Active hexose correlated compound

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Active Hexose Correlated Compound is a chemical isolated from the Shiitake mushroom.

Active Hexose Correlated Compound (AHCC) is an alpha-glucan rich nutritional supplement produced from the mycelia of shiitake (Lentinula edodes) of the basidiomycete family of mushrooms, and is not an approved drug.[1][2]

An evidence-based review concluded that AHCC may have immunostimulatory effects; whether this offers any benefit for infections and cancer remains to be determined.[3]

AHCC was originally designed to lower high-blood pressure. However, researchers at Tokyo University found that AHCC increased natural killer (NK) cell activity in cancer patients, and also enhanced the effects of killer T-cells, and cytokines (interferon, IL-12, TNF-alpha).[citation needed]

One cohort study published in 2003 reported improved survival associated with AHCC in primary liver cancer patients after surgical resection of the primary tumor. [4] The immunological effect of AHCC has been studied in a double-blind, placebo-controlled study with 21 healthy volunteers.[5] The AHCC group showed a significantly higher number of total dendritic cells compared with baseline, a significantly higher number of DC1 cells compared with baseline, a significantly higher number of DC2 cells compared with controls, and a significantly increased mixed-leukocyte reaction compared with controls. There was no significant difference in cytokine production, NK cell activity or other immune function parameters between the two groups.

AHCC – Active Hexose Correlated Compound[edit]

AHCC (Active Hexose Correlated Compound), a registered trademark of Amino Up Co. Ltd. is a functional food made from the hybridized mycelia of shiitake and other mushrooms fermented in rice bran[citation needed]. It was developed by Professor Toshihiko Okamoto, Department of Pharmacology, Tokyo University in conjunction with Amino Up Chemical Co. Ltd. of Sapporo, Japan. It was developed as a therapeutic aid for life-style related diseases, including liver diseases and diabetes. AHCC adheres to international quality and safety standards, including the HACCP9000 system[citation needed]. This system is a combination of HACCP (Hazard Analysis Critical Control Point) systems, which is an international level hygiene control system for foods and ISO9002 (International Organization for Standardization 9002), a quality assurance system.

Manufacturing process[edit]

AHCC is manufactured by culturing the mycelia of basidiomycetes (mushroom root threads) for a period of 45 –60 days in a large holding tank. Several types of mycelia are initially cultured to form a colony (a mass of mycelia). After the culture is completed, the product is subjected to enzyme reaction, sterilization, concentration and freeze drying[citation needed].

Chemical composition[edit]

Polysaccharides comprise 40% of the composition of AHCC[citation needed]. These include beta-glucan (β-glucan) and acetylated α-glucan. Acetylated α-glucan, produced by culturing the mushroom mycelia, is unique to AHCC[citation needed]. Glucans are polysaccharides and these polysaccharides are known to have immune stimulating effects.[6] The low molecular weight of acetylated α -glucan (around 5000 daltons) is easily absorbed into the system compared to the higher molecular weight of β-glucan, which is in the range of tens to hundreds of thousands of daltons[citation needed] .

Safety of AHCC[edit]

AHCC has been studied for safety in human trials[1] as well as safety with conventional chemotherapy.[7]

Safety studies have been conducted according to GLP standards. The LD50 according to tests with SD rats is > 12,500 mg/kg by oral administration. Toxic activity was not seen even in intra-peritoneal administration of AHCC: Male: LD50 = 8,490 mg/kg, estimated intraperitoneal fatal dose =7,430 mg/kg Female: LD50 = 9,849 mg/kg and estimated fatal dose = 8,340 mg/kg[citation needed].

AHCC as a supplemental alternative medicine[edit]

AHCC is widely used in Japan and China. AHCC is used to protect the immune system of cancer patients undergoing chemotherapy and radiation in over 700 clinics and hospitals in Japan alone[citation needed]. It is available to the general public in Japan and China without a prescription and many people use it for general health maintenance and treatment of acute infections. Its legal status is that of a “functional food.” Research on AHCC has been carried out in Japan, China, Korea, Thailand, Spain and the United States. Results of research show that AHCC may work in the prevention and treatment of numerous diseases.[8]

In Japan, AHCC is the 2nd most popular complementary and alternative medicine used by cancer patients. Agaricus blazei supplements are the most popular, outpacing AHCC use by a factor of 7:1.[9]

AHCC and cell-mediated immunity[edit]

AHCC stimulates cell-mediated immunity by activating the white blood cells, particularly natural killer cells (NK cells) and macrophages, which directly attack abnormal cells, virus-infected cells or external viral and bacterial pathogens that enter the body.[10]

Some research shows that the fundamental mechanism of how AHCC activates immunity is by means of stimulating the number of dendritic cells[citation needed]. Dendritic cells capture and process antigens (disease-causing proteins) and carry them to the lymphoid organs, such as the spleen and lymph nodes, and secrete cytokines to induce an immune response. B cells and T cells (B and T lymphocytes) are the mediators of immunity, but their function is under the control of dendritic cells. AHCC stimulated an increase in the number of dendritic cells compared to a placebo group. The stimulatory activity of the dendritic cells was also increased. These results suggest that AHCC might be useful in increasing immune competence.[5] AHCC also protects the thymus gland,[11] improves the immune system’s ability to recognize tumors,[12] and strengthens cellular immunity in healthy human volunteers.[13]

AHCC and cancer[edit]

There have been reports of tumor reduction and even cures of cancer using Reishi mushrooms and Chinese herbs. It has been observed that these traditional remedies may work by up-regulation of the immune system.[14]

A study published in the Journal of Hepatology compared the outcomes of 113 post-operative liver cancer patients taking AHCC with 156 patients in the control group. The results showed the rate of recurrence of malignant tumors was significantly lower (34% versus 66%) and patient survival was significantly higher in the AHCC group (80% vs. 52%). The level of speculation was low because actual survival figures were recorded and the patients had all been carefully observed internally at the time of surgery with photographs of tumors and lesions.[4]

In Japan, AHCC is the 2nd most popular complementary and alternative medicine used by cancer patients. Agaricus blazei supplements are the most popular, outpacing AHCC use by a factor of 7:1.[9]

AHCC and cancer patients[edit]

Patients at Kansai Medical University in Osaka, Japan, who were treated for pancreatic or biliary tract cancer with gemcitabine were given AHCC and compared to a control group. The AHCC group showed no differences in leukocyte counts, platelet counts or liver function, but there was a significant difference in hemoglobin levels, thus preventing anemia, and c-reactive protein levels indicating an anti-inflammatory response.[15]

Another study that showed improvement of quality of life with cancer patients was carried out in China. There was an 84% improvement in the quality of life in 100 patients undergoing treatment for a variety of types of cancer with chemotherapy and radiation measured according to indices such as side effects, and mood. There was no obvious improvement in 16%.[16]

In a study with mice published in the Japanese Journal of Cancer Research, a chemotherapy drug (cytosine arabinoside) was used to induce hair loss in rats. The rats who also received AHCC had a significantly lower rate and less severity of hair loss.[17]

AHCC and viral infections[edit]

Animal research suggests AHCC can help prevent influenza[18] and the West Nile virus.[19]

A study on avian flu was conducted at the College of Veterinary Medicine at the South China Agricultural University. The H5N1 virus was administered nasally to two groups of mice, one group pre-treated with AHCC. The death rate was recorded from 14 days after infection and the post-infection survival rates were compared between the two groups. All mice in the untreated control group were dead by the 11th day post-infection. In the AHCC-treated group 20% of the mice were still alive 21 days post-infection. In the control group 50% were dead at the end of 8 days. In the AHCC group the 50% mark was the 11th day. AHCC significantly raised the survival rate, and even after re-infection with the virus on the 21st and 28th days after treatment the survival rate stayed at 20-30%.[20]

A clinical trial at The University of Texas Health Science Center at Houston (UTHealth) Medical School shows that AHCC appears to be effective for the eradication of human papillomavirus (HPV), which is associated with more than 99 percent of cervical cancer cases. In the pilot clinical trial, ten HPV-positive women were treated orally with AHCC once daily for up to six months. Five achieved a negative HPV test result – three with confirmed eradication after stopping AHCC – with the remaining two responders continuing on the study.[21]

AHCC and prevention[edit]

Oxidative stress can cause tissue damage by creating reactive oxygen species (ROS) and accelerate the aging process[citation needed]. A study at Dokkyo University School of Medicine showed that AHCC protects rats from oxidative damaged caused by a powerful oxidant used in research to induce oxidative stress and ROS called Ferric nitrilotriacetate. This chemical can cause cancer and damage various organs, especially the kidney and liver[citation needed]. Pre-treatment with AHCC showed protective effects with (1) significantly lower urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetes; (2) a normalized level of creatinine, a marker of kidney damage; (3) significantly lower levels of serum AST and ALT, markers of liver damage; (4) and much lower level of thymic apoptosis, a marker for loss of immunity. These results suggest a wide-ranging, high level of protection from oxidative stress.[22] The antioxidant property of AHCC protected thyroid and testosterone production from being lowered by reactive oxygen species (ROS) in another study using ferric nitrilotriacetate (FNT).[23]

AHCC might have anti-inflammatory properties. A study carried out in Thailand with liver cancer patients used C-reactive protein (CRP) as a marker of inflammation. Inflammation drives the cancer process, and hepatitis is well known to be a precursor of liver cancer[citation needed]. Thailand has the highest rate of liver cancer in the world[citation needed]. Terminal liver cancer patients were given 3 grams a day of AHCC. After 6 months of taking AHCC, liver function tests returned to normal. The levels of CRP also returned to normal and rose again if the AHCC dosage was stopped in all 28 of the tested patients. C-reactive protein (CRP) is high when there is hepatitis and other infections, inflammatory bowel disease, pancreatitis and some cancers. There is a relationship between circulating CRP with heart attacks and strokes[citation needed]. It is possible that the anti-inflammatory properties of AHCC can prevent disorders caused by an unresolved inflammatory process.[24]

Animal studies show the potential of AHCC to prevent opportunistic infections in chronically ill or hospitalized patients. Opportunistic infections occur in weakened patients: patients who are immune compromised, patients who are traumatized or enfeebled by chronic disease. “Methicillin-resistant Staphylococcus aureus” (MRSA) is a well-known example. MRSA runs rampant in many hospitals. Klebsiella pneumoniae is also a problem in hospitals particularly in weak and compromised patients. Neither of these infections is responsive to treatment with antibiotics. The key factor that leads to opportunistic infections is a loss of immunity rather than an exposure to a disease-causing germ. Japanese researchers at Teikyo University investigated the potential of AHCC to prevent opportunistic infections.

They chose to research infections from Candida albicans, Staphylococcus aureus (MRSA), which cause staphylococcal skin infections. These infections generally start as small red bumps, boils or spider bites. They can quickly deteriorate into deep, painful abscesses that require surgical draining. Sometimes the bacteria can penetrate into the body, causing potentially life-threatening infections in bones, joints, the bloodstream, heart valves and lungs. Another opportunistic infection included in the study was Pseudomonas aeruginosa, which can cause urinary tract infections, pneumonia, chronic lung infections, skin, heart and joint infections. Mice were pre-treated with a chemotherapy drug to lower their resistance and white cell counts. Then high doses of Candida albicans were inoculated into the abdomen. Within 7 days the entire control group died of infection. A group that was given AHCC for four days from the day the drug was administered prevented the death of most of the mice. Even after 28 days, 80% were alive.[25]

Using the same model testing mice with impaired immunity because of the effect of the chemotherapy drug lowering resistance and the white cell count, the researchers investigated the protective effect of AHCC for Pseudomonas aeruginosa infection. Within 3 days all of the controls were dead. In the AHCC-treated group, 6 out of 8 were still alive after 14 days. The effects on MRSA were less pronounced. Half on the mice in the control group were dead 6 days after inoculation with MRSA and almost all of them dead by the 28th day. There was a significant extension of longevity in the mice treated with a high dose of AHCC injected directly into the abdomen, but there was no significant effect from taking AHCC orally. The research team was not willing to speculate on the mechanism of action of AHCC in its preventive effect on infections, but their conclusion was that AHCC is able to protect patients with lowered immunity from fungal and bacterial opportunistic infections.[26]

Critical remarks concerning AHCC[edit]

It should be noted that the majority if not all research concerning AHCC and its assumed therapeutic effects was funded either partially or in whole by Amino Up, the only manufacturer of the product. Many studies were carried out by Amino Up themselves or included employees of Amino Up. This makes the objectivity of the reported therapeutic results questionable.[citation needed]

See also[edit]


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  2. ^ AHCC Research Association. Summary Book. AHCC Research. [1], July 24, 2009.
  3. ^ Shinil K. Shah, Peter A. Walker, Stacey D. Moore-Olufemi, et al. (July 2011). "An Evidence-Based Review of a Lentinula edodes Mushroom Extract as Complementary Therapy in the Surgical Oncology Patient". J Parenter Enteral Nutr 35 (4): 449–458. doi:10.1177/0148607110380684. FREE TEXT
  4. ^ a b Matsui Y, Uhara J, Satoi S, Kaibori M, Yamada H, Kitade H, Imamura A, Takai S, Kawaguchi Y, Kwon A, Kamiyama Y (2002). "Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study". J Hepatol 37 (1): 78–86. doi:10.1016/S0168-8278(02)00091-0. PMID 12076865. 
  5. ^ a b Terakawa, N; Matsui, Y; Satoi, S; Yanagimoto, H; Takahashi, K; Yamamoto, T; Yamao, J; Takai, S; Kwon, AH; Kamiyama, Y (2008). "Immunological effect of active hexose correlated compound (AHCC) in healthy volunteers: a double-blind, placebo-controlled study". Nutr Cancer 60 (5): 643–651. doi:10.1080/01635580801993280. PMID 18791928. 
  6. ^ Fujii H, Nakagawa T: Novel substance having physiological activity, process for producing the same, and use, U.S. Patent Application Publication, Mar 6, 2003.
  7. ^ Mach C, Fujii H, Wakame K, Smith J, Evaluation of Active Hexose Correlated Compound Hepatic Metabolism and Potential for Drug Interactions with Chemotherapy Agents, J Soc Integrat Oncol 6(3): 105-109, 2008
  8. ^ Pescatore Fred, The Science of AHCC, Laguna Beach, CA, 2009.
  9. ^ a b Hyodo I, Amano N, Eguchi K (April 2005). "Nationwide survey on complementary and alternative medicine in cancer patients in Japan". Journal of Clinical Oncology 23 (12): 2645–54. doi:10.1200/JCO.2005.04.126. PMID 15728227. 
  10. ^ Ghoneum M, et al, Enhancement of NK cell activity in cancer patients by Active Hemicellulose Compound (AHCC) - Adjuvant Nutrition in Cancer Treatment Symposium, Tulsa, Oklahoma Nov. 6-7, 1992
  11. ^ Burikhanov R, Wakame K, Igarashi Y, Wang S, Matsuzaki S, Suppressive effect of Active Hexose Correlated Compound on Thymic apoptosis induced by dexamethasone in the rat, Endocrine Res 34: 181 – 188, 2000
  12. ^ Gao Y, Zhang D, Sun BX, Fujii H, Kosuna K, Yin Z, Active Hexose Correlated Compound enhances tumor surveillance through regulating both innate and adaptive immune responses, Cancer Immunol Immunother 55(10): 1258-1266, 2006.
  13. ^ Yin Z, Fujii H, Walshe T, Determining the frequency of CD4+ and CD8+ T cells producing IFN-γ and TNF-α in healthy elderly people using flow cytometry before and after active Hexose correlated compound intake.
  14. ^ Wasser S, Weis A, Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective, Crit Rev Immunol 19: 65-96, 1999.
  15. ^ Yanagimoto H, Yamamoto T, Satoi S, Toyokawa H, Yamao J, Kato E, Matsui Y, Kwon A, Alleviating function of health food (AHCC) for side effects in chemotherapy patients, 16th International Symposium of the AHCC Research Association, 2008
  16. ^ Tang J, Du L, Wang T, Song D, Report on a follow-up investigation in cancer patients using AHCC in China, 9th International Symposium of the AHCC Research Association, 2001.
  17. ^ Mukoda T, Sun B, Kosuna K, "Active hexose correlated compound (AHCC) protects against cytosine arabinoside induced alopecia in the newborn rat animal model," Japanese Journal of Cancer Research 89: 2405, AHCC: Research and Commentary, 2009.
  18. ^ Ritz B, Nogusa S, Ackerman E, Gardner E, Supplementation with Active Hexose Correlated Compound increases the innate immune response of young mice to primary influenza infection Nutr Immunol 136: 2868-2873, 2006.
  19. ^ Wang T, Active Hexose Correlated Compound (AHCC) enhances host resistance to West Nile encephalitis, 15th International Symposium of the AHCC Research Association, July 21 – 22, Sapporo, Japan, submitted for publication in the Japanese Journal of Nutrition.
  20. ^ Fujii H, Nishioka H, Wakame K, Sun BX, Nutritional food Active Hexose Correlated Compound (AHCC) enhances resistance against bird flu, Japanese J Comp Alt Med 1(4): 37-39 (2007).
  21. ^ "UTHealth research shows mushroom extract, AHCC, helpful in treating HPV". The University of Texas Health Science Center at Houston (UTHealth) Medical School. Retrieved 2014-10-29. 
  22. ^ Ye S, Ichimura K, Wakame K, Ohe M, Suppressive effects of active hexose correlated compound on the increased activity of hepatic and renal ornithine decarboxylase induced by oxidative stress, Life Sci 74(5): 693-602, 2003.
  23. ^ Ye S, Wakame K, Ichimura K, Kosuna K, Matsuzaki S, Amelioration of AHCC of endocrine disturbances induced by oxidative stress in the rat, Dokkyo School of Medicine, 11th International Symposium of the AHCC Research Association, 2003.
  24. ^ Srivatanakul P, Study on chemoprevention of Active Hexose Correlated Compound in high risk group for liver cancer development, 11th International Symposium of the AHCC Research Association, 2003.
  25. ^ Ishibashi H, Ikeda T, Tansho S, et al, Prophylactic efficacy of basidiomycetes preparation AHCC against lethal opportunistic infection in mice, J Pharmacol (Japan) 120(8): 715-719, 2000.
  26. ^ Abe S, Ishibashi H, Ikeda T, Tansho S, Yamaguchi H, AHCC in prevention of opportunistic infections, AHCC: Research and Commentary,2009.