Glutathione Deficiency and Risk of Severe COVID-19

Researchers suggest low levels of 'master antioxidant' could be key to understanding severe COVID
May 17, 2021 Updated: May 17, 2021

Glutathione is an antioxidant made from three amino acids in your body. It’s produced by your liver and plays an important role in combating reactive oxygen species that can damage your cells.

Now, researchers have linked glutathione deficiency with more severe COVID infections. Data shows that people who are deficient in glutathione can experience some of the more serious symptoms of COVID-19, according to an article published in ACS Infectious Diseases.

A previous study published in Nature in January, evaluated the differences in the blood clotting potential between COVID-19 and other respiratory viral infections not triggered by a coronavirus.

It found blood clotting rates weren’t different between the two groups in mild disease. However, they found hypercoagulability, an increased tendency to produce blood clots, in COVID-19 was a dynamic process and the highest risk occurred in severely ill people. The complications of hypercoagulability include shortness of breath and severe lung complications.

Severe cases of COVID-19 frequently include hypercoagulability. While the physiology of this abnormal state isn’t completely understood, researchers have found anticoagulant therapy helps improve health outcomes.

In one study published in Thrombosis and Haemostasis in June 2020, patients admitted to Padova University Hospital in Italy for acute respiratory failure showed “markedly hypercoagulable thromboelastometry profiles,” which “correlated with a worse outcome.”

It appears one of the differences between those who have a mild illness and severe illness is related to the body’s ability to reduce the hyperimmune response that leads to a cytokine storm and the hypercoagulability that often accompanies it. Glutathione plays a role in the fight against the severe inflammatory response triggered by SARS-CoV-2.

The research published in ACS Infectious Disease called a glutathione deficiency “most likely cause of serious manifestations and deaths in COVID-19 patients.”

In that study, they theorized the higher infection rate in older individuals and those with comorbidities suggest these groups are sensitive to environmental factors. Certain medical conditions have been identified that increase the risk of severe illness from COVID-19. These include chronic lung disease, Type 2 diabetes, heart conditions, obesity, and smoking, which all add oxidative stress that depletes glutathione.

Glutathione plays a crucial role in keeping the inflammatory response in check, which the researchers theorize is a feasible means in the treatment and prevention of COVID-19.

“The hypothesis that glutathione deficiency is the most plausible explanation for serious manifestation and death in COVID-19 patients was proposed on the basis of an exhaustive literature analysis and observations,” they wrote.

“The hypothesis unravels the mysteries of epidemiological data on the risk factors determining serious manifestations of COVID-19 infection and the high risk of death and opens real opportunities for effective treatment and prevention of the disease.”

A paper published in Antioxidants in July 2020 also proposed glutathione may be “critical in extinguishing the exacerbated inflammation that triggers organ failure in COVID-19.”

In the paper, the scientists presented a review of biochemical mechanisms that are counterbalanced by glutathione and the pathways that may explain endogenous (made in the body) glutathione depletion in older people and those with comorbidities known to increase the risk of severe illness.

Glutathione Mediates Reduction in Lung Inflammation

One medical student put this theory to the test when his 48-year-old mother was diagnosed with pneumonia. She was prescribed hydroxychloroquine and azithromycin, which helped to improve some symptoms, but her breathing remained labored. When she developed severe respiratory problems, her son contacted Dr. Richard Horowitz, a specialist who was treating his sister for Lyme disease.

He suggested adding glutathione to help reduce inflammation and protect lung tissue. The results were dramatic. Within one hour after receiving a 2,000-milligram dose of glutathione, her breathing had improved. She continued taking the glutathione for five days and didn’t relapse. Horowitz published two case studies, documenting the results of oral and IV glutathione.

Around a year ago, Dr. Alexi Polonikov from Kursk State Medical University in Russia published papers proposing glutathione plays a crucial role in the body’s ability to respond to a COVID-19 infection.

In addition to using glutathione during an illness, Polonikov postulates that glutathione may be used as a preventive agent. Based on an exhaustive literature analysis, he later gave an explanation for why he believes glutathione deficiency is a plausible reason for serious illness from COVID-19.

“(1) oxidative stress contributes to hyper-inflammation of the lung leading to adverse disease outcomes such as acute respiratory distress syndrome, multiorgan failure, and death;

“(2) poor antioxidant defense due to endogenous glutathione deficiency as a result of decreased biosynthesis and/or increased depletion of GSH is the most probable cause of increased oxidative damage of the lung, regardless which of the factors aging, chronic disease comorbidity, smoking or some others were responsible for this deficit.”

In a couple of YouTube videos, pulmonologist Dr. Roger Seheult explains how COVID-19 sets the stage for significantly increased oxidative stress by raising levels of superoxide, a damaging reactive oxygen species (ROS).

Glutathione: A Master Antioxidant

This increase in superoxide occurs in people who have high levels due to chronic diseases that are comorbidities for COVID-19. These include heart disease, Type 2 diabetes, and high blood pressure.

The powerful antioxidant function in glutathione has earned it the nickname “master antioxidant.”Antioxidants help keep other molecules from oxidizing. One function of glutathione is to recycle other antioxidants. This helps increase their effectiveness. Deficiencies in certain vitamins such as C, E, and A can cause a glutathione deficiency.

Comorbid Risk Factors Linked to Glutathione Deficiency

In a review of the literature evaluating the effect of lung disease in COVID-19 that was published in 2020 in the Journal of Infectious Diseases and Epidemiology, researchers wrote that, in 2002, data showed glutathione protected against chronic inflammation during respiratory disease. They postulated that directly increasing glutathione levels in the lungs “would be a logical approach to protection against chronic inflammation and oxidant-mediated injury in lung disease.”

In addition to protecting lung tissue, glutathione has been studied in many of the comorbid conditions associated with severe COVID-19. For over a decade, researchers have noted that people with obesity, heart disease, and Type 2 diabetes, and who are elderly, have a higher incidence of glutathione deficiency associated with those conditions.

Improve Glutathione Production

Those looking to boost glutathione levels produced by their body can practice dietary and lifestyle habits shown to help. Foods that have a positive impact on glutathione production include cruciferous vegetables such as broccoli, green tea, curcumin, rosemary, and milk thistle. Getting quality sleep may also help.

Different types of exercise can influence your levels as well. In one study published in the European Journal of Cardiovascular Prevention and Rehabilitation, researchers enrolled 80 healthy but sedentary volunteers to measure the type of exercise that may have the greatest effect. They found that aerobic training in combination with circuit weight training showed the greatest benefit.

Dr. Joseph Mercola is the founder of An osteopathic physician, best-selling author, and recipient of multiple awards in the field of natural health, his primary vision is to change the modern health paradigm by providing people with a valuable resource to help them take control of their health. This article was originally published on