AHCC® Clinical Studies

Onuma M, et al. Effect of AHCC and GCP on oral malignant melanoma in dog: two case reports. Poster presented at International Congress on Nutrition and Integrative Medicine. July 2010. Sapporo, Japan.

Topic: Does AHCC contribute to improved quality of life in dogs presenting oral melanoma?

Background: Malignant melanoma is a disease that causes tumors in the oral cavity, which is commonly diagnosed in older dogs. Unfortunately, these cases are often metastatic in nature. Here are two case studies of dogs presenting oral malignant melanoma showing response to administration of Active Hexose Correlated Compound (AHCC) and Genistein Combined Polysaccharide (GCP).

Case Summary

Case 1

A 16-year old, male, mix-breed dog presenting with anorexia, cough, pain, and 50mm x 30mm x 30mm mass located in right maxillary gingiva was the subject of this case study. No abnormalities were detected in the dog’s complete blood count, serum biochemistry or urinalysis; however, radiography revealed evidence of metastasis in the lungs. Histological investigation of the mass in the oral cavity revealed proliferation of abnormal cells with prominent anisokaryosis and intracytoplasmic melanin pigmentation. The mass was histopathologically diagnosed as malignant melanoma (T3b, N1X, M1) and treatment withAHCC® (60mg/ kg BW/day), GCP (0.005mg/kg BW/day),and NSAIDS as pain control was post-operatively initiated. Following initiation of treatment, appetite and general status of patient showed improvement and after only 55 days of treatment, the size of the tumor was reduced. 122days following initiation of treatment, the patient died of respiratory failure resulting from carcinomatous pleurisy.

Case 2

A 15-year old, male, mix-breed dog presenting with a 3mm diameter mass on its left lip was the subject of this case study. No additional abnormalities were observed in complete blood count, serum biochemistry, urinalysis, or radiography. The mass was removed and histopathologically diagnosed as malignant melanoma (T1, N0, M0). Following surgery, treatment with AHCC (60mg/kg BW/day) and NSAIDS was initiated. After 271 days of treatment, recurrence of the oral tumor, enlargement of superficial lymph nodes, and splenomegaly with multifocal nodular lesions were recognized. Both the oral tumor and spleen were surgically removed and the patient was diagnosed with malignant melanoma (T2b, N2, M0) and lymphoma (Class V).Following recurrence, Dendritic Cell Vaccine (Cell count: 5-3 x 105-6) and IL-12 (20ng/kg BW) were subcutaneously administered on post-operative days 4 and 5. Beginning 6weeks after operation, treatment with Prednisolone (1mg/kg BW EOD) and AHCC (60mg/kg BW/day) was initiated. Lomustine (50mg/ mm2) was also administered during post-operative weeks 6 and 9. The treatment regimen was modified on post-operative week 12 to consist of Prednisolone (0.5mg/kg BW EOD) and AHCC (60mg/kg BW/day). Patient died 144 days following reoccurrence.

Conclusion These cases suggest treatment with AHCC and/or GCPmay have the potential to increase quality of life and delay reoccurrence or progression of disease in dogs presenting malignant neoplasm, therefore suggesting that AHCC and GCP are valuable complementary and alternative medicine treatments in veterinary oncology settings.

Takahashi T, et al. Augmentation of canine cellular immune response by administration of AHCC®. Paper presented at International Congress on Nutrition and Integrative Medicine. July 2001. Sapporo, Japan.

Topic: Does AHCC contribute to enhanced cellular immunity in dogs as previously demonstrated in human and mouse studies?

Background The ability of Active Hexose Correlated Compound (AHCC) to enhance cellular immunity has been demonstrated in both human and mouse studies, however the therapeutic potential of AHCC to enhance cellular immunity has not been demonstrated in dogs. Here the ability of AHCC to enhance cellular immunity in dogs is investigated. Specifically, the activity of macrophages, neutrophils, and natural killer (NK) cells isolated from the peripheral blood of healthy dogs is assessed employing a chemoluminescence assay.

Subjects 12 Healthy dogs

Study Design Subjects were divided into two treatment groups (n=6) receiving 100mg/kg BW and 50mg/kg BW AHCC respectively. Following single administration of respective AHCC dosages, peripheral blood was collected at 12 hours, 24 hours, 48 hours, 3 days, 5 days, and 7 days. Peripheral blood lymphocytes and macrophages were isolated by centrifugation. Following isolation activity of immune cells was assayed.

Results: AHCC treatment did not result in significant changes in while blood cell population dynamics-

• Neutrophil Activity

- 50mg/kg BW AHCC® Treatment

• AHCC increased neutrophil activity

- Avg: 2x increase from baseline

- Max: 3x increase from baseline

• Returned to baseline within 24 hours

- 100mg/kg BW AHCC Treatment

• AHCC increased neutrophil activity

- Avg: 2x increase from baseline

- Max: 3.5x increase from baseline

• Returned to baseline within 48 hours

• Macrophage Activity

- 50mg/kg BW AHCC Treatment

• AHCC increased macrophage activity

- Avg: 2.2x increase from baseline

- Max: 3x increase from baseline

• Returned to baseline after 48 hours

- 100mg/kg BW AHCC® Treatment

• AHCC Treatment increased macrophage activity

- Avg: 2.7x increase from baseline

- Max: 4.6x increase from baseline

• Returned to baseline after 48 hours

• NK Cell Activity

- 50mg/kg BW AHCC Treatment

• AHCC increased NK cell activity

- Avg: 1.8x increase from baseline

- Max: 3x increase from baseline

• Returned to baseline after 3 days

- 100mg/kg BW AHCC Treatment

• AHCC increased NK cell activity

- Avg: 2.2x increase from baseline

- Max: 3.9x increase from baseline

• Returned to baseline after 3 days

Conclusion: WBC population dynamics were normal following AHCC treatment:

• Neutrophil activity increased ~2.2x above baseline after 12 hours in both treatments

• Macrophage activity increased ~1.8x and ~2.2x above baseline after 12 hours in 50mg/kg BW and 100mg/ kg BW groups respectively

• NK cell activity increased ~1.8x and ~2.2x above baseline after 24 hours in 50mg/kg BW and 100mg/ kg BW groups respectively

Masuyama, T et al. Application of the new immunotherapy using AHCC® for animal disease II. Paper presented at International Congress on Nutrition and Integrative Medicine. July 2000. Sapporo, Japan.

Topic: Does AHCC contribute to improved outcome and quality of life in dogs clinically presenting neoplasia?

Background: AHCC has been shown to contribute to improved quality of life in a variety of human clinical settings, including oncological settings, by supporting immune function. While the efficacy of AHCC in supporting immune function has been repeatedly investigated in humans, here are a series of case reports describing the treatment of dogs who were clinically presenting neoplasia that were given AHCC.

Case Summary:

Case 1

A 12-year old, female, Shetland sheepdog presenting with 52mm x 50mm x 32mm soft swelling located from the base of the tail to the lumbar was the subject of this case study. Pathological tests resulted in the diagnosis of fibrosarcoma and blood analysis indicated ALP 58IU/L, T-BIL 0.2g/dL, and GOT 10U/L. Treatment regime consisted of 0.5g/day AHCC, 3g/day Better Shark™. Treatment resulted in increased activity of macrophage and natural killer cells as measured by chemoluminescence assay as well as a softening of the mass and a reduction in its size.

Case 2

A 13-year old, female, beagle presenting with swelling in 2nd left mammary gland (15mm), that was pathologically diagnosed as mammary adenoma, was the subject for this case study. Additionally, blood analysis indicated GOT 10IU/L, and LDH 113IU/L. Treatment regime consisted of 0.5g/day AHCC, which resulted in a slight increase in macrophage activity following administration. Following treatment, activity of NK cells also showed a marked increase.

Conclusion: These data indicate that AHCC increased the cellular immune activity in tumor-bearing animals, therefore suggesting that AHCC may have potential for effective treatment in animals bearing tumors.

Matuo A, et al. Application of the new immunotherapy using AHCC® for animal disease I. Paper presented at International Congress on Nutrition and Integrative Medicine. July 2000. Sapporo, Japan.

Topic: Does AHCC contribute to improved outcome and quality of life in dogs clinically presenting neoplasia?

Background: AHCC has been shown to contribute to improved quality of life in a variety of human clinical settings, including oncological settings, by supporting immune function. While the efficacy of AHCC in supporting immune function has been repeatedly investigated in humans, here are a series of case reports describing the treatment of dogs who were clinically presenting neoplasia that were given AHCC.

Case Summary:

Case 1

A 12-year old, male, Labrador retriever presenting with a tumor located on the mandibular lympha, which was diagnosed as lymphomatosa, was the subject of this case study. The patient was treated with chemotherapy in August of 1999 but in March of 2000, the patient was re-examined presenting with a blood clot in the urine, BUN 35.2mg/dL, and CREA 2.18mg/dL. An MRI scan indicated hypertrophy of the bladder wall. Pathological analysis resulted in a diagnosis of malignant bladder cancer. Initially 270mg/kg BW AHCC® BID was administered alone as treatment. Following 20 days of treatment, treatment regime was modified to include 270mg/kg BW AHCC BID, 2.5g/kg BW Better Shark™ BID, 75mg/kg BW Ursodeoxycholic acid BID, Multivitamin BID, and 0.5g/kg BW PSK BID. Despite progression of bladder cancer, the patient did not present frequent urination and appeared well clinically following initiation of AHCC treatment. Treatment also showed significantly higher immune activity but as a complication of progressive renal failure, the levels tended to decrease.

Case 2

A 14-year old, female shiba presenting with intermittent hemorrhage from left nasal cavity and a 3cm tumor on the left femoral muscle is the subject of this case study. CT examination revealed that the tumor located in the Sinus frontalis of the left nasal cavity. Following extirpation of the left ceruminosa, results of a pathology test indicated a diagnosis of apocrine adenoma. Treatment consisting of 270mg/kg BW AHCC BID, 2.5g/kg BW Better Shark™ BID, 75mg/ kg BW Ursodeoxycholic acid BID, Multivitamin BID, and 0.5g/kg BW PSK BID was initiated. Following initiation of treatment, immune activity was increased and blood vessel formation was decreased.

Conclusion: These data indicate that AHCC increased the cellular immune activity in tumor-bearing animals, therefore suggesting that AHCC may have potential for effective treatment in animals bearing tumors.

Horiuchi Y, et al. The effect of AHCC® on adoptive T-Lymphocyte immunotherapy for dogs with cancer. Poster presented at International Congress on Nutrition and Integrative Medicine. July 2010. Sapporo, Japan.

Topic: Does treatment with AHCC improve outcomes in dogs undergoing adoptive T-lymphocyte transfer?

Background: Adoptive T-lymphocyte transfer therapy has been increasingly employed in veterinary settings as treatment for cancer. One challenge in utilizing this therapeutic modality is that lymphocytes from dogs with advanced stage cancer present poor quality immune response and proliferative activity. The following case studies investigate the ability of AHCC to modulate immune response and proliferative activity.

Subjects: 4 dogs presenting with stage IV cancer 

Dosage: 60mg/kg BW/day AHCC

Study Design: Blood samples (20mL) were taken from each subject before initiating treatment with AHCC. Following 2 weeks of AHCC treatment, an additional 20mL blood sample was taken. The percentages of Th1 cells and the total lymphocyte count present in the sample following 2 weeks of expansion were reported.

Results: The mean percentage of Th1 cells significantly increased with AHCC® treatment from 16.5±1.41% Th1 cells to 28.1±2.34% Th1 cells (p<0.05). The mean number of cultured lymphocytes significantly increased following AHCC treatment from 1.0±0.15x108 Cells to 5.2±1.12x108 Cells (p<0.05).

Conclusion: Treatment with AHCC significantly increased the percentage of Th1 cells present in the peripheral blood lymphocytes and the proliferative activity of lymphocytes in dogs with cancer, suggesting that treatment with AHCC potentially improves immunological condition in tumor bearing animals and effect of adoptive T-lymphocyte transfer.

Mamoru O, et al. The Supplementation therapy of canine dermatology in my hospital. Clinical Note Regarding Small-sized Animal. 2008:27(6):17.

Topic: Does Treatment with AHCC contribute to improved outcomes in dogs undergoing treatment for dermatological conditions?

Background Dermatological conditions may present as comorbidities associated with compromised immunity. AHCC has been shown to enhance immune function. Here are a series of case reports describing the treatment of dogs who were clinically presenting dermatological conditions that were given AHCC.

Case Summary:

Case 1

A 13-year old, male, ShihTzu presenting with abdominal pigmentation and scaling was the subject of this case study. Additionally, reddening was observed with leftright symmetry over the entire body excluding the four limbs. Diagnosis of spontaneous adrenal cortical hyper function was made. Treatment with AHCC and D-12 was initiated. Following 2 weeks of treatment, symptoms began to show minor improvement. Furthermore, after 22 weeks of treatment, there was a reduction in fur loss and rash.

Case 2

A 12-year old, male, Kishu Inu presenting with loss of fur in the antebrachial region, abdomen, and nose was the subject of this case study. The patient also presented with pigmentation, scaling, and severe itching localized to these regions. Photodermatosis and diet adverse reaction were suspect causes of these conditions. Initial treatment consisted of administration of griseofulvin, melatonin, and a medicated bath with chlorhexidine shampoo. However, symptoms did not improve after the initiation of the treatment regime. Following this observation, AHCC was added to the treatment regime. Following 12 weeks of treatment with AHCC, improvement in symptoms was observed.

Conclusion In the above two case studies, improvement of symptoms was observed in conjunction with inclusion of AHCC in the therapeutic regimen.

Veterinary Parasitology

Segarra S. et al. “Randomized, Allopurinol-Controlled Trial of the Effects of Dietary Nucleotides and Active Hexose Correlated Compound in the Treatment of Canine Leishmaniasis.” 2017. 239:50–56.

Topic: What’s the effect of dietary nucleotides and AHCC in treating canine leishmaniasis?

Background: Canine leishmaniasis (CanL) is a zoonotic disease caused by Leishmania parasites transmitted by the bite of an infected phlebotomine sand fly. Currently, the most effective treatment for CanL consists of subcutaneous N-methylglucamine antimoniate (MGA) for four to six weeks combined with oral allopurinol for six to 12 months. However, the use of allopurinol has some side effects, including increased urinary xanthine levels, which may ultimately cause urolithiasis and renal mineralization. 

Study Type: Multicenter, open-label, randomized, allopurinol-controlled clinical trial

Study Design: Dogs with naturally occurring clinical leishmaniasis were included in this trial and were randomly assigned to the allopurinol group (n = 38, 10 mg/kg allopurinol PO BID) or supplement group (n = 31, 17 mg/kg AHCC plus 32 mg/kg nucleotides PO SID). All dogs were also given 50 mg/kg MGA SC BID during the first 28 days. At 0, 30, and 180 days of the trial, the dogs underwent a clinical examination, and blood, urine, and bone marrow samples were collected for analysis.

Subjects: 69 dogs with naturally occurring clinical leishmaniasis

Dosage: Oral treatment of 17 mg/kg AHCC plus 32 mg/kg nucleotides per day for 180 days

Results: Both groups showed a significant improvement in clinical scores and antibody titers after treatment. The supplement group showed a significantly lower clinical score and significantly higher antibody titers after 180 days, compared with the allopurinol group. The supplement group reached a similar reduction in parasite load measured by RT-PCR. Both treatments led to a significant increase in CD4+/CD8 ratio and improvements in protein electrophoretic pattern and accurate phase response.

Conclusion: Six-month treatment with nucleotides and AHCC in addition to MGA showed efficacy similar to the current first-line treatment for CanL, without producing xanthinuria and related side effects. This combination could be a good alternative to MGA-allopurinol combination treatment for CanL, especially for dogs suffering allopurinol-related adverse events.