AHCC and Cancer
The most aggressive and far-reaching studies involving the use of AHCC have been in the area of cancer. Since the 1990s, AHCC has been used as complementary therapy in cancer patients who are undergoing conventional therapy as an immune system booster and in the process, a way to help improve their quality of life. Because AHCC was developed and registered in Japan, the vast majority of the studies have been conducted there as well. By the end of the 1990s, AHCC was being used in about 700 medical institutions, most of which were in Japan and AHCC was already accepted and used there as a food supplement for cancer because individual cases and study results suggested it was highly beneficial. In fact, AHCC became known as the “health food for cancer.”
The good news is that the anticancer benefits of AHCC are being noticed and explored outside Japan, with studies in the United States at institutions such as Yale University in Connecticut, Drexel University in Philadelphia, Pennsylvania and Colorado State University, among others. Although much research remains to be done regarding the potential of AHCC in the prevention and treatment of cancer, there is a promising body of literature already available and we will review some of the work in this section. But first, let’s look at the
different types of cancer treatment and how AHCC differs from and fits into this scenario. Some of these studies discussed in this section have been published in journals; others have been presented at any of the International Symposium of the AHCC Research Association gatherings and/or are case reports.
Traditional Cancer Treatments
The three main conventional treatments approaches for cancer are chemotherapy, radiation therapy and surgery. All of these treatments can have a positive effect on reducing cancer, yet they also have a dramatic, detrimental impact on the immune system and the body. A fourth, up-and-coming therapy is immunotherapy, which is the category into which AHCC falls.
Chemotherapy involves the use of drugs that are toxic to both cancer cells and to normal, healthy cells. This type of cell toxicity, called cytotoxicity, affects the cells when they are dividing, which cancer cells do excessively. However, because chemotherapy also impacts healthy cells, individuals who undergo chemotherapy also experience side effects related to the damage to these cells. The cells most affected are hair root, blood and gastrointestinal tract, because all of the cells also divide rapidly. This is why chemotherapy patients typically lose their hair, experience nausea and vomiting and suffer with fatigue and increased susceptibility to infection due to damage to blood cell production. AHCC has a role to play here, as it can help alleviate symptoms associated with chemotherapy. (Read about the effect of AHCC on patients undergoing chemotherapy on page 48.)
Radiation therapy (or radiotherapy) involves the use of high-energy radiation in the form of x-rays, gamma rays and charged particles to shrink tumors and kill cancer cells. Radiation may be delivered via a machine outside the body (called external beam radiation) or from radioactive material implanted in the body (brachytherapy). Another type of radiation therapy, systemic radiation therapy, uses radioactive substances that are injected or taken by mouth and travel throughout the bloodstream to kill cancer cells. Radiation therapy kills cancer cells by destroying their DNA either directly or by creating free radicals within the cells that in turn damage the DNA.
Unfortunately, radiation therapy also damages healthy cells and in the process is responsible for a variety of side effects that depend on the area of the body treated, the dose given per day, the total dose and other factors. Some of the side effects can include hair loss, urinary problems, skin irritation, fatigue, nausea and vomiting. Although some symptoms disappear when treatment stops, others can continue or late side effects may develop after treatment has ended, such as damage to the bowels that result in bleeding and diarrhea, memory loss, infertility and fibrosis. In most cases, surgery for cancer involves removal of the tumor and some of the tissue that surrounds it. Lymph nodes are also extracted in some cases. Surgery is a major traumatic event and so has a negative impact on the immune system. Side effects associated with surgery depend mostly on the size and location of the tumor and the type of surgery performed.
Cancer Stages and Categories
Staging refers to the severity of cancer based on the extent of the original (primary) tumor and whether it has spread (metastasized) in the body. Clinicians depend on cancer staging to help them develop the most appropriate treatment for a patient, to help estimate a patient’s prognosis and to determine whether patients are eligible for specific clinical trials. Because
cancer staging utilizes standard terminology, it also allows healthcare providers and researchers to be “on the same page” in most cases when they exchange information and compare research findings. That said, there are differences within the staging system for the different types of cancer. For example, the criteria to assign the label “stage II” to a case of bladder cancer differs somewhat from a designation of stage II for a case of colon cancer. In addition, the prognosis for a given cancer stage depends on what kind of cancer is involved, so a stage II lung cancer has a different prognosis from a stage II cervical cancer. To help assign a cancer stage to a specific case of cancer, several elements are considered, including the site of the primary tumor, tumor size, number of tumors, involvement of the lymph nodes (spread of the cancer into lymph nodes), cell type, tumor grade and the presence or absence of metastasis.
Here is a basic outline of the stages of cancer.
Stage 0: Carcinoma in situ the cancer cells are present only in the layer in which they developed
Stages I–III: The higher the number, the more extensive the disease larger tumor sizes and/or spread of the cancer beyond the organ in which it first developed to nearby lymph nodes and/or organs near the primary tumor
Stage IV: The cancer has metastasized (spread to other organs and/or parts of the body)
As you might expect, identifying cancer stages is more complex than this and overall staging is further divided with classification such as IIA and IIB. Depending on the type of cancer, the difference in prognosis between a stage IIA and stage IIB may be very significant. Therefore, patients need to get a thorough explanation from their healthcare providers about the stage of cancer that pertains to them. Another factor that goes along with staging is tumor grade. Tumor grade is a system used to classify cancer cells in terms of how abnormal they appear under a microscope and how quickly the tumor is expected to grow and spread. The factors used to determine tumor grade are different for each type of cancer.
Cancer is also classified by category, a system that allows clinicians and researchers to use a uniform system when describing cancer and exchanging information. Those categories are:
In situ: Abnormal cells are found only in the layer of cells in which they developed
Localized: Cancer cells are present only in the organ in which they first appeared, with no evidence of spread Regional: Cancer has spread beyond the primary site to nearby lymph nodes or organs and tissues
Distant: Cancer has spread from the primary site to distant organs or distant lymph nodes
Unknown: There is not enough information to identify the stage of cancer
Immunotherapy, BRMs and AHCC
Conventional medicine has recently added another cancer treatment modality to the mix: immunotherapy. Immunotherapy is a nontoxic method of cancer treatment that utilizes certain parts of the immune system to fight cancer or to reduce the side effects that are associated with treatment. These goals can be accomplished by stimulating the body’s immune system to work harder or smarter or by taking synthetic immune system proteins or other components, known collectively as biological response modifiers (BRMs). Although immunotherapy is sometimes used alone to treat cancer, in most cases it is combined with chemotherapy or radiation therapy to enhance its effects.
In conventional medicine, some antibodies, cytokines, vaccines and other immune system substances are synthesized in the lab to be used in cancer treatment. These BRMs change how the body’s immune defenses interact with cancer cells in an attempt to enhance or restore the body’s ability to fight the disease.
Does this sound familiar? If so, then you probably already know that AHCC is a biological response modifier. In fact, in Japan AHCC is widely considered to be the strongest known immune system strengthening BRM and it is often used alongside conventional cancer treatments. When clinicians are able to halt the development of cancer using immunotherapy, a “truce” has been established between the cancer and the immune system. The cancer is dormant, and as long as the patient can maintain this state of truce, it is possible to postpone future treatment. Following are two examples of studies that explored the impact AHCC can have on the immune systems of cancer patients.
Example One: The study was conducted at the Seoul Internal Medicine Clinic, Cancer Diagnostic Center by Dr. Jang Seok Won and included 12 cancer patients: four with stomach cancer, three with colorectal cancer, two with lung cancer and one each with breast cancer, ovarian cancer or melanoma. Won evaluated the effect of AHCC on a variety of components, including lymphocytes and NK cells, as well as various blood elements. All the patients received three to six grams of AHCC daily for three months in addition to their conventional treatment of radiotherapy or chemotherapy and they were then followed up at three, six and nine months.
Overall, Won noted the following:
• There was no significant change in white blood cell count, hemoglobin and other blood factors that would indicate a worsening of immune function, even though the patients were undergoing radiation or chemotherapy. This finding suggests AHCC can be helpful in preventing depression of bone marrow from cancer treatment.
• There was a slight increase or no change in peripheral blood lymphocytes. This was a positive sign, as lymphocyte levels tend to decrease as cancer progresses.
• The percentage of NK cells, which are important for eliminating tumor cells, increased by 21 percent after three months and was still at 20 percent six months after treatment.
Overall, AHCC appeared to be a safe and effective BRM for these cancer patients and may be helpful in preventing bone marrow depression associated with chemotherapy.
Example Two: The effects of AHCC were examined in 11 patients who had advanced cancer: three patients each with prostate, breast or ovarian cancer and two who had multiple myeloma. All the patients were treated with conventional therapies. In addition, all were administered three grams daily of AHCC. After two weeks, the researchers observed a 2.5-fold increase in the level of NK cell activity in nine of the 11 patients and the increased activity was maintained at a high level over time. They also observed a decline in PSA (prostate specific antigen) in the three prostate cancer patients. (PSA is an indicator of malignancy in prostate cancer.) Two of the three breast cancer patients showed a significant decline in the level of CA125 (cancer antigen 125), which is an antigen and a marker for this type of cancer. The rapid decrease in CA125 occurred after taking AHCC for one month and continued to decline until it reached normal values three to four months after treatment with AHCC.
The study’s authors, who published their findings in the International Journal of Immunotherapy, also examined the impact of AHCC on tumor cell growth in two different tumor cell lines: K562 (a leukemia cell line) and Raji (a Burkitt’s cell lymphoma). They found that AHCC suppressed the growth of both cell lines, with a higher concentration of AHCC (one mg/mL) providing the most effect when compared with a lower one. Overall, a one mg/mL concentration of AHCC resulted in a 21 percent reduction in the leukemia- like cell line and a 43 percent decline in the lymphoma cell line. Although the study populations in the above two studies were small, their findings suggest AHCC offers some potent anticancer activity and thus has a place in the treatment of patients who have cancer.
AHCC and Immune Surveillance
A healthy immune system performs a function called immune surveillance, in which it uncovers the presence of cancer cells and tumors throughout the body. This surveillance function is critical because cancer cells have an ability to hide, thus avoiding detection by the immune system. Restoring immune surveillance means that tumor cells can be “unmasked,” which then allows the immune system to once again detect and destroy them. White blood cells and the interferon they release are necessary for the immune system to “sniff out” and unmask cancer cells and tumors and so researchers set out to determine how AHCC may be helpful in this effort. Researchers at Yale University and Amino Up Chemical Co., Ltd. explored the effect of AHCC on immune surveillance by administering the supplement to test animals. AHCC significantly delayed the formation of melanoma and reduced tumor size. Specifically, AHCC significantly increased levels of tumor antigen-specific immune cells and their ability to produce gamma interferon and also increased the numbers of NK cells. The authors of the study concluded that their results demonstrated that AHCC can enhance tumor immune surveillance through regulating both humoral and cell-mediated responses.
AHCC’s Other Anticancer Activities
While traditional cancer treatments destroy both cancerous and healthy cells, AHCC focuses solely on the latter. That is, rather than kill cancer cells directly, AHCC strengthens and stimulates the healthy immune cells lymphocytes, natural killer cells, macrophages and other immune compounds whose job is to attack and/or destroy cancer cells. AHCC also improves the body’s inherent immunity. AHCC can be a powerful healing force for people who have cancer.
Scores of research studies and individual case reports have illustrated the benefits associated with AHCC in patients who have cancer. Because AHCC strengthens the function of the immune system, it can be appropriate for addressing cancer that affects any part of the body. A review of the available research shows that more than 100,000 cancer patients with different types of cancer have been treated with AHCC. Results indicate that the supplement has been effective in people who have breast, colon, kidney, liver, lung, ovarian, pancreatic, stomach, testicular and tongue cancers. It appears AHCC may have an impact on cancer cells wherever they are in the body.
Overall, 60 percent of cancer patients who use AHCC along with cancer treatment have reportedly derived some benefit from the supplement. Some individuals have had a reduction in tumor mass while in others the tumor stopped growing, the cancer stopped spreading to other parts of the body, survival time increased and, in most cases, they experienced an improvement in their quality of life. For some patients, AHCC has reportedly been effective enough to induce remission from their disease. It is important to emphasize that AHCC is used in addition to conventional cancer treatment; that is, AHCC does not replace chemotherapy, radiation therapy and/or surgery or even other immunotherapies. Doctors in Japan typically use AHCC along with mainstream cancer treatments and it is gradually gaining acceptance in other countries throughout Asia and in the United States.
AHCC and Survival from Cancer
Some studies have examined the effect of AHCC on cancer survival, including patients who are in advanced stages of the disease. For example, a total of 195 patients who were in the last stages of various cancers (e.g., gastric, colon, liver, pancreatic, lung, breast and ovarian) were given six grams of AHCC daily for six months. The patients also took other immune stimulants. The investigators monitored levels of various immune system components during the study period, including NK cells and Th1 cytokine production (e.g., interferongamma, IL-12). The scientists observed a significant increase in NK cell activity and in the production of interferon-gamma and IL-12, all of which support optimal immune system functioning.
Dr. Katsuaki Uno, managing director of Comfort Hospital and the head of the previously mentioned study, reported that 114 people experienced a partial or complete recovery after starting AHCC treatment. Forty percent (81 patients) experienced no change or had progression of their disease. Although researchers often cite the immune-stimulating properties
of AHCC as the reason for their helping to prolong survival from cancer, AHCC’s anti-inflammatory and anti-stress properties have also been studied for this purpose. In the studies discussed in the following sections, you will see examples of how AHCC is associated with an improvement in quality of life and survival in cancer patients, including those with final stage or advanced disease.
AHCC and Cancer Studies
In addition to the results of other cancer studies we have already covered, several other studies have focused on one specific type of cancer and reported on the impact of AHCC in the treatment of these patients. Therefore the following cancer studies are examples of the types of research that has been done in cancer patients who included AHCC as part of their regimen for liver, gastrointestinal and breast cancer.
Liver Cancer and AHCC
Many of the cancer studies and case reports done so far have involved the use of AHCC in patients who have liver cancer. According to the World Health Organization (WHO), liver cancer is the fourth leading cause of death due to cancer (following behind lung, stomach and colorectal cancers) in the world. The American Cancer Society estimated that 24,120 adults in the United States would be diagnosed with primary liver cancer and that nearly 19,000 people would die of the disease in 2010. Liver cancer is the fifth most common cause of cancer death among men in the United States and the ninth most common among women.
Given these statistics, one would expect that the five-year relative survival rate associated with liver cancer would be poor and it is: at about 10 percent when all stages of liver cancer are considered (i.e., localized, regional and metastatic). One reason for this low survival rate is that most patients who have liver cancer also have other liver problems such as cirrhosis (scarring of the liver), which can be fatal. In patients who have small, resectable tumors (tumors that can be removed by surgery) and who do not have other liver problems, however, five-year survival can be more than 50 percent.
Generally, however, survival is poor and this is why any improvement in survival associated with the use of AHCC in liver cancer patients is especially noteworthy. Even though liver resection (surgical removal) is the most effective treatment for liver cancer, many patients are diagnosed in the late stages of the disease, when surgery would not be effective. At that point, the most commonly used treatment option is chemotherapy. However, some clinicians are also turning to BRMs and that is where AHCC can enter the picture. Two examples of AHCC’s impact on liver cancer patients and survival are illustrated here.
Example One: The Journal of Hepatology published the results of a prospective study that covered a time span of nearly a decade, from February 1, 1992 to December 31, 2001. A total of 269 patients who had hepatocellular carcinoma were evaluated in the study. Hepatocellular carcinoma is the most common type of liver cancer and it is usually caused by cirrhosis, which can be the result of alcohol abuse, certain autoimmune diseases of the liver, hepatitis B or C, excess iron in the body (hemochromatosis) or diseases that cause long term inflammation of the liver.
All of the patients underwent resection of the liver tumor, which is a surgical procedure to remove the affected portion of the liver. AHCC supplementation was assigned to 113 patients after surgery. The investigators noted a significantly higher overall survival rate (14 percent) among patients who took AHCC when compared with the control patients. In addition, the recurrence of cancer was significantly lower (49 percent) among the AHCC patients compared with controls (67 percent).
The mechanisms responsible for the benefits observed in the patients who took AHCC were not explored in this study. Therefore, while the authors note that AHCC intake improved liver function, reduced recurrence of liver cancer after resection and prolonged five-year survival, further research is necessary to both confirm their findings and identify the reasons behind them.
Example Two: A subsequent study was conducted in Thailand and included 44 patients with advanced liver cancer and unresectable (inoperable) tumors. All of the patients were randomly assigned to receive either AHCC (six grams daily) or a placebo until the end of their lives.
The investigators examined the patients’ clinical parameters monthly or as specified to determine quality of life and various blood, biochemical and immunological parameters, such as gamma interferon and interleukin-12 levels. Magnetic resonance imaging (MRI) was performed on patients who survived longer than one year.
By week six of the study period, five (50 percent) of the patients in the placebo group had died, while all the patients in the AHCC group were alive. The follow-up period ranged from six weeks to 24 months in the AHCC group and from two weeks to 3.5 months in the control group. Overall, the median survival time was 3.5 months in the AHCC-treated patients and 1.5 months in the control patients. The investigators also noted that the percentage of lymphocytes did not decline as rapidly after AHCC treatment when compared with controls. This suggested that AHCC provided some immune system benefits for these patients in their final months. Plasma levels of IL-12 showed a slight increase in the AHCC treated patients, but it was not significant. The authors noted that their findings suggest AHCC helps to prolong the lives of patients who have advanced liver cancer. As in the previous study, the authors did not explore the mechanisms responsible for these benefits.
Cancers of the gastrointestinal system include esophageal cancer, stomach cancer (also known as gastric cancer), colorectal cancer and anal cancer. According to the National Cancer Institute, approximately 142,570 people were diagnosed with colorectal cancer in 2010 in the United States. National Cancer Center estimates for other gastrointestinal cancers include 21,000 people diagnosed with stomach cancer, 5,260 with anal cancer and 16,640 with esophageal cancer.
Dr. Yusai Kawaguchi of the Kansai Medical University Department of Surgery in Osaka, Japan, treated two groups of cancer patients with AHCC. One group included 132 individuals with stomach cancer who took AHCC following their surgeries. Patients who had stages I–II cancer were given three grams daily of AHCC while those who had stage IV cancer took six grams per day. Patients who had stages II–IV also were taking low-dose chemotherapy. A second group consisted of 113 patients with colon cancer. Individuals with stage I–II cancer were given three grams of AHCC daily while those with stages II–IV took six grams daily.
When the investigators compared the five-year cumulative survival rates from their two study groups with those of other institutions where AHCC was not administered, they found that in patients with stomach cancer, survival rates were superior in patients with stage I to stage IIA cancers. (Stage II stomach cancer can be classified as IIA and IIB and stage IIA has a better prognosis than does stage IIB cancer.) Among colon cancer patients with stage II and stage IIA cancer in the study, five-year cumulative survival rates were superior to those at other institutions where AHCC was not given.
Kawaguchi and his team noted that overall, use of AHCC in patients with stomach cancer and colon cancer resulted in an improvement in cumulative survival rates in some stages of cancer. These findings suggest AHCC can be beneficial as a complementary treatment for patients who have these types of cancer.
In addition to all the studies we have mentioned already, there are many other individual case reports from different doctors and their experiences with patients who had pancreatic, brain, ovarian, lung, stomach, breast and other cancers and whom they treated with AHCC along with conventional treatment. Virtually without exception, the patients treated by these doctors seemed to benefit in some way from their treatment with AHCC, with an improvement in quality of life and/or pain relief being the most common advantages of taking AHCC. In some cases, patients reportedly defied their cancer and lived on for years after doctors had given up hope and beyond when conventional medicine said they would pass on. It is important to remember, however, that AHCC is not a cure for cancer and that its place is alongside conventional treatment for cancer, as a potent immunotherapy that may provide patients with a stronger immune system and a better quality of life.
AHCC is frequently administered to patients who have cancer to strengthen, enhance and boost the immune system response, which often has the effect of improving quality of life and improving survival rates. There have been reports of patients with advanced cancer whose disease appeared to vanish after they began treatment with AHCC as a complement to conventional therapy. Any definitive relationship between use of AHCC and the disappearance of cancer in any given patient has not been determined.