For more on NAC research and outcomes in schizophrenia please consider viewing the archived presentation:
“New Options in the Treatment of Negative and Cognitive Symptoms in Schizophrenia – PART 1”
N-Acetyl Cysteine, or NAC, is an antioxidant molecule that provides raw material for the production of Glutathione, the body’s master antioxidant. It is derived from cysteine, a sulfur containing amino acid that can significantly slow glutathione production by limiting supply. NAC is already used to treat many inflammatory medical conditions. Its safety profile, efficacy and lack of significant side effects make it a viable natural option for the treatment of schizophrenia.
Benefits to Negative and Cognitive Symptoms
NAC’s special properties are likely to be helpful in schizophrenia. Double-blind placebo-controlled research has demonstrated that NAC can improve both positive and negative symptoms. This may result from the fact that NAC has the capacity to correct one to the most serious issues identified in schizophrenia – the loss of fundamental antioxidant protection due glutathione depletion.
Precursor for Glutathione
Glutathione levels have repeatedly been shown to be dangerously low in schizophrenia, with reductions of 27-52% depending on the study cited or the brain region examined. Depletion is likely due to genetics affecting the glutamate-cysteine ligase gene in many cases, but there are likely multiple factors at work.
Low glutathione levels may also help explain another serious issue in schizophrenia – increased inflammation, oxidative stress and free radical formation, as evidenced by increased lipid peroxidation products. Free radical related damage is a likely contributor to the illness, and to continued deterioration over time.
NAC powerfully raises the levels of Glutathione in the body by providing the main limited precursor. In emergency rooms around the country it rescues patients at risk of acute liver failure through this exact mechanism. Increased production of glutathione adds protection to neurons under significant metabolic stress and helps to reduce the damage caused by environmental toxins and the toxic byproducts of energy metabolism.
Affecting the NMDA Receptor
NMDA Receptors are particularly affected by inflammation. It is likely that improved antioxidant protection with increased Glutathione levels affects NMDA Receptor function, but a second mechanism is also likely at work. These important receptors are known to work better in a more “reduced,” or less “oxidized” environment. As a reductant, NAC (and Glutathione) has the power to “reduce” or add electrons to other molecules, improving NMDA Receptor function at a redox level.
Berk M et al. Biol Psychiatry. 2008 Sep 1;64(5):361-8.
Description: Evaluated the safety and efficacy of adding 1 gram of NAC twice per day vs. placebo added to regular medication regimen in schizophrenia.
Design: 24-week trial with 140 patients with schizophrenia; Double Blinded and Placebo Controlled;
Considerations: Patients in this study had significant symptom severity. Many were on Clozapine, reflecting treatment resistance. This was a long study.
Results: Overall improvement in the NAC group was significant with negative symptoms showing the most improvement at 10.6%. General Symptom Severity was reduced by 9.1%. Akathisia Symptoms (Restlessness) improved by 24% while worsening in Placebo Group. There was no reported difference between Clozapine and other Neuroleptics. Effects grew significantly over 4 months, so NAC may require months to completely assess effects. There were no reported adverse effects or side effects.
Lavoie S. et al. Neuropsychopharmacology. 2008 Aug;33(9):2187-99.
Description: Looked at changes in brain electricity (EEG) called “Mismatch Negativity” (MMN) with addition of one gram of NAC vs. placebo added to current antipsychotic regimen in schizophrenia patients
Design: Randomized, Double-Blind, Placebo Controlled. 60 days with crossover to other agent for 60 more days. 11 patients with schizophrenia vs. 11 healthy controls.
Considerations: MMN is considered a measurement tool for generally assessing NMDA receptor dysfunction, which is a large contributing factor in schizophrenia. It measures brain wave changes when a repeated sound suddenly changes pitch, evoking a reaction. Decreased MMN signal strength is a common reproducible deficit in schizophrenia.
Results: NAC successfully corrected one of the major sensory deficits believed to contribute broadly to symptoms of Schizophrenia, significantly improving MMN signal over 4 times that seen with placebo (p=0.025). Results were not found to be due to differences in selective attention or ability to focus, or due to general differences in EEG power levels. NAC was also successful at significantly increasing blood levels of Glutathione (p=0.001).