Can early intervention with vitamin D, selenium, and zinc bolster the body’s defense against COVID-19?

COVID-19 represents a serious global threat against public health and the economy because we still lack a vaccine and effective therapies. When COVID-19 becomes life-threatening it is primarily because the immune defense overreacts with a cytokine storm and hyperinflammation that destroys healthy tissue in the lungs, the circulatory system, and other places. Older people and heart failure patients already suffer from chronic low-grade, uncontrolled inflammation, to which nutrient deficiencies contribute and make the patients increasingly vulnerable. This also applies to people with metabolic syndrome and diabetes, many of which are overweight. For that reason, scientists affiliated with universities and research centers in Norway, Sweden, and Russia have searched the scientific literature to find studies that focus on whether supplementation with vitamin D, selenium, and zinc can help prevent a COVID-19 infection from escalating and becoming life-threatening.

To date, COVID-19 is the single most dangerous type of coronavirus with the ability to infect humans and animals worldwide. COVID-19 attacks the lower respiratory tract and can cause bronchitis and pneumonia combined with fever. Most cases are relatively mild, but the disease can also become life-threatening in cases where the immune system overreacts with a cytokine storm and hyperinflammation from activated cells, especially in the respiratory tract. This may cause acute respiratory distress syndrome (ARDS) that attacks healthy tissue in the cardiovascular system and other organs. It is this condition with hyperinflammation that causes the weakest patients to succumb to the disease. Therapy where doctors use immunosuppressive corticosteroids typically aggravate the clinical condition of ARDS patients, and there is still no vaccine. That is why we desperately need other therapies that not only prevent COVID-19 from spreading but also prevent the life-threatening complications by reducing hyperinflammation. The most vulnerable groups in society are old people, diabetics, and heart failure patients that already suffer from chronic, uncontrolled inflammation. The same goes for many overweight individuals that have metabolic syndrome (an early stage of diabetes) without actually knowing it.
This condition is characterized by oxidative stress, which is an imbalance between free radicals and antioxidants. In addition, clinical or subclinical deficiencies of nutrients and antioxidants such as vitamin D, selenium, and zinc are widespread among these groups of people. It is also a fact that lack of selenium is common among many populations because of nutrient-depleted soil, and lack of vitamin D is frequent because of our modern lifestyle combined with lack of sunlight. It is a good idea to make sure that you get enough of these nutrients by eating a balanced diet, possibly with the help from supplements. One can easily lack nutrients without showing signs of any symptoms, and that can increase otherwise healthy people’s risk of reacting violently to a COVID-19 infection.
The authors of the new article in Nutrients have trawled the scientific literature from the period 2010-2020 to uncover how vitamin D, selenium, and zinc affect the immune system and inflammation, and how they are able to prevent and treat various types of coronavirus and other RNA virus types. Although vitamin A and vitamin C are also important for the immune capacity, the authors have not focused on these nutrients in their article.

Vitamin D

The powerful sun during the summer period is our main source of vitamin D. Not surprisingly, there are more virus infections during the winter period where people are more likely to have too little vitamin D in the blood. The vitamin D deficiency problem is only made worse by limiting factors such as spending too much time indoors and avoiding the sun because of sun awareness campaigns. Furthermore, being dark-skinned gives you a disadvantage because dark skin does not synthesize vitamin D as easily as lighter skin types. Ageing, being overweight, and having diabetes can also increase the need for vitamin D.
The first step is synthesis of vitamin D in a process were sunlight turns a cholesterol precursor in our skin into cholecalciferol, a form of vitamin D that is also found in supplements. In the liver, cholecalciferol is converted to 25-hydroxyvitamin D3, the form of the nutrient that is measured in blood. When the body needs vitamin D, it converts this form of the nutrient to the active form. The activation takes place in the kidneys.
Vitamin D is primarily known for its role in calcium uptake and bone health, but vitamin D is also vital for the immune defense in several ways.
We have in our airways the type of white blood cells called macrophages that depend on vitamin D for being able to attack germs. The T cells, which constitute the special forces of the immune system, also require vitamin D to become activated. At the same time, vitamin D controls various inflammatory processes and make sure that they do not get out of hand.
Epidemiological studies have revealed an inverse relation between circulating vitamin D (25-hydroxyvitamin D3) in the blood and inflammatory markers such as CRP (C-reactive protein) and IL-6 (interleukin-6).
It is theorized that being deficient of vitamin D may influence the severity of a COVID-19 infection. Two large studies have demonstrated that the infection rate is higher at northern latitudes and/or if blood levels of vitamin D are low.
Patients that lack vitamin D are twice as likely to develop life-threatening complications from a COVID-19 infection, according to a study from Northwestern University in the United States, where scientists collected patient data from 10 different countries.
Vitamin D protects against infections in the respiratory tract, and low vitamin D level are often observed in critically ill patients with an unfavorable prognosis.
With older patients in particular, lack of vitamin D is known to cause normal virus infections like influenza to develop into pneumonia with an increased risk of the patients being admitted to the intensive care unit due to life-threatening complications.
Lack of vitamin D is also seen with ARDS (Acute Respiratory Distress Syndrome) that destroys the epithelial cells in the airways and causes hypoxia (lack of oxygen). Around 5-10 percent of our genes are controlled by various on-off switches that are vital for a well-functioning immune defense.
Several in vitro studies have shown vitamin D’s positive effect on mechanisms that are designed to combat virus infections in the respiratory tract. There is also research showing how vitamin D is able to control the inflammatory process and prevent it from overreacting and causing damage to healthy tissue. There are, however, also a few studies of vitamin D and pneumonia that failed to show an effect. This could be because the study participants were not vitamin D-deficient to begin with, that the dose was too small, or that the vitamin D intervention was introduced too late. Lack of magnesium may also inhibit the enzyme processes that convert vitamin D into its active forms.
Blood levels of vitamin D should be at least 50 nmol/L or, better yet, 75-120 nmol/L. To reach these levels, people living at northern latitudes normally need to take a vitamin D supplement during the period between October and May. For those who do not get enough sunlight during the summer period, all-year supplementation is required.
In cases where levels of vitamin D in the blood are low (below 50 nmol/L), supplementation with 40 micrograms of vitamin D daily may contribute to the prevention of virus infections and may also help prevent COVID-19 from causing hyperinflammation.
The need for vitamin D varies from one person to another, and deficiencies should always be prevented. According to the European Food Safety Authority (EFSA), the safe upper daily intake level for vitamin D is 100 micrograms. We can easily synthesize that amount from daily sun exposure during the summer period.

Selenium

Selenium support different selenium-containing proteins that have a number of vital functions that include the immune defense and its capacity and communication. This is especially true for its ability to fight virus infections in the respiratory tract.
Selenium also supports the unique GPx antioxidants (glutathione peroxidase) that protect the body against oxidative stress. If we lack antioxidants, it may cause an uncontrollable inflammatory immune response, even when there is no actual infection. Other selenium-containing proteins such as selenoprotein K and selenoprotein S also have key roles in maintaining normal immune response.
The selenium content in agricultural soil varies largely depending on geography. Around one billion people worldwide are believed to lack this micronutrient due to this.
A Chinese study has shown a direct link between the body’s selenium status and the ability to recover from a COVID-19 infection. The scientists investigated the selenium content in hair samples from people living outside of Hubei in China, where selenium levels in the soil vary quite a lot. They found that patients with COVID-19 had a much higher recovery rate in the areas that had had the highest selenium content in the soil.
When animals and humans lack selenium, it reduces their immunity, which makes it a lot easier for different types of virus to mutate and become increasingly virulent. That is exactly what happens with COVID-19, which belongs to the coronavirus family.
Earlier research has shown that the normally harmless Coxsackievirus 3B can cause the life-threatening Keshan’s disease that is named after the Chinese Keshan province, where the soil is notoriously low in selenium.
Selenium supplementation of people with clinical and subclinical selenium deficiency is a both safe and relevant way to treat virus infections and sequelae. The average selenium intake among Danes is below the official recommendation (reference intake level) that is 55 micrograms/day. In fact, many scientists recommend 100 micrograms daily, which is an amount that effectively saturates selenoprotein P that is used as a gauge of the body’s selenium status.
Several published studies have looked at the effect of 200 micrograms daily. According to EFSA, the safe upper intake level for selenium is 300 micrograms per day
Supplements with selenium yeast that contains a variety of different selenium species are ideal for supplementation, as this is the closest you can come to a balanced diet with the natural selenium variety that you get by eating many different types of food.

Q10 and selenium supplements reduce inflammation and lower the risk of cardiovascular disease

Coenzyme Q10 plays a role in the cellular energy turnover and serves as a very important antioxidant that protects the body against oxidative stress. To function optimally, coenzyme Q10 depends on the presence of selenium. We humans synthesize most of the Q10 that we need, but the endogenous production of the substance starts to decrease around the age of 20 years. Many people notice a drop in vitality and energy levels when they reach mid-life.
In a randomized, placebo-controlled, Swedish study (KiSel-10), scientists supplemented healthy seniors with either 200 micrograms of selenium and 200 mg of pharmaceutical-grade Q10 daily or placebo. This combination made perfect sense for two reasons: The endogenous Q10 synthesis decreases with age, and the Swedish soil contains very little selenium.
The researchers discovered that the two supplements lowered the non-specific inflammatory response, which they measured by looking at plasma levels of CRP (C-reactive protein) and certain other inflammation markers. This is a very important observation, as ageing is typically associated with low-grade inflammation that increases the risk of cardiovascular disease and other chronic diseases.
The study lasted five years. One of the milestone discoveries of this study was that the participants in the group that got Q10 and selenium had a 54% lower cardiovascular mortality rate and significantly lower hospitalization rate than the control group. A 10-year and 12-year follow-up study revealed that supplementation with Q10 and selenium has a notable long-term effect on heart function and life expectancy.

Zinc

Zinc is involved in over 1,000 enzyme processes, many of which are directly or indirectly linked to the immune system. Zinc also supports the powerful SOD (superoxide dismutase) antioxidant that counteracts oxidative stress.
Zinc regulates the T cells of the immune system and the production of various proteins that are of importance to the inflammatory processes. A zinc deficiency can therefore weaken the immune defense. If a zinc deficiency lasts long, it may result in inflammation caused by cytokines such as IL-6 (interleukin-6), IL-8 (interleukin-8), and TNF-α (tumor necrosis factor- α).
In a study, researchers gave four COVID-19 patients aged 26-63 years high-dosed zinc lozenges (115-184 mg) for 10-14 days. All patients recovered. Other studies of zinc supplementation given to COVID-19 patients have been conducted but are too limited to form the basis for a conclusion.
According to an older, Finnish meta-analysis, zinc supplementation of patients with the common cold showed that the immune defense was able to fight the infection at a faster rate. Colds are often caused by another type of coronavirus.
Several studies suggest that early intervention with zinc supplementation is preferable in connection with acute respiratory infections.
Australian scientists have initiated the first clinical trial to test the effect of intravenous zinc therapy for COVID-19 patients.
Other studies show that zinc supplements have a positive effect on hepatitis C, which is caused by a different type of RNA virus.
The daily reference intake (RI) level for zinc is 10 mg (in Denmark). The EFSA has set a safe upper intake level of 25 mg for adults. It is perfectly safe to take a larger dose of zinc for a short period of time, for instance in the case of an infection. But prolonged intake of zinc in high doses may disrupt the balance between zinc and copper.

Discussion and conclusion

More research is needed to clarify whether vitamin D, selenium, and zinc are involved in the spreading and severity of COVID-19. However, based on an array of studies that also include SARS and other RNA virus infections, the authors of the new article in Nutrients recommend the use of supplementation in geographical areas and among populations where deficiencies are widespread and/or as soon as the COVID-19 infection is detected. Therapy with vitamin D, selenium, and zinc in combination with other types of therapy must be given first priority in high-risk groups, including older and chronically ill people. These nutrients also play a role in the prevention of COVID-19 and other virus infections.

Referencer

Jan Alexander et al. Early Nutritional Intervention with Zinc, Selenium and Vitamin D for Raising Anti-Viral resistance Against Progressive COVID-19. Nutrients 2020

Puja Metha et el. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. March 16, 2020

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