N-acetylcysteine, or NAC, is a cheap over-the-counter supplement that has shown promise in treating a number of illnesses, not least among them mental illnesses. Before I show how and why this works, we need to know a little about oxidative stress and glutathione.
Normal physiological processes cause the release of free radicals, or reactive oxygen species (ROS). ROS are well known for the damage they cause to cell structures, proteins, and other substructures, and in fact an entire theory of aging has been built around this, the free radical theory of aging. (Lately that theory is appearing somewhat threadbare, but that’s for another time.) Less well known is that ROS are completely necessary for cell signaling functions. The body wants to keep ROS within a certain range, neither too high nor too low. For that purpose, the body uses glutathione, the body’s main internal antioxidant.
Glutathione is a simple tripeptide (composed of three amino acids), and can quench ROS and other free radicals. It can be recycled from it oxidized (used) state to its reduced from, which is ready to be used again. (Vitamin C is required for this recycling.) It is also made and turned over quite a bit, and using amino acids in the bloodstream to make glutathione on a daily basis is an important function of cells.
As mentioned, glutathione is made from three amino acids, but one amino acid is in short supply, the bottleneck as it were, or what biochemists call the rate-limiting amino acid, and that is cysteine, which contains sulfur. If enough cysteine is not present, glutathione cannot be made, and then bad things can happen.
While free radicals are necessary, too many of them cause damage, and then a condition of oxidative stress is said to exist. As the name implies, this is a stress on cells consisting of damage caused by free radicals. In this condition, glutathione is used up, and if enough of the materials for glutathione, particularly cysteine, cannot be supplied, then oxidative stress goes on unabated, causing or exacerbating illness and preventing recovery.
Oxidative stress is nearly synonymous with low glutathione levels, and the number of illnesses associated with low glutathione is huge. I can’t cover all of them in this article, but to take one example, oxidative stress and glutathione deficiency are prominent in AIDS, and are associated with impaired survival.
Among the illnesses associated with, caused by, or exacerbated by low glutathione levels and oxidative stress are many mental illnesses, including bipolar disorder, schizophrenia, and major depression. And to the extent that it has been considered a mental illness – although I don’t myself – chronic fatigue syndrome.
Why would this be? Well, it appears that many mental illnesses feature disrupted mitochondrial metabolism, and this can cause an increase in ROS, with subsequent oxidative stress. There’s very likely a genetic component to the brain’s susceptibility to disrupted mitochondrial function, although I (and some others) are convinced that environmental factors, including nutrition, hormesis, and stress, play a role. In any case, in mental illnesses, low glutathione levels and oxidative stress cause the brain to malfunction, with the particular manifestation of that malfunction displaying as a mental illness, whether depression, bipolar, schizophrenia, obsessive-compulsive disorders, perhaps autism, maybe even personality disorders such as psychopathy.
So, one tactic to ameliorate these mental illnesses is to control oxidative stress, which can be done by raising glutathione levels. As mentioned above, cysteine is the rate-limiting amino acid in glutathione production, and NAC supplies cysteine. (Cysteine cannot be taken in its simple form, since it is highly subject to oxidation; NAC, which does not readily oxidize, is taken up by cells and deacetylated into acetate and cysteine.)
Hence, a number of psychiatric researchers have looked into using NAC. They have found, among other things, that it may be useful in preventing relapse into shizophrenia. In a study of patients with bipolar, there was “a robust decrement in depression scores with NAC treatment”. NAC has shown promising results in patients with addiction and compulsive and grooming disorders.
Although I don’t advocate its indiscriminate use, I’ve mentioned n-acetylcysteine prominently in both my book on chronic fatigue, in which I consider it essential for managing that condition, and my book on supplements for men.
I mentioned above that I believe that diet and nutrition play a role in many mental illnesses, because diet can contribute to oxidative stress and to fixing it. Low-protein, high-carbohydrate diets can, if other conditions are right, contribute to oxidative stress. Conversely, diets higher in protein can ameliorate it by supplying the constituents of glutathione. One should especially consider whey in this light, since it contains a high fraction of cysteine. Cold-processed, undenatured whey is best for this.
Oxidative stress in parts of the brain is a feature of many mental illnesses, and NAC can have role in ameliorating this, and improving symptoms. This has been shown in a number of clinical studies. NAC is cheap and over-the-counter. You won’t hear much about it in the mainstream, since it’s not an expensive psychiatric drug promoted by Big Pharma.