N-Acetylcysteine (NAC)

 syn. N-acetyl-L-cysteine
 syn. mercapturic acid





 Description:
 N-acetylcysteine (NAC) is the n-acetyl derivative of the amino acid L-cysteine. It serves as a precursor in the synthesis of glutathione, one of the body’s primary antioxidant (free radical scavenging) molecules. N-acetylcysteine itself is considered to be a potent antioxidant, and may directly and indirectly help protect body tissues from oxidative damage. NAC is also regarded as an immunostimulatory compound,466 and might help increase resistance to viral or bacterial infection. The potential health benefits of NAC supplementation are the subject of much ongoing research. In sports nutrition, n-acetylcysteine is commonly used to reduce oxidative stress subsequent to heavy training, and to increase exercise endurance.


 N-acetylcysteine is sold as a drug product in many countries, and prescribed for a number of ailments. For example, it is commonly used to reduce the thickness of mucous in patients with pneumonia, flu, bronchitis, or other forms of respiratory congestion. It acts by breaking some of the protein disulfide bonds holding the mucous together. NAC is also widely used to protect and detoxify the liver, and even to treat cases of acetaminophen overdose or toxicity. It is also used to prevent kidney toxicity during contrast imaging in patients with impaired renal function. In addition to its accepted clinical uses, n-acetylcysteine is also being investigated for a host of other health conditions including cognitive dysfunction, diabetes, HIV infection, and cystic fibrosis.

 While n-acetylcysteine has been the subject of compelling clinical studies with regard to ergogenic properties, specifically demonstrating an ability to reduce muscle fatigue in exercising adults, these investigations have tended to involve continuous intravenous (IV) infusions of NAC during exercise, which are impractical for general use. Additional research does suggest that the oral use of n-acetylcysteine supplements can also impart performance-enhancing benefits in exercising individuals. However, further research is needed to validate (and better understand) these potential properties of oral n-acetylcysteine.

 Promoted Benefits:
 N-acetylcysteine is promoted to reduce fatigue and increase muscle endurance during prolonged exercise.

 Clinical Studies:
 This ingredient has been shown in human placebo-controlled studies to improve metabolic markers (respiratory muscle fatigue, erythropoietin, hemoglobin) linked to positive changes in body composition or performance. It’s Clinical Support Rating is 3 (3/5).
 One placebo-controlled study examined the effects of oral n-acetylcysteine on various blood parameters in a group of healthy adults.467 A dosage of 1,200 mg was used, which was taken for a period of eight days. The supplementation of NAC was shown to increase erythropoietin levels by 26%. This hormone stimulates the production of red blood cells. This result was accompanied by a 9% increase in both hemoglobin and hematocrit, representing a tangible increase in oxygen carrying capacity. This effect should enhance aerobic exercise performance.

 Another placebo-controlled investigation looked at the effects of oral NAC on respiratory muscle fatigue during heavy exercise.468 Subjects consumed 1,800 mg of n-acetylcysteine and exercised for 30 minutes at 85% maximum oxygen consumption (VO2max). Measurements of respiratory pressure were taken at rest and every five minutes during exercise. The supplementation of n-acetylcysteine maintained 14% higher inhalation pressure at 25 and 30 minutes of exercise, suggesting reduced respiratory fatigue. Studies have shown that respiratory muscle fatigue and reduced inhalation pressure can impair oxygen uptake and exercise performance.469
 In addition to these oral supplementation studies, there have been a number of positive investigations with the intravenous infusion of n-acetylcysteine with exercise.470,471,472 One of the most widely referenced studies examined the effects on NAC on exercise performance in a group of well-trained adults.473 Subjects were given a 15-minute IV infusion of n-acetylcysteine beginning 20 minutes prior to exercise. The rate of delivery was 125 mg/kg per hour. After 15 minutes this was switched to a rate of 25 mg/kg per hour, which continued throughout exercise. The subjects were evaluated with the use of a stationary cycle ergometer, and initially performed at 71% peak oxygen consumption (VO2peak) for 45 minutes. This was followed by a cycle sprint at 92% VO2peak until exhaustion. The subjects that were given n-acetylcysteine improved their time to exhaustion by an average of 23.8% compared to those given placebo.
 While these results suggest ergogenic action with oral n-acetylcysteine, further research is needed to confirm such activity, and to understand the most ideal applications for using this supplement.
 Empirical Evidence:
 N-acetylcysteine is widely available as a stand-alone nutritional supplement. The feedback on its use as a sport supplement tends to be positive. Most athletic users seem to notice a reduction in muscle fatigue during exercise, especially those subject to prolonged endurance-type activities. NAC is also widely used by athletes and bodybuilders as a general health-supporting supplement, given its strong ability to act as an antioxidant and liver detox agent. While the feedback on this supplement is generally positive, many other users feel NAC offers no tangible ergogenic value. Whether this is due to an individual insensitivity to the supplement, or particular applications in which it is, and is not, metabolically useful, remains unclear. N-acetylcysteine has an Empirical Evidence Rating of 4 (4/5).

 Effective Dosage:
 Based on clinical studies, a dosage of 1,200-1,800 mg per day is recommended.

 Side Effects / Safety:
 N-acetylcysteine was well tolerated during clinical studies, with few side effects reported. A small percentage of users appear to notice dermatological issues (rash, itch, and skin allergy) and/or gastrointestinal distress (loose stool, nausea, diarrhea, vomiting). The effects of chronic high dose NAC supplementation are unknown.