Current research is limited on coronavirus, which was labeled as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) on January 31st, 2020. The SARS-COv-19 pandemic has generated an onrush of interest in both the mechanisms and in potential risk factors, that may provide a basis for disease control. Vitamin D3 has emerged as a key component in both these mechanisms and adaptive immunity to COVID-19.
What Is Vitamin D3?
Obtained from the sun and synthesized through the skin, vitamin d is an integral component of overall health and wellness. Vitamin D is unique in the fact, that it doesn’t function like a vitamin, but more like a hormone. Classified as a pro-hormone, Vitamin D is an essential component in bone and mineral metabolism. Often hard to obtain through dietary sources alone, supplementation is crucial for health and wellness.
It's estimated that 1 billion people or 50% of the world population that has a Vitamin D deficiency. According to a national nutrition examination survey 41.6% of US adults exhibited vitamin d deficiency, with the highest rate seen in African Americans at 82.1% followed by those of Hispanic descent at 69.2% [R]. Since Vitamin D is a fat-soluble vitamin, it’s crucial that you pair vitamin d with a fat, to enable optimal absorption and calcium uptake. Swolverine’s Vitamin D3 is 10,000 IUS suspended in olive oil for optimal absorption and potency.
Vitamin D regulates a host of different biological functions such as inhibition of cellular proliferation, inducing terminal differentiation, stimulating insulin production, building strong bones, and aiding immune system health. Without a sufficient amount of Vitamin D, only 10–15% of dietary calcium and about 60% of phosphorus are absorbed. With abnormalities in calcium and phosphorous, bone metabolism is severely affected, resulting in a mineralization defect in the skeleton, or what is more commonly known as rickets.
How Does Vitamin D Support Covid-19?
One of the devastating pathophysiological aspects of SARS-CoV-19, is the so-called pulmonary cytokine storm, a major cause of mortality and morbidity. The cytokine storm results from the dysregulation of the innate immune system, with an onslaught of proinflammatory cytokines and chemokines leading to abnormal activation of the adaptive immune pathway. This causes serious damage to the upper and lower respiratory system. Vitamin D may have a potential role by modulating the pathophysiological aspects of the cytokine storm [R].
What Does The Current Research Say?
Recent evidence suggests a statistically significant correlation between vitamin d deficiency and increased infection rates of COVID-19. Intriguing links exist to vitamin d in the cytokine storm that foretells serious acute respiratory distress.
An Italian study published in the Journal of Endocrinological Investigation examined 42 patients and found that after 10 days of hospitalization, 50% of patients with severe vitamin D deficiencies died, compared with just 5% of patients who did not have severe deficiencies.
A preprint study, awaiting peer-review from the Philippines found that normal vitamin D levels were more likely to be observed in patients with mild cases of COVID-19. It is estimated that normal vitamin D levels increase the odds of having a mild clinical outcome by approximately 19.6 times [R].
An observational study found that low vitamin D3 levels may increase a greater risk of Covid-19 severity and positive diagnosis. A paper published in JAMA Network Open examined 489 Covid-19 patients. Those likely deficient in vitamin D3 had a 1.77-times increased risk of testing positive for Covid-19 than those with likely sufficient levels. "Likely’ was used because vitamin D3 levels were measured one-year prior to Covid-19 testing.
A previously published paper in Nutrients found that 107 Covid-19 cases in Switzerland, which tested positive had significantly lower vitamin D3 levels (median 11.1 ng/ml) than those tested negative (22.0 ng/ml) for SARS-CoV-2. And vitamin D3 measurement was done three days after the testing.
A recent pilot study conducted in Spain published in the Journal Of Steroid Biochemistry And Molecular Biology has shown the strongest evidence to date using Vitamin D3 (Calcifediol) as a potential therapy for reducing the severity of Covid-19. The study findings support prior cohort and observational studies that discovered low vitamin D3 levels in the blood as an independent risk factor for Covid-19.
Researchers at the Reina Sofia University Hospital, in Córdoba Spain, randomized 76 consecutive patients diagnosed with Covid-19 were selected through electronic randomization, into either oral calcifediol (50 patients) or no-calcifediol control (26 patients) groups on the day of the hospital admission. Oral administration of calcifediol was given with a three-day protocol, with maintenance, at a mega-dose of 0.532 mg on the first day, followed by 0.266 mg on day three and day seven, then weekly until discharge.
All patients also received the best available therapy and the same standard of care per hospital protocol of a combination of hydroxychloroquine (400 mg every 12 hours on the first day, and 200 mg every 12 hours for the following 5 days, azithromycin 500 mg orally for 5 days.)
Both calcifediol and control groups had comparable and similar baseline characteristics, such as sex, age, existing comorbidities (lung, diabetes, hypertension, kidney disease, immunosuppression). Patients assigned to calcifediol were slightly (not significantly) older, whereas the control group had a higher percentage of hypertension. Although at baseline, there was no significant difference in the number of patients with at least one risk factor.
What The Study Found
Study results concluded that among 26 patients not treated with calcifediol, 13 required ICU admission (50%), with 2 mortalities while out of 50 patients treated with calcifediol only 1 required admission (2%) to the ICU with no mortalities, whereas the other patients remained in conventional hospitalization. Study results were statically significant, with a 93% reduction in odds of ICU admission after adjusting for possible confounders.
Oral calcifediol, the main metabolite of vitamin D3, reduced ICU admission from 50% to 2% among Covid-19 patients.
This pilot study demonstrated that the administration of a mega-dose of calcifediol may improve clinical outcomes of patients requiring hospitalization for Covid-19. Therefore, a multicenter randomized controlled trial, using calcifediol properly matched for (Prevention and Treatment With Calcifediol of COVID-19 Induced Acute Respiratory Syndrome (COVIDIOL) will be conducted in 15 Spanish hospitals.
You can read the full study at Science Direct.
Thoughts On Study Results
Treatment of Care
Calcifediol is a controlled medical pharmaceutical drug. Therefore it is unclear if Vitamin d supplementation alone would have the same effect. Calcifediol is also 3.2-fold more effective than native vitamin D3 supplements in restoring low blood levels of vitamin D3. Secondly, all patients received the same standard of care. Thus it is also unclear if Calcifediol would be effective on it's own.
Other possible confounders in this study such as obesity rates, ethnicity, and socioeconomic status were not measured or accounted for. Vitamin D3 levels were also not measured before the administration of Calcifediol treatment, yet prior population data does suggest they were probably deficient. Yet it remains unclear if Vitamin D3 would have the same efficacy of calcifediol treatment for Covid-19
Vitamin D3 Therapy For COVID-19: Takeaway
The clinical trial from Spain shows the strongest evidence to date, that Vitamin D3 therapy could help reduce the severity and symptoms of COVID-19. The results support prior cohort and observational studies that low vitamin d3 levels, are an independent risk factor for COVID-19.
From a purely scientific and mechanistic view, having higher vitamin D3 levels can be helpful as it regulates the RAS and immune system, both of which are critical factors on CVOID-19 response.
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Bilezikian, J.P. , Bikle, D., Hewison, M., Lazaretti-Castro, M., Formenti, A., Gupta, A., Madhavan, M., Nair, N., Babalyan, V., Hutchings, N., Napoli, N., Accili, D., Binkley, N., Landry, D., & Giustina, A. (2020). MECHANISMS IN ENDOCRINOLOGY: Vitamin D and COVID-19, European Journal of Endocrinology, , EJE-20-0665. Retrieved Sep 12, 2020, from https://eje.bioscientifica.com/view/journals/eje/aop/eje-20-0665/eje-20-0665.xml