AHCC

• How It Works

  AHCC appears to have 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.

  Lab studies suggest AHCC may enhance the activity of some types of immune cells. Animal studies suggest that AHCC has antioxidant and anti-inflammatory effects, and may improve immune system response in mice with chemotherapy-weakened immune systems. In a few human studies, AHCC improved liver function in patients with hepatocellular carcinoma and cirrhosis, and reduced blood levels of some tumor markers.

• Purported Uses

  To prevent and treat cancer
  Laboratory experiments suggest anticancer activity. A clinical study supported the use of AHCC in patients undergoing surgical resection of hepatocellular carcinoma, but another study found it ineffective for early stage prostate cancer. More research is needed.

• Do Not Take If

  You are taking drugs that are substrates of Cytochrome P450 2D6: Lab studies suggest AHCC may make these drugs less effective. Clinical significance is not known.

• Side Effects

  Diarrhea and itching have been reported in patients following consumption of AHCC.

• Clinical Summary

  Active hexose correlated compound (AHCC) is a nutritional product prepared from the mycelia of shiitake (Lentinus edodes) mushrooms. Like other mushrooms, it contains a mixture of polysaccharides, amino acids, and minerals. AHCC is also rich in alpha-1,4-glucan oligosaccharides, which are believed to enhance its biologic activities ⁽⁵⁾. Patients use AHCC to prevent and treat cancer.

  Animal models suggest that AHCC has antioxidant effects and may protect against disorders induced by oxidative stress ⁽¹⁾. It also enhanced resistance against bacterial ⁽³⁾ and viral infections ⁽⁴⁾, and has anti-inflammatory effects against colitis ⁽²⁰⁾. In healthy human subjects, AHCC improved T-cell immune responses ⁽¹⁹⁾, increased dendritic cell number and function ⁽⁶⁾, and improved antibody response to influenza vaccine ⁽²¹⁾.

  Preclinical findings suggest anticancer effects ^{(7) (8) (29)}. In cisplatin-treated mice, AHCC increased antitumor activity while reducing side effects ⁽⁹⁾, and showed synergistic effects with gemcitabine in pancreatic cancer cells ⁽²²⁾. In humans, findings from a prospective cohort study suggest AHCC improved prognosis after curative resection of hepatocellular carcinoma ⁽¹⁰⁾. AHCC may also reduce chemotherapy-associated adverse effects in patients with advanced cancer ⁽²³⁾, and in those with pancreatic ductal adenocarcinoma (PDAC) ⁽²⁵⁾. However, an open-label multicenter study of patients with early stage prostate cancer found AHCC was ineffective in reducing prostate-specific antigen levels by 50% or more ⁽¹¹⁾. Further research is needed.

• Purported Uses
  • Cancer prevention
  • Cancer treatment
• 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 compounds with reported immunomodulatory properties ⁽⁷⁾. One of the proposed mechanisms includes orchestrating immune response and maintaining immune homeostasis in part by priming TLR-2 and TLR-4 (toll-like receptor) gates at the intestinal epithelium ⁽²⁴⁾. AHCC enhanced natural killer (NK) cell activity to induce endogenous IL-12 in mice ⁽⁸⁾, and improve murine response to influenza infection ⁽¹⁵⁾. In other animal studies, AHCC protected against disorders induced by oxidative stress ⁽¹⁾, increased resistance to West Nile virus by improving T-cell response ⁽¹⁶⁾, and increased resistance to bacterial infection ⁽³⁾, perhaps by increasing inflammatory cytokine and chemokine expression as well as lymphocytes ⁽¹³⁾.

  Studies in healthy older humans suggest AHCC may enhance CD4(+) and CD8(+) T cell immune response ⁽¹⁹⁾. In patients with hepatocellular carcinoma and cirrhosis, beneficial effects on liver function ⁽¹⁰⁾ may occur via regulation of nitric oxide production ⁽¹⁴⁾.

  In tumor tissue, AHCC enhanced antitumor effects of 5-fluorouracil by enhancing apoptosis, upregulating expression of BCl-2 associated X protein, and downregulating B cell lymphoma 2 ⁽²⁶⁾. Proposed mechanisms for overcoming drug resistance in cancer cells include downregulation of Heat Shock Factor 1, which induces heat shock protein HSP27, known to be involved in gemcitabine resistance in pancreatic cancer cells ⁽²⁷⁾.

• Adverse Reactions

  Diarrhea and itching have been reported in patients following consumption of AHCC  ⁽¹¹⁾.

• Herb-Drug Interactions

  Cytochrome P450 substrates: AHCC induces CYP450 2D6, which may decrease the activity of substrate drugs such as doxorubicin or ondansetron. Clinical significance is not known ⁽¹²⁾.
  Aromatase inhibitors: AHCC induces aromatase and may reduce activity of aromatase inhibitor drugs such as letrozole. Clinical relevance has not been determined ⁽²⁸⁾.

• 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. Suknikhom W, Lertkhachonsuk R, Manchana T. The Effects of Active Hexose Correlated Compound (AHCC) on Levels of CD4+ and CD8+ in Patients with Epithelial Ovarian Cancer or Peritoneal Cancer Receiving Platinum Based Chemotherapy. Asian Pac J Cancer Prev. Mar 1 2017;18(3):633-638.

  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]

  25. Yanagimoto H, Satoi S, Yamamoto T, et al. Alleviating Effect of Active Hexose Correlated Compound (AHCC) on Chemotherapy-Related Adverse Events in Patients with Unresectable Pancreatic Ductal Adenocarcinoma. Nutr Cancer. 2016;68(2):234-40.

  26. Cao Z, Chen X, Lan L, Zhang Z, Du J, Liao L. Active hexose correlated compound potentiates the antitumor effects of low-dose 5-fluorouracil through modulation of immune function in hepatoma 22 tumor-bearing mice. Nutr Res Pract. 2015 Apr;9(2):129-36.

  27. Tokunaga M, Baron B, Kitagawa T, Tokuda K, Kuramitsu Y. Active Hexose-correlated Compound Down-regulates Heat Shock Factor 1, a Transcription Factor for HSP27, in Gemcitabine-resistant Human Pancreatic Cancer Cells. Anticancer Res. 2015 Nov;35(11):6063-7.

  28. Mathew L, Gaikwad A, Gonzalez A, et al. Evaluation of Active Hexose Correlated Compound (AHCC) in Combination With Anticancer Hormones in Orthotopic Breast Cancer Models. Integr Cancer Ther. 2017 Apr 1:1534735417704948. doi: 10.1177/1534735417704948.

  29. Kuhara K, Tokuda K, Kitagawa T, et al. CUB Domain-containing Protein 1 (CDCP1) Is Down-regulated by Active Hexose-correlated Compound in Human Pancreatic Cancer Cells. Anticancer Res. 2018 Nov;38(11):6107-6111.