In-Human Studies

Studies in healthy volunteers suggest that even high doses of AHCC administered for 14 days are well-tolerated and do not cause laboratory abnormalities, and may increase the number and function of dendritic cells.6,7 One study found no changes in natural killer–cell activity or cytokine production.7

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A study of 28 patients with ovarian cancer who were randomly assigned to receive 3 g per day of AHCC or placebo demonstrated an increase in CD8-positive T cells at the sixth cycle of chemotherapy, but no difference in CD4-positive T cells or CD8-positive T cells earlier in treatment.8

Though most other studies evaluated the effect of AHCC on toxicities caused by anticancer treatment, 2 studies investigated the effect of AHCC on liver cancer outcomes. A prospective cohort study of 269 patients with hepatocellular carcinoma (HCC) who underwent liver resection demonstrated that AHCC administration after surgery resulted in a longer time to recurrence (hazard ratio [HR], 0.64; 95% CI, 0.43-0.95; P = .028) and increased overall survival (OS; HR, 0.42; 95% CI, 0.25-0.70; P = .0009) compared with those who did not receive AHCC.9

Another prospective cohort study evaluated 44 patients with advanced liver cancer who were not eligible for resection or chemoembolization.10 Those who received AHCC demonstrated prolonged OS at 3.5 months compared with 1.5 months with placebo.

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Several studies showed that AHCC reduced toxicities associated with anticancer treatment. A retrospective review of 41 women with breast cancer receiving anthracyclines and taxanes found that AHCC reduced the number of neutrophil-related events (odds ratio [OR], 0.30; 95% CI, 0.1-0.8; P = .016) and the need for granulocyte colony–stimulating factor (P = .008).11 In another study, 24 patients with different types of cancer received AHCC with their second cycle of chemotherapy.12

AHCC treatment resulted in improved quality of life scores and decreased markers of hematotoxicity and hepatotoxicity compared with the first cycle of chemotherapy, during which no AHCC was administered.

A study of 75 patients with pancreatic cancer receiving gemcitabine demonstrated that 6 g of AHCC for 2 months resulted in significantly fewer grade 3 adverse events (17% vs 53%; P = .0005) and fewer taste disorders (17% vs 56%; P = .0007) compared with patients who did not take AHCC.13

Conclusions

Animal studies suggest that AHCC may have anticancer and immune-enhancing properties. In-human studies suggest that AHCC is well-tolerated and may reduce the incidence of adverse effects among patients receiving chemotherapy.

Two small studies suggest that AHCC may improve outcomes among patients with liver cancer. Larger, randomized controlled studies, however, are needed to confirm these findings.

References

  1. Gao Y, Zhang D, Sun B, Fujii H, Kosuna K, Yin Z. Active hexose correlated compound enhances tumor surveillance through regulating both innate and adaptive immune responses. Cancer Immunol Immunother. 2006;55:1258-66.
  2. Fatechand K, Santhanam R, Shen B, et al. Active hexose-correlated compound enhances extrinsic-pathway-mediated apoptosis of acute myeloid leukemic cells. PLoS ONE. 2017;12:e0181729.
  3. 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. 2007;222:152-8.
  4. Mathew L, Gaikwad A, Gonzalez A, Nugent EK, Smith JA. Evaluation of active hexose correlated compound (AHCC) in combination with anticancer hormones in orthotopic breast cancer models. Integ Cancer Ther. 2017;16:300-7. doi: 10.1177/1534735417704948
  5. 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;9:129-36. doi: 10.4162/nrp.2015.9.2.129
  6. Spierings ELH, Fujii H, Sun B, Walshe T. A phase I study of the safety of the nutritional supplement, active hexose correlated compound, AHCC, in healthy volunteers. J Nutr Sci Vitaminol (Tokyo). 2007;53:536-9.
  7. 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;60:643-51. doi: 10.1080/01635580801993280
  8. 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. 2017;18:633-8. doi: 10.22034/APJCP.2017.18.3.633
  9. 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. 2002;37:78-86.
  10. Cowawaintaweewat S, Manoromana S, Sriplung H, et al. Prognostic improvement of patients with advanced liver cancer after active hexose correlated compound (AHCC) treatment. Asian J Allergy Immunol. 2006;24:33-45.
  11. Hangai S, Iwase S, Kawaguchi T, et al. Effect of active hexose-correlated compound in women receiving adjuvant chemotherapy for breast cancer: a retrospective study. J Alter Compl Med. 2013;19:905-10. doi: 10.1089/acm.2012.0914
  12. Ito T, Urushima H, Sakaue M, Yukawa S, Honda H. 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;1-6. doi: 10.1080/01635581.2014.884232
  13. 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;68:234-40. doi: 10.1080/01635581.2016.1134597

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