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,^[21] and in humans, a reduction in serum lead has been found.^[22] 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.

Lead is a heavy mineral that can be toxic to the human body. Exposure to lead causes oxidative stress in the body, which seems to deplete both cellular and enzymatic antioxidants, including glutathione.^[23] NAC is thought to alleviate the toxic effects of lead by aiding in its removal from the body while also acting as a building block for the synthesis of new glutathione.^[21][24]

In animal studies, NAC has shown protective effects (assessed by biomarkers in serum and histopathological examination) against lead toxicity in the kidneys,^[21] the brain,^[24][25] and liver tissue.^[25] In workers with high levels of occupational lead exposure, oral supplementation of 200–800 mg of N-acetylcysteine daily for 12 weeks reduced blood concentrations of lead and improved markers of oxidative stress.^[22]

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).^[26]

In women with infertility due to polycystic ovarian syndrome (PCOS), NAC may reduce testosterone and increase follicle stimulating hormone levels.^[27] Compared to placebo, NAC seems to increase rate of pregnancy and ovulation rates, but not when compared to metformin (a medication commonly used in PCOS).^[28]

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.^[29] 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,^[20] making it a potentially helpful supplement for a variety of conditions.

When used in addition to standard care, NAC has shown small benefits for the management of schizophrenia,^[30][31][32] depression symptoms (including bipolar depression),^[33][34] autism spectrum disorder (specifically hyperactivity and irritability),^[35] and substance use disorder.^[36]

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.^[37][38][39]

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).^[40] NAC seems to display the most consistent benefit when exercise is being performed in a fatigued state,^[41][42][43] but it may negatively affect muscle adaptations to training.^[44] Ultimately, further research is needed to determine if NAC supplementation is beneficial in this context, and if so, in what setting and dosage.

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.^[45]

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.^[5]

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.^[55]

Research suggests that NAC may reduce the risk of drug-induced hearing loss when used concurrently with potentially ototoxic drugs (i.e., drugs that are toxic to the ear, such as aminoglycoside antibiotics or cisplatin).^[56][57] NAC may also have a protective effect against noise-induced shifts in hearing thresholds (i.e., exposure to noises so loud that they temporarily or permanently raise the minimum volume at which a sound can be detected), specifically for higher sound frequencies (4–6 kHz).^[55] For sudden hearing loss (an unexplainable, rapid loss of hearing), combining NAC with corticosteroids may be more effective for regaining hearing than corticosteroids alone.^[58]

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.^[59] 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.

In two small studies, people with Parkinson’s disease who received NAC for 3 months demonstrated increased dopamine functioning in the brain (determined by a brain scan done before and after the intervention which measured dopamine transporter binding) alongside reduced disease symptoms compared to a control group. NAC was given as a weekly intravenous infusion (50 mg per kg of body weight) in addition to daily oral NAC (1,000 to 1,200 mg). The control groups received standard care, but no placebo, which could bias these findings in favor of NAC.^[60]

It’s important to note that while intravenous NAC does appear to increase glutathione levels in the brain, NAC taken orally (6,000 mg daily) has not currently been found to have this effect in humans. Currently, there’s no evidence in humans that oral NAC alone can improve Parkinson’s disease.^[61][62]

On one hand, excessive reactive oxygen species (ROS) can damage molecules in the body, including DNA, and induce biochemical pathways that may increase the risk of cancer. Additionally, some cancers, like triple-negative breast cancer, use increased ROS signaling for their own survival and progression.^[47] In these contexts, antioxidants such as NAC may play a beneficial role.

On the other hand, the generation of ROS is a defense mechanism the body can use to induce cancer cell death and prevent cancer progression. While antioxidants might protect against ROS-induced damage and reduce cancer progression in some instances,^[48] in other contexts they might promote cancer cell survival by reducing oxidative stress within the cell.^[49] In fact, there’s evidence to suggest that one mechanism by which cancer cells promote their own survival is by increasing the body's antioxidant defense mechanisms within the cell.^[50][51]

There is no evidence from human clinical trials that NAC causes cancer or increases cancer progression. In breast cancer, one uncontrolled pilot study suggested that NAC might actually inhibit cancer cell proliferation.^[48] However, research in mice has suggested that NAC supplementation might promote the progression of certain pre-existing cancers, including skin, liver, and lung cancer, and increase the risk of metastatic disease — in both cases, by reducing oxidative stress in the cancer cells.^{[52][53][54][49]} In mice without pre-existing cancer, the effects are less clear. NAC supplementation did not induce liver cancer in otherwise healthy mice in one study,^[54] but it did increase the risk of lung cancer in healthy aged mice in another.^[49]

Clearly, the question of how NAC interacts with cancer risk or progression is incredibly nuanced, and more research is needed to understand this relationship.