fucoidan training materials - prevention...

Fucoidan training materialsフコイダン研修資料

Copyright(C) NPO Fucoidan Reserch Institute All Rights Reserved.

1. Introduction of fucoidan

フコイダンとの出会い


Reason for the research and development of fucoidan

フコイダンの研究開発に至った理由

Longevity = Okinawa

長寿沖縄

Okinawa = Longevity

Okinawa crisis (2000)おきなわクライシス


Age of 0 Age of 40 Age of 65 Age of 75

Japan 79.59 Japan 40.77 Japan 18.78 Japan 11.50

1 長野県 80.88 長野県 42.13 長野県 19.71 沖縄県 12.352 滋賀県 80.58 福井県 41.66 沖縄県 19.50 長野県 12.053 福井県 80.47 滋賀県 41.65 熊本県 19.46 熊本県 11.914 熊本県 80.29 熊本県 41.36 京都府 19.20 大分県 11.865 神奈川県 80.25 奈良県 41.34 福井県 19.19 京都府 11.756 京都府 80.21 京都府 41.33 滋賀県 19.18 神奈川県 11.737 奈良県 80.14 岐阜県 41.33 大分県 19.17 広島県 11.738 大分県 80.06 神奈川県 41.27 広島県 19.10 島根県 11.699 山形県 79.97 大分県 41.26 神奈川県 19.06 東京都 11.6710 静岡県 79.95 香川県 41.15 香川県 19.06 宮崎県 11.66

Japan 86.35 Japna 47.13 Japan 23.84 Japan 15.33

1 長野県 87.18 沖縄県 47.98 沖縄県 24.89 沖縄県 16.462 島根県 87.07 島根県 47.93 熊本県 24.57 熊本県 15.983 沖縄県 87.02 熊本県 47.84 島根県 24.51 島根県 15.954 熊本県 86.98 長野県 47.82 長野県 24.36 石川県 15.765 新潟県 86.96 福井県 47.76 広島県 24.31 広島県 15.746 広島県 86.94 新潟県 47.75 福井県 24.29 宮崎県 15.717 福井県 86.94 広島県 47.72 新潟県 24.28 富山県 15.708 岡山県 86.93 富山県 47.71 鳥取県 24.27 福井県 15.679 大分県 86.91 大分県 47.70 富山県 24.26 北海道 15.6510 富山県 86.75 岡山県 47.64 石川県 24.23 鳥取県 15.64

Life expectancy by ages（Health, Labour and Welfare Ministry )


Prefectures Expectancyof life

Male

Female

Order Prefectures Expectancyof life



Okinawa

Okinawa

Okinawa

OkinawaOkinawa

Okinawa

Why did Okinawa crisis occur?なぜおきなわクライシスが起きたのか？

Older generation（高齢者）： traditional Okinawa food culture伝統的な沖縄の食文化

Younger generation（中年～若年）： alternation of dietary habits from Okinawa

food culture to Western 食生活の欧米化


Traditional Okinawa food culture伝統的な沖縄の食文化

（nuchigusui※

）

●Large intake of green and yellow vegetable緑黄色野菜の摂取量が多い

●Large intake of beans represented by Tofu豆腐等の豆類の摂取量が多い

●Large intake of fruits フルーツの摂取量が多い

●Large intake of seaweeds (Mozuku, Kombu)海藻（もずく・こんぶ）の摂取量が多い

●Less intake of salt塩分の摂取量が少ない


※ nuchigusui…Meaning of “medicine of life” in Okinawa dialect

Longevity food in Okinawa


1. Snail mugwort

2. Beninacasa

3. A type of

cucumber

4. Island carrots

5. Goya

6. Loofah

7. Papaya

Components of Kusuimun※

diet健康長寿食材の成分

※ Kusuimun…Healthy food, Medicine food in Okinawa dialect

Island Tofu：Isoflavone, lecithin, oligosaccharide島豆腐：イソフラボン・レシチン・オリゴ糖

Island vegetable：Carotenoid, Vitamin C 島野菜：カロテノイド・ビタミンC

Fruits ：Polyphenol, Nobiletin 果物：ポリフェノール・ノビレチン

Seaweeds：Fucoidan, Alginate海藻：フコイダン・アルギン酸



Okinawa foods have a lot of

Kusuimun nutrients, meaning “healthy

food with medicinal powers.”

沖縄食材には、医食同源につながるクスイムンの成分が多く含まれているのではないか？

⇒ We focused on seaweed (Mozuku and Mekabu). 海藻（モズク、メカブ）に着目

Okinawa Mozuku（Sunui）


Mekabu（Kelp）


Ingredients and effects of Mozuku, Mekabu

Surely, Nuchigusui

Effects:

Anti-tumor effect

Anti-oxidant effect

Anti-allergic

Anti-Helicobacter pylori effect

Anti-aging effect

Lifestyle diseases prevention effect（such as hypertension, diabetes, hyperlipidemia, arteriosclerosis)


Component

Fucoidan, Alginate, Arachidonate, EPA, Fucosterol,

Fucoxanthin

What is fucodian?

Fucoidan is one of the water-soluble dietary fibers in a slimy

component of brown algae like kelp, Mekabu and Mozuku.

They have immuno-stimulatory effects

Functions of fucoidan in seaweed

・ Restoration of damage

caused by the water impact

・ Protection from surrounding

microorganisms

・Protection from drying during low tide

Fucoidan is sulfated polysacharide, which contains

two main components: fucose and sulfate-groups.

Mozuku Kelp

Mekabu


2. What is fucocidan?

Let’s understand the structure of fucoidan


Entire structure of fucoidan フコイダンの全体構造

In the broad sense it is “sulfated polysaccharide ” which contains fucose and sulfate group, also includes various substance such as pigment and minerals.

Fucoidan is extracted from seaweed like Mozuku and Mekabu , and concentrated into powder.

It has been proved from past studies and clinical results fucoidan that is refined excessively has the best effect. Fucoidan Umi No Shizuku has not only sulfated polysaccharide, but also pigment and minerals, which have beneficial effects.


sulfated

polysaccharide

pigmentsulfate

groupminerals

Fucoidan is composed of the sulfated polysaccharide 1 mainly.

This sulfated polysaccharide can be called Fucoidan in the narrow sense.

Broad sense: contains things like minerals, pigment

Narrow sense: only sulfated polysaccharide

Structure of Fucoidan（For sulfated polysaccharide）


12

Fucoidan (sulfated polysaccharide) in the narrow sense is comprised of various ingredients, like above illustration. The narrow sense of fucoidan will vary greatly depending on to raw materials (Mozuku or Mekabu). Fucoidan configuration varies according to an origin, but it is the same polysaccharides which is comprised by many sugars, and each fucoidan molecule weight is different (there are ten and hundred thousands of macromolecules




The structure of the sulfated polysaccharide is different in every origin. The characteristic of Okinawa Mozuku Fucoidan has many fucose and Mekabu has many sulfate groups.

Fucose

Sulfate groups Sulfate groups

Okinawa Mozuku Wakame (Mekabu）


Fucose

Components of the sulfated polysaccharidesFucose Uronic acid （Glucuronic acid）Galactose RhamnoseMannose Sulfate groups Xylose



Component of sulfated polysaccharide


Sulfate groups It is the basic slime of seaweed. It is the important component to induce apoptosis (self destruction).

FucoseIt is a main sugar component of fucoidan , and binds to the carbohydrate chain of protein in the body and affect to a cancer, inflammation and immunoresponse.

Galactose It is existed as component s such as lactose, and an important component of oligosaccharides that contains in nerve system.

MannoseIt is present as a ingredient of the konjac mannan. It is important as a constituent sugar of glycoprotein.

XyloseIt has the characteic of indigestibility, non-fermetable, and non-carious （not have a carious tooth) and it is used as a sweetener.

Uronic acid（Glucuronic

acid）

It will be changed to a substance with a strong anti-tumor effect called DHCP (dihydroxy /cyclopentene) by heating fro a long hours.

There is some scientific evidence if there are many sulfate groups, it has more effective. The left-hand figures are part of the experimental results of cytokine comparison between Mozuku fucoidan and Mekabu fucoidan. We did compare every cytokine, but if an effect of fucoidan is determined by the content of sulfate groups, Mekabu fucoidan will have the high evaluation of fucoidan efficacy. However, as shown in the left figure, there is disadvantage and advantage between Mekabu fucoidan and Mozuku fucoidan, it does not mean one is the best one. Therefore, should not pay attention only on the content of sulfate groups, it is good to focus on a well-balanced mixed type of fucodian.

※On the left side experimental results is a part of the preliminary experiment, thus indicate only simple result,


IFN-γ

IL-17

IP-10


IFN-γ

Refereances：For cytokine-chemokine production of Mozuku and Mekabu fucoidan

GMCSF

IL-1α

TNF-α

IL-17

IP-10

KC

MIP-1α

The above results shows only few measured types cytokine and chemokine, because so many cytokine and chemokine are discovered. We only shows them as a reference because of a preliminary experiment.

Structure of Fucoidan（Components contained in the fucoidan）

Minerals

PotassiumSodiumCalciumMagnesiumIronZinc


sulfated

polysaccharide

pigmentsulfate

groupminerals

Minerals


Sodium It perform the adjustment of the hydrogen ion concentration (pH) in the blood and the osmotic pressure.

Potassium

It perform the adjustment of the hydrogen ion concentration (pH) in the blood and the osmotic pressure. It helps a discharge of excess sodium and prevent hypertension.

Calcium

It is important as an ingredient of a bone and tooth . It works for suppressing irritation of the nerve and activating heat regularly to contract the muscle.

Magnesium

It need for formation of bones and teeth. It helps with energy production and normal function of many internal enzymes.

Iron

It is important to transport oxygen by red blood cells. It works as an component of enzyme to involve removing free radicals and producing energy.

Zinc

It works as a component of 40 different types of enzyme. It also works for keeping taste normally, mucous membranes and skin healthy.


Pigment

Fucoxanthinβ-carotene, and Chlorophyll


sulfated

polysaccharide

pigmentsulfate

groupminerals

Pigment


Fucoxanthin

It is one of carotenoid containing in the seaweed. It has a strong ant-tumor effect stopping proliferation or lower the growth of cancer cell. Apoptosis effect has also reported.

β-carotene

It has a powerful antioxidant effect. It protect the cellular tissue such as eyes, skin and internal organs from damage of free radicals. It remove free radicals and inhibit carcinogenesis.

Chlorophyll

It shows the antioxidant effect in conjunction with β-carotene and inhibit carcinogenesis. It lower the cholesterol in the blood. It works for preventing and improving anemia.It count on detoxification, intestines and anti-inflammatory effect.


Other

Dietary fiberProteinLipidPolyphenolAnd Fucosterol


sulfated

polysaccharide

pigmentsulfate

groupminerals

Other ingredients


Dietary fiber

It induce defecation, and it also adsorbed cholesterol and carcinogens in the large intestine and promote to exclude them. It increase the good bacteria in the intestines.

Proteinit is the material to build the body. It is used as synthesis of biological material or energy source.

LipidIt make biological membranes such as cell membranes. It inhibits absorption such as fat soluble vitamins.

Polyphenol（Phlorotannin ）

Polyphenol contains in a seaweed a lot is Phlortannin. It remove free radical and inhibit the activation of carcinogens, in additionally, inhibit angiogenesis in cancer cells.

Fucosterol It is a kind of plant sterols, and reduce the cholesterol in the blood.

【Components】【Detail 】

Sulfated polysaccharide

It is macromolecular polysaccharide made from sugar and other

sulfated fucose.

MineralsPotassium, sodium, calcium and

magnesium

PigmentFucoxanthin, -carotene and

chlorophyll

OthersDietary fiber, protein, lipids, polyphenols, and fucosterol

【Summary 】What is fucoidan …


3. What is agaricus ？

Let’s understand Agaricus

（Agaricus blazei Murill）correctly


What is Agaricus？

Agaricus grew wild near plateau city of Sao Paulo Brazil (792 m above sea level) and since it inhabited under a specific environment, Agaricus used to be called the “mushroom of illusion”. Agaricus has various kinds, but the one used as a health supplement called a scientific name with Agaricus blazi Muril, and as for Japanese name called Himematsutake, or Kawariharatake. In Japan, “Iwade 101 Strain ” is the famous agaricus because they has many scientific data. Function of Agaricus research has been started and attracted attention at the Cancer Society because the local people who consumed Agaricus had extremely low pathogenesis. Agaricus contains β-D-glucan, glucan protein complex, acidic hetero glucan, xyloglucah, hetero glucan complex RAN protein complex and glucoprotein (lectin), and it has variety of biological effects such as immunostimulatory effect, anti-tumor effect and hypoglycemic effect.


Fruit body and mycelium子実体と菌糸体

Fruit body is the mushroom that we

usually eat. Mycelium is the one that grew

silky like form at the root part before

mushroom grow.

As for componets, β-glucan that is the

pharmaceutical product such as “Krestin”

or “Lentinan” is famous, but in general,

fruit body contains more β-glucan than

mycelium part. However, fruit body

contains slight weak carcinogenic

substance called “Agaritine”. Mycelium

part has used as supplement because of

safer than fruit body. In addition,

comparing with fruit body and mycelium

part, mycelium part has excellent

nutrients, such as protein and amino-acid,

and well-balanced mineral, in as well as

β-glucan.

What are fruit body and mycelium？

Fruit body

Mycelium

Culture

medium

Metabolite

Features of mushroom


Comparison between fruit body and mycelium of Agaricus blazei Murill

資料提供：株式会社沖縄発酵化学

Test of activation of

macrophage as an index to

the amount of glucose

the tumor cell growth inhibitory

effect against Sarcoma180



In the comparison experiment between

Agaricus mycelium and fruit body, we

found that mycelium has excellent

immunostimulatory effect and anti-

tumor effect.

Comparison between fruit body and mycelium of Agaricus blazei Murill

The fruit body of mushroom contains ”Agaritine” which is weak

carcinogenic substance and may cause cancer. Agaricus fruit body

contains Agaritine was reported. As for the safe standpoint, Mycelium is

safe because mycelium does not contain “Agaritine”.


About culture mediumThe mushroom bed generally uses “sawdust (waste wood)” but Agariscus blazei

Murill is vulnerable to various germs and it is difficult to cultivate in sawdust,

therefore it is adapted “Liquid culture” contains liquid such as glucose for culturing

mycelium. The liquid culture can do mass production for short period of time, but

there is a disadvantage that the functionality is lower than solid culture due to the

short growing period. Therefore, “Bagasse medium” was made instead of the solid

culture.

Bagasse medium is an solid medium that made with remaining fiber (bagasse)

which squeezed molasses of sugar cane. Study of the sugar cane cultivation that

is one of the major industries of Okinawa and study of culture of Agaricus blazei

Munill matches that is the reason bagasse medium was produced. Now it has

excellent functionality of Agaricus culture than the liquid medium.

Left：sugar cane field Above：sugar caneThe refined sugar is eaten as “brown sugar” in Okinawa

Comparison between Bagasse and liquid mediumバガス培地と液体培地の比較

資料提供：株式会社沖縄発酵化学

The glucose consumption sthenia activity against Agaricus mycelium

Influence on Molt4 (T lymphocytic leukemia) cell



In the comparison experiment of the

culture method with liquid culture

commonly used for the cultivation of

Agaricus blazei Murill, we found that

bagasse medium has excellent action

for immunostimuratory and anti-tumor

effects.

Comparison between Bagasse and liquid mediumバガス培地と液体培地の比較

Comparison between Agaricus and Reishi myceliumアガリクス菌糸体とレイシ菌糸体


IL-12 producing promotion effect on macrophages of Agaricus mycelium* IL-12 stimulates the growth and function of T cells and alters the normal cycle of apoptotic cell death


We found that Agaricus extract powder

cultured in bagasse medium has the

excellent effect of immunostimulatory.

Regarding to the frequent question of Reishi, we

did the comparative experiment between Reishi

mycelium extract powder and Agaricus extract

powder cultured in bagasse medium .

Comparison between Agaricus and Reishi myceliumアガリクス菌糸体とレイシ菌糸体

4. About Fucoidan mix AG

Let’s understand about fucoidan mix

AG and the functionality

Copyright(C) VENTUNO Co.,Ltd. All Rights Reserved.

What is fucoidan mix AG

Fucoidan mix AG is the one is mixed with Okinawa Mozuku fucoidan , Mekabu fucodian and Agaricus mycelium extracted powder in the constant combination ratio.

We developed fucoidan mix AG to focus on the difference effect between the origin of fuccoidan and synergy with agaricus.

We have explained our fucoidan under the name of “fucoidan mix AG” instead of “fucoidan mix” because we mixed with Agaricus mycelium extract powder, therefore may mislead under the name of “fucoidan mix”.


The following are a mechanism of apoptosis

① Inhibition of DNA synthesis incancer cells by apoptic factor

② Destruction of the cell membrane of cancer cells by perforine released fro T cells and NK cells

③ Inhibition of apoptosis by various caspase (any of a group of proteases 蛋白質分解酵素 that mediate apoptosis) and Fas.

We are still in middle of research, but we found that fucoidan involved in some sort of function in all mechanism except Fas.

•Fas ligand is a type a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. Its binding with its

Induces apoptosis.

Apoptosis inducing effectアポトーシス誘導作用


Mozuku fucoidan has superior

Apoptosis inducing effect


Angiogenesis inhibitory effect血管新生抑制作用


control Mozku fucoidan Mekabu fucoidan

Mekabu fucoidan has superior

Angiogenesis inhibitory effect


Immune enhancing effect免疫賦活作用


Agaricus

mycelium

Immune enhancing effect due to

superior Agaricus mycelium extract

powder, but of course as well as

Mozuku and Mekabu fucodian.


Fucoidan

mix AG



Mekabu fucoidan Agaricus mycelium

Mozuku fucoidan

Immune enhancing effect


Fucoidan mix AG has three effects against anticancer

Synergistic effect of three kinds of mixture in immunostimulatory power


Why Fucoidan mix AG is effective ?

Fucoidan mix AG

Reduction of chemo-side effect


5-fluorouracil and side effect

control control fucoidanmix AG

fucoidan

mix AG

About fucoiddan content in fucoidan mix AGWe will explain the content of

fucoidan in the broad sense and the narrow sense as a premise. Fucoidan mix AG is the form that contains Agaricus, therefore fucoidan content will be 85%. This 85 % means fucoidan in a broad sense. Fucodian in the narrow sense refers to the sulfated polysaccharide. Our previous explanation of fucodian contaent is approx. 45 % , but this 45 % means the content in the fucoidan mix (including Agaricus). Considering only fucoidan, the content of fucoidan is 53 % in the broad sense by our calculation.(45%÷85%=0.529… →≒53%)


Fucoidan Mix AG summary

Sulfated polysaccaride

Macromolecular polysaccharide made from other sugar and sulfated

fucose

Minerals Potassium, sodium, calcium and

magnesium

Pigment Fucoxantin, -carotene

andchlorophyll

Others Dietary fiber, protein, lipids, and

fucosterol

Mycelium extract ‐ glucan 、and -glucan

Agaricus（AG）

Fucoidan （Okinawa Mozuku, Mekabu Mix）


Effect of fucoidan mix AG

Fucoidan

Mix AG

Reduction of chemo side effect


(Metastasis suppression)



Immune enhancing effect

Why two kinds of fucoidan and agaricus

blazei muril is better mixture?

Ingredient of immune function

enhancement and regulation

○Agaricus（fruit body・mycelia）○Phellinus linteus○Ganoderma lucidum○Cordyceps militaris○Fucoidan○Panax ginseng

○Curcuma longa○Arabinoxylan○Isoflavone○Shark caritage○Propolis○Tabebuia avellanedae

・・・and so on


・Agaricus（fruit body or mycelia）・Phellinus linteus（ fruit body or mycelia ）・Cordyceps militaris（fruit body or mycelia）・Pleurotus cornucopiae（ fruit body ）・Hericium erinacium（ fruit body ）

・Sparassis crispa（ fruit body ）

・Ganoderma lucidum（ fruit body ）

・Arabinoxylan・Tabebuia avellandae・Propolis

・Panax ginseng・Curcuma longa・Isoflavon・Glycine max・Shark caritage

・Mozuku fucoidan・Mekabu fucoidan

We compared the effect of cytokine production of like macrophage cell, RAW264.7

by mixing these immune enhance ingredient we could get into two kinds of fucoidan

(mozuku and mekabu) as same as fucoidan mic AG.


Why two kinds of fucoidan and agaricus

blazei muril is better mixture?

Macrophage enhancement effect of

Fucoidan mix + the immune enhance ingredient

Fucoidan mix=MozukuFucoidan and MekabuFucoidan

M=Mycelia

F=Fruit body

FucoidanMix


Fucoidan mix AG is the best mixture

Two kinds of fucoidan and

agaricus brazei murill mixture is

the strongest immune

enhancement. (=anti cancer

effect)


5. Fucodan intake method・Safety


Fucoidan intake Q&A

Q1.How to take fucodian?

A1. We recommend to take before meal.

Reason - diabetes in particular, you can expect glucose

level will elevate slowly by taking fucoidan before meal.

As for ingestion time and the number of intake time for

fucoidan, we recommend four times a day.

Activity of NK cells as a representative index of immunity

is decrease 6~8 hours after intake fucoidan, it is better

to take fucoidan for several times a day because of

keeping high level of immunity. In addition, cancer will be

activated at night, thus more effective way is to take it

before sleep.


Fucoidan intake Q&A

Q2.Which one is better, drink or capsule type to take ?

A2. Quality of drink and capsule type has no different, it

is only difference in shape.

However if you take large quantity, it is better to take

drink type. Also, the combination of liquid and capsule

type is recommended for adjusting intake volume and

times.

Drink type has flavor, even if you are used to drink liquid

type, it may not take it due to chemo, radiation or other

reasons. In that case, it is good idea to switch to capsule

type. Either way if your symptom is severe, you can take

large quantity of fucoidan. Whatver the quantity, it is a

good idea to emphasize taking fucoidan every day.


Fucoidan intake Q&A

Q3. Do effects of fucoidan depended on dosage?

A3.Yes.

As you see the figure, the

higher dosage of fucoidnan

will show NK cells will

activate more. However,

since fucoidan is dietary fiber,

it may cause soft bowel

movement when you take

large amount of fucoidan.


Fucoidan intake Q&A

Q4. What should you confirm before taking fucoidan mix AG

(Umi No Shizuku) ?

A4.The person who has cancer in particular please ask

following items in advance and if necessary, please consult

Dr. Tachikawa.

--- Consulting items---

□ Ask presence of seaweed and mushroom allergy□ Ask present and past medical history, where primary cancer was before metastasis and where it

metastasized

□ Ask the method of treatment (chemo, radiation) or medication

□ If having cancer, ask cancer type and stageCopyright(C) VENTUNO Co.,Ltd. All Rights Reserved.

Thank you


fucoidan training materials - prevention...

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