AHCC

Purported Benefits, Side Effects & More
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AHCC

Purported Benefits, Side Effects & More
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AHCC

Common Names

  • Active Hexose Correlated Compound

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For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.

What is it?

Active Hexose Correlated Compound (AHCC) is a group of chemicals that are taken from fungi, like mushrooms, and turned into a supplement. People take this supplement to help their immune system.

What are the potential uses and benefits?

AHCC is taken to:

  • Treat cancer
  • Treat infections
  • Improve liver function

While AHCC is used for these reasons, there isn’t enough research to say that it works. Talk with your healthcare provider before taking AHCC.

Herbal supplements can interact with some medications and affect how they work. For more information, read the “What else do I need to know?” section below.

What are the side effects?

Side effects reported in a clinical study included:

  • Diarrhea (loose or watery bowel movements)
  • Mild itching
What else do I need to know?
  • Talk to your doctor if you’re taking doxorubicin (Lipodox®) and ondansetron (Zuplenz) as part of your cancer treatment. AHCC may decrease the effects of these medications.
  • Talk to your doctor if you’re taking aromatase inhibitors. AHCC can reduce their activity.

    Aromatase inhibitors are medications that stop an enzyme called aromatase from changing hormones into estrogen. Examples of aromatase inhibitors include letrozole (Femara ®) and anastrozole (Arimidex). 
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For Healthcare Professionals

Clinical Summary

Active hexose correlated compound (AHCC) is a proprietary extract derived from the mycelia of shiitake (Lentinus edodes) mushrooms. It is rich in alpha-1,4-glucan oligosaccharides that are thought to enhance its biological effects (5). Patients use AHCC to prevent and treat cancer.

AHCC showed anti-inflammatory (20) and anticancer effects (7) (8) (9) (29) (22), enhanced resistance to microbial infections (3) (4), and may protect against oxidative stress-induced disorders (1). In healthy adults, AHCC improved T-cell immune responses (19), increased dendritic cell number and function (6), improved antibody response to influenza vaccine (21), and when used with Bifidobacterium longum, modulated T regulatory and dendritic cell phenotypes to favor anti-inflammatory responses after antibiotic use (30).

Preliminary findings suggest that AHCC may improve prognosis and prevent recurrence after curative resection of hepatocellular carcinoma (10) (31), improve nutritional status when given during neoadjuvant therapy (32), and reduce chemo-associated adverse effects (23) (25). However, in an open-label multicenter study of patients with early stage prostate cancer, AHCC was ineffective in reducing prostate-specific antigen levels by 50% or more (11). Further research is needed to determine the therapeutic potential of this extract.

Purported Uses and Benefits
  • Cancer
  • Infections
  • Liver function
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). Proposed mechanisms include orchestrating immune responses 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 cell activity to induce endogenous IL-12 in mice (8), improved murine response to influenza infection (15), increased resistance to West Nile virus by improving T-cell response (16), and increased resistance to bacterial infection (3) likely via increasing inflammatory cytokine and chemokine expression as well as lymphocytes (13).

In healthy adults, AHCC enhanced CD4+ and CD8+ T-cell immune responses (19). In patients with hepatocellular carcinoma and cirrhosis, beneficial effects on liver function (10) are thought to  be via regulation of nitric oxide production (14).

AHCC also enhanced antitumor effects of 5-fluorouracil by enhancing apoptosis, upregulating expression of BCl-2 associated X protein, and by 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 (27).

Adverse Reactions
  • Diarrhea and itching were reported in a clinical trial (11).
Herb-Drug Interactions

CYP450 substrates: AHCC induces CYP2D6, 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).

Dosage (OneMSK Only)
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. 2016 Feb;55(1):139-46.
  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.
  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.
  30. Chowdhury AH, Cámara M, Verma C, et al. Modulation of T Regulatory and Dendritic Cell Phenotypes Following Ingestion of Bifidobacterium longum, AHCC® and Azithromycin in Healthy Individuals. Nutrients. 2019 Oct 15;11(10). pii: E2470.
  31. Kamiyama T, Orimo T, Wakayama K, et al. Preventing Recurrence of Hepatocellular Carcinoma After Curative Hepatectomy With Active Hexose-correlated Compound Derived From Lentinula edodes Mycelia. Integr Cancer Ther. 2022 Jan-Dec;21:15347354211073066.
  32. Hashimoto D, Satoi S, Yamamoto T, et al. Nutritional impact of active hexose-correlated compound for patients with resectable or borderline-resectable pancreatic cancer treated with neoadjuvant therapy. Surg Today. 2021 Nov;51(11):1872-1876.
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