Glutathione in dogs and cats:
the master antioxidant explained
What is glutathione, why does it get depleted, and what does liposomal supplementation do? Substantiated with literature, with a focus on veterinary applications.
By Stefan Veenstra DVM
What is glutathione?
Glutathione (GSH) is a body’s own tripeptide made up of the amino acids glutamate, cysteine and glycine. It is produced in the liver and is present in virtually every cell of the body, with the highest concentrations in liver, lungs, kidneys and immune cells. [1] GSH functions both as a direct antioxidant and as a cofactor for a range of enzymes involved in detoxification and cell repair.
Glutathione is the body’s “master antioxidant” and refers to glutathione’s central position in the antioxidant network: GSH regenerates other antioxidants, including vitamin C, vitamin E and Coenzyme Q10 back to their active, reduced form after oxidation. [2] Without enough glutathione, the entire antioxidant system loses efficiency.
Core Functions of Glutathione
GSH directly neutralizes reactive oxygen species (ROS) and reactive nitrogen compounds, itself oxidizing to GSSG (oxidized glutathione). GSSG is converted back to GSH via glutathione reductase, provided that sufficient NADPH is available. [3]
In the liver, glutathione-S-transferase (GST) links GSH to toxic compounds including heavy metals, drug residues, pesticides and waste metabolites. As a result, they become water-soluble and excreted through urine or bile. [4]
Lymphocytes and macrophages are particularly sensitive to oxidative stress. GSH plays a direct role in the proliferation of T cells and in the regulation of cytokine production. Impaired GSH status correlates with impaired immune response. [5]
Mitochondrial glutathione (mGSH) protects mitochondrial DNA and the respiratory chain protects against oxidative damage. Exhaustion of mGSH is associated with mitochondrial dysfunction and accelerated cell aging. [6]
GSH directly protects DNA from oxidative damage and indirectly supports nucleotide excision repair via redox regulation of involved enzymes.[7]
GSH reduces oxidized ascorbate (vitamin C) back to ascorbic acid via the Foyer-Halliwell-Asada cycle, and indirectly supports the regeneration of tocopherol (vitamin E).[2]
When does glutathione deplete?
The glutathione status is dynamic and reacts quickly to the degree of oxidative and toxic load. In animals and humans, the following factors are associated with a reduced GSH status:
Liposomal Formulation: Bioavailability of Oral Glutathione
Glutathione ingested orally is partially broken down in the gastrointestinal tract by peptidases, especially gamma-glutamyl transpeptidase (GGT) in the intestinal wall, which means that the intact molecule reaches the systemic circulation only to a limited extent. [11] This was historically an objection to oral glutathione supplementation.
Liposomal encapsulation offers a solution here: the phospholipids protect the GSH molecule from enzymatic degradation in the gastrointestinal tract, after which absorption takes place partly via endocytosis and lymphatic transport. Research by Richie et al. (2015) showed that liposomal glutathione significantly increased plasma concentrations of GSH compared to unprotected oral GSH. [12]
Phosphatidylcholine as a carrier
NGD Care uses high-quality phosphatidylcholine (PC) as a liposomal carrier. PC is itself a structural component of cell membranes, supporting membrane integrity and fluidity. In animals with liver problems, where PC synthesis may be impaired, this has an additional therapeutically relevant effect. [13]
Veterinary applications
Liver detoxification and hepatoprotection
The liver is the central detoxification organ and has the highest glutathione concentration of all tissues. In dogs and cats with liver disease, hepatotoxic medication exposure (such as long-term NSAID use), or elevated liver enzyme levels, GSH support is mechanistically well-founded. [4],[8]
N-acetylcysteine (NAC) is a widely used precursor of GSH and works on the same principle as direct GSH supplementation, but along the synthesis route.
Allergies and chronic skin problems
In atopic dermatitis and chronic allergic skin conditions in dogs, increased oxidative stress has been demonstrated in skin tissue and systemically. [14] GSH support may contribute to dampening the oxidative component of the inflammatory response, in addition to its direct immune-modulatory action.
Immune disruption and recovery after infections
In dogs and cats after severe infections, long-term antibiotic use or immunosuppressive therapy, GSH status is reduced. Immune cell quality support via glutathione supplementation aligns with the documented role of GSH in T cell function and cytokine balance. [5]
Cognitive support in senior animals
Canine Cognitive Dysfunction (CCD) is associated with increased oxidative stress in brain tissue and decreased antioxidative capacity. [15] GSH is one of the primary antioxidants in the central nervous system. Supplementation to support cognitive health in senior dogs is mechanistically plausible, although direct clinical evidence in the veterinary literature is limited.
Behavioral problems and mental stress
Chronic stress increases cortisol levels and oxidative stress, resulting in accelerated GSH depletion. In animals with anxiety disorders, chronic stress or behavioural problems, GSH support can be part of a broader neuro-oxidative protocol.
Synergy with other NGD Care products
Glutathione works synergistically with multiple other ingredients in the NGD Care range. NAD+ (Longevity Complex) provides NADPH for the regeneration of GSH via glutathione reductase. Ergothioneine and resveratrol support antioxidative capacity via complementary pathways. PEA and boswellia reduce inflammatory GSH demand. Lactoferrin supports immune function and iron metabolism, which indirectly affects ROS production.
Possible areas of application — dog & cat
- Liver support in case of hepatotoxic load or elevated liver enzyme levels
- Detoxification in case of exposure to heavy metals, pesticides or mycotoxins
- Chronic allergies and atopic skin conditions
- Immune recovery after infections, long-term antibiotic use, or immune suppression
- Recovery after anesthesia, surgery or vaccinations
- Cognitive support in senior animals (CCD)
- Chronic stress and behavioural problems
- Part of an integral antioxidative protocol
Conclusion
Glutathione is mechanistically one of the best-founded antioxidants in biochemistry, the challenge has always been in its bioavailability when administered orally. Liposomal formulation with phosphatidylcholine largely solves this and makes oral supplementation clinically relevant.
In veterinary practice, the breadth of applications is large: from liver and detox to immune system, skin, brain and behavior. NGD Care Liposomal Glutathione is also a part of the aging protocol.
View Liposomal Glutathione in the NGD Care webshop
Literature
- Meister A, Anderson ME. Glutathione. Annu Rev Biochem. 1983; 52:711–760.
- Foyer CH, Noctor G. Ascorbate and glutathione: the heart of the redox hub. Plant Physiol. 2011; 155(1):2–18. [Mechanism Applicable to Mammalian Systems]
- Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009; 30(1–2):1–12.
- Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005; 45:51–88.
- Hamilos DL, Wedner HJ. The role of glutathione in lymphocyte activation. J Immunol. 1985; 135(4):2740–2747.
- Fernández-Checa JC, Kaplowitz N. Hepatic mitochondrial glutathione: transport and role in disease and toxicity. Toxicol Appl Pharmacol. 2005; 204(3):263–273.
- Mistry P, Bhatt DL. Role of glutathione in DNA repair and mutagenesis. Mutat Res. 1995; 339(2):91–96.
- Jaeschke H, Gores GJ, Cederbaum AI, et al. Mechanisms of hepatotoxicity. Toxicol Sci. 2002; 65(2):166–176.
- Julius M, Lang CA, Gleiberman L, et al. Glutathione and morbidity in a community-based sample of elderly. J Clin Epidemiol. 1994; 47(9):1021–1026.
- Lassen CL, Schmid M, Sütterlin M, et al. Oxidative stress and antioxidant status in patients undergoing general anesthesia. Antioxidants (Basel). 2022; 11(3):440.
- Witschi A, Reddy S, Stofer B, Lauterburg BH. The systemic availability of oral glutathione. Eur J Clin Pharmacol. 1992; 43(6):667–669.
- Richie JP Jr., Nichenametla S, Neidig W, et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr. 2015; 54(2):251–263.
- Zeisel SH. Choline: critical role during fetal development and dietary requirements in adults. Annu Rev Nutr. 2006; 26:229–250. [Phosphatidylcholine and Membrane Function]
- Olivry T, DeBoer DJ, Favrot C, et al. Treatment of canine atopic dermatitis: 2015 updated guidelines. BMC Vet Res. 2015;11:210.
- Landsberg GM, Nichol J, Araujo JA. Cognitive dysfunction syndrome: a disease of canine and feline brain aging. Fat Clin North Am Small Anim Pract. 2012; 42(4):749–768.
This information is educational in nature and based on available scientific literature. The studies mentioned are not always directly veterinary or specific to the formulation described here. This text does not replace a veterinary consultation and does not contain any therapeutic claims.