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.
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.
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.
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
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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
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
"The incidence and mortality rates from most cancers increase exponentially
with age. It is likely that this aging phenomenon is partially due to specific
changes that occur in the host resulting in an increased susceptibility
to neoplasia. Our hypothesis is that one such host factor is a deficiency
in GSH, based on the importance of this compound in the detoxification
of a wide variety of exogenous and endogenous carcinogens and free radicals,
as well as in the maintenance of immune function." PubMed.gov
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:
- Aidic 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."
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
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
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.
Medical Professionals on the Benefits of Glutathione
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, Parkinson's,
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. The ELF concentration of GSH is 140 times that of
serum concentrations with a redox ratio of > 9 : 1. 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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