Glutathione: The Great Protector

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Glutathione: The Great Protector

Find out why this little-known antioxidant is key to fighting toxicity and premature aging — and warding off chronic disease.

By Catherine Guthrie / April 2011

If biochemistry were the stuff of comic books, antioxidants would be the superheroes — with glutathione (gloota-thigh-own) being no less than a cross between Superman and Underdog. As the most powerful antioxidant in the body, glutathione works around the clock to fend off nefarious characters. And yet, few people recognize its importance.

Glutathione is likely to get more attention in the near future, as experts begin to connect the dots between depleted stores of the antioxidant and the likelihood of chronic disease. “If you haven’t heard of glutathione yet, you will,” says Mark Hyman, MD, founder of The UltraWellness Center in Lenox, Mass., and a pioneer in the field of functional medicine. “In terms of staying healthy, it is one of the most important molecules in the body.”
Glutathione is a triple threat to toxins. It neutralizes free radicals, enhances the immune system and detoxifies the liver. But some worry that it has met its match. The trappings of modern life — everything from refined foods to over-the-counter painkillers to stress — rob the body of this vital antioxidant. And, even if you’re doing everything right, aging takes a bite. Around age 45, our glutathione levels start to slip. Ultimately, those levels can dip as much as 50 percent below optimal as we age.

Some scientists are now wondering if low glutathione levels aren’t partly to blame for the free-radical-induced illnesses so common in middle age and later, such as Alzheimer’s, cancer and heart disease. Indeed, research published in the New England Journal of Medicine found that, among people with heart disease, those with the least amount of glutathione in their blood were 30 percent more likely to have a heart attack than those with the most glutathione.

Hyman didn’t understand the full ramifications of a glutathione deficiency until his own health was in peril. In the mid-1990s, he was besieged by muscle pain, brain fog and “bone-numbing” exhaustion. “I went from feeling really healthy one day to really sick the next,” he says.

After months of medical sleuthing, he discovered he had mercury poisoning —  probably due to eating contaminated fish and breathing tainted air while working in China. He suspects that the burden of detoxifying the mercury depleted his glutathione levels, leading his body to break down under the strain. “As you detoxify, your body uses up more and more of your glutathione stores until it’s gone,” he says. “That’s when you end up with toxic overload.

In exploring what went wrong, Hyman discovered he lacked a gene, called GSTM1, crucial to making and recycling glutathione. He estimates that roughly half of Americans are missing one or more of the genes necessary to produce enough of the antioxidant. The percentage climbs even higher among his critically ill patients, the vast majority of whom have rock-bottom glutathione levels. “At first I thought it was just a coincidence,” he says, “but I’ve come to realize that making and keeping a high level of glutathione is critical to preventing disease.


Found in every cell in the body, glutathione protects the cell’s engine, called the mitochondria, from bacteria and viruses as well as toxins. It’s considered “the mother of all antioxidants,” as Hyman calls it, because all other antioxidants, including vitamin C and vitamin E, rely on it to give them a second life.

The average antioxidant has a short life span, sacrificing itself whenever it wipes out a free radical. But glutathione carries enough extra zip to not only bring spent antioxidants back from the dead but also to recharge itself, explains Leslie Fuller, ND, an educator at the National College of Natural Medicine and practitioner at the Nature Cures Clinic, both in Portland, Ore.

Most glutathione is made inside the body from three amino acids: glutamic acid, cysteine and glycine. In addition, some foods, particularly asparagus, spinach, avocado and squash, are high in a plant version of glutathione that the body converts to replenish its supply.

Under healthy conditions, and in a healthy environment, our bodies would be able to churn out plenty of glutathione to meet our daily needs. But cigarettes, alcohol, caffeine, processed foods and certain medications deplete the body’s stash. So does stress. And as Hyman discovered, toxic surroundings may pose an even bigger threat to our body’s glutathione supply.

Radical Riff-Raff

To fully appreciate glutathione, it helps to know a little more about its nemesis: free radicals. Free radicals are unstable oxygen molecules created by our metabolism. The instability stems from a missing electron. In a mad attempt to find balance, the misfit molecules rip electrons from their neighbors. As a result, those molecules also turn into free radicals. This damage can eventually snowball and disrupt a cell’s integrity, causing it to behave abnormally.

“Almost every chronic illness known to humankind has been linked in some measure to free-radical-induced tissue damage,” says Lise Alschuler, ND, FABNO, coauthor of The Definitive Guide to Cancer: An Integrative Approach to Prevention, Treatment, and Healing, Third Edition (Celestial Arts, 2010).

That’s not to say the goal is zero emissions. Indeed, some free-radical damage is natural. Every breath inhaled, every calorie burned, every muscle contracted leaves a wisp of free radicals in its wake. “Even if we lived in a pristine environment, our bodies would make free radicals,” says Alschuler. And, as she explains, some free-radical damage is a good thing because a damaged cell is triggered to be either repaired or destroyed. By sparking either a renovation or a demolition, free-radical damage gets the body’s attention, and, if the body is healthy enough and the free-radical damage is not overly extensive, free radicals may play a role in preventing diseases like heart disease and cancer.

Unfortunately, our bodies must contend with an ever-growing onslaught of free radicals in the environment. Free radicals hitchhike into the body on the backs of chemicals in the air, the water supply and the food chain. The cumulative load is called oxidative stress. Corrosion caused by oxidative stress (or oxidation) inside the body is often compared to the slow rusting of metal when it’s exposed to the elements.

Protecting cells from oxidation is where antioxidants, particularly glutathione, come into play. All antioxidants retard oxidative stress, but because glutathione recharges its allies, it plays a particularly important role in helping the body keep up with our accelerated modern-day demands.

“We are in a situation where our manufacturing and our recycling of glutathione is maxed out,” says David Perlmutter, MD, FACN, ABIHM, author of Power Up Your Brain: The Neuroscience of Enlightenment (Hay House, 2011). “We just can’t detoxify fast enough.”

Cleanup Crew

Found throughout the body, glutathione is concentrated in the liver. The body’s primary detox organ, the liver is charged with giving nutrients the nod to be absorbed and giving toxins the boot. But expelling a toxin isn’t easy. In phase one, liver enzymes must convert the toxin into a compound that can be flushed. In phase two, glutathione is used to grab hold of the toxin and escort it out of the body via urine or bile. If there isn’t enough glutathione on hand, the toxins stack up like so many cars in a traffic jam.

Glutathione owes much of its detoxifying prowess to cysteine. A sulfur-rich amino acid, cysteine is abundant in eggs, garlic and whey protein. “Sulfur is a sticky, smelly molecule that acts like flypaper trapping toxins in the body,” explains Hyman. This is why vegetables high in sulfur, including garlic and onions, have been at the heart of detoxification diets for years.

Another plant substance, called cyanohydroxybutene (found in broccoli, cauliflower and cabbage) helps restock the body’s glutathione supply. “We’ve always been taught that broccoli and other cruciferous veggies are important to the detox protocol, but we didn’t fully understand why,” says Perlmutter. “Now we know that it’s because they enhance glutathione production.”

Green tea, fish oil and resveratrol also house substances that switch on genes responsible for making glutathione, Perlmutter notes. Aerobic exercise and yoga are thought to goose glutathione levels as well.

Although glutathione doesn’t come in a simple pill form, Perlmutter says, “You can take and do things that turn on your body’s genes to make more glutathione, and that’s pretty powerful stuff. You are modifying your own genetic expression.”

Logically, if more glutathione means better detoxification, people with the highest levels of the stuff should live the longest. That was the theory that drove Danish researchers to enroll 41 centenarians in a study of glutathione levels. Their results, published in the journal Age and Ageing, found that glutathione levels were highest in the healthiest seniors. Additionally, they discovered that the centenarians had higher levels of glutathione than people 20 to 40 years younger, hinting that glutathione may be one reason why their subjects had lived to such a ripe age.

Need More? Make More

Recognizing when the body is running low on glutathione takes some detective work. Because it oxidizes quickly outside the body, the antioxidant does not lend itself to a blood test. So some healthcare practitioners, like Hyman, look for missing genes. Others consult indirect biochemical markers, such as short telomeres (the caps of DNA on either end of a chromosome, like handles on a jump rope) or high levels of oxidation in the blood. A history of chronic illness is also a clue.

But don’t wait until you’re sick to think about glutathione. High stress levels, certain medications, past infections and a poor diet can all nibble away at the body’s glutathione stash. The average American consumes only 35 milligrams of glutathione per day, says Alschuler, far short of the optimal daily intake of 250 milligrams. “This, coupled with decreasing glutathione production as we age, leaves most of us deficient.”

The good news: Protecting your glutathione levels is fairly simple, says Perlmutter, and “the health implications can be profound.”

Easy Ways to Maximize Glutathione Production and Activity

Eat lots of glutathione-rich foods, such as asparagus, spinach, avocado, squash, melons, grapefruit and peaches. Whenever possible, eat these foods raw or minimally heated, since heat — and microwaving — tends to destroy antioxidants.

Eat more colorful, antioxidant-packed produce, such as strawberries, bell peppers and mangoes, all of which are particularly high in vitamin C. The more one-shot antioxidants you’ve got on board, the less your body needs to lean on its glutathione reserves.

Eat more foods high in cysteine. The sulfur-rich amino acid is a key building block for glutathione. The best sources are eggs, garlic and whey protein. If you buy whey protein, make sure it is bioactive and made from undenatured (or nondenatured) proteins, meaning the bond between the amino acids is preserved, and the cysteine is more bioavailable.

Limit exposure to toxins by buying organic produce, filtering your water, cutting down on refined foods, and avoiding chemical-packed personal-care  and cleaning products. Minimizing your toxic burden will help preserve your body’s ability to produce glutathione, and also reduce excess demands on your body’s glutathione supplies.

Catherine Guthrie is a health writer in Bloomington, Ind., and a contributing editor to Experience Life.

Brain Buffer

The brain makes up only 2 percent of the body’s weight but eats up roughly 20 percent of its oxygen. Because the body spews free radicals when it uses oxygen, the brain is awash in rogue molecules. Glutathione helps protect the brain against their ravaging effects.

Uncontrolled free-radical damage is the tie that binds a handful of diseases that target the brain, including schizophrenia and Alzheimer’s. Evidence suggests that a shortage of glutathione is a factor in all of the above, but some of the most telling evidence is in people with Parkinson’s disease.

Parkinson’s disease corrupts the files in the brain that make dopamine, a chemical instrumental in coordinating the body’s movements. When researchers looked at the brains of people with Parkinson’s disease, they discovered that the area that makes dopamine, the substantia nigra, contained up to 40 percent less glutathione than the rest of the organ. “So, here’s an area that’s being damaged by free radicals, that’s low in glutathione, and therefore [is] at more risk for free-radical damage,” says neurologist David Perlmutter, MD, FACN, ABIHM.

While much about Parkinson’s disease remains a mystery, a role for glutathione seems certain. For his part, Perlmutter sees glutathione as a vital treatment option. “We are all about getting as much glutathione to the brain as possible,” he says. “It really is one of the most protective agents around.”

Free-Radical Fighter

Some free-radical damage is the natural byproduct of our body’s cellular processes; however, our bodies are made ever more vulnerable to an increasing amount of free-radical damage due to environmental factors, including the sun, pollution, poor nutrition and chronic stress.

Enter glutathione, “the mother of all antioxidants,” which helps to recharge other antioxidants, thus protecting our cells from free-radical-induced oxidation.

Toxin-Clearing Escort

Glutathione is concentrated in the liver, the body’s primary detox organ. Glutathione grabs hold of toxins in the liver and escorts them out along with the body’s waste products.

Too little glutathione? Toxins accumulate in the body and can contribute to many inflammation-based diseases.

The Next-Best Things: Glutathione Precursors

One reason that glutathione wallows in relative obscurity is that, unlike vitamin C or E, it isn’t easily shoehorned into a supplement you can swallow. “With glutathione it’s not that easy,” says David Perlmutter, MD, FACN, ABIHM, author of Power Up Your Brain: The Neuroscience of Enlightenment (Hay House, 2011).

That’s because to succeed as an oral supplement, a nutrient must be able to wiggle through the intestinal wall and into the bloodstream, he explains. Otherwise it’s doomed to be destroyed in the gut. Here is where glutathione’s size works against it. A large molecule, called a tripeptide, glutathione cannot sneak through the intestinal wall intact. Instead, its three amino acids are broken apart during digestion and reassembled in the blood. (To get around this problem, many practitioners give therapeutic doses of glutathione intravenously.)

Experts disagree on exactly how much oral glutathione reaches its final destination, but all agree the best bet is to deliver plenty of building blocks (a.k.a. precursors) the body needs to make glutathione on its own.

In addition to eating glutathione-rich foods (see above) here are four more ways to get the raw materials you need:

N-acetyl-cysteine (NAC): NAC supplements are made synthetically from the amino acid l-cysteine. The small molecule slips seamlessly into the blood where it combines with glutamic acid and glycine to restock the liver’s supply of glutathione. A potent liver detoxifier, NAC is approved by the Food and Drug Administration as a tool to limit liver damage caused by acetaminophen overdose.

Alpha-lipoic acid (ALA): A key antioxidant, alpha-lipoic acid (not to be confused with alpha-linolenic acid) is both water- and fat-soluble, meaning it can vanquish free radicals throughout the body, including in the brain. That’s no small matter, since oxidative damage is tied to many brain diseases, including Parkinson’s and Alzheimer’s. The best dietary sources of ALA are organ meats (such as liver) and brewer’s yeast.

Selenium: A mineral found in Brazil nuts, meat and seafood, selenium boosts the body’s ability to recycle glutathione. “Eating just one to two Brazil nuts daily supplies enough selenium for most people,” says Lise Alschuler, ND, FABNO, coauthor of The Definitive Guide to Cancer: An Integrative Approach to Prevention, Treatment, and Healing, Third Edition (Celestial Arts, 2010).

Vitamin C: One of the most well-known antioxidants, vitamin C is glutathione’s crime-fighting cohort. In studies, people with high levels of vitamin C typically have high glutathione levels, as well. The two antioxidants work in tandem to rid the body of water-soluble toxins