Vitamin D versus Covid-19: part three expert opinion

See part one here and part two here.

Grant, Lahore, McDonnell, Baggerly, French, Aliano, and Bhattoa [1]

Seven authors publishing in the peer-reviewed journal Nutrients (2020) reviewed the evidence on Vitamin D and Covid-19. Their study is titled “Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths” [1]. They point out that vitamin D can reduce risk of infection, and also reduce the vicious cycle of immune system over-reaction and hyper-inflammation that kills many Covid-19 patients:

“Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines.” [1]

And their conclusion is that people should consider taking vitamin D.

“To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful.” [1]

Their advice: 10,000 IU of vitamin D per day, which is 250 micrograms (mcg) or 0.25 milligrams (mg). After a few weeks, they recommend cutting the dose in half, to 5,000 IU per day. That’s the advice for persons who are well. They also state that, for persons “who become infected with COVID-19, higher vitamin D3 doses might be useful.” [1]. This advice agrees with that of other experts.

Dr. Grant’s position was criticized in a BMJ article here: Vitamin D and SARS-CoV-2 virus/COVID-19 disease. His reply, quoted from NutraIngredients.com was as follows:

He argues that evidence has shown​ that, when starting near 20 ng/ml, it takes about 35 days to reach 60 ng/ml with 10,000 IU/d and 85 days with 4000 IU/d.

“We strongly disagree that vitamin D supplementation should be held in abeyance for prevention until such RCTs are completed and reported. Those at highest risk of infection due to having chronic disease, low 25(OH)D status, and/or being in frequent contact with others likely to be infected should be taking vitamin D,” ​he says.

“As noted, there is mounting evidence that vitamin D can reduce risk and severity of RTIs including that the mechanisms are known, that there are many health benefits of higher 25(OH)D concentrations, and that there are very few adverse effects of vitamin D3 supplementation… Thus, there is much to gain and little to lose by taking vitamin D supplements now for COVID-19 prevention.”​

We don’t need to wait for RCTs (randomized controlled trials), as we have sufficient evidence that vitamin D supplementation does much good with little risk of harm. (RTIs are respiratory tract infections.)

I should also point out that many RCTs have been done on vitamin D supplementation, and these studies establish without doubt that taking vitamin D supplements is beneficial. For example, Autier and Gandini did a meta-analysis of 18 RCTs on vitamin D, establishing that supplementation with vitamin D lowers total mortality, i.e. your overall risk of death [8]. We simply don’t have RCTs on vitamin D versus Covid-19.

But we do know that 10,000 IU per day of vitamin D is safe:

“Evidence from clinical trials shows, with a wide margin of confidence, that a prolonged intake of 10,000 IU/d of vitamin D3 poses no risk of adverse effects for adults, even if this is added to a rather high physiologic background level of vitamin D.” [9]

Hastie, Pell, and Sattar

In this brief communication, the authors analyzed data from patients in the UK and found that, after adjustment for confounders, there was no correlation between vitamin D and Covid-19 mortality or severe infection. The authors then stated that “Recommendations for vitamin D supplementation to lessen COVID-19 risks may provide false reassurance.” [10]

However, in studies on any type of correlation or causation, it is common for some studies to find no relation, while other studies do find a relation in the data. One study finding no correlation does not justify the conclusion that supplementation with an essential nutrient, confirmed as helpful by over a dozen other studies, is “false reassurance”.

Garland, French, Baggerly, and Heaney [2]

In a study unrelated to Covid-19, Garland et al. in Anticancer Research, recommended high doses of vitamin D to reduce the risk of cancer. They recommended high blood levels of vitamin D: “60-80 ng/ml may be needed to reduce cancer risk” [2]. How might this blood level be achieved? “The supplemental dose ensuring that 97.5% of this population achieved a serum 25(OH)D of at least 40 ng/ml was 9,600 IU/d.” [2]. Just under 10,000 IU/day is needed for only 40 ng/ml, but the goal proposed in the study, to reduce risk of cancer (this study was from 2001 before Covid), might require an even higher level of 60-80 ng/ml. And that’s why the authors then state that: “Universal intake of up to 40,000 IU vitamin D per day is unlikely to result in vitamin D toxicity.” [2]

I currently take 10,000 IU/day of vitamin D. And if I get sick with Covid-19, I’ll be taking a higher dose, as that “might be useful”. High levels of vitamin D are not only useful against Covid-19 and other infections, it may also reduce your risk of cancer.

Panarese and Shahini [3]

These authors did a brief study of Covid-19 by nation versus latitude. They also reviewed the research on Vitamin D.

“It therefore seems plausible that Vitamin D prophylaxis (without over-dosing) may contribute to reducing the severity of illness caused by SARS-CoV-2, particularly in settings where hypovitaminosis D is frequent. This will include people currently living in Northern countries and those with underlying gastroenterological conditions where vitamin D deficiency is more prevalent. This may become even more important with absence of sunlight exposure as a consequence of ‘shut-down’ measures to control the spread of Covid-19.” [3]

The authors recommended vitamin D be taken prior to becoming ill (as a prophylaxis) as it may reduce “the severity of illness caused by SARS-CoV-2” (i.e. Covid-19). They noted that “Covid-19 outbreaks and particularly mortality exhibit a decreasing North-South gradient,” [3] meaning that nations at higher latitudes are worse off, due to lower amounts of sunlight, especially in winter. They also explained the severity of the Covid-19 outbreak in Italy as due to lower levels of vitamin D in the elderly: “Elderly Italians display a very high prevalence of hypovitaminosis D, especially during the winter” [3]. Hypovitaminosis D is simply a vitamin D deficiency.

Hribar, Cobbold, and Church [4]

These authors are experts on Parkinson’s disease (PD). They note that vitamin D may benefit Covid-19 as well as Parkinson’s disease.

“In addition to its immune-system-modulating effects, it has been suggested that vitamin D supplementation plays a role in slowing PD progression and improving PD-related quality of life. We completed a review of the literature to determine the relationship between vitamin D, PD, and COVID-19. We concluded that the daily supplementation of 2000–5000 IU/day of vitamin D3 in older adults with PD has the potential to slow the progression of PD while also potentially offering additional protection against COVID-19.”

In addition to the benefit of reducing the risk of cancer, explained by Garland et al., vitamin D may possibly slow the progression of PD, and then also protect against Covid-19. These authors recommended 2000 to 5000 IU/day for older adults. Other authors recommended vitamin D more generally, for adults of all ages.

Arboleda-Alzate and Urcuqui-Inchima [5]

These researchers specialize in immunovirology, how viruses affect the immune system. They propose that vitamin D might reduce the ability of SARS-CoV-2 (the virus that causes Covid-19) to infect cells by interfering with the viruses ability to attach to the cell. They also note that vitamin D has effects on the immune system, down regulating inflammation and possibly protecting against the cytokine storm. The cytokine storm is an over-reaction of the immune system, initiated by Covid-19, which kills many patients by hyper-inflammation and fluid in the lungs.

“we postulate that Vitamin D might attenuate SARS-CoV-2 infection by impairing viral attachment to target cells. Furthermore, we highlight the anti-inflammatory features of vitamin D-derived regulation via ACE2 receptor under lung injury models as a protective factor for the cytokine storm that fuels the severity of symptoms. Although this commentary is aimed to suggest a research pathway on COVID-19 pathogenesis, it also provides insights into the extent of conventional vitamin D supplementation as an accessible, quick and low-cost strategy to reduce infection and progression of the symptoms caused by SARS-CoV-2” [5]

Vitamin D is an “accessible, quick and low-cost strategy” [5] to address Covid-19, especially in persons who are not yet ill, and so cannot be given prescription medications.

McCullough, Amend, Repas, Travers, and Lehrer [6]

These authors reviewed the evidence on the effects vitamin D has on the immune system, and they recommended that the tolerable upper limit (TUL) of vitamin D be raised to 10,000 IU/day [6]. They note that this dose produced much greater beneficial effects than the more common lower doses.

“We propose that increased vitamin D supplementation could provide a safe and cost-effective way to protect all populations from infections, in particular those from pandemic COVID-19.” [6]

Their conclusion is that vitamin D has many benefits, in fighting against multiple diseases, and may well be a simple inexpensive way to reduce the harm from the Covid-19 pandemic. Many other experts are speaking similarly.

Kasahara, Singh, and Noymer [7]

These authors published an article in 2013 (before the pandemic) about vitamin D. The title is: “Vitamin D (25OHD) Serum Seasonality in the United States.” Levels of vitamin D in the blood rise and fall with the seasons in the United States. In winter, vitamin D levels are at their lowest (Dec., Jan., Feb.). In summer, they are at their highest (June, July, Aug.).

Given the evidence found in this three-part article series for the beneficial effects of vitamin D on Covid-19, we can expect the pandemic to show a resurgence this coming winter (2020-2021). And it will be worse than it was earlier this year, because now the virus has spread throughout the world. The infection rate and death rate could rise sharply, especially if there is no lockdown by that time.

How can we avoid this scenario? Vitamin D supplements are the primary means. In winter, people receive far less exposure to the sun. And diet is seldom sufficient to raise vitamin D blood levels. The sunnier hotter nations might raise vitamin D levels by sun exposure even in their winter season. But other nations will need to undertake a massive swift programs of vitamin D supplementation. Otherwise, the resurgence of Covid-19 will be worse than ever before.

Many organizations are developing vaccine candidates. But we might not have a vaccine before winter, or it might not be distributed by then. Another issue with vaccines is that the effectiveness of the earliest successful vaccines might be quite limited. Yearly flu vaccines in the U.S. range in effectiveness from 19% to 60%. So a vaccine is not sufficient to stem the pandemic.

Rhodes, Subramanian, Laird, Griffin, and Kenny [11]

Substantial evidence supports a link between vitamin D deficiency and COVID‐19 severity but it is all indirect. Community‐based placebo‐controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID‐19 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile vitamin D supplementation should be strongly advised for people likely to be deficient.

The authors of the above study concluded that UV light increases vitamin D levels in some populations more than others, benefiting those with higher vitamin D in the blood. At this point, we should not wait for an RCT — which might not even be moral considering the weighty evidence in favor of vitamin D. People should be told to supplement with vitamin D or get plenty of sunlight on their skin.

Arboleda and Urcuqui-Inchima [12]

In the article “Vitamin D Supplementation: A Potential Approach for Coronavirus/COVID-19 Therapeutics?” the authors note that vitamin D has multiple effects — on the immune system, on ACE2 expression, and on other surface proteins — which should benefit Covid-19 patients considerably.

Charoenngam and Holick [13]

“Apart from the immunomodulatory and anti-viral effects, 1,25(OH)2D acts specifically as a modulator of the renin–angiotensin pathway and down-regulates the expression of angiotensin converting enzyme-2 expression, which serves as the host cell receptor that mediates infection by SARS-CoV-2. It is therefore proposed that supplementation of vitamin D can reduce the risk and severity of COVID-19 infection.

“Although the efficacy of vitamin D is still unclear as the results of ongoing clinical trials are still pending, it is advisable that one should maintain adequate vitamin D intake to achieve the desirable serum 25(OH)D level of 40–60 ng/mL (100–150 nmol/L) in order to minimize the risk and severity of COVID-19 infection.” [13]

What Next?

We need a vitamin D program, regardless of whether there is a vaccine or a treatment for Covid-19 by winter. This would have to be a nation-by-nation worldwide program to raise vitamin D levels in populations at risk for vitamin D. In nations afflicted by economic hardship, exposure of the skin to the sun can raise vitamin D to a sufficiently high level. In developed nations, vitamin D supplementation may be more practical. And the benefits are not limited to reducing the severity of Covid-19. Many diseases are reduced in prevalence or severity when a population has high levels of vitamin D.

Ronald L. Conte Jr.
Covid.us.org
Note: the author of this article is not a doctor, nurse, or healthcare provider.

See part one here and part two here.

1. Grant, William B., et al. “Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths.” Nutrients 12.4 (2020): 988.

2. Garland, Cedric F., et al. “Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention.” Anticancer research 31.2 (2011): 607-611.

3. Panarese, Alba, and Endrit Shahini. “Covid‐19, and vitamin D.” Alimentary Pharmacology & Therapeutics 51.10 (2020): 993.

4. Hribar, Casey A., Peter H. Cobbold, and Frank C. Church. “Potential Role of Vitamin D in the Elderly to Resist COVID-19 and to Slow Progression of Parkinson’s Disease.” Brain Sciences 10.5 (2020): 284.

5. Arboleda, John, and Silvio Urcuqui-Inchima. “Vitamin D supplementation: a potential approach for COVID-19 therapeutics?.” (2020).

6. McCullough, Patrick J., et al. “The Essential Role of Vitamin D in the Biosynthesis of Endogenous Antimicrobial Peptides May Explain Why Deficiency Increases Mortality Risk in COVID-19 Infections.” (2020).

7. Kasahara, Amy K., Ravinder J. Singh, and Andrew Noymer. “Vitamin D (25OHD) serum seasonality in the United States.” PloS one 8.6 (2013).

8. Autier, Philippe, and Sara Gandini. “Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials.” Archives of internal medicine 167.16 (2007): 1730-1737.

9. Vieth, Reinhold. “Vitamin D and cancer mini-symposium: the risk of additional vitamin D.” Annals of epidemiology 19.7 (2009): 441-445.

10. Hastie, et al. “Short Communication: Vitamin D and COVID-19 infection and mortality in UK Biobank.” medRxiv (2020).

11. Rhodes, Jonathan M., et al. “Perspective: Vitamin D deficiency and COVID‐19 severity–plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2, and thrombosis (R1).” Journal of Internal Medicine.

12. Arboleda, John F., and Silvio Urcuqui-Inchima. “Vitamin D Supplementation: A Potential Approach for Coronavirus/COVID-19 Therapeutics?.” Frontiers in Immunology 11 (2020).

13. Charoenngam and Holick, “Immunologic Effects of Vitamin D on Human Health and Disease.” Nutrients 2020, 12(7), 2097; https://doi.org/10.3390/nu12072097
https://www.mdpi.com/2072-6643/12/7/2097/htm