The corona crisis has shed new light on the importance of having a strong immune defense, one that protects us against virus infections in the long run. Selenium plays a vital role for a number of different reasons but, unfortunately, there is widespread deficiency which increases the risk of infections and related complications. In a new review article that is published in International Journal of Molecular Sciences, the authors look closer at selenium’s role in connection with different types of virus infections such as influenza, HIV, and hepatitis with particular focus on COVID-19. The purpose of their article is to inform about new nutritional strategies that may contribute to a strong and well-functioning immune defense – mainly when it comes to COVID-19 and virus types that tend to mutate all the time.
Selenium is incorporated in around 25 or more selenoproteins that have a host of different functions in the body such as energy turnover, immune defense, etc. Selenoproteins primarily operate inside the cells. Only two selenoproteins have been identified outside the cells: the GPX-3 antioxidant (glutathione peroxidase-3) and selenoprotein P. The latter transports selenium through the body and is normally used as a marker of the body’s selenium status.
With regard to the immune defense, selenoproteins are important for the innate immune defense that fights germs silently in the background. Selenium is also part of the adaptive immune defense that has the ability to specialize, form antibodies, and immunity. In connection with virus infections, T cell activation is most important for strong immunity.
Both the innate and adaptive immune systems consist of many different cell types, and selenoproteins are involved in the vital communication between the cells. Selenoprotein S regulates various cytokines that are important for the body’s inflammatory response.
At the same time, selenium is incorporated in different antioxidants (GPX and TXNRD) that protect healthy cells against oxidative stress. The immune defense itself forms free radicals when launching inflammatory attacks. Even more free radicals are generated by ageing, poisoning, diabetes, and other chronic diseases and that contributes to the problem.
Oxidative stress is when the antioxidants are outnumbered by free radicals. The free radicals become extremely harmful when they wreak havoc and start attacking healthy tissue. This is where selenium enters the stage. It supports some of the primary antioxidants which no other antioxidants are able to replace.
Another protective mechanism that selenium uses is to prevent virus from mutating and becoming increasingly virulent. In connection with infections, the selenium levels in blood drop drastically as a result of the selenium that is consumed by the activity of white blood cells and the body’s stepped-up antioxidant defense.
Lack of selenium is therefore bound to weaken the immune defense and make you more susceptible to infections. There is even a risk of related complications and oxidative stress that may cause virus infections to become potentially life-threatening.
In their review article, the authors look at different virus infections such as coxsackie, influenza, HIV, hepatitis, polio, and SARS-CoV-2 caused by COVID-19. All of these are RNA viruses that are highly likely to mutate, which makes it challenging to come up with effective vaccines.
First discovery of life-threatening coxsackie virus that was caused by selenium deficiency
The Keshan province in the Northeastern part of China has extremely little selenium in the soil, and this is where a lethal heart disease known as Keshan disease was originally discovered. The disease is caused by an otherwise harmless RNA virus called Coxsackie B, which the immune defense is unable to fight without selenium. In 1965, the Chinese population in that area started using selenium supplementation to prevent and eradicate the disease.
Years later, a US scientist named Professor Melinda A. Beck demonstrated that selenium-depleted mice infected with coxsackie virus had decreased T cell activity and an increased rate of RNA virus mutations, which made the disease far more dangerous. Their lack of selenium made it more difficult to fight the infection when compared with mice that had plenty of selenium. The selenium-depleted mice developed severe heart and lung complications as a result of the infection, while the mice with adequate selenium levels only developed mild symptoms.
It is believed that lowered activity of the selenium-containing GPX antioxidants is what causes virus to mutate. Professor Beck’s unique study reveals selenium’s vital role in supporting the immune system and antioxidant defense and shows how virulent a virus can become if there is too little selenium.
Influenza and flu vaccines
Most the time, influenza is just a harmless virus infection. Still, there are 3-5 million flu cases every year that become severe, killing off half a million people. The Spanish disease that erupted in 1918 had a death toll of 50 million people. After some years, the disease slowly disappeared by itself. Influenza virus belongs to the RNA viruses. New, mutated variants often originate from selenium-depleted regions. As the first scientist ever, Professor Melinda A. Beck demonstrated with studies of mice that influenza A becomes more dangerous if the host lacks selenium. This is because the virus is able to mutate. Studies show that selenium supplementation may benefit the human immune defense, especially in older people and in those with chronic disease.
In order to test the hypothesis, a randomized, double-blinded, placebo-controlled 12-week study was carried out on six groups of people with insufficient levels of selenium in their blood. The participants were given different doses of selenium yeast (0 µg, 50 µg, 100 µg, or 200 µg) or diets with onions that had either high or low selenium content. The group that was supplemented with 0 mcg of selenium yeast served as a placebo group.
After 10 weeks, all participants received a flu vaccine. When compared with the placebo group, the participants that received selenium yeast responded better to the vaccine, especially the group that got 200 micrograms daily. They had higher levels of cytokine IL-10 (interleukin-10) that is responsible for a normal immune response. When a flu becomes complicated it is usually because the immune defense overreacts by launching a cytokine storm and hyperinflammation, which causes oxidative stress and destroys healthy tissue. During a virus infection, a derailed immune defense may even cause gut bacteria to migrate to the lungs and cause life-threatening pneumonia.
An estimated 37 million people worldwide have HIV. The majority of patients will die of AIDS-related diseases within two years if they do not receive life-long retroantiviral combination therapy. HIV is an RNA virus that attacks the central parts of the immune defense, which is why the patients are so vulnerable.
It is reported that selenium deficiency occurs in up to nearly 70 in percent of people with HIV. Also, it has been seen that blood levels of selenium drop a long time before the HIV-positive people start to feel ill.
In Africa and the United States, scientists have discovered that the less selenium there is in the soil, the faster the disease spreads. Also, the AIDS mortality is higher in the low-selenium regions. Scientists have even found a link between selenium deficiency, oxidative stress, AIDS development, and mortality – even in connection with the combination therapy.
Blood samples taken from HIV-infected people with low selenium status show signs of fewer T helper cells (CD4), which are the conductors of the immune system. A number of studies carried out in the United States, Tanzania, Botswana, and Rwanda have shown that daily supplementation with 200 micrograms of selenium can delay the development of HIV infections and lower AIDS-related mortality by increasing levels of T helper cells. Selenium-containing antioxidants and their ability to counteract oxidative stress is also significant.
WHO estimates that 257 million people worldwide are infected with hepatitis B and that 71 million are infected with hepatitis C. Both viruses can cause acute and chronic hepatitis that can turn into liver cirrhosis and liver cancer.
Hepatitis is characterized by oxidative stress in the liver. Researchers have found that levels of the selenium-containing GPX antioxidants are lower in patients with hepatitis C, compared with healthy controls. Studies reveal that lack of selenium increases the risk of the disease becoming chronic and life-threatening.
Other studies have shown that if patients with hepatitis B take selenium supplements it lowers the risk of their disease turning into liver cancer. Interestingly, when the supplementation was stopped the risk of liver cancer was the same as in the patients in the control group. This shows that it is important to continue taking selenium in order to control the virus and to avoid oxidative stress.
Polio and polio vaccine
Polio is an RNA virus that can attack the brain and spinal cord and cause pediatric paralysis. Healthy people, however, rarely become sick when they are exposed to polio virus. A polio virus infection generates large amounts of free radicals and the antioxidant defense in the infected cells is weakened. Selenium supplementation has been shown to improve the immune response to polio vaccines, especially by bolstering the T cells that offer the best protection against virus infections.
Corona and COVID-19
Coronavirus is a family of RNA viruses that is found in birds and mammals. The common coronavirus types cause harmless cold infections. COVID-19 is caused by SARS-CoV-2 that already exists in several variants. Most people who are infected only develop mild symptoms or no symptoms at all. The vulnerable groups include seniors, overweight individuals, or those with chronic disease such as diabetes, hypertension, cardiovascular disease, kidney ailments, lung diseases, or cancer
A COVID-19 infection typically begins when virus particles infect the cells in the upper airways and spread to the lower airways. In rare and severe cases, acute respiratory distress syndrome develops. Some of the major reasons why this happen include oxidative stress, cytokine storm, and hyperinflammation in the pulmonary epithelial cells. Cytokine storm and hyperinflammation can also occur in the epithelial cells of blood vessels and other organs and result in circulatory failure and death.
In severe cases of COVID-19, low levels of T cells, B cells, and NK cells have been found together with increased levels of inflammation markers (cytokines and chemokines) and markers of blood clots (D-dimer). Many old people or people with chronic disease are particularly vulnerable because they already suffer from chronic low-grade inflammation as a sign of having a derailed immune defense that can more easily respond with cytokine storm and hyperinflammation.
It seems that there is a link between the body’s selenium status and the outcome of a COVID-19 infection. In their review article, the authors refer to selenium’s important role in the immune defense and how the GPX and TXNRD antioxidants reduce oxidative stress, thereby protecting cells and the epithelium in the blood vessels, lungs, heart, brain, and other organs. The antioxidants also prevent blood platelets from aggregating and forming blood clots.
In 2020, the British selenium researcher Margaret Rayman found a link between selenium levels in the soil in different parts of China and the risk of dying of COVID-19. In South Korea, India, Iran, and Russia, studies show that patients hospitalized with COVID-19 have significantly lower levels of selenium in the blood compared with healthy controls.
A German study has shown that survivors of a COVID-19 infection have higher selenium levels in the blood than non-survivors.
A study conducted by Mahmoodpoor et al. shows that selenium supplementation of patients with acute respiratory distress syndrome (ARDS) increases the antioxidant capacity in the lungs and reduces hyperinflammation. However, there is a general lack of published clinical studies to show the effect of selenium used as therapy in severe COVID-19 cases. According to the new review article, however, selenium has huge potential both in terms of therapy and prevention. It would be advisable to measure the selenium status of vulnerable COVID-19 patients and address any deficiencies. The authors also mention that low intake of vitamins A, B6, B12, C, D, and E plus zinc, magnesium, and omega-3 are linked to severe COVID-19. The new review article is published in International Journal of Molecular Sciences.
Selenium sources and recommendations
There is selenium in fish, shellfish, organ meat, eggs, dairy products, and Brazil nuts. European diets contain very little selenium due to the nutrient-depleted soil, which is the main reason why so many people lack selenium.
The daily reference intake (RI) level for selenium in Denmark is 55 micrograms but according to studies, this is not enough to properly saturate selenoprotein P, which is used as a marker for the body’s selenium status. Proper saturation of selenoprotein P takes more than 100 micrograms of selenium daily. It is best to supplement with selenium yeast because it provides a combination of different selenium compounds similar to the natural variety of selenium species found in a balanced diet with many different selenium sources. The European Food Safety Authority (EFSA) has established a safe upper intake level for selenium at 300 micrograms daily. In many studies of selenium, scientists have given volunteers daily doses of 200 micrograms.
|Important selenoproteins – immune defense and antioxidant defense|
|GPX 1-6 (glutathione peroxidase)||Antioxidants|
|Selenoptotein S||Regulation of cytokines and cellular inflammatory response|
|Selenoprotein P||Transportation of selenium in the body and antioxidant function. Used as a marker of the body’s selenium status.|
|TXNRD 1-3||Antioxidants, energy turnover, and metabolism|
|Even minor selenium deficiency prevents selenium-dependent selenoproteins from working optimally.|
Sabrina Sales Martinez et al. Role of Selenium in Viral infection with a Major Focus of SARS-CoV-2. International Journal of Molecular Sciences. 28 December 2021
Lutz Schomburg. Selenium Deficiency Due to Diet, Pregnancy, Severe Illness or COVID-19 – A Preventable Trigger for Autoimmune Disease. International Journal of Molecular Sciences. 2021
Qiyuan Liu et al. Selenium (Se) plays a key role in the biological effects of some viruses: Implications for COVID-19. Environmental Research. 2021
Olivia M. Guillan et al. Selenium, Selenoproteins and Viral Infection. Nutrients 2019
Aparna Shreenath. Selenium Deficiency. StatPearls. May 6, 2019
Jones GD et al. Selenium deficiency risk predicted to increase under future climate change. Proceedings of the National Academy of Sciences 2017
Roma Pahwa; Ishwarial Jialal. Chronic Inflammation. NCBI April 2018
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