How to increase cellular glutathione levels
Learn about the only theoretical and clinically proven way to increase cellular glutathione levels.
Glutathione – what is it?
- The antioxidant Glutathione used by all aerobic living organisms from bacteria to humans and is often referred to as the “major antioxidant”.
- We don’t need to include glutathione in our diet as it is produced by every cell in our body
- Glutathione has many important physiological functions, including neutralizing the free radicals produced by the mitochondria of our cells during breathing.
Glutathione Deficiency and Illness
- It has been shown that most chronic diseases are related to decreased cellular glutathione levels in the affected tissues.
- Insufficient glutathione leads to oxidative stress, which leads to progressive damage to cell components including nucleic acids, lipids and proteins.
- As this oxidative damage builds up, the cells and associated tissues lose their physiological function, which manifests itself in symptoms and loss of health.
- If you search the internet, you will find numerous websites recommending certain supplements and foods to increase your glutathione levels. Supplements include glutathione itself, liposomal glutathione, NAC, and the Ribocene. Recommended foods are spinach, avocados, and asparagus.
- You can try these options, but none of them will raise your glutathione beyond homeostasis. As a result, they are unlikely to improve your health (related to glutathione).
- The only supplement clinically proven to increase glutathione beyond homeostasis is the immediate precursor glyteine (gamma-glutamylcysteine).
Benefits of Glutathione Supplement
- In general, glutathione supplements do not offer any clinically proven benefits. To understand why not, we need to look at how glutathione is made in each of our cells.
- Glutathione is a relatively simple compound. It consists of three amino acids (the building blocks of proteins). Our cells use two enzymes (biological catalysts) to make their own supply of glutathione. The first enzyme combines glutamate and cysteine to produce gamma-glutamylcysteine, and the second adds a glycine to produce glutathione.
- Glutamate and glycine can be easily synthesized by cells.
- Cysteine must either be obtained as cysteine from food or converted from the other sulfur-containing amino acid methionine. As such, cysteine is considered to be the rate-limiting amino acid for glutathione synthesis. It should be noted that Western diets contain all of the cysteine (e.g., it is commonly added to bread) that we need to meet our glutathione manufacturing needs.
- Glutathione homeostasis in your cells is controlled by a feedback inhibition mechanism. When glutathione reaches the homeostatic set point (which varies between cell types), it interacts with the first enzyme synthesizing glutathione, glutamate cysteine ligase (GCL), to slow down its activity and limit the production of gamma-glutamylcysteine (GGC).
- When glutathione is depleted due to an increased need, for example during exercise, the interaction between glutathione and GCL weakens and GCL activity increases in order to produce more GGC for the second enzyme, glutathione synthase (GS), and in To convert glutathione.
- GS activity always exceeds that of GCL, which means that the GGC level in cells is always negligible compared to glutathione.
- So it doesn’t matter how much glycine, glutamate or cysteine is lying around in a cell, they are not used for glutathione synthesis when the cell is already at its homeostatic setpoint.
- It should be noted that when glutathione is used to neutralize free radicals, it oxidizes itself. The oxidized glutathione is then returned to the reduced form by the NADPH, which the enzyme glutathione reductase requires.
The cause of chronic glutathione deficiency
- The reason why glutathione is constantly depleted in many chronic diseases is often related to a glutathione homeostasis disorder.
- Essentially, this means that the interaction between glutathione and the GCL enzyme is disrupted to the extent that GCL activity is switched off at glutathione concentrations that are insufficient to protect the cell from oxidative stress.
- In fact, it means that the GCL enzyme starves the GGC cells, which are necessary to maintain healthy levels of glutathione.
- Numerous studies have examined the role of GCL dysfunction in the wide variety of conditions associated with glutathione deficiency.
- These adverse changes in the regulation of GCL activity can have genetic, developmental, environmental, and age-related causes.
Overdose of NAC and paracetamol
- Some benefit from NAC has been shown in conditions involving acute glutathione deficiency due to exposure to toxins.
- In fact, NAC is the standard treatment for acetaminophen overdose and has saved many lives since it was first used medicinally in 1968.
- Excessive consumption of acetaminophen can quickly break down glutathione in the liver.
- In response, the liver tries to produce more glutathione but depletes its cysteine supply, with glutathione levels continuing to decrease so much that the resulting extreme oxidative stress leads to cell apoptosis, tissue necrosis, complete liver failure, and often death if a liver transplant is not performed available.
- Timely administration of NAC will meet the liver’s need for cysteine to bring glutathione levels back into homeostasis and consequently manage the detoxification of the acetaminophen overdose.
Benefits of glutathione supplements, or more precisely the failure of NAC and glutathione supplements
On the other hand, glutathione and NAC have repeatedly shown no tangible benefit in clinical trials in the treatment of disorders associated with chronic glutathione deficiency. The reason why this is the case can be explained through biochemistry and physics.
Glutathione Biochemistry and Why Glutathione and NAC Supplements Don’t Work
- Although glutathione has some protective functions outside the cell in the various body fluids, most of its activity is required inside the cell.
- This is reflected in the fact that cells contain a concentration of glutathione a thousand times higher than that of extracellular fluids (e.g. plasma). So if you take a glutathione preparation, an unfavorable concentration gradient means that it cannot passively (via osmosis) enter the cells where it is often needed.
- Most cell types do not have an energy-dependent (ATP) active transport system for the uptake of glutathione against this concentration gradient.
- What most cell types have is an enzyme bound to the outer membrane, gamma-glutamyl transferase (also known as gamma-glutamyl transpeptidase, GGT). Doctors will be familiar with this enzyme as it is often measured in pathology tests to confirm healthy liver function. High serum GGT levels indicate damage to liver cells, which may be due to a liver infection or chronic alcohol abuse.
- This GGT enzyme effectively hydrolyzes extracellular glutathione to its amino acid component, which can then enter the cell. In the cell, these amino acids can then serve as substrates for the resynthesis of glutathione. However, this does not mean that this increased supply of glutathione building blocks enables the cell to increase its glutathione content beyond any dysfunctional homeostasis.
How to increase the level of glutathione in the body
- Most doctors are aware of the role of glutathione deficiency and the associated oxidative stress in the chronic illness of many of their patients.
- Before GGC (Glyein) was launched under the Continual G brand for dietary supplements, they had few (and none of them effective) options for increasing cellular glutathione.
- All they could recommend is glutathione, or NAC. But what can they really do? The GGT enzyme breaks down the glutathione into the amino acid components that can enter the cell. However, they are fed into the faulty GCL enzyme and do nothing to bring the glutathione to healthier levels.
- Similarly, the NAC enters the cell, becomes deacetylated, and supplies cysteine to the faulty GCL enzyme, which in turn offers no benefit in increasing glutathione to healthier levels. This will help explain any errors in clinical trials for glutathione, NAC, and other similar cysteine prodrugs.
Benefits of Glutathione
- Glytein (GGC) is the only compound that can theoretically enter cells passively due to the lack of a concentration gradient, bypass impaired GCL activity and increase glutathione levels via homeostasis.
- This theoretical bioavailability has been confirmed in clinical studies. Please visit continuualg.com for more information.
Photo credit: verywellhealth.com