Glutathione, often referred to as “the mother of all antioxidants”, is one of the most talked-about supplements in the healthcare industry…and for good reason. Glutathione is produced and used by every single cell in the human body. Boosting its levels can have a very wide range of scientifically-proven health benefits.

In this article, we will explore the science of glutathione, the benefits of naturally raising it in the body, and the best measures you can take to ensure your levels are optimally balanced.

What Is Glutathione?

Glutathione is your body’s meta-antioxidant. It has an enormous capacity to combat oxidative stress and neutralize harmful free radicals.

Chemically speaking, glutathione is a tripeptide. This means it is made up of 3 amino acids [1]:

Each amino acid has important roles in the human body. When combined into a glutathione molecule, and with the help of the sulfur-rich cystine, they gain the superpower to render dangerous free radicals, toxic drugs, and heavy metals harmless. This detox mechanism protects cells, deep tissues, and organs throughout the body from disease [1, 2, 3].

At first glance, glutathione is similar to other well-known nutrients. Glutathione, vitamin C, and vitamin E all act as antioxidants.

What’s remarkable is that, unlike most antioxidants think resveratrol and quercetin – your body can make glutathione. It just needs the right building blocks. In fact, your body needs to make glutathione to survive and live a healthy life. Scientists have even suggested that its levels in a person’s cells are a great predictor of their lifespan [4, 5].

And it’s not just that your body makes glutathione, but where and how it goes about it. Glutathione doesn’t simply bind to the surface of your cell – it is created and lives inside your cells, perfectly placed to carry out its vital job.

As amazing as this is, we humans are not special in our capacity to make glutathione. Almost all living organisms need this tiny molecule – from animals and plants (especially avocados) to yeast and some bacteria – to prevent damage from reactive oxygen species [6].

Glutathione deficiency increases susceptibility to oxidative stress. And as much as we need a healthy level of oxidative stress in some situations, its chronic excess may be the underlying cause of many diseases, including cancer, heart disease, Parkinson’s, and Alzheimer’s disease [7].

Because of its unparalleled role in the body, preventing a drop in glutathione levels is essential for maintaining good health. At the same time, correcting low levels may help overcome various diseases [8, 9].

Glutathione Snapshot

Pros

  • Great antioxidant
  • Good detoxifier
  • Supports the liver
  • Raising levels helps prevent many chronic diseases

Cons

  • Unpleasant taste
  • Absorption and bioavailability are poor unless taken in specialized forms

Health Benefits of Glutathione

The benefits of glutathione are so numerous, it’s almost impossible to list them all. However, taking supplements is only one way to raise your levels, and it may not be the best strategy. Keep in mind that this section focuses on the benefits of healthy glutathione levels in the body, not on the effects of its supplements.

If you’re interested in ways to raise your levels, skip to this part of the article.

1) Fights Oxidative Stress in the Body

Glutathione reduces reactive oxygen species (ROS) and oxidative stress in the body, which would otherwise damage cells and DNA. This benefit underlies all the other ones we’ll cover in more detail below [10, 2, 11, 10].

Essentially, lowering chronically-high oxidative stress may reduce the risk of cancer, inflammation, brain damage, and a range of other health problems.

Glutathione is equally important for the regeneration of other antioxidants your body needs, such as vitamins C and E. It increases your overall antioxidant defense, a task that can never be accomplished just with one substance [1].

2) Lowers Inflammation

Glutathione blocks the production of most inflammatory cytokines. If you suffer from chronic health issues, cytokines are the products of activated immune cells that keep you in a state of constant low-grade inflammation [12].

On one hand, glutathione deficiency caused inflammation in mice. Blocking inflammatory pathways (MAPK and iNOS) restored its levels. This suggests that glutathione and inflammation are in a very tight, mutually-bound relationship. If you suffer from inflammation, solving the underlying cause will be key to raising your levels in the long run [13].

On the other hand, glutathione does block NF-κ, the master controller of inflammation in the body. This protein complex increases the activity of various inflammatory genes and their products [14].

A number of airway and lung diseases are caused by excessive inflammation, while restoring healthy glutathione levels protects from damage [12].

What’s more, people with rheumatoid arthritis may have impaired antioxidant mechanisms and lower glutathione. They have increased levels of an enzyme that uses glutathione to neutralize free radicals (glutathione peroxidase). Its increased levels point to more oxidative stress and a greater demand for glutathione. Accordingly, it makes sense to use supplements and diet to boost your levels [15, 16].

To sum it up, raising your glutathione levels – especially if deficient  will lower inflammation in the body. But it will be equally important to uncover the underlying cause of your inflammation-related issues to truly overcome them. Glutathione is no panacea.

3) Anti-Aging

With less glutathione, free radicals can harm the body and accelerate the aging process and cognitive decline. Imbalances in glutathione levels also affect the immune system and weaken its ability to fight off invaders. Multiple studies uncovered that the body makes less of this antioxidant as it ages [17, 7, 17].

In women, its levels drop at the beginning of menopause and remain lower after. Increased oxidative stress from low levels in older people can make the bones more fragile and contribute to osteoporosis [18, 19].

Cells depleted of glutathione are susceptible to damage (especially from arachidonic acid). Low levels trigger a cascade that ultimately leads to cell injury and death, which accelerates aging [20].

Interestingly, myricitrin, an antioxidant compound from southern wax myrtle used in preventing age-related osteoporosis may work by increasing glutathione [19].

For all these reasons, replenishing glutathione levels may slow the aging process, strengthen the bones, and prevent age-related cognitive decline [21].

4) Mental health

Preventing Anxiety, Depression & Stress

Research uncovered that people with depression have low glutathione levels [22, 23].

Accordingly, glutathione prevented depression in animals under stress. What’s more, anti-anxiety drugs may work, in part, by raising its levels. For example, the anti-anxiety medication alprazolam (Xanax) increased glutathione in mice [24, 25].

All in all, since some people with anxiety, depression, and poor stress resilience have low glutathione, restoring normal levels may help balance the stress response and calm the mind.

OCD and Schizophrenia

The importance of glutathione for mental health goes beyond anxiety and depression. It also touches upon other mental disorders, such as schizophrenia, bipolar disorder, and OCD.

For one, people with schizophrenia have low glutathione levels. NAC, which increases glutathione levels in the brain, improved symptoms of schizophrenia in clinical studies [26].

On the other hand, people with OCD may have low levels in certain parts of their brain and high blood levels of free radicals. In turn, boosting glutathione may improve antioxidant defense, stress resilience, and overall symptom severity [27, 22, 25].

Since multiple drugs used to treat bipolar disorder work by increasing glutathione levels, it’s possible that naturally boosting it may also help stabilize mood and symptoms [28].

5) Autism & ADHD

Children diagnosed with autism have about 20 – 40% lower than normal levels of glutathione. They also have lower cysteine levels and other abnormalities in making and restoring the active form of glutathione (transsulfuration pathway) [29, 30, 31. 1].

Oral and transdermal glutathione are being developed to restore levels in autistic children. This approach may target the malfunctioning metabolic pathways and compensate for their weakness, according to early research [1].

People with ADHD have low glutathione and high oxidative stress levels. Pycnogenol, another natural glutathione booster, normalized glutathione and overall antioxidant levels in children with ADHD [32, 32, 33].

Until additional come out, you should be cautious with glutathione supplements for children with autism or ADHD. The bioavailability of most commercially-available products is problematic, and some have not been tested in children. NAC, pycnogenol, cysteine-rich and sulfur-containing foods are a safer option for raising glutathione levels in children.

6) Protecting the Brain

The brain is an extremely demanding, high-energy organ. It consumes about 20% of the oxygen in the whole body, although it takes only about 2% of the body weight.

Reactive oxygen species are continuously generated while the brain burns fuel for energy (this is referred to as oxidative metabolism). The brain needs to detox them to stay healthy, and glutathione plays a key role in making this possible [34].

Alzheimer’s Disease

Alzheimer’s disease is, in part, caused by oxidative stress. Antioxidants can neutralize it and may prevent or slow the disease. Several clinical studies showed that oral vitamin E (a powerful antioxidant) slowed the progression of Alzheimer’s [35].

To make matters worse, Alzheimer’s is characterized by an accumulation of a DNA-binding protein (TDP-43) in the nervous system. Its buildup further lowers glutathione levels, putting Alzheimer’s patients at a very increased risk of deficiency [36].

In mice with Alzheimer’s, increasing glutathione could boost memory, reduce plaque buildup, improving overall symptoms [35].

Parkinson’s Disease

Glutathione may help combat the oxidative stress that damages dopamine neurons in Parkinson’s disease. In the very early stages, people with Parkinson’s have low glutathione levels in the region of the brain where this damage occurs (substantia nigra). Boosting brain glutathione may be an early measure to prevent it before symptoms arise [37].

Diverse therapeutic strategies for combating Parkinson’s may work by increasing brain glutathione. In one study, a drug (3,4-dihydroxy benzalacetone) prevented Parkinson’s disease by increasing levels of glutathione [38].

Huntington’s Disease

The culprits of Huntington’s disease are oxidative stress and mitochondrial dysfunction. Boosting antioxidant defense and supporting the mitochondria may be key. In fact, some natural anti-inflammatories target both: curcumin in nanoparticles improved mitochondrial health by increasing glutathione levels in rats with Huntington’s disease [39, 39].

Supplement Considerations for Brain Health

If you have a brain disorder or poor cognitive function, it’s crucial to supply the brain with enough of the building blocks it needs to make glutathione and other antioxidants. If supplementing, you need to go for glutathione-boosting products with superior bioavailability that can cross the blood-brain barrier.

7) Fighting Infections

Viral infections flood the body and cells with oxidative stress, due to inflammation and using up more glutathione [40, 40].

In many diseases – from AIDS and tuberculosis to COPD, the flu and alcoholism – poor immunity and an increased risk of infections are linked to low glutathione levels [R, R].

Once glutathione is depleted, immune cells lose their ability to fight infections. NAC, which is used to make glutathione in the body, restored the ability of immune cells to kill the bacteria that cause tuberculosis in cells [41].

In another study, maintaining cysteine levels helped keep glutathione in check. In turn, immune cells regained to power to destroy microbes. The sulfur-rich amino acid cysteine is the most important building block for glutathione, and the one that determines how fast this antioxidant will be produced [42].

NAC, which boosts glutathione, is another option. It may reduce the HIV virus load and inflammation (TNF). Older AIDS patients produce less glutathione, which weakens their already fragile immune systems, muscles, and decreases insulin sensitivity. Increasing glutathione levels may help improve symptoms and reduce the risk of bacterial infections [43, 44, 43, R, R].

8) Gut Health & Healing

People with IBS have decreased activity of the enzymes involved in glutathione synthesis. They also tend to have lower levels of glutathione’s main ingredient, cysteine [45].

The most important enzyme involved in quenching free radicals is called glutathione peroxidase. This enzyme uses glutathione and requires selenium to work with harmful substances. High levels of this enzyme point to more oxidative stress that needs to be neutralized [46, 47].

This enzyme also helps renew the gut wall. It protects the mucus layer that coats the intestines, strengthening the gut lining. In animals, glutathione protected the gut lining, preventing its weakening that can lead to leaky gut [48].

To sum it up, you can take the following steps to enhance your gut health and healing:

  • Increase your intake of cysteine-rich foods, such as high-protein animal sources. You can also go with plant-based foods, but these will more likely trigger a negative reaction if you already have gut problems.
  • Supplement with glutathione or its building blocks (glutamine, glycine, and cysteine)
  • Up your selenium food intake and make sure your selenium blood levels aren’t low

9) Preventing Cancer

Glutathione has a profound impact on the division and survival of cancer cells. Its deficiency leads to increased damage from the oxidative stress involved in the progression of cancer [3, 49].

Researchers uncovered a significant link between increased glutathione intake and a lower risk of oral and throat cancer. Glutathione also may help reduce and repair the damage from cancer drugs. But it’s not that straightforward [6, 50].

Glutathione is generally the good guy. However, malicious cells have learned how to take advantage of it. In this sense, glutathione can be both good and bad when it comes to cancer:

  • The good: it is crucial in the removal and detoxification of carcinogens. Its deficiency may trigger the growth of cancers.
  • The bad: cancerous cells can misuse the benefits it offers. Cancers can increase their glutathione levels, which protects them and increases their resistance to chemotherapy drugs.

As always, perfect balance is imperative. Maintaining healthy glutathione levels will probably aid in prevention more than it will help actually fight cancers once they have developed [51, 52].

10) Heart Health

Low activity of glutathione peroxidase, as well as low levels of systemic and cardiac glutathione, are linked with high oxidative stress and an increased risk of heart attacks [53, 54, 55].

Cardiovascular disease is largely caused by oxidative stress in heart tissues. Perhaps this is why insulin resistance, impaired glucose tolerance, and diabetes (3 conditions that cause oxidative stress), are linked to heart attacks [56, 57].

Glutathione can help in reducing these reactive species and, in turn, limit the risk of stroke or heart attack [58].

11) Diabetes

Type 2 diabetes and high blood sugar lower glutathione in the body. As a result, the buildup of harmful free radicals causes many complications, such as heart problems, brain and nerve damage. Boosting glutathione prevents or limits these issues [40, 40, 40].

12) Kidney Health

Oxidative stress in the kidneys can mild kidney problems, or even full-blown kidney failure, depending on its severity. In rats, the glutathione-booster NAC prevented kidney disease from the artificial sweetener aspartame [59, 59].

In another study of 20 people with chronic kidney disease undergoing hemodialysis, glutathione (IV) improved kidney function and reversed anemia [60].

13) Protecting the Liver

Glutathione keeps the liver healthy by neutralizing the oxidative stress that can lead to liver disease. It plays an important role in detoxing the liver and protecting its sulfur-rich antioxidant pathways [61, 62, 63].

When faced with harmful substances, the liver will make more glutathione to prevent damage. A diet high in saturated fats is one trigger. However, its supplies are limited. Once it runs out, low glutathione will make it more susceptible to injury. Since glutathione reduced liver damage in cells, raising its levels may help prevent more serious liver damage [64].

14) Addictions

Various drugs of abuse (such as cocaine and methamphetamines), as well as alcohol, increase the production of reactive oxygen species. These, in turn, can alter the brain and behavior, or cause damage. Some studies suggest that increasing glutathione will lower their levels and help overcome addictive behaviors, which spans eating disorders aside from alcohol/drug abuse [65, 66, 67].

Increasing antioxidant defense not only protects the brain, but it also helps detox harmful substances from the body. In the early abstinence phase, this would be crucial. Chronic alcohol abuse reduces glutathione in the liver, but raising its levels improved liver function only during abstinence [65, 65].

Chronic 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 [68].

15) Lungs & Airways

Low glutathione levels can increase inflammation in the airways and cause asthma. Often times, environmental toxins will be the underlying trigger of low levels. In mice with asthma, increasing glutathione with NAC lowered the inflammation and symptoms [69, 69].

Chronic Obstructive Pulmonary Disease (COPD) is a lung disease caused by long-term oxidative damage. Although the most common cause is smoking, chemical and fumes can also lead to it. Increasing glutathione lowers oxidative damage in the lungs, which reduced the risk of developing this disease in the first place [70, 71].

16) Sleep Apnea

People with sleep apnea have very high levels of oxidative stress and, consequently, depleted glutathione levels. In one study, people diagnosed with sleep apnea had low glutathione levels, while increasing levels to normal improved sleep quality [72, 73, 72].

17) Skin Health

Acne

Oxidative stress lower glutathione reserves in people with acne. The resulting decline in antioxidative activity may trigger acne, while constantly low antioxidants will worsen skin health. Increasing glutathione levels may reduce your acne by neutralizing oxidative stress and promoting skin regeneration [74, 75, 76].

Skin Lightening

Interestingly, glutathione lightens the skin in healthy women. It reduces the activity of skin cells that make dark pigments (melanin). As such, glutathione may help reduce the visibility of dark skin patches, especially those that appear with aging [77, 78, 77].

18) Eye Health

Glaucoma and cataracts can gradually lead to blindness. Since oxidative stress partially underlies both, boosting glutathione may protect the eyes and enhance eye health. Clinical studies would need to look into this benefit, though [79].

19) Healthy Pregnancy

Low glutathione levels may predispose pregnant women to depression and impair brain development in unborn babies. Increased oxidative stress in the fetus has been linked to preterm labor [80, 81].

Boosting glutathione and antioxidants through sulfur and cysteinerich foods may help maintain a healthy pregnancy. Supplements are not recommended unless prescribed by your doctor.

20) Cystic Fibrosis

People with cystic fibrosis have low glutathione levels throughout the body and high oxidative stress in inflammatory cells. Low levels in the lungs in people with this disease impair breathing and airway damage. More broadly, specialized glutathione formulation (buffered) for inhalation could lower the symptoms of cystic fibrosis [40, 82, 83, 40, 84, 85].

More research about inhaled glutathione is needed, as regular oral supplements may not be potent or bioavailable enough to target people with this disease.

Ways to Increase Glutathione

Glutathione Supplements

Glutathione is made in the body from 3 amino acids: glutamate, cysteine, and glycine. Once produced and used, it is broken down by an enzyme called GGT. This enzyme serves as a sort of border control officer. It stops glutathione on the surface of the cell, breaks it down into pieces, and only lets its important amino acid building blocks – like cysteine – enter the inside [86]

However, if you take a glutathione supplement, it has to pass the liver before it reaches your bloodstream. The liver can contain high amounts of GGT, which will greedily break down glutathione. As a result, most oral forms of glutathione will not achieve the desired effects [87].

There are several ways to bypass this limitation, such as the following forms of glutathione [88]:

  • Liposomal [89]
  • Sublingual (absorbed directly into the bloodstream) [90]
  • Slow-release tablets dissolved in the mouth (orobuccal) or lozenges [91, 92]
  • Inhaled formulations [93]
  • Methyl glutathione, where another compound (the methyl group) is attached so GGT cannot break it down[94]
  • Coated tablets [95]
  • IV injections are also available, but the safety has not been established [96]
  • Taking vitamin C to increase absorption (this still won’t influence liver breakdown much) [97].

New formulations are being researched every day. These include patches, creams, nanoparticles, and other advances products that may maximize its concentration in the body.

Other Supplements

Cysteine

Out of three amino acids that glutathione is made from, cysteine is the most important one; the amount of cysteine governs the speed and quantity of glutathione that can be made inside the cell.

We recommend cysteine in the form of NAC at 500 – 1,000 mg/day

Selenium

Selenium is important for maintaining healthy glutathione levels as it is a component of the enzyme that uses glutathione and neutralizes free radicals (glutathione peroxidase).

Alpha Lipoic Acid (ALA)

R-Lipoic acid is one of the main boosters of glutathione levels in cells [98].

Methionine

S-adenosyl-methionine is a supplement that contains methionine and can also help boost glutathione levels.

A lot of glutathione-boosting supplement brands will contain all 4 of the above. Selenium is not included in some products and you may wish to take an additional supplement if you’re deficient in this nutrient, or simply ensure you get enough selenium from the food you eat.

Food

A number of foods contain the building blocks for glutathione. These can be a great addition to your diet.

  • Garlic, asparagus, and cruciferous vegetables such as broccoli and kale boost glutathione through their sulfur components.
  • Animal food sources, which are higher in cysteine and methionine, can also help increase glutathione levels. These include red meat and poultry, as well as eggs, fish, and dairy. Calcium and riboflavin also increase glutathione, dairy being a source of both [99, 100].

Side Effects & Safety

Taking glutathione supplements during pregnancy or breastfeeding is not recommended.

Glutathione promotes immune system function (enhances T cell growth and activates mTOR), while low levels weaken it [101, 101].

However, glutathione can a two-edged sword if you have chronic inflammation. If you experience side effects, the glutathione-boosting supplements may be over-stimulating your immune system. Always carefully track your response to determine if they are working or not. This often means keeping track of your labs and symptoms, especially if you struggle with unrelenting inflammation that’s hard to pinpoint.

Side effects to 4-week oral glutathione (1g/day) were limited in clinical trials and included the following [102]:

  • Flatulence
  • Loose stools
  • Flushing
  • Weight gain

Side effects to higher doses (up to ~150 mg/kg/day) in people with cystic fibrosis included chest tightness, diarrhea, and fever. These may not apply to the general population and lower doses [103].

More research is needed on high-dose and long-term supplementation.

Buy Glutathione

Take-Away:

Boosting your glutathione levels is a great way to enhance your antioxidant and immune defense. Optimal glutathione levels will help your body detox, support the liver, and protect your brain and heart. However, taking glutathione supplements may not be the best way to go. Only specialized glutathione formulations (liposomal or other) may stop the liver from breaking this antioxidant down before it even reaches your bloodstream.
Other good ways to boost your glutathione levels include:

  • NAC (cysteine), alpha lipoic acid, and methionine supplements
  • Sulphur-rich foods
  • Selenium-containing foods or supplements
  • Curcumin and Pycnogenol
  • Avoiding stress and toxins that deplete glutathione in the body

 

About the Author

Ana Aleksic - MS (PHARMACY) - Writer at Selfhacked

Ana Aleksic, MSc (Pharmacy)

MS (PHARMACY)

Ana received her MS in Pharmacy from the University of Belgrade.

Ana has many years of experience in clinical research and health advising. She loves communicating science and empowering people to achieve their optimal health. Ana spent years working with patients who suffer from various mental health issues and chronic health problems. She is a strong advocate of integrating scientific knowledge and holistic medicine.

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