Calcium-butyrate

SINTOBUTYL

Product and specifications

Calcium-butyrate : Product and specifications

- Chemically pure calciumbutyrate (slight surplus of Ca) – fine powder

- Doesn’t smell if not touched with humid surfaces (hands, ...).

- May partly dissociate in contact with humidity and release unpleasant smell

- Min. 76.6 % butyrate-ANION and approximately 17% Calcium

Sintobutyl

Sintobutyl Coating: incapsulates the active compound (Ca-butyrate)

Fat components from vegetable origin

( Very good nutritional properties)

• Fatty acids with high melting point

•Hydrogenated fatty acids :

C14 and lower (%) 1 %

C16 palmitic acid (%) 45 %

C18 stearic acid (%) 53 %

C18’oleic acid (%) 0.5 %

C20 and higher 0.4%

Sintobutyl (calcium butyrate) and Antibiotic Growth Promoters

How Sintobutyl ranks between other claimed alternatives ?

Sintobutyl versus Other “Gut Modifiers” “Gut Flora Stabilisers” . Are they all the same ?

GUT Morphology

& Functioning

(villi, epithelium, mucosa)

IN-DIRECT EFFECT

(some even stimulate butyric acid, -producing

bacteria)

DIRECT

AGENT / NUTRIENT

IN-DIRECT EFFECT

+ and -

GUT Micro flora

- Bacterial Load - Metabolism, - Pathogens (C-Cl-Salm)

IN-DIRECT EFFECT

- Attachment

- VFA –production (BA)

- Substrate interaction

DIRECT INHIBITION

Low MIC-value’s at intestinal pH = 6

In vivo flora studies

DIRECT / INDIRECT

EFFECT

+ and -

Encapsulated Yeast Components Botanical extracts

Feature / Effect Calcium-butyrate (MOS, hydrolysed yeast) (herbs, roots,fruits)

Probiotics,Prebiotics, enzymes acidifiers “coated”)

More Feed Additives claim, support BUTYRATE effects

Butyrate (butyric acid)

Protection and regeneration of intestinal villi

(mucosa integrity)

So, why not adding butyrate (Sintobutyl) directly !!??!!

Selective bacterial inhibition at intestinal,

ceacal level : Coli, Clostridium,

Salmonella

Stimulation of immunity

Stimulation of enzyme synthesis

Zootechical effects : FI, DWG, FCR, Egg Shell strength

Non Digestible Oligosaccharides

Herbal Extracts

MCFA’s

F.O.S. (inuline, profeed)

M.O.S. (yeast cell walls)

Bacterial shift (LAB, Bifido)

Fermentation to VFA and more Butyric (Megasphera LA -> BA)

Immuno-stimulant

Bacteria attachment (lectins)

Some induce BA production ()

Part is converted at intestinal level to Butyric

Mode of action of PROGUT(Vuorenmaa J & Vaahtovua J. (2006)

PROGUT = Hydrolysed brewery yeast product;

Prebiotic effects + Yeast Cell Wall effects are claimed

- Stabilize gut flora

- Support natural immunity

- Prevent attachment of E.Coli, Salmonella to mucus

Increases the MBI with piglets and poultry !!!

MICROBIAL BALANCE INDEX = ---------------------------------------------------------------Bifidobacteria + butyric acid producing bacteria

Enteric group bacteria + bacteroides

Significant correlation with DWG and FCR

MBI

Means more Butyrate in the gut, so just give

straight Sintobutyl !!!

Comparative mode of action and benefits of : ABGP ButyProl Coated MOS FOS MCFA Benzoic E.O. Butical Acids YCW’s Acid Herbs• Gut integrity

• Enzyme synthesis

• Immunity

• Microbial Shift (beneficial)

• Metabolic activity flora

• Inhibition - Coli

- Clostridium

- Salmonella

• Digestibility of nutrients

• Absorption

• FCR

• Intestinal disorders

• Pathogens

• Litter quality

- / + + + + - - +/- - - + /- - - +/-

- - + + - - - - - - - - - - +/-

- - + + - - + +/- - - - - +/-

+ + + + + + + + colon + ? ? ++

+ + + + - - - - + colon + ? ? ?

indirect direct ++ indirect + colon direct + + ?

++ / - - + + - - - - - - + ? - ? - ?

- - / + + + + +++ - - ++ + - ? - ?

+ + + + + - - - - - ? + +?

- + - - -/+ -/+ (c) - ? + - ? - -

+ + + + + + +? + - - - ? + ? +

+ + + + + ++ + + + ++

- - / + + + + ++ ++ +?- + + ++

- /+ + + - - - - -/+ - ? +/- -/+

Comparative mode of action and benefits of : ABGP ButyProl Probiotics Butical • Gut integrity

• Enzyme synthesis

• Immunity

• Microbial Shift (beneficial)

• Metabolic activity flora

• Inhibition - Coli

- Clostridium

- Salmonella

• Digestibility of nutrients

• Absorption

• FCR

• Intestinal disorders

• Pathogens

• Litter quality

- / + + + + +/-

- - + + - -

- - + + +/-

+ + + + + +

+ + + + - -

indirect direct indirect

++ / - - + + -/+

- - / + + + + --/+

+ + + + - -

- + - -

+ + + + + + indirect

+ + + -- /+

- - / + + + --/+

- /+ + + - -

Sintobutyl versus Aromabiotic (medium chain fatty acids)

in rabbits

Totally untrue !!!!!!!!!!! Pure Marketing !!!!!

Sept 06 : so far limited use in 2-3 countries of EU-25 and on the way back (“fashion”)

Ca-butyrate (Sintobutyl) versus MCFA’sCLAIM-ACTIVITY MCFA Calciumbutyrate

Bacterial Inhibition

E. Coli

Clostridium

Villi integrity

Performance (dwg,fcr)

MCFA soluble both in water and lipids, which would influence the speed of

penetration of the product through the bacterial cell wall. Molecules have

medium length C10-C14 and may be quite big to penetrate.

Butyric acid is also soluble in water and in fat, both lipofylic and

hydrofylic. On top the molecule is smaller (C-4), which normally could

be easier to penetrate.

1.0-1.5 log reduction (10-15 days) at 0.2 % - MIC = 0.5% !!

1.0 -1.2 log reduction (25-50 mmol) – J . Decuyper 2003-U.G.

MCFA would inhibit lipase production by bacteria, which seems needed for bacteria to attach to the gutwall. So attachment may be hindered and

bacteria lessivate !? INDIRECT effect

Calciumbutyrate has a DIRECT inhibition effect at pH=6 on all pathogenic clostridium strains

(A.Decostere). Inhibtion of anaerobes by 0.5 log (J. Decuyper)

MCFA would Increase villi length and vili/crypt ratio, but this is again

INDIRECT (as more additives may do by fermentation or transformation to

butyric acid)

Butyrate is the FUEL (nutrient) of the gutwallcell (villi), having a DIRECT effect on the gutwall integrity and regeneration. Besides systemic

effect, also the topical effect (local)

Effects seems limited, nihil to negative (on feed intake). Few data !

Significant Positive Effect (higher feed intake -attractant). Full data base !

Butyrate – MCFA’s : similarities & differences !?

Property, advantage MCFA’s Butyrate (butyric acid) Specific Characteristics

Chain length caproic C6, Caprylic C-8, Capric C10 C4 (longest SCFA)

pK-value 4.88 4.89 4.89 4.86

Solubility fat and water soluble fat and water soluble

ME 26.6 kJ/gr 17.4 kJ/gr

Human application as functional lipid (“slimming”) as anti-cancer (colon)

Absorption enhancing (paracellular permeability) enhancing (idem +emulsifyer)

Bacterial Inhibition mg/ml

E. Coli > 5 2 5 < 5.0 (UG-AF)

Salmonella > 5 3 > 5 < 5.0 (UG-VF)

Clostridium > 5 1-2 1 4-16 (UG-VF)

C-12 = 0.1-0.2

Butyrate – MCFA’s : similarities & differences !?

Property, advantage MCFA’s Butyrate (butyric acid) Specific Characteristics

Ketosis effects (negative !!) Risk : C6-C8 in neonatals (piglets) not (only in ruminants)

Association with C-4, VFA Antagonist (drop in C-4, VFA) Synergistic (= or >)

=>Compatible with FOS,YCW, NOT YES

Some Probiotics, ....

Risk of lipolysis in feed Real NOT

(lipase)

Required antimicrobial 3-5 gr/l pure, stomach, gut concentration

FI piglet 300 g/d => 10-17 kg per ton pure

X 2 = 20-34 kg per ton of feed 0.5-3.0 kg/ton

Accumulation in fat at high dosages (4 %) NOT

MCFA’s = Butyrate antagonist !!!!! – Conflicting – Worrying ???

1) J. Goris (2006), ILVO : C8 or caprylic acid changes fermentation profile in caecum of piglets : increase lactate, decrease butyrate and propionate (reversible)

2) F.Boyen & Pasmans (2006) – Effect on salmonella invasion of caprylic and caproic acid + butryic acid is antagonistic. Butyric alone decreases invasion !

3) Leeson & Antongiovanni (2005) – Triglycerides of mcfa + butyric less effective in broilers than Triglycerides of butyric acid alone.

4) Van Oeckel (2005) - ILVO – Piglets trial : performance of combination of mcfa-product + butyrate less good than mcfa, butyrate, but also than negative control.

5) Maertens L (2006) – ILVO – Rabbits : mcfa-product decreased significantly VFA’s and Butyric concentration in caecum. Unbalancing cecal flora !!!

Salmonella invasion through epithelial cells of broiler chickens after treatment with butyric acid

or MCFA (caproic acid) IN VITRO !!

“MCFA seem to decrease invasion at least to the same extent as butyric acid but at lower

concentrations”

F. Van Immerseel et All (2004) – Appl. Environ.Microbiol. 6/2004 : 3582-3587

- In Vitro data : what happens in intestine with additive ? How much caproic acid is liberated from coconut-oil ?

- Related only to eventual accumulation in liver and spleen, not in caecum (see in vivo test)

Salmonella in different organs of broiler chickens after treatment with butyric acid or MCFA (caproic acid)

0

1

2

3

4

5

6

7

8

9

1,56 kg Butyric 3,0 kg caproic acid

CECUM-controleCECUM-treatmentLIVER controleLIVER-treatmentSPLEEN-ControleSPLEEN-Treatment

Log cfu/gr

a b a’ a’ a” a” a b a’ b’ a” a”

Inoculation with 10exp3 Salmonella Enteritidis on day 5, counts on day 8 (Van Immerseel - University Ghent)

-2.2 log

-1.66 log

= 6-30 kg MCFA-product ?? = 3 kg Butical 60

IN VIVO !!

Composition of a commercial MCFA product

Method : saponification BF3/MeOH (hot) BF3/MEOH (cold)

+ BF3/MeOH (hot)

Fatty Acid % rel g/100 gram % rel g/100 gram % rel g/100 gram

Caproic C6:0 8.1 5 8.6 5 6.9 3

Caprylic C8:0 62.1 32 60.8 30 59.6 23

Capric C10:0 29.4 15 30.2 14 33.0 12

Undecanoic C11:0 0.2 0 0.2 0 0.3 0

Lauric C 12:0 0.2 0 0.2 0 0.2 0

53 49 38

Sample from Belgium – 2004 ; Independent industrial laboratory, analysis in 2005