In October of 2022, Vitamin Retailer’s sister publication—Natural Practitioner—published my article, “The Use of AHCC in the Treatment of Human Papillomavirus (HPV).” In the current article, I’m also going to review the value of this nutraceutical for HPV, but in addition I’ll be discussing AHCC’s value for immune function, COVID-19 and Lyme disease as well. Let’s start with a background review of AHCC.
Shiitake (Lentinula edodes) is a mushroom that has been used as a food and traditional medicine for thousands of years,1 and is currently used for promoting healthy immune function,2 healthy liver function3 and modulating the stomach4 and pancreas cancer cells,5 and has been validated in scientific literature for these purposes. This data was sufficiently promising to inspire one R&D focused nutraceutical company in Japan to develop a novel shiitake-based compound called AHCC, a unique cultured extract derived from the cell wall of the Shiitake mushroom mycelia, which is rich in several different polysaccharides, including alpha-glucans and axoglucan fractions, as well as amino acids, lipids and minerals. Oligosaccharides make up about 74 percent of AHCC.6 AHCC is thought to act as a biological response modifier and is supported by more than 30 human clinical studies and 50-plus papers in PubMed-indexed journals.
AHCC & Immune Function
AHCC demonstrated early clinical promise in promoting healthy immune response.7 This was shown in animal research where AHCC helped restore immune response that had been negatively affected by trauma, infection and food deprivation.8 In humans, the effect of AHCC on immune response was investigated by measuring the number and function of circulating dendritic cells (DCs), a type of immune cell, in healthy volunteers. Twenty-one healthy volunteers were randomized to receive placebo or AHCC for four weeks. The results were that the AHCC group had a significantly higher number of total DCs compared to when they first started the study and compared to the control subjects.
Other types of immune cells were also significantly increased in the AHCC group compared to controls.9 For example, AHCC promoted the activity of natural killer (NK) cells in patients with cancer. In animal models, it also protected against carbontetrachloride-induced liver damage, promoted healthy blood glucose levels and decreased apoptosis (i.e., programmed cell death) of the thymus.10 AHCC is utilized by more than 1,000 health care facilities worldwide to reduce the incidence of infections in both healthy and immune-compromised patients, improve cancer patient outcomes, decrease chemo side-effects, manage viral loads in hepatitis-C patients and help those with liver disease—and of course help control HPV infections.11
AHCC & HPV
HPV is the most common sexually transmitted infection (STI) in the United States.12,13 While there is an HPV vaccine, which the Centers for Disease Control and Prevention (CDC) recommends for all preteens, and everyone through age 26,14 the CDC also indicates that there is not any treatment for the virus itself—although there are treatments for the health problems that HPV can cause.15 However, AHCC has been shown to have effectiveness in the treatment of HPV.
Two pilot studies16 of 10 human patients each were conducted in women with confirmed persistent high risk-HPV/HR-HPV infections. The first study evaluated AHCC 3 g/day from five weeks up to six months, and the second study evaluated AHCC 1 g/day for less than eight months. In the first human study with 3 g/day AHCC, four of six (66.7 percent) patients had confirmed HR-HPV clearance after three to six months. In the second study with 1 g/day AHCC, four of nine (44 percent) patients had confirmed HR-HPV clearance after seven months. The researchers concluded that these studies demonstrated the effectiveness of AHCC in clearing HR-HPV infections.
Likewise, a subsequent randomized, double-blind, placebo-controlled study17 examined the efficacy, safety and durability of the use of AHCC supplementation for six months to support the host immune system for clearing HPV infections in 41 women over 30 years of age with confirmed persistent HR-HPV infections for greater than two years. Patients received placebo or AHCC 3-g supplementation by mouth once daily on empty stomach. The results were that 14 (63.6 percent) of the 22 patients in the AHCC supplementation arm were HPV negative after six months, with 64.3 percent (9/14) achieving an HPV negative status after they were off supplementation for six months. On the placebo arm, two (10.5 percent) of 19 patients had HPV negative status at 12 months. AHCC also improved immune markers. In conclusion, AHCC 3 g/day was effective in supporting the host immune system to eliminate persistent HPV infections and was well tolerated, with no significant adverse side effects reported.
AHCC & COVID-19
Since COVID-19 needs no introduction, I’ll dive right into it: In 2020, researchers wrote an article in a scientific journal, speculating that AHCC may be useful “in the prevention of diseases provoked by human pathogenic coronavirus, including COVID-19.”18 Then, in April of 2022, other researchers published an article in another scientific journal, examining the effectiveness of AHCC in preventing and treating COVID-19 complications in mice. This study19 evaluated the effects of the oral administration of AHCC on the host response to infection by SARS-CoV-2 (the COVID-19 virus).
Oral administration of AHCC took place every other day for one week before and one day post SARS-CoV-2 infection. Results were that AHCC decreased the viral load and reduced inflammation in the lungs. AHCC treatment also significantly reduced SARS-CoV-2-induced lethality in the mice. AHCC administration enhanced the expansion of γδ T cells (i.e., important immune cells) in the spleen and lungs before and after viral infection and promoted T helper 1-prone mucosal and systemic T cell responses as well. In summary, AHCC supplementation enhanced host resistance against mild and severe COVID-19 infection primarily via the promotion of innate and adaptive T cell immune responses in mice.
AHCC & Lyme Disease
Lyme disease is the most reported vector-borne illness (i.e., infection transmitted to humans and other animals by blood-feeding insects, such as mosquitoes, ticks and fleas) in the U.S. The disease is caused by the bacterium Borrelia burgdorferi and is transmitted to humans through the bite of infected ticks. Typical symptoms include fever, headache, fatigue, a skin rash and joint pain. If left untreated, infection can spread to the joints, heart and nervous system, resulting in inflammation and long-term symptoms that include arthritis and/or intermittent pain in joints and muscles, facial palsy, cardiovascular abnormalities and cognitive disturbances. Recent research suggests that late-stage Lyme disease may be a result of malfunctioning immune function.
A pilot open-label study was conducted in 12 Lyme disease patients to evaluate the effects of supplementation with 3 g of AHCC daily for eight weeks. Results were that after eight weeks of AHCC administration, AHCC ameliorated flu-like symptoms and manifestations in the eye, joint, muscle, nervous system and cardiovascular system. In addition, markers of inflammation significantly decreased. In conclusion, this study provides preliminary evidence that AHCC may be effective in treating patients with Lyme disease.
AHCC Safety Research
To assess AHCC safety, a study was conducted in which high doses (9 g) of AHCC were given to healthy subjects. The results were that AHCC caused no significant abnormality in laboratory parameters, and the adverse effects were minimal with the high dose being tolerated by 85 percent of the subjects.20 Research has not demonstrated adverse effects at the lower doses typically used. Furthermore, in a study, AHCC was examined for potential drug interactions with chemotherapy agents. The results were that AHCC does have the potential for drug-drug interactions involving chemotherapy agents such as doxorubicin or ondansetron, which are metabolized by the liver enzyme CYP450 2D6. However, the overall data suggest that AHCC would be safe to administer with most other chemotherapy agents that are not metabolized via the CYP450 2D6 pathway.21
Confusion on Terminology Opens the Door to Fake Products
Early research referenced that among other fractions, AHCC contained a complex of polysaccharides of a certain structure and referred to them using a fabricated term “Active Hexose Correlated Compound.”22 The term stuck, creating confusion until researchers reverted to using established chemical terms to reference the different constituents of AHCC, such as “alpha-1,4-glucans.”23 Unfortunately, fake products seeking to capitalize on the use of the term appeared in e-commerce, misleading consumers into thinking they are buying AHCC. This fact underscores the importance of purchasing products from trusted sources who carefully screen their assortment and select genuine products from reputable brands.
AHCC has demonstrated efficacy in promoting immune function and treating HPV infection. Research in mice also suggests that it may be effective against COVID-19. Furthermore, preliminary research has shown positive results in the use of AHCC for treating Lyme disease. Additional research has likewise demonstrated the safety of AHCC. To avoid fake or adulterated materials, it is important utilize AHCC products with the registered trademark. VR
1 Jones K. Shiitake: The Healing Mushroom. Rochester, VT: Healing Arts Press, 1995.
2 Chang R. Functional properties of edible mushrooms. Nutr Rev 1996;54(11 Pt 2):S91-3.
3 Jones K. Shiitake” A major medicinal mushroom. Alt Compl Ther 1998;4:53–9.
4 Taguchi I. Clinical efficacy of lentinan on patients with stomach cancer: End point results of a four-year follow-up survey. Cancer Detect Prevent Suppl 1987;1:333–49.
5 Matsuoka H, Seo Y, Wakasugi H, et al. Lentinan potentiates immunity and prolongs survival time of some patients. Anticancer Res 1997;17:2751–6.
6 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 2003;74:593-602.
7 Kidd PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev 2000;5(1):4-27. 8 Aviles H, O’Donnell P, Sun B, Sonnenfeld G. Active hexose correlated compound (AHCC) enhances resistance to infection in a mouse model of surgical wound infection. Surg Infect (Larchmt) 2006;7(6):527-35.
9 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):643-51.
10 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 2003;74:593-602.
11 Studies. AHCC® Association. Retrieved August 2, 2022 from www.ahcc.net/studies/.
12 Genital HPV Infection – Basic Fact Sheet. Division of STD Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention. Page last reviewed: April 12, 2022. Retrieved August 2, 2022 from www.cdc.gov/std/hpv/stdfact-hpv.htm.Fu.
13 Cates JR, Wong T, Semenciw R, Creel L. Human Papillomavirus: A Hidden Epidemic in the United States. Population Reference Bureau. May 1, 2001. Retrieved August 2, 2022 from www.prb.org/resources/human-papillomavirus-a-hidden-epidemic-in-the-united-states/#:~:text=The%20human%20papillomavirus%20is%20the,to%20the%20National%20Cancer%20Institute.
14 Genital HPV Infection – Basic Fact Sheet. Division of STD Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention. Page last reviewed: April 12, 2022. Retrieved August 2, 2022 from www.cdc.gov/std/hpv/stdfact-hpv.htm.Fu.
15 Human Papillomavirus (HPV) Treatment and Care. Division of STD Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention. Page last reviewed: July 22, 2021. Retrieved August 2, 2022 from www.cdc.gov/std/hpv/treatment.htm#:~:text=There%20is%20no%20treatment%20for,grow%20in%20size%20or%20number.
16 Smith JA, Mathew L, Gaikwad A, 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.
17 Smith JA, Gaikwad A, Mathew L, et al. AHCC ® Supplementation to Support Immune Function to Clear Persistent Human Papillomavirus Infections. Front Oncol. 2022 Jun 22;12:881902.
18 Di Pierro F, Bertuccioli A, Cavecchia I. Possible therapeutic role of a highly standardized mixture of active compounds derived from cultured Lentinula edodes mycelia (AHCC) in patients infected with 2019 novel coronavirus. Minerva Gastroenterol Dietol. 2020 Jun;66(2):172-176.
19 Singh A, Adam A, Rodriguez L, Peng BH, Wang B, Xie X, Shi PY, Homma K, Wang T. 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.
20 Spierings EL, 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(6):536-9.
21 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 2008;6(3):105-9.
22 Uno K, Chikumaru S, Hosokawa T, “Cancer immunotherapy by a phyto-polysaccharide (AHCC): its effects and strategy,” AHCC Research Association 8th Symposium, Sapporo, Japan, 2000.
23 Perez-Cantero A, Serrano D, Navarro-Rodriguez P, et al. Increased Efficacy of Oral Fixed-Dose Combination of Amphotericin B and AHCC® Natural Adjuvant against Aspergillosis. Pharmaceutics. 2019 Sep; 11(9): 456.
Gene Bruno, MS, MHS, the provost for Huntington University of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 40 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. He can be reached at email@example.com.