AXCESS GLOBAL SCIENCES, LLC

A method of managing glucose tolerance in an individual includes orally administering to the individual a pharmaceutically effective amount of beta-hydroxybutyrate. The pharmaceutically effective amount of beta-hydroxybutyrate includes: (a) approximately 0.5 g to approximately 15 g of R-beta-hydroxybutyrate; and (b) less than approximately 10% of L-beta-hydroxybutyrate relative to the amount of total beta-hydroxy-butyrate in the composition. Managing glucose tolerance can treats diabetes, modulate circulating insulin levels, reduce insulin excursion following nutrient intake, reduce insulin demand required to maintain normoglycemia. Managing glucose tolerance can be achieved without stimulation of pancreatic insulin secretion. Managing glucose tolerance can improve glucose regulation with reduced insulin exposure relative to baseline.

Beta-hydroxybutyrate compositions formulated for ingestion by oral delivery as a beverage, or as a dietary supplement for addition to water or beverage, include a liquid carrier, such as water, milk, drinkable liquid, coconut water, watermelon water, or electrolyte water, and beta-hydroxybutyrate. The beta-hydroxybutyrate composition can include enantiomerically pure R-beta-hydroxybutyrate or a non-racemic mixture enriched in R-beta-hydroxybutyrate relative to S-beta-hydroxybutyrate. Alternatively, the beta-hydroxybutyrate composition can include enantiomerically pure S-beta-hydroxybutyrate or a non-racemic mixture enriched in S-beta-hydroxybutyrate relative to R-beta-hydroxybutyrate. Alternatively, the beta-hydroxybutyrate composition can include a racemic mixture of R-beta-hydroxybutyrate and R-beta-hydroxybutyrate. The beta-hydroxybutyrate compositions comprise beta-hydroxybutyric acid and optionally one or more beta-hydroxybutyrate salts or esters.

S-Beta-hydroxybutyric acid compositions for oral delivery are effective in rapidly raising blood ketone levels without causing acute acidosis or gastrointestinal (GI) distress when consumed in sufficiently dilute form and/or as a gel or suspension. By limiting added beta-hydroxybutyrate salts containing alkali or alkaline earth metal ions, beta-hydroxybutyric acid solutions, gels, or suspensions can deliver exogenous ketone bodies without significantly altering electrolyte balance. Although aqueous beta-hydroxybutyric acid solutions are moderately acidic with a pH of about 3.5 to 4, when diluted with sufficient water, the water acts as a pseudo buffering agent that offsets otherwise harsh acidic effects when consumed orally. Gels and suspensions can also ameliorate acidic effects by partially encapsulating the beta-hydroxybutyric acid. Beta-hydroxybutyric acid can be pure S-beta-hydroxybutyric acid or a non-racemic mixture enriched with S-beta-hydroxybutyric acid relative to R-beta-hydroxybutyric acid.

Compositions for improving metabolic function in a subject include optically pure S-beta-hydroxybutyrate or non-racemic mixtures enriched with the S-enantiomer. S-beta-hydroxybutyrate in pure or enriched form provides energy to the heart, dilates the arteries, decreases blood pressure and systemic vascular resistance, and increases cardiac output. S-Beta-hydroxybutyric acid is more rapidly absorbed and utilized by the body than salts or esters, enhances taste, and reduces the need to include citric acid or other edible acids. S-Beta-hydroxybutyrate salts are more slowly absorbed and utilized by the body and provide one or more electrolytes. S-Beta-hydroxybutyrate esters provide more controlled release without adding electrolytes. Compositions for improving heart function in a subject may contain a dietetically or pharmaceutically acceptable carrier and optically pure S-beta-hydroxybutyrate or non-racemic mixture enriched with S-beta-hydroxybutyrate, wherein the compositions contain from about 50.5% to 100% by enantiomeric equivalents of S-beta-hydroxybutyrate and from about 49.5% to 0% by enantiomeric equivalents of R-beta-hydroxybutyrate.

Compositions and methods for administering ketone bodies to a subject include a ketone body or ketone body precursor complexed with or coupled to at least one amino acid. The compositions and methods cause one or more of: weight loss, weight maintenance, reduced blood glucose level, maintenance of blood glucose level, increased muscle and physical performance, enhanced metabolic and cellular repair, improved detoxification and gut health, targeted bioavailability, sustained release and controlled absorption, increased metabolic efficiency, enhanced cellular uptake, minimized side effects, multifunctional therapeutics, improved focus, improved energy, improved cognitive function, improved mental acuity, treatment of traumatic brain injury, treatment of diabetes, treatment of neurological disorder, treatment of cancer, treatment of inflammatory condition, appetite suppression, anti-aging effects, anti-glycation effects, treatment of epilepsy, treatment of depression, improved performance, improved muscle mass, improved motor function, increased strength, increased metabolism, increased fat loss, increased fat oxidation, improved body composition, and improved mood.

Compositions for delivering ketone bodies to a subject include one or more beta-hydroxybutyrate salts, one or more acetoacetate salts, beta-hydroxybutyric acid, and optionally acetoacetic acid. The compositions may optionally include one or more ketone body esters, such as one or more beta-hydroxybutyrate esters and/or one or more acetoacetate esters. An example composition contains about 2% to about 98% on a molar basis of the one or more beta-hydroxybutyrate salts and the one or more acetoacetate salts, about 2% to about 98% on a molar basis of the beta-hydroxybutyrate free acid and optionally the acetoacetate free acid, and optionally about 2% to about 98% on a molar basis of one or more ketone body esters.

In various implementations, berberine metabolites, such as dihydroberberine and/or tetrahydroberberine, may be administered to manage blood glucose levels, increase ketone levels (e.g., blood concentration of ketones), and/or for therapeutic purposes in humans. The administration of a pharmaceutically effective amount of berberine metabolites, such as dihydroberberine, may reduce fasting blood glucose levels, improve glucose tolerance, and/or improve blood ketone response. In some implementations, berberine metabolites may be administered with one or more other compounds.

S-Beta-hydroxybutyric acid compositions for oral delivery are effective in rapidly raising blood ketone levels without causing acute acidosis or gastrointestinal (GI) distress when consumed in sufficiently dilute form and/or as a gel or suspension. By limiting added beta-hydroxybutyrate salts containing alkali or alkaline earth metal ions, beta-hydroxybutyric acid solutions, gels, or suspensions can deliver exogenous ketone bodies without significantly altering electrolyte balance. Although aqueous beta-hydroxybutyric acid solutions are moderately acidic with a pH of about 3.5 to 4, when diluted with sufficient water, the water acts as a pseudo buffering agent that offsets otherwise harsh acidic effects when consumed orally. Gels and suspensions can also ameliorate acidic effects by partially encapsulating the beta-hydroxybutyric acid. Beta-hydroxybutyric acid can be pure S-beta-hydroxybutyric acid or a non-racemic mixture enriched with S-beta-hydroxybutyric acid relative to R-beta-hydroxybutyric acid.

In various implementations, a composition comprising R-beta-hydroxybutyrate, related compounds, and/or one or more other compounds may be administered to an individual to cause weight loss, weight maintenance, elevate blood ketone levels, maintain blood ketone levels, reduce blood glucose levels, maintain blood glucose levels, improve energy, focus, mood, cognitive function, or aide with neurological or inflammatory disorders and/or combinations thereof. The composition may include sodium R-beta-hydroxybutyrate salts; potassium R-beta-hydroxybutyrate; and one or more other salts of R-beta-hydroxybutyrate.

Compositions for inducing and maintaining a state of flow in a subject include optically pure S-beta-hydroxybutyrate or non-racemic mixtures enriched with the S-enantiomer. The S-beta-hydroxybutyrate enantiomer modulates the effect of ketone bodies in the subject and controls the rate at which ketosis is achieved. Beta-hydroxybutyric acid is more rapidly absorbed and utilized by the body than salts or esters, enhances taste, and reduces the need to include citric acid or other edible acids. Beta-hydroxybutyrate salts are more slowly absorbed and utilized by the body and can provide one or more electrolytes. Compositions for controlling ketone body level in a subject may contain a dietetically or pharmaceutically acceptable carrier and optically pure S-beta-hydroxybutyrate or non-racemic mixture enriched with S-beta-hydroxybutyrate, wherein the compositions contain from about 50.5% to 100% by enantiomeric equivalents of S-beta-hydroxybutyrate and from about 49.5% to 0% by enantiomeric equivalents of R-beta-hydroxybutyrate.