This is a very controversial question with studies on both sides: some say a higher level of Vitamin D3 does help and others say it makes no difference.
As with many issues, it is complex and may depend on a variety of factors, such as viral load, overall health parameters, genetics, aging, diet, etc.
I personally believe it helps, but particularly in the context of a person who has a low inflammatory diet and follows a protocol to decrease viral loads naturally.
Remember it took years to prove tobacco smoking "caused" cancer. Proving something is beneficial can take years and lots of money.
Performing a large, prospective, randomized, controlled, double-blinded study where all key confounders are controlled is very difficult if not impossible. Thus patients can look at the data and determine how best to live, which foods and supplements to take.
SLC
https://jamanetwork.com/journals/jama/fullarticle/2775003
Sorting Out Whether Vitamin D Deficiency Raises COVID-19 Risk
One of the risk factors du jour for coronavirus disease 2019 (COVID-19) has been vitamin D deficiency.
Even Anthony Fauci, MD, has said he takes a vitamin D supplement. Vitamin D “does have an impact on your susceptibility to infection,” Fauci, director of the National Institute of Allergy and Infectious Diseases, told actress Jennifer Garner in a September interview. “I would not mind recommending—and I take it myself—taking vitamin D supplements.”
Most people get some vitamin D from sunlight exposure, although individuals in the US get the nutrient mainly from fortified foods, such as milk, orange juice, and breakfast cereals.
At higher latitudes, people with more melanin content in their skin have lower blood levels of vitamin D because their skin doesn’t produce as much in response to sunlight. A recent article in the Journal of the National Medical Association speculated that vitamin D deficiency “is likely a significant factor” behind disproportionately high COVID-19 cases and deaths among US Black and Latino populations.
An analysis of data from 4962 participants in the National Health and Nutrition Examination Survey found that 1981 (39.92%) were vitamin D deficient, defined as a blood level lower than 20 ng/mL (<50 nmol/L). Vitamin D deficiency was greater in certain subpopulations, such as people with obesity or with type 1 or type 2 diabetes—all 3 of which have been associated with worse COVID-19 outcomes.
Despite Fauci’s recommendation and claims by many supplement sellers, conclusions about vitamin D blood levels’ connection to a host of diseases, including infections, cannot be determined because of mixed or sparse evidence, according to a recent report written for the US Preventive Services Task Force, which is updating its recommendation on vitamin D deficiency screening. The draft updated recommendation, like its 2014 predecessor, concludes that the evidence is insufficient to assess the benefits and harms of screening in asymptomatic adults for any reason.
“Vitamin D might be helpful in that there is evidence it can attenuate immune responses,” which could prevent the “cytokine storms” seen in some patients with COVID-19, A. Catharine Ross, PhD, chair of nutrition sciences at Penn State, wrote in an email. “On the other hand, attenuation might not be beneficial in terms of helping the antibody response.”
Mixed Signals
Research findings about vitamin D and COVID-19 have been mixed and sparse:
A study of 77 frail elderly patients hospitalized with COVID-19 in France concluded that vitamin D supplements taken regularly during the year before a COVID-19 diagnosis were associated with less severe disease and better survival than taking no vitamin D or receiving supplementation shortly after diagnosis. And a pilot randomized clinical trial of 76 patients hospitalized with COVID-19 in Spain found that treatment with high-dose vitamin D significantly reduced the risk of intensive care unit admission. However, only larger trials could provide a definitive answer, the authors wrote.
On the other hand, a study in a northern Italy hospital found no association between vitamin D and COVID-19. In a review article published in a different journal the same day as their study, the researchers in Italy concluded that poor vitamin D status appears to be linked to an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but age, sex, and comorbidities seem to play a more important role in COVID-19 severity and mortality. Nine days later, a different group of Italian researchers published an observational study of 324 patients with COVID-19 that found taking vitamin D supplements was not linked to risk of hospitalization but was associated with a higher risk of dying if hospitalized.
A recent study in JAMA Network Open by University of Chicago researchers linked vitamin D deficiency with a greater likelihood of testing positive for SARS-CoV-2. However, an earlier study of UK Biobank participants found no such connection. The Chicago researchers noted that vitamin D levels examined in the UK study predated COVID-19 diagnoses by at least a decade, so they could have changed by the time SARS-CoV-2 testing took place.
Behind the Headlines
Some of the evidence about vitamin D and COVID-19 doesn’t pass the smell test, according to a July letter to the editor of the British Journal of Nutrition.
The authors focused on an Indonesian retrospective study linking low vitamin D levels to a higher risk of dying from COVID-19. Although the publication had not been peer-reviewed, “it has taken the internet by storm,” garnering thousands of tweets, not to mention headlines in major news outlets, the letter writers noted.
The problem, they said, was that they couldn’t track down the authors of the study, which didn’t mention the names or number of hospitals involved. Plus, vitamin D levels aren’t routinely checked in Indonesia, so it’s unclear how the authors would have acquired that information retrospectively. Although the paper is no longer on SSRN, the preprint repository, it can still be found online.
In mid-October, the editors of PLoS One issued an “expression of concern” about a vitamin D study they had published 3 weeks earlier, which found that among patients hospitalized with COVID-19, those with vitamin D levels lower than 30 ng/mL were twice as likely to die than the others.
Only 31.06% of study participants had a laboratory-confirmed COVID-19 diagnosis and potential confounders might not have been adequately addressed. “Vitamin D levels may be indicative of comorbidities that may themselves impact COVID outcomes,” explained the editors, who said they are reassessing the article.
The editors also questioned the authors’ declaration of no competing interests. Public information suggests that corresponding author Michael Holick, MD, PhD, of the Boston University School of Medicine, does have competing interests, including consulting work, industry funding, and authorship of books (such as 2011’s The Vitamin D Solution), the editors wrote.
Conflicts of Interest?
By early December 2020, dozens of studies examining vitamin D and COVID-19, most of which had not yet started recruiting participants, were listed on ClinicalTrials.gov.
Whether any of these studies can settle the debate isn’t clear. The “sponsors and collaborators” section for several planned US studies lists parties that stand to profit if vitamin D deficiency is shown to worsen COVID-19 outcomes, raising the specter of conflicts of interest. In addition, at least 3 US studies plan to test vitamin D in conjunction with hydroxychloroquine, which has repeatedly been shown to be ineffective against COVID-19, most recently in JAMA.
“The credibility of clinical trials requires a hands-off approach from funders,” Ross noted. For that reason, she said, research sponsored by the National Institutes of Health (NIH) is preferred to that funded by the supplement industry.
However, none of the vitamin D and COVID-19 studies on ClinicalTrials.gov appears to be NIH-funded.
JoAnn Manson, MD, chief of preventive medicine at the Brigham and Women’s Hospital, is a principal investigator for one of the largest. In July, Manson coauthored a “call to action” to eliminate vitamin D deficiency during the pandemic. Two of the 11 sources it cited were the questionable preprint from Indonesia and a BMJ “Rapid Response” that also cited the preprint. Tishcon Corporation, a vitamin supplement manufacturer, and Quest Diagnostics, which markets a $69 vitamin D test directly to consumers, are among the sponsors and collaborators of Manson’s study, as are Sweden’s prestigious Karolinska Institute and Harvard Medical School.
Pediatrician Carol Wagner, MD, of the Medical University of South Carolina, is leading a study with 2 sponsors and collaborators that have a vested interest in the findings. ZRT Laboratory, a Beaverton, Oregon, company, sells a $75 vitamin D test directly to consumers. Grassroots Health Nutrient Research Institute operates “D*action,” “a global vitamin D population intervention program” that charges participants $65 for a vitamin D test. Holick serves on the institute’s International Scientists Panel.
The Upshot
Regardless of whether vitamin D protects against COVID-19, adequate levels are important for bone health.
“Avoiding vitamin D deficiency is always a goal,” Ross wrote. “If the diet doesn’t include vitamin D fortified milk or natural products like fish, then a supplement of the RDA [recommended dietary allowance] amount (600-1000 IU per day) provides good assurance. I consider this a ‘good idea,’ but I don’t want to leave the impression that diet cannot be sufficient.”
Accompanying this article is the JAMA Medical News Summary, an audio review of news content appearing in this month’s issues of JAMA. To listen to this episode and more, visit the JAMA Medical News Podcast.
Scouring through as much data on all available servers there is a significant amount of data regarding correlation between Vitamin D and respiratory Illness in general.
I absolutely agree with Dr. Silverstein in his comment regarding relevance of dose. There are many variables that can stymie supplementation and normal physiological levels between 40-60 ng/mL appear to be plausible and I say that from experience.
I work night shift in a clinical lab and we all analyzed our levels in late March. Those who were not supplementing had vitamin D levels < 14 ng/mL. (We reside between the 30th line of latitude)
We started dosing with 10,000 IU for the first week and dropped down to 5000 IU for the following week and that brought our levels in the ballpark of 20 ng/mL. On 5000 IU daily since we were able to achieve levels >40 <60 by the end of the April (Surprised it took that long).
While maintaining this dosage my personal summer peak was 59 ng/mL for (25OHD) and this included vacationing to Florida. Calcium levels never became a factor.
Three weeks ago while on the same 5000 IU daily dosage I was surprised that my personal level of 25(OH)D fell by 17-18% to 48 ng/mL and was likely attributed to lower direct sunlight as we approached winter solstice.
It made me wonder about people at higher latitudes who in the summer might have been straddling the line of clinical deficiency. What would their levels look like if they dropped 17% from summer to winter? It also begs to ask, could the drop be greater at higher latitudes given the less direct sun angle?
Given the lockdown orders and the fact that people are scared to go outside it might be reasonable to think that the RDA's on vitamin D might be too low to be of any benefit to first help people maintain a replete state going into winter from summer or even worse try to correct a deficiency in any reasonable amount of time.
The whole study on Vitamin D is very interesting regarding Innate and adaptive Immune signaling which includes modulation of mitochondrial oxidative stress in many studies in general. Something that could be seemingly important as well is the type of fat intake while supplementing vitamin D to aid in absorption. Monounsaturated (MUFA) fats like real olive, avocado, and high oleic acid safflower oil has been studied to be better over polyunsaturated and saturated fats for aiding in Vitamin D absorption. MUFA's have also shown to lower LDL cholesterol mitochondrial oxidative stress as well which might be beneficial to those who have insulin resistance (1-3).
References
(1) https://academic.oup.com/qjmed/article/93/2/85/1517901
(2) https://www.nature.com/articles/nrendo.2011.150
(3) https://doi.org/10.1210/jc.2013-2103
One aspect that has been ignored frequently in previous RCTs of Vitamin D is the baseline level of 25(OH)D and the geographic region. Whereas in the U.S. most of the population are living below 41 degrees of latitude thus getting enough UVB radiation for vitamin D production via the skin all year long, this is not the case for European countries. Depending on the latitude in Europe there may be a "vitamin D winter" of 5-7 months duration, where there isn´t any vitamin D production via the skin.
In our own unpublished data from Germany with thousands of measurements during the year, average 25(OH)D was 12 ng/ml in March and 24 ng/ml in September with a SD +/-5 ng/ml. So the effect of vitamin D supplementation may be different in different geographic regions due to different baseline levels of vitamin D.
Previous studies and a Cochrane meta-analysis have shown that compared to very low baseline levels of vitamin D, supplementing vitamin D to achieve levels >30 ng/ml will reduce the risk of acquiring respiratory infections and seasonal influenza. Mechanisms that mediate a better immune response of T-cells have been published, as well as an effect of vitamin D on insulin sensitivity. Insulin resistance of T8-helper-cells is one aspect of a slower immune response to seasonal influenza and other viral infections, as T-cells are lacking the "energy boost" mediated by insulin in the first phase response to an infection.
Part of the higher COVID19 risk in black and hispanic patients, obesity, diabetes and older age may be mediated by the observed lower vitamin D levels in these populations. This was suggested by a recent paper in Nature Scientific Reviews:
"Vitamin D deficiency markedly increases the chance of having severe disease after infection with SARS Cov-2. The intensity of inflammatory response is also higher in vitamin D deficient COVID-19 patients. This all translates to increase morbidity and mortality in COVID-19 patients who are deficient in vitamin D. Keeping the current COVID-19 pandemic in view authors recommend administration of vitamin D supplements to population at risk for COVID-19." (1)
What we would need is a rigorous RCT with early / high-dose vitamin D supplementation like 2 x 40 000 IU in week 1 vs. placebo at hospital admission in a high-risk population for severe course of COVID19. It would be easy to undertake, but unlike trials with largely inefficient drugs like remdesivir there is no relevant economic interest in undertaking such a study.
Reference
1. Jain, A., Chaurasia, R., Sengar, N.S. et al. Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. Sci Rep 10, 20191 (2020). https://doi.org/10.1038/s41598-020-77093-z
Furthermore, one may question whether it is correct that the above-mentioned figures were obtained by pooling data of two studies. The first study, published in June, was performed between March and May 12th, 2020. It regarded 105 Parkinson's patients and 92 of their family members with COVID-19 (2). The conclusion of the study was that COVID-19 patients were younger, more likely to suffer from chronic obstructive pulmonary disease and obesity, and not using vitamin D supplements than unaffected patients.
The second study, not published, was performed later and regarded 127 consecutive COVID-19 patients admitted to a hospital. In this group of patients, 40% has ischemic heart disease versus 5% and 4% in the Parkinson group respectively the family members and 20% has cancer versus 1% and 2% in the Parkinson group respectively the family members.
References
1. Cereda E, Bogliolo L, Lobascio F, Barichella M, Zecchinelli AL, Pezzoli G, et al. Vitamin D supplementation and outcomes in coronavirus disease 2019 (COVID-19) patients from the outbreak area of Lombardy, Italy. Nutrition 00 (2020) 111055.
2. Fasano A, Cereda E, Barichella M, Cassani E, Ferri V, Zecchinelli AL, et al. COVID-19 in Parkinson’s Disease Patients Living in Lombardy, Italy. Movement Disorders, 2020; 35: 1089-1093.
References
1. Yisak H et al. Effects of Vitamin D on COVID-19 Infection and Prognosis: A Systematic Review. Risk Manag Healthc Policy. 2021 Jan 7;14:31-38.
2. Ali N. Role of vitamin D in preventing of COVID-19 infection, progression and severity. J Infect Public Health. 2020 Oct;13(10):1373-1380.
Dr Grzegorz Wisniewski (aka Jan Kuziemski on Facebook)
Seven additional peer-reviewed studies showing positive associations are omitted: 1) Ling’s observational study where high-dose vitamin D therapy (~3,000 IU/day) reduced mortality >80%; 2) Katz’s large (>100,000 person) observational study finding ~5-fold COVID-19 risk increase among patients with inadequate vitamin D; 3) Kaufman’s cohort study showing an inverse association between infection risk and vitamin D levels; 4) Merzon’s cohort study finding a 50% increase in SARS CoV-2 positivity among vitamin D-deficient patients; 5) Tan’s cohort study showing vitamin D supplementation decreased supplemental oxygen requirements; 6) Rastogi’s small treatment RCT showing quicker viral clearance among COVID-19 patients who received vitamin D; and 7) Pereira’s systematic review/meta-analysis concluding vitamin D deficiency was associated with COVID-19 hospitalization, severity, and mortality.
Though such comparisons are difficult, these positive studies arguably present stronger evidence than the two negative observational studies Rubin cites: one failed to account for well-documented hypovitaminosis D in non-COVID respiratory disease; the other failed to adjust for unsuccessful repletion in the vitamin D-treated group (an error that Meltzer et al. carefully avoided).
Of the many prominent US public health physicians who have voiced support for investigating potential vitamin D-COVID-19 links (including a former CDC Director and former U.S. Surgeon General) Rubin mentions only Dr. Fauci’s endorsement. Unfortunately, federally funded research has yet to begin. Rubin notes that none of the vitamin D trials listed on clinicaltrials.gov are government funded, but does not mention that, through 1/17/2021, not one of the 607 NIH COVID-19-related notices of grant policies, guidelines, and funding opportunity announcements even mentions vitamin D.
Rubin cautions that, given this absence of federal funding, commercial bias may influence vitamin D/COVID-19 research. A more pertinent conclusion would be to ask why, in the face of considerable published evidence and high-level interest, the U.S. government has yet to direct its considerable resources to confirming whether an inexpensive and virtually risk-free intervention (vitamin D supplementation) can modulate SARS CoV-2 infection and COVID-19.
With a few exceptions, most of the studies that have been circulating thus do not address the question of whether vitamin D supplementation is helpful, either prophylactically or as a treatment.
References
1. https://pubmed.ncbi.nlm.nih.gov/23454726/
2. https://pubmed.ncbi.nlm.nih.gov/25631715/
Walrand's analysis is strong but inference at a patient level from national data is not possible. Also, Nordic countries have mandated vitamin D supplementation in food but still followed the insolation date trend, so further factors must be at work. Foods most commonly supplemented with vitamin D are dairy products and margarines; research in subpopulations who do not benefit from this is warranted.
Reference
1. Nature Scientific Reports, 21 Jan. 2021, "Autumn COVID-19 surge dates in Europe correlated to latitudes, not to temperature-humidity, pointing to vitamin D as contributing factor."
We can understand the value of vitamin D as a drug by comparing it with dexamethasone. Both drugs release hepatic selenium stores and supply Se to monocytes in circulation (1,2). Selenium increase in immune cells allows improved function and in endothelialcirculatory cells is anti-inflammatory. Selenium intake and status has been associated with COVID-19 mortality - and with mutation rates of other RNA viruses (3,4)
The conversion of vitamin D3 to active hormone requires magnesium, iron and vitamin C - cellular handling of these nutrients is impaired in diabetes and chronic illness, so that use of pre-formed D may be essential in critical illness.
References
[1] Schütze N, Fritsche J, Ebert-Dümig R, et al. The selenoprotein thioredoxin reductase is expressed in peripheral blood monocytes and THP1 human myeloid leukemia cells--regulation by 1,25-dihydroxyvitamin D3 and selenite. Biofactors. 1999;10(4):329-338. doi:10.1002/biof.5520100403
[2] Rock C, Moos PJ. Selenoprotein P regulation by the glucocorticoid receptor. Biometals. 2009;22(6):995-1009. doi:10.1007/s10534-009-9251-2
[3] Zhang J, Taylor EW, Bennett K, Saad R, Rayman MP. Association between regional selenium status and reported outcome of COVID-19 cases in China, The American Journal of Clinical Nutrition, Volume 111, Issue 6, June 2020, Pages 1297–1299, https://doi.org/10.1093/ajcn/nqaa095
[4] Moghaddam A, Heller RA, Sun Q et al. L. Selenium Deficiency Is Associated with Mortality Risk from COVID-19. Nutrients 2020, 12, 2098.
However, data re COVID-related biweekly mortality as per 20th Feb are even contraindicating a hypothesis that blood vitamin D level may reduce mortality, as Slovakia has the highest biweekly COVID mortality in the world (236.1/million). On the other side, a second country with the highest biweekly mortality in the world is indeed Portugal (190.55/million).
Based on these data only it would be premature to suggest that vitamin D causes higher COVID-related mortality. Probably more likely is a hypothesis that its blood level has no impact on mortality, but I think that this topic needs urgent attention, taking into account number of people taking vitamin D who believe that this supplement may protect them from COVID infection and its potentially fatal consequences.
Dr Grzegorz Wisniewski (aka Jan Kuziemski on Facebook)
References:
1. https://ourworldindata.org/grapher/biweekly-covid-deaths-per-million-people?stackMode=absolute&country=CAN~FRA~DEU~IND~GBR~USA®ion=World
Meta-analysis of All-Cause Mortality According to Serum 25-Hydroxyvitamin D
Conclusions
There was a downward slope in hazard ratios of mortality according to the serum 25(OH)D concentration. This confirms observations from the National Academy of Sciences–Institute of Medicine Committee to Review Dietary Reference Intakes for Vitamin D and Calcium69 that concentrations less than 20 ng/mL are too low for safety. The present analysis also suggests that serum 25(OH)D concentrations of less than 30 ng/mL may be too low for safety.