Skip to main content
SpringerLink
Log in

The Physiological Effects of N-Acetylcysteine in Clinical Studies

  • Chapter
  • First Online:
The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine

  • 1077 Accesses

Abstract

The previous chapters in this book have presented the empirical studies demonstrating the therapeutic effect of N-acetylcysteine (NAC) on various disease processes. For many diseases, the proposed biological mechanisms of action of NAC include improving glutathione availability, acting as an antioxidant, and having an immunomodulatory and anti-inflammatory effect. In this chapter we present some of the clinical studies that investigate the biological mechanism of action for the effect of NAC on disease on an in vivo basis. In addition, to these proposed mechanisms, NAC is also shown to improve vascular physiology by having a positive effect on endothelial function, nitric oxide metabolism, and vascular flow. Furthermore, NAC has been shown to improve exercise by influencing some of the same physiological processes that are involved in medical disease. This chapter provides a more in-depth understanding of the effects of NAC on human physiology to improve the understanding of its mechanism of action on disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Akerlund B, Jarstrand C, Lindeke B, Sonnerborg A, Akerblad AC, Rasool O (1996) Effect of N-acetylcysteine(NAC) treatment on HIV-1 infection: a double-blind placebo-controlled trial. Eur J Clin Pharmacol 50(6):457–461

    Article  CAS  Google Scholar 

  • Alfonso H, Franklin P, Ching S, Croft K, Burcham P, Olsen N, Reid A, Joyce D, de Klerk N, Musk AB (2015) Effect of N-acetylcysteine supplementation on oxidative stress status and alveolar inflammation in people exposed to asbestos: a double-blind, randomized clinical trial. Respirology (Carlton, Vic) 20(7):1102–1107. https://doi.org/10.1111/resp.12592

    Article  Google Scholar 

  • Arstall MA, Yang J, Stafford I, Betts WH, Horowitz JD (1995) N-acetylcysteine in combination with nitroglycerin and streptokinase for the treatment of evolving acute myocardial infarction. Safety and biochemical effects. Circulation 92(10):2855–2862

    Article  CAS  Google Scholar 

  • Bailey SJ, Winyard PG, Blackwell JR, Vanhatalo A, Lansley KE, Dimenna FJ, Wilkerson DP, Campbell IT, Jones AM (2011) Influence of N-acetylcysteine administration on pulmonary O(2) uptake kinetics and exercise tolerance in humans. Respir Physiol Neurobiol 175(1):121–129. https://doi.org/10.1016/j.resp.2010.10.002

    Article  CAS  PubMed  Google Scholar 

  • Bastin AJ, Davies N, Lim E, Quinlan GJ, Griffiths MJ (2016) Systemic inflammation and oxidative stress post-lung resection: effect of pretreatment with N-acetylcysteine. Respirology (Carlton, Vic) 21(1):180–187. https://doi.org/10.1111/resp.12662

    Article  Google Scholar 

  • Behr J, Degenkolb B, Krombach F, Vogelmeier C (2002) Intracellular glutathione and bronchoalveolar cells in fibrosing alveolitis: effects of N-acetylcysteine. Eur Respir J 19(5):906–911

    Article  CAS  Google Scholar 

  • Bernhard MC, Junker E, Hettinger A, Lauterburg BH (1998) Time course of total cysteine, glutathione and homocysteine in plasma of patients with chronic hepatitis C treated with interferon-alpha with and without supplementation with N-acetylcysteine. J Hepatol 28(5):751–755

    Article  CAS  Google Scholar 

  • Bostom AG, Shemin D, Yoburn D, Fisher DH, Nadeau MR, Selhub J (1996) Lack of effect of oral N-acetylcysteine on the acute dialysis-related lowering of total plasma homocysteine in hemodialysis patients. Atherosclerosis 120(1–2):241–244

    Article  CAS  Google Scholar 

  • Buyukhatipoglu H, Sezen Y, Yildiz A, Bas M, Kirhan I, Ulas T, Turan MN, Taskin A, Aksoy N (2010) N-acetylcysteine fails to prevent renal dysfunction and oxidative stress after noniodine contrast media administration during percutaneous coronary interventions. Pol Arch Med Wewn 120(10):383–389

    CAS  PubMed  Google Scholar 

  • Cheraghi E, Mehranjani MS, Shariatzadeh MA, Esfahani MH, Ebrahimi Z (2016) N-Acetylcysteine improves oocyte and embryo quality in polycystic ovary syndrome patients undergoing intracytoplasmic sperm injection: an alternative to metformin. Reprod Fertil Dev 28(6):723–731. https://doi.org/10.1071/rd14182

    Article  CAS  PubMed  Google Scholar 

  • Ciftci H, Verit A, Savas M, Yeni E, Erel O (2009) Effects of N-acetylcysteine on semen parameters and oxidative/antioxidant status. Urology 74(1):73–76. https://doi.org/10.1016/j.urology.2009.02.034

    Article  PubMed  Google Scholar 

  • Corn SD, Barstow TJ (2011) Effects of oral N-acetylcysteine on fatigue, critical power, and W′ in exercising humans. Respir Physiol Neurobiol 178(2):261–268. https://doi.org/10.1016/j.resp.2011.06.020

    Article  CAS  PubMed  Google Scholar 

  • Csontos C, Rezman B, Foldi V, Bogar L, Bognar Z, Drenkovics L, Roth E, Weber G, Lantos J (2011) Effect of N-acetylcysteine treatment on the expression of leukocyte surface markers after burn injury. Burns 37(3):453–464. https://doi.org/10.1016/j.burns.2010.10.008

    Article  CAS  PubMed  Google Scholar 

  • Csontos C, Rezman B, Foldi V, Bogar L, Drenkovics L, Roth E, Weber G, Lantos J (2012) Effect of N-acetylcysteine treatment on oxidative stress and inflammation after severe burn. Burns 38(3):428–437. https://doi.org/10.1016/j.burns.2011.09.011

    Article  CAS  PubMed  Google Scholar 

  • da Silva ND Jr, Roseguini BT, Chehuen M, Fernandes T, Mota GF, Martin PK, Han SW, Forjaz CL, Wolosker N, de Oliveira EM (2015) Effects of oral N-acetylcysteine on walking capacity, leg reactive hyperemia, and inflammatory and angiogenic mediators in patients with intermittent claudication. Am J Phys Heart Circ Phys 309(5):H897–H905. https://doi.org/10.1152/ajpheart.00158.2015

    Article  CAS  Google Scholar 

  • De Backer J, Vos W, Van Holsbeke C, Vinchurkar S, Claes R, Parizel PM, De Backer W (2013) Effect of high-dose N-acetylcysteine on airway geometry, inflammation, and oxidative stress in COPD patients. Int J Chron Obstruct Pulmon Dis 8:569–579. https://doi.org/10.2147/copd.s49307

    Article  PubMed  PubMed Central  Google Scholar 

  • De Backer WA, Amsel B, Jorens PG, Bossaert L, Hiemstra PS, van Noort P, van Overveld FJ (1996) N-acetylcysteine pretreatment of cardiac surgery patients influences plasma neutrophil elastase and neutrophil influx in bronchoalveolar lavage fluid. Intensive Care Med 22(9):900–908

    Article  Google Scholar 

  • De Rosa SC, Zaretsky MD, Dubs JG, Roederer M, Anderson M, Green A, Mitra D, Watanabe N, Nakamura H, Tjioe I, Deresinski SC, Moore WA, Ela SW, Parks D, Herzenberg LA, Herzenberg LA (2000) N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Investig 30(10):915–929

    Article  Google Scholar 

  • Drager LF, Andrade L, Barros de Toledo JF, Laurindo FR, Machado Cesar LA, Seguro AC (2004) Renal effects of N-acetylcysteine in patients at risk for contrast nephropathy: decrease in oxidant stress-mediated renal tubular injury. Nephrol Dial Transplant 19(7):1803–1807. https://doi.org/10.1093/ndt/gfh261

    Article  CAS  PubMed  Google Scholar 

  • Efrati S, Dishy V, Averbukh M, Blatt A, Krakover R, Weisgarten J, Morrow JD, Stein MC, Golik A (2003) The effect of N-acetylcysteine on renal function, nitric oxide, and oxidative stress after angiography. Kidney Int 64(6):2182–2187. https://doi.org/10.1046/j.1523-1755.2003.00322.x

    Article  CAS  PubMed  Google Scholar 

  • Ege T, Eskiocak S, Edis M, Duran E (2006) The role of N-acetylcysteine in lower extremity ischemia/reperfusions. J Cardiovasc Surg 47(5):563–568

    CAS  Google Scholar 

  • Ferreira LF, Campbell KS, Reid MB (2011) N-acetylcysteine in handgrip exercise: plasma thiols and adverse reactions. Int J Sport Nutr Exerc Metab 21(2):146–154

    Article  CAS  Google Scholar 

  • Friedman AN, Bostom AG, Laliberty P, Selhub J, Shemin D (2003) The effect of N-acetylcysteine on plasma total homocysteine levels in hemodialysis: a randomized, controlled study. Am J Kidney Dis 41(2):442–446. https://doi.org/10.1053/ajkd.2003.50054

    Article  CAS  PubMed  Google Scholar 

  • Harrison PM, Wendon JA, Gimson AE, Alexander GJ, Williams R (1991) Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med 324(26):1852–1857. https://doi.org/10.1056/nejm199106273242604

    Article  CAS  PubMed  Google Scholar 

  • Heller AR, Groth G, Heller SC, Breitkreutz R, Nebe T, Quintel M, Koch T (2001) N-acetylcysteine reduces respiratory burst but augments neutrophil phagocytosis in intensive care unit patients. Crit Care Med 29(2):272–276

    Article  CAS  Google Scholar 

  • Hildebrandt W, Sauer R, Bonaterra G, Dugi KA, Edler L, Kinscherf R (2015) Oral N-acetylcysteine reduces plasma homocysteine concentrations regardless of lipid or smoking status. Am J Clin Nutr 102(5):1014–1024. https://doi.org/10.3945/ajcn.114.101964

    Article  CAS  PubMed  Google Scholar 

  • Hilmi IA, Peng Z, Planinsic RM, Damian D, Dai F, Tyurina YY, Kagan VE, Kellum JA (2010) N-acetylcysteine does not prevent hepatorenal ischaemia-reperfusion injury in patients undergoing orthotopic liver transplantation. Nephrol Dial Transplant 25(7):2328–2333. https://doi.org/10.1093/ndt/gfq077

    Article  CAS  PubMed  Google Scholar 

  • Hsu SP, Chiang CK, Yang SY, Chien CT (2010) N-acetylcysteine for the management of anemia and oxidative stress in hemodialysis patients. Nephron Clin Pract 116(3):c207–c216. https://doi.org/10.1159/000317201

    Article  CAS  Google Scholar 

  • Jenkins DD, Wiest DB, Mulvihill DM, Hlavacek AM, Majstoravich SJ, Brown TR, Taylor JJ, Buckley JR, Turner RP, Rollins LG, Bentzley JP, Hope KE, Barbour AB, Lowe DW, Martin RH, Chang EY (2016) Fetal and neonatal effects of N-acetylcysteine when used for neuroprotection in maternal chorioamnionitis. J Pediatr 168:67–76.e66. https://doi.org/10.1016/j.jpeds.2015.09.076

    Article  CAS  PubMed  Google Scholar 

  • Kelly MK, Wicker RJ, Barstow TJ, Harms CA (2009) Effects of N-acetylcysteine on respiratory muscle fatigue during heavy exercise. Respir Physiol Neurobiol 165(1):67–72. https://doi.org/10.1016/j.resp.2008.10.008

    Article  CAS  PubMed  Google Scholar 

  • Koca K, Yurttas Y, Cayci T, Bilgic S, Kaldirim U, Durusu M, Cekli Y, Ozkan H, Hanci V, Purtuloglu T, Akgul EO, Oguz E, Yildiz C, Basbozkurt M (2011) The role of preconditioning and N-acetylcysteine on oxidative stress resulting from tourniquet-induced ischemia-reperfusion in arthroscopic knee surgery. J Trauma 70(3):717–723. https://doi.org/10.1097/TA.0b013e3181f30fb0

    Article  CAS  PubMed  Google Scholar 

  • Kurian GA, Paddikkala J (2010) N-acetylcysteine and magnesium improve biochemical abnormalities associated with myocardial ischaemic reperfusion in South Indian patients undergoing coronary artery bypass grafting: a comparative analysis. Singap Med J 51(5):381–388

    CAS  Google Scholar 

  • Lai ZW, Hanczko R, Bonilla E, Caza TN, Clair B, Bartos A, Miklossy G, Jimah J, Doherty E, Tily H, Francis L, Garcia R, Dawood M, Yu J, Ramos I, Coman I, Faraone SV, Phillips PE, Perl A (2012) N-acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 64(9):2937–2946. https://doi.org/10.1002/art.34502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leelarungrayub D, Khansuwan R, Pothongsunun P, Klaphajone J (2011) N-acetylcysteine supplementation controls total antioxidant capacity, creatine kinase, lactate, and tumor necrotic factor-alpha against oxidative stress induced by graded exercise in sedentary men. Oxidative Med Cell Longev 2011:329643. https://doi.org/10.1155/2011/329643

    Article  CAS  Google Scholar 

  • Look MP, Rockstroh JK, Rao GS, Barton S, Lemoch H, Kaiser R, Kupfer B, Sudhop T, Spengler U, Sauerbruch T (1998) Sodium selenite and N-acetylcysteine in antiretroviral-naive HIV-1-infected patients: a randomized, controlled pilot study. Eur J Clin Investig 28(5):389–397

    Article  CAS  Google Scholar 

  • Lukas R, Scharling B, Schultze-Werninghaus G, Gillissen A (2005) Antioxidant treatment with N-acetylcysteine and vitamin C in patients with chronic bronchitis. Dtsch Med Wochenschr (1946) 130(11):563–567. https://doi.org/10.1055/s-2005-865062

    Article  CAS  Google Scholar 

  • Martina V, Masha A, Gigliardi VR, Brocato L, Manzato E, Berchio A, Massarenti P, Settanni F, Della Casa L, Bergamini S, Iannone A (2008) Long-term N-acetylcysteine and L-arginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes. Diabetes Care 31(5):940–944. https://doi.org/10.2337/dc07-2251

    Article  CAS  PubMed  Google Scholar 

  • McKenna MJ, Medved I, Goodman CA, Brown MJ, Bjorksten AR, Murphy KT, Petersen AC, Sostaric S, Gong X (2006) N-acetylcysteine attenuates the decline in muscle Na+,K+-pump activity and delays fatigue during prolonged exercise in humans. J Physiol 576(Pt 1):279–288. https://doi.org/10.1113/jphysiol.2006.115352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Medved I, Brown MJ, Bjorksten AR, Leppik JA, Sostaric S, McKenna MJ (2003) N-acetylcysteine infusion alters blood redox status but not time to fatigue during intense exercise in humans. J Appl Physiol 94(4):1572–1582. https://doi.org/10.1152/japplphysiol.00884.2002

    Article  CAS  PubMed  Google Scholar 

  • Medved I, Brown MJ, Bjorksten AR, McKenna MJ (2004a) Effects of intravenous N-acetylcysteine infusion on time to fatigue and potassium regulation during prolonged cycling exercise. J Appl Physiol 96(1):211–217. https://doi.org/10.1152/japplphysiol.00458.2003

    Article  CAS  PubMed  Google Scholar 

  • Medved I, Brown MJ, Bjorksten AR, Murphy KT, Petersen AC, Sostaric S, Gong X, McKenna MJ (2004b) N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals. J Appl Physiol 97(4):1477–1485. https://doi.org/10.1152/japplphysiol.00371.2004

    Article  CAS  PubMed  Google Scholar 

  • Merry TL, Wadley GD, Stathis CG, Garnham AP, Rattigan S, Hargreaves M, McConell GK (2010) N-Acetylcysteine infusion does not affect glucose disposal during prolonged moderate-intensity exercise in humans. J Physiol 588(Pt 9):1623–1634. https://doi.org/10.1113/jphysiol.2009.184333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meyer A, Buhl R, Magnussen H (1994) The effect of oral N-acetylcysteine on lung glutathione levels in idiopathic pulmonary fibrosis. Eur Respir J 7(3):431–436

    Article  CAS  Google Scholar 

  • Miner SE, Cole DE, Evrovski J, Forrest Q, Hutchison SJ, Holmes K, Ross HJ (2002) N-acetylcysteine neither lowers plasma homocysteine concentrations nor improves brachial artery endothelial function in cardiac transplant recipients. Can J Cardiol 18(5):503–507

    CAS  PubMed  Google Scholar 

  • Nascimento MM, Suliman ME, Silva M, Chinaglia T, Marchioro J, Hayashi SY, Riella MC, Lindholm B, Anderstam B (2010) Effect of oral N-acetylcysteine treatment on plasma inflammatory and oxidative stress markers in peritoneal dialysis patients: a placebo-controlled study. Perit Dial Int 30(3):336–342. https://doi.org/10.3747/pdi.2009.00073

    Article  CAS  Google Scholar 

  • Nielsen HB, Kharazmi A, Bolbjerg ML, Poulsen HE, Pedersen BK, Secher NH (2001) N-acetylcysteine attenuates oxidative burst by neutrophils in response to ergometer rowing with no effect on pulmonary gas exchange. Int J Sports Med 22(4):256–260. https://doi.org/10.1055/s-2001-13817

    Article  CAS  PubMed  Google Scholar 

  • Nielsen HB, Secher NH, Kappel M, Pedersen BK (1998) N-acetylcysteine does not affect the lymphocyte proliferation and natural killer cell activity responses to exercise. Am J Physiol 275(4 Pt 2):R1227–R1231

    CAS  PubMed  Google Scholar 

  • Ozdemir ZC, Koc A, Aycicek A, Kocyigit A (2014) N-Acetylcysteine supplementation reduces oxidative stress and DNA damage in children with beta-thalassemia. Hemoglobin 38(5):359–364. https://doi.org/10.3109/03630269.2014.951890

    Article  CAS  PubMed  Google Scholar 

  • Paterson RL, Galley HF, Webster NR (2003) 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 31(11):2574–2578. https://doi.org/10.1097/01.ccm.0000089945.69588.18

    Article  CAS  PubMed  Google Scholar 

  • Pelaia P, Rocco M, De Blasi RA, Spadetta G, Alampi D, Araimo FS, Nicolucci S (1995) Assessment of lipid peroxidation in hyperbaric oxygen therapy: protective role of N-acetylcysteine. Minerva Anestesiol 61(4):133–139

    CAS  PubMed  Google Scholar 

  • Petersen AC, McKenna MJ, Medved I, Murphy KT, Brown MJ, Della Gatta P, Cameron-Smith D (2012) Infusion with the antioxidant N-acetylcysteine attenuates early adaptive responses to exercise in human skeletal muscle. Acta Physiol 204(3):382–392. https://doi.org/10.1111/j.1748-1716.2011.02344.x

    Article  CAS  Google Scholar 

  • Purwanto B, Prasetyo DH (2012) Effect of oral N-acetylcysteine treatment on immune system in continuous ambulatory peritoneal dialysis patients. Acta Med Indones 44(2):140–144

    PubMed  Google Scholar 

  • Raijmakers MT, Schilders GW, Roes EM, van Tits LJ, Hak-Lemmers HL, Steegers EA, Peters WH (2003) N-Acetylcysteine improves the disturbed thiol redox balance after methionine loading. Clin Sci (Lond) 105(2):173–180. https://doi.org/10.1042/cs20030052

    Article  CAS  Google Scholar 

  • Renke M, Tylicki L, Rutkowski P, Larczynski W, Neuwelt A, Aleksandrowicz E, Lysiak-Szydlowska W, Rutkowski B (2010) The effect of N-acetylcysteine on blood pressure and markers of cardiovascular risk in non-diabetic patients with chronic kidney disease: a placebo-controlled, randomized, cross-over study. Med Sci Monit 16(7):Pi13–Pi18

    CAS  PubMed  Google Scholar 

  • Roes EM, Raijmakers MT, Peters WH, Steegers EA (2002) Effects of oral N-acetylcysteine on plasma homocysteine and whole blood glutathione levels in healthy, non-pregnant women. Clin Chem Lab Med 40(5):496–498. https://doi.org/10.1515/cclm.2002.086

    Article  CAS  PubMed  Google Scholar 

  • Saddadi F, Alatab S, Pasha F, Ganji MR, Soleimanian T (2014) The effect of treatment with N-acetylcysteine on the serum levels of C-reactive protein and interleukin-6 in patients on hemodialysis. Saudi J Kidney Dis Transplant 25(1):66–72

    Article  Google Scholar 

  • Sahin G, Yalcin AU, Akcar N (2007) Effect of N-acetylcysteine on endothelial dysfunction in dialysis patients. Blood Purif 25(4):309–315. https://doi.org/10.1159/000106103

    Article  CAS  PubMed  Google Scholar 

  • Saitoh T, Satoh H, Nobuhara M, Machii M, Tanaka T, Ohtani H, Saotome M, Urushida T, Katoh H, Hayashi H (2011) Intravenous glutathione prevents renal oxidative stress after coronary angiography more effectively than oral N-acetylcysteine. Heart Vessel 26(5):465–472. https://doi.org/10.1007/s00380-010-0078-0

    Article  Google Scholar 

  • Sandhu C, Belli AM, Oliveira DB (2006) The role of N-acetylcysteine in the prevention of contrast-induced nephrotoxicity. Cardiovasc Intervent Radiol 29(3):344–347. https://doi.org/10.1007/s00270-005-0127-8

    Article  PubMed  Google Scholar 

  • Santiago FM, Bueno P, Olmedo C, Muffak-Granero K, Comino A, Serradilla M, Mansilla A, Villar JM, Garrote D, Ferron JA (2008) Effect of N-acetylcysteine administration on intraoperative plasma levels of interleukin-4 and interleukin-10 in liver transplant recipients. Transplant Proc 40(9):2978–2980. https://doi.org/10.1016/j.transproceed.2008.08.103

    Article  CAS  PubMed  Google Scholar 

  • Schaller G, Pleiner J, Mittermayer F, Posch M, Kapiotis S, Wolzt M (2007) Effects of N-acetylcysteine against systemic and renal hemodynamic effects of endotoxin in healthy humans. Crit Care Med 35(8):1869–1875. https://doi.org/10.1097/01.ccm.0000275385.45557.25

    Article  CAS  PubMed  Google Scholar 

  • Scholze A, Rinder C, Beige J, Riezler R, Zidek W, Tepel M (2004) Acetylcysteine reduces plasma homocysteine concentration and improves pulse pressure and endothelial function in patients with end-stage renal failure. Circulation 109(3):369–374. https://doi.org/10.1161/01.cir.0000109492.65802.ad

    Article  CAS  PubMed  Google Scholar 

  • Shahbazian H, Shayanpour S, Ghorbani A (2016) Evaluation of administration of oral N-acetylcysteine to reduce oxidative stress in chronic hemodialysis patients: a double-blind, randomized, controlled clinical trial. Saudi J Kidney Dis Transplant 27(1):88–93. https://doi.org/10.4103/1319-2442.174084

    Article  Google Scholar 

  • Silva LA, Silveira PC, Pinho CA, Tuon T, Dal Pizzol F, Pinho RA (2008) N-acetylcysteine supplementation and oxidative damage and inflammatory response after eccentric exercise. Int J Sport Nutr Exerc Metab 18(4):379–388

    Article  CAS  Google Scholar 

  • Slattery KM, Dascombe B, Wallace LK, Bentley DJ, Coutts AJ (2014) Effect of N-acetylcysteine on cycling performance after intensified training. Med Sci Sports Exerc 46(6):1114–1123. https://doi.org/10.1249/mss.0000000000000222

    Article  CAS  PubMed  Google Scholar 

  • Smith JR, Broxterman RM, Ade CJ, Evans KK, Kurti SP, Hammer SM, Barstow TJ, Harms CA (2016) Acute supplementation of N-acetylcysteine does not affect muscle blood flow and oxygenation characteristics during handgrip exercise. Physiol Rep 4(7):e12748. https://doi.org/10.14814/phy2.12748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soltan-Sharifi MS, Mojtahedzadeh M, Najafi A, Reza Khajavi M, Reza Rouini M, Moradi M, Mohammadirad A, Abdollahi M (2007) 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 26(9):697–703. https://doi.org/10.1177/0960327107083452

    Article  CAS  PubMed  Google Scholar 

  • Stravitz RT, Sanyal AJ, Reisch J, Bajaj JS, Mirshahi F, Cheng J, Lee WM (2013) Effects of N-acetylcysteine on cytokines in non-acetaminophen acute liver failure: potential mechanism of improvement in transplant-free survival. Liver Int 33(9):1324–1331. https://doi.org/10.1111/liv.12214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swarnalatha G, Ram R, Neela P, Naidu MU, Dakshina Murty KV (2010) Oxidative stress in hemodialysis patients receiving intravenous iron therapy and the role of N-acetylcysteine in preventing oxidative stress. Saudi J Kidney Dis Transplant 21(5):852–858

    CAS  Google Scholar 

  • Szkudlarek U, Zdziechowski A, Witkowski K, Kasielski M, Luczynska M, Luczynski R, Sarniak A, Nowak D (2004) Effect of inhaled N-acetylcysteine on hydrogen peroxide exhalation in healthy subjects. Pulm Pharmacol Ther 17(3):155–162. https://doi.org/10.1016/j.pupt.2004.01.007

    Article  CAS  PubMed  Google Scholar 

  • Szkudlinska MA, von Frankenberg AD, Utzschneider KM (2016) The antioxidant N-Acetylcysteine does not improve glucose tolerance or beta-cell function in type 2 diabetes. J Diabetes Complicat 30(4):618–622. https://doi.org/10.1016/j.jdiacomp.2016.02.003

    Article  PubMed  PubMed Central  Google Scholar 

  • Talasaz AH, Khalili H, Jenab Y, Salarifar M, Broumand MA, Darabi F (2013) N-Acetylcysteine effects on transforming growth factor-beta and tumor necrosis factor-alpha serum levels as pro-fibrotic and inflammatory biomarkers in patients following ST-segment elevation myocardial infarction. Drugs R D 13(3):199–205. https://doi.org/10.1007/s40268-013-0025-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thaha M, Pranawa W, Yogiantoro M, Tomino Y (2008) Intravenous N-acetylcysteine during hemodialysis reduces asymmetric dimethylarginine level in end-stage renal disease patients. Clin Nephrol 69(1):24–32

    Article  CAS  Google Scholar 

  • Thaha M, Yogiantoro M, Tomino Y (2006) Intravenous N-acetylcysteine during haemodialysis reduces the plasma concentration of homocysteine in patients with end-stage renal disease. Clinical Drug Invest 26(4):195–202

    Article  CAS  Google Scholar 

  • Thiele H, Hildebrand L, Schirdewahn C, Eitel I, Adams V, Fuernau G, Erbs S, Linke A, Diederich KW, Nowak M, Desch S, Gutberlet M, Schuler G (2010) Impact of high-dose N-acetylcysteine versus placebo on contrast-induced nephropathy and myocardial reperfusion injury in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. The LIPSIA-N-ACC (Prospective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate Percutaneous Coronary Intervention Acute Myocardial Infarction N-ACC) Trial. J Am Coll Cardiol 55(20):2201–2209. https://doi.org/10.1016/j.jacc.2009.08.091

    Article  CAS  PubMed  Google Scholar 

  • Tirouvanziam R, Conrad CK, Bottiglieri T, Herzenberg LA, Moss RB, Herzenberg LA (2006) High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis. Proc Natl Acad Sci U S A 103(12):4628–4633. https://doi.org/10.1073/pnas.0511304103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tossios P, Bloch W, Huebner A, Raji MR, Dodos F, Klass O, Suedkamp M, Kasper SM, Hellmich M, Mehlhorn U (2003) N-acetylcysteine prevents reactive oxygen species-mediated myocardial stress in patients undergoing cardiac surgery: results of a randomized, double-blind, placebo-controlled clinical trial. J Thorac Cardiovasc Surg 126(5):1513–1520. https://doi.org/10.1016/s0022

    Article  CAS  PubMed  Google Scholar 

  • Trewin AJ, Lundell LS, Perry BD, Patil KV, Chibalin AV, Levinger I, McQuade LR, Stepto NK (2015) Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle. Am J Phys Endocrinol Metab 309(4):E388–E397. https://doi.org/10.1152/ajpendo.00605.2014

    Article  CAS  Google Scholar 

  • Trewin AJ, Petersen AC, Billaut F, McQuade LR, McInerney BV, Stepto NK (2013) N-acetylcysteine alters substrate metabolism during high-intensity cycle exercise in well-trained humans. Appl Physiol Nutr Metab 38(12):1217–1227. https://doi.org/10.1139/apnm-2012-0482

    Article  CAS  PubMed  Google Scholar 

  • Trimarchi H, Mongitore MR, Baglioni P, Forrester M, Freixas EA, Schropp M, Pereyra H, Alonso M (2003) N-acetylcysteine reduces malondialdehyde levels in chronic hemodialysis patients – a pilot study. Clin Nephrol 59(6):441–446

    Article  CAS  Google Scholar 

  • Vento AE, Nemlander A, Aittomaki J, Salo J, Karhunen J, Ramo OJ (2003) N-acetylcysteine as an additive to crystalloid cardioplegia increased oxidative stress capacity in CABG patients. Scand Cardiovasc J SCJ 37(6):349–355. https://doi.org/10.1080/14017430310015406

    Article  CAS  PubMed  Google Scholar 

  • Ventura P, Panini R, Abbati G, Marchetti G, Salvioli G (2003) Urinary and plasma homocysteine and cysteine levels during prolonged oral N-acetylcysteine therapy. Pharmacology 68(2):105–114. https://doi.org/10.1159/000069535

    Article  CAS  PubMed  Google Scholar 

  • Weigand MA, Plachky J, Thies JC, Spies-Martin D, Otto G, Martin E, Bardenheuer HJ (2001) N-acetylcysteine attenuates the increase in alpha-glutathione S-transferase and circulating ICAM-1 and VCAM-1 after reperfusion in humans undergoing liver transplantation. Transplantation 72(4):694–698

    Article  CAS  Google Scholar 

  • Wiklund O, Fager G, Andersson A, Lundstam U, Masson P, Hultberg B (1996) N-acetylcysteine treatment lowers plasma homocysteine but not serum lipoprotein(a) levels. Atherosclerosis 119(1):99–106

    Article  CAS  Google Scholar 

  • Wittstock A, Burkert M, Zidek W, Tepel M, Scholze A (2009) N-acetylcysteine improves arterial vascular reactivity in patients with chronic kidney disease. Nephron Clin Pract 112(3):c184–c189. https://doi.org/10.1159/000218107

    Article  CAS  PubMed  Google Scholar 

  • Yesilbursa D, Serdar A, Senturk T, Serdar Z, Sag S, Cordan J (2006) Effect of N-acetylcysteine on oxidative stress and ventricular function in patients with myocardial infarction. Heart Vessel 21(1):33–37. https://doi.org/10.1007/s00380-005-0854-4

    Article  Google Scholar 

  • Yilmaz H, Sahin S, Sayar N, Tangurek B, Yilmaz M, Nurkalem Z, Onturk E, Cakmak N, Bolca O (2007) Effects of folic acid and N-acetylcysteine on plasma homocysteine levels and endothelial function in patients with coronary artery disease. Acta Cardiol 62(6):579–585. https://doi.org/10.2143/ac.62.6.2024017

    Article  PubMed  Google Scholar 

  • Zembron-Lacny A, Slowinska-Lisowska M, Szygula Z, Witkowski K, Szyszka K (2009) The comparison of antioxidant and hematological properties of N-acetylcysteine and alpha-lipoic acid in physically active males. Physiol Res 58(6):855–861

    CAS  PubMed  Google Scholar 

  • Zembron-Lacny A, Slowinska-Lisowska M, Szygula Z, Witkowski Z, Szyszka K (2010) Modulatory effect of N-acetylcysteine on pro-antioxidant status and haematological response in healthy men. J Physiol Biochem 66(1):15–21. https://doi.org/10.1007/s13105-010-0002-1

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Barrow Neurological Institute, Phoenix Children’s Hospital, University of Arizona College of Medicine – Phoenix, Phoenix, AZ, USA

    Richard Eugene Frye

Authors
  1. Richard Eugene Frye
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard Eugene Frye .

Editor information

Editors and Affiliations

  1. Barrow Neurological Institute, Phoenix Children’s Hospital, University of Arizona, College of Medicine – Phoenix, Phoenix, AZ, USA

    Richard Eugene Frye

  2. IMPACT SRC, Deakin University & Barwon Health, Geelong, VIC, Australia

    Michael Berk

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Frye, R.E. (2019). The Physiological Effects of N-Acetylcysteine in Clinical Studies. In: Frye, R., Berk, M. (eds) The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine. Adis, Singapore. https://doi.org/10.1007/978-981-10-5311-5_19

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-5311-5_19

  • Published:

  • Publisher Name: Adis, Singapore

  • Print ISBN: 978-981-10-5310-8

  • Online ISBN: 978-981-10-5311-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation