Administration of R-beta-hydroxybutyrate and related compounds in humans

Abstract

In various embodiments, beta-hydroxybutyrate, related compounds, and / or one or more other compounds can be administered to an individual to aid in weight loss, weight maintenance, increasing blood ketone body levels, maintaining blood ketone body levels, decreasing blood glucose levels, maintaining blood glucose levels, improving energy, focus, mood, cognitive function, or neurological or inflammatory disorders, and / or combinations thereof.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application is incorporated by reference for all purposes. ADMINISTRATION OF HYDROXYBUTYRATE AND RELATED COMPOUNDS This application claims the benefit of U.S. patent application Ser. No. 17 / 367,206, filed July 2, 2021, entitled "R-BETA-HYDROXYBUTYRATE AND RELATED COMPOUNDS IN HUMANS."

[0002]

[0002] The present invention relates to the administration of butyrate, beta-hydroxybutyrate, and related compounds. Concerning giving. [Background technology]

[0003]

[0003] Currently, beta-hydroxybutyrate is being used to promote weight loss and / or ketosis. It can be administered orally or intravenously to humans to promote ketosis. However, excessive intake of salts such as sodium, magnesium, and potassium can lead to undesirable consequences (e.g., hypertension, stroke, organ damage, gastrointestinal disorders, etc.). Thus, many people may not tolerate the administration of amounts of beta-hydroxybutyrate that promote or maintain weight loss and / or ketosis. Beta-hydroxybutyrate polymers have also been administered to humans to promote ketosis. However, because the polymers must be processed in the body to deliver beta-hydroxybutyrate to the individual, delivery is slower and / or larger amounts of the polymer must be administered to deliver a specified amount of beta-hydroxybutyrate. Summary of the Invention

[0004] In various embodiments, a pharma- tically effective amount of butyrate, beta-hydroxybutyrate, administering to the individual a compound, a related compound, and / or one or more other compounds For example, a pharma- tically effective amount of beta-hydroxybutyrate, related compounds, and / or one or more other compounds may be administered for weight loss, weight maintenance, increasing blood ketones, maintaining blood ketones, decreasing blood glucose, maintaining blood glucose, focus, energy, cognitive function, traumatic brain injury, diabetes, neurological disorders, cancer, inflammatory conditions, appetite suppression, anti-aging, anti-glycation, epilepsy, depression, performance, strength, muscle mass, fat loss, improving body composition, and / or for use as a pharmaceutical, etc. A pharma- tically effective amount of butyrate, beta-hydroxybutyrate, related compounds, and / or combinations thereof may be administered to healthy and / or non-healthy individuals (e.g., having a disease and / or disorder).

[0005]

[0005] Embodiments may include one or more of the following features. The beta-hydroxybutyrate may include racemic mixtures and / or individual isomers of beta-hydroxybutyrate, such as R-beta-hydroxybutyrate (also known as D-beta-hydroxybutyrate). The beta-hydroxybutyrate may include related compounds. The beta-hydroxybutyrate may be combined with compounds such as amino acids. In some embodiments, the beta-hydroxybutyrate may include beta-hydroxybutyrate salts and beta-hydroxybutyrate esters. The other compounds may include short chain fatty acids, short chain triglycerides, medium chain fatty acids, medium chain triglycerides, long chain fatty acids, long chain triglycerides, berberine, berberine metabolites, dihydroberberine, tetrahydroberberine, and / or combinations thereof. One or more of the other compounds may be unencapsulated and / or encapsulated.

[0006] In various embodiments, the composition induces and / or maintains ketosis. The composition may comprise from about 0.5 g to about 10 g of R-beta-hydroxybutyrate.

[0007]

[0007] Embodiments may include one or more of the following features: The amount of the composition administered is: The composition may include about 0.5 to about 3 g of R-beta-hydroxybutyrate. The composition may include additional compositions, such as compositions that can independently increase ketone levels, induce ketosis and / or maintain ketosis. In some embodiments, the composition may include additional compositions to provide other health benefits (e.g., improved mental acuity, strength, etc.). For example, the composition may include fatty acids and / or esters of fatty acids. For example, the composition may include short chain fatty acids, esters of short chain fatty acids, medium chain fatty acids, esters of medium chain fatty acids, long chain fatty acids, or esters of long chain fatty acids. The composition may include flavorings, vitamins, minerals, and / or binders. The composition may be administered up to five times per day. Administration of the composition may increase strength, mental acuity, metabolism, fat loss, fat oxidation, motor function, muscle mass, and / or combinations thereof. In some embodiments, the 0.5 to 10 g of R-beta-hydroxybutyrate administered comprises at least one of R-beta-hydroxybutyrate and a polymer of R-beta-hydroxybutyrate or an R-beta-hydroxybutyrate complex.

[0008] In various embodiments, the composition comprises about 0.5 g to about 10 g of R-beta-hydroxybutyrate. The composition may include sibutyrate and one or more additional compounds capable of independently maintaining ketosis. Administration of the composition may induce and / or maintain ketosis in an individual.

[0009]

[0009] Embodiments may include one or more of the following features. The fatty acid may include R-beta-hydroxybutyrate, R-beta-hydroxybutyrate-amino acid complexes, and / or R-beta-hydroxybutyrate polymers. The additional compounds may include fatty acids and / or esters of fatty acids. The esters may include natural (e.g., cream, coconut oil, macadamia oil, etc.) and / or artificial fatty acids and / or esters of fatty acids. For example, the composition may include short chain fatty acids, esters of short chain fatty acids, medium chain fatty acids, esters of medium chain fatty acids, long chain fatty acids, or esters of long chain fatty acids. In some embodiments, the additional compounds may include beta-hydroxybutyrate, D,L-beta-hydroxybutyrate, butyrate, butyric acid, and / or polymers of the triglyceride tributyrin. The additional compounds may include berberine, dihydroberberine, and / or tetrahydroberberine.

[0010] In various embodiments, a pharmaceutical agent is used to induce and / or maintain ketosis. In one embodiment, an effective amount of R-beta-hydroxybutyrate and an amino acid can be administered.

[0011]

[0011] Embodiments may include one or more of the following features. The amount of R-beta-hydroxybutyrate to induce and / or maintain ketosis may be less than half or equal to the amount of D,L-beta-hydroxybutyrate to induce and / or maintain the same level of ketosis (e.g., as measured by blood ketone levels). In some embodiments, the amount of R-beta-hydroxybutyrate to induce and / or maintain ketosis in an individual may be less than the amount of D,L-beta-hydroxybutyrate or L-beta-hydroxybutyrate to induce and / or maintain the same level of ketosis. The composition may include about 1 g to about 5 grams of R-beta-hydroxybutyrate and about 0.5 to 2 g of an amino acid. The amino acid may include leucine. The composition may include a mixture and / or complex of R-beta-hydroxybutyrate and an amino acid. In some embodiments, at least a portion of the R-beta-hydroxybutyrate may be complexed with an amino acid. For example, a portion of the R-beta-hydroxybutyrate may be administered in the composition as a salt and / or polymer, and another portion of the R-beta-hydroxybutyrate may be administered as a complex with an amino acid (e.g., leucine). In some embodiments, the composition may include at least one R-beta-hydroxybutyrate salt (e.g., in addition to and / or as a pharma- tically effective amount of R-beta-hydroxybutyrate in the composition).

[0012] In various embodiments, the composition for maintaining or increasing weight loss comprises about The composition may comprise 0.5 g to about 15 g of R-beta-hydroxybutyrate, one or more flavorings, one or more vitamins, one or more minerals, one or more binders, and / or one or more liquid carriers. The R-beta-hydroxybutyrate comprises one or more salts of R-beta-hydroxybutyrate. The composition may be orally administered to maintain and / or increase weight loss in an individual.

[0013]

[0013] Embodiments may include one or more of the following features: The liquid carrier may include water. The amount of R-beta-hydroxybutyrate may comprise about 0.5 to about 5 g of R-beta-hydroxybutyrate. The composition may comprise at least one polymer of beta-hydroxybutyrate and at least one salt of R-beta-hydroxybutyrate. Administration of the composition increases mental acuity. Administration of the composition increases at least one of metabolism, fat loss, fat oxidation, motor function, and / or muscle mass. The composition may be administered up to five times per day. The R-beta-hydroxybutyrate in the composition may comprise sodium R-beta-hydroxybutyrate, potassium R-beta-hydroxybutyrate, magnesium R-beta-hydroxybutyrate, and / or calcium salt of R-beta-hydroxybutyrate.

[0014] In various embodiments, the composition for maintaining or inducing ketosis comprises about The composition may include 0.5 g to about 15 g of R-beta-hydroxybutyrate, one or more flavorings, one or more vitamins, one or more minerals, one or more binders, and / or one or more liquid carriers. The R-beta-hydroxybutyrate includes one or more salts of R-beta-hydroxybutyrate. The composition may be administered orally to maintain and / or induce ketosis in an individual.

[0015]

[0015] Embodiments may include one or more of the following features. The amount of hydroxybutyrate may comprise about 0.5 to about 5 g of R-beta-hydroxybutyrate. The one or more salts of R-beta-hydroxybutyrate may comprise sodium R-beta-hydroxybutyrate, potassium R-beta-hydroxybutyrate, calcium R-beta-hydroxybutyrate, and / or magnesium R-beta-hydroxybutyrate. The liquid carrier may comprise water, milk, coconut water. Administration of the composition may increase metabolism, fat loss, fat oxidation, motor function, and / or muscle mass. Administration of the compound may increase mental acuity, cognitive function, mood, energy, attention, focus, and / or performance.

[0016] In various embodiments, the composition for maintaining or inducing ketosis comprises about The composition may include 0.5 g to about 15 g of R-beta-hydroxybutyrate, an additional compound capable of independently increasing ketone levels, one or more flavorings, one or more vitamins, one or more minerals, one or more binders, and / or one or more liquid carriers. The R-beta-hydroxybutyrate includes one or more salts of R-beta-hydroxybutyrate. The additional compound may include less than about 500 mg of caffeine. The composition may be administered orally to maintain and / or induce ketosis in an individual.

[0017]

[0017] Embodiments may include one or more of the following features. The composition comprises from about 5 mg to about 5 The composition may include about 0.5 g to about 5 g of R-beta-hydroxybutyrate and about 5 mg to about 50 mg of caffeine. The one or more salts of R-beta-hydroxybutyrate may include sodium R-beta-hydroxybutyrate, potassium R-beta-hydroxybutyrate, calcium R-beta-hydroxybutyrate, and / or magnesium R-beta-hydroxybutyrate. Administration of the composition may increase at least one of weight loss, metabolism, fat loss, fat oxidation, motor function, muscle mass, mental acuity, cognitive function, mood, energy, attention, concentration, and / or performance. The liquid carrier may include water, milk, and / or coconut water.

[0018] The details of one or more embodiments are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the embodiments will become apparent from the description and the drawings.

[0019] For a more complete understanding of the present disclosure and its features, the following description, taken in conjunction with the accompanying drawings, in which: See description. [Brief description of the drawings]

[0020] [Figure 1] 1 is a table showing the time course of blood ketone levels in four subjects during an example administration of D,L-beta-hydroxybutyrate and R / D-beta-hydroxybutyrate. [Diagram 2]

[0021] 1 is a table showing blood ketone changes over time for an example administration of microencapsulated butyrate compared to conventional sodium butyrate. [Diagram 3]

[0022] 1 is a graph including the life span of rats subjected to administration of R-beta-hydroxybutyrate. [Figure 4]

[0023] 1 is a graph showing the results of exercise capacity testing following implementation of an example administration protocol. [Figure 5A]

[0024] 1 is a graph showing fat loss results following implementation of an example dosing protocol. [Figure 5B]

[0025] 1 is a graph showing fat mass and lean mass results following implementation of an example dosing protocol. [Figure 6]

[0026] 1 is a graph showing LPL levels in rats following an example administration protocol. [Figure 7]

[0027] 1 is a graph showing blood ketone levels following implementation of an example dosing protocol. [Figure 8]

[0028] 1 is a graph showing improvement versus placebo following implementation of an example dosing protocol. [Figure 9]

[0029] 1 is a graph showing perceived exertion following implementation of an example administration protocol. [Figure 10]

[0030] 1 is a graph showing blood ketone levels following implementation of an example dosing protocol. [Figure 11]

[0031] 1 is a graph showing blood ketone levels following implementation of an example dosing protocol. [Figure 12A]

[0032] 1 is a graph showing RER levels following implementation of an example dosing protocol. [Figure 12B]

[0033] 1 is a graph showing RER levels following implementation of an example dosing protocol. [Figure 13A]

[0034] 1 is a graph showing subjective hunger following implementation of an example dosing protocol. [Figure 13B]

[0035] 1 is a graph showing perceived satiety following implementation of an example administration protocol. [Figure 13C]

[0036] 1 is a graph showing perceived energy following implementation of an example administration protocol. [Figure 14A]

[0037] 1 is a graph showing the results of a physical fitness test following implementation of an example dosing protocol. [Figure 14B]

[0038] 1 is a graph showing the results of a physical fitness test following implementation of an example dosing protocol. [Figure 14C]

[0039] 1 is a graph showing the results of force testing following implementation of an example administration protocol. [Figure 15]

[0040] 1 is a graph showing blood ketone levels following implementation of an example dosing protocol. [Figure 16]

[0041] 1 is a graph showing blood ketone levels following implementation of an example dosing protocol. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021]

[0042] Like reference symbols in the various drawings indicate like elements.

[0022]

[0043] In various embodiments, butyrate, beta-hydroxybutyrate, and Compounds such as butyrate, beta-hydroxybutyrate and / or related compounds (e.g., derivatives, esters, polymers, etc.) can be administered alone or in combination with one or more other compounds. Administering pharma- tically effective amounts of these compounds may promote and / or maintain weight loss and / or ketosis. In some embodiments, administering pharma- tically effective amounts of one or more compounds may reduce and / or maintain blood ketone and / or blood glucose levels within a predefined range. In some embodiments, the health status of an individual (e.g., physical strength, symptoms of disease, mental acuity, fasting glucose levels, etc.) may be improved and / or maintained by administering compounds including butyrate, beta-hydroxybutyrate and / or related compounds (e.g., derivatives, esters, polymers, etc.).

[0023]

[0044] In various embodiments, butyrate, beta-hydroxybutyrate and / or Or related compounds may be administered to humans. Beta-hydroxybutyrate (e.g., R-beta-hydroxybutyrate, L-beta-hydroxybutyrate, and / or D,L-beta-hydroxybutyrate) may include beta-hydroxybutyrate salts and / or beta-hydroxybutyrate esters. In some embodiments, beta-hydroxybutyrate may include beta-hydroxybutyrate bound to another compound (e.g., an amino acid), and / or a polymer of beta-hydroxybutyrate. For example, beta-hydroxybutyrate (e.g., R-beta-hydroxybutyrate, L-beta-hydroxybutyrate, and / or D,L-beta-hydroxybutyrate) may include beta-hydroxybutyrate salts, beta-hydroxybutyrate esters, sodium salts of beta-hydroxybutyrate (e.g., sodium beta-hydroxybutyrate), potassium salts of beta-hydroxybutyrate (e.g., potassium beta-hydroxybutyrate), calcium salts of beta-hydroxybutyrate (e.g., calcium beta-hydroxybutyrate), beta-hydroxybutyrate esters, and the like. The beta-hydroxybutyrate may include magnesium salts of beta-hydroxybutyrate (e.g., magnesium beta-hydroxybutyrate), lithium salts of beta-hydroxybutyrate (e.g., lithium beta-hydroxybutyrate), sodium beta-hydroxybutyrate, arginine beta-hydroxybutyrate, lysine beta-hydroxybutyrate, histidine beta-hydroxybutyrate, ornithine beta-hydroxybutyrate, creatine beta-hydroxybutyrate, agmatine beta-hydroxybutyrate, or citrulline beta-hydroxybutyrate, other suitable organic salts including beta-hydroxybutyrate, and / or combinations thereof. In some embodiments, the beta-hydroxybutyrate may include beta-hydroxybutyrate with calcium, sodium, magnesium, potassium, zinc, selenium, chromium, other suitable minerals, and / or combinations thereof.In some embodiments, beta-hydroxybutyrate may be complexed and / or bound to another compound (e.g., amino acids and / or berberine), and beta-hydroxybutyrate may include complexes (e.g., chelates) with minerals (e.g., calcium, zinc, etc.), and beta-hydroxybutyrate compounds bound to another compound. Beta-hydroxybutyrate may include single isomer beta-hydroxybutyrate and / or polymeric beta-hydroxybutyrate. For example, R-beta-hydroxybutyrate may include single isomer R-beta-hydroxybutyrate and / or polymeric R-beta-hydroxybutyrate. In some embodiments, beta-hydroxybutyrate may be administered with 1,3-butanediol, ethyl acetoacetate, ethyl beta-hydroxybutyrate.

[0024]

[0045] Beta-hydroxybutyrate is a racemic mixture of beta-hydroxybutyrate The chirality of beta-hydroxybutyrate may include isomers and / or individual isomers. In some embodiments, one or more specific chiralities of beta-hydroxybutyrate may be utilized. For example, R-beta-hydroxybutyrate (also called D-beta-hydroxybutyrate), S-beta-hydroxybutyrate (also called L-beta-hydroxybutyrate), and / or mixtures thereof (e.g., racemic mixtures) may be used. In some embodiments, the composition may include R-beta-hydroxybutyrate (e.g., a more purified form of R-beta-hydroxybutyrate rather than D,L-beta-hydroxybutyrate). For example, R-beta-hydroxybutyrate may include less than about 10 percent, less than about 5 percent, or less than about 1 percent of L-beta-hydroxybutyrate. R-beta-hydroxybutyrate may be more bioavailable than other chiralities of beta-hydroxybutyrate. R-beta-hydroxybutyrate may have a greater impact on an individual's health (e.g., through fewer side effects, increased ketone levels, weight loss, mental acuity, fat loss, etc.) than L-beta-hydroxybutyrate and / or D,L-beta-hydroxybutyrate. In some embodiments, R-beta-hydroxybutyrate may provide improved health not achieved by L-beta-hydroxybutyrate and / or D,L-beta-hydroxybutyrate. R-beta-hydroxybutyrate may have less impurities from manufacture, such as crotonic acid, that may be harmful to an individual, than other forms of beta-hydroxybutyrate (e.g., L-beta-hydroxybutyrate and / or D,L-beta-hydroxybutyrate). In some embodiments, R-beta-hydroxybutyrate may be more capable of combining with other compounds (e.g., purines, lysine, potassium, and / or other amino acids, dihydroberberine, etc.) to deliver beta-hydroxybutyrate to a human. Thus, a mixture of R-beta-hydroxybutyrate (e.g., greater than 90 percent pure R-beta-hydroxybutyrate and less than 10 percent pure L-beta-hydroxybutyrate) and / or R-beta-hydroxybutyrate may be administered to a human. In some embodiments, unexpectedly, smaller amounts of R-beta-hydroxybutyrate may exhibit the same or greater pharmaceutical effects (e.g., increasing and / or maintaining weight loss, increasing and / or maintaining elevated ketone levels, etc.) as D,L-beta-hydroxybutyrate (e.g., a racemic mixture of D- and L-beta-hydroxybutyrate). For example, about half the amount of R-beta-hydroxybutyrate may be administered to achieve approximately the same efficacy as D,L-beta-hydroxybutyrate and / or L-beta-hydroxybutyrate. R-beta-hydroxybutyrate may be more bioavailable than other chiralities of beta-hydroxybutyrate, and therefore may require less effective doses than other chiralities. Thus, by utilizing R-beta-hydroxybutyrate, the dosage of beta-hydroxybutyrate can be reduced (e.g., when compared to the dosage of D,L-beta-hydroxybutyrate) while still providing a pharma- ceutically effective amount (e.g., for weight loss and / or maintenance, for increasing and / or maintaining blood ketone levels). When beta-hydroxybutyrate is provided in the form of a salt, reducing the amount of beta-hydroxybutyrate can reduce the user's intake of the salt's cations (e.g., sodium, potassium, etc.).Some of these cations, such as sodium, potassium, magnesium, and calcium, found in beta-hydroxybutyrate, can cause health problems (e.g., organ damage, gastrointestinal problems, etc.) when consumed in excess of predetermined recommended amounts, so reducing the amount of beta-hydroxybutyrate using R-beta-hydroxybutyrate may reduce side effects and / or health problems associated with administering salts in combination with beta-hydroxybutyrate to users.

[0025]

[0046] In some embodiments, the present invention provides a method for promoting and / or maintaining ketosis and increasing weight loss. A pharma- tically effective amount of R-beta-hydroxybutyrate can be administered to an individual to induce and / or control weight and / or increase blood ketone levels. For example, about 0.1 g to about 50 g of R-beta-hydroxybutyrate can be administered to an individual. In some embodiments, about 0.1 g to about 15 g of R-beta-hydroxybutyrate can be administered to an individual. In some embodiments, about 1 g to about 10 g of beta-hydroxybutyrate can be administered, for example, once a day to five times a day (e.g., up to a maximum administration of 50 g of beta-hydroxybutyrate). Administration may result in weight loss and / or maintenance, increasing blood beta-hydroxybutyrate levels, increasing, decreasing and / or maintaining blood ketones, inducing and / or maintaining and / or decreasing ketosis, improving mental acuity, improving focus, improving energy, improving cognitive function, reducing traumatic brain injury, improving diabetes, improving glucose tolerance, reducing blood sugar levels, reducing neurological disorders and / or symptoms thereof, improving cancer and / or symptoms thereof, improving inflammatory conditions, suppressing appetite, improving symptoms associated with aging, providing an anti-glycation effect, improving epilepsy and / or symptoms thereof, improving depression and / or symptoms thereof, improving performance, improving strength, increasing muscle mass, increasing fat loss, improving body composition, improving energy, improving focus, improving cognitive function, improving mood and / or well-being, and / or combinations thereof. Beta-hydroxybutyrates (e.g., R-beta-hydroxybutyrate) are an important component of the dietary supplements that are effective in treating and preventing chronic conditions in healthy individuals. The therapeutic agent may be administered to healthy individuals as well as to non-healthy individuals (eg, individuals having a disease and / or disorder).

[0026]

[0047] In some embodiments, a beta-hydroxybutyrate such as R-beta-hydroxybutyrate. The hydroxybutyrate may be administered with and / or conjugated to a compound such as an amino acid. For example, beta-hydroxybutyrate may be conjugated (e.g., chemically bound) to an amino acid such as leucine, lysine, arginine, histidine, ornithine, creatine, agmatine, citrulline, and / or combinations thereof. In some embodiments, R-beta-hydroxybutyrate may be utilized rather than other chiralities because R-beta-hydroxybutyrate can be more readily conjugated to leucine, purine, lysine, and / or other amino acids. Administration of beta-hydroxybutyrate conjugated to an amino acid may reduce the intake of cations associated with beta-hydroxybutyrate (e.g., may inhibit side effects associated with administration) and / or may allow administration of another compound with health benefits (e.g., administration of some amino acids may promote smooth muscle growth and / or cell repair). In some embodiments, about 0.5 g to about 10 g of an amino acid may be administered with the beta-hydroxybutyrate. For example, less than about 50 g of R-beta-hydroxybutyrate and less than about 60 mg of an amino acid such as leucine may be administered daily. In some embodiments, about 0.5 g to about 2 g of an amino acid such as leucine may be administered with the beta-hydroxybutyrate. For example, a composition administered may include about 0.1 to about 7 g of R-beta-hydroxybutyrate and about 1 to 3 g of leucine. The R-beta-hydroxybutyrate and leucine may be in a mixture, may be administered separately and closely timed, may be in a complex, and / or may be administered in any other suitable manner.

[0027]

[0048] In some embodiments, the composition comprises R-beta-hydroxybutyrate and beta. The dosage form may include a tert-hydroxybutyrate-amino acid complex (e.g., beta-hydroxybutyrate bound to an amino acid, such as an R-beta-hydroxybutyrate-leucine complex). For example, an individual may be administered a first weight of sodium beta-hydroxybutyrate and a second weight of a beta-hydroxybutyrate amino acid complex. The first and second amounts may be different or the same.

[0028]

[0049] In some embodiments, the beta-hydroxybutyrate composition comprises a beta-hydroxybutyrate. The beta-hydroxybutyrate and beta-hydroxybutyrate ester may comprise sodium beta-hydroxybutyrate and beta-hydroxybutyrate ester. For example, an individual may be administered a first weight of sodium beta-hydroxybutyrate and a second weight of beta-hydroxybutyrate ester. The first and second amounts may be different or the same. The beta-hydroxybutyrate and beta-hydroxybutyrate ester may be administered separately, as a combined complex, a mixture of compounds, and / or at about the same time. In some embodiments, the beta-hydroxybutyrate ester may be in powder form (e.g., beta-hydroxybutyrate ester in a slab powder form), liquid and / or gel form. The combination of beta-hydroxybutyrate and beta-hydroxybutyrate ester during administration may allow for less salt utilization while producing results (e.g., maintaining and / or reducing body weight, enhancing and / or maintaining ketosis, increasing blood ketone levels, reducing and / or maintaining blood glucose, increasing energy, improving mood, improving performance, and / or improving cognitive function). In some embodiments, increasing ketone levels (e.g., increasing blood ketone levels) may increase the energy, mood, performance, and / or cognitive function of a user. For example, administration of a first amount of beta-hydroxybutyrate salt may result in a first level of blood ketones that may be maintained by the administration of a second amount of beta-hydroxybutyrate ester (e.g., when an individual's body processes a beta-hydroxybutyrate ester, the level of beta-hydroxybutyrate in the blood may be increased). The blood levels, and therefore blood ketone levels, may increase over time, reinforcing and / or maintaining the initial rise caused by the administered beta-hydroxybutyrate. For example, the ratio of beta-hydroxybutyrate to beta-hydroxybutyrate esters may be from about 1 beta-hydroxybutyrate:about 1 beta-hydroxybutyrate ester to about 1 beta-hydroxybutyrate:about 20 beta-hydroxybutyrate esters. The ratio of beta-hydroxybutyrate to beta-hydroxybutyrate esters may be from about 20 beta-hydroxybutyrate:about 1 beta-hydroxybutyrate ester to about 1 beta-hydroxybutyrate:about 20 beta-hydroxybutyrate esters. In some embodiments, the ratio of beta-hydroxybutyrate to beta-hydroxybutyrate esters may be from about 1 beta-hydroxybutyrate:about 1 beta-hydroxybutyrate ester to about 1 beta-hydroxybutyrate:about 5 beta-hydroxybutyrate esters.

[0029]

[0050] Related compounds that may be included in the composition as beta-hydroxybutyrate are (R Derivatives of beta-hydroxybutyrate may include esters of (R)-3-hydroxybutyrate and oligomers of (R)-3-hydroxybutyrate. For example, beta-hydroxybutyrate esters derived from alcohols such as altrose, arabinose, dextrose, erythrose, fructose, galactose, glucose, glycerol, gulose, idose, lactose, lyxose, mannose, ribitol, ribose, ribulose, sucrose, talose, threose, xylitol, xylose, galactosamine, glucosamine, mannosamine, N-acetylglucosamine, mannitol, sorbitol, threitol, (S)-1,2-propanediol and / or (R)-1,3-butanediol. In some embodiments, derivatives of beta-hydroxybutyrate may include the structure of (R)-3-hydroxybutyric acid and its exemplary esters (glycerol monoesters). In some embodiments, the R chirality of the derivative can be selected for inclusion in a composition (eg, to deliver R-beta-hydroxybutyrate with administration of the compound).

[0030]

[0051] In some embodiments, butyrate, beta-hydroxybutyrate (e.g. , R-beta-hydroxybutyrate), related compounds, and / or combinations thereof may be administered with one or more additional compounds. The additional compounds may or may not be capable of independently increasing ketone levels, maintaining ketone levels, inducing ketosis, and / or maintaining ketosis. For example, additional compounds capable of independently increasing blood ketone levels may include short chain fatty acids (e.g., fatty acids having 2-6 carbons), short chain triglycerides (e.g., triglycerides having less than 6 carbons), medium chain fatty acids (e.g., fatty acids having 6-12 carbons), medium chain triglycerides (e.g., triglycerides having 7-12 carbons), long chain fatty acids (e.g., fatty acids having more than 12 carbons), long chain triglycerides (e.g., triglycerides having more than 12 carbons), and / or combinations thereof. In some embodiments, the short chain fatty acids and / or triglycerides may include acetate, propionate, and / or butyrate. The medium chain fatty acids and / or triglycerides may include lauric acid and / or coconut oil, coconut milk powder, fractionated coconut oil, isolated hexanoic acid, isolated octanoic acid, isolated decanoic acid, ethoxylated triglycerides, triglyceride derivatives thereof, aldehyde triglyceride derivatives thereof, monoglyceride derivatives thereof, diglyceride derivatives thereof, triglyceride derivatives thereof, and / or alkyl esters thereof. The long chain fatty acids and / or triglycerides may include dairy products and / or palm oil. In some embodiments, a composition comprising R-beta-hydroxybutyrate and an additional compound capable of independently increasing ketone levels can increase ketone levels to a greater extent (e.g., greater than an additive increase) than the mere individual capabilities of each component. For example, a composition may comprise R-beta-hydroxybutyrate and an additional compound capable of independently increasing ketone levels, such as caffeine. and additional compounds that can be independently increased. In some embodiments, the composition may include about 0.5 mg to about 50 g of R-beta-hydroxybutyrate and caffeine. In some embodiments, the composition may include about 0.5 mg to about 15 g of R-beta-hydroxybutyrate and less than about 500 mg of caffeine. In some embodiments, the composition may include about 0.5 mg to about 15 g of R-beta-hydroxybutyrate and about 5 mg to about 500 mg of caffeine. In some embodiments, the composition may include about 0.5 mg to about 15 g of R-beta-hydroxybutyrate and about 10 mg to about 150 mg of caffeine. In some embodiments, the composition may include about 0.5 mg to about 15 g of R-beta-hydroxybutyrate and about 10 mg to about 50 mg of caffeine. Compositions comprising R-beta-hydroxybutyrate (e.g., R-beta-hydroxybutyrate comprising at least one R-beta-hydroxybutyrate salt) and caffeine can increase and / or maintain ketosis, weight loss, fat loss, and / or mental acuity. In some embodiments, compositions comprising R-beta-hydroxybutyrate (e.g., R-beta-hydroxybutyrate comprising at least one R-beta-hydroxybutyrate salt) and caffeine can enhance mental processes (e.g., cognitive function, mood, energy, attention, focus, performance, acuity including effects of aging, etc.), improve and / or maintain body composition, act as a therapeutic agent for one or more of the conditions or disorders described (e.g., treat neurological disorders), and / or combinations thereof. In some embodiments, the composition may include R-beta-hydroxybutyrate and an additional compound that can independently increase ketone levels, such as 1,3,7,9-tetramethyluric acid (commercially available as Theacrine and / or available as TeaCrine® from Compound Solutions, Inc., California, USA). In some embodiments, the composition may include about 0.5 mg to about 15 g of R-beta-hydroxybutyrate and less than about 500 mg of 1,3,7,9-tetramethyluric acid.In some embodiments, the composition may comprise about 5 mg to about 15 g of R-beta-hydroxybutyrate and less than about 500 mg of 1,3,7,9-tetramethyluric acid.

[0031]

[0052] For example, a pharma- ceutical effective amount of one or more short chain fatty acids and / or one Or a plurality of short chain triglycerides (e.g., butyric acid and / or butyrate) may be administered with a pharma- tically effective amount of beta-hydroxybutyrate. In some embodiments, about 1 g to about 10 g of beta-hydroxybutyrate and about 0.1 g to about 50 g of short chain fatty acids and / or triglycerides may be administered once a day to about 5 times a day. In some embodiments, about 1 g to about 3 g of beta-hydroxybutyrate and about 1 g of short chain fatty acids and / or triglycerides may be administered once a day to about 5 times a day. In some embodiments, the short chain fatty acids and / or triglycerides may include butyrate or a derivative of butyrate. Butyrate and / or a derivative of butyrate may be administered with and / or without beta-hydroxybutyrate to manage metabolic conditions such as ketosis and / or other suitable therapeutic purposes. Administered butyrate may be converted to beta-hydroxybutyrate in the human body, thereby increasing the amount of beta-hydroxybutyrate delivered to the user. In some embodiments, administration of butyrate and beta-hydroxybutyrate may promote hGH synthesis, improve basal and GHRH-induced hGH secretion, increase muscle fiber cross-sectional area, inhibit intramuscular fat accumulation; reduce fat mass in the user; improve glucose metabolism; increase skeletal muscle mitochondrial biogenesis markers and / or whole body oxygen consumption; reduce oxidative stress and apoptosis markers and alter antioxidant enzyme activity; increase intracellular free cytosolic calcium levels by butyrate (e.g., by acting through GPR41 and 43); increase beta-hydroxybutyrate levels; and / or support gut barrier function and / or reduce inflammation associated with ulcerative colitis. Butyrate is processed in the body to provide beta-hydroxybutyrate. Therefore, delivery of beta-hydroxybutyrate via butyrate may supplement directly administered beta-hydroxybutyrate and maintain levels of beta-hydroxybutyrate in the blood (e.g., promoting ketosis, weight loss and / or management, etc.).

[0032]

[0053] However, butyrate and butyric acid may be unpalatable to some people (e.g. (Because the odor and taste are often compared to vomit). Thus, in some embodiments, butyrate and / or beta-hydroxybutyrate (e.g., R-beta-hydroxybutyrate) may be treated to reduce sensory reactions. For example, butyrate and / or beta-hydroxybutyrate (e.g., R-beta-hydroxybutyrate) may be treated by encapsulation, microemulsion, liposomes, aggregation, masking / flavoring techniques, and / or other suitable treatments to reduce sensory reactions from individuals administered the described compositions. In some embodiments, microencapsulated butyrate, beta-hydroxybutyrate, and / or butyric acid may be utilized (e.g., in combination with beta-hydroxybutyrate). Using microencapsulated butyrate, beta-hydroxybutyrate, and / or butyric acid (e.g., compared to using non-encapsulated forms) may improve individual satisfaction and / or compliance with the dosing schedule due to the reduced and / or eliminated odor from butyrate and / or butyric acid. Microencapsulated butyrate, beta-hydroxybutyrate, and / or butyric acid can be a free-flowing granular powder, dispersible in water, stable for 30 minutes in acidic aqueous solution, allow for controlled release in the stomach and / or small intestine, inhibit glucose response (e.g., relative to any added substance), and / or allow for delivery of high butyrate content (e.g., about 70%).

[0033]

[0054] In some embodiments, a pharma- tically effective amount of butyrate is added to the triglyceride triglyceride. Butyrate may be administered via butyrin (e.g., glyceryl tributyrate or tributyrin). Butyrate via triglyceride tributyrin may be administered separately and / or in combination with one or more of the other compounds described (e.g., beta-hydroxybutyrate, fatty acids and / or esters, etc.). For example, up to about 200 mg per kg of an individual may be administered (e.g., up to three times a day). Administration of tributyrin may result in delayed release of butyrate into the body as the tributyrin is processed in the individual's body. Tributyrin may be unencapsulated and / or encapsulated (e.g., microencapsulated).

[0034]

[0055] In some embodiments, beta-hydroxybutyrate and short chain compounds (e.g. Administration of a medium chain compound (e.g., short chain fatty acids and / or short chain triglycerides) may unexpectedly increase blood beta-hydroxybutyrate levels more than administration of a similar amount of beta-hydroxybutyrate and a medium chain compound (e.g., short chain fatty acids and / or short chain triglycerides) and / or may increase blood beta-hydroxybutyrate levels more than administration of each component individually.

[0035]

[0056] In some embodiments, a pharma- ceutical effective amount of beta-hydroxybutyrate is , may be administered together with a pharma- tically effective amount of long chain fatty acid and / or triglyceride. For example, 0.1 to 50 g of beta-hydroxybutyrate and 0.1 to 50 g of long chain fatty acid may be administered to an individual 1 to 5 times per day. In some embodiments, about 1 g to about 3 g of beta-hydroxybutyrate and about 1 g of long chain fatty acid and / or triglyceride may be administered once per day to about 5 times per day.

[0036]

[0057] In some embodiments, beta-hydroxybutyrate, a short chain compound (e.g. , fatty acids and / or triglycerides, butyrates), and / or medium chain compounds (e.g. For example, about 0.1 g to about 50 g of beta-hydroxybutyrate, about 0.1 g to about 50 g of short chain triglycerides, and about 0.1 g to about 50 g of medium chain fatty acids, such as lauric acid and / or coconut oil, may be administered once to about five times per day. In some embodiments, about 1 g to about 3 g of beta-hydroxybutyrate and about 1 g of short chain fatty acids and / or triglycerides and / or about 1 g of medium chain fatty acids and / or triglycerides may be administered once to about five times per day. In some embodiments, about 0.1 g to about 20 g of beta-hydroxybutyrate (e.g., salts, esters, isomers, and / or other suitable forms) may be administered to a human. In some embodiments, about 0.1 g to about 20 g of butyrate may be administered to a human.

[0037]

[0058] In some embodiments, glucose levels can be independently reduced Other compounds such as compounds may be administered with beta-hydroxybutyrates such as berberine and / or related metabolites (e.g., dihydroberberine and / or tetrahydroberberine). U.S. Patent Application No. 15 / 491,933, filed April 19, 2017, entitled "ADMINISTRATION OF DIHYDROBERBERINE" to Lowery et al., and U.S. Provisional Patent Application No. 62 / 324,794, filed April 19, 2016, entitled "ADMINISTRATION OF DIHYDROBERBERINE" to Lowery et al., describe the administration of dihydroberberine in combination with ketone sensitizers such as beta-hydroxybutyrates, and are incorporated herein in their entirety. In some embodiments, one or more beta-hydroxybutyrates and / or other compounds described herein may be utilized as ketone sensitizers with dihydroberberine.

[0038]

[0059] In some embodiments, beta-hydroxybutyrate and beta-hydroxy A first level of beta-hydroxybutyrate in the blood may be maintained over a period of time by direct administration over time with another compound (e.g., beta-hydroxybutyrate esters, beta-hydroxybutyrate polymers, butyrate, other suitable compounds, and / or combinations thereof) that is processed to deliver sibutyrate. For example, directly administered beta-hydroxybutyrate can raise the beta-hydroxybutyrate level in the blood to a first concentration, and then approximately maintain this concentration over a period of time by providing additional beta-hydroxybutyrate via another compound (e.g., short chain fatty acids and / or triglycerides, beta-hydroxybutyrate esters, beta-hydroxybutyrate polymers, beta-hydroxybutyrate amino acid complexes, etc.) administered at approximately the same time.

[0039]

[0060] In some embodiments, the one or more other compounds may be butyrate (e.g., , microencapsulated butyrate), beta-hydroxybutyrate (e.g., R-beta-hydroxybutyrate) and / or short chain fatty acids or esters (e.g., included in the composition and / or administered separately). Other ingredients include: amino acids, amino acid metabolites, vitamins, minerals, coconut milk powder, flavors, colors, binders, electrolytes, tetrahydrobiopeptin, nucleic acids, alpha-ketoglutaric acid, alpha-lipoic acid, nutritional cofactors, beta-methyl-beta-hydroxybutyrate, arginine alpha-ketoglutaric acid, R-alpha lipoic acid, thiamine, NAD+, NADH, riboflavin, FAD+, FADH, riboflavin-5-phosphate, niacin, nicotinic acid, niacinamide, inositol hexanicotinate, pyridoxine, pyridoxal, pyridoxamine, ascorbic acid and ascorbate salts, citric acid, malic acid, sodium benzoate, pyridoxal-5-phosphate, methylcobalamin, cyanocobalamin, adenosylcobalamin, hydroxycobalamin, paclitaxel, phenylalanine ... Ingredients that may be used include, but are not limited to, anthraquinone, pantetheine, potassium sorbate, acesulfame K, aspartame, sucralose, stevia, monk fruit extract, allulose, prebiotic fiber, XOS, GOS, MOS, IMO, LOS, xanthan gum and other organic gums / thickening / suspending agents, and combinations thereof.

[0040]

[0061] In various embodiments, administration of a composition comprising beta-hydroxybutyrate , may improve the health of an individual. R-beta-hydroxybutyrate may have a greater impact on the health of an individual than D,L-beta-hydroxybutyrate and / or L-beta-hydroxybutyrate. Although not previously known, L-beta-hydroxybutyrate may reduce the effectiveness of R-beta-hydroxybutyrate with respect to at least some of the health effects. With respect to health effects, L-beta-hydroxybutyrate may not have an impact on health. In some embodiments, doubling the amount of D,L-beta-hydroxybutyrate may not achieve some of the same results (e.g., improved health) as R-beta-hydroxybutyrate. Thus, unexpectedly, administering D,L-beta-hydroxybutyrate rather than R-beta-hydroxybutyrate may not have the same impact on the health of an individual and / or may have less impact on the health of an individual. For example, administering a composition containing R-beta-hydroxybutyrate (e.g., and / or other compounds) may improve and / or maintain the health of an individual.

[0041]

[0062] When administered as described, R-beta-hydroxybutyrate can be used to supplement a diet plan (e.g. The life span may be increased in individuals following a diet plan (e.g., standard American low-fat, ketogenic, paleo, Mediterranean, etc.) and / or individuals not following a diet plan. For example, about 10 g of R-beta-hydroxybutyrate to about 30 g of R-beta-hydroxybutyrate can be administered to increase life span. In some embodiments, other suitable amounts of R-beta-hydroxybutyrate may be included in the composition.

[0042]

[0063] In some embodiments, administration of R-beta-hydroxybutyrate improves cognitive function. The effects of symptoms of diseases and / or disorders, such as diseases that affect cognitive function, can be treated and / or reduced. Administration of R-beta-hydroxybutyrate may enhance motor function in individuals with Parkinson's disease. For example, about 5 g of R-beta-hydroxybutyrate to about 15 g of R-beta-hydroxybutyrate can be administered to enhance motor function. In some embodiments, other suitable amounts of R-beta-hydroxybutyrate may be included in the composition.

[0043]

[0064] Administration of R-beta-hydroxybutyrate may increase fat loss Unlike conventional dietary therapy, where weight loss often occurs through water retention and / or muscle mass loss, administration of R-beta-hydroxybutyrate can cause weight loss through fat loss (see, for example, FIG. 5B). Furthermore, administration of R-beta-hydroxybutyrate can reduce LPL levels in the body, thus reducing or inhibiting fat storage and / or promoting the utilization of existing fat stores in the body. For example, about 1 g of R-beta-hydroxybutyrate to about 20 g of R-beta-hydroxybutyrate can be administered to cause fat loss and / or reduce fat storage. In some embodiments, other suitable amounts of R-beta-hydroxybutyrate may be included in the composition. Administration of R-beta-hydroxybutyrate can allow for fat loss of more than 5 kg while maintaining lean mass. In some embodiments, administration of R-beta-hydroxybutyrate increases the amount of fat used as fuel.

[0044]

[0065] In some embodiments, administration of R-beta-hydroxybutyrate enhances C Health markers such as reactive protein and / or fasting glucose may be improved and / or maintained. Administration of R-beta-hydroxybutyrate may reduce inflammation (e.g., as indicated by levels of C-reactive protein). Administration of R-beta-hydroxybutyrate may reduce fasting glucose. For example, about 3 g of R-beta-hydroxybutyrate to about 20 g of R-beta-hydroxybutyrate may be administered to lower and / or keep fasting glucose low. In some embodiments, other suitable amounts of R-beta-hydroxybutyrate may be included in the composition. In some embodiments, R-beta-hydroxybutyrate may be administered with one or more other compounds to lower glucose levels and / or sensitivity. For example, administering a composition of berberine, such as R-beta-hydroxybutyrate and dihydroberberine, may lower and / or keep fasting glucose low. Administering a composition of berberine, such as R-beta-hydroxybutyrate and dihydroberberine, may lower and / or keep glucose low. In some embodiments, less than about 15 g of R-beta-hydroxybutyrate may be administered along with less than about 600 mg of dihydroberberine.

[0045]

[0066] Administration of R-beta-hydroxybutyrate may lower ketone levels (See, e.g., Figures 11A and 11B). Lowering blood ketone levels may result in increased weight loss, sustained weight loss, improved performance, improved mental acuity, and / or other health-improving and health-maintaining functions. For example, even at levels below 10 g (e.g., about 5 g), administration of R-beta-hydroxybutyrate may lower ketone levels, but not LR-beta-hydroxybutyrate, and not to the same extent with D,L-beta-hydroxybutyrate. R-beta-hydroxybutyrate may increase blood ketone levels 5-fold more than a similar dose of D,L-beta-hydroxybutyrate. The amount of R-beta-hydroxybutyrate administered (e.g., compared to administering D,L-beta-hydroxybutyrate) may be reduced to achieve the same results, and therefore the amount of cations administered (e.g., sodium, potassium, etc.) may also be reduced. Because some individuals may prefer and / or not tolerate high doses of R-beta-hydroxybutyrate cations, utilizing R-beta-hydroxybutyrate may allow for larger dosing populations, improve user satisfaction, and / or reduce side effects (e.g., those associated with additional intake of these cations). In some embodiments, about 0.1 g of R-beta-hydroxybutyrate to about 10 g of R-beta-hydroxybutyrate may be administered to increase blood ketone levels. About 0.5 g of R-beta-hydroxybutyrate to about 3 g of R-beta-hydroxybutyrate may be administered to maintain blood ketone levels. In some embodiments, other suitable amounts of R-beta-hydroxybutyrate may be included in the composition.

[0046]

[0067] Administration of R-beta-hydroxybutyrate improves performance and subjective well-being It may reduce perceived exertion (e.g., as opposed to administering D,L-beta-hydroxybutyrate). For example, about 3 g of R-beta-hydroxybutyrate to about 15 g of R-beta-hydroxybutyrate may be administered to improve performance and / or reduce perceived exertion. In some embodiments, other suitable amounts of R-beta-hydroxybutyrate may be included in the composition.

[0047]

[0068] In various embodiments, oral administration of R-beta-hydroxybutyrate is Although it may increase protein synthesis, D,L-beta-hydroxybutyrate does not increase muscle protein synthesis. For example, taking about 10 g of R-beta-hydroxybutyrate to about 30 g of R-beta-hydroxybutyrate to increase muscle protein synthesis In some embodiments, other suitable amounts of R-beta-hydroxybutyrate may be included in the composition.

[0048]

[0069] In some embodiments, administration of R-beta-hydroxybutyrate is Unlike D,L-beta-hydroxybutyrate, administration of R-beta-hydroxybutyrate may decrease perceived hunger and / or increase satiety, which may inhibit overeating and therefore promote weight loss (see, e.g., Figures 13A and 13B). In some embodiments, administration of R-beta-hydroxybutyrate may increase perceived energy, unlike D,L-beta-hydroxybutyrate (see, e.g., Figure 13C).

[0049]

[0070] In some embodiments, administration of R-beta-hydroxybutyrate improves cognitive function. Improved mental acuity. For example, about 0.1 g of R-beta-hydroxybutyrate to about 10 g of R-beta-hydroxybutyrate may be administered to enhance mental acuity. In some embodiments, other suitable amounts of R-beta-hydroxybutyrate may be included in the composition.

[0050]

[0071] In some embodiments, the administration of R-beta-hydroxybutyrate may include other forms of Beta-hydroxybutyrate, butyric acid, and / or butyrate may be supplemented.

[0051]

[0072] In some embodiments, the composition administered is R-beta-hydroxybutyrate. The amount of R-beta-hydroxybutyrate included in the composition can be selected (e.g., a pharma- tically effective amount can be administered at a dose and / or over a given period of time) to obtain a result upon administration (e.g., to induce ketosis, maintain ketosis, increase ketone levels, mental acuity, strength, etc.). In some embodiments, the dose and / or frequency of administration can vary over time (e.g., an initial dose and a lower dose for maintenance, varying based on time of day, varying based on the presence or absence of food, etc.).

[0052]

[0073] The R-beta-hydroxybutyrate in the composition may be present in the form of a salt, derivative (e.g., ester ), polymers, and / or complexes with other compounds. For example, the composition may include R-beta-hydroxybutyrate (e.g., sodium R-beta-hydroxybutyrate, magnesium R-beta-hydroxybutyrate, and / or potassium R-beta-hydroxybutyrate) and / or another form of R-beta-hydroxybutyrate (e.g., esters, polymers, complexes, etc.). In some embodiments, the composition may include an R-beta-hydroxybutyrate ester. The composition may include an amino acid such as leucine (e.g., individually and / or complexed with R-beta-hydroxybutyrate). The use of a non-salt base R-beta-hydroxybutyrate may increase user satisfaction (e.g., due to reduced cationic load such as sodium and / or potassium from ingestion of the composition, reduced side effects, etc.) and may increase applicability of administration (e.g., because users who are sensitive to cations of R-beta-hydroxybutyrate may be less sensitive to the non-salt and / or low salt plus non-salt forms of the composition). Administration of the compositions may result in increased blood ketone levels, induction of ketosis, maintenance of blood ketone levels, maintenance of ketosis, improved health, increased strength, enhanced mental acuity, etc. In some embodiments, a first composition comprising R-beta-hydroxybutyrate may be administered to cause a first effect (e.g., inducing ketosis, rapidly increasing mental acuity, rapidly increasing strength, etc.) and a second composition comprising non-salt R-beta-hydroxybutyrate (e.g., esters, polymers, complexes, etc.) and / or low levels of R-beta-hydroxybutyrate may be administered to cause a second effect (e.g., increasing ketosis, rapidly increasing mental acuity, rapidly increasing strength, etc.). For example, it may be used to induce ketosis, maintain mental acuity, maintain increased physical strength, etc.

[0053]

[0074] In some embodiments, the form of R-beta-hydroxybutyrate included is , can be selected based on the delivery form. For example, depending on the food form, the composition may include R-beta-hydroxybutyrate polymer (e.g., for taste, since increased cations such as sodium may decrease palatability, for nutrition, since increased cations such as sodium may decrease nutrition, for mixability, etc.). As another example, the composition may include R-beta-hydroxybutyrate or other forms (e.g., microencapsulated) to provide a fast-dissolving powder.

[0054]

[0075] In various embodiments, the composition comprises R-beta-hydroxybutyrate. The R-beta-hydroxybutyrate may be in any suitable form (e.g., salt, ester, polymer, complex, derivatives thereof, and / or combinations thereof). The composition may include one or more additional compositions. The additional compositions may be capable of independently increasing blood ketone levels (e.g., fatty acids or esters, berberine or berberine metabolites such as dihydroberberine, etc.). The additional compositions may have the ability to independently lower blood glucose levels (e.g., berberine or berberine metabolites such as dihydroberberine). In some embodiments, the additional compounds may not be capable of independently increasing blood ketone levels and / or lowering blood glucose levels (e.g., additives, flavors, colors, minerals, vitamins, binders, anti-caking agents, etc.). The composition may be administered in an amount effective to cause a predetermined health effect (e.g., a predetermined ketosis level, blood ketone levels, mental acuity, increased strength, perceived energy, fat loss, weight loss, etc.). The composition may be administered to an individual in a predetermined amount and / or in different amounts over a dosing schedule. In some embodiments, once a first criterion (e.g., duration, number of doses, predetermined health effect) is met, the dose may be altered. For example, a first dose of the composition may be administered to induce a predetermined health effect, and an additional lower dose of the composition may be administered to maintain the predetermined health effect (e.g., caused in part by the first dose).

[0055]

[0076] The compositions can be administered in any suitable delivery form (e.g., tablet, capsule, mixed into food, beverage, etc. The compositions can be administered in food, beverage products, such as powdered products that can be mixed into and / or ingested directly. The compositions can be administered according to any suitable schedule (e.g., regular doses, doses according to the desires of the user, etc.). The dosing schedule can, in some embodiments, prohibit dosing that excessively raises blood ketone levels, excessively lowers blood glucose levels, and / or causes an individual to ingest a dose that significantly increases the risk of adverse and / or side effects.

[0056]

[0077] In some embodiments, the composition comprises a long-acting component, and / or It may be long-acting. For example, the body digests polymers and / or esters of beta-hydroxybutyrate (e.g., R-beta-hydroxybutyrate), so that delivery of R-beta-hydroxybutyrate may be slower than digestion of beta-hydroxybutyrate (e.g., R-beta-hydroxybutyrate). In some embodiments, the composition may include R-beta-hydroxybutyrate and a long-acting R-beta-hydroxybutyrate form (e.g., a form that is polymerized, esterified, coated and / or processed to provide sustained release). In some embodiments, the first dose may include at least one non-long-acting beta-hydroxybutyrate and the second dose may include at least one long-acting beta-hydroxybutyrate. The first dose may be administered to cause a predetermined health effect, and the second dose may be administered to maintain the caused predetermined health effect. In some embodiments, the use The user can select the appropriate dose based on the user's preferences and / or characteristics (e.g., a user following a ketogenic diet can select the second dose because they may already be in a state of ketosis).

[0057]

[0078] EXAMPLES

[0058]

[0079] Example 1

[0080] Four subjects were given 10 mg of sodium D,L-beta-hydroxybutyrate. After administration, subjects were tested for blood ketone levels (mmol / dL) at 30, 60, 90, 120, and 180 minutes after administration. Each subject was then studied after receiving 10 g of sodium R-beta-hydroxybutyrate and 5 g of sodium R-beta-hydroxybutyrate. As shown in Figure 1, on average, administration of 5 mg of sodium R-beta-hydroxybutyrate produced similar blood ketone levels in subjects as administration of 10 g of D,L-beta-hydroxybutyrate at 30, 60, 90, 120, and 180 minutes after administration.

[0059]

[0081] Example 2

[0082] Three subjects were given 10 grams of medium-chain triglycerides and 10 grams of beta-hydroxybutyrate. Subjects were administered 8 grams of short-chain triglycerides and 8 grams of beta-hydroxybutyrate and blood beta-hydroxybutyrate concentrations were monitored over time. The same subjects were then administered 10 grams of short-chain triglycerides and 8 grams of beta-hydroxybutyrate and blood beta-hydroxybutyrate concentrations were monitored. Figure 2 shows the subjects' mean blood ketone concentrations (mmol / L) at 30, 60, 90, 120, and 180 minutes after administration. As shown in Figure 2, administration of a short-chain compound such as short-chain triglycerides (represented by the red bars or the second bar in each set) with beta-hydroxybutyrate resulted in a greater increase in blood ketone levels than administration of a similar amount of a medium-chain compound (represented by the blue bars or the first bar in each set), at least at 30, 60, 90, and 180 minutes after administration. Thus, administration of short chain compounds (e.g., fatty acids and / or triglycerides) may unexpectedly result in the same results (e.g., blood ketone levels, weight loss, weight control) in a smaller amount than a medium chain compound administered to achieve the same result, and / or may result in greater results (e.g., when compared to a similar amount of a medium chain compound).

[0060]

[0083] Example 3

[0084] Sixteen Fischer 344 rats were used for the study. The effect of R-beta-hydroxybutyrate on lifespan was studied. A first group of eight rats was fed a diet equivalent to a low-fat standard American diet, and a second group of eight rats was fed a diet equivalent to a low-fat standard American diet and supplemented with R-beta-hydroxybutyrate (e.g., sodium R-beta-hydroxybutyrate). The second group of rats was supplemented with R-beta-hydroxybutyrate in middle age. Figure 3 shows the average lifespan of the rat groups. As shown in the figure, at 20 months, about half of the rats in the first group fed the standard diet had died, while only 12.5% ​​of the rats in the second group had died at 20 months. Thus, supplementing the rat diet with R-beta-hydroxybutyrate extended the lifespan of the rats by at least about 38.5%. Since the rat study was conducted as an analogy for the effects on humans, adding R-beta-hydroxybutyrate to a standard American low-fat diet may extend lifespan.

[0061]

[0085] Example 4

[0086] Approximately 10 grams of R-beta-hydroxybutyrate was administered to individuals with Parkinson's disease. Motor function was tested with and without administration of . The tests included a right eye visual and motor performance device to track motor function through eye movements.

[0062]

[0087] FIG. 4 shows an example of the administration of R-beta-hydroxybutyrate in an exercise performance test. 4 shows the results of a similar study of a non-Parkinson's disease population, the average results of patients before and after administration of R-beta-hydroxybutyrate. As shown in the figure, administration of R-beta-hydroxybutyrate improved motor function (e.g., about 30 minutes after administration of R-beta-hydroxybutyrate).

[0063]

[0088] Example 5

[0089] Individuals were administered 5 g of R-beta-hydroxybutyrate twice daily for three months. X-ray absorptiometry was performed to determine the effect of R-beta-hydroxybutyrate administration on fat weight loss. FIG. 5A is a graph showing the results after three months of administration. As shown, the individuals experienced greater than about a 10% reduction in fat mass. FIG. 5B shows that fat weight loss was sustained while lean mass was maintained. Thus, R-beta-hydroxybutyrate may cause weight loss through fat loss rather than lean mass (e.g., muscle mass).

[0064]

[0090] Example 6

[0091] The first group of 10 rats (labeled SC) was fed a standard diet, and the second group A group of 10 rats (labeled KD) was fed a ketogenic diet, a third group of 10 rats (labeled SC+MS) was fed a standard diet except that they were given a first dose (e.g., equivalent to 5 g) of R-beta-hydroxybutyrate, and a fourth group was fed a standard diet except that they were given a second dose (e.g., equivalent to 10 g) of R-beta-hydroxybutyrate. Figure 6 shows the average lipoprotein lipase (LPL) of the rats. Since LPL is necessary for transporting fat to adipose tissue, lowering LPL levels inhibits fat storage and promotes the use of fat stores. As shown in the figure, supplementing the standard diet with an additional low dose of R-beta-hydroxybutyrate reduces LPL levels and therefore inhibits fat storage.

[0065]

[0092] Example 7

[0093] R-beta-hydroxybutyrate was administered to individuals with elevated C-reactive protein, which is associated with inflammation. Titreate was administered. After administration, C-reactive protein levels were significantly reduced (e.g., from 62.5 to 4.4). In addition, fasting glucose was also reduced (e.g., from 104 to 95).

[0066]

[0094] Example 8

[0095] Five healthy individuals were randomly assigned to receive either a placebo, 10 g of R-beta-hydroxybutyrate, or and 30 minutes after administration of 10 g of R-beta-hydroxybutyrate, a 2 km time test (e.g., 4 cycles of low to very high intensity exercise on a Wingate cycle ergometer) was performed. Figure 7 shows the average blood ketone levels, and Figure 8 shows the percent improvement relative to placebo administration. As shown in the figures, blood ketone levels unexpectedly increased more than two-fold during administration of R-beta-hydroxybutyrate when compared to administration of D,L-beta-hydroxybutyrate. Furthermore, performance (e.g., time improvement) improved more than two-fold during administration of R-beta-hydroxybutyrate when compared to D,L-beta-hydroxybutyrate. Figure 9 shows the perceived exertion experienced by the individuals. As shown in the figures, the individuals did not experience an impact on perceived exertion after administration of D,L-beta-hydroxybutyrate compared to the improvement in perceived exertion experienced after administration of R-beta-hydroxybutyrate. Thus, R-beta-hydroxybutyrate has an unexpected impact on ketone levels and performance.

[0067]

[0096] Example 9

[0097] The individuals were fed either a standard diet or a ketogenic diet. Some individuals were R-beta-hydroxybutyrate (e.g., 10 g) was administered. R-beta-hydroxybutyrate can numerically increase superoxide dismutase 2 (SOD) levels in the brain, indicating greater antioxidant capacity in the brain.

[0068]

[0098] Example 10

[0099] Individuals were administered 5g or 10mg of R-beta-hydroxybutyrate, L-beta In the study, subjects were administered D,L-beta-hydroxybutyrate or D,L-beta-hydroxybutyrate, and blood ketone levels were measured. Figures 10 and 11 show the measured blood ketone levels. As shown in the figures, administration of R-beta-hydroxybutyrate can reduce ketone levels (see, for example, Figures 11A and 11B). The reduction in ketone levels occurs even when R-beta-hydroxybutyrate is administered in a dose of less than 10 g (e.g., about 5 g). Furthermore, unexpectedly (e.g., because both the D and L forms of R-beta-hydroxybutyrate were expected to behave similarly), administration of L-beta-hydroxybutyrate does not reduce blood ketones. Even more unexpectedly, D,L-beta-hydroxybutyrate does not reduce blood ketone levels to the same extent as R-beta-hydroxybutyrate. This indicates that L-beta-hydroxybutyrate may inhibit some of the effects of R-beta-hydroxybutyrate, which is unexpected.

[0069]

[0100] Example 11

[0101] Ten subjects were administered approximately 5 g or 10 g of D,L-beta-hydroxybutyrate or R-beta-hydroxybutyrate and the respiratory exchange ratio (RER, carbon dioxide / oxygen ratio) was examined. In general, a ratio of 1.0 indicates that 100% of carbohydrates are used as fuel, and 0.7 indicates that 100% of fats are used as fuel. As shown in FIG. 12A, at 10 g, administration of R-beta-hydroxybutyrate reduces the RER by approximately 3 times more than D,L-beta-hydroxybutyrate. As shown in FIG. 12B, 5 g of R-beta-hydroxybutyrate can achieve results that cannot be achieved with even more D,L-beta-hydroxybutyrate (e.g., D,L-beta-hydroxybutyrate does not reduce the RER, but rather increases it by 17%).

[0070]

[0102] Example 12

[0103] Individuals were administered 5 g to 10 g of D,L-beta-hydroxybutyrate or R-beta-hydroxybutyrate and tested for perceived hunger, satiety, and perceived energy. Figures 13A-13C show the results of the study. Figure 13A shows perceived hunger, Figure 13B shows perceived satiety, and Figure 13C shows perceived energy. As shown in Figure 13B, at 30 minutes after ingestion, R-beta-hydroxybutyrate improved satiety levels 2.3 times more than DL-beta-hydroxybutyrate compared to baseline levels. As shown in Figure 13C, R-beta-hydroxybutyrate improved perceived energy 2 times more than D,L-beta-hydroxybutyrate between 0 and 30 minutes after ingestion. R-beta-hydroxybutyrate, in contrast to D,L-beta-hydroxybutyrate, continued to increase perceived energy levels at 0 minutes, 60, 90, and 120 minutes after ingestion. As shown in the figure, R-beta-hydroxybutyrate was able to increase perceived energy by 18%, which was sustained for 2 hours after ingestion (i.e., more than twice the peak increase seen with DL-beta-hydroxybutyrate).

[0071]

[0104] Example 13

[0105] Five resistance-trained young men (in their 20s) lifting 50% of their 1-RM on the bench press were tested before and after administration of 5 g of R-beta-hydroxybutyrate or D,L-beta-hydroxybutyrate. Figures 14A-B show the results of the study. As shown in the figures, administration of R-beta-hydroxybutyrate resulted in an 11% increase in An increase in β-hydroxybutyrate was seen in the 14.1% group, whereas administration of DL-beta-hydroxybutyrate only resulted in a 2% decrease. Thus, R-beta-hydroxybutyrate experienced a greater than expected effect when compared to D,L-beta-hydroxybutyrate.

[0072]

[0106] Individuals were also tested for force. Figure 14C shows the results of the testing (e.g., average force measurements). As can be seen, administration of R-beta-hydroxybutyrate increased minimum force by 26%, while administration of DL-beta-hydroxybutyrate increased force by 2%.

[0073]

[0107] Example 14

[0108] Individuals were tested for mental acuity before and after administration of 5–10 g of R-beta-hydroxybutyrate or D,L-beta-hydroxybutyrate. A circular pursuit test (e.g., assessment of an individual's cognitive function) was performed, and administration of R-beta-hydroxybutyrate (e.g., 10 g) improved tracking accuracy by approximately 3%, whereas administration of DL-beta-hydroxybutyrate (e.g., 10 g) did not improve performance. A vertical pursuit test (e.g., assessment of an individual's cognitive function) was performed, and administration of D,L-beta-hydroxybutyrate (e.g., 10 g) improved performance by 4.6%, whereas administration of R-beta-hydroxybutyrate (e.g., 10 g) improved performance by 13.8%, approximately three times larger. A horizontal saccade test was performed (e.g., a saccade is a one-eye movement that is known to slow significantly when cognitive function declines and to improve when cognitive function improves). In horizontal saccade tests, the performance improvement when R-beta-hydroxybutyrate (e.g., 5 g) was administered was four times larger than when D,L-beta-hydroxybutyrate was administered (e.g., 13.8% vs. 3.2%). A processing speed test was performed (e.g., processing speed is considered to be a true measure of cognitive performance). R-beta-hydroxybutyrate (e.g., 5 g) administration improved processing speed by 27.7%, whereas DL-beta-hydroxybutyrate (e.g., 5 g) administration improved processing speed by only about 18%. Response accuracy was also tested. R-beta-hydroxybutyrate (e.g., 5 g) administration improved accuracy by 37 percentage points, compared to 12.7% accuracy when DL-beta-hydroxybutyrate was administered.

[0074]

[0109] Thus, administration of R-beta-hydroxybutyrate increased mental acuity more than a similar amount of D,L-beta-hydroxybutyrate. In fact, as studies have shown, administration of R-beta-hydroxybutyrate often increased mental acuity by more than two-fold compared to a similar amount of D,L-beta-hydroxybutyrate.

[0075]

[0110] Example 15

[0111] Compounds for administration were prepared to contain R-beta-hydroxybutyrate amino acid complexes. R-beta-hydroxybutyrate agmatine complexes were prepared, and R-beta-hydroxybutyrate arginine complexes were prepared. Figure 15 shows the average blood ketone levels achieved with R-beta-hydroxybutyrate amino acid complexes (e.g., average of both complexes) compared to D,L-beta-hydroxybutyrate. As shown in the figure, blood ketone levels are more than double the blood ketone levels achieved with the same amount of D,L-beta-hydroxybutyrate as R-beta-hydroxybutyrate amino acid complexes (e.g., 10 g), as well as exceeding the results of the addition of similar amounts of R-beta-hydroxybutyrate and amino acids.

[0076]

[0112] The use of R-beta-hydroxybutyrate amino acid complexes may reduce the amount of cations delivered (e.g., because the complexes may deliver R-beta-hydroxybutyrate rather than R-beta-hydroxybutyrate). This may result in fewer side effects (e.g., increased sodium, potassium, and / or magnesium intake), improved user satisfaction, and / or a larger population of individuals who can tolerate R-beta-hydroxybutyrate administration (e.g., because some individuals may not be able to increase their loading of these cations due to underlying disease and / or disorder). The use of R-beta-hydroxybutyrate amino acid complexes also allows for the administration of a higher yield of R-beta-hydroxybutyrate (90.8% R-beta-hydroxybutyrate, 5% amino acids) when compared to a similar weight of R-beta-hydroxybutyrate (e.g., average yield of 83% for sodium BHB).

[0077]

[0113] Example 16

[0114] The composition for administration may include amino acids such as R-beta-hydroxybutyrate and leucine. R-beta-hydroxybutyrate and leucine may be complexed and / or mixed for administration. R-beta-hydroxybutyrate and leucine may be administered separately but at about the same time. FIG. 16 shows blood ketone levels after administration of R-beta-hydroxybutyrate (5 g) and leucine (2 g). As shown in the figure, administration of R-beta-hydroxybutyrate and leucine causes a greater rise in blood ketone levels than administration of R-beta-hydroxybutyrate (5 g). Administration of R-beta-hydroxybutyrate and leucine causes a greater rise in blood ketone levels than the mere additive effect of similar amounts of R-beta-hydroxybutyrate and leucine administered separately.

[0078]

[0115] End of Example

[0116] In some embodiments, one or more additives may be included in the composition, such as flavors (e.g., natural and / or artificial), vitamins, minerals, binders, and / or other suitable additives. The additives may alter flavor, color, and / or texture. The additives may enhance palatability and / or facilitate inclusion in a delivery vehicle (e.g., tablets, foods, beverage products such as drink mixes, etc.). The additives may be any suitable solid and / or liquid to which the compound is added. For example, the additives may include a liquid carrier, such as water, milk, and / or any other suitable drinkable liquid. In some embodiments, the composition may include a pharma- ceutically inert liquid carrier, such as water (e.g., tap water, filtered water, distilled water, etc.). The liquid carrier may include other drinkable liquids, such as coconut water, watermelon water, electrolyte water, and / or combinations thereof. The liquid carrier may include milk, such as dairy milk, non-dairy milk, coconut milk, other milk, and / or combinations thereof. In some embodiments, the liquid carrier may include an electrolyte solution.

[0079]

[0117] The described compositions may be administered by any suitable method of administration. For example, the described compositions may be administered enterally and / or parenterally. In some embodiments, the described compositions may be administered by tablets and / or capsules. The described compositions may be provided in the form of a powder, which allows the described compositions to be sprinkled on food, mixed with liquids to provide beverages, and / or administered directly. The described compositions may be provided in the form of a gel. The compounds in the composition may be mixed, combined with each other, and / or provided separately. For example, the composition may include beta-hydroxybutyrate combined with another compound (e.g., beta-hydroxybutyrate esters and / or amino acids). In some embodiments, beta-hydroxybutyrate and one or more other compounds may be provided separately (e.g., in a pill). An individual may be administered beta-hydroxybutyrate and other compounds sequentially and / or simultaneously (e.g., swallowing a pill).

[0080]

[0118] The described compositions, in some embodiments, cause weight loss, and and / or can be administered according to a dosing protocol for maintaining an individual's weight, increasing and / or maintaining blood ketone levels, increasing and / or maintaining ketosis, and / or improving glucose tolerance (e.g., can reduce fasting glucose levels and / or can improve glucose metabolism). For example, the described compositions may be administered once a day via extended release formulations and / or multiple times a day (e.g., 1-5 times a day, 2-5 times a day, 3-5 times a day, etc.). The described compositions may be substituted for other pharmaceuticals or dietary supplements taken to promote weight loss, maintain weight, promote ketosis, and increase blood ketone levels, and / or may be utilized in combination with one or more other pharmaceuticals or dietary supplements, as appropriate. The described compositions may be substituted for other pharmaceuticals or dietary supplements taken to improve glucose tolerance, such as metaformin, and / or may be utilized in combination with one or more other pharmaceuticals or dietary supplements, as appropriate, in some embodiments.

[0081]

[0119] In various embodiments, the described compositions (e.g., butyrate, beta-hydroxybutyrate, R-beta-hydroxybutyrate, related compounds, and / or one or more other compounds) may include one or more of the described components, equivalents of the described components, derivatives of the described components, complexes of the described components, salts of the described components, and / or combinations thereof.

[0082]

[0120] In various embodiments, one or more of the described compositions can be administered in a pharmacologic effective amount, which can induce and / or maintain ketosis, maintain and / or promote weight loss, improve mental processes (e.g., cognitive function, mood, energy, attention, concentration, performance, acuity, including the effects of aging, etc.), improve and / or maintain body composition, act as a therapeutic agent for one or more of the described conditions or disorders (e.g., treat neurological disorders), and / or combinations thereof.

[0083]

[0121] Although various types of mental acuity enhancement have been described, other aspects of mental acuity, such as memory, concentration, attention span, and / or comprehension (e.g., processing speed, processing accuracy), may also be enhanced by administration of an effective amount of a composition comprising R-beta-hydroxybutyrate.

[0084]

[0122] Although the subjects and / or individuals are described as humans, the subjects and / or individuals may be a person or a group of people. Although the various systems and processes described are described as being administered to humans, the systems and processes described may also be administered to other mammals, such as rats, dogs, etc.

[0085]

[0123] In various embodiments, beta-hydroxybutyrate may be administered simultaneously and / or sequentially with one or more other compounds (e.g., short-, medium-, and / or long-chain fatty acids). For example, beta-hydroxybutyrate and / or one or more other compounds may be mixed and delivered in a powder, liquid, gel, and / or other suitable form. In some embodiments, beta-hydroxybutyrate and / or one or more other compounds may be administered by pill, tablet, capsule, other oral dosage form, intravenously, nasal spray, sublingual tab / strip, or topical delivery, rectally, other suitable dosage form, and / or combinations thereof.

[0086]

[0124] The term beta-hydroxybutyrate is the term used in the described embodiments, however, beta-hydroxybutyrate can also be used for beta-hydroxybutyrate, (R)-3-hydroxybutyric acid, (R)-3-hydroxybutanoic acid, (3R)-3-hydroxybutanoic acid, (4R)-3-hydroxybutanoic acid, (5R)-3-hydroxybutanoic acid, (6R)-3-hydroxybutanoic acid, (7R)-3-hydroxybutanoic acid, (8R)-3-hydroxybutanoic acid, (9R)-3-hydroxybutanoic acid, (10R)-3-hydroxybutanoic acid, (11R)-3-hydroxybutanoic acid, (12R)-3-hydroxybutanoic acid, (13R)-3-hydroxybutanoic acid, (14R)-3-hydroxybutanoic acid, (15R)-3-hydroxybutanoic acid, (16R)-3-hydroxybutanoic acid, (1 xybutanoic acid, (R)-3-hydroxybutanoate, (R)-(-)-3-hydroxybutyric acid, (R)-(-)-beta-hydroxybutyric acid, 3-D-hydroxybutyrate, BHIB, BHB, 3-delta-hydroxybutyrate, delta-3-hydroxybutyrate, 3-D-hydroxybutyric acid, D-3-hydroxybutyric acid, 3R-hydroxy-butanoic acid, delta-beta-hydroxybutyrate, D-3-hydroxybutyrate, D-(-)-3-hydroxybutyrate, delta-3-hydroxybutyric acid, (-)-3-hydroxybutyric acid, D-beta-hydroxybutyrate, (R)-(-)-b-hydroxybutyrate, It may also be referred to as (R)-beta-hydroxybutyric acid, delta-(-)-3-hydroxybutyrate, (R)-3-hydroxybutyrate, (R)-beta-hydroxybutanoic acid, (R)-(-)-beta-hydroxybutyrate, (-)-3-hydroxy-n-butyric acid, (R)-(-)-b-hydroxybutyric acid, butanoic acid, 3-hydroxy-, (R)-butyric acid, 3-hydroxy-, D-(-)-(R)-3-82578-46-9, beta-D-hydroxybutyric acid, D-beta-hydroxybutyric acid, (3R)-3-delta-hydroxybutyric acid, 3-(R)-hydroxybutyric acid, and / or (-)-beta-hydroxybutyrate.

[0087]

[0125] In various embodiments, beta-hydroxybutyrate is described as being in a composition, administered in a certain amount, in a certain form, and / or on a certain schedule, and / or in a particular form (e.g., complexed and / or conjugated). R-beta-hydroxybutyrate may be utilized in various embodiments of the described beta-hydroxybutyrate, optionally in the same or lesser amounts as the described beta-hydroxybutyrate.

[0088]

[0126] It should be understood that the embodiments are not limited to the particular systems and processes described, which may, of course, vary. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. As used herein, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to "a compound" includes a combination of two or more compounds, and reference to "beta-hydroxybutyrate" includes different types and / or combinations of beta-hydroxybutyrate.

[0089]

[0127] Although the present disclosure has been described in detail, it should be understood that various changes, substitutions, and modifications can be made herein without departing from the spirit and scope of the present disclosure as defined by the appended claims. Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the processes, machines, manufacture, compositions of matter, means, methods, and steps described herein. As one skilled in the art can readily appreciate from this disclosure, any currently existing or later developed process, machine, manufacture, composition of matter, means, method, or step that performs substantially the same function or achieves substantially the same result as the corresponding embodiment described herein can be utilized in accordance with the present disclosure. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps.

Claims

1. A composition for use in a method of maintaining or increasing weight loss in an individual, comprising orally administering from about 0.5 g to about 15 g of R-beta-hydroxybutyrate, wherein the oral administration induces or maintains weight loss in the individual, the composition comprises R-beta-hydroxybutyrate, and the R-beta-hydroxybutyrate comprises one or more of R-beta-hydroxybutyrates, and the composition may comprise at least one of one or more flavors, one or more vitamins, one or more minerals, one or more binders, or one or more liquid carriers.

2. The composition according to claim 1, wherein the liquid carrier comprises water.

3. The composition according to claim 1, wherein the amount of R-beta-hydroxybutyrate comprises from about 0.5 g to about 5 g of R-beta-hydroxybutyrate.

4. From about 0.5 g to about 15 g of beta-hydroxybutyrate, at least one polymer of beta-hydroxybutyrate, and at least one salt of R-beta-hydroxybutyrate The composition according to claim 1.

5. The composition according to claim 1, wherein the administration increases mental acuity.

6. The composition according to claim 1, wherein the administration increases at least one of metabolism, fat loss, fatty acidification, motor function, or muscle mass.

7. The composition according to claim 1, wherein the composition is administered up to 5 times a day.

8. The composition according to claim 1, wherein one or more of the R-beta-hydroxybutyrates comprise at least one of sodium R-beta-hydroxybutyrate, potassium R-beta-hydroxybutyrate, magnesium R-beta-hydroxybutyrate, or calcium R-beta-hydroxybutyrate salt.

9. A composition for use in a method of maintaining or inducing ketosis in an individual, the method comprising orally administering from about 0.5 g to about 15 g of R-beta-hydroxybutyrate, wherein the oral administration induces or maintains ketosis in the individual, the composition comprises R-beta-hydroxybutyrate, and the R-beta-hydroxybutyrate comprises one or more of R-beta-hydroxybutyrates, and The composition may comprise at least one of one or more fragrances, one or more vitamins, one or more minerals, one or more binders, or one or more liquid carriers, said composition.

10. The composition according to claim 9, wherein the amount of R-beta-hydroxybutyrate comprises from about 0.5 g to about 5 g of R-beta-hydroxybutyrate.

11. The composition according to claim 9, wherein one or more of the R-beta-hydroxybutyrates comprise at least one of sodium R-beta-hydroxybutyrate, potassium R-beta-hydroxybutyrate, calcium R-beta-hydroxybutyrate, or magnesium R-beta-hydroxybutyrate.

12. The composition according to claim 1 or 9, wherein the liquid carrier comprises at least one of water, milk, or coconut water.

13. The composition according to claim 9, wherein administration increases at least one of metabolism, fat loss, fatty acidification, motor function, or muscle mass.

14. The composition according to claim 9, wherein administration increases at least one of mental acuity, cognitive function, mood, energy, attention, concentration, or performance.

15. A composition for use in a method of maintaining or inducing ketosis in an individual, the method comprising orally administering from about 0.5 g to about 15 g of R-beta-hydroxybutyrate and less than about 500 mg of caffeine, the administration inducing or maintaining ketosis in the individual, the composition comprising R-beta-hydroxybutyrate and caffeine, the R-beta-hydroxybutyrate comprising one or more salts of R-beta-hydroxybutyrate, the composition may comprise at least one of one or more fragrances, one or more vitamins, one or more minerals, one or more binders, or one or more liquid carriers, said composition.

16. The composition according to claim 15, wherein the composition comprises from about 5 mg to about 50 mg of caffeine.

17. The composition according to claim 15, wherein the composition comprises from about 0.5 g to about 5 g of R-beta-hydroxybutyrate and from about 5 mg to about 50 mg of caffeine.

18. The composition according to claim 15, wherein one or more of the R-beta-hydroxybutyrate salts comprises at least one of sodium R-beta-hydroxybutyrate, potassium R-beta-hydroxybutyrate, calcium R-beta-hydroxybutyrate, or magnesium R-beta-hydroxybutyrate. **Claim 19** The composition according to claim 15, wherein administration increases at least one of weight loss, metabolism, fat loss, fat acidification, motor function, muscle mass, mental acuity, cognitive function, mood, energy, attention, concentration, or performance. **Claim 20** The composition according to claim 15, wherein the liquid carrier comprises at least one of water, milk, or coconut water.

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