More rational on this topic is found in following link. I have been taking NAC following this rational. I hope to have comments on this and if any body is taking NAC
http://www.ninds.nih.gov/funding/res...maries/nac.htm
N-ACETYL-CYSTEINE
N-Acetyl-Cysteine (NAC) is a precursor of glutathione (which used to prevent oxidative stress in most cells and helps to trap free radicals that can damage DNA and RNA in the body), and a protected sulfur-containing amino acid. It is a modified form of the amino acid cysteine and is commonly used in hospitals both to help break down mucus and to protect from acetaminophen toxicity. NAC shows no adverse effects more common than in placebo except perhaps headache however can cause nausea, and vomiting at higher doses.
Scientific Rationale
NAC is a precursor of glutathione and is a thiolic antioxidant. Glutathione (GSH) is markedly reduced in the substantia nigra (SN) early in PD, even before there is a detectable complex I defect. Decreased GSH has even been reported in Lewy body disease.1,2 GSH depletion has been hypothesized to result from oxidative stress. Many studies have demonstrated increased markers of oxidative damage in the SN in PD. However, experimental GSH depletion has been shown to induce a defect specifically in complex I.3
NAC also may be neuroprotective through:
scavenging reactive oxygen species
inhibiting apoptosis through interference with c-fos, c-jun, TGFb
increasing complex I, IV and V activity ( mitochondrial oxidative phosphorylation)4,5,6
Glutathione protects human neuronal cells from DA-induced apoptosis.7 However, high-dose NAC (1 g/kg IP) in rats caused a depletion of brain glutathione.8
1. Dexter DT, Ann Neurol 1994;35:38-44.
2. Jenner P. Acta Neurol Scand Suppl 1993;146:6-13.
3. Jha N. J Biol Chem 2000;275:26096-101.
4. Banaclocha, Med Hypotheses 2001;56: 472-477
5. Martinez, Life Sciences 1999; 64: 1253-1257
6. Banaclocha, Brain Res 2000; 859:173-175
7. Gabbay, Neurpharm 1996;35:571-578
8. Vina, Experientia 1983;39:164-165
Animal Model Data
RODENT: Subcutaneous (SC) NAC (500mg/kg) injected once daily for 5 days partially protected against SN dopamine depletion induced by a single SC injection of MPTP on the 3rd day in mice. Mice fed ad libitum with pellets containing 0.3% NAC had significantly lower levels of protein carbonyls18 and increased complex I activity19 in brain synaptic mitochondria. A significant increase in GSH concentrations was not detected, consistent with theories that NAC may act, in part, by acting directly as an antioxidant.
1. Perry, Neurosci Lett 1985;60:109-114
2. Banaclocha MM, Brain Res 1997;762:256-8.
Pharmacokinetics (including blood brain barrier (BBB) penetration)
Unknown BBB penetration in humans, but there is evidence that low concentrations of NAC are achieved in the brain 2 hours after systemic administration in laboratory animals1,2 T ½ is 6.25 h after oral administration to healthy volunteers. The oral bioavailability is 9.1%.3
1. Banaclocha, Med Hypotheses 2001;56: 472-477
2. Martinez, Life Sciences 1999; 64: 1253-1257
3. Olsson, Eur J Clin Pharmacol 1988; 34:77-82
Safety/Tolerability in Humans
In a double-blind, placebo-controlled randomized trial involving 43 Alzheimer's patients given either 50 mg/kg/day orally or placebo, there were no adverse effects more common than in placebo (except perhaps headache). In APAP overdose, 140 mg/kg load followed by 70 mg/kg q4 hours x 17 doses is used. At this dosage, NAC can cause nausea, vomiting and sometimes generalized urticaria.Highest nontoxic dosage in normal volunteers was determined to be 800 mg/m2. Major toxicities at higher doses were bad taste and gastrointestinal disturbances. NAC also has been tested in HIV-infected humans. A double-blind, placebo-controlled randomized trial tested oral NAC in HIV-infected patients with evidence for decreased GSH levels in lymphocytes but without active opportunistic infections. Subjects were given 10 tablets of NAC (800mg/tablet) per day divided in 3 or 4 doses for 8 weeks. As in the Alzheimer's disease trial, adverse effects in this trial were minimal. Some subjects reduced the dose due to side effects, with the average dosage by the end of the trial being 6.3 grams/day however the reduction in "dose" was similar for the placebo arm. NAC treatment was associated with a significant increase in GSH concentration in lymphocytes.
1. Adair, Neurology 2001;57:1515-1517
2. Mosby's Drug Consult, 2002
3. Pendyala, Cancer Epid Biomarkers and prevention 1995; 4:245-251
3. De Rosa SC, Zaretsky MD, Dubs JG, et al. N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest 2000;30:915-29.
Drug Interaction Potential
UNKNOWN
Clinical Trial/Epidemiological Evidence in Human PD
NONE
Last updated February 09, 2005