June 30, 2020 7 min read

Introduction

Vitamin D3 is a fat-soluble vitamin that is involved in several important biologic processes. The most important natural source of the vitamin is the synthesis of cholecalciferol in the lower layers of the skin epidermis by a chemical reaction that depends on sun exposure (specifically UVB radiation). Excessive use of sunblock can result in reduced production leading to a deficiency if dietary intake is unable to balance the required amount. 

The vitamin D that is consumed by diet or formed in the skin cells is in an inactive form. It is then converted to the active form,calcitriol (D3), by systemic enzymatic reactions that take place in the liver and the kidney.

Since the skin cells can synthesize vitamin D, many researchers believe that it is a hormone, rather than an essential vitamin.The recommended daily intake of vitamin D is 400-800 IU.

Vitamin D is involved in the regulation of several physiologic functions of the human body.

  • It helps in the intestinal absorption of calcium, magnesium, and phosphorus.
  • It is necessary for building bones.
  • It helps maintain bone strength.
  • It is a key regulator of calcium homeostasis.
  • It is involved incell growth, neuromuscular and immune functions, and reduction of inflammation.
  • Maintaining in gut health.

Vitamin D has profound effects on the body, today we have articulated this article to review how it boosts and optimizes the immune system.

Prevalence of Vitamin D Deficiency

Vitamin D deficiency (VDD) is a fairly common disease. A research study published on VDD and its potential complications found that around 41.6% of the adult US population (>20 years of age) has VDD i.e. blood vitamin D levels < 50mmol/L. Not surprisingly enough, 82.1% of these VDD patients were blacks.    

Effects of Vitamin D3 on the Immune System

Vitamin D can modulate innate and adaptive immune responses. Vitamin D receptors are found on the immune cells and these cells can also synthesize active vitamin D metabolites that then proceed to act in an autocrine manner i.e.acting on the cell by which it is secreted. A deficiency of vitamin D increases susceptibility to infections and also increases the risk of autoimmune diseases. (1)

A study published in 2009, reported results of an analysis of a survey that was conducted in the USA from 1988-1994, which stated that individuals with low levels of serum vitamin D, reported an increased incidence of upper respiratory tract infections (URTI). The association between low levels of calcitriol (VitaminD3) and incidence of URTI were stronger in people with asthma and chronic obstructive pulmonary disease. (2) 

A research conducted in 2009 studied the association of bacterial vaginosis in pregnant women and serum vitamin D3 levels. It was concluded that low levels of vitamin D3 resulted in an increased prevalence of bacterial vaginosis and when the women were supplemented with vitamin D3 there was a dose-dependent response and the prevalence of the infection declined. Thus providing evidence that vitamin D3 levels have a strong association with a healthy immune response. (3)

A genetic study that was performed in 2018,  showed that vitamin D3 is an important regulator of the TPH1 gene. It reduces the amount of serotonin produced from tryptophan in the gut and prevents gut inflammation. This indicates that vitamin D deficiency may result in serotonin dysregulation and cause inflammatory bowel syndrome (IBS). In addition it also suggests that vitamin D3 supplementation is an explorable treatment option for IBS. (4) The reduced serotonin in the gut does not cause depression as the brain produces its own serotonin. (5)  

Vitamin D3 deficiency has been implicated in several autoimmune diseases, for example, multiple sclerosis, type 1 diabetes mellitus, systemic lupus erythematosus (SLE), and rheumatoid arthritis. Vitamin D3 dysregulation due to impaired absorption, dietary deficiency, or reduced sunlight exposure increases the risk of developing autoimmune diseases. More clinical trials should be performed to advocate vitamin D supplementation in the prevention of autoimmune diseases. (6),(7). 

A meta-analysis of 25 randomized controlled trials performed in 2019, reported that vitamin D supplementation was safe and protected against acute respiratory infections (ARI). Individuals receiving a daily dose of the supplements had greater protective effects. (8)

A survey of existing literature regarding the role of vitamin D in preventing or treating influenza suggested that vitamin D supplementation can be an adjuvant to the influenza vaccine. (9)

A study conducted in 2019, studied the role of Vitamin D in HIV positive patients with a non-AIDS disease having other inflammatory diseases. The participants were suffering from a persistent inflammatory state despite effective antiviral therapy. A review of 29 clinical studies showed that low levels of vitamin D correlated with the inflammatory state and that vitamin D supplementation resulted in reduced inflammation and increased anti-bacterial response. There is also evidence regarding the role of vitamin D in reducing the infection of CD4 +T cells. The study suggested that along with antiviral drugs adding vitamin D supplements to the treatment regime may be effective in preventing morbidity and mortality. More clinical trials are required to ensure proper and detailed treatment guidelines. (10) 

Darker skin and Vitamin D3 Levels

As already discussed, the synthesis of cholecalciferol (Vitamin D3 precursor) by the deeper layers of the skin is by a chemical reaction that requires UVB light. Thus, exposure to sunlight is essential for the synthesis of Vitamin D3 in our body. Vitamin D deficiency (VDD) can occur due to a number of causes, the most important of which is less exposure to the UVB component of natural sunlight. This can happen in a number of scenarios such as little to no outdoor activities, wearing sunscreen when going out, darker skin that prevents UVB penetration, obesity or metabolic diseases, etc.

Research studies have demonstrated that people with a naturally dark skin tone have natural sun protection and require at least three to five times longer exposure to make the same amount of vitamin D as a person with a white skin tone (11,12). This is due to the fact that melanin - the pigment present in superficial layers and responsible for the skin color - filters the UV light coming from the sun. Another study found that wearing a sunscreen that has an SPF (Sun Protection Factor) of 30 reduces vitamin D synthesis in the skin by more than 95% (13). 

Therefore, people with darker skin tone are more vulnerable to develop Vitamin D deficiency (VDD) and are recommended to take dietary supplements to overcome the demand and supply gap. Also, fair skin people using high SPF sunscreen can potentially develop Vitamin deficiency too and are thus encouraged to overcome that loss via dietary supplements. 

Vitamin D3 and Virology

Scientists have been trying to study the role of vitamin D3 as an antiviral agent. Although it has been implicated to induce an antiviral state, promote autophagy of infected cells, bring about several genetic and epigenetic alterations, and modulation of viral gene transcription. The mechanisms by which these events occur are very complex and not very well understood. (14)

Recent research conducted in 2020, suggested that there is an inverse correlation between vitamin D3 levels and high levels of inflammatory markers in patients infected with COVID-19. It is a possibility that vitamin D3 deficiency may result in mortality and sufficient levels may help in reducing the severity of the disease but more research is necessary before forming any treatment guidelines. (15)

Conclusion

Vitamin D receptors are present on several cells of the body and therefore it has multiple extraskeletal effects. Its role in the immune response is indispensable and a recommended serum level should be maintained by adequate dietary intake, sufficient exposure to sunlight (exposure should be limited and during the early hours after sunrise as increased exposure may cause skin cancer) or supplements to ensure an optimum body function, and prevent diseases.


Vitamin D supplements are an effective preventive option for many immune-mediated diseases. Use the supplements with caution and immediately consult your health care provider if you develop any side effects.

References

  1. Aranow C. (2011). Vitamin D and the immune system. Journal of investigative medicine: the official publication of the American Federation for Clinical Research, 59(6), 881–886. 
  2. Ginde, A. A., Mansbach, J. M., & Camargo, C. A., Jr (2009). Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Archives of internal medicine, 169(4), 384–390. 
  3. Bodnar LM, Krohn MA, Simhan HN. Maternal vitamin D deficiency is associated with bacterial vaginosis in the first trimester of pregnancy. J Nutr. 2009;139(6):1157‐1161. 
  4. Dussik, C. M., Hockley, M., Grozić, A., Kaneko, I., Zhang, L., Sabir, M. S., Park, J., Wang, J., Nickerson, C. A., Yale, S. H., Rall, C. J., Foxx-Orenstein, A. E., Borror, C. M., Sandrin, T. R., & Jurutka, P. W. (2018). Gene Expression Profiling and Assessment of Vitamin D and Serotonin Pathway Variations in Patients With Irritable Bowel Syndrome. Journal of neurogastroenterology and motility, 24(1), 96–106.
  5. Gustafson C. (2014). Bruce Ames, phd, and Rhonda Patrick, phd: Discussing the Triage Conceptand the Vitamin D-Serotonin Connection. Integrative medicine (Encinitas, Calif.), 13(6), 34–42.
  6. Szodoray P, Nakken B, Gaal J, et al. The complex role of vitamin D in autoimmune diseases. Scand J Immunol. 2008;68(3):261‐269.
  7. Yang, C. Y., Leung, P. S., Adamopoulos, I. E., & Gershwin, M. E. (2013). The implication of vitamin D and autoimmunity: a comprehensive review. Clinical reviews in allergy & immunology, 45(2), 217–226. 
  8. Martineau AR, Jolliffe DA, Greenberg L, et al. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol Assess. 2019;23(2):1‐44.
  9. Gruber-Bzura B. M. (2018). Vitamin D and Influenza-Prevention or Therapy?. International journal of molecular sciences, 19(8), 2419. 
  10. Alvarez, N., Aguilar-Jimenez, W., & Rugeles, M. T. (2019). The Potential Protective Role of Vitamin D Supplementation on HIV-1 Infection. Frontiers in immunology, 10, 2291. 
  11. Clemens TL, Henderson SL, Adams JS, Holick MF. Increased skin pigment reduces the capacity of skin to synthesise vitamin D3. Lancet. 1982;1:74–6.
  12. 38. Hintzpeter B, Scheidt-Nave C, Müller MJ, Schenk L, Mensink GB. Higher prevalence of vitamin D deficiency is associated with immigrant background among children and adolescents in Germany. J Nutr. 2008;138:1482–90.
  13. Matsuoka LY, Ide L, Wortsman J, MacLaughlin JA, Holick MF. Sunscreens suppress cutaneous vitamin D3 synthesis. J Clin Endocrinol Metab. 1987;64:1165–8.
  14. Teymoori-Rad, Majid & Shokri, Fazel & Salimi, Vahid & Marashi, Mahdi. (2019). The interplay between vitamin D and viral infections. Reviews in Medical Virology. 29. e2032. 10.1002/rmv.2032. 
  15. The Role of Vitamin D in Suppressing Cytokine Storm in ... www.medrxiv.org/content/medrxiv/early/2020/04/10/2020.04.08.20058578.full.pdf?mod=article_inline.

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