Vitamin D and COVID-19 Studies 2021

Vitamin D plays an important role in most diseases, including infectious disease. Since then, mounting evidence reveals that higher vitamin D levels reduce rates of positive tests, hospitalizations and mortality related to this infection. 

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Vitamin D3 Reduces ICU Admissions and Mortality

Most recently, a Spanish study (which has yet to undergo peer-review) found giving supplemental vitamin D3 (calcifediol) to hospitalized patients with PCR-confirmed COVID-19 reduced ICU admissions by 82% and mortality by 64%. People who already had higher vitamin D at baseline were 60% less likely to die.

The study included 930 patients, 551 of whom received vitamin D3 — 532 micrograms on the first day of admission followed by 266 mcg on days 3, 7, 15 and 30. The remaining 379 patients served as controls.

All were given standard of care, which included hydroxychloroquine and an antibiotic (or two antibiotics in cases where bacterial infections were diagnosed), plus a steroid in cases involving pulmonary inflammation and/or cytokine storm. As reported by the authors:

“ICU assistance was required by 110 (11.8%) participants. Out of 551 patients treated with calcifediol at admission, 30 (5.4%) required ICU, compared to 80 out of 379 controls (21.1%).

Logistic regression of calcifediol treatment on ICU admission, adjusted by age, gender, linearized 25(OH)D levels at baseline, and comorbidities showed that treated patients had a reduced risk to require ICU (RR 0.18).

Baseline 25(OH)D levels inversely correlated with the risk of ICU admission (RR 0.53). Overall mortality was 10%. In the Intention-to-treat analysis, 36 (6.5%) out of 551 patients treated with calcifediol at admission died compared to 57 patients (15%) out of 379 controls.

Adjusted results showed a reduced mortality for more of 60%. Higher baseline 25(OH)D levels were significantly associated with decreased mortality (RR 0.40).

Age and obesity were also predictors of mortality. Interpretation: In patients hospitalized with COVID-19, calcifediol treatment at the time of hospitalization significantly reduced ICU admission and mortality.”

Renewed Calls for Vitamin D Recommendations

In response to the Spanish findings, British MP David Davis tweeted that "The findings of this large and well conducted study should result in this therapy being administered to every COVID patient in every hospital in the temperate latitudes,” adding that:

“Since the study demonstrates that the clear relationship between vitamin D and COVID mortality is causal, the U.K. government should increase the dose and availability of free vitamin D to all the vulnerable groups. These approaches will save many thousands of lives. They are overdue and should be started immediately."

Many others are also calling for official vitamin D recommendations to be issued by their governments. Among them, Emer Higgins, a member of the Irish political party Fine Gael, who called on the Irish health minister, Stephen Donnelly, to include vitamin D supplementation in its “Living with COVID-19” strategy, slated for launch at the end of February 2021.

Higgins leaned on evidence from the Irish Covit-D Consortium, which shows vitamin D helps optimize your immune response. “There is negligible risk in this strategy and potentially a massive gain,” she said. According to the Covit-D Consortium, the nutrient can lower the risk of death from COVID-19 in the elderly by as much as 700%.

Low Vitamin D Linked to COVID-19 Outbreaks and Severity

Another study published in the journal Scientific Reports confirmed vitamin D is a contributing factor to COVID-19 outbreaks and infection severity. According to the authors, the surges in daily positive test results during the fall of 2020 in 18 European countries linearly correlate with latitude, and hence sun exposure and vitamin D levels. They point out that:

“The country surge date corresponds to the time when its sun UV daily dose drops below ≈ 34% of that of 0° latitude. Introducing reported seasonal blood 25-hydroxyvitamin D (25(OH)D) concentration variation into the reported link between acute respiratory tract infection risk and 25(OH)D concentration quantitatively explains the surge dynamics ...

The date of the surge is an intrapopulation observation and has the benefit of being triggered only by a parameter globally affecting the population, i.e. decreases in the sun UV daily dose.

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.”

While it’s well-recognized that most elderly individuals are deficient in vitamin D, the problem is widespread in all age categories, including children.

As noted in a February 2021 study comparing vitamin D levels in breast milk collected in 1989 and 2016/2017, vitamin D concentrations are consistently higher during the summer, but overall, vitamin D levels have declined since 1989. As a result, pregnant and lactating mothers and their infants may require vitamin D supplementation for optimal health.

Vitamin D Recommended Dosage for COVID-19

For prevention, the Front Line COVID-19 Critical Care Working Group, FLCCC recommends (updated January 12, 2021):
  • Vitamin D3 — 1000–3000 IU/day. Note RDA (Recommended Daily Allowance) is 800–1000 IU/day. The safe upper-dose daily limit is likely < 4000 IU/day. Vitamin D deficiency has been associated with an increased risk of acquiring COVID-19 and from dying from the disease. Vitamin D supplementation may therefore prove to be an effective and cheap intervention to lessen the impact of this disease, particularly in vulnerable populations, i.e. the elderly, those of color and obese. (Amazon)
  • Vitamin C - 1,000 mg BID (twice daily) (Amazon)
  • Quercetin 250 mg daily. It is likely that vitamin C and quercetin have synergistic prophylactic benefit. Quercetin should be used with caution in patients with hypothyroidism and TSH levels should be monitored. (Amazon > 1 capsule daily)
  • Melatonin: 6 mg before bedtime (causes drowsiness).
  • Zinc: 50 mg/day (elemental zinc). Zinc lozenges are preferred. (Amazon)
  • Ivermectin for prophylaxis in high-risk individuals (> 60 years with co-morbidities, morbid obesity, long term care facilities, etc). 0.2 mg/kg Day 1, Day 3 and then followed by biweekly dosing (one dose every two weeks). (also see ClinTrials.gov NCT04425850). NB. Ivermectin has a number of potentially serious drug-drug interactions. Please check for potential drug interaction at Ivermectin Drug Interactions - Drugs.com. The most important drug interactions occur with cyclosporin, tacrolimus, anti-retroviral drugs, and certain anti-fungal drugs. 
For early outpatient protocol (COVID-19 positive), the Front Line COVID-19 Critical Care Working Group, FLCCC recommends (updated January 12, 2021):
  • Vitamin D3 — 4000 IU/day. (Amazon)
  • Vitamin C - 2,000 mg BID (twice daily) (Amazon)
  • Quercetin 250 mg twice a day.  (Amazon)
  • Melatonin: 10 mg before bedtime (causes drowsiness). (Amazon)
  • Zinc: 100 mg/day. Zinc lozenges are preferred. (Amazon)
  • Ivermectin 0.2 mg/kg per dose. One dose daily - minimum 2 days, maximum 5 days.
  • FLCCC also recommend monitoring your oxygen saturation with a pulse oximeter and to go to 
    the hospital if you get below 94%.
  • Aspirin 325 m/day unless contraindicated.

High Dosage Vitamin D COVID-19 Studies

Two studies in France (C Annweiler, Nov 2020; G Annweiler, Nov 2020), one in India (A Rastogi, Nov 2020) and one in Spain (M Castillo, Oct 2020) showed that Vitamin D supplementation seems to decrease the mortality rate, the severity of the disease, and the inflammatory markers' levels among the COVID-19 infected patients, leading to a better prognosis and increased survival.

Annweiler et al.: All residents in the nursing-home receive chronic vitamin D supplementation with regular maintenance boluses (single oral dose of 80,000 IU vitamin D3 every 2–3 months), without systematically performing serum control test as recommended in French nursing-homes due to the very high prevalence of hypovitaminosis D reaching 90–100 % in this population.

Rastogi et al.: Participants were randomised to receive daily 60 000 IU of cholecalciferol (oral nano-liquid droplets) for 7 days with therapeutic target 25(OH)D>50 ng/ml (intervention group) or placebo (control group).

Castillo et al.: Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths. Do take note that 0.25 mg is equivalent to 10,000 IU.

Editor's Note: Vitamin D Upper Limit is 4,000 IU per day. The above dosages of vitamin D are NOT your normal maintenance dosage and are done under medical supervision and clinical trial setting. Do not self-medicate at this dosage!

Vitamin D and COVID vaccine

When the immune system isn’t properly fuelled and is impaired, this can lead to poor vaccine responses. A review of nine studies – together involving 2,367 people – found that individuals deficient in vitamin D were less well protected against two strains of flu after having been vaccinated compared to those who had adequate vitamin D levels.

COVID and Vitamin D - CDC 

According to CDC:

Dietary supplements aren’t meant to treat or prevent COVID-19. Certain vitamins and minerals (e.g., Vitamins C and D, zinc) may have effects on how our immune system works to fight off infections, as well as inflammation and swelling.

Vitamin D and COVID-19 Treatment Guidelines from NIH

According to the NIH recommendation (last updated July 17, 2020):

There are insufficient data to recommend either for or against the use of vitamin D for the prevention or treatment of COVID-19.

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