EP3764817A1 - Feeds for improving health and performance of mammals - Google Patents

Feeds for improving health and performance of mammals

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Publication number
EP3764817A1
EP3764817A1 EP19715223.4A EP19715223A EP3764817A1 EP 3764817 A1 EP3764817 A1 EP 3764817A1 EP 19715223 A EP19715223 A EP 19715223A EP 3764817 A1 EP3764817 A1 EP 3764817A1
Authority
EP
European Patent Office
Prior art keywords
high intensity
feed
intensity sweetener
mammals
ppm
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP19715223.4A
Other languages
German (de)
French (fr)
Inventor
Emma WALL
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Adm International Sarl
Original Assignee
Pancosma SA
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Filing date
Publication date
Application filed by Pancosma SA filed Critical Pancosma SA
Publication of EP3764817A1 publication Critical patent/EP3764817A1/en
Pending legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/163—Sugars; Polysaccharides
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/10—Feeding-stuffs specially adapted for particular animals for ruminants
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/30—Feeding-stuffs specially adapted for particular animals for swines
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/50—Feeding-stuffs specially adapted for particular animals for rodents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/30—Artificial sweetening agents

Definitions

  • This invention relates to feeds and feed additives containing a high intensity sweetener and/or capsicum oleoresin and their use to improve health and performance of mammals.
  • Enteritis is an infection of the digestive tract that can be caused by a variety of different pathogens. In rabbits, enteritis is a devastating disease that accounts for the majority of illnesses, deaths, and economic losses. Young and recently-weaned rabbits are especially susceptible and the primary symptom is diarrhea, combined with a decrease in growth and performance. Colibacillosis is enteritis caused by the bacterial pathogen Escherichia coli (E. Coii), which in rabbits infects both the small intestine and the cecum. Colibacillosis is very common in young rabbits and mortality rates can be very high; the disease can be passed from the doe to the kits with often the entire litter impacted by the sickness.
  • E. Coii bacterial pathogen Escherichia coli
  • Phytonutrients are naturally-occurring bioactive chemicals found in plants. In monogastric species, supplementation of the feed with the phytonutrient capsicum oleoresin has been shown to mitigate oxidative stress (Karadas et al., 2014. Br Poult Sci. 55: 329-334) and prevent disease symptoms (Liu et al ., 2012. J Anim Sci. 90: 2774-2783, Lee et al., 2013. Br J Nutr. 110: 840-847, Liu et al., 2013. J Anim Sci. 91: 5668-5679, Liu et al., 2013. J Anim Sci. 91: 5294-5306) by enhancing immunity.
  • Capsicum oleoresin has also been shown to improve gut health during normal and disease conditions (Liu et al., 2014. J Anim Sci. 92: 3426-3440, Liu et al., 2014. J Anim Sci. 92: 2050-2062).
  • GLP-2 glucagon-like peptide
  • the effective doses vary but normally range between 20 and 400 ppm for phytonutrients and >200 ppm for high intensity artificial and natural sweeteners (Moran et al., 2010. Br J Nutr. 104: 637-646, Moran et al., 2014. J Dairy Sci. 97: 4955-4972, Ponce et al., 2014. J Anim Sci. 92: 1630- 1638, Siurana et al., 2014. J. Dairy Sci. 97 (E-Suppl. 1): 811 (Abstr.), Connor et al., 2017. J Dairy Sci. 100: 3004-3018). Often even higher doses of these molecules are used especially for phytonutrients which are often used for their anti-microbial properties. The doses used depend on the species, molecules tested and the objectives of the study.
  • the challenge addressed in the current invention is to improve the health and performance of mammals, in particular rabbits, without the use of antibiotics.
  • the inventors explored the use of high intensity artificial and natural sweetener or capsicum oleoresin fed alone and in combination.
  • doses that have previously been established as beneficial in other species are in fact highly detrimental in rabbits.
  • the current invention therefore introduces a novel approach using additives to decrease the negative impact of enteritis in rabbits.
  • a combination of the two additives is used for synergistic effects on health (decreased morbidity - including diarrhea and bloat - and mortality) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of rabbits.
  • a range of specific ratios of high intensity sweetener to capsicum oleoresin is used for synergistic effects on health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of rabbits.
  • a combination of high intensity sweetener and capsicum oleoresin when supplemented at very low doses, improves zootechnical performance of other mammals including calves and piglets.
  • the invention relates to a feed including:
  • At least one artificial high intensity sweetener in an amount greater than zero and less than or equal to 50 ppm; or - at least one natural high intensity sweetener in an amount greater than zero and less than or equal to 180 ppm.
  • the invention pertains to a feed including capsicum oleoresin in an amount greater than zero and less than or equal to 2 ppm.
  • the invention relates to a feed additive including at least one high intensity artificial or natural sweetener and capsicum oleoresin, wherein the weight ratio of high intensity sweetener to capsicum oleoresin is less than 100:1 and preferably less than or equal to 25:1.
  • SW artificial high intensity sweetener
  • SWN natural high intensity sweetener
  • CO capsicum oleoresin
  • SW artificial high intensity sweetener
  • SWN natural high intensity sweetener
  • CO capsicum oleoresin
  • SWN high intensity sweetener
  • CO capsicum oleoresin
  • Figure 4 illustrates that an optimal weight ratio between natural high intensity sweetener (SWN) and capsicum oleoresin (CO) is shown by a linear decrease in morbidity in rabbits inoculated with Escherichia coli.
  • Figure 7 shows that a supplement including natural high intensity sweetener (SWN) at 26 ppm and capsicum oleoresin (CO) at 2 ppm is efficient at decreasing veterinary treatments in calves.
  • SWN natural high intensity sweetener
  • CO capsicum oleoresin
  • Figure 8 shows that a supplement including natural high intensity sweetener (SWN) at 30 ppm and capsicum oleoresin (CO) at 2 ppm is efficient at increasing body weight in piglets.
  • SWN natural high intensity sweetener
  • CO capsicum oleoresin
  • feed additive is herein meant an additive which is not aimed at being used alone but added to the usual ingredients of a conventional feed of the mammal.
  • final feed is herein meant the feed obtained after the addition of the feed additive of the invention and ready to be fed to the mammal.
  • This invention proposes a novel approach for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) in mammals including rabbits, swine, and calves by using low doses of a high intensity sweetener, capsicum oleoresin, or a combination of the two.
  • This invention may be used during normal rearing conditions or during phases where enteritis may be present.
  • enteritis By enteritis, the inventors refer to any inflammation of the gastrointestinal tract of mammals, no matter what the causative agent (including but not limited to: coccidiosis, enterotoxemia, colibacillosis, mucoid enteritis, proliferative enteropathy, or Tyzzer's disease).
  • the high intensity sweetener can be a high intensity artificial sweetener, a high intensity natural sweetener, or their combinations.
  • the high intensity artificial sweetener used for this invention may include and is not limited to: saccharin and its salts, acesulfame-K, cyclamate, aspartame, sucralose, neotame, advantame alone or in combination.
  • the high intensity artificial sweetener may also include a potentiator.
  • the high intensity artificial sweetener includes at least 96wt% sodium saccharinate, and at least 0.2wt% neohesperidin dihydrochalcone (NH DC).
  • the dose of artificial high intensity sweetener used in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) in rabbits includes all doses that are ⁇ 50 ppm in the final feed.
  • the high intensity natural sweetener used for this invention may include and is not limited to: stevia leaf, stevia extracts, steviosides including steviol glycosides, rebaudioside A, rebaudioside C, dulcoside A, rubusoside, steviolbiosode, rebaudioside B, or any other high intensity sweetener from natural origin alone or in combination.
  • the high intensity sweetener from natural origin can also originate from the flowing plants and/or their extracts and/or active compounds: Pentadiplandra brazzeana (pentadina and brazzein), lllicium verum, Piper marginatum or Myrrhis odorata (trans-anethole and estragole), Osmorhiza longistylis (anethole), Citrus paradis (naringin), Hydrangea macrophylla (dihydro-coumarin).
  • the high intensity natural sweetener may also include a potentiator.
  • the high intensity natural sweetener used includes at least 75wt% steviol glycosides (at least 25wt% of which was rebaudioside A), and also a potentiator: at least 0.3wt% ammonium glycyrrhizinate.
  • the potentiator included in the high intensity artificial or natural sweetener may be selected from the list including but not limited to: glycyrrhizin, ammonium glycyrrhizinate, potassium glycyrrhizinate, sodium glycyrrhizinate, thaumatin, kokumi, NHDC, ribotides, sodium glutamate.
  • very low doses of high intensity natural sweetener were discovered to be beneficial for health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of rabbits.
  • the inventors first tested a dose that made sense based on the state of the art as this dose had been previously established as beneficial for other small mammals (360 ppm in the feed). Surprisingly, the inventors found that in rabbits this dose was highly detrimental because it greatly increased mortality during an enteritis challenge. Next, the inventors tested a new lower dose of 180 ppm supplemented to rabbits, followed by an enteritis challenge and it was discovered that mortality was greatly reduced at this low dose.
  • the dose of high intensity natural sweetener used in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth and feed efficiencies) in rabbits includes all doses that are ⁇ 200 ppm and preferably ⁇ 180 in the final feed.
  • the capsicum used for this invention may include and is not limited to: capsicum oleoresin that is plant- derived (natural) or any product containing at least 6wt% capsaicinoids (capsaicin and dihydrocapsaicin).
  • capsicum oleoresin was supplemented as a product that was manufactured using capsicum oleoresin (22wt%) incorporated into a matrix of 78wt% rape seed oil (via spray cooling), the method that is described in document EP2088871 (US20100055253; W02008062368).
  • the final encapsulated product contained 20wt% capsicum oleoresin.
  • capsicum oleoresin were discovered to be beneficial for health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of rabbits.
  • the inventors first tested a dose (4 ppm in the feed) that had been previously established as beneficial for other small mammals, and found that in rabbits it was detrimental because it increased mortality during an enteritis and/or colibacillosis challenge.
  • the inventors tested a new lower dose of 2 ppm supplemented to rabbits, followed by an enteritis challenge and it was discovered that mortality was greatly reduced at this low dose.
  • the dose of capsicum oleoresin used in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) in rabbits includes all doses that are ⁇ 2 ppm in the final feed.
  • the dose of a mixture of high intensity sweetener and capsicum oleoresin used in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) in rabbits includes all doses that are ⁇ 200 ppm and preferably ⁇ 180 ppm of high intensity sweetener and ⁇ 2 ppm of capsicum oleoresin in the final feed (weight ratio of high intensity sweetener: capsicum oleoresin ⁇ 100:1 and preferably ⁇ 25:1).
  • the dose of a mixture of high intensity artificial sweetener and capsicum oleoresin used in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) in rabbits includes all doses that are ⁇ 100 ppm and preferably ⁇ 50 ppm of high intensity artificial sweetener and ⁇ 2 ppm of capsicum oleoresin in the final feed (weight ratio of high intensity artificial sweetener: capsicum oleoresin ⁇ 50:1 and preferably ⁇ 25:1).
  • the inventors then tested the use of such low doses of high intensity sweetener and capsicum oleoresin fed in combination to other mammals including swine and calves. In both cases, the low doses fed improved digestive health and zootechnical performance.
  • the dose of a mixture of high intensity natural sweetener and capsicum oleoresin used in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of mammals includes all doses that are ⁇ 200 ppm and preferably ⁇ 180 ppm of high intensity natural sweetener and ⁇ 2 ppm of capsicum oleoresin in the final feed (weight ratio of high intensity artificial sweetener: capsicum oleoresin ⁇ 100:1 and preferably ⁇ 25:1).
  • the examples provided in this invention include weight ratios of natural high intensity sweetener: capsicum oleoresin of 12.5:1, 45:1, 90:1 (Example 2), 11.5:1 (Example 3), 13:1 (Example 4) and 15:1 (Example 5).
  • the product including high intensity sweetener and capsicum oleoresin that was created in this invention contains up to 66wt% stevia extract (comprising at least 75wt% steviol glycosides of which at least 25wt% is rebaudioside A) and up to 3wt% capsicum oleoresin (containing at least 6wt% capsaicinoids (capsaicin and dihydrocapsaicin)).
  • the final product includes >49wt% steviol glycosides, >12wt% rebaudioside A, and >0.18wt% capsaicinoids. It also includes up to 3wt% NHDC and up to 3wt% Glycyrrhizin NH 3 .
  • the product may include some technological agents such as arabic gum, modified starch, maltodextrin, etc.
  • the product can be obtained via standard atomization technologies (e.g. fluidized bed spray granulation, spray drying, etc.).
  • the effective dose of the product including high intensity sweetener and capsicum oleoresin that was created in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of mammals includes all doses that are ⁇ 100 ppm in the final feed.
  • the effective dose of the product including high intensity artificial sweetener and capsicum oleoresin that was created in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of mammals includes all doses that are ⁇ 100 ppm in the final feed.
  • the effective dose of the product including high intensity natural sweetener and capsicum oleoresin that was created in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of mammals includes all doses that are ⁇ 100 ppm in the final feed.
  • the analysis of high intensity natural sweetener in the product created in this invention can be quantified through steviol glycoside levels using high performance liquid chromatography (HPLC).
  • capsicum oleoresin in the product created in this invention can be quantified through capsaicinoid levels (capsaicin and dihydrocapsaicin) using HPLC or gas chromatography.
  • capsaicinoid levels capsaicin and dihydrocapsaicin
  • Rabbits were assigned to supplementation with no additive (control), 150 ppm of an high intensity artificial sweetener (SW) containing at least 96wt% sodium saccharine, NHDC, and maltodextrin; 360 ppm of a high intensity natural sweetener (SWN) containing at least 70wt% steviosides, ammonium glycyrrhizinate, and maltodextrin; or 4 ppm of capsicum oleoresin (CO) containing at least 6wt% capsaicinoids.
  • SW high intensity artificial sweetener
  • SWN high intensity natural sweetener
  • CO capsicum oleoresin
  • This example is used to illustrate synergy between high intensity natural sweeteners and phytonutrients.
  • Rabbits were assigned to one of 6 dietary treatments: control or supplementation with 180 ppm of SWN of Example 1, 2ppm of CO, or 2 ppm of CO combined with various levels of SWN (23, 90, or 180 ppm) of Example 1.
  • the same enteritis challenge was utilized (rabbits were inoculated with 500 pL containing 5 x 106 CFU/mL of E. Coli inoculum from INRA) and the same parameters were measured as for Example 1.
  • SWN at 180ppm actually increased morbidities (disease symptoms including diarrhea and bloat) during disease challenge (Figure 3).
  • the third example demonstrates the effect of an optimum weight ratio of SWN:CO on rabbit health and performance when supplemented at various doses. Rabbits were assigned to control diets or
  • the fourth example demonstrates the response to calves when supplemented with a diet containing a combination of SWN and CO on intestinal health of calves.
  • Calves were assigned to control diets or diets containing 26 ppm SWN of Example 1 and 2 ppm CO.
  • the supplementation decreased the number of pens treated with electrolytes or antibiotics (Figure 7); results illustrate sensitivity of calves to the low dose of supplements fed in combination.
  • the fifth example demonstrates the effect of a combination of SWN and CO on zootechnical performance of piglets.
  • Piglets were assigned to control diets or supplementation with the 30 ppm SWN of Example 1 and 2 ppm CO.
  • the supplementation increased daily gain and final body weight (Figure 8); results illustrate sensitivity of swine to the low dose of supplement fed in combination.

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Abstract

The invention concerns feed additives containing a combination of a high intensity sweetener and capsicum oleoresin. More precisely, the invention relates to a feed additive to be supplemented to a feed in order to prepare a final feed for mammals, including a combination of - at least one high intensity sweetener; and - capsicum oleoresin; wherein the weight ratio of the high intensity sweetener to capsicum oleoresin is less than or equal to 25:1. The invention also pertains to a final feed including the above feed additive in an amount greater than zero and less than or equal to 200 ppm based on the weight of the total final feed. Further the invention relates to the use of the above feed additive or final feed to improve zootechnical performance of mammals, in particular rabbits, swine and calves.

Description

FEEDS FOR IMPROVING HEALTH AND PERFORMANCE OF MAMMALS
FIELD OF INVENTION
This invention relates to feeds and feed additives containing a high intensity sweetener and/or capsicum oleoresin and their use to improve health and performance of mammals. BACKGROUND OF THE INVENTION
Enteritis is an infection of the digestive tract that can be caused by a variety of different pathogens. In rabbits, enteritis is a devastating disease that accounts for the majority of illnesses, deaths, and economic losses. Young and recently-weaned rabbits are especially susceptible and the primary symptom is diarrhea, combined with a decrease in growth and performance. Colibacillosis is enteritis caused by the bacterial pathogen Escherichia coli (E. Coii), which in rabbits infects both the small intestine and the cecum. Colibacillosis is very common in young rabbits and mortality rates can be very high; the disease can be passed from the doe to the kits with often the entire litter impacted by the sickness. Recently-weaned rabbits are especially susceptible and even those that survive will go on to underperform even after the disease has passed. The primary treatment for colibacillosis in rabbits is antibiotics and also culling of infected animals (both approaches lead to major economic losses). Antibiotic treatment is costly and can lead to problems with resistant strains of bacteria and/or residues in the meat. Therefore, additives that can prevent disease or help animals to fight against the disease - without the use of antibiotics - are of great interest.
Phytonutrients are naturally-occurring bioactive chemicals found in plants. In monogastric species, supplementation of the feed with the phytonutrient capsicum oleoresin has been shown to mitigate oxidative stress (Karadas et al., 2014. Br Poult Sci. 55: 329-334) and prevent disease symptoms (Liu et al ., 2012. J Anim Sci. 90: 2774-2783, Lee et al., 2013. Br J Nutr. 110: 840-847, Liu et al., 2013. J Anim Sci. 91: 5668-5679, Liu et al., 2013. J Anim Sci. 91: 5294-5306) by enhancing immunity. Capsicum oleoresin has also been shown to improve gut health during normal and disease conditions (Liu et al., 2014. J Anim Sci. 92: 3426-3440, Liu et al., 2014. J Anim Sci. 92: 2050-2062).
Another type of feed supplement that can improve gut health is high intensity artificial and natural sweeteners. These molecules activate the sweet taste receptor T1R2/3 in the intestine (as described in document WO2014033218), which stimulates the release of glucagon-like peptide (GLP)-2 from the enteroendocrine cells of the gut (Moran et al 2010. Br J Nutr. 104: 637-646). GLP-2 is a potent gastroprotective agent that increases blood flow, stimulates mucosal growth and prevents cell death during challenging conditions (Connor et al., 2016. Domest Anim Endocrinol. 56 Suppl: S56-65). The response of the gut to high intensity artificial and natural sweeteners is characterized by increased villus height, increased nutrient absorption, and improved tight junction strength and together this leads to improved health and performance. In addition, document WO2014033218 describes the use of high intensity artificial and natural sweeteners to alter the gut microbiota and intestinal glucose absorption of monogastrics.
For both types of additives, the effective doses vary but normally range between 20 and 400 ppm for phytonutrients and >200 ppm for high intensity artificial and natural sweeteners (Moran et al., 2010. Br J Nutr. 104: 637-646, Moran et al., 2014. J Dairy Sci. 97: 4955-4972, Ponce et al., 2014. J Anim Sci. 92: 1630- 1638, Siurana et al., 2014. J. Dairy Sci. 97 (E-Suppl. 1): 811 (Abstr.), Connor et al., 2017. J Dairy Sci. 100: 3004-3018). Often even higher doses of these molecules are used especially for phytonutrients which are often used for their anti-microbial properties. The doses used depend on the species, molecules tested and the objectives of the study.
In rabbits, supplementation of capsicum in the form of ground chili at a dose of 1% of the diet (10000 ppm) has been observed to decrease body weight (Yu et al., 2012. Mol Biol Rep. 39: 7583-7589). In another study, a range of doses (0.5 to 2%; 5000 to 20000 ppm) of a powder containing capsicum frutescens was shown to decrease blood glucose but had no effect on rabbit performance (Dougnon and Gbeassor, 2016. Vet World. 9: 281-286). Supplementation of hyperglycemic rabbits with approximately 1000 ppm of stevia extract decreased blood glucose levels and restored liver glycogen levels, indicating that high intensity natural sweeteners can influence glucose metabolism (Aghajanyan et al., 2017. Biomed Res Int. 2017:
9251358). In the studies for both capsicum and high intensity sweeteners in rabbits, the supplements used were in the form of plants with no indication as to the composition or the level of active ingredients. In addition, the doses used were extremely high and had no effect on animal health and performance.
Because most of the available literature in rabbits describes doses that are far higher than the doses shown to be beneficial in other species, and none of the studies are done in the context of enteric disease, it is necessary to look to the publications in other species for insights. The inclusion of 10 ppm of capsicum oleoresin has been shown to decrease disease symptoms in piglets infected with E. Coli (Liu et al., 2013. J Anim Sci. 91: 5294-5306). In addition, supplementation of milk-fed calves with 400 ppm of a high intensity sweetener was protective against Cryptosporidium parvum challenge (Connor et al., 2017. J Dairy Sci. 100: 3004-3018). The use of plant extracts and/or high intensity artificial and natural sweeteners alone or in combination to improve health and performance during enteritis has not been explored. If these molecules improve gut health in rabbits, it may be possible to observe beneficial effects on animal performance similar to what has been observed in other species. SUMMARY OF TH E INVENTION
The challenge addressed in the current invention is to improve the health and performance of mammals, in particular rabbits, without the use of antibiotics. Based on the state of the knowledge, the inventors explored the use of high intensity artificial and natural sweetener or capsicum oleoresin fed alone and in combination. Surprisingly, doses that have previously been established as beneficial in other species are in fact highly detrimental in rabbits. The current invention therefore introduces a novel approach using additives to decrease the negative impact of enteritis in rabbits.
The use of this invention comprises one or more of the following features:
• High intensity sweeteners or capsicum oleoresin, when supplemented individually at very low
doses, are used to improve health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of rabbits.
• A combination of the two additives is used for synergistic effects on health (decreased morbidity - including diarrhea and bloat - and mortality) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of rabbits. · A range of specific ratios of high intensity sweetener to capsicum oleoresin is used for synergistic effects on health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of rabbits.
• A combination of high intensity sweetener and capsicum oleoresin, when supplemented at very low doses, improves zootechnical performance of other mammals including calves and piglets.
Therefore, according to a first aspect, the invention relates to a feed including:
- at least one artificial high intensity sweetener in an amount greater than zero and less than or equal to 50 ppm; or - at least one natural high intensity sweetener in an amount greater than zero and less than or equal to 180 ppm.
According to a second aspect, the invention pertains to a feed including capsicum oleoresin in an amount greater than zero and less than or equal to 2 ppm.
According to a third aspect, the invention relates to a feed additive including at least one high intensity artificial or natural sweetener and capsicum oleoresin, wherein the weight ratio of high intensity sweetener to capsicum oleoresin is less than 100:1 and preferably less than or equal to 25:1.
Other characteristics and advantages of the invention will now be described in detail in the following disclosure which is given with reference to the accompanying figures.
BRIEF DESCRIPTION OF TH E DRAWINGS
Figure 1 illustrates that standard doses of artificial high intensity sweetener (SW), a natural high intensity sweetener (SWN), or capsicum oleoresin (CO) increase mortality in rabbits inoculated with Escherichia coli (** = p < o.Ol compared to control;† = P < 0.10 compared to control). Values shown in the figure are percentages of mortality relative to control.
Figure 2 illustrates that low doses of artificial high intensity sweetener (SW), a natural high intensity sweetener (SWN), or capsicum oleoresin (CO) decrease mortality in rabbits inoculated with Escherichia coli (** = p < o.Ol compared to control). Values shown in the figure are percentages of mortality relative to control.
Figure 3 shows that a natural high intensity sweetener (SWN) and capsicum oleoresin (CO) exhibit synergies for decreasing morbidity in rabbits inoculated with Escherichia coli (** = P < 0.01; * = P < 0.05 compared to control). Values shown in the figure are the numbers of morbidities relative to control.
Figure 4 illustrates that an optimal weight ratio between natural high intensity sweetener (SWN) and capsicum oleoresin (CO) is shown by a linear decrease in morbidity in rabbits inoculated with Escherichia coli. Figure 5 illustrates that a natural high intensity sweetener (SWN) and capsicum oleoresin (CO) exhibit synergies for improving growth efficiency in rabbits inoculated with Escherichia coli († = P < 0.10 compared to control). Values shown in the figure are ratio of body weight gain ÷ feed consumed relative to control. Figure 6 shows that a supplement containing an optimal weight ratio of natural high intensity sweetener (SWN) and capsicum oleoresin (CO) (23SWN:2CO), fed at a range of doses, is efficient at decreasing morbidity in rabbits inoculated with Escherichia coli (** = P < 0.01 compared to control). Values shown are the total number of morbidities observed per group over time. Figure 7 shows that a supplement including natural high intensity sweetener (SWN) at 26 ppm and capsicum oleoresin (CO) at 2 ppm is efficient at decreasing veterinary treatments in calves.
Figure 8 shows that a supplement including natural high intensity sweetener (SWN) at 30 ppm and capsicum oleoresin (CO) at 2 ppm is efficient at increasing body weight in piglets.
DETAILED DESCRIPTION OF THE INVENTION
By « feed additive » is herein meant an additive which is not aimed at being used alone but added to the usual ingredients of a conventional feed of the mammal.
By « final feed » is herein meant the feed obtained after the addition of the feed additive of the invention and ready to be fed to the mammal.
This invention proposes a novel approach for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) in mammals including rabbits, swine, and calves by using low doses of a high intensity sweetener, capsicum oleoresin, or a combination of the two. This invention may be used during normal rearing conditions or during phases where enteritis may be present.
By enteritis, the inventors refer to any inflammation of the gastrointestinal tract of mammals, no matter what the causative agent (including but not limited to: coccidiosis, enterotoxemia, colibacillosis, mucoid enteritis, proliferative enteropathy, or Tyzzer's disease). The high intensity sweetener can be a high intensity artificial sweetener, a high intensity natural sweetener, or their combinations.
The high intensity artificial sweetener used for this invention may include and is not limited to: saccharin and its salts, acesulfame-K, cyclamate, aspartame, sucralose, neotame, advantame alone or in combination. The high intensity artificial sweetener may also include a potentiator.
During the creation of the invention, the high intensity artificial sweetener includes at least 96wt% sodium saccharinate, and at least 0.2wt% neohesperidin dihydrochalcone (NH DC).
During the creation of the invention, very low doses of artificial high intensity sweetener were discovered to be beneficial for health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of rabbits. The inventors first tested a dose that made sense based on the state of the art as these doses (150 ppm in the feed) had been previously established as beneficial for other small mammals. Surprisingly, the inventors found that in rabbits this dose was highly detrimental because it greatly increased mortality during an enteritis challenge. Next, the inventors tested new lower doses of 50 ppm supplemented to rabbits, followed by an enteritis challenge and it was discovered that mortality was greatly reduced at this low dose. The inventors tested the dose of 50 ppm supplemented to rabbits, followed by a colibacillosis challenge and it was discovered that mortality was greatly reduced at this dose.
Therefore, the dose of artificial high intensity sweetener used in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) in rabbits includes all doses that are < 50 ppm in the final feed.
The high intensity natural sweetener used for this invention may include and is not limited to: stevia leaf, stevia extracts, steviosides including steviol glycosides, rebaudioside A, rebaudioside C, dulcoside A, rubusoside, steviolbiosode, rebaudioside B, or any other high intensity sweetener from natural origin alone or in combination. The high intensity sweetener from natural origin can also originate from the flowing plants and/or their extracts and/or active compounds: Pentadiplandra brazzeana (pentadina and brazzein), lllicium verum, Piper marginatum or Myrrhis odorata (trans-anethole and estragole), Osmorhiza longistylis (anethole), Citrus paradis (naringin), Hydrangea macrophylla (dihydro-coumarin). The high intensity natural sweetener may also include a potentiator. During the creation of the invention, the high intensity natural sweetener used includes at least 75wt% steviol glycosides (at least 25wt% of which was rebaudioside A), and also a potentiator: at least 0.3wt% ammonium glycyrrhizinate.
The potentiator included in the high intensity artificial or natural sweetener may be selected from the list including but not limited to: glycyrrhizin, ammonium glycyrrhizinate, potassium glycyrrhizinate, sodium glycyrrhizinate, thaumatin, kokumi, NHDC, ribotides, sodium glutamate.
During the creation of the invention, very low doses of high intensity natural sweetener were discovered to be beneficial for health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of rabbits. The inventors first tested a dose that made sense based on the state of the art as this dose had been previously established as beneficial for other small mammals (360 ppm in the feed). Surprisingly, the inventors found that in rabbits this dose was highly detrimental because it greatly increased mortality during an enteritis challenge. Next, the inventors tested a new lower dose of 180 ppm supplemented to rabbits, followed by an enteritis challenge and it was discovered that mortality was greatly reduced at this low dose.
Therefore, the dose of high intensity natural sweetener used in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth and feed efficiencies) in rabbits includes all doses that are <200 ppm and preferably <180 in the final feed.
The capsicum used for this invention may include and is not limited to: capsicum oleoresin that is plant- derived (natural) or any product containing at least 6wt% capsaicinoids (capsaicin and dihydrocapsaicin). During the creation of this invention, the capsicum oleoresin was supplemented as a product that was manufactured using capsicum oleoresin (22wt%) incorporated into a matrix of 78wt% rape seed oil (via spray cooling), the method that is described in document EP2088871 (US20100055253; W02008062368). The final encapsulated product contained 20wt% capsicum oleoresin.
During the creation of the invention, very low doses of capsicum oleoresin were discovered to be beneficial for health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of rabbits. The inventors first tested a dose (4 ppm in the feed) that had been previously established as beneficial for other small mammals, and found that in rabbits it was detrimental because it increased mortality during an enteritis and/or colibacillosis challenge. Next, the inventors tested a new lower dose of 2 ppm supplemented to rabbits, followed by an enteritis challenge and it was discovered that mortality was greatly reduced at this low dose. The inventors tested the dose of 2 ppm supplemented to rabbits, followed by a colibacillosis challenge and it was discovered that mortality was greatly reduced at this dose.
Therefore, the dose of capsicum oleoresin used in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) in rabbits includes all doses that are <2 ppm in the final feed.
During the creation of the invention, a strong synergy was discovered between the high intensity sweetener and the capsicum oleoresin. In addition, the strongest synergy was observed when the inclusion of high intensity sweetener was less than 180 ppm in the feed and the inclusion of capsicum oleoresin was 2 ppm. When these inclusion rates were tested as a combination supplement, rabbit health was improved
(decreased mortality - including diarrhea and bloat - and morbidity) and efficiency of growth was also improved.
Therefore, the dose of a mixture of high intensity sweetener and capsicum oleoresin used in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) in rabbits includes all doses that are < 200 ppm and preferably < 180 ppm of high intensity sweetener and < 2 ppm of capsicum oleoresin in the final feed (weight ratio of high intensity sweetener: capsicum oleoresin < 100:1 and preferably < 25:1).
Therefore, the dose of a mixture of high intensity artificial sweetener and capsicum oleoresin used in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) in rabbits includes all doses that are < 100 ppm and preferably < 50 ppm of high intensity artificial sweetener and < 2 ppm of capsicum oleoresin in the final feed (weight ratio of high intensity artificial sweetener: capsicum oleoresin < 50:1 and preferably < 25:1).
During the creation of this invention, the inventors then tested the use of such low doses of high intensity sweetener and capsicum oleoresin fed in combination to other mammals including swine and calves. In both cases, the low doses fed improved digestive health and zootechnical performance.
The dose of a mixture of high intensity natural sweetener and capsicum oleoresin used in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of mammals includes all doses that are < 200 ppm and preferably < 180 ppm of high intensity natural sweetener and < 2 ppm of capsicum oleoresin in the final feed (weight ratio of high intensity artificial sweetener: capsicum oleoresin < 100:1 and preferably < 25:1). The examples provided in this invention include weight ratios of natural high intensity sweetener: capsicum oleoresin of 12.5:1, 45:1, 90:1 (Example 2), 11.5:1 (Example 3), 13:1 (Example 4) and 15:1 (Example 5). The product including high intensity sweetener and capsicum oleoresin that was created in this invention contains up to 66wt% stevia extract (comprising at least 75wt% steviol glycosides of which at least 25wt% is rebaudioside A) and up to 3wt% capsicum oleoresin (containing at least 6wt% capsaicinoids (capsaicin and dihydrocapsaicin)). Therefore, the final product includes >49wt% steviol glycosides, >12wt% rebaudioside A, and >0.18wt% capsaicinoids. It also includes up to 3wt% NHDC and up to 3wt% Glycyrrhizin NH3. The product may include some technological agents such as arabic gum, modified starch, maltodextrin, etc. The product can be obtained via standard atomization technologies (e.g. fluidized bed spray granulation, spray drying, etc.).
The effective dose of the product including high intensity sweetener and capsicum oleoresin that was created in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of mammals includes all doses that are < 100 ppm in the final feed.
The effective dose of the product including high intensity artificial sweetener and capsicum oleoresin that was created in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of mammals includes all doses that are < 100 ppm in the final feed.
The effective dose of the product including high intensity natural sweetener and capsicum oleoresin that was created in this invention for improving health (decreased mortality - including diarrhea and bloat - and morbidity) and performance (increased intake, daily gains and/or improved growth or feed efficiencies) of mammals includes all doses that are < 100 ppm in the final feed. The analysis of high intensity natural sweetener in the product created in this invention can be quantified through steviol glycoside levels using high performance liquid chromatography (HPLC).
The analysis of capsicum oleoresin in the product created in this invention can be quantified through capsaicinoid levels (capsaicin and dihydrocapsaicin) using HPLC or gas chromatography. The current invention is not limited by the details described herein, but includes variations that are contained within the scope of the claims.
EXAMPLES EXAMPLE 1
In this example, the effect of high and low doses of high intensity artificial and natural sweeteners or capsicum oleoresin on mortality of rabbits is described. Rabbits were assigned to supplementation with no additive (control), 150 ppm of an high intensity artificial sweetener (SW) containing at least 96wt% sodium saccharine, NHDC, and maltodextrin; 360 ppm of a high intensity natural sweetener (SWN) containing at least 70wt% steviosides, ammonium glycyrrhizinate, and maltodextrin; or 4 ppm of capsicum oleoresin (CO) containing at least 6wt% capsaicinoids. All ppm are expressed as final concentration of supplement in the feed. An enteritis challenge was employed: rabbits were inoculated with 500 pL containing 5 x 106 CFU/mL of E. Coli inoculum from INRA. Feed intake and weight gain were measured daily. In addition, health parameters including diarrhea and bloat were assessed daily and mortalities were recorded. Surprisingly, all three supplements significantly increased mortality (Figure 1), despite the use of doses that have been established as beneficial in other mammals.
A follow-up experiment was conducted to determine if lower doses of the supplements would have an effect on mortality. The exact same protocol was followed as the first experiment, except that the additives were supplemented at 50 ppm for SW, 180 ppm for SWN, or 2 ppm of CO. In contrast to what was observed in the first study, low doses of all three additives significantly decreased mortality relative to control (Figure 2). Each additive on its own was highly effective in reducing mortality, at doses that have not been described previously.
EXAMPLE 2
This example is used to illustrate synergy between high intensity natural sweeteners and phytonutrients. Rabbits were assigned to one of 6 dietary treatments: control or supplementation with 180 ppm of SWN of Example 1, 2ppm of CO, or 2 ppm of CO combined with various levels of SWN (23, 90, or 180 ppm) of Example 1. The same enteritis challenge was utilized (rabbits were inoculated with 500 pL containing 5 x 106 CFU/mL of E. Coli inoculum from INRA) and the same parameters were measured as for Example 1. Despite the decrease in mortality (few deaths) observed previously, SWN at 180ppm actually increased morbidities (disease symptoms including diarrhea and bloat) during disease challenge (Figure 3). The 2ppm of CO alone had no effect; nor did the combination of 2ppm CO and 180ppm SWN. However, the combination of 2ppm CO and 23ppm SWN significantly reduced morbidities (Figure 3) and also increased efficiency of growth (Figure 4). In addition, a regression analysis of the three combinations illustrates a very strong linear relationship and allowed the identification of an optimal weight ratio of SWN:CO for improving performance (Figure 5).
EXAMPLE 3
The third example demonstrates the effect of an optimum weight ratio of SWN:CO on rabbit health and performance when supplemented at various doses. Rabbits were assigned to control diets or
supplementation with the 23SWN:2CO combination of Example 2 fed at 100, 75, or 50ppm. The inoculation was done as described previously and the same parameters were measured. Across all three doses, the combination additive decreased morbidity after the E. Coli challenge (Figure 6). This validated the benefit of the lOOppm dose (Figure 5) and also illustrated sensitivity and efficacy of even lower doses as well. EXAMPLE 4
The fourth example demonstrates the response to calves when supplemented with a diet containing a combination of SWN and CO on intestinal health of calves. Calves were assigned to control diets or diets containing 26 ppm SWN of Example 1 and 2 ppm CO. The supplementation decreased the number of pens treated with electrolytes or antibiotics (Figure 7); results illustrate sensitivity of calves to the low dose of supplements fed in combination.
EXAMPLE 5
The fifth example demonstrates the effect of a combination of SWN and CO on zootechnical performance of piglets. Piglets were assigned to control diets or supplementation with the 30 ppm SWN of Example 1 and 2 ppm CO. The supplementation increased daily gain and final body weight (Figure 8); results illustrate sensitivity of swine to the low dose of supplement fed in combination.

Claims

1.- A feed additive to be supplemented to a feed in order to prepare a final feed for mammals, including a combination of
- at least one high intensity sweetener; and
- capsicum oleoresin;
wherein the weight ratio of the high intensity sweetener to capsicum oleoresin is less than or equal to 25:1.
2.- Feed additive according to claim 1, wherein the high intensity sweetener is an artificial high intensity sweetener.
3.- Feed additive according to claim 2, wherein the artificial high intensity sweetener is selected from the group consisting of saccharin and its salts, acesulfame-K, cyclamate, aspartame, sucralose, neotame, advantame and combinations thereof.
4.- Feed additive according to claim 1, wherein the high intensity sweetener is a natural high intensity sweetener.
5.- Feed additive according to claim 4, wherein the natural high intensity sweetener is selected from the group consisting of stevia leaf, stevia extracts, steviosides including steviol glycosides, rebaudioside A, rebaudioside C, dulcoside A, rubusoside, steviolbiosode, rebaudioside B, and combinations thereof.
6.- Feed additive according to claim 5, wherein the steviol glycosides include at least 25 wt% of rebaudioside A.
7.- Feed additive according to claims 6, comprising 66 wt% stevia extract (comprising at least 75 wt% steviol glycosides of which at least 25wt% is rebaudioside A) and up to 3wt% capsicum oleoresin (containing at least 6wt% capsaicinoids (capsaicin and dihydrocapsaicin)).
8.- Feed additive according to any one of claims 1 to 7, further comprising a potentiator.
9.- Feed additive according to claim 8, wherein the potentiator is selected from the group consisting of glycyrrhizin, ammonium glycyrrhizinate, potassium glycyrrhizinate, sodium glycyrrhizinate, thaumatin, kokumi, NFIDC, ribotides, sodium glutamate and combinations thereof.
10.- A final feed including a feed additive according to any one of claims 1 to 9 in an amount greater than zero and less than or equal to 200 ppm based on the weight of the total final feed.
11.- A final feed according to claim 10, wherein if the high intensity sweetener is an artificial high intensity sweetener, it is present in an amount less than or equal to 100 ppm.
12.- Final feed according to claim 11, wherein the artificial high intensity sweetener is present in an amount less than or equal to 50 ppm.
13.- Final feed according to claim 10, wherein if the high intensity sweetener is a natural high intensity sweetener, it is present in an amount less than or equal to 180 ppm.
14.- Use of a feed additive according to any one of claims 1 to 9 to improve the zootechnical performances of mammals.
15.- Use according to claim 14, wherein the mammals are rabbits, swine and/or calves.
16.- Use according to claim 15, wherein the mammals are rabbits.
17.- Use of a final feed according to any one of claims 10 -13 to improve the zootechnical performances of mammals.
18.- Use according to claim 17, wherein the mammals are rabbits, swine and/or calves.
19.- Use according to claim 18, wherein the mammals are rabbits.
20.- Use according to any one of claims 14 to 19, wherein said zootechnical performances are selected in the group consisting of feed intake, average daily gain and feed efficiency.
EP19715223.4A 2018-03-15 2019-03-11 Feeds for improving health and performance of mammals Pending EP3764817A1 (en)

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FR2926440B1 (en) * 2008-01-23 2012-08-24 Pancosma Sa Pour L Ind Des Produits Biochimiques CAPSICUM-BASED FOOD ADDITIVE AND USES THEREOF
FR2971402A1 (en) * 2011-02-11 2012-08-17 Pancosma Sa Pour L Ind Des Produits Biochimiques USE OF AN ADDITIVE COMPRISING AT LEAST ONE SWEETENER IN THE FEEDING AND / OR WATER OF FRESH BEVERAGE (S)
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