There is worldwide focus on finding better ways to prevent and treat COVID-19 because of the limited effect of vaccines. It is important to understand why the infections are harmless in most cases and why only a small number of people are affected by ARDS (acute respiratory distress syndrome), which is complicated and involves hyperinflammation. What represents the real problem here and what makes these infections life-threatening is a derailed and overactive immune defense. Multiple studies have already demonstrated that lack of vitamin D increases the risk of being infected with COVID-19 ending up in intensive care, and the studies also show that vitamin D supplements have a therapeutic potential. In a new review article that is published in Clinical and Molecular Allergy, researchers look closer at the synergy between vitamin D, magnesium, and zinc in relation to their ability to regulate the immune system and as potential therapeutic agents. It is also vital to have enough selenium, a nutrient that many people lack.
Virus particles are ultramicroscopic. In order to replicate they are forced to leech on other cells. This process is enabled through matching cell receptors into which the virus particles fit like a key in a lock. COVID-19 (SARS-Cov-2) has so-called spike proteins on the surface. These spike proteins bind to ACE2 receptors on the surface of the cells.
A COVID-19 infection normally starts by virus particles entering the nose where they infect cells that have ACE2 receptors. If the immune defense functions optimally, it will be able to fight off the virus on the spot before it can replicate. If, however, the immune defense is not running on all cylinders, the virus will replicate in the nasal cells and spread to other cells that have ACE2 receptors – beginning in the respiratory tract. In rare cases, the virus can spread to the arteries, the heart, the intestines, and the kidneys, which helps explain some of the symptoms that occur when these organs and tissues are infected. COVID-19 can also affect ACE2 enzymes (angiotensin-converting enzymes) that are involved in regulating blood pressure, wound healing, and cellular production of proinflammatory cytokines. This increases the risk of an overactive immune defense with cytokine storm and hyperinflammation that can destroy healthy tissue.
Acute respiratory distress syndrome (ARDS) normally occurs around seven days or later after the first signs of a COVID-19 infection. This is typically seen in seniors, overweight people, diabetics, and those with other chronic diseases.
When blood poisoning and influenza become life-threatening it is also a result of a derailed immune defense that results in cytokine storm and hyperinflammation. The capacity of the immune defense is what determines if the body is able to reject it, if we develop mild symptoms, or if we end up with life-threatening complications.
To explain the background for their new study, the scientists mention vitamin D, magnesium, and zinc and their many important roles in the immune defense and circulatory system. It is also important to understand the mechanisms that can suddenly turn the otherwise essential immune defense into our own enemy.
The functions of the immune defense and building immunity
Our innate immune defense serves as storm troops. It fights off most germs without us noticing. It consists of different complement proteins plus interferon that prevents virus from replicating in our cells. Various types of white blood cells (dendrite cells, macrophages, monocytes, granulocytes, and NK cells) attack most microbes. Once their mission is accomplished, the innate immune defense should be able to shut down the attack, which is a crucial job. The innate immune defense may even call on help from white cells from the adaptive immune defense that consists of different types of T cells and B cells.
Under normal circumstances, the Th1 cells launch a proinflammatory phase. Once the enemy is defeated, an anti-inflammatory phase is started. The proinflammatory phase involves the use of free radicals, which are highly reactive and aggressive molecules. This phase is designed to be swift, effective, and tightly controlled in order to prevent damage to healthy tissue.
B cells are important for the production of antibodies. The production of T memory cells and/or B memory cells is important for future immunity. With regard to the body’s defense against and immunity towards virus infections, T cell activation plays the greatest role.
The overall communication of the immune defense is controlled by cytokines that are produced by white blood cells. It is essential to have the correct balance between pro- and anti-inflammatory cytokines.
Vitamin D for the immune defense and for controlling inflammation
Most cells in the body have vitamin D receptors. Vitamin D regulates around 5-10 percent of our genes by means of different on/off switches. We have in our respiratory system a large number of white blood cells (macrophages) that depend on vitamin D. The same goes for monocytes in our blood. The process is supported by antibiotic peptides in our airways (cathelicidin) that depends on vitamin D. It looks as if cathelicidin is able to destroy the surface of certain virus types – including coronavirus.
Vitamin D helps maintain the barrier in the pulmonary epithelium and it stimulates certain mechanisms involved in local tissue repair.
Moreover, the T cells – the special troops of the immune defense – are totally dependent on vitamin D. The vitamin helps them divide explosively and form an army of targeted T cells that attacks viruses. B cells also need vitamin D.
Once an infection has been defeated, vitamin D is vital for helping T cells shut down the different inflammatory processes.
Vitamin D also contributes to regulating the renin-angiotensin system (RAS) that is heavily challenged by complicated COVID-19 infections.
Numerous studies have shown that lack of vitamin D increases the risk of contracting COVID-19 and other respiratory virus infections. Lack of vitamin D also increases your risk of hyperinflammation that makes infections complicated and potentially life-threatening.
Earlier studies demonstrate that vitamin D supplements can reduce respiratory infections and asthma. The scientists behind the new review article therefore suggest that vitamin D supplementation could have a potentially positive effect in the prevention of COVID-19, and it could even be used as an adjuvant in severe cases. The need for vitamin D varies from person to person. In any case, it is important to have optimal blood levels of the nutrient all year round, and there are different high-dosed vitamin D supplements on the market that make it easier to keep levels in the ideal range. EU’s Scientific Committee on Food has established a daily safe upper intake level of 100 micrograms for adults and children aged 11 years and older. When taking supplements, it is best to choose one that contains vitamin D in oil because the nutrient is lipid-soluble. This guarantees the best absorption and utilization of the nutrient. We also need magnesium to make proper use of vitamin D.
Optimal utilization of vitamin D requires magnesium
The new review article mentions that studies have found a relation between low magnesium levels, impaired immunity, and increased inflammation which may be related to cytokine storm and hyperinflammation in connection with COVID-19. A major reason for this is that the body uses magnesium-dependent enzymes to utilize and activate vitamin D. Cholecalciferol, the form of vitamin D that we produce in our skin when we are exposed to UVB rays and that we get from supplements, is not yet biologically active. First, it must be converted in a two-step process in the body. The first step takes place in the liver. Here, cholecalciferol is converted into 25(OH)D – or calcidiol – with help from an enzyme called CYP2R1. When vitamin D is needed by the cells in the body, 25(OH)D is converted in the next step into biologically active vitamin D, also called
1,25(OH)2 D (calcitriol). This conversion requires an enzyme named CYP27B1. The process takes place in the kidneys, immune cells, blood vessels, and certain other tissues. Afterwards, the active steroid form of vitamin D can bind to vitamin D receptors in the white blood cells and most other cells in the body. The enzymes that activate vitamin D need magnesium. Therefore, magnesium is bound to play a major role in the body’s ability to utilize vitamin D and also in the immune defense’s ability to tackle severe COVID-19 infections.
|Vitamin D synthesis||Form of vitamin D and enzyme activity|
Synthesized from 7-dihydroxycholesterol (a form of cholesterol) and UVB rays from sunlight
25(OH)D, the type of vitamin D that is measured in blood
Synthesized by way of the enzyme CYP2R1
Blood vessels and other tissues
Calcitriol (biologically active)
1,25 (OH)2 D
Synthesized by way of the enzyme CYP27B1
Zinc for the immune defense, sense of smell, and regulation of inflammation
Zinc is involved in various enzyme processes in the innate and the adaptive immune defense. Here, it is needed for maturation of white blood cells and for controlling inflammation. Zinc also supports the essential SOD antioxidants that counteract oxidative stress and cellular damage caused by free radicals in connection with inflammatory processes. In addition, zinc is important for our sense of smell and taste, which a virus can otherwise destroy.
If we get an infection, blood levels of zinc drop. This is because there is an increased need for zinc in the innate and adaptive immune defense that use it to direct swift and effective attacks on the virus. Numerous studies have shown a link between zinc deficiency and an increased risk of respiratory diseases, including COVID-19.
A double-blind, placebo-controlled study (Reak Suppaphol et al.) showed that zinc supplementation can lower the rate of acute respiratory infections by 45 percent.
A randomized, double-blind, placebo-controlled study (Singh et al.) demonstrated that zinc supplementation reduces the duration of a common cold. Other studies indicate that zinc has antiviral properties against different types of viruses such as influenza, rhino, and herpes.
Zinc has several immune-stimulating, immune-regulating, and cell-protective properties, suggesting that zinc supplementation has a therapeutic potential in the prevention and treatment of COVID-19. The new review article about vitamin D, magnesium, and zinc in relation to COVID-19 is published in Clinical and Molecular Allergy.
|Around 25 percent of the world’s population is believed to lack zinc|
Selenium’s role in the immune defense and in preventing virus from mutating
Selenium has many different roles in the immune defense, it works as an antioxidant, and it counteracts unwanted inflammation. Moreover, selenium prevents virus from mutating. One billion people worldwide are believed to be selenium-deficient, which is mainly because of selenium-depleted farmland. This is a problem in places like Europe, India, and South America.
Mohsen Nabi-Afjadi et al. The effect of vitamin D, magnesium and zinc supplements on interferon signaling pathways and their relationship to control SARS-CoV-2 infection. Clinical and Molecular Allergy. 2021
Daniel Chauss et al. Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells. Nature Immunology. 2021
Purdue University. Researchers study the link between vitamin D and inflammation. ScienceDaily 2021.
Krishna Sriram et al. What is the ACE2 receptor, how is it connected to coronavirus and why might it be key to treating COVID-19? The Conversation. 2020
Qi Dai et al. Magnesium status and supplements influence vitamin D status and metabolism: results from a randomized trial. The American Journal of Clinical Nutrition. 2018
Nikki Hancocks. Diet and supplements: Swiss panel publishes COVID-19 recommendations. 2020
Luke Maxfield, Jonathan S. Crane. Zinc Deficiency. NCBI March 18, 2019
University of Helsinki. Zink acetate lozenges may increase the recovery rate from the common cold by three-fold. ScienceDaily May 11, 2017
Zink for Colds, Rashes and the Immune system. WebMD. 2017
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