The Glutathione System is Key to Optimal Detoxification

Sponsored by Quicksilver Scientific

By Christopher Shade, PhD

In my last Natural Medicine Journal blog I discussed the importance of high quality mercury testing that includes hair, urine, and blood analysis. In this article, I’d like to address clinically-significant ways to enhance detoxification, in particular, the detoxification of heavy metals such as mercury.

There are nearly as many opinions about effective detoxification protocols as there are protocols. Although opinions abound, there is a core focus that is hard to argue with: strengthening the glutathione system is critical.

As humans, we have a built-in natural detoxification system that works on a deep cellular level. This is the glutathione system. We know that up-regulating all aspects of this system will help rid the body of toxins, especially heavy metals such as mercury.1 By strengthening the glutathione system, we positively enhance all three phases of detoxification, but in particular phases II and III:

  • Phase I—Oxidation, reduction and hydrolysis of substances via cytochrome P450 enzymes
  • Phase II—Sulfation, glucuronidation, and glutathione conjugation of toxins
  • Phase III—Cellular transport and elimination of the conjugated substances

Optimal phase II and III detoxification requires the activation of the “cellular master switch” which is known as the Nrf2 protein.2 This protein turns on the intracellular production of several antioxidants, including glutathione, and glutathione-S-transferase, the phase II enzyme that serves to bind glutathione to toxins for subsequent elimination from the cell.

There are many natural substances that can activate Nrf2 including lipoic acid, selenium, kelp extract, pine bark extract, and haritaki fruit. In addition, intracellular levels of glutathione can be enhanced with vitamin C and R-lipoic acid.3-5 Obviously, one of the most direct ways to increase glutathione levels is via supplementation of glutathione directly to the cell, which thankfully can be done with properly designed liposomal delivery systems. In cell cultures, liposomal glutathione has been demonstrated to be 100 times more effective for increasing intracellular levels than non-liposomal glutathione.6

Gastrointestinal health also has an effect on detoxification, as inflammation in the intestine increases susceptibility of the organism to toxicity from external and internal agents.7 Leaky gut and damage to the gastrointestinal barrier allows endotoxin, also known as lipopolysaccharide (LPS), to be released into circulation. Exposure to endotoxin has an effect on other stages of detoxification, downregulating expression of some of the CYP enzymes and Phase III transporters.8,9 Many herbs which we use as bitters such as dandelion, burdock, goldenrod, and milk thistle actually also increase glutathione, or levels of glutathione-S-transferase, while simultaneously supporting function of the liver, kidneys, and intestines.10-14 By using metal-specific binding substances such as thiol-functionalized silica and other binding agents such as clay and charcoal we also are able to eliminate the enterohepatic recirculation of toxins and remove the blockages that they create for detoxification.

When substances such as glutathione, lipoic acid, and vitamin C are delivered in liposomes, detoxification is enhanced even further.15 Liposomes are microscopic spheres made of phospholipids that encapsulate therapeutic compounds, such as glutathione, in order to bypass the digestive processes that can degrade the substance or limit its absorption. Liposomes can also cross the blood-brain barrier, deposit their cargo intracellularly and enhance lymphatic circulation of therapeutic compounds. Additionally, cell membranes are nourished by the phospholipids that compose the liposome. This ensures the proper function for the absorption of nutrients and the excretion of cellular waste products and toxins. A functional membrane and transportation system is necessary for the transport of toxins and bile in hepatocytes, and similarly in the proximal tubules for elimination at the level of the kidneys.

While protocols can vary, for successful and comprehensive detoxification one must focus on supporting all of these critical things: the glutathione system, the phases of cellular detoxification, proper function of cellular membranes, and healthy elimination by the liver, kidneys, and intestines. At Quicksilver Scientific, we have created several comprehensive protocols and packages to make this process simple and effective for both patients and practitioners. By using the many natural substances that are available as supplements, the body is supported in its own endogenous processes of detoxification and healing.

About the Author

Christopher Shade, PhD, obtained bachelor of science and masters of science degrees from Lehigh University in environmental and aqueous chemistry, and a PhD from the University of Illinois where he studied metal-ligand interactions in the environment and specialized in the analytical chemistries of mercury. During his PhD work, Shade patented analytical technology for mercury speciation analysis and later founded Quicksilver Scientific, LLC, to commercialize this technology. Shortly after starting Quicksilver Scientific, Shade turned his focus to the human aspects of mercury toxicity and the functioning of the human detoxification system. He has since researched and developed superior liposomal delivery systems for the nutraceutical and wellness markets and also specific clinical analytical techniques for measuring human mercury exposure. He used his understanding of mercury and glutathione chemistry to design a unique system of products for detoxification that repairs and then maximizes the natural detoxification system.

References

  1. Lushchak VI. Glutathione homeostasis and function: potential targets for medical interventions. J Amino Acids. 2012(2012).
  2. Keum YS. Regulation of Nrf2-mediated phase II detoxification and anti-oxidant genes. Biomol Ther. 2012;20(2):144-151.
  3. Meister A. Glutathione-ascorbic acid antioxidant system in animals. J Biol Chem. 1994;269(13):9397-400.
  4. Packer L, et al. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001;17:888-895.
  5. Packer L, et al. Alpha-lipoic acid as a biological antioxidant. Free Radical Bio Med. 1995;19:227-250.
  6. Zeevalk GD, Bernard LP, Guilford FT. Liposomal-glutathione provides maintenance of intracellular glutathione and neuroprotection in mesencephalic neuronal cells. Neurochem Res. 2010;10:1575-87.
  7. Ganey PE, Roth RA. Concurrent inflammation as a determinant of susceptibility to toxicity from xenobiotic agents. Toxicology. 2001;169(3):195-208.
  8. Tang W, Yi C, Kalitsky J, Piquette-Miller M. Endotoxin downregulates hepatic expression of P-glycoprotein and MRP2 in 2-acetylaminofluorene-treated rats. Mol Cell Biol Res Commun. 2000;4(2):90-7.
  9. Kalitsky-Szirtes J, Shayeganpour A, Brocks DR, Piquette-Miller M. Suppression of drug-metabolizing enzymes and efflux transporters in the intestine of endotoxin-treated rats. Drug Metab Dispos. 2004;32(1):20-7.
  10. Wang BS, et al. Protective effects of burdock (Arctium lappa Linne) on oxidation of low-density lipoprotein and oxidative stress in RAW 264.7 macrophages. Food Chemistry. 2007;101(2):729-38.
  11. Apáti P, et al. In-vitro effect of flavonoids from Solidago canadensis extract on GSH S-transferase. J Pharm Pharmacol. 2006;58(2):251-6.
  12. Valenzuela A, Aspillaga M, Vial S, Guerra R. Selectivity of silymarin on the increase of the GSH content in different tissues of the rat. Planta Med. 1989;55(5):420-2.
  13. Rui YC. Advances in pharmacological studies of silymarin. Mem Inst Oswaldo Cruz. 1991;86 Suppl 2:79-85.
  14. You Y, et al. In vitro and in vivo hepatoprotective effects of the aqueous extract from Taraxacum officinale (dandelion) root against alcohol-induced oxidative stress. Food Chem Toxicol. 2010;48(6):1632-7.
  15. Shade C. Liposomes as advanced delivery systems for nutraceuticals. Integr Med. 2016;15(1):33-36.