NAC is one of the most studied of all supplements. Interest in it began during the 1960s when it was found to be useful to people with cystic fibrosis and other pulmonary ailments. In the 1990s medical researchers took a strong interest in it as an anti-HIV treatment, and it has been in the spotlight ever since.
N-acetylcysteine (NAC) is converted in the body to the amino acid L-cysteine — a building block for the production of countless proteins needed by the body. While NAC supplementation undoubtedly provides the body with all the benefits that derive from L-cysteine, the principal reason it is used as a supplement is to increase the body’s production of glutathione — a very important antioxidant that protects cells from being damaged or killed by certain metabolic byproducts.
The list of medical applications of NAC is a very long one, and these applications fall into a variety of categories:
NAC is an inexpensive supplement that is safe and easy to obtain — so it would be foolish not to take advantage of it.
N-acetylcysteine (NAC) is a substance which is converted in the body to the amino acid L-cysteine. For reasons that are poorly understood, L-cysteine itself is neurotoxic when taken as a supplement; this toxicity is avoided by using NAC instead.1
L-cysteine, like the other standard amino acids, is a building block for the production of countless proteins needed by the body: enzymes, structural proteins, signalling molecules and their receptors, and a number of small polypeptide molecules with specialized functions. One such polypeptide is the tripeptide called ‘glutathione’ (GSH), a very important antioxidant that protects cells from being damaged or killed by certain metabolic byproducts.2
While NAC supplementation undoubtedly provides the body with all the benefits that derive from L-cysteine, the principal reason it is used as a supplement is to raise glutathione levels.
A good review of NAC and its medical applications is the one by Thorne Research3. Since NAC is a precursor for the body’s production of glutathione, Wikipedia’s article on glutathione2 is relevant for understanding why NAC has such a broad range of actions. The review by Arakawa and Ito4, of NAC’s value in preventing or treating neurodegenerative diseases, also makes good reading. A technically written review of what is known about NAC’s mechanisms of action is found in the article by Zafarullah, et al.5
In the U.S. and some other industrialized countries, government agencies like the U.S. Food and Drug Administration have adopted censorship as a method for intensifying their control over the supplement industry and its customers. Thus, FDA regulations prohibit us from telling you that any of our products are effective as medical treatments, even if they are, in fact, effective.
Accordingly, we will limit our discussion of N-acetylcysteine to a brief summary of relevant research, and let you draw your own conclusions about what medical conditions it may be effective in treating.
NAC is one of the most studied of all supplements. Interest in it began during the 1960s when it was found to be useful as a ‘mucolytic’ agent — i.e., it lowers the viscosity of mucus in the respiratory tract, assisting people with cystic fibrosis and other pulmonary ailments.6 In the early 1990s medical researchers took a strong interest in it as an anti-HIV treatment,7 and it has been in the spotlight ever since.
The list of medical applications of NAC is a very long one, as can be seen from the outline that follows.
Pulmonary and respiratory ailments:
Accelerated aging:
Neurodegenerative diseases:4,23
Other neurological conditions:
Muscle-degenerative conditions:
Cancer:
Cardiovascular ailments:
Addictions:
Immune system problems:
Infections:
Toxicity:
Other applications:
These are far too many applications to discuss in detail, so let us just look at one of them, as an example of the medical power of this supplement: the prevention of vascular damage caused by dietary AGEs — chemicals created in food by cooking.
Whenever food is cooked, some of the sugars in the food are converted into substances called ‘AGEs’ (Advanced Glycation Endproducts).79 These are inflammatory chemicals that, when consumed, cause damage to the walls of arteries and veins, as well as accelerated aging in other tissues in the body. The body actually produces its own AGEs, but usually in smaller amounts than are found in the diet. Diabetics, however, often have higher levels of sugar in their blood, and so AGEs are produced in larger amounts in these people. The total AGE burden is therefore much higher in diabetics.
In an important 2004 paper, researchers at Mount Sinai School of Medicine showed that diabetics experience substantially less damage to arteries when their consumption of AGEs is reduced.21 The research also showed that NAC interferes with a key process through which AGEs produce inflammation and tissue damage. Interestingly, this research project was motivated by the idea that atherosclerosis can be prevented by reducing dietary AGEs, not the idea that NAC can be used to counteract the effects of high AGE consumption. Yet NAC did, in fact, prevent AGEs from damaging vascular cells.
This is just one example of NAC’s far-ranging effects on harmful processes taking place in the body. NAC is an inexpensive supplement that is safe and easy to obtain — so it would be foolish not to take advantage of it.
Are N-acetylcysteine supplements useful for the conditions and purposes mentioned above? We aren’t allowed to tell you, so you should take a look at some of the references cited here, and then decide for yourself.
[1] Neurotoxicity of cysteine: interaction with glutamate. Brain Res. 1995 Dec 24; 705(1-2):65-70 Puka-Sundvall M, Eriksson P, Nilsson M, Sandberg M, Lehmann A
[2] Glutathione Wikipedia website
[3] N-acetylcysteine. Altern Med Rev. 2000 Oct; 5(5):467-71
[4] N-acetylcysteine and neurodegenerative diseases: Basic and clinical pharmacology. Cerebellum. 2007 Jan 19; :1-7 Arakawa M, Ito Y
[5] Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci 2003 Jan;60(1):6-20 Zafarullah M, Li WQ, Sylvester J, Ahmad M
[6] THE USE OF N-ACETYLCYSTEINE IN THE TREATMENT OF CYSTIC FIBROSIS. South Med J. 1963 Nov; 56:1271-8 REAS HW
[7] N-acetylcysteine: a new approach to anti-HIV therapy. AIDS Res Hum Retroviruses. 1992 Feb; 8(2):209-17 Roederer M, Ela SW, Staal FJ, Herzenberg LA, Herzenberg LA
[8] Improvement by N-acetylcysteine of acute respiratory distress syndrome through increasing intracellular glutathione, and extracellular thiol molecules and anti-oxidant power: evidence for underlying toxicological mechanisms. Hum Exp Toxicol. 2007 Sep; 26(9):697-703 Sadegh Soltan-Sharifi M, Mojtahedzadeh M, Najafi A, Reza Khajavi M, Reza Rouini M, Moradi M, Mohammadirad A, Abdollahi M
[9] Blesa S, Cortijo J, Mata M, Serrano A, Closa D, Santangelo F, Estrela JM, Suchankova J, Morcillo EJ Oral N-acetylcysteine attenuates the rat pulmonary inflammatory response to antigen.
[10] [N-acetylcystein in the therapy of chronic bronchitis] Pneumologie. 2002 Dec; 56(12):793-7 Reichenberger F, Tamm M
[11] Effect of N-acetylcysteine on neutrophil activation markers in healthy volunteers: in vivo and in vitro study. Pharmacol Res. 2006 Mar; 53(3):216-25 Sadowska AM, Manuel-y-Keenoy B, Vertongen T, Schippers G, Radomska-Lesniewska D, Heytens E, De Backer WA
[12] Does oxidative stress alter quadriceps endurance in chronic obstructive pulmonary disease? Am J Respir Crit Care Med. 2004 May 1; 169(9):1022-7 Koechlin C, Couillard A, Simar D, Cristol JP, Bellet H, Hayot M, Prefaut C
[13] Respiratory and allergic diseases: from upper respiratory tract infections to asthma. Prim Care 2002 Jun;29(2):231-61 Jaber R
[14] [Medical maintenance treatment of chronic obstructive pulmonary disease (COPD)] Ned Tijdschr Geneeskd 2002 Aug 31;146(35):1631-5 Kerstjens HA, Postma DS
[15] [Mucolytics in acute and chronic respiratory tract disorders. II. Uses for treatment and antioxidant properties] Pol Merkuriusz Lek 2002 Mar;12(69):248-52 Kupczyk M, Kuna P
[16] [Pulmonary fibrosis--a therapeutic dilemma?] Med Klin (Munich). 2006 Apr 15; 101(4):308-12 Günther A, Markart P, Eickelberg O, Seeger W
[17] High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2005 Nov 24; 353(21):2229-42 Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen HM, MacNee W, Thomeer M, Wallaert B, Laurent F, Nicholson AG, Verbeken EK, Verschakelen J, Flower CD, Capron F, Petruzzelli S, De Vuyst P, van den Bosch JM, Rodriguez-Becerra E, Corvasce G, Lankhorst I, Sardina M, Montanari M
[18] Oxygen therapy at low flow causes oxidative stress in chronic obstructive pulmonary disease: Prevention by N-acetyl cysteine. Free Radic Res. 2005 Oct; 39(10):1111-8 Foschino Barbaro MP, Serviddio G, Resta O, Rollo T, Tamborra R, Elisiana Carpagnano G, Vendemiale G, Altomare E
[19] New developments in the treatment of COPD: comparing the effects of inhaled corticosteroids and N-acetylcysteine. J Physiol Pharmacol. 2005 Sep; 56 Suppl 4:135-42 van Overveld FJ, Demkow U, Górecka D, de Backer WA, Zielinski J
[20] High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis. Proc Natl Acad Sci U S A. 2006 Mar 21; 103(12):4628-33 Tirouvanziam R, Conrad CK, Bottiglieri T, Herzenberg LA, Moss RB, Herzenberg LA
[21] High levels of dietary advanced glycation end products transform low-density lipoprotein into a potent redox-sensitive mitogen-activated protein kinase stimulant in diabetic patients. Circulation. 2004 Jul 20; 110(3):285-91 Cai W, He JC, Zhu L, Peppa M, Lu C, Uribarri J, Vlassara H
[22] Can antioxidant diet supplementation protect against age-related mitochondrial damage? Ann N Y Acad Sci 2002 Apr;959:508-16 Miquel J
[23] Therapeutic potential of N-acetylcysteine in age-related mitochondrial neurodegenerative diseases. Med Hypotheses 2001 Apr;56(4):472-7 Banaclocha MM
[24] Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease. Cochrane Database Syst Rev. 2007; (1):CD002829 Orrell RW, Lane RJ, Ross M
[25] [New approaches to antioxidant therapy in multiple sclerosis] Zh Nevrol Psikhiatr Im S S Korsakova. 2002; Suppl:72-5 Odinak MM, Bisaga GN, Zarubina IV
[26] Advanced glycation endproducts cause lipid peroxidation in the human neuronal cell line SH-SY5Y. J Alzheimers Dis 2003 Feb;5(1):25-30 Gasic-Milenkovic J, Loske C, Munch G
[27] The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. J Neurochem 2003 Mar;84(5):1173-83 Farr SA, Poon HF, Dogrukol-Ak D, Drake J, Banks WA, Eyerman E, Butterfield DA, Morley JE
[28] Antioxidants inhibit the human cortical neuron apoptosis induced by hydrogen peroxide, tumor necrosis factor alpha, dopamine and beta-amyloid peptide 1-42. Free Radic Res 2002 Nov;36(11):1179-84 Medina S, Martinez M, Hernanz A
[29] H(2)o(2) and 4-hydroxynonenal mediate amyloid beta-induced neuronal apoptosis by activating jnks and p38(mapk). Exp Neurol 2003 Apr;180(2):144-55 Tamagno E, Robino G, Obbili A, Bardini P, Aragno M, Parola M, Danni O
[30] Pigment epithelium-derived factor prevents advanced glycation end products-induced monocyte chemoattractant protein-1 production in microvascular endothelial cells by suppressing intracellular reactive oxygen species generation. Diabetologia 2003 Feb;46(2):284-7 Inagaki Y, Yamagishi S, Okamoto T, Takeuchi M, Amano S
[31] Graded sensitiveness of the various retinal neuron populations on the glyoxal-mediated formation of advanced glycation end products and ways of protection. Graefes Arch Clin Exp Ophthalmol 2003 Mar;241(3):213-25 Reber F, Geffarth R, Kasper M, Reichenbach A, Schleicher ED, Siegner A, Funk RD
[32] N-acetyl-L-cysteine improves outcome of advanced cerebral adrenoleukodystrophy. Bone Marrow Transplant. 2007 Feb; 39(4):211-5 Tolar J, Orchard PJ, Bjoraker KJ, Ziegler RS, Shapiro EG, Charnas L
[33] Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008 Jan 21; :1-26 Ng F, Berk M, Dean O, Bush AI
[34] Protection from noise-induced lipid peroxidation and hair cell loss in the cochlea. Brain Res 2003 Mar 21;966(2):265-73 Ohinata Y, Miller JM, Schacht J
[35] Chronic fatigue syndrome: oxidative stress and dietary modifications. Altern Med Rev 2001 Oct;6(5):450-9 Logan AC, Wong C
[36] The treatment of complex regional pain syndrome type I with free radical scavengers: a randomized controlled study. Pain. 2003 Apr; 102(3):297-307 Perez RS, Zuurmond WW, Bezemer PD, Kuik DJ, van Loenen AC, de Lange JJ, Zuidhof AJ
[37] N-Acetyl cysteine protects against injury in a rat model of focal cerebral ischemia. Brain Res 2003 May 2;971(1):1-8 Sekhon B, Sekhon C, Khan M, Patel SJ, Singh I, Singh AK
[38] Treatment of four siblings with progressive myoclonus epilepsy of the Unverricht-Lundborg type with N-acetylcysteine. Neurology. 1996 Nov; 47(5):1264-8 Hurd RW, Wilder BJ, Helveston WR, Uthman BM
[39] Mechanical stress activates the nuclear factor-kappaB pathway in skeletal muscle fibers: a possible role in Duchenne muscular dystrophy. FASEB J 2003 Mar;17(3):386-96 Kumar A, Boriek AM
[40] Improvement in muscular performance and decrease in tumor necrosis factor level in old age after antioxidant treatment. J Mol Med. 2003 Feb; 81(2):118-25 Hauer K, Hildebrandt W, Sehl Y, Edler L, Oster P, Dröge W
[41] Reactive oxygen species, antioxidant mechanisms and serum cytokine levels in cancer patients: impact of an antioxidant treatment. J Cell Mol Med. 2002 Oct-Dec; 6(4):570-82 Mantovani G, Macciò A, Madeddu C, Mura L, Massa E, Gramignano G, Lusso MR, Murgia V, Camboni P, Ferreli L
[42] Antiangiogenic activity of chemopreventive drugs. Int J Biol Markers 2003 Jan-Mar;18(1):70-4 Pfeffer U, Ferrari N, Morini M, Benelli R, Noonan DM, Albini A
[43] Slowing tumorigenic progression in TRAMP mice and prostatic carcinoma cell lines using natural anti-oxidant from spinach, NAO--a comparative study of three anti-oxidants. Toxicol Pathol 2003 Jan-Feb;31(1):39-51 Nyska A, Suttie A, Bakshi S, Lomnitski L, Grossman S, Bergman M, Ben-Shaul V, Crocket P, Haseman JK, Moser G, Goldsworthy TL, Maronpot RR
[44] Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points. Carcinogenesis. 2001 Jul; 22(7):999-1013 De Flora S, Izzotti A, D’Agostini F, Balansky RM
[45] In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats. Br J Pharmacol 2003 Mar;138(6):1037-48 Serrano-Mollar A, Closa D, Prats N, Blesa S, Martinez-Losa M, Cortijo J, Estrela JM, Morcillo EJ, Bulbena O
[46] N-acetylcysteine reduces malondialdehyde levels in chronic hemodialysis patients--a pilot study. Clin Nephrol. 2003 Jun; 59(6):441-6 Trimarchi H, Mongitore MR, Baglioni P, Forrester M, Freixas EA, Schropp M, Pereyra H, Alonso M
[47] Urinary and plasma homocysteine and cysteine levels during prolonged oral N-acetylcysteine therapy. Pharmacology. 2003 Jun; 68(2):105-14 Ventura P, Panini R, Abbati G, Marchetti G, Salvioli G
[48] Formation of DNA adducts in the aorta of smoke-exposed rats, and modulation by chemopreventive agents. Mutat Res. 2001 Jul 25; 494(1-2):97-106 Izzotti A, Camoirano A, Cartiglia C, Tampa E, De Flora S
[49] The effect of N-acetylcysteine on blood coagulation and platelet function in patients undergoing open repair of abdominal aortic aneurysm. Blood Coagul Fibrinolysis. 2006 Jan; 17(1):29-34 Niemi TT, Munsterhjelm E, Pöyhiä R, Hynninen MS, Salmenperä MT
[50] Effect of N-acetylcysteine on oxidative stress and ventricular function in patients with myocardial infarction. Heart Vessels. 2006 Jan; 21(1):33-7 Yesilbursa D, Serdar A, Senturk T, Serdar Z, Sa S, Cordan J
[51] Significant changes of peripheral perfusion and plasma adrenomedullin levels in N-acetylcysteine long term treatment of patients with sclerodermic Raynauds phenomenon. Int J Immunopathol Pharmacol. 2005 Oct-Dec; 18(4):761-70 Salsano F, Letizia C, Proietti M, Rossi C, Proietti AR, Rosato E, Pisarri S
[52] It is important to lower homocysteine in dialysis patients. Semin Dial. 2007 Nov-Dec; 20(6):530-3 Zoccali C, Mallamaci F, Tripepi G
[53] An open-label trial of N-acetylcysteine for the treatment of cocaine dependence: a pilot study. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30; 31(2):389-94 Mardikian PN, LaRowe SD, Hedden S, Kalivas PW, Malcolm RJ
[54] Safety and tolerability of N-acetylcysteine in cocaine-dependent individuals. Am J Addict. 2006 Jan-Feb; 15(1):105-10 LaRowe SD, Mardikian P, Malcolm R, Myrick H, Kalivas P, McFarland K, Saladin M, McRae A, Brady K
[55] Is cocaine desire reduced by N-acetylcysteine? Am J Psychiatry. 2007 Jul; 164(7):1115-7 LaRowe SD, Myrick H, Hedden S, Mardikian P, Saladin M, McRae A, Brady K, Kalivas PW, Malcolm R
[56] N-acetylcysteine attenuates alcohol-induced oxidative stess in rats. World J Gastroenterol 2003 Apr;9(4):791-4 Ozaras R, Tahan V, Aydin S, Uzun H, Kaya S, Senturk H
[57] N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study. Biol Psychiatry. 2007 Sep 15; 62(6):652-7 Grant JE, Kim SW, Odlaug BL
[58] Nutritional modulation of immune function. Proc Nutr Soc 2001 Aug;60(3):389-97 Grimble RF
[59] A double-blind, cross-over, study of oral N-acetylcysteine in Sjögren's syndrome. Scand J Rheumatol Suppl. 1986; 61:253-8 Walters MT, Rubin CE, Keightley SJ, Ward CD, Cawley MI
[60] N-acetylcysteine in severe falciparum malaria in Thailand. Southeast Asian J Trop Med Public Health. 2003 Mar; 34(1):37-42 Treeprasertsuk S, Krudsood S, Tosukhowong T, Maek-A-Nantawat W, Vannaphan S, Saengnetswang T, Looareesuwan S, Kuhn WF, Brittenham G, Carroll J
[61] Protective effect of n-acetylcysteine in a model of influenza infection in mice. Int J Immunopathol Pharmacol. 2000 Sep-Dec; 13(3):123-128 Ungheri D, Pisani C, Sanson G, Bertani A, Schioppacassi G, Delgado R, Sironi M, Ghezzi P
[62] Hepatitis C: epidemiology and review of complementary/alternative medicine treatments. Altern Med Rev. 1999 Aug; 4(4):220-38 Patrick L
[63] [A multi-center clinical study of N-acetylcysteine on chronic hepatitis B] Zhonghua Gan Zang Bing Za Zhi. 2005 Jan; 13(1):20-3 Shi XF, Guo SH, Wu G, Mao Q, Yu YS, Wang JK, Zhang L, Wang ZY, Zhang XQ, Zhang QH, Zhao YR, Zeng WQ
[64] Role of NF-kappaB and AP-1 on Helicobacter pylori-induced IL-8 expression in AGS cells. Dig Dis Sci. 2003 Feb; 48(2):257-65 Chu SH, Kim H, Seo JY, Lim JW, Mukaida N, Kim KH
[65] Effects of N-acetylcysteine against systemic and renal hemodynamic effects of endotoxin in healthy humans. Crit Care Med. 2007 Aug; 35(8):1869-75 Schaller G, Pleiner J, Mittermayer F, Posch M, Kapiotis S, Wolzt M
[66] N-acetylcysteine in clinical sepsis: a difficult marriage. Crit Care. 2004 Aug; 8(4):229-30 Spapen H
[67] The effect of N-acetylcysteine on nuclear factor-kappa B activation, interleukin-6, interleukin-8, and intercellular adhesion molecule-1 expression in patients with sepsis. Crit Care Med. 2003 Nov; 31(11):2574-8 Paterson RL, Galley HF, Webster NR
[68] Management of paracetamol overdose: current controversies. Drug Saf. 2001; 24(7):503-12 Kozer E, Koren G.
[69] Treatment of amatoxin poisoning: 20-year retrospective analysis. J Toxicol Clin Toxicol. 2002; 40(6):715-57 Enjalbert F, Rapior S, Nouguier-Soule J, Guillon S, Amouroux N, Cabot C
[70] Zinc toxicity on neonatal cortical neurons: involvement of glutathione chelation. J Neurochem. 2003 Apr; 85(2):443-53 Chen CJ, Liao SL
[71] Effects of antioxidant supplementation on postprandial oxidative stress and endothelial dysfunction: a single-blind, 15-day clinical trial in patients with untreated type 2 diabetes, subjects with impaired glucose tolerance, and healthy controls. Clin Ther. 2005 Nov; 27(11):1764-73 Neri S, Signorelli SS, Torrisi B, Pulvirenti D, Mauceri B, Abate G, Ignaccolo L, Bordonaro F, Cilio D, Calvagno S, Leotta C
[72] N-Acetylcysteine--a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol. 2007 Aug; 7(4):355-9 Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA
[73] N-acetylcysteine attenuates the decline in muscle Na+,K+-pump activity and delays fatigue during prolonged exercise in humans. J Physiol. 2006 Oct 1; 576(Pt 1):279-88 McKenna MJ, Medved I, Goodman CA, Brown MJ, Bjorksten AR, Murphy KT, Petersen AC, Sostaric S, Gong X
[74] N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals. J Appl Physiol. 2004 Oct; 97(4):1477-85 Medved I, Brown MJ, Bjorksten AR, Murphy KT, Petersen AC, Sostaric S, Gong X, McKenna MJ
[75] Current best treatment for non-alcoholic fatty liver disease. Expert Opin Pharmacother. 2003 May; 4(5):611-23 Angulo P
[76] Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants. Nutr Rev 2002 Sep;60(9):289-93 Mehta K, Van Thiel DH, Shah N, Mobarhan S
[77] Treatment of non-alcoholic steatohepatitis. Best Pract Res Clin Gastroenterol 2002 Oct;16(5):797-810 Angulo P, Lindor KD
[78] Effects of N-acetylcysteine on dense cell formation in sickle cell disease. Am J Hematol. 2003 May; 73(1):26-32 Pace BS, Shartava A, Pack-Mabien A, Mulekar M, Ardia A, Goodman SR