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N-acetylcysteine Clinical Studies

  1. Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease

    John C. Adair, MD; Janice E. Knoefel, MD; and Nancy Morgan, RPh
    Neurology. 2001;57:1515-1517.

    Abstract
    The antioxidant N-acetylcysteine (NAC) or placebo was administered in a double-blind fashion to patients who met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable AD. Testing for efficacy occurred after 3 and 6 months of treatment. Comparison of interval change favored NAC treatment on nearly every outcome measure, although significant differences were obtained only for a subset of cognitive tasks.

  2. Plasma homocysteine and thiol compound fractions after oral administration of N-acetylcysteine

    B. Hultberg, A. Andersson, P. Masson, M. Larson and A. Tunek
    Scand J Clin Lab Invest 1994;54:417-422.

    Abstract
    The total concentration of the atherogenic aminothiol acid homocysteine in plasma of healthy volunteers was decreased after oral administration of N-acetylcysteine (NAC), whereas the reduced and free (non-protein bound) fractions of homocysteine were increased. The decrease of the total fraction varied between 20 and 50% and was dose-related. Cysteinylglycine was also decreased afer the administration of NAC, whereas cysteine did not change. Administration of high amounts of NAC probably displaces homocysteine and cysteinylglycine from their protein binding sites by disulfide interchange reactions. This leads to the formation of mixed low molecular-weight cysteine and NAC disulfides with high renal clearance and possible also increased metabolic bio-availability, thereby eliminating homocysteine and cysteinylglycine from plasma. Since only a small amount of additional urinary homocysteine was recovered it is likely that this aminothiol acid is taken up by the tubular cells and further metabolized.

  3. Clinical Applications of N-acetylcysteine

    Gregory S. Kelly, N.D.
    Alt Med Rev 1998;3(2):114-127
    http://www.thorne.com/pdf/journal/3-2/n_acetylcysteine.pdf

    Abstract
    N-acetylcysteine (NAC), the acetylated variant of the amino acid L-cysteine, is an excellent source of sulfhydryl (SH) groups, and is converted in the body into metabolites capable of stimulating glutathione (GSH) synthesis, promoting detoxification, and acting directly as free radical scavengers. Administration of NAC has historically been as a mucolytic agent in a variety of respiratory illnesses; however, it appears to also have beneficial effects in conditions characterized by decreased GSH or oxidative stress, such as HIV infection, cancer, heart disease, and cigarette smoking. An 18- dose oral course of NAC is currently the mainstay of treatment for acetaminophen induced hepatotoxicity. N-acetylcysteine also appears to have some clinical usefulness as a chelating agent in the treatment of acute heavy metal poisoning, both as an agent capable of protecting the liver and kidney from damage and as an intervention to enhance elimination of the metals.

  4. Co-administration of N-acetylcysteine, vitamin B12 and folate in cognitively impaired hyperhomocysteinaemic patients.

    McCaddon A, Davies G.
    International Journal of Geriatric Psychiatry. 2005;20(10):998-1000.

    Abstract not available

  5. Homocysteine and cognitive impairment; a case series in a General Practice setting

    Andrew McCaddon
    Nutrition Journal. 2006;5:6 http://www.nutritionj.com/content/5/1/6

    Abstract
    Background: An elevated blood level of homocysteine is a risk factor for cognitive impairment and dementia. Homocysteine can be lowered by folate and/or vitamin B12 supplementation; antioxidants might also be required for optimal reduction in neurovascular tissue. This report presents clinical and radiological findings from administering the antioxidant N-acetylcysteine together with B vitamins to cognitively impaired patients with hyperhomocysteinaemia.

    Methods: A case series (n = 7) performed in a semi-rural General Practice setting. Formal cognitive assessments were performed in five patients, and radiological assessments in one patient, before and after supplementation.

    Results and discussion: The addition of N-acetylcysteine resulted in subjective clinical improvement in all patients, and an objective improvement in cognitive scores in five patients. One patient had radiological evidence of halted disease progression over a twelve month period.

    Conclusion: N-acetylcysteine, together with B vitamin supplements, improves cognitive status in hyperhomocysteinaemic patients. Randomized controlled clinical trials are required to formally evaluate this treatment approach.

  6. Congeners Of NGAMMA-Acetyl-L-Cysteine But Not Aminoguanidine Act As Neuroprotectants From The Lipid Peroxidation Product 4-Hydroxy-2-Nonenal

    M. Diana Neely, Lisa Zimmerman, Matthew J. Picklo, Joyce J. Ou, Catha R. Morales, Kathleen S. Montine, Venkataraman Amaranth, and Thomas J. Montine
    Free Radical Biology & Medicine, Vol. 29, No. 10, pp. 1028-1036, 2000

    Abstract
    Increased generation of neurotoxic lipid peroxidation products is proposed to contribute to the pathogenesis of Alzheimer's disease (AD). Current antioxidant therapies are directed at limiting propagation of brain lipid peroxidation. Another approach would be to scavenge the reactive aldehyde products of lipid peroxidation. NGAMMA-acetyl-L-cysteine (NAC) and aminoguanidine (AG) react rapidly and irreversibly with 4-hydroxy-2-nonenal (HNE) in vitro, and both have been proposed as potential scavengers of HNE in biological systems. We have compared NAC, AG, and a series of congeners as scavengers of HNE and as neuroprotectants from HNE. Our results showed that while both NAC and AG had comparable chemical reactivity with HNE, only NAC and its congeners were able to block HNE-protein adduct formation in vitro and in neuronal cultures. Moreover, NAC and its congeners, but not AG, effectively protected brain mitochondrial respiration and neuronal microtubule structure from the toxic effects of HNE. We conclude that NAC and its congeners, but not AG, may act as neuroprotectants from HNE.

  7. Urinary and Plasma Homocysteine and Cysteine Levels during Prolonged Oral N-acetylcysteine Therapy

    Paolo Ventura, Rossana Paninib, Gianluca Abbatia, Germano Marchettia, and Gianfranco Salviolib
    Pharmacology. 2003;68(2):105-14

    Abstract
    Acute administration of N-acetylcysteine (NAC) may induce alterations in plasma and urinary levels of homocysteine (Hcy) and cysteine (Cys). We studied the effects of continuous oral NAC therapy on different Hcy and Cys plasma and urinary forms in 40 healthy subjects assigned to three groups (groups A: n = 13, no therapy; group B: n = 14, NAC 600 mg/day, and group C: n = 14, NAC 1,800 mg/day) for 1 month (T1). After a 1-month washout period without therapy (T2), all subjects were treated with oral NAC (1,800 mg/day) for 2 months and (T3 and T4) reassessed monthly for plasma and urinary thiols. The treated subjects showed a significant decrease in plasma total Hcy and a slight increase in total Cys levels; the alterations of different forms of plasma thiols suggested an NAC-induced increase in disulfide forms and an increase in urinary Hcy and Cys excretion as disulfide forms. The effects appeared to be dose dependent, being more marked in subjects treated with higher dosages. This approach may be important, as an association or alternative therapy in hyperhomocysteinemic conditions of poor responses to vitamins.

  8. N-acetylcysteine treatment lowers plasma homocysteine but not serum lipoprotein(a) levels

    Olov Wiklund, Gunnar Fager, Anders Andersson, Ulf Lundstam, Parvesh Masson, Bjiirn Hultberg
    Atherosclerosis 119 (1996) 99-106

    Abstract
    High levels of lipoprotein(a) (Lp(a)) or homocysteine in plasma have both been associated with an increased risk for premature cardiovascular disease. For both components, the plasma levels are primarily genetically determined, and they have been very restintant to therapeutic approaches. It has been suggested that N-acetylcysteine (NAC) breaks disulphide bonds in Lp(a) as well as between homocysteine and plasma proteins. In the present study we analyze if this mechanism, in vivo, could be used to lower plasma concentrations of Lp(a) and homocysteine. Treatment with NAC and placebo was performed in a double blind cross over design with 2 weeks wash-out between treatments. Eleven subjects with high plasma Lp(a) ( > 0.3 g/l) were recruited from the Lipid Clinic at Sahlgren's Hospital, Goteborg, Sweden. Main outcome measures were treatment effects on plasma Lp(a) and plasma amino thiols (homocysteine, cysteine and cysteinyl glycine). There was no significant effect on plasma Lp(a) levels. Plasma thiols were significantly reduced during treatment with NAC: homocysteine by 45% (P < 0.0001), cysteinyl glycine by 24% (P < 0.0001) and cysteine by 11% (P = 0.0002). The high dose of NAC was well tolerated. In conclusion NAC has no effect on plasma Lp(a) levels while the reduction in homocysteine is considerable and might be of clinical significance in cases with high plasma homocysteine levels.