The American Herbal Products Association (AHPA) and others have provided the FDA with details regarding NAC products sold before 15 October 1994. Additionally, NAC itself is found in a variety of foods (garlic, onions, asparagus, and others).In 2020 FDA sent warning letters to several companies regarding the use of NAC in dietary supplements. In those letters FDA noted that NAC could not be marketed as a dietary supplement because NAC had NOT been marketed as a food or dietary supplement prior to its approval as a drug. FDA had confirmed in response to two citizen petitions (CRN and NPA) that NAC is excluded from the definition of a dietary supplement. FDA had not yet reached a decision, however, regarding a petitioners (NPA) request to issue a regulation that would permit the use of NAC in dietary supplements. On April 21, 2022, the FDA announced the availability of a draft guidance on FDAs policy regarding products labeled as dietary supplements that contain N-acetyl-L-cysteine. The draft guidance, when finalized, will explain the agencys intent to exercise enforcement discretion with respect to the sale and distribution of certain NAC-containing products that are labeled as dietary supplements. The FDA has asked for comments on its NAC Guidance and has stated that they will use enforcement discretion with respect to NAC supplements.
Adverse effects for inhalational formulations of acetylcysteine include nausea, vomiting, stomatitis, fever, rhinorrhea, drowsiness, clamminess, chest tightness, and bronchoconstriction. Although infrequent, bronchospasm has been reported to occur unpredictably in some patients.Adverse effects for oral formulations of acetylcysteine have been reported to include nausea, vomiting, rash, and fever.Large doses in a mouse model showed that acetylcysteine could potentially cause damage to the heart and lungs. They found that acetylcysteine was metabolized to S-nitroso-N-acetylcysteine (SNOAC), which increased blood pressure in the lungs and right ventricle of the heart (pulmonary artery hypertension) in mice treated with acetylcysteine. The effect was similar to that observed following a 3-week exposure to an oxygen-deprived environment (chronic hypoxia). The authors also found that SNOAC induced a hypoxia-like response in the expression of several important genes both in vitro and in vivo. The implications of these findings for long-term treatment with acetylcysteine have not yet been investigated. The dose used by Palmer and colleagues was dramatically higher than that used in humans, the equivalent of about 20 grams per day. Nonetheless, positive effects on age-diminished control of respiration (the hypoxic ventilatory response) have been observed previously in human subjects at more moderate doses.Although N-acetylcysteine prevented liver damage in mice when taken before alcohol, when taken four hours after alcohol it made liver damage worse in a dose-dependent fashion. Pharmacology
Pharmacodynamics
Acetylcysteine serves as a prodrug to L-cysteine, a precursor to the biologic antioxidant glutathione. Hence administration of acetylcysteine replenishes glutathione stores.