Active Hexose Correlated Compound

Scientifically-proven patented dietary supplement for optimal immune system

100% Natural SourceProcessed polysaccharide of cultured mushroom mycelium Partially-acylated α-1,4 glucan as main component

Worldwide Recognized Dietary Supplement#1 immune supplement in Japan Developed and fully-manufactured in Japan Used in more than 20 countries for over 20 years Scientifically safety proven without reported side effects

Extensive Scientific ResearchStudied at more than 70 leading institutions worldwide Over 30 publications listed in PubMed

Immune Response ImprovementEnhances immune cell number and activity Helps prevent infections Supports intestinal immunity

Integrative Medicine & Clinical Nutrition Use in oncology field Improves liver function

Amino Up Chemical Co., Ltd.

AHCC is a product of Amino Up Chemical (AUC), a biotech company of Sapporo, Japan. AUC is specialized in developing and manufacturing novel bioactive substances from natural sources. Our products are all based on scientific evidences as we devote to research and conduct collaborations with leading universities and institutes worldwide. Our products are manufactured in a dietary supplement GMP-certified eco-friendly plant in Sapporo that complies with ISO 9001:2008 and ISO 22000:2005.

Hajime Fujii, Ph.D. hfujii@aminoup.co.jpKohei Homma, Ph.D. kohei.homma@aminoup.co.jp

References Abe, S. et al. (Teikyo University, Japan) Yakugaku Zasshi 120 (8), 715-719 (2000) Chutaputthi, A. et al. (Phramongkutklao Hospital, Thailand) The 18th International Congress on Nutrition and Integrative Medicine, Sapporo, Japan (2010) Fujii, H. et al. (Amino Up Chemical Co., Ltd., Japan) Journal of Experimental Therapeutics and Oncology 8, 43-51 (2009) Gardner, E. et al. (Michigan State University, USA) Experimental Biology, Anaheim CA, USA (2010) Hisajima, T. et al. (Teikyo Heisei University, Japan) The 18th International Congress on Nutrition and Integrative Medicine, Sapporo, Japan (2010) Kamiyama, Y. et al. (Kansai Medical University, Japan) Journal of Hepatology 37, 78-86 (2002) Kamiyama, Y. et al. (Kansai Medical University, Japan) Nutrition and Cancer 60 (5), 643-651 (2008) Martinez-Augustin, O. et al. (University of Granada, Spain) The Journal of Nutrition, Nutritional Immunology 137 (5), 1222-1228 (2007) Nishioka, H. et al. (Amino Up Chemical Co., Ltd., Japan) Toxicology and Applied Pharmacology 222, 152-158 (2007) Sumiyoshi, Y. et al. (Shikoku Cancer Center, Japan) Japanese Journal of Clinical Oncology 40 (10), 967-972 (2010) Wakame, K. et al. (Amino Up Chemical Co., Ltd., Japan) Cancer Epidemiology 33, 293-299 (2009) Walshe, T. et al. (Harvard Medical School, USA) Human Immunology 71, 1187-1190 (2010) Wang, T. et al. (University of Texas Medical Branch, USA) The Journal of Nutrition, Nutritional Immunology 139, 598-602 (2009)

Roberts, A. et al. (Cantox Health Sciences International, Canada) Regul. Toxicol Pharmacol. doi:10.1016/j.yrtph.2010.10.006 (2010) Walshe, T. et al. (Harvard Medical School, USA) J Nutr Sci Vitaminol. 53, 536-539 (2007)

Future Developments

Safety

About Us

Various studies to date revealed that AHCC has numerous applications in many fields. We are now conducting research to prove the effects conclusively through phase II and III clinical trials, and to elucidate the fundamental action of AHCC in immune response modulation as well. In addition since 1994 an increasing body of researchers worldwide are affiliating to the AHCC Research Association to share the foremost research from the fields of molecular biology, pharmacy, medicine, veterinary medicine and integrative medicine. The AHCC Research Association gathers every year in Japan at the International Congress on Nutrition and Integrative Medicine.

For more information on AHCC: http://www.ahccresearch.com/

AHCC is confirmed to be nontoxic and safe food product by numerous in vitro, in vivo, and clinical studies. Genotoxicity was tested by reverse mutation test and micronucleus test, single dose oral toxicity and 90-day repeated dose oral toxicity were examined in rodents, and a phase I clinical test was conducted in healthy subjects. In addition, AHCC is a compound made from mushroom with a long history of human consumption. Moreover, several hundred thousands people have used AHCC with no reports related to its toxicity or side effects since its introduction to the market in 1989.

AwardIndustrial Forms AvailableAHCC received the NutrAward for the Best New Product of the Year 2002 at the Natural Products Expo West.

Fine granule Freeze dry Hard capsule Soft capsule Liquid

363-32 SHIN-EI, KIYOTASAPPORO, 004-0839 JAPANTEL: +81-11-889-2277FAX: +81-11-889-2288

http://www.aminoup.co.jp/e/

Research use only

Immune Cell Production Oncology Field

0

20

40

60

80

100

120

140

160

180

AST ALT

ControlAHCC6MP+MTXAHCC+6MP+MTX

Enzy

me

activ

ity (I

U)

p<0.05p<0.05

Wakame, K. et al. Cancer Epidemiology (2009)

ControlDrugs onlyDrugs + AHCC

0

50

100

150

Control TAX TAX+

CDDP5FU

+CPT

CDDP+

5FUDXR

+CY

* p<0.01 vs Control, ** p<0.01 vs Control, AHCC group

Cel

l via

bilit

y (%

of C

ontro

l)

HUMAN Study Overview

Benefits for Healthy People Immunity Reinforcement

p<0.05 p<0.05

pre post pre postAHCC Control

Num

ber o

f DC

(×10

3 )

30

20

10

0

Method: double-blind placebo-controlledSubjects: 21 healthy adults (10 AHCC treated, 11 control)Dose: 3 g/dayPeriod: 4 weeksMeasurement: number of dendritic cell (DC)

HUMAN Study OverviewHUMAN Study Overview

HUMAN Study Overview

HUMAN Study Overview

Method: open-labelSubjects: 30 healthy adults at age over 50Dose: 3 g/dayPeriod: 60 days of AHCC intake, 30 days after discontinuing AHCCMeasuement: population of CD4+ T cell producing IFN-γ and TNF-α

Longer Postoperative Survival

Kamiyama, Y. et al. Journal of Hepatology (2002)

0.0

0.5

1.0

Tota

l sur

viva

l rat

e

Years after surgery0 1 2 3 4 5 6 7 8 9

Postoperative survival

ControlAHCC

Nishioka, H. et al. Toxicology and Applied Pharmacology (2007)

Sumiyoshi, Y. et al. Japanese Journal of Clinical Oncology (2010)

Chutaputthi, A. et al. presented at 18th ICNIM (2010)

Fujii, H. et al. Journal of Experimental Therapeutics and Oncology (2009)

Kamiyama, Y. et al. Nutrition and Cancer (2008)

Walshe, T. et al. Human Immunology (2010)

Method: prospective cohort, open-labelSubjects: 269 hepatocellular carcinoma patients that underwent resection of liver tumor (113 AHCC treated, 156 control)Dose: 3 g/dayPeriod: from hospital discharge until death or the end of observation periodMeasurement: survival rate

Side Effects Reduction ofMost Common Chemotherapy Agents

Chemotherapy Support

Liver Function

Improvement ofQuality of Life

Animals: ddY mice, male (n=8~11 each group)Treatment: AHCC; 360~1000 mg/kg/day, anticancer drugs used per day; TAX (paclitaxel; 15~20 mg/kg), CDDP (cisplatin; 8 mg/kg), 5FU (5-fluorouracil; 100 mg/kg), CPT (irinotecan; 50 mg/kg), DXR (doxorubicin; 8 mg/kg), CY (cyclophosphamide; 120 mg/kg) Period: 25 daysMeasurement: bone marrow cell viability

Animals: 6 week-old BALB/cA mice, female (n=17 each group)Treatment: Colon-26 tumor cells were inoculated (5 x 105 cells/mouse) 3 days before cisplatin initial injection. AHCC; 100 mg/kg/day, Cisplatin; 8 mg/kg at day 0, 6, 13, 20Period: 28 daysMeasurement: tumor size

Method: open-labelSubjects: 74 patients with early prostate cancerDose: 4.5 g/dayPeriod: 6 monthsMeasurement: state anxiety, trait anxiety

Animals: 8 week-old ddY mice, male (n=6 each group) Treatment: AHCC; 1000 mg/kg, liver damage was induced by 6MP (6-mercaptopurine; 2.5 mg/kg) and MTX (methotrexate; 30 mg/kg). Period: 28 days Measurement: serum hepatic enzyme activity

0

10

20

30

40

50

60

70

State TraitBefore After Before After

Anx

iety

sco

re

p<0.01 p<0.01

Days after tumor inoculation

ControlCisplatinCisplatin + AHCC

8,000

6,000

4,000

2,000

00 10 20 30

Tum

or s

ize

(mm

3 )

*p<0.01 vs Control

*p<0.01 vs Control

**p<0.01 vs Control, p<0.05 vs Cisplatin

*

*

**** ** **

**

** *

*

*

**Method: open-label Subjects: 29 healthy adults after immunization with influenza vaccine [A(H1N1), A(H3N2), B] (14 AHCC treated, 15 control) Dose: 3 g/day started on the day of vaccination Period: 2 weeks Measurement: blood immune cell phenotypic analysis using flow cytometry, CD8+ T cell and CD56+/CD3+ NKT cell

Method: double-blind placebo-controlledSubjects: 39 hepatitis C virus (HCV) carrier (19 AHCC treated, 20 control)Dose: 6 g/dayPeriod: 24 weeksMeasuement: HCV-RNA amount, ALT level in blood

ControlAHCC

Fold

cha

nge

1

2

0

* ControlAHCC

Young (<60)

Fold

cha

nge

Elderly (>60)Young (<60) Elderly (>60)

1

2

0

*

Gardner, E. et al. presented at Experimental Biology (2010)

Prevention of Wide Range of Infections

Animals: 4 week-old Crl:CD1(ICR) mice, femaleTreatment: mice were infected with methycillin-resistant Staphylococcus aureus (MRSA) at day 0 and AHCC was given 50 or 500 mg/kg/day from day 4. Period: 28 days Measurement: survival rate

0 7 14 21 280

20

40

60

80

100

Days after infection

Sur

viva

l rat

e (%

)

Animals: 21-22 month-old C57BL/6 miceTreatment: 600 mg/kg every other day for 1 week before infection and at day 1 and 3 postinfection. 80 PFU (close to 100% lethal dose) of WNV isolate NY99 was innoculated intraperitoneally.Period: 28 days until mice showed signs of morbidityMeasurement: WNV-specific IgG and viremia at day 4, and survival rate post infection

Abe, S. et al. Yakugaku Zasshi (2000)

Wang, T. et al. The Journal of Nutrition (2009)

80

85

90

95

100

105

110

115

120

Baseline After 24 weeks

ControlAHCC

*

*p<0.01 vs Control

Baseline After 24 weeks

ControlAHCC

*

*p=0.01 vs Control

*p<0.05 vs Control*p<0.05 vs Control

*p<0.05 vs Control *p<0.05 vs Control

*p<0.05 vs Control

80

85

90

95

100

105

110

115

120

MRSA

West Nile virus

Influenza

0.0Control

(n=8)

IgG

OD

AHCC(n=8)

0.1

0.2

0.3

0.4

0.5 *

0Control(n=10)

WN

VE

/β-a

ctin

x10

-5

AHCC(n=9)

20

40

60

80

100

*

Control (n=10)

Days post infection

Per

cent

sur

viva

l AHCC (n=11)

00 4 8 12 16 20

20

40

60

80

100

TNBS Sulfasalazine AHCC0

2

4

6

8

10

12D

AM

AG

E S

CO

RE

* p < 0.05 vs TNBS

Colonic DamageMartinez-Augustin, O. et al. The Journal of Nutrition (2007)

Control TNBS Sulfasalazine AHCC0

2

4

6

8

* p < 0.05 vs Control

Intestinal Flora

Log

CFU

Intestinal Condition Improvement

Reduction of Liver Damege Improvement of Hepatitis C Symptoms

Immune Stimulation

Hisajima, T. et al. presented at 18th ICNIM (2010)

Intestinal Immunity

A B C A B C A B C A B C

Pathogenic ClostridiumABifidobacteriaBLactic Acid BacteriaC

Animals: Wister rats, female (200-250 g, n=6 each group)Treatment: AHCC (500 mg/kg/day) or sulfasalazine (200 mg/kg/day) to TNBS(10 mg/rat)-induced colitis ratsPeriod: 2 days pre-colitis-induction + 6 days post-colitis-inductionMeasurement: colonic damage, intestinal flora

Secr

eted

IgA

leve

ls (μ

g/m

l/0.

1g)

Day 1 Day 3

*p<0.05 vs Control, Day 1

ControlAHCC

0

100

200

300

400

500

*

Day 5

Animals: 6 week-old ICR mice, male (n=5 each group) Treatment: 1000 mg/kg/dayPeriod: 5 daysMeasurement: secreted IgA

0

1

2

3

4

5

6

*

*

**

**

% o

f cel

ls

* p<0.01 vs day 0** p<0.05 vs day 0

IFN-γATNF-αBIFN-γ and TNF-αC

*

Control (n=9)AHCC 50 mg (n=8)AHCC 500 mg (n=8)

HUMAN Study OverviewANIMAL Study Overview

ANIMAL Study Overview

ANIMAL Study Overview

ANIMAL Study Overview

ANIMAL Study Overview

ANIMAL Study Overview

ANIMAL Study Overview

HCV genotype 3 RNA

NKT cell CD8+ T cell

ALT (all genotype)

Chan

ge o

f HCV

-RNA

(%)

Chan

ge o

f ALT

(%)

A B CA B CA B CA B C0 30 60 90 (day)

AHCC

WNV-specific IgG Viremia Survival rate

**

*

**

*

*