Common Name

N-acetylcysteine | acetylcysteine | NAC

Top Benefits of N-acetylcysteine

• Supports the production of glutathione*
• Supports liver detoxification*
• Supports healthy immune function*
• Supports healthy gut microbiota*

What is N-acetylcysteine?

N-acetylcysteine (NAC), a sulfur-containing amino acid, is the acetylated form of L-cysteine. The acetylation increases bioavailability compared to cysteine. NAC increases body stores of L-cysteine, which, along with glutamine and glycine, is used to make an important detoxification and antioxidant molecule called “glutathione”^[1]. This ability to support production of glutathione is NAC’s main mechanism of action^[2]. L-cysteine availability limits the rate of glutathione production (it is thought to be rate-limiting)^[3]. Supplying NAC allows the body to restore intracellular glutathione levels when demand has been increased or under circumstances when it is lower (such as older age or increased toxin exposure) in tissues throughout the body (including the brain, liver, and muscles). The combination of NAC and glycine appears to be additive^[4,5], which makes sense since both are used in glutathione production. NAC promotes glutathione-related antioxidant defenses, which helps protect cells and mitochondria against free radicals, cell membrane damage, damage from metals and toxins, and other oxidative stress-related and aging issues. 

NEUROHACKER’S N-ACETYLCYSTEINE SOURCING

NAC is non-GMO, gluten-free and vegan.

N-ACETYLCYSTEINE DOSING PRINCIPLES AND RATIONALE

NAC is generally considered to be dose-dependent (see Neurohacker Dosing Principles) in the range it’s most commonly dosed (between 400-2400 mg a day). Minor side-effects of NAC also go up with higher doses. Since our use is solely to augment the supply of molecular precursors to make glutathione in combination with other ingredients, and not to use NAC alone, we opted to use a low dose, primarily to benefits of having a glutathione precursor while being at a dose that’s sufficiently low enough to minimize the risk of producing unwanted effects.

N-ACETYLCYSTEINE KEY MECHANISMS 

Antioxidant defenses

• Supports glutathione levels in the plasma^[6]
• Supports glutathione levels in red blood cells^[7]
• Crosses the blood brain barrier and supports glutathione levels in the brain^[6,8,9]

Mitochondrial function

• Supports mitochondrial function^[10]
• Supports mitochondrial biogenesis^[11]
• Supports mitophagy (mitochondrial autophagy)^[12]

Brain function

• Supports neuroprotection (secondary to boosting glutathione and antioxidant defenses)^[13–15]
• Supports the auditory system from fatigue and noise-induced hearing loss^[16–19]

Immunity 

• Supports general immune health^[20–22]
• Supports innate immunity^[21–31]
• Supports adaptive immunity^{[20,22,27,32]}
• Supports mucosal immunity^[33,34]
• Supports immune tolerance^[35–39]
• Supports cellular intrinsic immune defenses^[40–48]   
• Supports immune signaling^{[22,23,44,49–51]}
• Supports antioxidant defenses and oxidative stress^{[22,25,27,52]} 
• Supports leukocyte glutathione (GSH) levels^[22,25,52]
• Supports healthy natural killer cell function^{[21,22,30,31,53–55]}
• Supports healthy macrophage function^{[24,25,27,56]}
• Supports healthy neutrophil function^{[22,26,28,57,58]}  
• Supports healthy T cell function^[50,59–62]    

Gastrointestinal function and gut microbiota

• Supports gut microbiota^[49,63–65]
• Supports gut barrier function^[34,63]
• Supports gut antioxidant defenses and oxidative stress^[63–65]
• Supports gut immune signaling^[34,66]

Synergies

• L-Theanine in support of general immune health^[67–73]
• Sulforaphane in support of cellular antioxidant defenses^[74–76]
• Glycine in support of glutathione synthesis^[5,77,78]

REFERENCES

[1] G. Wu, Y.-Z. Fang, S. Yang, J.R. Lupton, N.D. Turner, J. Nutr. 134 (2004) 489–492.
[2] K.R. Atkuri, J.J. Mantovani, L.A. Herzenberg, L.A. Herzenberg, Curr. Opin. Pharmacol. 7 (2007) 355–359.
[3] S.C. Lu, Biochim. Biophys. Acta 1830 (2013) 3143–3153.
[4] S. Xie, W. Zhou, L. Tian, J. Niu, Y. Liu, Fish Shellfish Immunol. 55 (2016) 233–241.
[5] K.A. Cieslik, R.V. Sekhar, A. Granillo, A. Reddy, G. Medrano, C.P. Heredia, M.L. Entman, D.J. Hamilton, S. Li, E. Reineke, A.A. Gupte, A. Zhang, G.E. Taffet, J. Gerontol. A Biol. Sci. Med. Sci. 73 (2018) 1167–1177.
[6] M.J. Holmay, M. Terpstra, L.D. Coles, U. Mishra, M. Ahlskog, G. Öz, J.C. Cloyd, P.J. Tuite, Clin. Neuropharmacol. 36 (2013) 103–106.
[7] S. Kasperczyk, M. Dobrakowski, A. Kasperczyk, A. Ostałowska, E. Birkner, Clin. Toxicol. 51 (2013) 480–486.
[8] S.A. Farr, H.F. Poon, D. Dogrukol-Ak, J. Drake, W.A. Banks, E. Eyerman, D.A. Butterfield, J.E. Morley, J. Neurochem. 84 (2003) 1173–1183.
[9] O.M. Dean, M. van den Buuse, M. Berk, D.L. Copolov, C. Mavros, A.I. Bush, Neurosci. Lett. 499 (2011) 149–153.
[10] O.E. Aparicio-Trejo, L.M. Reyes-Fermín, A. Briones-Herrera, E. Tapia, J.C. León-Contreras, R. Hernández-Pando, L.G. Sánchez-Lozada, J. Pedraza-Chaverri, Free Radic. Biol. Med. 130 (2018) 379–396.
[11] W.-C. Lee, L.-C. Li, J.-B. Chen, H.-W. Chang, ScientificWorldJournal 2015 (2015) 620826.
[12] V.S. Van Laar, N. Roy, A. Liu, S. Rajprohat, B. Arnold, A.A. Dukes, C.D. Holbein, S.B. Berman, Neurobiol. Dis. 74 (2015) 180–193.
[13] M. Günther, J. Davidsson, S. Plantman, S. Norgren, T. Mathiesen, M. Risling, J. Clin. Neurosci. 22 (2015) 1477–1483.
[14] E. Olakowska, W. Marcol, A. Właszczuk, I. Woszczycka-Korczyńska, J. Lewin-Kowalik, Adv. Clin. Exp. Med. 26 (2017) 1329–1334.
[15] W.A. Keshk, M.A. Ibrahim, S.M. Shalaby, Z.A. Zalat, W.S. Elseady, Arch. Biochem. Biophys. 680 (2020) 108227.
[16] C.-Y. Lin, J.-L. Wu, T.-S. Shih, P.-J. Tsai, Y.-M. Sun, M.-C. Ma, Y.L. Guo, Hear. Res. 269 (2010) 42–47.
[17] A.-C. Lindblad, U. Rosenhall, A. Olofsson, B. Hagerman, Noise Health 13 (2011) 392–401.
[18] M.E. Hoffer, C. Balaban, M.D. Slade, J.W. Tsao, B. Hoffer, PLoS One 8 (2013) e54163.
[19] R. Kopke, M.D. Slade, R. Jackson, T. Hammill, S. Fausti, B. Lonsbury-Martin, A. Sanderson, L. Dreisbach, P. Rabinowitz, P. Torre 3rd, B. Balough, Hear. Res. 323 (2015) 40–50.
[20] S. De Flora, C. Grassi, L. Carati, Eur. Respir. J. 10 (1997) 1535–1541.
[21] R. Breitkreutz, N. Pittack, C.T. Nebe, D. Schuster, J. Brust, M. Beichert, V. Hack, V. Daniel, L. Edler, W. Dröge, J. Mol. Med. 78 (2000) 55–62.
[22] L. Arranz, C. Fernández, A. Rodríguez, J.M. Ribera, M. De la Fuente, Free Radic. Biol. Med. 45 (2008) 1252–1262.
[23] A.M. Sadowska, B. Manuel-y-Keenoy, T. Vertongen, G. Schippers, D. Radomska-Lesniewska, E. Heytens, W.A. De Backer, Pharmacol. Res. 53 (2006) 216–225.
[24] M. Linden, E. Wieslander, A. Eklund, K. Larsson, R. Brattsand, Eur. Respir. J. 1 (1988) 645–650.
[25] D. Morris, C. Guerra, M. Khurasany, F. Guilford, B. Saviola, Y. Huang, V. Venketaraman, J. Interferon Cytokine Res. 33 (2013) 270–279.
[26] A.R. Heller, G. Groth, S.C. Heller, R. Breitkreutz, T. Nebe, M. Quintel, T. Koch, Crit. Care Med. 29 (2001) 272–276.
[27] M. Puerto, N. Guayerbas, V. Víctor, M. De la Fuente, Pharmacol. Biochem. Behav. 73 (2002) 797–804.
[28] L. Ohman, C. Dahlgren, P. Follin, D. Lew, O. Stendahl, Agents Actions 36 (1992) 271–277.
[29] V.M. Víctor, M. Rocha, M. De la Fuente, Int. Immunopharmacol. 3 (2003) 97–106.
[30] S. Kojima, H. Ishida, M. Takahashi, K. Yamaoka, Radiat. Res. 157 (2002) 275–280.
[31] M. Viora, M.G. Quaranta, E. Straface, R. Vari, R. Masella, W. Malorni, Immunology 104 (2001) 431–438.
[32]C. Spada, A. Treitinger, M. Reis, I.Y. Masokawa, J.C. Verdi, M.C. Luiz, M.V.S. Silveira, C.M. Michelon, S. Avila-Junior, L.D.O. Gil, S. Ostrowskyl, Clin. Chem. Lab. Med. 40 (2002) 452–455.
[33] O.V. Kalyuzhin, Ter. Arkh. 90 (2018) 89–95.
[34] S.I. Lee, K.S. Kang, Sci. Rep. 9 (2019) 1004.
[35] J.M. Oldham, L.J. Witt, A. Adegunsoye, J.H. Chung, C. Lee, S. Hsu, L.W. Chen, A. Husain, S. Montner, R. Vij, M.E. Strek, I. Noth, BMC Pulm. Med. 18 (2018) 30.
[36] S. Pathak, C. Stern, A. Vambutas, Immunol. Res. 63 (2015) 236–245.
[37] K. Shimada, H. Uzui, T. Ueda, J.-D. Lee, C. Kishimoto, J. Cardiovasc. Pharmacol. Ther. 20 (2015) 203–210.
[38] G. Wang, J. Wang, H. Ma, G.A.S. Ansari, M.F. Khan, Toxicol. Appl. Pharmacol. 273 (2013) 189–195.
[39] D. Lehmann, D. Karussis, R. Misrachi-Koll, E. Shezen, H. Ovadia, O. Abramsky, J. Neuroimmunol. 50 (1994) 35–42.
[40] A. Andreou, S. Trantza, D. Filippou, N. Sipsas, S. Tsiodras, In Vivo 34 (2020) 1567–1588.
[41] G.P. Sreekanth, J. Panaampon, A. Suttitheptumrong, A. Chuncharunee, J. Bootkunha, P.-T. Yenchitsomanus, T. Limjindaporn, Antiviral Res. 166 (2019) 42–55.
[42] X. Gao, E.-M. Lampraki, S. Al-Khalidi, M.A. Qureshi, R. Desai, J.B. Wilson, PLoS One 12 (2017) e0189167.
[43] M. Mata, I. Sarrion, M. Armengot, C. Carda, I. Martinez, J.A. Melero, J. Cortijo, PLoS One 7 (2012) e48037.
[44] M. Mata, E. Morcillo, C. Gimeno, J. Cortijo, Biochem. Pharmacol. 82 (2011) 548–555.
[45] P. Ghezzi, D. Ungheri, Int. J. Immunopathol. Pharmacol. 17 (2004) 99–102.
[46] M.-M.O. Garigliany, D.J. Desmecht, J. Negat. Results Biomed. 10 (2011) 5.
[47] A. Garozzo, G. Tempera, D. Ungheri, R. Timpanaro, A. Castro, Int. J. Immunopathol. Pharmacol. 20 (2007) 349–354.
[48] D. Ungheri, C. Pisani, G. Sanson, A. Bertani, G. Schioppacassi, R. Delgado, M. Sironi, P. Ghezzi, Int. J. Immunopathol. Pharmacol. 13 (2000) 123–128.
[49] Z. Luo, X. Xu, T. Sho, W. Luo, J. Zhang, W. Xu, J. Yao, J. Xu, J. Anim. Sci. 97 (2019) 1757–1771.
[50] Y. Delneste, P. Jeannin, L. Potier, P. Romero, J.Y. Bonnefoy, Blood 90 (1997) 1124–1132.
[51] G.V. Guibas, E. Spandou, S. Meditskou, T.A. Vyzantiadis, K.N. Priftis, G. Anogianakis, Int. Forum Allergy Rhinol. 3 (2013) 543–549.
[52] A.M. Gamage, K.O. Lee, Y.-H. Gan, Microbes Infect. 16 (2014) 661–671.
[53] N. Guayerbas, M. Puerto, M.D. Ferrández, M. De La Fuente, Clin. Exp. Pharmacol. Physiol. 29 (2002) 1009–1014.
[54] M. De La Fuente, J. Miquel, M.P. Catalán, V.M. Víctor, N. Guayerbas, Free Radic. Res. 36 (2002) 119–126.
[55] W. Malorni, A. D’Ambrosio, G. Rainaldi, R. Rivabene, M. Viora, Immunol. Lett. 43 (1994) 209–214.
[56] N. Guayerbas, M. Puerto, P. Alvarez, M. de la Fuente, Cell. Mol. Biol. 50 Online Pub (2004) OL677–81.
[57] C. Gaykwad, J. Garkhal, G.E. Chethan, S. Nandi, U.K. De, J. Vet. Pharmacol. Ther. 41 (2018) 68–75.
[58] R.-H. Zhang, C.-H. Li, C.-L. Wang, M.-J. Xu, T. Xu, D. Wei, B.-J. Liu, G.-H. Wang, S.-F. Tian, Int. Immunopharmacol. 22 (2014) 1–8.
[59] K. Pilipow, E. Scamardella, S. Puccio, S. Gautam, F. De Paoli, E.M. Mazza, G. De Simone, S. Polletti, M. Buccilli, V. Zanon, P. Di Lucia, M. Iannacone, L. Gattinoni, E. Lugli, JCI Insight 3 (2018).
[60] M.J. Scheffel, G. Scurti, P. Simms, E. Garrett-Mayer, S. Mehrotra, M.I. Nishimura, C. Voelkel-Johnson, Cancer Res. 76 (2016) 6006–6016.
[61] M.J. Scheffel, G. Scurti, M.M. Wyatt, E. Garrett-Mayer, C.M. Paulos, M.I. Nishimura, C. Voelkel-Johnson, Cancer Immunol. Immunother. 67 (2018) 691–702.
[62] K. Schlie, A. Westerback, L. DeVorkin, L.R. Hughson, J.M. Brandon, S. MacPherson, I. Gadawski, K.N. Townsend, V.I. Poon, M.A. Elrick, H.C.F. Côté, N. Abraham, E.J. Wherry, N. Mizushima, J.J. Lum, J. Immunol. 194 (2015) 4277–4286.
[63] J. Zheng, X. Yuan, C. Zhang, P. Jia, S. Jiao, X. Zhao, H. Yin, Y. Du, H. Liu, J. Diabetes (2018).
[64] C.C. Xu, S.F. Yang, L.H. Zhu, X. Cai, Y.S. Sheng, S.W. Zhu, J.X. Xu, J. Anim. Sci. 92 (2014) 1504–1511.
[65] C. Wan, R. Xue, Y. Zhan, Y. Wu, X. Li, F. Pei, OMICS 21 (2017) 540–549.
[66] D. Yi, Y. Hou, H. Xiao, L. Wang, Y. Zhang, H. Chen, T. Wu, B. Ding, C.-A.A. Hu, G. Wu, Amino Acids 49 (2017) 1915–1929.
[67] K. Miyagawa, Y. Hayashi, S. Kurihara, A. Maeda, Geriatr. Gerontol. Int. 8 (2008) 243–250.
[68] S. Kawada, K. Kobayashi, M. Ohtani, C. Fukusaki, J. Strength Cond. Res. 24 (2010) 846–851.
[69] S. Murakami, S. Kurihara, N. Koikawa, A. Nakamura, K. Aoki, H. Yosigi, K. Sawaki, M. Ohtani, Biosci. Biotechnol. Biochem. 73 (2009) 817–821.
[70] S. Murakami, S. Kurihara, C.A. Titchenal, M. Ohtani, J. Int. Soc. Sports Nutr. 7 (2010) 23.
[71] S. Kurihara, S. Shibahara, H. Arisaka, Y. Akiyama, J. Vet. Med. Sci. 69 (2007) 1263–1270.
[72] S. Kurihara, T. Shibakusa, K.A. Tanaka, Springerplus 2 (2013) 635.
[73] S. Kurihara, T. Hiraoka, M. Akutsu, E. Sukegawa, M. Bannai, S. Shibahara, J. Amino Acids 2010 (2010) 307475.
[74] H.-J. Liu, L. Wang, L. Kang, J. Du, S. Li, H.-X. Cui, Cell. Physiol. Biochem. 51 (2018) 528–542.
[75] E.S. Son, J.-W. Park, Y.J. Kim, S.H. Jeong, J.H. Hong, S.-H. Kim, S.Y. Kyung, Toxicol. In Vitro 67 (2020) 104883.
[76] A. Langston-Cox, D. Anderson, D.J. Creek, K. Palmer, E.M. Wallace, S.A. Marshall, Molecules 25 (2020).
[77] M.D. Borges-Santos, F. Moreto, P.C.M. Pereira, Y. Ming-Yu, R.C. Burini, Nutrition 28 (2012) 753–756.
[78] S. Xie, L. Tian, J. Niu, G. Liang, Y. Liu, Fish Physiol. Biochem. 43 (2017) 1011–1020.