Vitamin D versus Covid-19

Over 30 studies have shown that normal levels of vitamin D in the blood reduce Covid-19 risk in a number of ways, including lowering the risk of becoming infected with Covid-19, lowering the risks of needing hospitalization, needing ICU care, and needing mechanical ventilation, and lowering the risk of death from Covid-19. All you need to obtain these risk reductions is normal vitamin D levels in the blood, which you can easily obtain by a vitamin D supplement.

How large is the benefit from vitamin D? It is immensely beneficial; and this large effect is obtained merely by raising vitamin D levels to within the normal range. Normal range is 30 to 100 ng/ml (75 to 250 nmol/liter). And optimal range is probably 40 to 60 ng/ml (100 to 150 nmol/liter).

All this has been well proven by studies. Here are the reference numbers (found in the endnotes) for each benefit. Normal blood levels of vitamin D reduces Covid-19 risk of infection [7, 8, 9, 11, 12, 14, 16, 23, 27, 32, 33], of having a severe case [1, 3, 4, 5, 15, 17, 20, 22, 24, 25, 26, 30, 34], of needing hospitalization, ICU care, and/or mechanical ventilation [2, 10, 14, 15, 21, 22, 24, 26, 30, 35], as well as the risk of dying from Covid-19 [4, 6, 7, 9, 12, 13, 17, 18, 19, 22, 24, 25, 31, 34].

There are additional benefits of vitamin D. Studies have shown that a high intake of vitamin D reduces risk of respiratory tract infections [101], stroke [102], multiple sclerosis [103], rheumatoid arthritis [104], type 2 diabetes [105], breast cancer [106], prostate cancer [107], colon cancer [108], and all-cause mortality [109].

Low Vitamin D in Winter

A study by Kroll et al. [85] of over 3 million U.S. adults found that in winter about three-fourths of the population has either vitamin D deficiency or vitamin D insufficiency. And low vitamin D increases risk of contracting Covid-19. Therefore, the cause of the current increase in Covid-19 cases in many nations, including the U.S. and the U.K., is the typical yearly lowering of vitamin D in the blood during late autumn and winter, through early spring. That is what is causing this increase in Covid-19 cases: low vitamin D.

Vitamin D levels rise in the summer, when many people are outdoors. Sunshine on skin produces vitamin D. This vitamin D lasts about a month once people stop spending time outside with skin exposed to sun. And that is why, once November hit, Covid-19 cases began to increase. Low vitamin D makes people susceptible to contracting Covid-19 and susceptible to having a more severe case. Low vitamin D also makes people more likely to die from Covid-19.

My article reviewing studies of coronaviruses in winter is here. Four studies of human coronaviruses found that cases increase greatly in wintertime. The increase, as compared to a month such as July or August, can be anywhere from 3 to 4 times, all the way up to 9 times or more in the worst winter months (Jan. or Feb.). July in the U.S. had about 2 million cases. A multiple of 9 times would be 18 million cases in one month; a multiple of 3 times would be 6 million cases. And as cases rise, so also do deaths rise.

Doctors and hospitals are getting better at treating Covid-19. But even with a death rate of about 1.5% (current rate calculated with a 2-week lag), the deaths per month would be between 90,000 and 270,000. And that is assuming that the death rates does not rise as a percentage. A higher death rate could occur, due to the effect of vitamin D deficiency causing not only more cases, but more severe cases. And that could cause deaths per month to go even higher.

The Solution is Vitamin D

A program to increase the level of vitamin D in any population is almost certain to have the effect of lowering the case rate, the severity, and the death rate for Covid-19 in that population. Programs should target nursing home patients, all elderly persons, all persons with comorbidities, all hospital patients, all medical staff and all other first responders, and the general population in towns, cities, States or Provinces, and nations.

The result is known. Higher vitamin D will cause Covid-19 to return to its low summer levels as we already saw in July, August, and September. In the month of September, people retain their vitamin D from being out in the sun in summer. It takes a month or so for vitamin D levels to decline. If we fail to undertake a vitamin D program, then this result is also known, Covid-19 cases and deaths will continue to climb, until the government undertakes a massive shutdown to stop the spread of the disease.

We do not need a shutdown. A vaccine would certainly be helpful, but we do not need to wait for a vaccine. Vitamin D supplementation will have a very large beneficial effect in reducing Covid-19 cases and severity. The effect should be sufficient to avert a shutdown, but only if we being the program immediately.

Raising national average vitamin D levels does work. A study [7] by Petre Ilie et al., reviewed and updated with more recent data here, found that EU nations with the highest average level of vitamin D had the lowest rates for infection and for death from Covid-19. And a study [23] by Ariel Israel, in Israel, found that blood levels in the range of 50 to 60 ng/ml (which is 125 to 150 nmol/liter) can reduce the risk of infection with Covid-19 by more than 50% as compared to a blood level of 20 ng/ml (which is one point above vitamin D deficiency). Several other studies looked at the effect of vitamin D blood levels on Covid-19 at a national level, and they found the same risks of low vitamin D and benefits of normal vitamin D levels as for individuals.

Which Dosage To Recommend?

A group of vitamin D experts should quickly determine the best dosage for each age group. What follows is an initial discussion of possible doses.

The article “Vitamin D in the prevention and treatment of Covid-19” recommends a single dose of 600,000 IU of vitamin D3, and then, beginning 30 days later, either 10,000 IU or 20,000 IU of vitamin D3 per day continuously, to fight against Covid-19. Many studies in past years have shown the safety and effectiveness of this type of bolus dose of vitamin D.

This video by 4 vitamin D experts — Holick, Grant, Davies, Grimes — recommends 50,000 IU of vitamin D3 once a week, with no initial high dose to raise vitamin D deficiency to normal levels. This approach will take weeks or months for some persons to normalize their blood levels. So 50,000 IU once a week is fine, but probably an initial higher dose would be better, to reach normal levels faster.

Other experts recommend Vitamin D supplementation as a measure against Covid-19 [81, 83, 84], at a dosage of 10,000 IU per day for a few weeks or a month, reducing to 5,000 IU/day thereafter [81, 84]. Doses of 10,000 IU/day are necessary to raise vitamin D levels in 97.5% of the population to optimal levels; lower doses may not be effective in everyone [82]. Doses as high as 40,000 IU/day are unlikely to result in vitamin D toxicity [82].

Conclusion

I’m asking Vitamin D experts and study authors to form an advisory committee, consult with one another, and publish a Vitamin D plan which will work for any nation, city, nursing home, hospital, school, or family. The idea is to quickly raise blood levels of vitamin D to obtain the reduction in infection, severity, and deaths indicated by over 30 studies. I am also asking these experts to decide upon a dosage for children, teenagers, and adults, with special concern for the elderly and those with comorbidities or obesity.

Until then, my recommendation is 100,000 IU of vitamin D3 on each of 5 consecutive days. Then, 30 days from day one, begin taking 100,000 IU of vitamin D3 once per week. Alternately, you can take the same 5-day dosing, and then, 30 days later, start taking 20,000 IU once a day continuously.

ENDNOTES

1. Alipio, Mark. “Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-19).” SSRN 3571484 (9 April 2020).
Study Link

2. Lau, Frank H., et al. “Vitamin D insufficiency is prevalent in severe COVID-19.” medRxiv (28 April 2020).
Study Link

3. Daneshkhah, Ali, et al. “The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients.” medRxiv (2020).
Study Link

4. Davies, Gareth, Attila R. Garami, and Joanna C. Byers. “Evidence Supports a Causal Model for Vitamin D in COVID-19 Outcomes.” medRxiv (2020).
Study Link

5. De Smet, Dieter, et al. “Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics.” medRxiv (2020).
Study Link

6. Raharusun, Prabowo, et al. “Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study.” (2020).
PDF file

7. Ilie, Petre Cristian, Simina Stefanescu, and Lee Smith. “The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality.” Aging Clinical and Experimental Research (2020): 1.
Study Link

8. D’Avolio, Antonio, et al. “25-hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2.” Nutrients 12.5 (2020): 1359.
Study Link

9. Laird, E., et al. “Vitamin D and Inflammation: Potential Implications for Severity of Covid-19.” Ir Med J; Vol 113; No. 5; P81: 2020.
PDF file

10. Faul, J.L., et al. “Vitamin D Deficiency and ARDS after SARS-CoV-2 Infection.” Ir Med J; Vol 113; No. 5; P84: 2020.
PDF file

11. Meltzer, David O., et al. “Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence.” medRxiv (2020).
Study Link

12. Li, Yajia, et al. “Sunlight and vitamin D in the prevention of coronavirus disease (COVID-19) infection and mortality in the United States.” (2020).
PDF file

13. Pugach, Isaac Z. and Pugach, Sofya “Strong Correlation Between Prevalence of Severe Vitamin D Deficiency and Population Mortality Rate from COVID-19 in Europe.” medRxiv (2020).
Study Link

14. Merzon, Eugene, et al. “Low plasma 25(OH) vitamin D3 level is associated with increased risk of COVID-19 infection: an Israeli population-based study.” medRxiv (2020). — Low vitamin D increased risk (adjusted OR) of infection with Covid-19 by 45% and of hospitalization for Covid by 95%.
Study Link

15. Panagiotou, Grigorios et al., “Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID-19 are associated with greater disease severity: results of a local audit of practice.” medRxiv (2020). Conclusion: “we found that patients requiring ITU admission [in the ICU] were more frequently vitamin D deficient than those managed on medical wards [on the floor], despite being significantly younger.”
PDF file Link

16. Chang, Timothy S., et al. “Prior diagnoses and medications as risk factors for COVID-19 in a Los Angeles Health System.” medRxiv (2020).
Study Link
~ Risk factors included vitamin D deficiency, which increased risk of COVID-19 diagnosis by 80% (OR 1.8 [1.4-2.2], p=5.7 x 10-6).

17. Maghbooli, Zhila, et al. “Vitamin D Sufficiency Reduced Risk for Morbidity and Mortality in COVID-19 Patients.” Available at SSRN 3616008 (2020).
Study Link
~ Vitamin D sufficiency reduced clinical severity and inpatient mortality.

18. Panarese and Shahini, “Letter: Covid-19 and Vitamin D” Alimentary Pharmacology and Therapeutics, April 12, 2020.
Link to Letter
~ Covid-19 mortality increases with increasing latitude (by nation), and vitamin D blood levels decrease with increasing latitude. The authors propose that low levels of vitamin D increase Covid-19 mortality.

19. Carpagnano, Giovanna Elisiana, et al. “Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19.” Journal of Endocrinological Investigation (2020): 1-7. Study Link
~ “A survival analysis highlighted that, after 10 days of hospitalization, severe vitamin D deficiency patients had a 50% mortality probability, while those with vitamin D = 10 ng/mL had a 5% mortality risk (p = 0.019).”

20. Mardani, R., et al. “Association of vitamin D with the modulation of the disease severity in COVID-19.” Virus Research (2020): 198148. Study Link

21. Castillo, Marta Entrenas, et al. “Effect of Calcifediol Treatment and best Available Therapy versus best Available Therapy on Intensive Care Unit Admission and Mortality Among Patients Hospitalized for COVID-19: A Pilot Randomized Clinical study.” The Journal of Steroid Biochemistry and Molecular Biology (2020): 105751. Study Link
** This was a peer-reviewed randomized placebo-controlled trial (RCT). It’s sufficient. See the Chris Masterjohn, Ph.D. commentary here.

22. Radujkovic, et al. “Vitamin D Deficiency and Outcome of COVID-19 Patients.” Nutrients 2020, 12(9), 2757; Study Link
— “The present study demonstrates an association between VitD deficiency and severity of COVID-19.
VitD-deficient patients had a higher hospitalization rate and required more (intensive) oxygen therapy
and IMV. In our patients, when adjusted for age, gender, and comorbidities, VitD deficiency was
associated with a 6-fold higher hazard of severe course of disease and a ~15-fold higher risk of death.”

23. Israel, Ariel, et al. “The link between vitamin D deficiency and Covid-19 in a large population.” MedRxiv 9/7/2020. Study Link

24. Jae Hyoung Im, et al. “Nutritional status of patients with coronavirus disease 2019 (COVID-19).”
International Journal of Infectious Diseases. August 7, 2020. PDF Link

25. Gennari L, et al “Vitamin D deficiency is independently associated with COVID-19 severity and mortality” ASBMR 2020; Abstract 1023. Study Link

26. Baktash, Vadir, et al. “Vitamin D status and outcomes for hospitalised older patients with COVID-19.” Postgraduate Medical Journal (2020). Study Link
— “The main findings of our study suggest that older patients with lower serum concentrations of 25(OH)D, when compared with aged-matched vitamin D-replete patients, may demonstrate worse outcomes from COVID-19. Markers of cytokine release syndrome were raised in these patients and they were more likely to become hypoxic and require ventilatory support in HDU.” [HDU is high dependency unit]

27. Kaufman HW, et al. “SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels.” (2020) PLoS ONE 15(9): e0239252. Study Link
— Optimum vitamin D blood level for reducing Covid-19 infection was found to be in the 50’s (ng/ml). This is the first study to show that 25(OH)D at levels above 30 have additional benefits.

28. Brenner, Hermann, Bernd Holleczek, and Ben Schöttker. “Vitamin D Insufficiency and Deficiency and Mortality from Respiratory Diseases in a Cohort of Older Adults: Potential for Limiting the Death Toll during and beyond the COVID-19 Pandemic?.” Nutrients 12.8 (2020): 2488.
— “Compared to those with sufficient vitamin D status, participants with vitamin D insufficiency and deficiency had strongly increased respiratory mortality, with adjusted hazard ratios (95% confidence intervals) of 2.1 (1.3–3.2) and 3.0 (1.8–5.2) overall, 4.3 (1.3–14.4) and 8.5 (2.4–30.1) among women, and 1.9 (1.1–3.2) and 2.3 (1.1–4.4) among men. Overall, 41% (95% confidence interval: 20–58%) of respiratory disease mortality was statistically attributable to vitamin D insufficiency or deficiency. Vitamin D insufficiency and deficiency are common and account for a large proportion of respiratory disease mortality in older adults, supporting the hypothesis that vitamin D3 supplementation could be helpful to limit the burden of the COVID-19 pandemic, particularly among women.”

29. Pepkowitz, Samuel H., et al. “Vitamin D Deficiency is Associated with Increased COVID-19 Severity: Prospective Screening of At-Risk Groups is Medically Indicated.” (2020). PDF File
— Persons hospitalized for Covid-19 were more than twice as likely to need ICU care if they had with vitamin D deficiency.

30. Mandal, Amit KJ, et al. “Vitamin D status may indeed be a prognosticator for morbidity and mortality in patients with COVID‐19.” Journal of Medical Virology. PDF Link
— Findings: “patients with low concentrations of 25OH-D (<or=30nmol/l) demonstrated clinically relevant, elevated markers of cytokine release syndrome and were more likely to become hypoxic and require ventilatory support.”

31. Karahan and Katkat. “Impact of Serum 25(OH) Vitamin D Level on Mortality in Patients with COVID-19 in Turkey.” The journal of nutrition, health & aging (2020). PDF File

32. Faniyi, et al. “Vitamin D status and seroconversion for COVID-19 in UK healthcare workers who isolated for COVID-19 like symptoms during the 2020 pandemic.” medRxiv 6 Oct. 2020. PDF Link
— “Vitamin D deficiency is a risk factor for COVID-19 seroconversion for NHS healthcare workers especially in BAME male staff.”

33. Yılmaz, Kamil, and Velat Şen. “Is Vitamin D Deficiency a Risk Factor for Covid 19 in Children?.” Pediatric Pulmonology. Study Link
— “The symptom of fever was significantly higher in COVID‐ 19 patients who had deficient and insufficient vitamin D levels than in patients who had sufficient vitamin D level.”
— “Patients with COVID‐19 had significantly lower vitamin D levels 13.14 ng/ml than did the controls 34.81 ng/ml.”

34. Annweiler, C. et al. “Vitamin D and survival in COVID-19 patients: A quasi-experimental study.” The Journal of Steroid Biochemistry and Molecular Biology, 13 October 2020. Study Link
— Bolus vitamin D3 supplementation during or just before COVID-19 was associated with less severe COVID-19 and better survival rate in frail elderly.

35. Han, Jenny E., et al. “High dose vitamin D administration in ventilated intensive care unit patients: a pilot double blind randomized controlled trial.” Journal of clinical & translational endocrinology 4 (2016): 59-65. Study Link
— Hospital stay cut in half for patients needing ICU care and ventilation and receiving 100,000 IU Vitamin D3 daily for 5 days.

Vitamin D versus Covid, Commentary

81. 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. Study Link
— “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…. For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful.”

82. 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. Study Link
— “Results: Serum 25(OH)D rose as a function of self-reported vitamin D supplement ingestion in a curvilinear fashion, with no intakes of 10,000 IU/d or lower producing 25(OH)D values above the lower-bound of the zone of potential toxicity (200 ng/ml). Unsupplemented all-source input was estimated at 3,300 IU/d. 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. Conclusion: Universal intake of up to 40,000 IU vitamin D per day is unlikely to result in vitamin D toxicity.”

83. Charoenngam and Holick, “Immunologic Effects of Vitamin D on Human Health and Disease.” Nutrients 2020, 12(7), 2097; Study Link
— “It is therefore proposed that supplementation of vitamin D can reduce the risk and severity of COVID-19 infection.”

84. Sharma, Suresh K., et al. “Vitamin D: A cheap yet effective bullet against coronavirus disease-19–Are we convinced yet?.” National Journal of Physiology, Pharmacy and Pharmacology 10.7 (2020): 0-0.
Study Link
“Therefore, from reviewed literature, it seems fairly appropriate to suggest taking Vit-D at 10,000 IU/day as an adequate dose to enhance circulatory concentration of Vit-D into the optimal range of 40–60 ng/mL; after 1 month the dose can be reduced to 5000 IU/day to maintain serum levels.”

85. Kroll, Martin H., et al. “Temporal relationship between vitamin D status and parathyroid hormone in the United States.” PloS one 10.3 (2015): e0118108. Study Link
— Based on 3.8 million lab results of adults in the U.S.: “Vitamin D deficiency and insufficiency was common (33% <20 ng/mL; 60% <30 ng/mL)…. The percentage of patients deficient in 25(OH)D3 seasonally varied from 21% to 48%…."

86. Matthews, L. R., et al. "Aggressive Treatment of Vitamin D Deficiency in Hispanic and African American Critically Injured Trauma Patients Reduces Health Care Disparities (Length of stay, Costs, and Mortality) in a Level I trauma center surgical intensive care unit." Glob J Medical Clin Case Rep 4.2 (2017): 042-046.

Vitamin D versus Other Diseases

101. Martineau, Adrian R., et al. “Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data.” bmj 356 (2017).
Study Link
— Recommend daily or weekly dose, but not bolus dosing.

102. Marniemi et al., Dietary and serum vitamins and minerals as predictors of myocardial infarction and stroke in elderly subjects; Nutrition, Metabolism & Cardiovascular Diseases. Volume 15, Issue 3 , Pages 188-197, June 2005. Study Link

103. Munger et al., Vitamin D intake and incidence of multiple sclerosis; Neurology. January 13, 2004 vol. 62 no. 1, p. 60-65. Study Link

104. Merlino et al., Vitamin D intake is inversely associated with rheumatoid arthritis: Results from the Iowa Women’s Health Study; Arthritis & Rheumatism. Volume 50, Issue 1, pages 72-77, January 2004. Study Link

105. Pittas et al., Vitamin D and Calcium Intake in Relation to Type 2 Diabetes in Women; Diabetes Care. March 2006 vol. 29 no. 3 650-656. Study Link

106. Garland et al., Vitamin D and prevention of breast cancer: Pooled analysis; The Journal of Steroid Biochemistry and Molecular Biology, Volume 103, Issues 3-5, March 2007, Pages 708-711; Study Link

107. Garland et al., The Role of Vitamin D in Cancer Prevention; American Journal of Public Health. 2006 February; 96(2): 252-261. Study Link

108. Gorham et al., Optimal Vitamin D Status for Colorectal Cancer Prevention: A Quantitative Meta-Analysis; American Journal of Preventive Medicine. Volume 32, Issue 3 , Pages 210-216, March 2007; Study Link

109. Antonio, Leen, et al. “Free 25-hydroxyvitamin D, but not free 1.25-dihydroxyvitamin D, predicts all-cause mortality in ageing men.” 22nd European Congress of Endocrinology. Vol. 70. BioScientifica, 2020.