L-Glutathione is a short peptide composed of just cysteine, glutamate, and glycine. It occurs naturally throughout the body and acts primarily as an antioxidant and as a supportive agent to a number of processes in the central nervous system. Glutathione is especially important in the detoxification processes of the liver and as a free-radical scavenger in the brain. There is ample evidence to suggest that loss of glutathione can contribute to neurodegenerative diseases like Parkinson’s disease as well as diseases of the eye like cataracts and diabetic retinopathy. Reduced glutathione levels are thought to be both a consequence of aging as well as a contributor to the aging process. Chronic disease also reduces glutathione levels.
Oral glutathione supplementation appears to be ineffective due to the breakdown of the peptide in the gastrointestinal system. Though much is made of oral supplementation with glutathione precursors like N-acetyl cysteine (NAC), research shows that glutathione levels tend to decrease with age due to a loss of production capacity (usually starting around middle age). This loss of production capacity, of course, limits the effectiveness of NAC and other precursors to generate glutathione. The best evidence indicates that glutathione is most effective when injected or inhaled via nasal preparations.
Molecular Formula: C10H17N3O6S
Molecular Weight: 307.33 g/mol
PubChem CID: 124886
CAS No: 170-18-8
Alternative Names: Glutathione, Isethion, GSH
L-Glutathione has long been recognized as one of the most important low-molecular weight antioxidants synthesized by cells of the body. By virtue of the sulfur contained in the cysteine component of GSH, it is able to remove potent free radicals, such as peroxides, nitrogen dioxide, HOCl, and a multitude of other toxins, from the body. It does this through a basic redox reaction, thus protecting cells, DNA, and extracellular matrix components from the damage done by free radicals. Glutathione not only neutralizes free radicals directly, but assists other antioxidants, such as vitamins C and E, in their roles as antioxidants[1].
Glutathione is found both inside cells and as a secreted substance in the extracellular matrix. It is found in very high levels in lung tissue, the brain, and the liver. It is synthesized in humans via a simple redox reaction as follows.
Glutathione is so important in the human body that deficiency has been associated with a wide range of diseases such as diabetes, HIV, cancer, and even tuberculosis. Research suggests that glutathione levels may be an important marker of disease severity and progression. Measuring glutathione may offer clinicians a more quantitative means of assessing prognosis and helping to determine the efficacy and timing of various interventions[2]. Despite understanding the role of glutathione in aging and disease, no routine means of measuring and assessing glutathione levels has been established. Researchers are now looking into how measuring this simple peptide could provide critical into everything from overall health to the efficacy of specific treatments in disease. In the near future, measuring glutathione levels may be as commonplace and useful as measuring things like blood pressure, cholesterol, and blood sugar levels.
While glutathione is best known for its antioxidant functions, the peptide does play other roles in the human body. It is an important, indeed required, molecule in the production of leukotrienes (inflammatory mediators) and prostaglandins. This makes it a potent regulator of certain immune responses as well as the inflammatory cascade. It is also a cofactor in a number of biochemical reactions and enhances the function of citrulline in the nitric oxide cycle. In other words, glutathione is an essential component of cellular metabolism and particularly important in regulating blood pressure and cardiac health.
Glutathione is also critical to proper protein folding in the endoplasmic reticulum. Research shows that glutathione helps proteins to fold into the correct 3D shape to bind to receptors and function normally. It is particularly important in the formation of disulfide bonds. Though it is not the only mechanism that cells harbor to promote proper protein folding, glutathione is an important aspect of this cellular function and thus contributes heavily to the proper functioning of cells[3], [4].
There is currently some debate as to whether glutathione acts a neurotransmitter. It certainly modulates the redox states of things like the NMDA receptor (a function that would make it a neuromodulator). It also appears to activate ionotropic receptors as well as the purinergic P2X7 receptor on Muller cells. Muller cells are found in the retina where they maintain the structure and function of retinal cells. This includes the regulation of neurotransmitter levels. This, again, suggests that even if glutathione is not a neurotransmitter, it plays an important role in the regulation of neurotransmitters[5].
The world’s foremost expert on glutathione is Dr. Nayan Patel. In 2020 he wrote a book entitled The Glutathione Revolution in which he discusses the benefits and safety of glutathione supplementation. He likens oxidation in the body to rust, an apt analogy if ever there was one. Glutathione is the body’s main rust preventative, warding off all of the negative consequences of oxidation in the body in the same way that proper care of your car wards off rust and the detrimental effects it has on everything. According to Dr. Patel, glutathione levels drop by about 20% after age 40, setting us up for poor performance, increased risk of disease, and accelerated aging. The only way to overcome this deficit is through supplementation.
Research shows that glutathione is not well absorbed from dietary sources or as a result of oral intake. It is thought that enzymes in the GI tract may break it apart before it can be absorbed. There is some evidence to suggest that curcumin, N-acetyl cysteine, and certain components of foods like broccoli and spinach may help to boost glutathione levels by providing more precursors for its synthesis or by directly upregulating the process of synthesis itself.
Unfortunately, there is limited evidence to support the above options as being the optimal way to increase glutathione. While they do increase glutathione levels to some extent, the magnitude of their effect appears to be limited primarily because they cannot overcome the decrease in GSH levels that results from the loss of synthetic capacity. Research suggests that the only reliable way to significantly alter glutathione levels is to inject the peptide or to inhale it. Dr. Nayan Patel has developed a transdermal delivery system for glutathione, but it is not yet widely used.
Oxidative damage to cells is one of the leading components of both the visual signs of aging as well as aging processes like senescence (cellular/tissue aging), hormonal aging, metabolic aging, and DNA damage that led to both disease and dysfunction. Given the importance of glutathione in fighting against oxidative damage, it should come as no surprise that the peptide is critical to reducing the effects of aging.
Of course, glutathione itself, as discussed, is subject to the effects of aging. With age comes a decrease in the capacity of most mammals to synthesize glutathione. Fortunately, supplementation is possible. Research, shows, however, that the best forms of glutathione supplementation are either injecting the peptide or inhaling it through a nasal preparation. Injection provides for the easiest administration of large doses of glutathione is the method most commonly used in research studies.
Decreased glutathione levels are associated with the common signs of aging as well as more serious disorders like neurodegenerative disease. In particular, glutathione pathology plays a prominent and perhaps pivotal role in the onset of Parkinson’s disease (PD). New research indicates that glutathione is a potent mediator of a process called iron-dependent cell death or ferroptosis. Without glutathione, this type of programmed cell death runs uncontrolled in cells of the central nervous system, causing premature aging and contributing to the development of neurodegenerative disease. Abundant research shows that supplementation with glutathione or its precursors (e.g. N-acetyl cysteine) is especially useful in offsetting neurological aging[10].
Perhaps the best-known role of glutathione is in the retina of the eye where it acts both as an antioxidant and as a supportive agent to Muller cells. Muller cells are cells within the retina that support the health and function of retinal neurons. Mujller cells, also called Muller glia, mediate acetylcholine and GABA neurotransmitter degradation, help to funnel light to retinal cells, and maintain the nutrient supply and waste removal of retinal cells. They are critical to eyesight and the long-term health of the retina, protecting the eye against everything from viral infection to diabetic retinopathy[12].
Glutathione is also an important component of lens health where it maintains protein thiols in their reduced state and thus maintains the normal light-scattering properties of the eye. A reduction in glutathione levels in the lens has been associated with cataract formation as well as changes in the permeability of the lens that make it harder for nutrient exchange to occur[13], [14].
Research shows that glutathione plays a critical role in protecting visual acuity and supporting retinal health. Combined with other anti-oxidants, research in animal models shows that glutathione supplementation (in this case delivered in the form of eye drops) can reduce oxidative stress in the eye and slow the typical changes that occur with aging such as cataracts and loss of visual acuity[15].
Supplementation with glutathione thus appears to support long-term health of all aspects of the eye including the retina, lens, and cornea. Research suggests that glutathione may help to ward off both ocular diseases as well as the “normal” effects of aging on the eye. Researchers are currently working on a topical (i.e., drop-based) delivery system for direct delivering of the peptide to the eye, but injected and inhaled glutathione likely provide benefit to the eye as well.
One of the underlying causes of osteoarthritis (the wear-and-tear arthritis) is the inability of cells that maintain cartilage health to adapt to stress. Research shows that glutathione plays an important role in this process. Interestingly, supplementation is not the only means of maximizing glutathione function in cartilage. In fact, research in cows indicates that supplementation is only part of the answer to healthy cartilage. The other part of the answer is unloading the cartilage. In other words, resting joints is critical to increasing glutathione levels within them. The best research indicates that inducing oxidant stress, such as through careful exercise, followed by proper rest boosts glutathione levels in our joints and delays the aging process in cartilage[16].
USD
EUR
GBP
CAD