According to the Centers for Disease Control and Prevention (CDC), human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the United States. There were about 43 million HPV infections in 2018, many among people in their late teens and early 20s.1 Furthermore, there are an estimated 5.5 million new cases each year.2 There are different types of HPV, some of which can cause health problems including genital warts and cancers. There is also an HPV vaccine, which the CDC recommends for all preteens, and everyone through age 26 years.3 Unfortunately, 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.4 There is, however, a proprietary, standardized extract of cultured Lentinula edodes mycelia (AHCC), which has been shown to have effectiveness in the treatment of HPV. Although AHCC has multiple applications for human health, this article will focus on its use in treating HPV.
For thousands of years, mushrooms have been used as both food and medicine in various cultures. One of those mushrooms, shiitake (Lentinula edodes),5 is currently used for promoting healthy immune function,6 healthy liver function7 and modulating the stomach8 and pancreas cancer cells9 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.
AHCC is a unique cultured extract derived from the cell wall of the shiitake mushroom mycelia, rich in a number of different polysaccharides including alpha-glucans and axoglucan fractions as well as amino acids, lipids and minerals. Oligosaccharides make up about 74 percent of AHCC.10 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. It 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 Before getting into a discussion of this, let’s first briefly review the impact of AHCC on immune function.
AHCC & Immune Function
AHCC demonstrated early clinical promise in promoting healthy immune response.12 This was shown in animal research where AHCC helped restore immune response that had been negatively affected by trauma, infection and food deprivation.13 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.14 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.15
AHCC & HPV Infection
Researchers predominantly from the Department of Obstetrics, Gynecology and Reproductive Sciences, UTHealth McGovern Medical School in Houston, TX evaluated the potential use of AHCC supplementation to support clearance of high risk-human papillomavirus (HR-HPV) infections. The primary objective of this research16 was to evaluate the effect of AHCC supplementation in modulating the hosts immune system in clearing HR-HPV infections. This was accomplished with an in-vitro study, a mouse study and two human studies. The in-vitro study treated cervical cancer with AHCC daily for seven days. The mouse study examined cervical cancer where groups were treated AHCC in water, water alone, or no supplementation (N = 10) for a total of 90 days followed by 30 days of observation.
Two pilot studies of 10 human patients each were conducted in women with confirmed persistent 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. The results of this research were that HR-HPV clearance was observed in-vitro and confirmed in the mouse studies. 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. They also indicated that a randomized, double-blind, placebo-controlled study was being conducted to confirm the results.
Three years later the same group of researchers published their randomized, double-blind, placebo-controlled study17 which 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. Subjects included 41 women over 30 years of age with confirmed persistent high-risk HPV infections for greater than two years. Patients were randomized to placebo once daily for 12 months (N = 25) or AHCC 3-g supplementation by mouth once daily on empty stomach for six months followed by six months of placebo (N = 25). Every three months, patients were evaluated with HPV testing as well as a blood sample collected to evaluate a panel of immune markers. At the completion of the 12-month study period, patients on the placebo arm were given the option to continue on the study to receive AHCC supplementation unblinded for six months. 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 a HPV negative status after they were off supplementation for six months. On the placebo arm, two (10.5 percent) of 19 patients were HPV negative at 12 months. In the 12 placebo arm patients who elected to continue on in the unblinded study, 50 percent (n = 6) were HPV negative after six months of AHCC supplementation. At the time of completion of the study, there were a total of 34 patients (22 blinded and 12 unblinded) who had received AHCC supplementation with an overall response rate of 58.8 percent that cleared HPV persistent infections. 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 Safety Research
Regarding AHCC safety, a safety study was conducted in which high doses (9 grams) of AHCC were given to healthy subjects in a liquid form. 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.18 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.19
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.”20 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.”21 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.
HPV is the most common sexually transmitted infection in the United States, and yet there is not any official treatment for the virus itself. In-vitro, animal and human research has demonstrated that AHCC helps promote a healthy immune response, and also helps in the elimination persistent HPV infections. To avoid fake or adulterated materials, it is important utilize AHCC products with the registered trademark.
1 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.
2 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.
3 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.
4 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.
5 Jones K. Shiitake: The Healing Mushroom. Rochester, VT: Healing Arts Press, 1995.
6 Chang R. Functional properties of edible mushrooms. Nutr Rev 1996;54(11 Pt 2):S91-3.
7 Jones K. Shiitake” A major medicinal mushroom. Alt Compl Ther 1998;4:53–9.
8 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.
9 Matsuoka H, Seo Y, Wakasugi H, et al. Lentinan potentiates immunity and prolongs survival time of some patients. Anticancer Res 1997;17:2751–6.
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 Kidd PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev 2000;5(1):4-27.
13 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.
14 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.
15 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.
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 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.
19 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.
20 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.
21 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 firstname.lastname@example.org.