Reduced Glutathione Deficiency

Glutathione is a protein composed of the amino acids L-cysteine, L-glutamic acid, and glycine. Reduced glutathione, most commonly called glutathione or GSH, is a relatively small molecule ubiquitous in living systems. Its intracellular depletion ultimately results in cell death and its importance has been researched for decades. Reduced glutathione is a potent antioxidant and works in the liver to protect the body from toxins. It also functions as a precursor to glutathione peroxidase, a key antioxidant enzyme, which protects against lipid peroxidation (fats turning rancid).

Another important function of this protein is binding to drugs to make them more soluble for excretion. GSH is a primary protectant of skin, lens, cornea, and retina against radiation damage, and the biochemical foundation of P450 (a family of the body's more powerful detox enzymes) detoxication in the liver, kidneys, lungs, intestinal epithelia, and other organs. Individuals with inherited deficiencies of the GSH-synthesizing enzymes (gamma-glutamycysteine synthetase, gamma-GSC; and glutathione synthetase) have limited or generalized GSH deficiency, with hemolytic anemia, progressive degeneration of the spinal cord, disorders of the peripheral nervous system, diseases of the skeletal muscles, abnormal presence of amino acids in the urine (aminoaciduria), and severe neurological complications.

Glutathione exists in two forms: the reduced form (GSH) and the oxidized form (GSSG, or glutathione disulfide). The -SH suffix indicates that reduced glutathione contains a compound called sulfhydryl. The body gets sulfhydryl it needs to make GSH from precursor amino acids cysteine and methionine, which contain sulfur. Several additional enzymes are necessary for glutathione to function properly. The most important is glutathione peroxidase. Glutathione reductase is a support enzyme which will recycle glutathione and other antioxidants after they have neutralized free radicals.

GSH levels in human tissues normally range from 0.1 to 10 millimolar (mM), most concentrated in the liver (up to 10 mM) and in the spleen, kidney, lens, erythrocytes, and leukocytes. Low GSH values are common in inflammatory liver disorders, bile duct obstruction, and feline hepatic lipidosis. Cats may have higher risk than dogs for low liver GSH concentrations. Agents that can deplete GSH include ultraviolet and other radiation, viral infections, environmental toxins, household chemicals, heavy metals, surgery, inflammation, burns, septic shock, dietary deficiencies of GSH precursors and enzyme cofactors. Amounts available from foods are limited (less than 150 mg/day). In order to maintain an optimal level of glutathione production, the body must maintain an optimal level of amino acid raw materials. The body also needs to maintain an optimal level of cofactors that help glutathione do its work: the minerals selenium and zinc, lipoic acid and vitamin B2 (riboflavin). Selenium is particularly important because it is a vital component of the enzyme glutathione peroxidase.

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A number of products that help increase glutathione levels are available. Dr. Earl Mindell recommends supplementing with alpha lipoic acid for dogs who have been on medications for an extended period of time. Gluta-DMG by Vetri Science which combines a patented whey protein component (Gluta Syn) with DMG (dimethylglycine or vitamin B15) is used to produce a sustained cellular increase of glutathione in the body.


  1. Ruocco L, Del Corso L, Giordani R, Pagni V, Pentimone F. Blood reduced glutathione (GSH) concentrations in healthy and ill subjects.
  2. Glutathione, reduced - GSH - Monograph. Alternative Medicine Review, Dec, 2001
  3. Howard Peiper. New Hope for Serious Diseases: The Healing Power of Glutathione.
  4. Alan H. Pressman, Sheila Buff. Glutathione: The Ultimate Antioxidant.
  5. Dr. Earl Mindell's Nutrition and Health for Dogs. Earl Mindell, Elizabeth Renaghan
  6. Shawn Messonnier, Russell L. Blaylock . The Natural Vet's Guide to Preventing and Treating Cancer in Dogs (Natural Vets Guide)

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