AHCC®: What the Research Says

There is extensive research behind AHCC, from cancer trials to diabetes support. Read about the studies that have promoted AHCC as a leading extract for immunity.

AHCC: What the Research Says

The mushroom-derived extract, AHCC, is praised for its abundant wellness benefits. Over the years, it has accumulated an impressive amount of clinical research to examine its role in human health. The data on AHCC strongly reflects its ability to enhance the immune system and promote a better quality of life. From cancer patients to diabetics, the findings of AHCC clinical studies consistently report improvements in people’s health and well-being.

Background

AHCC was discovered in Japan by Dr. Toshihiko Okoamoto and the Amino Up Chemical Co., LTD. in 1981. AHCC originates from the shiitake mushroom, which is native to Japan. It includes other derivatives of the species Basidiomycetes. The active compounds in AHCC are beta and alpha-glucans, which are known to improve cholesterol levels and promote heart health. In fact, AHCC was introduced to the medical market as a solution for high blood pressure. Since then, research has focused on how AHCC affects the immune system.

An Immune System Primer

When it comes to wellness concerns, a healthy immune system is a driving factor of health. The immune system is our body’s defense response. Its job is to protect you from harm. It does this by scanning for pathogens that have made their way into your body and could disrupt healthy functions. Pathogens include bacteria, viruses, toxins, parasites, and other foreign bodies that can cause harm. The immune system also looks to see if any of our cells have mutated and become abnormal.

Our immune system can be divided into two categories: Innate and adaptive.

Innate immunity: Reacts immediately to any threat in a generalized manner. It attacks all types of threats with nonspecific defense mechanisms to get a head start on the fight.

Adaptive immunity: Does not react immediately but analyzes the specific threat and responds in a precise manner to defend against a particular microbe.

There are a variety of unique immune cells that carry out specific jobs in both our innate and adaptive immune systems.

Cells that support innate immunity function:

Cytokines: Chemical messengers that coordinators immune response, communicating information between immune cells.
Natural killer (NK) cells: White blood cells responsible for destroying infected or mutated cells.
Macrophages: White blood cells that “eat” bacteria and other foreign cellular matter.
Dendritic cells: White blood cells that hand over pathogens to B and T cells.

Cells that support the adaptive immune function:

B and T cells: White blood cells called lymphocytes that recognize past invaders and eliminate them with a learned response. B cells mature in the bone marrow. T cells mature in the thymus.

AHCC and Innate Immune Response

The innate immune system is made up of a network of white blood cells that communicate with each other and expel foreign entities from the body.

In vivo and human clinical trials have shown that AHCC can support the innate immune response through several mechanisms.

Increases the production of cytokines
Increases the action of NK cells
Increases the creation of macrophages
Increases the population of dendritic cells.

AHCC and Adaptive Immune Response

The adaptive immune response is made up of a network of cells known as T cells and B cells. During in vitro and clinical studies, AHCC was shown to support the adaptive immune response by increasing T cells’ production.

The Research

As the world’s most researched extract for immune system health, AHCC has been the subject of over 30 unique pre-clinical and clinical studies. These studies have looked at AHCC’s effects on everything from cancer outcomes, severity and frequency of HPV infections, immune response in healthy and compromised patients, liver disease and more.

AHCC has been administered to patients in over 1,000 healthcare facilities. Healthy patients, as well as patients that are immune-compromised, have reaped the benefits of AHCC.

Pre-Clinical and In Vitro Studies

Infection

The human body is highly susceptible to infection during and after surgery. Healing a surgical wound is strenuous to our immune system since it is working simultaneously to repair damaged cells while eliminating pathogens that may have entered the body during the procedure and through the incision site during recovery.

A 2006 study published in the journal Surgical Infections showed AHCC exhibited a strong immune response in mice that were given simulated surgical wound infections. The mice that were given AHCC before and during the procedure had significantly higher survival and recovery rate when compared to the group of mice that did not receive AHCC. The findings strongly suggest AHCC had a significantly positive effect on the immune response.

The correlation between AHCC and infection recovery is important to consider in the context of humans undergoing surgery. Compounds like AHCC can help diminish the possible complications of surgical infections and promote better recovery

Inflammation

Inflammation in humans is commonly linked to injury, arthritis, and bowel diseases. It is an immune response that helps expel pathogens from the body. Cytokines are immune response messengers that can be anti-inflammatory, meaning they work to reduce inflammation and heal an infection. However, there are also proinflammatory cytokines, which promote excessive inflammation in some cases, which can become chronic.

The Journal of Nutrition published a study that administered AHCC to rats with colitis, inflammation of the bowel. The efficacy of AHCC was reflected in the examination of gut bacteria. It was found that levels of good gut bacteria were increased and clostridia, a bacteria responsible for food poisoning and inflammation, had diminished.

Treating inflammation is crucial because, in the long term, chronic inflammation can chip away at healthy tissue. Diseases such as arthritis become degenerative over time. Using extracts like AHCC can help produce those anti-inflammatory cytokines to relieve inflammation, pain and promote longevity.

Diabetes

Diabetes is becoming overwhelmingly common in America. Diabetes affects a person’s ability to create or use insulin, which is responsible for ultimately helping cells use glucose from the bloodstream for energy. Type 1 Diabetes is often diagnosed when a person is young and is known as an immune disorder that attacks the pancreas, the organ responsible for creating insulin. Type 2 is typically diagnosed later in life and is commonly brought on by poor diet and being overweight, and is associated with insulin resistance versus inability to produce insulin.

In an experiment published by Biomedical Research, Koji Wakame examined the effects of AHCC on rats with diabetes. As the rats showed signs of diabetes such as decreased insulin levels, high blood glucose, and weight loss, Wakame administered AHCC in their drinking water. Wakame observed that blood sugar returned to normal, and insulin levels were restored.

Without treatment, the lack of blood glucose absorption was causing high blood sugar, which can cause damage to major internal organs. Diabetics must take insulin to avoid fatal consequences, and AHCC may assist in helping to lower and control blood sugar.

Clinical and In Vivo Studies

Cancer

Cancer is one of the most widely researched diseases in the world. This mutational cell disease can destroy the immune system and cause tumors. Cancer patients commonly undergo surgery, transfusions, chemotherapy, and immunotherapy.

Research conducted on groups with various forms of cancer has concluded AHCC increases the quality of life during and after recovery from surgeries and chemotherapy. A study on 269 patients with liver cancer concluded that the control group, those who did not take AHCC after major surgery, had a lower survival rate and higher relapse rate than those administered AHCC. It was also recorded that patients who took AHCC, we’re generally of better health and able to live more fulfilling lives down the line.

AHCC has also been administered to cancer patients undergoing chemotherapy. It has been known to lessen chemo’s side effects such as hair loss, nausea, loss of bone marrow, and liver damage. It’s been observed that patients who receive chemo and take AHCC experience little to no hair loss. In some cases, AHCC can even subside nausea. Since chemotherapy kills healthy cells, it jeopardizes the body’s white blood cells, and AHCC supports them through and through.

Liver

The liver is the body’s filtration system; it also metabolizes foods and secretes proteins. The liver is responsible for filtering the toxins of the blood. However, the liver can become injured either by hereditary ailments, hepatitis-C, and poor lifestyle choices. Hep-C is a virus that is transferred intravenously, which causes damage to the liver.

In a study done by the Department of Medicine at the Phramongkutklao Hospital in Bangkok, Thailand, an experiment was conducted on patients with Chronic Hepatitis-C. It was found that the group which was administered AHCC experienced lower levels of liver enzymes. High levels of these enzymes incite liver damage. Therefore, the patients were able to get a better handle on their illness before more damage occurred.

Heart and Stress

There are many factors that can affect the heart: high cholesterol, obesity, smoking, not enough physical activity, diet, etc. A large oversight is that high stress can be a precursor to cardiovascular problems. Stress can also weaken the immune system. The original release of AHCC was as a treatment for high blood pressure. Treating high blood pressure is important because it can otherwise lead to damage to the heart and blood vessels.

Conclusion

AHCC is not a cure for any ailment, but it can undoubtedly alleviate symptoms and work to improve some of the most serious conditions we currently face.

AHCC has become a leading extract in immunotherapy, and will continue to be pridefully and extensively researched.

Sources

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Review AHCC research pertaining to a particular ailment.

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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%.

AHCC^® supplementation resulted in the following observations:

Results from this phase II study demonstrated that AHCC 3 g once daily was effective to support the host immune system to eliminate persistent HPV infections and was well tolerated with no significant adverse side effects reported. The duration of AHCC supplementation required beyond the first negative result needs more evaluation to optimize success for durable outcomes. The suppression of the IFN-β level to less than 20 pg/ml correlated with clearance of HPV infections and merits further evaluation as a clinical tool for monitoring patients with HPV infections.

AHCC^® supplementation resulted in the following observations:

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

The DNA levels of herpes virus type 6, often found in people with compromised immune systems and thought to be related to chronic fatigue syndrome, were significantly increased after chemotherapy. AHCC^® significantly decreased the levels of HHV-6 in saliva during chemotheraphy, improved AOL scores in the EORTC QLQ-C30 questionnaire and reduced blood and liver toxicity.

It was found that compared with the control group, the AHCC group had significantly fewer neutrophil-related events (odds ratio: 0.30; p = 0.016), significantly lower use of granulocyte colony-stimulating factor, and a higher (although not significant) rate of adverse events associated with c-glutamyl transpeptidase, a liver enzyme.

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.

After 12 weeks of supplementation, the percentage change in alanine aminotransferase (ALT) levels was significantly different between the placebo and both AHCC groups (1 g of AHCC^® and 3 g of AHCC^®). Serum levels of tumor necrosis (p < 0.05) and interleukin-1β ( p < 0.01) were significantly lower, while those of adiponectin were higher in both AHCC^® groups than in the placebo group (p < 0.01). AHCC^® supplementation for 12 weeks may improve the levels of liver enzymes and circulating pro-inflammatory and anti-inflammatory cytokines in patients with alcohol-induced mildly elevated liver enzyme levels. The liver enzyme levels, lipid profiles, insulin resistance, and scores on fatigue and stress-related questionnaires did not show significant differences between the groups (p < 0.05); however, cytokine levels did show significant differences (TNF-α, IL-1β, and adiponectin, p < 0.05). Comparing the percentage changes at 12 weeks as analyzed by a paired t-test, a decrease in liver enzymes in both AHCC groups and a change in IL-1β and adiponectin in the 1-g AHCC^® group were found to be statistically significant. When analyzed with ANOVA, the percentage changes of serum levels of inflammatory cytokines, such as TNF-α (p < 0.05) and IL-1β (p < 0.01), were lower in the AHCC^® supplementation groups than in the placebo group. Serum levels of adiponectin were higher in both AHCC^® groups than in the placebo group (p < 0.05).

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)

Five subjects achieved a negative HPV test result — three with confirmed eradication after stopping AHCC^® — with the remaining two responders continuing on the study.

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

Children with pharmacoresistant epilepsy had decreased mature T lymphocytes (CD3+) and T cells and an imbalance in the subset. The amount of CD3+ T lymphocytes in the epilepsy group was 42.42%±14.65%, which is 82.8% of average. The amount of CD4+ T lymphocytes was 71.6%, and cytotoxic CD8+ was 112.7%. The CD4+/CD8+ lymphocytes subset distribution and regulatory balance had a ratio of 1.28±0.55, which was below average or only 58.6% of the average value. After AHCC^® intake, patients had positive changes of peripheral T cell pool (CD3+) and T-helpers (CD4+). They also showed an improvement and increase in the ratio of T suppressors-killers (CD8+) to lymphocytes to 1.4. Due to increases in the CD4+ lymphocytes subset, the immunoregulatory balance of the CD4+ to CD8+ ratio improved. There was a 35% decrease of frequency and intensity of epileptic seizures. The patients’ bodily health status and physiological functions also improved.

Natural killer cell activity significantly increased in both groups during the study period. The natural killer cell number, however, was not altered in the active hexose correlated compound group, while the placebo group showed remarkable decline. In addition, the score of immunological vigor, an index of total immune competence, was maintained in the AHCC^® group, although that of the placebo group decreased during the test period.

AHCC®: What the Research Says