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Clinical Studies
References
N-Acetyl Cysteine is a stable form of the essential amino acid L-cysteine. Cysteine is a precursor for glutathione, an important antioxidant in the body. Cysteine also serves as a major sulfur source for many body components. N-Acetyl Cysteine (NAC) has also shown the ability to improve immune function and retard aging. Other studies have shown that aged animals can have dramatic improvements in immune function after NAC supplementation.
Among the most exciting recent research are indications that NAC may be of benefit both for preventing and treating Alzheimer's disease due to it's ability to lower the toxicity and production of beta-amyloid protein. Other research has shown NAC to be particularly effective at preventing damage from light within the eye.
It may also be helpful for unstable angina, amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), high homocysteine levels, reducing risk of cardiovascular events in patients with end-stage renal disease, chronic bronchitis, chronic obstructive pulmonary disease (COPD), allergic rhinitis, head and neck cancer and lung cancer, preventing sports injury complications, increasing immunity to flu and for detoxifying heavy metals such as mercury, leadnand cadmium. It may also be helpful in alcoholic liver damage, for protecting against environmental pollutants including carbon monoxide, chloroform, urethanes and certain herbicides, as a hangover remedy and for human immunodeficiency virus (HIV).
Published Clinical Studiesclin
1
Different susceptibility to the development of nitroglycerin tolerance in the arterial and venous circulation in humans. Effects of N-acetylcysteine administration.
Ghio S, de Servi S, Perotti R, Eleuteri E, Montemartini C, Specchia G.
Division of Cardiology, IRCCS S. Matteo Hospital, Pavia, Italy.
BACKGROUND. Tolerance to the effects of organic nitrates develops rapidly during continuous exposure to these drugs; its main mechanism seems to be an intracellular sulfhydryl group depletion. However, the relative susceptibility to the development of nitroglycerin tolerance of the arterial or venous circulation in humans is still a matter of dispute. METHODS AND RESULTS. Twenty patients with coronary artery disease underwent a continuous 24-hour nitroglycerin infusion followed by a bolus administration of N-acetylcysteine. Forearm blood flow (ml/100 ml/min) and venous volume (ml/100 ml) were measured by strain gauge plethysmography under control conditions, at the end of nitroglycerin titration, after 24-hour infusion, and after N-acetylcysteine; vascular resistance was calculated as mean cuff blood pressure divided by flow. After 24 hours of nitroglycerin infusion, the initial increase in venous volume was reduced 48% (p less than 0.01), whereas the acute effects on vascular resistance were not attenuated in the whole group. N-Acetylcysteine completely restored nitroglycerin venodilator effects in all 10 patients in whom attenuation of the venous effects was observed during the infusion period. CONCLUSIONS. The data indicate that the susceptibility to the development of nitrate tolerance in humans is higher in the venous than in the arterial circulation, and that the sulfhydryl group donor N-acetylcysteine is extremely effective in reversing nitroglycerin tolerance in the venous circulation in humans.
PMID: 1516191 [PubMed - indexed for MEDLINE]
2
L-cysteine administration prevents liver fibrosis by suppressing hepatic stellate cell proliferation and activation.
Horie T, Sakaida I, Yokoya F, Nakajo M, Sonaka I, Okita K.
Pharmaceuticals Research Laboratories, Ajinomoto Co, Inc, 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki 210-8681, Japan.
Recent studies showed that the function of some amino acids is not only nutritional but also pharmacological. However, the effects of amino acids on liver fibrosis and hepatic stellate cell (HSC) remain unclear. In this research, as a result of screening of amino acids using liver fibrosis induced by DMN administration, L-cysteine was selected as a suppressor of liver fibrosis. Furthermore, the number of activated HSCs, which increased in the fibrotic liver after DMN administration, was decreased in L-cysteine-fed rats. Treatment of freshly isolated HSCs with L-cysteine resulted in inhibition of the increase in smooth muscle alpha-actin (alphaSMA) expression by HSCs and BrdU incorporation into the activated HSCs. These findings suggest that L-cysteine is effective against liver fibrosis. The mechanism of inhibition of fibrosis in the liver is surmized to be direct inhibition of activated HSC proliferation and HSC transformation by L-cysteine.
PMID: 12732201 [PubMed - indexed for MEDLINE]
Metabolic bases of amino acid requirements in acute diseases.3
Obled C, Papet I, Breuille D.
Human Nutrition Research Center Clermont-Ferrand, Unite de Nutrition et Metabolisme Proteique, INRA Theix, 63122 Ceyrat, France. obled@clermont.inra.fr
Acute diseases are characterized by a catabolic state, resulting in a negative nitrogen balance and muscle wasting. Increasing protein intake often proves to have little effect in limiting muscle protein loss. This suggests a qualitative inadequacy of the usual nutritional supports to meet the amino acid requirements of the critically ill patient. Therefore, it can be assumed that the additional intake of limiting amino acids would allow the sparing of muscle proteins. The aim of this review is to examine whether metabolic and kinetics studies using labelled amino acids can help identify the pathways activated in injury and their specific amino acid requirements. The kinetics of cysteine, arginine and glutamine, which are mainly cited as conditionally indispensable in stress situations, are presented. Moreover, amino acids can act as mediators or signal molecules and modulate numerous functions. The optimal conditions allowing the best expression of these activities are discussed.
Publication Types:
PMID: 11844987 [PubMed - indexed for MEDLINE]
4
Differentiation-specific alterations to glutathione synthesis in and hormonally stimulated release from human skeletal muscle cells.
Cotgreave IA, Goldschmidt L, Tonkonogi M, Svensson M.
Division of Biochemical Toxicology, Institute of Environmental Medicine, S-17177 Stockholm, Sweden. Ian.Cotgreave@Imm.Ki.Se
Muscle atrophy and cachexia are associated with many human diseases. These catabolic states are often associated with the loss of glutathione (GSH), which is thought to contribute to the induction of oxidative stress within the muscle. Glutathione synthesis and secretary characteristics were studied in human skeletal muscle myoblasts and myotube-like cells derived from the myoblasts by growth factor restriction. Differentiation was associated with a shift in the sulfur amino acid precursor specificity for synthesis of GSH from cystine to cysteine, as well as loss in ability to use extracellular glutathione and activation of methionine use. The thiol drug N-acetylcysteine was also shown to be an effective precursor irrespective of the state of differentiation. Additionally, myoblasts and myotube cultures were shown to secrete GSH continually, but only the differentiated cells responded to stress hormones such as glucagon, vasopressin, and phenylephrine, by increased secretion of the tripeptide. The data suggest that the skeletal muscle cells may provide an important hormonally regulated extra-hepatic source of systemic GSH and also shed light on the mechanisms of accelerated turnover of GSH operating during strenuous muscle activity and trauma. The data may also provide biochemical rationales for the nutritional and/or pharmacological manipulation of GSH with sulfur amino acid precursors during the treatment of muscle-specific oxidative stress and atrophy.
PMID: 11821257 [PubMed - indexed for MEDLINE]
Nutritional modulation of immune function.5
Grimble RF.
Institute of Human Nutrition, School of Medicine, University of Southampton, UK. rfg1@soton.ac.uk
The inflammatory response to injury and infection, although an essential part of immune function, carries the risk of severe tissue depletion and immunosuppression. These outcomes increase morbidity and delay recovery. Evidence is accumulating that single-nucleotide polymorphisms in the genes controlling pro-inflammatory cytokine production adversely influence the response. Immunonutrition provides a means of modulating the inflammatory response to injury and infection, and thereby improves clinical outcome. n-3 Polyunsaturated fatty acids (n-3 PUFA), glutamine, arginine, S amino acids and nucleotides are important components of immunonutrient mixes. While animal model studies suggest that all these components may exert a beneficial effect in patients, the number of large randomized placebo-controlled trials utilizing immunonutrition is fairly limited and the observed effects are relatively small. Meta-analyses suggest that while immunonutrition may not reduce mortality rates, a reduction in hospital length of stay, decreased requirements for ventilation and lower infection rates are achieved by this mode of nutrition. The present paper discusses some underlying reasons for the difficulty in demonstrating the clinical efficacy of immunonutrition. Paramount among these reasons is the antioxidant status and genetic background of the patient. A number of studies suggest that there is an inverse relationship between inflammation and T-cell function. Immuno-enhancive effects have been shown in a number of studies in which n-3 PUFA, glutamine and N-acetyl cysteine have been employed. All these nutrients may exert their effects by suppressing inflammation; n-3 PUFA by direct suppression of the process and glutamine and N-acetyl cysteine by acting indirectly on antioxidant status. Glutamine and nucleotides exert a direct effect on lymphocyte proliferation. Preliminary data suggests that not all genotypes are equally sensitive to the effects of immunonutrition. When further studies have been conducted to discern the precise interaction between each individual's genotype of relevance to the response to injury and infection, and immunonutrients, the level of precision in the application of immunonutrition will undoubtedly improve.
Publication Types:
PMID: 11681814 [PubMed - indexed for MEDLINE]
Nutrition and HIV.6
Lichtenstein BS.
Natural Health Clinic of Bastyr University, Seattle, WA.
AIDS: Nutritional status directly affects immune competence; therefore, dietary supplements can be beneficial. Vitamin A, a fat-soluble nutrient obtained exogenously from animal protein or synthesized endogenously from carotenoids, is important in vision, epithelial tissue maintenance, reproduction, and growth. It is also an antioxidant, and can interfere with HIV-related oxidative destruction. Vitamin C, a water-soluble antioxidant important in hydroxylation reactions and required by erythrocytes for retrieving stored iron, can suppress HIV in vitro. However, this requires long-term administration, and its effect ceases upon termination of treatment. Vitamin E, fat-soluble tocopherols, can be found in plants, vegetable oils, milk, eggs, fish, meats, and cereals. A potent antioxidant because of its electron-donating ability, vitamin E reduces HIV replication. Deficiency reduces inhibition of tumor necrosis factor alpha (TNF-a) and protein kinase C, therefore limiting immunocompetence. Additionally, damaging side effects of AZT, normally reversed or minimized by vitamin E, may induce low leukocyte counts and anemia. Vitamin E acts synergistically with selenium, another antioxidant, to block the rate of lipid peroxidation. Its administration may reduce diarrhea, cramping, and weight loss, and may improve epithelial conditions and reduce the frequency of illness. N-acetylcysteine (NAC), a sulfur-containing amino acid, inhibits HIV replication by raising serum glutathione levels through inhibition of TNF-a. Finally, HIV-infected patients should consider gluten-free diets during times of acute gastric distress.
Publication Types:
PMID: 11362399 [PubMed - indexed for MEDLINE]
Nutrients and HIV: part three - N-acetylcysteine, alpha-lipoic acid, L-glutamine, and L-carnitine.7
Patrick L.
The role of antioxidants in preventing apoptosis and viral activation in HIV is well documented. N-acetylcysteine, glutathione, and alpha-lipoic acid have been shown to interrupt the process of viral activation and CD4 cell death. L-glutamine has been shown to improve glutathione levels and significantly increase lean body mass in HIV infection. The literature on the use of L-carnitine and acetyl-L-carnitine in treating mitochondrial toxicity, both in muscle and nerve pathologies is relevant in nutritional treatment of HIV, given the mitochondrial toxicity of nucleoside analog reverse transcriptase inhibitor therapy. The current use of highly active antiviral therapies, their toxicity, and significant failure rates have created the need for a more conservative reassessment of HIV treatment. The adjunctive use of nutrient therapy in the treatment of HIV is reviewed here.
Publication Types:
PMID: 10956377 [PubMed - indexed for MEDLINE]
Referencesref