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ADIMIX® ADIMIX® Sodium Butyrate For animal’s Health & Performance

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Presentation on theme: "ADIMIX® ADIMIX® Sodium Butyrate For animal’s Health & Performance"— Presentation transcript:

1 ADIMIX® ADIMIX® Sodium Butyrate For animal’s Health & Performance
Improves Feed Conversion Stimulates Early Feed Intake Enhances Intestinal Health Natural Attractant

2 ADIMIX® CH3 - [CH2]2 - COOH 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 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

3 Physical and Chemical Characteristics of Short Chain Fatty Acids (SCFA)
Chemical formula Trivial name Mol mass Boiling point (°C) Melting 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 Water soluble Water & Fat Distribution in chloroform/water. Increasing number indicates higher solubility in lipids Na-n-butyrate: white stable non-volatile powder up till 250°C

4 What is ADIMIX® ? CH3 - [CH2]2 - COONa
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 - [CH2]2 - COONa

5 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.

6 Antibacterial effect : G- & G+
Only at 10 X normal dose 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 ( > FAT !! ) Butyric acid Favours / does not harm / even stimulates Lactobacillus

7 Antibacterial effect pKa Bacterial Cell
RCOOH (Organic Acid – Undissociated) pKa RCOO- H+ Bacterial Cell pH drop H+ DNA ATP ADP + P

8 Antibacterial effect Stop of DNA transcription
(prevents growth and cell multiplication) Bacterial Cell exhausts No energy for multiplication  Bacterial Cell collapses Bacterial Cell

9 Antibacterial effect Antibacterial effect
RCOOH (Organic Acid – Undissociated) pKa RCOO- H+ Bacterial Cell pH drop H+ DNA ATP ADP + P

10 BACTERIA Gram + Gram Bacillus anthracis Anaerob Clostridium
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

11 Dissociation of n-Butyric acid: pH dependent
pKa value 4.82 3.75 3.79 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).

12 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

13 Metabolism of n-butyrate
Cellulose and/or Starch (from diet) Bacterial fermentation pigs, (poultry)  colon multigastrics  rumen n-butyrate Blood absorption 30% 70% Volatile fatty acids (VFA's) are produced in large amounts through ruminal fermentation and are of paramount importance in that they provide greater than 70% of the ruminant's energy supply. Virtually all of the acetic, proprionic and butyric acids formed in the rumen are absorbed across the ruminal epithelium, from which they is carried by ruminal veins to the portal vein and hence through the liver. Continuous removal of VFA's from the rumen is important not only for distribution, but to prevent excessive and damaging drops in pH of rumen fluid. The rumen is lined with stratified squamous epithelium similar to skin, which is generally not noted for efficient absorption. Nonetheless, this squamous epithelium has a structure which functions similarly to the columnar epithelium in the small gut and performs efficient absorption of VFA's, as well as lactic acid, electrolytes and water. Recall also, that the epithelial surface is expanded greatly by formation of well-vascularized papillae. It is of considerable practical importance that the size and length of ruminal papillae respond to concentrations of VFA's in the rumen. Animals that have been on a high plane of nutrition, with abundant VFA production, have long, luxuriant papillae well suited to promote absorption. In contrast, animals which have been under nutritional deprivation have small, blunted papillae, and require time on a high quality diet to allow for development of their papillae and absorptive capacity. All the VFA's appear to be absorbed by the same mechanism, which is diffusion through the epithelium, down a concentration gradient. As they pass through the epithelium, the different VFA's undergo different degrees of metabolism. Acetate and proprionate pass through the epithelium largely unchanged, but almost all of the butyric acid is metabolized in the epithelium to beta-hydroxybutyric acid, a type of ketone body. The three major VFA's absorbed from the rumen have somewhat distinctive metabolic fates: Acetic acid is utilized minimally in the liver, and is oxidized throughout most of the body to generate ATP. Another important use of acetate is as the major source of acetyl CoA for synthesis of lipids. Proprionic acid is almost completely removed from portal blood by the liver. Within the liver, proprionate serves as a major substrate for gluconeogenesis, which is absolutely critical to the ruminant because almost no glucose reaches the small intestine for absorption. Butyric acid, most of which comes out of the rumen as the ketone beta-hydroxybutyric acid, is oxidized in many tissues for energy production. Secretion via respiratory tract, skin, . . . Metabolisation by rumen and intestinal eptithelium cells (villi) High levels in human : leaves body via sweat and breath  socially unacceptable

14 Biological effect of Adimix® :
effect on the gastro-intestinal cell wall Absorbed n-butyrate Messenger molecules Insulin hormone Biological effect of n-butyrate: Aborbed butyrate arrives at different organs, including the pancreas and stimulates the production of various messanger molecules including insulin. These messangers behave like growth promoters and stimulate the growth of the gastro-intestinal wall. Hence, n-butyrate increases the growth and development of the gastro-intestinal lining. 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.

15 ADIMIX® Biological Functions Cell metabolism Immune system
Selective action on bacterial micro-flora

16 ADIMIX® : Biological Functions
Differs it from any other acid 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

17 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

18 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)

19 ADIMIX® : Biological Functions
Hyperacetylation of histones Modifications of cell morphology and membrane composition Increased hormone synthesis Modifications in the structure of the cell skeleton 4 1 3 2 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.

20 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

21 New Spray Drying Tower installed
Finalized early 2003

22 Anti-Salmonella / Anti-Dysenterie Effect
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) + ++ +++

23 Adimix® C 30 Coated

24 "Protected"

25 LIPASE 1 "Slow release"

26 LIPASE 2 "Gradual release"

27 "Target release" LIPASE 3

28 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 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 Calcium Butyrates are not spray-dried ( 1 - 2% free, volatile But.-acid) ADIMIX (Na-Butyrate) is spray-dried (< 0.1% free, volatile But.-acid) ADIMIX : high concentration active ingredient ADIMIX : captured and covered odeur

29 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 (>4%) compared to ADIMIX (2%) ADIMIX (spray-dried) has a much more uniform particle size than Ca-Butyrate (dry mix)

30 Granulometry and particle size distribution
Fines / dust ADIMIX More uniform particle size distribution Significantly less fine particles  less dusty product

31 ADIMIX Calcium-butyrate
Spray-dried powder Uniform particles Low dust Dry mix (butyric acid + mineral support) Variable particle size High dust

32 ADIMIX : superior solubility
Calcium Butyrate: 300 g in 1000 ml of water Adimix Butyrate 1000 g in 1000 ml of water Poor water solubility Risk of complex formation of calcium with other dietary components Perfectly water soluble, no sedimentation Higher bio-availability Preferred source for all in-feed applications -specifically for milk replacers & liquid applications-

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