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NAC vs. Glutathione: How They Work in the Body

Jun 15, 2023
NAC vs. Glutathione: How They Work in the Body

NAC vs. glutathione, how are they related? This relationship is pretty straightforward. N-acetylcysteine (NAC) is a precursor for glutathione. Glutathione functions as a cellular antioxidant. It is a tripeptide made up of three amino acids—cysteine, glycine, and glutamate. NAC is a cysteine derivative. By increasing cysteine levels in the body, NAC boosts glutathione levels.

As more information is available on the internet and many people focus on preventative healthcare and wellness instead of treating disease, the interest in understanding the biochemistry behind normal cellular function and the changes associated with aging has grown. Glutathione is an essential antioxidant, frequently called the master antioxidant, that decreases with aging and when your body is under stress.  

What is glutathione?

Glutathione is an antioxidant with multiple roles in the body, supporting the immune system, providing antioxidant protection, and removing toxins.1 These roles include:2

  • Neutralizing free radicals produced as a byproduct of metabolism
  • Assisting enzymes involved in antioxidant processes
  • Regenerating vitamins C and E
  • Neutralizing free radicals produced by metabolizing cellular toxins
  • Transporting mercury out of cells
  • Regulating cell division and programmed cell death
  • Maintaining mitochondrial DNA

What is NAC?

NAC is a derivative of cysteine and a glutathione precursor. Medically, NAC is used to replenish cysteine and glutathione levels secondary to acetaminophen toxicity. When administered intravenously, NAC is less toxic, less prone to oxidation, and more soluble in water than cysteine. It can also reduce protein disulfide bonds, scavenge free radicals, and bind metals to form complexes.3

When NAC is taken by mouth, it is absorbed, distributed to the liver, and metabolized into cysteine. From there, most cysteine is incorporated into the reduced form of glutathione.3

NAC vs. Glutathione: How They Work in the Body

How is glutathione produced?

Glutathione is found in high concentrations in nearly every cell in the body. It is found in two states, reduced (GSH) and oxidized (GSSG).

When cells are under stress, the ratio of GSH to GSSG drops.

Due to its importance, your body has three ways to produce glutathione:2

  • Making glutathione from scratch in a two-step process. The enzymes glutamate cysteine ligase and glutathione synthetase catalyze this process.
  • Regenerating GSH from oxidized GSSG by glutathione reductase.
  • Recycling of cysteine from conjugated glutathione via GGTP.

Cysteine availability is the rate-limiting step for making glutathione.

glutathione chemical structure

What foods can increase glutathione?

Foods that are high in sulfur or cysteine to increase glutathione levels naturally include the following:

  • Asparagus
  • Avocado
  • Broccoli
  • Cabbage
  • Cucumber
  • Garlic
  • Green beans
  • Green tea
  • Kale
  • Leeks
  • Meats
  • Mushrooms
  • Onions
  • Papaya
  • Pomegranate juice
  • Spinach
  • Whey
foods high in antioxidants

What causes low glutathione levels?

Glutathione depletion is strongly associated with disease and the loss of function associated with aging.4

Factors that deplete glutathione include:5,6

  • Aging
  • Infections
  • Poor nutrition
  • Excessive exercise
  • Excessive alcohol consumption
  • Environmental toxins
  • Pollution
  • Heavy metal exposure
  • DNA damage
  • Exposure to radiation
  • Chronic diseases
  • Sleep deprivation
  • Smoking

Is NAC the same thing as glutathione?

No, NAC is a precursor of cysteine and glutathione. Administering NAC increases cysteine levels in your cells. Cysteine is the rate-limiting step in producing glutathione.7

Is supplementing glutathione more effective than NAC?

Glutathione can be administered orally, topically, intravenously, intranasally, or via a nebulizer. Research suggests that when glutathione is administered intravenously, inhaled, and or taken intranasally it increases systemic glutathione levels.2,8 Oral glutathione supplementation is controversial. Research shows inconsistent results about whether oral supplementation increases glutathione levels.2

Supplementing with whey or N-acetylcysteine (NAC) increases cysteine, the rate-limiting step in producing glutathione.2

A doctor answering a question about NAC vs. glutathione

Should I take glutathione and NAC?

It depends. Glutathione and NAC both increase glutathione levels. Ideally, your diet should provide the amino acids your body needs to produce glutathione. Choose sulfur-rich and cysteine-rich foods. When taking oral supplements, NAC seems to be more stable than glutathione. However, some people have difficulty tolerating NAC, experiencing diarrhea, nausea, vomiting, and skin rashes. Contact an Invigor Medical treatment specialist to learn more about and buy glutathione injections.

Frequently Asked Questions

Is glutathione better than NAC?

The effectiveness of glutathione versus NAC (N-acetyl cysteine) depends on individual needs and health conditions. Both substances play crucial roles in antioxidant defense and overall health. Consulting with a healthcare professional can help determine which may be more suitable for specific concerns.

Is NAC the strongest antioxidant?

While NAC (N-acetyl cysteine) is a potent antioxidant, it may not necessarily be considered the strongest antioxidant overall. Different antioxidants have varying mechanisms of action and may target different types of oxidative stress. The efficacy of antioxidants can vary based on factors such as dosage, bioavailability, and individual health status.

What does NAC deplete?

NAC (N-acetyl cysteine) can deplete certain minerals, including zinc and copper, due to its role in promoting the synthesis of metallothionein, a protein involved in metal ion regulation. Supplementing with NAC may necessitate monitoring and potentially supplementing with these minerals as well.

What are the cons of NAC?

Some potential drawbacks or considerations associated with NAC supplementation include gastrointestinal side effects such as nausea and vomiting, potential interactions with certain medications, and the risk of allergic reactions in individuals sensitive to sulfur-containing compounds. As with any supplement, it’s advisable to discuss the pros and cons with a healthcare provider before use.

Disclaimer
While we strive to always provide accurate, current, and safe advice in all of our articles and guides, it’s important to stress that they are no substitute for medical advice from a doctor or healthcare provider. You should always consult a practicing professional who can diagnose your specific case. The content we’ve included in this guide is merely meant to be informational and does not constitute medical advice.

NAC vs. Glutathione: How They Work in the Body

Leann Poston, M.D.

Dr. Leann Poston is a licensed physician in the state of Ohio who holds an M.B.A. and an M. Ed. She is a full-time medical communications writer and educator who writes and researches for Invigor Medical. Dr. Poston lives in the Midwest with her family. She enjoys traveling and hiking. She is an avid technology aficionado and loves trying new things.

References

  • Dröge W, Breitkreutz R. Glutathione and immune function. Proc Nutr Soc. 2000 Nov;59(4):595-600. doi: 10.1017/s0029665100000847. PMID: 11115795.
  • Pizzorno J. Glutathione! Integr Med (Encinitas). 2014 Feb;13(1):8-12. PMID: 26770075; PMCID: PMC4684116.
  • Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine–a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol. 2007 Aug;7(4):355-9. doi: 10.1016/j.coph.2007.04.005. Epub 2007 Jun 29. PMID: 17602868; PMCID: PMC4540061.
  • Julius M, Lang CA, Gleiberman L, Harburg E, DiFranceisco W, Schork A. Glutathione and morbidity in a community-based sample of elderly. J Clin Epidemiol. 1994 Sep;47(9):1021-6. doi: 10.1016/0895-4356(94)90117-1. PMID: 7730904.
  • Kanagasabai T, Ardern CI. Inflammation, Oxidative Stress, and Antioxidants Contribute to Selected Sleep Quality and Cardiometabolic Health Relationships: A Cross-Sectional Study. Mediators Inflamm. 2015;2015:824589. doi:10.1155/2015/824589
  • Flora SJ, Mittal M, Mehta A. Heavy metal induced oxidative stress & its possible reversal by chelation therapy. Indian J Med Res. Oct 2008;128(4):501-23.
  • Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine–a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol. 2007 Aug;7(4):355-9. doi: 10.1016/j.coph.2007.04.005. Epub 2007 Jun 29. PMID: 17602868; PMCID: PMC4540061. 8. Buhl R, Vogelmeier C, Critenden M, Hubbard RC, Hoyt RF Jr, Wilson EM, Cantin AM, Crystal RG. Augmentation of glutathione in the fluid lining the epithelium of the lower respiratory tract by directly administering glutathione aerosol. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4063-7. doi: 10.1073/pnas.87.11.4063. PMID: 2349219; PMCID: PMC54047

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