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The Use of Glutathione, Master Antioxidant in Clinical Settings

12272 Views Posted on: 2019-11-08
Posted by: Ireneusz Adamczyk
The Use of Glutathione, Master Antioxidant in Clinical SettingsEven 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)

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

Attention deficit and mood disordersIncreased 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 toxicityGlutathione 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.

[i]Devasagayam TP, et al. Free radicals and antioxidants in human health: current status and future prospects. J Assoc Physicians India. 2004 Oct;52:794-804.
[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.
[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.
[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.
[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.
[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.
[x] Kern JK, et al. A clinical trial of glutathione supplementation in autism spectrum disorders. Med Sci Monit. 2011 Dec;17(12):CR677-82.
[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.
[xii]Moylan S, Berk M, Dean OM, et al. Oxidative andamp; nitrosative stress in depression: why so much stress? Neurosci Biobehav Rev. 2014;45:46-62.
[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.
[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.
[xv] de Oliveira IJ, et al. Effects of Oral Vitamin C Supplementation on Anxiety in Students: A Double-Blind, Randomized, Placebo-Controlled Trial. Pak J Biol Sci. 2015 Jan;18(1):11-8.
[xvi] Amr M, et al. Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. Nutr J. 2013 Mar;12(1):1.
[xvii] Berk M, et al. Glutathione: a novel treatment target in psychiatry. Trends Pharmacol Sci. 2008 Jul;29(7):346-51.
[xviii] Perricone C, et al. Glutathione: a key player in autoimmunity. Autoimmun Rev. 2009 Jul;8(8):697-701.
[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.
[xx]Cai J, et al. Inhibition of influenza infection by glutathione. Free Radic Biol Med. 2003 Apr 1;34(7):928-36
[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.

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Scientific Sources

Master antioxidant definition?

Glutathione called "master antioxidant" because it regenerates other antioxidants like vitamins C and E after they neutralize free radicals. Also most abundant intracellular antioxidant and essential for Phase II detoxification. Central role in cellular defense systems.

Phospholipid-encapsulated delivery?

System overcomes problem that otherwise prevents absorption of oral glutathione supplements. Additionally, phospholipid-encapsulated sphere which delivers glutathione into cell simultaneously replenishes and nourishes cell by providing phospholipids of which cellular membranes are composed. Dual benefit delivery system.

Autism oxidative stress connection?

Increased oxidative stress and mitochondrial dysfunction may contribute to development and clinical manifestation of autism. Children on autistic spectrum have documented glutathione deficiencies. Addressing oxidative stress through glutathione supplementation represents rational therapeutic approach.

Phase II detoxification role?

Glutathione is necessary for cellular detoxification. Process of Phase II detoxification involves binding of toxins with substances such as glutathione to create large water-soluble molecules that can be excreted. Without adequate glutathione, body cannot effectively eliminate toxins.

Clinical settings applications?

Even if not doing deep dive into detoxification protocols, there is vast array of clinical settings in which glutathione applicable: autism spectrum, ADHD, mood disorders, liver disease, oxidative stress conditions, mitochondrial dysfunction, heavy metal exposure, chronic illness support.

  • Master antioxidant status regenerates other antioxidants
  • Most abundant intracellular antioxidant cellular defense
  • Phospholipid-encapsulated delivery overcomes absorption problem
  • Cellular membrane replenishment dual benefit system
  • Phase II detoxification essential toxin conjugation
  • Autism oxidative stress mitochondrial dysfunction link
  • Glutathione deficiencies documented autistic spectrum children
  • ADHD oxidative stress contribution attention deficit support
  • Mood disorders mechanism antioxidant therapies directed
  • Liver detoxification support
  • Mitochondrial function optimization
  • Heavy metal chelation binding and excretion
  • Water-soluble conjugates formation excretion pathway
  • Vast clinical applications multiple settings
  • Vitamins C and E regeneration antioxidant recycling

Glutathione Master Antioxidant Clinical Protocol

Step 1: Understand Master Antioxidant Status

Glutathione called "master antioxidant" because it regenerates other antioxidants like vitamins C and E after they neutralize free radicals. Also most abundant intracellular antioxidant and essential for Phase II detoxification. Central coordinating role in cellular defense systems - not just another antioxidant but orchestrator of entire antioxidant network.

Step 2: Phospholipid-Encapsulated Delivery System

System overcomes problem that otherwise prevents absorption of oral glutathione supplements. Standard oral glutathione poorly absorbed due to breakdown in digestive tract. Phospholipid-encapsulated sphere delivers glutathione into cell while simultaneously replenishing and nourishing cell by providing phospholipids of which cellular membranes are composed. Dual benefit: delivery plus membrane support.

Step 3: Phase II Detoxification Function

Glutathione is necessary for cellular detoxification. Process of Phase II detoxification involves binding of toxins with substances such as glutathione to create large water-soluble molecules that can be excreted. Without adequate glutathione, body cannot effectively eliminate toxins which then accumulate causing cellular damage. Critical for environmental toxin exposure, heavy metals, medication metabolites.

Step 4: Autism Spectrum Oxidative Stress

Increased oxidative stress and mitochondrial dysfunction may contribute to development and clinical manifestation of autism. Children on autistic spectrum have documented glutathione deficiencies. Addressing oxidative stress through glutathione supplementation represents rational therapeutic approach targeting underlying biochemical abnormality rather than just managing symptoms.

Step 5: ADHD and Mood Disorders Application

Increased oxidative stress may contribute to attention deficit and mood disorders via numerous mechanisms. Therapies directed at supporting antioxidant status including glutathione supplementation may help. Oxidative damage to neurons affects neurotransmitter function, synaptic plasticity, and neuronal signaling - all relevant to attention and mood regulation.

Step 6: Vast Clinical Settings Array

Even if not doing deep dive into detoxification protocols, there is vast array of clinical settings in which glutathione applicable: autism spectrum disorders, ADHD, mood disorders, liver disease, oxidative stress conditions, mitochondrial dysfunction, heavy metal exposure, chronic illness support. Master antioxidant status and Phase II detoxification role make glutathione relevant across diverse pathologies sharing oxidative stress component.

  • Autism spectrum disorders (F84.0 - oxidative stress, mitochondrial dysfunction)
  • ADHD (F90.9 - attention deficit, oxidative stress)
  • Mood disorders (F39 - oxidative mechanisms)
  • Glutathione deficiency documented in autism
  • Mitochondrial dysfunction (G71.3)
  • Oxidative stress conditions increased free radicals
  • Phase II detoxification impaired
  • Liver disease (K76.9 - detoxification support)
  • Heavy metal exposure (T56 - chelation needs)
  • Chronic illness oxidative burden
  • Cellular membrane dysfunction
  • Toxin accumulation excretion impairment
  • Glutathione hypersensitivity
  • Asthma severe (inhaled glutathione may trigger bronchospasm)
  • Chemotherapy active (may interfere - consult oncologist)

Master Antioxidant - Regenerates Vitamins C and E: Glutathione called "master antioxidant" because it regenerates other antioxidants like vitamins C and E after they neutralize free radicals. Also most abundant intracellular antioxidant providing first line of defense against oxidative damage within cells. Central coordinating role in cellular antioxidant defense network distinguishes it from other antioxidants.

Phospholipid-Encapsulated Delivery Overcomes Absorption: System overcomes problem that otherwise prevents absorption of oral glutathione supplements. Standard oral glutathione broken down in digestive tract before absorption. Additionally, phospholipid-encapsulated sphere which delivers glutathione into cell simultaneously replenishes and nourishes cell by providing phospholipids of which cellular membranes are composed. Liposomal delivery technology enables effective oral supplementation previously impossible.

Citation: Pharmacokinetic studies demonstrating phospholipid-encapsulated (liposomal) glutathione achieves significantly higher plasma and intracellular levels compared to standard oral glutathione, overcoming first-pass metabolism and degradation barriers.

Autism Spectrum - Oxidative Stress and Mitochondrial Dysfunction: Increased oxidative stress and mitochondrial dysfunction may contribute to development and clinical manifestation of autism. Children on autistic spectrum have documented glutathione deficiencies particularly in specific metabolic pathways. Addressing oxidative stress through glutathione supplementation represents rational therapeutic approach targeting underlying biochemical abnormality.

Citation: Studies in children with autism spectrum disorders documenting reduced glutathione levels, increased oxidative stress markers, and mitochondrial dysfunction, with glutathione supplementation showing potential to address underlying metabolic abnormalities.

Phase II Detoxification Essential Role: Glutathione is necessary for cellular detoxification. Process of Phase II detoxification involves binding of toxins with substances such as glutathione to create large water-soluble conjugates that can be excreted via kidneys or bile. Without adequate glutathione, body cannot effectively eliminate environmental toxins, heavy metals, and medication metabolites leading to accumulation and cellular damage.