Beta-hydroxybutyric acid compositions and methods for delivery of ketone bodies

Abstract

Beta-hydroxybutyric acid compositions for oral delivery are substantially free of beta-hydroxybutyrate salts and 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 excluding beta-hydroxybutyrate salts (e.g., less than 1% by weight) 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 enriched with the R- or the S-enantiomer, a racemic mixture, pure R-beta-hydroxybutyric acid, or pure S-beta-hydroxybutyric acid.

1 . A method for exogenously increasing ketone body level in a subject, comprising:
 administering to the subject an aqueous beta-hydroxybutyric acid composition comprised of:
 water; and 
 about 0.4% w/v to about 60% w/v of exogenous beta-hydroxybutyric acid at least partially dissolved in the water, 
 wherein the aqueous beta-hydroxybutyric acid composition is free or substantially free of beta-hydroxybutyrate salts so as to contain less than 1% of total beta-hydroxybutyrate salts and greater than 99% of the exogenous beta-hydroxybutyric acid by combined weight of the beta-hydroxybutyric acid and any beta-hydroxybutyrate salts, 
 wherein the aqueous beta-hydroxybutyric acid composition is optionally free of 1,3-butanediol and ketone esters, 
 wherein the aqueous beta-hydroxybutyric acid composition provides a unit dose of about 0.5 gram to about 25 grams of the exogenous beta-hydroxybutyric acid in order to exogenously increase blood ketone level in the subject. 
   
     
     
         2 . The method of  claim 1 , wherein the aqueous beta-hydroxybutyric acid composition is a dilute composition containing about 0.4% w/v to about 6% w/v of the exogenous beta-hydroxybutyric acid. 
     
     
         3 . The method of  claim 2 , wherein the method comprises:
 providing a concentrated beta-hydroxybutyric acid composition containing about 6% w/v to about 60% w/v of the exogenous beta-hydroxybutyric acid;   diluting the concentrated beta-hydroxybutyric acid composition with water, juice, drink, or other aqueous composition to form the dilute composition; and   administering to the dilute composition to the subject.   
     
     
         4 . The method of  claim 3 , wherein the concentrated beta-hydroxybutyric acid composition contains about 8% w/v to about 55% w/v, or about 10% w/v to about 50% w/v, or about 12.5% w/v to about 45% w/v, or about 15% w/v to about 40% w/v of the exogenous beta-hydroxybutyric acid. 
     
     
         5 . The method of  claim 3 , wherein the dilute composition contains about 0.6% w/v to about 5.5% w/v, or about 0.9% w/v to about 5% w/v, or about 1.2% w/v to about 4.5% w/v, or about 1.5% w/v to about 4% w/v of the exogenous beta-hydroxybutyric acid. 
     
     
         6 . The method of  claim 1 , wherein about 4 oz. (about 120 ml) to about 16 oz. (about 475 ml) of the composition provides the unit dose of about 0.5 gram to about 25 grams of the exogenous beta-hydroxybutyric acid to the subject. 
     
     
         7 . The method of  claim 7 , wherein about 4 oz. (about 120 ml) to about 16 oz. (about 475 ml) of the composition provides a unit dose of about 0.75 gram to about 20 grams, or about 1 gram to about 15 grams, or about 1.5 grams to about 12 grams, or about 2 grams to about 10 grams 0.5 gram to about 25 grams of the exogenous beta-hydroxybutyric acid to the subject. 
     
     
         8 . The method of  claim 1 , wherein the aqueous beta-hydroxybutyric acid composition contains less than about 0.9%, or less than about 0.8%, or less than about 0.7%, or less than about 0.6%, or less than about 0.5%, or less than about 0.4%, or less than about 0.3%, or less than about 0.2%, or less than about 0.1% of total beta-hydroxybutyrate salts by combined weight of the exogenous beta-hydroxybutyric acid and any beta-hydroxybutyrate salts. 
     
     
         9 . The method of  claim 1 , wherein the exogenous beta-hydroxybutyric acid is enantiomerically pure R-beta-hydroxybutyric acid or a non-racemic mixture enriched with R-beta-hydroxybutyric acid that contains greater than 50% and less than 100% by enantiomeric equivalents of R-beta-hydroxybutyric acid and less than 50% and greater than 0% by enantiomeric equivalents of S-beta-hydroxybutyric acid. 
     
     
         10 . The method of  claim 1 , wherein the exogenous beta-hydroxybutyric acid is enantiomerically pure S-beta-hydroxybutyric acid or a non-racemic mixture enriched with S-beta-hydroxybutyric acid that contains greater than 50% and less than 100% by enantiomeric equivalents of S-beta-hydroxybutyric acid and less than 50% and greater than 0% by enantiomeric equivalents of R-beta-hydroxybutyric acid. 
     
     
         11 . The method of  claim 1 , wherein the exogenous beta-hydroxybutyric acid is a racemic mixture of R-beta-hydroxybutyric acid and S-beta-hydroxybutyric acid. 
     
     
         12 . The method of  claim 1 , wherein the method comprises:
 providing exogenous beta-hydroxybutyric acid in solid or powder form;   adding the exogenous beta-hydroxybutyric acid in solid or powder to water, juice, drink, or other aqueous composition to form the aqueous beta-hydroxybutyric acid composition.   
     
     
         13 . The method of  claim 1 , further comprising at least one additive selected from the group consisting of gelling agents, flavoring agents, vitamins, minerals, central nervous system stimulants, edible acids, amino acids, muscle-promoting compounds, and cannabinoids. 
     
     
         14 . The method of  claim 13 , wherein the composition is a gel and comprises at least one gelling agent selected from the group consisting of gellan gum, pectin, agar, carrageenan, xanthan gum, alginate, starch, modified starch, gum Arabic, guar gum, locust bean gum, konjac, gum tragacanth, acacia gum, gum karaya, methyl cellulose, agar, pullulan, konjac, hydroxypropylmethyl cellulose, other cellulosic compounds, other polysaccharide gums, gelatin, collagen, casein, other proteins, silica fume, and milled chia seeds. 
     
     
         15 . The method of  claim 1 , wherein the aqueous beta-hydroxybutyric acid composition contains greater than 99% by weight of the exogenous beta-hydroxybutyric acid and less than 1% by combined weight of beta-hydroxybutyrate salts, 1,3-butanediol, and ketone esters by total combined weight of the exogenous beta-hydroxybutyric acid and any beta-hydroxybutyrate salts, 1,3-butanediol, or ketone ester that may be present. 
     
     
         16 . The method of  claim 1 , wherein exogenously increasing ketone body level in the subject results in one or more of appetite suppression, weight loss, fat loss, reduced blood glucose level, improved mental alertness, increased physical energy, improved cognitive function, reduction in traumatic brain injury, reduction in effect of diabetes, improvement of neurological disorder, reduction of cancer, reduction of inflammation, anti-aging, antiglycation, reduction in epileptic seizer, improved mood, increased strength, increased muscle mass, or improved body composition. 
     
     
         17 . A method for exogenously increasing ketone body level in a subject, comprising:
 providing a concentrated beta-hydroxybutyric acid composition containing about 6% w/v to about 60% w/v of beta-hydroxybutyric acid;   diluting the concentrated beta-hydroxybutyric acid composition with water, juice, drink, or other aqueous composition to form a dilute beta-hydroxybutyric acid composition containing about 0.4% w/v to about 6% w/v of the exogenous beta-hydroxybutyric acid; and   administering to the dilute beta-hydroxybutyric acid composition to the subject,   wherein the dilute beta-hydroxybutyric acid composition is free or substantially free of beta-hydroxybutyrate salts so as to contain less than 1% of total beta-hydroxybutyrate salts and greater than 99% of the exogenous beta-hydroxybutyric acid by combined weight of the beta-hydroxybutyric acid and any beta-hydroxybutyrate salts,   wherein the dilute beta-hydroxybutyric acid composition is optionally free of 1,3-butanediol and ketone esters,   wherein the dilute beta-hydroxybutyric acid composition provides a unit dose of about 0.5 gram to about 25 grams of the exogenous beta-hydroxybutyric acid in order to exogenously increase blood ketone level in the subject.   
     
     
         18 . The method of  claim 17 , wherein the dilute beta-hydroxybutyric acid composition contains greater than 99% by weight of beta-hydroxybutyric acid and less than 1% by combined weight of beta-hydroxybutyrate salts, 1,3-butanediol, and ketone esters by total combined weight of the beta-hydroxybutyric acid and any beta-hydroxybutyrate salts, 1,3-butanediol, or ketone ester that may be present. 
     
     
         19 . The method of  claim 16 , the dilute beta-hydroxybutyric acid composition further comprising at least one additive selected from the group consisting of gelling agents, flavoring agents, vitamins, minerals, central nervous system stimulants, edible acids, amino acids, muscle-promoting compounds, cannabinoids, acetoacetic acid, acetoacetate, 1,3-butanediol, and beta-hydroxybutyrate esters. 
     
     
         20 . A method for exogenously increasing ketone body level in a subject, comprising:
 providing exogenous beta-hydroxybutyric acid in solid or powder form;   adding the exogenous beta-hydroxybutyric acid in solid or powder to water, juice, drink, or other aqueous composition to form an aqueous beta-hydroxybutyric acid composition containing about 0.4% w/v to about 60% w/v of the exogenous beta-hydroxybutyric acid; and   administering to the beta-hydroxybutyric acid composition to the subject,   wherein the beta-hydroxybutyric acid composition is free or substantially free of beta-hydroxybutyrate salts so as to contain less than 1% of total beta-hydroxybutyrate salts and greater than 99% of the exogenous beta-hydroxybutyric acid by combined weight of the beta-hydroxybutyric acid and any beta-hydroxybutyrate salts,   wherein the beta-hydroxybutyric acid composition is optionally free of 1,3-butanediol and ketone esters,   wherein the beta-hydroxybutyric acid composition provides a unit dose of about 0.5 gram to about 25 grams of the exogenous beta-hydroxybutyric acid in order to exogenously increase blood ketone level in the subject.