N-acetylcysteine (NAC) is a precursor for the amino acid L-cysteine. It has antioxidant, anti-inflammatory, and mucus thinning properties. NAC can act as a direct antioxidant, but more importantly, it provides the cysteine required for the production of glutathione, a powerful antioxidant produced in the body. NAC is commonly taken as a supplement for health and wellness and is used in clinical settings to treat drug overdose, cystic fibrosis, and chronic obstructive pulmonary disease.
N-Acetylcysteine is most often used for
N-acetylcysteine (NAC) is an acetylated form of the amino acid L-cysteine. It has antioxidant and anti-inflammatory properties and is a mucolytic agent, meaning that it helps break down mucus in the respiratory tract. NAC is converted to L-cysteine after ingestion, which, in turn, is converted into glutathione (GSH), a powerful antioxidant.
L-cysteine can’t be supplemented on its own because free L-cysteine is highly unstable, becoming readily oxidized in solution which can encourage the formation of insoluble precipitates. Similarly, glutathione is rapidly broken down in the gastrointestinal tract and blood, limiting its availability in the body when supplemented directly. In contrast, NAC is more stable and has a much lower toxicity than free L-cysteine, making it safer and more effective for increasing cysteine and glutathione levels in the body.
NAC reduces levels of proinflammatory cytokines and oxidative stress. Because NAC increases glutathione levels in the body, which are rapidly depleted by stress, disease, or drug toxicity, it has applications in clinical settings, in addition to general health and wellness. NAC has been used for the treatment of cystic fibrosis (due to its mucolytic properties), acetaminophen (paracetamol) toxicity, and chronic obstructive pulmonary disease (COPD).
In COPD, NAC may improve lung function and speed the rate of symptom improvement when used during a symptom flare up (an exacerbation). Long-term use (more than 3–6 months) may improve symptoms of chronic bronchitis and reduce the risk of COPD exacerbations, although the latter effect has not been found consistently. Additionally, NAC does not seem to prevent declining lung function when used over a long period of time.
NAC is safe and effective at reasonable doses through oral supplementation. NAC toxicity mostly occurs in clinical settings, with one case of overdose occurring due to an error in the preparation of an IV solution. An excessive dose of NAC in a short time period can cause red blood cell lysis (hemolysis), low blood platelet count (thrombocytopenia), kidney failure, and possibly death.
NAC has cytoprotective (cell-protecting) effects, which work through antioxidant and anti-inflammatory mechanisms. On the antioxidant side, although the NAC molecule itself has the ability to scavenge reactive oxygen species (ROS), the antioxidant effects of NAC in the body mainly occur through increasing glutathione levels and other indirect mechanisms. NAC increases glutathione levels by acting as a source of the amino acid cysteine, which is a rate-limiting building block for glutathione production. The anti-inflammatory effects of NAC are indirect and work through its antioxidant activity, which in turn inhibits the pro-inflammatory transcription factor NFKB-Activity and reduces pro-inflammatory cytokines like IL-8, IL-6, and TNF-α.
As a mucolytic agent, NAC decreases the thickness of mucus (sputum) by reducing oxidized sulfur bonds between mucus proteins, breaking them up. In the respiratory tract, this effect allows for better mucociliary clearance (the self-cleaning mechanism within the airways) so mucus can be more effectively expelled from the lungs.
N-acetylcysteine also appears to modulate glutamate and dopamine neurotransmission in a way that may be beneficial for certain neuropsychiatric disorders such as schizophrenia and substance use disorder. However, further research is needed to support these effects.
NAC is safe and effective at reasonable doses through oral supplementation. The most common side effects from oral NAC include nausea, vomiting, and diarrhea. Due to the sulfur content of NAC, supplements can have an unpleasant rotten-egg odor. When inhaled, NAC may cause cough and bronchospasm (constriction of the airways).
NAC toxicity mostly occurs in clinical settings, with one case of overdose occurring due to an error in the preparation of an IV solution. An excessive dose of NAC in a short time period can cause red blood cell breakdown (hemolysis), low blood platelet count (thrombocytopenia), kidney failure, and possibly death.
- N-Acetyl Cysteine
N-acetylcysteine can be given orally, intravenously, topically, or through inhalation. Research suggests that in order to achieve the mucolytic effects in the respiratory tract, NAC needs to be administered through inhalation. Alternatively, oral or intravenous administration is the best way to benefit from NAC’s antioxidant effects.
The suggested dosage of NAC depends on what it’s being used for and the route through which it’s being administered. Orally, NAC is most often given in the dosage range of 600–1,800 mg daily (often divided into two or three daily doses), although higher doses are sometimes used in clinical research. Further research is needed to determine the optimal therapeutic dosages for other uses and methods.
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- ^Micaely Cristina Dos Santos Tenório, Nayara Gomes Graciliano, Fabiana Andréa Moura, Alane Cabral Menezes de Oliveira, Marília Oliveira Fonseca GoulartN-Acetylcysteine (NAC): Impacts on Human HealthAntioxidants (Basel).(2021 Jun 16)
- ^Guerini M, Condrò G, Friuli V, Maggi L, Perugini PN-acetylcysteine (NAC) and Its Role in Clinical Practice Management of Cystic Fibrosis (CF): A Review.Pharmaceuticals (Basel).(2022-Feb-11)
- ^Gerry K SchwalfenbergN-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)J Nutr Metab.(2021 Jun 9)
- ^A L SHEFFNERThe reduction in vitro in viscosity of mucoprotein solutions by a new mucolytic agent, N-acetyl-L-cysteineAnn N Y Acad Sci.(1963 Mar 30)
- ^Forman HJ, Zhang HTargeting oxidative stress in disease: promise and limitations of antioxidant therapy.Nat Rev Drug Discov.(2021-Sep)
- ^S M BIRNBAUM, M WINITZ, J P GREENSTEINQuantitative nutritional studies with water-soluble, chemically defined diets. III. Individual amino acids as sources of non-essential nitrogenArch Biochem Biophys.(1957 Dec)
- ^Vered Gazit, Ron Ben-Abraham, Chaim G Pick, Izhar Ben-Shlomo, Yeshayahu KatzLong-term neurobehavioral and histological damage in brain of mice induced by L-cysteinePharmacol Biochem Behav.(2003 Jul)
- ^Chad Kerksick, Darryn WilloughbyThe antioxidant role of glutathione and N-acetyl-cysteine supplements and exercise-induced oxidative stressJ Int Soc Sports Nutr.(2005 Dec 9)
- ^M Gracey, V Burke, C M AndersonTreatment of abdominal pain in cystic fibrosis by oral administration of n-acetyl cysteineArch Dis Child.(1969 Jun)
- ^Kennon J HeardAcetylcysteine for acetaminophen poisoningN Engl J Med.(2008 Jul 17)
- ^Jiang C, Zou J, Lv Q, Yang YSystematic review and meta-analysis of the efficacy of N-acetylcysteine in the treatment of acute exacerbation of chronic obstructive pulmonary disease.Ann Palliat Med.(2021-Jun)
- ^Cazzola M, Calzetta L, Page C, Jardim J, Chuchalin AG, Rogliani P, Matera MGInfluence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis.Eur Respir Rev.(2015-Sep)
- ^Fowdar K, Chen H, He Z, Zhang J, Zhong X, Zhang J, Li M, Bai JThe effect of N-acetylcysteine on exacerbations of chronic obstructive pulmonary disease: A meta-analysis and systematic review.Heart Lung.(2017)
- ^Wei J, Pang CS, Han J, Yan HEffect of Orally Administered N-Acetylcysteine on Chronic Bronchitis: A Meta-analysis.Adv Ther.(2019-Dec)
- ^Huang C, Kuo S, Lin L, Yang YThe efficacy of -acetylcysteine in chronic obstructive pulmonary disease patients: a meta-analysis.Ther Adv Respir Dis.(2023)
- ^Ghafar Ali Mahmoudi, Peyman Astaraki, Azita Zafar Mohtashami, Maryam AhadiN-acetylcysteine overdose after acetaminophen poisoningInt Med Case Rep J.(2015 Feb 27)
- ^Anatoly ZhitkovichN-Acetylcysteine: Antioxidant, Aldehyde Scavenger, and MoreChem Res Toxicol.(2019 Jul 15)
- ^Aldini G, Altomare A, Baron G, Vistoli G, Carini M, Borsani L, Sergio FN-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why.Free Radic Res.(2018-Jul)
- ^S Oka, H Kamata, K Kamata, H Yagisawa, H HirataN-acetylcysteine suppresses TNF-induced NF-kappaB activation through inhibition of IkappaB kinasesFEBS Lett.(2000 Apr 28)
- ^Faghfouri AH, Zarezadeh M, Tavakoli-Rouzbehani OM, Radkhah N, Faghfuri E, Kord-Varkaneh H, Tan SC, Ostadrahimi AThe effects of N-acetylcysteine on inflammatory and oxidative stress biomarkers: A systematic review and meta-analysis of controlled clinical trials.Eur J Pharmacol.(2020-Oct-05)
- ^Smaga I, Frankowska M, Filip MN-acetylcysteine as a new prominent approach for treating psychiatric disorders.Br J Pharmacol.(2021-Jul)
- ^Rhodes K, Braakhuis APerformance and Side Effects of Supplementation with N-Acetylcysteine: A Systematic Review and Meta-Analysis.Sports Med.(2017-Aug)
- ^Wang L, Wang Z, Liu JProtective effect of N-acetylcysteine on experimental chronic lead nephrotoxicity in immature female rats.Hum Exp Toxicol.(2010-Jul)
- ^Kasperczyk S, Dobrakowski M, Kasperczyk A, Ostałowska A, Birkner EThe administration of N-acetylcysteine reduces oxidative stress and regulates glutathione metabolism in the blood cells of workers exposed to leadClin Toxicol (Phila).(2013 Jul)
- ^Dobrakowski M, Pawlas N, Hudziec E, Kozłowska A, Mikołajczyk A, Birkner E, Kasperczyk SGlutathione, glutathione-related enzymes, and oxidative stress in individuals with subacute occupational exposure to lead.Environ Toxicol Pharmacol.(2016-Jul)
- ^Nehru B, Kanwar SSModulation by N-acetylcysteine of lead-induced alterations in rat brain: reduced glutathione levels and morphology.Toxicol Mech Methods.(2007)
- ^Ercal N, Treeratphan P, Hammond TC, Matthews RH, Grannemann NH, Spitz DRIn vivo indices of oxidative stress in lead-exposed C57BL/6 mice are reduced by treatment with meso-2,3-dimercaptosuccinic acid or N-acetylcysteine.Free Radic Biol Med.(1996)
- ^H J Engels, J C WirthNo ergogenic effects of ginseng (Panax ginseng C.A. Meyer) during graded maximal aerobic exerciseJ Am Diet Assoc.(1997 Oct)
- ^Zahra Shahveghar Asl, Karim Parastouei, Eslam EskandariThe effects of N-acetylcysteine on ovulation and sex hormones profile in women with polycystic ovary syndrome: a systematic review and meta-analysisBr J Nutr.(2023 Jan 4)
- ^Song Y, Wang H, Huang H, Zhu ZComparison of the efficacy between NAC and metformin in treating PCOS patients: a meta-analysis.Gynecol Endocrinol.(2020-Mar)
- ^Ganesh Raghu, Michael Berk, Peter A Campochiaro, Hartmut Jaeschke, Giancarlo Marenzi, Luca Richeldi, Fu-Qiang Wen, Ferdinando Nicoletti, Peter M A CalverleyThe Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative StressCurr Neuropharmacol.(2021)
- ^Xu X, Shao G, Zhang X, Hu Y, Huang J, Su Y, Zhang M, Cai Y, Zhou HThe efficacy of nutritional supplements for the adjunctive treatment of schizophrenia in adults: A systematic review and network meta-analysis.Psychiatry Res.(2022-May)
- ^Kishi T, Sakuma K, Hatano M, Iwata NN-acetylcysteine for schizophrenia: A systematic review and meta-analysis.Psychiatry Clin Neurosci.(2023-Feb)
- ^Yolland CO, Hanratty D, Neill E, Rossell SL, Berk M, Dean OM, Castle DJ, Tan EJ, Phillipou A, Harris AW, Barreiros AR, Hansen A, Siskind DMeta-analysis of randomised controlled trials with -acetylcysteine in the treatment of schizophrenia.Aust N Z J Psychiatry.(2020-May)
- ^Nery FG, Li W, DelBello MP, Welge JAN-acetylcysteine as an adjunctive treatment for bipolar depression: A systematic review and meta-analysis of randomized controlled trials.Bipolar Disord.(2021-11)
- ^Fernandes BS, Dean OM, Dodd S, Malhi GS, Berk MN-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis.J Clin Psychiatry.(2016-Apr)
- ^Lee TM, Lee KM, Lee CY, Lee HC, Tam KW, Loh EWEffectiveness of -acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials.Aust N Z J Psychiatry.(2021-Feb)
- ^Duailibi MS, Cordeiro Q, Brietzke E, Ribeiro M, LaRowe S, Berk M, Trevizol APN-acetylcysteine in the treatment of craving in substance use disorders: Systematic review and meta-analysis.Am J Addict.(2017-Oct)
- ^Reid MBFree radicals and muscle fatigue: Of ROS, canaries, and the IOC.Free Radic Biol Med.(2008-Jan-15)
- ^Shindoh C, DiMarco A, Thomas A, Manubay P, Supinski GEffect of N-acetylcysteine on diaphragm fatigue.J Appl Physiol (1985).(1990-May)
- ^Reid MB, Haack KE, Franchek KM, Valberg PA, Kobzik L, West MSReactive oxygen in skeletal muscle. I. Intracellular oxidant kinetics and fatigue in vitro.J Appl Physiol (1985).(1992-Nov)
- ^Cobley JN, McGlory C, Morton JP, Close GLN-Acetylcysteine's attenuation of fatigue after repeated bouts of intermittent exercise: practical implications for tournament situationsInt J Sport Nutr Exerc Metab.(2011 Dec)
- ^Slattery KM, Dascombe B, Wallace LK, Bentley DJ, Coutts AJEffect of N-acetylcysteine on cycling performance after intensified training.Med Sci Sports Exerc.(2014-Jun)
- ^Medved I, Brown MJ, Bjorksten AR, Murphy KT, Petersen AC, Sostaric S, Gong X, McKenna MJN-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individualsJ Appl Physiol (1985).(2004 Oct)
- ^Petersen AC, McKenna MJ, Medved I, Murphy KT, Brown MJ, Della Gatta P, Cameron-Smith DInfusion with the antioxidant N-acetylcysteine attenuates early adaptive responses to exercise in human skeletal muscleActa Physiol (Oxf).(2012 Mar)
- ^Agrawal S, Khazaeni BAcetaminophen ToxicityStatPearls.(2023-01)
- Cocaine Addiction Symptoms - LaRowe SD, Mardikian P, Malcolm R, Myrick H, Kalivas P, McFarland K, Saladin M, McRae A, Brady KSafety and tolerability of N-acetylcysteine in cocaine-dependent individualsAm J Addict.(2006 Jan-Feb)
- Mineral Bioaccumulation - Kasperczyk S, Dobrakowski M, Kasperczyk A, Ostałowska A, Birkner EThe administration of N-acetylcysteine reduces oxidative stress and regulates glutathione metabolism in the blood cells of workers exposed to leadClin Toxicol (Phila).(2013 Jul)
- Anaerobic Capacity - Cobley JN, McGlory C, Morton JP, Close GLN-Acetylcysteine Attenuates Fatigue Following Repeated-Bouts of Intermittent Exercise: Practical Implications for Tournament SituationsInt J Sport Nutr Exerc Metab.(2011 Aug 29)
- Trichotillomania Symptoms - Grant JE, Odlaug BL, Kim SWN-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled studyArch Gen Psychiatry.(2009 Jul)
- COPD Symptoms - van Overveld FJ, Demkow U, Górecka D, de Backer WA, Zielinski JNew developments in the treatment of COPD: comparing the effects of inhaled corticosteroids and N-acetylcysteineJ Physiol Pharmacol.(2005 Sep)
- Neutrophil Activity - van Overveld FJ, Vermeire PA, De Backer WAInduced sputum of patients with chronic obstructive pulmonary disease (COPD) contains adhesion-promoting, therapy-sensitive factorsInflamm Res.(2000 Jan)
- OCD Symptoms - Afshar H, Roohafza H, Mohammad-Beigi H, Haghighi M, Jahangard L, Shokouh P, Sadeghi M, Hafezian HN-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trialJ Clin Psychopharmacol.(2012 Dec)
- COPD Symptoms - Peter N Black, Althea Morgan-Day, Tracey E McMillan, Phillippa J Poole and Robert P YoungRandomised, controlled trial of N-acetylcysteine for treatment of acute exacerbations of chronic obstructive pulmonary diseasePulmonary Medicine.()
- COPD Symptoms - Decramer M, Rutten-van Mölken M, Dekhuijzen PN, Troosters T, van Herwaarden C, Pellegrino R, van Schayck CP, Olivieri D, Del Donno M, De Backer W, Lankhorst I, Ardia AEffects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trialLancet.(2005 Apr 30-May 6)
- COPD Symptoms - De Benedetto F, Aceto A, Dragani B, Spacone A, Formisano S, Pela R, Donner CF, Sanguinetti CMLong-term oral n-acetylcysteine reduces exhaled hydrogen peroxide in stable COPDPulm Pharmacol Ther.(2005)
- COPD Symptoms - Jiang C, Zou J, Lv Q, Yang YSystematic review and meta-analysis of the efficacy of N-acetylcysteine in the treatment of acute exacerbation of chronic obstructive pulmonary disease.Ann Palliat Med.(2021-Jun)
- COPD Symptoms - Huang C, Kuo S, Lin L, Yang YThe efficacy of -acetylcysteine in chronic obstructive pulmonary disease patients: a meta-analysis.Ther Adv Respir Dis.(2023)
- Bronchitis Symptoms - Wei J, Pang CS, Han J, Yan HEffect of Orally Administered N-Acetylcysteine on Chronic Bronchitis: A Meta-analysis.Adv Ther.(2019-Dec)
- Irritability - Hardan AY, Fung LK, Libove RA, Obukhanych TV, Nair S, Herzenberg LA, Frazier TW, Tirouvanziam RA randomized controlled pilot trial of oral N-acetylcysteine in children with autismBiol Psychiatry.(2012 Jun 1)
- Irritability - Ghanizadeh A, Moghimi-Sarani EA randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disordersBMC Psychiatry.(2013 Jul 25)
- Autism Symptoms - Lee TM, Lee KM, Lee CY, Lee HC, Tam KW, Loh EWEffectiveness of -acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials.Aust N Z J Psychiatry.(2021-Feb)
- Urinary NOx - Dimitrios Tsikas, Jonas Niemann, Markus Flentje, Alexandra Schwarz, Paschalis TossiosN-Acetylcysteine (NAC) inhibits renal nitrite and nitrate reabsorption in healthy subjects and in patients undergoing cardiac surgery: risk of nitric oxide (NO) bioavailability loss by NAC?Int J Cardiol.(2014 Nov 15)
- Tobacco Addiction Symptoms - Knackstedt LA, LaRowe S, Mardikian P, Malcolm R, Upadhyaya H, Hedden S, Markou A, Kalivas PWThe role of cystine-glutamate exchange in nicotine dependence in rats and humansBiol Psychiatry.(2009 May 15)
- Marijuana Addiction - Gray KM, Watson NL, Carpenter MJ, Larowe SDN-acetylcysteine (NAC) in young marijuana users: an open-label pilot studyAm J Addict.(2010 Mar-Apr)
- Acne Symptoms - Ahmed Salih Sahib, Haidar Hamid Al-Anbari, Mohammed Salih, and Fatima AbdullahEffects of Oral Antioxidants on Lesion Counts Associated with Oxidative Stress and Inflammation in Patients with Papulopustular AcneJournal of Clinical and Experimental Dermatology Research .()
- Depression Symptoms - Fernandes BS, Dean OM, Dodd S, Malhi GS, Berk MN-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis.J Clin Psychiatry.(2016-Apr)
- Cocaine Addiction Symptoms - Duailibi MS, Cordeiro Q, Brietzke E, Ribeiro M, LaRowe S, Berk M, Trevizol APN-acetylcysteine in the treatment of craving in substance use disorders: Systematic review and meta-analysis.Am J Addict.(2017-Oct)
- Forced Expiratory Volume - Ciofu O, Smith S, Lykkesfeldt JAntioxidant supplementation for lung disease in cystic fibrosis.Cochrane Database Syst Rev.(2019-Oct-03)
- Schizophrenia symptoms - Yolland CO, Hanratty D, Neill E, Rossell SL, Berk M, Dean OM, Castle DJ, Tan EJ, Phillipou A, Harris AW, Barreiros AR, Hansen A, Siskind DMeta-analysis of randomised controlled trials with -acetylcysteine in the treatment of schizophrenia.Aust N Z J Psychiatry.(2020-May)
- Kidney Function - Magner K, Ilin JV, Clark EG, Kong JWY, Davis A, Hiremath SMeta-analytic Techniques to Assess the Association Between N-acetylcysteine and Acute Kidney Injury After Contrast Administration: A Systematic Review and Meta-analysis.JAMA Netw Open.(2022-Jul-01)
- Helicobacter Pylori Infection Signs - Biswas DP, Tk DSThe efficacy of adjuvant N acetyl cysteine for the eradication of H pylori infections: A systematic review and meta-analysis of randomized clinical trials.Clin Res Hepatol Gastroenterol.(2022-Mar)
- Liver Enzymes - Jia D, Guo S, Jia Z, Gao Z, You K, Gong J, Li SN-acetylcysteine in the Donor, Recipient, or Both Donor and Recipient in Liver Transplantation: A Systematic Review With Meta-analysis and Trial Sequential Analysis.Transplantation.(2023-May-08)
- Length of hospitalization - Pereira JEG, El Dib R, Braz LG, Escudero J, Hayes J, Johnston BCN-acetylcysteine use among patients undergoing cardiac surgery: A systematic review and meta-analysis of randomized trials.PLoS One.(2019)
- Cycling Performance - Rhodes K, Braakhuis APerformance and Side Effects of Supplementation with N-Acetylcysteine: A Systematic Review and Meta-Analysis.Sports Med.(2017-Aug)
- Depression Symptoms - Nery FG, Li W, DelBello MP, Welge JAN-acetylcysteine as an adjunctive treatment for bipolar depression: A systematic review and meta-analysis of randomized controlled trials.Bipolar Disord.(2021-11)
- Rate Of Pregnancy - Devi N, Boya C, Chhabra M, Bansal D-acetyl-cysteine as adjuvant therapy in female infertility: a systematic review and meta-analysis.J Basic Clin Physiol Pharmacol.(2020-Nov-19)
- Testosterone - Zahra Shahveghar Asl, Karim Parastouei, Eslam EskandariThe effects of N-acetylcysteine on ovulation and sex hormones profile in women with polycystic ovary syndrome: a systematic review and meta-analysisBr J Nutr.(2023 Jan 4)
- Neuropathic Pain Symptoms - Mohiuddin M, Pivetta B, Gilron I, Khan JSEfficacy and Safety of N-Acetylcysteine for the Management of Chronic Pain in Adults: A Systematic Review and Meta-Analysis.Pain Med.(2021-Dec-11)
- Forced Vital Capacity - Rogliani P, Calzetta L, Cavalli F, Matera MG, Cazzola MPirfenidone, nintedanib and N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis: A systematic review and meta-analysis.Pulm Pharmacol Ther.(2016-Oct)