N-acetylcysteine

N-acetylcysteine (also known as NAC, acetylcysteine, N-acetyl-L-cysteine) is a supplement and drug used to increase levels of glutathione (GSH), the most common natural antioxidant in the body. For this reason, NAC itself is sometimes referred to as an antioxidant. NAC is a pro-drug for cysteine, which is the rate-limiting ingredient in the biosynthesis of glutathione. It is thought that NAC is better than cysteine at increasing GSH in the brain since most cysteine will be consumed by the liver during first-pass metabolism, and NAC may bypass first-pass metabolism. Since orally consumed GSH will be broken down in the stomach, NAC is a more efficient means of enhancing GSH in cells. NAC was originally approved as a medicine to breakdown excess mucus in the lungs.

Evidence
In a presentation to the 2016 IACFS/ME conference Dr Dikoma Shungu of Cornell University gave a presentation on a trial of NAC in ME/CFS patients. Previously his team had found a 36% deficit of the tissue anti-oxidant occipital cortex glutathione (GSH) in the cortical areas of the brains of ME/CFS patients.

The trial supplemented patients (meeting the CDC criteria for CFS) with 1800mg daily of GSH precursor n-acetylcysteine for 4 weeks and looked at levels of cortical GSH. The study found that cortical GSH had increased in patients and that CFS symptoms (as assessed with the CDC CFS symptom inventory) were significantly reduced.

In 2020, a double-blind placebo controlled clinical trial of NAC was registered, and is due to take place at Cornell University in conjunction with NINDS, to measure the effects of 900mg and 3600mg of NAC compared to a placebo in ME/CFS patients. The trial will take part in two different locations, with the principle investigator is Dikoma Shungu. The trial aims to measure the effect of NAC on patients with ME/CFS who have low GSH levels.

Clinical use
NAC is clinically used as a mucolytic agent and antidote in case of paracetamol overdose.

AXA1125, also known as LIVRQNac, is an experimental drug, is in clinical trials for a number of different illnesses.

Learn more

 * Examine: Glutathione
 * Examine: N-acetylcysteine
 * Health Rising: Brain on Fire (October 2013)
 * N-Acetylcysteine Alleviates Cortical Glutathione Deficit and Improves Symptoms in CFS: An In Vivo Validation Study using Proton Magnetic Resonance Spectroscopy: Dikoma Shungu et al (IACFS/ME Syllabus 2016)