Glutathione: The "Master" Antioxidant

By Bogdan Popa, M.D.

TABLE OF CONTENTS

1. Intro
2. What Is Glutathione?
3. Glutathione’s Role in the Body
4. Depletion and Disease
5. Glutathione-Rich Diet
6. Glutathione Supplementation
7. Best Practices to Boost Glutathione
8. References

It seems everyone today is touting the latest and greatest to cure all of our health woes. Take this to turn back the hands of time, that for more energy, those to remove those unwanted pounds or erase wrinkles, and these to help us remember where the heck we put the car keys.

Wouldn’t be great if there really was some “magic elixir” you could take to improve all of these areas of health and more? And wouldn’t it be even better if there were no side effects from this pill?

Wishful thinking, right? Maybe not. Maybe such a thing exists right in your body, right now.

Obviously it’s not a “magic elixir” that we will be talking about. It is a natural and indispensable molecule. It’s called glutathione, and it is found in every cell in the body. In fact, there is virtually no organism on Earth that doesn’t have some glutathione in its cells.1

And for good reason. This powerful antioxidant is one of most protective molecules in the human body. Without adequate levels of glutathione, you are at risk some of the most feared health conditions facing us today, including stroke, Alzheimer’s disease, and heart disease.

But when levels are adequate or high, that’s when the magic happens. You’ll not only have protection from the conditions above, but you’ll have amazing energy, glowing skin, healthy detoxification, strong heart and brain function, and possibly even a longer life!

Sound too good to be true? Keep reading to learn about the evidence…

What Is GlutaTHIONE?

Glutathione is a tripeptide—i.e. a very small protein—composed of three amino acids: cysteine, glycine, and glutamic acid (or glutamate). Often called the “master” antioxidant, glutathione boosts the utilization and recycling of other antioxidants, namely vitamins C and E, as well as alpha lipoic acid and CoQ10.1

There are two different forms of glutathione: reduced glutathione (GSH, or L-glutathione), which is the active form, and oxidized glutathione (GSSG), the inactive form. As GSH patrols the cellular environment and puts out oxidative “free radical” fires, it becomes oxidized itself and inactive, thus turning into GSSG.

Fortunately, inactive GSSG can be recycled back into the active GSH form, thanks to an enzyme called glutathione reductase. When this enzyme is overwhelmed and too much oxidized GSSG accumulates (as compared to the active GSH), your cells become susceptible to damage.

MITOCHONDRIAL PROTECTION

Mitochondria are the “power plants” of each cell, converting food into ATP (adenosine triphosphate) to use for all of our cells’ energy needs. To compare it to the human body, mitochondria are like the heart, constantly pumping out ATP instead of blood. Without a heartbeat—and without mitochondria—life ceases to exist.

But mitochondria do much more then pump out energy. They also have their own DNA, they can communicate information, sense danger when the cell energy levels drop, and are even involved in sending the final "death" message (apoptosis) when a cell is damaged beyond repair and needs to die. In this way, the mitochondria are the heart AND soul of the body.

Obviously, this sophisticated heart and soul needs to be protected, and the “knight in shinning armor” who guards our source of energy and life is none other than glutathione.

In this role, glutathione makes sure that toxins like heavy metals, organic toxins, and even the actual byproducts of the process of making energy by the mitochondria themselves (oxidative byproducts or free radicals) don’t damage the mitochondria. For example, in the final stage of energy production, your body uses oxygen to make ATP but in the process it can create Superoxide, an oxygen with too many electrons that is poisonous to everything around it be it mitochondria, DNA, proteins, cell membranes, etc.. Glutathione is there to extinguish and neutralize Superoxides as well as other similar damaging oxidative molecules.

GLUTATHIONE RECYCLING

As you can imagine, it takes a lot of energy (ATP) to make glutathione or recycle from inactive GSSG back to active GSH.2 Fortunately, our cells contain large amounts of glutathione. In fact, they contain as much glutathione as glucose, potassium, and cholesterol! Given that we can’t survive without these other substances, the fact that we have so much glutathione around tells us that it is just as important.2,3

GLUTATHIONE's Role IN THE BODY

Glutathione has many key roles in your health and well-being.4 Four of the most critical are:

• Aging defense
• Antioxidant protection
• Detoxification
• Energy production

Glutathione is also responsible for:

• Cysteine carrier/storage
• Cell signaling
• Enzyme function
• Gene expression
• Cell differentiation/proliferation

That’s a lot of detailed medical and biochemical jargon that means, in short, the antioxidant properties of glutathione work to improve communication between the cells, stabilize, and reduce oxidation in the cells, fight free radical damage, support protein function, and take out the cellular trash.

Let’s take a few of these in more detail.

Aging Defense

People who live to into their 80s and beyond are found to have higher levels of glutathione. Low levels of glutathione send messages to trigger apoptosis, or cell death.5 Plus, given the critical role glutathione plays at the cellular and mitochondrial levels, the overall health and longevity benefits are vast and wide.

Long story short, the more glutathione in your body, the healthier your cells and mitochondria. The less glutathione in your body, the more likely you are to have cellular breakdown, increased risk of disease, and cellular death.

Antioxidant Protection

If you’ve ever made a fruit salad, then you likely know the chef’s trick to sprinkling a little lemon or lime juice over the fruit to keep it from turning brown. In many ways, antioxidants are like that lemon juice. By consistently “sprinkling” your body with antioxidants, you can prevent your body from “browning.”

Antioxidants are the “anti-agers” of the nutrient world, working to protect your body from free radical, or “oxidative” damage. Every time you eat, breathe, or move, your body uses fuel created from the food you eat to produce energy. But just as a car using gas to produce energy releases harmful byproducts of this process as exhaust, so too does your own body’s energy-producing efforts produce a dangerous byproduct—free radicals.

Free radicals are highly reactive forms of oxygen that are missing an electron. When they come into contact with normal molecules, they try to steal an electron, damaging the healthy cell and its DNA. In fact, some estimates show that every cell in your body takes 10,000 oxidative hits to its DNA daily! Antioxidants work to counteract the damage caused by free radicals.

Glutathione is your body’s “master antioxidant,” directly binding to oxidative compounds that damage cell’s membranes, DNA, energy production, etc. It directly neutralizes a wide range of oxidants, including superoxide, nitric oxide, carbon radicals, hydroperoxides, peroxynitrites, and lipid peroxides.6

Detoxification

All across America, people have one day designated as trash removal day. They collect garbage, waste, and recycling that has accumulated throughout the week, put it into specially designated bins, and place it on the curb for pick up and removal.

But did you know your body has the exact same process of waste collection and even recycling? It’s called your detoxification system.

Here’s how it works.

Detoxification has three phases. During Phase 1 detoxification, toxins from car exhaust, smoke, alcohol, caffeine, dioxin, drugs, radiation, heavy metals, pesticides, and other carcinogens are partially processed by specialized proteins inside mitochondria called cytochromes.

Unfortunately, Phase 1 processing can turn partially processed toxins into even more dangerous free radicals. These are not only damaging, but they can single handedly deplete glutathione, creating an imbalance between Phase 1 and Phase 2 (see below) activity.7 Toxic reactions can occur due to buildup of reactive intermediate forms resulting from phase 1 detoxification, so further work needs to be done to process and eliminate toxins.

In Phase 2 detoxification, various enzymes act directly on the toxic substances partially degraded and processed in Phase 1, such as heavy metals and organo-toxins, by binding them with protective compounds, thereby either inactivating the toxins. This binding is called “conjugation” and glutathione is the central figure. One such specialized group of enzymes called Glutathione-S-Transferase (GST) attach glutathione to the byproducts of Phase 1 detoxification and neutralizes their toxic potential while simultaneously making these toxic substances more water-soluble and ready to be eliminated. There are other Phase 2 enzymes and proteins that perform similar functions, but without glutathione, these other enzymes couldn’t adequately function.6

Once conjugated, toxins are ready to be eliminated from your body mainly by the kidneys (urine) and liver (bile). Elimination is considered to be Phase 3 of detoxification.

Energy Production

As we have already discussed, energy production is located in all cells (except red blood cells) inside mitochondria. Glutathione is involved in protecting mitochondria from free radical or other “oxidative” damage. If mitochondria are attacked and damaged by oxidative molecules they slow down and start to make less ATP. With less ATP the rest of the cell also becomes sluggish.

To make things worse, damaged mitochondria also become more error prone and start to create more “exhaust” or free radicals. In turn these free radicals cause further mitochondrial damage and so create a vicious cycle of less energy and more damage.

Stress also comes into play in energy production. The higher the energy needs (higher metabolism, exercise, stress, etc.), the harder the mitochondria have to work and the more free radicals they produce.

As we mentioned in the beginning of this article, GSH binds these free radicals and relieves “oxidative stress” not just on the mitochondria but on the rest of the cell. In doing so, GSH becomes oxidized and converts to GSSG. With the help of the enzyme glutathione reductase, it can be recycled and turned back into active glutathione or GSH. However, if this process is overwhelmed or it doesn’t work properly, GSSG accumulates and the ratio of GSH/GSSG becomes distorted.

The ratio of GSH/GSSG can actually be measured and is a very dependable measure of “oxidative stress” or how fast we are aging and deteriorating. This means we can actually measure how susceptible our cell’s DNA, cell membranes, proteins, and cholesterol are to damage.

Healthy cells at rest have a GSH/GSSG ratio >100. However, that ratio drops to 10 or less in susceptible cells exposed to oxidative stress.

How does a low GSH/GSSG manifest? It can be fatigue, lack of mental focus, brain fog, muscle fatigue, and aches and pains.

Sound familiar?

These symptoms are not only associated with many chronic diseases, but are also a result of “mitochondrial dysfunction,” which occurs when mitochondria lose the protection of GSH, free radicals attack the mitochondria, and cellular energy decreases.8 In fact, autoimmune conditions like multiple sclerosis, Crohn’s disease, rheumatoid arthritis, diabetes, Lyme disease, heavy metal load, organotoxins, and more all have “mitochondrial dysfunction,” low levels of GSH, and profound fatigue.

Restoring active glutathione (GSH) levels and the ratio of active reduce to inactive “oxidized” GSH/GSSG can correct some, if not all, of the energy depletion.

And speaking of depletion…

Depletion and Disease

Glutathione deficiency makes you vulnerable to oxidative stress and inflammation, both of which are markers of accelerated aging and chronic illness. If you have too little GSH, then you can’t fight off damage to your cell’s mitochondria. As a result, you start to feel more tired because the mitochondria are less efficient when they get oxidized or “rusted.”

The free radical damage caused by oxidation then triggers your immune system to clean up the damage, which results in inflammation.

As such, it’s no surprise that depleted levels of glutathione can increase your risk for a number of adverse health conditions, including heart disease and diabetes, among others.

This is made even more problematic, given the number of factors that can deplete glutathione levels. In addition to natural aging, environmental causes include:

• Chronic exposure to chemical toxins
• Cadmium exposure
• Alcohol use
• Smoking
• Pollution
• Poor diet (Standard American Diet (SAD))
• Stress
• Certain medications (Tylenol)
• UV radiation exposure

Certain illnesses are known to decrease glutathione levels. Some of the more common low glutathione-related disease are:9,10,11

• AIDS/HIV
• Macular degeneration
• Parkinson’s disease
• Diabetes
• Hepatitis
• Cancer
• COPD
• Alzheimer’s disease
• Liver disease
• Sickle cell anemia
• Stroke
• Heart disease
• Infertility

Brain Health

As we age, it’s not uncommon to experience a bit of forgetfulness, or maybe have difficulty concentrating or remembering names or where we left our car keys. This is technically called “neuro-degeneration,” a process by which the neurons in our brains become damaged and may even die, leaving us with “shrinking” brains that don’t function to their full capacity. While this process is unavoidable as we age, it can be slowed, or even reversed, and glutathione (GSH) plays an important role.

There are certain brain disorders that have accelerated neuro-degeneration that give us clues. For example, Parkinson’s and Alzheimer’s diseases have high levels of oxidative stress and damage to the brain with correspondingly low active glutathione (GSH) levels. GSH can help ease and decrease the rate of damage to neural tissue. Other neurologic illness like Lyme disease also greatly benefits from improved levels of glutathione.12

While these results are promising, a 2017 study involving Alzheimer’s patients using intranasal GSH found that GSH and placebo had equally good results.13 The study was ultimately inconclusive as a result, but it did show some improvement did occur with glutathione.

Heart and Cardiovascular System

Heart attack is the number one cause of death in the United States. It is also one of the top fears of Americans, prompting national campaigns regarding heart health and early detection of risk factors.

But what is missing in all this is a discussion of glutathione and the role it plays in preventing heart attack and stroke thanks to it’s ability to neutralize the “lipid oxidation” process.

This is important because virtually all heart disease starts with accumulation of arterial plaques, or deposits, inside the arteries’ walls. Coronary and arterial plaque (atherosclerosis) develop gradually as cholesterol particles such as LDL in the blood are “lipid oxidized” and damage the lining of the blood vessels, forming a plaque. When these plaques eventually rupture and break off, they cause clogs that block blood flow and cause heart attacks or strokes.

With the help of an enzyme called glutathione peroxidase, glutathione inactivates the superoxide, free radicals, hydrogen peroxide, lipid peroxides, and peroxinitrites that cause this “lipid oxidation” and wreak havoc on your health. In this way, glutathione helps to prevent damage and lowers the risk of heart attacks.

In a study of 643 cardiac patients who underwent coronary angiography in Germany, those who died of heart attacks had much lower levels of glutathione peroxidase than those who survived.14 In the end, what this means is that if we don’t have enough glutathione to neutralize damage to our arteries, we are at increased risk of heart and vascular disease events.

Inflammation

Inflammation has been a hot topic in the natural health world for the past decade; however, many people still don’t fully understand exactly why inflammation lies at the root of most of the health concerns plaguing Americans today.

Inflammation is present in virtually every chronic illness, from diabetes and heart disease to cancer. However inflammation is also necessary (in short bursts) to fight things like infectious invaders.

Any injury can incite an inflammatory response. Whether you are talking about trauma, an infection, toxins, or allergies, your immune system answers with the same chemical cascade.

First, the blood vessels and capillaries in the injured area begin to expand and open wide to allow your body’s natural healing compounds to get the injured site as quickly as possible. Soon, fluid and waste flood the area, often overwhelming it.

To offset the damage, helper cells seal off the damaged area by creating blockades of protein that help prevent the spread of bacteria and toxins to the surrounding areas. This blockage of the blood and lymph vessels is what causes the physical manifestations of inflammation, namely redness, pain, stiffness and lack of mobility, and swelling.

Like everything in your body, there is a set of built-in checks and balances when it comes to inflammation. When an injury is detected your body produces an enzyme called cyclooxygenase-2 (or COX-2), which sets this inflammation process into motion.

In turn, COX-2 signals for the production of a short-lived signaling molecules called series-2 prostaglandins. These pro-inflammatory hormones encourage this inflammation process and help your body heal the injured area.

Once your body has done its job, it then needs to restore your body back to normal and switch off these hormones. To do that, it releases COX-1 enzymes that signal for the release of series-1 and series-3 prostaglandins, which are anti-inflammatory.

In an ideal world, this yin and yang work together beautifully. The inflammatory response comes to your rescue when it’s needed and cools itself off once the healing is completed. But we don’t live in an ideal world.

In the real world, environmental toxins, your diet, stress, and other lifestyle issues have disabled the checks and balances of this system, encouraging your body to make more of the pro-inflammatory prostaglandins and less of the anti-inflammatory ones. As a result, many people suffer from chronic, systemic inflammation.

When this happens, you’re in trouble. You need a lot of extra protection.

It appears that glutathione (GSH) controls when inflammation increases or decreases as need be by instructing and influencing our immune white cells. Additionally, autoimmune disease also appears to be hallmarked by imbalanced glutathione levels.15

Rebalancing glutathione levels can restore immune system competence and bring chronic inflammation under better control.

Immunity

Glutathione helps your immune systems stay strong and ready to fight infections. While vitamin C seems to get all the accolades when it comes to immunity, glutathione is the under-recognized supporting actor who deserves the starring role.

Research shows that active glutathione (GSH) primes white cells such as natural killer (NK) and T cells, your body’s front-line infection fighters. GSH-enhanced T cells are able to produce more infection-fighting substances like interleukins-2 and -12 (IL-2, IL-12) and interferon-gamma, working to control both bacterial and viral infections in this way.16

One study in particular found that GSH doubled NK cells ability to be cytotoxic (kill invaders) after just six months of use.17 It also appears that glutathione actually has a direct antibacterial effect actually as it helps macrophages—a cell of the immune system—fight the bacterium that causes tuberculosis (Mycobacterium tuberculosis).18 In this study, researchers found that “GSH works to modulate the behavior of many cells including the cells of the immune system, augmenting the innate and the adaptive immunity as well as conferring protection against microbial, viral and parasitic infections.”18

There are many chronic infections suck as EBV, Hepatitis, Herpes Viruses and Lyme, to name a few, which can deregulate and suppress the immune system. Glutathione can turn this suppression around.

Athletic Performance

It appears that glutathione can boost athletic performance when used before workouts. Best of all, you don’t have to an ultramarathoner or Mr. or Ms. America. Even the average 5Ker, avid gardener, or weekend warrior can benefit from this “secret weapon.”

In a small study of eight men receiving 1,000 mg of glutathione before exercise, those men taking the glutathione performed better, felt less fatigued, and had lower blood lactic acid levels than the placebo controlled group.19 This is key, as increased lactic acid in the body can result in fatigue, low blood pressure, muscle aches, a drop in body temperature, and respiratory problems.

Similarly, in an article published in Muscle and Fitness, glutathione combined with L-citrulline boosted nitric oxide production (NO) better than placebo or L-citrulline alone.20 Nitric oxide is well known to dilate blood vessels improving blood flow and oxygen delivery to muscles and tissues.

Autism

Autism is on the rise in the United States, and a key priority of parents with children on the autism spectrum is improving function. Glutathione has been shown to be very beneficial in treating the autistic child.

In fact, one warning sign we see in children with autism is low levels of glutathione. Fortunately, promising new research shows that liposomal and transdermal glutathione might help raise levels of GSH in plasma in children with autism.21

Peripheral Vascular Disease

Along with heart disease and stroke, atherosclerosis can also affect arteries supplying blood to the periphery, such as your arms and legs. Peripheral vascular disease (PVD) occurs when narrowed blood vessels do not supply enough blood supply to muscles when needed. Fatigue and pain with walking are hallmark symptoms of PVD.

In a double blind study, 40 PVD patients were given either reduced active glutathione (GSH) IV infusions twice a day or placebo. The patients receiving glutathione were able to walk pain-free much further than the patients receiving placebo injections.22

IV clinics, which offer glutathione injections are not yet mainstream, but they are certainly gaining in popularity. Finding such a clinic and engaging on a course of therapy may be a worthwhile pursuit for those afflicted by severe PVD.

Skin Health

Men and women of all ages are fascinated—even obsessive—when it comes to their skin. Whether they are concerned with acne, wrinkles, dryness, eczema, or puffy eyes, everyone wants beautiful flawless skin.

However, a lifetime of sun, wind, housework, and outdoor activities can take its toll on exposed skin, resulting in dry, wrinkled skin and age spots that can belie a person’s actual age. Combine this with poor nutrition, stress, lack of exercise, and hormonal changes that occur at midlife and beyond, and it’s no wonder that moisturizers, creams, and anti-aging serums are a billion-dollar market.

Fortunately, you don’t have to empty your wallet to restore the structure and health of your skin and its underlying tissues. You can actually solve problem internally and have cells heal and regenerate themselves, thanks to glutathione.

Glutathione not only decreases the melanin (pigmentation) of skin, but has also been found to decrease the appearance of wrinkles AND increase elasticity of skin.

Glutathione works on the skin pigment production mainly by inhibiting tyrosinase, one of the enzymes involved in the process of making melanin. Interestingly, in one study, both GSH and GSSG worked in achieving the skin lightening effect, which appears to be very gradual and will take weeks to develop.23 The effect on pigmentation is transient, so you need to continue using glutathione to maintain the skin-whitening effect.

A scientific review of four small-scale studies confirmed that glutathione use does result in some skin lightening.24 Additionally, glutathione has also been shown to decrease psoriasis when levels are bolstered by intake of whey protein, which contains glutamylcysteine, a precursor to GSH.25

Most impressively perhaps the same studies mentioned above also show that glutathione doesn’t just lighten, but it improves skin elasticity and decreases the appearance of wrinkles.

Type 2 Diabetes

Type 2 diabetes is common and on the rise in the United States. The debilitating, slow damage created by high levels of blood sugar (glucose) destroys everything from your blood vessels to your eyes, kidneys, and nerves over time due to “oxidative stress” (remember the “free radicals” or reactive oxygen species (ROS)?). As oxidative stress increases, glutathione is used up as an antioxidant and levels of active GSH get depleted.

This has been confirmed to be a fact in Type 2 diabetics. Glutathione levels were found to be very low as a results of the high oxidative stress that can damage tissues especially when blood glucose levels are high. When diabetics were given the glutathione precursors cysteine and glycine, their levels of glutathione went up and their oxidative stress went down, suggesting that GSH supplementation may be very beneficial in preventing type 2 diabetes-related oxidative stress and tissue damage.26

COPD

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States. As damage from smoking or even pollution accumulates to the respiratory tract and the lungs, oxygen and carbon dioxide (CO2) exchange suffers, making it difficult to breathe.

Low glutathione levels have been linked to abnormalities in the lining of the lungs, and having normal glutathione levels may protect from inflammation by protecting lung tissue from free radical damage.27 Additionally, animal studies found that intravenous glutathione supplementation helped maintain normal lung function and prevent damage such as decreased lung compliance, increased swelling, and decreased lung tissue. Researchers concluded that glutathione supplementation helps maintain normal air flow and lung tissue, as well as lessening “the changes in lung mechanics associated with oxygen-induced lung injury.”28

Vitamin D Levels

Vitamin D3—or the active form of vitamin D—has been a hot topic in medicine because it controls and modulates the immune system. Initially thought to play just a role calcium metabolism and bone formation, we now know that low vitamin D3 levels can increase your risk of heart attack, asthma, diabetes, high blood pressure, multiple sclerosis, and decreased brain function in the elderly.

Interestingly, low vitamin D3 levels have also been correlated with low glutathione. In fact, when glutathione levels are low, vitamin D3 doesn’t work as efficiently.

In a study in animals deficient in vitamin D3, supplementing with vitamin D3 and cysteine (a GSH precursor) restored glutathione levels, increased the bioavailability of vitamin D3, and lowered inflammation.29 Researchers noted that the vitamin D supplements widely consumed by the public “are unlikely to be successful unless the GSH status is also corrected.”29 In other words, simply taking vitamin D isn’t enough. You need to be sure you have adequate glutathione levels as well to make sure that your Vitamin D3 is working as it should.

METHYLATION

Methylation is critical for human survival. For example, it as like an electrical switch that turns genes on and off. Additionally methylation is also integral to how we function every second of the day. It regulates neurotransmitters, brain function, mood, energy, and hormone levels. It is fair to say that methylation is almost synonymous to physical function.

One of the most well-studied products of the methylation cycle, homocysteine, is the common link between methylation and the process of making glutathione, also called the “trans-sulfuration” pathway. (See figure below showing the methylation and trans-sulfuration pathways.)

Glutathione production starts with the amino acid cysteine. This first step is also the most important “rate limiting” step. As noted above, the usual source of cysteine comes from homocysteine, a major product of the methylation cycle. So making glutathione depends on a well functioning methylation cycle that provides enough homocysteine.

Conversely, if glutathione production process (or the “trans-sulfuration” pathway) is not functioning properly, the process backs up and homocysteine levels accumulate putting additional strain on the methylation cycle to remove it.

High homocysteine levels are problematic because they have been linked to heart disease and atherosclerosis.32 In people who are deficient or have mutations in the enzymes that catalyze the production of glutathione from homocysteine, the methylation cycle will be under pressure to remove excess homocysteine.

One such enzyme is cystathione beta synthase (CBS), which catalyzes the first and most important (rate limiting) step in trans-sulfuration from homocysteine to cystathione. Individuals with CBS mutations will be slow to make glutathione.33

Flipping this around, individuals who have “slow” methylation cycle enzymes will have lower homocysteine levels. Since it’s the first step in making glutathione, slow methylation can directly affect and lower levels of glutathione.

By now you may have heard of the most famous enzymes—MTHFR and MTR— regulating the speed of the methylation cycle as physicians are now ordering more and more genetic testing. These enzymes control the methylation cycle speed and efficiency, determine homocysteine levels, and indirectly affect glutathione production.

In conclusion, for those of you who have been tested and know you have MTHFR and MTRR or CBS mutations, you might be struggling with low glutathione production and levels without realizing it.

Clearly methylation is a critical process—as well as a complicated one. The key to remember is that low methylation equals low glutathione and that low glutathione slows methylation. They are interdependent. The solution? Maintain normal glutathione levels and all will be good.

Tough stuff, right? But before you run for the hills, take comfort in the fact that there are a few simple steps you can take to restore and replenish your glutathione levels, starting first and foremost with diet.

GLUTATHIONE-RICH DIET

There are a handful of foods that naturally contain glutathione, including asparagus, avocado, cabbage, Brussels sprouts, spinach, broccoli, garlic, chives, tomatoes, cucumber, almonds, and walnuts. However, a variety of factors can affect the levels of this vital nutrient, including storage and cooking. In fact, cooking these foods can reduce their glutathione content by 30 to 60 percent.

Fortunately, you can eat other foods that provide the building blocks needed to boost your glutathione levels naturally. These foods are rich in the precursors to glutathione, namely cysteine and other sulfur-containing foods, as well as selenium.

When looking to boost dietary glutathione, focus on the following:

Whey Protein

GSH is very sulfuric, so you need a protein rich in amino acids like cysteine, glutamate, and glycine. Eating a “clean” grass-fed milk source of whey can make it easier to make GSH. Whey protein contains gamma-glutamylcyteine, which is glutamine bound to cysteine. Because this combination bypasses the first (and rate-limiting) step to make glutathione in your cells, it is key in supporting higher glutathione levels through diet.

Allium-Containing Foods

Allium is a family (genus) of plants rich in sulfur, a precursor for Glutathione synthesis. Allium foods include:

• Garlic
• Onion
• Chives
• Scallions
• Shallots
• Leeks

Cruciferous Foods

Cruciferous vegetables are packed with glucosinolates. These compounds give Brassica plants their distinctive sulfuric aroma. Great cruciferous foods include:

• Broccoli
• Cabbage
• Cauliflower
• Kale
• Brussels sprouts
• Bokchoy
• Arugula
• Collard greens
• Watercress
• Radishes

Alpha Lipoic Acid-Rich Foods

Alpha lipoic acid regenerates and increases levels of glutathione within the body. Good food sources of alpha lipoic acid include:

• Organ meats
• Beef
• Brewer’s yeast
• Broccoli
• Spinach
• Brussels sprouts
• Peas
• Tomatoes

Selenium-Rich Foods

Selenium is a trace mineral that is part of the building blocks that make up antioxidant enzymes. It is also key in the production of glutathione. Good dietary sources of selenium include:

• Seafood
• Oysters
• Brazil nuts
• Eggs
• Mushrooms
• Whole grains
• Organ meats
• Dairy products

DIRECT GLUTATHIONE SUPPLEMENTATION

While diet is the best (and preferred) way to boost glutathione levels, there are a variety of glutathione supplements available. However, you need to know the details and do your homework because glutathione is a finicky molecule and not all forms are absorbable.

For example, glutathione can be taken orally in its plain powder form, but it is destroyed by digestive enzymes in the small intestine, which cleave it to the three amino acids it is made up of—glycine, glutamine, and cysteine. This digestive cleaving process is so effective that nearly all of the plain glutathione you would take by mouth would never make it into circulation.

A better option for oral supplementation is to take liposomal glutathione on an empty stomach. Liposomes are microscopic spheres made of the same natural phospholipids that make up our cell membranes with an active ingredient like glutathione contained and protected in the center of the sphere. Liposomal formulations have been shown to increase GSH levels and absorption.17 To use liposomal glutathione, start with 500 mg and increase to 1,000-2,000 mg per day as needed and tolerated under supervision and advice of a doctor. Be sure to wait 45 minutes to allow for absorption of liposomal glutathione before eating and drinking or taking other supplements.

Glutathione can also be taken as an inhaled form in a nebulizer. However a physician needs to write a prescription for this form, which can then obtained from a compounding pharmacy. Other forms of supplemental glutathione include transdermal, creams, and IV use. The intravenous (IV) form is the most efficient way to deliver glutathione, but is invasive and may also require a prescription and doctor’s supervision of the treatment.

Additionally, you can use targeted nutrients to increase your body’s natural production of glutathione indirectly. These include selenium, alpha lipoic acid, NAC, and SAMe.

Glutathione Supplementation Summary

• Oral powder (recommended)
• Liposomal glutathione formulation (recommended)
• Inhaled GSH with special nebulizer (recommended but need a prescription)
• Transdermal and lotions (variable levels of absorption)
• IV (most effective but also most invasive)
• Boost levels with selenium, ALA, NAC, and/or SAMe (recommended)

Glutathione supplementation has a few rare side effects, including abdominal cramps, bloating, loose stools, gas, and possible allergic reactions such as rash. If you have asthma, avoid using inhaled GSH. Also, check with your doctor before taking glutathione if you are pregnant or breastfeeding.

Practices to Boost Glutathione

Glutathione is the master antioxidant, the knight in shining armor to your cell’s structure, DNA, proteins, lipids, membranes, and most importantly, your mitochondria. It is, quite possibly, the secret to lasting health and longevity. Take care to maintain and even boost your levels every day.

This means eating a glutathione-rich diet, avoiding dietary saboteurs like processed foods and sugar, drinking 64 ounces of water a day, getting 7-8 hours of sleep per night, reducing stress, and exercising at least five days a week. Your body, your mind, and your cells will thank you.


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REFERENCES

1. Pubchem Glutathione https://pubchem.ncbi.nlm.nih.gov/compound/glutathione#section=Top

2. Pizzorno – Glutathione! https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684116/

3. Antioxidants and Redox Signaling https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661824/

4. Impaired Glutathione Synthesis in Neurodegeneration https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821656/

5. Glutathione Peroxidase 1 Activity and Cardiovascular Events in Patients with Coronary Artery Disease https://www.nejm.org/doi/full/10.1056/NEJMoa030535#t=article

6. Antioxidants and Redox Signaling https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661824/

7. Liver Detoxification https://www.biohealthlab.com/patient/resources/popular-topics/liver-detoxification/

8. Glutathione and mitochondria https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079069/

9. Glutathione metabolism and its implications for health. https://academic.oup.com/jn/article/134/3/489/4688681?utm_source=TrendMD&utm_medium=cpc&utm_campaign=J_Nutr_TrendMD_0

10. Unveiling the mechanisms for decreased glutathione in individuals with HIV infection. https://www.ncbi.nlm.nih.gov/pubmed/22242038

11. Andrology: Placebo-controlled, double-blind, cross-over trial of glutathione therapy in male infertility https://academic.oup.com/humrep/article-abstract/8/10/1657/694212

12. The emerging role of glutathione in Alzheimer's disease. https://www.ncbi.nlm.nih.gov/pubmed/24496077

13. Phase IIb Study of Intranasal Glutathione in Parkinson’s Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438472/

14. Glutathione Peroxidase 1 Activity and Cardiovascular Events in Patients with Coronary Artery Disease https://www.nejm.org/doi/full/10.1056/NEJMoa030535#t=article

15. Glutathione a key player in autoimmunity https://www.ncbi.nlm.nih.gov/pubmed/19393193

16. Glutathione and adaptive immune responses https://www.ncbi.nlm.nih.gov/pubmed/22164280

17. Randomized controlled trial of oral glutathione https://www.ncbi.nlm.nih.gov/pubmed/24791752

18. Glutathione and infection. https://www.ncbi.nlm.nih.gov/pubmed/23089304

19. Glutathione supplementation suppresses muscle fatigue induced by prolonged exercise via improved aerobic metabolism https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4328900/

20. Muscle and Fitness; The science behind Setria https://setriaglutathione.com/uploads/pdf/Setria-Science-on-Muscle-and-Fitness.pdf

21. A clinical trial of glutathione supplementation in autism spectrum disorders. https://www.ncbi.nlm.nih.gov/pubmed/22129897

22. Effect of Glutathione Infusion on Leg Arterial Circulation, Cutaneous Microcirculation, and Pain-Free Walking Distance in Patients With Peripheral Obstructive Arterial Disease: A Randomized, Double-Blind, Placebo-Controlled Trial https://www.mayoclinicproceedings.org/article/S0025-6196(11)62019-3/abstract

23. Glutathione and it’s anti-aging and antimelanocitic effects https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413479/

24. Glutathione for skin lightening: a regnant myth or evidence-based verity? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808366/

25. Psoriasis Improvement in Patients Using Glutathione-enhancing, Nondenatured Whey Protein Isolate: A Pilot Study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3805302/

26. Glutathione Synthesis Is Diminished in Patients With Uncontrolled Diabetes and Restored by Dietary Supplementation With Cysteine and Glycine http://care.diabetesjournals.org/content/34/1/162

27. Significance of glutathione in lung disease and implications for therapy. https://www.ncbi.nlm.nih.gov/pubmed/8141138

28. Glutathione supplements protect preterm rabbits from oxidative lung injury https://www.physiology.org/doi/abs/10.1152/ajplung.1996.270.3.L446

29. Glutathione Stimulates Vitamin D Regulatory and Glucose-Metabolism Genes, Lowers Oxidative Stress and Inflammation, and Increases 25-Hydroxy-Vitamin D Levels in Blood: A Novel Approach to Treat 25-Hydroxyvitamin D Deficiency. https://www.ncbi.nlm.nih.gov/pubmed/30160165

30. The role of the glutathione antioxidant system in gut barrier failure in a rodent model of experimental necrotizing enterocolitis. https://www.ncbi.nlm.nih.gov/pubmed/15349102

31. Role of Glutamine in Protection of Intestinal Epithelial Tight Junctions https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369670/

32. WebMD Heart Disease and Homocysteine https://www.webmd.com/heart-disease/guide/homocysteine-risk

33. Glutathione & Detoxification: The Methylation Connection https://metabolichealing.com/methylation-detoxification-glutathione-connection/