Mounting evidence suggests that vitamin D has a much broader role than initially thought — including regulating many genes and participating in the immune system. In the setting of COVID-19, vitamin D deficiency can lead to imbalances in the renin-angiotensin-system, a critical regulator of blood pressure, inflammation, and body fluid homeostasis. Disturbances in this system may heighten oxidative stress contributing to worse COVID-19 outcomes. In this clip, Dr. Roger Seheult and Dr. Rhonda Patrick discuss how vitamin D levels might affect the renin-angiotensin-system and how this relates to COVID-19 outcomes.
Dr. Patrick: But are you aware of the role vitamin D plays in the ACE2 and renin-angiotensin system?
Dr. Seheult: I know there is a connection.
Obviously plays an important role in regulating blood pressure and fluid homeostasis, and, you know, I think even in the lungs too. But what's interesting about the vitamin D renin-angiotensin system kind of it converges on the ACE2 receptor, which, as you know, and probably most of the world has heard by now is how the SARS-CoV-2 virus enters into ourselves, it binds that receptor. Well, what's been shown with SARS-CoV-1 is when the virus which also binds to the same receptor to get inside of the cell, it binds to the receptor and it internalizes the receptor and down-regulates ACE2, which is not good because that is really important for this renin-angiotensin regulation, as you know, Dr. Seheult. So that's been shown with SARS-CoV-1.
And what happens when the ACE2 gets down-regulated, acute lung injury gets really bad. And so there's been some animal studies that have found, for example, if you high-dose with the active form of vitamin D, the animals, and then you cause acute lung injury, ACE2 goes down, acute lung injury goes up in the placebo group, but the vitamin D group, it normalizes the ACE2 levels.
So if you think about it, you know, this is a hypothesis, of course, another potential way vitamin D could be playing an important role in this specific virus is through regulating ACE2 levels. And what's interesting is that there was just a very recent study that came out. ACE2, the gene, it's located on the X chromosome. And women have two X chromosomes most of the time. One of those X chromosomes, the gene is inactivated. But there are genes that escape that. And ACE2 is one of those. And so women have much higher levels of ACE2. And so researchers are thinking this is protecting them from a more severe COVID-19 outcome because they're getting that ACE2 levels, like, you know, higher in terms of, you'd think, Oh, well, more ACE2, that means the virus is getting in and, but actually, biology always tricks you. You know, you always think one thing, and then it's like this beautiful, you know, sort of complex scenario.
But I'm digressing. And I just, kind of, wanted to bounce it off you because you're such a scholar, and I thought you probably would find that interesting, and I certainly hope scientists are testing that hypothesis because it seems very relevant.
A protein that plays a critical role in regulation of blood volume, systemic vascular resistance, and cardiovascular homeostasis. ACE2 is present on the cells of many organs in the human body, particularly those of the lungs, arteries, heart, kidney, and gastrointestinal tract, and is a critical element of the renin-angiotensin biochemical pathway. SARS-CoV-2, the virus that causes COVID-19, exploits the ACE2 receptor to gain entry into cells.
A tightly coiled molecule of DNA found in the nucleus of a cell. Chromosomes contain the genes and other genetic material for an organism. Humans have 46 chromosomes arranged in 23 pairs. Each chromosome is comprised of long stretches of DNA wrapped around proteins called histones, which provide structural support. At the end of each chromosome is a repetitive nucleotide sequence called a telomere. Telomeres form a protective “cap” – a sort of disposable buffer that gradually shortens with age – that prevents chromosomes from losing genes or sticking to other chromosomes during cell division.
An infectious disease caused by the novel coronavirus SARS-CoV-2. COVID-19, or coronavirus disease 2019, was first identified in Wuhan, China, in late 2019. The disease manifests primarily as a lower respiratory illness, but it can affect multiple organ systems, including the cardiovascular, neurological, gastrointestinal, and renal systems. Symptoms include fever, cough, fatigue, shortness of breath, and loss of smell and taste. Some infected persons, especially children, are asymptomatic. Severe complications of COVID-19 include pneumonia, sepsis, acute respiratory distress syndrome, kidney failure, multiple organ dysfunction syndrome, and cytokine storm. Treatments currently involve symptom management and supportive care. Mortality varies by country and region, but approximately 6 percent of people living in the United States who are diagnosed with COVID-19 expire. 1
An organism’s ability to maintain its internal environment within defined limits that allow it to survive. Homeostasis involves self-regulating processes that return critical bodily systems to a particular “set point” within a narrow range of operation, consistent with the organism’s survival.
A chemical that causes Parkinson's disease-like symptoms. MPTP undergoes enzymatic modification in the brain to form MPP+, a neurotoxic compound that interrupts the electron transport system of dopaminergic neurons. MPTP is chemically related to rotenone and paraquat, pesticides that can produce parkinsonian features in animals.
A critical regulator of blood pressure, inflammation, and body fluid homeostasis. The renin-angiotensin system is commonly described as a counter-regulatory system that plays a central role in the pathogenesis and development of various cardiovascular diseases. It is a therapeutic target for many antihypertensive drugs. Vitamin D deficiency in the setting of COVID-19 can lead to over-expression of renin and subsequent activation of the renin-angiotensin system. Disturbances in this system can drive poor outcomes in COVID-19.
The virus that causes severe acute respiratory syndrome, or SARS. First identified in China in 2002, SARS-CoV-2 is a type of coronavirus. It was responsible for an epidemic that killed nearly 800 people worldwide.
The virus that causes COVID-19. SARS-CoV-2 is one of seven coronaviruses known to infect humans. Others include SARS-CoV-1 (which causes severe acute respiratory syndrome, or SARS) and MERS-CoV (which causes Middle East respiratory syndrome, or MERS). SARS-CoV2 exploits the angiotensin-converting enzyme 2, or ACE2, receptor to gain entry into cells. The ACE2 receptor is widely distributed among the body's tissues but is particularly abundant in lung alveolar epithelial cells and small intestine enterocytes. SARS-CoV-2 binds to a cell's ACE2 receptor and injects its genetic material (RNA) into the cytosol. Once inside, the viral RNA molecules are translated to produce RNA-dependent RNA polymerase, also known as replicase, the enzyme critical for the reproduction of RNA viruses. The viral RNA is then packaged into infective virion particles and released from the cell to infect neighboring cells.
The highest level of intake of a given nutrient likely to pose no adverse health effects for nearly all healthy people. As intake increases above the upper intake level, the risk of adverse effects increases.
A fat-soluble vitamin stored in the liver and fatty tissues. Vitamin D plays key roles in several physiological processes, such as the regulation of blood pressure, calcium homeostasis, immune function, and the regulation of cell growth. In the skin, vitamin D decreases proliferation and enhances differentiation. Vitamin D synthesis begins when 7-dehydrocholesterol, which is found primarily in the skin’s epidermal layer, reacts to ultraviolet light and converts to vitamin D. Subsequent processes convert D to calcitriol, the active form of the vitamin. Vitamin D can be obtained from dietary sources, too, such as salmon, mushrooms, and many fortified foods.
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