NAC, Glutathione and COVID-19: Research Review 2022

As of January 2022, there are still more than 3,000 clinical trials of COVID-19 treatments or vaccines that are either ongoing or recruiting patients. New ones are being added every day. The drugs or treatments being tested range from vaccines, repurposed flu treatments to failed ebola drugs, to stem cell therapy, to malaria treatments that were first developed decades ago.

We know that while a large percentage of the population only experiences mild to moderate symptoms of COVID-19 and won’t require hospitalization, others experience severe symptoms and complications, require hospitalization, or may even die. 

NAC weakens the binding of spike protein with ACE2 receptor

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 (tendency for blood clots) that often accompanies it. 

Image credit: ClevelandClinic

           

Immune Nutrients to Calm Cytokine Storm

If you want to optimize your immune health and reduce your risk of a cytokine storm, there are various immune nutrients and foods that may reduce cytokines. It is important to note that since COVID-19 is a new virus, there is no research suggesting that these immune nutrients would specifically benefit COVID-19 prevention or recovery.

However, there are scientific studies that show their immune benefits for other viral infections, including the flu, other coronavirus infections, and other respiratory infections. As with other infections, we recommend protecting your body and optimizing your immune health with the best immune nutrients.

While at this point, research is on-going and scientists are working hard to understand COVID-19 and find treatment options, these are some promising developments. The good news is that you don’t have to wait to take steps to protect your health. There are a number of things that you can do to improve your immune system, including using immune nutrients that may help to calm a cytokine storm (J Biol Regul Homeost Agents, The Lancet, Microbiol Mol Biol Rev).

NAC (N-Acetyl Cysteine)

N-acetyl L-cysteine (NAC) is a precursor of glutathione, helps to replenish intracellular glutathione, a vital cellular antioxidant. NAC has a low molecular weight and is well absorbed via oral administration. 

Glutathione or GSH (tripeptide of glutamic acid, cysteine, and glycine) is referred to as the body’s “master antioxidant” or the “mother of all antioxidants” because it is your body’s primary and most prevalent protector, found in all mammalian tissue.

NAC may protect against coagulation problems associated with COVID-19, as it has both anticoagulant (source) and thrombolytic effects (source), meaning it may both prevent clots and break up clots that have already formed.

NAC, Glutathione and COVID-19

As of July 2021, more than 10 clinical trials are underway to assess the efficacy of NAC in the context of highly infectious respiratory viral infections.

An in vitro study from India (July 2020) indicated that NAC weakens the binding of spike protein with ACE2 (Angiotensin Converting Enzyme 2) receptors. This provides evidence for the plausible protective virtue of N-acetyl cysteine against Covid-19.

Studies published in ACS Infectious Disease (ACS Infect Dis. 2020) and Antioxidants proposed that glutathione plays a crucial role in the body's fight against the severe inflammatory response triggered by the SARS-CoV-2 virus. The research group in the ACS Infectious Disease study called it the “most likely cause of serious manifestations and deaths in COVID-19 patients.”

NAC inhibits cellular entry and replication of some respiratory viruses, assists in clearing thickened mucous from the airways, suppresses inflammatory signaling, and may help mitigate viral infection-induced cytokine storm (source).

N-acetylcysteine (NAC) is a precursor to glutathione. In a paper on NAC for COVID-19, published in the October 2020 issue of Clinical Immunology titled “Therapeutic Blockade of Inflammation in Severe COVID-19 Infection With Intravenous N-acetylcysteine”, which is a case series report of 10 patients (including one with G6PD deficiency) given intravenous NAC. NAC elicited clinical improvement and markedly reduced inflammatory marker, CRP in all patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm.

Another study, "Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients" was led by Dr Alexey Polonikov from Russia (ACS Infect Dis. 2020).

What he found was that the reactive-oxygen-species-to-glutathione ratio was able to predict the severity of COVID-19 and the patient’s outcome. When the patient had a low ROS-to-glutathione ratio, the patient had a very mild case. The fever disappeared on the fourth day without any treatment whatsoever.

When the ROS-to-glutathione ratio was high, the patient developed air hunger on the fourth day, experienced significant fever, hoarseness, myalgia and fatigue persisting for 13 days. A patient with even higher ROS and lower reduced glutathione had critical disease requiring hospitalization for COVID-19-related pneumonia. 

In another publication on Respiratory Medicine Case Reports:

Two patients living in New York City (NYC) with a history of Lyme and tick-borne co-infections experienced a cough and dyspnea and demonstrated radiological findings consistent with novel coronavirus pneumonia (NCP). A trial of 2 g of PO or IV glutathione was used in both patients and improved their dyspnea within 1 h of use. Repeated use of both 2000 mg of PO and IV glutathione was effective in further relieving respiratory symptoms.

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, 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.

What Is the Primary Cause of Severe COVID-19 Illness: Glutathione or Vitamin D Deficiency?

The hypothesis that vitamin D (VD) deficiency is responsible for severe manifestations and death in COVID-19 patients has been proposed and is actively being discussed by the scientific community. 

Several studies reported that glutathione levels positively correlate with active vitamin D. (PubMed, PubMed) 

Interestingly, a recent experimental study (PubMed) showed that Glutathione deficiency and the associated increased oxidative stress epigenetically alters vitamin D regulatory genes and, as a result, the suppressed gene expression decreases Vitamin D production, ultimately leading to a secondary deficiency of vitamin D. This study provides important information that glutathione is essential for the control of endogenous vitamin D production and demonstrates potential benefits of Glutathione treatment in reducing the deficiency of vitamin D. Taken together, these findings suggest that glutathione deficiency rather than vitamin D deficiency is a primary cause underlying biochemical abnormalities, including the decreased biosynthesis of vitamin D, and is responsible for serious manifestations and death in COVID-19 patients.

Glutathione and Zinc

To improve your glutathione, you need zinc, and zinc in combination with hydroxychloroquine (a zinc ionophore or zinc transporter) has been shown effective in the treatment of COVID-19.

Glutathione and Molecular Hydrogen 

One of the best ways to increase glutathione, though, is molecular hydrogen. Molecular hydrogen does so selectively and will not increase glutathione unnecessarily if you don’t need it. You can view Tyler LeBaron’s lecture on the details of how it does this in “How Molecular Hydrogen Can Help Your Immune System.”

Glutathione and Selenium

Selenium is also important, as some of the enzymes involved in glutathione production are selenium-dependent.

Types of Glutathione

There is a lot of confusion about GSH and what makes an effective glutathione supplement. There are different types, different formulas, and a lot of different companies saying different things.

L-Glutathione or Reduced Glutathione because it is the most commonly found, least expensive, and the true core behind other forms you will find. There is some debate whether L-Glutathione alone can be effective taken orally. The theory being the enzymes in your stomach break it down before it can ever reach the blood stream and become useful. Some evidence suggests using newer technology and measurement technique that reduced glutathione will actually be absorbed.

Liposomal glutathione is a form of glutathione with a protective barrier made of a fat that keeps it safe in transport through the stomach lining and into the blood stream. It's normally paired with Phosphatidylcholine, which creates the protective lipid layer. This technique is used in other medical technologies like vaccines. and should prove an effective way to protect the sensitive glutathione molecule.

Acetyl-Glutathione is an acetylated form of glutathione. Adding an acetyl function group to an existing molecule is something that has been done in medicine for many years. In fact “acetyl” is the difference between heroine and morphine. You have probably used an acetylated product in the form of acetyl-salicylic acid… or aspirin. The concept is the acetyl function group makes the molecule more stable and enhances delivery through the blood stream including to the brain. Unfortunately there are very few studies regarding acetyl-glutathione but the science behind it is strong, and anecdotal evidence would suggest this is the best glutathione form currently in supplements. It also tends to come at a higher price due to a more complicated production.

Whey Protein is technically a glutathione precursor. Whey protein get it’s own category because it’s so significant as one of the first and best ways to promote glutathione production in your body. Only a few years ago, the only reliable and simple way to boost GSH was to consume a good quality non-denatured whey protein powder. Cysteine tends to be the limiting factor in GSH production, and is found in good quality whey, making it strong healthy source of a good amino acid profile that boosts glutathione.

Conclusion

Macronutrients and micronutrients are essential to a human body, there are no ifs and buts about it. Optimizing your immune system is critical to improve your health whether there is a pandemic or not.

Cytokines are an important part of your immune response. However, when your body releases excessive or uncontrolled levels of cytokines it results in hyper-inflammation called a cytokine storm. A cytokine storm may lead to serious complications and even death in serious COVID-19 cases and in other infections.

Optimizing your immune system with diet and lifestyle changes are critical to improving your health and to decrease your risk of a cytokine storm. However, therapeutics, vaccines and other physical strategies such as social distancing and mask wearing are also needed in order to protect yourself and your loved ones. It doesn't have to be an 'either or' situation. Combination strategies are normally more effective.

NB: NAC supplements are not available on Amazon US. You can buy NAC Supplements from Lazada Singapore.

Related: 

• 15 Best Supplements for Cytokine Storm

Supplements you can purchase from Amazon for COVID-19 prevention. Inspired by the FLCCC prevention protocol >

Disclaimer: The information on this website is not intended to replace a one-on-one relationship with a qualified health care professional and is not intended as medical advice. It is intended as a sharing of knowledge and information from the research and experience of third party sites. If you are pregnant, nursing, taking medication, or have a medical condition, consult your health care professional before using products based on this content.

This article is subject to change as new evidence emerge. One Day MD has not performed independent verification of the data contained in the referenced materials, and expressly disclaims responsibility for any error in the literature.