β-hydroxybutyric acid-containing composition

Abstract

An object of the present invention is to provide a novel β-hydroxybutyric acid-containing composition. [Solution] A β-hydroxybutyric acid-containing composition.

Description

[Technical Field]

[0001] The present invention relates to a β-hydroxybutyric acid-containing composition. [Background technology]

[0002] Patent Document 1 discloses a 3-hydroxybutyric acid-containing fat and oil composition containing 3-hydroxybutyric acid and / or a salt thereof, edible fat and oil, and protein.

[0003] Patent Document 2 discloses a method for maintaining or increasing weight loss in an individual, which comprises orally administering a composition comprising about 0.5 g to about 10 g of R-β-hydroxybutyric acid, amino acids, and optionally at least one of a flavoring, a vitamin, a mineral, or a binder, and which induces or maintains ketosis in the individual by administration.

[0004] Patent document 3 discloses a method for treating a metabolic disorder in a subject, the method comprising administering to the subject a therapeutically effective amount of N-β-hydroxybutyrylamino acid (N-β-hydroxybutyrylphenylalanine (BHB-Phe)) to treat the metabolic disorder in the subject.

[0005] Patent Document 4 discloses a method for producing hydroxyalkanoic acid, which includes a fermentation step of obtaining a fermentation liquid produced by fermenting hydroxyalkanoic acid (such as 3-hydroxybutyric acid (3HB)) from a hydroxyalkanoic acid-producing bacterium (a Halomonas bacterium capable of producing 3HB); an esterification step of distilling off the water serving as a solvent from the fermentation liquid and replacing it with an alcohol solvent as an esterifying agent for the hydroxyalkanoic acid, adding an esterification catalyst, and heating to produce an ester-containing liquid in which a hydroxyalkanoic acid ester has been produced; a distillation step of distilling the ester-containing liquid and separating the hydroxyalkanoic acid ester from the ester-containing liquid to obtain a distilled liquid; and a hydrolysis step of contacting the distilled liquid with a solid acid catalyst to hydrolyze the hydroxyalkanoic acid ester to obtain hydroxyalkanoic acid.

[0006] Patent Document 5 discloses a visceral fat-reducing agent containing R-3-hydroxybutyric acid and / or a salt thereof as an active ingredient.

[0007] Non-Patent Document 1 discloses that daily intake of D-β-hydroxybutyric acid (D-BHB) reduces body fat in Japanese adult participants.

[0008] Non-Patent Document 2 discloses that ketone ester drinks reduce human ghrelin and appetite. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] WO-A1-2022 / 254764 [Patent Document 2] US-B2-011173138 [Patent Document 3] WO-A1-2024 / 192165 [Patent Document 4] Patent Publication No. 2019-176839 [Patent Document 5] Patent Publication No. 2023-173641 [Non-patent literature]

[0010] [Non-Patent Document 1] J. Nutr. Sci. Vitaminol., 69, 121-128, 2023 [Non-patent document 2] Obesity (Wiley), 2018 Feb, 26(2), 269-273 Summary of the Invention [Problem to be solved by the invention]

[0011] An object of the present invention is to provide a novel β-hydroxybutyric acid-containing composition. [Means for solving the problem]

[0012] Beta-hydroxybutyrate (hereinafter referred to simply as "BHB", also known as 3-hydroxybutyrate (3HB)) is a substance that is naturally present in the human body and is attracting attention as an innovative energy source that can replace carbohydrates.

[0013] BHB is obtained by ingesting medium-chain fatty acids (MCTs) found in foods such as coconut oil, and is then metabolized in the body, enters the bloodstream, and is converted into energy more quickly than carbohydrates, which are converted into energy via glycolysis.

[0014] In addition, when 1,3-butanediol and acetoacetate are ingested, they are converted into BHB in the body and converted into energy in the same way as MCTs.

[0015] BHB has the effect of inhibiting the absorption of fat and sugar by cells. In other words, taking BHB externally has the effect of inhibiting sugar absorption and promoting fat burning, which is a diet effect. In addition to serving as a simple energy source, BHB is also said to improve cognitive function and long-term memory function, and to have a preventive effect against Alzheimer's disease.

[0016] It has been reported that BHB has diet effects such as reducing visceral fat (Non-Patent Document 1). It has also been reported that a BHB derivative (BHB-Phe) acts as an appetite-suppressing hormone, but there is no mention of the appetite-suppressing effect of orally ingesting BHB and Phe together (Patent Document 3). It is not mentioned whether orally administered BHB and Phe are absorbed in the same way, or whether they are efficiently synthesized into BHB-Phe in the tissues where they are absorbed, further exerting an appetite-suppressing effect.

[0017] According to the present invention, by orally ingesting BHB and Phe together, appetite can be suppressed when BHB-Phe is synthesized in the body.

[0018] The present invention encompasses the following beta-hydroxybutyric acid-containing compositions (BHB-containing compositions):

[0019] Section 1. containing beta-hydroxybutyric acid (BHB) and / or its salts and phenylalanine (Phe) and / or its salts, and / or Contains a complex of beta-hydroxybutyric acid (BHB) and / or its salt with phenylalanine (Phe) and / or its salt (BHB-Phe complex), Beta-hydroxybutyrate (BHB)-containing compositions.

[0020] Section 2. Item 1. The BHB-containing composition according to Item 1, further comprising an amino acid.

[0021] Section 3. Item 1. The BHB-containing composition according to item 1, wherein the BHB salt is at least one BHB salt selected from the group consisting of alkali metal salts, alkaline earth metal salts, and ammonium salts of BHB.

[0022] Section 4. Item 1. The BHB-containing composition according to Item 1, wherein the BHB and / or salt thereof has an R configuration.

[0023] Section 5. Item 1. The BHB-containing composition according to item 1, which is for oral administration.

[0024] Section 6. Item 6. A nutritional supplement comprising the BHB-containing composition according to any one of items 1 to 5.

[0025] Section 7. A method of activating CNDP2 by ingesting histidine (His) and alanine (Ala) to increase the effects of ingesting BHB and Phe.

[0026] According to the present invention, by orally ingesting BHB and Phe together, whether BHB-Phe is synthesized in the body or the BHB-Phe complex (an amide bond between BHB and Phe) is ingested directly, the blood BHB-Phe concentration can be increased, thereby suppressing appetite.

[0027] BHB has been reported to have diet effects such as reducing visceral fat, and it is necessary to ingest approximately 3g to 10g of BHB to achieve a blood concentration of approximately 0.3mM (mmol / L) to 1mM (mmol / L).

[0028] According to the present invention, appetite can be suppressed by taking BHB and Phe as supplements or by taking a BHB-Phe complex, which causes the body to produce the BHB-Phe complex.

[0029] According to the present invention, appetite can be suppressed more efficiently by taking alanine (Ala) and histidine (His) in addition to taking BHB and Phe. [Effects of the Invention]

[0030] The present invention can provide a novel composition containing β-hydroxybutyric acid (BHB). DETAILED DESCRIPTION OF THE INVENTION

[0031] The present invention will be described in detail below. The embodiments of the present invention are intended to provide a better understanding of the gist of the invention, and unless otherwise specified, do not limit the content of the invention. It goes without saying that the present invention can be embodied in various forms without departing from the gist of the present invention.

[0032] In this specification, the terms "comprise" and "contain" are concepts that encompass all of "comprise," "consist essentially of," and "consist only of."

[0033] In this specification, when a numerical range is expressed as "A to B," it means "not less than A and not more than B."

[0034] In this specification, when parts, % and the like are used, they represent parts by mass, parts by weight, mass %, or weight % (wt%).

[0035] [1] Beta-hydroxybutyric acid (BHB)-containing composition The beta-hydroxybutyric acid (BHB)-containing composition of the present invention comprises: containing beta-hydroxybutyric acid (BHB) and / or its salts and phenylalanine (Phe) and / or its salts, and / or It contains a complex of beta-hydroxybutyric acid (BHB) and / or its salts with phenylalanine (Phe) and / or its salts (BHB-Phe complex).

[0036] The BHB-containing compositions of the present invention preferably further comprise an amino acid.

[0037] In the BHB-containing composition of the present invention, the salt of BHB is preferably at least one salt of BHB selected from the group consisting of alkali metal salts, alkaline earth metal salts, and ammonium salts of BHB.

[0038] In the BHB-containing composition of the present invention, the BHB and / or salt thereof preferably has an R configuration.

[0039] The BHB-containing compositions of the present invention are preferably for oral consumption.

[0040] The BHB-containing compositions of the present invention can preferably be formulated as a dietary supplement.

[0041] (1-1) β-hydroxybutyric acid (BHB) and / or its salts The BHB-containing composition of the present invention contains BHB and / or a salt thereof and Phe and / or a salt thereof. BHB (also known as 3-hydroxybutyric acid (3HB)) is a compound represented by the following formula:

[0042] [ka]

[0043] BHB may be in the form of a salt, and the salt form of BHB is not particularly limited, and examples thereof include alkali metal salts (sodium salt, potassium salt, lithium salt, etc.), alkaline earth metal salts (magnesium salt, calcium salt, etc.), ammonium salts, and amino acid salts.

[0044] In BHB-containing compositions, these BHB salts may be used alone or in a blend of two or more. To avoid excessive salt intake, it is preferable for the BHB salt to contain potassium salt, which has a high upper limit for salt intake.

[0045] The three-dimensional structure of BHB may be either the R-configuration (R-isomer) or the S-configuration (S-isomer). The R-configuration (R-isomer) is preferred from the viewpoints of energy delivery to the body, water dispersibility, suppression of deliquescence, suppression of sourness, etc.

[0046] BHB may be in the form of either a liquid (e.g., an aqueous solution or an ethanol solution) or a solid. Solid BHB is preferred, as a solid form makes it easier to suppress deliquescence in the resulting composition. When BHB and / or a salt thereof is prepared from a liquid, the content of BHB and / or a salt thereof in the composition can be increased by removing the water and solvent remaining in the composition using an evaporator during or after mixing, or by adding seed crystals to promote crystallization.

[0047] The size of BHB and / or its salt is not particularly limited, and the size of the BHB salt can be determined appropriately depending on the type of salt.

[0048] The method for producing BHB is not particularly limited. BHB can be produced by conventionally known methods. Similarly, salts of BHB can be produced by conventionally known methods, such as a salt formation process, a desalination process, or a salt exchange process.

[0049] When ingested, acetoacetate, 1,3-butanediol, short-chain, medium-chain (MCT), and long-chain fatty acids and their derivatives, including salts and esters, are converted into BHB in the body, which is then converted into energy in the same way as medium-chain triglycerides (MCT).

[0050] The present invention encompasses compositions comprising acetoacetic acid, 1,3-butanediol, and at least one derivative selected from the group consisting of short-chain fatty acids, medium-chain fatty acids (MCTs), long-chain fatty acids, and salts or esters thereof.

[0051] (1-2) Phenylalanine (Phe) The BHB-containing composition of the present invention contains BHB and / or its salts and phenylalanine (Phe) and / or its salts. Like other amino acids, Phe has two enantiomers, D- and L-, respectively. L-Phe (LPA) is a naturally occurring compound, while D-Phe (DPA) is an artificially synthesized compound.

[0052] [ka]

[0053] Phe may be, for example, hydrochloride. In addition, peptides such as aspartame, which are decomposed into phenylalanine in the body, may also be used as Phe.

[0054] (1-3) BHB and / or its salt complex with Phe (BHB-Phe complex) The BHB-containing compositions of the present invention contain a complex of BHB and / or a salt thereof with Phe: N-β-hydroxybutyryl-phenylalanine (BHB-Phe complex).

[0055] BHB-Phe conjugates are phenylalanine (Phe) modified with a β-hydroxybutyryl group, where the amino group of phenylalanine is linked to the carboxyl group of β-hydroxybutyric acid (BHB). BHB-Phe conjugates contain L-Phe and / or D-Phe.

[0056] [ka]

[0057] The BHB-Phe complex exerts appetite suppressant effects such as reduced food intake, reduced food consumption, anorexia, and reduced hunger.

[0058] (1-4) Amino acids The BHB-containing compositions of the present invention preferably contain amino acids, which can act as an energy source and impart flavor and functionality to the BHB-containing compositions.

[0059] A variety of amino acids can be used, and amino acids exist as both L and D enantiomers.

[0060] The amino acids preferably used are L-alanine (Ala), L-arginine (Arg), L-asparagine (Asn), L-aspartic acid (Asp), L-cysteine ​​(Cys), L-glutamic acid (Glu), L-glutamine (Gln), glycine (Gly), L-histidine (His), L-isoleucine (Ile), L-leucine (Leu), L-lysine (Lys), L-methionine (Met), L-phenylalanine (Phe), L-proline (Pro), L-serine (Ser), L-threonine (Thr), L-tryptophan (Trp), L-tyrosine (Tyr), L-valine (Val), etc. The amino acids more preferably used are L-alanine (Ala), L-histidine (His), etc.

[0061] When the BHB-containing composition contains a BHB-Phe conjugate, it may further contain L-phenylalanine (Phe).

[0062] The amino acid may be added as a salt. The salt may preferably be an alkali metal salt such as a sodium salt, a potassium salt, or a lithium salt; or an alkaline earth metal salt such as a magnesium salt or a calcium salt. Sodium glutamate may be added instead of glutamic acid, or sodium aspartate may be added instead of aspartic acid.

[0063] In the BHB-containing composition, these amino acids and / or salts thereof may be used alone or in a mixture (blend) of two or more.

[0064] In BHB-containing compositions, appetite can be suppressed more effectively by ingesting Ala and / or His in addition to BHB and Phe. Ingesting Ala and His for a certain period of time provides the most effective appetite suppression. Amino acids also function as an energy source and have excellent taste-masking properties.

[0065] By taking the BHB-containing composition of the present invention as a supplement containing BHB and Phe, appetite can be suppressed by producing BHB-Phe in the body.

[0066] (1-5) Ingredients contained in the BHB-containing composition The BHB-containing composition of the present invention may contain other ingredients as appropriate, as long as the ingredients are edible and do not impair the objects and effects of the present invention.

[0067] The BHB-containing composition may also contain other ingredients, preferably edible oils and fats, protein, dietary fiber, carbohydrates (powdered), emulsifiers, flavorings, skim milk powder, whole milk powder, cocoa powder, sugar, dextrin, sweeteners, colorings, flavorings, vitamins, minerals, binders, etc.

[0068] The BHB-containing composition may contain, for synergistic effects, physiologically active substances such as berberines, vasodilator components, stimulant components, stimulant components, nootropic components, energy-boosting compositions, and tranquilizers. The BHB-containing composition may further contain or be encapsulated in a phytosome complex, liposome, or cytochrome P450 inhibitor to facilitate their uptake into the body.

[0069] The vasodilator ingredients include nitric oxide promoters, arginase inhibitors, and nitric oxide synthase promoters, quercetin, L-citrulline, L-citrulline salts, L-arginine, L-arginine salts, agmatine, agmatine salts, nitrates, gallic acid, coenzyme Q10 (CoQ10), trimethylglycine, niacin, theanine, theobromine, garlic, magnesium, grape seed extract, green The composition contains at least one component selected from the group consisting of tea extract, cocoa, proanthocyanidins, galloylated proanthocyanidins, L-norvaline, β-alanine, niacin, theanine, catechin, or epicatechin, epicatechin-(4-8)-epicatechin-(4-8)-epicatechin or epicatechin-(4-8)-epicatechin-gallate, cacatin, glutathione, and taurine.

[0070] The vasodilator component comprises at least one component selected from the group consisting of mucuna pruriens, tyrosine, L-DOPA (i.e., L-3,4-dihydroxyphenylalanine), huperzine-A, dimethylaminoethanol, phenylalanine, phenylethylamine, choline, α-glycerophosphocholine, uridine, citicoline, tryptophan, 5-hydroxytryptophan (5-HTP), D-serine, phosphatidylserine, Panax ginseng, Ginkgo biloba, Rhodiola rosea, Polygala tenuifolia, Muira puama, Huperzia serrata, Eschscholzia californica, Convolvulus pluricaris, Centella asiatica, Evolvulus alsinoides, Bacopa monnieri, Epimedium herb, Ashwagandha herb, forskolin, and vinpocetine.

[0071] The stimulant component comprises at least one component selected from the group consisting of adenosine receptor antagonists, phosphodiesterase inhibitors, epinephrine and / or norepinephrine promoters, caffeine, theacrine, theobromine, theophylline, methylliberine, and caffeine analogs.

[0072] The stimulant component includes at least one component selected from the group consisting of caffeine, theacrine, theobromine, theophylline, methylliberine, and paraxanthine.

[0073] The nootropic ingredient includes at least one ingredient selected from the group consisting of methylliberine, theacrine, mucuna pruriene, tyrosine, L-DOPA (i.e., L-3,4-dihydroxyphenylalanine), huperzine-A, dimethylaminoethanol, phenylalanine, phenylethylamine, choline, α-glycerophosphocholine, uridine, citicoline, and racetams.

[0074] The energy-boosting composition, wherein the nootropic ingredient comprises at least one ingredient selected from the group consisting of tryptophan, 5-hydroxytryptophan (5-HTP), D-serine, phosphatidylserine, Panax ginseng, Ginkgo biloba, Ginkgo biloba, Rhodiola rosea, Polygala tenuifolia, Muira puama, Huperzia serrata, Eschscholzia californica, Convolvulus pluricaulis, Centella asiatica, Evolvulus alsinoides, Bacopa monnieri, Epimedium herb, Ashwagandha, forskolin, and vinpocetine.

[0075] The energy-boosting composition comprises at least one component selected from the group consisting of methylliberine, an adenosine receptor antagonist, a phosphodiesterase inhibitor, an epinephrine and / or norepinephrine promoter, and a xanthan alkaloid.

[0076] The psychoactive substance comprises at least one component selected from the group consisting of suboptimal levels of THC (tetrahydrocannabidiol), a THC compound having BHB or acetoacetate attached to THC via an ester bond, cannabidiol (CBD), a CBD compound having BHB or acetoacetate attached to a CBD compound via an ester bond.

[0077] CBD compounds include at least one component selected from the group consisting of one or more beta-hydroxybutyric acid (BHB) salts, cannabidiol (CBD), tetrahydrocannabivarin (THCV), cannabigerol (CBG), cannabidivarin (CBDV), cannabichromene (CBC), cannabinol (CBN), cannabielsoin (CBE), tetrahydrocannabinol (THC), iso-THC, cannabicyclolol (CBL), cannabicitran (CBT), cannabivarin (CBV), cannabichromalin THC (CBCV), cannabigerovarin (CBGV), and cannabigerol monomethyl ether (CBGM).

[0078] (edible fats and oils) The edible oils and fats are not particularly limited, and preferably include vegetable oils and fats such as milk fat, shea butter, olive oil, soybean oil, safflower oil, corn oil, sunflower oil, rapeseed oil, coconut oil, palm oil, palm kernel oil, and fractionated palm oil; and animal oils and fats such as head, lard, and fish oil.

[0079] The edible fats and oils include fats and oils synthesized from glycerin and fatty acids, fractionated oils thereof, interesterified oils, hydrogenated oils, and the like.

[0080] The oils and fats synthesized from glycerin and fatty acids include monoglycerides, diglycerides, and triglycerides, and preferably, medium-chain triglyceride (MCT) oils and fats are used.

[0081] As the fractionated oil, preferably used are fractionated oils of palm oil (long chain) such as palm olein, palm superolein, palm stearin, palm mid fraction, and palm kernel oil (short chain).

[0082] As the interesterified oil, interesterified oils of the above-mentioned oils or fractionated oils thereof with other liquid oils or fats, or interesterified oils of medium-chain triglyceride (MCT) oils with vegetable oils or the like are preferably used.

[0083] The hydrogenated oil may be the above-mentioned oils and fats, hydrogenated oils of fractionated oils thereof, hydrogenated oils of interesterified oils, etc. The hydrogenated oil may also contain trans fatty acids.

[0084] Edible fats and oils also include refined fats and oils. When refined fats and oils are used as edible fats and oils, the refining method of the fats and oils is not particularly limited. The refining method of the fats and oils preferably includes chemical refining, physical refining, etc.

[0085] Chemical refining is a method of refining fats and oils by subjecting crude oil that has been pressed and extracted from raw materials to degumming, deacidification, bleaching, dewaxing, deodorization, etc. Physical refining is a method of refining fats and oils by subjecting crude oil that has been pressed and extracted from raw materials to degumming, bleaching, deacidification, deodorization, etc.

[0086] In the BHB-containing composition, these edible oils and fats may be used alone or in a mixture (blend) of two or more.

[0087] The form of the edible oil or fat is not particularly limited, and the form of the edible oil or fat may be solid or liquid.

[0088] (protein) The protein is not particularly limited, and preferred proteins include whey protein, casein protein, soy protein, pea protein, wheat protein, egg protein, and rice protein.

[0089] Proteins that can suppress the deliquescence and sourness of BHB include not only water-soluble whey proteins such as whey protein, but also water-insoluble proteins. Among these, whey protein, casein protein, soy protein, etc. are preferably used as proteins from the viewpoint of suppressing deliquescence and sourness, and whey protein is more preferably used.

[0090] The protein may be a partial hydrolyzate of a protein, which is easily improved in water dispersibility and absorbability. The partial hydrolyzate of a protein is preferably a water-soluble protein hydrolyzate obtained by partially hydrolyzing the protein contained in a protein raw material using a protease, an acid, or the like.

[0091] When using the protein, it is preferable to use a powdered protein, which may be in the form of pulverized, powdered, powdered, flakes, granules, or particles.

[0092] Known or commercially available proteins may be used.

[0093] In the BHB-containing composition, these proteins may be used alone or in a mixture (blend) of two or more.

[0094] (Dietary fiber) As dietary fiber, preferably used are wheat bran, corn bran, oat bran, cellulose-based fiber extracted from plants (e.g., corn fiber, soybean dietary fiber, beet fiber, etc.), cellulose, crystalline cellulose, agar, chitosan, chitin, hemicellulose, lignin, glucan, etc.

[0095] In the BHB-containing composition, these dietary fibers may be used alone or in a mixture (blend) of two or more types.

[0096] (Carbohydrates) The term "carbohydrate" generally refers to carbohydrates other than dietary fiber. Preferred examples of carbohydrates include edible sugars such as monosaccharides, disaccharides, oligosaccharides, sugar alcohols, isomerized sugars, and starch hydrolysates.

[0097] As carbohydrates, preferably used are glucose (monosaccharide), sugar, maltose, lactose, trehalose (all disaccharides), maltitol, palatinit (all sugar alcohols), glucose-fructose syrup, fructose-glucose syrup (all isomerized sugars), starch syrup (a mixture of glucose, maltose, and dextrin), dextrin (starch hydrolyzate), etc.

[0098] In the BHB-containing composition, these carbohydrates may be used alone or in a mixture (blend) of two or more.

[0099] The BHB-containing composition of the present invention can be used to suppress appetite by taking BHB and Phe as a supplement. Intake of Ala and / or His in addition to BHB and Phe can further suppress appetite. Taking Ala and / or His for a certain period of time can most effectively suppress appetite.

[0100] By taking the BHB-containing composition of the present invention as a supplement containing BHB and Phe, appetite can be suppressed by producing the BHB-Phe complex in the body.

[0101] (1-6) Composition of BHB-containing composition In the BHB-containing composition of the present invention, the contents of BHB and / or a salt thereof, Phe, and BHB-Phe complex are not particularly limited.

[0102] In BHB-containing compositions (solid or liquid), the content of BHB and / or its salts, Phe, and BHB-Phe complexes is adjusted appropriately, taking into consideration factors such as energy provided to the body, water dispersibility, suppression of deliquescence, and suppression of sourness.

[0103] In the BHB-containing composition, the total amount of the BHB-containing composition is taken as 100% by mass, and the content of each component, BHB and / or its salt, Phe, and BHB-Phe complex, is adjusted so that each component preferably contains approximately 5% to 70% by mass, and more preferably approximately 10% to 40% by mass.

[0104] The BHB-containing composition of the present invention can be ingested, for example, as a supplement containing BHB and Phe, to produce the BHB-Phe complex in the body, or by ingesting a supplement containing the BHB-Phe complex, appetite can be suppressed.

[0105] In the BHB-containing composition, the amino acid content is adjusted to preferably about 5% to 70% by mass, and more preferably about 10% to 40% by mass, with the total amount of the BHB-containing composition being 100% by mass.

[0106] With the BHB-containing composition of the present invention, appetite can be suppressed more efficiently by ingesting amino acids (preferably Ala and / or His) in addition to ingesting BHB and Phe.

[0107] In the BHB-containing composition of the present invention, the content of other ingredients can be adjusted to any amount that does not impair the effects of the present invention, taking into consideration the intended use for oral ingestion.

[0108] [2] Method for producing BHB-containing compositions The BHB-containing compositions of the present invention can be prepared by mixing the components BHB and / or its salts, Phe, and BHB-Phe complex, and optionally other components.

[0109] The method for mixing the components is not particularly limited. Any known mixing method can be used to mix the components, and preferably, a method is used in which the components are mechanically mixed using a mixer, mill, or the like. After the components are mixed and pulverized, the water remaining in the mixture may be evaporated (volatilized) using an evaporator, or the like.

[0110] [3] Nutritional supplements The BHB-containing composition of the present invention can be in the form of a solid or a liquid (aqueous dispersion). The BHB-containing composition can be stored as a solid, such as a powder, and taken orally either directly or in combination with water. Alternatively, the BHB-containing composition can be dispersed in water and taken orally as an aqueous dispersion.

[0111] BHB-containing compositions are suitable for oral ingestion and allow for convenient intake of BHB, an energy source, making them useful as nutritional supplements.

[0112] Appetite can be suppressed by taking BHB and / or its salts with Phe, or a BHB-Phe complex, as a supplement using a BHB-containing composition. Appetite can be suppressed even more effectively by taking Ala and / or His in addition to BHB and Phe. Appetite can be most effectively suppressed by taking Ala and / or His for a certain period of time.

[0113] By taking BHB and Phe as a supplement using a BHB-containing composition, appetite can be suppressed by producing the BHB-Phe complex in the body.

[0114] The BHB-containing composition can be used in foods and food products containing BHB for oral consumption, and is preferably used in food supplements, functional foods, food additives, diet foods, power snacks, appetite suppressants, and sports supplements.

[0115] Ingestion of BHB-containing compositions can suppress appetite, as well as regulate weight loss, weight maintenance, increased blood ketone levels (induction of ketosis, increased blood BHB levels) and maintenance (maintaining ketosis), decreased and maintained blood glucose levels, improved mental strength, improved concentration, improved energy, improved cognitive function, reduced traumatic brain injury, improved diabetes, improved relief of neuropathy, improved inflammatory conditions, anti-aging, improved diabetes, improved epilepsy, improved depression, improved and increased muscle mass, reduced fat mass, improved body composition, metabolism, fat loss, fat oxidation, motor function, increased muscle mass, and improved mental and mood.

[0116] [4] How to Increase the Intake Effects of BHB and Phe (CNDP2 activity in tissues) CNDP2 (Carnosine dipeptidase II) is an enzyme that breaks down carnosine, a bond between alanine and histidine. The higher the carnosine concentration in tissues, the higher the activity of CNDP2 is expected to be. In addition, since alanine and histidine are found in large amounts in meat diets, CNDP2 activity is expected to be higher when a low-carbohydrate diet is consumed.

[0117] The present invention encompasses a method for activating CNDP2 by ingesting histidine (His) and alanine (Ala) to enhance the effects of BHB and Phe uptake.

[0118] According to the present invention, by taking Ala and / or His in addition to BHB and Phe, the effects of BHB and Phe intake can be increased, resulting in more efficient appetite suppression. Taking Ala and / or His for a certain period of time can most efficiently suppress appetite.

[0119] Although the embodiments of the present invention have been described above, the present invention is not limited to these examples, and it goes without saying that the present invention can be embodied in various forms without departing from the spirit of the present invention. [Example]

[0120] The embodiments of the present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0121] [1] The appetite suppression effect of a composition containing beta-hydroxybutyric acid (BHB) D-β-hydroxybutyric acid (D-BHB, R-β-hydroxybutyrate) Osaka Gas Co., Ltd. has developed BHB (naturally derived ketone body, fermented ketone body) produced from Halomonas bacteria. D-BHB can also be produced by fermentation using Halomonas bacteria, as described in JP 2019-176839 A.

[0122] Example 1 (Method for evaluating appetite suppression) (1) At 4 p.m., subjects ingested a placebo (BHB + vitamin C), BHB + phenylalanine (Phe), or BHB + Phe + alanine (Ala) + histidine (His). (2) The subjects' appetite at 6 p.m. was quantified, with normal appetite set at 100.

[0123] (Sensory evaluation of appetite suppression) Appetite rating 100: Normal appetite Appetite rating 81-99: Compared to normal appetite, appetite feels somewhat diminished. Appetite rating 61-80: Compared to normal appetite, there is a clear decrease in appetite. Appetite rating 41-60: Compared to normal appetite, appetite feels significantly reduced. Appetite rating below 40: No appetite compared to normal appetite strength.

[0124] [Table 1]

[0125] (Amount per serving) BHB: D-β-hydroxybutyric acid 1g Phe: Phenylalanine 500mg Ala: Alanine 750mg His: Histidine 500mg Placebo: Vitamin C 1g

[0126] Example 2 (Method for evaluating appetite suppression) (1) Subjects were instructed to take Ala and His for one week, and then one week later, at 4:00 p.m., they were instructed to take BHB+Phe. (2) One week later, the subjects' appetite at 6 p.m. was quantified, with normal appetite set at 100.

[0127] (Sensory evaluation of appetite suppression) Appetite rating 100: Normal appetite Appetite rating 81-99: Compared to normal appetite, appetite feels somewhat diminished. Appetite rating 61-80: Compared to normal appetite, there is a clear decrease in appetite. Appetite rating 41-60: Compared to normal appetite, appetite feels significantly reduced. Appetite rating below 40: No appetite compared to normal appetite strength.

[0128] [Table 2]

[0129] Taking BHB and Phe as supplements was able to suppress appetite. Taking Ala and His in addition to BHB and Phe was able to suppress appetite even more efficiently. Taking Ala and His for a certain period of time was the most effective way to suppress appetite.

[0130] [2] Industrial Applicability By taking the BHB-containing composition of the present invention as a supplement containing BHB and Phe, appetite can be suppressed by producing the BHB-Phe complex in the body.

Claims

1. Contains β-hydroxybutyric acid (BHB) and / or its salts and phenylalanine (Phe), and / or Contains a complex of β-hydroxybutyric acid (BHB) and / or a salt thereof with phenylalanine (Phe), Further, it contains histidine (His) and alanine (Ala), Composition for suppressing appetite.

2. The composition described in claim 1, which is for suppressing appetite by activating CNDP2 and increasing the intake effect of BHB and Phe.

3. 2. The composition according to claim 1, wherein the salt of BHB is at least one salt of BHB selected from the group consisting of alkali metal salts, alkaline earth metal salts, and ammonium salts of BHB.

4. The composition according to claim 1, wherein the BHB and / or salt thereof has an R configuration.

5. The composition of claim 1, which is for oral administration.

6. A dietary supplement comprising the composition according to any one of claims 1 to 5.

7. CNDP2 is activated by taking histidine (His) and alanine (Ala) as supplements, Method for suppressing appetite by increasing the intake effect of BHB and Phe (However, said methods do not include methods for treating humans).

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