The recommended dose for NAC is not simply 600mg, 1g or more has been highly recommended by pharmacologists for years. Before anyone says anything, i don't think that the doses we'd be using would warrant worry over pro-oxidant effects. I had seen some data talking about 2.4g being a daily limit but i don't know how relevant that is now.
Regardless of the baseless argument about dosing nac over 600mg, Cycle Assist still the best formulated health supp around, not to mention you can use 1 serving a day for 60 days. Good luck beating that.
I obviously take no credit for this:
Dosage/ Toxicity:
Recommended dosage of NAC has been variable. Oral dosage ranges from 200mg to 3000mg daily have been used in pulmonary conditions while a 140mg/kg-loading dose followed by fourteen 70mg/kg-maintenance doses every 4 hours have been used for acetaminophen toxicity. Typical dosing for pulmonary conditions, and preventing hepatic glutathione depletion in conditions of increased oxidant stress is 500mg 2-3 times a day between meals [2,3,18]. Nebulized NAC, is dosed at 1-10ml (20% solution) or 2-20mls (10% solution) 1-4 times a day depending on desired effect and patient response [2,3]. The nebulized tissue-specific delivery method is understandably preferred in the treatment of acute and chronic pulmonary conditions.
NAC appears to have extremely low toxicity, as animal studies using doses of 1000mg/kg/day provided no evidence of oncogenic activity [2]. NAC's LD50 is 7888mg/kg in mice and over 6000mg/kg in rats [5], however patients with advanced liver cirrhosis have decreased clearance of intravenously administered NAC, and optimal dosing in these patients needs to be determined individually [19].
NAC is not mutagenic in the Ames test, both with and without metabolic activation, and no adverse effects on fertility or teratogenic effects have been noted in animal studies at oral doses of 1000 and 500mg/kg/day respectively [3].
NAC is rated as pregnancy category B, and since it has been shown to cross the placenta with increased levels in newborn circulationfollowing delivery, use in pregnancy is either not recommended or recommended only in cases of acetaminophen toxicity [3,20].
Adverse Effects/ Contraindications:
NAC is extremely well tolerated at the doses recommended, with adverse reactions occurring in just 1.5% of patients [16]. Adverse reactions for nebulized NAC, when occurring, have included bad taste, stomatitis, nausea, vomiting, fever, rhinorrhea, drowsiness,clamminess, chest tightness, bronchoconstriction and headache [3]. Clinically overt acetyl asthmatic bronchospasm can infrequently and unpredictably occur during use of the nebulized NAC, and therefore use in asthmatics should be closely monitored [3].
Anaphylactoid reactions have been reported with intravenous delivery of NAC, although in most cases no treatment or treatment with diphenhydramine alone allowed resumption of NAC therapy [21,22].
Oral administration of N-acetylcysteine, especially in the large doses needed to treat acetaminophen toxicity, may result in headache,nausea, vomiting and other gastrointestinal symptoms. Rash with or without mild fever has been observed rarely, but a low occurrence of side effects occurs with oral dosage patterns as listed for pulmonary conditions [3].
It is not clear if NAC is passed in breast milk, but it does cross the placenta resulting in therapeutic levels in the fetal bloodstream the effects of which are unascertained. The use of NAC during pregnancy and in nursing mothers therefore should be avoided unless addressing acetaminophen toxicity [3,20]. Even in such cases, NAC administration should take place in an inpatient setting with adequate support for untoward anaphylactoid reactions.
Use of therapeutic levels of NAC is not recommended for patients with liver cirrhosis as they have been shown to have decreased clearance and resultantly may have an increased tendency for anaphylaxis compared with controls [19].
Long term use of NAC can lead to depletion of Cu and Zn through its chelating effects, which in turn can cause impaired immunefunction or frequent infections, delayed wound healing and poor collagen integrity, anemia or poor glucose tolerance, undesirable lipidstatus, decreased appetite, etc [4,23,24,25]. Therefore it is important to supplement the diet with these minerals or foods rich in these minerals if employing long term use of NAC.
Conclusion:
Although NAC has possible application in many conditions including HIV, influenza, cancer, and heart disease, it has documented efficacy in acetaminophen and heavy metal toxicity. Likewise, its use in pulmonary disease is empirically well established. Studies document NAC's efficacy in not only reducing viscosity of sputum and sputum retention, but also in potentially modulating alveolar macrophage and polymorphonuclear leukocyte activity thereby providing benefit in pulmonary infection, and/or conditions of increased pulmonary oxidant stress. NAC is well tolerated with a low incidence of side effects and toxicity, although its use in pregnancy, nursing mothers or patients with liver cirrhosis is not advised. It has documented efficacy in idiopathic pulmonary fibrosis, and fibrosing alveolitis, typically found following radiation therapy. NAC has been shown to improve subjective as well as objective parameters in chronic and acute bronchitis, as well as asthma, and emphysema, and therefore may be of benefit in the management of patients with these acute or chronic pulmonary conditions.
References:
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