Mushroom Compound Shows Promise in Cancer Studies

Dr Aaron Van Gaver BSc ND reports on the potential benefits of Active Hexose Correlated Compound (AHCC), derived from mushrooms belonging to the basidiomycotina class of fungi

There was a time when refrigerators didn't exist. So how did people preserve their vegetables? The Germans pickled cabbage during the winter months (and then we got sauerkraut).

The Japanese also pickled their food. Fresh vegetables harvested during the summer months were placed in a crock pot with rice bran and sea salt for several weeks.

Not only did this preserve the vegetables, but the fermentation process also enhanced their nutritional value. Salt fermentation increases the growth of friendly microbes and enzymes, which in effect improves the food's digestibility.

The Japanese also found that certain medicines could be made through this pickling process. The shiitake and reishi mushrooms were touted for their ability to maintain health and longevity.

Could we get these beneficial effects from eating raw mushrooms?

The answer, unfortunately, is 'no'. What the fermentation process does is to break down nutrients from the mycelial threads of the mushroom into a more absorbable form. Most mushrooms have a molecular weight of hundreds of thousands of daltons, whereas Active Hexose Correlated Compound (AHCC) - the compound produced after fermentation of the mushroom blend - has a molecular weight of only 5,000 daltons. The lower the molecular weight, the more easily digestible it becomes, once in the intestines.

In 1989, a research team consisting of Amino Up Chemical Co Ltd and Dr Toshihiko Okamoto, from Tokyo University, found that extracts from the basidiomycetes mushroom (sp. Reishi etc) could increase the survival rates of patients with various forms of cancer. They then developed a manufacturing process which enabled them to isolate the active ingredients.

During the pre-cultivation phase, basidiomycetes form colonies which are then cultured in a 15-ton tank for 45 days. The Active Hexose Correlated Compound (AHCC) is obtained from this cultivation process, which includes enzymatic decomposition, sterilisation, concentration, and lyophilisation (freeze-drying).

It is this unique and patented process which produces the special ingredients found in AHCC. It is not found in typical mushrooms.

Active Ingredients

The active ingredients in AHCC contain α and β-glucans. It is the partially acetylated α-glucan which is uniquely formed during the basidiomycetes cultivation process.

Having a molecular weight of 5,000 daltons, the potent nutrients found in AHCC can be easily assimilated by white blood cells and used in the destruction of tumours or in strengthening the body's immune system.

Most drugs used in treating cancer, either affect the tumour directly, by cutting off the blood supply, or by working on a molecular level to prevent replication of the dysplastic (cancer) cells. What the researchers found with AHCC, is that it may function as a Biological Response Modifier (BRM), interferon being the most recognised drug in this class.

BRMs function differently from typical chemotherapeutic drugs in that they have both immuno-modulatory and immunostimulatory effects.

For cancer cells to grow into a tumour, the body's immune system needs to be in a "diseased state". It is this weakened immune system that is the target for BRMs. Although AHCC seems to strengthen the body's immune system, it is not clear how this is achieved.

Immune system and AHCC:

When the body is exposed to free radicals, mutations within cells can cause cancer to form. Indeed, the body is constantly developing and destroying dysplastic cells.

The immune system responds to this insult by producing Tcells that are able to distinguish mutated cells from normal ones. However, if the immune system is not operating at optimum level, the body has more difficulty recognising the mutated cells, thereby allowing them to grow uncontrollably.

To compound the situation, cancer cells also release various immune suppressive factors, causing a decrease in antigen and macrophage activity.

In a healthy immune system, T-cells isolate the mutated cells, signalling to the macrophages to come and deal with the dysplasia. Once the macrophage interacts with the cancerous cells, it produces Interleukin 12 (IL-12), which allows Th0 cells to proliferate and differentiate into Th1 and Th2 cells.

The Th1 cells exert an anti-tumor effect, including the production of IL-2 and interferon gamma (IFN-γ). The end result is the proliferation of cytotoxic lymphocytes (CTL), lymphokine activated killer cells (LAK), and natural killer (NK) cells which finish off the job.

Research

The Institute for Genetic Medicine at Hokkaido University evaluated the effectiveness of AHCC on patients undergoing UFT chemotherapy. The results showed that NK activity was decreased in the UFT only group, whereas the UFT+AHCC group had less of a NK suppression.

In addition, AHCC was tested to determine whether it had an effect on macrophage activity. Macrophages were harvested from cancerous breast tissue of rats treated with UFT or UFT+AHCC. Nitrogen oxide (NO) production was measured (as macrophages produce NO in order to kill cells); showing that NO production in the UFT+AHCC treated group was higher than the UFT only treated group.

The overall conclusion seem to be that AHCC has the ability to reverse both NK suppression as well as macrophage suppression caused by chemotherapy.

Another study completed by Dr Kamiyama et al of Kansai Medical University in Osaka, Japan, treated patients with hepatocellular carcinoma with AHCC to find out the disease free survival rates.

Every patient had tumour resection. However, of the 167 patients, 83 received a daily dosage of AHCC. The disease-free survival rates after five years were 34 per cent for the AHCC group, and 20 per cent for the control group.

Another interesting finding was that the liver markers AST, gamma-GTP, and bilirubin were significantly lower in the AHCC group four years after surgery, suggesting that AHCC also provided some hepatoprotective effects.

The overall conclusion from this study was that AHCC supplementation proved to be beneficial for hepatitis patients, improving the disease-free survival rates for those developing hepatocellular carcinoma.

Besides the cancers mentioned, AHCC was also studied in gastric cancer, lung cancer, thyroid cancer, oesophageal cancer, ovarian cancer, prostate cancer, testicular cancer, renal cancer, tongue cancer, and pancreatic cancer patients.

In all cases studied, except for cancers of the blood, AHCC has been found to be suitable for all cancers.

Side Effects

Another important aspect of cancer treatment is the side effects that individual treatment options cause. Most notably are the alopecia, fatigue, myelosuppression, liver damage, nausea and vomiting, and loss of appetite caused by chemotherapeutic drugs. According to cancer patients undergoing chemotherapy,

alopecia is singled out as being the most psychologically distressing.

Animal studies show that AHCC when used with the chemotherapeutic agent Cytosinearabinoside (Ara-C) seems to protect against alopecia.

Myelosuppression - the reduction of blood forming and immune forming products - occurs in patients undergoing intensive chemotherapy. Attacking the bone marrow, chemotherapy reduces the amount of white blood cells with the risk to the patient that infection and anaemia may develop. This is a huge problem with cancer patients, as their weakened immune system is the basis for cancer development.

When a patient is weakened by chemotherapy, even a common cold can become as dangerous as pneumonia is to an infant.

Dr Gye Hoon Ahn in Ok-Cherm Hospital reported that treating patients on chemotherapy with AHCC raised the total leukocyte count. Other studies suggest that AHCC is effective in protecting the liver from damage caused by chemotherapy.

Most patients experience moderate discomfort during cancer treatment with chemotherapeutic agents. Among the most common causative factors for this discomfort is the feeling of nausea resulting in vomiting.

Dr Gye Hoon Ahn examined stage III and IV cancer patients to find out whether AHCC could improve their quality of life (QOL). The results showed, when asking patients through a standard questionnaire, that AHCC did indeed improve patients QOL relating to symptoms of nausea and vomiting.

Another QOL issue is the lack of appetite patients experience during and after chemotherapy treatment. Studies indicated that using AHCC helped to gradually increase patients' appetite resulting in an increase in the patients' body weight. The study also reflected an overall improvement in a feeling of well-being - hence improving their QOL.

Psychological Effects

It happens that sometimes conditions are just too far gone to be treated, but it is important that patients feel mentally stable and are able to interact socially.

Researchers devised a way to test how AHCC contributed to

the well being of patients. Three categories were specifically

looked at:

• Physical function and performance

• Psychological state

• Social interaction

When assessing Physical Function and Performance, factors such as a patient's physical ability in daily life were looked at. Psychological state was assessed by asking patients about their emotional state, including fear, depression and uneasiness during and after treatment. Social interactions were assessed

by finding out if the patient was able to keep relationships running smoothly. Dr Iwamoto, of the Enzankai Medical Corporation, reviewed researcher Dr Ishihara's notes to determine the QOL in 28 patients who had undergone AHCC treatment for two months. He found a significant improvement in all three parameters for QOL.

Dr Contreras, from Oasis of Hope Hospital in Tijuana, Mexico, studied the QOL of patients undergoing chemotherapy. Of 18 patients who were on AHCC for six months, 83 per cent reflected an improvement of QOL. AHCC achieves this improvement by ameliorating the side effects of chemotherapy and by improving the symptoms of the cancer itself. In addition, improving patients' overall feeling causes a refractory effect on their immune system. When a patient experiences an improvement in immune function, their body is better able to fight the cancer.

Viral Hepatitis

Viral hepatitis makes up on average 90 per cent of all cases of hepatitis in Japan - HepB (20 per cent) and HepC (70 per cent). When viral hepatitis becomes chronic, it can progress into cirrhosis, thereby increasing the chance of the patient developing hepatocellular carcinoma.

We know that AHCC offers protection of the hepatocytes, and has been shown to improve the five-year survival rate of patients undergoing hepatocellular carcinoma resection.

Diabetes

Medical treatments for diabetes consist of hypoglycaemic drugs, exercise, low-glycaemic diets, insulin injections and nutritional supplements. AHCC has been shown to add to this list by being able to lower blood glucose levels, normalise glycated haemoglobin levels and has been generally shown to prevent the onset of diabetes.

The difficulty with human glucose levels is that glucose is affected by various other factors. However, haemoglobin has about a 90-day life cycle, which has an affinity for not just oxygen, but also glucose. Glycated haemoglobin is a more stable way of measuring glucose levels over a longer period of time (about three months).

If a person has high levels of glycated haemoglobin, this is because the glucose which was unable to enter the cells has been incorporated into the matrix of haemoglobin. An increase of more than seven per cent glycation can mean there is a high probability of developing diabetic complications.

Dr Iwamoto examined 13 patients who were administered 3g/day of AHCC over a six-month period. Results showed that glycated haemoglobin (HbA1C) levels steadily declined from an average level of 9.1 per cent to 6.8 per cent over the six months.

One patient had started off with a combination of diabetic neurosis and paralysis of the left leg. After two months' treatment, his paralysis had disappeared.

Inflammation

Inflammation is used by the body as a defence mechanism against toxic material. But excessive inflammation can result in injury to many organ systems. AHCC has been shown to enhance the body's immune system enabling it to naturally suppress excessive inflammation.

One of the largest and most devastating forms of auto-immune inflammation is rheumatoid arthritis (RA). This chronic condition afflicts many people, initially affecting the joints. This disease progressively encompasses complete degradation of the bones and cartilage of the joint capsule. Large amounts of calprotectin (a protein found in the inflammatory mediator - neutrophil) are found in the synovial fluid of RA patients. AHCC can improve the status of RA patients by suppressing TNF production, hence inhibiting the cytotoxicity of calprotectin.

Dosage

Researchers have determined through acute toxicology studies that the LD50 of AHCC taken orally is more than 12g/kg, and more than 8.5g/kg when given intraperitoneally. This means that AHCC can be given in large doses without the risk of toxicity and death in humans.

But as clinicians and researchers, we like to be a bit more cautious when giving anything to patients, because it is the dose, not the substance that makes the poison.

AHCC is most commonly found in the form of a water soluble, micro-coated (in hardened oil) gelatine capsule containing 300mg AHCC. For the treatment of cancer, and the prevention of cancer drugs' side effects, a dosage of 3.0 - 6.0g/day has been used. For the use of cancer prevention in recurring cancer,

a dosage of 3.0g/day was used. As for maintenance and general health prevention, 1.0 - 3.0g/day was the standard.

Although there is no predetermined amount of time one needs to be on AHCC to get the beneficial effects, it can be assumed that when treating for chemotherapeutic side effect reduction, one should pre-dose the body two weeks prior to administration of the cancer drug, and continue this for two to four weeks after cessation of the chemotherapy protocol.

For general health benefits, 1.0 - 3.0g/day can be used indefinitely, with the occasional breaks (cycling on and off).

Conclusion

Whether used for cancer treatment, diabetes, hepatitis, inflammation or just general health, AHCC shows promise in a world where the incidence of chronic disease seems to be increasing exponentially.

References

1. Tasaki S, Kamiyama et al. Immunotherapy with AHCC in hepatocellular carcinoma patients, The 32nd Congress of the European Society for Surgical Research, May 1997.

2. Sun B. et al., Anti-mutagenic effects of AHCC, The 4th Research Association of Cancer Prevention, May 1997.

3. Sun B. et al., Protective effects of AHCC on carbon tetrachloride induced liver injury in mice, Natural Medicines 51(4), 310-315, Aug 1997.

4. Sun B., Kosuna, Effects of AHCC in both the prevention and treatment of carcinomas, Critical Appraisal of Unconventional /Alternative Interventions for carcinoma of the prostate, May 1998.

5. Kitade H., Matsui S., Takai A., Imamura A., Kawaguchi Y., Kamiyama Y., Sun B., Kosuna K, Preventive Effects of AHCC on the Recurrence of Postoperative Hepatocellular Carcinoma Patients, The 33rd Congree of the European Society for Surgical Research (ESSR), May 1998.

6. Kanazawa T., et al., The components in AHCC activating macrophage and inhibiting tumor cell proliferation, The 5th Research Association of Cancer Prevention, Jul 1998.

7. Sun B., et al., Fractions of AHCC and their effects on macrophages and tumor cell lines, The 57th Annual Meeting of the Japanese Cancer Association, Set 1998.

8. Mukoda T., et al., AHCC protects against cytosine Arabinoside induced alopecia in the newborn rat animal model, The 57th Annual Meeting of the Japanese Cancer Association, Sep 1998.

9. Matsushita K., et al., Combination therapy of AHCC plus UFT significantly reduces the metastasis of rat mammary carcinoma, Anti-Cancer Drugs, 343-350, Sep 1998.

10. Sun B., Fukuhara M., Kosuma K., Reduction of side effects of anti-cancer drugs by AHCC, mycelian extracts of cultured basidiomycetes, The 4th International Symposium on Predictive Oncology and

Therapy, Oct 1998.

11. Matsui Y., et al., Effects of the postoperative therapy with AHCC administration on postoperative hepatocellular carcinoma patients, The 34th Annual Meeting of Liver Cancer Study Group, Oct 1998.

12. Sun B., et al., Improving effect of AHCC on anemia and alopecia induced by anti-cancer drugs, The 1st Annual Meeting of the Japanese Society for Alternative Medicine & Treatment, Nov 1998.

13. Sun B., Fukuhara M., Kosuna K., Reduction of side effects of anticancer drugs by AHCC, mycelian extracts of cultured basidiomycetes, Impact of Biotechnology on cancer (nice, France), Nov 1998.

14. Wakame K., Effect of AHCC on diabetes induced by stretozotocin in the rat, The 119th Annual Meeting of the Japanese Society for Pharmacology, Mar 1999.

15. Sun B., et al., Reduction of the side effects of anticancer drugs by AHCC, The 90th Proceedings of the American Association for Cancer Research, Apr 1999.

16. Iwamoto M., et al., Effects of AHCC on diabetes by clinical and basic researches, The 2nd Annual Meeting of the Japanese Society for Alternative Medicine & Treatment, Oct 1999.

17. Iwamoto M., et al., A study on dose-dependence of AHCC for Cancer patients, The 2nd Annual Meeting of the Japanese society for alternative medicine & Treatment, Oct 1999.

18. Uno K., et al., The introduction of immunological parameters to the screening of cancer, The 2nd Annual Meeting of the Japanese Society for Alternative Medicine & Treatment, Oct 1999.

19. Ishiguro A., et al., Anticarcinogenic activity of AHCC and PMP, The 2nd Annual Meeting of the Japanese Society for Alternative Medicine & Treatment, Oct 1999.

20. Sun B., et al., Anti-carcinogenic effect of AHCC and buckwheat polyphenol, The 37th Annual Meeting of Japanese Society of Cancer Treatment, Oct 1999.

21. Wakame K., Protective effect of AHCC on the onset of diabetes induced by streptozotocin in the rat, Biomedical Research, 20(3) 145-152, Oct 1999.

22. Uno K., et al., AHCC improves immunological parameters and performance Status of Patients with Solid Tumors, Biotherapy, 14(3) 303-307, May 2000.