Presentation on theme: "ADIMIX® ADIMIX® Sodium Butyrate For animal’s Health & Performance"— Presentation transcript:
1ADIMIX® ADIMIX® Sodium Butyrate For animal’s Health & Performance Improves Feed ConversionStimulates Early Feed IntakeEnhances Intestinal HealthNatural Attractant
2ADIMIX® CH3 - [CH2]2 - COOH Active substance butyric acid an organic acid with specific characteristicsa short chain fatty acid (SCFA)a viscous liquidmiscible 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
3Physical and Chemical Characteristics of Short Chain Fatty Acids (SCFA) Chemical formulaTrivial nameMol massBoilingpoint (°C)MeltingpK valueKp*CH3- COOHAcetic acid60.05126.96.36.1990.02CH3CH2- COOHPropionic acid74.08141.1-224.870.15CH3(CH2)2COOHN-Butyric acid88.11163.5-4.74.820.44WatersolubleWater & FatDistribution in chloroform/water. Increasing number indicates higher solubility in lipidsNa-n-butyrate: white stable non-volatile powder up till 250°C
4What is ADIMIX® ? CH3 - [CH2]2 - COONa N – Butyric acid sodium salt, orN – Butyrate, sodium salt, orButanoic acid, sodium salt, orSodium butanoate, orE 470Spray-dried white powderPure form contains98% sodium butyrate or 78% butyric acidCH3 - [CH2]2 - COONa
5Adimix® : dissociation pHCH3 - [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 liquidThe 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.
6Antibacterial effect : G- & G+ Only at10 X normal doseOrganic AcidsThe combination of Organic Acids & Adimix®Performs better than single approach (synergy)Is the most economical applicationXG-bacteriaG+bacteriaMore complex membrane( > FAT !! )Butyric acidFavours / does not harm / even stimulatesLactobacillus
11Dissociation of n-Butyric acid: pH dependent pKa value4.823.753.79Butyric acid travels further down the digestive tractpHAt 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).
12Short Chain Fatty Acids: metabolism Butyric acid, Acetic acid, Propionic acidmetabolic end-productsof carbohydrate digestion by bacteriain the rumen or large intestine ofpigs, poultry, rabbits and ruminantsLow Fibre-fermentation capacity for young animalsNaturally present, but insuffient ?1 - 2 % in milk fat
13Metabolism of n-butyrate Cellulose and/or Starch (from diet)Bacterial fermentation pigs, (poultry) colonmultigastrics rumenn-butyrateBlood absorption30%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.Secretionvia respiratory tract, skin, . . .Metabolisation by rumen and intestinal eptithelium cells (villi)High levels in human : leaves body via sweat and breath socially unacceptable
14Biological effect of Adimix® : effect on the gastro-intestinal cell wallAbsorbed n-butyrateMessenger moleculesInsulin hormoneBiological 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.
15ADIMIX® Biological Functions Cell metabolism Immune system Selective action on bacterial micro-flora
16ADIMIX® : Biological Functions Differs it from any other acidCell metabolismEnergy 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 system3. Selective action on bacterial micro-flora
17ADIMIX® : Biological Functions 1. Cell metabolism2. Immune systemIncreased haemoglobin synthesisStimulation 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 production3. Selective action on bacterial micro-flora
18ADIMIX® : Biological Functions 1. Cell metabolism2. Immune systemSelective action on bacterial micro-floraIncrease in Bifido-bacteria + LactobacilsColonisation resistance against harmful / bad-natured bacteria, like E. Coli, SalmonellaDirect anti-bacterial action (organic acid effect)
19ADIMIX® : Biological Functions Hyperacetylation of histonesModifications of cell morphology and membrane compositionIncreased hormone synthesisModifications in the structure of the cell skeleton4132Butyric 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.
20Butyric acid in human gut pathology Prevention of inflammatory diseases in the gastro-intestinal tractChrone diseaseEnterocolitisNecrotic enteritisRegression of colon and rectum cancers‘A deficiency of butyric acid or other SCFA to the colon causes inflammation’ (Kien et al., 1999)Inhibitsgrowth ofabnormal cells
21New Spray Drying Tower installed Finalized early 2003
22Anti-Salmonella / Anti-Dysenterie Effect TrialVeterinary Faculty of the University of Gent – BelgiumAnti-Salmonella / Anti-Dysenterie Effect“Power”in the hindgutCoated Formic Acid (C1)Coated Acetic Acid (C2)Coated Propionic acid (C3)Coated Butyric Acid (C4)++++++
28Na-Butyrate versus Ca-Butyrate A small molecule penetrates the bacterial cell more easyCalcium Butyrate has a lower anti-bacterial effect, as its molecularweight 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 crystalCalcium 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 ingredientADIMIX : captured and covered odeur
29Na-Butyrate versus Ca-Butyrate Calcium Butyrate has a much stronger ‘typical’ odeur/smell thanspray-dried Sodium Butyrate (= related to the level of ‘free butericacid’, which is an extremely volatile molecule)Calcium Butyrate have lower levels of active ingredients, and oftencontains a rather high level of (non-nutritional) anti-caking productsDust 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 thanCa-Butyrate (dry mix)
30Granulometry and particle size distribution Fines / dustADIMIXMore uniform particle size distributionSignificantly less fine particles less dusty product
32ADIMIX : superior solubility Calcium Butyrate:300 g in 1000 ml of waterAdimix Butyrate1000 g in 1000 ml of waterPoor water solubilityRisk of complex formation of calciumwith other dietary componentsPerfectly water soluble, no sedimentationHigher bio-availabilityPreferred source for all in-feed applications-specifically for milk replacers & liquid applications-