N-Acetylcysteine (NAC) protects the brain
NAC tends to raise or lower various neurotransmitters based on the circumstance, primarily, glutamate and dopamine. In situations where one of these neurotransmitters is lacking, NAC can elevate levels. If in excess, NAC can lower levels. Hence, NAC can act as a master "stabilizing" agent.
NAC also serves as an efficient precursor to our master antioxidant, glutathione, which serves a vital role in structurally protecting the brain. Part of that role is to protect the mitochondria, which can become damaged and cease energy production without sufficient glutathione. This also gives it a powerful anti-inflammatory effect.
Clinical trials have also shown that NAC can help in cases of
- ADHD
- anxiety
- depression
- post traumatic stress disorder (PTSD)
- inflammation
Currently NAC has the most evidence of having a beneficial effect as an adjuvant agent in the negative symptoms of severe autism, depression, and obsessive compulsive and related disorders. Future research with well-powered studies that are of sufficient length will be critical to better understand the utility of NAC in the treatment of such disorders.
NAC has multiple relevant actions including
- antioxidant effects
- reduction of cytokine activity
- modulation of dopamine release
- reversal of mitochondrial dysfunction
- reductions in apoptosis and ferroptosis
- anti-inflammatory activity
- increased neurogenesis, and
- increased glutamate release
Perhaps the most important of these for the treatment of psychiatric disorders is its antioxidant activity, which it achieves through multiple mechanisms. NAC functions as an antioxidant through
- stimulating the synthesis of glutathione
- enhancing glutathione-S-transferase activity
- scavenging free radicals, and
- stimulating group II metabotropic glutamate receptors to decrease glutamate transmission
Glutathione is the primary antioxidant in the brain. Its production rate is limited by L-cysteine availability, so increasing the supply of L-cysteine via NAC supplementation leads to an increase in brain glutathione.
Antioxidants reduce oxidative stress, which is implicated in the pathogenesis of many mental disorders. Oxidative stress represents a state in which there is an imbalance between reactive oxygen species (ROS), such as hydrogen peroxide, superoxide, and peroxynitrite, and tissue redox defenses. It can be the result of having increased reactive oxygen species, decreased antioxidant defenses, or unrepaired oxidative damage.
Reactive oxygen species (ROS) cause
- cellular lipid peroxidation
- inactivation of important enzymes
- malfunction of the respiratory chain, and
- DNA modification
Antioxidant enzymes, such as superoxide dismutase, glutathione reductase and peroxidase, metabolize reactive oxygen species into less toxic molecules, protecting the brain from harms caused by oxidative stress. Severe prolonged oxidative stress can lead to glutathione depletion and is linked to mitochondrial dysfunction, which NAC has been also shown to prevent.