VITAMIN D SUPPLEMENTATION

A Review of its Role in Preventing and Treating viral or bacterial Respiratory Tract Infections.

Decreased levels of vitamin D in winter permits viral epidemics of respiratory tract infections. This is a realistic conclusion drawn from observational studies that looked into this association. One of these studies conducted in Connecticut in the United States on 198 healthy adults in the fall and winter of 2009–2010 examined the relationship between serum vitamin D concentration and the incidence of acute RTIs (ARTIs). A minority of people who maintained vitamin D levels higher than 38 ng/ml throughout the study developed ARTIs, whereas 45% of the others who didn’t have adequate levels of vitamin D had the respiratory infection. Concentrations of vitamin D equal to 38 ng/ml or more, were associated with a significant twofold reduction in risk of developing ARTIs and with a marked reduction in percentage of days of illness. (1) 

Observational studies report consistent independent associations between low serum concentrations of vitamin D and susceptibility to acute respiratory tract infection. (2,3) Vitamin D supports induction of antimicrobial peptides in response to both viral and bacterial stimuli, suggesting a potential mechanism by which vitamin D mediates an inducible protection against respiratory pathogens. (4,5,6)

In 2016, a meta-analysis of individual participant data from 10,933 participants in 25 randomized controlled trials showed an overall protective effect of vitamin D supplementation against acute respiratory tract infection. (7) These protective benefits were greater in people receiving daily (800 – 3000 IU) or weekly vitamin D (>30,000), and the protective effects against acute respiratory tract infection in this group were strongest in those with profound vitamin D deficiency at baseline in whom the risk of infection was decreased by 70%. Even in those who were less deficient in vitamin D, the risk of RTI decreased by 25%. 

Epidemiological and observational studies show a clear association between low vitamin d levels in blood and suscueptibility to develop respiratory infection

All the scientific evidence stated above along with the well-studied physiological action of vitamin D allow to say that vitamin D enhances the person’s natural immunity to combat viruses, bacteria and even fungi. Indeed, vitamin D has many mechanisms by which it reduces the risk of microbial infection that could lead to death in case of progression to severe pneumonia. A recent review regarding the role of vitamin D in reducing risk of common cold allowed to group those mechanisms into three categories: physical barrier, cellular natural immunity and adaptive immunity [8].

A large study involving almost 11,000 patients shows that daily or weekly supplementation with vitamin D reduces the frequency of acute respiratory infection by up to 70 percent

While adaptive immunity is more about protection from secondary infection, physical barrier and cellular natural immunity are more implicated in the occurring infection. With regards to the mechanisms of physical barrier properties of vitamin D, Vitamin D helps maintain tight junctions, gap junctions, and adherens junctions between cells (e.g., E-cadherin) [9]. Viruses can disturb cells junction integrity and hence increase infection by the virus and other microorganisms like bacteria. [10, 11]. That nasty property of viruses is an important reason why viral infections progress to pneumonia. 

About cellular natural immunity, vitamin D promotes cellular natural immunity partly through induction of antimicrobial proteins, including human cathelicidin, LL-37, by 1,25-dihdroxyvitamin D (12,13) and defensins (14). Cathelicidins exhibit direct antimicrobial activities against a spectrum of microbes, including gram-positive and gram-negative bacteria, enveloped viruses, and fungi. Coronaviruses are classified among the enveloped viruses.

By boosting immunity, vitamin D promotes the production of special proteins like “Cathelicidin” that exhibit direct antmicrobial activity against bacteria and enveloped viruses. Coronavirus is an enveloped virus 

Vitamin D also enhances cellular natural immunity in part by reducing the cytokine storm induced by the innate immune system. The innate immune system generates both pro-inflammatory and anti-inflammatory cytokines in response to viral infections as observed in COVID-19 patients and also in bacterial infections. [15]. Vitamin D modulates the production of cytokines involved in what is called the cytokine storm – mainly tumor necrosis factor α and some bad cytokines and interferons –  in a way that can decrease its occurrence and prevent complications arising from that strong inflammatory body response.  [16]. Administering vitamin D reduces the expression of pro-inflammatory cytokines and increases the expression of anti‐inflammatory cytokines

Vitamin D modulates the inflammatory response to infection in a good way. “The cytokine storm” has been implicated in severe complications and even death from respiratory infection – like from covid-19. Vitamin D reduces the occurrence of the cytokine storm

Who would benefit of raising the vitamin D levels to fight against infections? In simple words, Everyone. However, it is well known that older people and people with chronic illnesses are more susceptible to develop severe pneumonia following RTI. So these patients with chronic diseases and the elderly population would benefit most from increasing their vitamin D levels in the blood to levels above 30ng/ml. In fact, this is usually the cohort of people presenting with low levels of vitamin D in their blood. Indeed, people with chronic diseases have lower vitamin D concentrations and increased inflammation. An Italian study reported that older patients with a mean age of 67 years who developed acute myocardial infarction had mean serum vitamin D concentrations in winter of 11 ng/ml [17]. In the Chinese city of Wenzhou, diabetic people of a mean age of 43 years had lower vitamin D concentrations than the non-diabetic population [18]. An observational study conducted in Qinhuangdao, China, in hospitalized patients, showed that those with pneumonia had much lower vitamin D levels than those without [19]. 

Older people and patients with chronic diseases have lower vitamin D levels than others. These would benefit from vitamin D supplementation to bring the blood levels to > 30Ng/ml

In conclusion, there is no doubt that the above review and findings show a strong correlation between low vitamin levels and risk of viral or bacterial respiratory infection. Based on its mechanism of action and scientific evidence, authorities should support the introduction of public health measures such as food fortification with vitamin D or vitamin D supplementation to improve vitamin D status, particularly in settings where profound vitamin D deficiency is common, especially in older population or in people with chronic illnesses. This also should encourage supplementation with vitamin D at end of summer and start of fall where flu and common cold seasons would usually begin.

Vitamin D levels should be normal during the fall when respiratory infections usually begin

References: 

  1. Sabetta, J.R.; DePetrillo, P.; Cipriani, R.J.; Smardin, J.; Burns, L.A.; Landry, M.L. Serum 25-hydroxyvitamin d and the incidence of acute viral respiratory tract infections in healthy adults. PLoS One 2010, 5, e11088, doi:10.1371/journal.pone.0011088
  2. Cannell JJ, Vieth R, Umhau JC, et al. Epidemic influenza and vitamin D. Epidemiol Infect 2006;356:1129-40. doi:10.1017/S0950268806007175 pmid:16959053.
  3. Jolliffe DA, Griffiths CJ, Martineau AR. Vitamin D in the prevention of acute respiratory infection: systematic review of clinical studies. J Steroid Biochem Mol Biol 2013;356:321-9. doi:10.1016/j.jsbmb.2012.11.017 pmid:23220552
  4. Hansdottir S, Monick MM, Hinde SL, Lovan N, Look DC, Hunninghake GW. Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol 2008;356:7090-9. doi:10.4049/jimmunol.181.10.7090 pmid:18981129.
  5. Olliver M, Spelmink L, Hiew J, Meyer-Hoffert U, Henriques-Normark B, Bergman P. Immunomodulatory effects of vitamin D on innate and adaptive immune responses to Streptococcus pneumoniae. J Infect Dis 2013;356:1474-81. doi:10.1093/infdis/jit355 pmid:23922371.
  6. Greiller CL, Martineau AR. Modulation of the immune response to respiratory viruses by vitamin D. Nutrients 2015;356:4240-70. doi:10.3390/nu7064240 pmid:26035247
  7. Adrian R Martineau, David A Jolliffe, Richard L Hooper et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017;356:i6583 | doi: 10.1136/bmj.i6583
  8. Rondanelli, M.; Miccono, A.; Lamburghini, S.; Avanzato, I.; Riva, A.; Allegrini, P.; Faliva, M.A.; Peroni, G.; Nichetti, M.; Perna, S. Self-Care for Common Colds: The Pivotal Role of Vitamin D, Vitamin C, Zinc, and Echinacea in Three Main Immune Interactive Clusters (Physical Barriers, Innate and Adaptive Immunity) Involved during an Episode of Common Colds-Practical Advice on Dosages and on the Time to Take These Nutrients/Botanicals in order to Prevent or Treat Common Colds. Evid Based Complement Alternat Med 2018, 2018, 5813095, doi:10.1155/2018/5813095.
  9. Schwalfenberg, G.K. A review of the critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D deficiency. Mol Nutr Food Res 2011, 55, 96-108, doi:10.1002/mnfr.201000174
  10. Kast, J.I.; McFarlane, A.J.; Globinska, A.; Sokolowska, M.; Wawrzyniak, P.; Sanak, M.; Schwarze, J.; Akdis, C.A.; Wanke, K. Respiratory syncytial virus infection influences tight junction integrity. Clin Exp Immunol 2017, 190, 351-359, doi:10.1111/cei.13042
  11. Rossi, G.A.; Fanous, H.; Colin, A.A. Viral strategies predisposing to respiratory bacterial superinfections. Pediatr Pulmonol 2020, 10.1002/ppul.24699, doi:10.1002/ppul.24699
  12. Liu, P.T.; Stenger, S.; Li, H.; Wenzel, L.; Tan, B.H.; Krutzik, S.R.; Ochoa, M.T.; Schauber, J.; Wu, K.; Meinken, C., et al. Toll-like receptor triggering of a vitamin Dmediated human antimicrobial response. Science 2006, 311, 1770-1773, doi:10.1126/science.1123933. 
  13. Adams, J.S.; Ren, S.; Liu, P.T.; Chun, R.F.; Lagishetty, V.; Gombart, A.F.; Borregaard, N.; Modlin, R.L.; Hewison, M. Vitamin d-directed rheostatic regulation of monocyte antibacterial responses. J Immunol 2009, 182, 4289-4295, doi:10.4049/jimmunol.0803736. 
  14. Laaksi, I. Vitamin D and respiratory infection in adults. Proc Nutr Soc 2012, 71, 90-97, doi:10.1017/S0029665111003351.
  15. Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 10.1016/S0140-6736(20)30183-5, doi:10.1016/S0140-6736(20)30183-5
  16. Sharifi, A.; Vahedi, H.; Nedjat, S.; Rafiei, H.; Hosseinzadeh-Attar, M.J. Effect of singledose injection of vitamin D on immune cytokines in ulcerative colitis patients: a randomized placebo-controlled trial. APMIS 2019, 127, 681-687, doi:10.1111/apm.12982
  17. Aleksova, A.; Belfiore, R.; Carriere, C.; Kassem, S.; La Carrubba, S.; Barbati, G.; Sinagra, G. Vitamin D Deficiency in Patients with Acute Myocardial Infarction: An Italian Single-Center Study. Int J Vitam Nutr Res 2015, 85, 23-30, doi:10.1024/0300- 9831/a000220. 
  18. Chen, X.; Wu, W.; Wang, L.; Shi, Y.; Shen, F.; Gu, X.; Jia, Z. Association Between 25- Hydroxyvitamin D and Epicardial Adipose Tissue in Chinese Non-Obese Patients with Type 2 Diabetes. Med Sci Monit 2017, 23, 4304-4311, doi:10.12659/msm.904755. 
  19. Lu, D.; Zhang, J.; Ma, C.; Yue, Y.; Zou, Z.; Yu, C.; Yin, F. Link between communityacquired pneumonia and vitamin D levels in older patients. Z Gerontol Geriatr 2018, 51, 435-439, doi:10.1007/s00391-017-1237-z.

Send me

a newsletter