Human Clinical Studies

AHCC supplementation resulted in the following observations: • All patients tolerated AHCC with no added symptoms • 20 patients reported feeling better and stronger than before at the time of initiation of chemotherapy cycles • Almost all patients reported better appetites after they started to take AHCC • In 12 patients who required blood transfusions before chemotherapy cycles, a decrease in the rate of fall of hemoglobin was observed and only 3 patients subsequently required blood transfusions prior to chemotherapy • 22 patients has a reduction of chemotherapy side effects like nausea, vomiting, loose motion/ constipation, etc. • Tumors regressed in 11 patients • 8 patients stabilized

The AHCC group had the following significant differences compared with control group: • Longer non-recurrence period • Increased overall survival rate

The self-administration of AHCC resulted in a dramatic PSA decrease within 1 month, which continued to control his disease for over 6 months from initial supplementation with AHCC.

Using the national breast cancer patient registration as reference data, this retrospective study reported the improved prognosis of stage IV patients relative to the national average. Since the stage I-III patients at the center all had recurring cancer while the national average includes both recurring and non-recurring cancers, a meaningful comparison could not be made and the results were not statistically significant.

The following results were reported for patients supplemented with AHCC when compared with control group: • A significantly prolonged survival • Quality of life in terms of mental stability, general physical health status and the ability to have normal activities were significantly improved after 3 months of supplementation • Serum level of albumin and percentage of lymphocytes in blood, were significantly higher • Slightly increased levels of total IL-12 and neopterin

AHCC supplementation resulted in the following changes: • Changes in PSA before and after treatment were substantially stable • In patients for which expectant management had been continued for 6 months or more before the trial, a prolonged PSA doubling time (PSADT) was seen with AHCC administration – Prior to AHCC, 12/31 (39%) of patients had PSADT of 120 months or more, and after 6 months of AHCC administration, 17/31 (55%) had PSADT of 120 months or more. To the lower end, 12/31 (39%) of patients showed a PSADT less than 24 months, and following 6 months of AHCC, this fell to 9/31 (29%).

AHCC supplementation resulted in the following changes compared with the control group: • The hemoglobin (Hb) level after chemotherapy in AHCC group was significantly higher • The taste alteration after chemotherapy in AHCC group was significantly lower

AHCC supplementation resulted in the following difference in survival rate: • Improved cumulative 5-year survival rates for patients with gastric cancer (stage IA to stage IIIA) compared with other Japanese institutions • Improved cumulative 5-year survival rates for patients with colon cancer (stage II to stage IIIA) compared with other Japanese institutions

Supplementation with AHCC had the following results: • A significant decline in TAA occurred in 8 out of the 11 patients with different types of malignancies • PSA levels in prostate cancer patients and CA 125 levels in ovarian cancer patients decreased as early as 1 to 2 months and reached normal levels within 1 to 4 months • 9 out of 11 patients demonstrated marked increase in NK activity as early as 2 weeks after treatment • The percentages of patients with complete remission were as follows: (i) prostatic (66%); (ii) ovarian (66%). (iii) multiple myeloma (50%); (iv) breast, 33% complete remission and 2 partial • In vitro studies showed that AHCC possesses suppressive effects on tumor cell growth

Compared against the survival rates in American Society of Clinical Oncology (ASCO) reference data, this retrospective study reported the following observations: • 1-year, 2 year and 3-year survival rates for stage IV lung cancer increased to 77.1%, 54.3% and 31.4%, respectively • Improvement of 1-year to 3-year survival rates and prolongation of median survival time (MST) for lung cancer stage IV • QOL scores of 35 cases were rated A to C by 77.2% of patients, which contributed to reducing final hospitalization time •Survival terms for breast cancer patients for 3 years, 4 years and 5 years were 65.6%, 43.8% and 28.1%, respectively • Mean survival terms for breast cancer patients were 5 years, 2 months after recurrence and 7 years, 11 months after initial diagnosis • Extension of survival terms was confirmed • QOL scores on living cases reported a score of A or B (100%), and scores for those who did not survive were A-B (50%) and C (50%)

Health and functional foods are used by progressive cancer patients who hope increased survival time regardless of ambiguous information that includes phrases used to describe these foods, such as "might be effective against cancer." However, we fear that non evidence-based foods might shorten the lifetime of patients, whose life has already been shortened by cancer. Although our data is retrospective, AHCC does not increase the risk of shortening the lifetime of cancer patients, at least in the case of hepatocellular carcinoma. Clinical doctors should neither deny alternative medicine without studying, nor accept alternative medicine easily without critical investigation. Based on scientific, rational data, alternative medicine should be applied.

Group A was given 1-3g/day of modified arabinoxylane with meals. Group B was given 6000 mg/day of coriolus mushroom. Group C was given 4g/day of antigen-infused dialyzable bovine colostrum/whey extract and Group D was given 3-6g/day of active hexose correlated compound (AHCC). NK cell activities were assessed before treatment and after an average of 16 weeks of therapy. AHCC was the only supplement that consistently and statistically increased NK cell activity. The average increase was 249%.

In a study of the beneficial effects of AHCC supplementation on the alleviation of adverse events in female breast cancer patients receiving chemotherapy, the results found that those receiving AHCC experienced fewer side-effects, most notably related to neutrophils. Neutrophils make up 50%-75% of white blood cells and are the first immune cells to respond to and arrive at the site of infection. Chemotherapy frequently causes a drastic drop neutrophils (a condition called neutropenia), putting the patient at a greater risk of infection. Patients also to wait for their neutrophil levels to recover before proceeding to their next cycle of chemotherapy which prolongs the length of treatment. So the ability to maintain healthy neutrophil levels not only reduces the risk of infections but also enables women to get through their treatment faster. This is why this latest study showing that AHCC, a natural compound with an excellent safety profile, can help maintain healthy neutrophil levels is very significant. The researchers at the University of Tokyo retrospectively analyzed 41 consecutive adult patients who underwent adjuvant chemotherapy to see how many of them had to undergo injections of “G-CSF” which are used to stimulate bone marrow production but also entail a number of potential side-effects affecting an estimated 30% of users. They found that those taking AHCC had significantly lower use of G-CSF drugs than those without the supplement, indicating that AHCC helped the patients maintain normal neutrophil levels without having to use these side-effect inducing drugs.

AHCC supplementation resulted in the following changes compared with the status before intake: • Significant improvement in NK cell activity • Significant improvement in IFN-γ and IL-2 production • Significant improvement in PS evaluation

AHCC supplementation resulted in the following changes compared with baseline: • The ratio of NK cells to total lymphocytes increased from 21.67% before taking AHCC to 26.21% and 26.0% 3 to 6 months after taking AHCC, respectively • There was no change in white blood cells, hemoglobin, hematocrit and thrombocyte numbers after taking AHCC, even though patients were undergoing radiotherapy or chemotherapy • No adverse effects were observed

AHCC supplementation resulted in the following changes: • Significant enhancement of NK activity against K562 as early as 2 weeks, two- to threefold increase compared with base line • Activity was further increased at subsequent time periods up to 6 months post-treatment with AHCC • NK activation was also detected against Raji cells, but at later stages 1-2 months with two- to ten fold increase compared with base line

AHCC supplementation resulted in the following changes: • Improved hematologic toxicity (neutropenia) and hepatotoxicity • A decreased tendency of QLQ-C30 fatigue scale • A decrease in levels of HHV-6 in saliva by AHCC Administration

AHCC supplementation resulted in the following changes: • 1 g AHCC significantly decreased AST, ALT and γ-GT values • 3 g AHCC significantly decreased AST, ALT and γ-GT values except the 4-week γ-GT • AHCC supplementation had a more dramatic effect on immune cell phenotypes after vaccination of subjects over 60 years old

AHCC supplementation resulted in the following changes: •Although no significant reduction of HCV RNA levels was noticed in AHCC group patients compared with those of placebo group, subgroup analysis of genotype-3 had a significant HCV RNA decline • Although the reduction of ALT levels within AHCC group was not significant, a significant difference was found between AHCC and placebo groups • AHCC group ALT levels were stable, while ALT levels increased in placebo group. Such difference was initially noted within the first 6 weeks of the study.

AHCC supplementation resulted in the following significant changes compared with base line: • The frequency of CD4+ and CD8 + T cells producing IFN-γ alone, TNF-α alone or both increased during AHCC intake • The frequency of such cells remained high even 30 days after discontinuing AHCC

Giving nutritional supplements before flu shots boosts immunity and makes the vaccine more effective. The mushroom extract Active hexose correlated compound (AHCC) improved survival in studies of mice given a flu virus. Also when AHCC was given to mice before getting a flu vaccine they had improved survival from the bird flu virus compared to mice that only had the vaccine. It is thought that AHCC will improve protection against getting the flu when given around the same time as receiving a flu shot. A well designed study was performed with 30 healthy adults to see if AHCC supplementation could improve protection against the flu if also flu shots were given. This was during the 2009-2010 flu season. Blood was drawn from patients before vaccination and then 1 week after. Immediately after the flu shot, the AHCC group took 3 grams per day of AHCC. The analysis of white blood cells in these subjects after vaccination showed that AHCC supplementation increased the natural killer cells and T cell types of white blood cells when compared to the group who didn't receive AHCC. Antibody levels against the influenza B virus were also higher in the AHCC group 3 weeks after being given the shot. The AHCC supplementation group had better immunity with greater levels of white blood cells and antibodies against the flu virus compared to the control group.

Volunteers supplemented with AHCC had the following significant changes: • Greater number of total DCs than at base line and compared with control • The number of DC1 cells was greater after AHCC intake than at base line and the AHCC group had a tendency to have higher DC1s than control • DC2s were significantly increased after 4 weeks compared with control • The allo-stimulatory activity of DC1s was also increased after intake compared with control as measured by the mixed lymphocyte reaction (MLR)

Laboratory results and adverse events were reported as follows: • Two subjects (7%) dropped out because of nausea and intolerance of the liquid • Nausea, diarrhea, bloating, headache, fatigue and foot cramps occurred in a total of 6 subjects (20%) but were mild and transient • There were no laboratory abnormalities

AHCC supplementation resulted in the following observations: • All patients tolerated AHCC with no added symptoms • 20 patients reported feeling better and stronger than before at the time of initiation of chemotherapy cycles • Almost all patients reported better appetites after they started to take AHCC • In 12 patients who required blood transfusions before chemotherapy cycles, a decrease in the rate of fall of hemoglobin was observed and only 3 patients subsequently required blood transfusions prior to chemotherapy • 22 patients has a reduction of chemotherapy side effects like nausea, vomiting, loose motion/ constipation, etc. • Tumors regressed in 11 patients • 8 patients stabilized

The AHCC group had the following significant differences compared with control group: • Longer non-recurrence period • Increased overall survival rate

The self-administration of AHCC resulted in a dramatic PSA decrease within 1 month, which continued to control his disease for over 6 months from initial supplementation with AHCC.

Using the national breast cancer patient registration as reference data, this retrospective study reported the improved prognosis of stage IV patients relative to the national average. Since the stage I-III patients at the center all had recurring cancer while the national average includes both recurring and non-recurring cancers, a meaningful comparison could not be made and the results were not statistically significant.

The following results were reported for patients supplemented with AHCC when compared with control group: • A significantly prolonged survival • Quality of life in terms of mental stability, general physical health status and the ability to have normal activities were significantly improved after 3 months of supplementation • Serum level of albumin and percentage of lymphocytes in blood, were significantly higher • Slightly increased levels of total IL-12 and neopterin

AHCC supplementation resulted in the following changes: • Changes in PSA before and after treatment were substantially stable • In patients for which expectant management had been continued for 6 months or more before the trial, a prolonged PSA doubling time (PSADT) was seen with AHCC administration – Prior to AHCC, 12/31 (39%) of patients had PSADT of 120 months or more, and after 6 months of AHCC administration, 17/31 (55%) had PSADT of 120 months or more. To the lower end, 12/31 (39%) of patients showed a PSADT less than 24 months, and following 6 months of AHCC, this fell to 9/31 (29%).

AHCC supplementation resulted in the following changes compared with the control group: • The hemoglobin (Hb) level after chemotherapy in AHCC group was significantly higher • The taste alteration after chemotherapy in AHCC group was significantly lower

AHCC supplementation resulted in the following difference in survival rate: • Improved cumulative 5-year survival rates for patients with gastric cancer (stage IA to stage IIIA) compared with other Japanese institutions • Improved cumulative 5-year survival rates for patients with colon cancer (stage II to stage IIIA) compared with other Japanese institutions

Supplementation with AHCC had the following results: • A significant decline in TAA occurred in 8 out of the 11 patients with different types of malignancies • PSA levels in prostate cancer patients and CA 125 levels in ovarian cancer patients decreased as early as 1 to 2 months and reached normal levels within 1 to 4 months • 9 out of 11 patients demonstrated marked increase in NK activity as early as 2 weeks after treatment • The percentages of patients with complete remission were as follows: (i) prostatic (66%); (ii) ovarian (66%). (iii) multiple myeloma (50%); (iv) breast, 33% complete remission and 2 partial • In vitro studies showed that AHCC possesses suppressive effects on tumor cell growth

Compared against the survival rates in American Society of Clinical Oncology (ASCO) reference data, this retrospective study reported the following observations: • 1-year, 2 year and 3-year survival rates for stage IV lung cancer increased to 77.1%, 54.3% and 31.4%, respectively • Improvement of 1-year to 3-year survival rates and prolongation of median survival time (MST) for lung cancer stage IV • QOL scores of 35 cases were rated A to C by 77.2% of patients, which contributed to reducing final hospitalization time •Survival terms for breast cancer patients for 3 years, 4 years and 5 years were 65.6%, 43.8% and 28.1%, respectively • Mean survival terms for breast cancer patients were 5 years, 2 months after recurrence and 7 years, 11 months after initial diagnosis • Extension of survival terms was confirmed • QOL scores on living cases reported a score of A or B (100%), and scores for those who did not survive were A-B (50%) and C (50%)

Health and functional foods are used by progressive cancer patients who hope increased survival time regardless of ambiguous information that includes phrases used to describe these foods, such as "might be effective against cancer." However, we fear that non evidence-based foods might shorten the lifetime of patients, whose life has already been shortened by cancer. Although our data is retrospective, AHCC does not increase the risk of shortening the lifetime of cancer patients, at least in the case of hepatocellular carcinoma. Clinical doctors should neither deny alternative medicine without studying, nor accept alternative medicine easily without critical investigation. Based on scientific, rational data, alternative medicine should be applied.

Group A was given 1-3g/day of modified arabinoxylane with meals. Group B was given 6000 mg/day of coriolus mushroom. Group C was given 4g/day of antigen-infused dialyzable bovine colostrum/whey extract and Group D was given 3-6g/day of active hexose correlated compound (AHCC). NK cell activities were assessed before treatment and after an average of 16 weeks of therapy. AHCC was the only supplement that consistently and statistically increased NK cell activity. The average increase was 249%.

In a study of the beneficial effects of AHCC supplementation on the alleviation of adverse events in female breast cancer patients receiving chemotherapy, the results found that those receiving AHCC experienced fewer side-effects, most notably related to neutrophils. Neutrophils make up 50%-75% of white blood cells and are the first immune cells to respond to and arrive at the site of infection. Chemotherapy frequently causes a drastic drop neutrophils (a condition called neutropenia), putting the patient at a greater risk of infection. Patients also to wait for their neutrophil levels to recover before proceeding to their next cycle of chemotherapy which prolongs the length of treatment. So the ability to maintain healthy neutrophil levels not only reduces the risk of infections but also enables women to get through their treatment faster. This is why this latest study showing that AHCC, a natural compound with an excellent safety profile, can help maintain healthy neutrophil levels is very significant. The researchers at the University of Tokyo retrospectively analyzed 41 consecutive adult patients who underwent adjuvant chemotherapy to see how many of them had to undergo injections of “G-CSF” which are used to stimulate bone marrow production but also entail a number of potential side-effects affecting an estimated 30% of users. They found that those taking AHCC had significantly lower use of G-CSF drugs than those without the supplement, indicating that AHCC helped the patients maintain normal neutrophil levels without having to use these side-effect inducing drugs.

AHCC supplementation resulted in the following changes compared with the status before intake: • Significant improvement in NK cell activity • Significant improvement in IFN-γ and IL-2 production • Significant improvement in PS evaluation

AHCC supplementation resulted in the following changes compared with baseline: • The ratio of NK cells to total lymphocytes increased from 21.67% before taking AHCC to 26.21% and 26.0% 3 to 6 months after taking AHCC, respectively • There was no change in white blood cells, hemoglobin, hematocrit and thrombocyte numbers after taking AHCC, even though patients were undergoing radiotherapy or chemotherapy • No adverse effects were observed

AHCC supplementation resulted in the following changes: • Significant enhancement of NK activity against K562 as early as 2 weeks, two- to threefold increase compared with base line • Activity was further increased at subsequent time periods up to 6 months post-treatment with AHCC • NK activation was also detected against Raji cells, but at later stages 1-2 months with two- to ten fold increase compared with base line

AHCC supplementation resulted in the following changes: • Improved hematologic toxicity (neutropenia) and hepatotoxicity • A decreased tendency of QLQ-C30 fatigue scale • A decrease in levels of HHV-6 in saliva by AHCC Administration

AHCC supplementation resulted in the following changes: • 1 g AHCC significantly decreased AST, ALT and γ-GT values • 3 g AHCC significantly decreased AST, ALT and γ-GT values except the 4-week γ-GT • AHCC supplementation had a more dramatic effect on immune cell phenotypes after vaccination of subjects over 60 years old

AHCC supplementation resulted in the following changes: •Although no significant reduction of HCV RNA levels was noticed in AHCC group patients compared with those of placebo group, subgroup analysis of genotype-3 had a significant HCV RNA decline • Although the reduction of ALT levels within AHCC group was not significant, a significant difference was found between AHCC and placebo groups • AHCC group ALT levels were stable, while ALT levels increased in placebo group. Such difference was initially noted within the first 6 weeks of the study.

AHCC supplementation resulted in the following significant changes compared with base line: • The frequency of CD4+ and CD8 + T cells producing IFN-γ alone, TNF-α alone or both increased during AHCC intake • The frequency of such cells remained high even 30 days after discontinuing AHCC

Giving nutritional supplements before flu shots boosts immunity and makes the vaccine more effective. The mushroom extract Active hexose correlated compound (AHCC) improved survival in studies of mice given a flu virus. Also when AHCC was given to mice before getting a flu vaccine they had improved survival from the bird flu virus compared to mice that only had the vaccine. It is thought that AHCC will improve protection against getting the flu when given around the same time as receiving a flu shot. A well designed study was performed with 30 healthy adults to see if AHCC supplementation could improve protection against the flu if also flu shots were given. This was during the 2009-2010 flu season. Blood was drawn from patients before vaccination and then 1 week after. Immediately after the flu shot, the AHCC group took 3 grams per day of AHCC. The analysis of white blood cells in these subjects after vaccination showed that AHCC supplementation increased the natural killer cells and T cell types of white blood cells when compared to the group who didn't receive AHCC. Antibody levels against the influenza B virus were also higher in the AHCC group 3 weeks after being given the shot. The AHCC supplementation group had better immunity with greater levels of white blood cells and antibodies against the flu virus compared to the control group.

Volunteers supplemented with AHCC had the following significant changes: • Greater number of total DCs than at base line and compared with control • The number of DC1 cells was greater after AHCC intake than at base line and the AHCC group had a tendency to have higher DC1s than control • DC2s were significantly increased after 4 weeks compared with control • The allo-stimulatory activity of DC1s was also increased after intake compared with control as measured by the mixed lymphocyte reaction (MLR)

Laboratory results and adverse events were reported as follows: • Two subjects (7%) dropped out because of nausea and intolerance of the liquid • Nausea, diarrhea, bloating, headache, fatigue and foot cramps occurred in a total of 6 subjects (20%) but were mild and transient • There were no laboratory abnormalities