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Diseases of the Lungs: Potential Benefit of Glutathione in Asthma, Cystic Fibrosis

Increasing glutathione levels in the lungs may be beneficial in lung disease. Although there are few studies using glutathione (GSH) ehnancement therapies or nebulized (aerosolized and inhaled) glutathione in lung diseases, there is good data (mostly in animal models) suggesting increasing the potent antioxidant and free-radical scavenger glutathione would be beneficial in certain degenerative lung conditions associated with increased free radical load including asthma, cystic fibrosis, bronchiectasis and bronchiolitis obliterans. A Glutathione deficiency can cause a lack of coordination,
mental disorders, tremors, and difficulty maintaining balance.

Glutathione - A Radical Treatment for Cystic Fibrosis Lung Disease?

Brian J. Day, PhD

There are now three small clinical trials that have examined the effects of inhaled glutathione in patients with cystic fibrosis. Roum and colleagues16 were first to report the use of inhaled glutathione (600 mg bid for 3 days, approximately 17 mg/kg/d) in seven patients with cystic fibrosis. The glutathione therapy was well tolerated and produced a twofold increase in epithelial lining fluid glutathione levels. In addition, these investigators found diminished superoxide production from BAL cells after glutathione therapy. One concern raised by these studies was the rapid rise in oxidized glutathione levels in the treated patients with cystic fibrosis.

The percentage of oxidized glutathione in untreated patients with cystic fibrosis was 46%, and increased to 66% after treatment. This increase in oxidized glutathione can adversely change the redox status of the epithelial lining fluid, and may explain why Griese and colleagues17 failed to see a change in the oxidative state of the epithelial lining fluid proteins and lipids in their inhaled glutathione study. The study by Griese and colleagues17 used a highly efficient inhalation delivery system (86% of the emitted dose) to treat 17 patients with cystic fibrosis with two different regimens of glutathione (300 mg and 450 mg tid for 14 days, approximately 13 mg/kg/d and 20 mg/kg/d, respectively). Again, these regimens were well tolerated, increased epithelial lining fluid glutathione levels threefold to fourfold, and were associated with a significant improvement in the patient’s FEV1. Dr Yariv Malimovka's Clinical Cases

In aerosol form, glutathione quenches inflammation in cystic fibrosis patients. This wonderful substance has even been shown to increase insulin production in older individuals who have impaired sugar metabolism. Glutathione also seems to inhibit herpes viruses and has been shown to help reduce viral load in hepatitis C patients. David Perlmutter, a Florida neurologist, found that intravenous glutathione helps relieve the symptoms of Parkinson’s disease. Glutathione increases sensitivity to dopamine, which is depleted in Parkinson’s. It may also protect against neurotoxins that may be implicated in the disease.

Increasing glutathione levels in the lungs may be beneficial in lung disease. Although there are few studies using glutathione (GSH) enhancement therapies or nebulized (aerosolized and inhaled) glutathione in lung diseases, there is good data (mostly in animal models) suggesting increasing the potent antioxidant and free-radical scavenger glutathione would be beneficial in certain degenerative lung conditions associated with increased free radical load including asthma, cystic fibrosis, bronchiectasis and bronchiolitis obliterans.

Glutathione tablets are ineffective in increasing glutathione levels in the tissues and organs (such as the lung) because they are digested in the stomach and never reach the blood stream or the tissues of the body. Oral GSH simply is metabolized as a protein (digested). Researchers found that 3 grams of glutathionetaken orally were ineffective in increasing circulating glutathione (glutathione in the bloodstream) in a clinical study evaluating the benefits of oral glutathione.

Conventional medicine holds that there is no remedy for COPD. Yet at the Whitaker Wellness Institute, we recently began utilizing a safe new therapy that has shown great promise: inhaled glutathione. Glutathione is the most efficient free radical scavenger in the airways, and dozens of studies have confirmed that free radical damage is a primary player in COPD. Although not particularly well absorbed when taken orally, the effects of inhaled glutathione are remarkable.

Glutathione therapy Previous clinical trials of nebulized reduced glutathione have demonstrated the bioavailability and safety of up to 600 mg twice daily. The absorption of oral glutathione remains controversial, with animal studies suggesting significant absorption and some human studies showing little to none. Based on these findings, it appears inhalation might be the preferred route of administration for respiratory and perhaps systemic effect. We report the case of a man with an acute respiratory crisis due to emphysema and apparent bronchial infection that responded favorably to treatment with nebulized glutathione.

In his book, "Emphysema and Chronic Obstructive Pulmonary Disease: Therapeutic Approaches Through - Nutrition, Natural Medicine, Alternative Medicine", Dr. Green discusses inhaled glutathione extensively. Not only is inhaled glutathione positively discussed and thoroughly explained, but Dr. Green also gives other nebulizer formulas of which glutathione is an ingredient. The book also gives resources to obtain glutathione through a network of practicing physicians who utilize glutathione in their practices.

We present the case of a 95-year-old man with an acute respiratory crisis secondary to emphysema and apparent bronchial infection. Treatment with nebulized glutathione led to a rapid resolution of the crisis, as well as a marked improvement in the chronic course of the disease. This treatment has been used since for a number of patients with emphysema. The safety and bioavailability of this method of delivery have been established in human studies. Preliminary results suggest efficacy for nebulized administration of glutathione in this patient population. We suggest this treatment can be considered an option for acute respiratory crises due to COPD.

Case Report In 1997, a 95-year-old male with emphysema presented in a wheelchair and using an oxygen tank and mask necessitated by his acute illness. He was alert, responsive, and reported a productive cough with colorless sputum. His breathing was obviously labored. He refused hospitalization and antibiotic treatment. We chose to try a single trial dose of 2 ml of a 60 mg/ml glutathione solution (prepared by Apothecure Pharmacy, Dallas, TX) nebulized and inhaled over a 5-10 minute period.) Due to the obvious immediate benefit, it was decided to continue this treatment with twice-daily administration and close monitoring by his family of his overall condition. He returned to the office in three days without wheelchair or oxygen tank. He showed no signs of respiratory distress, and no adventitious lung sounds were noted on auscultation. The patient reported his breathing was better than it had been in years.

Glutathione tablets are ineffective in increasing glutathione levels in the tissues and organs (such as the lung) because they are digested in the stomach and never reach the blood stream or the tissues of the body. Oral GSH simply is metabolized as a protein (digested). Small hydrophobic molecules are thought to be rapidly absorbed (within seconds) throughout the lungs by passive diffusion through the plasma membrane.

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The Healing Power of Glutathione

Dr. Jimmy Gutman, MD - "Your life depends on glutathione. Without it, your cells would disintegrate from unrestrained oxidation, your body would have little resistance to bacteria, viruses and cancer, and your liver would shrivel up from the eventual accumulation of toxins." Glutathione, taken as a supplement (capsule, tablet or powder), may not be able to cross across the cell membrane of the digestive track. Practitioners recently began utilizing a safe new therapy that has shown great promise.

The concentration of glutathione declines with age and in some age-related diseases. Glutathione deficiency contributes to oxidative stress, which plays a key role in aging and the worsening of many diseases including Alzheimer's disease, cancer, Parkinson's disease, heart attack, liver disease, cystic fibrosis, HIV, AIDS, sickle cell anemia, and diabetes.

Glutathione has been described as a 'food for the immune system', enabling the body to do its own healing. White blood cells are the body’s major defense system. They need glutathione in order to act properly. By raising the levels of this powerful antioxidant, the body can produce more white blood cells, which, in turn, means a more effective identification and elimination of germs and other invaders including cancer cells. Glutathione depletion will eventually exhaust any ability of the white blood cells to keep fighting, which means: You lose the battle.

New Hope For Serious Diseases

Dr. Howard Peiper

Glutathione deficiencylinked to disease Our immune systems are under attack from toxic substances that are everywhere - in the air we breathe, the food we eat, and the water we drink. Serious disease doesn't just happen. The accumulation of toxins compromises our immune system and wears the body down leaving us vulnerable to all sorts of maladies. The body has an amazing ability to recover from illness and restore itself if we give it the tools to work with.

The level of Glutathione in our cells is predictive of how long we will live. We need this miraculous antioxidant to survive, and without it, our liver would soon become overwhelmed with the accumulation of toxins, resulting in organ failure and death. Glutathione is manufactured by every one of our trillions of cells and is one of the most important healing and cleansing agents. Low glutathione levels are linked to diseases such as Cancer, Multiple Sclerosis, AIDS, Alzheimer’s, Parkinson’s, Atherosclerosis, pregnancy complications, male infertility and Cataracts. Every moment Glutathione is defending our body against attacks from disease, toxins, poisons, viruses, pollutants, radiation and oxidative stress.

The liver uses glutathione to process; alcohol, caffeine, medications, nicotine as an example, to process such substances and remove them from the blood. It also helps in the filtering of alcohol and other toxic substances from the blood. It helps in the processing drugs and medications absorbed through the digestive system, enabling the body to use them effectively and ultimately dispose of them. Reduced glutathione plays a critical role in the cellular detoxification processes including the metabolism of peroxides, the conjugation with electrophils and the scavenging of the free radicals. The relevance of glutathione in ethanol metabolism consists mainly in compensating for alcohol-related oxidative stress. Glutathione acts as a detoxifying agent by combining with undesirable substances and ridding the body of them through urine and bile .

The Role of Glutathione in Aging and Cancer

Glutathione  is needed to survive High blood glutathione levels accompany excellent physical and mental health in women ages 60 to 103 years. Earlier we found a high percentage of subnormal total glutathione (G(T)) levels in blood from elderly subjects and patients with chronic diseases. These findings suggested a hypothesis that high levels of (G(T) in the blood occur in old persons who are in excellent physical and mental health. To this end, we recruited 87 white women who ranged in age from 60 to 103 years and reported that they felt healthy. Their health was verified with physical examinations, clinical chemistry profiles, psychosocial assessments, and blood G(T) determinations. This evaluation was performed in three waves over a 5-year period. The values were compared with those from representative individuals in this region and with normal national data. The results verified that these healthy subjects were in top physical and mental health. We also found that subjects of all ages had very high blood G(T) levels in waves I and II but only normal levels in wave III. These findings confirm that high blood G(T) concentrations and excellent physical and mental health are characteristics of long-lived women. Department of Biochemistry, University of Louisville, KY.

Some well-known causes of glutathione depletion are as follows:
  • Acidic lifestyle and diet
  • Air and Water pollution
  • Prescription and recreational drugs
  • Ultraviolet and Radiation from cells phones, computers, electrical cars, power lines, hair dryers, etc.
  • Emotional and physical stress
  • Injury, trauma or burns
  • Heavy metals
  • Cigarette smoke
  • Household chemicals
  • Acetaminophen poisoning
  • Exhaust from motor vehicles
  • Septic shock

All of these above factors lead to a build up of acidic toxins that cause the loss of glutathione
as a non-nutritive buffer leading to cellular aging, dis-ease and finally death."

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Glutathione and Cancer

Joan Amtoft-Nielsen, MD, PhD, DC - "Most cancer patients suffer from nutritional deficiencies before diagnosis and even more so during the early conventional treatment of their disease, since chemotherapeutic agents affect levels of such nutrients as glutathione, vitamin B6, vitamin E and beta carotene. Inappropriate foods consumed during the course of disease may linger in the body longer since they are improperly digested, absorbed and excreted. The greater the body’s toxicity, the lower the functioning of the immune system."

Dr. Nielsen was a Medical Advisor for The National Foundation for Alternative Medicine in Washington DC and currently serves on the Scientific Advisory Board of the Journal of Longevity, on the Advisory Board of the C.A.R.E.S. Foundation and on the Board of Governors for the South Carolina Naturopathic Physicians Organization.

Glutathione in Cancer Biology and Therapy Critical Reviews in Clinical Laboratory Sciences, Volume 43, Issue 2 March 2006 , pages 143 - 181

Metabolism and Functions of Glutathione

Liver metastasis of colon cancer The oxygen we breathe helps to burn sugar and fat inside our body cells to produce energy. But about 2% of the converted oxygen remains as highly reactive molecules that modify, disrupt and impair the stable structure within our body. These are called “free radicals.” If free radicals are not neutralized, cell membranes breakdown and DNA is damaged, resulting in a compromised immune system, disease and rapid aging. Many environmental and ingested agents spur free radical production – air pollution, pesticides, radiation, alcohol, sugar, cigarette smoke, illegal drugs and prescription medications. To combat the hostile effect of free radicals, our bodies use antioxidants (free radical scavengers) that extinguish the biochemical fire. Bruce Ames, Ph.D. at the University of California, Berkley, estimates that every single one of our cells suffers from 10,000 hits by free radicalsdaily.

Glutathione is used more than any other antioxidant in the body, and is the most abundant natural antioxidant that protects our vision, boosts the immune system, helps turn carbohydrates into energy and prevents the buildup of oxidized fats that contribute to heart disease. Glutathione supports us at the cellular level by protecting every cell of the body, but our levels decline dramatically with age. Our bodies are constantly replacing and repairing free-radical damaged cells, but the demands of the modern age have created high levels of free radicals with limited supplies of Glutathione to correct the damage. Without Glutathione, other antioxidants such as vitamins C and E cannot perform their functions adequately to protect the body against disease.

The brain consumes about 20% of the oxygen utilized by the body but constitutes only 2% of the body weight and is therefore particularly susceptible to free radical attacks. Glutathione acts to prevent and protect the brain from the damage of free radicals.Glutathione protects both the mother and the developing fetus from the damaging effects of free radicals, and minimizes the oxidative stress that occurs during labor and the birth process. The placenta contains a significant amount of glutathione to filter pollutants before they reach the baby.

In the last 75 years, clean and healthy food supplies have been replaced by sugar, processed food, chemicals, genetically altered fruit and vegetables, chemical and hormone laced dairy products, hormone and preservative laden meats, high saturated fats with sugar and thousands of medications. There are tens of thousands of confirmed toxic substances in our environment and as a result, obesity, heart disease, diabetes, allergies and mental health issues are rampant. By age 20 we are losing Glutathione at 8-12% per decade. But compromised health and excessive use of medications can deplete the body more rapidly. Some scientists estimate that a 30% reduction of Glutathione is enough for cellular dysfunction to set in.

The liver is our ultimate cleaner and has two critical functions: to process nutrients and eliminate toxins from the body. It does this by filtering the blood at about two quarts a minute. Approximately 25% of all the blood in the body is filtered through the liver at any one time. Some glutathione is released directly by the liver into the bloodstream where it helps to maintain the strength of red blood cells while also protecting the white blood cells. Large quantities of Glutathione are found in the liver where a two-stage detoxification process takes place. Phase One begins the chemical conversion of harmful compounds that are mainly fat-soluble into intermediate forms. But Phase Two is where the final transformation takes place to converts the intermediate toxins into water-soluble substances that can be excreted thru the bowel or kidneys. Only water-soluble substances can be excreted. If there is not enough Glutathione to generate the Phase two enzymes, toxins will build to dangerous levels in the liver.

Unlike unnatural detoxification supplements, the use of Glutathione is a natural process that allows our body to perform its filtering capability organically and comfortably. Many herbs that detoxify will also deplete – Glutathione inherently builds and nourishes. Glutathione is a critical element for good health, strong immune function, cancer prevention and the slowing of the aging process. Basically, increasing Glutathione levels enhances life.

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Medical Professionals on the Benefits of Glutathione

Glutathione levels enhances life. Dr. Earl Mindell - "We literally cannot survive without this miraculous antioxidant" Glutathione (GSH) : Your Body's Most Powerful Healing Agent

Patrick J.D. Bouic, Ph.D - "No other antioxidant is as important to overall health as glutathione. It is the regenerator of immune cells and the most valuable detoxifying agent in the body. Low levels are associated with early aging and even death." The Immune System Cure.

Dr. Allan Somersall, Ph.D., M.D. with Dr. Gustavo Bounous, M.D. - "Without glutathione, other important antioxidants such as vitamins C and E cannot do their job adequately to protect your body against disease."

Dr. Paul Cheney - "Glutathione has potent anti-viral properties - if you raise the glutathione level you can stop the replication of most any, at least, intracellular pathogen....but glutathione deficiency produces a pro-viral effect."

Dr. Jimmy Gutman, MD - " - "Healthy people also benefit from elevated glutathione levels through an enhanced ability to fight off toxins, infectious disease, pre-cancerous cells and the aging process itself. Many world-class athletes are discovering that well-maintained glutathione levels give them the edge over their competitors, bringing greater strength and endurance, decreased recovery time from injury, less muscle pain and fatigue, and muscle-promoting activity."

"It is well known that aging is accompanied by a precipitous fall in glutathione levels. Lower glutathione levels are implicated in many diseases associated with aging, including cataracts, Alzheimer's disease, atherosclerosis and others."

Journal of Clinical Epidemiology 47: 1021-26 1994

"Doctors have used glutathione-promoting drugs to treat many lung diseases including asthma, chronic bronchitis and emphysema. Newer potential therapeutic roles can be found for cigarette smoke damage, pulmonary fibrosis and other illnesses." - American Journal of Medical Science 307: 119-127, 1994

"Glutathione protects the body from the inflammation of gastritis, stomach ulcers, pancreatitis and inflammatory bowel disease including ulcerative colitis and Crohn's disease." - Gut 42: 485-492, 1998

"The liver is the major storehouse for glutathione. Glutathione is impaired in alcoholic hepatitis as well as in viral hepatitis A, B, and C. Raised glutathione levels restore liver function." - American Journal of Gasteroenterology 91: 2569-2573, 1996

"Glutathione detoxifies a variety of pollutants, carcinogens and poisons, including many found in fuel exhaust and cigarette smoke. It also retards damage from radiation exposure due to the eroding ozone layer" . - Annual Reviews of Biochemistry 52: 711-760 1983

"Raised glutathione levels help increase strength and endurance. Those interested in physical fitness can benefit from a definite athletic edge." Journal of Applied Physiology 87: 1381-1385, 1999

"Strong muscular activity, such as that experienced by athletes, generates oxyradicals [free radicals] leading to muscle fatigue and poorer performance. Glutathione neutralizes these radicals". - Sport Medicine 21: 213-238, 1996

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

"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 Dr Yariv Malimovka's Clinical Cases

Ray Sahelian, M.D. - "L Glutathione is a powerful antioxidant found within every cell. Glutathione plays a role in nutrient metabolism, and regulation of cellular events (including gene expression, DNA and protein synthesis, cell growth, and immune response. Glutathione, taken as a supplement, may not be able to cross across the cell membrane and thus it is not clear how effective a glutathione supplement would be if taken orally as a supplement. Consider acetylcysteine which is an antioxidant that can regenerate glutathione within cells. This antioxidant, made from the combination of three amino acids cysteine, glutamate, and glycine, forms part of the powerful natural antioxidant glutathione peroxidase which is found in our cells. Glutathione peroxidase plays a variety of roles in cells, including DNA synthesis and repair, metabolism of toxins and carcinogens, enhancement of the immune system, and prevention of fat oxidation. However, glutathione is predominantly known as an antioxidant protecting our cells from damage caused by the free radical hydrogen peroxide. Glutathione also helps the other antioxidants in cells stay in their active form. Brain glutathione levels have been found to be lower in patients with Parkinson's disease."

Treatment of Pulmonary Diseases and Respiratory-Related Conditions With Inhaled Glutathione

The field of nanotechnology may hold the promise of significant improvements in the health and well being of patients, as well as in manufacturing technologies. The knowledge of this impact of nanomaterials on public health is limited so far. This paper briefly reviews the unique size-controlled properties of nanomaterials, their disposition in the body after inhalation, and the factors influencing the fate of inhaled nanomaterials. The physiology of the lung makes it an ideal target organ for non-invasive local and systemic drug delivery, especially for protein and poorly water-soluble drugs that have low oral bio-availability via oral administration. The potential application of pulmonary drug delivery of nanoparticles to the lungs, specifically in context of published results reported on nanomaterials in environmental epidemiology and toxicology is reviewed in this paper.

Glutathione in the epithelial lining fluid (ELF) of the lower respiratory tract is thought to be the first line of defense against oxidative stress.[6] The ELF concentration of GSH is 140 times that of serum concentrations with a redox ratio of > 9 : 1.[7] In fact, alternations in alveolar and lung GSH metabolism are widely recognized as a central feature among many inflammatory lung diseases.[8-14] In healthy lungs, the oxidant burden is balanced by local antioxidant defenses. However, in lung diseases cellular damage and injury is mediated by an increased oxidant burden and/or decreased antioxidant defenses. Given that inhalation is the only known method that increases GSH levels in the ELF for a significant duration, a review of the literature was conducted to examine the clinical effectiveness of inhaled GSH as a treatment for various pulmonary diseases and respiratory-related conditions. Only reports involving human subjects were included in the analysis. The clinical and theoretical indications for GSH inhalation were summarized and potential concerns with this treatment reported. Other pertinent details such as its presumed mechanisms of action and optimal doses to be administered were compiled and evaluated.

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