Introduction to vitamin D
- Vitamin D is a fat soluble vitamin but perhaps best described as a pre-pro-hormone.
- The major source of vitamin D for most people on the planet is the sun and vitamin D is often lacking in modern diets.
- Vitamin D3 (cholecalciferol) is the most potent form of vitamin D. Dietary vitamin D3 and most supplementary vitamin D3 is derived from animal sources.
Summary of COVID-19 and vitamin D
- As of writing (May 2022), there are 1,100 papers regarding COVID-19 and vitamin D. The vast majority of these 1,100 papers are commentaries and theory/opinion papers with no new data
- Many studies report low vitamin D levels in COVID patients, however some do not
- Some studies report low vitamin D levels in COVID patients was associated with more severe COVID, however other studies did not report this
- 6 studies assessing genetics, vitamin D levels and COVID-19 reported no evidence that vitamin D was protective against COVID-19 infection or severity
- There are 13 studies of vitamin D supplementation in COVID-19:
5 gold standard trials reported no benefit
8 studies of variable quality reported some benefit
As of writing (May 2022), there are 1,100 papers regarding COVID-19 and vitamin D. The vast majority of these 1,100 papers are commentaries and theory/opinion papers with no new data.
However, some studies have measured vitamin D levels in COVID-19 patients, including a study I was involved in (details here). Many of these studies reported low vitamin D levels in COVID-19 patients. However, some didn't find lower vitamin D levels in COVID-19 patients. Then some studies reported that lower vitamin D levels were associated with more severe COVID-19. However, some other papers did not and some even found that higher vitamin D levels were associated with more severe COVID-19!
These type of studies are called observational whereby these studies measure vitamin D levels and observe what happens. These studies don't involve any treatment such as vitamin D supplementation.
COVID-19 and vitamin D: Mendelian randomization studies
Vitamin D levels and the effect of vitamin D is influenced by several genes. Scientists can use a technique called 'mendelian randomization' to take account of genetic variation with regard to an outcome. There are six Mendelian randomisation studies of vitamin D levels and COVID-19, all of which were published in 2021. These studies measured genetic variation in genes known to influence vitamin D and examined the effect on COVID-19 rate and severity. Each of these six studies reported no evidence that vitamin D was protective against COVID-19 infection or severity.
COVID-19 and vitamin D: Human studies
Intervention studies are complex. Vitamin D intervention trials have additional complications including baseline vitamin D levels, seasonal effects and more.
A group of doctors and scientists in Brazil published 3 trials of vitamin D supplementation in COVID-19 patients, using the gold standard methodology (double-blinded, randomized, placebo-controlled trials). These 3 with trials used large doses of vitamin D (200,000IU, which is equivalent 4,500 large eggs!) or placebo. There was no benefit regarding hospital length of stay, need for mechanical ventilation or 14 different biomarkers.
A subsequent open label study of 175 severe COVID patients in the ICU with vitamin D deficiency (<25nmol/L) administered 300,000IU vitamin D3 (equivalent to 6,750 large eggs!) via intramuscular injection vs. no vitamin D. Vitamin D administration had no benefit regarding need for intubation, length of hospital stay or inhospital mortality.
Another randomised, open label, clinical study utilised 100,000IU vitamin D3 bolus (equivalent to 2,250 large eggs!) and similarly reported no benefit with regard to hospitalisation, ICU admission or death rate.
It is possible that very large doses of vitamin D are not appropriate. And there are some reports of benefit from vitamin supplementation.
An early case series of 4 vitamin D deficient COVID cases, reported diverse benefits of daily vitamin D supplementation.
An open label, controlled study of 10,000IU vitamin D3 daily for 14d was associated with fewer symptoms compared to no supplementation.
Another 14 day vitamin D study assigned COVID patients to either low dose (1,000IU) of high dose (5,000IU) vitamin D3 daily. Higher vitamin D dose was associated with quicker recovery regarding cough and loss of taste.
A small, double-blind, placebo-controlled trial reported that 2,000IU vitamin D3/day for 6 weeks led to quicker resolution of muscle damage but lung function tests and 6 minute walking tests didn't improve.
A non-randomised, open label study of COVID cases supplemented with vitamin D vs. COVID cases not supplemented, reported a 1.9-fold increased risk of hospitalization >8 days in the non-supplemented group. Additionally, vitamin D treatment decreased the death rate by 2.14 times in conjunction with decreases in inflammatory biomarkers.
Another study, this time a randomised, placebo-controlled study assessed the effects of 60,000IU vitamin D3 daily for 7 days in vitamin D deficient COVID cases. Inflammatory markers were not different except for fibrinogen which decreased with vitamin D supplementation. In addition, 62.5% of subjects in the vitamin D group became COVID-19 negative during the study compared to only 20.8% in the placebo group.
Finally, an open label study randomised COVID cases to standard treatment alone or standard treatment + 60,000IU vitamin D3/day for 8-10 days. Vitamin D treatment was associated with decreases in inflammatory markers (CRP, LDH, IL-6, ferritin). However, this study had many flaws and the paper was retracted by the journal (meaning the journal withdrew the publication), with the editors 'no longer have confidence in the conclusions of this study'. Retracting an article means that the original research is essentially not trustworthy.
Existing data suggest that the role, if any, of vitamin D in preventing or treating COVID-19 is minor and limited to daily dosing as opposed to large dosing, one-off dosing.
Other supplements and nutraceuticals backed by scientific evidence to help with COVID-19 include:
The best evidence we have suggests that regarding COVID-19 infection, earlier supplementation is better!
*Full references list and full text manuscripts available upon request
Written by our founder, Dr. Conor Kerley
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