A Look at the Benefits of Liposomal Glutathione

The amino acid tripeptide glutathione is an important antioxidant that may help support healthy aging, the immune system, and liver, sexual, and cardiovascular health.

This tripeptide is naturally comprised of three core components: L-cysteine, L-glutamate and glycine. All three of these amino acids are known to play core roles with regards to human health.

Glutathione is reported to play a key role in the destruction of free radicals and supports against oxidative stress damage to the cells [1]. It is able to minimize the peroxidation of cellular membranes and is one of the main redox buffering systems found in the mitochondria (the others being the glutaredoxin and thioredoxin pathway systems). 

Glutathione can be added to target molecules by glutathione S-transferases; this protective enzymatic action allows unwanted components to be exported from the cell. The antioxidant activity of glutathione helps to support both human health and exercise performance [2]. 

Glutathione Core Amino Acid Components

L-cysteine: this non-essential amino acid can be synthesized by the liver using serine derived from L-methionine [3]. When it becomes incorporated into glutathione it is involved antioxidant activities via redox reactions. Cysteine is usually the limiting substrate in the creation of glutathione by the body. Cysteine is also involved in metal ion binding, and plays a key role in the structure of numerous proteins. 

L-glutamate (glutamic acid): this amino acid plays a key role in neurotransmission, the biosynthesis of proteins, and is also a component of DNA. As well as being the most abundant excitatory neurotransmitter [4] it also acts as a GABA precursor, and is involved in non-synaptic brain signaling. 

Glycine: this is a simple amino acid having just one hydrogen side chain. Like with cysteine, the body naturally synthesizes it from serine. It has numerous biological roles including being an inhibitor of neurotransmission and is a core component of purines. It has also been reported to support healthy sleep through activation of NMDA receptors [5]. 

Glutathione Delivery and Bioavailability 

As glutathione supplements are not very well absorbed by the intestinal system and face difficulties in crossing cell membranes they are usually not very effective at crossing the stomach lining and reaching the parts of the cells where they are required.

There are two core ways of overcoming this problem. The first involves adding an acetyl component to the compound and taking it along with silymarin flavonoid (found in milk thistle).

The second way of increasing the absorption of glutathione is to enclose it in a liposomal layer; this greatly increases its bioavailability.

The encasing of glutathione in phospholipids spheres allows for greater affinity to cell membranes, greatly increasing delivery efficiency and increasing overall absorption. 

Role as an Antioxidant in the Mitochondria

Glutathione naturally exists in two distinct forms in the cell: reduced (GSH) and oxidized (GSSH) [6]. The cysteine group of this compound is able to diminish the effects of free radicals and reactive oxygen species through donating an electron. Thus glutathione, through cysteine, plays a key role in protecting the body’s cells from oxidative stress.

Once glutathione has donated an electron it itself becomes reactive. This is not usually a problem as it is able to form a Glutathione disulfide with another glutathione molecule so long as there is a high enough amount of free glutathione (GSH) available.

Many people take liposomal glutathione supplements to ensure that there is always enough GSH available for the production of GSSH. The ratio of GSH (reduced) to GSSH (oxidized) is typically 9:1. Under stressful conditions, such as occurs under heavy exercise, the percentage of free GSH may become reduced. 

A further role of glutathione as an antioxidant is as a cofactor for glutathione peroxidase; this enzyme may help to support lung tissue from damage [7]. As a reducing agent, glutathione also supports the antioxidant activities of ascorbate and tocopherol. 

Role in Detoxification (Liver Health)

Glutathione plays a key role in the elimination of free radicals, peroxidized lipids, and other xenobiotics from liver tissue. These detoxification processes are carried out by glutathione S-transferase enzymes [8].

Glutathione is also able to convert fat-soluble toxins into water-based forms, thus lowering their accumulation [9]. 

Support of the Immune System 

Glutathione may be required for the correct functioning of T-cells. These lymphocytes are involved in cell-mediated immunity through the recognition and destruction of invasive species [10].

Reduced levels of glutathione may inhibit in-vitro T-cell activation, leading to a reduced efficiency of the immune system.

Other Health Aspects

As a common antioxidant it is no surprise to learn that glutathione plays a major role in the support of many health aspects. It is reported to be involved in the beneficial support of sexual health through its effects upon sperm motility and morphology [11]. 

Glutathione levels naturally decrease as a person ages. This may result in a poorer response to oxidative stress. It has been reported that the consumption of oral glutathione supplements may help to overcome some of the effects associated with age associated glutathione loss [12]. 

Further Reading 

• Harvard school of public health: Antioxidants beyond the hype {https://www.hsph.harvard.edu/nutritionsource/antioxidants/} 
• EMBL-EBI: Chemical Entities of Biological Interest {http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:16856} 
• Body Building: glutathione: the forgotten nutrient {https://www.musclesportmag.com/2009/03/10/glutathione-the-forgotten-nutrient/} 

Citations, Reviews, Abstracts, and References

[1] Kerksick and Willoughby. The Antioxidant Role of Glutathione and N-Acetyl-Cysteine Supplements and Exercise-Induced Oxidative Stress. Journal Int Soc Sports Nutrition. 2005; 2(2): 38–44. 

[2] Elokda and Nielsen. Effects of exercise training on the glutathione antioxidant system. Eur J Cardiovasc Prev Rehabil. 2007 Oct;14(5):630-7. 

[3] Stipanuk. Role of the liver in regulation of body cysteine and taurine levels: a brief review. Neurochem Res. 2004 Jan;29(1):105-10. 

[4] Meldrum. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr. 2000 Apr;130(4S Suppl):1007S-15S. 

[5] Kawai et al. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology. 2015 May;40(6):1405-16

[6] Mari et al. Mitochondrial Glutathione, a Key Survival Antioxidant. Antioxid Redox Signal. 2009 Nov; 11(11): 2685–2700. 

[7] Comhair and Erzurum. The regulation and role of extracellular glutathione peroxidase. Antioxid Redox Signal. 2005 Jan-Feb;7(1-2):72-9. 

[8] Doctor Salinas and Wong. Glutathione S-transferases--a review. Curr Med Chem. 1999 Apr;6(4):279-309.

[9] Barclay et al. The cooperative antioxidant role of glutathione with a lipid-soluble and a water soluble antioxidant during peroxidation of liposomes initiated in the aqueous phase and in the lipid phase. J Biol Chem. 1988 Nov 5;263(31):16138-42.

[10] Dr Chang et al. Glutamine protects activated human T cells from apoptosis by up-regulating glutathione and Bcl-2 levels. Clin Immunol. 2002 Aug;104(2):151-60. 

[11] Mora-Esteves and Shin. Nutrient supplementation: improving male fertility fourfold.

[12] Sekhar et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am J Clin Nutr. 2011 Sep;94(3):847-53. doi: 10.3945/ajcn.110.003483.