Production of free radicals is a determinant of performance and fatigue
One of the crucial determinants of fatigue is the production of radical oxygen species (ROS, also known as free radicals) and internal antioxidant status, the latter mainly consisting of total, reduced, and oxidized glutathione. Glutathione is a tripeptide consisting of three amino acids, and the rate-limiting amino acid – the bottleneck to production – is cysteine. So, if more cysteine is provided, more glutathione will be produced. N-acetylcysteine, the cheap over-the-counter supplement, provides cysteine, which cannot be taken in its native form due to high potential for oxidation.
When one performs any kind of intense or prolonged exercise, a large quantity of ROS is generated, and it’s mainly glutathione that mops them up and keeps the body from entering a condition of oxidative stress. Glutathione can be thought of as an exercise buffer. But when it is depleted, the body is overwhelmed with ROS, and fatigue ensues.
N-acetylcysteine increases glutathione
The main function of n-acetylcysteine (NAC) is to increase glutathione levels. When ingested, it is rapidly taken up by cells, de-acetylated to cysteine, and then used in glutathione production. Since NAC does this, and since glutathione is a determinant of fatigue, it follows that NAC should increase exercise performance.
N-acetylcysteine significantly increases endurance and time to fatigue
Lo and behold, NAC does work this way: N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals. In this study, trained cyclists who received NAC increased their endurance performance, that is, time to fatigue, by a remarkable 26%. NB: the cyclists received a lot of NAC, in fact a constant IV infusion.
Another study that used a special type of whey as a cysteine donor found increased peak power and 30-second work capacity: Effect of supplementation with a cysteine donor on muscular performance.
And in a study on rats, those that had a glutathione deficiency had a 50% reduced endurance performance.
Fatigue of any kind is related to glutathione levels
In my book on chronic fatigue, I discuss at some length the relation between chronic fatigue and glutathione levels, which is critically important for those suffering from long-term fatigue from any cause. NAC can be of help in that condition as well. So we see that fatigue, whether from unknown cause, illness, bad nutrition, or prolonged exercise is related to glutathione. This is not the sole determinant of fatigue, but an important one.