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N-acétylcystéine

Also known as: NAC, acetylcysteine, N-acetylcysteine

Overview

N-acetylcysteine (NAC) is a derivative of the amino acid cysteine, primarily recognized for its role as a precursor to glutathione, a crucial intracellular antioxidant. While present in small amounts in foods like garlic and onions, it is predominantly utilized as a pharmaceutical or dietary supplement. Its main applications include treating acetaminophen overdose, acting as a mucolytic agent in chronic respiratory conditions, and mitigating oxidative stress and inflammation due to its antioxidant properties. NAC has a robust evidence base, supported by numerous randomized controlled trials and systematic reviews, particularly for acetaminophen toxicity and emerging uses in conditions like cardiac surgery and liver failure. It is available in oral and intravenous forms.

Benefits

NAC offers several evidence-based benefits, primarily through its antioxidant and anti-inflammatory actions. It effectively replenishes glutathione, thereby reducing oxidative stress markers and inflammation across various conditions. For individuals undergoing cardiac surgery, a systematic review and meta-analysis of 29 randomized controlled trials (n=2,486) indicated that NAC supplementation significantly reduced perioperative complications such as acute renal insufficiency and arrhythmias, although its impact on mortality was less conclusive. In cases of non-acetaminophen acute liver failure, a meta-analysis of prospective studies demonstrated that NAC treatment improved transplant-free survival rates and reduced hospital length of stay. Furthermore, NAC has been shown to reduce circulating inflammatory cytokines and oxidative biomarkers, underscoring its role in modulating inflammation. The onset of benefits can range from rapid in acute settings to several weeks for chronic conditions, depending on the clinical context.

How it works

NAC primarily functions by providing cysteine, which is the rate-limiting substrate for the synthesis of glutathione. By boosting glutathione levels, NAC restores the body's intracellular antioxidant capacity. Beyond this, NAC directly scavenges free radicals, neutralizing harmful reactive oxygen species. It also modulates redox-sensitive signaling pathways that are involved in inflammatory responses, helping to reduce inflammation. Furthermore, NAC positively influences mitochondrial function and helps to reduce oxidative damage to essential cellular components like lipids, proteins, and DNA. While its oral bioavailability is moderate (approximately 6-10%), intravenous forms are utilized in acute situations to achieve rapid therapeutic effects.

Side effects

N-acetylcysteine (NAC) is generally considered safe with a well-established safety profile in clinical use. The most common side effects, affecting more than 5% of users, are gastrointestinal symptoms such as nausea, vomiting, and diarrhea. Less common side effects, occurring in 1-5% of individuals, include rash and headache. Rare but serious adverse reactions, such as allergic reactions and anaphylactoid responses, can occur, particularly with intravenous administration. Caution is advised when combining NAC with nitroglycerin, as it may potentiate its vasodilatory effects, or with activated charcoal, which can reduce NAC's absorption. Contraindications include known hypersensitivity to NAC. While generally well-tolerated, pregnant individuals and pediatric populations should use NAC under medical supervision.

Dosage

The minimum effective dose of NAC varies significantly depending on the indication. For acute acetaminophen overdose, the standard protocol involves a loading dose of 140 mg/kg, followed by subsequent maintenance doses. For general antioxidant support, oral dosages typically range from 600 mg to 1,800 mg daily. In specific acute conditions like cardiac surgery or liver failure, optimal dosing is usually intravenous and protocol-specific, often starting with a bolus (e.g., 150 mg/kg over 15 minutes) followed by continuous infusions. The maximum safe doses are dependent on the route of administration and the specific indication, but NAC is generally well tolerated up to several grams per day under medical supervision. Timing is crucial in acute poisoning, while consistent daily dosing is important for chronic conditions. Oral absorption can be enhanced when taken with food and adequate hydration.

FAQs

Is NAC safe for long-term use?

Yes, with appropriate medical monitoring, NAC is generally considered safe for chronic use at doses up to 1,800 mg/day, particularly for its antioxidant benefits.

Does NAC improve lung function?

Evidence supports NAC's mucolytic effects, which can be beneficial in chronic bronchitis by thinning mucus. However, overall clinical benefits on lung function can vary among individuals.

How quickly does NAC work?

In acute settings, such as acetaminophen overdose, NAC's effects are rapid. For antioxidant and anti-inflammatory benefits in chronic conditions, noticeable effects may take days to several weeks to manifest.

Can NAC be combined with other antioxidants?

Yes, NAC can generally be combined with other antioxidants. However, it is always advisable to monitor for any potential interactions or adverse effects, especially when introducing new supplements.

Research Sources

https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0213862 – This systematic review and meta-analysis of 29 RCTs (n=2,486) investigated NAC's role in adults undergoing cardiac surgery. It found that NAC reduced perioperative complications like acute renal insufficiency and arrhythmias, though a clear mortality benefit was not established. The study highlights NAC's potential in mitigating specific surgical risks.
https://pubmed.ncbi.nlm.nih.gov/35371352/ – This meta-analysis of prospective studies focused on NAC treatment for non-acetaminophen acute liver failure. The findings indicated that NAC improved transplant-free survival and reduced the length of hospital stay, suggesting a beneficial role in managing this severe condition. The study contributes to understanding NAC's broader therapeutic applications beyond overdose.
https://pubmed.ncbi.nlm.nih.gov/32726657/ – This systematic review and meta-analysis examined the effects of NAC on inflammation and oxidative stress across various conditions. It concluded that NAC significantly reduced inflammatory cytokines and oxidative markers, supporting its role as a potent antioxidant and anti-inflammatory agent. The study underscores the molecular mechanisms behind NAC's therapeutic effects.