Glutathione, often referred to as “the mother of all antioxidants,” is one of the most talked-about supplements in the healthcare industry. It has a range of purported benefits that include enhancing heart, liver, and brain health. Read on to learn about the science behind glutathione and how to naturally increase it for optimal health.
What is Glutathione?
Why do Some Call it “the Master Antioxidant?”
Glutathione (GSH) is your body’s strongest antioxidant. It has an enormous capacity to combat oxidative stress and neutralize harmful free radicals. Chemically speaking, glutathione is a tripeptide made up of 3 amino acids [1]:
- Glutamic acid
- Cysteine
- Glycine
The body uses glutamic acid to make glutamine [2, 3].
When these three amino acids are combined into glutathione, they gain the power to detox dangerous free radicals, toxic drugs, and heavy metals. This mechanism protects your entire body from dysfunction and disease [1, 4, 5].
At first glance, glutathione is similar to other well-known antioxidants such as vitamin C and vitamin E. What’s remarkable is that unlike most antioxidants – think resveratrol and quercetin – your body can make its own glutathione. It just needs the right building blocks.
In fact, your body needs to make glutathione in order for you to live a healthy life. Scientists have even suggested its levels as a great predictor of one’s lifespan [6, 7].
Glutathione deficiency increases susceptibility to oxidative stress, which may be the underlying cause of many diseases including cancer, heart disease, Parkinson’s, and Alzheimer’s [8].
Snapshot
Proponents:
- Great antioxidant
- Enhances detox
- Supports the liver
- May help with diabetes
- Supports the brain, gut, kidneys, and lungs
Skeptics:
- Unpleasant taste
- Poor absorption and bioavailability
- May disturb digestion
- Insufficient evidence for medical use of supplements
- Incomplete safety profile and possible unknown side effects
Functions & Benefits of Glutathione
Glutathione is a broadly beneficial compound that the human body makes on its own. It is available as a supplement, but supplemental glutathione has poor bioavailability, meaning that not a lot of it is absorbed from the gut to the bloodstream. Plus, the FDA has not approved glutathione supplements for any medical purpose.
Thus, this section focuses primarily on the benefits of healthy glutathione levels in the body, not on the effects of taking it as a supplement.
1) Fights Oxidative Stress
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 [4, 9, 10].
Essentially, oxidative stress is associated with 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 vitamin C and vitamin E. It increases your overall antioxidant defense, a task that can never be accomplished just with one substance [1].
2) Lowers Inflammation
Glutathione (GSH) blocks the production of most inflammatory cytokines. If you suffer from chronic health issues, cytokines may keep you in a state of constant low-grade inflammation [11].
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, mutual relationship [12].
On the other hand, glutathione blocks NF-κ, the master controller of inflammation in the body. This protein complex increases the activity of various inflammatory genes and their products [13].
A number of airway and lung diseases are caused by excessive inflammation, and they can benefit from restoring healthy glutathione levels [11].
3) Anti-Aging
With less glutathione, free radicals may harm the body and accelerate the aging process and cognitive decline. Multiple studies uncovered that the body makes less of this antioxidant as it ages [8, 14].
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 [15, 16].
Cells depleted of glutathione are susceptible to damage. Low levels trigger a cascade that ultimately leads to cell injury and death, which accelerates aging [17].
4) Mental Health
Anxiety, Depression & Stress
Research uncovered that people with depression have low glutathione levels [18, 19].
Accordingly, glutathione prevented depression in animals under stress. What’s more, anti-anxiety drugs may work, in part, by raising its levels [20, 21].
OCD and Schizophrenia
People with schizophrenia have low glutathione levels. NAC, which increases glutathione levels in the brain, improved symptoms of schizophrenia in clinical studies [22].
People with OCD may have low GSH levels in certain parts of their brain and high blood levels of free radicals. Boosting glutathione may improve antioxidant defense, stress resilience, and overall symptom severity [23, 18, 21].
Since multiple drugs used to treat bipolar disorder work by increasing glutathione levels, naturally boosting it may also help stabilize mood and symptoms [24].
5) Autism & ADHD
Children diagnosed with autism have about 20-40% lower levels of glutathione than their non-autistic peers. They have different abnormalities in making and restoring the active form of glutathione [25, 26, 27, 1].
Oral and transdermal glutathione are being developed to restore levels in autistic children [1].
People with ADHD have low glutathione and high oxidative stress levels. Pycnogenol, another natural GSH booster, normalized glutathione and overall antioxidant levels in children with ADHD [28, 29].
Until additional studies 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 may be safer options for raising glutathione levels in children. Remember to talk to your doctor before adding any new supplements to your own regimen, let alone a child’s.
6) Protecting the Brain
Reactive oxygen species are continuously generated while the brain burns fuel for energy. The brain needs to detox them to stay healthy, and glutathione plays a key role in making this possible [30].
Alzheimer’s Disease
Alzheimer’s disease is, in part, caused by oxidative stress. Antioxidants may prevent or slow the disease. Several clinical studies showed that oral vitamin E (a powerful antioxidant) slowed the progression of Alzheimer’s [31].
The buildup of toxic proteins in Alzheimer’s further lowers GSH levels, making the patients more likely to be deficient [32].
In mice with Alzheimer’s, increasing glutathione could boost memory, reduce plaque buildup, and improve overall symptoms [31].
Parkinson’s Disease
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 boosting GSH may be an early measure to prevent this disease [33].
In one study, a drug (3,4-dihydroxy-benzalacetone) prevented Parkinson’s disease by increasing levels of glutathione [34].
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 you decide to supplement, you need to go for glutathione-boosting products with superior bioavailability that can cross the blood-brain barrier. Remember to talk to your doctor before adding supplements of any kind, including glutathione, to your daily routine.
7) Fighting Infections
Viral infections flood the body with oxidative stress due to inflammation, using up more glutathione [35].
In many chronic diseases, poor immunity and an increased rate of infections are linked to low GSH levels [11].
Once glutathione is depleted, immune cells lose their ability to fight infections. NAC, which boosts glutathione in the body, restored the ability of immune cells to kill the bacteria that cause tuberculosis [36].
In another study, maintaining cysteine levels helped keep glutathione in check. In turn, immune cells regained the power to destroy microbes [37].
Older AIDS patients produce less GSH, which weakens their already fragile immune systems and decreases insulin sensitivity. Increasing glutathione levels may help improve symptoms and reduce the incidence of bacterial infections [38, 39, 40].
8) Gut Health
People with IBD have decreased activity of the enzymes involved in glutathione synthesis. They also tend to have lower levels of its main ingredient, cysteine [41].
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 [42, 43].
This enzyme also helps renew and strengthen the gut lining. In animals, glutathione protected the gut lining, which may help prevent leaky gut [44].
9) Heart Health
Low activity of glutathione peroxidase and low levels of glutathione are linked with high oxidative stress and an increased likelihood of heart attack [45, 46, 47].
Cardiovascular disease is largely caused by oxidative stress in heart tissues. Glutathione can reduce free radicals and, in turn, may prevent stroke or heart attack [48, 49, 50].
10) 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 may prevent or limits these issues [35].
11) Kidney Health
Oxidative stress in the kidneys can cause mild kidney problems or even full-blown kidney failure, depending on its severity. In a study of 20 people with chronic kidney disease on hemodialysis, glutathione improved kidney function and reversed anemia [51].
In rats, the glutathione-booster NAC prevented kidney disease from the artificial sweetener aspartame [52].
12) 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 [53, 54, 55].
When faced with harmful substances, the liver will make more glutathione to prevent damage [56].
13) 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 can help overcome addictive behaviors, which span from eating disorders to alcohol/drug abuse [57, 58, 59].
Increasing antioxidant defense not only protects the brain, but it also helps detox harmful substances from the body. Chronic alcohol abuse reduces glutathione in the liver. Raising the GSH levels improved liver function during abstinence [57].
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 [60].
14) Lungs & Airways
Low glutathione levels can increase inflammation in the airways and cause asthma. In mice with asthma, increasing glutathione with NAC lowered inflammation and improved the symptoms [61].
Chronic Obstructive Pulmonary Disease (COPD) is a lung disease caused by long-term oxidative damage. Increasing glutathione lowers free-radical damage in the lungs, which reduced the likelihood of developing COPD [62, 63].
15) Sleep Apnea
People with sleep apnea have high levels of oxidative stress and, consequently, depleted GSH levels. In one study, increasing the levels to normal improved their sleep quality [64, 65].
16) Skin Health
Acne
Oxidative stress lowers glutathione in people with acne. Increasing glutathione levels may clean your acne by neutralizing oxidative stress and promoting skin regeneration [66, 67, 68].
Spots & Aging
Glutathione lightens the skin in healthy women. It reduces the activity of skin cells that make dark pigments (melanin). As such, glutathione may help even out the appearance of dark skin patches that appear with aging [69, 70].
17) Eye Health
Glaucoma and cataracts can gradually lead to blindness. Since oxidative stress underlies both, boosting glutathione may protect the eyes. Clinical studies would need to look into this benefit, though [71].
18) Healthy Pregnancy
Low glutathione levels may predispose pregnant women to depression and impair fetal brain development. Increased oxidative stress in the fetus has been linked to preterm labor [72, 73].
Boosting glutathione and antioxidants through sulfur- and cysteine-rich foods may help maintain a healthy pregnancy. Supplements are not recommended unless prescribed by your doctor.
19) Cystic Fibrosis
People with cystic fibrosis have low glutathione levels and high oxidative stress. Low GSH levels in the lungs impair breathing and trigger airway damage. Glutathione inhalation may improve the symptoms of cystic fibrosis [35, 74, 75, 76, 77].
Ways to Increase Glutathione
GSH 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 gamma-glutamyl transferase, GGT.
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 break down GSH. As a result, most oral forms of glutathione will not achieve the desired effects [78].
There are several ways and supplement forms to bypass this limitation [79]:
- Liposomal [80]
- Sublingual (absorbed directly into the bloodstream) [81]
- Slow-release tablets dissolved in the mouth or lozenges [82, 83]
- Inhaled formulations [84]
- Methyl glutathione (GGT cannot break it down) [85]
- Coated tablets [86]
- IV injections (the safety has not been established!) [87]
New formulations are being researched every day. These include patches, creams, nanoparticles, and other advanced products that may maximize its concentration in the body.
Other Supplements
Cysteine
Out of three amino acids that make glutathione, cysteine is the most important one; the amount of cysteine governs the speed and quantity of produced GSH. Supplemental cysteine is available as L-cysteine and N-acetylcysteine (NAC).
Selenium
Selenium is important for maintaining healthy glutathione levels as it supports the enzyme that uses GSH to neutralize free radicals: glutathione peroxidase.
Alpha Lipoic Acid (ALA)
R-Lipoic acid is one of the main boosters of glutathione levels [88].
Methionine
S-adenosyl-methionine (SAM-e) is a supplement that contains methionine and can also help boost glutathione levels.
A lot of glutathione-boosting supplements will contain all 4 of the above. Selenium is not included in some products and you may wish to take an additional supplement or ensure you get enough from the food you eat (read: Brazil nuts).
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 boost glutathione through their sulfur components.
- Animal food sources, which are higher in cysteine and methionine, can also help increase glutathione levels. Calcium and riboflavin also increase glutathione, dairy being a source of both [89, 90].
Glutathione Side Effects & Safety
Taking GSH supplements during pregnancy or breastfeeding is not recommended.
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 of 4-week oral glutathione (1 g/day) in clinical trials included [91]:
- Flatulence
- Loose stools
- Flushing
- Weight gain
Side effects of higher doses (up to around 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 [92].
Takeaway
Boosting your glutathione levels is a great way to enhance your antioxidant and immune defense.
Glutathione will help your body detox and protect your liver, brain, and heart. However, taking glutathione supplements may not be the best way to go.
Only specialized liposomal and sublingual formulations may reach your bloodstream. Oral supplements don’t work as the liver breaks them down before they can have an effect.
To boost your glutathione levels, get enough of its building blocks: NAC (cysteine), alpha-lipoic acid, and SAM-e (methionine). Eat more sulfur-rich foods like garlic and cruciferous vegetables and make sure you get enough selenium. Additionally, aim to de-stress and avoid toxins that deplete your glutathione levels.
