There is a remarkable molecule circulating through your bloodstream: glutathione. Not only is it a virtual powerhouse of antioxidant defense and enzyme production, but it’s also fundamental to a wide range of metabolic and regulatory functions. So essential is this substance to maintaining your health that deficiency states have been linked to a multitude of diseases, even aging. Let’s take a look at glutathione, its vital roles and the importance of maintaining optimal levels of this key nutrient.
Glutathione’s Chemistry underlies its Biological Functions
The following is a short primer on glutathione biochemistry, provided in order to fully grasp its physiological significance. Please bear with the following paragraphs, because a wealth of information crucial to your health follows.
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Glutathione is a tripeptide synthesized from the amino acids glutamine, cysteine and glycine and is intimately involved in maintaining the antioxidant status of cells and tissues. Remember from Chemistry 101 (if it’s not too unpleasant!) that oxidation and reduction are complementary chemical reactions described as the loss or gain of electrons, respectively, by a molecule, atom, or ion. In addition to glutathione’s relatively high concentration within cells, the presence of the sulfhydryl (–SH) group on the cysteine portion of the molecule is at the foundation of its powerful antioxidant capacity 1234 ? electrons of this sulfur-containing group are readily donated to quench, or reduce, damaging free radicals and reactive oxygen species (ROS), which are highly reactive, unstable, and deleterious to the body. Glutathione exists within cells in its reduced form, denoted GHS, but in the process of neutralizing ROS, it becomes oxidized to glutathione disulfide, GSSG. Redox is chemical shorthand for reduction-oxidation reaction, and in biological systems, the term redox ratio is used to describe the balance of reduced to oxidized metabolites, in this case GSH/GSSG.
Now that we have digested this information, we’re ready to appreciate these two gems of information: first, the ratio of reduced to oxidized glutathione, GSH/GSSG, within the cell is fundamental to cell function and viability and is under tight regulation4 and second, GSH/GSSG is the major redox pair that determines antioxidant capacity in animal cells. 1356. There in a nutshell is the basis of glutathione’s vast biological significance. Under normal physiological conditions this ratio should be greater than 10.18 However, in response to oxidative stress, a dangerous imbalance between the production and removal of ROS, glutathione concentrations can plummet,13568 shifting the GSH/GSSG redox toward the damaging oxidizing state. We will see below the link between increased oxidation and disease and then later how we can positively impact our glutathione redox ratio toward a more healthy balance. First, let’s expand our discussion of glutathione’s functions in the body.
Biological Roles of Glutathione
We have just seen that the reduced to oxidized glutathione ratio plays a crucial role in the maintenance and regulation of the antioxidant status of the cell. This characteristic underlies glutathione’s importance in a multitude of physiological processes.
Glutathione is used as a substrate for certain enzymes that detoxify ROS generated from free radical attack on DNA, proteins and other biomolecules, as well as other enzymes that complex glutathione with potentially harmful substances such as estrogens, and xenobiotics (substances foreign to the body) in order to detoxify them.134
Besides the antioxidant defense glutathione provides as an enzyme substrate, it also acts as an endogenous (originating within the body) antioxidant by directly quenching oxygen free radicals.134 Interestingly, it also helps reduce and then recycle oxidized forms of other antioxidants such as ascorbate (vitamin C) and alpha-tocopherol (a form of vitamin E).4
And besides maintaining the redox balance of the cell, glutathione plays an important role in many other regulatory pathways including signal transduction, gene expression, DNA and protein synthesis, cell proliferation, apoptosis, cytokine production and immune response, and preserving mitochondrial function.126
Glutathione Depletion Linked to Disease States
By now, it’s clear that glutathione is crucial to regulating and neutralizing deleterious oxidative processes, among other essential roles in the body. Medical experts agree that a deficiency of glutathione (and corresponding decrease in the redox ratio) contributes to increased oxidation and is implicated in aging and the onset and progression of many diseases.12346
Many oxidative stressors can deplete glutathione levels: ultraviolet and other radiation, viral infections, environmental toxins, household chemicals, heavy metals, surgery, inflammation, burns, septic shock, and overuse of certain pharmaceuticals such as acetaminophen4. Diminished glutathione levels can also be a result of limited synthesis due to fasting or inadequate protein or amino acid intake.14
- hemolytic anemia
- neuropathy, myopathy
- cirrhosis, viral hepatitis
- chronic obstructive pulmonary disease, acute respiratory distress syndrome, asthma
- Crohn’s Disease, gastritis, duodenal ulcer, pancreatitis
- heart attack, coronary artery disease
- Wilson’s Disease
- neurodegenerative diseases including Alzheimer’s and Parkinson’s
- Cystic fibrosis
Supplementation to Improve Glutathione Status
You may very well be asking by this point, “But what can I do about it? How can I optimize my body’s antioxidant capacity?” With so many disorders associated with oxidative stress as a result of lowered glutathione levels, nutritional strategies to restore a more favorable redox ratio may offer therapeutic potential in treating the abundance of human diseases mentioned above, and may even provide an effective anti-aging strategy.
Several substances have been shown to increase glutathione synthesis in vivo such as n-acetyl cysteine (an orally bioavailable source of cysteine, sufficient quantities of which are necessary for glutathione synthesis); the amino acids glutamine, glycine and taurine; alpha-lipoic acid, s-adenosylmethionine (SAM-e), and ascorbate.14
And research continues on glutathione itself as a therapeutic agent. Although there is conflicting data in the medical literature, a growing number of studies have demonstrated that oral administration of glutathione can directly increase plasma and tissue glutathione concentrations and exert positive physiological benefits.
In a study evaluating plasma glutathione concentration in rats after glutathione dosing as either a liquid bolus or mixed in feed, researchers observed a substantial increase in plasma glutathione which peaked at 90 to 120 minutes after administration and remained high for over three hours.8
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