COVID-19: the vitamin D debate

BLUF: there is growing interest in vitamin D supplements as a low risk intervention for COVID-19

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Vitamin D and respiratory infection.

There is a long-standing interest in the value of vitamin D supplements in management of infectious diseases, particularly in influenza and other acute viral respiratory infections. Just over a decade ago, as the world learned to cope with pandemic influenza A/H1N1/09, a meta-analysis concluded that these claims were worth investigating in properly designed trials [1]. More recent analysis of multiple studies supports the association between vitamin D deficiency and acute respiratory infection [2], and the use of vitamin D supplements to prevent acute respiratory infection [3].

Occurrence of COVID-19.

As the world began to recognise the gravity of COVID-19, a case was made for vitamin D supplementation as a potential antiviral intervention [4]. The hypothesis that vitamin D deficiency might explain epidemiological features of the COVID-19 pandemic, was explored in detail. Grant and colleagues listed a series of reasons for their hypothesis:

  • the occurrence of the epidemic during the Northern Hemisphere’s winter when natural vitamin D synthesis is at its lowest
  • the lower number of cases in the Southern Hemisphere, then in summer
  • the association of vitamin D deficiency with acute respiratory distress syndrome
  • an increased case-fatality rate in the elderly and chronically diseased who are also prone to vitamin D deficiency

 

Vitamin D deficiency in Europe during COVID-19

Interest in using vitamin D to prevent progression from mild to severe COVID-19 has been raised further by discussion about the recent publication of the Irish Longitudinal Study into Ageing (TILDA) which specifically addresses COVID-19 [5]. Finding that 13% adults over 55 years of age are deficient in vitamin D all year-round, they note that vitamin D supplements could be used for the at-risk elderly, particularly those being coccooned for their own protection. As the Irish population already has a low exposure to sunlight for much of the year, it is a logical recommendation. The authors note Finland’s elimination of vitamin D deficiency through an effective national policy. At the time of writing there have been 174 deaths and 5,364 COVID-19 cases reported from Eire (popn.; 4.9 million), compared to 28 deaths and 2,176 COVID-19 cases in Finland (popn.; 5.5 million). In an unreviewed pre-publication report, there was an interesting correlation between a population’s mean vitamin D levels, the number of cases and fatal COVID-19 infections [6]. This preliminary data does not prove a causal association between vitamin D deficiency and infection, severe or otherwise. However, this observation merits closer study as the COVID-19 pandemic runs its course.

And where the sun does shine?

In sunnier climates, the benefit of vitamin D supplementation might not be so obvious. However, the high-risk elderly who are being coccooned indoors may not have sufficient sunlight exposure to sustain higher blood levels of vitamin D. In Australasia, where there are many of Anglo-Celtic and other northern European heritage, the not-quite-so-elderly may also choose to retreat indoors during the summer months to reduce their skin cancer risk. Now, with restrictions on outdoor movement and the autumn well under way, it is possible that there will be an unintended consequence of reduced natural vitamin D synthesis in the winter months if COVID-19 persists until then.

Targetable outcomes.

So, how might vitamin D supplementation help counter the COVID-19 threat? The benefit of vitamin D supplements against influenza and other viral respiratory infections appears to be quite widely supported, but evidence has yet to be presented for clinical benefit in COVID-19. It remains to be seen what can be prevented of disease, progression, complications and mortality. Any advance would be noteworthy.

Conclusion

In view of our current lack of approved, effective anti-coronavirus drugs with evidence-based indications, known dose-effect profile and proven efficacy, claims for low risk preventive and immunomodulatory interventions need close examination. The jury might still be out, but surely there is a good case for carefully designed clinical trials of vitamin D supplements for the over 60s and others at risk of high level exposure such as first responders, emergency department and intensive care unit staff during this time of COVID-19.

Micrognome, 11-APR-20.

References

  1. Yamshchikov AV, Desai NS, Blumberg HM, Ziegler TR, Tangpricha V. Vitamin D for treatment and prevention of infectious diseases: a systematic review of randomized controlled trials. Endocr Pract. 2009;15: 438-49.
  2. Zhou YF, Luo BA, Qin LL. The association between vitamin D deficiency and community-acquired pneumonia: A meta-analysis of observational studies. Medicine (Baltimore). 2019; 98: e17252.
  3. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017; 356: i6583.
  4. Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, et al. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients. 2020 Apr 2;12(4). pii: E988.
  5. Laird E, Kenny RA and the TILDA Team. Vitamin D deficiency in Ireland – implications for COVID-19. Results from the Irish Longitudinal Study on Ageing (TILDA). The Irish Longitudinal Study on Ageing, Apr. 2020. Trinity College, Dublin, Eire.
  6. Ilie PC, Stefanescu S, Smit L. The role of Vitamin D in the prevention of Coronavirus Disease 2019 infection and mortality. Research Square. Posted Apr 8, 2020. Doi: 21203/rs.3.rs-21211/v1

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