AHCC and Immunity: Evidence-Based Insights into Comprehensive Immune Support

From infection protection to disease prevention—how this shiitake mushroom extract offers comprehensive immune support for all your patients.

For centuries, shiitake (Lentinula edodes) mushrooms have been a cornerstone of traditional medicine, valued for their ability to promote immunity, vitality and longevity. AHCC (active hexose correlated compound), a standardized extract derived from the mycelia of shiitake mushrooms, bridges historical wisdom and modern science for a comprehensive, evidence-based approach to immune support.

“AHCC is a proprietary blend of fermented mushroom mycelia extract with naturally occurring low molecular weight oligosaccharides, alpha-glucans and other polysaccharides,” says Céline Torres-Moon, Senior Scientist, Protocol For Life Balance®. “These bioactive compounds play a role in modulating the innate and adaptive immune responses. AHCC has been shown to enhance dendritic cell and natural killer (NK) cell activity, promote T-cell proliferation and cytokine regulation, support immune surveillance by increasing interferon-gamma and tumor necrosis factor-alpha (TNF-α) production and improve host defense mechanisms under stress or seasonal immune variations.” ^{1, 2, 3, 4, 5, 6, 7, 8}

Both human studies and animal models highlight AHCC’s ability to modulate immune response, improve resistance to infections, enhance immune surveillance in oncology settings and counteract age-related declines in immunity. Here’s what the science says:

Overall immune function and maintenance.

AHCC’s antioxidant and anti-inflammatory effects maintain healthy immunity, and research suggests AHCC supplementation further supports the body’s own natural antioxidant enzyme systems, restoring levels of glutathione peroxidase and glutathione reductase in conditions where they’ve been disrupted, neutralizing ROS and protecting cells from oxidative damage. Additionally, AHCC directly impacts the immune system through interacting with toll-like receptors and various signaling pathways in the gut and influencing the release of immune messengers. Alpha-glucans and oligosaccharides in AHCC also act as prebiotics, encouraging beneficial microbes, reducing harmful strains and promoting microbial diversity.^{9, 10, 11, 12, 13}

Other research confirms AHCC’s activities in regulating physiological stress response and minimize the immune-suppressing effects of chronic stress. AHCC is known to modulate the autonomic nervous system, increasing parasympathetic activity and reducing the negative consequences of both short-term and long-term stress. In studies of people experiencing chronic mental stress, AHCC enhanced sleep, improved resilience and hastened recovery from fatigue, compared to a control group. AHCC’s ability to preserve antioxidant status also offsets decreases in plasma concentrations of antioxidants, increased ROS production and impaired immune response associated with pervasive stress.^{14, 15, 16, 17}

Cancer treatment and protection.

A growing body of research points to multiple roles of alpha-glucans in cancer, with studies suggesting AHCC not only augments the effects of chemotherapy and minimizes adverse reactions but also inhibits tumor development and progression and improves survival rates in cancer patients.^{18, 19, 20, 21, 22}

As an adjunct intervention in conventional cancer treatment, AHCC supports immunity during chemotherapy, maintaining or increasing immune cell counts and potentiating the anti-tumor activities of cancer treatment drugs. In a number of studies, AHCC supplementation was associated with lower toxicities, significantly fewer adverse events and taste disorders, and patients who received AHCC along with cancer treatment drugs experienced greater tolerability and higher quality of life scores.^{23, 24, 25, 26, 27, 28}

Other research suggests AHCC has anti-cancer properties of its own. AHCC has been shown to enhance immune surveillance and amplify the body’s ability to fight cancer cells, and in animal models, AHCC delayed tumor development, induce apoptotic pathways in cancer cells, reduced tumor size and inhibited the growth of certain cancers. Additionally, in human trials, AHCC supplementation improved long-term immune health of cancer patients, lengthened time to recurrence, slowed the gradual decline of physiological status and increased overall survival rates. ^{29, 30, 31, 32, 33, 34, 35, 36, 37}

Viral infections.

Numerous studies demonstrate AHCC’s ability to modulate immunity, hinder the infectious process, decrease the risk of viral infection and alleviate symptoms of existing infections. Research shows AHCC inhibits viral replication and activates immune response against a range of viruses, including West Nile virus, influenza and avian flu. AHCC treatment may also promote the production of antibodies, important for preserving immunity and preventing re-infection.

In studies, AHCC treatment was linked with decreased severity and shorter duration of influenza symptoms in healthy adults. AHCC has been shown to boost NK activity and numbers, reduce the infiltration of lymphocytes and macrophages and lessen the severity of influenza infection. In some research, certain effects of AHCC, including NK cell count, T cell responses and overall immune competence, continued after the cessation of treatment, compared to placebo groups that experienced a decline in the same effects.^{38, 39, 40, 41, 42, 43}

AHCC appears to be especially promising for addressing persistent, hard-to-treat infections like hepatitis C and HPV. In trials of patients with chronic hepatitis C, AHCC supplementation improved immune function, reduced viral load, lowered the incidence of viral persistence and slowed the progression of liver disease. In one study of patients with chronic high-risk HPV, nearly 64 percent had confirmed viral clearance after six months of AHCC treatment. AHCC is also being investigated for its therapeutic application against other viral pathogens, including herpes simplex and cytomegalovirus, and emerging research points to a potential role for AHCC in promoting resistance to SARS-CoV-2 infection.^{44, 45, 46, 47, 48}

Bacterial and fungal infections.  

While human research in this area is more limited, AHCC’s immune-enhancing properties are thought to decrease the risk of bacterial and fungal infections, support recovery and increase survival rates. Animal models demonstrate AHCC’s activities in treating intramuscular infections, surgical wound infections and genital infections, suggesting a broad benefit for various bacterial challenges.^{49, 50, 51}

In both human trials and animal models, AHCC was effective for several pathogens, including Klebsiella pneumoniae, C. albicans, P. aeruginosa, chlamydia trachomatis and methicillin-resistant Staphylococcus aureus (MRSA). AHCC supplementation was associated with slowed bacterial growth and motility, rapid clearance of bacteria, reduced fungal load, improved immune response and heightened resistance to infection. In post-surgical infections—a primary cause of late complications and death—AHCC significantly prolonged survival time after acute infection. Additionally, its protective effects against deadly, antibiotic-resistant bacterial infections, including P. aeruginosa and MRSA, hint at its potential use in addressing the increasing problem of antibiotic resistance.^{52, 53, 54, 55, 56, 57, 58, 59}

Aging and chronic disease.

Immunosenescence, the age-related decline in immune system function, is strongly implicated in a range of serious conditions, including cancers, cardiovascular disease and neurodegenerative disorders. This dysfunctional state of the immune system, accompanied by higher levels of inflammation, increased oxidative stress and cellular senescence, diminishes resistance to infection and escalates susceptibility to diseases of aging. Alpha-glucans from mushrooms are known to play multiple roles in chronic illness, with research suggesting AHCC supplementation delays declines in immunity and lowers the risk of cardiovascular diseases, metabolic disorders, neurogenerative disease and other conditions associated with aging, inflammation and oxidative stress.^{60, 61, 62, 63, 64, 65, 66}

AHCC’s ability to modulate inflammation may also arrest chronic, low-grade inflammation during aging—inflammaging—a prominent factor in age-related morbidity, disability and frailty. In studies, AHCC significantly affected markers of inflammation, dramatically reducing the expression of pro-inflammatory cytokines, minimizing inflammatory status and improving immune response.  As a potent antioxidant, AHCC has been shown to decrease markers of cellular and DNA damage, highlighting its therapeutic value for protecting against oxidative stress-induced disorders.^{67, 68, 69}

Other research suggests AHCC’s promise in addressing immunosenescence. In human trials, AHCC stimulated T cell function in adults over the age of 50, enhancing CD4(+) and CD8(+) T cell responses, with results persisting up to 30 days after discontinuing treatment. In another study, healthy adults with an average age of 60 years old who received AHCC supplementation showed significantly higher levels and increased function of dendritic cells compared to a control group. Additionally, scores of immunological vigor—measures of total immune competence—were maintained in the AHCC group, while those measures decreased in the placebo group.^{70, 71, 72}

References:

1. Suknikhom W et al. 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 Mar 1;18(3):633-638.
2. Sato K, Kashimoto M. Profile summary of AHCC: composition. In: Kulkarni AD, Calder PC, Ito T, editors. Clinician’s Guide to AHCC. International Congress on Nutrition and Integrative Medicine; 2017. pp. 24–33
3. Lindequist U et al. The pharmacological potential of mushrooms. Evid Based Complement Alternat Med. 2005 Sep;2(3):285-99.
4. Wasser SP. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol. 2002 Nov;60(3):258-74.
5. Shin MS et al. The Effects of AHCC®, a Standardized Extract of Cultured Lentinura edodes Mycelia, on Natural Killer and T Cells in Health and Disease: Reviews on Human and Animal Studies. J Immunol Res. 2019 Dec 20;2019:3758576.
6. Miura T, Kitadte K, Nishioka H, Wakame K. Basic and Clinical Studies on Active Hexose Correlated Compound. In: Bagchi D, Lau FC, Ghosh DK, editors. Biotechnology in Functional Foods and Nutraceuticals. London, UK: CRC Press Taylor and Francis Group; (2010). p. 51–9
7. Xu X et al. Polysaccharides in Lentinus edodes: isolation, structure, immunomodulating activity and future prospective. Crit Rev Food Sci Nutr. 2014;54(4):474-87.
8. Sari M et al. Screening of beta-glucan contents in commercially cultivated and wild growing mushrooms. Food Chem. 2017 Feb 1;216:45-51.
9. Ye SF et al. Suppressive effects of Active Hexose Correlated Compound on the increased activity of hepatic and renal ornithine decarboxylase induced by oxidative stress. Life Sci. 2003 Dec 19;74(5):593-602
10. Ye SF et al. Amelioration by active hexose correlated compound of endocrine disturbances induced by oxidative stress in the rat. Endocr Regul. 2004 Mar;38(1):7-13.
11. Wang S et al. Preventive effects of active hexose correlated compound (AHCC) on oxidative stress induced by ferric nitrilotriacetate in the rat. Dokkyo J Med Sci. 2001; 28: 745–752.
12. Mallet JF et al. 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.
13. Daddaoua A et al. The nutritional supplement Active Hexose Correlated Compound (AHCC) has direct immunomodulatory actions on intestinal epithelial cells and macrophages involving TLR/MyD88 and NF-κB/MAPK activation. Food Chem. 2013 Feb 15;136(3-4):1288-95.
14. Takanari J et al. Effects of AHCC® on Immune and Stress Responses in Healthy Individuals. J Evid Based Integr Med. 2018 Jan-Dec;23:2156587218756511.
15. Ng F et al. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008;11:851–876.
16. Doursout MF et al. Active hexose correlated compound modulates LPS-induced hypotension and gut injury in rats. Int Immunopharmacol. 2016 Oct;39:280-286.
17. O’Riordan KJ et al. The gut microbiota-immune-brain axis: Therapeutic implications. Cell Rep Med. 2025 Mar 18;6(3):101982.
18. Yagita A et al. H-2 haplotype-dependent serum IL-12 production in tumor-bearing mice treated with various mycelial extracts. In Vivo. 2002 Jan-Feb;16(1):49-54.
19. Kidd PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev. 2000 Feb;5(1):4-27. PMID: 10696116.
20. Kuhara K 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.
21. Matsushita K et al. Combination therapy of active hexose correlated compound plus UFT significantly reduces the metastasis of rat mammary adenocarcinoma. Anticancer Drugs. 1998; 9: 343–350.
22. Spierings ELH et al. 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.
23. Cao Z et al. 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.
24. Choi JY et al. Active Hexose Correlated Compound (AHCC) Inhibits the Proliferation of Ovarian Cancer Cells by Suppressing Signal Transducer and Activator of Transcription 3 (STAT3) Activation. Nutr Cancer. 2018 Jan;70(1):109-115.
25. Ito T 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.
26. Gao Y et al. Active Hexose Correlated Compound Enhances Tumor Surveillance Through Regulating Both Innate and Adaptive Immune Responses. Cancer Immunol Immunother (2006) 55:1258–66.
27. Hunter RJ et al. Evaluation of Active Hexose Correlated Compound (AHCC) in Combination With PEGylated Liposomal Doxorubicin for Treatment of Ovarian Cancer. Int J Appl Res Natural Products (2011) 4(3):6–11.
28. Shigama K et al. 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.
29. Hirose A et al. 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.
30. Ignacio RM et al. Therapeutic effect of Active Hexose-Correlated Compound (AHCC) combined with CpG-ODN (oligodeoxynucleotide) in B16 melanoma murine model. Cytokine. 2015 Dec;76(2):131-137.
31. Uno K et al. Active Hexose Correlated Compound (AHCC) Improves Immunological Parameters and Performance Status of Patients With Solid Tumors. Biotherapy. 2000; 14:303–9.
32. Cowawaintaweewat S 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.
33. Yanagimoto H 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.
34. Hangai S 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.
35. Matsui Y et al. Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study. J Hepatol. 2002 Jul;37(1):78-86.
36. Kamiyama T 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.
37. Sun B et al. Anti-tumor effects of genestein combined polysaccharide (GCP) and active hexose correlated compound (AHCC). Biotherapy (Japan). 2001; 15: 379–382.
38. Ritz BW et al. Supplementation with active hexose correlated compound increases the innate immune response of young mice to primary influenza infection. J Nutr. 2006 Nov;136(11):2868-73.
39. Nogusa S et al. Low-dose supplementation with active hexose correlated compound improves the immune response to acute influenza infection in C57BL/6 mice. Nutr Res. 2009 Feb;29(2):139-43.
40. Wang S et al. Oral administration of active hexose correlated compound enhances host resistance to West Nile encephalitis in mice. J Nutr. 2009 Mar;139(3):598-602.
41. Doorbar J. Host Control of Human Papilloma Virus Infection and Disease. Best Prac Res Clin Obstet Gynecol (2018) 47:27–41
42. Roman BE et al. Short-term supplementation with active hexose correlated compound improves the antibody response to influenza B vaccine. Nutr Res. 2013 Jan;33(1):12-7.
43. Fujii H et al. Nutritional food active hexose correlated compound (AHCC) enhances resistance against bird flu. Jap J Complemen Altern Med. 2007; 1: 37–39.
44. Smith JA et al. From Bench to Bedside: Evaluation of AHCC Supplementation to Modulate the Host Immunity to Clear High-Risk Human Papillomavirus Infections. Front Oncol. 2019 Mar 20;9:173.
45. Derosa G et al. Nutraceutical Approach to Preventing Coronavirus Disease 2019 and Related Complications. Front Immunol. 2021 Jun 28;12:582556.
46. Smith JA et al. AHCC® Supplementation to Support Immune Function to Clear Persistent Human Papillomavirus Infections. Front Oncol. 2022 Jun 22;12:881902.
47. Singh A et al. Oral Supplementation with AHCC®, a Standardized Extract of Cultured Lentinula edodes Mycelia, Enhances Host Resistance against SARS-CoV-2 Infection. Pathogens. 2023 Apr 3;12(4):554.
48. Yeh ML et al. Eradication of hepatitis C virus preserve liver function and prolong survival in advanced hepatocellular carcinoma patients with limited life expectancy. Kaohsiung J Med Sci. 2021 Feb;37(2):145-153.
49. Pérez-Cantero A et al. Increased Efficacy of Oral Fixed-Dose Combination of Amphotericin B and AHCC® Natural Adjuvant against Aspergillosis. Pharmaceutics. 2019 Sep 3;11(9):456.
50. Segarra S et al. Prevention of disease progression in Leishmania infantum-infected dogs with dietary nucleotides and active hexose correlated compound. Parasit Vectors. 2018 Feb 21;11(1):103.
51. Aviles H et al. Active hexose correlated compound activates immune function to decrease bacterial load in a murine model of intramuscular infection. Am J Surg. 2008 Apr;195(4):537-45.
52. Aviles H et al. Active hexose correlated compound (AHCC) enhances resistance to infection in a mouse model of surgical wound infection. Surg Infect (Larchmt). 2006 Dec;7(6):527-35.
53. Belay T et al. Active Hexose Correlated Compound Activates Immune Function to Decrease Chlamydia trachomatis Shedding in a Murine Stress Model. J Nutr Med Diet Care. 2015;1(1):JNMDC-1-006.
54. Aviles H et al. Active hexose correlated compound enhances resistance to Klebsiella pneumoniae infection in mice in the hindlimb-unloading model of spaceflight conditions. J Appl Physiol (1985). 2003 Aug;95(2):491-6.
55. Ikeda T et al. [Prophylactic efficacy of a basidiomycetes preparation AHCC against lethal Candida albicans infection in experimental granulocytopenic mice]. Nihon Ishinkin Gakkai Zasshi. 2003;44(2):127-31.
56. Ritz BW. Supplementation with active hexose correlated compound increases survival following infectious challenge in mice. Nutr Rev. 2008 Sep;66(9):526-31.
57. Tena-Garitaonaindia M et al. A Standardized Extract of Lentinula edodes Cultured Mycelium Inhibits Pseudomonas aeruginosa Infectivity Mechanisms. Front Microbiol. 2022 Mar 16;13:814448.
58. Aviles H et al. Active hexose correlated compound enhances the immune function of mice in the hindlimb-unloading model of spaceflight conditions. J Appl Physiol (1985). 2004 Oct;97(4):1437-44.
59. Ishibashi H et al. [Prophylactic efficacy of a basidiomycetes preparation AHCC against lethal opportunistic infections in mice]. Yakugaku Zasshi. 2000 Aug;120(8):715-9.
60. Mascaraque C et al. Active hexose correlated compound exerts therapeutic effects in lymphocyte driven colitis. Mol Nutr Food Res. 2014 Dec;58(12):2379-82.
61. Corradetti B et al. Bioactive Immunomodulatory Compounds: A Novel Combinatorial Strategy for Integrated Medicine in Oncology? BAIC Exposure in Cancer Cells. Integr Cancer Ther. 2019 Jan-Dec;18:1534735419866908.
62. Maes M et al. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro) degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:676–692.
63. Wrona MV et al. The 3 I’s of immunity and aging: immunosenescence, inflammaging, and immune resilience. Front Aging. 2024 Oct 16;5:1490302.
64. Santoro A et al. Immunosenescence and inflammaging in the aging process: age-related diseases or longevity? Ageing Res Rev. 2021 Nov;71:101422.
65. Wang Y et al. Immunosenescence, aging and successful aging. Front Immunol. 2022 Aug 2;13:942796.
66. Liu Z et al. Immunosenescence: molecular mechanisms and diseases. Signal Transduct Target Ther. 2023 May 13;8(1):200.
67. Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018 Sep;15(9):505-522.
68. Daddaoua A et al. Active hexose correlated compound acts as a prebiotic and is antiinflammatory in rats with hapten-induced colitis. J Nutr. 2007 May;137(5):1222-8.
69. Pizzino G et al. Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev. 2017;2017:8416763.
70. Yin Z et al. 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 Dec;71(12):1187-90.
71. Terakawa N et al. Immunological effect of active hexose correlated compound (AHCC) in healthy volunteers: a double-blind, placebo-controlled trial. Nutr Cancer. 2008;60(5):643-51.
72. Takanari J et al. Effects of active hexose correlated compound on the seasonal variations of immune competence in healthy subjects. J Evid Based Complementary Altern Med. 2015 Jan;20(1):28-34.