Does NAC Prevent Cytokine Storm in COVID-19?

N-acetylcysteine (NACis a precursor to glutathione. It is an antioxidant and increases glutathione levels in the body (Source). NAC has a long history of use as a first-aid remedy for acetaminophen poisoning. It neutralizes the toxic effects of the drug by recharging glutathione, thereby preventing liver damage.

NAC may be able to inhibit Cytokine Storm

Researchers have confirmed that in severe COVID-19 cases, cytokines such as interleukin-6 (IL6), interleukin-10 (IL10) and TNF-ɑ are all elevated. Once they reach excessive levels, a so-called cytokine storm develops, causing significant tissue damage. NAC may be able to inhibit this damaging cascade.

In the "Therapeutic Blockade of Inflammation in Severe COVID-19 Infection With Intravenous N-acetylcysteine" paper, the researchers focus on a specific group of patients, namely those with glucose 6-phosphate dehydrogenase (G6PD) deficiency, which has been shown to facilitate human coronavirus infection due to the fact that G6PD depletes glutathione.

G6PD deficiency is a genetic disorder that typically affects males and is more prevalent among Black men and those from the Mediterranean area, Africa and Asia. (Women with this genetic anomaly are carriers and can pass it on to their children but rarely display symptoms.)

G6PD is an enzyme needed for the proper function of red blood cells. It also protects your red blood cells from free radicals in your blood by limiting oxidative stress.When your body doesn't produce enough of this enzyme, hemolytic anemia — a condition in which red blood cells are broken down faster than they are made — can result due to unneutralized oxidative stress from insufficient amounts of NADPH being produced.

In addition to that G6PD-deficient patient, NAC was also given to nine other COVID-19 patients who were on respirators but did not have G6PD deficiency. In these patients, "NAC elicited clinical improvement and markedly reduced CRP in all patients and ferritin in 9/10 patients." The authors hypothesize that NAC's mechanism of action "may involve the blockade of viral infection and the ensuing cytokine storm."

That said, they point out that it's difficult to discern whether these anti-inflammatory effects were specific to the use of NAC, as steroids and other anti-inflammatory drugs were sporadically used. Still, they believe NAC does have the ability to reduce inflammation in patients with COVID-19.

NAC Also Protects Against Blood Clots

Importantly, NAC may also protect against other problems associated with COVID-19, including the hypercoagulation that can result in stroke and/or blood clots that impair the ability to exchange oxygen in the lungs.

Many COVID-19 patients experience serious blood clots, and NAC counteracts hypercoagulation, as it has both anticoagulant and platelet-inhibiting properties

A 2017 paper also found NAC has potent thrombolytic effects, meaning it breaks down blood clots once they've formed. According to the authors, "NAC is an effective and safe alternative to currently available antithrombotic agents to restore vessel patency after arterial occlusion." (Restoring vessel patency means the blood vessel is now unobstructed so that blood can flow freely.)

Another paper (Blood Adv. 2020) showed the same thing.

NAC and COVID-19

As of October 2022, there have been more than 10 published studies of NAC against COVID-19. 
 
For a compilation of more than 10 studies of NAC and COVID-19, check out the list of studies here (constantly updated).


However, in terms of early treatment, the improvement rate is not as impressive as the other natural alternatives i.e. quercetin, black seed oil and vitamin A.

That said, NAC is a natural alternative for aspirin and an over-the-counter supplement that both prevents blood clots and breaks up existing ones i.e. anticoagulant effects. 

NAC may also protect against coagulation problems associated with COVID-19, as it counteracts hypercoagulation and breaks down blood clots.

Safety: As an FDA-approved drug, the safety profile of NAC has been evaluated (Source). Reported side effects of oral NAC include nausea, vomiting, abdominal pain, diarrhea, indigestion, and epigastric discomfort. No safety concerns have been reported for products labeled as dietary supplements that contain NAC. (Source)

For NAC contra-indications, check out here.

Standard of Care for COVID-19 Should Include NAC

Considering many COVID-19 cases involve blood clots in addition to excessive oxidative stress, and NAC effectively addresses both, NAC should be included in standard of care for COVID-19. As noted in "Rationale for the Use of N-acetylcysteine in Both Prevention and Adjuvant Therapy of COVID-19," published August 11, 2020, in the FASEB Journal:

"COVID-19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokine storm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID-19 patients.

N- Acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH). Due to its tolerability, this pleiotropic drug has been proposed not only as a mucolytic agent, but also as a preventive/therapeutic agent in a variety of disorders involving GSH depletion and oxidative stress …

Thiols block the angiotensin-converting enzyme 2 thereby hampering penetration of SARS-CoV-2 into cells. Based on a broad range of antioxidant and anti-inflammatory mechanisms … the oral administration of NAC is likely to attenuate the risk of developing COVID-19, as it was previously demonstrated for influenza and influenza-like illnesses.

Moreover, high-dose intravenous NAC may be expected to play an adjuvant role in the treatment of severe COVID-19 cases and in the control of its lethal complications … including pulmonary and cardiovascular adverse events."

Summary

NAC is a natural alternative for aspirin and an over-the-counter supplement that has both anticoagulant (source) and thrombolytic effects (source), meaning it may both prevent clots and break up clots that have already formed.

Another 2021 paper from China also concluded that 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.

Consider taking around 500 milligrams/day of NAC, as it helps prevent blood clots and is a precursor for your body to produce the important antioxidant glutathione.

Glutathione is also one of the natural blood thinners as it is known to reverse the build-up of plaque and lessen the tendency of abnormal blood clots.

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