L-glutathione

The sulphur-containing amino acid glutathione was first described as part of yeast. Its structure as a sulphur-containing tripeptide was elucidated in 1935. Glutathione is the body's most powerful antioxidant. It has an enormous capacity to combat oxidative stress and neutralize harmful free radicals. Chemically speaking, glutathione is a tripeptide consisting of the three amino acids glutamic acid, cysteine and glycine. Glutathione is formed from these three amino acids in the liver. The amount synthesized depends on the cysteine intake from food. When these three amino acids are combined to form glutathione, they gain the power to neutralize dangerous free radicals, toxic drugs and chemicals and heavy metals. This mechanism protects the entire body from dysfunction and disease.

At first glance, glutathione is similar to other well-known antioxidants such as vitamin C and vitamin E. However, the amazing thing about glutathione is that, unlike other antioxidants such as resveratrol and quercetin, it can be produced by the body itself if the necessary building blocks are available. In fact, the body needs to produce glutathione in order to lead a healthy life. Scientists even go so far as to consider the levels of glutathione in the body as an indicator of expected lifespan (1).

A lack of glutathione increases susceptibility to oxidative stress, which may be the underlying cause of many diseases including cancer, heart disease, Parkinson's and Alzheimer's (2). Glutathione is present in high concentrations in almost all body cells, with active, reduced glutathione in equilibrium with glutathione disulfide. Glutathione is used for many metabolic processes. It supports the structures of body proteins and helps to transport amino acids through the cell membranes (cell walls).

What are the health benefits of glutathione?

Does glutathione have antioxidant effects?

Glutathione plays a particularly important role in the body's antioxidant defense system. It works together with the selenium-containing enzyme glutathione peroxidase. Glutathione can detoxify free radicals and recycle oxidized vitamins C and E so that the body can use these vitamins again. The active, reduced form of glutathione is relatively unstable and is quickly used up, especially in the case of oxidative stress. Glutathione is also important for the immune system, especially for the reproduction of lymphocytes. It contributes to the production of leukotrienes (mediators), which control the functions of leukocytes (white blood cells) and other immune reactions in the event of inflammation, for example. Glutathione can also help the liver to detoxify a range of chemicals and pollutants, for example the heavy metal cadmium. Glutathione also contributes to the repair of DNA damage.

Can glutathione reduce inflammation?

Glutathione blocks most pro-inflammatory cytokines. When suffering from chronic health problems, cytokines can maintain a constant state of underlying inflammation. In mice, glutathione deficiency caused inflammation. Blockade of pro-inflammatory pathways (MAPK and iNOS) was able to restore the seals. This suggests that glutathione and inflammation have a very close, reciprocal relationship (3). In addition, glutathione blocks NF-k, the primary controller of inflammation in the body.

This protein complex increases the activity of various pro-inflammatory genes and their products (4). A number of lung and respiratory diseases are caused by excessive inflammation and people suffering from these diseases can benefit from restoring healthy glutathione levels (5). While increasing glutathione levels can reduce inflammation, one must also address the underlying causes of inflammation to achieve full recovery.

Does glutathione have anti-ageing benefits?

With less glutathione in the body, free radicals can damage the body and accelerate the aging process and cognitive decline. Several studies have found that the body produces less glutathione as we age. In women, levels begin to fall at the onset of menopause and remain at lower levels thereafter. Increased oxidative stress from low glutathione levels can make bones in older people more fragile and contribute to osteoporosis (6). Cells that lack glutathione are more susceptible to damage. Low glutathione levels trigger a cascade of events that ultimately lead to cell injury and cell death, accelerating the aging process (7). Restoring healthy glutathione levels could slow down the aging process, strengthen bones and prevent age-related cognitive decline.

What effects does glutathione have on mental health?

Can glutathione relieve anxiety, depression and stress?

Scientists have discovered that people with depression have low glutathione levels (8). Accordingly, it is not surprising that glutathione can prevent depression in animals suffering from stress. Interestingly, anti-anxiety drugs may work in part by increasing glutathione levels (9, 10).

Can glutathione alleviate obsessive-compulsive disorder and schizophrenia?

People with schizophrenia have low glutathione levels. NAC, which increases glutathione levels in the brain, has been shown in clinical studies to alleviate symptoms of schizophrenia (11). People with OCD also have low glutathione levels in certain areas of their brain and high levels of free radicals in the blood. Increasing glutathione levels could reduce antioxidant defense, resistance to stress and overall severity of symptoms (12). Since several medications used to treat bipolar disorder work by increasing glutathione levels, naturally increasing glutathione levels could help stabilize mood and symptoms (13).

Can glutathione help with autism and ADHD?

Children diagnosed with autism have about 20 to 40% lower glutathione levels than non-autistic children. They have different abnormalities in the production and restoration of the active form of glutathione (14). Oral and transdermal forms of glutathione are produced to restore normal glutathione levels in autistic children. People suffering from ADHD also have low glutathione levels and high levels of oxidative stress. Pycnogenol, a natural glutathione booster, has been shown to normalize glutathione and antioxidant levels in children with ADHD (15). Until further studies are published, caution should be exercised with glutathione supplements in children with ADHD. The bioavailability of most commercially available products is problematic and some of these products have not been tested in children. NAC, pycnogenol, and cysteine-rich and sulfur-containing foods may be safer options for increasing glutathione levels in children.

Can glutathione protect the brain?

Reactive oxygen species are continuously generated in the brain as the brain burns fuel for energy. The brain needs to neutralize these free radicals to stay healthy and glutathione plays a key role in making this possible (16).

Can glutathione help with Alzheimer's?

Alzheimer's is caused, at least in part, by oxidative stress. Antioxidants can prevent the disease or slow its progression. Several studies have shown that vitamin E (a powerful antioxidant) can slow the progression of Alzheimer's (17). The accumulation of toxic proteins in Alzheimer's further lowers glutathione levels, further increasing the likelihood of deficiency (18). In mice with Alzheimer's disease, increasing glutathione levels improved memory, reduced plaque accumulation and alleviated Alzheimer's symptoms (17). However, it should be noted that there have been no human studies on glutathione and Alzheimer's disease.

Can glutathione help with Parkinson's?

Glutathione may help combat the oxidative stress that damages dopamine neurons in Parkinson's disease. People with Parkinson's have low glutathione levels in the brain and increasing glutathione levels could be an early precautionary measure to prevent this disease (19). In one study, a drug (3,4-dihydroxy benzalacetone) was able to prevent Parkinson's by increasing glutathione levels (20).

What should be considered when increasing glutathione levels to promote brain health?

When suffering from a brain dysfunction, it is crucial to provide the brain with enough of the building blocks it needs to produce glutathione and other antioxidants. When choosing to supplement, opt for glutathione level-boosting products with superior bioavailability that can cross the blood-brain barrier.

Can glutathione fight infections?

Viral infections flood the blood with oxidative stress due to inflammation, which depletes more glutathione (21). Many chronic diseases, poor immune function and increased rates of infections are associated with low glutathione levels (22). Once glutathione levels are depleted, immune cells lose their ability to fight infection. NAC, which increases glutathione levels in the body, can restore the ability of immune cells to kill bacteria that cause tuberculosis (23). In another study, maintaining cysteine levels helped keep glutathione levels in the green zone. In turn, the immune cells regained their ability to fight microbes (24).

Older AIDS patients produce less glutathione, which further weakens their already fragile immune system and reduces their insulin sensitivity. Increasing glutathione levels could help reduce symptoms and decrease the incidence of bacterial infections (25). In summary, microbial infections deplete glutathione reserves and some research suggests that increasing glutathione levels may enhance the immune response against bacteria and viruses.

Can glutathione promote digestive health?

People who suffer from irritable bowel syndrome have reduced activity of the enzymes involved in glutathione synthesis. They also tend to have lower levels of the amino acid cysteine, which is required for the production of glutathione (26). The main enzyme involved in neutralizing free radicals is called glutathione peroxidase. This enzyme uses glutathione and requires selenium to work with harmful substances. High levels of this enzyme indicate more oxidative stress that needs to be neutralized (27). This enzyme also helps to renew and strengthen the inner lining of the gut. In animals, glutathione has been shown to protect the intestinal lining, which may help protect against a permeable intestinal barrier (28).

Can glutathione promote heart health?

Low glutathione peroxidase activity and low glutathione levels are associated with oxidative stress and an increased risk of heart attack (29). Cardiovascular disease is largely caused by oxidative stress in heart tissue. Glutathione can reduce the levels of free radicals and in turn could prevent strokes and heart attacks (30).

Can glutathione protect against diabetes complications?

Type 2 diabetes and high blood sugar levels lower glutathione levels in the body. As a result, the resulting accumulation of free radicals causes many complications such as heart problems and damage to the brain and nerves. Increasing glutathione levels could prevent or limit these problems (31).

Can glutathione promote kidney health?

Oxidative stress in the kidneys can cause anything from mild kidney problems to kidney failure, depending on the severity. In a study of 20 patients with chronic kidney disease, glutathione improved kidney function and alleviated anemia (32). In rats, the glutathione booster NAC was able to prevent kidney disease caused by the artificial sweetener aspartame (33).

Can glutathione protect the liver?

Glutathione can help keep the liver healthy by neutralizing oxidative stress that can lead to liver disease. Glutathione plays an important role in detoxifying the liver and protecting its sulfur-rich antioxidant pathways (34). When the liver is exposed to harmful substances, it begins to produce more glutathione to prevent damage (35).

Can glutathione help with addictive behavior?

A number of drugs (such as amphetamine and cocaine), as well as alcohol, can increase the production of reactive oxygen species. In turn, these can alter the brain and behavior and cause damage. Studies suggest that increasing glutathione levels can help overcome addictive behaviors ranging from eating disorders to alcohol abuse (36). Increasing antioxidant defenses not only protects the brain, but also helps detoxify harmful substances. Chronic alcohol abuse reduces glutathione levels in the liver. Increasing glutathione levels can improve liver function during abstinence (37). Alcohol abuse also increases oxidative stress in the lungs, which can often lead to infections such as pneumonia. Glutathione may be able to protect the lungs by reducing oxidative stress (38).

Can glutathione protect the lungs and airways?

Low glutathione levels can cause inflammation in the airways and asthma. In mice with asthma, increasing glutathione levels with NAC reduced inflammation and alleviated symptoms (39). Chronic obstructive pulmonary disease is a lung disease caused by long-term oxidative damage. Increasing glutathione levels reduces free radical damage in the lungs, which lowers the risk of developing chronic obstructive pulmonary disease (40).

Can glutathione help with sleep apnea?

People who suffer from sleep apnea have high levels of oxidative stress and reduced glutathione levels. In one study, an increase in glutathione levels improved sleep quality in subjects with sleep apnea (41).

Can glutathione improve skin health?

Can glutathione alleviate acne?

Oxidative stress lowers glutathione levels in people with acne. Increasing glutathione levels could alleviate acne by neutralizing oxidative stress and promoting skin regeneration (42).

Can glutathione slow down skin aging and reduce skin spots?

Glutathione brightens the skin of healthy women. It reduces the activity of skin cells that produce dark pigments. As a result, glutathione may help reduce dark skin spots that can occur as the skin ages (43).

Can glutathione promote eye health?

Glaucoma and cataracts can gradually lead to blindness. Since oxidative stress underlies both, increasing glutathione levels could protect the eyes. However, further studies are needed to investigate these benefits (44).

Can glutathione promote a healthy pregnancy?

Low glutathione levels can make pregnant women prone to depression and impair fetal brain development. Increased oxidative stress in the fetus has also been linked to premature birth (45). Increasing glutathione levels and levels of other antioxidants through foods rich in sulfur and cysteine could help support a healthy pregnancy.

Can glutathione help with cystic fibrosis?

People with cystic fibrosis have low levels of glutathione and high levels of oxidative stress. Low glutathione levels in the lungs impair breathing and cause damage to the airways. Glutathione inhalation can alleviate symptoms of cystic fibrosis (46).

How can glutathione levels be increased?

What glutathione supplements are available?

Glutathione is made in the body from the 3 amino acids glutamate, cysteine and glycine. When it is produced and consumed in the body, it is broken down by an enzyme called gamma-glutamyl transferase, or GGT for short. When you take a glutathione supplement, it has to pass through the liver before it enters the bloodstream. The liver can contain large amounts of the enzyme GGT, which breaks down glutathione. As a result, most oral forms of glutathione do not achieve the desired effects (47).

There are several ways and supplement forms to circumvent these limitations (48):

Liposomal
Sublingual (absorbed directly into the bloodstream)
Slow-release tablets that dissolve in the mouth or lozenges
Inhalable forms
Methyl glutathione (cannot be broken down by GGT)
Coated tablets
Intravenous injections (the safety of this dosage form has not yet been researched)

New forms are being investigated every day. These include patches, creams, nanoparticles and other advanced products that maximize glutathione concentrations in the body.

What other supplements can increase glutathione levels?

Can cysteine increase glutathione levels?

Of the three amino acids from which glutathione is made, cysteine is the most important. The amount of cysteine determines the rate and amount of glutathione that is produced. Cysteine as a supplement is available in the form of cysteine, L-cysteine and N-acetyl-cysteine (NAC).

Can selenium increase glutathione levels?

Selenium is important for maintaining healthy glutathione levels because it supports the enzyme that glutathione uses to neutralize free radicals (glutathione peroxidase).

Can alpha lipoic acid (ALA) increase glutathione levels?

R-Lipoic acid is one of the primary boosters of glutathione levels.

Can methionine increase glutathione levels?

S-adenoosyl-methionine (SAM-e) is a supplement that contains methionine and can help increase glutathione levels. A lot of glutathione level boosting supplements contain all four of the above ingredients. Selenium is not included in some products.

What foods can increase glutathione levels?

A number of fruits and vegetables contain natural glutathione, including avocados, watermelon, asparagus, potatoes, oranges, tomatoes, broccoli, zucchini and spinach. Limonene is a terpene hydrocarbon found in some plants. It can promote the body's synthesis of an enzyme containing glutathione, which has antioxidant properties. This helps to detoxify chemical substances. Limonene is found in cherries, celery, fennel, soy and wheat products. In addition, a number of foods contain the building blocks for glutathione. Garlic, asparagus and cruciferous vegetables, for example, can increase glutathione levels in the blood through their sulphur content. Animal foods rich in the amino acids cysteine and methionine can also help to increase glutathione levels. Calcium and ribofvavin, which are contained in dairy products, can also increase glutathione levels.

Which groups of people have an increased need for glutathione?

Glutathione in the cells decreases significantly with age, which can accelerate degradation processes. Cysteine and glutathione can slow down ageing processes, particularly through their antioxidant effects, as they can protect the DNA from damage caused by free radicals. With increasing age, the level of glutathione in the eye lenses also decreases. As a result, susceptibility to oxidative damage caused by UV light and the risk of cataracts increase. Glutathione can reduce the harmful effects of medication, heavy metals, bacterial toxins, peroxidized fats and air pollution. High alcohol consumption leads to increased production of acetaldehyde as a degradation product of ethanol (alcohol). Glutathione can reduce the toxic effects of acetaldehyde.

What side effects can glutathione have?

If side effects occur, this may be due to the fact that supplements that increase glutathione levels overstimulate the immune system. For this reason, you should pay close attention to the reactions to these supplements.

In scientific studies, the following side effects were observed when taking 1 gram of glutathione per day for 4 weeks (49):

Flatulence
Soft stools
Reddening of the skin
Weight gain

Side effects of higher doses (up to 150 mg per kilogram of body weight per day) in people with cystic fibrosis included chest tightness, diarrhea and fever. This may not apply to normal people and lower doses.