Vitamin D and our immune system, and how it may support us against COVID19

April 30, 2020

What is vitamin D and how is it made?

 

Vitamin D is not just a vitamin, but a steroid hormone which regulates a huge proportion of our biological functions. Modulating our immune system is one of the expansive roles of vitamin D which we require to function optimally. Vitamin D is normally synthesized in skin by exposure of our skin to the sun, where UV light generates pre-Vitamin D. This undergoes further reactions to make an active form of vitamin D, cholecalciferol or Vitamin D3.

In northern latitudes such as the UK, Northern American and Norther Europe, there isn’t enough UV radiation of the right wavelength to make Vitamin D in the winter when the sun is low in the sky, particularly in polluted cities. Many of us are vulnerable to suboptimal levels of vitamin D3, even in the summer, as we often spend most of our time inside at work and are covered with clothes. Whilst there are some foods high in vitamin D, mainly oily fish with eggs, liver and butter providing small amounts, with fortified foods being another source. As Vitamin D is fat-soluble, people eating a low-fat diet will also have low absorption of Vitamin D. Public Health England and other organisations suggest that we take a dietary supplement during the winter months, between October and March[i].

Vitamin D deficiency

Lack of vitamin D is associated to an ever-increasing range of diseases[ii] and ill health[iii] including poor musculoskeletal health. One of the main functions of vitamin D is the maintenance of plasma concentration of calcium but it also modulates a huge diversity of physiological functions including insulin secretion, synthesis and secretion of parathyroid and thyroid hormones, and function within the immune system[iv].

Recent research has found that vitamin D can regulate both the innate and adaptive immune system[v], potentially as the B and T cells, and APC cells have vitamin D receptors. Vitamin D is required for the following immune system functions:

  • Dendritic cells activating T cells – in healthy people, T cells are a really important part of the adaptive immune system in fighting infections as killer T cells destroy infected or cancerous cells, whilst helper T cells modulate the immune response
  • Inhibition of production of interleukin by activated T-lymphocytes and of immunoglobulin by activated B-lymphocytes
  • Differentiation of monocyte precursor cells
  • Modulation of cell proliferation

Vitamin D deficiency is linked to increased susceptibility to infection[vi] and increased autoimmune disease. In people with autoimmune diseases, the immune system (T cells) mistakenly attacks your body and its own cells. Having optimal levels of vitamin D helps to increase the amount of a molecule CD31 and this regulates the immune system[vii] so that it doesn’t attack the body’s own cells.

In the UK, at least one in 5 people is deficient in Vitamin D with levels lower than 25nmol/ L.[viii]  IN the US, The Endocrine Society define deficiency as blood serum levels of 25-hydroxycholecalcifer0l (25 (OH)D3) under 20nmol/L deficient as this is the level that parathyroid levels involved in calcium balance  start to rise outside of healthy ranges and there is a physiological instigation of Vitamin D deficiency.  In the UK[ix], Vitamin D deficiency are blood serum levels under 25nmol/l and insufficiency are levels under 50nmol/l.

 

Populations with vitamin D deficiency

Epidemiological studies have discovered what populations most likely to have deficiency[x] [xi]:

Elderly vitamin D levels are lower as you age as the synthesis of vitamin D in skin declines with age. Older adults 63% more likely to have vitamin D deficiency (NHANES) and 46%  have vitamin D insufficiency compared to young adults

Obese – Obese individuals have lower levels of Vitamin D as fat soluble vitamin D has greater difficulty being released into the blood stream. Obese individuals have greater than 50% less bio-availabilty of vitamin D than non-obese individuals. Obese adults in the US had 3 times higher prevalence of vitamin D deficiency and 1.9 times prevalence of vitamin D insufficiency than non-obese adults.

Northern latitudes – anyone living in the UK, Canada, northern US and Europe has lower levels of vitamin D as there is less UVB radiation reaching the atmosphere so there less of it to reach our skin to facilitate the production of vitamin D.

In darker skinned people – Those with darker skin often have lower levels of vitamin D synthesis  as it is decreased to compensate for the role of protection by melanin[xii], a natural sun screen which protects us from the damaging effects of UV radiation. Non-Hispanic blacks have 24.6% higher vitamin D deficiency and 3.7 times higher vitamin D insuffiency than non-Hispanic whites (NHANES).

These groups coincide with the groups that have had higher hospitalisations and deaths as result of being infected with SARS-Cov-2 and COVID19.  A CDC study in 14 US states 48% of people hospitalised for COVID19 were obese[xiii].  We know that there is a higher risk of COVID19 complications and hospitalisation for those over 65. There are suggestions that African Americans are at higher risk of complications with COVID19 - 33% of people hospitalised for COVID19 were African- American who only constitute 13% of of US population in comparison of 45% of hospitalisations were of white people who makeup 76% of the population in US.

A study in BMJ in March 2020[xiv] found that Somali immigrants living in Stockholm Sweden make up 40% of COVID 19 related deaths at that time whilst Somalis only make up 0.84% of population.  Somalis living in Sweden  have extreme vitamin D deficiency due to hereditary and cultural factors (wearing the hijab), and the northern latitude decreasing UV radiation required for Vitamin D synthesis. These possible correlation or association of vitamin D deficiency  may also partly explain why there is a higher prevalence of COVID19 complications and death in the BAME community although socio-economic factors and higher prevalence of metabolic disease including diabetes, cardiovascular disease and hypertension.

Vitamin D supplementation

I haven’t gone into the potential mechanisms of how vitamin D might support the immune system, and in particular against SARS-Cov-2 (via normalising ACE2 receptor levels which are downregulated when SARS-Cov-2 binds via spike protein[xv] to gain entry to our cells[xvi]), but we know that people with deficiency may have weaker innate immune response. A meta-analysis in the BMJ[xvii] looked at 25 randomised controlled studies that show that Vitamin D is protective of respiratory tract infections. Daily or weekly supplementation reduced the risk of respiratory tract infection by more than 50% in people with low base line Vitamin D levels. People with higher base line vitamin D had 10% reduced risk with supplementation. 

As Vitamin D status could impact our resilience to SARS-Cov-2 and associated complications including death[xviii], PHE has revised its advice during the COVID19 pandemic and suggested that we continue to supplement whilst we are in lockdown as we are spending more time inside.  We know that 1000iu of Vitamin D increases 25-hydroxy vitamin D (active precursor) by 5 ng/ml so to ensure we are all over the threshold nearer to optimal levels of 50 to 125ng/ml, suggest taking a supplement of 3000 to 4000iu a day[xix]. Genetic factors can affect how much we absorb.  In addition, there are small genetic changes in vitamin D metabolism genes called polymorphisms  (SNPs)which have an effect on serum concentrations of 25-hydroxyvitamin D.

In order to cope with COVID19 pandemic , preventative measures could include vitamin D administration to high risk populations – darker skinned, older and obese adults with low sun exposure and individuals with respiratory tract infections as this is unlikely to be harmful and may be beneficial.  We may also want to look at supplementing those with co-morbidities that affect risks involved with SARS-Cov-2 infection including cancer, diabetes, hypertension and cardiovascular disease. As we learn more about this novel coronavirus and how it affects our physiology, we will be able to learn how we can best protect ourselves.

References

[i] https://www.gov.uk/government/news/phe-publishes-new-advice-on-vitamin-d
[ii] Laaksi I, et al. An association of serum vitamin D concentrations < 40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr. 2007;86(3):714–7
[iii]  Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab. 2009;94(1):26–34.
[iv] Rezaei R. Immunomodulatory effects of Vitamin D in influenza infection. Curr Immunol Rev. 2018;14:40–49.
[v] Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: modulator of the immune system. Curr Opin Pharmacol. (2010) 10:482–96.
[vi] chottker B, Jorde R, Peasey A, Thorand B, Jansen EH, Groot L, et al. Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ. (2014) 348:g3656.
[vii] Louise Saul, Iris Mair, Alasdair Ivens, Pamela Brown, Kay Samuel, John D. M. Campbell, Daniel Y. Soong, Nadine Kamenjarin, Richard J. Mellanby. 1,25-Dihydroxyvitamin D3 Restrains CD4 T Cell Priming Ability of CD11c Dendritic Cells by Upregulating Expression of CD31. Frontiers in Immunology, 2019; 10
[viii]https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/537616/SACN_Vitamin_D_and_Health_report.pdf
[ix] https://www.bjfm.co.uk/prevention-of-vitamin-d-deficiency
[x]Palacios C., Gonzalez L. Is vitamin D deficiency a major global health problem. J Steroid Biochem Mol Biol. 2014;144:138–145
[xi] van schoor NM, Lips P. Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab 2011; 25:671–80
[xii] McLaughlin J., Holick M.F. Aging decreases the capacity of human skin to produce Vitamin D3. J Clin Invest. 1985;76:1536–1538.
[xiii] Garg S, Kim L, Whitaker M, et al. Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 — COVID-NET, 14 States, March 1–30, 2020. MMWR Morb Mortal Wkly Rep 2020;69:458–464
[xiv] Bejerot S The Burning Building BMJ 2020; 36
[xv] Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS Coronavirus. J Virol. 2020;94(7)
[xvi] Li, W. et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426, 450–454 (2003)
[xvii] Martineau Adrian R, Jolliffe David A, HooperRichard L, Greenberg Lauren, Aloia John F, Bergman Peter et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data BMJ  2017;  356 :i6583
[xviii] Marik PE, Kory P, Varon J. Does vitamin D status impact mortality from SARS-CoV-2 infection? [published online ahead of print, 2020 Apr 29]. Med Drug Discov. 2020;100041. doi:10.1016/j.medidd.2020.100041
 
[xix] Bergman P., Lindh A.U., Bjorkhem-Bergman L. Vitamin D and respiartory tract infections: A systematic review and meta-analysis of randomized controlled trials. PloS ONE. 2013;8



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