inulation ® - inulin - guardians nutraceuticals guardians nutraceuticals presents

Inulation® - Inulin - Guardians Nutraceuticals™

Guardians Nutraceuticals™

Presents

What is Inulation

O HOCH2

HO

CH2

HO

CH2OH

n (2-60)

CH2OH

HO

O

O HOCH2

HO

HO

O

OH

HO

O®

Inulin is a polydisperse GFn

molecule Linear chain of fructose units

- having mainly one terminal glucose molecule

Fructose units linked by ß (2-1) bonds


Guardians Nutraceuticals™

Natural Occurrence Inulation® - Inulin is found widely in over 36,000 plants,

including common vegetables, as its reserve energy food e.g.:

Source Inulin contentChicory 15 - 20 %Wheat 1 - 4 %Garlic 9 - 16 %Onion 1 - 8 %Banana 0.3 - 0.7%Asparagus 2 - 3 %Leek 3 - 10 %J. artichoke 16 - 20 %

• common in human food, and as an ingredient GRAS


Primary US inulin intake by food source

69%

23%2%

3%3%

Source: CSFII 1994-96, 2 days, all individuals, midpoint values.

Wheat

Onion

Banana

Garlic

Other


Health concern/disease

Preventative Food Type

ColonCancer

Bran/grains19%

Fiber22%

Fruit6%

Vegetables21%

Source: International Food Information Council (IFIC) 1998


Health concern/disease

Preventative Food Type

HeartDisease

Fish/fish oil

11%

Fiber/grains10%

Fruit12%

Vegetables17%

Low fat/Cholesterol

Food7%

Source: International Food Information Council (IFIC) 1998



Harmful BeneficialPs. aeruginosa

vibrionaceae

staphylococci

clostridia

veillonellae

enterobacteria

E . coli

lactobacilli

sulphate reducers

anaerobic G+ cocci

methanogens

eubacteria

bifidobacteria

bacteroides

diarrhea/constipationinfectionssystemic effects

prodn. of potentialcarcinogens

prodn. of toxic H2S

intestinal putrefaction

aid in digestion and/or absorption of food ingredients/minerals synthesis of vitamins

Inhibit growthof exogenus and/or harmful bacteria (competitive exclusion, antimicrobials, low pH)

stimulate immunefunctions through non-pathogenic means, anti-tumor properties, cholesterol reduction

2

6

8

pathogenic(incl. productionof toxins)

number/g feces log10 scale

lower gas distension


Disease conditions associated with unbalanced eco-system

Autoimmune diseases, such as rheumatoid arthritis, Grave’s Disease, and lupus

Candida yeast overgrowth Urinary tract infections IBS, IBD, Crohn’s Ulcers Food allergies and

intolerances

Diarrheal disorders (rotavirus, antibiotic effects, E. coli)

Cirrhosis of the liver Colo-rectal cancer Digestive problems Intestinal gas and bloating CVD (Heart Disease)


METABOLIC FATE

no hydrolysisnegligible bacterial utilization

negligible acid hydrolysisno enzymatic hydrolysisno absorption

no enzymatic hydrolysisno absorptionnegligible fermentation

complete anaerobic fermentationno absorption of inulin or itsmonomeric building blocks

No excretion

Oral cavity

Stomach

Small intestine Colon

Stools


Bifidogenic effectsHuman in vivo study (15 g/d)

Source: Gibson et al. Gastroenterology, 1995

Bacteroides

Bifidobacteria

Fusobacteria

Clostridia

65%

20%

12%

3%

71%

26% 3%

0.3%

Before intake After inulin intake

Clostridia

Fuso.


Health promoting functions of Lactic acid bacteria

Bifidobacteria & Lactobacilli spp. and SCFA mediated effects

General bacteria effects

produce B-vitamins, vitamin K, digestive enzymes

produce immune-stimulating factors

absorb procarcinogens

inhibit growth of pathogens

reduce food intolerance & allergies, I.e. lactose, protein

breakdown

SCFA effects

colonic pH via acetate & lactate production

acid environment inhibits activity of certain

procarcinogenic enzymes

convert NH3 to NH4, lowering it as a liver

toxin

improve absorption of calcium, iron, etc.

provide positive effects on carbohydrate and

lipid metabolism


Physiological Effects (1)

Local (colonic) bacteria & SCFA effects pH of colon contents / stools Stool weight Colon mucosal weight Stool frequency Intestinal mean transit time Constipation


Physiological effects (2) Systemic effects

Glycemic plasma response Serum cholesterol/triglycerides (propionate influence, bacterial assimilation)

HDL/LDL cholesterol ratio

Immune response (GALT, ACP)


Physiological effects (3)

Reduced incidence of colon cancer

Decrease in potential carcinogens

Decrease of secondary bile acids

Butyrate prevents carcinogenesis in colon cells

Reduced fecal transit time


Inulin improves mineral bioavailability

Several animal (rodents) and human studies have demonstrated significant improvement of mineral balance, particularly (Ca++, Mg++) and bone density with inulin.


Mineral absorptionHuman study (Healthy young men)

Ca Mg Fe Zn0

10

20

30

40

50

60

% a

bs

orp

tio

n

Ca Mg Fe Zn

Control dietInulin diet

Source: Coudray et al. 1997, Eur. J. Clin. Nutr., 51:375-80.


INULIN IN CALCIUM SUPPLEMENTATION

Improves calcium absorption and balance

Reduces bone loss

Improves bone density

Improved recycling estrogen reduces bone

loss in women


Lipid Effects Double blind, cross-over, randomized

human clinical study

Serumtriglycerides

Totalcholesterol

LDL-cholesterol

HDL-cholesterol

050

100150200

250300

mg/

dL

Serumtriglycerides

Totalcholesterol

LDL-cholesterol

HDL-cholesterol

Control dietInulin diet

Source: Causey JL, Xin-Chu Y, Tungland BC, Feirtag JM & Slavin JL, Nutr. Res. 1999, in press.


INULIN IN LIPID CONTROL

Reduces serum and LDL-cholesterol

Reduces serum triglycerides

Promotes reduction in cholesterol synthesis

Increases HDL/LDL ratio

Inhibits biosynthesis of fatty acids


Inulin and cancer preventionHIGH FIBER DIET WITH INULIN

Putrefactive bacteria (E. coli, clostridia)

Procarcinogens Carcinogens

Glycosides

Nitro groups

Bile acids

aglycones

aromatic amines, hormonal subt.

secondary bile acids

ß-glucuronidase

nitroreductase, NO3 reductase

glycocholic acid hydroxylase

reductase enzymes


Inulin and colon cancer

0

20

40

60

80

100

120

140

Control Inulin B.longum

Inulin+B.longum

AC

F/c

olo

n

5% inulin diet

Total ACF

Source: Rowland et al. 1998, Carcinogenesis, v19(2):281-85

12 week rat study


Inulin and reductase enzymes

0

10

20

30

4050

60

70

80

90

100

Control Inulin B.longum

Inulin+B.longum

acti

vity

h/g

Source: Rowland et al. 1998, Carcinogenesis, v19(2):281-85

5% inulin w/w diet

ß-glucuronidase activity


AS

IMMUNOSTIMULANT

REDUCTION IN TOXIC AND CARCINOGENIC

BACTERIAL METABOLITES

HELPS REDUCE ECZEMA

HELPS CONTROL ALLERGIES & ASTHMA

DOWN REGULATES AUTOIMMUNE CONDITIONS

ACTIVATES THE ACP STIMULATION (IMPROVED

MACROPHAGE ACTIVITY)


Candida albicans suppression

Opportunistic pathogen

• systemic infections common with immunologically

compromised or with long term

antibiotics

Invasion from GI tract important mechanism of

entry

Competitively suppressed by SCFA and anti-

microbial-producing bifidobacteria &

lactobacilliKennedy, 1995. Infection and Immunity, 654-63.


SCFA and Ulcerative Colitis

SCFA: acetate, propionate, n-butyrate irrigations

reduce inflammation in distal UC

Intestinal cells prefer butyrate as an energy

source over glucose or glutamine

Colonic epithelial starvation may lead to atrophy

and colitis

Low SCFA levels are associated with active UC


Inulin/AAD Mechanism

Inulin specifically supports growth of healthy bacteria*

Bifidobacteria sp.Lactobacilli sp.

produce antimicrobial cmpds. acetic, lactic & benzoic acids, H2O2, & bacteriocins-type cmpds.

Inhibits growth of Clostridium difficile**

* Roberfroid et al. 1998. J. Nutr. 128:11-19. ** Rolfe, 1981. J. Inf. Dis., 143-3.


Inulin and AAD

000.0E+0

500.0E+6

1.0E+9

1.5E+9

2.0E+9

2.5E+9

3.0E+9

3.5E+9

Control Inulin

CF

U

BifidobacteriaLactobacilli

000.0E+0

500.0E+6

1.0E+9

1.5E+9

2.0E+9

2.5E+9

3.0E+9

3.5E+9

Control Inulin

CF

U

Clostridium

Human study (20 g/d inulin)

Source: Causey JL, Xin-Chu Y, Tungland BC, Feirtag JM & Slavin JL, 1998

3-week double blind, crossover study


inulation ® - inulin - guardians nutraceuticals guardians nutraceuticals presents

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