N-acetylcysteine

N-acetylcysteine Common Name

N-acetylcysteine | acetylcysteine | NAC

Top Benefits of N-acetylcysteine

  • Supports the production of glutathione*
  • Upregulates antioxidant defenses*
  • 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 used as a precursor (i.e., substrate) by the body to make glutathione. It’s this mechanism that’s our reason for including it.

In general, NAC is additive with glycine (another glutathione substrate), so it can be useful to stack the two together in formulations.

NAC sourcing is focused on identifying and purchasing from a reputable supplier and ensuring it 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 commonly dosed (between 400-2400 mg a day). But, 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, and not to use NAC as part of a clinical treatment protocol, we opted to use a very low dose, primarily to gain some benefits of having a glutathione precursor (if it’s needed) while being at a dose that’s sufficiently low enough to minimize the risk of producing unwanted effects.

N-acetylcysteine Key Mechanisms

Antioxidant defenses

  • Upregulates glutathione levels in the plasma (6)
  • Upregulates glutathione levels in red blood cells (7)
  • Crosses the blood brain barrier and upregulates glutathione levels in the brain (6, 8, 9)

Mitochondrial function

  • Protects from mitochondrial dysfunction (10)
  • Supports mitochondrial biogenesis (11)
  • Supports mitophagy (mitochondrial autophagy) (12)

Brain function

  • Supports neuroprotection (secondary to boosting glutathione and antioxidant defenses) (13, 14)
  • Protects auditory system from fatigue and noise-induced hearing loss (15–18)

Immune system and cell signaling

  • Supports balanced immune mechanisms and cell signaling (19, 20)
  • Protects from age-related cellular responses and immune function declines (immunosenescence) (19, 21–23)

Gut microbiota

  • Downregulates gut oxidative stress (24–26)
  • Regulates the composition of the gut microbiota (24, 26)
  • Regulates gut microbial metabolism (24, 25)
  • Supports gut barrier function (24)

REFERENCES 

1. G. Wu, Y.-Z. Fang, S. Yang, J. R. Lupton, N. D. Turner, J. Nutr. 134, 489–492 (2004).
2. K. R. Atkuri, J. J. Mantovani, L. A. Herzenberg, L. A. Herzenberg, Curr. Opin. Pharmacol. 7, 355–359 (2007).
3. S. C. Lu, Biochim. Biophys. Acta. 1830, 3143–3153 (2013).
4. S. Xie, W. Zhou, L. Tian, J. Niu, Y. Liu, Fish Shellfish Immunol. 55, 233–241 (2016).
5. K. A. Cieslik et al., J. Gerontol. A Biol. Sci. Med. Sci. 73, 1167–1177 (2018).
6. M. J. Holmay et al., Clin. Neuropharmacol. 36, 103–106 (2013).
7. S. Kasperczyk, M. Dobrakowski, A. Kasperczyk, A. Ostałowska, E. Birkner, Clin. Toxicol. . 51, 480–486 (2013).
8. S. A. Farr et al., J. Neurochem. 84, 1173–1183 (2003).
9. O. M. Dean et al., Neurosci. Lett. 499, 149–153 (2011).
10. O. E. Aparicio-Trejo et al., Free Radic. Biol. Med. 130, 379–396 (2018).
11. W.-C. Lee, L.-C. Li, J.-B. Chen, H.-W. Chang, ScientificWorldJournal. 2015, 620826 (2015).
12. V. S. Van Laar et al., Neurobiol. Dis. 74, 180–193 (2015).
13. M. Günther et al., J. Clin. Neurosci. 22, 1477–1483 (2015).
14. E. Olakowska, W. Marcol, A. Właszczuk, I. Woszczycka-Korczyńska, J. Lewin-Kowalik, Adv. Clin. Exp. Med. 26, 1329–1334 (2017).
15. C.-Y. Lin et al., Hear. Res. 269, 42–47 (2010).
16. A.-C. Lindblad, U. Rosenhall, A. Olofsson, B. Hagerman, Noise Health. 13, 392–401 (2011).
17. M. E. Hoffer, C. Balaban, M. D. Slade, J. W. Tsao, B. Hoffer, PLoS One. 8, e54163 (2013).
18. R. Kopke et al., Hear. Res. 323, 40–50 (2015).
19. L. Arranz, C. Fernández, A. Rodríguez, J. M. Ribera, M. De la Fuente, Free Radic. Biol. Med. 45, 1252–1262 (2008).
20. A. Perl et al., Metabolomics. 11, 1157–1174 (2015).
21. B. Purwanto, D. H. Prasetyo, Acta Med. Indones. 44, 140–144 (2012).
22. F. Saddadi, S. Alatab, F. Pasha, M. R. Ganji, T. Soleimanian, Saudi J. Kidney Dis. Transpl. 25, 66 (2014).
23. A. Jeremias et al., Heart Int. 4, e7 (2009).
24. J. Zheng et al., J. Diabetes (2018), doi:10.1111/1753-0407.12795.
25. C. Wan et al., OMICS. 21, 540–549 (2017).
26. C. C. Xu et al., J. Anim. Sci. 92, 1504–1511 (2014).

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.