WO2017083067A1 - Nutritional compositions containing butyrate and uses thereof - Google Patents

Nutritional compositions containing butyrate and uses thereof Download PDF

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Publication number
WO2017083067A1
WO2017083067A1 PCT/US2016/057641 US2016057641W WO2017083067A1 WO 2017083067 A1 WO2017083067 A1 WO 2017083067A1 US 2016057641 W US2016057641 W US 2016057641W WO 2017083067 A1 WO2017083067 A1 WO 2017083067A1
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WIPO (PCT)
Prior art keywords
nutritional composition
butyrate
protein
dietary
nutritional
Prior art date
Application number
PCT/US2016/057641
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English (en)
French (fr)
Inventor
Juan M. Gonzalez
Teartse Tim. LAMBERS
Eric A.F. Van Tol
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Mjn U.S. Holdings Llc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from US14/936,014 external-priority patent/US20170127693A1/en
Priority claimed from US14/959,107 external-priority patent/US10034937B2/en
Priority claimed from US15/011,797 external-priority patent/US20170215464A1/en
Priority to CA3004737A priority Critical patent/CA3004737A1/en
Priority to JP2018523455A priority patent/JP2018532417A/ja
Priority to MX2018005659A priority patent/MX2018005659A/es
Application filed by Mjn U.S. Holdings Llc filed Critical Mjn U.S. Holdings Llc
Priority to CN201680065418.8A priority patent/CN108347985A/zh
Priority to BR112018008726A priority patent/BR112018008726A2/pt
Priority to EP16791172.6A priority patent/EP3373749A1/en
Priority to SG11201803125XA priority patent/SG11201803125XA/en
Priority to AU2016351454A priority patent/AU2016351454A1/en
Publication of WO2017083067A1 publication Critical patent/WO2017083067A1/en
Priority to PH12018500994A priority patent/PH12018500994A1/en

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    • 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
    • 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
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • 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
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • 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
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/18—Peptides; Protein hydrolysates
    • 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
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/19—Dairy proteins
    • 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
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/11—Lactobacillus

Definitions

  • the present disclosure relates generally to nutritional compositions comprising dietary butyrate that are suitable for administration to pediatric subjects. Additionally, the disclosure relates to methods for improving the shelf-stability of nutritional compositions inciuding dietary butyrate, and methods for improving the organoleptic properties of nutritional compositions including dietary butyrate.
  • the disclosed nutritional compositions may provide additive and or/synergistic beneficial health effects.
  • compositions including butyrate or butyrate derivatives often suffer from difficulties regarding the availability of butyrate upon administration.
  • certain butyrate derivatives undergo degradation or oxidation, which ultimate affect the bioavailability of the butyrate derivative upon ingestion.
  • compositions including butyrate derivatives may not provide nutritional efficacy upon ingestion given the degradation of the butyrate derivative.
  • compositions including butyrate may suffer from poor palatability.
  • the unpleasant taste and odor of compositions inciuding butyrate can make the oral administration of certain nutritional compositions including butyrate difficult, especially in the pediatric population.
  • certain butyric acid derivatives at room temperature are present as a dense liquid having an unpleasant intense odor.
  • a nutritional composition that includes dietary butyrate having improved shelf-stability and organoleptic properties. Additionally, it is beneficial to provide methods of producing a nutritional composition including dietary butyrate having improved shelf stability and organoleptic properties.
  • the present disclosure is directed, in an embodiment, to a nutritional composition that includes dietary butyrate.
  • the dietary butyrate may be encapsulated.
  • the dietary butyrate may be provided by an enriched lipid fraction derived from milk.
  • the nutritional composition includes dietary butyrate that has improved organoleptic properties.
  • the nutritional composition including dietary butyrate has improved shelf-stability.
  • the disclosure is directed to a methods for improving the shelf stability and/or organoleptic properties of a nutritional composition including dietary butyrate.
  • the present disclosure relates generally to nutritional compositions comprising dietary butyrate. Additionally, the disclosure relates to methods for improving the shelf stability and/or organoleptic properties of nutritional compositions including butyrate.
  • Nutritional composition means a substance or formulation that satisfies at least a portion of a subject's nutrient requirements.
  • the terms “nutritional (s)”, “nutritional formula(s)”, “enteral nutritional (s)”, and “nutritional supplement(s)” are used as non- limiting examples of nutritional composition ⁇ ) throughout the present disclosure.
  • nutritionai composition(s) may refer to liquids, powders, gels, pastes, solids, concentrates, suspensions, or ready-to-use forms of enteral formulas, oral formulas, formulas for infants, formulas for pediatric subjects, formulas for children, growing-up milks and/or formulas for adults.
  • a pediatric subject means a human less than 13 years of age.
  • a pediatric subject refers to a human subject that is between birth and 8 years old.
  • a pediatric subject refers to a human subject between 1 and 6 years of age.
  • a pediatric subject refers to a human subject between 6 and 12 years of age.
  • the term “pediatric subject” may refer to infants (preterm or fullterm) and/or children, as described below.
  • infant means a human subject ranging in age from birth to not more than one year and includes infants from 0 to 12 months corrected age.
  • corrected age means an infant's chronological age minus the amount of time that the infant was born premature. Therefore, the corrected age is the age of the infant if it had been carried to full term.
  • infant includes low birth weight infants, very low birth weight infants, and preterm infants.
  • Preterm means an infant born before the end of the 37 th week of gestation.
  • Full term means an infant born after the end of the 37 th week of gestation.
  • Child means a subject ranging in age from 12 months to about 13 years. In some embodiments, a child is a subject between the ages of 1 and 12 years old. in other embodiments, the terms “children” or “child” refer to subjects that are between one and about six years old, or between about seven and about 12 years old. In other embodiments, the terms “children” or “child” refer to any range of ages between 12 months and about 13 years.
  • infant formula means a composition that satisfies at least a portion of the nutrient requirements of an infant. In the United States, the content of an infant formula is dictated by the federal regulations set forth at 21 C.F. . Sections 100, 106, and 107.
  • Fractionation procedure includes any process in which a certain quantity of a mixture is divided up into a number of smaller quantities known as fractions. The fractions may be different in composition from both the mixture and other fractions. Examples of fractionation procedures include but are not limited to melt fractionation, solvent fractionation, supercritical fluid fractionation and/or combinations thereof.
  • Milk fat globule membrane includes components found in the milk fat globule membrane including but not limited to milk fat globule membrane proteins such as Mucin 1 , Butyrophilin, Adipophilin, CD36, CD 14, Lactadherin (PAS6/7), Xanthine oxidase and Fatty Acid binding proteins etc.
  • growing-up milk refers to a broad category of nutritional
  • “Milk” means a component that has been drawn or extracted from the mammary gland of a mammal.
  • the nutritional composition comprises components of milk that are derived from domesticated ungulates, ruminants or other mammals or any combination thereof.
  • “Nutritionally complete” means a composition that may be used as the sole source of nutrition, which would supply essentially all of the required daily amounts of vitamins, minerals, and/or trace elements in combination with proteins, carbohydrates, and lipids. Indeed, “nutritionally complete” describes a nutritional composition that provides adequate amounts of carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, conditionally essential amino acids, vitamins, minerals and energy required to support normal growth and development of a subject.
  • a nutritional composition that is "nutritionally complete" for a full term infant will, by definition, provide qualitatively and quantitatively adequate amounts of all carbohydrates, lipids, essential fatty acids, proteins, essential amino acids, conditionally essential amino acids, vitamins, minerals, and energy required for growth of the full term infant.
  • a nutritional composition that is "nutritionally complete” for a child will, by definition, provide qualitatively and quantitatively adequate amounts of all
  • Dietary butyrate refers to butyrate and butyrate derivatives.
  • Non-limiting examples of dietary butyrate include butyric acid, butyrate salts, and glycerol esters of butyric acid.
  • degree of hydrolysis refers to the extent to which peptide bonds are broken by a hydrolysis method.
  • the degree of protein hydrolysis for purposes of characterizing the hydro!yzed protein component of the nutritional composition is easily determined by one of ordinary skill in the formulation arts by quantifying the amino nitrogen to total nitrogen ratio (AN/TN) of the protein component of the selected formulation.
  • the amino nitrogen component is quantified by USP titration methods for determining amino nitrogen content, while the total nitrogen component is determined by the jeidahl method, all of which are well known methods to one of ordinary skill in the analytical chemistry art.
  • molar mass distribution when used in reference to a hydrolyzed protein or protein hydrolysate pertains to the molar mass of each peptide present in the protein hydrolysate.
  • a protein hydrolysate having a molar mass distribution of greater than 500 Daltons means that each peptide included in the protein hydrolysate has a molar mass of at least 500 Daltons.
  • a protein hydrolysate may be subjected to certain filtering procedures or any other procedure known in the art for removing peptides, amino acids, and/or other proteinaceous material having a molar mass of less than 500 Daltons.
  • any method known in the art may be used to produce the protein hydrolysate having a molar mass distribution of greater than 500 Dalton.
  • protein equivalent or “protein equivalent source” includes any protein source, such as soy, egg, whey, or casein, as well as non-protein sources, such as peptides or amino acids. Further, the protein equivalent source can be any used in the art, e.g., nonfat milk, whey protein, casein, soy protein, hydrolyzed protein, amino acids, and the like. Bovine milk protein sources useful in practicing the present disclosure include, but are not limited to, milk protein powders, milk protein
  • the protein equivalent source can, in some embodiments comprise hydrolyzed protein, including partially hydrolyzed protein and extensively hydrolyzed protein.
  • the protein equivalent source may, in some embodiments, include intact protein.
  • protein equivalent source also encompasses free amino acids.
  • the amino acids may comprise, but are not limited to, histidine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine, threonine, tryptophan, valine, alanine, arginine, asparagine, aspartic acid, glutamic acid, glutamine, glycine, proline, serine, carnitine, taurine and mixtures thereof, in some embodiments, the amino acids may be branched chain amino acids.
  • small amino acid peptides may be included as the protein component of the nutritional composition. Such small amino acid peptides may be naturally occurring or synthesized.
  • partially hydrolyzed means having a degree of hydrolysis which is greater than 0% but less than about 50%.
  • extent of hydrolysis means having a degree of hydrolysis which is greater than or equal to about 50%.
  • extent of hydrolysis means casein having a degree of hydrolysis which is greater than or equal to about 50%.
  • extensively hydrolyzed may include a degree of hydrolysis of greater than about 80%. !n further embodiments, extensively hydrolyzed may include a degree of hydrolysis of greater than about 90%.
  • protein-free means containing no measurable amount of intact protein, as measured by standard protein detection methods such as sodium dodecyl (lauryl) sulfate-polyacryiamide gel electrophoresis (SDS-PAGE) or size exclusion chromatography.
  • the nutritional composition is substantially free of protein, wherein “substantially free” is defined hereinbeiow.
  • the nutritional composition of the present disclosure may be substantially free of any optional or selected ingredients described herein, provided that the remaining nutritional composition stiil contains all of the required ingredients or features described herein.
  • the term “substantially free” means that the selected composition may contain less than a functional amount of the optional ingredient, typically less than 0.1 % by weight, and also, including zero percent by weight of such optional or selected ingredient.
  • Ail percentages, parts and ratios as used herein are by weight of the total composition, unless otherwise specified.
  • Ail references ⁇ o singular characteristics or limitations of the present disclosure shall include the corresponding plural characteristic or limitation, and vice versa, unless otherwise specified or clearly implied to the contrary by the context in which the reference is made.
  • compositions of the present disclosure can comprise, consist of, or consist essentially of the essentia! elements and limitations of the embodiments described herein, as well as any additional or optional ingredients, components or limitations described herein or otherwise useful in nutritional compositions.
  • the present disclosure is directed to nutritional compositions including dietary butyrate.
  • the nutritional compositions may further include a carbohydrate source, a protein source, and a fat source.
  • the nutritional composition includes a source of dietary butyrate that is present in an amount of from about 0.2 g/ 00 g fatty acids to about 1 .8 g/100 g fatty acids where the fat source constitutes from about 4 g fat/ 100 Kcal to about 6 g fat/100 Kcal.
  • the dietary butyrate is provided by one or more of the following: butyric acid; butyrate salts, including sodium butyrate, potassium butyrate, calcium butyrate, and/or magnesium butyrate; glycerol esters of butyric acid; and/or corresponding mixtures and corresponding salts of pharmaceutically acceptable bases or acids, pure diastereoisomeric forms and enantiomeric forms or mixtures thereof.
  • the dietary butyrate is supplied by any suitable source known in the art.
  • Non-limiting sources of dietary butyrate includes animal source fats and derived products, such as but not limited to miik, milk fat, butter, buttermilk, butter serum, cream,; microbial fermentation derived products, such as but not limited to yogurt, fermented buttermilk, cheese, beverages; and plant source derived seed oil products, such as pineapple, and apricot.
  • the dietary butyrate is synthetically produced.
  • the chemical structure of the dietary butyrate can be formed and modified as necessary.
  • the dietary butyrate produced synthetically can be purified by any means known in the art to produce a purified dietary butyrate additive that can be incorporated into the nutritional compositions disclosed herein.
  • the dietary butyrate may be provided in an
  • the encapsulation of the dietary butyrate may provide for longer shelf-stability and may provide for improved organoleptic properties of the nutritional composition.
  • the dietary butyrate may be coated or encapsulated by the use of, or combination of, fat derived materials, such as mono- and di-glycerides, sugar and acid esters of glycerides, phospholipids; plant, animal and microbial derived proteins and
  • hydrocolloids such as starches, maltodextrins, gelatin, pectins, glucans, caseins, soy proteins, whey proteins.
  • the dietary butyrate comprises glycerol esters of butyric acid and/or alkyl esters of butyric acid.
  • Glycerol esters of butyric acid may offer minimal complexity when formulated and processed in the nutritional composition. Additionally, glycerol esters of butyric acid may improve the shelf life of the nutritional composition including dietary butyrate and may further have a low impact on the sensory attributes of the finished product.
  • dietary butyrate may comprise butyric acid amide derivatives using other amino acids, for example, tyrosine and/or histidine.
  • any suitable amino acid known in the art may be utilized in preparing the butyric acid amide derivative used as a source of dietary butyrate. Without being bound by any particular theory, it is believed that dietary butyrate comprised of butyric acid amide derivatives may resist the action of gastric acids and the processing conditions encountered in nutritional composition, such as infant formula,
  • the resulting nutritional composition includes a stable dietary butyrate formulation with improved organoleptic properties.
  • the dietary butyrate may in some embodiments comprise butyrate salts, for example, sodium butyrate, potassium butyrate, calcium butyrate, magnesium butyrate, and combinations thereof.
  • the use of selected dietary butyrate salts may improve intestinal health when provided to target subjects.
  • dietary butyrate comprises a suitable butyrate salt that has been coated with one or more fats or lipids.
  • the nutritional composition may be a dry-powdered composition into which the dietary butyrate is incorporated.
  • the dietary butyrate may comprise any of the butyrate compounds disclosed herein that are formulated to be in complex form with chitosan or one or more cyclodextrins.
  • cyclodextrins are cyclic oligosaccharides composed of six (a-cyclodextrin), seven ( ⁇ -cyciodextrin), or eight (gamma- cyclodextrin) units of a-l ,4-glucopyranose.
  • Cyclodextrins are further characterized by a hydrophilic exterior surface and a hydrophobic core.
  • the aliphatic butyrate chain would form a complex with the cyclodextrin core, thus increasing its molecular weight and, thus, reducing the volatility of the butyrate compound. Accordingly, the bioavailability of dietary butyrate may be improved when the dietary butyrate includes butyrate compounds in complex form with one or more cyclodextrins. Further, cyclodextrins are bulky hydrophobic molecules that are resistant to stomach acid as well as gastrointestinal enzymes, thus
  • the dietary butyrate can be provided from an enriched lipid fraction derived from miik in certain embodiments.
  • bovine milk fat has a butyric acid content that may be 20 times higher than the butyric acid content present in human milk fat.
  • SCFAs short chain fatty acids
  • C4 butyric acid
  • bovine milk fat and/or enriched fractions of bovine milk fat may be included in a nutritional composition to provide dietary butyrate.
  • the enriched lipid fraction derived from milk may be produced by any number of fractionation techniques. These techniques include but are not limited to melting point fractionation, organic solvent fractionation, super critical fluid fractionation, and any variants and combinations thereof.
  • mixtures that may be subjected to the fractionation procedures to produce the enriched lipid fraction include, but are not limited to, bovine whole milk, bovine cream, caprine milk, ovine milk, yak milk and/or mixtures thereof.
  • the milk mixture used to create the enriched lipid fraction is bovine milk.
  • the enriched lipid fraction may comprise an one of the following ingredients: saturated fatty acids; trans-fatty acids; branched-chain fatty acids ("BCFAs”), including odd-branched chain fatty acids (“OBCFAs” ⁇ ; conjugated linoieic acid (“CLA”); monounsaturated fatty acids;
  • BCFAs branched-chain fatty acids
  • OBCFAs odd-branched chain fatty acids
  • CLA conjugated linoieic acid
  • monounsaturated fatty acids CLA
  • polyunsaturated fatty acids cholesterol; phospholipids; and milk fat globule membrane, including milk fat globule membrane protein.
  • the enriched lipid fraction includes, per 100 Kcal, one more of the following:
  • dietary butyrate is incorporated into a nutritional composition that is an infant formula.
  • Certain butyrate compounds such as acid salts and alkyl esters of butyric acid, exhibit an odor that makes consuming the nutritional composition in which they are incorporated an unpleasant experience.
  • the pediatric and infant population will not readily consume products having an unpleasant odor, taste, and/or mouthfeel.
  • the incorporation of certain dietary butyrate compounds disclosed herein, i.e. glycerol esters of butyric acid, butyrate enriched milk fat fractions, and amide derivatives of amino acids, into pediatric and infant nutritional compositions will provide a source of dietary butyrate while still providing a pleasant sensory experience.
  • the nutritional composition(s) of the present disclosure may also comprise a carbohydrate source.
  • Carbohydrate sources can be any used in the art, e.g., lactose, glucose, fructose, corn syrup solids, ma!todextrins, sucrose, starch, rice syrup solids, and the like.
  • the amount of carbohydrate in the nutritional composition typically can vary from between about 5 g and about 25 g/100 Kcai. In some embodiments, the amount of carbohydrate is between about 6 g and about 22 g/ 100 Kca!. In other
  • the amount of carbohydrate is between about 12 g and about 14 g/100 Kcai.
  • corn syrup solids are preferred.
  • hydrolyzed, partially hydrolyzed, and/or extensively hydrolyzed carbohydrates may be desirable for inclusion in the nutritional composition due to their easy digestibility.
  • hydrolyzed carbohydrates are less likely to contain allergenic epitopes.
  • Non-iimiting examples of carbohydrate materials suitable for use herein include hydrolyzed or intact, naturally or chemically modified, starches sourced from corn, tapioca, rice or potato, in waxy or non-waxy forms.
  • suitable carbohydrates include various hydrolyzed starches characterized as hydrolyzed cornstarch, maltodextrin, maltose, corn syrup, dextrose, corn syrup solids, glucose, and various other glucose polymers and combinations thereof.
  • Non-limiting examples of other suitable carbohydrates include those often referred to as sucrose, lactose, fructose, high fructose corn syrup, indigestible oligosaccharides such as
  • fructooligosaccharides and combinations thereof.
  • the nutritional composition(s) of the disclosure may also comprise a protein source.
  • the protein source can be any used in the art, e.g., nonfat milk, whey protein, casein, soy protein, hydrolyzed protein, amino acids, and the like.
  • Bovine milk protein sources useful in practicing the present disclosure include, but are not limited to, milk protein powders, milk protein concentrates, milk protein isolates, nonfat milk solids, nonfat milk, nonfat dry milk, whey protein, whey protein isolates, whey protein concentrates, sweet whey, acid whey, casein, acid casein, caseinate (e.g. sodium caseinate, sodium calcium caseinate, calcium caseinate) and any combinations thereof.
  • the proteins of the nutritional composition are provided as intact proteins. In other embodiments, the proteins are provided as a combination of both intact proteins and partially hydrolyzed proteins, with a degree of hydrolysis of between about 4% and 10%. in certain other embodiments, the proteins are more completely hydrolyzed. In still other embodiments, the protein source comprises amino acids. In yet another embodiment, the protein source may be supplemented with g!utamine-containing peptides.
  • the nutritional composition may include a protein equivalent source, wherein at least 1 % of the protein equivalent source comprises extensively hydrolyzed casein and up to 99% of the protein equivalent source comprises an intact protein, a partially hydrolyzed protein, amino acids, or
  • 1 % to 80% of the protein equivalent source comprises extensively hydrolyzed casein and 20% to 99% of the protein equivalent source comprises intact protein, partially hydrolyzed protein, amino acids, or combinations thereof.
  • from 40% to 100% of the protein equivalent source comprises extensively hydrolyzed casein and from 0 to 60% of the protein equivalent source comprises an intact protein, a partially hydrolyzed protein, amino acids, or combinations thereof
  • from 40% to 70% of the protein equivalent source comprises extensively hydrolyzed casein and from 30% to 60% of the protein equivalent source comprises an intact protein, a partially hydrolyzed protein, amino acids, or combinations thereof.
  • extensively hydrolyzed casein may be present in the nutritional composition in an amount from about 0.2 g/100 kca! to about 5.6 g/100 kcai. In other embodiments extensively hydrolyzed casein may be present in the nutritional composition in an amount from about 1 g/100 kcal to about 4 g/100 kcal. In still other embodiments, extensively hydrolyzed casein may be present in the nutritional composition in an amount from about 2 g/100 kcal to about 3 g/100 kcal.
  • the protein equivalent source disclosed herein may be formulated with other ingredients in the nutritional composition to provide appropriate nutrient levels for the target subject, in some embodiments, the protein equivalent source is included in a nutritionally complete formula that is suitable to support normal growth.
  • the protein equivalent source comprises a hydrolyzed protein, such as casein, which includes partially hydrolyzed protein and extensively hydrolyzed protein (i.e., the extensively hydrolyzed casein) .
  • the extensively hydrolyzed casein comprises an extensively hydrolyzed casein and/or fractions thereof including peptides having a molar mass distribution of greater than 500 Daitons.
  • the extensively hydrolyzed casein comprises peptides having a molar mass distribution in the range of from about 500 Daitons to about 1 ,500 Daitons.
  • the extensively hydrolyzed casein may comprise peptides having a molar mass distribution range of from about 500 Daitons to about 2,000 Daitons.
  • the protein equivalent source comprises partially hydrolyzed protein having a degree of hydrolysis of less than 40%.
  • the protein equivalent source may comprise partially hydrolyzed protein having a degree of hydrolysis of less than 25%, or less than 15%.
  • the nutritional composition is protein-free and contains free amino acids as a protein equivalent source.
  • the amino acids may comprise, but are not limited to, histidine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine, threonine, tryptophan, valine, alanine, arginine, asparagine, aspartic acid, glutamic acid, glutamine, glycine, proline, serine, carnitine, taurine and mixtures thereof.
  • the amino acids may be branched chain amino acids.
  • small amino acid peptides may be included as the protein component of the nutritional composition.
  • Such small amino acid peptides may be naturally occurring or synthesized.
  • the amount of free amino acids in the nutritional composition may vary from about 1 to about 5 g/100 kcal. In an embodiment, 100% of the free amino acids have a molecular weight of less than 500 Daitons. In this embodiment, the nutritional composition may be
  • the intact proteins comprise from about 40% to about 85% whey protein and from about 15% to about 60% casein.
  • the whey:casein ratio of the protein source is similar to that found in human breast milk.
  • the protein source comprises from about 40% to about 80% whey protein and from about 20% to about 60% casein.
  • the nutritionai composition comprises between about 1 g and about 7 g of a protein source per 100 Kcal. In other embodiments, the nutritionai composition comprises between about 3.5 g and about 4.5 g of protein per 100 Kcal.
  • the nutritional composition described herein comprises a fat source.
  • the enriched lipid fraction described herein may be the sole fat source or may be used in combination with any other suitable fat or lipid source for the nutritionai composition as known in the art.
  • Appropriate fat sources include, but are not limited to, animal sources, e.g., milk fat, butter, butter fat, egg yolk lipid; marine sources, such as fish oils, marine oils, single cell oils; vegetable and plant oils, such as corn oil, cano!a oil, sunflower oil, soybean oil, palm o!ein oil, coconut oil, high oleic sunflower oil, evening primrose oil, rapeseed oil, olive oil, flaxseed (linseed) oil, cottonseed oil, high oleic saff!ower oil, palm stearin, palm kernel oil, wheat germ oil; medium chain triglyceride oiis and emulsions and esters of fatty acids; and any combinations thereof.
  • the nutritional composition may also include a source of long chain polyunsaturated fatty acids (LCPUFAs).
  • LCPUFAs long chain polyunsaturated fatty acids
  • the amount of LCPUFA in the nutritional composition is advantageously at least about 5 mg/100 Kcal, and may vary from about 5 mg/100 Kcal to about 100 mg/100 Kcal, more preferably from about 10 mg/100 Kcal to about 50 mg/100 Kcal.
  • LCPUFAs include, but are not limited to, docosahexaenoic acid (DHA), arachidonic acid (A A), linoleic (18:2 n-6), ⁇ -!inoienic (18:3 n-6), dihomo- ⁇ -!inoienic (20:3 n-6j acids in the n-6 pathway, a-linolenic (18:3 n-3) , stearidonic ( 18:4 n-3), eicosatetraenoic (20:4 n-3) , eicosapentaenoic (20:5 n-3), and docosapentaenoic (22:6 n-3) .
  • the LCPUFA included in the nutritional composition may comprise DHA.
  • the amount of DHA in the nutritional composition is advantageously at least about 1 7 mg/100 Kcal, and may vary from about 5 mg/100 Kcal to about 75 mg/100 Kcal, more preferably from about 10 mg/100 Kcal to about 50 mg/100 Kcal.
  • the nutritional composition is supplemented with both DHA and A A.
  • the weight ratio of ARA:DHA may be between about 1 :3 and about 9:1 .
  • the ratio of ARA:DHA is from about 1 :2 to about 4:1 .
  • the DHA and ARA can be in natural form, provided that the remainder of the LCPUFA source does not result in any substantial deleterious effect on the infant.
  • the DHA and ARA can be used in refined form.
  • the disclosed nutritional composition described herein can, in some aspects
  • Giucans are polysaccharides, specifically polymers of glucose, which are naturally occurring and may be found in cell walls of bacteria, yeast, fungi, and plants.
  • Beta giucans ⁇ -glucans
  • ⁇ -glucans are themselves a diverse subset of glucose polymers, which are made up of chains of glucose monomers linked together via beta-type glycosidic bonds to form complex
  • p-l ,3-glucans are carbohydrate polymers purified from, for example, yeast, mushroom, bacteria, algae, or cereals.
  • Stone BA Clarke AE. Chemistry and Biology of (l -3)-Be ⁇ a-Glucans. London:Por ⁇ iand Press Ltd; 1993.
  • the chemical structure of ⁇ -1 ,3- giucan depends on the source of the ⁇ -l ,3-glucan.
  • various physiochemical parameters such as solubility, primary structure, molecular weight, and branching, play a role in biological activities of ⁇ -l ,3-glucans.
  • Yadomae T. Structure and biological activities of fungal beta- i,3-glucans. Yakugaku Zasshi. 2000;120:413-431 .
  • ⁇ -1 ,3 ⁇ are naturally occurring polysaccharides, with or without ⁇ -1 ,6- glucose side chains that are found in the cell walls of a variety of plants, yeasts, fungi and bacteria
  • ⁇ -l ,3; 1 ,6-g!ucans are those containing glucose units with (1 ,3) links having side chains attached at the (1 ,6) position(s).
  • ⁇ -l ,3;1 ,6 giucans are a
  • heterogeneous group of glucose polymers that share structural commonalities including a backbone of straight chain glucose units linked by a ⁇ -1 ,3 bond with ⁇ -1 ,6- linked glucose branches extending from this backbone. While this is the basic structure for the presently described class of ⁇ -giucans, some variations may exist. For example, certain yeast ⁇ -giucans have additional regions of ⁇ (1 ,3) branching extending from the ⁇ (1 ,6) branches, which add further complexity to their respective structures.
  • ⁇ -glucans derived from baker's yeast, Saccharomyces cerevisiae are made up of chains of D-giucose molecules connected at the 1 and 3 positions, having side chains of glucose attached at the 1 and 6 positions.
  • Yeast-derived ⁇ -glucan is an insoluble, fiber-like, complex sugar having the general structure of a linear chain of glucose units with a ⁇ -1 ,3 backbone interspersed with ⁇ -1 ,6 side chains that are generally 6-8 glucose units in length. More specifically, ⁇ -glucan derived from baker's yeast is poly-(l ,6) ⁇ -D-glucopyranosy!-(l ,3) ⁇ -D-giucopyranose.
  • ⁇ -glucans are well tolerated and do not produce or cause excess gas, abdominal distension, bloating or diarrhea in pediatric subjects.
  • Addition of ⁇ - g!ucan to a nutritional composition for a pediatric subject, such as an infant formula, a growing-up milk or another children's nutritional product, will improve the subject's immune response by increasing resistance against invading pathogens and therefore maintaining or improving overall health.
  • the ⁇ -glucan is ⁇ -l ,3;1 ,6-glucan.
  • the ⁇ -l ,3;1 ,6-glucan is derived from baker's yeast.
  • the nutritional composition may comprise whole glucan particle ⁇ -glucan, particulate ⁇ -glucan, PGG-glucan (poly-1 ,6- ⁇ -D-giucopyranosyl-l ,3 ⁇ -D-glucopyranose) or any mixture thereof.
  • the amount of ⁇ -glucan in the nutritional composition is between about 3 mg and about 17 mg per ] 00 Kcai. In another embodiment the amount of ⁇ -glucan is between about 6 mg and about 1 7 mg per 100 Kcal.
  • the disclosed nutritional composition described herein can, in some aspects
  • probiotic means a microorganism that exerts beneficial effects on the health of the host. Any probiotic known in the art may be acceptable in this embodiment.
  • the probiotic may be selected from any Lactobacillus species, Lactobacillus rhamnosus GG (ATCC number 53103), Bifidobacterium species, Bifidobacterium longum BB536 (BL999, ATCC: BAA-999), Bifidobacterium longum AH1 206 (NCIMB: 41382),
  • the nutritional composition may comprise between about 1 x 10 4 to about 1 .5 x 10'° cfu of probiotics per 100 cal, more preferably from about 1 x 10 6 to about 1 x 10 9 cfu of probiotics per 100 Kcal.
  • the probiotic(s) may be viable or non-viable.
  • viable refers to live microorganisms.
  • non-viable or nonviable probiotic means non-living probiotic microorganisms, their cellular components and/or metabolites thereof. Such non-viable probiotics may have been heat-kilied or otherwise inactivated, but they retain the ability to favorably influence the health of the host.
  • the probiotics useful in the present disclosure may be naturally-occurring, synthetic or developed through the genetic manipulation of organisms, whether such new source is now known or later developed.
  • the disclosed nutritional composition described herein can, in some aspects
  • prebiotics also comprise a source of prebiotics.
  • prebiotic refers to indigestible food ingredients which exert health benefits upon fhe host. Such health benefits may include, but are not limited to, selective stimulation of the growth and/or activity of one or a limited number of beneficial gut bacteria, stimulation of the growth and/or activity of ingested probiotic microorganisms, selective reduction in gut pathogens, and favorable influence on gut short chain fatty acid profile.
  • Such prebiotics may be naturally-occurring, synthetic, or developed through the genetic manipulation of organisms and/or plants, whether such new source is now known or developed later.
  • Prebiotics useful in the present disclosure may include
  • oligosaccharides oligosaccharides, polysaccharides, and other prebiotics that contain fructose, xylose, soya, galactose, glucose and mannose.
  • prebiotics useful in the present disclosure may include polydextrose, polydextrose powder, lactulose, !actosucrose, raffinose, g!uco- o!igosaccharide, inuii , fructo-oligosaccharide, isomaito-oligosaccharide, soybean oligosaccharides, lacfosucrose, xy!o-oligosaccharide, chifo-oligosaccharide, manno- oligosaccharide, aribino-oligosaccharide, siailyl-oligosaccharide, fuco- oligosaccharide, galacto-oligosaccharide, and gentio-oligosaccharides.
  • the prebiotic comprises galacto-oligosaccharide,
  • polydextrose or mixtures thereof.
  • the amount of galacto-oligosaccharide in the nutritional composition may, in an embodiment, be from about 0.1 g/100 Kcal to about 1 .5 g/100 Kcal. In another embodiment, the amount of galacto-oligosaccharide in the nutritional composition may be from about 0.1 g/100 Kcal to about 1 .0 g/100 Kcal. The amount of polydextrose in the nutritional composition may, in an embodiment, be within the range of from about 0.1 g/100 cai to about 1 .5 g/100 Kcal. In a particular
  • galacto-oiigosaccharide and polydextrose are supplemented into the nutritional composition in a total amount of about at least about 0.2 g/100 Kcal and can be about 0.2 g/100 Kcal to about 1 .5 g/100 Kcal.
  • the nutritional composition may comprise galactooligosaccharide and polydextrose in a total amount of from about 0.6 to about .8 g/100 Kcal.
  • the disclosed nutritional composition described herein can, in some aspects
  • inventions also comprise an effective amount of iron.
  • the iron may comprise encapsulated iron forms, such as encapsulated ferrous fumarate or encapsulated ferrous sulfate or less reactive iron forms, such as ferric pyrophosphate or ferric orthophosphate.
  • vitamins and/or minerals may also be added in to the nutritional composition in amounts sufficient to supply the daily nutritional requirements of a subject. It is to be understood by one of ordinary skill in the art that vitamin and mineral requirements will vary, for example, based on the age of the child. For instance, an infant may have different vitamin and mineral requirements than a child between the ages of one and thirteen years. Thus, the embodiments are not intended to limit the nutritional composition to a particular age group but, rather, to provide a range of acceptable vitamin and mineral components.
  • the composition may optionally include, but is not limited to, one or more of the following vitamins or derivations thereof: vitamin Bi (thiamin, thiamin pyrophosphate, TPP, thiamin
  • vitamin B2 riboflavin, flavin mononucleotide, FMN, flavin adenine dinucleotide, FAD, !actoflavin, ovoflavin
  • vitamin B3 niacin, nicotinic acid, nicotinamide, niacinamide, nicotinamide adenine dinucleotide, NAD, nicotinic acid mononucleotide, NicMN, pyridine-3-carboxylic acid
  • vitamin B3-precursor tryptophan vitamin ⁇ (pyridoxine, pyridoxa!, pyridoxamine, pyridoxine hydrochloride), pantothenic acid (pantothenate, panthenoi), folate (folic acid, folacin, pteroylglutamic acid), vitamin B12 (cobalamin, methyicoba!
  • menaquinone-8H menaquinone-9, menaquinone-9H, menaquinone-10,
  • menaquinone-1 menaquinone-1 , menaquinone-12, menaquinone-13), choline, inositol, ⁇ -carotene and any combinations thereot.
  • the composition may optionally include, but is not limited to, one or more ot the following minerals or derivations thereof: boron, calcium, calcium acetate, calcium gluconate, calcium chloride, calcium lactate, calcium phosphate, calcium sulfate, chloride, chromium, chromium chloride, chromium picoionate, copper, copper sulfate, copper gluconate, cupric sulfate, fluoride, iron, carbonyl iron, ferric iron, ferrous fumarate, ferric orthophosphate, iron trituration, polysaccharide iron, iodide, iodine, magnesium, magnesium carbonate, magnesium hydroxide, magnesium oxide, magnesium stearate, magnesium sulfate, manganese, molybdenum, phosphorus, potassium, potassium phosphate, potassium iodide, potassium chloride, potassium acetate, se
  • the minerals can be added to growing-up milks or to other children's nutritional compositions in the form of salts such as calcium phosphate, calcium glycerol phosphate, sodium citrate, potassium chloride, potassium phosphate, magnesium phosphate, ferrous sulfate, zinc sulfate, cupric sulfate, manganese sulfate, and sodium selenite. Additional vitamins and minerals can be added as known within the art.
  • the nutritional compositions of the present disclosure may optionally include one or more of the following flavoring agents, including, but not limited to, flavored extracts, volatile oils, cocoa or chocolate flavorings, peanut butter flavoring, cookie crumbs, vanilla or any commercially available flavoring.
  • flavoring agents including, but not limited to, flavored extracts, volatile oils, cocoa or chocolate flavorings, peanut butter flavoring, cookie crumbs, vanilla or any commercially available flavoring.
  • useful flavorings include, but are not limited to, pure anise extract, imitation banana extract, imitation cherry extract, chocolate extract, pure lemon extract, pure orange extract, pure peppermint extract, honey, imitation pineapple extract, imitation rum extract, imitation strawberry extract, or vanilla extract; or volatile oils, such as balm oil, bay oil, bergamot oil, cedarwood oil, cherry oil, cinnamon oil, clove oil, or peppermint oil; peanut butter, chocolate flavoring, vanilla cookie crumb, butterscotch, toffee, and mixtures thereof.
  • the amounts of flavoring agent can vary greatly depending upon the flavoring agent used. The type and amount of flavoring agent can be selected as is known in the art.
  • the nutritional compositions of the present disclosure may optionally include one or more emulsifiers that may be added for stability of the final product.
  • suitable emulsifiers include, but are not limited to, lecithin (e.g., from egg or soy), alpha lactalbumin and/or mono- and di-giycerides, and mixtures thereof.
  • lecithin e.g., from egg or soy
  • alpha lactalbumin e.g., from egg or soy
  • mono- and di-giycerides e.g., from egg or soy
  • Other emulsifiers are readily apparent to the skilled artisan and selection of suitable emuisifier(s) will depend, in part, upon the formulation and final product.
  • the nutritional compositions of the present disclosure may optionally include one or more preservatives that may also be added to extend product shelf life.
  • Suitable preservatives include, but are not limited to, potassium sorbate, sodium sorbate, potassium benzoate, sodium benzoate, calcium disodium EDTA, and mixtures thereof.
  • the nutritional compositions of the present disclosure may optionally include one or more stabilizers.
  • Suitable stabilizers for use in practicing the nutritional composition of the present disclosure include, but are not limited to, gum arable, gum ghatti, gum karaya, gum tragacanth, agar, furcellaran, guar gum, gellan gum, locust bean gum, pectin, low methoxyl pectin, gelatin, microcrystalline cellulose, CMC (sodium
  • DATEM diacetyl tartaric acid esters of mono-
  • the nutritional compositions of the disclosure may provide minimal, partial or total nutritional support.
  • the compositions may be nutritional supplements or meal replacements.
  • the compositions may, but need not, be nutritionally complete, in an embodiment, the nutritional composition of the disclosure is nutritionally complete and contains suitable types and amounts of lipid, carbohydrate, protein, vitamins and minerals.
  • the amount of lipid or fat typically can vary from about 1 to about 25 g/100 cal.
  • the amount of protein typically can vary from about 1 to about 7 g/100 cal.
  • the amount of carbohydrate typically can vary from about 6 to about 22 g/100 Kcal.
  • the children's nutritional composition may contain between about 10 and about 50% of the maximum dietary recommendation for any given country, or between about 10 and about 50% of the average dietary recommendation for a group of countries, per serving of vitamins A, C, and E, zinc, iron, iodine, selenium, and choline.
  • the children's nutritional composition may supply about 10 - 30% of the maximum dietary recommendation for any given country, or about 10 - 30% of the average dietary recommendation for a group of countries, per serving of B-vi ⁇ amins.
  • the levels of vitamin D, calcium, magnesium, phosphorus, and potassium in the children's nutritional product may correspond with the average ieveis found in milk, in other embodiments, other nutrients in the children's nutritional composition may be present at about 20% of the maximum dietary recommendation for any given country, or about 20% of the average dietary recommendation for a group of countries, per serving.
  • the nutritional composition is an infant formula.
  • Infant formulas are fortified nutritional compositions for an infant.
  • the content of an infant formula is dictated by federal regulations, which define macronutrient, vitamin, mineral, and other ingredient levels in an effort to simulate the nutritional and other properties of human breast milk, infant formulas are designed to support overall health and development in a pediatric human subject, such as an infant or a child.
  • the nutritional composition of the present disclosure is a growing-up milk.
  • Growing-up milks are fortified milk-based beverages intended for children over 1 year of age (typically from 1-3 years of age, from 4-6 years of age or from 1 -6 years of age). They are not medical foods and are not intended as a meal replacement or a supplement to address a particular nutritional deficiency. Instead, growing-up milks are designed with the intent to serve as a complement to a diverse diet to provide additional insurance that a child achieves continual, daily intake of all essential vitamins and minerals, macronutrients plus additional functional dietary components, such as non-essential nutrients that have purported health-promoting properties.
  • compositions according to the disclosure can vary from market-to-market, depending on local regulations and dietary intake information of the population of interest.
  • nutritional compositions according to the disclosure consist of a milk protein source, such as whole or skim milk, plus added sugar and sweeteners to achieve desired sensory properties, and added vitamins and minerals.
  • the fat composition includes an enriched lipid fraction derived from milk.
  • Total protein can be targeted to match that of human milk, cow milk or a lower value.
  • Total carbohydrate is usually targeted to provide as little added sugar, such as sucrose or fructose, as possible to achieve an acceptable taste.
  • Vitamin A, calcium and Vitamin D are added at Ieveis to match the nutrient contribution of regional cow milk.
  • vitamins and minerals can be added at levels that provide approximately 20% of the dietary reference intake (DRI) or 20% of the Daily Value (DV) per serving.
  • nutrient values can vary between markets depending on the identified nutritional needs of the intended population, raw material contributions and regional regulations.
  • the disclosed nutritional composition (s) may be provided in any form known in the art, such as a powder, a gei, a suspension, a paste, a solid, a liquid, a liquid concentrate, a reconstituteable powdered milk substitute or a ready-to-use product.
  • the nutritional composition may, in certain embodiments, comprise a nutritional supplement, children's nutritional product, infant formula, human milk fortifier, growing- up milk or any other nutritional composition designed for an infant or a pediatric subject.
  • Nutritional compositions of the present disclosure include, for example, orally- ingestible, health-promoting substances including, for exampie, foods, beverages, tablets, capsules and powders.
  • the nutritional composition of the present disclosure may be standardized to a specific caloric content, it may be provided as a ready-to-use product, or it may be provided in a concentrated form.
  • the nutritional composition is in powder form with a particle size in the range of 5 Mm to 1500 Mm, more preferably in the range of 10 m to 300 ⁇ .
  • the disclosure is directed to a method of producing a nutritional composition comprising dietary butyrate that has improved organoleptic properties.
  • the nutritional composition includes dietary butyrate that has been encapsulated or coated according to the disclosure provided herein.
  • compositions of the present disclosure can comprise, consist of, or consist essentially of the essential elements and limitations of the embodiments described herein, as well as any additional or optional ingredients, components or limitations described herein or otherwise useful in nutritional compositions.
  • Table 1 illustrated below, provides an example embodiment of the nutritional profile of a nutritional composition including dietary butyrate and describes the amount of each ingredient to be included per 100 Kcal serving of nutritional composition.
  • Vitamin E 0.8 5.4 Vitamin K (meg) 2.9 18
  • references cited in this specification including without limitation, all papers, publications, patents, patent applications, presentations, texts, reports, manuscripts, brochures, books, internet postings, journal articles, periodicals, and the like, are hereby incorporated by reference into this specification in their entireties.
  • the discussion of the references herein is intended merely to summarize the assertions made by their authors and no admission is made that any reference constitutes prior art. Applicants reserve the right to challenge the accuracy and pertinence of the cited references.

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