Making a case for Vitamin D during COVID 19 - Subhasree Ray (Clinical & Public Health Nutritionist)

It’s been six months since the World Health Organization has declared COVID 19 pandemic. COVID 19 is defining the global health crisis of our time and one of the major threats posed to the world since world war two. Worldwide, scientists are racing for a safe vaccine or medicine. Amid these hustles, nutrition, one of the most crucial aspects in COVID recovery and prevention is overlooked. Specific micronutrients (Vitamins and Minerals) are potential antioxidant and play a vital role in boosting immunity as well as keep the pathogens at bay. Vitamin D, among these micronutrients, found be of utmost importance during COVID 19 as researchers’ uncovered prevalence of Vitamin D deficiency in people who succumbed to death. Observational studies on mortality and severity in COVID 19 patients also revealed that the pandemic is affecting people who are either overweight, obese, living with diabetes, hypertension, malnourished, and immune suppressants. Vitamin D deficiency is associated with all these conditions, directly or indirectly. 

Global Literature: Vitamin D Deficiency and COVID 19 Mortality:

A most recent study (Merzon E et al, 2020) published in FEBS Journal shows, out of 7807 COVID 19 patients, 782 (10.1%) were COVID‐19 positive, and 7,025 (89.9%) were COVID‐19 negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID‐19. The authors also stated people who are aged over 50 years, male and from low socio-economic status were having a positive association with the risk of COVID 19 infection and the likelihood of hospitalization.

Hans K. Biesalki (June 2020) in an article titled “Vitamin D Deficiency and Comorbidities in COVID 19 patients – A Fatal Relationship” explains the vitamin’s crucial role in the immune system that raises the question whether an inadequate Vitamin D supply has an influence on the progression and severity of COVID 19 disease.

Physicians, Dr Issac Pugach and Dr Sofya Pugach at the Complete Med Care clinic in Dallas, Texas, have conducted a study showing that the prevalence of severe vitamin D deficiency is strongly correlated with COVID 19 mortality rate in European countries. The study found, EU countries, with the prevalence of severe Vitamin D deficiency, reported more COVID 19 deaths/million than countries who had lower prevalence. 

Importance of Vitamin D in Human Physiology:

• Role of Vitamin D in Immune Regulation and Inflammatory Responses

Vitamin D receptor (VDR) is expressed on immune cells (B cells, T cells and antigen-presenting cells) and these immunologic cells are all are capable of synthesizing the active vitamin D metabolite, vitamin D has the capability of acting in an autocrine manner in a local immunologic milieu. Vitamin D can modulate innate and adaptive immune responses. Deficiency in vitamin D is associated with increased autoimmunity as well as increased susceptibility to infection. Global data, stating deficiency of vitamin D in COVID 19 positive patients and those who succumbed to death supports the theory that vitamin D is one of the most important factors in regulating the basic immunological functions in the body. 

Fig 1: The influence of 1,25(OH)2D on the different cell types of these immune system segments (Shymanskyi I et al, 2019)

 

• Obesity

Studies (Arunabh S et al, 2003; Parikh S et al, 2004) reporting, obesity is associated with alterations in the vitamin D endocrine system. Lower levels of serum 25-hydroxyvitamin D (25-OHD) in morbidly obese individuals may be related to deposition of adipose cells. Therefore, morbidly obese individuals are expected to need higher doses of vitamin D supplementation than the general population. However, it is still unknown whether adiposity (or percentage body fat) should be taken into consideration while assessing vitamin D requirements in the general population. Another theory stated that certain enzymes are needed to convert vitamin D into its active form, and levels of these enzymes may differ between obese and non-obese individuals.

A 2012 study (Drincic A et al.) reported adjusting Vitamin D levels in obese individuals reduced the difference in Vitamin D levels among obese and non-obese individuals. This indicates vitamin D needs to depend on body size, & obese need more than normal-weight people.

Interestingly, losing weight can also affect vitamin D levels. RCT (Rock C et al, 2012) reported weight loss, presumably associated with a reduction in body fat, is associated with increased serum 25(OH)D concentration in overweight or obese women (n=383).

These studies conclude that there is an intricate relationship between vitamin D status and body weight or body fat percentage and getting enough vitamin D may help in preventing body weight gain or accumulation of fat cells. In turn, losing weight can increase vitamin D levels and help maximizing its other benefits.

 

• Insulin Resistance and Diabetes:

Inadequate vitamin D status and inflammation can contribute to pancreatic β-cell dysfunction and the formation of insulin resistance. Comprehensive results of experimental and clinical studies have shown that vitamin D is a potential regulator of pancreatic β-cell survival, Ca2+ levels, insulin secretion, and insulin signalling (Shymanskyi I et al, 2019).

• Respiratory Health:

Multiple studies have reported the role of vitamin D in immune function, specifically in response to viral infections of the respiratory system. The latest study by Grant WB et al, 2020 discusses how Vitamin D supplementation could reduce Risk of Influenza and COVID-19 Infections and Deaths. The study concluded, to reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For the treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. 

Conclusion:

An optimum level of vitamin D has a crucial function beyond bone health and curing rickets. The discovery of VDRs and Vitamin D associated enzymes in a variety of cells including cells of the innate and adaptive immune system was crucial in appreciating its role as a potent immunomodulator. Immune cells are not only a target for Vitamin D but are also able to activate the hormone locally, thus postulating for an autocrine and paracrine role for the active Vitamin D. Inadequate amounts of Vitamin D could be linked to defective functioning of the associated autocrine and paracrine circuits eventually leading to various immune abnormalities. Large clinical trials are recommended to assess the role of vitamin D in COVID 19 disease severity and mortality. State and National Govt. are encouraged to prioritize a thorough screening of vitamin D status in population followed by initiating mass prophylaxis to fight this deadly pandemic. 

 

Author Bio:

Subhasree Ray
A clinical and public health nutritionist with 8 years of experience in the field of nutrition and dietetics. Her research work (PhD) is on Ketogenic diet and refectory epilepsy. She is the recipient of ‘Young Researcher Award’ in General Pediatrics 2018, Abu Dhabi, UAE, 12-13 December 2018 and Women Leadership Award in Healthcare from World Health & Wellness Congress 2019, ABP News, 14-15 February 2019. She has authored 17 research article so far and spoke at many international and national conferences. 

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References: 

[1] Arunabh, S., Pollack, S., Yeh, J., & Aloia, J. F. (2003). Body fat content and 25-hydroxyvitamin D levels in healthy women. Journal of Clinical Endocrinology and Metabolism, 88(1), 157–161. https://doi.org/10.1210/jc.2002-020978

[2] Biesalski, H. K. (2020). Vitamin D deficiency and co-morbidities in COVID-19 patients – A fatal relationship? NFS Journal, 20, 10–21. https://doi.org/10.1016/j.nfs.2020.06.001

[3] Drincic, A. T., Armas, L. A. G., Van Diest, E. E., & Heaney, R. P. (2012). Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity. Obesity, 20(7), 1444–1448. https://doi.org/10.1038/oby.2011.404

[4] Grant, W. B., Lahore, H., Mcdonnell, S. L., Baggerly, C. A., French, C. B., Aliano, J. L., & Bhattoa, H. P. (2020). Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients, 12, 988. https://doi.org/10.3390/nu12040988

[5] Merzon, E., Tworowski, D., Gorohovski, A., Vinker, S., Golan Cohen, A., Green, I., & Frenkel‐Morgenstern, M. (2020). Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: an Israeli population‐based study. The FEBS Journal, febs.15495. https://doi.org/10.1111/febs.15495

[6] Parikh, S. J., Edelman, M., Uwaifo, G. I., Freedman, R. J., Semega-Janneh, M., Reynolds, J., & Yanovski, J. A. (2004). The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults. Journal of Clinical Endocrinology and Metabolism, 89(3), 1196–1199. https://doi.org/10.1210/jc.2003-031398

[7] Pugach, I. Z., & Pugach, S. (2020). Strong Correlation Between Prevalence of Severe Vitamin D Deficiency and Population Mortality Rate from COVID-19 in Europe. MedRxiv, 2020.06.24.20138644. https://doi.org/10.1101/2020.06.24.20138644

[8] Rock, C. L., Emond, J. A., Flatt, S. W., Heath, D. D., Karanja, N., Pakiz, B., Sherwood, N. E., & Thomson, C. A. (2012). Weight loss is associated with increased serum 25-hydroxyvitamin D in overweight or obese women. Obesity, 20(11), 2296–2301. https://doi.org/10.1038/oby.2012.57

[9] Shymanskyi, I., Lisakovska, O., Mazanova, A., & Veliky, M. (2020). Vitamin D Deficiency and Diabetes Mellitus. In Vitamin D Deficiency. IntechOpen. https://doi.org/10.5772/intechopen.89543

 

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