Glutathione: A Closer Look at the Master Antioxidant

By Adam Swenson

If you look at longevity of a species—mice, humans, horses, and so on—and you measure the amount of glutathione it produces, the more glutathione a species produces, the longer it lives.

—Joe Pizzorno, ND

Just how important is glutathione? Well, the medical community seems to think it is pretty significant, as there are 76,000 journal articles devoted to its study. (This, of course, says as much about the effects of progress on the medical system as it does about glutathione.)

Mark Hyman, MD, says it is the most important molecule to prevent aging, cancer, and heart disease, and that our culture has an epidemic deficiency of it. Is this a reason cancer and heart disease and chronic diseases are on the rise? Certainly.

OK, so if it’s so important, why haven’t most people heard of it? That is a fair and important question, one we’ll address in the following pages.

A peek behind the curtain at the master antioxidant

We know that antioxidants are crucial for our health and longevity. As the name implies, antioxidants fight oxidation, a normal chemical process that takes place in the body every day. Examples of oxidation we’re all familiar with are rust on a car fender or the browning of an apple slice when exposed to the air.

The oxidation process produces free radicals—if left uncontrolled they can cause rampant damage to your cells and age the body like nothing else. The secret to longevity is keeping the oxidative process at bay, and the secret to keeping the oxidative process at bay is antioxidants. Among antioxidants, glutathione is the top of the heap, hence the quote from Dr. Pizzorno about the direct link between mammalian species and the levels of glutathione they are capable of producing.

The phrase “capable of producing” is a hint at one of the things that makes glutathione unique. It is “endogenous,” meaning we make it in our bodies (there are a few other endogenous antioxidants: CoQ10 would be a good example). This is opposed to antioxidants like vitamin C or omega-3s, which are “exogenous,” meaning they have to come from outside, i.e. diet or supplements.

Often when we think of endogenous substances in our bodies, we tie them to the point of origin: Insulin is made by the pancreas, testosterone is secreted by the testes and ovaries, bile is produced by the liver. Glutathione, a small peptide made of three amino acids, is not made just by one organ—rather it is literally produced in every cell of the body.

“Glutathione,” says Dr. Pizzorno, “is the most important intracellular and intramitochondrial antioxidant … it is hard to overstate the importance of glutathione. When the mitochondria are producing energy, it protects the mitochondria from oxidative byproducts of the production of energy. But glutathione does a lot more than that. It binds to chemical toxins we are exposed to—like pesticides and such—and excretes them out through the liver. It also binds to mercury and helps excrete mercury out through the urine. It protects the cells from oxidative damage from these chemicals.”

Dr. Pizzorno goes on to talk about the link between glutathione and longevity, finishing his thought with this telling observation: “In people with low levels, it is being used up to help protect [them] from environmental toxins so it is not there to help with longevity of the cells.”

Peptide economics: an issue of supply and demand

Glutathione production is ratcheted up (or upregulated in medical speak) in response to extra load brought to bear on the immune system by toxins. The toxic load in the body is comprised of pesticides in our food supply, heavy metals in things we eat, airborne pollutants, BPA in our water, and so on. Glutathione plays a key role in protecting us from all these assaults to our immune system. You could think of it like a war: as more attacks are mounted, more defenders (antioxidants, specifically glutathione) are needed. They are “produced and transported to war,” so to speak, by GGT, a standard liver enzyme that can be easily measured via a blood test.

As Dr. Pizzorno wrote in an article called “Measuring Oxidative Stress,” in our sister journal, IMCJ, “As the need for glutathione production increases—for example, as a protective response to oxidative stress or heavy metal exposure—so does the production of GGT to facilitate glutathione production. Serum GGT correlates with F2-isoprostanes, fibrinogen, and C-reactive protein—all markers of inflammation.”

To unpack this a little bit, some people have innately higher levels of glutathione in their bodies that are ready to protect the cells from the oxygenation that is a natural byproduct of producing energy in the mitochondria. This is a healthy state. If you were to test someone’s GGT levels in this condition, they would fall within the normal range.

You would find elevated GGT levels when toxic load spikes and glutathione production is ramped up to meet demand. Both situations will be marked by higher levels of glutathione, but one is a healthy state and one is definitely not.

Ramping up production

The glutathione level in your body can be influenced by a number of factors. As with most other health indices, dietary and lifestyle factors can either harm or help your glutathione levels.

The dietary and lifestyle factors that hinder glutathione levels are the usual suspects: obesity, a sedentary lifestyle, eating processed foods, and use of alcohol and tobacco. To boost glutathione levels, start with exercise (resistance and/or cardio); eat a diet high in fruits and vegetables, along with unprocessed meats; get adequate hydration; and lastly reduce your levels of stress and your level of exposure to toxins. (And so we find that what is good advice for glutathione production is also good advice for reversing or avoiding most other ailments known to man.)

By taking these steps, you will create an environment conducive to better health. When we get down into the nitty gritty of producing glutathione, we find that this small peptide’s production is limited by a few necessary precursors. To use a domestic metaphor, if you’re trying to make blueberry muffins, you’re going to need flour, butter, and blueberries (among other things). If you run out of flour, you’re not going to be making any more muffins until more flour is procured.

Glutathione is just like that except in place of butter, blueberries, and flour, we’ll substitute in N-acetylcysteine (NAC), alpha-lipoic acid, whey protein, and selenium. Ajinomoto North America recently launched a new supplement called amino Defense. Ajinomoto says amino Defense “contains” AJI-C&T, a patented blend of amino acids cysteine and theanine, which are the necessary building blocks for the body’s production of glutathione, leading to improved immune health.” (It is worth noting that this supplement can only be obtained through a healthcare professional.)

Dr. Pizzorno adds that, “There are two interventions clearly documented to raise glutathione levels. One is whey powder. Taking 15 grams of whey powder twice a day is shown to raise glutathione levels. The other is NAC: five milligrams a day will also raise glutathione levels. I always prefer getting things from the diet, but some people can’t tolerate dairy products, so NAC is the better choice for them.”

The direct approach

Everyone agrees that glutathione production can be boosted by providing your body with the precursors. Less clear is the effect of actual glutathione supplements (or glutathione in foods) on the level of glutathione circulating in your bloodstream. Many studies in the past have shown that oral glutathione supplements are not bioavailable, meaning they are broken down before they enter the bloodstream and actually do the work they were meant to do. (To return to our earlier war metaphor, this would be akin to soldiers not surviving to reach the battleground and actually do battle.)

Recent studies have called this into question, however. Danielle Citrolo is a pharmacist and technical services manager for Kyowa Hakko USA, the maker of Setria glutathione. (Setria is the main ingredient in a number of consumer products by manufacturers like Life Extension and TwinLab, and professional brands like Pure Encapsulations and Integrative Therapeutics.) “John Richie, PhD, worked out of Penn State: he did some research on taking glutathione orally,” Citrolo said. “Fifty-four healthy patients supplemented with 250 mg of glutathione daily or 1,000 mg of glutathione daily orally. They did a battery of blood tests to look at whole blood, red blood cells and also white blood cells and immune cell function tests. We did find a time-and-dose-dependent increase in the blood glutathione.”

Addressing how oral glutathione is absorbed, the “Facts for Health Professionals About Setria Glutathione” paper by Kyowa says, “Early studies did not find an appreciable increase in plasma levels after supplementation, and thus it was thought that oral glutathione was not bioavailable. However, over the past 20 years numerous studies have demonstrated that plasma levels are not indicative of levels in other tissues and that oral glutathione is bioavailable … Oral glutathione enters tissues by three routes: 1) it can be absorbed intact in the intestines and taken up by tissues; 2) it can be broken down in the GI tract to its constituent amino acids, which are then absorbed and glutathione is resynthesized in tissues; 3) it can be taken up directly into GI tissues by cells that line the GI tract.”

Foods high in glutathione include unprocessed meats, garlic, broccoli, asparagus, avocados, and spinach. As Citrolo noted, “The biggest thing with food is that the more it is processed, the less glutathione in it: so the fresher you can get it, the better it is. Right from the farm, the more glutathione you’re going to have.”

Aging (and other conditions)

The aging process, all things being equal, leads to lower amounts of glutathione being produced, so it is especially important to pay attention to this once you hit your 50s.

“One of the things you see with aging is that as the mitochondria produce ATP they get damaged,” says Dr. Pizzorno. “The more a person produces energy, like a long-distance runner, the more they are going to damage their mitochondria if they don’t have adequate antioxidants around. Turns out that for the average person by the time you hit age 55 their mitochondria become so damaged they start leaking a lot of free oxidants into the mitochondria and the cells. Without adequate glutathione they are going to have a lot of damage going on.”

The ability to fight oxidation is important at such a fundamental level that it’s difficult to even address specific conditions, as that would imply that there are others that would not be affected. Dr. Hyman says, “Glutathione deficiency is found in almost all very ill patients, including chronic fatigue, heart disease, cancer, autoimmune disease, diabetes, Alzheimer’s, and Parkinson’s … If you are sick, old, or out of shape, you have glutathione deficiency. Keeping yourself healthy depends on keeping glutathione high.”

While the consequences of glutathione deficiency might be depressing, the inverse is also true. Helping to guard your glutathione production can restore a youthfulness you thought you’d never see again. Dr. Pizzorno says, “I’m an avid basketball player. I play with guys half to one-third my age. But no one else in my age group is still playing. This is a group of guys I have been playing with for 20 years. All the guys that started then are gone. The difference is that I paid attention to protecting my mitochondria and facilitating regeneration of my joints and they didn’t. I think glutathione plays a huge role in that.”

Boiling it down

To ensure your body is getting what it needs, first pay attention to eating a healthy diet and living a healthy lifestyle with reduction in stress and exposure to toxins. Once you’ve done that, make sure you’re getting enough of the precursors, including either NAC or whey protein, plus ALA and selenium.

In doing so, you just might find a vitality you never knew you had.


Glutathione at a Glance

>> Glutathione is an essential antioxidant composed of cysteine, glutamate, and glycine

>> Our bodies make it

>> It is protective against the cell damage that causes premature aging and many chronic diseases

>> It detoxifies us by binding to heavy metals and other toxins until they are excreted from our bodies

>> You can ensure adequate supply by eating “precursors,” most importantly cysteine, and secondly ALA and selenium

>> It supports the immune system

>> If the body goes 24 hours without food, the liver will steal glutathione precursors from the muscles so it can maintain adequate levels

Top Glutathione Picks

Ajinomoto Amino Defense (available from healthcare professionals), // TwinLab Mega L-Glutathione, // Life Extension Glutathione, Cysteine & C,