Transcript Slide 1

Performance Enhancement
®
ADIMIX
Sodium Butyrate
Performance Enhancement
For animal’s Health & Performance
Improves Feed Conversion
Stimulates Early Feed Intake
Enhances Intestinal Health
Natural Attractant
Performance Enhancement
Performance Enhancement
ADIMIX®
Active substance
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butyric acid
an organic acid with specific characteristics
a short chain fatty acid (SCFA)
a viscous liquid
miscible with water, ethanol and ether (lipids)
(unlike other SCFA’s, like propionic acid / acetic acid)
 the characteristic smell of rancid butter
(when it is present as -very volatile- free fatty acid)
CH3 - [CH2]2 - COOH
Performance Enhancement
Performance Enhancement
Physical and Chemical Characteristics of
Short Chain Fatty Acids (SCFA)
Boiling Melting
pK
point
point
value
(°C)
(°C)
Chemical
formula
Trivial name
Mol
mass
CH3- COOH
Acetic acid
60.05
118.1
CH3CH2- COOH
Propionic acid
CH3(CH2)2COOH N-Butyric acid
Kp*
0.02
74.08
141.1
16.7
4.76
Water
soluble
-22
4.87
88.11
163.5 Water
-4.7 & Fat4.82
soluble
0.44
 Distribution in chloroform/water. Increasing number indicates higher solubility in lipids
 Na-n-butyrate: white stable non-volatile powder up till 250°C
0.15
Performance Enhancement
Performance Enhancement
What is ADIMIX® ?
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N – Butyric acid sodium salt, or
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N – Butyrate, sodium salt, or
Butanoic acid, sodium salt, or
Sodium butanoate, or
E 470
Spray-dried white powder
Pure form contains
98% sodium butyrate or 78% butyric acid
CH3 - [CH2]2 - COONa
Performance Enhancement
Performance Enhancement
Adimix® : dissociation
pH
CH3 - [CH2]2 – COOH
CH3 - [CH2]2 – COO¯ + H+
n-butyric acid
n-butyrate
(Undissociated)
(Dissociated)
In the undissociated state, butyric acid is strongly lipophilic and can easily
cross membranes (both bacterial and cellular membranes)
The dissociation rate of organic acids is mainly influenced by the pKa value
(pH at which 50% of the acid is in the dissociated state and 50% is in the
undissociated state) and the pH of the intestinal liquid
The pKa value of butyric acid is about 1 pH unit higher than ‘traditional’
organic acids like formic and lactic acid (see next slide). As a result, butyric
acid has different characteristics with respect to its anti-microbial activity, but
also the biological effect of butyric acid is linked with its high pKa value.
Performance Enhancement
Performance Enhancement
Antibacterial effect : G- & G+
Only at
10 X normal dose
Organic Acids
X
G-
G+
bacteria
bacteria
Butyric acid
Favours / does not harm / even stimulates
Lactobacillus
More complex membrane
( > FAT !! )
Performance Enhancement
Performance Enhancement
Antibacterial effect
RCOOH (Organic Acid – Undissociated)
pKa
RCOO-
H+
Bacterial Cell
pH drop
DNA
ATP
H+
ADP + P
Performance Enhancement
Antibacterial effect
 Stop of DNA transcription
Performance Enhancement
(prevents growth and cell multiplication)
 Bacterial Cell exhausts
 No energy for multiplication
 Bacterial Cell collapses
Bacterial Cell
120
Not dissociated (%)
Performance Enhancement
Performance Enhancement
Dissociation of n-Butyric acid: pH dependent
pKa value
100
Butyric acid
Formic acid
80
4.82
3.75
3.79
Lactic acid
60
Butyric acid
travels further
down the
digestive tract
40
20
0
3
3.5
4
4.5
5
5.5
6
6.5
pH 7
pH
At higher pH values (5-6), more butyric acid is present in the undissociated form compared
to formic or lactic acid (differences in pKa value)
 This means there is a synergy between Butyric acid and Formic/Lactic acid in terms of
their anti-microbial effect (this is the basis for the Nutri-Ad acidification program for pigs).
Performance Enhancement
Performance Enhancement
Short Chain Fatty Acids:
metabolism
Butyric acid, Acetic acid, Propionic acid
metabolic end-products
of carbohydrate digestion by bacteria
in the rumen or large intestine of
pigs, poultry, rabbits and ruminants
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Low Fibre-fermentation capacity for young animals
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Naturally present, . . . but insuffient ?
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1 - 2 % in milk fat
Performance Enhancement
Performance Enhancement
Metabolism of n-butyrate
Cellulose and/or Starch (from diet)
Bacterial fermentation
pigs, (poultry)  colon
multigastrics  rumen
n-butyrate
Blood absorption
30%
Secretion
via respiratory tract, skin, . . .
70%
Metabolisation by rumen and
intestinal eptithelium cells (villi)
High levels in human : leaves body via sweat and breath  socially unacceptable
Performance Enhancement
Performance Enhancement
ADIMIX®
Biological Functions
 Cell metabolism
 Immune system
 Selective action on bacterial micro-flora
Performance Enhancement
Performance Enhancement
ADIMIX® : Biological Functions
1. Cell metabolism
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Differs it from any other acid
Energy source for intestinal mucosa (brush border)
Differentiation of enterocytes +++
Contact surface of intestinal microvilli +++
Calcium aborption +++
Secretion of pancreatic enzymes +++
Secretion of intestinal digestive enzymes ++++
2. Immune system
3. Selective action on bacterial micro-flora
Performance Enhancement
Performance Enhancement
ADIMIX® : Biological Functions
1. Cell metabolism
2. Immune system
 Increased haemoglobin synthesis
 Stimulation of non-specific immunity (phagocytosis by macrophages)
 Stimulation of local immunity in the intestine
(Gut Associated Lymphoid Tissue)
 Increase in haptoglobine values
(indicator for immune stimulation)
 Correlation with LPS (liposaccharides) from pathogenic
bacteria in a way that it controls the nitric oxide production
3. Selective action on bacterial micro-flora
Performance Enhancement
Performance Enhancement
ADIMIX® : Biological Functions
1. Cell metabolism
2. Immune system
3. Selective action on bacterial micro-flora
 Increase in Bifido-bacteria + Lactobacils
 Colonisation resistance against harmful / bad-natured
bacteria, like E. Coli, Salmonella
 Direct anti-bacterial action (organic acid effect)
Performance Enhancement
Performance Enhancement
Butyric acid in human gut pathology
 Prevention of inflammatory diseases in the
gastro-intestinal tract
 Chrone disease
Inhibits
 Enterocolitis
growth of
abnormal cells
 Necrotic enteritis
 Regression of colon and rectum cancers
 ‘A deficiency of butyric acid or other SCFA to
the colon causes inflammation’ (Kien et al., 1999)
Performance Enhancement
Performance Enhancement
New Spray Drying Tower installed
Finalized early 2003
Performance Enhancement
Performance Enhancement
Trial
Veterinary Faculty of the University of Gent – Belgium
Anti-Salmonella / Anti-Dysenterie Effect
“Power”
in the hindgut
Coated Formic Acid
Coated Acetic Acid
Coated Propionic acid
Coated Butyric Acid
(C1)
(C2)
(C3)
(C4)
+
+
++
+++
Performance Enhancement
Performance Enhancement
Adimix® C 30 Coated
Performance Enhancement
Performance Enhancement
Performance Enhancement
Performance Enhancement
LIPASE
1
Performance Enhancement
Performance Enhancement
LIPASE
2
Performance Enhancement
Performance Enhancement
LIPASE
3
Performance Enhancement
Performance Enhancement
Na-Butyrate versus Ca-Butyrate
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A small molecule penetrates the bacterial cell more easy
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Calcium Butyrate has a lower anti-bacterial effect, as its molecular
weight is 2 X higher than Sodium Butyrate
(  resp. 216 and 111, resulting in less diffusion capacity)
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Sodium Butyrate is perfectly water-soluble (1.0 kg in 1 kg water)
Calcium Butyrate’s water-solubility is poor (0.3 kg in 1 kg water)
 the higher the solubility, the easier the reaction to salt vice versa ;
otherwise it only stays as a crystal
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Calcium Butyrates are not spray-dried ( 1 - 2% free, volatile But.-acid)
ADIMIX (Na-Butyrate) is spray-dried (< 0.1% free, volatile But.-acid)
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ADIMIX : high concentration active ingredient
ADIMIX : captured and covered odeur
Performance Enhancement
Performance Enhancement
Na-Butyrate versus Ca-Butyrate
 Calcium Butyrate has a much stronger ‘typical’ odeur/smell than
spray-dried Sodium Butyrate (= related to the level of ‘free buteric
acid’, which is an extremely volatile molecule)
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Calcium Butyrate have lower levels of active ingredients, and often
contains a rather high level of (non-nutritional) anti-caking products
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Dust level (measured by ITECH) is twice as high in Ca-Butyrate (>4%)
compared to ADIMIX (2%)
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ADIMIX (spray-dried) has a much more uniform particle size than
Ca-Butyrate (dry mix)
% of total volume
Performance Enhancement
Performance Enhancement
Granulometry and particle size distribution
ADIMIX Butyrate 98C
7
6
5
4
3
2
1
0
Calciumbutyrate
0
200
400
600
800
1000 1200 1400 1600
Particle size (µm)
Fines / dust
ADIMIX
More uniform particle size distribution
Significantly less fine particles  less dusty product
Performance Enhancement
Performance Enhancement
ADIMIX
Calcium-butyrate
Spray-dried powder
Dry mix (butyric acid + mineral support)
Uniform particles
Variable particle size
Low dust
High dust
Performance Enhancement
Performance Enhancement
ADIMIX : superior solubility
Calcium Butyrate:
Adimix Butyrate
300 g in 1000 ml of water
1000 g in 1000 ml of water
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Poor water solubility
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Risk of complex formation of calcium
with other dietary components
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Perfectly water soluble, no sedimentation
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Higher bio-availability
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Preferred source for all in-feed applications
-specifically for milk replacers & liquid applications-