Vitamin D and COVID-19

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), disproportionately affects the elderly, African Americans, individuals with obesity (BMI > 30), and those who are institutionalized (i.e. nursing home residents). In addition, belonging to any one of these groups indicates “high-risk” for vitamin D deficiency (and probable liver and/or kidney dysfunction, the drivers of Vitamin D activation). They go hand in hand. This is why it’s thought that low storage levels of vitamin D contribute to higher COVID-19 morbidity and mortality rates in the most high-risk populations.

You may have heard in the national news recently that Vitamin D supplementation is ineffective at preventing SARS-CoV-2 infection. In short, to say vitamin D is ineffective is hogwash since the evidence on its protective role for other respiratory viral infections or critical illness is well established (de Haan et al., 2014; Martineau et al., 2017). 

In a recent cross-sectional study of around 300 COVID-19 patients hospitalized at the Boston University Medical Center, Charoenngam and colleagues (2021) found that among 136 patients aged 65 years and older, most were found to have vitamin D deficiency. When Vitamin D supplementation was given to jumpstart their storage levels to “sufficient” levels, it led to statistically significant lower rates of death, acute respiratory distress syndrome (ARDS), and severe sepsis/septic shock

The association remained even after adjustment for potential confounders. Note:  “Sufficiency” was defined as vitamin D [25(OH)D] levels greater than 30 ng/mL.  Personally, I like to see my patients’ levels at least ≥ 100 ng/mL since it safeguards them against most infections. Regardless, this study shows that the higher the blood concentration of vitamin D, the better the outcome, even if vitamin D isn’t at functional concentrations.


How Does Vitamin D Fight Against COVID-19 Morbidity and Mortality?

Circulating 25(OH)D is further metabolized by the enzyme 1α-hydroxylase in the kidneys into its active form known as 1,25-dihydroxyvitamin D or [1,25(OH)2D]. Interestingly, the vitamin D activation enzyme is expressed by many bodily tissues—not just the kidneys. The activation enzyme is also found in activated macrophages of the immune system, microglia (the primary innate immune cells of the brain), parathyroid glands, breast cells, colon cells, and the outermost layer of the skin (keratinocytes) where 1,25(OH)2D is synthesized on site. Please note vitamin D activation can only occur when the blood is alkaline and then directly controls many endocrine functions (Holick, 2007; Charoenngam & Holick, 2020). 

Thus, you can see that if the liver and kidney are down for the count, then the body’s ability to fully activate vitamin D and fight infection-induced inflammation is extremely limited. 

Now, similar to Melatonin and its role in quelling inflammatory damage caused by SARS-CoV-2, vitamin D is believed to work on multiple cellular pathways simultaneously:

  1. Activated vitamin D [1,25(OH)2D] triggers macrophage production of the endogenously produced antimicrobial peptide cathelicidin LL-37, which protects against invading respiratory viruses. Basically, this antimicrobial protein is also an antiviral protein—it disrupts the viral envelopes and alters viability of host target cells (Liu et al., 2006; Shahmiri et al., 2016). 
  2. Active vitamin D [1,25(OH)2D} changes the expression of angiotensin converting enzyme-2 (ACE2). ACE2 is the main host cell receptor of  SARS-CoV-2 (Aygun, 2020; Ortega et al., 2020). ACE2 is expressed in: 
  3. Alveolar cells of the lungs (type II)
  4. Absorptive cells in the esophagus, small and large intestines 
  5. Kidney, bladder, and heart cells
  6. Inside the mouth (epithelial cells of the oral mucosa)

Since ACE2 is expressed all over the body, it sheds light on myriad infection routes of SARS-CoV-2. After infection, some patients go on to develop acute respiratory distress syndrome which quickly leads to multiple organ failure. Hence, closing the “ACE2 door”, which vitamin D has been shown to do, prevents SARS-CoV-2 entry into various cells (Lin et al., 2016; Ali et al., 2018). 

Finally, it has been shown that upon viral infection, inactive vitamin D can be converted to the active form by the lungs’ epithelial cells and cause the expression of a host defense gene that turns on the production of cathelicidin (Hansdottir et al., 2008). Cathelicidins are known to have protective effects against lung damage due to hyperoxia (Jiang et al. 2020). Theoretically, vitamin D could reduce the risk of SARS-CoV-2 infection by enhancing the production of cathelicidin and defensins which lead to decreased the ability for the virus to survive and replicate.

Clearly, vitamin D plays a powerful role in quelling inflammation, but the extent to which it's helpful depends on one’s underlying disease factor(s). This is what is so hard for everyone to understand, and why so many conflicting results exist. Let’s go back to the results of those hospitalized at the Boston University Medical Center, showing that vitamin D sufficiency was associated with statistically significantly decreased rates of death, ARDS, and severe sepsis. 

All in all, do remember that vitamin D deficiency (measured by functional medicine physicians to be less than 100) is directly related to underlying liver and kidney damage.  The treatment and prevention of cOVID-19 infections and their associated complications are directly caused by other pre-existing organ damage which has never been adequately investigated and addressed. 


Dr. Bhandari and the Advanced Health Team Are Here to Support Your Health.

Our expert team of integrative holistic functional medical practitioners work closely together to better understand the root cause of our patients’ ailment and how they are directly causing chronic diseases. By knowing exactly how to reshift the body into optimal functioning and providing each patient with personalized treatment plans based on their unique constitution and circumstances, our team is extremely effective at reversing any disease into wellness. To learn more and book an appointment, contact Advanced Health or call 1-415-506-9393.


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Payal Bhandari M.D. Dr. Payal Bhandari M.D. Dr. Payal Bhandari M.D. is one of U.S.'s top leading integrative functional medical physicians and the founder of San Francisco' top ranked medical center, SF Advanced Health. Her well-experienced holistic healthcare team collaborates together to deliver whole-person personalized care and combines the best in Western and Eastern medicine. By being an expert of cell function, Dr. Bhandari defines the root cause of illness and is able to subside any disease within weeks to months. She specializes in cancer prevention and reversal, digestive & autoimmune disorders. Dr. Bhandari received her Bachelor of Arts degree in biology in 1997 and Doctor of Medicine degree in 2001 from West Virginia University. She the completed her Family Medicine residency in 2004 from the University of Massachusetts and joined a family medicine practice in 2005 which was eventually nationally recognized as San Francisco’s 1st patient-centered medical home. To learn more, go to

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