Monday, February 18, 2008

How Ganoderma (Ling Zhi) help in Liver diseases

Role of Ganoderma in Liver Protection



Tragic events often take place around us, changing not only our life but also the lives of our family and friends. Of all the organs in the human body, there is nothing more capable of causing these emergencies than the liver. One reason for this is that the liver does not possess any nerves, so it does not feel pain until it swells to a point that the pressure on nearby organs causes pain in the upper right abdomen. Fulminating hepatitis causes damage to liver cells at a rapid, abrupt speed. This will lead to a failure of cell reproduction, hepatic failure, and inevitably loss of liver function. Survival rates always fall below 30%, and current medical treatment cannot alter this. This type of hepatitis is common in men between 20 and 40 years of age and they leave behind them endless sadness and regret. There is a saying that aptly describes the importance of the liver which states, “A good liver means a colorful life while a poor liver leaves a life of black and white”.


Multifunctional yet a Silent Organ: The Liver



The liver is the largest internal organ in the human body; it weighs 1200 to 1500 grams in an adult, approximately one fiftieth of the body weight. It is a great chemical factory playing several important roles from nutrient absorption, conversion and storage to protein synthesis and digestive system tasks such as clearance of waste and detoxification. These are some of the tasks accomplished by the liver. The following is a brief explanation of some of the main functions of the liver:

1. Metabolism and Storage:
A variety of nutrients that enter the body through food intake, including sugar, protein, fat and vitamins, are all metabolized in the liver. For instance, the liver converts digested starch or saccharides into glycogen for storage. It can also convert digested fatty acid into lipoprotein and cholesterol.

2. Conversion:
Most medicines entering the body have to be transported via the liver in order to exert their effects. Oral medicines will pass into digestive tract, be digested and absorbed via the blood vessels in the intestinal wall, then via the hepatic portal vein (one of the two blood vessels providing nutrition to the liver) into the liver where they will be transformed.

3. Detoxification:
Many and various foreign substances entering the gastrointestinal tract, toxic chemicals (e.g ammonia) synthesized in the gastrointestinal tract and inhaled chemical substances all enter the liver via the hepatic portal vein. After undergoing detoxification in the liver cells they become innocuous and are excreted from the body via the urine, feces or bile.


4. Protein Synthesis:
Protein synthesis is the most important function of the liver. Proteins in blood, especially globulin, albumin and fibrinogen, are all synthesized in the liver. Albumin is the most important of these proteins for if the amount of albumin in blood decreases; osmotic pressure will decline, resulting in swelling of the face or limbs, or even ascites. In addition, the “blood coagulation factor” is produced by the liver. A dysfunctional liver can easily result in bruising and bleeding.

5. Excretion and Involvement in Digestion:
Hemoglobin released by the breakdown of dead red blood cells is converted in the liver into bilirubin, the main pigment of bile. After absorption and processing in the liver cells, bilirubin turns into water-soluble bilirubin (direct bilirubin) and flows in bile through the gallbladder. Via the gallbladder, the bile enters the intestinal tract to aid in digestion and is, finally, excreted from the body. If this function of the liver fails, bile accumulates in the liver and then escapes into the bloodstream causing a yellowish discoloration of the skin (jaundice).

Even though the liver remains reticent, it possesses a strong reproductive capability. As long as it receives sufficient nutrition, its damaged tissues can be repaired quickly. Protein is the most important among all nutrients and so sufficient protein consumption will not only benefit the reproduction of the liver cells but will also slow the degeneration of liver cells. Another important factor in maintaining a healthy liver is to follow a normal daily routine; staying up late will definitely cause harm to the liver. So, people working night shifts, such as assembly line workers, police officers and medical personnel, tend to have a higher abnormal liver function than average.


Main Causes of Liver Disease



The causes of liver disease can be divided to three main categories: viral, alcoholic, and chemical. The viruses causing damages can be further categorized into A, B, C, D and E type viruses. The most prevalent are hepatitis B and C, especially hepatitis B, whose latent period is extremely long, turning individuals into carriers, a state that may be permanent. Such viruses are easily contracted by casual contact with blood, body fluids or saliva left in food, and are difficult to avoid. Alcoholic damage results form excessive consumption of alcohol and alcohol abuse. The sources of chemical damage include ingestion or injection of excessive amounts of chemical drugs, and consumption of excessive amounts of toxic substances, such as heavy metal or fertilizers in food, and the inhalation of toxic fumes from cigarettes, vehicles or factories. These gases are often neglected as important sources when describing liver disease due to chemicals. Substances such as benzenes and aldehydes, released from solvents (e.g. paints and detergents) into the air, can also cause chemical liver disease. Whatever the cause, damage to liver cells may cause hepatitis and chronic hepatitis may progress to fibrosis or even cirrhosis.

The Dynamic function of the liver is attributed to its basic unit, the liver cell. Damage to liver cells, the restoration of them, producing new cells and replacing old cells constitute a repetitive and on going process in the liver. This restorative processes affects liver function, utilizing up to 10% of it functional capability for maintenance. The relatively low percentage (i.e 10%) indicates the possibility of fibrosis and sclerosis. When the liver sustains damage it will excrete specific enzymes, such as GPT (ALT) and GOT (AST). Abnormal values of these two enzymes indicate a problem in the liver. Normal levels of the two enzymes, however, do not indicate a healthy liver; they only imply initial normal liver function. In many cases of cirrhosis, GPT and GOT levels alone did not detect the disease, but coupled with other examinations, such as ultrasonic scan, alpha-fetoprotein (AFP) and hepatitis B examination, the condition was diagnosed.

Some doctors describe liver cancer as a trilogy: chronic hepatitis followed by cirrhosis, leading, finally to liver cancer. Since the liver lacks nerves, damage at the initial stage may go unrecognized. To date, viral hepatitis remains incurable and can only be controlled by western medicines such as silymarin, the one most commonly used. Providing protection for the liver, rather than waiting to treat liver disorders when they arise, may be the best way forward since it is almost impossible to avoid contact with the toxic substances that may affect the liver.


Research into the effects of Ganoderma on Liver Function



Anecdotal reports from people who have taken ganoderma over a long period of time suggest that ganoderma may have a significant role in protecting the liver. In addition, over 30 scientific studies have been published on the usage of ganoderma in liver protection. Listed below are some of the references on studies published since 2000:
































AuthorsReferencesModel of TestTitle of the Study
Wen Chuan, Lin, etcWorld J. Gastroenterol. 2006; 12(2):265-70.Chronic chemical-poisoning in ratsAmeliorative Effect of G.Lucidum on carbon tetrachloride-induced liver Fibrosis in Rats
Wen Chuan, Lin. etcAm. J. Chin. Med. 2004;32(6):841-50Chronic chemical-poisoning in ratsEffect of G.tsugae on chronically carbon tetrachloride-intoxicated Rats
Kimura Y, etcAnticancer Res. 2002;22(6A):3309-18.Mice bearing lung tumorAntitumor and antimesastatic effects on liver of triterpenoids fractions of G.Lucidum: Mechanism of action and isolation of an active substance
Zhi-Bin Lin, etcWorld J. Gastroenterol. 2006; 8(4):728-33.Acute chemical-poisoning in miceHepatoprotective role of G.Lucidum polysaccharide against BCG-induced liver injury in mice.


In contrast to the difficulty in establishing in-vivo models for viral or alcoholic hepatic injury, the chemical in-vivo model has been employed in research for many years. The pathological study of the chemical-induced injury of the livers in mice shows them to be similar to be corresponding hepatic injury in human beings and so the in-vivo study on the liver protection of ganoderma focused mainly on chemical hepatic damage. This chemical-induced injury model has been used as an official evaluation method to support claims of liver protection in health food accreditation. This method involved the use of carbon tetrachloride (CCl4) to induce chronic hepatic injury in rats, following which the rats were treated with a variety of substances (herbs) so as to gain insight on the impact of these herbs on protecting the liver.

Most research on the liver-protection actions of ganoderma, and other herbs, is “short term” and tends to use the CCl4 liver injury method when the rats are dissected for evaluation within seven days. However, in order to reflect, more closely, the situation in humans exposed to poisons with unidentified chemicals, the official testing method used a strict and rigorous approach employing a “chronic poisoning” model. This required eight weeks (two months) of feeding the toxic substances to examine their effects on the liver. The rats in the tests were fed for eight weeks with the toxic compounds together with the ganoderma products being examined. This testing method provided as stark contrast to other scientific research on the ability of ganoderma to protect the liver.

Once liver cells are damaged, or are experiencing necrosis, they will release GPT (ALT) and GOT (AST), which are regarded as liver function indices – the greater the damage, the higher the values of the two liver indices. GPT is a more representative index on account of its liver specificity, whereas GOT also exists in the heart, kidneys, skeletal muscle and brain. The rats were divided into five groups: a control group (no medication given), a carbon tetrachloride (CCl4) group, a silymarin group, a low-dosage ganoderma group and a high-dosage ganoderma group. The results are shown below:


























Items/GroupControl Group(no Medication given)CCl4 groupLow-Dosage Ganoderma GroupHigh-Dosage GanodermaGroup Silymarin Group
GPT/ALT* (U/L), 3rd Week40.9758423391474
GOT/AST (U/L), 3rd Week136.8869537444560

*Variation is omitted for clarification purpose.



After the rats were given CCl4 orally their livers started to develop observable inflammation and GPT and GOT values were found to be higher than those in the control group. After being fed with CCl4, the two groups receiving ganoderma products (extracted from YK-01 strain) showed significant decrease in GPT and GOT values after three weeks. This shows that ganoderma was able to reduce hepatic injury induced by CCl4. Although the rats were subject to CCl4-induced hepatic inflammation, they experienced less inflammation when fed ganoderma. The efficacy is dose-dependent. i.e, the more the ganoderma (from 0.5g/Kg to 3.0g/Kg) taken, the more the inflammation was alleviated and liver function indices lowered. Thus, in the animal testing model for lowering serum GPT and GOT values, ganoderma extract was shown to have the effect of alleviating hepatic injury.

When the liver is injured, it will activate the function of liver cell regeneration. As mentioned earlier, the consumption of sufficient protein is a key factor at the time of liver cell reproduction. The rats given CCl4 experienced obvious liver inflammation, as well as lower amounts of protein than those in the control group. Upon dissection at the end of the experiment (8th week), the mice taking CCl4 simultaneously with ganoderma were found to have high levels of protein in their livers, even higher than those of the control group. This tendency is also does-dependent, the higher dosage (0.5g/Kg~3g/Kg) of ganoderma led greater levels of liver protein. Ganoderma is not a high-protein food; such as fish, meat, eggs and other soy proteins, but interestingly, the results demonstrated that it help to increase the quantity of protein in the liver. As well as the increase in liver protein, the liver cells show greater powers of regeneration. Thus, the function of increasing protein content in the liver indicates that ganoderma extract is capable of enhancing liver cell regeneration.

To summarize the above findings, ganoderma reduces hepatic injury as well as, simultaneously increasing liver cell regeneration. That is, it helps to protect the liver from harm, and in case of injury, it promotes liver cell reproduction. This animal test model has provided strong evidence that ganoderma provides “all-round” liver protection.


Further evidence of Liver Protection: Improving Splenomegaly (Spleen enlargement) and Alleviating Hepatic Fibrosis



Evidence from the pathological histology of related organs needs to be demonstrated in support of the claims for protecting the liver. The most important of these organs are the directly injured liver and the indirectly affected spleen. When the liver is fibrosed or atrophied, the flow of blood into the liver is blocked. Such an obstruction also blocks the blood flow to the spleen, leading to splenomegaly. These two pathological conditions will reflect the extent of the protective effect of the tested ganoderma products in the liver. At the end of the tests, the rats with CCl4-induced chronic hepatitis showed symptoms of typical cirrhosis and splenomegaly. According to the evaluation report of Prof. Wen-Chuan Lin, the scientist who fed ganoderma to the rates, ‘ganoderma can improve the conditions of the denaturing of hepatic tissues, fibrosis in the central venous area and tubercles in the portal venous area, as well as splenomegaly, demonstrating its effect in alleviating hepaticfibrosis.’ When Professor Lin first learned of ganoderma he was doubtful of its effects but, after seeing positive evidence from this experiment, his attitude changed. Unexpectedly, this study on the effect of ganoderma on liver protection, the first to use the CCl4-induced chronic hepatitis as an in-vivo model, was later published in The American Journal of Chinese Medicine in 2004.
Tuberculous fibrosis (cirrhosis) consists mainly of collagen and since hydroxyproline is a chemical compound exclusive to collagen, the measurement of hydroxyproline content represents an assay for collagens, indicating the degree of fibrosis. In tests, a significant increase in hydroxyproline in CCl4-induced chronic hepatitis rats had been observed. However, administration of a high dosage of ganoderma can reduce the hydroxyproline content, substantiating ganoderma’s effect on reducing hepatic fibrosis.












This effect has been confirmed by histopathology; the CCl4 group showed clear signs of fibrosis (figure, section B) under liver biopsy, the high-dosage ganoderma group showed no signs of fibrosis(figure, C section), and silymarin group showed a lower level of hepatic fibrosis(figure, D section). This led to the interesting conclusion that, despite the fact that silymarin is considered to be an effective treatment of hepatitis it demonstrated a lesser effect on reducing fibrosis than that of ganoderma. Increasing the dose of silymarin might provide better results but with the increased possibility of more side effects. Silymarin is a prescription medicine only available form a doctor. Compare this with the safe dosage of ganoderma, which is much higher, promising a greater potential for ganoderma in protecting the liver.


Research on the Protective Effect of Ganoderma on the Livers of Healthy Mice



In 2006, Bi-Fong Lin, Miao-Ling Chen and co-workers at the National Taiwan University fed ganoderma extracts from the fruiting body of the YK-01 strain to Balb/c (a type of mouse) for seven consecutive weeks. The result was a lowering of the TBARS value (an index of oxidation) in the liver, indicating the anti-oxidation properties of ganoderma. In other words, ganoderma can raise hepatic anti-oxidation ability, thereby preventing the liver from oxidation. This means that ganoderma not only has a protective effect on a chemically injured liver, but it also has an anti-oxidation effect in a normal liver (preventing the liver from oxidation), accelerating the rate of liver metabolism.


Study on the Effect of Ganoderma on Protecting the Liver in Healthy Humans



In 2005, Prof. Jin-Kun Wang and his research team at Chung Shan Medical University conducted a double-blind crossover clinical trial using Ganoderma YK-01 fruiting body extracts on 40 healthy volunteers. Their average GPT values during consumption of ganoderma were measured and are listed in the table below:






















Control GroupGanoderma YK-01 Group
Before Admistration22.05 ± 20.4422.58 ± 18.92
3 Consecutive Months of Usage20.25 ± 20.1016.85 ± 12.64
6 Consecutive Months of Usage21.32 ± 20.1013.08 ± 9.92







The changes in GPT (ALT) in the Ganoderma group indicate that the YK-01 extract tends to decrease liver indices values. The longer the extract is used, the more hepatic GPT value dropped (22 to 13). Likewise, when the extract is used on healthy persons with normal liver function indices, the liver function is maintained and the liver cells are less likely to perish. Following long-term use the liver indices drop and liver performance increases.


Exploration of the Active Components of Ganoderma in Liver Protection



The components of ganoderma exerting the most obvious effects in protection the liver are triterpenes and polysaccharides-peptides. Animal test show that polysaccharides-peptides from G.Lucidum (6mg/day/rat) could significantly decrease serum GPT and GOT in biliary obstruction-induced cirrhosis while improving hepatic fibrosis, increasing liver weight and reducing splenomegaly. Pathological biopsies confirmed the findings that polysaccharides-peptides are effective in protecting the liver. Other studies demonstrated that ganoderenic acid A (a triterpene) from G.Lucidum could also lower the high GPT, GOT and TG (triglyceride) indices caused by carbon tetrachloride (CCl4) administration. In research, conducted by Prof. Ching-Hua Su of Taipei Medical University, it was found that by feeding ganoderic acid B and C (C2), the GPT and GOT values in mice with acute liver dysfunctions declined, thereby further demonstrating the efficacy of ganoderma triterpenes in protecting the liver. Ganoderic acid B and C (C2) are found mainly in the triterpenes of G.tsugae (or some G.Lucidum). In some strains (e.g YK-01), the content of triterpenes is high and so they can be easily isolated.


Conclusion:



Most pathological changes in the liver are undetectable, and most people pay no heed to them. One should not wait until a worsening condition or tragedy occurs, and panicking begins before acting. The contribution of ganoderma to liver protection is not limit to the academic forum, numerous statistical data have been collected from tens of thousands of people who showed improvements in their health after taking ganoderma. The advantages of ganoderma are well acknowledged in its role in protecting the liver.



The fallacy that 'Liver disease is incurable' should be abandoned
The liver is one of the most important organs for health. Liver function is quite complicated. Therefore, liver disease is considered difficult to treat, and dietetic
treatment is the only method adopted by Western physicians. However, Lingzhi is able to make the complicated organ function and have it return to normal. Based on our practical investigation, Lingzhi can contribute a very positive effect. Dr. Shigeru Yuji reported that 10% of liver disorders could be cured after taking it for two months. 40% of the patients were relieved of their symptoms, and their liver sizes were reduced. 50% of the patients felt their symptoms diminished.

Glory II



Shuang Hor Supreme Ganoderma" was 1st separately awarded Immuno-regulatory Health Food Accreditation(Taiwan's Health Ministry Food Accreditation with Reference Number A00003)and Liver Function Food Accreditation(Taiwan's Health Ministry Food Accreditation with Reference Number A000015) based on the results of experiments

Immuno-regulatory Health:
1. Enhance antibody production
2. Enhance immune cells proliferation.
3. Modulate T cells function
4.Enhance natural killer cells activity
5. Enhance phagocytes activity


Liver Function
1. Decrease GOT and GPT value of serum
2.Increase protein content in liver
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