The Use of Glutathione, Master Antioxidant in Clinical Settings

Even if you are not doing a deep dive into detoxification protocols, there is a vast array of clinical settings in which glutathione may impact health conditions

No matter what clinical setting your medical or nutrition-focused practice is in, the antioxidant glutathione has undoubtedly been a topic of discussion. Collectively, we understand that glutathione is the body’s main antioxidant and therefore the master detoxifier.[i] However, a simple statement of such, albeit grandiose, fails to capture the vast array of health conditions that glutathione may impact. Clinically, glutathione has importance in settings ranging from mental health to viral infections to heavy metal detoxification. It is worthy of a moment or two to highlight the research and clinical studies surrounding glutathione, and how the body’s glutathione status may impact various health conditions.

Typical oral delivery of glutathione is greatly inhibited by breakdown in the stomach and minimally impacts intracellular levels. Thus, much research pertaining to glutathione involves the use of other substances which support intracellular glutathione levels.[ii] N-acetylcysteine (NAC) is one example, as this compound primarily has antioxidant benefits due to replenishing glutathione.[iii] Liposomal delivery systems protect glutathione from breakdown in the digestive system that otherwise prevents absorption of oral glutathione supplements. Additionally, the phospholipid-encapsulated sphere which delivers glutathione into the cell simultaneously replenishes and nourishes the cell by providing phospholipids of which cellular membranes are comprised. In cell cultures, liposomal glutathione has been demonstrated to be 100 times more efficiency for intracellular delivery than non-liposomal glutathione.^[iv]

Autism spectrum disorder (ASD)

Increased oxidative stress and mitochondrial dysfunction may contribute to the development and clinical manifestation of autism.[v],[vi] Children on the autistic spectrum have been shown to have lower levels of glutathione, which may be caused by metabolic abnormalities and nutritional deficiencies, but also may further contribute to them.[vii] In addition to this, significantly lower levels of phospholipids have been reported in children with autism.[viii] Supplemental NAC and glutathione have been studied specifically in the setting of ASD, and have been shown to increase glutathione levels.[ix][x] Utilization of glutathione in a liposomal format also provides the essential phospholipids which may be deficient and are necessary for mitochondrial and cellular repair.

Attention deficit and mood disorders

Increased oxidative stress may contribute to attention deficit and mood disorders via numerous mechanisms.^[xii] Therapies directed at supporting antioxidant levels such as NAC, vitamin C, and a pine back extract known as pycogenol have been studied in conditions of anxiety, depression, and/or attention deficit hyperactivity disorder (ADHD). [xiii][xiv][xv][xvi] With therapies such as these, improvements have been seen clinically, possibly associated with their impact on glutathione levels.[xvii]

Of course, this has thus become a topic of interest for those involved in development of pharmaceutical therapies, however substantial evidence exists for one to consider utilizing these nutritional substances, as well as glutathione, which already are readily available.

Autoimmune disease and immune balance

In settings of autoimmune disease, there is an increased level of oxidative stress associated with immune activation and related inflammation. With this, glutathione levels become depleted.^[xviii] Glutathione is integral to the proper function of our immune system, especially for resistance to viruses.[xix][xx] Experimentally, a Th2 dominant (allergic state) is created with depletion of intracellular glutathione, and introduction of glutathione restores immune balance.[xxi] Given these relationships it is easy to see how supplemental glutathione may be supportive for balancing immune function, in addition to restoring levels which often are deficient in autoimmunity.

Mercury and cellular toxicity

Mercury and cellular toxicity Glutathione is necessary for cellular detoxification. The process of Phase II detoxification involves the binding of toxins with substances such as glutathione to create larger, inactive, water soluble molecules.[xxii] Toxins such as mercury are linked to glutathione, transported out of the cell, into the bile, and out of the body via stool. Glutathione is thus necessary to both protect the cell’s delicate chemical machinery and to transport toxins out. Because glutathione is utilized for the removal and elimination of mercury and other toxins from the cell, it also can become depleted in settings of toxicity.^[xxiii]Material used with permission of Quicksilver Scientific®. All rights reserved.

+ References

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[ii] Exner R, et al. Therapeutic potential of glutathione. Wiener Klinische Wochenschrift. 2000 Jul;112(14):610-6.
[iii] Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther. 2014 Feb;141(2):150-9.
[iv]Zeevalk GD, Bernard LP, Guilford FT. Liposomal-glutathione provides maintenance of intracellular glutathione and neuroprotection in mesencephalic neuronal cells. Neurochem Res. 2010 Oct;35(10):1575-87.
James SJ, et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004 Dec;80(6):1611-7.
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[xiv]Trebatická J, et al. Treatment of ADHD with French maritime pine bark extract, Pycnogenol®. Euro Child andamp; Adol Psych. 2006 Sep 1;15(6):329-35.
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[xxi] Peterson JD, et al. Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3071-6.
Zamek-Gliszczynski MJ, et al. Integration of hepatic drug transporters and phase II metabolizing enzymes: mechanisms of hepatic excretion of sulfate, glucuronide, and GSH metabolites. Eur J Pharm Sci. 2006 Apr;27(5):447-86.
[xxiii] Patrick L. Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev. 2002 Dec;7(6):456-71.