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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
Inulation® - Inulin - Guardians Nutraceuticals™
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
Inulation® - Inulin - Guardians Nutraceuticals™
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
Inulation® - Inulin - Guardians Nutraceuticals™
Health concern/disease
Preventative Food Type
ColonCancer
Bran/grains19%
Fiber22%
Fruit6%
Vegetables21%
Source: International Food Information Council (IFIC) 1998
Inulation® - Inulin - Guardians Nutraceuticals™
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
Inulation® - Inulin - Guardians Nutraceuticals™
Inulation® - Inulin - Guardians Nutraceuticals™
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
Inulation® - Inulin - Guardians Nutraceuticals™
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)
Inulation® - Inulin - Guardians Nutraceuticals™
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
Inulation® - Inulin - Guardians Nutraceuticals™
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.
Inulation® - Inulin - Guardians Nutraceuticals™
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
Inulation® - Inulin - Guardians Nutraceuticals™
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
Inulation® - Inulin - Guardians Nutraceuticals™
Physiological effects (2) Systemic effects
Glycemic plasma response Serum cholesterol/triglycerides (propionate influence, bacterial assimilation)
HDL/LDL cholesterol ratio
Immune response (GALT, ACP)
Inulation® - Inulin - Guardians Nutraceuticals™
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
Inulation® - Inulin - Guardians Nutraceuticals™
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.
Inulation® - Inulin - Guardians Nutraceuticals™
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.
Inulation® - Inulin - Guardians Nutraceuticals™
INULIN IN CALCIUM SUPPLEMENTATION
Improves calcium absorption and balance
Reduces bone loss
Improves bone density
Improved recycling estrogen reduces bone
loss in women
Inulation® - Inulin - Guardians Nutraceuticals™
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.
Inulation® - Inulin - Guardians Nutraceuticals™
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
Inulation® - Inulin - Guardians Nutraceuticals™
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
Inulation® - Inulin - Guardians Nutraceuticals™
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
Inulation® - Inulin - Guardians Nutraceuticals™
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
Inulation® - Inulin - Guardians Nutraceuticals™
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)
Inulation® - Inulin - Guardians Nutraceuticals™
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.
Inulation® - Inulin - Guardians Nutraceuticals™
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
Inulation® - Inulin - Guardians Nutraceuticals™
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.
Inulation® - Inulin - Guardians Nutraceuticals™
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™