NAC: Is this the one supplement everyone should be taking?

The nutritional supplement N-acetylcysteine is like the Swiss Army knife of supplements. It’s used to treat a wide range of health conditions, including allergies, Alzheimer disease, bipolar disorder, bronchitis, chronic kidney disease, cirrhosis, heart disease, hepatitis, infertility, schizophrenia, and upper respiratory infections.

The nutritional supplement N-acetylcysteine is used to treat a wide range of health conditions.

Then again, many dietary supplements are believed to have a variety of uses. The big question is whether they actually work. To answer that question, here’s some of the research that supports a few of the many uses of N-acetylcysteine.

Contents

• What is N-acetylcysteine?
• Acetaminophen toxicity
• High blood pressure
• COPD
• PCOS
• NAFLD (Non Alcoholic Fatty Liver Disease)
• COVID-19?
• NAC Also Protects Against Blood Clots
• Standard of Care for COVID-19 Should Include NAC
• Glutathione vs NAC
• NAC (N-AcetylCysteine) Dosage
• Precaution
• US FDA Cracks Down on NAC
• Conclusion

What is N-acetylcysteine?

N-acetylcysteine is a precursor of the amino acid cysteine, which bonds with two other amino acids in the body—glutamate and glycine—to form the powerful antioxidant glutathione.

Therefore, NAC (N-Acetyl Cysteine) is a precursor to glutathione. It is an antioxidant and increases glutathione levels in the body (source). NAC has mucolytic activity, so it helps reduce respiratory mucus levels. Laboratory research suggests that NAC might boost immune system function and suppress viral replication. NAC also decreases levels of interleukin-6 and has other anti-inflammatory effects. 

Glutathione is found in high concentrations in most cells of the body. It regulates a range of cellular functions and immune responses. Glutathione neutralizes free radicals, detoxifies harmful compounds, directly scavenges oxidative chemicals, and targets the causes of oxidative stress. It also protects against oxidants by recycling vitamin C and vitamin E.

Because glutathione is involved in so many cellular activities and processes—and because N-acetylcysteine can increase the production of glutathione—researchers have been studying N-acetylcysteine for use in a wide variety of medical conditions.

NAC Updates

• On April 21, 2022 US FDA announced the issuance of draft guidance on FDA’s policy regarding dietary supplements containing N-acetyl cysteine (NAC). The guidance details the agency’s intent to exercise enforcement discretion on the sale and distribution of such products.
• In 2020 FDA sent warning letters to several companies regarding the use of NAC in dietary supplements. In the letters, FDA warned against the use of drug claims, but also noted that NAC could not be marketed as a dietary supplement because there was no evidence that NAC had been marketed as a food or dietary supplement prior to its approval as a drug in 1963. More recently, we reported that FDA had confirmed in response to citizen petitions that NAC is excluded from the definition of a dietary supplement. FDA had not yet reached a decision, however, regarding a petitioner’s request to issue a regulation that would permit the use of NAC in dietary supplements.

Acetaminophen toxicity

Acetaminophen is widely used and is generally considered safe. But overdosing can happen. In fact, acetaminophen toxicity causes 500 deaths per year, not to mention thousands of emergency department visits and hospitalizations. Acetaminophen toxicity is also the most common cause of liver transplantation in the United States.

N-acetylcysteine has been used for years as a reliable antidote to acetaminophen toxicity, administered either intravenously or orally. It’s believed to protect the liver by boosting glutathione levels, which deactivate toxic metabolites.

N-acetylcysteine is most effective at reducing liver injury when administered within 8-10 hours of an overdose. This can bring down the rate of liver toxicity to about 3%.

Non Acetaminophen Induced Acute Liver Failure (NAI-ALF)

A 2015 meta-analysis of 4 clinical studies concluded that NAC is safe for NAI-ALF. It can prolong patients' survival with native liver without transplantation and survival after transplantation.

A 2017 multi-center study on Effect of NAC in Non-Acetaminophen-Induced Acute Liver Failure (NAI-ALF) concluded that intravenous NAC caused a reduction in NAI-ALF mortality and need for transplantation. NAC also decreased encephalopathy, hospital stay, ICU admission, and failure of other organs.

Life-threatening liver damage can also be caused by various drugs, toxins, or hepatitis. NAC helped protect the liver in 80 such cases. Patients with liver damage from drugs experienced the best results [R].

NAC injections helped increase liver function better than glutathione in one study of 75 patients with Hepatitis B [R].

COPD

N-acetylcysteine is already used as a mucolytic for people with chronic obstructive pulmonary disease (COPD). Because of its antioxidant and anti-inflammatory properties, N-acetylcysteine is also being investigated as a direct therapy for COPD. In a large, randomized controlled trial published in The Lancet Respiratory Medicine, researchers showed that N-acetylcysteine 600 mg twice daily prevented acute exacerbations of COPD, particularly in patients with moderate disease. Other studies found that N-acetylcysteine improved pulmonary function and reduced hospital readmissions.

A large randomized clinical trial is now underway to determine the efficacy of N-acetylcysteine in patients with early-stage COPD.

High blood pressure

N-acetylcysteine has been shown to lower blood pressure. In a study reported in the American Journal of Clinical Nutrition, a 4-week treatment of 1.8 g daily N-acetylcysteine in middle-aged men significantly lowered serum homocysteine—an independent risk factor for cardiovascular disease. The treatment also significantly decreased both systolic and diastolic blood pressure in all individuals, with a significant reduction of diastolic blood pressure in those with hyperlipidemia.

PCOS

There is no single effective treatment for polycystic ovary syndrome (PCOS), but N-acetylcysteine may be able to help, according to a study published in Obstetrics and Gynecology International. In this meta-analysis of eight randomized clinical trials involving 910 women with PCOS, researchers found that women who took N-acetylcysteine had higher odds of ovulating, getting pregnant, and having a live birth compared with those taking placebo. However, N-acetylcysteine had no effect on rates of miscarriage, menstrual regulation, acne, hirsutism, body mass index, testosterone, insulin levels, or adverse events.

NAFLD (Non Alcoholic Fatty Liver Disease)

Oxidative stress is believed to play a central role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), so researchers have studied antioxidants for treating these patients. For instance, a study of 30 people with NAFLD showed that a 3-month regimen of N-acetylcysteine 600 mg twice daily lowered levels of ALT (alanine transaminase) and decreased the size of the spleen compared with participants taking vitamin C.

COVID-19?

As of May 2022, there have been more than 15 published studies of NAC against COVID-19. For the list of studies, check out c19nac.

N-acetylcysteine is one of the many agents researchers are investigating as a treatment for COVID-19. As noted in the beginning of this article, N-acetylcysteine boosts levels of glutathione, which decreases the production of proinflammatory cytokines. Given this, researchers hypothesized that early administration of antioxidants such as N-acetylcysteine could be used to combat the cytokine storm that presages acute respiratory distress syndrome (ARDS) in COVID-19 patients.

Other researchers have found that N-acetylcysteine has antiviral activity against a number of viruses. They noted that increased levels of glutathione reduce viral load by inhibiting viral replication, notably in H3N2 and H5N1 strains of influenza A. However, this indicates that N-acetylcysteine’s efficacy against viruses depends on the particular strain it faces.

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.

NAC Also Protects Against Blood Clots

NAC may also 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.

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.

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."

Glutathione vs NAC

Taking glutathione by mouth does not appear to be an effective way to get it into your body. Its bioavailability is low and is also thought that glutathione may be broken down by enzymes in the stomach.

NAC has a low molecular weight and is well absorbed via oral administration.

Related: NAC in Preventing and Treating COVID-19

NAC (N-Acetyl Cysteine) Dosage

Cysteine is a semi-essential amino acid. It’s considered semi-essential because your body can produce it from other amino acids, namely methionine and serine. It becomes essential only when the dietary intake of methionine and serine is low.

There is no specific dietary recommendation for cysteine because your body can produce small amounts.

For your body to make the amino acid cysteine, you need adequate amounts of folate, vitamin B6 and vitamin B12. These nutrients can be found in beans, lentils, spinach, bananas, salmon and tuna.

While most protein-rich foods, such as chicken, turkey, yogurt, cheese, eggs, sunflower seeds and legumes, contain cysteine, some people choose to supplement with NAC to increase their cysteine intake.

NAC has low bioavailability as an oral supplement, meaning that it’s not well absorbed. The accepted daily supplement recommendation is 600–1,800 mg of NAC (Trusted Source, Trusted Source).

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.

NAC can be administered as an IV or taken orally, as an aerosol spray or in liquid or powder form.

N-acetyl cysteine (NAC) is a supplement form of cysteine.

Consuming adequate cysteine and NAC is important for a variety of health reasons — including replenishing the most powerful antioxidant in your body, glutathione.

NAC is valued primarily for its role in antioxidant production. Along with two other amino acids — glutamine and glycine — NAC is needed to make and replenish glutathione.

Precaution

People with bleeding disorders or taking blood thinning medications should not take NAC, as it may slow blood clotting (Trusted Source).

NAC has an unpleasant smell that makes it hard to consume. If you choose to take it, consult with your doctor first.

US FDA Cracks Down on NAC 

Ironically, just as we're starting to realize its benefits against this pandemic virus, the U.S. Food and Drug Administration is suddenly cracking down on NAC, claiming it is excluded from the definition of a dietary supplement.

Why are some retailers and Amazon no longer selling NAC? As mentioned above, the US FDA made it clear in 2020 that it considers NAC to be a drug and not a dietary supplement, so, for legal reasons, some companies have stopped selling it in United States.

Conclusion

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. There are not many natural supplements that have these anticoagulant, thrombolytic, mucolytic, liver protection, antioxidant and anti-inflammatory properties.

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 master anti-oxidant, glutathione.

Although N-acetylcysteine needs large clinical trials to really confirm whether it improves many of these conditions, it continues to be investigated for a myriad of health problems. Some of these include 

dermatologic conditions, neurodegenerative conditions like Alzheimer disease and dementia, and psychiatric disorders like obsessive-compulsive spectrum disorder and bipolar disorder. It’s also shown some promise in post-traumatic stress disorder and substance use disorders.

Where to Buy NAC?

Before adding a new supplement to your routine, discuss its use with your healthcare provider, especially if you have an underlying health condition or are taking medication.

 

NAC supplements are not available on Amazon US.