Drugs and Hepatitis

Complementary Medicine

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 LFT’s and loss of the “e” antigen 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: Milk Thistle as it may prevent liver damage; Licorice as it may help due to it’s antiviral properties; N-Acetyl-Cysteine due to antiviral properties and the chance that it my enhance the probability of a response to interferonHepatitis B V4.1 – 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

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 femaleproblems. 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)

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 BergnerMilk 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 alcoholic 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 surface antigen 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 silymarin 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 DRUGN-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.
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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: 3485-3487. L. DeCaro, A. Ghizzi, R. Costa, et al, Arzneimettel-Forschung 1989; 39: 382-386.
7) E. Piperno, D.A. Berssenbruegge, Lancet 1976; 2: 738.
8) L.F. Prescott, Drugs 1983; 25: 290-314.
9) L.F. Prescott, A.T. Proudfoot, R.J. Cregeen, Br Med Journal 1982: 284: 421-422.
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.
27) See reference 15.
28) S. DeFlora, A. Izzotti, F. D’Agostini, et al, Am J Med 1991; 91 (Suppl.3C): 122-130.
29) S. DeFlora, C. Bennicelli, A. Camoirano, et al, Carcinogenesis 1985; 6:1735-1745.
30) A. Izzotti, R. Balansky, N. Coscia, et al, Carcinogenesis 1992; 13:2187-2190.
31) See reference 26.

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