“No evidence” to support vitamin D for COVID-19, says UK authority

30 Jun 2020 --- Three separate reviews from UK health authorities have investigated the connection between vitamin D and respiratory illness in light of COVID-19. The National Institute for Health and Care Excellence (NICE)’s appraisal of five published studies concludes that there is no evidence to support taking vitamin D supplements to prevent or treat COVID‑19 specifically. This is in line with Public Health England (PHE)’s researchers stating that at this time, the evidence does not support recommending vitamin D supplementation to prevent acute respiratory tract infections (ARTIs) in the general UK population. However, the Royal Society notes that more research is required to test the possibility that vitamin D deficiency predisposes people to COVID-19.

“There is no good evidence supporting vitamin D improving your COVID-19 risks. There is plenty of good evidence to take low dose supplements between September 21 and March 21 through the winter to avoid vitamin D deficiency and to improve general health. For those people who are not going out or at risk of deficiency, this can be extended into other times of the year,” Keith Neal, Emeritus Professor of the Epidemiology of Infectious Diseases at the University of Nottingham, comments on the slew of findings.

These reviews follow weeks of speculation about the role vitamin D could play in the fight against COVID-19. In April, some researchers called for “urgent supplementation” in vulnerable groups following the discovery of an association between vitamin D deficiency and acute viral respiratory infections. However, the following month saw a consensus paper warn against taking large doses of vitamin D as a way to address the virus. 

In addition to finding a link between COVID-19 and obesity, a PHE review published in June also revealed that Black, Asian and minority ethnic (BAME) people are more at risk of COVID-19 than White counterparts, which was hypothesized by some to be linked to higher rates of vitamin D deficiency in these groups. 

NICE finds no evidence
The NICE rapid evidence summary reviewed five published studies that looked retrospectively at the association between vitamin D status and development of COVID‑19. Four of the studies found an association or correlation between a lower vitamin D status and subsequent development of COVID‑19. However, confounders such as body mass index (BMI) or underlying health conditions, which may have independent correlations with vitamin D status or COVID‑19, were not adjusted for. 

The largest UK study found an association between vitamin D status and COVID‑19 only in univariable analysis (with this single potential causative factor). Importantly, no causal relationship between vitamin D status and COVID‑19 was found after adjustment for confounders such as comorbidity, socio-demographics, ethnicity, BMI and other baseline factors.

The researchers conclude that while there is no evidence to support taking vitamin D supplements to specifically prevent or treat COVID‑19, all people should continue to follow UK government advice on daily vitamin D supplementation to maintain bone and muscle health during the COVID‑19 pandemic.

“The authors of this report are right to highlight that these studies are limited by their observational nature – where lower vitamin D status is linked to poorer outcomes, it is impossible to know whether associations are causal,” weighs in Adrian Martineau, Clinical Professor of Respiratory Infection and Immunity, Queen Mary University of London. 

He continues that vitamin D enthusiasts will point to a large number of other studies published on pre-print websites that were not included in this review. “However, these studies have not yet undergone peer review, so their findings should not be relied on to guide clinical practice or public health policy. The report makes no comment on the need for research into vitamin D and COVID-19.”

The Royal Society recommends that hospitals consider assaying serum vitamin D levels in patients with SARS-CoV-2 infection.Royal Society flags need for further research
In contrast to NICE’s lack of calls for further research, a preprint rapid review from the Royal Society says that more research is, in fact, needed. The scientists also recommend that hospitals consider assaying serum vitamin D levels in patients with SARS-CoV-2 infection. “It will be important to compare the 25OHD levels [which reflect vitamin D status] between those with asymptomatic or mild SARS-CoV-2 infection and those with COVID-19,” they state. 

The researchers point to numerous laboratory studies finding that vitamin D metabolites support innate immune responses to respiratory viruses other than SARS-CoV-2. Additionally, they note that vitamin D also diminishes the production of inflammatory cytokines, which appear to play a central part in the pathogenesis of severe COVID-19.

“This shorter report from the Royal Society adopts a more upbeat tone [than NICE] in considering the potential for vitamin D to have a role in prevention or treatment of COVID-19, and there is a stronger focus on the findings of laboratory studies that underpin scientific interest in this field. This call for further research into vitamin D deficiency and COVID-19 is welcome,” comments Martineau.

PHE’s broader assessment of ARTIs
While the two prior studies examined vitamin D in direct connection with COVID-19, a rapid review from PHE’s Scientific Advisory Committee on Nutrition (SACN) weighs up vitamin D for ARTIs. This piece of research is a follow-up to its prior 2016 summary of vitamin D and broad health. It takes into account five randomized controlled trials that have been published in the following years. 

Out of the five trials, three – including the largest with 5,110 participants – reported no evidence of a difference in ARTI risk between the vitamin D and placebo groups. One reported URTI symptoms were significantly lower in the vitamin D group, while the last reported no difference between groups for influenza infections but a significantly greater reduction in the vitamin D group for non-influenza virus infections. 

Additionally, it is not known if reported effects can be generalized to BAME groups as only one study included non-White populations, and no studies specifically compared if race or ethnicity modified the effect of vitamin D supplementation on ARTI risk. Overall, the evidence at this time does not support recommending vitamin D supplementation to prevent ARTIs in the general UK population, states SACN. 

“Two limitations of the SACN report are that a) no attempt is made to analyze pooled data from the trials, and b) that a number of seemingly relevant trials were not considered. My group is in the final stages of an updated meta-analysis, including data from the new trials identified by SACN as well as nine others. We hope to submit our findings next month,” concludes Martineau.

By Katherine Durrell