N-Acetylcysteine

What is N-acetylcysteine?

N-acetylcysteine (NAC) is an acetylated form of the amino acid L-cysteine. It has antioxidant and anti-inflammatory properties and is a mucolytic agent, meaning that it helps break down mucus in the respiratory tract. NAC is converted to L-cysteine after ingestion, which, in turn, is converted into glutathione (GSH), a powerful antioxidant. L-cysteine can’t be supplemented on its own because free L-cysteine is highly unstable, becoming readily oxidized in solution which can encourage the formation of insoluble precipitates. Similarly, glutathione is rapidly broken down in the gastrointestinal tract and blood, limiting its availability in the body when supplemented directly. In contrast, NAC is more stable and has a much lower toxicity than free L-cysteine, making it safer and more effective for increasing cysteine and glutathione levels in the body.

What are N-acetylcysteine’s main benefits?

NAC reduces levels of proinflammatory cytokines and oxidative stress. Because NAC increases glutathione levels in the body, which are rapidly depleted by stress, disease, or drug toxicity, it has applications in clinical settings, in addition to general health and wellness. NAC has been used for the treatment of cystic fibrosis (due to its mucolytic properties), acetaminophen (paracetamol) toxicity, and chronic obstructive pulmonary disease (COPD). In COPD, NAC may improve lung function and speed the rate of symptom improvement when used during a symptom flare up (an exacerbation). Long-term use (more than 3–6 months) may improve symptoms of chronic bronchitis and reduce the risk of COPD exacerbations, although the latter effect has not been found consistently. Additionally, NAC does not seem to prevent declining lung function when used over a long period of time.

Does N-acetylcysteine help with lead toxicity?

NAC seems to have a direct mineral chelating effect, meaning it can bind tightly to certain minerals and aid in their removal from the body. In rodents, decreased tissue accumulation and increased urinary excretion of lead has been observed following NAC supplementation, and in humans, a reduction in serum lead has been found. Standard oral doses of NAC appear to be protective against lead toxicity in humans, possibly related to a reduction in lead accumulation in the body and reducing oxidative stress.

Does N-acetylcysteine affect fertility?

NAC has shown positive effects on parameters of both male and female infertility. NAC may improve sperm health and quality (e.g., motility, concentration, morphology, volume) in infertile men, likely through reductions in oxidative stress in the testicular tissue and semen. However, NAC hasn’t consistently been found to influence hormones involved in male fertility (testosterone, luteinizing hormone, follicle stimulating hormone (FSH), and prolactin).

Does N-acetylcysteine affect mental disorders?

Many mental disorders are associated with dysregulation of the neurotransmitters glutamate and/or dopamine, as well as increased levels of oxidative stress in the brain. Aside from its antioxidant effects, research shows that NAC crosses the blood-brain barrier and can directly alter glutamate neurotransmission, with an indirect effect on dopamine as well, making it a potentially helpful supplement for a variety of conditions.

Does N-acetylcysteine affect exercise performance?

During physical exercise, cells produce a high level of ROS. While this actually serves a biological role that positively affects skeletal muscle adaptations and force production, in vitro and animal studies suggest that excessively high levels of ROS can contribute to impaired muscle function and muscle fatiguing. NAC has been explored as a potential ergogenic due to its antioxidant effects, but research supporting its use is limited. A 2017 meta-analysis was unable to find any evidence of a performance benefit with NAC supplementation, but the analysis included studies using vastly different dosages, exercise regimens, and study populations (e.g., elite athletes, untrained individuals). NAC seems to display the most consistent benefit when exercise is being performed in a fatigued state, but it may negatively affect muscle adaptations to training.

How does N-acetylcysteine work for acetaminophen toxicity?

Acetaminophen (paracetamol) is a widely available medication used to treat fever and pain. It is also the leading cause of liver transplantation in the U.S. and the second leading cause worldwide due to liver toxicity that can occur with overdose. When acetaminophen is overdosed, a toxic metabolite (N-acetyl-p-benzoquinone imine (NAPQI)) begins to build up in the liver. Normally, glutathione is responsible for neutralizing NAPQI, but when glutathione levels become depleted, NAPQI begins reacting with molecules within liver cells, leading to irreversible liver cell death. NAC is an effective antidote for acetaminophen (paracetamol) toxicity primarily because it replenishes glutathione levels, but it can also directly bind to and neutralize NAPQI to minimize liver cell damage and convert NAPQI back to acetaminophen temporarily.

What is oxidative stress?

Oxidative stress describes a state of imbalance between oxidants and antioxidant defense mechanisms in the body. When oxidants (e.g., ROS, reactive nitrogen species (RNS)) outweigh the body’s natural antioxidant defenses (e.g., antioxidant enzymes, glutathione), cellular damage can occur, including damage to proteins, lipids, and DNA. This is thought to contribute to the development or worsening of a wide range of diseases.

Does N-acetylcysteine affect hearing loss?

NAC may have a role in the prevention or early treatment of hearing loss, although research is still in the early stages. Hearing loss is complex and can occur for many reasons, but increased levels of oxidative stress within the ear is an important contributing factor. Excessive levels of reactive oxygen species (ROS) within the ear canal can damage or kill auditory hair cells — the cells responsible for converting sound vibrations into electrical signals that the brain can understand — leading to hearing loss.

Does N-acetylcysteine affect Parkinson’s disease?

Parkinson’s disease is characterized by the progressive loss of dopamine-producing neurons in the brain and is associated with increased levels of oxidative stress and a relative depletion of glutathione in brain tissue. N-acetylcysteine (NAC) reliably increases glutathione levels in the body, and preclinical and preliminary clinical research has pointed to a possible therapeutic effect of NAC in Parkinson’s disease.