'The relationship between vitamin D and Covid-19 is still not very clear'

Rod Tucker discusses the research behind vitamin D and its possible protective role against viral infections.

As the world anxiously awaits the arrival of a Covid-19 vaccine, there has been much interest in finding alternative strategies to help minimise the effects of infection with the virus. One strategy attracting much interest in the media is the importance of having sufficient vitamin D levels and even taking a supplement to help prevent infection.

Why has vitamin D achieved such elevated status, and is there any evidence that it might help either protect against Covid-19 or prevent progression of the virus?

What do we know?

Vitamin D₃ is known as the sunshine vitamin, because the majority of our intake comes from the action of UV radiation from sunlight on the skin. Sufficient production only occurs in the Northern hemisphere between April and September, as the sun is too low during the winter months. The vitamin D₃ produced in the skin is subsequently converted to 25-hydroxyvitamin D (25(OH)D) and finally to 1,25(OH)₂D (calcitriol). Although calcitriol is the active metabolite, it is the level of 25(OH)D which is measured and used to monitor vitamin D status.

Interest in the possible protective role of vitamin D on Covid-19 has arisen because of its multiple actions on the immune system. In response to microbial or viral infections, the innate immune system generates several pro-inflammatory cytokines including tumour necrosis factor alpha and interferon Vitamin D enhances the production of several different innate immune system peptides, which possess anti-microbial, anti-fungal and anti-viral activity. Furthermore, vitamin D enhances cellular immunity, in part by reducing the cytokine storm induced by the innate immune system due to bacterial or viral infections, by increasing the expression of anti-inflammatory cytokines by macrophages. This may be of value given the proinflammatory cytokine milieu observed in those infected with Covid-19 and how this ‘cytokine storm’  leads to acute respiratory distress syndrome.

What has research shown?

Given these possible immune-enhancing effects, is there evidence that vitamin D has a protective effect against viral infections? Prior to Covid-19, several meta-analyses have explored the potential role of vitamin D in acute respiratory infections and the World Health Organisation (WHO) offered a summary of these in 2017. The review noted how results were inconsistent with significant heterogeneity in terms of the patients included, vitamin D regimes and baseline levels, making the generalisability of the findings more difficult. WHO suggested that future trials should explore whether the benefits are achieved once vitamin D status is satisfactory.

If vitamin D does help with viral infections, then one group likely to benefit from supplementing with vitamin D are those from the Black and Ethnic Minority groups, who are often deficient in vitamin D. People with darker skin have a higher melanin content and, as this pigment absorbs more UV radiation (and thus offers more sun protection), there is less UV radiation available to make vitamin D. In addition, some people from an ethnic background may also cover their body more when out in public for religious reasons, which will clearly reduce UV exposure.

Ensuring sufficient vitamin D levels could help to reduce the incidence of viral infections, including Covid-19 in BAME groups. However, in practice this theoretical advantage has not been realised.

In a randomised, placebo trial of the impact on acute respiratory infections of supplementing with vitamin D in 260 black American women, one group received vitamin D supplements to ensure adequate 25(OH)D levels (> 30 ng/ml) and the other a placebo. Over a three-year period, supplementing with vitamin D made no difference to the incidence of upper respiratory tract infections. In fact, this probably wasn’t a surprise to the researchers who had conducted an earlier trial in which patients were given either 50 mcg/day of vitamin D or placebo for 12 weeks during the winter months. Although at baseline, both groups had vitamin D levels within the normal range, supplementation had no effect on the incidence of upper respiratory tract infections.

Evidence in Covid-19?

What about Covid-19? There has been limited evidence to show that vitamin D helps with Covid-19, but the most recent study was a placebo controlled trial with patients given calcifediol (a vitamin D supplement). The results showed that of 50 patients treated with vitamin D, only one required admission to intensive care, compared to 13 of the 26 untreated patients. While these preliminary data do suggest a benefit from vitamin D, the authors noted that baseline vitamin D levels were not recorded, and concluded that calcifediol ‘may improve the clinical outcome’ of subjected requiring hospitalisation for Covid-19. This latest study had several limitations, which were addressed in detail in a summary by NICE.

In conclusion, while vitamin D is known to have immune-enhancing properties, the value of either supplementing or maintaining adequate levels to reduce the symptom burden or progression in those with Covid-19 infection remains unclear. Hopefully, ongoing vitamin D trials will provide more compelling evidence of benefit. While at present vitamin D doesn’t seem to be a Covid-19 panacea, it is still important to ensure adequate levels for optimal health and because ultimately, this might prove to lessen the effects of the virus and possibly save more lives.