Learn about the body's master antioxidant and how to benefit from it

This tripeptide composed of cysteine, glycine and glutamic acid is found in surprisingly high concentrations - 5 millimolar - in most cells.

Glutathione (GSH) has the same concentration in cells as glucose, potassium and cholesterol!

Given the high level of metabolic activity required to produce glutathione and in such high concentrations, its importance is evident. The problem is that its absorption is not so evident.

One of the main functions of antioxidants is to inhibit the action of free radicals, highly reactive particles that bounce around the cell, damaging everything in their path.  Most of them originate during the process of metabolism, but they can also be produced during exercise, exposure to toxins, irradiation and toxic metals.

Glutathione or GSH, unlike other antioxidants, works intracellularly and has the unique ability to enhance the activity of all other antioxidants .  These include, but are not limited to, vitamins C and E, CoQ10, and alpha-lipoic acid.  It also removes toxins from cells and protects against the harmful effects of radiation, chemicals and environmental pollutants.

Perhaps one of the people who has studied GSH the most is Dr. Joseph Pizzorno, an expert in integrative medicine, specifically for its properties at the level of detoxification, mitochondrial function and healthy aging.

The fundamental role of adequate GHS glutathione for health has become increasingly evident and highlights the importance of this powerful antioxidant in several reports for its protection against oxidative stress,  protection against mercury and other toxic metals; protection against alcohol; and protection against persistent organic pollutants.

The crucial role of glutathione in detoxification, inflammation and much more

It is difficult to overstate the importance of GSH, whose key functions are summarized in the  next table. It plays a crucial role in shielding cellular macromolecules against endogenous and exogenous reactive oxygen and nitrogen species (ROS and ERNs). While it directly quenches some free radicals, perhaps more importantly, it directly addresses the causes of oxidative stress, such as mercury and POPs (persistent organic pollutants).

The most important functions of glutathione (GSH)

Direct chemical neutralization of singlet oxygen, hydroxyl radicals and superoxide radicals. Neutralizes several different types of radicals.

Cofactor of several antioxidant enzymes, that is, it helps them function well

Regeneration of vitamins C and E so that they continue to provide their antioxidant action

Neutralization of free radicals produced by phase I of the hepatic metabolism of chemical toxins .  A super antioxidant that does a lot of work in the liver.

One of approximately 7 phase II reactions of the liver, which conjugate activated intermediates produced by phase I to make them water-soluble for excretion by the kidneys.  That is, it helps the liver and gallbladder to metabolize fats effectively.

Transport of mercury out of cells and the brain

Regulation of cell proliferation and apoptosis.  That is, it helps regulate the death of old or damaged cells that accumulate in the body.

Vital for mitochondrial function and maintenance of mitochondrial DNA (mtDNA), which gives us plenty of energy for our activities

Glutathione (GSH) and NAC (N-Acetyl-Cysteine)

NAC is a precursor and limiting nutrient for the formation of GSH. Because glutathione is poorly absorbed, it is easier to raise its levels by taking NAC instead.

According to an article by Dr. Joseph Mercola, NAC is used very effectively in two cases:  as an antidote for acetaminophen toxicity resulting from overdose and which can be effectively prevented if administered promptly.

Along the same lines, NAC supplementation  It can also help "pretoxify" the body when taken before alcohol, thus minimizing the harm associated with alcohol consumption .

Taking NAC (at least 200 milligrams) 30 minutes before drinking helps to reduce the toxic effects of alcohol . Vitamin B6 can also help reduce hangover symptoms.

While NAC's most common use is for liver support, it is also showing promise as a neuroprotectant.  ( Study )

It is currently being investigated by scientists as a possible treatment for Parkinson 's disease, where a deficiency of glutathione has been detected in the substantia nigra, a region that houses dopamine neurons. ( Study )

Another area where NAC shows promise is in the treatment of mental health disorders such as post-traumatic stress disorder, depression and substance abuse disorders, says Dr. Mercola.

Epigenesis and glutathione

Epigenesis is a doctrine according to which the traits that characterize a living being are configured during the course of development, without being pre-established in the fertilized egg.  And furthermore, it says that if you have inherited a certain characteristic, disease, etc., with certain changes in your habits you can alter or eliminate a genetic fault, for example.

Glutathione has been found to have an effect on regulating epigenetic disease mechanisms.  As mentioned in a November 2017 paper in Free Radical Biology and Medicine:

"Epigenetics is a rapidly growing field that studies modifications of genetic expression that do not involve changes in the DNA sequence.

Effects of NAC on the human body

Improved cardiovascular and mitochondrial function

Cardiovascular aging produces metabolic, inflammatory and functional changes that can be derived from oxidative stress and that can be remedied with antioxidants. Glutathione, which is an intracellular antioxidant, decreases with age, and supplementation with glutathione or, better, with NAC and glycine (Gly), increases tissue glutathione.

According to a 2018 study conducted on laboratory rats where they were supplemented with NAC or NAC+ Gly, the results were,

• Improvement of diastolic function in filling and reduction of relaxation time; and of the final diastolic pressure of the left ventricle.
• Regarding cardiac function, the results occurred with the NAC+Gly mixture since this combination reduced the formation of ROS (Reactive Oxygen Species), had anti-inflammatory effects and a reduction in leukocyte infiltration in the hearts of elderly mice.
• This same mixture allowed the normalization of fatty acid metabolism, which was not possible without adding NAC+Gly to the diet.
• Increased critical mitochondrial genes in elderly hearts.

These results potentially have the same effects in humans.

Deficient glutathione levels reduce vitamin D levels in obese people

A study published on October 15, 2019 in the journal Nature, points out that vitamin D (VD) deficiency is a significant and more common risk factor for chronic diseases, including insulin resistance, obesity, diabetes and atherosclerosis.

Several studies report deficiency of Glutathione (GSH) and 25(OH)VD3 in obese and type 2 diabetic subjects.  In this study, a decrease in circulating plasma GSH and 25(OH)VD3 was also observed in mice fed a high-fat diet (HFD).

Glutathione biosynthesis pathway activity was reduced in the livers of mice fed with FAG. Inflammation, steatosis, ballooning, and fibrosis are the hallmarks of non-alcoholic fatty liver disease (NAFLD), and associated genes such as MCP-1, TNF, TNFR1, TGFβ1, Colα1, αSMA, Timp1, and Hp were significantly enriched in the livers of mice fed with FAG.

Furthermore, glutathione (GSH) levels decreased with increased oxidative stress markers in the HFD-fed mice, reflecting the depletion of antioxidant potential and increased oxidative stress. This suggests that GSH deficiency was initiated at the cellular level.  This study reports a link between decreased GSH and impaired vitamin D (VD) metabolism genes in the liver.

Glutathione for COPD

According to the publication CoreMedScience , low serum glutathione (GSH) appears to lead to abnormalities in the lungs. Preliminary research suggests a clear link between low GSH and the onset of COPD (Chronic Obstructive Pulmonary Disease).

As damage caused by tobacco or even pollution builds up in the respiratory tract and lungs, the exchange of oxygen and carbon dioxide (CO2) is impaired, making breathing difficult.

Low levels of GSH have been linked to abnormalities in the lining of the lungs, which can lead to COPD. Having normal levels of glutathione protects lung tissue from free radical damage, such as inflammation.

According to an article in the American Physiological Society, intravenous glutathione supplementation maintained normal lung function, when exposed to otherwise toxic oxygen levels. It also increased lung function, decreased swelling, and increased lung tissue.

The researchers concluded that GHS supplementation promotes normal airflow and lung tissue, as well as reducing the risk of "oxygen-induced lung injury."

Improves exercise-induced stress

We have already talked before about the many benefits that exercise brings to our lives.  But it is also known that subjecting the body to periods of stress, such as when practicing a high-performance sport or strength exercises with heavy weights, produces free radicals and, consequently, oxidative stress.

The key is adaptation, and this must occur without overtraining the body or taking breaks so long that any physical progress made is lost.

But beware, because under more extreme conditions such as 1) inadequate intake of foods containing antioxidants, 2) excessive intake of pro-oxidants, 3) exposure to harmful chemicals or ultraviolet light, 4) wounds/injuries, and/or 5) intense exercise, especially eccentric exercise, the body's endogenous antioxidant system is not able to effectively eliminate the excessive production of ROS, according to researchers and that is when oxidative stress occurs.

Why is it important to control oxidative stress in the body?

Oxidative stress has been linked to diseases ranging from atherosclerosis, pulmonary fibrosis, cancer, Parkinson's disease, multiple sclerosis to aging.

It is important to understand that it is regular training that allows the body to adapt and thus improve its ability to respond effectively to the increase in oxidative products in the body, but this must be done in the proper cycles.

On the other hand, exercise increases your glutathione levels.

When intense exercise is performed, the level of glutathione in the blood decreases significantly while circulating levels of oxidized glutathione increase, indicating that it has been used within the muscle to quench free radicals produced during the effort.

Considering the importance of glutathione in counteracting free radicals, effective regulation of glutathione levels during exercise is something that must be taken into account. The good news is that the more you exercise, the higher your baseline glutathione levels become.

Adaptation is what allows your body to effectively counteract the increase in free radicals that exercise produces. While exercise itself will increase your glutathione level over time, increasing glutathione through supplementation is a widely used strategy among athletes, but as we saw above, glutathione itself is not a good supplement, while its precursor NAC (N-acetyl-cysteine) performs the function more effectively.

Several studies show that NAC supplementation helps delay muscle fatigue during exercise, thus improving endurance.  In one study , NAC infusion increased time to exhaustion by 26.3%.

GSH may help in the treatment of chronic fatigue syndrome (CFS)

In his article , Dr. Mercola places special emphasis on the importance of glutathione in treating chronic fatigue syndrome (CFS).  Chronic fatigue is characterized by "overwhelming fatigue that does not improve with rest," according to the U.S. Centers for Disease Control.  Fatigue is often such that it challenges your ability to perform even the most common tasks of daily living, such as showering or preparing a meal.

According to Dr. Rich Van Konynenburg, developer of the methylation protocol used widely in the CFS community, “Oxidative stress is probably the best-proven biochemical aspect of chronic fatigue syndrome,” and for your oxidative stress to overload your system, something must be placing too much strain on your glutathione supply.

Several factors such as inadequate intake of antioxidants ( The question has arisen as to whether a nutrient with antioxidant activity can cause the opposite effect with pro-oxidant activity if too much is taken. Therefore, the use of an antioxidant supplement with a single isolated substance may not be an effective strategy for everyone and that is why your diet should be balanced ); and/or excess pro-oxidants, exposure to toxins and physical injuries. Long-term emotional stress can also cause CFS.

The connection between glutathione and vitamin B-12 in the body to combat CFS

When toxin levels in the body rise and there is not enough glutathione to eliminate them, two things happen that sabotage the function of vitamin B12 when glutathione is not present in sufficient quantities.

Vitamin B12 helps the body convert food into glucose for energy, and fatigue is one of the symptoms of low B12 levels.  The body cannot use it effectively and it is believed that this is due to the low availability of glutathione.

The most important job B12 has in the body is to form methylcobalamin, which is one of the two active forms of B12. This form is necessary for the enzyme methionine synthase to do its job.

When there is not enough methylcobalamin, methionine synthase has to slow down its reaction. Its reaction is at the junction of the methylation cycle and the folate cycle, so when this reaction slows down, it affects both cycles.

The methylation cycle has some important tasks to do that have an effect on various reactions in the body such as producing  creatine, carnitine, coenzyme Q10, phosphatidylcholine, melatonin and many other substances crucial for the proper functioning of the body.

How fatigue occurs according to Konynenburg:

Cells have tiny power plants in them called mitochondria. Their job is to use food as fuel to produce ATP (adenosine triphosphate). ATP acts as an energy source to power a large number of reactions in cells.

For example, it drives muscle fiber contraction and provides the energy to send nerve impulses. It also supplies the energy to produce stomach acid and digestive enzymes to digest our food, and many, many other things.

When glutathione becomes too low in muscle cells, levels of oxidative free radicals increase, and these react with parts of the "machinery" of small power plants, decreasing their ATP production.

So the muscle cells experience an energy crisis, and that's what causes fatigue. Over time, due to a lack of sufficient glutathione, more problems build up in the mitochondria, including toxins, viral DNA, and mineral imbalances."

All of these factors will eventually decimate your immune function as well, allowing pathogenic bacteria, viruses, and fungi to take over. CFS patients will often have several ongoing infections at the same time. Low glutathione also impedes your body's natural detoxification pathways, allowing toxicity to build up over time, thus causing increasing dysfunction.

To reverse this process, there is a methylation treatment proposed by Dr. Konynenburg and which can be found at www.HealthrRising.org

Specific causes of glutathione deficiency in the body

According to CoreMedScience , age is the most natural depletor of glutathione levels. However, there are a number of environmental factors and medical conditions that increase the risk of deficiency.

Environmental risk factors for glutathione deficiency include:

Exposure to chemical toxins (including pollution)

Exposure to UV radiation

Exposure to cadmium

Chronic stress

Excessive alcohol use

Smoke

A nutrient-poor diet

Certain medications (such as Tylenol)

Certain diseases are known to cause decreased glutathione levels. Researchers are still determining whether low glutathione causes some of these diseases, or the other way around.

According to the same publication, the most common diseases related to low levels of glutathione are:

AIDS/HIV

Macular degeneration

Parkinson's disease

Alzheimer's disease

Diabetes

Hepatitis

Cancer

COPD

Liver disease

Sickle cell anemia

Cystic fibrosis

Stroke

Heart disease

Infertility

Benefits of glutathione

These are the fields where GHS is already used as part of the treatment to treat the following conditions.

Ulcerative colitis

Some research suggests that N-acetylcysteine ​​(NAC), a precursor to L-cysteine ​​that can increase glutathione levels in the body, may help treat ulcerative colitis by reducing the impact of oxidative stress and decreasing inflammation in the injured colon, notes an article in the journal Cell.

Skin health

Several personal products contain glutathione for skin whitening purposes, while others consume it orally for the same purpose.  However, there are not enough studies to corroborate this.

There is currently little convincing evidence in favor of glutathione as a therapy for hyperpigmentation, and there are many unresolved controversies surrounding its use. The trials available to date that have evaluated the role of glutathione in skin lightening administered through different modalities have numerous limitations. ( Study )

Glutathione has, however, been shown to reduce psoriasis. Glutathione levels in this clinical trial were increased by consumption of whey protein isolate, which contains glutamylcysteine, a precursor of GSH.

The same studies also show that glutathione may not only lighten skin, but it may improve skin elasticity and reduce wrinkles.

Waterfalls

The ocular lens is richly endowed with a complex system of non-enzymatic and enzymatic antioxidants that scavenge reactive oxygen species to preserve lens proteins. Depletion and/or failure of this primary antioxidant defense system contributes to the observed damage to lenticular molecules and their repair mechanisms, ultimately causing cataracts.

A study using several anti-cataract compounds including plant extracts and natural compounds, based on their antioxidant and/or free radical scavenging and/or anti-inflammatory effects.

A wide range of compounds, including antioxidants and herbal remedies/extracts, have shown anti-cataract activity in vitro, ex vivo, and in vivo. So far, compounds possessing antioxidant and free radical scavenging activity have shown enormous potential in these experimental studies, including glutathione.

Foods that contain glutathione

A variety of factors can affect levels of this vital nutrient, including storage and cooking. Cooking these foods can reduce their glutathione content by up to 60 percent.

Here are some simple examples of foods you can add to your diet to help keep glutathione levels in your body at a healthy level.

Foods of the Allium genus

Allium is a plant genus rich in sulfur, a precursor to glutathione synthesis. The more sulfur, the more natural the production of glutathione.

Plant foods that belong to the allium genus include:

Garlic, Onions, Chives, Spring Onions, Shallots and Leeks

Cruciferous vegetables

Cruciferous vegetables are packed with glucosinolates , which will boost your body’s glutathione levels. These compounds give Brassica plants their distinctive sulfuric aroma.

Great cruciferous vegetables include:

Broccoli (especially the sulforaphane present in its sprouts)

Cabbage, Cauliflower, Kale, Brussels Sprouts, Chinese Chard, Arugula, Collard Greens, Watercress and Radishes

Foods rich in alpha-lipoic acid (ALA)

α-Lipoic acid regenerates and increases glutathione levels in the body. Adding it to your diet should provide you with many of the health benefits of glutathione.

Good food sources of α-lipoic acid include:

Spinach, Peas and Tomatoes

Foods rich in selenium

Selenium is a trace element that is part of the basic components that make up antioxidant enzymes. It is also key in the production of glutathione.

Good dietary sources of selenium include:

Brazil nuts, eggs, mushrooms, asparagus and whole grains

NAC Dosage and Usage Guidelines

For many people, NAC (N-acetyl cysteine) can be safely used to increase glutathione levels.  It is widely available as an oral dietary supplement and is relatively inexpensive. Unfortunately, like glutathione, NAC is poorly absorbed when taken orally, although it is better absorbed than glutathione.

According to some studies, oral bioavailability of NAC can range from 4% to 10%, so the recommended dose can be as high as 1,800 milligrams (mg) per day. Its half-life is also about two hours, so most subjects in the studies conducted so far take it two or three times a day.

The maximum safe dose has not yet been determined, but as a general rule, it is well tolerated, although some experience gastrointestinal side effects such as nausea, diarrhea, or constipation. Should this occur, reduce your dose.

Lifestyle changes that can ensure your natural glutathione levels remain healthy:

- Eat a diet rich in glutathione. Avoid processed foods and sugar.
- Drink 2 liters of filtered water a day.
- Sleep 7 to 8 hours per night.
- Reduce stress.
- Exercise at least four days a week.