The Glutathione Revolution

1—WHAT IS GLUTATHIONE?

I’M A PHARMACIST, SO I HAVE GREAT APPRECIATION FOR ALL THE THINGS we can take to improve our health and even save our lives. It’s hard to picture modern civilization without the prescription drugs that have made it possible for us to live considerably longer than our ancestors. Or the over-the-counter medicines that cure and comfort, not to mention the vitamins, minerals, and herbs that boost vitality and offer protection against illness. These remedies are some of the most ingenious and important discoveries human beings have ever made.

But as much as I value all the elixirs, pills, and potions produced in a laboratory, I am even more in awe of the remedies our body manufactures by itself. In most cases, we are born with the ability to make disease-fighting, detoxifying agents that so elegantly and effectively protect us from harm that we don’t even know they’re working! Every minute of every day, these self-generated properties endeavor to ensure that we avoid all kinds of illnesses, be it of the merely bothersome sort (say, the common cold) or something very serious (cancer being a prime example). Our own body makes them! Incredible.

And what is first among these physiological wonders? An antioxidant known as glutathione.

Glutathione, or if you want to get technical about it, glutathione sulfhydryl, GSH for short, is found in every cell in the body. It’s ubiquitous because it’s so important. As one of nature’s most powerful antioxidants—and I’ll explain just exactly what antioxidants do further on in this chapter—glutathione is extremely versatile, taking on many jobs. It is also first on the front lines of our defense against molecular marauders that damage DNA and other cellular matter, helping to prevent disease and accelerated aging. Glutathione is a detoxifier too. There’s an especially large concentration of the compound hanging around in the liver, where it assists the body in eliminating waste and potentially poisonous substances. And as a player in the immune system, GSH enhances the production and activity of the cells that wipe out bacteria, viruses, and other invaders.

To my mind, it’s truly a wonder that glutathione is not better known. It’s the body’s workhorse, toiling away, getting little of the glory heaped on other antioxidants, such as beta-carotene and vitamins C and E (though, of course, they’re important too). But that, thankfully, is changing. I think that as you learn more about the mechanics of glutathione, you’ll understand not only how underappreciated it’s been, but how worth your while it is to take steps to heighten your GSH levels.

HOW THE BODY BUILDS GLUTATHIONE

Glutathione is new to a lot of people, but researchers have known about it for a long time. It was first discovered in 1921 by Sir Frederick Gowland Hopkins, a former insurance clerk who segued into science and ultimately became chair of the biochemistry department at Cambridge University. Hopkins isolated GSH in yeast (the compound exists in plant as well as animal cells), setting the stage for other scientists to uncover the many roles it plays in keeping the body up and running. Hopkins, by the way, was also known for isolating tryptophan, an essential nutrient we derive from food, and he was awarded a Nobel Prize in 1929 for his work establishing the important role vitamins play in physiology.

So, what exactly was it that Hopkins saw under his microscope all those years ago? A very simple protein. Proteins play all kinds of different roles in the body. You probably already know that they are integral to creating muscle and hair and the collagen that gives our skin structure. But some proteins function as antibodies, some catalyze chemical reactions, and some act as messengers. And some, like glutathione, are antioxidants.

Amino acids, as you may remember from high school biology, are the building blocks of all proteins. To create glutathione, the body must string together three particular amino acids: glutamic acid, cysteine, and glycine. There is no substitute for any of these ingredients. All proteins have a biological blueprint that must be followed to the letter or they will not be able to do their jobs. In other words, it’s not like a recipe for spaghetti marinara, where you can leave out the red pepper flakes, or add the salt at the end instead of the beginning of cooking, and still have a perfectly fine dish. To build glutathione, you must have all of its components on hand and assemble them in the proper sequence.

Fortunately, glutathione needs only three amino acids, unlike, say, human growth hormone, which requires a whopping 191. What’s more, the body can make glutamic acid, cysteine, and glycine itself. And yet, as we age and the tiny manufacturing plants in our body slow down, and during times when glutathione is in high demand (needed, say, to help purge the remnants of too many gin and tonics after a birthday celebration), we can’t synthesize enough glutamic acid, cysteine, and glycine to fill the order. That’s when dietary sources of the three amino acids become particularly important. In subsequent chapters, I’ll talk more about how food affects your glutathione levels, and give you tips on how to adjust your diet to maximize GSH production.

MEET THE ENEMY: FREE RADICALS

Not too long ago, nobody but medical professionals and avid readers of health literature had even heard of antioxidants. But, these days, judging from food, supplement, and beauty-product advertisements and labels, most people not only know what antioxidants are, they’re actively seeking them out. It’s not unusual to see a manufacturer boasting of its corn chips’ “antioxidant power” or the “antioxidant advantage” of its orange juice. Beauty products are regularly touted as “antioxidant treatments,” and antioxidant supplements fill the shelves of mainstream pharmacies and natural grocery stores alike. That’s a good indication that most of us know that antioxidants like glutathione are good for us.

So, what do they do?

Biochemists have defined antioxidant as “any substance that delays, prevents, or removes oxidative damage to a target molecule.” They do this by neutralizing and disarming harmful molecules called free radicals. This is both a full-time job—free radicals are constantly on the warpath—and an essential one. Perhaps the antioxidant expert Lester Packer said it best: “As the adage goes, wherever there is smoke, there is fire. Similarly, wherever there is disease and destruction, there are free radicals.”

The main (though not the only) cause of free radicals in our body is… our body. Or more specifically, chemical reactions involving oxygen that take place in our body. One place that free radicals are typically generated is in the mitochondria, tiny structures inside cells where oxygen molecules are converted into energy. During the conversion process, some oxygen molecules end up losing one or more of their electrons, leaving them unstable, reactive, and a threat to other molecules in their path.

A regular, harmless oxygen molecule is encircled with an equal number of negatively charged particles (electrons) and positively charged particles (protons). This balanced pairing renders the molecule neutral; it’s neither positively nor negatively charged, and happy just the way it is. But when the tumult of a chemical process causes one or more of its electrons to go missing, the molecule—now a free radical—gets as purposeful as a member of the lonely hearts club swiping right on Tinder: It’s highly motivated to find a soulmate for that unpaired proton, and it wants to do it fast.

What follows are acts of theft. Because the imbalance of protons and electrons has left the free radical electrically charged, it has the ability to easily steal electrons from other molecules, and steal it does—a process called oxidation. But it doesn’t end there. The robbed molecules then cannibalize the electrons of their neighbors, who then snatch away the electrons of their neighbors. The chain of theft can go on and on, leaving damage in its wake. If you want to have a picture in your mind of what oxidation is like, think of rust. In the presence of moisture—H2O—iron loses electrons to oxygen molecules, creating the corroding we have come to know as rust.

A number of things besides energy production increase the formation of free radicals in the body. Exercise, for all its benefits, ramps up the creation of the errant molecules as a by-product of fat burning. (This isn’t necessarily all bad; see Chapter 6). When the immune system snaps into action it, too, through various pathways, elevates free radicals’ presence in the body. Such things as sun exposure, environmental pollutants (smog, cigarette smoke), food additives, pharmaceuticals, and pesticides can also produce an upswing in their formation. Worse, many of these invaders contain free radicals themselves, magnifying the problem as they dump them into your system.

It should be noted that free radicals aren’t completely villainous. They are integral to helping the immune system fight viruses and bacteria and are even generated by certain chemotherapy drugs as part of the plan to treat cancer. One study showed that they may help heal wounds too. Plus, our body provides a counterpart to free radicals: antioxidants, which are nature’s way of making sure the harmful effects of free radicals can be modulated. But when free radicals outpace antioxidants—not an uncommon occurrence given the realities of modern life—the imbalance creates something called oxidative stress. Oxidative stress is a result of having more free radicals than your body can get rid of, and that’s where the trouble begins.

A long list of diseases are associated with oxidative stress and the chronic inflammation it can cause. Cancer is one of them. Free-ranging free radicals can damage DNA, causing cells to mutate and become cancerous. (Didn’t I just say that free radicals can help cure cancer? Yes, but oddly enough, they can both cause and cure tumor development, depending on what molecules they’re targeting. When the target of free radicals is healthy DNA, they’re harmful; when the target is a cancer cell, they’re helpful.)

Free radicals also have the ability to oxidize fats in the body, leading to deposits on artery walls and making the arteries harden, both precursors to heart disease. There’s an oxidative stress link to just about every malady you can think of, including stroke, Alzheimer’s disease, diabetes, rheumatoid arthritis, and macular degeneration. Free radicals are known to accelerate aging too. The lines on your face as you grow older may be due to oxidative stress helping to spur the breakdown of the proteins that give the skin its plumped-up shape and keep it looking smooth. Free radicals can’t get all the blame for wrinkles, but there’s demonstrable evidence that they speed up the wrinkling process.

There is also evidence that oxidative stress shortens telomeres, another way free radicals contribute to aging. Telomeres are most often described as caps composed of protein and DNA that sit on the ends of chromosomes (think of the little plastic thingy on the ends of a shoelace and you’ll have a pretty good picture of a telomere). As the years go by and cells divide, telomeres become smaller. When they get small enough, they tell their cells to stop dividing, effectively hampering the body’s ability to regenerate and refresh itself. Hastening this natural process is another way free radical damage makes us not only more vulnerable to disease, but more likely to suffer the deterioration of our tissues that comes with aging. I’ll tell you more about telomeres in Chapter 5.

ANTIOXIDANTS STRIKE BACK

As I said before, the body doesn’t just let free radicals run rampant without fighting back. Antioxidants regularly neutralize free radicals, stopping them in their otherwise injurious tracks. And as long as they’re in ample supply, antioxidants retain the edge over free radicals.

There are hundreds of different types of antioxidants. You have probably heard of vitamins C and E, beta-carotene, and, maybe, coenzyme Q10, which all have the power to squelch free radicals and prevent oxidative stress. Maybe you’re even aware of some of the less well-known antioxidants, such as selenium and alpha lipoic acid. (Also see “Glutathione’s Brothers in Arms,” here.) Some of these compounds, vitamins C and E among them, can only be obtained from food; your body doesn’t make them. Other antioxidants, such as glutathione, the body can synthesize itself.

Antioxidants attack free radicals in a few different ways. One is by preventing their formation in the first place. Glutathione in its role as a detoxifier does this by removing many toxic elements from the body before they can create free radicals. It’s the body’s ounce of prevention. The other way antioxidants protect against damage is by donating their own electrons to free radicals so that the charged molecules don’t steal them from DNA and other essential compounds. Antioxidants have electrons that they want to give away. Once they do and the free radicals are turned into harmless water molecules, those reactive atoms cease their pilfering and pillaging, and damage is averted.

While all antioxidants are generous in this way, glutathione is by far the most magnanimous. Say you and I are sitting in a room with a few other people and someone comes in and says, “Can anybody spare a hundred dollars?” You’re the first one to pull out your wallet, and even when others offer to contribute, you say, “No, no, I got this!” That’s how glutathione behaves in the presence of other antioxidants. If it’s sitting next to a selenium molecule, the selenium isn’t going to lose a single electron, because GSH is on the job.

Still, one antioxidant can’t do it all. Going back to the hypothetical room where you and I sit, say that once you have loaned out the $100, a second, then a third, then a fourth person comes along and makes the same request. That’s when everyone else in the room has to pull out their wallets too. And so it is with the band of free radical scavengers. Glutathione, as effective as it is, can’t be the end-all, be-all, so other antioxidants must contribute as well. A lot of who does what depends on how much GSH there is in the body at the time and where the interactions are taking place. Different antioxidants are concentrated in different parts of the body, and that can affect which of the defenders end up donating their electrons.

The way antioxidants work in the body is a little complicated. It’s not like a game of Mousetrap, where the red paddle hits the bucket that sends a ball rolling down an alley, which causes a bigger ball to glide through a bathtub, falling on a diving board and launching a swimmer into a pool, which then activates the mousetrap—over and over again. Success at Mousetrap, in other words, always involves the same cascade of events. With antioxidants, the chain of action is not always the same. Neutralizing free radicals can work in several different ways.

We need antioxidants, such as vitamins C and E, on the front lines of the body’s defense system. So, after those soldiers have given up their electrons to stabilize free radicals, they don’t just end up spent, lying in the body’s trash heap. Nor do they become destructive free radicals themselves (which would, of course, defeat the whole purpose of their work). Instead, they go through a process called recycling, and glutathione is integral in this endeavor.

When another antioxidant, say, vitamin C, hands off an electron to placate a roving free radical, glutathione replenishes the C molecule with one of its own electrons. Now the C molecule is good to go back to work, but the glutathione molecule is missing an electron. So what does it do? It replenishes itself by fusing with another electron-deficient GSH molecule. Together they create a new, stable glutathione molecule. In essence, glutathione not only goes to war against invaders, it reloads itself, rearms its fellow soldiers, and prepares to meet the next threat.

But sometimes the role is reversed, and my personal theory is that it’s reversed much of the time. As the most important antioxidant—it’s known as the mother of all antioxidants (see “The Mother or the Master of All Antioxidants? Both” here)—glutathione needs to stay in the game. We need as much of it as possible. But in the metabolic sense, glutathione is very expensive to make. It “costs” the body enzymes and energy and other elements to make. There is, however, a cheaper way to keep the coffers full of GSH and that is to recycle it. The body can do that all day long. And how does glutathione get recycled? It does it itself by grabbing electrons from other antioxidants, such as vitamins C and E. These antioxidants are themselves low cost. The body doesn’t have to make them; it gets them from food. So, even though these other antioxidants do work of their own, my theory is that their main role is to help glutathione recycle itself. Here is how it works:

Glutathione can’t always be recycled—something different happens when GSH is functioning as a detoxifier, which I’ll get into in Chapter 4—but a great deal of it can and that helps keep the wheels of the free radical defense system turning.

BEYOND ANTIOXIDANT ACTIVITY

In subsequent chapters, I will tell you more about glutathione’s role in keeping your body healthy. But here is a little preview. Aside from its antioxidant activity, one of GSH’s main jobs is to help detoxify the body. Glutathione is concentrated in the liver, the organ that’s a clearinghouse for toxic substances. The body is continually confronted with harmful compounds, some that are natural by-products of things you might not think of as unsafe (e.g., medications) and some that are unnatural by-products of modern life (e.g., ozone and fine particles in smog). When glutathione meets up with toxins, it deactivates them in one of two ways: either by neutralizing them and turning them into water molecules, or by helping to eliminate them from the body.

Our immune system also relies on glutathione. In fact, macrophages—white blood cells that scavenge infectious invaders—don’t leave home without GSH. Think of it this way. If you were a firefighter called to fly up to Alaska and fight a big old raging blaze, you would make sure to bring your tool bag. And you would make sure that the tool bag had all the flame-battling gear you needed, including, say, your ax. Glutathione is the macrophage’s ax, an instrument in its tool bag that’s going to help it do its job properly.