Vitamin D may reduce susceptibility to COVID-19-associated lung injury

Vitamin D is a steroid hormone. It is available in small quantities in food, but the primary source is via endogenous synthesis. This process occurs in a stepwise manner that starts in the skin following exposure to ultraviolet light and continues in the liver and kidneys, where the vitamin’s active hormone form is made. Since ultraviolet light is required for vitamin D synthesis, reduced exposure to the sun or having dark-colored skin impairs vitamin D production. Approximately 70 percent of people living in the United States are vitamin D insufficient and ~30 percent are deficient.

According to the Endocrine society, blood levels of 25-hydroxyvitamin D below 20ng/ml is considered deficient, and less than 30ng/ml is insufficient. The reason the Endocrine Society defines vitamin D deficiency as below 20 ng/ml (50 nmol/L), by the way, is because this is the cut-off point where parathyroid hormone levels, which are involved in calcium homeostasis, start to rise outside of healthy ranges. This point at which the balance of parathyroid hormone begins to shift is the physiological definition for the beginning of vitamin D deficiency.

The epidemiology of vitamin D deficiency

When we look at the demographics, epidemiologists have long known where vitamin D deficiency tends to concentrate and what populations are the most affected:

1. The elderly where the efficiency of cutaneous biosynthesis of vitamin D declines with age. According to NHANES data, older adults were 63 % more likely to have vitamin D deficiency and 46 % more likely to have vitamin D insufficiency than young adults while other sources have suggested a 70-year-old may produce 4 times less vitamin D than their former 20-year-old selves.
2. The obese where fat-soluble vitamin D has greater difficulty being released into the bloodstream. Obese individuals have greater than 50% less bioavailability of vitamin D compared to non-obese individuals. Obese adults in the US had 3 times higher prevalence of vitamin D deficiency and 1·9 times higher prevalence of vitamin D insufficiency than non-obese adults.
3. Those living in Northern latitudes where less UVB radiation reaching the atmosphere means less of it reaches our skin to facilitate the production of vitamin D.
4. The darker-skinned where the synthesis of vitamin D is naturally reduced, as a biological bargain made by melanin, a natural sunscreen, which protects us from the damaging effects of UV. According to NHANES data, African Americans have 24.6 times higher vitamin D deficiency and 3·7 times higher vitamin D insufficiency than Caucasians.

Populations with vitamin D deficiency at high risk for COVID-19 mortality

A retrospective study in the Philippines found that for each standard deviation increase in serum vitamin D people were 7.94 times more likely to have a mild rather than severe COVID-19 outcome and were 19.61 times more likely to have a mild rather than critical outcome. Another small retrospective study pre-print in New Orleans found that 84.6% of COVID-19 patients had vitamin D deficiency compared to 4% of patients not in ICU. Another study in Indonesia found in cohort of 780 patients, after adjusting for age, gender, and comorbidities COVID-19 patients found: – 98.9% of patients with vitamin D deficiency died – 88% of patients with vitamin D insufficiency died – 4% of patients with sufficient vitamin D died.

Vitamin D and respiratory tract infections

Robust evidence suggests that vitamin D is protective against respiratory tract infections. Data from 25 randomized controlled trials from around the world demonstrate that daily or weekly supplementation of vitamin D reduced the risk of acute respiratory infection by more than 50 percent in people with low baseline vitamin D levels. People with higher baseline vitamin D levels also benefited, although the effect was more modest, with only a 10 percent risk reduction. 

Genetically low plasma vitamin D levels have also been associated with higher mortality from respiratory infections. Additionally, three different SNPs in the vitamin D receptor are all associated with a higher risk of respiratory tract infections in both adults and children.

Vitamin D and the renin-angiotensin-system

SARS-CoV-2 virus enters human cells via the ACE2 receptor. Viral particles bind to the ACE2 receptor and together they are internalized into the cell. These viral particles can bind to a large number of ACE2 molecules, sequestering the ACE2 molecules from the cell surface and decreasing ACE2. This accompanying loss of ACE2 function can cause serious health consequences due to ACE2’s participation in key physiological processes. This also occurs with infection via SARS-CoV-1, which also binds to the ACE2 receptor, decreasing cellular ACE2 expression levels and increasing disease severity.

Vitamin D deficiency leads to over-expression of renin (an enzyme produced in the kidneys) and subsequent activation of the renin-angiotensin-system, a critical regulator of blood pressure, inflammation, and body fluid homeostasis. Disturbances in this system due to the loss of ACE2 function in the setting of SARS-CoV-2 infection can promote neutrophil infiltration, excessive inflammation, and lung injury. Once lung infection progresses to hypoxia, renin is released, setting up a vicious cycle for decreasing ACE2. Lower levels of ACE2 promote more damage, culminating in acute respiratory distress syndrome, or ARDS. Vitamin D acts as an endocrine repressor of the renin-angiotensin-system by downregulating the expression of renin, the rate-limiting enzyme of the renin-angiotensin cascade. 

In a preclinical model of acute lung injury, the administration of the active form of vitamin D provided protection against lung injury by balancing the renin-angiotensin-system via increasing ACE2 levels and decreasing renin production. It is important to note that the acute lung injury itself led to a decrease in ACE2 and this resulted in worse disease outcomes. The vitamin D increased ACE2 receptor levels only in conditions of acute lung injury where ACE2 levels decreased. When vitamin D was given to control animals, it did not cause an increase in ACE2 receptor levels. This means that vitamin D normalizes ACE2 receptor levels in situations where it is down-regulated.

Since vitamin D insufficiency is widespread (and perhaps exacerbated in quarantine conditions, due to limited sunlight exposure), supplemental vitamin D might be a viable means to increase vitamin D to sufficient levels.

Maintaining a healthy vitamin D status, an imminently solvable but often ignored problem, may turn out to be an important factor in protecting against susceptibility to lung injury in COVID-19. Learn more in this short clip taken from a COVID-19 Q&A #1 with Dr. Rhonda Patrick.

To review the full article and video click here: https://www.foundmyfitness.com/episodes/vitamin-d-covid-19