NEW YORK—Activated Hexose Correlated Compound (AHCC) and Genistein Combined Polysaccharide (GCP), two immunomodulatory compounds produced by or derived from Basidiomycetes mushrooms are proving safe and effective in the treatment of a range of neoplastic, inflammatory and autoimmune disorders.
Clinical investigators, immunologists, oncologists and cell biologists gathered last month to review current data on these compounds for the treatment of bladder, breast and prostate cancer, as well as hepatitis, heart disease, asthma, and allergies. Widely used in Japan, where they were developed, AHCC and GCP are relatively new in the US. This first US conference was sponsored by the AHCC & GCP Research Association.
AHCC and Cancer
AHCC, which is derived from Basidiomycetes mycelium cultured on rice bran, is an oligosaccharide with a molecular weight of 5,000 daltons. Human trials have shown AHCC can increase natural killer (NK) cell activity by as much as 300-fold. Consequently, it was initially promoted as an anti-neoplastic agent. Since the late 1980’s, it has been routinely used in hundreds of Japanese oncology clinics as an adjunct to chemotherapy and radiation treatment for a wide variety of cancers.
“NK cells are the sentinel cells, the first line of defense against neoplastic cells, as well as bacterial and viral pathogens,” explained Fred Pescatore, MD, director of Partners in Integrative Medicine, a clinic with offices in New York City and Dallas. Dr. Pescatore has been working with AHCC for years. “NK cells are the key to removal of cancer cells, and NK activity is an important predictor of cancer progression and prognosis. Enhancing NK cell activity should be the central tenet of any immune system nutritional supplementation strategy,” he said. In Japan, AHCC is commonly used to restore normal immune system function following chemotherapy. Typically, the dose is 2,000 mg, thrice daily.
Immunosenescence and Chronic Disease
Beyond cancer care, Dr. Pescatore has found AHCC helpful for patients with a wide-range of immune system mediated disorders. He believes common conditions like diabetes, atherosclerosis, asthma, allergies, and infectious disorders like hepatitis and pneumonia are reflections of “immunosenescence,” the gradual diminution and dysregulation of immune function that occurs with aging, stress, poor diet and exposure to environmental toxins.
Immunosenescence is characterized by constantly elevated cortisol levels, low DHEA, reduced NK activity, low T cell and macrophage function, suppression of interleukin 2, and overproduction of interleukin 6 and other inflammatory cytokines. The condition is widespread in the US, said Dr. Pescatore.
In his own practice, Dr. Pescatore has been using AHCC as part of a comprehensive strategy to re-balance patients’ immune function. His strategy also includes nutritional efforts to increase omega-3 fatty acids, with the goal of creating a healthier balance between anti-inflammatory omega-3’s and pro-inflammatory omega-6 fatty acids.
He said AHCC has a solid safety profile and can be used as a long-term maintenance supplement for a variety of conditions. The recommended dose for adjunctive treatment of breast cancer and other cancers is 1,000 mg, thrice daily. He uses this dose for patients with chronic asthma and allergies, as well as sinusitis. For fibromyalgia, he increases the dose to 1,500 mg thrice daily.
Patients with cardiovascular disease may benefit from 500 mg twice daily. “It reduces oxidative damage in the vasculature and lowers oxidative stress.”
Dr. Pescatore has also found AHCC effective in managing patients with hepatitis C, but this requires high doses. “At 6,000 mg per day, it can reduce viral loads by up to 85%.” It also increases detoxification by inducing cytochrome p450 enzymes. Double-blind trials of AHCC in hepatitis patients are underway.
GCP and Urologic Cancers
GCP is produced by fermenting soy with the β-glucosidase enzyme produced by the Basidiomycetes mycelium. This enzyme breaks down soy isoflavones, which are difficult for humans to absorb, into the easily absorbed genistein aglycones that make up GCP. In cell culture studies, GCP has proven to be a powerful inducer of angiogenesis, cancer cell apoptosis, and immune cell activator.
Debra Bemis, PhD, an investigational biologist at the Department of Urology, Columbia Presbyterian Medical Center, has been studying GCP’s effects on human bladder cancer cell lines and human cancer xenografts in mice.
Her data indicate that GCP can markedly inhibit in vitro growth of bladder cancer cell lines within 72 hours. It can induce apoptosis, especially in wild-type bladder cancer lines.
Immunodeficient mice carrying human bladder cancer grafts and fed a diet containing 2% GCP showed tumor growth suppression. The difference was statistically significant for mice carrying wild-type human tumors. The compound is most effective in tumor types that express p53 cell-signalling proteins. “This distinction has significant implications for the ability of dietary GCP™ to be an effective chemopreventive agent for prostate and bladder cancers, as p53 expression is most often lost or mutated during the progression of these tumors,” she said.
The promising in vitro and animal findings have laid the groundwork for a clinical trial of GCP in treatment of bladder cancer at Columbia’s Center for Holistic Urology. Aaron Katz, MD, who heads the center, will lead the trial.
Primary superficial bladder cancers are fairly easy to treat through conventional surgical interventions and chemotherapeutic agents like mitomycin C. However, recurrence rates are high, with up to 30% of recurrent lesions invading surrounding muscle.
“Currently, there are no medical therapies proven to reduce the rate of progression, though a combination of transurethral resection of visible tumor and adjuvant intravesical chemotherapy or immunotherapy is usually effective in eradicating existing disease and decreasing recurrence rate. We are conducting this trial to determine if daily ingestion of GCP will reduce the recurrence rate of bladder cancer,” said Dr. Katz.
The Phase II trial will involve 165 patients with new or recurrent superficial bladder tumors, treated with 5 g oral GCP per day for two years. Evaluation will include cytoscopy, urine cytology, and intravenous pyelogram imaging to look for evidence of recurrence in both the lower and upper urinary tract. Biopsies will only be required when cystoscopy or cytology suggest the presence of disease recurrence.
“The 2 year incidence of recurrence following an induction course followed by a year of monthly maintenance treatments of mitomycin C is about 40%. With 165 patients we will have 80% power to detect about 15% improvement or worsening of recurrence, Dr. Katz said.
Patients who are found on follow-up to have any visible tumor, positive biopsy, positive urine cytology, or evidence of metastasis, will be released from the study and treated according to conventional medical protocols.
One of the secondary objectives of the trial will be to gather more data on the safety and tolerability of GCP. Previously published studies have shown few adverse effects. “GCP has no significant toxicities. The manufacturers report a study where 2 g/day of GCP were orally administered to 27 healthy human volunteers for 28 days. Blood tests measured at days 0, 14, and 28 found that liver enzymes, blood glucose, cholesterol, triglycerides, blood urea nitrogen, serum creatinine, and complete blood counts were all within normal limits,” said Dr. Katz.
Investigators at University of California–Davis have been studying GCP, 5 grams per day, in a cohort of 62 men with prostate cancer. Data at six months show no adverse effects beyond flatulence and diarrhea.
The UC-Davis team is assessing the effect of GCP on prostate-specific antigen levels in a cohort of 62 men with prostate cancer. The patients are taking 5 g/day of GCP for a period of 6 months. So far, there have been no alterations in clinical chemistries and only three patients discontinued therapy due to diarrhea, which resolved on discontinuation of the supplement.
“Our department’s experience with patients taking GCP orally as a daily nutritional supplement is that GCP has no significant toxicities. The most common complaint is that of flatulence,” said Dr. Katz. “Based on the experience of the group at UC Davis, we expect about 5% of our subjects to develop significant diarrhea that may require discontinuation of therapy,” said Dr. Katz.
Enrollment in the Columbia bladder cancer trial has already begun. “With approximately 15 eligible patients a month seen in our department, we can potentially recruit 165 patients within a year.”
For more information on AHCC, visit: www.ahccpublishedresearch.com.
For more on GCP, visit www.gcpresearch.com.
