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.[xi],[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

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]


Author, Dr. Carrie Decker 

Dr. Decker is a certified Naturopathic Doctor, graduating with honors from the National College of Natural Medicine (now the National University of Natural Medicine) in Portland, Oregon. Dr. Decker also has graduate degrees in biomedical and mechanical engineering from the University of Wisconsin-Madison and University of Illinois at Urbana-Champaign respectfully. Dr. Decker sees patients at her office in Portland, OR, as well as remotely, with a focus on gastrointestinal disease, mood imbalances, eating disorders, autoimmune disease, chronic fatigue, and skin conditions. Dr. Decker also supports integrative medicine education as a writer and a contributor to various resources.

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[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. View Abstract

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[v] 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. View Full Paper

[vi] Palmieri L, Persico AM. Mitochondrial dysfunction in autism spectrum disorders: cause or effect? Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):1130-7. View Abstract

[vii] Omata Y, et al. Decreased zinc availability affects glutathione metabolism in neuronal cells and in the developing brain. Toxicol Sci. 2013 May;133(1):90-100. View Abstract

[viii] El-Ansary AK, et al. Impaired plasma phospholipids and relative amounts of essential polyunsaturated fatty acids in autistic patients from Saudi Arabia. Lipids Health Dis. 2011 Apr 22;10:63. View Full Paper

[ix] Hardan AY, et al. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol Psychiatry. 2012 Jun 1;71(11):956-61. View Full Paper

[x] Kern JK, et al. A clinical trial of glutathione supplementation in autism spectrum disorders. Med Sci Monit. 2011 Dec;17(12):CR677-82. View Full Paper

[xi] Ross MA. Could oxidative stress be a factor in neurodevelopmental disorders? Prostaglandins Leukot Essent Fatty Acids. 2000 Jul-Aug;63(1-2):61-3. View Abstract

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[xiii] Dvořáková M, et al. The effect of polyphenolic extract from pine bark, Pycnogenol® on the level of glutathione in children suffering from attention deficit hyperactivity disorder (ADHD). Redox Report. 2006 Aug 1;11(4):163-72. View Abstract

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[xix] Palamara AT, et al. Evidence for antiviral activity of glutathione: in vitro inhibition of herpes simplex virus type 1 replication. Antiviral Res. 1995 Jun;27(3):237-53. View Abstract

[xx] Cai J, et al. Inhibition of influenza infection by glutathione. Free Radic Biol Med. 2003 Apr 1;34(7):928-36. View Abstract

[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. View Full Paper

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[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. View Full Paper



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