User:Nutriveg/Glutathione supplements

Glutathione Supplements For the purpose of this article, glutathione supplements are defined as compounds that naturally occur in food and have been shown to either increase glutathione levels or increase effectiveness of glutathione mediated processes, like the glutathione antioxidant system. They may also be available in supplement products.

Uses of supplementation
Glutathione is an endogenous antioxidant tripeptide that mediates many processes in the body associatd with reducing oxidative stress and removal of xenobiotics. Glutathione is believed to play a role in many normal and disease processes within the body. Glutathione supplementation has been shown to increase plasma glutathione levels in different diseases such as Parkinsons disease, HIV , cystic fibrosis , liver disease and cancer . However improvements in disease course have not been measured or seen in these studies. Observational studies in human and controlled animal studies suggest that glutathione supplementation with whey protein may mitigate progression of age-related health issues. More research is still needed to study long term effects of glutathione supplementation and to improve evaluation and validation of supplementation methods.

Basic methods of supplementation
Basic approaches to supplementation of glutathione include:
 * Cysteine donors. Availability of the amino acid cysteine can limit production of glutathione. Two supplements effective in making cysteine available for glutathione production are N-acetyl cysteine (NAC) and whey protein. Animal studies suggest that whey protein makes cysteine available as the dimer form of cysteine (called cystine) and perhaps another glutathione precursor, gamma-glutamyl-cysteine.
 * Metabolic support. The metabolism of glutathione involves not only production but also regulation and recycling. Supplements such as alpha lipoic acid (ALA), conjugated linoleic acid (CLA) and S-adenosylmethionine (SAMe) are known to increase glutathione levels or effectiveness by supporting these other aspects of glutathione metabolism.
 * Direct delivery. Oral supplements containing reduced glutathione are very common but available evidence suggests that this is one of the least effective methods of supplementation . Various delivery methods have been tried to improve effectiveness. Glutathione is available in IV form. There are also nasal and sublingual products. Liposome enclosed glutathione taken orally in liquid form is a plausible idea but there isn't a great deal of evidence indicating its effectiveness.

Glutamine
Glutamine is a glutathione precursor. Experimental animal studies have shown that the administration of GLN increases tissue concentrations of reduced glutathione Other studies however have found that oral glutamine supplementation increases glutathione levels in plasma but not in red cell (whole-blood).

Cysteine
{{main|Cysteine]] Cysteine is the crucial limiting amino acid for intracellular GSH synthesis.

Whey protein
Whey protein has been shown to increase intracellular glutathione levels in trials on human subjects. However the protein composition of whey protein powders varies.

N acetyl cysteine
N-acetyl cysteine is a synthetic derivative of the amino acid cysteine, generally abbreviated NAC. It does not occur naturally, so it is not a nutritional supplement in the strict sense. It provides a much higher level of oral bioavailability of cysteine compared with ingesting cysteine directly. There are some concerns about long term use and side effects caused by S-nitroso-N-acetylcysteine, a metabolite of NAC causing pulmonary arterial hypertension. Long term effects of NAC or products containing this chemical should be evaluated more extensively.

Alpha lipoic acid
Alpha lipoic acid seems to increase expression of Gamma-glutamylcysteine synthetase, the rate-controlling enzyme for glutathione synthesis. It has been shown to reverse the age-related loss of glutathione and its redox status in animal studies of rats Lipoic acid increases intracellular levels of glutathione in human lymphocytes in vitro.

Unsaturated Fatty Acids
Various fatty acid such as docosahexaenoic acid (DHA) have been shown to upregulate glutathione content via an induction of Gamma-glutamylcysteine synthetase and glutathione reductase in cell cultures. The same researchers found that this upregulation was often accompanied by an increase in lipid peroxidation. Conjugated linoleic acid (CLA) produced the same regulation without any attendant lipid peroxidation. These studies were done in cell cultures. Fatty acids have been used in conjunction with S-adenosylmethionine to mitigate the early onset of dementia.

S-adenosylmethionine
S-adenosylmethionine (SAMe) contains cysteine although there do not appear to be any studies that evaluate its effectiveness as a cysteine donor. It does increase glutathione S-transferase activity and in this respect it increases neuroprotective effectiveness of glutathione. It has been evaluated for mitigating early onset of dementia.

Evaluation of supplementation
Glutathione occurs in most tissues of the body including the liver and the heart. In the case of animal studies, it is common to terminate the lab animal in order to obtain specimens of various tissues. Biopsies of liver and heart tissue would be impractical in the case of human studies, therefore, the level of reduced glutathione in the lymphocyte fraction of a blood sample is generally viewed as being indicative of glutathione levels in other body tissue. This measurement is affected by the characteristics of the lymphocyte population. Therefore, flow cytometry might be used to characterize the lymphocyte population thus providing an adjustment of such a measurement.