ADIMIX

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ADIMIX
ADIMIX Sodium Butyrate For animals Health
Performance
Improves Feed Conversion Stimulates Early Feed
Intake Enhances Intestinal Health Natural
Attractant
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ADIMIX

• Active substance 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 SCFAs, like propionic acid /
  acetic acid)
• the characteristic smell of rancid butter
• (when it is present as -very volatile- free
  fatty acid)

CH3 - CH22 - COOH
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Physical and Chemical Characteristics of Short
Chain Fatty Acids (SCFA)
Chemical formula Trivial name Mol mass Boiling point (C) Melting point (C) pK value Kp
CH3- COOH Acetic acid 60.05 118.1 16.7 4.76 0.02
CH3CH2- COOH Propionic acid 74.08 141.1 -22 4.87 0.15
CH3(CH2)2COOH N-Butyric acid 88.11 163.5 -4.7 4.82 0.44

• Distribution in chloroform/water. Increasing
  number indicates higher solubility in lipids
• Na-n-butyrate white stable non-volatile
  powder up till 250C

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What is ADIMIX ?

• N Butyric acid sodium salt, or
• 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 - CH22 - COONa
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Adimix dissociation
pH
CH3 - CH22 COOH CH3 - CH22
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.

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Antibacterial effect G- G
Organic Acids

• The combination of Organic Acids Adimix
• Performs better than single approach (synergy)
• Is the most economical application

X
G- bacteria
G bacteria
More complex membrane ( gt FAT !! )
Butyric acid
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Antibacterial effect
RCOOH (Organic Acid Undissociated)
pKa
RCOO-
H
Bacterial Cell
pH drop
DNA
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Antibacterial effect

• Stop of DNA transcription
• (prevents growth and cell multiplication)
• Bacterial Cell exhausts
• No energy for multiplication
• ? Bacterial Cell collapses

Bacterial Cell
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Antibacterial effect
Antibacterial effect
RCOOH (Organic Acid Undissociated)
pKa
RCOO-
H
Bacterial Cell
pH drop
DNA
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BACTERIA
Gram Cocci Staphylococci
Streptococci
Enterococci Rods Aerob
Bacillus anthracis
Corynebacterium Listeria
Anaerob Clostridium
Gram Cocci Neisseria meningitidis
Moraxella Rods Enterobacteria
(E.Coli, Salmonella, Klebsiella,
Proteus) Acinetobacter
Bacteroides Bordetella
Brucella Coxiella
Haemophilus Helicobacter
Legionella Pseudomonas
Streptobacullus moniliformis
Ehrlichia Vibrio
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Dissociation of n-Butyric acid pH dependent
Butyric acid travels further down the digestive
tract
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).

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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

• Low Fibre-fermentation capacity for young
  animals
• Naturally present, . . . but insuffient ?
• 1 - 2 in milk fat

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Metabolism of n-butyrate
Cellulose and/or Starch (from diet)
Bacterial fermentation pigs,
(poultry) ? colon
multigastrics ? rumen
n-butyrate
Blood absorption
70
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Secretion via respiratory tract, skin, . . .
Metabolisation by rumen and intestinal
eptithelium cells (villi)
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Biological effect of Adimix effect on the
gastro-intestinal cell wall
Absorbed n-butyrate

• Messenger molecules
• Insulin hormone

• Although the exact mode of action of butyrate on
  rumen and intestinal epithelium is not yet fully
  understood, the stimulatory effect is probably
  mediated via messenger molecules and the insulin
  hormone. The result is the presence of readily
  available energy to epithelial cells, having a
  very intesive metabolism and turnover rate.

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ADIMIX Biological Functions

• Cell metabolism
• Immune system
• Selective action on bacterial micro-flora

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ADIMIX Biological Functions

• Cell metabolism
• 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
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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

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ADIMIX Biological Functions

• 1. Cell metabolism
• 2. Immune system
• 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)

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ADIMIX Biological Functions

1. Hyperacetylation of histones
2. Modifications of cell morphology and membrane
   composition
3. Increased hormone synthesis
4. Modifications in the structure of the cell
   skeleton

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1
3
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Butyric acid has extensively been studied in
human cell biology. Multiple effects on cell
metabolism like modulation of protein synthesis
(RNA transcription, ...) and gene expression,
viral transformation of cells and cell morphology
/ membrane structure have been described.
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Butyric acid in human gut pathology

• Prevention of inflammatory diseases in the
  gastro-intestinal tract
• Chrone disease
• Enterocolitis
• 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)

Inhibits growth of abnormal cells
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New Spray Drying Tower installed Finalized early
2003
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Trial Veterinary Faculty of the University of
Gent Belgium Anti-Salmonella / Anti-Dysenterie
Effect
Power in the hindgut
Coated Formic Acid (C1) Coated Acetic Acid (C2) Coated Propionic acid (C3) Coated Butyric Acid (C4)
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Adimix C 30 Coated
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"Protected"
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LIPASE
1
"Slow release"
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LIPASE
2
"Gradual release"
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LIPASE
3
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Na-Butyrate versus Ca-Butyrate

• A small molecule penetrates the bacterial cell
  more easy
• 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)
• Sodium Butyrate is perfectly water-soluble
  (1.0 kg in 1 kg water)
• Calcium Butyrates 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
• Calcium Butyrates are not spray-dried ( 1 -
  2 free, volatile But.-acid)
• ADIMIX (Na-Butyrate) is spray-dried (lt
  0.1 free, volatile But.-acid)
• ADIMIX high concentration active ingredient
• ADIMIX captured and covered odeur

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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)
• Calcium Butyrate have lower levels of active
  ingredients, and often
• contains a rather high level of
  (non-nutritional) anti-caking products
• Dust level (measured by ITECH) is twice as high
  in Ca-Butyrate (gt4)
• compared to ADIMIX (2)
• ADIMIX (spray-dried) has a much more uniform
  particle size than
• Ca-Butyrate (dry mix)

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Granulometry and particle size distribution
ADIMIX More uniform particle size distribution
Significantly less fine particles ? less dusty
product
Fines / dust
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ADIMIX Calcium-butyrate
Spray-dried powder Uniform particles Low dust
Dry mix (butyric acid mineral support)
Variable particle size High dust
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ADIMIX superior solubility
Adimix Butyrate 1000 g in 1000 ml of water
Calcium Butyrate 300 g in 1000 ml of water
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