- 1 Section A
- 2 Glutathione Physiology, Production, and Recycling
- 3 GGT as Measure of Glutathione Need
- 4 Section B
- 5 Glutathione’s role in increasing Detoxification and decreasing Inflammation and Oxidative stress
- 6 Gluthation’s Longevity Boost Impact
- 7 Section C
- 8 Holistic Techniques to Increase Intracellular and Intramitochondrial Glutathione
- 9 Bioavailability and supplementation
- 10 Case in Point: Cancer
- 11 Discussion
- 12 Conclusion
- 13 Reference and Precision Notes
Once oxidized, glutathione can be reduced back by glutathione reductase, using NADPH as an electron donor. The ratio of reduced glutathione to oxidized glutathione within cells is often used as a measure of cellular oxidative stress. (1)
GGT as Measure of Glutathione Need
GGT (gamma-glutamyl transferase) is upregulated in proportion to the need for glutathione such as for the detoxification of POPs. (Source). It provides the rate-limiting cysteine through a catabolic “salvage pathway.” Increases in GGT correlate with many diseases: metabolic syndrome, both fatal and nonfatal coronary heart disease (CHD) events, atherosclerosis, fatty liver, diabetes, cancer, hypertension, and carotid intima-media thickness. (Source) Research also shows a GGT 30 to 40—well within the normal range—is associated with a doubling of the risk of all-cause mortality. (Source).
Glutathione’s role in increasing Detoxification and decreasing Inflammation and Oxidative stress
Bioavailability and supplementation
As we noted, systemic bioavailability of orally consumed glutathione is poor because the molecule, a tripeptide, is the substrate of proteases (peptidases) of the alimentary canal, and due to the absence of a specific carrier of glutathione at the level of cell membrane. (19).
Because direct supplementation of glutathione is not always successful, supply of the raw nutritional materials used to generate GSH, such as cysteine and glycine, may be more effective at increasing glutathione levels. Other antioxidants such as ascorbic acid (vitamin C) may also work synergistically with glutathione, preventing depletion of either. The glutathione-ascorbate cycle, which works to detoxify hydrogen peroxide (H2O2), is one very specific example of this phenomenon.
Additionally, as we saw, compounds such as N-acetylcysteine (20) (NAC) and alpha lipoic acid (21) (ALA, not to be confused with the unrelated alpha-linolenic acid) are both capable of helping to regenerate glutathione levels. NAC in particular is commonly used to treat overdose of acetaminophen, a type of potentially fatal poisoning which is harmful in part due to severe depletion of glutathione levels.
S-adenosylmethionine (SAMe), a cosubstrate involved in methyl group transfer, has also been shown to increase cellular glutathione content in persons suffering from a disease-related glutathione deficiency. (22).
Case in Point: Cancer
Low glutathione is commonly observed in wasting and negative nitrogen balance, as seen in cancer, HIV/AIDS, sepsis, trauma, burns, and athletic overtraining. Low levels are also observed in periods of starvation. These effects are hypothesized to be influenced by the higher glycolytic activity associated with cachexia, which result from reduced levels of oxidative phosphorylation. (23)
However, once a tumor has been established, elevated levels of glutathione may act to protect cancerous cellsby conferring resistance to chemotherapeutic drugs. The antineoplastic mustard drug canfosfamide was modelled on the structure of glutathione. So for those patients on cytotoxic chemo, we don’t recommend taking Glutathione. (24)
Glutathione is a simple molecule made up of three amino acids – cysteine, glycine and glutamine. This simple molecule packs a seriously healing punch and is essential for proper immune function, detoxification, and controlling inflammation in the body.
For patients struggling with fatigue and chronic illness, maximizing glutathione is a top priority. Insufficient glutathione prevents the mitochondria (the power house of the cell) from producing ATP which is the primary source of energy for all living cells. Without the ability to make sufficient ATP, we feel exhausted and our body’s ability to heal is greatly reduced.
Not only is glutathione our body’s main antioxidant, protecting our cells from oxidative stress and facilitating energy production, it is the most critical component in our bodies’ detoxification system. It acts like a magnet to grab toxins and free radicals, delivering them into the bile and stool for safe removal from the body. Normally glutathione is recycled in the body, providing continuous protection from oxidative stress or toxicity, but when our bodies accumulate too high a toxic load, this process is inhibited.