L-Glutathione

Synonym(s): glutathione

Nutrient group: Amino acids

Sources and physiological effects

Dietary sources
Glutathione is found in foods in very different amounts. High concentrations are found shoots and sprouts, asparagus, yeast and meat. However, storage, processing and heating destroy the key substance. Processed foods therefore contain only small amounts of nutrient.
Physiological effects
Antioxidant	Most important intracellular antioxidant
Liver	Glutathione is essential for detoxification processes in the liver
Immune system	Participation in prostaglandin and leukotriene metabolism
Muscles	Anti-catabolic effect Regulation of muscle protein balance

Recommended intake

Requirement
Increased demand	Use of paracetamol, radiotherapy, cytostatic drugs, age, premature babies, stress, physical strain, low alimentary protein intake

Recommended intake to the food labelling regulations (= 100 % TB marking on label)
		N/A
Nutrient safety
UL	Long-term daily intake, at which no negative health effects are to be expected	N/A
NOAEL	Maximum intake, with no observed adverse effect in studies harmful effects caused	N/A

Detailed information

The physiological significance of L-glutathione

The tri-peptide L-glutathione is quantitatively the most important intracellular sulfur compound. It is synthesized endogenously in the cell from the amino acid cysteine. Glutathione and the resulting selenium-containing glutathione peroxidase form one of the most important antioxidative redox systems in the intracellular space. L-glutathione protects cell structures, lipids, proteins and nucleic acids from oxidative damage by oxygen and hydrogen peroxide radicals. When these free radicals are broken down, the reduced glutathione form changes into the oxidized glutathione disulfide, which in turn is regenerated with the help of a vitamin B₂-dependent enzyme and with the participation of niacin during redox recycling (1). There is a close connection between vitamin C supply and glutathione synthesis. With a limited vitamin C supply, the glutathione plasma concentration decreases and the ratio of reduced to oxidized glutathione deteriorates (2).

Glutathione as adjuvant therapy in cancer

In cancers, a lowered intracellular glutathione level correlates significantly with the patient's physical deterioration. In breast cancer patients a reduced glutathione status and an associated increase in oxidative stress could be demonstrated (3). Since physical deterioration is directly related to the survival rate of a cancer patient, the maintenance of immunocompetent body cells and the normalization of glutathione status are of central therapeutic importance (2). The strengthening of antioxidative systems during inflammatory processes in cancer, such as those caused by the supply of glutathione, is an essential prerequisite for successful treatment (4). Clinical applications also show that glutathione leads to apoptosis of tumor cells (5) (6) and has cytotoxic effects on tumor cells (7).

Detoxification and Liver Protecti

Glutathione is significantly involved in the detoxification of toxic metabolic products and in the detoxification of aflatoxins, xenobiotics and heavy metals in hepatocellular biotransformation (2). In particular, formaldehyde and acetaldehyde, two cytotoxins produced by alcohol, drugs or pesticides in the liver, are neutralized by reduced glutathione. In addition to the detoxification capacity, the synthesis capacity of liver cells is also directly influenced by intracellular glutathione levels (8).

Glutathione status and degenerative aging processes

Aging processes are closely linked to the functionality of intracellular redox systems. In a number of tissues, the amount of reduced glutathione continuously decreases with increasing age. The resulting oxidative stress is blamed for degenerative changes. For example, low glutathione and vitamin C concentrations are found in patients with macular degeneration and cataract (2). An increased glutathione intake can be used preventively and therapeutically in degenerative processes in which oxidation damage plays a role (9).

Inflammatory gastrointestinal diseases

Glutathione status also plays an important role in the development of inflammatory gastrointestinal diseases. Glutathione is generally indispensable for maintaining the integrity and energy metabolism of small intestine cells. In Crohn's disease, celiac disease and ulcerative colitis, glutathione depletion can often be observed (10). The inflammatory process is perpetuated by the activity of the free radicals produced by inflammatory processes, which can lead to morphological mucosal changes. A corresponding oral supplementation of glutathione supply can counteract these processes (11).

Deficiency symptoms

Impact on	Symptoms
General health	Chronic fatigue syndrome, fatigue, decreased performance
Risk of disease	Increased susceptibility to free radical-associated diseases, increased susceptibility to infections due to reduced immune defense function
Musculature	Decrease in body cell mass, increase in extracellular fluid (edema), catabolic metabolism

Indications

Effect	Indication	Dosage
Physiological effects at a low intake	Complementary therapy for cancer and tumor-related malnutrition	100 - 400 mg/d
	Therapeutic to avoid oxidative cell damage associated with chemo and radiation therapies	100 - 400 mg/d
	To support the liver function, to strengthen the deoxification performance especially with a high heavy metal load	100 - 400 mg/d
	For general strengthening of antioxidative protection systems, especially in age-related macular degeneration and degenerative diseases	100 - 200 mg/d
	Complementary therapy for inflammatory gastrointestinal diseases	100 - 200 mg/d

Administration

General mode of administration
When	L-glutathione should be taken in between meals.
Side effects
In rare cases, gastrointestinal complaints (nausea, diarrhea, heartburn) may occur. There are individual reports of allergic reactions with itching, skin redness and bronchospasms.
Contraindications
Infants and small children

Interactions

Drug interactions
None	No relevant interactions are known to date.
Nutrient interactions
Vitamins	Vitamin C and L-glutathione support each other in their activity when administered in combination.

Description and related substances

Description

The body's own tripeptide from the amino acids L-glutamic acid, L-cysteine and glycine

Related Substances

L-Glutathione

References

1) Hahn, A. et al. 2005. Ernährung. Physiologische Grundlagen, Prävention, Therapie.
2) Gröber, U. 2002. Orthomolekulare Medizin. Ein Leitfaden für Apotheker und Ärzte.
3) Yeh, C. C. et al. 2005. Superoxide anion radical, lipid peroxides and antioxidant status in the blood of patients with breast cancer. Clin Chim Acta.
4) Huber, W., Messerschmitt, T. M. Entzündungssyndrom. 2006.Erfahrungen, Diagnose und begleitende Maßnahmen mit Antioxidantien. Zs f Orthomol Med. 1:16-21.
5) Locigno, R. et al. 2002. S-acetyl-glutathione selectively induces apoptosis in human lymphoma cells through GSH-independent mechanism. Int J Oncol. 20(1):69-75.
6) Donnerstag, B. et al. 1996. Reduced Glutathione and s-acetylglutathione as selective apoptosis-inducing agents in cancer therapy. Cancer Letters. 10):63-70.
7) Dalhoff, K. et al. 1999 Glutathione treatment of hepatocellular carcinoma. Liver. 12(5):341-3.
8) Fuchs, N. 2001. Mit Nährstoffen heilen.
9) Maher, P. 1997. The effects of stress and aging on glutathione metabolism. Ageing Res Rev. Jun 2005; Epub.
10) Ruan, E. et al: Glutathione levels in chronic inflammatory disorders of the human colon. Nut.Research. 17(3):463-473.
11) Iantomasi, T. et al. 1998. Glutathione metabolism in Crohn’s disease. Biochem Med Metab Biol. 53(2):87-91. doi:10.1023/A:1006801803664.

References Interactions
Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.
Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.