Immunological benefits of Active Hexose Correlated Compound Ari Marks Department of Psychology, Beloit College Beloi

1. Abstract Active Hexose Correlated Compound (AHCC) is a nutritional supplement derived from mushrooms, which is marketed as an immune boosting pill. My hypothesis is that healthy people are unlikely to benefit from taking active hexose correlated compound. I looked at peer reviewed academic literature experimenting on the efficacy of AHCC. The studies examined preventative and suppressive effects of AHCC in immunodeficiency diseases. The consensus among the present body of research suggests that AHCC is safe, effective, and works to maintain healthy immune system functioning. Discussion The first set of studies involved mice and rat models. While not the best, they provide some insight into how the compound works in connection with immunodeficiency diseases. The evidence found clearly supportsAHCC’seffectiveness in prevention of diabetes onset, specifically with the STZ model (Wakame, 1999). AHCC’s role in the maintenance of insulin immunoreactive B-cells clearly demonstrates positive effects on the adaptive immune system. AHCC also plays a positive role in the innate immune system functioning. In vitro studies have shown that AHCC enhances natural killer (NK) cell activity (Matsui et al., 2002). NK cells attack host cells of diseases, such as tumor cells and infected cells. Whether direct or indirect, AHCC is associated with a decrease in negative side effects from toxic therapies (Cowawintaweewat et al., 2006; Matsui et al., 2002). Some scientists theorize that the up-regulation in the immune system allows macrophages to better target toxic compounds within the blood (Hirsose et al., 2007). Other theories are that the anti-tumor effects are significant enough alone to reduce the toxic secondary effects of the diseases. In human trials, AHCC has been shown to reduce toxic effects and have anti-tumor properties (Cowawintaweewat et al., 2006; Matsui et al., 2002; Sun et al., 2001). Pancreatic cancer patients treated with AHCC have also been shown to have reduced levels of c-reactive protein, suggesting an anti-inflammatory response (Spierings et al., 2007). AHCC has significantly prolonged life in cancer patients, in addition to the quality of life (Matsui et al., 2002). Ultimately, there is a significant basis to claim AHCC has some positive effects on immune system functioning. The Phase I trial examined the safety of the drug. Spierings et al. (2007) gave their healthy participants high dosage (9g/day), compared to other studies (~1-3g/day). However the LD50 in rats was found to be 8,490 mg/kg in males, and 9,849 mg/kg in females (Spierings et al., 2007), so 9g was far from dangerous. They found that AHCC is relatively safe to take, meaning that healthy users will likely not have negative repercussions. Figure 1 represents the growth of tumors in mice injected with prostate cancer cells. AHCC treated mice show less of a preventative effect, but significantly decrease the tumor size during the retreatment phase (The Sun et al., 2001). Introduction Active Hexose Correlated Compound (AHCC) is derived from the mycelia of the basidiomycete family of mushrooms. It contains polysaccharides, amino acids and minerals (Wakame, 1999). Available in liquid, it is most commonly available isolated into a pill form for oral ingestion. AHCC is an unapproved drug and is currently available in the United States as a food supplement. An estimated 25 to 50 thousand persons use AHCC daily, mostly in Japan, and a total of 300 thousand persons have taken AHCC from 1992 to 2002 (Spierings, Fujii, Sun, & Walshe, 2007). First used to lower high-blood pressure, AHCC has since been regarded as an immunomodulator (Spierings et al., 2007). Studies have been focused on the use of AHCC in tumor reduction, prevention of liver damage, reduction of the side effects of chemotherapy, and increasing life span in patients with advanced stage illnesses (Spierings et al., 2007). Method I started with commercial websites promoting AHCC that referenced articles. Then I used google scholar to branch out and search for related articles, particularly about the safety and efficacy of AHCC. Spierings et al. (2007) executed a phase I study of AHCC in healthy volunteers. Through the references of this study I found most of the important prior work studying the effects of AHCC. After analyzing the academic sources I compared the accuracy of the commercial sites.  All of the information used in this poster is from peer reviewed academic sources. Immunological benefits of Active Hexose Correlated Compound Ari MarksDepartment of Psychology, Beloit CollegeBeloit, Wisconsin Conclusion AHCC may have far reaching medical effects. The evidence here supports the claim that AHCC acts to improve innate and adaptive immune system functioning.  While AHCC may have negative side effects, phase I trials have presented the side effects as transient and tolerable. Additionally they have only been shown at levels significantly above the effective dose of AHCC. Someday AHCC, or AHCC in combination with other polysaccharides, could replace the extremely dangerous current cancer treatments such as chemotherapy. The information still missing in order to disprove my hypothesis, is whether or not daily AHCC usage can prevent disease. The results supported that AHCC has preventative effects upon the onset of disease. However. A long term study is still needed to discover any possible negative effects of long-term use in healthy subjects. Results Hirose et al. (2007) found that supplementing chemotherapy treatments with AHCC in mice was correlated to a reduction in the size and weight of cancerous tumors. The experimental mice also, compared to controls, ate more food, sustained more bone marrow, and did not suffer as much kidney damage (Hirose et al., 2007), all detrimental side effects of chemotherapy. Wakame(1999) studied AHCC’s possible role in prevention of diabetes in rats. He administered AHCC alongside Streptozotocin (STZ), a drug which induces diabetes, and analyzed blood samples and pancreatic tissue. The AHCC treated group showed stable insulin immunoreactive B-Cells compared to a drop in the STZ only group. In treated rats without AHCC, there were increases in blood glucose levels, decreases in serum insulin levels and suppression of body weight gain, along with an increase in serum GOT and GPT activity and levels of lipid peroxides. The AHCC treated rats maintained stable levels of all of these factors compared to untreated controls (Wakame, 1999). Spieringset al. (2007) looked at the effects of AHCC in twenty-six healthy participants between the ages of 18 and 61. Participants were given 9g of AHCC, administered orally, daily for 14 days. Two participants were intolerant to the liquid form and dropped out of the study. Out of the remainder of the subjects, four reported nausea, diarrhea, bloating, headache, fatigue, and foot cramps. All reports were mild and endured for one day (Spierings et al., 2007). The dose was tolerated by 85% of participants (Spierings et al., 2007). In a longitudinal cohort study, 292 patients with hepatocellular carcinoma who had part of the liver removed were given AHCC or a placebo (Matsui et al., 2002).  Matsui et al. (2002) measured the time until disease recurrence and liver function for 9 years. The AHCC group had significantly more time before a recurrence of the cancer than controls (P=0.0277) and a much higher survival rate (Matsui et al., 2002). Patients with advanced stages of liver cancer underwent a case-control study with AHCC. Those in the experimental group had a prolonged life, in addition to an increased quality of life (Cowawintaweewat et al., 2006). Quality of life was judged as mental stability, physical health, and ability to perform normal activities (Cowawintaweewat et al., 2006). Figure 2 Structural features of AHCC, specifically highlighting the active glucans(Hirsoeet al., 2007). References Cowawintaweewat, S., Manoromana, S., Sriplung, H., Khuhaprema, T., Tongtawe, P., Tapchaisri, P., & Chaicumpa, W. (2006). Prognostic improvement of patients with advanced liver cancer after active hexosecorrelated compound (AHCC) treatment. Journal of Immunotherapy, 29(6), 672.   Hirose, A., Sato, E., Fujii, H., Sun, B., Nishioka, H., & Aruoma, O. I. (2007). The influence of active hexose correlated compound (AHCC) on cisplatinevoked chemotherapeutic and side effects in tumor-bearing mice. Toxicology and applied pharmacology, 222(2), 152–158.   Matsui, Y., Uhara, J., Satoi, S., Kaibori, M., Yamada, H., Kitade, H., Imamura, A., et al. (2002). Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study. Journal of hepatology, 37(1), 78–86.   Spierings, E. L., Fujii, H., Sun, B., & Walshe, T. (2007). A phase I study of the safety of the nutritional supplement, active hexose correlated compound (AHCC) in healthy volunteers. Journal of nutritional science and vitaminology, 53(6), 536–539.   Sun, B., Mukoda, T., Miura, T., & others. (2001). Anti-tumor effects of genestein combined polysaccharide (GCP) and active hexose correlated compound (AHCC). Biotherapy (Japan), 15, 379–382.   Wakame, K. (1999). Protective effects of active hexose correlated compound (AHCC) on the onset of diabetes induced by streptozotocin in the rat. Biomedical Research (Tokyo) 20, 145–152.