What is Fucoidan AHCC?

Fucoidan & AHCC

®

Provided for non-commercial research and educational use only. Not for reproduction, distribution or commercial use.

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Fucoidan & AHCC® AHCC® Manufacturing Process (Sapporo, Japan) AHCC® is manufactured through a patented, extended liquid culturing process that makes its active components different from other mushroom extract products. AHCC® is manufactured by culturing the mycelia of basidiomycetes (mushroom root threads) for a period of 45~60 days in a large holding tank.

Several types of mycelia are initially cultured to form a colony (a mass of mycelia). After the culture is completed, the product is subjected to enzyme reaction, sterilization, concentration and freeze drying.

While most medicinal mushroom extracts have a molecular weight of more than 200,000 daltons, the presence of acetylated alpha glucans with a molecular weight of around 5,000 daltons is considered one of the attributes of AHCC® that provides it with superior absorption and strong clinical efficacy. There is probably no other similar product among health foods with the uniqueness of AHCC®.

ScienceDirect US National Library of Medicine National Institutes of Health

A leading full-text scientific database offering journal articles from 2,500 journals

PubMed is a free search engine

ScienceDirect is website operated by the Anglo-Dutch publisher Elsevier. It is a platform for access to nearly 2,500 academic journals.

For most articles abstracts are freely available.

accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine (NLM) at the National Institutes of Health maintains the database.

Regarding Fucoidan & AHCC®, more than 1,200 articles are listed in PubMed. Please type the word that relates to your health concern along with the word “fucoidan” in the search box. www.pubmed.gov

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Around 2,200 articles relating to Fucoidan & AHCC® are listed in ScienceDirect. Please type the word that relates to your health concern along with the word “fucoidan” in the search box.

www.sciencedirect.com

AHCC Research Association AHCC Research Association provides various clinical studies, books, testimonials, research papers regarding AHCC®. It holds an annual symposium in which many doctors, professors, and experts from major research institutes such as MD Anderson Cancer Center, Harvard University, Yale University participate to share AHCC®’s effectiveness relating to influenza, inflammation, infection, cancer, chemotherapy side effects, etc. If you want to know more about AHCC®, please visit the following link: www.ahccresearch.com

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Table of Contents Fucoidan and its Efficacy …… 04 • What is Fucoidan?

• Fucoidan's Suppressive Effect on Cancer Cell Growth • Characteristics and Anticancer Effects of Different Fucoidan Types • Fucoidan Alleviates the Side Effects Caused by Chemotherapy • Fucoidan's Effectiveness on Other Diseases

AHCC® and its Efficacy …… 08

• What is AHCC®?

• The Structure of AHCC® • β-glucans, α-glucans • AHCC® Activates the Immune Cells to Fight Cancer • AHCC® Alleviates the Side Effects Caused by Chemotherapy • AHCC®’s Effectiveness in Scientific Studies

Function of the β-glucans Present in the Agaricus mushroom …… 12 Synergistic Effectiveness of Fucoidan, Agaricus and AHCC® …… 12 Comparison & Synergy of Fucoidan, Agaricus and AHCC® …… 13 Q&A …… 14

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Fucoidan What is Fucoidan?

Fucoidan is a sulfated viscous polysaccharide, a main component of brown seaweeds such as Wakame, Kombu, and Mozuku. It was discovered

by Professor Kylin at Uppsala University in Sweden in 1913, which he described as a slippery kelp and a type of soluble fiber. Chemically, the major component of Fucoidan is sulfated fucose and other sugars such as galactose, mannose, xylose, uronic acid that are bound together. Fucoidan is a raw material of dietary supplements, functional food, and food additives. It has shown to lower blood cholesterol levels and prevent blood vessel damage by excreting cholesterol; thus this also prevent in advance lifestyle diseases caused by obesity. In addition, studies done in Japan and the United States reported that Fucoidan has anticoagulation activity, antitumor activity, peptic ulcer prevention, antimicrobial activity, balancing blood pressure, inducing hepatocyte growth factor (HGF) activity, lowering blood sugar activity, anti-allergic activity and antiviral activity. It has also been reported that Fucoidan is especially effective in healing 70~80% of gastrointestinal cancers and it is recognized as an excellent adjuvant substance for most cancer types.

Since the day Fucoidan was introduced as a substance which has the ability to induce cancer cells to self-destruct in the 55th Japan Cancer Society Conference in 1996, extensive research on Fucoidan has been done. As of April 2014, 1,140 research papers and reports have been reported in the National Library of Medicine’s database. <Source> Naver & Doo-San encyclopedia in Korea, and PubMed in USA

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Fucoidan

Fucoidan's Suppressive Effect on Cancer Cell Growth

❶

Activation of Apoptosis (Cancer Cell Destruction)

❶ Our body’s cells have an average life

of about three months, then they die. This phenomenon is called Apoptosis. However, cancer cells do not trigger Apoptosis be-

Fucoidan Three Main Actions

cause the cell structure is damaged. They only grow and metastasize. Fucoidan induces these cancer cells to undergo Apoptosis. ❷ To defeat cancer cells, NK cells (the

❷

Immune System Enhancement

❸

Tumor-Growth (Angiogenesis)

Suppression

representative body immune cells), T cells, macrophages, and other immune cells have to be activated.

By increasing these immune cells and by increasing the Fucoidan supply, they will suppress and remove the cancer cells. ❸ When cancer cells become more than

2mm in diameter they rapidly grow by making new blood vessels from the capillaries nearby.

Fucoidan prevents cancer from making new blood vessels and inhibits the cancer from spreading to other organs.

Articles on Fucoidan’s Cancer Apoptosis Induction Activity - PubMed ID 19754176 Kyushu University, Japan - PubMed ID 22363242 University of Denmark

Articles on Fucoidan’s Immune Boosting Activity - PubMed ID 12929574 Kitasawa University, Japan - PubMed ID 23544642 Korea University, Korea

Articles on Fucoidan’s Cancer Angiogenesis Suppression Activity - PubMed ID 12504793 Kyushu University, Japan - PubMed ID 23737842 Tianjin Unversity, China

Fucoidan

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Okinawa

Tasmania

Fucoidan Characteristics and Anticancer Effects of Different Fucoidan Types Mozuku Fucoidan

Mozuku fucoidan extracted from Okinawa in Japan is the most popular type of fucoidan. Okinawa is well known for its clear and beautiful pristine sea waters and widely known for its longevity. Mozuku fucoidan which is widely used cannot be easily extracted. 1kg of Mozuku is required in order to obtain 1gram of fucoidan. Compared to other fucoidan extracts, Mozuku fucoidan has shown to have a higher apoptosis inducing effect on cancer cells.

Mekabu Fucoidan

Mekabu is the ruffled, flowering sprout located at the base of the sea vegetable, Wakame Undaria pinnatifida just above the root. In Wakame, most of the Fucoidan is found in the Mekabu. One of the uniqueness of Mekabu Fucoidan is that it contains more than 34% of sulfated groups.

Tasmania in Australia is well-known for its very clean oceans. It has plenty of unpolluted natural Wakame, which makes the area possible to be Mecca for Mekabu Fucoidan in the world.

According to some studies from Japan, Mekabu has shown to be more effective in suppressing cancer Angiogenesis than other fucoidan extracts.

Kombu Fucoidan

Kombu was the first species used to extract fucoidan. However, it contains a relatively small amount of fucoidan and it is very expensive to obtain, therefore, not economical to mass-produce this raw material. There are two types of Kombu: GagomeKombu (Saccharina sculpera) and Ma-Kombu (Saccharina japonica). The fucoidan used for the research announced in Cancer Conference in Japan in 1996 was Gagome-Kombu. This species is very sticky and it has been widely enjoyed as one of the favorite foods in Japan.

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Fucoidan

Fucoidan Alleviates the Side Effects Caused by Chemotherapy Cancer patients undergoing conventional cancer treatments want to avoid some of the side effects such as vomiting, nausea, low appetite, skin rashes, nail damage, fatigue, and more. Surprisingly, the result of many studies has shown that people who have ingested fucoidan experienced reduction of side effects from anticancer treatments such as chemotherapy. This happened mainly because Fucoidan enhanced their immune system. By enhancing the immune activity, fucoidan may help to prevent a drop in the white blood cell counts and it will alleviate the pain caused by chemotherapy. When fucoidan is taken along with some of the chemotherapy drugs, the side effects are alleviated. Therefore, the anticancer drugs can be used for long term without causing strong side effects. The combination of fucoidan with the anticancer drugs can compensate for the disadvantages of chemotherapy in numerous ways.

Fucoidan's Effectiveness on Other Diseases • Mitigates high blood pressure & cholesterol* • Alleviates the symptoms caused by diabetes* • Reduces digestive disorders* • Eliminates the Helicobacter pylori bacteria* • Relieves pollen allergies* • Relieves eczema* • Improves blood circulation* • Mitigates the symptoms caused by atherosclerosis* • Prevents other common lifestyle diseases*

PubMed ID 22326809 Relieves Chemotherapy Side Effects Jeju University, Korea

PubMed ID 11321507 Mitigates High Blood Pressure University of Warsaw, Poland

PubMed ID 24388677 Diabetes Laval University, Canada

PubMed ID 18068106 Anti-Viral Activity University of Toyama, Japan

PubMed ID 22431003 Atopy & Allergy Catholic University, Korea

Fucoidan

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®

AHCC

What is AHCC®?

AHCC® (Active Hexose Correlated Compound), an activated sugar related compound is an α-glucan rich plant based polysaccharide mixture which is Fruiting body

extracted from the culture fluid of the basidiomycete in Shitake mushroom (Lentinula edodes). AHCC® as a health food, not a drug, which is sold widely in Japan where it was originally developed as well as in Europe, America, Asia, Oceania, etc. AHCC® is considered a complementary and alternative medicine.

In 1989, AHCC® was developed through joint research by Professor Toshihiko Okamoto from the Department of Pharmacology, in the University of Tokyo in partnership with Amino Up Chemical Co. Ltd. in Sapporo, Japan.

Since then, basic and clinical tests have been executed. In 1994, Hosokawa Mycelium

Masumi the professor of Hokkaido University School of Medicine (Cancer Research Institute of Pathology) founded “The AHCC Research Association." In 2002, the Kansai Medical University reported that AHCC® intake after surgery contributed to an increase in survival rate in patients with primary liver cancer. There are more AHCC® research papers published regarding cancer and other diseases. <Source> Japanese Wikipedia Encyclopedia

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AHCC®

The Structure of AHCC® AHCC® is a polysaccharide obtained from enzyme reaction after culturing the mycelium part of Basidiomycetes in fluid for about two months in large tanks. It has not only β-glucans, the primary component of mushroom based supplement, but also lots of α-glucans which have a lower weight molecule than β-glucan. The presence of acetylated α-glucan is the big difference between AHCC® from other mushroom-based supplement.

β-glucans, α-glucans In general most common mushroom based health foods consist of a polysaccharide called β-glucan which is a beta-combination of two monosaccha-

OH

ride of glucose. In contrast, alpha glucan is an alpha-combination. Not like

O

other mushroom based supplement, AHCC®’s primary ingredient is acetylated α-glucan. Glucans are polysaccharides and are well known to have a physio-

OH O

OR

OR

O

O OR

logical activation function, an action to stimulate the body’s ability. Acetylating is

OR

α-1, 4 glucan(R : H or CH3CO-)

adding acetyl group (CH3CO-) to the glucans. This acetylated α-glucan is the ®

uniqueness of AHCC . It is not commonly seen in other health supplements.

n

< α-1, 4 glucan >

Acetylated α-glucan has a comparatively low molecular weight (around 5,000 CH2OH O

daltons) while β-glucan has the molecular weight in the range of tens to hundreds of thousands of daltons. Therefore, acetylated α-glucan has different

CH2OH O

digestive process and functions in the body. High molecular weight β-glucans are difficult to digest and absorb, they demonstrate some immune boosting action by stimulating the intestinal tract, but acetylated α-glucan demonstrate a direct systemic immune boosting action after they are digested and absorbed.

O

OH

O

OH

OH OH β-1, 3

β-1, 4

m

n

< β-glucan >

AHCC®

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®

AHCC

AHCC® Activates the Immune Cells to Fight Cancer AHCC® activates white blood cells and lymphocytes which directly attacks viruses that penetrate from outside of the body, abnormal cells created inside the body, and strange viruses that invaded but are hardened. Unlike chemotherapy drugs, AHCC® is not directly attacking cancer cells. It stimulates the immune cells to indirectly fight cancer by adjusting the body’s natural balance.

According to many basic research on AHCC®, it is known that AHCC® helps balance and boost overall the biological immune system. Here are some of the highlights on AHCC®’s research ■ AHCC® induce cell-mediated immune cytokines such as TNF-α, IFN-γ, IL-1, IL-2, IL-12 ■ AHCC® activates cancer attacking immune cells such as macrophages, NK cells, LAK cells, and Killer T cell (CTL) ■ AHCC® activates Th1 immune cells (Helper T1 type), the key to cell-mediated immunity ■ AHCC® suppress cell-mediated immune cytokines such as TGF-β

Articles on AHCC®’s Immune Boosting

®

AHCC Alleviates the Side Effects Caused by Chemotherapy Anti-cancer drugs (chemotherapy) cause side effects including nausea, vomiting, hair loss, loss of appetite, liver dysfunction, loss of WBC & RBC, Platelet and more. These side effects can cause unbearable pains and more worryingly lower immunity and vitality.

It is well known that AHCC® is effectively alleviating chemo side effects. This AHCC®’s effectiveness was observed from the human ®

tests in which cancer patients took both chemotherapy and AHCC .

The same result was observed in animal tests as well.

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- PubMed ID 20732368 Yale University , Havard medical school - PubMed ID 22531483 Yale University, Seoul University microorganism - PubMed ID 19087767 M.D. Anderson Cancer Center

Articles on AHCC®’s Alleviating Chemotherapy Side Effects - PubMed ID 19699163 Amino Up Chemical Co.Ltd., Japan - PubMed ID 23829813 University of Tokyo Oncolgy

Articles on AHCC®’s Liver Dysfunction Prevention - PubMed ID 19699163 Amino Up Chemical Co.Ltd., Japan

Articles on AHCC®’s Other Effectiveness - PubMed ID 15147233 nUniversity of Tokyo Biochemstry - PubMed ID 17449585 Uiversity of Granada, Spain

Fucoidan & AHCC®

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AHCC®

AHCC®’s Effectiveness in Scientific Studies 1. AHCC® efficacy on liver related diseases • Prevents liver dysfunction caused by free radicals* • Prevents hepatitis* • Prevents liver dysfunction caused by chemotherapy* • Improves chronic liver disease caused by alcohol*

Activation

2. AHCC® prevents liver dysfunction caused by chemotherapy Liver plays a role as detoxifier to remove toxins which embedded in 180 Control drugs that enter the body with treatment. The more work is assigned to the 160 AHCC 6MP+MTX 140 liver, the more damage the liver gets. In this regard among all organs, the AHCC+6MP+MTX 120 100 liver is at high risk when chemo drugs are treated. One of the critical side 80 effects that the liver gets is liver dysfunction. In this test, researchers ex60 ® 40 plored the effect of AHCC on hair loss in rats exposed to a chemotherapy 20 ® 0 drug and the impact of AHCC on modulating liver damage. They adminissGOT sGPT tered a single dose of 6-MP plus MTX, two antimetabolite, cancer-fighting drugs, to two groups of rats: one group received the drugs only and a second group received AHCC® for 28 days plus a single dose of 6-MP plus MTX. The scientists found that rats given AHCC® had normal levels of SGOT and SGPT while the untreated rats had large increases in these enzyme levels. All these factors together indicated that AHCC® significantly reduced the side effects associated with the chemotherapy drugs and improve the function of the liver.

3. AHCC’s additional effectiveness In addition to AHCC® research papers for anti-tumor or liver improvement, there are many other reports that introduced AHCC®’s additional effectiveness including anti-diabetic action, antioxidant ability, anti-inflammatory, and tranquilizers (improving Quality of Life). These effectiveness are not contradictory to each other since they can be shown while AHCC® adjusts the body’s natural balance.

AHCC®

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Function of the β-glucans Present in the Agaricus mushroom Agaricus mushroom is originally from Brazil and has been known as anticancer mushroom. Its major anticancer ingredient is β-glucan. They have the ability to stimulate the immune cells in our body such as macrophages and NK cells. This stimulation boosts the body’s natural ability to fight against foreign cells and viruses.

Agaricus

Synergistic Effectiveness of Fucoidan, Agaricus and AHCC® From a number of animal and clinical studies, Fucoidan, Agaricus and AHCC® are well known for their powerful anticancer effect and chemotherapy side effect mitigation functions. Other than their anti-cancer effects, not Fucoidan and Agaricus, but especially AHCC® has unique effectiveness on liver function and prevention from damage. AHCC® effectively detoxifies toxins accumulated inside the body from long-term chemotherapy. AHCC®’s unique effectiveness has been studied and reported. In this regard, the formula of Fucoidan, Agaricus, and AHCC® mixture is one of the best health ingredient combinations and is expected to have a powerful synergistic effect.

Synergistic effectiveness Agaricus mushroom ®

AHCC Fucoidan

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Comparison & Synergy of Fucoidan, Agaricus and AHCC®

Effectiveness & Benefits

Anticancer activity

Fucoidan

Agaricus

AHCC®

Induce cancer cell death (Apoptosis)

√

Suppress cancer Angiogenesis

√

Boost immunity (Enhance immune cells)

√

√

√

√

√

√

Alleviate chemotherapy side effects Prevent liver dysfunction caused by chemotherapy (Enhance liver’s detoxifying activity)

√

Improve liver function (effectiveness on advanced liver cancer cirrhosis)

√

Important role in managing hypertension, hyperlipidemia, diabetes, inflammation and viral infections

√

√

√

Molecular weight

High

High

Low

Primary anticancer ingredient and structure

Sulfated fucose polysaccharide

Beta-glucan

Acetylated alpha-glucan

Anticancer studies in hospitals in Japan and USA

★★

★

★★★★★

Comparison & Synergy of Fucoidan, Agaricus and AHCC®

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Q&A How are Fucoidan and AHCC® different?

Fucoidan is a very precious substance which can be extracted an extremely small amount from brown seaweeds such as Wakame, Kombu and Mozuku. It is a type of soluble dietary fiber and a viscous polysaccharide. AHCC® (Active Hexose Correlated Compound) primarily consists of an α-glucan polysaccharide mixture which is acetylated from the sterile culture enzyme of the basidiomycete in Shitake mushroom mycelium. Both Fucoidan and AHCC® are well know for outstanding anticancer effects.

Are Fucoidan and AHCC® likely to be approved as a drug?

Many anti-cancer drugs are synthetically made by chemically imitating natural substances. For example, Lentinan and Krestin are approved chemotherapy drugs made by using mushroom extracts. However, it is not easy to develop this type of natural substance based drug because the process requires enormous investment which only a few major pharmaceutical companies afford to invest. Based on many researches and studies, Fucoidan and AHCC® have been found to be highly reliable substances, but the reason for not seeking to be classified as a pharmaceutical has nothing to with their effectiveness. The main reason to be remain classified as a health food is to make the best use of their wide-ranging properties.

Are there any problems in taking chemo drugs with Fucoidan and AHCC®?

There were many studies showing that Fucoidan and AHCC® alleviate chemo side effects, reduce edema, and extend lifespan when being treated together with chemo drugs in animal tests. By the same token, cancer patients may consider extending lifespan, preventing and alleviating chemo side effects by taking Fucoidan and AHCC® with chemotherapy drugs. Especially the side effects like hair loss, bone marrow suppression, loss of appetite, vomiting can be critical problems in terms of QOL (quality of life), and because of these side effects sometimes cancer patients are not able to continue with the chemotherapy.

Fucoidan and AHCC® are well known for helping to alleviate the chemotherapy side effects and boost the immune system which can be easily damaged by these drugs.

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Q&A Are there any side effects on Fucoidan and AHCC®?

Since Fucoidan is extracted from natural brown seaweeds such as Wakame and Mozuku there should be no concern on regards to any side effects. AHCC® safety test was carried out according to GLP (Good Laboratory Practice).

Even though a megadose of 600 g was administrated on rats, no toxic effects were observed.

What is the synergistic effect by taking Fucoidan and AHCC®?

Other than an immune boosting effect, not like that of Fucoidan and Agaricus, AHCC® is well known for improving liver fatigue and damage caused by long-term chemotherapy. This liver support is the one of the uniqueness of AHCC® and has been studied and reported through many studies. The mixture formula of Fucoidan, Agaricus and AHCC® is the best unprecedented supplement combination that is expected to demonstrate powerful synergistic effect.

Is cancer going to be cured or improved by taking Fucoidan and AHCC®?

No. Even though the anticancer effects of Fucoidan and AHCC® have been reported through more than 1,000 research papers including effectiveness of producing cytokines, and most of cases immunity enhancement by taking Fucoidan and AHCC® was confirmed, it does not mean that cancer will be certainly cured or improved. Based on user’s physical constitution and disease condition, there might be no response to Fucoidan and AHCC®. Fucoidan and AHCC® should be considered as heath dietary supplement, not a drug. It is highly recommended to take them along with your conventional treatments.

Would you advise when to take and the recommended daily intake?

If you take a product that contains Fucoidan and AHCC® and your main concern is health maintenance and disease prevention, 1-2 g/day of the mixture is suggested. For preventing cancer relapse, 2-3 g/day are suggested, and when taking together with cancer treatment, 4-8 g/day are suggested. You can divide the suggested dosage in 3~4 times a day. Since there is no side effect when taking together with chemotherapy and radiation therapy, it is perfectly okay to begin taking even before you start the chemotherapy and radiation therapy. However, Fucoidan and AHCC® are health dietary supplements, not drugs and they should not be considered as drugs to cure cancer or other diseases.

Q&A

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FOR EDUCATIONAL PURPOSES ONLY Disclaimer This catalog is watermarked because it includes certain information that has not been evaluated by the U.S. Food and Drug Administration. This catalog is intended for educational purposes only and is subject to the following conditions: (a) the content may be used solely for information purposes and may not be used for commercial purposes; and (b) the content may not be modified or altered in any way. You may not republish, distribute or prepare derivative works.

The information is intended to help the reader round out their understanding of some of the complexities and difficulties involved in the research of complex carbohydrates as is the case of polysaccharides. None of the information contained herein or materials provided are intended to constitute medical advice or professional services. The information provided should not be used for diagnosing or treating a health problem or disease. It is not a substitute for professional care.

If you have -- or suspect you may have – a health problem, you should consult your health care provider. The information provided regarding the functional ingredients mentioned does not, in any way, relate to any finished dietary supplements. *These statements have not been evaluated by the Food and Drug Administration. The information on this catalog is not intended to diagnose, treat, cure or prevent any disease.

ⓒAll Rights Reserved 2014

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AHCC® is a registered trademark of Amino Up Chemical Co., Ltd.

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