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03-11-2015

AHCC, a powerful immunostimulant developed by Japanese researchers

AHCC Research shows that AHCC, or Active Hexose Correlated Compound, may offer benefits in the prevention and treatment of diabetes, hyperlipidaemia and hepatitis. It may also have an anti-tumour effect and reduce the side-effects of chemotherapy. In Japan, AHCC is used in more than 600 hospitals for treating cancer, hepatitis and other chronic diseases.

AHCC is a fermented extract obtained from the mycelia of a hybrid of various types of mushroom used in traditional Japanese medicine. It is distinguishable from other mushroom-based supplements by its low molecular weight (5000 daltons), achieved via an enzymatic process, which facilitates oral absorption.

The active compounds in AHCC are found in many kinds of mushroom. Some are derivatives of alpha and beta-glucan, polysaccharides known for their beneficial effect on the immune system.
Exerting a modulating effect on the immune system, they increase concentrations of T and B lymphocytes and stimulate macrophage activity, thus boosting the body’s defences against viruses, bacteria, parasites and neoplastic cells.
Active Hexose Correlated Compound (AHCC) has been the subject of more than 200 clinical studies, mostly conducted in Japan. Studies are ongoing in over 150 Japanese and American university research centres and hospitals. Every year since 1994, more than 300 doctors and scientists have gathered in Sapporo, Japan for the annual symposium of the AHCC Research Association.

The immune system’s ‘sentinels’

Discovered in the 1980s, natural killer (NK) cells are a type of white blood cell; they are regarded as the immune system’s ‘sentinels’. As such, they are the body’s first line of defence against attack from viruses, bacteria or emerging malignancies. They have an innate or natural ability to distinguish between normal and abnormal cells, and can kill multiple targets either simultaneously or in rapid succession. When NK cells are operating at full capacity, pathogenic organisms are ‘snuffed out’ before they have a chance to take root; the rest of the immune system tends to be downregulated, rested and better prepared to respond to any new demands made on it.
In healthy individuals, NK cells systematically destroy cancers at a microscopic, undetectable stage.
Measuring the efficacy of NK cells’ cancer-killing function is considered a primary indicator in clinical prognosis. Research shows that such function is often very poor in people with a family history of cancer, and that it declines with age, thus accounting for the increased incidence of cancer seen with ageing. It is also compromised by surgery to remove tumours as well as by radiation and chemotherapy, potentially explaining why cancer metastasises even more aggressively following these treatments.
Stimulating NK cell function and supporting the immune system’s first line of defence represents one of the most promising lines of research in cancer prevention and treatment.

Stimulates NK cell activity

Since 1986, 29 scientific studies have been published on AHCC’s effects on the cancer-killing activity of NK cells.
One study examined such effects in three patients suffering from different types of advanced cancer (multiple myeloma, rhabdomyosarcoma and breast cancer). They were given 3-6g of AHCC a day for two weeks after which the cytotoxicity of their NK cells was measured.
In the rhabdomyosarcoma patient, AHCC administration resulted in a significant increase in NK cell activity (from 91% to 135%) and a two-fold increase in NK cell population. These increases were observed at the end of the treatment period and continued at a high level for one week before declining at two weeks post-treatment. There was a similar increase in NK cell anti-cancer activity in the patients suffering from multiple myeloma (87%) and breast cancer (93%), and in both these patients, NK cell populations increased either two- or three-fold.
1.
Another study examining AHCC’s immunomodulatory function included 17 patients with various advanced malignancies [cancer of the ovary (3), stomach (2), breast (5), lungs (2), prostate (2) multiple myeloma (2), and rhabdomyosarcoma (1)].
The patients were given 3g of AHCC a day for two to six months. Tests on NK cell activity showed an increase from the second week of treatment with further increments up to six months post-treatment. The AHCC appeared to activate NK cells by boosting (two-fold) their binding capacity to tumour cell targets, and also by increasing NK cell granularity. The researchers concluded that AHCC was a powerful immunomodulator likely to be useful in cancer immunotherapy2.

Promotes production of specific cytokines

Cytokines are chemical messengers of the immune system. Scientific studies show that AHCC increases production of certain cytokines:
    interferon, which directly inhibits virus and other parasite replication while increasing NK cell activity;
    tumour necrosis factor (TNF), a group of proteins that help destroy cancer cells by triggering apoptosis (programmed cell death);
    interleukins IL-2 and IL-12, which suppress production of tumour growth factor, stimulate NK cell activity and accelerate differentiation and proliferation of T cells.

Boosts the immune system

In another study, in which tumour associated antigen was measured before, during and after AHCC administration in 11 cancer patients – three with cancer of the prostate, three of the ovary, three of the breast and two with multiple myeloma, results showed:
    a significant decline in PSA levels in all the prostate cancer patients;
    a significant decline in CA 125 levels in two of the three ovarian cancer patients;
    a significant decline in BJP levels in one of the two multiple myeloma patients and a slight decline in that of the other patient;
    • in the breast cancer patients, CA 15-3 levels were low and remained unaffected by the treatment.
    In nine of the eleven subjects, AHCC treatment resulted in a sharp increase in both NK cell and T and B cell activity. In other words, the reduction in tumour markers correlated with the increase in strength of their immune systems, supporting the belief that a strong, resistant immune system can help fight cancer3.

Counteracts the side-effects of anti-cancer treatments

A number of animal studies have shown that AHCC may relieve some of the side-effects of different anti-cancer treatments.
In mice treated daily with fluorouracil (5-FU), cyclophosphamide, or both, AHCC given simultaneously had a significant restorative effect on weight, red blood cells and bone marrow. A similar effect was found in mice treated with mercaptopurine (6-MP) and methotrexate (MTX) – concomitant administration of AHCC produced improvements in weight loss, serum albumin and liver function4. Severe hair loss or alopecia, caused by cytosine arabinoside (ARA-C), was reduced to ‘slight’ when AHCC was administered simultaneously5.
Damage to liver function is responsible for many of chemotherapy’s side-effects. A study on mice using carbon tetrachloride as a model of a liver damage-inducing drug showed that concomitant administration of AHCC stimulated metabolism, while preventing liver function decline, accumulation of carcinogens and development of the hormone problems often associated with liver impairment 6.
Hair loss is a common and – though temporary – extremely stressful side-effect of cancer treatment. AHCC’s protective effect in this respect was confirmed by a study in which five out of seven rats treated with ARA-C-based chemotherapy presented with severe alopecia, and the remaining two - moderate alopecia. Those animals given AHCC at the same time as the chemotherapy were protected from significant hair loss. Microscopic analysis revealed severe follicle loss in the control mice compared with slight loss in the AHCC-supplemented animals.

Boosts the efficacy of chemotherapy

AHCC’s ability to boost the efficacy of chemotherapy was demonstrated in a study on rats implanted with a cell line of spontaneous mammary adenocarcinoma. Three groups of animals were observed for 38 days – one group served as a control, the second was given UFT, an oral form of the chemotherapy drug fluorouracil, and the third was given UFT in conjunction with AHCC.
Tumour growth was greatest in the control group. There was a slight but significant suppression of tumour growth in the group given AHCC+UFT compared with the UFT-only group. The greatest difference was found in the growth of distant metastases – which was inhibited by the AHCC+UFT treatment and stimulated by UFT alone. One possible explanation for this may be the fact that AHCC prevents chemotherapy-induced suppression of immune function 7.

Prevents recurrence of liver cancer

A study was conducted to evaluate the effects of AHCC in preventing the recurrence of hepatocellular carcinoma in patients who had undergone surgery. Of the 121 patients involved in the study, all of whom had histologically proven liver cancer, 38 (group A) were given 3-6g/day of AHCC after surgery, 18 began the treatment after recurrence of the disease was confirmed (group B) and the remaining 65 (group C) served as controls. The longest follow up periods were 39, 65 and 56 months for groups A, B and C respectively. There were no significant differences between the three groups in distribution of age, gender, clinical stage, hepatitis type B or C viral infection, or the resection volume of the liver. The disease-free survival rate in group A was significantly higher than that in group C. One year after surgery, the serum levels of tumour markers in group A were significantly lower than those in groups B and C.
This retrospective study suggests that taking AHCC has a preventive effect in patients who have undergone surgery for hepatocellular carcinoma. Other studies are needed to determine its mechanism of action8.
These results were confirmed by those of another study conducted between February 1992 and December 2001. It involved 269 patients with diagnosed liver cancer who had undergone surgical removal of their tumours. 113 were given AHCC after surgery. Compared with controls, this group had a longer period of no recurrence of their cancer and an overall increase in survival rate. This study therefore shows that AHCC can improve the post-operative prognosis of patients with liver cancer9.

AHCC and diabetes

Research also shows that AHCC has liver-protective and detoxifying benefits which come from its antioxidant and liver enzyme-inducing effects.
A study on rats was conducted to examine AHCC’s effects in preventing the onset of streptozotocin (STZ)-induced diabetes which can be regarded as an experimental model of type 1 diabetes. Researchers looked at the preventive effects of AHCC on impairment of Langerhans islets responsible for insulin secretion. Results showed that AHCC was able to avert the onset of STZ-induced diabetes by preventing deterioration in Langerhans islet cells and by reducing oxidative damage to cells of various organs 10.

Stress and chronic fatigue

The link between stress and chronic fatigue is the result of interactions between the immune system and the nervous and endocrine systems. Emotional or physical stress triggers the production of a neurotransmitter in the brain which helps initiate the ‘fight or flight’ response. It directly suppresses NK cell function and other aspects of cellular immunity linked to innate immunity 11.
A number of stress-reducing methods, such as regular exercise, music, massage or simply smiling, can increase NK cell activity. And many NK cell-boosting strategies can reduce the effects of stress.
Research into physically- or chemically-induced models of stress show that AHCC reduces both glucocortoid production which generally increases with stress, as well as increases in blood sugar levels caused by stress-induced secretion of epinephrine 12


1. Ghoneum Mamdooh et al., Enhancement of NK cell activity in cancer patients by AHCC, Adjuvant nutrition in cancer treatment symposium, Tulsa, Oklahoma, Nov 6-7, 1992.
2. Ghoneum Mamdooh, NK-immunomodulation by AHCC in 17 cancer patients, 2nd Meeting of the Society for natural immunity, Taormina, Italy, May 1994.
3. Ghoneum M. et al., Immunomodulatory and anticancer effects of AHCC, Int. J. Immunotherapy, 1995, XI (1) 23-28.
4. Sun B. et al., Reduction of side effects of anticancer drugs by AHCC, 90th Proceedings of the American association for cancer research, 1999.
5. Mukoda T. et al., AHCC protects against cytosine arabinoside induced alopecia in the newborn rat animal model, 57th annual meeting of the Japanese cancer association, 1998.
6. Sun et al., Protective effects of AHCC on carbon tetrachloride induced liver injury in mice, Natural medicines 51(4), 310-315 (1997) B.
7. Matsushita et al., Combination therapy of AHCC plus UFT significantly reduces the metastasis of rat mammary carcinoma, Anti-Cancer Drugs, 1998, 9, 343-350 K.
8. Kamiyama et al., Improving effect of AHCC on the prognosis of postoperative hepatocellular carcinoma patients, 34th Congress of European society for surgical research, Bern, Switzerland, 1999.
9. Matsui Y. et al., Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study.
10. Wakame K. Protective effets of AHCC on the onset diabete induced by streptozotocin in rat. Biomedical research 20 (3) 145-152, 1999.
11. Glaser et al., Stress-associated immune modulation: relevance to viral infection and chronic fatigue syndrome, Am. J. Med., 1998, Sept 28, 105 (3A): 35S-42S.
12. Wang S. et al., AHCC on immobilization stress in rat: beneficial effects of Active Hexose Correlated Compound, Dokkyo Journal of Medical Sciences, 2001, p. 559 28(1): 559-565.
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