New Clinical Trial Shows Why Vitamin D Matters in Covid-19

In August, a randomized clinical trial first showed that oral calcifediol (also called vitamin D3) reduced the odds of intensive care unit (ICU) admission from 50% (13 out of 26) to 2% (one out of 50) among Covid-19 patients. “Although this was a small trial, the ICU results are so dramatic that they are statistically highly significant,” stated a featured letter in The BMJ.

This month, another Covid-19 clinical trial on vitamin D3 from India was published in the Postgraduate Medical Journal of the British Medical Journal, titled “Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study).” And this study shows why healthy vitamin D status matters in Covid-19.

What the new clinical trial did and found

The trial randomly allocated asymptomatic or mild Covid-19 participants to the treatment (vitamin D3 liquid) or placebo (distilled water) groups. The treatment group had 16 participants, and the control group had 24. Notably, all participants were vitamin D3 deficient (<20 ng/ml), received standard care, and free of any major comorbidities.

The study used oral cholecalciferol, which is less potent than calcifediol used in the previous clinical trial. So, at the same dose, cholecalciferol is slower to raise vitamin D3 levels than calcifediol.

Regardless, the study gave high doses of oral cholecalciferol at 60,000 IU daily for seven days. On day-7, those still deficient in vitamin D3 received 60,000 IU daily again for another seven days, whereas those with sufficient levels received 60,000 IU weekly. The treatment lasted until day-14, and participants were monitored until day-21.

Since over 80% of infections show mild or no symptoms, early viral clearance would dramatically reduce the disease’s spread.

On day-14, cholecalciferol treatment restored proper vitamin D3 levels in the treatment group (~50 ng/ml), whereas the placebo group remained vitamin D3 deficient (<20 ng/ml).

And 62.5% (10 out of 16) of the treatment group tested negative for SARS-CoV-2 within 21 days; this number was only 20.8% (five out of 24) in the placebo group. That is a 3-fold statistically significant change. And there was no apparent vitamin D toxicity in anyone.

“In this first cholecalciferol intervention study for asymptomatic and mildly symptomatic SARS-CoV-2 positive individuals, we found that a greater proportion of patients could attain SARS-CoV-2 RNA negativity on high-dose vitamin D supplementation…compared to vitamin D-deficient individuals,” the authors concluded.

What the study means for the pandemic

The study does have several drawbacks. The geographical restriction and small sample size limit generalizability to the broader population. Although participants were free of comorbidities, there may be other confounding variables the study overlooked, such as socioeconomic status or sex. And moderate-to-severe Covid-19 patients were not examined.

Despite these caveats, the study tells us that adequate vitamin D3 status is important in swift viral clearance in people with asymptomatic or mild Covid-19. Since over 80% of infections show mild or no symptoms, early viral clearance would dramatically reduce the disease's spread. “RNA negativity by cholecalciferol supplementation may help in reducing transmission rates of the highly contagious SARS-CoV-2 infection,” the study authors wrote.

Vitamin D3 deficiency is highly prevalent—ranging from 35% of adults in the U.S. to 80% of adults in Pakistan, India, and Bangladesh. These numbers are even higher in senior populations at, for example, 61% in the U.S. and 96% in India. This widespread vitamin D3 issue also begs an interesting thought: Is vitamin D3 deficiency, which makes people carry the coronavirus longer, fueling the spread of Covid-19? While there is no robust supporting data at the moment, it is certainly a possibility to consider.

Is vitamin D3 deficiency, which makes people carry the coronavirus longer, fueling the spread of Covid-19?

For more information on how vitamin D3 counters and affects Covid-19 disease progression, kindly see here. In brief, vitamin D3 regulates both the immune system and renin-angiotensin system (RAS) to prevent cytokine storm and bradykinin accumulation, respectively, which are the two primary means by which Covid-19 kills. As follows, multiple studies have linked low vitamin D3 levels to increased risks of SARS-CoV-2 positivity and poor Covid-19 clinical outcomes.

Short abstract

A newly published clinical trial shows that treatment to restore proper vitamin D3 levels in deficient people with asymptomatic or mild Covid-19 quickens viral clearance. Specifically, 62.5% of people receiving oral cholecalciferol for 14 days tested negative for SARS-CoV-2 within the next seven days, compared to 20.8% in the placebo group. This result agrees with the first published clinical trial in August, where vitamin D3 therapy prevents ICU admission among Covid-19 patients. If people with healthy vitamin D3 status carry the coronavirus for a shorter duration, it suggests that vitamin D3 may play a role in Covid-19 spread. But this notion remains speculative, especially when the new clinical trial is just a preliminary phase.