glutathione dr pravin

GLUTATHIONE

Dr. Pravin Tripathi

“ Aging is the progressive accumulation of diverse, deleterious changes with time that increase the chance of disease and death. The basic chemical

process underlying aging was first advanced by the free radical theory of aging in 1954: the reaction of

active free radicals, normally produced in the organisms, with cellular constituents initiates the

changes associated with aging.”—Denham Harmon, M.D., Ph.D.

Are you feeling rusty? Perhaps you should be since every process that occurs in the human body—from breathing to

eating to moving our limbs—creates oxidation. While breathing, eating and moving are certainly essential to life, they also generate oxidative stress in the form of reactive

oxygen molecules—so-called free radicals. In fact, the very process of creating energy within our cells produces reactive

oxygen molecules. These free radicals, like the polluting exhaust from an automobile, are the unfortunate by-

products of our own cellular engines. Free radicals, if left unchecked, will exert tremendous damage to our tissues. In

fact, the existence of free radicals and their oxidative damage is at the core of aging and of chronic disease.

The process of free radical-induced tissue damage is mimicked in nature in the corrosion of metals. When iron is exposed to moisture in the air, rust

forms. This rust is the result of iron molecules donating electrons to the reactive oxygen

molecules in air. This changes the structure of the remaining iron molecules, creating a brown, brittle metal which flakes off. We refer to this

altered form of iron as rust. In a sense, unchecked free radical damage in our own bodies is akin to

causing our organs and tissues to rust!

This process begins with the production of energy in our cells. Within each of one of our cells there is a small, but powerful mitochondria. Mitochondria

are like the batteries of our cells because this is where energy is produced. Within the inner

membrane of the mitochondria, oxygen is used to produce energy as ATP, the universal currency of

energy in our body. The process used to make ATP uses electrons from oxygen molecules and is, most simply, a process of transferring electrons from one

molecule to another.

In doing this, some oxygen molecules are left missing an electron. These electron-hungry oxygen molecules become free radicals. Free radicals have at least one

unpaired electron in their outer orbit, essentially giving it an electrical charge. Free radicals are very unstable and react quickly with other compounds, in order to steal an electron. The stolen electron fills the outer ring of the oxygen molecule, allowing it to regain its electrical stability. Free radicals are so greedy for an electron that they literally rip electrons off of other molecules. This violent electron robbery leaves the

victim molecule missing an electron in its outer orbit.

The victim, in turn, becomes a free radical and it too rips an electron off of a nearby molecule. When these molecules are part of our bodily tissue—for instance, the molecules that comprise the inner membrane of the mitochondria—the rapid fire chain of electron robbery will, over time, cause injury to the membrane. If this injury isn’t repaired, it will ultimately damage the DNA and impair the mitochondrial production of energy. Energy is required to fuel other cellular processes critical to our healthy survival. When energy production is impaired, the cellular production of proteins needed for cell repair, cell growth, and cellular communication declines. The loss of these critical cellular functions leads to the development of chronic diseases. In fact, almost every chronic illness known to humankind has been linked in some measure to free radical-induced tissue damage. If the damage is extensive enough, the energy demands of the body exceed its supply. Combining this lack of cellular energy with free-radical damage speeds up the aging process.

Conditions Linked to Oxidative Stress*Cardiovascular disease, stroke*Cancer*Neurodegenerative diseases (Parkinson’s, Alzheimer’s)*Diabetes*Cataracts, macular degeneration*Human immunodeficiency virus (HIV), hepatitis B*Asthma, chronic obstructive pulmonary disease (COPD)*Psychiatric diseases (schizophrenia, bipolar disorder)*Inflammatory diseases and disorders

*Aging

Producing energy is not the only cause of free radicals. Tobacco is oneof the worst offenders. Each puff of cigarette smoke contains over 1,000free radicals. Imagine the load of free radicals that enter the body of apack-a-day smoker! In addition to cigarette smoke, there are many othersources of environmentally-derived free radicals. Industrial pollutantsgenerate free radicals and contribute to associated free-radical tissue damage.Free radicals are found in diesel fuel exhaust, in the hydrocarbons,ozone and nitrous oxide from carbon-based fuel exhaust, in pesticides,and herbicides. We are also exposed to free radicals when we eat food out of plastic containers (particularly if these containers have been heated) due to the phthalates in plastic. Phthalates are mainly used as plasticizers (substances added to plastics to increase their flexibility). Ionizing radiation also generates free radicals. This is, in fact, the way in which radiation is used to destroy cancerous tumors.

Oxidative Damage to Cells and Tissues

Reactive Oxygen Species (ROS) DiseasesProtein Damage

Cell Functioning , & Signaling

Mutation

DNA DamageLipid Peroxidation

AGING

Ultraviolet radiation from the sun causes oxidative damage to our skinwhich manifests as wrinkles, age spots, and even skin cancer. Alcoholmetabolized in the liver turn into free radical compounds. This is one ofthe reasons why excessive and prolonged alcohol ingestion is linked withliver disease, neurological diseases, and cancer. Digestion generates freeradicals as this energy-intensive process breaks down food particles. Saturated fat and trans fats are potent dietary sources of free radicals.Exercise also generates free radicals in our muscles as energy production increases to meet the demands on the working muscles. There is no escaping free radical exposure—we produce them and we encounter them in the environment every minute of every day.While this may seem like a dismal state of affairs, it should be pointed out that free radicals are not always bad. The destructive nature of free radicals is an exceptionally useful way to destroy foreign invaders and mutated cells. Our immune cells use free radicals to destroy infected and cancerous cells. Certain immune cells carry specialized vesicles containing hydroxyl radicals. When these immune cells encounter an infected or damaged cell, they inject the contents of this vesicle into the target cell. The infected and mutated cells don’t stand much of a chance in the face of this free radical onslaught.

Antioxidant Protection

The ability to rapidly extinguish oxidative stress is clearly essential to our health. This is where antioxidants come to the rescue! Antioxidants are compounds whose primary function in the body is to quench free radicals and prevent oxidative stress to our tissues. Antioxidants are compounds that are able to donate electrons to the greedy electron-poor free radical molecules. When our body has sufficient antioxidant capacity, we are able to neutralize and eliminate free radicals and, in so doing, relieve oxidative stress. Our antioxidant defense system is built out of a number of different antioxidant compounds, each with different abilities to quench free radicals. These compounds work together to provide the greatest defense. There are two broad categories of antioxidants—those which are produced within our body (endogenous antioxidants) and those which we consume (exogenous antioxidants). Both types are critical, although endogenous antioxidants are more powerful.

Some of the antioxidants that we make are large enzymatic molecules like superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx). These compounds are enzymes and their production is increased in response to oxidative stress. Other endogenous antioxidants include smaller compounds like thiols (such as alpha lipoic acid), ubiquinone (coenzyme Q10), and uric acid. These molecules respond less dynamically to acute oxidative stress and instead exert consistent antioxidative actions. Antioxidant enzymes work as a team to neutralize free radicals.

Going back to our police metaphor, SOD is the first sheriff to step into the gun fight with a free radical robber. SOD fires the first shot and wounds the free radical, transforming it into a less harmful oxygen-based free radical. The next two sheriffs, catalase and glutathione peroxidase then step in and finish the job, converting the oxygen-based free radical into harmless water and oxygen. The smaller antioxidants such as alpha lipoic acid could be thought of as the sheriff’s deputies and they are essential in providing complete defense. Alpha-lipoic acid, for instance, is able to regenerate glutathione (as well as vitamins E and C) after a show-down with a free radical.

Exogenous antioxidants include compounds such as vitamin C (ascorbic acid), vitamin E (tocopherols and tocotrienols), carotenes, flavonoids, and phenols. The richest sources of dietary antioxidants are fruits and vegetables. In fact, fruits and vegetables are jam-packed with antioxidants, which is why a diet high in these foods over a lifetime is consistently correlated with lowered risk of major chronic diseases.

Many consider glutathioneto be the most important

of our body’s antioxidants,especially since it is found in

every cell of the body.

What is The Role of Glutathione?

GlutathionePeroxidases

(GPXs)

• Detoxified products

GlutathioneS-

transfereses(GSTs)


Peroxidestoxins, drugs, carcinogensfree radicals


Glutamic acid

cystein

glycin

Inside the cell, glutathione acts as the primary antioxidant against free radicals produced by toxic chemicals and viruses. It also plays an essential role in the liver’s detoxification process by binding detoxified reactive molecules into non-reactive compounds that can then be excreted. This powerful antioxidant is also involved in DNA repair. Glutathione preserves the structure and function of key cellular proteins and helps to transport amino acids across the cell membrane. It also boosts our immunity.The role of GSH as an antioxidant is extremely important. It is able to trade electrons in such a way as to regenerate itself and other antioxidants into their active forms. Glutathione is produced within our cells; the amount produced is dependent upon the availability of cysteine, one of its component amino acids. When the cellular concentration of glutathione reaches a certain level, the cell will not produce more until the level goes down. Despite being the most common antioxidant within cells, glutathione deficiency does occur. Deficiency is linked with several diseases and presumably replenishing glutathione in individuals with these diseases may beneficial.

Aging is associated with a depletion of glutathione. Oxidative tissue damage, particularly to the mitochondria, is now a widely accepted explanation for aging. Intracellular glutathione is one of the most important antioxidants to prevent this oxidative aging process. Various animal studies have found that aged animals have lower glutathione levels in all of their major organs than young animals. This decline in tissue glutathione is associated with a decline in the function of those organs. This same phenomenon has been observed in adults. People with chronic kidney disease have very low levels of glutathione in their kidneys and, as the kidney damage progresses, the ability of the kidney cells to make glutathione decreases even further. This creates a vicious cycle of continued kidney damage.

As we age, our production of glutathione decreases in all cells. Sixty-year olds have significantly less glutathione in their blood than 20-year olds. Also, as we age, we may inadvertently do things which empty out our glutathione stores. Many older people experience various body aches and pains and turn to anti-inflammatory medications for relief. Unfortunately, frequent use of acetaminophen (Tylenol), a commonly used anti-inflammatory, depletes glutathione. A low glutathione level in older adults worsens their health status in many more ways than experiencing pain. Older people with deficient glutathione feel unhealthy overall. This is because the decline in antioxidant protection associated with aging is coupled with the effects of cumulative oxidative damage from a lifetime of exposure to free radicals. The net result is chronic disease and poor health.

The Glutathione-Rich Lifestyle

• Red meat, organ meats (such as liver), and yeast (particularly Brewer’s yeast)

• Sunflower seeds, spinach, and avocado

• Broccoli, cauliflower, Brussels sprouts, and cabbage

• Brazil nuts, meat, and seafood

• Asparagus, spinach, garlic, avocado, squash, zucchini, potatoes, melons, grapefruit, strawberries, and peaches Glutathione selenium

Alpha lipoic acidRiboflavin

Cyanohydroxybute

ne

Increasing Glutathione Production

If you think you might benefit from glutathione supplementation, you may be interested in first determining if you are low in glutathione. Unfortunately, testing for glutathione is not

easy. There are some tests which purport to measure the glutathione in red blood cells. The problem with these tests is that the blood drawn from the person is transported in a

test tube to the central lab and then analyzed some time later. Glutathione is a strong antioxidant, but the blood that surrounds it is easily damaged by oxidation as soon as the test tubes are exposed to light. As glutathione soaks up the free radicals formed by this

oxidative damage, the amount of glutathione in the red blood cells decreases. This makes these blood tests generally inaccurate.

Supplements to Increase Glutathione

N-acetyl cysteine:

One way to increase glutathione levels is to supplement with glutathione precursors. One of the most effective of these

supplements is N-acetyl-cysteine (NAC). NAC is derived from the amino acid l-cysteine, and is a precursor to glutathione. NAC is quickly metabolized into glutathione once it enters the body. It

has been shown to increase glutathione levels in numerous scientific studies and clinical trials. Of note, NAC is approved by

the FDA for the treatment of acetaminophen overdose. Acetaminophen depletes glutathione and rapid depletion as the result of overdose is the cause of the life threatening damage to

the liver. NAC is typically taken in doses between 250 mg and 1,500 mg and is well tolerated.

Alpha lipoic acid:Another supplement that will increase glutathione is

alpha-lipoic acid (ALA). ALA has demonstrated benefit in a number of diseases including diabetes,

drug-induced heart damage, kidney disease, glaucoma, and poorly-healing wounds. It has been studied in doses ranging from 300 mg to 1,200 mg

daily, although doses above 1,200 mg can cause nausea, vomiting, and dizziness. ALA should not be

taken by people with hypothyroidism, thiamine deficiency or concurrently with chemotherapy drugs

unless under medical supervision.

Milk thistle:Milk thistle, or Silymarin officinalis, is an herb that exerts potent antioxidant effects, especially in the liver. A group of flavonoids

in milk thistle, collectively referred to as silymarin, is responsible for the antioxidant effects. One of the most important ways milk

thistle protects the liver is by preventing the depletion of glutathione. By preserving glutathione stores, milk thistle can protect the liver from many industrial toxins such as carbon

tetrachloride, as well as alcohol and even the very poisonous Amanita mushroom. Milk thistle supplements are often

standardized to contain 70 to 80 percent silymarin. Dosages ranging from 160 to 800 mg of a standardized extract have been studied in the treatment of hepatitis and diabetic cirrhosis. Milk

thistle is generally well tolerated and without side effects.

Other nutrients which help to raise the level of glutathione in the body can be supplemented individually. These nutrients include choline,

pycnogenol (pine bark extract), vitamin B12, and selenium. In addition, supplementation with

vitamins C and E will increase glutathione levels. All of these nutrients have other health benefits so, depending upon the health conditions you may

have, different supplements may be more appropriate.

Glutathione Supplementation

While supplementing glutathione precursors as a means to increase tissue levels of glutathione can be effective, this does not always work. For instance, numerous studies using NAC to increase glutathione levels in individuals with COPD failed to show higher concentrations of glutathione in the blood or the lungs, even at doses of 1,800 mg daily. Various aerosol preparations of glutathione have been developed as a way to raise glutathione levels, primarily in the lung. While glutathione levels do increase, glutathione disulfide or oxidized glutathione levels increase as well. Glutathione disulfide can be problematic in people with COPD or asthma because this compound increases bronchiole constriction, which, in turn, compromises airflow. Furthermore, and rather disappointingly, aerosolized glutathione in some studies has failed to decrease oxidation in the lung.

An alternative way to augment tissue glutathione levels is to supplement directly with glutathione. Many healthcare professionals assert that directly supplementing glutathione will not result in increased tissue levels. Because glutathione is a large molecule composed of three amino acids, these individuals believe that glutathione is too big to be absorbed through the intestine and into the blood. Instead, it has been said that orally ingested glutathione is broken down in the intestines and in the liver, and the component amino acids are either eliminated or perhaps used for a variety of other purposes. The truth about what happens to orally administered glutathione appears to be much more complex.

While the most effective daily dose is unknown, preclinical data suggests that fairly high levels of this supplement are necessary to produce significant increases in tissue levels of glutathione. Without the guidance of human trial data, dosage recommendations for glutathione range from 100 mg to 3,000 mg daily. Too much supplemental glutathione could worsen the body’s own production of glutathione. It would seem most prudent to utilize as many diverse ways of increasing glutathione as possible.

Including glutathione-rich foods in the daily diet, avoiding, Coupled with the natural decline of our most prevalent antioxidant, glutathione, tissue oxidation and the subsequent diseases seems inevitable unless we take charge of our health and commit ourselves to diligently strengthening our antioxidant defenses.glutathione-destroying foods, and supplementing with both glutathione precursors and glutathione itself may be an effective strategy to appropriately increase tissue glutathione levels. It is also important to remember that the need for glutathione appears to be the greatest in the morning before the first meal of the day, an optimal time for supplementation.

Setria® is a widely studied glutathione ingredient that is available in several different natural health products. This reduced, concentrated pure form of L-glutathione is made available through Kyowa Hakko Bio Co Ltd., a world leader in the development, manufacturing, and marketing of pharmaceuticals, nutraceuticals, and food products.

In general, glutathione appears to be a safe supplement. There have been no reported adverse reactions to supplemental glutathione taken orally, inhaled, used intramuscularly or intravenously. However, people with cancer should not supplement with glutathione because, theoretically, it may stimulate the growth of existing cancerous tumors. Doses of 3 g of oral glutathione have been used experimentally with no adverse effects. The long-term effects of glutathione supplementation at any level are unknown. Glutathione is not recommended for children and is unlikely to be of benefit to young adults.

Final ThoughtsThe seemingly inevitable march of aging seems fraught with degenerative diseases and ill health. This unhealthy aging is, for the most part, the result of accumulating oxidative damage. Free radicals produced during the normal course of the activities of daily living combined with those produced from environmental pollutants slowly but surely overwhelm our body’s antioxidative defenses. Coupled with the natural decline of our most prevalent antioxidant, glutathione, tissue oxidation and the subsequent diseases seems inevitable—unless we take charge of our health and commit ourselves to diligently strengthening our antioxidant defenses. Including glutathione-rich foods in our diet, spending time in contact with the earth, and supplementing with glutathione precursors and glutathione itself will help to rebuild our antioxidant protection. Although we may not be able to reverse aging, we can certainly help ourselves age with more health and vitality.

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