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Explaining the Research on Covid-19

Vitamin D

Can Vitamin D help against Covid-19?

Substantial evidence from scientific studies shows that vitamin D reduces risk of infection, of a severe case, and of death from Covid-19.

* Here is an Open Letter on Vitamin D and Covid-19, signed by over 200 physicians, researchers, and other experts on vitamin D and Covid-19. They recommend 10,000 IU of vitamin D3 daily for 2 to 3 weeks, followed by 4,000 IU daily continuously (at least as long as the pandemic continues).

* Good information at: Vitamin D Wiki

* Vitamin D is effective for COVID-19: meta analysis of 36 studies. December 17, 2020 (Version 5, December 31, 2020).

* Conservative MP calls for nationwide rollout of vitamin D tablets to people at-risk from Covid-19 after a Spanish region sees 82% drop in deaths following supplement programme – Why isn’t every city, state, and nations doing this?
* Op-Ed: Don’t Let COVID-19 Patients Die With Vitamin D Deficiency – the evidence to-date is more than sufficient; risk is very low, benefits are very high.

Media Coverage of Vitamin D

* Rome employees partake in plan to raise vitamin D to combat COVID-19 – “The vitamin D testing for the city of Roma revealed that 95% of the employees have dangerously low vitamin D,” Mussett said. “The vitamin D was so dangerously low, that they are at much higher risk of becoming infected and at much higher risk of death or getting very, very sick from COVID.”
* Vitamin D can help reduce coronavirus risk by 54%: Boston University doctor – “People have been looking for the magic drug or waiting for the vaccine and not looking for something this simple,” said Dr. Michael Holick, professor of medicine, physiology and biophysics at Boston University School of Medicine.
* See also this video from 4 vitamin D experts
* 110-Plus International Experts Release Open Letter: COVID-19 Preys on Those with Vitamin D Deficiency – – COVID-19 is disproportionately worse for people with low vitamin D levels; 35-40% of the world’s population is deficient in vitamin D, which is worse during wintertime; rates are highest for those who are overweight/obese, have dark skin, are elderly or residents of care homes; These experts themselves take, on average, more than 6 times the recommended daily amount of vitamin D.

Vitamin D articles

* List of Vitamin D and Covid-19 Studies and Results

* Vitamin D versus Covid-19: part one
* Vitamin D versus Covid-19: part two
* Vitamin D versus Covid-19: part three
* Fighting Covid-19: Vitamin D, Magnesium, Vitamin B12

* Vitamin D and Covid-19 Clinical Trials from ClinicalTrials.gov ongoing trials.

Vitamin D videos

* Vitamin D NOW for COVID-19 by Allan Mishra, MD and DareToBeVital.com
* Video: Does Vitamin D Protect Against COVID-19? by Dr. JoAnn E. Manson, MD, DrPH
* Dr. Mobeen Syed on immune system benefits of vitamin D
* Dr. Syed again on Vitamin D overview and description of an RCT
* Dr. Roger Seheult of MedCram on vitamin D

Vitamin D commentary

* Vitamin D Insufficiency May Account for Almost Nine of Ten COVID-19 Deaths Nutrients 2020, 12, 2757.” Nutrients 12.12 (2020): 3642.

* For more vitamin D commentary, see this article.

Other Vitamins and Minerals

Selenium:
Smith, Joyce. “Selenium Deficiency Linked to Increased Mortality Risk from COVID-19.” Study Link

Kieliszek, Marek, and Boguslaw Lipinski. “Selenium supplementation in the prevention of coronavirus infections (COVID-19).” Medical hypotheses 143 (2020): 109878. Study Link

Dr. Been Medical Lectures (YouTube) on Selenium

Summary

Having normal healthy blood levels of vitamin D reduces Covid-19 risks, including risk of infection [7, 8, 9, 11, 12, 14, 16, 23, 27, 32, 33, 37, 41, 52, 57, 58], of having a severe case [1, 3, 4, 5, 15, 17, 20, 22, 24, 25, 26, 30, 34, 39, 40, 42, 43, 44, 45, 50, 51, 55. 56], of needing hospitalization, ICU care, and/or mechanical ventilation [2, 10, 14, 15, 21, 22, 24, 26, 30, 35, 40, 44, 53], as well as the risk of dying from Covid-19 [4, 6, 7, 9, 12, 13, 17, 18, 19, 22, 24, 25, 31, 34, 36, 38, 40, 45, 46, 47, 48, 49, 53, 54, 58] and improve overall outcome for Covid-19 cases [1, 4, 22, 26, 44, 52, 54, 55].

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].

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]. Severe vitamin D deficiency more than doubles risk of death from cancer in-hospital, and more than triples death from cancer after one year [111].

Vitamin D can be taken daily or once-a-week. A one-time bolus of 300,000 IU of vitamin D is safe [87, 90] and may be useful when vitamin D cannot be taken daily, or when someone becomes ill and needs to raise their vitamin D levels as quickly as possible. Calcifediol can be used in-hospital to treat patients with Covid-19 and low vitamin D [21].

Sunlight on skin can produce significant amounts of vitamin D, butt he amount of skin exposed must be more than the face and hands [89]. Face, hands, and arms exposed to sunlight is a minimum for reaching vitamin D normal levels [88, 89].

Other Vitamins

articles:
* Riboflavin (Vitamin B2) as an Inhibitor of Covid-19
* MATH+ Protocol for prophylaxis and mild cases (Vitamins D, C, B1)

videos:
* Dr. Mobeen Syed: Vitamin K Deficiency Leads to Poor COVID-19 Outcome

Vitamin D versus Covid-19, Studies

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 | PDF Link

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

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

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 | PDF 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 | PDF 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 | PDF Link

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 | PDF Link

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

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 | PDF 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 | PDF 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 | PDF 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 | PDF 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 | PDF Link
~ Vitamin D sufficiency reduced clinical severity and inpatient mortality.
* See this Expression of Concern by the editors of PLoS One

18. Panarese and Shahini, “Letter: Covid-19 and Vitamin D” Alimentary Pharmacology and Therapeutics, April 12, 2020.
Link to Letter | PDF Link
~ 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 | PDF 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 | PDF 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 | PDF Link

22. Radujkovic, et al. “Vitamin D Deficiency and Outcome of COVID-19 Patients.” Nutrients 2020, 12(9), 2757; Study Link | PDF 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 | PDF 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 | 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 | PDF Link

26. Baktash, Vadir, et al. “Vitamin D status and outcomes for hospitalised older patients with COVID-19.” Postgraduate Medical Journal (2020). Study Link | PDF 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 | PDF 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. PDF Link
— “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. Kloc, Malgorzata, et al. “Effects of vitamin D on macrophages and myeloid-derived suppressor cells (MDSCs) hyperinflammatory response in the lungs of COVID-19 patients.” Cellular Immunology (2020): 104259. Study Link
— “Vitamin D deficiency increases the severity of the ARDS in COVID-19 infection…. Vitamin D supplementation may influence macrophage inflammatory response, subdue the cytokine storm and lessen the ARDS in COVID-19 patients.” [ARDS is Acute Respiratory Distress Syndrome; it is responsible for the deaths of many Covid-19 patients.]

36. De Smet, Dieter, et al. “Serum 25 (OH) D Level on Hospital Admission Associated With COVID-19 Stage and Mortality.” American journal of clinical pathology (2020). Study Link
— Covid-19 patients admitted to hospital were 3.87 times more likely to die from Covid-19, if they had vitamin D deficiency.

37. Rastogi, Ashu, et al. “Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study).” Postgraduate medical journal (2020). Study Link
— Covid-19 patients were given 60,000 IU vitamin D daily for 7 days; these patients were 3.0 times more likely to become negative for Covid-19 than patients not given vitamin D.

38. Afshar, Parviz, Mohammad Ghaffaripour, and Hamid Sajjadi. “Suggested role of Vitamin D supplementation in COVID-19 severity.” Journal of Contemporary Medical Sciences 6.4 (2020). Study Link
— 300,000 IU vitamin D3 once, then 100 IU per kilogram of body weight per day; greatly reduced deaths and length of hospital stay for Covid-19.

39. Luo, Xia, et al. “Vitamin D Deficiency Is Inversely Associated with COVID-19 Incidence and Disease Severity in Chinese People.” The Journal of Nutrition (2020). Study Link
— vitamin D deficiency (<30 nmol/L) (OR: 2.72) was significantly associated with COVID-19 severity.

40. Pereira, Marcos, et al. “Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis.” Critical reviews in food science and nutrition (2020): 1-9. Study Link
— severe cases of COVID-19 present 64% more vitamin D deficiency compared with mild cases. A vitamin D concentration insufficiency increased hospitalization and mortality from COVID-19. We observed a positive association between vitamin D deficiency and the severity of the disease.

41. Katz, Joseph, Sijia Yue, and Wei Xue. “Increased risk for Covid-19 in patients with Vitamin D deficiency.” Nutrition (2020): 111106. Study Link
— “patients with vitamin D deficiency were 5 times more likely to be infected with Covid-19 than patients with no deficiency after adjusting for age groups”

42. Arvinte, Cristian, Maharaj Singh, and Paul E. Marik. “Serum Levels of Vitamin C and Vitamin D in a Cohort of Critically Ill COVID-19 Patients of a North American Community Hospital Intensive Care Unit in May 2020: A Pilot Study.” Medicine in drug discovery 8 (2020): 100064. Study Link
— “Serum levels of vitamin C and vitamin D were low in most of our critically ill COVID-19 ICU patients.”

43. Yılmaz, Kamil, and Velat Şen. “Is vitamin D deficiency a risk factor for COVID‐19 in children?.” Pediatric Pulmonology 55.12 (2020): 3595-3601. Study Link | Explanation of Study
— Children in this study with higher vitamin D blood levels (20 ng/ml or higher) were 4.6 times more likely to have no symptoms while infected with Covid-19, and 72% less likely to have a moderate/severe case of Covid-19 than children with vitamin D deficiency.

44. Tan, Chuen Wen, et al. “A cohort study to evaluate the effect of combination Vitamin D, Magnesium and Vitamin B12 (DMB) on progression to severe outcome in older COVID-19 patients.” medRxiv (2020). Study Link
— “a vitamin D / magnesium / vitamin B12 combination in older COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen support, intensive care support, or both.”

45. Jain, Anshul, et al. “Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers.” Scientific reports 10.1 (2020): 1-8. Study Link
— “The fatality rate was high in vitamin D deficient (21% vs 3.1%). Vitamin D level is markedly low in severe COVID-19 patients.” In this study, patients with low vitamin D had a mortality rate of 21%; those with higher vitamin D had a mortality rate of only 3.1%. Those with higher vitamin D were more likely to have a mild case, and less likely to die; those with low vitamin D were more likely to have a severe case, and more likely to die.

46. Ling, Stephanie F., et al. “High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-Centre Observational Study.” Nutrients 12.12 (2020): 3799. Study Link
— “In this observational study, treatment with cholecalciferol booster therapy, regardless of baseline serum 25(OH)D levels, appears to be associated with a reduced risk of mortality in acute in-patients admitted with COVID-19.” In one group, the reduction in risk of death was 87%; in the other group, the reduction was 62%.

47. Vassiliou, Alice G., et al. “Low 25-Hydroxyvitamin D Levels on Admission to the Intensive Care Unit May Predispose COVID-19 Pneumonia Patients to a Higher 28-Day Mortality Risk: A Pilot Study on a Greek ICU Cohort.” Nutrients 12.12 (2020): 3773. Study Link
— “All patients who died within 28 days belonged to the low vitamin D group…. Critically ill COVID-19 patients who died in the ICU within 28 days appeared to have lower ICU admission 25(OH)D levels compared to survivors.”

48. Anjum, S., et al. “Examine the association between severe Vitamin D deficiency and mortality in patients with Covid-19.” Pakistan Journal of Medical and Health Sciences (2020): 1184-1186. Study Link
— “Patients with severe vitamin D deficiency had high rate of mortality (26.67%) as compared to patients with no vitamin D deficiency (7.5%)”

49. Biagio Cangiano et al. “Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests.” December 22, 2020. in the journal: Aging. Study Link

50. Kapoor, Sumit, et al. “Thromboembolic Events and Role of Point of Care Ultrasound in Hospitalized Covid-19 Patients Needing Intensive Care Unit Admission.” Journal of intensive care medicine (2020): 0885066620964392. Study Link
— Higher d-dimer levels are known to be associated with vitamin D insufficiency or deficiency. In this study, higher d-dimer levels were associated with increased risk of thromboembolisms (blood clots that block blood vessels).

51. Nadiger, Meghana, Sophia Hassor, and Balagangadhar Totapally. “138: Vitamin D Levels in Children With COVID-19 Admitted to the PICU.” Critical Care Medicine 49.1: 54. Study Link
— The majority of patients admitted to the pediatric ICU were obese vitamin D deficient adolescents. This underscores the need to find obesity in children and to give them vitamin D supplements.

52. Liu, Nanyang, et al. “Low vitamin D status is associated with coronavirus disease 2019 outcomes: A systematic review and meta-analysis.” International Journal of Infectious Diseases. Study Link
— “This systematic review and meta-analysis indicated that low vitamin D status may be associated with an increased risk of COVID-19 infection.”

53. Angelidi, Angeliki M., et al. “Vitamin D Status is Associated With In-hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients.” Mayo Clinic Proceedings. Elsevier. Study Link
— “Among patients admitted with laboratory-confirmed COVID-19, 25(OH)D levels were inversely associated with in-hospital mortality and the need for invasive mechanical ventilation.” In other words, patients with higher levels of vitamin D in the blood had a lower death rate and were less likely to need mechanical ventilation.

54. Giannini, Sandro, et al., “Effectiveness of In-Hospital Cholecalciferol Use on Clinical Outcomes in Comorbid COVID-19 Patients: A Hypothesis-Generating Study.” 14 January 2021; Nutrients 2021, 13(1), 219; Study Link
— “two consecutive doses of 200,000 IU cholecalciferol [i.e. Vitamin D3] (total of 400,000 IU) can significantly improve the outcome inpatients affected by COVID-19 that are also burdened with three or more comorbid diseases.”

55. Vasheghani, Maryam, et al., “The Association of 25(OH)Vitamin D Levels and Severity and Outcome of COVID-19: A Cross-sectional Study.” Research Square, 17 Jan 2021. Study Link

56. Walrand, Stephan. “Autumn COVID-19 surge dates in Europe correlated to latitudes, not to temperature-humidity, pointing to vitamin D as contributing factor.” Scientific Reports 11.1 (2021): 1981-1981. Study Link
— “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.”

57. “Fewer COVID-19 deaths in those getting 400,000 IU of Vitamin D.” 29 January 2021. Myanmar Health.
Study Link (news report)
— Death rate was reduced to 0.07% as compared to nationwide average of 2.1%. That is a 30-fold reduction in the death rate. Study participants were given this set of supplements, twice: 200,000 IU of vitamin D; 25 mg of zinc; 1000 mg of vitamin C; 30 billion Probiotics.

58. Yadav, Dharmveer, et al. “Association of Vitamin D Status with COVID-19 Infection and Mortality in the Asia Pacific region: A Cross-Sectional Study.” Indian Journal of Clinical Biochemistry (2021): 1-6. Study Link
— “The negative correlation observed between Vitamin D levels and the number of COVID-19 cases in the Asia Pacific region points to the possible protective effect of Vitamin D in blunting the infectivity of COVID-19 in causing debilitating infection in the countries in the Asia Pacific region.”

59. Nogués, Xavier, Diana Ovejero, J. M. Quesada-Gomez, Roger Bouillon, Dolores Arenas, Julio Pascual, Judith Villar-Garcia et al. “Calcifediol Treatment and COVID-19-Related Outcomes.” Study Link
— “In patients hospitalized with COVID-19, calcifediol [a type of vitamin D] treatment at the time of hospitalization significantly reduced ICU admission and mortality.”

60. Nogués, Xavier, et al. “Calcifediol Treatment and COVID-19-Related Outcomes.” SSSRN (2021). Study Link

61. Susianti, Hani, et al. “Low Levels of Vitamin D were Associated with Coagulopathy among Hospitalized Coronavirus Disease-19 (COVID-19) Patient: a Single Centered Study in Indonesia.” Journal of Medical Biochemistry (2021). Study Link
— “Low vitamin D also increased the risk for developing” extensive intravascular coagulation (blood clots throughout the body) by 5.4x and normal levels of vitamin D greatly decreased the same risk.

.

The evidence is overwhelming. Everyone should be taking vitamin D supplementation, at appropriate levels for their age and medical condition.

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%…."

87. Kearns, Malcolm, Jessica Alvarez, and Vin Tangpricha. “Large, single-dose, oral vitamin D supplementation in adult populations: a systematic review.” Endocrine Practice 20.4 (2014): 341-351.
— “This review recommends that vitamin D3 be used for supplementation over vitamin D2 and concludes that single vitamin D3 doses ≥300,000 IU are most effective at improving vitamin D status and suppressing PTH concentrations for up to 3 months.”

88. Robert P. Heaney, The Vitamin D requirement in health and disease; Journal of Steroid Biochemistry & Molecular Biology. doi:10.1016/j.jsbmb.2005.06.020

89. Alagöl, Faruk, et al. “Sunlight exposure and vitamin D deficiency in Turkish women.” Journal of endocrinological investigation 23.3 (2000): 173-177.

90. Liu, Guoqiang, Tianpei Hong, and Jin Yang. “A Single Large Dose of Vitamin D Could be Used as a Means of Coronavirus Disease 2019 Prevention and Treatment.” Drug Design, Development and Therapy 14 (2020): 3429.

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.

110. 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. Note that this was not a Covid-19 specific study, but a study of ICU patients on mechanical ventilation.

111. Buchtele, Nina, et al. “Prevalence and Impact of Vitamin D Deficiency in Critically Ill Cancer Patients Admitted to the Intensive Care Unit.” Nutrients 13.1 (2020): 22. Study Link
— For cancer patients, severe vitamin D deficiency more than doubled risk of in-hospital death and more than tripled risk of death within one year.

112. Sistanizad, Mohammad, et al. “High dose vitamin D improves total serum antioxidant capacity and ICU outcome in critically ill patients-a randomized, double-blind clinical trial.” European Journal of Integrative Medicine (2020): 101271. Study Link
— one IM dose of 300,000 IU of vitamin D3 for ICU patients reduced length of stay in hospital by 28% and reduced time on mechanical ventilation by 30%.

113. Smith, Ellen M., et al. “High‐Dose Vitamin D3 Administration Is Associated With Increases in Hemoglobin Concentrations in Mechanically Ventilated Critically Ill Adults: A Pilot Double‐Blind, Randomized, Placebo‐Controlled Trial.” Journal of Parenteral and Enteral Nutrition 42.1 (2018): 87-94. PDF Study Link
— Patients on mechanical ventilation benefited from 100,000 IU of vitamin D3 per day for 5 days (total of 500,000 IU) by decreased inflammation and improvements in hemoglobin and hepcidin levels.