Antioxidant Support During Liver Detox

A superfamily of enzymes responsible for converting foreign substances in the body (‘xenobiotics’) into benign metabolites during Phase II of liver detoxification are the Glutathione S-transferases (GSTs). GSTs are supportive of both antioxidant and detoxification functions, including heavy metal detoxification.[i]

Particular heavy metals are metabolized by a powerful antioxidant - glutathione - the first step in the detoxification of these toxins.[ii] The resulting products are less reactive and may then be eliminated by the body.[iii]

Selenium, also an antioxidant, substantially contributes to the combining and neutralizing of substances such as heavy metals[iv], by acting as a helper molecule (‘cofactor’) for antioxidant enzyme glutathione peroxidase.[v] Selenium supplementation has been shown to increase the activity of both GSTs and glutathione peroxidase.[vi]

Individuals dealing with this issue are recommended to consume selenium-rich foods (e.g. Brazil nuts and wild-caught fish and/or shellfish). These foods would support Phase II of the liver detoxification process.

Another antioxidant, N-acetylcysteine (NAC), stimulates glutathione production and increases GST response and activity in the body by acting as a precursor to glutathione.[vii] NAC provides an important component of protein and enzymes - cysteine; the availability of cysteine is a determining factor in the production of glutathione.[viii]

Decreased activity of GSTs, due to genetic variations, may lead to increased oxidative damage and diseases (i.e. cancer, cardiovascular disease, insulin resistance and diabetes).[ix]

NAC supplementation may make circumstances more tolerable by supporting the inefficiency of a genetically-compromised system. Furthermore, glutathione tends to be poorly absorbed and less able to then enter the bloodstream because it is rapidly oxidized; therefore, oral supplementation of NAC may be preferred to supplementation of glutathione.[x] NAC is metabolized in the liver, replenishing the liver’s stores of glutathione before sending the rest into the bloodstream for use in the body.[xi] Current evidence shows NAC dosages ranging from 800-2400 grams/day, with 800 grams/day showing to be effective for helping with oxidative stress and glutathione status in the body.[xii]

While there are no food sources of NAC, one could benefit from consuming foods high in its precursor nutrient cysteine, including broccoli, eggs and meats. There is no Dietary Reference Intake (DRI) for NAC; exact dosage recommendations would depend on the severity of symptoms being experienced, as well as any genetic variation in the body that would contribute to inefficient GST activity.

ENDNOTES

[i] Gaxiola-Robles, R., Labrada-Martagón, V., Celis de la Rosa, Alfredo,de Jes, Acosta-Vargas, B., Méndez-Rodríguez, L. C., & Zenteno-Savín, T. (2014). Interaction between mercury (hg), arsenic (as) and selenium (se) affects the activity of glutathione S-transferase in breast milk; possible relationship with fish and shellfish intake. Nutricion Hospitalaria, 30(2), 436-446. doi:10.3305/nh.2014.30.2.7441.

[ii] Gaxiola-Robles, R., Labrada-Martagón, V., Celis de la Rosa, Alfredo,de Jes, Acosta-Vargas, B., Méndez-Rodríguez, L. C., & Zenteno-Savín, T. (2014). Interaction between mercury (hg), arsenic (as) and selenium (se) affects the activity of glutathione S-transferase in breast milk; possible relationship with fish and shellfish intake. Nutricion Hospitalaria, 30(2), 436-446. doi:10.3305/nh.2014.30.2.7441.

[iii] Goodrich, J. M., & Basu, N. (2012). Variants of glutathione s-transferase pi 1 exhibit differential enzymatic activity and inhibition by heavy metals. Toxicology in Vitro, 26, 630-635. doi:10.1016/j.tiv.2012.02.005.

[iv] Gaxiola-Robles, R., Labrada-Martagón, V., Celis de la Rosa, Alfredo,de Jes, Acosta-Vargas, B., Méndez-Rodríguez, L. C., & Zenteno-Savín, T. (2014). Interaction between mercury (hg), arsenic (as) and selenium (se) affects the activity of glutathione S-transferase in breast milk; possible relationship with fish and shellfish intake. Nutricion Hospitalaria, 30(2), 436-446. doi:10.3305/nh.2014.30.2.7441.

[v] Natural Medicine Database (2018). Retrieved from https://naturalmedicines-therapeuticresearch-com.uws.idm.oclc.org/databases/food,-herbs-supplements/professional.aspx?productid=1003

[vi] Natural Medicine Database (2018). Retrieved from https://naturalmedicines-therapeuticresearch-com.uws.idm.oclc.org/databases/food,-herbs-supplements/professional.aspx?productid=1003

[vii] Moradi, M., Mojtahedzadeh, M., Mandegari, A., Soltan-Sharifi, M., Najafi, A., Khajavi, M., …, & Ghahremani, M. (2009). The role of glutathione-S-transferase polymorphisms on clinical outcome of ALI-ARDS patient treated with N-acetylcysteine. Resp Med. 103(3).

[viii] Kasperczyk, S., Dobrakowski, M., Kasperczyk, A., Ostalowska, A., & Birkner, E. (2013). The administration of N-acetylcysteine reduces oxidative stress and regulates glutathione metabolism in the blood cells of workers exposed to lead. Clin Toxicol (Phila). 51(6).

[ix] Lin, Y., Hung, S., Wei, Y., & Tarng, D. (2008). GST M1 Polymorphism Associates with DNA Oxidative Damage and Mortality among Hemodialysis Patients. JASN. 20(2).

Zukowski, P., Maciejczyk, M., Matczuk, J., Kurek, K., Waszkiel, D., Zendzian-Piotrowska, M., & Zalewska, A. (2018). Effect of N-Acetylcysteine on Antioxidant Defense, Oxidative Modification, and Salivary Gland Function in a Rat Model of Insulin Resistance. Oxid Med Cell Longev. Epub Jan 30.

[x] Schmitt, B., Vicenzi, M., Garrel, C., & Denis, F. (2015). Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study. Redox Biol. Epub 2015 Jul 29.

[xi] Schmitt, B., Vicenzi, M., Garrel, C., & Denis, F. (2015). Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study. Redox Biol. Epub 2015 Jul 29.

[xii] Schmitt, B., Vicenzi, M., Garrel, C., & Denis, F. (2015). Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study. Redox Biol. Epub 2015 Jul 29.


Travis Cox