Vitamin D for COVID-19 and Acute Respiratory Tract Infections: SACN and NICE review the evidence

In June 2020 both the Scientific Advisory Committee on Nutrition (SACN) and National Institute for Health and Care Excellence (NICE) produced rapid evidence reviews of the best available evidence in response to suggestions that vitamin D supplementation (particularly high doses) could reduce the risk of COVID-19.

Current guidance on vitamin D supplementation

• Current government advice on vitamin D relates to the protection of bone and muscle health and is based on the recommendations of SACN following publication of its 2016 report on Vitamin D and Health.
• To protect bone and muscle health, the UK government advises that everyone needs vitamin D equivalent to an average daily intake of 10µg (micrograms), the equivalent of 400 international units (IU).
• Although sunlight exposure is the major source of vitamin D for most people, it can also be obtained from the diet or supplements. For more information on vitamin D and its link with the immune system see our resources below.
• The government advises that all people should consider taking a daily supplement containing 10µg of vitamin D during autumn and winter months. They also advise that people whose skin has little to no exposure to sunlight and ethnic minority groups with dark skin, from African, Afro-Caribbean and South Asian backgrounds, should consider taking a vitamin D supplement all year round.

People who are indoors shielding or self-isolating will not be getting sufficient exposure to sunlight and should therefore follow this advice.

• Supplements of the two major forms of vitamin D, vitamin D3 (colecalciferol) and vitamin D2 (ergocalciferol), are licensed for the prevention and treatment of vitamin D deficiency.

Vitamin D and COVID-19

• Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a coronavirus known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
• It has been hypothesised that vitamin D may have a role in the body's immune response to respiratory viruses. However, vitamin D supplements are not specifically licensed for preventing or treating any infection, including the novel coronavirus infection that causes COVID-19.

Vitamin D and Acute Respiratory Tract Infections (ARTI): SACN evidence review

• A systematic review and meta-analysis (Martineau et al. 2017) of randomised controlled trials (RCTs) has been widely cited as evidence to support that vitamin D supplementation reduces the risk of acute respiratory tract infections (ARTI, infection of the sinuses, throat, airways or lungs). In the context of the COVID-19 pandemic, SACN agreed to conduct a rapid review of the scientific evidence on vitamin D and ARTIs.

SACN conclusion

• Overall, the evidence at this time does not support recommending vitamin D supplementation to prevent ARTIs in the general UK population. This conclusion does not impact on existing government advice on vitamin D.
• UK government advice on vitamin D was reissued in April 2020 during the national lockdown. Whilst advice to stay at home remains largely in place it is recommended that, in order to protect musculoskeletal health, everyone should consider taking a daily vitamin D supplement of 10μg since people may not be getting enough from sunlight exposure.

Summary of the SACN evidence review

• The systematic review and meta-analysis by Martineau et al. (2017) reported that daily or weekly vitamin D supplementation reduces the risk of ARTIs, particularly among individuals with 25(OH)D concentrations <25nmol/L. However, study settings, vitamin D supplemental doses, reporting and assessment of ARTIs and trial results were very heterogeneous (different). Many of the included studies were in populations with pre-existing respiratory disease which may limit their applicability to the general population in the UK.
• The systematic review by Vuichard Gysin et al. (2016) included only healthy populations and reported that vitamin D supplementation did not reduce the risk of ARTIs. However, the included studies differed with respect to settings, vitamin D dosing regimens, definition of outcomes and their assessment.
• Evidence from supplement trials published after the Martineau et al. (2017) review suggest, overall, no effect of vitamin D supplementation on reducing ARTI risk.
• Differences in vitamin D supplementation doses and regimens, study settings, participants, study duration, definition and verification of outcomes (including type of respiratory infection) complicate interpretation of the evidence on vitamin D and ARTI risk.
• It is not known if reported effects can be generalised to populations from Black, Asian and minority ethnic (BAME) groups in the UK since only one study (in the US) included populations from an ethnic group and no studies specifically compared if race or ethnicity modified the effect of vitamin D supplementation on ARTI risk.
• This review did not include consideration of evidence on vitamin D and COVID-19 risk. Evidence on vitamin D and ARTI risk does not necessarily extrapolate to infection with SARS-COV-2.
• SACN will keep this topic under urgent review and consider updating this assessment if emerging evidence from ongoing RCTs on vitamin D and ARTI risk suggests a change to existing conclusions.

Vitamin D and COVID-19: NICE evidence review

• An evidence review of vitamin D and COVID-19 risk has been conducted by NICE to review the best available evidence (as of June 2020) on vitamin D for preventing or treating COVID-19, or for the susceptibility to COVID-19 based on vitamin D status.

NICE conclusion
There is no evidence to support taking vitamin D supplements to specifically prevent or treat COVID-19. However, 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. 

Summary of the NICE evidence review

• The review considered evidence from five published studies that looked retrospectively at the association between vitamin D status and development of COVID-19 (one cohort study, three prognostic studies involving published data sets using correlation or regression and one case-control survey). All five studies were assessed as being at high risk of bias (very low quality of evidence) and were limited by, for example, representativeness of their samples and issues with diagnostic criteria for either COVID-19 or its sequelae.
• None of the studies were intervention trials of vitamin D supplementation for the prevention or treatment of COVID-19. No data on appropriate doses or adverse events was given.
• Four of the studies found an association or correlation between a lower vitamin D status and subsequent development of COVID-19, but did not adjust for confounding factors, such as body mass index, higher socio-economic deprivation and poorer self-reported health, which may have independent correlations with vitamin D status or COVID-19.
• The largest UK study (Hastie et al. 2020) found an association between vitamin D status and COVID-19 only in a univariable analysis (a simple analysis with this single potential causative factor).
• Importantly, no causal relationship between vitamin D status and COVID-19 was found after adjustment for potential confounders such as comorbidity, socio-demographics, ethnicity, body mass index and other baseline factors.

References

• Martineau AR, Jolliffe DA, Hooper RL et al. (2017) Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 356 :i6583
• Vuichard Gysin D, Dao D, Gysin CM et al. (2016) Effect of Vitamin D3 Supplementation on Respiratory Tract Infections in Healthy Individuals: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS One. 11(9):e0162996.
• D'Avolio A, Avataneo V, Manca A, et al. (2020) 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2. Nutrients. 2020;12(5):1359.
• Fasano A, Cereda E, Barichella M, et al. (2020) COVID-19 in Parkinson's Disease Patients Living in Lombardy, Italy. Mov Disord. 10.1002/mds.28176.
• Hastie CE, Mackay DF, Ho F et al. (2020) Vitamin D concentrations and COVID-19 infection in UK Biobank, 2020 Diabetes Metab Syndr. 2020;14(4):561-565.
• Ilie PC, Stefanescu S, Smith L. (2020) The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging Clin Exp Res. 2020;32(7):1195-1198.
• Laird E, Rhodes J, Kenny RA (2020) Vitamin D and Inflammation: Potential Implications for Severity of Covid-19. Irish Medical Journal 113

Information reviewed July 2020.