Active Hexose Correlated Compound - Wikipedia, The Free Encyclopedia

Active Hexose Correlated Compound - Wikipedia, the free encyclopedia

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Active Hexose Correlated Compound

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

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

AHCC was originally designed to lower high-bloodpressure. However, researchers at Tokyo University foundthat AHCC increased natural killer (NK) cell activity incancer 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 livercancer patients after surgical resection of the primary tumor. [4] The immunological effect of AHCChas been studied in a double-blind, placebo-controlled study with 21 healthy volunteers.[5] TheAHCC group showed a significantly higher number of total dendritic cells compared with baseline, asignificantly higher number of DC1 cells compared with baseline, a significantly higher number ofDC2 cells compared with controls, and a significantly increased mixed-leukocyte reaction comparedwith controls. There was no significant difference in cytokine production, NK cell activity or otherimmune function parameters between the two groups.

Contents [hide]

1 AHCC Active Hexose Correlated Compound2 Manufacturing process3 Chemical composition4 Safety of AHCC5 Role of AHCC as a supplemental alternative medicine6 AHCC and cell-mediated immunity7 AHCC and cancer8 Improves quality of life for cancer patients9 AHCC and viral infections10 AHCC and prevention11 See also12 References13 External links

Active Hexose Correlated Compound isa chemical isolated from the Shiitakemushroom.

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AHCC (Active Hexose Correlated Compound), a registered trademark of Amino Up Co. Ltd. is afunctional food made from the hybridized mycelia of shiitake and other mushrooms fermented in ricebran. It was developed by Professor Toshihiko Okamoto, Department of Pharmacology, TokyoUniversity in conjunction with Amino Up Chemical Co. Ltd. of Sapporo, Japan. It was developed as atherapeutic aid for life-style related diseases, including liver diseases and diabetes. AHCC adheres tointernational quality and safety standards, including the HACCP9000 system. This system is acombination of HACCP (Hazard Analysis Critical Control Point) systems, which is an internationallevel hygiene control system for foods and ISO9002 (International Organization for Standardization9002), a quality assurance system.

AHCC is manufactured by culturing the mycelia of basidiomycetes (mushroom root threads) for aperiod of 45 60 days in a large holding tank. Several types of mycelia are initially cultured to form acolony (a mass of mycelia). After the culture is completed, the product is subjected to enzymereaction, sterilization, concentration and freeze drying.

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

AHCC has been studied for safety in human trials[7] as well as safety with conventionalchemotherapy.[8]

Safety studies have been conducted according to GLP standards. The LD50 according to tests withSD rats is > 12,500 mg/kg by oral administration. Toxic activity was not seen even in intra-peritonealadministration 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

AHCC is widely used in Japan and China. AHCC is used to protect the immune system of cancerpatients undergoing chemotherapy and radiation in over 700 clinics and hospitals in Japan alone. It isavailable to the general public in Japan and China without a prescription and many people use it forgeneral health maintenance and treatment of acute infections. Its legal status is that of a functionalfood. Research on AHCC has been carried out in Japan, China, Korea, Thailand, Spain and theUnited States. Results of research show that AHCC may work in the prevention and treatment ofnumerous diseases.[9]

In Japan, AHCC is the 2nd most popular complementary and alternative medicine used by cancerpatients. Agaricus blazei supplements are the most popular, outpacing AHCC use by a factor of7:1.[10]

[edit]AHCC Active Hexose Correlated Compound

[edit]Manufacturing process

[edit]Chemical composition

[edit]Safety of AHCC

[edit]Role of AHCC as a supplemental alternative medicine

[edit]AHCC and cell-mediated immunity



AHCC stimulates cell-mediated immunity by activating the white blood cells, particularly natural killercells (NK cells) and macrophages, which directly attack abnormal cells, virus-infected cells orexternal viral and bacterial pathogens that enter the body.[11]

Some research shows that the fundamental mechanism of how AHCC activates immunity is bymeans of stimulating the number of dendritic cells. Dendritic cells capture and process antigens(disease-causing proteins) and carry them to the lymphoid organs, such as the spleen and lymphnodes, and secrete cytokines to induce an immune response. B cells and T cells (B and Tlymphocytes) are the mediators of immunity, but their function is under the control of dendritic cells.AHCC clearly 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 strongly suggest thatAHCC is useful in increasing immune competence.[12] AHCC also protects the thymus gland,[13]

improves the immune systems ability to recognize tumors,[14] and strengthens cellular immunity inhealthy human volunteers.[15]

There have been reports of tumor reduction and even cures of cancer using Reishi mushrooms andChinese herbs. It has been observed that these traditional remedies may work by up-regulation of theimmune system.[16]

A study published in the Journal of Hepatology compared the outcomes of 113 post-operative livercancer patients taking AHCC with 156 patients in the control group. The results showed the rate ofrecurrence of malignant tumors was significantly lower (34% versus 66%) and patient survival wassignificantly higher in the AHCC group (80% vs. 52%). The level of speculation was low becauseactual survival figures were recorded and the patients had all been carefully observed internally atthe time of surgery with photographs of tumors and lesions.[17]

In Japan, AHCC is the 2nd most popular complementary and alternative medicine used by cancerpatients. Agaricus blazei supplements are the most popular, outpacing AHCC use by a factor of7:1.[10]

Patients at Kansai Medical University in Osaka, Japan, who were treated for pancreatic or biliary tractcancer with gemcitabine were given AHCC and compared to a control group. The AHCC groupshowed no differences in leukocyte counts, platelet counts or liver function, but there was asignificant difference in hemoglobin levels, thus preventing anemia, and c-reactive protein levelsindicating an anti-inflammatory response.[18]

Another study that showed improvement of quality of life with cancer patients was carried out inChina. There was an 84% improvement in the quality of life in 100 patients undergoing treatment fora variety of types of cancer with chemotherapy and radiation measured according to indices such asside effects, and mood. There was no obvious improvement in 16%.[19]

Numerous doctors in Japan have reported no loss of hair (alopecia) during radiation andchemotherapy in cancer patients taking AHCC.[citation needed] In a study with mice published in theJapanese Journal of Cancer Research, a chemotherapy drug (cytosine arabinoside) was used toinduce hair loss in rats. The rats who also received AHCC had a significantly lower rate and lessseverity of hair loss.[20]

Animal research suggests AHCC can help prevent influenza[21] and the West Nile virus.[22]

[edit]AHCC and cancer

[edit]Improves quality of life for cancer patients

[edit]AHCC and viral infections



A study on avian flu was conducted at the College of Veterinary Medicine at the South ChinaAgricultural University. The H5N1 virus was administered nasally to two groups of mice, one grouppre-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 controlgroup were dead by the 11th day post-infection. In the AHCC-treated group 20% of the mice werestill alive 21 days post-infection. In the control group 50% were dead at the end of 8 days. In theAHCC group the 50% mark was the 11th day. AHCC significantly raised the survival rate, and evenafter re-infection with the virus on the 21st and 28th days after treatment the survival rate stayed at20-30%.[23]

Oxidative stress can cause tissue damage by creating reactive oxygen species (ROS) and acceleratethe aging process. A study at Dokkyo University School of Medicine showed that AHCC protects ratsfrom oxidative damaged caused by a powerful oxidant used in research to induce oxidative stressand ROS called Ferric nitrilotriacetate. This chemical can cause cancer and damage various organs,especially the kidney and liver. 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 levelof thymic apoptosis, a marker for loss of immunity. These results suggest a wide-ranging, high levelof protection from oxidative stress.[24] The antioxidant property of AHCC protected thyroid andtestosterone production from being lowered by reactive oxygen species (ROS) in another study usingferric nitrilotriacetate (FNT).[25]

AHCC also has measurable anti-inflammatory properties. A study carried out in Thailand with livercancer patients used C-reactive protein (CRP) as a marker of inflammation. Inflammation drives thecancer process, and hepatitis is well known to be a precursor of liver cancer. Thailand has thehighest rate of liver cancer in the world. Terminal liver cancer patients were given 3 grams a day ofAHCC. After 6 months of taking AHCC, liver function tests returned to normal. The levels of CRP alsoreturned 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 boweldisease, pancreatitis and some cancers. There is a strong relationship between circulating CRP withheart attacks and strokes. It is possible that the anti-inflammatory properties of AHCC can preventdisorders caused by an unresolved inflammatory process.[26]

Animal studies show the potential of AHCC to prevent opportunistic infections in chronically ill orhospitalized patients. Opportunistic infections occur in weakened patients: patients who are immunecompromised, patients who are traumatized or enfeebled by chronic disease. Methicillin-resistantStaphylococcus 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 toopportunistic 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 preventopportunistic infections.

They chose to research infections from Candida albicans, Staphylococcus aureus (MRSA), whichcause staphylococcal skin infections. These infections generally start as small red bumps, boils orspider 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 inbones, joints, the bloodstream, heart valves and lungs. Another opportunistic infection included in thestudy was Pseudomonas aeruginosa, which can cause urinary tract infections, pneumonia, chroniclung infections, skin, heart and joint infections. Mice were pre-treated with a chemotherapy drug to

[edit]AHCC and prevention



lower their resistance and white cell counts. Then high doses of Candida albicans were inoculatedinto the abdomen. Within 7 days the entire control group died of infection. A group that was givenAHCC for four days from the day the drug was administered prevented the death of most of themice. Even after 28 days, 80% were alive.[27]

Using the same model testing mice with impaired immunity because of the effect of thechemotherapy drug lowering resistance and the white cell count, the researchers investigated theprotective effect of AHCC for Pseudomonas aeruginosa infection. Within 3 days all of the controlswere dead. In the AHCC-treated group, 6 out of 8 were still alive after 14 days. The effects onMRSA were less pronounced. Half on the mice in the control group were dead 6 days afterinoculation with MRSA and almost all of them dead by the 28th day. There was a significantextension of longevity in the mice treated with a high dose of AHCC injected directly into theabdomen, but there was no significant effect from taking AHCC orally. The research team was notwilling to speculate on the mechanism of action of AHCC in its preventive effect on infections, buttheir conclusion was that AHCC is able to protect patients with lowered immunity from fungal andbacterial opportunistic infections.[28]

Agaricus blazei mushroomMedicinal mushroomsShiitakeSmith JE, Rowan NJ, Sullivan R Medicinal Mushrooms: Their Therapeutic Properties and CurrentMedical Usage with Special Emphasis on Cancer Treatments Cancer Research UK, 2001

1. ^ Spierings, EL; Fujii, H; Sun, B; Walshe, T (2007). "A Phase I study of the safety of the nutritionalsupplement, active hexose correlated compound, AHCC, in healthy volunteers". J Nutr Sci Vitaminol 53(6): 536539. doi:10.3177/jnsv.53.536 . PMID 18202543 .

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 OncologyPatient" . J Parenter Enteral Nutr 35 (4): 449-458. doi:10.1177/0148607110380684 .FREE TEXT

4. ^ Matsui Y, Uhara J, Satoi S, Kaibori M, Yamada H, Kitade H, Imamura A, Takai S, Kawaguchi Y, KwonA, Kamiyama Y (2002). "Improved prognosis of postoperative hepatocellular carcinoma patients whentreated with functional foods: a prospective cohort study". J Hepatol 37 (1): 7886. doi:10.1016/S0168-8278(02)00091-0 . PMID 12076865 .

5. ^ Terakawa, N; Matsui, Y; Satoi, S; Yanagimoto, H; Takahashi, K; Yamamoto, T; Yamao, J; Takai, S etal. (2008). "Immunological effect of active hexose correlated compound (AHCC) in healthy volunteers: adouble-blind, placebo-controlled study". Nutr Cancer 60 (5): 643651.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. ^ Spierings, EL; Fujii, H; Sun, B; Walshe, T (2007). "A Phase I study of the safety of the nutritionalsupplement, active hexose correlated compound, AHCC, in healthy volunteers.". Journal of nutritionalscience and vitaminology 53 (6): 5369. doi:10.3177/jnsv.53.536 . PMID 18202543 .

8. ^ Mach C, Fujii H, Wakame K, Smith J, Evaluation of Active Hexose Correlated Compound HepaticMetabolism and Potential for Drug Interactions with Chemotherapy Agents, J Soc Integrat Oncol 6(3):105-109, 2008

9. ^ Pescatore Fred, The Science of AHCC, Laguna Beach, CA, 2009.10. ^ 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): 264554.doi:10.1200/JCO.2005.04.126 . PMID 15728227 .

[edit]See also

[edit]References



11. ^ Ghoneum M, et al, Enhancement of NK cell activity in cancer patients by Active HemicelluloseCompound (AHCC) - Adjuvant Nutrition in Cancer Treatment Symposium, Tulsa, Oklahoma Nov. 6-7,1992

12. ^ Terakawa, N; Matsui, Y; Satoi, S; Yanagimoto, H; Takahashi, K; Yamamoto, T; Yamao, J; Takai, S etal. (2008). "Immunological effect of active hexose correlated compound (AHCC) in healthy volunteers: adouble-blind, placebo-controlled trial.". Nutrition and cancer 60 (5): 64351.doi:10.1080/01635580801993280 . PMID 18791928 .

13. ^ Burikhanov R, Wakame K, Igarashi Y, Wang S, Matsuzaki S, Suppressive effect of Active HexoseCorrelated Compound on Thymic apoptosis induced by dexamethasone in the rat, Endocrine Res 34:181 188, 2000

14. ^ Gao Y, Zhang D, Sun BX, Fujii H, Kosuna K, Yin Z, Active Hexose Correlated Compound enhancestumor surveillance through regulating both innate and adaptive immune responses, Cancer ImmunolImmunother 55(10): 1258-1266, 2006.

15. ^ Yin Z, Fujii H, Walshe T, Determining the frequency of CD4+ and CD8+ T cells producing IFN- andTNF- in healthy elderly people using flow cytometry before and after active Hexose correlatedcompound intake.

16. ^ Wasser S, Weis A, Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms:a modern perspective, Crit Rev Immunol 19: 65-96, 1999.

17. ^ Matsui Y, Uhara J, Satoi S, Kaibori M, Yamada H, Kitade H, Imamura A, Takai S, Kawaguchi Y, KwonA, Kamiyama Y, Improved prognosis of postoperative hepatocellular carcinoma patients when treatedwith functional foods: a prospective cohort study, J Hepatology 37(1): 78-86, 2002

18. ^ Yanagimoto H, Yamamoto T, Satoi S, Toyokawa H, Yamao J, Kato E, Matsui Y, Kwon A, Alleviatingfunction of health food (AHCC) for side effects in chemotherapy patients, 16th International Symposiumof the AHCC Research Association, 2008

19. ^ Tang J, Du L, Wang T, Song D, Report on a follow-up investigation in cancer patients using AHCC inChina, 9th International Symposium of the AHCC Research Association, 2001.

20. ^ Mukoda T, Sun B, Kosuna K, "Active hexose correlated compound (AHCC) protects against cytosinearabinoside induced alopecia in the newborn rat animal model," Japanese Journal of Cancer Research89: 2405, AHCC: Research and Commentary, 2009.

21. ^ Ritz B, Nogusa S, Ackerman E, Gardner E, Supplementation with Active Hexose CorrelatedCompound increases the innate immune response of young mice to primary influenza infection NutrImmunol 136: 2868-2873, 2006.

22. ^ Wang T, Active Hexose Correlated Compound (AHCC) enhances host resistance to West Nileencephalitis, 15th International Symposium of the AHCC Research Association, July 21 22, Sapporo,Japan, submitted for publication in the Japanese Journal of Nutrition.

23. ^ 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).

24. ^ Ye S, Ichimura K, Wakame K, Ohe M, Suppressive effects of active hexose correlated compound onthe increased activity of hepatic and renal ornithine decarboxylase induced by oxidative stress, Life Sci74(5): 693-602, 2003.

25. ^ Ye S, Wakame K, Ichimura K, Kosuna K, Matsuzaki S, Amelioration of AHCC of endocrinedisturbances induced by oxidative stress in the rat, Dokkyo School of Medicine, 11th InternationalSymposium of the AHCC Research Association, 2003.

26. ^ Srivatanakul P, Study on chemoprevention of Active Hexose Correlated Compound in high risk groupfor liver cancer development, 11th International Symposium of the AHCC Research Association, 2003.

27. ^ Ishibashi H, Ikeda T, Tansho S, et al, Prophylactic efficacy of basidiomycetes preparation AHCCagainst lethal opportunistic infection in mice, J Pharmacol (Japan) 120(8): 715-719, 2000.

28. ^ Abe S, Ishibashi H, Ikeda T, Tansho S, Yamaguchi H, AHCC in prevention of opportunistic infections,AHCC: Research and Commentary,2009.

Amino Up Chemical Co.,Ltd.AHCC Research AssociationAHCC Nutrients Phil., Inc.

[edit]External links



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