Wednesday, January 23, 2008

Selenium

Selenium is a co-factor for the enzyme glutathione peroxidase.

Selenium supplements have become popular because some studies suggest they may play a role in decreasing the risk of certain cancers, and in how the immune system and the thyroid gland function.

However, too much selenium can cause some toxic effects including gastrointestinal upset, brittle nails, hair loss and mild nerve damage.

Click here for more about Glutathione and its benefits to our body.

Consult your health professional before taking any kind of medicines.

Glutathione Strenthens your immune system

Lymphocytes, cells vital for your immune system , depend on Glutathione for their proper function and replication.IMMUNOLOGY 61: 503-508 1987

Balloon Flower Root

Changkil saponins (CKS) isolated from the roots of the Chinese herbal medicine, Platycodon grandiflorum A.

DC (Campanulaceae), commonly called Balloon Flower Root or Jie Geng, have been found to increase intracellular glutathione (GSH) content and significantly reduce oxidative injury to liver cells, minimise cell death and lipid peroxidation.

Detoxifies your body
Antioxidants are well documented and known to possess vital roles in health maintenance and disease prevention. Glutathione is your cell's own major antioxidant.

Maintaining elevated Glutathione levels aids the body's natural antioxidant function.
Biochemical Pharmacology 47: 2113-2123 1994

Curcumin (Turmeric)

Treatment of brain cells called astrocytes, with the Indian curry spice, curcumin (turmeric) has been found to increase expression of the glutathione S-transferase and protect neurons exposed to oxidant stress.

Glutathione in Health and Disease

It is believed that glutathione has an important role to play in the prevention and treatment of disease.

It may in the future be considered as important to health as an alkaline diet, exercise and alkaline lifestyle.

Clinical tests show that raised glutathione levels may address some of the eight major health issues of our time. '

Click here for more about Glutathione and its benefits to our body.

Undenatured Whey Protein Isolate

Whey protein contains proteins like alpha-lactalbumin which is is rich in sulphur-containing amino acids.

Heating or pasteurization destroys the delicate disulphide bonds that give these proteins their bioactivity.

Undenatured whey protein is a non-heated product that preserves bioactive amino acids like cystine. It has been shown in numerous scientific studies and clinical trials to optimize glutathione levels.

Glutathione's three major roles in the body are summarized by the letters A-B-C.
- Anti-oxidant- Blood Booster- Cell Detoxifier

Click here for more about Glutathione and its benefits to our body.

Natural Foods That Boost Glutathione Levels

Asparagus is a leading source of glutathione.

Foods like broccoli, avocado and spinach are also known to boost glutathione levels.

Raw eggs, garlic and fresh unprocessed meats contain high levels of sulphur-containing amino acids and help to maintain optimal glutathione levels.

THE MAX GXL is a PATENTED High Performance

Glutathione is an important and powerful antioxidant and is the body’s best anti-aging agent.

Alpha Lipoic Acid

Food sources and dietary supplements that help boost glutathione levels naturally.

Alpha Lipoic Acid

Made naturally in body cells as a by-product of energy release, ALA increases the levels of intra-cellular glutathione, and is a natural antioxidant with free radical scavenging abilities.

It has the ability to regenerate oxidized antioxidants like Vitamin C and E and helps to make them more potent.

ALA is also known for its ability to enhance glucose uptake and may help prevent the cellular damage accompanying the complications of diabetes. It also has a protective effect in the brain.

Click here for more about Glutathione and its benefits to our body.

Milk Thistle, Silymarin

Food sources and dietary supplements that help boost glutathione levels naturally.

Milk Thistle, Silymarin

Milk thistle is a powerful antioxidant and supports the liver by preventing the depletion of glutathione. Silymarin is the active compound of milk thistle.

It is a natural liver detoxifier and protects the liver from many industrial toxins such as carbon tetrachloride, and more common agents like alcohol.

Click here for more about Glutathione and its benefits to our body.

N-Acetyl-Cysteine (NAC)

Food sources and dietary supplements that help boost glutathione levels naturally.

N-Acetyl-Cysteine (NAC)

It is derived from the amino acid L-Cysteine, and acts as a precursor of glutathione.

NAC is quickly metabolized into glutathione once it enters the body.

It has been proven in numerous scientific studies and clinical trials, to boost intracellular production of glutathione, and is approved by the FDA for treatment of accetaminophen overdose.

Because of glutathione mucolytic action, NAC is commonly used in the treatment of lung diseases like cystic fibrosis, bronchitis and asthma.

Click here for more about Glutathione and its benefits to our body.

Boost Glutathione Naturally

Glutathione, the body's master antioxidant and detoxifier, is one of the 14 "Superfoods" listed in SuperFoods Rx : Fourteen Foods That Will Change Your Life, co-authored by Dr Steven Pratt.

Glutathione levels cannot be increased to a clinically beneficial extent by orally ingesting a single dose of Glutathione.

This is because Glutathione is manufactured inside the cell, from its precursor amino acids, glycine, glutamate and cystine.

Hence food sources or supplements that increase Glutathione must either provide the precursors of glutathione, or enhance its production by some other means.

The manufacture of Glutathione in cells is limited by the levels of its sulphur-containing precursor amino acid, cysteine.

Cysteine - as a free amino acid - is potentially toxic and is spontaneously catabolized or destroyed in the gastrointestinal tract and blood plasma.

However, when it is present as a cysteine-cysteine dipeptide, called cystine, it is more stable than cysteine.

Consuming foods rich in sulphur-containing amino acids can help boost Glutathione levels. by: Priya F Shah

Click here for more about Glutathione and its benefits to our body.

Tuesday, January 22, 2008

Exercise builds brain health: key roles of growth factor cascades and inflammation

Human and other animal studies demonstrate that exercise targets many aspects of brain function and has broad effects on overall brain health.

The benefits of exercise have been best defined for learning and memory, protection from neurodegeneration and alleviation of depression, particularly in elderly populations.

Exercise increases synaptic plasticity by directly affecting synaptic structure and potentiating synaptic strength, and by strengthening the underlying systems that support plasticity including neurogenesis, metabolism and vascular function.

Such exercise-induced structural and functional change has been documented in various brain regions but has been best-studied in the hippocampus - the focus of this review.

A key mechanism mediating these broad benefits of exercise on the brain is induction of central and peripheral growth factors and growth factor cascades, which instruct downstream structural and functional change.

In addition, exercise reduces peripheral risk factors such as diabetes, hypertension and cardiovascular disease, which converge to cause brain dysfunction and neurodegeneration.

A common mechanism underlying the central and peripheral effects of exercise might be related to inflammation, which can impair growth factor signaling both systemically and in the brain.

Thus, through regulation of growth factors and reduction of peripheral and central risk factors, exercise ensures successful brain function.

by: Carl W Cotman, Nicole C Berchtold, Lori-Ann Christie
Trends in Neurosciences, Vol. 30, No. 9. (September 2007), pp. 464-472

Important Roles of Glutathione
Fight against oxidative cell damage (Free Radicals)
Protein Synthesis
Amino Acid transport
Cellular detoxification
Immune system enhancement
Enzyme activation
Fight Inflammation
ATP (energy) production
Our cells are constantly under attack by Free Radicals, which can cause a reduction of our cells ability to function optimally.

Click here for more about Glutathione and its benefits to our body.

Effect of glutathione depletion on antioxidant enzymes in the epididymis, seminal vesicles, and liver and on spermatozoa motility in the aging rat

Effect of glutathione depletion on antioxidant enzymes in the epididymis, seminal vesicles, and liver and on spermatozoa motility in the aging brown Norway rat.
by: EV Zubkova, B Robaire - Biol Reprod, Vol. 71, No. 3. (September 2004), pp. 1002-1008.

Reactive oxygen species (ROS) play a role in male infertility, where excessive amounts impair spermatozoal motility.

Epididymal antioxidant enzymes protect spermatozoa from oxidative damage in the epididymal lumen. Antioxidant secretions from the seminal vesicle protect spermatozoa after ejaculation.

As it is known that with age there is increased generation of ROS, the goals of this study were to determine how aging affects the response of antioxidant enzymes in the epididymis, seminal vesicles, and liver to l-buthionine-S,R-sulfoximine (BSO) mediated glutathione (GSH) depletion, and to examine the impact of GSH depletion on motility parameters of spermatozoa from the cauda epididymidis in young (4-mo-old) and old (21-mo-old) rats.

Levels of GSH and glutathione disulfide (GSSG), as well as activities of glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase, were measured in the caput, corpus and cauda epididymidis, seminal vesicles, and liver.

Spermatozoal motility was assessed by computer-assisted sperm analysis. Significant age-related changes in antioxidant enzyme activities were found in the liver and cauda epididymidis.

Glutathione age was most evident in the cauda epididymidis, seminal vesicles, and liver, where antioxidant enzyme activities changed significantly.

Additionally, spermatozoa motility was adversely affected after BSO treatment in both age groups, but significantly more so in older animals.

In summary, the male reproductive tissues and liver undergo age-related changes in antioxidant enzyme activities and in their response to GSH depletion.

THE MAX GXL is a PATENTED High Performance Formula which:Dramatically Raises Your Energy LevelSlows Down The Aging ProcessStrengthens Your Immune SystemFights Inflammation and Diseases of AgingImproves Athletic Performance & RecoveryDetoxify Your Body

Vitamin E on glutathione-dependent enzymes

Reactive oxygen species and various electrophiles are involved in the etiology of diseases varying from cancer to cardiovascular and pulmonary disorders.

The human body is protected against damaging effects of these compounds by a wide variety of systems. An important line of defense is formed by antioxidants.

Vitamin E (consisting of various forms of tocopherols and tocotrienols) is an important fat-soluble, chain-breaking antioxidant.

Besides working as an antioxidant, this compound possesses other functions with possible physiological relevance.

The glutathione-dependent enzymes form another line of defense.

Two important enzymes in this class are the free radical reductase and glutathione S-transferases (GSTs).

The GSTs are a family of phase II detoxification enzymes. They can catalyze glutathione conjugation with various electrophiles.

In most cases the electrophiles are detoxified by this conjugation, but in some cases the electrophiles are activated.

Antioxidant do not act in isolation but form an intricate network. It is, for instance, known that vitamin E, together with glutathione (GSH) and a membrane-bound heat labile GSH-dependent factor, presumably an enzyme, can prevent damaging effects of reactive oxygen species on polyunsaturated fatty acids in biomembranes (lipid peroxidation).

This manuscript reviews the interaction between the two defense systems, vitamin E and glutathione-dependent enzymes.

On the simplest level, antioxidant such as vitamin E have protective effects on glutathione-dependent enzymes; however, we will see that reality is somewhat more complicated.

by: RI van Haaften, GR Haenen, CT Evelo, A Bast
Drug Metab Rev, Vol. 35, No. 2-3. (g 2003), pp. 215-253.

Click here for more about Glutathione and its benefits to our body.

Role of glutathione in cellular resistance to alkylating agents

Both elevated glutathione levels and increased activity of the enzyme glutathione S-transferase have been associated with the resistance of cells to alkylating agents.

We have demonstrated that one mechanism of this resistance is the inactivation of the alkylating agents by conjugation with glutathione.

This conjugation can be catalyzed by glutathione S-transferase. For the nitrogen mustard agents we have studied, both the spontaneous and enzyme catalyzed reactions proceed through the aziridinium intermediates of the alkylating agents, and the [alpha] isoenzymes of GST are involved.

In a study of cyclophosphamide resistant medulloblastoma cell lines elevated cellular concentrations of glutathione correlated well with the resistance of the cell lines.

by: Michael O Colvin, Henry S Friedman, Michael P Gamcsik, Catherine Fenselau, John Hilton
Advances in Enzyme Regulation, Vol. 33 (1993), pp. 19-26

Involvement of uric acid and glutathione antioxidant defenses

Insulin neuroprotection against oxidative stress in cortical neurons-Involvement of uric acid and glutathione antioxidant defenses.

In this study we investigated the effect of insulin on neuronal viability and antioxidant defense mechanisms upon ascorbate/Fe(2+)-induced oxidative stress, using cultured cortical neurons.

Insulin (0.1 and 10 muM) prevented the decrease in neuronal viability mediated by oxidative stress, decreasing both necrotic and apoptotic cell death.

Moreover, insulin inhibited ascorbate/Fe(2+)-mediated lipid and protein oxidation, thus decreasing neuronal oxidative stress.

Increased 4-hydroxynonenal (4-HNE) adducts on GLUT3 glucose transporters upon exposure to ascorbate/Fe(2+) were also prevented by insulin, suggesting that this peptide can interfere with glucose metabolism.

We further analyzed the influence of insulin on antioxidant defense mechanisms in the cortical neurons. Oxidative stress-induced decreases in intracellular uric acid and GSH/GSSG levels were largely prevented upon treatment with insulin.

Inhibition of phosphatidylinositol-3-kinase (PI-3K) or mitogen-induced extracellular kinase (MEK) reversed the effect of insulin on uric acid and GSH/GSSG , suggesting the activation of insulin-mediated signaling pathways.

Moreover, insulin stimulated glutathione reductase (GRed) and inhibited glutathione peroxidase (GPx) activities under oxidative stress conditions, further supporting that insulin neuroprotection was related to the modulation of the glutathione redox cycle.

Thus, insulin may be useful in preventing oxidative stress-mediated injury that occurs in several neurodegenerative disorders.

by: AI Duarte, MS Santos, CR Oliveira, AC Rego

Click here for more about Glutathione and its benefits to our body.

Monday, January 21, 2008

Types of Free Radicals

Where do free radicals come from?

• Amino Acid transport
• Cellular detoxification
Immune system enhancement
• Enzyme activation

Types of Free Radicals
The fight against free radicals is often a tricky one. There is not a mythical, ambiguous, or singular form on free radical. Science has confirmed that there are many different types of free radicals including:

• Superoxide
• Hydrogen Peroxide
• Single Oxygen and Hydroxyl Radicals

Important Note: Not all antioxidants can sufficiently match up with all types of free radicals.

The great news about Glutathione is that regardless of the type of free radical, Glutathione has the ability to properly match up and neutralize it, thus increasing cellular protection and function

Click here for more about Glutathione and its benefits to our body.

Dr. Robert Keller and Glutathione

Robert Keller MD, MS, FACP, has been named as one of the world’s 2,000 Outstanding Scientists of the 21st Century, and has served on the scientific review panels for the National Institutes of Health and the VA.

The Consumers’ Research Council has named Dr. Keller one of America’s “Top Physicians in 2003, 2004, 2005, 2006, and 2007 in the fields of Internal Medicine, Immunology and Hematology.

Dr. Keller has served on the faculties of the Mayo Graduate School of Medicine, the University of Wisconsin and the Medical College of Wisconsin (Marquette Univ.) He has published more than 100 original articles in various scientific and medical journals and has been awarded several patents.

Dr Keller was elected to The Board of Governors of the American Academy of HIV medicine.

Read Robert H. Keller, MD, MS, FACP, AAHIVS CurriculmVitae

Dr. Robert H. Keller, one of the world’s leading scientists dedicated 10 years of research and development into MaxGXL to assist the world in its quest for a higher quality of health.Out of all the biological processes that Dr Keller could have focused his attention on, he chose to investigate a way to naturally optimize the body’s production of glutathione.

Glutathione is a fairly tricky word, but your body relies on its function every single day.


Important Roles of Glutathione

Fight against oxidative cell damage (Free Radicals)
Protein Synthesis
Amino Acid transport
Cellular detoxification
Immune system enhancement
Enzyme activation
Fight Inflammation
ATP (energy) production
Our cells are constantly under attack by Free Radicals, which can cause a reduction of our cells ability to function optimally.

Click here for more about Glutathione and its benefits to our body.

Glutathione - MaxGXL

Supplements Containing Glutathione Alone Will NOT Increase The Body’s GSH Levels!It is pointless to purchase supplements that merely contain glutathione, because the digestive system breaks down ingested glutathione and it will not be absorbed into your system.

MaxGXL™ provides the proper nutrients needed to promote the body's own ability to manufacture and absorb glutathione. MaxGXL™ also aids in liver support by destroying environmental poisons helping the liver to function as the main production site and storehouse for glutathione.

THE MAX GXL is a PATENTED High Performance Formula which:
Dramatically Raises Your Energy Level
Slows Down The Aging Process
Strengthens Your Immune System
Fights Inflammation and Diseases of Aging
Improves Athletic Performance & Recovery
Detoxify Your Body

Glutathione Fact 3

Increasing Age and Other Factors Reduce the Body’s Production and Utilization of GSH.

Research has shown that individuals who have low levels of glutathione are susceptible to chronic illness.

Research shows that GSH levels decline by 8% to 12% per decade, beginning at the age of 20.

Levels of glutathione are further reduced by continual stress upon the immune system such as illness, infection, and environmental toxins. As we now know, a lowered immune system can bring about illness and disease. This is a ferocious cycle.

While you need glutathione for a productive immune system , a weakened immune system hampers the production of glutathione.

Detoxifies your body
Antioxidants are well documented and known to possess vital roles in health maintenance and disease prevention. Glutathione is your cell's own majorAntioxidants. Maintaining elevated glutathione levels aids the body's natural antioxidant function.Biochemical Pharmacology 47: 2113-2123 1994

Glutathione Fact 2 - slow down the aging process

Glutathione has been shown to slow down the aging process, detoxify and improve liver function, strengthen the immune system, and reduce the chances of developing cancer.

Glutathione also works to help improve mental functions, increase energy, improve concentration, permit increased exercise, and improve heart and lung function - just to name a few.

Among the uses that have been reported for glutathione are:
treatment of poisoning, particularly heavy metal poisons
treatment of idiopathic pulmonary firbosis
increasing the effectiveness and reducing the toxicity of cis-platinum, a chemo drug used to treat breast cancer
treating Parkinson's disease
lowering blood pressure in patients with diabetes
increasing male sperm counts in humans and animals
treatment of liver cancer
treatment of sickle cell anemia

Glutathione Fact 1 - produced naturally in our cells

Glutathione (GSH) is a small protein produced naturally in our cells when certain required elements are present

It functions both as an antioxidant and an antitoxin and is a major defense system against illness and aging.

Our glutathione level actually indicates our state of health and can predict longevity. Although there are more than 60,000 published papers on the beneficial effects of glutathione replacement, it is still largely ignored by mainstream medicine.

In the near future the importance of glutathione will be widely recognized because it has the ability to boost the immune system and fight off the damage of free radicals on the cells.

Glutathione's three major roles in the body are summarized by the letters A-B-C.
- Anti-oxidant- Blood Booster- Cell Detoxifier

Glutathione - your body's master antioxidant

Glutathione (GSH) is the most powerful, prevalent antioxidant in your body!

GSH is manufactured by your cells and all you need to do is to provide the raw materials for your body to produce glutathione optimally.

Increasing your glutathione level will naturally increase your energy, detoxify your body and strengthen your immune system.

Dr. Robert Keller
Robert Keller MD, MS, FACP, has been named as one of the world’s 2,000 Outstanding Scientists of the 21st Century, and has served on the scientific review panels for the National Institutes of Health and the Veterans Administration.

MaxGXL™ provides the proper nutrients needed to promote the body's own ability to manufacture and absorb glutathione. MaxGXL™ also aids in liver support. by destroying environmental toxins, thus helping the liver to function as the main production site and storehouse for glutathione. The graph below shows the increase in glutathione levels experienced by 4 groups of patients. Group 1 (normal health patients) were tested after 6 months of use, while Groups 2, 3 and 4 (HIV, Hepatitis C, and Chronic Viral Illness respectively) were tested after only 3 months of the MaxGXL regimen.

Click here for more about Glutathione and its benefits to our body.

Friday, January 18, 2008

HOW TO GET GLUTATHIONE INTO YOUR CELLS

Glutathione is made up of three amino acids, glycine, glutamic acid and cysteine. Each cell produces its own GSH according to need within itself.

The determining factor as to how much it can make to ultimately keep levels up to the needed 70% in the active form...is determined by the availability of the amino acid cysteine. The production of cysteine becomes less and less efficient as we get older going into a steady decline by around age 55 onward.

This is just at a time when its most needed to protect our brains and neurological system from syndromes such as Alzheimer's Disease and dementia, which are now becoming more and more common.

Before we go further, let me explain "active" form (technically called the "reduced" form) and "inactive" (technically called the "oxidized" form) forms of glutathione. The active form is the one that can perform all the functions listed above act as a powerful antioxidant, work to combat diseases of aging and a potent player in detoxification. It is often shown in written works as "GSH".

The inactive form is present when GSH has done its work donating electrons and needs to regenerate itself which it can do. Its usually shown as GSSG (lacking the H..because it gave it away to stabilize some other molecule).

In a healthy situation, the percentage of GSH is about 90% with only 10% of Glutathione existing as GSSG. When these ratios change and there is more and more GSSG present, that is when the cell becomes sick, and is vulnerable to attack from toxins and microbes. If GSH falls below 70%...the cells/organ/person is in HUGE trouble!

There is one provison to this situation. If GSH is "used" to clear up a situation from our own metabolism, then it can regenerate itself just fine. HOWEVER if its used to combat "xenobiotics" or toxins from the outside of our bodies, such as chemicals, heavy metals, toxins, etc., then it cant regenerate.

This is where we run into trouble today as our food is not replenishing us the way it should and supplementing for Glutathione is tricky

Glutathione's three major roles in the body are summarized by the letters A-B-C.
- Anti-oxidant- Blood Booster- Cell Detoxifier

Learn more about Glutathione click here

GSH has five major functions

Antioxidant:
Antioxidant is a substance that neutralizes destructive free radicals; some are manufactured by the metabolic processes of the body, others are derived from foods, the air we breath, exercise, stress and disease.GSH is the most powerful Antioxidant occurring naturally in the cells of the body. Through its significant reducing power, GSH also makes major contributions to the recycling of other Antioxidant that have become oxidized. Healthy cells homeostatically oppose free radicals through the use of Antioxidant, of which GSH plays a significant role. The effectiveness of other Antioxidant like vitamins C and E depends on the availability of GSH.

Help Prevent Disease:
Oxidative related diseases: accelerated aging, cell destruction, causes damage to DNA cellular patterns which leads to cancer, arteriosclerosis, coronary artery disease, Parkinson’s disease, diseases of the immune system, diabetes, cataract formation, Alzheimer’s, macular degeneration, COPD, allergy/asthma, stroke.

Detoxification:
GSH also plays a main role in detoxification..primarily in Phase II Liver detox. It "binds" to many toxins by its sulfur molecules and aids in forming a complex which the body then rids itself of.

Immune System Support:
When the immune system responds to an invader, it releases a blitz of free radicals to aid in the offensive agent's demise. This could create damage to local tissue and your body, but GSH rallies around the area to quench the free radicals that are produced in excess.

Protection from Radiation:
A recent research article published in the journal Radiology states that “radiation from a single whole-body scan is equal to that from 100 mammograms and is similar to that received by survivors of the atomic bombings of Hiroshima and Nagasaki, Japan – about 1 mile from the explosions – according to radiation biologist, David J. Brenner of Columbia University. The radiation from one scan is enough to produce a tumor in one out of 1200 people, and for those who have annual scans the risk increases to one tumor in every 50 people. With inadequate intracellular GSH the risk is greatly increased.

How much glutathione is enough?

Unfortunately, there is no Recommended Dietary Allowance (RDA) for glutathione to indicate how much is enough.

One hundred milligrams each day is the usual recommended dosage for glutathione.

THE MAX GXL is a PATENTED High Performance Formula which:

Dramatically Raises Your Energy Level
Slows Down The Aging Process
Strengthens Your Immune System
Fights Inflammation and Diseases of Aging
Improves Athletic Performance & Recovery
Detoxifies Your Body

What conditions or problems is glutathione used for?

Glutathione peroxidase may help delay the physical effects and problems of aging.

Adequate amounts of Glutathione are needed to help the immune system fight against free-radical damage, infection, and illness.

Glutathione may help prevent or lessen symptoms of conditions like asthma and rheumatoid arthritis.

Learn more about Glutathione click here

Glutathione's three major roles in the body are summarized by the letters A-B-C.
- Anti-oxidant- Blood Booster- Cell Detoxifier

What are the potential advantages of taking glutathione ?

Glutathione peroxidase (GSH) is your body’s most abundant natural antioxidant, and appears to have an anti-aging effect on the body. Advantages of glutathione:

Glutathione helps eliminate toxins from the body, and keeps the eyes, central nervous system, and immune system healthy and strong.

GSH also helps turn carbohydrates into energy, and prevents the buildup of oxidized fats that may contribute to atherosclerosis.

Click here for more about Glutathione and its benefits to our body.

Glutathione peroxidase (GSH) is your body’s most abundant natural antioxidant.

GSH protects your vision, boosts your immune system, helps turn carbohydrates into energy, and prevents the buildup of oxidized fats that may contribute to atherosclerosis.

Glutathione is a compound classified as a tripeptide made of three amino acids: cysteine, glutamic acid, and glycine. Glutathione is also found in every part of the body, especially the lungs, intestinal tract, and liver.

The body produces and stores the largest amounts of GSH in the liver, where it is used to detoxify harmful compounds so that they can be removed from the body through the bile.

The liver also supplies GSH directly to red and white blood cells in the bloodstream; it helps keep red blood and white blood cells healthy to maximize the disease-fighting power of the immune system.

Glutathione also appears to have an anti-aging affect on the body. GSH levels decline with age, and a lack of Glutathione has been shown to leave the body more vulnerable to damage by free radicals, thus speeding up oxidation (wearing down) of the body.

A Glutathione deficiency can have a devastating effect on the nervous system, causing such symptoms as lack of balance and coordination, mental disorders, and tremors.

Any illness (even a bad cold), chronic disorders such as asthma and rheumatoid arthritis, injury, or heavy exposure to pollutants can cause a GSH deficiency.

This is because your body uses more GSH when it is supporting white blood cells and ridding the body of toxins.

Glutathione is found in almost all fruits and vegetables. Acorn squash, asparagus, avocado, cantaloupe, grapefruit, okra, orange, peach, potato, spinach, strawberries, tomato, watermelon, and zucchini are all good sources of GSH. Some vegetables, such as broccoli, cabbage, Brussels sprouts, cauliflower, kale, and parsley, not only provide GSH, but also actually stimulate the body produce more of this powerful antioxidant.

Cooking destroys a lot of the Glutathione in fresh fruits and vegetables, so you can get the most GSH from these foods by eating them raw or steamed.

Eating foods high in glutamine, such as lean meats, eggs, wheat germ, and whole grains, can also stimulate the liver to produce more GSH.

There is no Recommended Dietary Allowance (RDA) for GSH, but supplements have no known harmful side effects. Glutathione supplements can be expensive, but there is some question about the body’s ability to absorb GSH efficiently in supplemental form. If you want to take GSH supplements, just make sure to take them with meals to maximize absorption.

Click here for more about Glutathione and its benefits to our body.

7 Natural Ways To Increase Glutathione Production

L-Cysteine
Since the amount of cysteine in our body determines how much glutathione your body can make, why not just eat cysteine as a supplement? Well, you can, but research shows there would be negligible benefits and potential risks. Cysteine taken as a dietary supplement can promote hypercysteinemia and potential toxicity.
L-Methionine
Methionine is indeed a precursor of glutathione but the metabolic transformation of methionine into glutathione is a complex process which has the potential for "going astray".
Melatonin
Melatonin is produced by the pineal gland in the brain and has many roles in the body, one being its ability to raise glutathione levels in certain tissues of the body, including brain, liver, and muscle tissue. The long term safety of products that promote melatonin production has not been established and should be used in consultation with appropriate health professionals.
Glutamine
Glutamine is an amino acid found in abundance in our body. It is tremendously beneficial to the body and is easily found in a healthy diet. Also, supplemental glutamine must be kept absolutely dry or it will degrade into ammonia, a toxin to the body. Due to its abundance in a healthy diet and the risks of storing it, glutamine is not an ideal supplement.
Lipoic Acid (alpha-lipoic acid)
Lipoic acid occurs naturally in the body but can also be taken as a supplement with effectiveness. This supplement works well in conjunction with healthy levels of glutathione but studies show that if taken by a person whose glutathione levels are too low, lipoic acid actually promotes oxidation.
Silymarin (milk thistle)
This herbal extract seems to stimulate the growth and regeneration of damaged liver cells but also has been shown to significantly increase glutathione production. However, some toxic reactions are noted by some, such as gas, cramps and diarrhea.
Whey Proteins
Fresh or "bioactive" milk whey contains potent glutathione precursors. Unfortunately, by the time milk reaches your table, it has been pasteurized and has lost its bioactivity, and its glutathione enhancing benefits.

Click here for more about Glutathione and its benefits to our body.

The natural health community agrees that helping your body increase its glutathione production is extremely beneficial. Given the many choices above, it may be difficult to know where to start.

THE MAX GXL is a PATENTED High Performance.

Master Antioxidant

Despite the fact that you live in an unhealthy world, surrounded by unhealthy temptations, distractions and challenges, in one day you may…

Drive past McDonalds even when every animal instict is screaming for french fries.
Tell one of your kids you're not hungry (even though you are starving) when they wave a big spoonful of cookie dough ice cream in your face and offer to share.
Make a special trip to the whole foods store on the other side of town just to pick up and pay a hefty sum for organic, montmorency cherries because you heard how high in antioxidants they were.

Because:
Because you want to feel better!
You want more energy!
You want your clothes to fit again!

And, most importantly, you want to be healthy

So, in case you haven't met, let me introduce you to the "Master".The master antioxidant that is.

It is known as Glutathione or GSH.
Why is glutathione called the master antioxidant?

To put it simply, glutathione replenishes the action of many other antioxidants. In other words, glutathione makes those montmorency cherries go even farther as an antioxidants, enhancing the well documented and undeniable benefits of antioxidants.

For the scientific types, here is a brief explanation offered by Dr. Jimmy Gutman, a noted glutathione expert. He says,

"When vitamin C and E pick up an oxyradical they must hand it off to the GSH (glutathione) system so they are free to go back and get others. GSH similarly neutralizes peroxide and lipoic acid. In fact, all of the antioxidants help to neutralize each other and glutathione is at the center of cellular antioxidation. It is GSH -not the vitamin- that ultimately neutralizes the radical."
Perhaps, to make the point clear, you need an analogy.

Think of the activity in your body as a bustling metropolis with lots of people. Like dangerous free radicals, some of those people prowl around seeking to do harm. Fortunately, most cities have some form of Law Enforcement which, in most cases, finds and captures these less than desirables, much like your immune system which uses (among many other things) antioxidants to seek, finds and capture free radicals.

In this analogy, glutathione is like the patty wagon which then whisks the criminals away and, unlike our democratic society, makes that criminal disappear forever.

As a result, every extra "healthy" act you exert yourself to make each day is enhanced when you have optimal levels of naturally occurring glutathione in your cells.

Each supplement you take, each vitamin, each mineral, each antioxidants rich fruit and vegetable is assisted by the free radical neutralizing power of glutathione.

Click here for more about Glutathione and its benefits to our body.

Thursday, January 17, 2008

The 3 Distinct Benefits of Naturally Produced Glutathione

Glutathione: The Master Antioxidant
Antioxidants participate directly in the destruction of reactive oxygen compounds called free radicals. These by-products of a cell’s normal function can’t be avoided, but exposure to ultraviolet radiation from the sun or other sources promotes their emergence.
Free radicals have been linked to muscle fatigue during exercise and aging.

For this reason, the body is equipped with a variety of antioxidants. Vitamins C and E are natural antioxidants but do not occur naturally in the body.

These and other antioxidants actually depend on natural glutathione to function properly.

This is why Glutathione is called “The Master Antioxidant”.

Glutathione : Food for the Immune system

Glutathione helps build your Immune system resistance and improve your chances of staying healthy.

Lymphocytes are cells of your Immune system. Glutathione is essential for lymphocytes to increase in number, produce antibodies, and function efficiently.

Glutathione: A Cellular Level Detoxifier
Our food and water sources are becoming increasingly contaminated with chemicals, as is the air that we breathe.

Supplemental Detoxifier such as Glutathione help to counter the effects of the toxins we inhale and ingest.

By physically binding to toxic compounds in cells, Glutathione helps make them soluble - and harmless. The body can then eliminate these disarmed toxins in the bile and urine.

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GSH is the most abundant redox molecule in cells

Thus the most important determinant of cellular redox status. Thiols in proteins can undergo a wide range of reversible redox modifications (e.g., S-glutathionylation, S-nitrosylation, and disulfide formation) during times of increased exposure to reactive oxygen and nitrogen species, which can affect protein activity. These reversible thiol modifications regulated by GSH may be nanoswitches to turn on and off proteins, similar to phosphorylation, in cells. In the cytoplasm, an altered redox state can activate (e.g., MAPKs and NF-E2-related factor-2) and inhibit (e.g., phosphatases and caspases) proteins, whereas in the nucleus, redox alterations can inhibit DNA binding of transcription factors (e.g., NF-B and activator protein-1). The consequences include the promotion of expression of antioxidant genes and alterations of hepatocyte survival as well as the balance between necrotic versus apoptotic cell death. Therefore, the understanding of the redox regulation of proteins may have important clinical ramifications in understanding the pathogenesis of liver diseases.

GLUTATHIONE REDOX STATUS IN THE HUMAN CELL LINE

GLUTATHIONE REDOX STATUS IN THE HUMAN CELL LINE, A549, FOLLOWING INTRACELLULAR GLUTATHIONE DEPLETION AND EXTRACELLULAR GLUTATHIONE ADDITION
Pendergrass J. A.; Srinivasan J. V.; Clark E. P.; Kumar K. S.

The redox status of Glutathione (L-gamma-glutamyl-L-cysteinylglycine, GSH) plays an im portant role in a number of different cellular reactions including cellular oxidative stress.

Using A549 human sm all cell lung carcinoma fibroblasts, we investigated the role of exogenous GSH on the intracellular GSH/Glutathione disulfide (oxidized Glutathione, GSSG) redox ratio in GSH-depleted cells by treating with L-buthionine-(S,R)-sulfoximine (BSO).

GSH levels decreased after BSO treatment. Although BSO is a well-recognized inhibitor of GSH biosynthesis and has no known effect on GSSG reductase, surprisingly, the levels of GSSG also decreased. Incubation of control or GSH-depleted cells with exogenous GSH did not alter intracellular GSH or GSSG levels to any significant extent.

Therefore, the ratio of GSH/GSSG also was not altered significantly either in the controls or the BSO-treated cells. It appears that there m ay be cellular hom eostatic mechanisms that would maintain a constant GSH/GSSG ratio, irrespective of the changes in intracellular GSH concentration.

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Chronic Alcoholism Alters Systemic and Pulmonary Glutathione Redox Status

Rationale: Previous studies have linked the development and severity of acute respiratory distress syndrome with a history of alcohol abuse. In clinical studies, this association has been centered on depletion of pulmonary Glutathione and subsequent chronic oxidant stress.

Objectives: The impact on redox potential of the plasma or pulmonary pools, however, has never been reported.

Methods: Plasma and bronchoalveolar lavage fluid were collected from otherwise healthy alcohol-dependent subjects and control subjects matched by age, sex, and smoking history.

Measurements and Main Results: Redox potential was calculated from measured reduced and oxidized Glutathione in plasma and lavage. Among subjects who did and did not smoke, lavage fluid Glutathione redox potential was more oxidized in alcohol abusers by approximately 40 mV, which was not altered by dilution. This oxidation of the airway lining fluid associated with chronic alcohol abuse was independent of smoking history. A shift by 20 mV in plasma Glutathione redox potential, however, was noted only in subjects who both abused alcohol and smoked.

Conclusions: Chronic alcoholism was associated with alveolar oxidation and, with smoking, systemic oxidation. However, systemic oxidation did not accurately reflect the dramatic alcohol-induced oxidant stress in the alveolar space.

Although there was compensation for the oxidant stress caused by smoking in control groups, the capacity to maintain a reduced environment in the alveolar space was overwhelmed in those who abused alcohol. The significant alcohol-induced chronic oxidant stress in the alveolar space and the subsequent ramifications may be an important modulator of the increased incidence and severity of acute respiratory distress syndrome in this vulnerable population.
Mary Y. Yeh1, Ellen L. Burnham2, Marc Moss2 and Lou Ann S. Brown1

Glutathione redox cycle protects cultured endothelial cells against lysis by extracellularly generated hydrogen peroxide

We have examined the role of the Glutathione redox cycle as an Antioxidants defense mechanism in cultured bovine and human endothelial cells by disrupting the Glutathione redox cycle at several points.

Endothelial Glutathione reductase was selectively inhibited with 1,3-bis(chloroethyl)-1-nitrosourea (BCNU). Cellular stores of reducedGlutathione were depleted by reaction with diethylmaleate (DEM) or 1-chloro-2,4-dinitrobenzene (CDNB) or by inhibition of Glutathione synthesis with buthionine sulfoximine (BSO).

Whereas several strains of untreated bovine and human endothelial cells were resistant to lysis by enzymatically generated hydrogen peroxide, BCNU-treated cells were readily lysed in a time- and dose-dependent manner. Glucose-glucose oxidase-mediated lysis of BCNU-treated bovine endothelial cells was catalase-inhibitable and directly related to BCNU concentration and endogenous Glutathione reductase activity. Pretreatment of bovine endothelial cells with BCNU did not potentiate lysis by distilled water, calcium ionophore, lipopolysaccharide, or hypochlorous acid. Depletion of cellular reduced glutathione by reaction with DEM or CDNB or by inhibition of Glutathione synthesis by BSO also potentiated endothelial lysis by enzymatically generated hydrogen peroxide. Inhibition of endothelial Glutathione reductase by BCNU or depletion of reduced glutathione by BSO increased endothelial susceptibility to lysis by hydrogen peroxide generated by phorbol myristate acetate-activated neutrophils.

We conclude that the Glutathione redox cycle plays an important role as an endogenous Antioxidants defense mechanism in cultured endothelial cells
M Harlan, J D Levine, K S Callahan, B R Schwartz, and L A Harker

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Role of glutathione redox status in liver injury

GSH is the most abundant redox molecule in cells and thus the most important determinant of cellular redox status.

Thiols in proteins can undergo a wide range of reversible redox modifications (e.g. S-glutathionylation, S-nitrosylation, disulfide formation) during times of increased exposure to reactive oxygen and nitrogen species, which can affect protein activity.

These reversible thiol modifications regulated by GSH may be nano-switches to turn on and off proteins, similar to phosphorylation, in cells. In the cytoplasm, altered redox state can activate (e.g. MAP kinases, Nrf-2) and inhibit (e.g. phosphatases, caspases) proteins, whereas in the nucleus redox alterations can inhibit DNA binding of transcription factors (NF-kappaB, AP-1).

The consequences include promotion of expression of Antioxidants genes, and alterations of hepatocyte survival as well as the balance between necrotic versus apoptotic cell death.

Therefore the understanding of the redox regulation of proteins may have important clinical ramifications in understanding pathogenesis of liver diseases.
Han D , Hanawa N , Saberi B , Kaplowitz N

Glutathione, stress responses, and redox signaling in lung inflammation

Changes in the ratio of intracellular reduced and disulfide forms ofGlutathione (GSH/GSSG) can affect signaling pathways that participate in various physiological responses from cell proliferation to gene expression and apoptosis.

It is also now known that many proteins have a highly conserved cysteine (sulfhydryl) sequence in their active/regulatory sites, which are primary targets of oxidative modifications and thus important components of redox signaling.

However, the mechanism by which oxidants and GSH/protein-cysteine-thiols actually participate in redox signaling still remains to be elucidated.

Initial studies involving the role of cysteine in various proteins have revealed that cysteine-SH may mediate redox signaling via reversible or irreversible oxidative modification to Cys-sulfenate or Cys-sulfinate and Cys-sulfonate species, respectively.

Oxidative stress possibly via the modification of cysteine residues activates multiple stress kinase pathways and transcription factors nuclear factor-kappaB and activator protein-1, which differentially regulate the genes for proinflammatory cytokines as well as the protective antioxidant genes. Understanding the redox signaling mechanisms for differential gene regulation may allow for the development of novel pharmacological approaches that preferentially up-regulate key antioxidant genes, which, in turn, reduce or resolve inflammation and injury.

This forum article features the current knowledge on the role of GSH in redox signaling, particularly the regulation of transcription factors and downstream signaling in lung inflammation. Rahman I , Biswas SK , Jimenez LA , Torres M , Forman HJ

Glutathione's three major roles in the body are summarized by the letters A-B-C.- Anti-oxidant- Blood Booster- Cell Detoxifier

Wednesday, January 16, 2008

Substances that Boost Glutathione Levels and Protect Brain Cells

Taking Glutathione itself as a supplement does not boost cellular Glutathione levels, since it breaks down in the digestive tract before it reaches the cells.

However, intravenous Glutathione therapy and Glutathione precursors or dietary supplements are effective in boosting intracellular levels ofGlutathione.

Intravenous Glutathione Injections:
Intravenous Glutathione injections have been shown to produce amazing and rapid results, in patients with Parkinson's disease. Followingeven a single dosage of intravenous Glutathione, many of the symptoms of Parkinson's disease rapidly improve, often in as little as 15 minutes.

Glutathione Precursors:
In the Alzheimer's study conducted by Welsh GP, Andrew McCaddon, adding theGlutathione precursor, N-acetyl-cysteine (NAC) to a protocol thatlowered homocysteine levels by simple supplementation with B12 and folate, resulted in prompt, striking, and sustained clinical improvement in nearly all the patients.

Cucurmin (turmeric):
Studies have shown that the Indian curry spice, cucurmin, has neuroprotective effects because of its ability to induce the enzyme, hemeoxygenase-1(HO-1), which protects neurons exposed to oxidant stress. Treatment of brain cells called astrocytes, with curcumin, increases expression of HO-1 protein as well as Glutathione S-transferase.

Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7919-24. Epub 2003 Jun 05.
Am J Geriatr Psychiatry. 2003 Mar-Apr;11(2):246-9
Can Curry Protect Against Alzheimer's?; American Physiological Society (APS) Press Release; 16-Apr-2004

Glutathione's three major roles in the body are summarized by the letters A-B-C.
- Anti-oxidant- Blood Booster- Cell Detoxifier


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Alcohol Consumption and Glutathione

Alcohol abuse is known to impair memory and other brain functions and increase brain cell death.

A new study in rats has shown that alchol consumption causes fewer new brain cells to form and results in greater cell death.

But rats that were fed alcohol - a Glutathione peroxidase mimic that acts as a free radical scavenger - showed no similar reduction in brain-cell formation and no increase in cell death.

Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7919-24. Epub 2003 Jun 05.

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Glutathione and Mood Disorders

Studies have found that the mood stabilizing drug, valproate, used to treat epilepsy and bi-polar disorder, regulates expression of the genes that make Glutathione-S-transferase (GST).

In addition, chronic treatment with lithium, another commonly prescribed mood stabilizer used in treating manic-depression, also increased levels of GST.

These findings led researchers to conclude that Glutathione S-transferase may be a novel target for mood stabilizing drugs.

Journal of Neurochemistry, Vol. 88, No. 6, 2004 1477-1484

Glutathione's three major roles in the body are summarized by the letters A-B-C.
- Anti-oxidant- Blood Booster- Cell Detoxifier

Alzheimer's Disease and Glutathione

Free radicals and oxidative damage in neurons is known to be a primary cause of degenerative diseases like Alzheimer's disease.'

Amyloid-Я peptide (AЯ) accumulation in senile plaques, a pathological hallmark of Alzheimer's disease (AD), has been implicated in neuronal degeneration.

Amyloid plaques encroaching on the brain increase the production of free radicals, or oxidative stress. Antioxidants, such as vitamin C and E "mop up" the damaging free radicals.

Glutathione (GSH ) precursors can prevent death of brain cells induced by amyloid plaques in Alzheimer's disease, while substances that deplete GSH increase cell death.

Evidence has been piling up over the link between the amount of an amino acid called homocysteine in the blood and the chance of developing Alzheimer's.

For people not genetically predisposed to developing Alzheimer's, cholesterol and homocysteine, largely caused by an unhealthy lifestyle, are the core causal factors.

Welsh GP, Andrew McCaddon, showed that the more homocysteine that patients with Alzheimer's had, the worse their mental performance, and the worse their "cognitive impairment," the less they had of the antioxidant Glutathione.

The Journal of Cell Biology, Volume 164, Number 1, 123-131; 5 January 2004
Biol Psychiatry. 2003 Feb;53(3):254-60

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Brain Disorders and Glutathione

A Genetic Cause?

Genetics researchers have found that the Glutathione S-transferase gene controls the onset of Alzheimer's, Parkinson's disease and determines, not if we get these diseases, but when.

The Glutathione S-transferase gene has previously been linked to the risk for Parkinson's disease among people who used pesticides.

Human Molecular Genetics, 2003, Vol. 12, No. 24 3259-3267

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Brain Injury and Glutathione

The Gender Difference
Researchers at Children's Hospital of Pittsburgh have found that males and females respond differently to brain injury.

In animal models, levels of Glutathione remain constant in females who have suffered a brain injury, but drop by as much as 80 percent in males with the same injury.

WhenGlutathione levels drop, brain cells die much more quickly. This suggests that boys with brain injuries may require different life-saving treatments than girls.

N-acetyl-cysteine (NAC), a precursor of Glutathione, already approved for use by the U.S. Food and Drug Administration to treat people who have overdosed on acetaminophen, may be an effective treatment for brain injury in boys whose brains are deprived of oxygen.

Researchers Find Brain Cells Die Differently in Males and Females; Pediatric Academic Societies Press release; 21-Apr-2004

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Glutathione - Your Brain's Master Antioxidant Defense

Free radicals and oxyradicals play an important role in the development and progression of many brain disorders such as brain injury, neurodegenerative disease, schizophrenia and Down syndrome.

Glutathione is the brain's master antioxidant and plays an important protective role in the brain.
According to Dr. Jimmy Gutman, "The brain is particularly susceptible to free radical attack because it generates more oxidative by-products per gram of tissue than any other organ."

Many neurological and psychiatric disease processes are characterized by abnormalities Glutathione metabolism and antioxidant defenses.

Generation of reactive oxygen species (free radicals) and oxidative damage are an important cause of neuron (brain cell) death from brain injury.

Chemicals that cause toxicity to certain brain cells are known to decrease cerebral Glutathione (GSH), making the cells more vulnerable to reactive oxygen species (ROS).

On the other hand, over-expression of the Glutathione peroxidase (GPX) enzyme potently decreases cell death from brain injury.

Journal of Neurochemistry, Vol. 88, No. 3, 2004 513-531
Journal of Neurochemistry, Vol. 87, No. 6, 2003 1527-1534

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Tuesday, January 15, 2008

Glutathione in cancer biology and therapy

The Glutathione (GSH ) content of cancer cells is particularly relevant in regulating mutagenic mechanisms, DNA synthesis, growth, and multidrug and radiation resistance.

In malignant tumors, as compared with normal tissues, that resistance associates in most cases with higher GSH levels within these cancer cells. Thus, approaches to cancer treatment based on modulation of GSH should control possible growth-associated changes in GSH content and synthesis in these cells. Despite the potential benefits for cancer therapy of a selective GSH-depleting strategy, such a methodology has remained elusive up to now.

Metastatic spread, not primary tumor burden, is the leading cause of cancer death. For patient prognosis to improve, new systemic therapies capable of effectively inhibiting the outgrowth of seeded tumor cells are needed.

Interaction of metastatic cells with the vascular endothelium activates local release of proinflammatory cytokines, which act as signals promoting cancer cell adhesion, extravasation, and proliferation.

Recent work shows that a high percentage of metastatic cells with high GSH levels survive the combined nitrosative and oxidative stresses elicited by the vascular endothelium and possibly by macrophages and granulocytes. ?-Glutamyl transpeptidase overexpression and an inter-organ flow of GSH (where the liver plays a central role), by increasing cysteine availability for tumor GSH synthesis, function in combination as a metastatic-growth promoting mechanism.

The present review focuses on an analysis of links among GSH, adaptive responses to stress, molecular mechanisms of invasive cancer cell survival and death, and sensitization of metastatic cells to therapy. Experimental evidence shows that acceleration of GSH efflux facilitates selective GSH depletion in metastatic cells.

Estrela JM; Ortega A; Obrador EDepartment of Physiology, University of Valencia, Valencia, Spain.

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Why is Glutathione Essential to Health?

Glutathione's three major roles in the body are summarized by the letters A-B-C.
- Anti-oxidant- Blood Booster- Cell Detoxifier

Glutathione and Breast Cancer

Glutathione is protein that is produced naturally in the body.
It is an immune system booster, anti-oxidant and a natural detoxifier.

According to several studies supplementary Glutathione from whey proteins promotes health in your body, even during chemotherapy and radiation treatments.

Whey protein has the highest biological value rating of any protein. When the biological value is high, that means protein is absorbed, used and retained better in the body.

Studies indicate that supplementary Glutathione reduces the levels of the bodies home made Glutathione in tumors, thereby stopping the tumors ability to grow while at the same time increasing levels of Glutathione in the rest of the body.

The higher our liver Glutathione levels rise, the more effectively our body is detoxified.

Detoxifying your body effectively is seen as an effective way to be proactive about your health.

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Role of the Glutathione Metabolic Pathway in Lung Cancer Treatment and Prognosis

Inherent and acquired drug resistance is a cause of chemotherapy failure, and pharmacogenomic studies have begun to define gene variations responsible for varied drug metabolism, which influences drug efficacy. Platinum-based compounds are the most commonly used chemotherapeutic agents in the treatment of advanced stage lung cancer patients, and the glutathione metabolic pathway is directly involved in the detoxification or inactivation of platinum drugs. Consequently, genotypes corresponding to higher drug inactivation enzyme activity may predict poor treatment outcome. Available evidence is consistent with this hypothesis, although a definitive role for glutathione system genes in lung cancer prognosis needs to be elucidated. We present evidence supporting a role of the glutathione system in acquired and inherited drug resistance and/or adverse effects through the impact of either drug detoxification or drug inactivation, thus adversely effecting lung cancer treatment outcome. The potential application of glutathione system polymorphic genetic markers in identifying patients who may respond favorably, selecting effective antitumor drugs, and balancing drug efficacy and toxicity are discussed.
Ping Yang, Jon O. Ebbert, Zhifu Sun, Richard M. Weinshilboum

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Genetic determinants of lung cancer short-term survival: the role of glutathione-related genes

Survival of lung cancer patients has been dismal. Glutathione enzymes are directly involved in the metabolism of platinum compounds, a group of important chemotherapeutic drugs in cancer treatment. We tested the hypothesis that genes encoding Glutathione enzymes may predict lung cancer short-term survival. Methods: We studied DNA polymorphisms of 250 primary lung cancer patients at four Glutathione-related loci: GSTP1, GSTM1, GSTT1 and γ-GCS that encode Glutathione-S-transferase-π,Glutathione-S-transferase-μ, Glutathione-S-transferase-θ, and γ-glutamylcysteine synthetase, respectively. Pearson's χ2-square tests, Kaplan–Meier survival curves, log rank tests, and Cox regression models were applied in the analysis.

Results: There were 150 (60%) men and 100 (40%) women in this study. Seventeen percent of the patients had never smoked cigarettes, and 61% had stopped smoking at least 6 months prior to their lung cancer diagnosis. Among never smokers, those with null (N) or low (L) genotype experienced a better 1-year-survival rate than those with a positive (P) or high (H) genotype. Patients with P or H at two loci (PP or PH) were compared with patients with N or L at one or both loci (other). Among never smokers, 1-year-survival rates were 60–78% for patients with PP or PH genotypes compared with 89–100% for other types. The survival advantage was greater among advanced-stage patients who were NL or NN than low-stage patients. Similar results were not observed among smokers.

Conclusions: Glutathione-related genes may determine lung cancer survival. Our results, if confirmed, would suggest new directions to enhance cancer treatment, and provide easily measurable markers for clinicians to plan patient-specific therapy.

Ping Yangab, Akira Yokomizoc, Henry D Tazelaarc, Randolph S Markse, Timothy G Lesnicka, Daniel L Millerd, Jeff A Sloana, Eric S Edellf, Rebecca L Meyera, James Jettef, Wanguo Liuc

Glutathione could well be involved in protecting against cancer

The best known functions of selenium at nutritionally adequate, but not at excessive, levels are its role as a part of the enzyme Glutathione peroxidase and its interaction with heavy metals. Glutathione peroxidase destroys hydroperoxides and lipoperoxides, thereby protecting the constituents of the cells against free radical damage. Ip and Sinha (1981) have shown that selenium, through its function in Glutathione peroxidase, could well be involved in protecting against cancer induced by high intakes of fat, especially polyunsaturated fatty acids. Glutathione peroxidase activity in human blood increases with increasing selenium intakes, but reaches a plateau at intakes well below those customary in the United States (Thomson and Robinson, 1980). Thus, if the antitumorigenic effect of selenium is mediated through its function in Glutathione peroxidase, attempts to increase the enzyme activity by selenium supplementation, superimposed on an adequate diet in the United States, would not be successful. The second function of selenium is to protect against acute and chronic toxicity of certain heavy metals. Although selenium is known to interact with cadmium and mercury, the mechanism of action is not known. Selenium does not cause an increased elimination of the toxic elements, but, rather, an increased accumulation in some nontoxic form (National Academy of Sciences, 1971). It is conceivable that carcinogenic effects of these, and perhaps other heavy metals, could be counteracted by selenium, in a manner similar to its protection against their general toxicity. Diet Nutrition Cancer by National Research Council, page 168

Cancer

Numerous studies suggest that an inverse association exists between selenium levels and cancer incidence (Hocman, 1988; Willett and Stampfer, 1986; Milner, 1985). Associations appear to be particularly strong with cancers that are also associated with high-fat, low-fiber diets (i.e., breast, colon, prostrate, etc.). The mechanism for selenium's reported protective effects is likely due to its function in antioxidant synthesis. Glutathione peroxidase, the primary enzyme that converts hydrogen peroxide to water (and thus prevents lipid peroxidation) is selenium-dependent. Inhibition of lipid or bile acid oxidation may account for its protective role (reviewed by Linder 1991:496-7). Selenium may also act as an immune stimulant. Selenium deficiency inhibits macrophage-mediated tumor destruction, and inhibits tumor necrosis factor-alpha production in animals (Kiremidjian-Schumacher et al., 1992). Dietary supplementation with selenium produced the opposite effects. Cancer And Natural Medicine by John Boik, page 146

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