Health Care Professional Information

Common Name

Active Hexose Correlated Compound

Brand Name

AHCC

Clinical Summary

A proprietary extract prepared from co-cultured mycelia of several species of Basidiomycete mushrooms, including shiitake (Lentinus edodes), active hexose correlated compound (AHCC) is extracted using hot water following an enzyme pretreatment, but the specific mushroom source and procedural details have not been fully disclosed. Patients use AHCC to prevent and treat cancer.
Animal studies suggest that AHCC has antioxidant effects and may protect against many disorders that are induced by oxidative stress (1); enhances resistance against bacterial (2) (3) and viral infections (4); and due to its anti-inflammatory effects, is effective against colitis (20).
A study of healthy subjects aged 50 years and older suggests that AHCC improves T-cell immune responses via increased production of interferon-l and tumor necrosis factor-alpha for up to 30 days after treatment (5). In healthy humans, AHCC increased dendritic cell number and function (6) and short-term supplementation with AHCC was shown to improve the antibody response to influenza vaccine (21).

In vitro and animal studies show that AHCC exhibits anticancer activities (7) (8). In cisplatin-treated mice, AHCC increased its anti-tumor effects while reducing side effects (9) (3); and showed synergistic effects with gemcitabine in pancreatic cancer cells (22).
A prospective cohort study suggested that AHCC improves prognosis after curative resection of hepatocellular carcinoma (HCC) (10). AHCC may also reduce chemotherapy-associated adverse effects in patients with advanced cancer (23). However, an open-label multicenter study of patients with early stage prostate cancer found that AHCC was ineffective in reducing patient prostrate-specific antigen levels by 50% or more (11). More studies are needed.

Purported Uses
  • Cancer prevention
  • Cancer treatment
Constituents
  • Polysaccharides
  • Amino Acids
  • Minerals
    (2)
Mechanism of Action

AHCC glucans are low molecular weight (~5 KDa) polysaccharides with alpha-1,3 linkages. Both properties are unusual for this class of mushroom glucans with reported immunomodulatory properties (7). A proposed mechanism is by orchestrating immune response and the maintenance of immune homeostasis in part by priming the TLR-2 and TLR-4 (toll-like receptors) gate at the intestinal epithelium (24). AHCC has been shown to enhance natural killer (NK) cell activity in vitro, induces endogenous IL-12 in mice (8), and improves murine response to influenza infection (15). One animal study suggested that AHCC has antioxidant effects and may protect against disorders induced by oxidative stress (1). Other studies have shown AHCC to increase resistance to bacterial infection (3) by increasing inflammatory cytokine and chemokine expression as well as lymphocytes (13). AHCC also enhanced murine resistance to West Nile virus by improving T-cell response (16).

In chemotherapy-induced granulocytopenic mice, AHCC improved immune response to Candida albicans (2). AHCC also alleviated the side effects induced by several anticancer drugs in rodents but the molecular mechanism for this activity needs to be defined (17) (18). In healthy adults aged 50 years or more, AHCC enhanced CD4(+) and CD8(+) T cell immune responses (19). In patients with hepatocellular carcinoma (HCC) and cirrhosis, AHCC has shown beneficial effects on liver function (10) possibly by regulating nitric oxide (NO) production (14).

Adverse Reactions
  • Diarrhea and itching have been reported in patients following administration of AHCC (11).
Herb-Drug Interactions

Cytochrome P450 substrates: AHCC induces CYP450 2D6, which may decrease the activity of drugs, such as doxorubicin or ondansetron, which are substrates of this enzyme (12).

Literature Summary and Critique

Matsui Y, et al. Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: A prospective cohort study. J Hepatol 2002;37:78-86.
This is a prospective cohort study to determine whether AHCC improves the prognosis of hepatocellular carcinoma (HCC) patients following surgical treatment. 269 patients with histologically confirmed HCC were studied from February 1992 through December 2001. After undergoing curative surgery, some of the patients received 3.0 g/day oral AHCC. Participants were not randomized, nor were placebos administered. Results showed statistically significant lengthening of time to recurrence and overall survival rate when compared with those who did not take AHCC. Three participants in the AHCC group did not complete the trial due to nausea, but overall side effects were minimal. While the study implies a benefit for post-surgical HCC treatment, the lack of randomization and placebo control tempers that result.

Sumiyoshi, Y, et al. Dietary administration of mushroom mycelium extracts in patients with early stage prostate cancers managed expectantly: A phase II study. Jpn J Clin Oncol. 2010 Oct;40(10):967-72.
In an open label, multicenter clinical trial, 4.5 grams AHCC was taken daily for 6 months by 74 patients with early prostate cancer. The primary endpoint for this study was a reduction of prostrate-specific antigen (PSA) by at least 50%. Only 1 of 74 patients (1.4%) achieved a 50% or more reduction PSA value. However, severe anxiety observed in two groups of patients was found to significantly improve (n = 19, p < 0.0018, n = 15, p < 0.0099). Grade 2 diarrhea and Grade 1 itching was observed in one patient. The study concluded that AHCC was ineffective in achieving a 50% reduction in PSA values.

Dosage (Inside MSKCC Only)
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References
  1. Ye SF, 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. Dec 19 2003;74(5):593-602.
  2. Ikeda T, Ishibashi H, Fujisaki R, et al. Prophylactic efficacy of a basidiomycetes preparation AHCC against lethal Candida albicans infection in experimental granulocytopenic mice. Nippon Ishinkin Gakkai Zasshi. 2003;44(2):127-131.
  3. Aviles H, Belay T, Fountain K, Vance M, Sun B, Sonnenfeld G. Active hexose correlated compound enhances resistance to Klebsiella pneumoniae infection in mice in the hind limb-unloading model of spaceflight conditions. J Appl Physiol. Aug 2003;95(2):491-496.
  4. Wang S, Welte T, Fang H, et al. Oral Administration of Active Hexose Correlated Compound Enhances Host Resistance to West Nile Encephalitis in Mice. J Nutr. Jan 13 2009.
  5. Yin Z, Fujii H, Waishe T. Effects of active hexose correlated compound on frequency of CD4+ and CD8+ T cells producing interferon-ã and/or tumor necrosis factor-á in healthy adults. Hum Immunol. 2010 Dec;71(12):1187-90.
  6. Terakawa N, Matsui Y, Satoi S, et al. Immunological effect of active hexose correlated compound (AHCC) in healthy volunteers: a double-blind, placebo-controlled trial. Nutr Cancer. 2008;60(5):643-651.
  7. Kidd PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev. Feb 2000;5(1):4-27.
  8. Yagita A, Maruyama S, Wakasugi S, Sukegawa Y. H-2 haplotype-dependent serum IL-12 production in tumor-bearing mice treated with various mycelial extracts. In Vivo. Jan-Feb 2002;16(1):49-54.
  9. Hirose A, Sato E, Fujii H, Sun B, Nishioka H, Aruoma OI. The influence of active hexose correlated compound (AHCC) on cisplatin-evoked chemotherapeutic and side effects in tumor-bearing mice. Toxicol Appl Pharmacol. Jul 15 2007;222(2):152-158.
  10. Matsui Y, Uhara J, Satoi S, et al. Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study. J Hepatol. Jul 2002;37(1):78-86.
  11. Sumiyoshi Y, Hashine K, Kakehi Y, et al. Dietary administration of mushroom mycelium extracts in patients with early stage prostate cancers managed expectantly: a phase II study. Jpn J Clin Oncol. 2010 Oct;40(10):967-72.
  12. Mach CM, Fugii H, Wakame K, Smith J. Evaluation of active hexose correlated compound hepatic metabolism and potential for drug interactions with chemotherapy agents. J Soc Integr Oncol. Summer 2008;6(3):105-109.
  13. Aviles H, O'Donnell P, Orshal J, Fujii H, Sun B, Sonnenfeld G. Active hexose correlated compound activates immune function to decrease bacterial load in a murine model of intramuscular infection. Am J Surg. Apr 2008;195(4):537-545.
  14. Matsui K, Kawaguchi Y, Ozaki T, et al. Effect of active hexose correlated compound on the production of nitric oxide in hepatocytes. JPEN J Parenter Enteral Nutr. Sep-Oct 2007;31(5):373-380; discussion 380-371.
  15. Nogusa S, Gerbino J, Ritz BW. Low-dose supplementation with active hexose correlated compound improves the immune response to acute influenza infection in C57BL/6 mice. Nutr Res. 2009;29(2):139-43.
  16. Wang S, Welte T, Fang H, et al. Oral administration of active hexose correlated compound enhances host resistance to West Nile encephalitis in mice. J Nutr. 2009;139(3):598-602.
  17. Shigama K, Nakaya A, Wakame K, Nishioka H, Fujii H. Alleviating effect of active hexose correlated compound (AHCC) for anticancer drug-induced side effects in non-tumor-bearing mice. J Exp Ther Oncol. 2009;8(1):43-51.
  18. Sun B, Wakame K, Sato E, Nishioka H, Aruoma OI, Fujii H. The effect of active hexose correlated compound in modulating cytosine arabinoside-induced hair loss, and 6-mercaptopurine- and methotrexate-induced liver injury in rodents. Cancer Epidemiol. 2009;33(3-4):293-9.
  19. Yin Z, Fujii H, Walshe T. Effects of active hexose correlated compound on frequency of CD4+ and CD8+ T cells producing interferon-γ and/or tumor necrosis factor-α in healthy adults. Hum Immunol. 2010;71(12):1187-90.
  20. Mascaraque C, Suárez MD, Zarzuelo A, Sánchez de Medina F, Martínez-Augustin O. Active hexose correlated compound exerts therapeutic effects in lymphocyte driven colitis. Mol Nutr Food Res. 2014 Dec;58(12):2379-82.
  21. Roman BE, Beli E, Duriancik DM, Gardner EM. Short-term supplementation with active hexose correlated compound improves the antibody response to influenza B vaccine. Nutr Res. 2013 Jan;33(1):12-7.
  22. Suenaga S, Kuramitsu Y, Kaino S, et al.Active hexose-correlated compound down-regulates HSP27 of pancreatic cancer cells, and helps the cytotoxic effect of gemcitabine. Anticancer Res. 2014 Jan;34(1):141-6.
  23. Ito T, Urushima H, Sakaue M, et al. Reduction of adverse effects by a mushroom product, active hexose correlated compound (AHCC) in patients with advanced cancer during chemotherapy—the significance of the levels of HHV-6 DNA in saliva as a surrogate biomarker during chemotherapy. Nutr Cancer. 2014;66(3):377-82.
  24. Mallet JF, Graham É, Ritz BW, Homma K, Matar C. Active Hexose Correlated Compound (AHCC) promotes an intestinal immune response in BALB/c mice and in primary intestinal epithelial cell culture involving toll-like receptors TLR-2 and TLR-4. Eur J Nutr. 2015 Jan 18. [Epub ahead of print]

Consumer Information

How It Works

Bottom Line: AHCC has immunomodulatory and anticancer effects. But large human studies are lacking.

Active hexose correlated compound (AHCC) is an extract of mushrooms from the Basidiomycete class, including shiitake mushrooms. This product contains polysaccharides called glucans, which scientists think are responsible for its biological activity.  One study showed that it could enhance the activity of natural killer cells (a type of immune cell) in the test tube. Animal studies suggest that AHCC has antioxidant and anti-inflammatory effects, and can improve the response of the immune system in mice with chemotherapy-weakened immune systems. In humans, AHCC has been shown to improve liver function in patients with hepatocellular carcinoma and cirrhosis and reduce the levels of certain tumor markers in the blood.

Purported Uses

To prevent and treat cancer
Laboratory studies show some anti-cancer activity, but these results are not especially strong. One human study supported the use of AHCC in patients undergoing surgical resection of hepatocellular carcinoma, but this study had design flaws and much more research is needed.
Another study found AHCC to be an ineffective treatment for early stage prostate cancer.

Research Evidence

Hepatocellular carcinoma (liver cancer):
One study has looked at the effects of AHCC in humans. One hundred and thirteen patients with hepatocellular carcinoma (liver cancer), after undergoing surgical tumor resection, were treated with AHCC. When the disease-free period and overall survival rate of this group were compared to that of a similar group of patients who had not received AHCC, it was found that the AHCC group fared better. While this suggests that AHCC can improve the prognosis of patients undergoing surgery for liver cancer, this study had certain design flaws, including lack of placebo control group and random assignment of patients, and further clinical trials are needed.

Prostate cancer:
A study of patients with early prostate cancer found that AHCC failed to significantly reduce prostate specific antigen (PSA) levels. However, severe anxiety observed in some of the patients was found to improve.

Do Not Take If
  • You are taking drugs that are substrates of Cytochrome P450 2D6 (AHCC can decrease the effects of such drugs).
Side Effects
  • Diarrhea and itching have been reported in patients following administration of AHCC.
E-mail your questions and comments to aboutherbs@mskcc.org.