Introduction
To my knowledge there is no proven cure for hepatitis B in this or any
other area of medicine, but this is not to say these therapies are ineffective.
One problem is due to the lack of research in these areas and controlled
studies are uncommon. Due to this lack of double blind studies with reasonable
to large groups of people it is difficult to attribute "cures"
as the infection may have resolve spontaneously as occurs in between 2%-5%
of people each year or due to the complementary medicine.
However there are treatments available where it is believed that damage
due to hepatitis may be limited, cause relief of symptoms, help with interferon
side effects etc And there are many reports of a reduction in
and loss of the in those taking these complimentary medicines. And my own
opinion is that some of the items mentioned here can be beneficial and
deserve closer attention from the general medical community as there appear
to be data to support some of claims made, their low toxicity and low
cost. In particular: as it may prevent liver damage;
as it may help due to it's antiviral properties;
due to antiviral properties and the chance that it my enhance the probability
of a response to interferon.
A note of caution, some herbs and minerals given to people can have been
found to cause liver damage and some herbs increase liver enzymes and
so mask the results of conventional treatment/ongoing disease. Some in
only in a small percentage of people, some in all and some may be dosage
dependent, I therefore advise you to research any herbs and minerals you
decide to take and discuss them with your medical practitioner and make
an informed decision.
This is a large topic and information is taken from various sources and
is provided on an as is basis. Unfortunately the scientific rigour of
controlled studies, double blind trials and confirmation of results rarely
occurs with complementary therapy and sometimes outrageous claims are
made. Similarly often useful treatments are ignored by conventional medicine.
So please treat the information here as a pointer to your own research.
Artichoke (Cynara Scolymus, Caffeic
Acid)
An excerpt from the following article: SILYMARIN COMPLEX FOR LIVER
DISORDERS by Michael T. Murray, N.D. published in "Health World"
spring 1987
The artichoke has a long folk history in treating many liver diseases.
Recent evidence supports this long-time use. The active ingredient in
artichoke is cynarin. this compound is found in highest concentrations
in the leaves.
Like silymarin, cynara extract has also demonstrated significant liver-protecting
and regenerating effects. it also possesses choloeretic effect, promoting
the outflow of bile from the liver to the gall-bladder. This is a very
important property. If the bile is not being transported adequately
to the gallbladder, the liver has an increased risk of being damaged.
Choleretics are very useful in the treatment of hepatitis and other
liver diseases via this "decongesting" effect.
Choleretics typically lower cholesterol levels via their ability to
decrease the synthesis of cholesterol in the liver. Consistent with
its choleretic effect, cynara extract has been shown to lower blood
cholesterol and triglyceride levels in both human and animal studies.
CLINICAL TRIALS OF CYNARA SCOLYMUS
In a controlled trial, two groups of 30 patients having elevated serum
cholesterol and triglycerides were given either cynarin (500 mg. per
day) or a placebo. Cynarin proved to induce a significant reduction
of these elevated cholesterol and triglyceride levels. In addition,
the patients also displayed a reduction in body weight. This effect
was probably a result of cynarin's diuretic activity.
CAFFEIC ACID
It appears cynarin, the active component in artichoke leaves extracts,
is not the true active substance. Since cynarin can be broken down into
caffeic acid in the gastrointestinal tract, it is conceivable that the
true active component is caffeic acid. This compound has demonstrated
a significant liver-protecting effect as well as choloeretic activity.
Cynara Extract has also demonstrated significant liver-protecting and
regenerating effects.
Dandelion Root
Believed to cleanse the bloodstream and the liver and increase the production
of bile. Improves functions of the pancreas, spleen, stomach, and kidneys.
Take for Cirrhosis, hepatitis, anaemia, boils, cramps, fluid retention,
constipation. Reduces cholesterol and uric acid.
I have not found any information in medical journals to backup these
claims.
Kombucha Tea.
The Kombucha organism is a symbiotic colony of yeast's and bacteria that
form a strong membrane that covers the liquid/air interface of the vessel
it grows in. Most people who grow it do so in their own homes, under less
than sterile conditions, yet Kombucha rarely becomes contaminated with
rogue varieties of moulds and bacteria. To grow it, you take a batch of
weak to moderately-strong black tea, sweetened with white sugar, that
has been cooled to room temperature, and float the membrane in it. Within
a week to 10 days, the Kombucha organism converts the tea into a fluid
that is drunk several times daily by the patient. Since the Kombucha is
a form of life called a vinegar mother, the organism that converts, say,
apple cider into apple cider vinegar, the brew becomes more acidic as
it ages. After the brewing period is complete, the liquid is strained,
refrigerated and drunk. The organism is then put into a new batch of tea
(with a bit of the old liquid as a "starter"); often a second
membrane will appear, and they can be separated to start another batch.
The working of the organism in the liquid reduces greatly the sugar and
caffeine content of the tea, and produces large amounts of B vitamins,
minerals, substances that are reported to act as anti-bacterial and anti-viral
agents, and various acids, as well as unknown substances. It produces
a very tiny amount of alcohol as well, perhaps as much as 0.5%, making
it like non-alcoholic brews. The flavour takes some getting used to, but
is not unpleasant, a bit fruity and vinegary. The organism itself is not
consumed,only the tea.
Cautions: the greatest danger is inadvertently consuming a bad
batch of tea that has been contaminated with outside, disease-producing
fungi or bacteria. At least one disease-producing bacteria has been found
in a batch of tea and this has been linked with fatalities. People with
hepatitis don't need the added strain of an induced illness. Fortunately,
it is easy to detect a contaminated batch. Other concerns are that the
unnecessary consumption of antibiotic and antiviral substances could encourage
the mutation of existing pathogens into more resistant strains. I encourage
people who are not chronically ill to avoid taking kombucha as a dietary
supplement for this reason. Kombucha seems to have a slight laxative effect
on some people.
Liquorice root
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This herb appears to have promise for treatment of
hepatitis and many have reported favourably on it use.
However in large doses or if taken for extended periods it can
cause potassium depletion which can have serious consequences.
Please consult with your doctor if considering taking licorice
in large doses or for an extended period as he may wish to monitor
you potassium levels..
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From the "Encyclopaedia of Natural Medicine," Michael Murray,
N.D. and Joseph Pizzorno, N.D.
The recommended dosage of Liquorice (Glycyrrhiza glabra) for hepatitis
of all kinds is:
(Doses 3 times per day)
- Dried root (or as tea, 1 to 2 g.
- Tincture (1:5), 4-6ml (1 to 1.5 tsp)
- Fluid extract (1:1), 0.5-2.0 ml (1/4 to 1/2 tsp)
- Powdered solid extract (4:1), 250-500 mg
If liquorice is used over a long time it is necessary to increase the
intake of potassium rich foods.
Double-blind studies have shown a liquorice component to be effective
in treating viral hepatitis, particularly chronic active hepatitis.
This activity is probably due to its well documented antiviral activity.
A glycyrrhizin-containing product (Stronger Neo-minophagen C), consisting
of 0.2 per cent glycyrrhizin, 0.1 per cent cysteine and 2.0 per cent
glycine in physiological saline solution, is widely used intravenously
in Japan for the treatment of hepatitis. The other components, glycine
and cysteine, appear to modulate glycyrrhizin's actions. Glycine has
been shown to prevent the sodium- and water-retaining effects of glycyrrhizin,
while cysteine aids in detoxification via increased glutathione synthesis
and cystine conjugation.
From "Licorice as a liver herb" by Paul Bergner
Licorice root (Glycyrrhiza glabra) is a time-honoured herbal medicine
in all world herbal traditions. It is used as a primary herb in perhaps
more categories than any other medicinal plant. It is used with success
for acute respiratory problems, gastric ulcers, gastritis, inflammatory
conditions in general, and adrenal exhaustion. Components of licorice
root have both estrogenic and anti-estrogenic activity (Leung; Kraus;
Kumagai et al; Sharaf and Goma; Tamaya et al). It is thus an important
herb for treating hormone-related female
problems. It has not traditionally been used as a liver herb, but medical
research over the past two decades in Japan and China has shown that
licorice is also an important liver herb with strong hepatoprotectant
properties. This should not be thought of as just another minor use
for licorice. It is as significant a hepatoprotectant as the better-known
milk thistle seed, and acts through separate mechanisms than that herb.
The two together should be considered in any hepatoprotectant formula
or treatment plan. Form and dose Most of the Asian clinical research
and practice has been with glycyrrhizin, a major constituent of licorice
root. The product in most Japanese trials is Strong Neominophagen-C
(SNMC) which contains 40 mg glyzyhhrizin, 20 mg cysteine, and 400 mg
glycine in 20 ml saline solution. Cysteine and glycine are amino acids.
A typical treatment for hepatitis is 40 ml of SNMC a day for thirty
days delivering 80 mg of glycyrrhizin per day (Hikino). The upper range
of clinical trials has been 200 ml SNMC (400 mg glycyrrhizin) (Mori
et al, 1989, 1990), but trials above 100 ml (200 mg glycyrrhizin) have
been rare, due to concern over possible side effects (see below) (Hikino).
Oral extracts Comparable therapeutic levels of glycyrrhizin can probably
be reached with oral preparation; important active constituent of licorice,
and therapeutic levels for a wide variety of conditions are easily achieved
with oral administration. Licorice root (G. glabra) contains 6-14% glycyrrhizin
(Merck), so an oral dose of 7-8 grams powdered licorice would deliver
the highest range of glycyrrhizin used in the hepatitis trials to the
gut. This compares to a traditional Chinese oral dose of 3-12 grams
G uralensis (Bensky). How much of this would reach the plasma, and thus
be equivalent to the intravenous trials, has not been tested. Oral administration
of glycyrrhizin alone or as licorice root extract has been tested in
mice (Ozaki et al), and found to be comparable, with each form achieving
similar levels of glycyrrhizin or its active metabolites in the plasma.
Hepatitis
Clinical trials for hepatitis, especially chronic active hepatitis,
have been so successful in Japan that glycyrrhizin is now a standard
medical treatment there (Kumada et al; Matsunami et al.; Ohta et al;
Su et al; Suzuki et al; Wang; Zhang et al).
Mechanisms of hepatoprotection
The mechanisms of hepatoprotection are diverse, and include antioxidant
activity (Kiso et al; Abdugafurova et al; Tan; Ju et al), direct antiviral
effects (Hikino; Crance), enhancement of interferon production (Hikino;
Shinada); enhanced antibody production (Hikino), enhancement of extrathymic
T-Cell activity in the liver (Kimura et al), and protection from immunological
(auto-immune) injuries (Hikino; Mizoguchi et al). A number of animal
and in vitro trials have shown that glycyrrhizin can protect liver cells
from damage from a variety of chemical or immunological agents (Nakamura
et al; Mizoguchi et al; Shibayama; Shiki et al; Zhao et al).
Other Clinical trials
Glycyrrhiza has also been effective in treating HIV/ARC in haemophiliacs,
and, notably, improved liver dysfunction in these patients (Mori et
al, 1990; Mori et al, 1989). It has also been effective in preventing
the hepatic side effects of chemotherapy with a methotrexate combination
or interferon (Akimoto et al; Hayashi et al), and in treating general
hepatic failure (Acharya).
Enterohepatic cycling
One reason licorice is so effective in treatment of the liver is that
it enters the enterohepatic loop, that is, it is excreted in the bile,
then reabsorbed in the gut to recycle repeatedly through the liver (Ichikawa;
Ishida).
Side effects and drug interactions
Licorice produces well-documented side effects when taken in large
doses (>>50 g/day) or for long duration (>>six weeks) (Wichtl).
No such side effects have been observed in clinical trials of 40 ml
SNMC/day for thirty days, or with 100 ml SNMC (200 mg glycyrrhizin/day)
~for a short period~ (Hikino). With widespread use of SNMC in japan,
hyperaldosteronism was seen with larger doses and extended use (SNMC).
The side effect is reversible on discontinuation of glycyrrhizin. Licorice
or glycyrrhizin may also interact with herbs or other medications containing
cardiac glycosides.
From: CD-ROM "The Herbalist" by David L. Hoffman, B.Sc.
The root of licorice, Glycyrrhiza glabra L. and Chinese licorice, G.
uralensis, is an important medicine around the world. Glycyrrhizin is
one of the main components of licorice root. During the course of such
clinical use, glycyrrhizin preparations were found to be effective for
chronic hepatitis and have been widely used for chronic hepatitis and
liver cirrhosis in Japan.
- Glycyrrhizin inhibits liver cell injury but does not reverse reduced
protein synthesis. It is effective against carbon tetrachloride, benzene
hexachloride, PCB and GalN.
- Antibody production is enhanced by glycyrrhizin. When mononuclear
cells from human peripheral blood were stimulated with pokeweed mitogen
in the presence of glycyrrhizin, polyclonal antibody production was
significantly enhanced. Glycyrrhizin may facilitate antibody formation
through the production of interleukin I.
- glycyrrhizin inhibits the growth of several DNA and RNA viruses,
inactivating Herpes simplex virus particles irreversibly.
- its effect against chronic hepatitis was demonstrated in a double-blind
test with 133 patients. Elevated serum transaminase and y-GTP levels
were reduced.
- it appears to be effective on the pretreatment of post-transfusion
hepatitis. In one trial comparing glycyrrhizin and an inactive placebo
in 336 patients, a significant reduction of the incidence of non-B
hepatitis after transfusion was observed in the treated group. Because
a remarkable reduction of the incidence of post-transfusion hepatitis
was observed from 2 weeks to 6 weeks after transfusion, suggesting
that the incidence of short-incubation post-transfusion hepatitis
might be suppressed by using glycyrrhizin.
- it helps prevent post-transfusion hepatitis. When i.v. administration
was continued for about 2 weeks, starting on the day of transfusion,
the incidence of hepatitis was reduced from 17.6 to 12.8%. From these
and other results, it was concluded that the use of this phytochemical
is effective for the prevention of post-transfusion hepatitis.
Note: Many references available.
Milk Thistle (Silymarin, blessed
thistle, Chardon Marie)
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This is one of the most common herbal treatment for
hepatitis. It is non toxic and very few people report any side effects.
It is known to reduce
and has been shown to be effective in protecting the liver against
damage by certain toxins.
In Germany milk thistle is frequently prescribed to those on
interferon.
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Milk Thistle (Silymarin) is reported to be an anti-inflammatory and mast
cell stabilizer that helps protect the liver against toxin, drugs, and
the affects of alcohol (Better Nutrition for Today's Living, March 1993).I
. Two capsules of 100mg extract of milk thistle (Silybum marianum) containing
70% silymarin (ie 140mg of silymarin) are normally taken twice or three
times a day. European research shows that it stimulates regeneration of
liver cells and protects them from toxic injury" It is usually stocked
in health food stores under the names milk thistle, silybum, or silymarin.
From the Encyclopedia of Natural Medicine Michael Murray, N.D. and
Joseph Pizzorno, N.D.
The common milk thistle contains some of the most potent liver protective
substances known, a mixture of three flavanolignins colelctively referred
to as silymarin. (30-33) The concentration of silymarin is highest in
the fruit, but it is also found in the seeds and leaves.
Silymarin's effect in preventing liver destruction and enhancing liver
function relates largely to its ability to inhibit the factors that
are responsible for hepatic damage, i.e., free radicals and leukotrienes,
coupled with an ability to stimulate liver protein synthesis. (30-33)
Silymarin prevents free radical damage by acting as an antioxidant.
Silymarin is many times more potent in antioxidant activity than vitamin
E. Silymarin not only prevents the depletion of glutathione (GSH) induced
by alcohol and other liver toxins, but it was shown to increase the
basal GSH of the liver by 35 per cent over controls in one study. This
is extremely useful when exposure to toxic substances is high, due to
glutathione's vital role in detoxification reactions.
The protective effect of silymarin against liver damage has been demonstrated
in a number of experimental and clinical studies. (30-38) Experimental
liver damage in animals can be produced by such diverse toxic chemicals
as carbon tetrachloride, amanita toxin, galactosamine and praseodymium
nitrate. Silymarin has been shown to protect against liver damage by
all of these agents. (30-33)
Another way in which the liver can be damaged is by the action of leukotrienes.
These compounds are produced by the transfer of oxygen to a polyunsaturated
fatty acid. This reaction is catalysed by the enzume lipoxygenase. Silybum
components inhibit this enzyme, thereby inhibiting the formation of
these damaging compounds.
Perhaps the most interesting effect of silybum components on the liver
is their ability to stimulate protein synthesis. (30-33) The result
is an increase in the production of new liver cells to replace the damaged
old ones. This demonstrates that silymarin exerts both a protective
and restorative effect on the liver.
In human studies, silymarin has been shown to have positive effects
in treating liver diseases of various kinds, including cirrhosis, chronic
hepatitis, fatty infiltration of the liver (chemical and alcohol induced
fatty liver) and inflammation of the bile duct. (32-38) The therapeutic
effect of silymarin in all of these disorders has been confirmed by
histological (biopsy), clinical and laboratory data. Silymarin is especially
effective in the treatment and prevention of toxic chemical or alcohol
induced liver damage. (32-38)
REFERENCES:
30. Hikino, H. Kiso, Y., Wagner, H. and Fiegig, M.,
"Antihepatotoxic actions of flavonolignans from Silybum marianum
fruits", Planta Medica, 1984, 50, pp 248-50
31.Vogel, G., Trost, W., Braatz, R., et al., "Studies on pharmacodynamics,
site and mechanism of action of silymarin the antihpatotoxic principle
from Silybum marianum (L.) Gaert"., Arzneim-Forsch, 1975, 25, pp
179-85
32. Wagner, H., Antihepatotoxic flavonoids", in Cody, V., Middleton,
E. and Harbourne, J.D. (eds), Plant flavinoids in Biology and Medicine:
Biochemical, Pharmacological and Structure-Activity relationships, Alan
R. Liss, New York, NY 1986, pp545-5
33. Wagner, H., "Plant constituents with antihepatotoxic activity",
in Beal, J.L. and Reinhard, E. (eds) Natural Products as Medicinal Agents,
Hippokrates-Verlang, Stuttgart, 1981
34. Sarre, H., "Experience in the treatment of chronic hepatopathies
with silymarin", Arzneim-Forsch, 1971, 21, pp 1,209-12
35. Canini, F., Bartolucci, A., Cristallini, E., et al., "Use of
silymarin in the treatment of alcoholic hepatic stenosis", Clin.
Ther., 1985, 114, pp 307-14
36. Salmi, H.A., and Sarna, S., "Effect of silymarin on chemical,
functional, and morphological alteration of the liver. A double-blind
controlled study" Scand.J.Gastroenterol., 1982, 17, pp 417-21
37. Scheiber, V., and Wohlzogen, F.X., "Analysis of a certain type
of 2 x 3 tables, exemplified by biopsy findings in a controlled clinical
trial", Int.J.Clin.Pharmacol., 1978, 16, pp 533-5
38. Boari, C., Montanari, M., Galleti, G.P., et al., "Occupational
toxic liver diseases. Therapeutic effects of silymarin", Min.Med.,
1985, 72, pp 2,679-88.
Some Modern Uses of Milk Thistle Seed by Paul Bergner
Milk thistle seed extracts, usually standardized to 70% silymarin content,
are commonly used in conventional medicine in Europe, where it has been
officially available since 1969. More than $180 million in silymarin
products were sold in Germany alone in one recent year. The trials below
all used this 70%-silymarin
pharmacetuical preparation, but this does not in any way prove that
only such preparations would have this clinical result. See the accompanying
articles for reports of clinical use of other forms of milk thistle
seed.
HEPATITIS
In 77 patients with acute viral hepatitis, 42 were treated with placebo
and 35 with a milk thistle seed extract. Recovery time for the placebo
group averaged 43 days, and for the silymarin group, 29 days (Legalon).
Alcoholic cirrhosis
In a well-controlled double-blind study of ninety-six cases of alcholic
hepatic cirrhosis, forty-nine patients were treated with placebo and
forty-seven with silymarin. After a five-year period, there were only
five deaths (10.5%) in the silymarin group, and fourteen deaths (28.5%)
in the control group (Benda et al).
Pediatric liver disease
In a study of 166 children under the age of seventeen with chronic
liver disease, the following results were obtained: For cases of chronic
persistent hepatitis, 70% showed improvement, 27% stabilized; 4% had
no improvement or stabilization. For cases of chronic active hepatitis,
32% showed improvement; 44% stabilized, and 24% had no beneficial effect
(Jodl et al).
Fatty degeneration
In a group of 88 patients with toxic-metabolic liver damage due to
alcohol abuse or diabetes mellitus, elevated transmaminase values and
abnormal bromsulphalein test results tended to revert to normal. Ninety-one
abnormal test results fell to only 37 (59% improvement) after treatment
with silymarin (Fintelman V).
Pharmaceutical drugs
In a study of sixty-six female patients taking pychopharmacological
or anticonvulsant agents for neurological or psychiatric problems, liver
function tests gave a total of 71 abnormal results. Fifty-two of these
(73% responded to silymarin treatment, the gret majority of them returning
to normal ranges (Legalon).
Anesthesia
In sixty-one patients receiving anesthesia using halothane or hexobaribtal,
the thrity-two control showed a distinct post-operative rise in serum
enzymes. Twenty-nine patients receiving silymarin showed no such rise
(Benda and Zenz).
Occupational toxins
Studies showed that silymarin could rapidly cure workers producing
pesticides who had disturbed liver function; other studies showed that
in forty patients with posioning by silicon dioxide, the effect could
be completely antagonized by silymarin at certain doses (Legalon)
Phylanthus Amarus/Nituri/Nirruri
(the Ayurvedic name is Bhumy Amalaki)
Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus.
Lancet. 2(8614):764-6, 1988 Oct 1.
"Abstract: In a preliminary study, carriers of hepatitis B virus
were treated with a preparation of the plant Phyllanthus amarus for
30 days. 22 of 37 (59%) treated patients had lost hepatitis B when tested 15-20 days after the end of the treatment compared
with only 1 of 23 (4%) placebo-treated controls. Some subjects have
been followed for up to 9 months. In no case has the surface antigen
returned. Clinical observation revealed few or no toxic effects. The
encouraging results of this preliminary study recommend continued evaluation
of this plant and the active principles isolated from it."
Please note the small numbers of patients and the emphasis that this
is a preliminary study. A medline search shows that many researchers have
failed to confirm these findings, while others show promising, usually
in vitro, results.
Reishi Mushrooms.
From: HEALTH FOODS BUSINESS/JANUARY 1992 CONSUMER EDUCATION SERIES.
REISHI: ANCIENT MEDICINE IS MODERN HOPE
By Linda McGlasson, Assistant Editor
Western culture has often frowned on mushrooms, even fearing the
small innocuous forest growth. The French prize their truffles, but
even truffles and other edible fungi and mushrooms are not as highly
valued or show as much potential as a species of mushrooms called Ling
Zhi or Reishi (Ganoderma lucidum).
The late Hiroshi Hikino, recognized as the world's authority on thechemistry
of Oriental medicinal plants, called Reishi one of "the most important
elixirs in the Orient."
Relatively rare and undiscovered in the West, Reishi and other mushrooms
have been revered as herbal medicines for thousands of years in Japan
and China. Emperors of the great Chinese dynasties and Japanese royalty
drank teas and concoctions of the mushroom for vitality and long life.
The ancient Taoists were constantly searching for the elixir of eternal
youth, and Reishi was believed to be among the ingredients.
In modern times, Ganoderma lucidum and its fellow mushrooms have been
well-researched in Asian universities. It is currently being studied
in China as a sports performance enhancer. Its long History has sparked
interest in the West where it is used by herbalists to treat diverse
problems such as allergies, chronic Fatigue Syndrome, diabetes, liver
diseases and many immune-related diseases.
As little as 20 years ago, Reishi was rare and not widely found in
Asia. It grew in the wild, but was extremely hard to cultivate. Now
with an increased knowledge of the climates that it thrives in, scientists
are able to set up artificial growth conditions with the correct amounts
of oxygen and moisture for the spores to grow into the Reishi mushroom.
JUST ANOTHER FUNGUS?
Reishi mushrooms are polypore mushrooms. Mushrooms are the fruiting
body and reproductive structure of a higher order fungus organism, much
like an apple is the fruit of an apple tree. The actual mushroom "tree"
is a fine thread-like network called mycelium. This mycelium is for
the most part subterranean, living in soil, logs and other organic litter.
Unlike green plants, which produce many of their own nutrients by photosynthesis,
mushrooms primarily get their nutrients from dead organic matter or
soil. Mushrooms and their mycelium are nature's original recyclers.
Without them, the planet surface would be piled high with dead, decaying
material.
Mushrooms rise out of the mycelium when the right nutrients are amassed
and the right environmental conditions are present. Mushrooms release
spores at maturity. The wind spreads them and when they land on the
right spot, the cycle starts over again.
REISHI'S MEDICAL PROPERTIES
In the 16th Century pharmacopedia Pen T'sao Kang Mu, which contains
hundreds of natural medicines the Chinese have used for thousands of
years, compiler Le Shih-chen described the uses of Reishi. "It
positively affects the life energy, or qi of the heart, repairing the
chest area and benefiting those with a knotted and tight chest."
He wrote that it also increases intellectual capacity and banishes forgetfulness.
"Taken over a long period of time, agility of the body will not
cease, and the years are lengthened to those of the Immortal Fairies."
In the Orient, Reishi is considered a Fu Zhen herb (immune modulation).
Presently, Reishi has various applications including lowering or raising
blood pressure, stimulating liver actions, blood cleansing, and acting
as an adaptogen in helping the body fight the effects of stress.
Chinese herbalists prize it for its abilities to regenerate the liver.
In high doses, and to some degree normal doses, Ganoderma maybe classified
as a liver detoxicant and protectant.
In traditional Oriental applications Reishi is also used to treat insomnia,
gastric ulcers, neurasthenia, arthritis, nephritis, asthma, bronchitis,
hypertension and poisoning. It is also being used in treating neuromuscular
disorders -- stress-induced tension, myasthenia gravis and muscular
dystrophy -- all with varying degrees of success.
Toxicity studies show no toxic effects on humans. In research, patients
are given much higher doses, as high as 10 grams of extract per day,
with no ill effects.
ACTIVE INGREDIENTS
The potency of Reishi mushrooms is usually based on its level of triterpenoids.
One can determine the level of this by tasting it. The more bitter it
is, the higher the level of triterpenoids. Because Reishi is a polypore,
(a group of hard, woody, bracket-like mushrooms) it is not eaten, but
cut into pieces and made into a tea. In China, the average dose is 3
to 5 grams a day. Other popular forms of delivery are the water/alcohol
extracts and powders.
Reishi mushrooms and mushroom extracts are generally analyzed for specific
triterpenoids called Ganoderic acids. When buying a Reishi mushroom
product, check for the analysis of how much triterpenoids is in the
extract or powder.
"There is no standardization yet, either here or in Asia for Reishi.
You have to look for high ganoderic acid-A levels, which indicates high
levels of other ganoderic acids," said Kenneth Jones, a researcher/writer
specializing in the ethnopharmacology of medicinal plants.
One focus for future research is on Reishi spore extracts. In China,
it has been used in injectable form in clinical treatments of various
ailments with success. One of the things it has successfully treated
is low energy, and debilitation following long illness.
OTHER APPLICATIONS
Chinese women take Reishi for beautification of the skin. The results
are probably due to the mushroom's hormone-potentiating effects, Jones
said.
Reishi is included in many Japanese patents for hair loss formulas,
including products used for alopecia. Spore extract injections of Reishi
are also being used to treat lupus in China.
The mycelium of Reishi contains high levels of polysaccharides, which
have been shown in research to induce the production of interferon.
Interferon is a protein produced inside cells to fight viral infection.
Polysaccharides are also tumor fighters and help stimulate the immune
system.
Reishi is being recognized for its adjunct use as an immune system
stimulator when cancer therapy is being used. The use of Reishi as a
cancer treatment in the Orient is centuries old. In following the concept
of qi tonics, Reishi is used to strengthen the body's resistance to
outside forces.
Former heart surgeon Dr. Fukumi Morishige, a leading authority on vitamin
C in Japan, reports that when Reishi and vitamin C are combined the
results against cancer and other diseases are far better than when Reishi
is ingested. This is because the vitamin makes the polysaccharides more
accessible to the immune system.
It is also an adaptogen, with properties similar to ginseng. The adenosine
in Reishi may explain why the Chinese use it for patients suffering
from nervous tension. Adenosine relaxes skeletal muscles, calms the
central nervous system and operates against the stimulating action of
caffeine.
"Reishi mushrooms are certainly an herb for the 90s and beyond,"
commented Jeff Chilton, president of North American Reishi. "Considering
that Reishi has a history of use that spans 2,000 years and is more
highly revered than ginseng in the Orient, one could readily compare
its potential to that of ginseng."
Contributing to this article were Terry Willard, Ph.D. and Kenneth
Jones, authors of Reishi Mushroom: Herb of Spiritual Potency and Medical
Wonder.
Schizandra
From: a CD-ROM called The Herbalist by David L. Hoffman, BSc
The herb is prepared from the ripe fruits of Chinese magnolia vine,
Schizandra chinensis, and is extensively used in Oriental medicine.
Since the initial isolation of lignans (schizandrin and deoxyschizandrin)
from its seed oil, more than 30 lignans have been isolated and characterised.
.Schizandra given to 189 patients manifesting chronic viral hepatitis
with elevated serum GPT levels. 107 were given 100 mg. of the extract
(= 1.5 g of the herb) 82 cases received a liver extract-vitamin E complex
as control. After 16-24 weeks of treatment, 73 of those treated with
Schizandra showed a fall of serum GPT to normal levels. No rebound was
observed after withdrawal of the herb. The rate of effectiveness in
lowering the GPT level was 68.2% in the treated group and 44% in the
control group. The average time needed for lowering the level to normal
was about 4 weeks for the treated group and 8 weeks for the control
group. Schizandra was effective in relieving symptoms of sleeplessness,
fatigue, abdominal tension, and loose bowels. No side-effects were observed.
Thymus Extracts.
Excerpts from Dr. Julian Whitaker's "Health and Healing"
monthly newsletter. Oct. 1992, Vol. 2. No. 11.
The "proofs" offered re: oral thymus supplements are mostly
anecdotal.
The thymus gland controls your immune system in to basic ways. First
it is the source of T-lymphocytes or T-cells (T stands for thymus),
which are crucial in the fight against viruses, bacteria, yeast, and
all other foreign invaders. Early in life the thymus gland seeds the
bone marrow with immature T-cells, where they multiply and mature. It
is the T-cells that are destroyed by the HIV virus and their destruction
brings on full-blown AIDS.
Second, the thymus gland produces a variety of hormones that stimulate
the maturation of T-cells and increase the production of other immune
hormones, such as interferon and the immune globulin's. Several hormones
from the thymus gland have been isolated, but the one receiving the
most attention right now is thymosin alpha 1.
Researchers all over the world are exploring the therapeutic possibilities
of thymus hormone replacement, but none are more vigorously than Milton
Mutchnick, MD, head of the department of gastroenterology at Hutzel
Hospital and associate professor of medicine at Wayne State University
medical Centre in Detroit. He recently published a year-long study demonstrating
that a synthetic indictable version of a thymus hormone, thymosin alpha
1, given twice weekly, eliminated the hepatitis B virus in six out of
seven patients (86%), compared to a spontaneous conversion of one out
of five (20%) in the placebo group.
EUROPEAN STUDIES SHOW VALUE OF THYMUS EXTRACT
Oral products of thymus extract are shunned in this country because
most researchers believe that the digestive juices in the stomach and
intestines will destroy them before they are absorbed. However, in Europe,
an oral thymus product, Thymodulin, with sales of over $300 million
a year, has been sued and studied for almost a decade. Control trials
show that it significantly improves a variety of conditions and even
eliminated hepatitis b in 45% to 50% of children, compared to only 20%
in the control group.
In one convincing study, oral Thymodulin was administered to 29 patients:
eight with herpes zoster, eight with whooping cough, eight with chicken
pox and five with infectious mononucleosis. Another 29 patients with
the same diseases received a placebo. Various parameters were used to
measure the effectiveness of Thymodulin, and all patients who received
it showed significant improvement compared to controls.
Dr. Burgstiner (Savannah GA) contracted Dr. Mutchnick, who was very
interested in Dr. Burgstiner's experience and wanted to have a look
at the product he had used. Dr. Mutchnick took Immunoplex 402 and the
vitamin preparation himself, and then measured his blood levels of thymosin
alpha 1. He wrote Dr. Burgstiner: "You might be pleased to know
that I conducted a pilot study on myself by taking several of the Immunoplex
402 tablets after having first obtained a pre-treatment serum, which
was followed then by serums at 1/2 hour, 1 hour, 2 hours, 3 hours, and
4 hours. Lo an behold, by the first hour--and consistently for the next
several hours--the thymosin alpha 1 level, as determined by the ELISA,
increased. Clearly, I will have to repeat this on a number of subjects,
but this offers an exciting potential for turning thymosin alpha 1 from
a subcutaneous injection into an oral preparation."
Dr. Burgstiner encouraged Melvin L. Haysman, MD, who practices allergy
and clinical immunology in Savannah, to try the products with some of
his patients. Dr. Haysman collected before and after blood smaples of
about a dozen patients who took Immunoplex 402 with the vitamins and
minerals, and sent them to Dr. Mutchnick. Dr. Mutchnick found that the
products had increased the blood levels of thymosin alpha 1 in every
patient, and in some by 300% to 700%.
WHY NUTRITIONAL SUPPLEMENTS SHOULD BE ADDED
Vitamin and mineral supplements taken with the Immunoplex 402 markedly
enhance the effect of the product. Dr. Mutchnick found that three Immunoplex
402 tablets taken with one vitamin and mineral supplement elevated the
blood level by over 300%, and three Immunoplex 402 tablets plus two
of teh vitamin and mineral supplements caused an almost 450% rise in
thymosin alpha 1 hormone.
It should not be a surprise that supplemental nutrients would have
this effect on the oral preparation. In one recent study from italy,
zinc sulphate was added to the serum of patients with Down's syndrome
(known to have very low levels of thymus activity) and of elderly patients,
also with characteristically low levels of active thymus hormone. The
active hormone in their serum increased to that of young, healthy individuals.
The authors theorised that zinc is necessary to activate thymus hormone,
and that marginal zinc deficiencies could be a cause of immune dysfunction
and decreased function of thymus hormone even when it was present. The
same is likely true for other essential nutrients as well. One of the
first and most consistent signs of any nutrient deficiency is immune
dysfunction. But very few doctors prescribe nutritional supplements.
They all "know" they don't work. And blah blah blah....
THE POTENTIAL FOR PREVENTING AGE-RELATED DISORDERS
The ability to maintain high levels of thymus hormone activity has
enormous potential for alleviating suffering from age-related diseases,
and the anecdotal experience of Drs. Burgstiner and Haysman is remarkable.
Dr. Burgstiner has been keeping a running tally of the benefits reported
to him by patients and doctors of patients who have tried the preparations.
This is not a scientific study, but over the last two years...
- 63 patients have reported complete recovery from Hep B.
- 3 patients with Hep C recovered
- 26 patients with chronic fatigue syndrome reported marked improvement.
- 24 patients with rheumatoid arthritis -- some taking methotrexate,
cortisone, and gold shots, indicating very severe conditions -- reported
almost complete remission of symptoms and elimination of strong medications.
Tumeric (Curcumin)
An excerpt from the following article: SILYMARIN COMPLEX FOR LIVER
DISORDERS by Michael T. Murray, N.D. published in "Health World"
spring 1987
Curcumin is the yellow pigment of turmeric. Curcumin shares some of
the same effects on the liver as
and cynarin. It has demonstrated similar liver protection activity to
silymarin. Curcumin is believed to also be converted to a choleretic
compound, perhaps even caffeic acid. Curcumin's documented choleretic
effects support its historical use in treating liver and gallbladder
disorders. Like cynara extracts, curcumin has also been shown to lower
cholesterol levels.
Vitamin E and Selenium
Increased intake of Vitamin E (ie above the recommended daily allowance
(RDA)) and Selenium have been shown to reduce the amount of liver damage
in rats caused by carbon tetrachloride. Increased dosages of vitamin E
also have been shown to reduce the risk of coronary heart disease in humans.
In view of this supplementation above the RDA would apear a sensible thing
to consider.
Acetyl-L-Carnitine
(ALC)
Dosage 750mg - 2000mg per day
Carnitine helps convert fatty acids to energy and a high Carnitine level
is needed in the liver to handle increase fatty acid produced by alcohol
consumption, a high fat diet, chemical exposure or hepatitis. However
exposure to these can lead to a carnitine deficiency that can be reversed
by supplementing with Acetyl-L-Carnitine.
Although there are no studies that show that if ALC can be helpful in
reducing the damage done to the liver by chronic viral hepatitis it has
been reported that it is very useful in improving memory and mental functioning.
This has been found to be useful in removing the 'brain fog' often reported
by those with hepatitis. Carnitine is also believed to reduce TNF which
may be beneficial to those with chronic viral disease and to aid in detoxification
of ammonia in body tissues.
Please note the next paragraph is speculation as this area of research
is still quite new.
Acetyl-L-Carnitine and L-Carnitine may also play a role in modulating
the level or circulating tumor necrosis factor (TNF). High levels of TNF
appear to suppress the virus but low levels appear to improve recognition
of the virus by the immune system. It therefore appears that both increasing
and decreasing levels of TNF has benefits and drawbacks. To reduce viral
replication and liver damage high TNF would appear to be appropriate.
However if trying to gain immune recognition and induce seroconversion
(loss of the "e" antigen) then a low level of TNF is appropriate.
I hope to have more on this is the next version.
N-Acetyl-Cysteine
(NAC)
Dosage 600mg - 1800mg per day? Note: Although NAC is known to be very
safe please consult with your doctor before taking.
ANTI-HEPATITIS-B VIRUS ACTIVITY OF N-ACETYL-L-CYSTEINE (NAC) - NEW
ASPECTS OF A WELL-ESTABLISHED DRUG
N-acetyl-L-cysteine (NAC) is commonly administered as an antidote against
acetaminophen (paracetamol) intoxication and is the preferred agent
in the treatment of pulmonary diseases. It is furthermore commonly considered
that it restrains human immuodeficiency virus (HIV) replication by scavenging
reactive oxygen intermediates (ROI) and thus suppressing activation
of nuclear factor kappa B (NF kappa B). We Show here that NAC is in
addition able to inhibit hepatitis B virus (HBV) replication, but by
a mechanism independent of the intracellular level of reactive oxygen
intermediates. Treatment of HBV-producing cell lines with NAC resulted
in an at least 50-fold reduction of viral DNA in the tissue culture
supernatant within 48 h. This decrease of viral DNA and thus of virions
in the tissue culture supernatant is caused by a disturbance of the
virus assembly, rather than by a reduction of viral transcripts. Our
data strongly suggest a potential use of this well-established, non-toxic
drug for the treatment of HBV infection. Since NAC, in contrast to interferon,
exerts its anti-HBV activity at a post transcriptional level, a combination
of NAC with the established interferon therapy could also be considered.
Other preliminary studies indicate that NAC may improve the response
rate when taken in conjunction with interferon. NAC is commonly available
from health food stores.
NAC has been used safely at very high doses but side effects have been
reported including: stomach upset and diarrhoea. NAC can reduce mucous
secretions in the stomach so people with a history of ulcers need to be
more cautious if taking NAC The Martindale Extra Pharmacopoeia reports
that some antibiotics, including amphotericin, ampicillin, erythromycin
and tetracycline may be incompatible or inactivated when mixed with NAC.
It has also been reported that NAC can reduce the absorption of minerals
and some nutritionists advocate taking supplements.
Note: Although this article refers to Hepatitis C I have included it
here for information:-
Journal of Interferon Research 13:279-282 (1993)..Beloqui, Prieto,
et al
Abstract: Hepatitis C virus (HCV) is an RNA virus that replicates in
both the liver and lymphoid cells. Interferon-alpha (IFN) is a useful
treatment of chronic HCV although resistance to this drug occurs frequently.
<snip> In IFN-unresponsive patients, the addition of 600 mg tid
of oral N-acetyl cysteine (NAC), a glutathione precursor, resulted in
a steady decrease of ALT values in all patients, with complete normalisation
in 41% of cases after 5-6 months of combined therapy. <snip> HCV
replication was markedly inhibited in lymphocytes and viremia was cleared
in one of the 8 patients tested. In conclusion, NAC enhanced the response
to INF in CHC. Controlled studies are needed to ascertain whether antioxidant
therapy might act in synergy with IFN in chronic viral hepatitis.
This article first appeared in the April, May,
June 1994 issues of VRP's Nutritional News
Vitamin Research Products, Inc.
3579 Hwy. 50 East,
Carson City,
NV 89701
1-800-877-2447
fax 1-800-877-3292
VRP's HomePage
email:robert@inetworld.com
Disclaimer: This information may be copied and distributed freely as
long as all text remains intact, unchanged and with Vitamin Research
Products, Inc. listed as source. Commercial use or commercial distribution
may not occur without the express written permission of Vitamin Research
Products, Inc.
No information in this article should be taken as a recommendation.
If you have any questions about the relationship between N-Acetyl Carnitine
and your health, seek the advice of a qualified physician.
A.S. Gissen
Part 1
In 1963 it was demonstrated that N-Acetyl Cysteine (NAC), an endogenous
product of cysteine metabolism, could be used as a mucolytic.(1) This
had great potential in chronic lung diseases, and NAC quickly became
utilized in clinical practice, predominantly in Europe. Since it was
believed that NAC, due to its sulfhydryl group, liquefied mucus by directly
reducing disulfide bonds in the mucus, NAC was initially given only
by inhalation. Subsequently, NAC was also utilised orally, for this
mode of administration was also shown to be effective. In the years
following the discovery of its mucolytic property, research has shown
that NAC is a very effective precursor and stimulator of glutathione
synthesis. In fact, NAC's effects on lung disorders and mucus viscosity
now appear to be explained by its ability to augment glutathione production,
rather than the initial belief that NAC acted directly to break-up mucus.(2)
Glutathione is a cysteine-containing tripeptide whose cellular functions
include participation in numerous enzymatic reactions; transport of
amino acids; and defence from free radicals, reactive oxygen intermediates,
and certain toxic chemicals. Because glutathione is an important endogenous
antioxidant, NAC has emerged from its mucolytic role to become a potent
protective agent in many free-radical mediated conditions and diseases.
Indeed, NAC has become a better researched, more effective, and safer
antioxidant alternative to L-cysteine. This is because NAC is not only
less toxic than L-cysteine, it is much more effective in raising glutathione
levels.(3)
N-Acetyl Cysteine Metabolism NAC is quickly absorbed after oral administration,
with peak blood levels being obtained within one hour.(4) NAC is rapidly
and extensively metabolized in the gut wall and liver, resulting in
low blood levels of the parent compound, NAC. One of the major metabolic
pathways of NAC metabolism is the conversion of NAC to L-cysteine, and
ultimately, the incorporation of cysteine into glutathione. NAC administration
has been shown to increase glutathione levels in different tissues of
the body, both in animals and humans.(5) L- cysteine, on the other hand,
is much less effective than NAC at raising glutathione levels. This
is because the administration of L-cysteine results in its rapid oxidation
to L-cystine, its insoluble disulfide. NAC's greater effectiveness stems
from the preferential incorporation of NAC-derived L-cysteine into glutathione,
rather than its oxidation to cystine or metabolism to sulfate or taurine.
The majority of L-cysteine metabolism is into pathways that lead to
metabolites other than glutathione, while most of NAC metabolism can
be accounted for by glutathione synthesis.(6) This preferential distribution
of NAC to glutathione represents a novel means of augmenting glutathione
production, although the exact mechanism that makes this possible remains
the subject of scientific research.
NAC and Oxidation The antioxidant role of NAC, and the glutathione
formed from it, first became apparent when it was discovered that NAC
could be used for the treatment of acetaminophen poisoning.(7) Acetaminophen
is a commonly used analgesic that most of us have used at one time or
another. Although very safe when used at therapeutic doses, ingestion
of 10- 15 grams of acetaminophen in a single dose can result in liver
damage 2-5 days later and death from liver failure.(8) Renal damage,
sometimes leading to renal failure, can occur up to 14 days later even
without evidence of liver damage.(9) The cytotoxicity of acetaminophen
is now known to be mediated by a reactive metabolite (oxidizing agent)
normally detoxified by glutathione. When cellular glutathione levels
become depleted to less than 25% of normal, cell death can result. When
given within 12 hours of ingestion, NAC prevents acetaminophen-induced
cellular damage. By supplying the cells with a means of producing glutathione,
NAC helps maintain cellular glutathione levels, preventing cell death.
NAC is much less effective when given much later than 12-16 hours after
acetaminophen overdose, as the glutathione formed from NAC can prevent
oxidant-derived cellular damage, but cannot reverse it. In the years
following the discovery of its usefulness in acetaminophen poisoning,
it was proven that NAC worked because it was an antioxidant and was
converted to glutathione, an even more potent antioxidant.(10) The ensuing
research has shown NAC to be much more than the mucolytic it was once
regarded as. For example, NAC is itself an antioxidant. It has the capacity
to scavenge hydrogen peroxide, hypochlorous acid, and the hydroxyl radical.(11)
Most of its antioxidant potential, however, is due to its rapid metabolism
to glutathione. In this form NAC has demonstrated the ability to decrease
membrane damage from superoxide-generating systems,(12) as well as prevent
damage to human bronchial fibroblasts from tobacco smoke condensates.(13)
Recent years have shown NAC receiving growing interest among both scientists
and physicians, due to the enormous role that oxidation and free-radical
mediated damage plays in so many conditions and diseases. In fact, NAC
has been a featured topic of several international symposia on the potential
of antioxidants as therapeutic agents,(14) as well as being a supplement
in a large cancer chemoprevention trial currently taking place in Europe.(15)
Part 2
In part 1 of our examination of N-Acetyl Cysteine (NAC), we reviewed
the metabolism and antioxidant properties of NAC. We will continue our
review of NAC with an overview of the clinical and experimental evidence
of NAC's potential in lung disorders, and its role in immune function.
NAC and Lung Disorders
The use of NAC as a treatment for bronchitis was its first clinical
use over 30 years ago. NAC's ability to liquefy the mucus (mucolytic)
that contributes to this condition has been utilized in Europe and the
rest of the world for decades. Oral NAC has been shown to decrease the
exacerbation rate in people with chronic bronchitis.(16) NAC has also
been used with success in people with Chronic Obstructive Pulmonary
Disease, Adult Respiratory Distress Syndrome, and emphysema.(17) Research
into lung disorders other than bronchitis, as well as NAC's emergence
from mucolytic to antioxidant, has caused NAC to be viewed as a compound
with potential usefulness in many respiratory disorders and diseases.
NAC and Immune Function
One of the most exciting areas of NAC research is in the area of immunology.
It is generally accepted that immune responses are mediated by hormonelike
peptides, such as cytokines and lymphokines. However, other low-molecular
weight metabolites have the ability to regulate immune function. One
of the best researched of this class of immunoregulatory substances
is the amino acid cysteine. Because the activation and proliferation
of T cells normally requires oxidizing substances such as superoxide
and hydrogen peroxide, lymphocytes contain a limited amount of reducing
substances such as cysteine.(18) Interestingly, unlike most other cells,
lymphocytes can utilize cysteine or NAC for glutathione production,
but not cystine.(19) Thus, lymphocytes are very sensitive to the levels
of extracellular cysteine. Cysteine, however, is found in the lowest
concentration of all protein-forming amino acids in the blood. It is
during the interchange
between lymphocytes and macrophages that the macrophages consume cystine
from the blood plasma, and release cysteine to stimulate T-cell respones.(20)
In the course of the activation of T-cells, macrophages come into contact
with T-cells and transfer among other immunochemicals, cysteine. This
transfer of cysteine ensures adequate glutathione production for optimal
T-cell proliferation. Indeed, NAC has been found to significantly enhance
human T-cell function, especially in older individuals.(21)
No illness has contributed more to our understanding of the potential
roles of cysteine and its precursor NAC in immune function than HIV
infection and AIDS. Cysteine and glutathione levels have been found
to be significantly depressed in people with HIV infection and AIDS.(22)
In fact, this depression of cysteine and glutathione levels has been
observed in patients at all stages of the disease, including those presenting
no symptoms and appearing healthy. Many researchers feel that this glutathione
deficiency
plays a major role in the pathogenesis of HIV and the eventual development
of AIDS. NAC is currently undergoing clinical trials around the world
as an augmenter of immune function in people with AIDS. It has shown
the ability to not only restore cysteine and glutathione levels, but
also to inhibit the replication of HIV.(23) It has even been suggested
that NAC's ability to inhibit latent HIV expression may slow the development
of HIV infection to active AIDS.(24) Unfortunately, as many researchers
have lamented, NAC as an approved therapeutic for AIDS continues to
wallow in small-scale clinical trials. It is unconscionable that a compound
with very impressive laboratory results against HIV, along with a 30
year track record of safety in Europe, could be mired in clinical trials
that will not only take years to complete, but will examine primarily
NAC's usefulness in full-blown AIDS. This totally ignores NAC's greatest
potential, its ability to possibly prevent the progression to AIDS from
asymptomatic HIV-infection.
Using NAC+
With its well-documented superiority as a stable source of cysteine
and precursor of glutathione, NAC appears to be a very useful dietary
source of cysteine. The obvious question then is how much supplemental
NAC is adequate or desirable. In its long use as a therapy for respiratory
diseases and conditions, NAC has been utilised at dosages from 200 milligrams
to 1800+ milligrams daily. NAC has been given both in divided doses
and as one daily dose, usually with equal effectiveness. Higher doses
have been utilised in more severe disease states, while lower doses
have been used in less severe illness. For general use as an antioxidant,
most of us would want to consume from 250 milligrams to 1200 milligrams
daily. People exposed to large amounts of oxidants and glutathione depleters,
such as smokers, would probably want to take an amount of NAC at the
upper level of this range. For other uses, such as in HIV infection
and severe lung conditions, larger doses may be necessary for optimum
results. However, persons with such conditions wishing to take large
amounts of NAC should do so under a physician's care. This is not due
to any NAC-associated toxicity, as none has been reported, but rather
because you should not attempt to self-medicate serious conditions such
as HIV infection or lung diseases. One last consideration with NAC is
the consumption of other antioxidants, such as vitamin C, vitamin E,
and selenium. While almost all studies to date have examined NAC supplements
when taken alone, other antioxidants and vitamins that play a role in
the metabolism and regeneration of glutathione should enhance NAC's
properties.
Part 3
NAC and Carcinogenesis
One of the most exciting areas of research into the potential benefits
of N-Acetyl Cysteine (NAC) is that of cancer chemoprevention. Numerous
studies have documented antimutagenic effects of NAC against a wide
variety of mutagenic chemicals and mixtures.(25) In addition, NAC displays
anticarcinogenic effects in various organs of rodents, including the
mammary glands, skin, trachea, lung, bladder, and colon.(26) Because
of this experimental evidence, NAC is considered one of the most promising
chemopreventative agents. In fact, it is currently under investigation
in clinical intervention trials in both the U.S. and Europe for the
prevention of second primary tumours in patients previously treated
for cancer of the oral cavity, larynx, and lung.(27)
The mechanisms of action for NAC's antimutagenic and anticarcinogenic
properties has been shown to be multifaceted. To begin with, it detoxifies
direct-acting mutagens such as superoxide, hydrogen peroxide, and singlet
oxygen due to its antioxidant activity.(28) NAC also inhibits the mutagenicity
of procarcinogens such as cigarette smoke condensate, benzo(a)pyrene,
and aflatoxin by binding with their metabolites.(29) Inside cells, NAC
is rapidly converted to cysteine and then glutathione. As a result,
NAC enhances the detoxification of carcinogens inside cells. The glutathione
formed from NAC effectively blocks electrophilic compounds and metabolites,
as well as efficiently scavenging reactive oxygen species. Glutathione
also protects against the down regulation of nuclear enzymes that is
produced by carcinogens, decreases carcinogen-induced DNA damage, and
prevents the ultimate formation of carcinogen-DNA adducts.(30) All of
these mechanisms contribute to NAC's anticarcinogenic effects by inhibiting
the initiation of the carcinogenic process, as well as the later promotion
stage of carcinogenesis. The ability of NAC to prevent carcinogen-DNA
adducts offers hope for more than preventing cancer. For instance, multiple
DNA adducts were found not only in the lung, but also in the heart and
aorta in cigarette smoke exposed rats. Administration of NAC to these
animals inhibited the formation of these carcinogen-DNA adducts in all
organs.(31) These authors raised the hypothesis that while, for instance,
NAC inhibits dominant lethal mutations by lowering DNA adduct formation
in the testes, DNA adduct formation in other organs could explain numerous
consequences of carcinogen exposure. They hypothesised that DNA adducts
in the lung, heart, and aorta may be pathogenically related with lung
cancer, cardiomyopathies, and arteriosclerosis. This hypothesis was
supported by evidence that DNA adducts can be detected in human aorta
smooth muscle cells from arteriosclerotic patients. In its role as an
inhibitor of DNA adduct formation in various organs and tissues, NAC
may be a potent protector of not only cancer, but a wide variety of
degenerative diseases.
References:
1) A.L. Sheffner, Ann NY Acad Sci 1963; 106: 298-310.
2) I.A. Cosgreave, A. Eklund, K. Larsson, et al, Eur J Respir Dis 1987;
70: 73-77. Editorial, Eur J Respir Dis 1987; 70: 71-72.
3) T.J. Slaga, in: Carcinogenesis Vol. 5: Modifiers of Chemical Carcinogenesis
(Ed. T.J. Slaga). p. 111. Raven Press, New York (1980).
4) M. Holdiness, Clin Pharmacokinetics 1991; 20: 123-134.
5) M.M.E. Bridgeman, M. Marsden, W. MacNee, et al, Thorax 1991; 46:
39-42.
6) J.M. Estrela, G.T. Saez, L. Sucha, et al, Biochem Pharm 1983; 32:
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7) E. Piperno, D.A. Berssenbruegge, Lancet 1976; 2: 738.
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9) L.F. Prescott, A.T. Proudfoot, R.J. Cregeen, Br Med Journal 1982:
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10) R.J. Flanagan, T.J. Meredith, Am J Med 1991; 91 (Suppl. 3C): 131s-137s.
11) O.I. Aruoma, B. Halliwell, B.M. Hoey, et al, Free Rad Biol Med 1989;
6: 593-597.
12) S. DeFlora, A. Izzotti, F. D'Agostini, et al, Am J Med 1991; 91
(Suppl. 3C): 122s-130s.
13) P. Moldeus, I.A. Cotgreave, M. Berggren, Respiration 1986; 50 (Suppl.
1): 31-42.
14) R.G. Crystal, A. Bast, et al, Am J Med 1991; 91 (Suppl. 3C).
15) G.J. Kelloff, C.W. Boone, W.F. Malone, J Cell Biochem 1992; 161
(Suppl.): 1-72.
Part 2
16) Multicenter Study Group, Eur J Resp Dis 1980; 61 (Suppl. 111): 93-108.
G. Boman, U. Backer, S. Larsson, et al, Eur J Resp Dis 1983; 64: 405-415.
British Thoracic Research Commitee, Thorax 1985; 40: 832-835.
17) P. Suter, G. Domenighetti, M.D. Schaller, et al, Chest 1994; 105:
190-194. G.R. Bernard, Am J Med 1991; 91 (Suppl. 3C): 54s-59s. W. MacNee,
M.M.E. Bridgeman, M. Marsden, Am J Med 1991; 91 (Suppl. 3C): 60s-69s.
18) W. Droge, H.P. Eck, H. Gmunder, et al, Am J Med 1991; 91 (Suppl.
3C): 140s-144s.
19) H. Gmunder, H.P. Eck, W. Droge, Eur J Biochem 1991; 201: 113-117.
See also reference18.
20) H. Gmunder, H.P. Eck, B. Benninghoff, et al, Cell Immunol 1990;
129:32-46.
21) E. Eylar, C. Rivera-Quinones, C. Molina, et al, Int Immunol 1993;
5:97-101.
22) F.J.T. Staal, M. Roederer, D.M. Israelski, et al, AIDS Res Human
Retroviruses 1992; 2: 311. R. Buhl, K.J. Holroyd, A. Mastrangeli, et
al, Lancet 1989; 2: 1294.
23) M. Roederer, S. Ela, F.J.T. Staal, et al, AIDS Res Human Retroviruses
1992; 8:209-217.
24) M. Roederer, P.A. Raju, F.J.T. Staal, et al, AIDS Res Human Retroviruses
1991; 7: 563-570.
Part 3
25) S. DeFlora, A. Izzotti, F. D'Agostini, et al, in: Cancer Chemoprevention
(Eds., L. Wattenberg, et al), pp. 183-194. CRC Press, Boca Raton, FL
(1992). N.DeVries, S.DeFlora, J Cell Biochem 1993; Suppl. 17F: 270-277.
26) A. Izzotti, F. D'Agostini, M. Bagnasco, et al, Cancer Res 1994;
54 (Suppl.):1994s-1998s.
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