mortality (OR=2.42 95%CI=[0.73-8.04],p=0.148).
Conclusion: Vitamin D deficiency increases the risk of Covid-19 infection and the potential for the severity of the disease. Therefore, vitamin D supplements should be added to prevention and treatment protocols for Covid-19 disease." (Kaya et al. 2021)

Update 23 January 2022 (Narrative review)
"Despite the diversity of studies and the lack of randomized clinical trials and prospective cohorts, there is evidence of the potential protective and therapeutic roles of vitamin C, D, zinc, and selenium in COVID-19." (Pedrosa et al. 2022)