Here’s the study:

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.

This is a peer-reviewed, randomized, controlled study of hospitalized Covid-19 patients. So it is an “RCT”. [Correction: no placebo was used. The intervention group received calcifediol and the control group did not. Both groups received BAT, best available treatment.] This is the type of study that the press and various online critics demand. Some persons unwisely reject all other types of studies, which is not reasonable or scientific. But this is the type of study we’ve been waiting for, to confirm the other 20 studies here.

The study took place in a university hospital setting: Reina Sofia University Hospital, in Cordoba, Spain. The 76 patients were all hospitalized for confirmed cases of Covid-19. So these are not the mild to moderate, stay-at-home types of patients. The intervention group was 50 patients and the control group was 26 patients.

The intervention group received calcifediol, which is a type of vitamin D found in the blood. It is not the usual type of vitamin D found in supplements. Calcifediol is also known as 25(OH)D or 25-hydroxyvitamin D. The reason for giving this type of vitamin D is that the usual supplement type takes about 7 days to turn into calcifediol, so by giving patients calcifediol itself, you get the good effects without having to wait 7 or so days [per Wikipedia].

The dosage of calcifediol converts to IU (international units at a ratio of 200 to 1). So 10 micrograms of calcifediol is 2000 IU of vitamin D, whereas 10 micrograms of vitamin D3 is 400 IU (a 40:1 ratio). The dosage given to the patients, in IUs, was:

Day one: 106,400 IU of vitamin D
Day three: 53,200 IU
Day seven: 53,200 IU
Once-a-week thereafter: 53,200 IU

This is equivalent to about 30,000 IU per day for the first week, and 7,600 IU per day thereafter. Yes, you can take your vitamin D supplement in a once-a-week dosage, instead of daily.

The results were astounding (and highly statistically significant). “Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50%)”. Would you rather have a 50% risk of needing ICU care, or a 2% risk? Almost all hospitalized Covid-19 patients who die, die in the ICU. That is where the most severe cases are sent. So this study shows that vitamin D reduces the severity of Covid-19.

In the statistically adjusted results, vitamin D reduced the odds of ICU admission by 97%. The RR (risk reduction) for ICU admission in hospitalized Covid-19 patients was 0.03 as compared to the control, which is given the value of 1.00. The odds of Covid-19 patients in general, as compared to hospitalized Covid-19 patients, needing ICU care would be even lower, as you would first need to be hospitalized to enter that risk ratio, and vitamin D has been shown by other studies to reduce risk of hospitalization. So taking a vitamin D supplement has tremendous benefits.

For mortality, 2 patients in the control group died; no patients in the vitamin D group died. There were not enough deaths to make the results statistically significant. But hospitalized patients don’t usually die from Covid-19, unless they are in the ICU. We would expect the reduction in death to be of a similar order of magnitude to the reduction in need for ICU care. Also, if you need mechanical ventilation, that is ICU care. So the vitamin D would seem to reduce risk of ventilation as well.

There is now enough evidence for treatment with calcifediol, also known as 25(OH)D, to be STANDARD CARE for hospitalized patients with Covid-19. There is enough evidence for vitamin D supplementation to be recommended to everyone at risk of vitamin D, especially those at high risk. And since the elderly often have difficulty absorbing vitamin D, they should receive a higher dosage.

Here’s an article reviewing the study by Chris Masterjohn, Ph.D.: Finally Confirmed! Vitamin D Nearly Abolishes ICU Risk in COVID-19

Here’s a video on the study by Dr. Mobeen Syed (of DrBeen’s Medical Lectures)

Update

The study authors have decided to extend the study, so that the patient population will be larger. This might allow the study to reach statistical significance for the endpoint of death. I’m concerned that such a study is not ethical, as we already are fairly certain that calcifediol reduces risk of death (since most hospital deaths from Covid occur on ICU not the floor).

Effect on the Pandemic

If every hospitalized Covid-19 patient were given calcifediol, the reduction in need for ICU beds and mechanical ventilation would be anticipated to be large. And since Covid-19 patients, if they are going to die from the disease, usually die in ICU, this should reduce deaths by at least half as well.

Vitamin D reduces Covid-19 risks, including: risk of infection [7, 8, 9, 11, 12, 14, 16, 20], of having a severe case [1, 3, 4, 5, 15, 17], of needing hospitalization, ICU care, and/or mechanical ventilation [2, 10, 14, 15, 21], as well as the risk of dying from Covid-19 [4, 6, 7, 9, 12, 13, 17, 18, 19, 20].

Every adult should take 10,000 IU of vitamin D per day, except the elderly, who should take twice that amount — 20,000 IU/day — due to their greater risk of dying from Covid and their lower absorption of vitamin D.

More Reading:
* List of Studies on Vitamin D and Covid-19
* The LongCovid Supplements List
* What Causes LongCovid also called Longhaulers Syndrome?
* Immune Privileged Cells affected by Longhaulers Syndrome
* The Longhaulers Hidden Virus Hypothesis

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

Consider supporting Covid.us.org with a one-time or recurring donation via PayPal

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

22. 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.”

23. 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.”

24. 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.”