Abstract: Ketone supplementation, such as through use of precursors of beta-hydroxybutyrate (BHB) and acetoacetate (AcAc), increased blood levels of ketone bodies, increases blood flow and wound closure in ischemic young and aged fisher rats significantly earlier compared to standard diet in aged rats. In vitro experiments with ketone bodies demonstrate decreased mitochondrial and cytosolic ROS in young and aged primary human dermal fibroblasts (PHDF). Ketone bodies increased migration in young and aged PHDFs.

Abstract: Methods of treating anxiety disorders or reducing anxiety-related behaviors. The methods include administering a therapeutically effective amount of ketone supplementation, such as butanediol, ketone esters (e.g., 1,3-butanediol-acetoacetate diester) and/or ketone salts (e.g., beta-hydroxybutyrate-mineral salt), chronically, sub-chronically, or acutely, with or without admixture with a medium chain triglyceride or in combination. It was determined herein that ketone supplementation reduced anxiety in rats on elevated plus maze as measured by less entries to closed arms, more time spent in open arms, more distance travelled in open arms, and delayed latency to entrance to closed arms, when compared to control. Along with reducing anxiety-related behavior, the chronic, sub-chronic, and acute ketone supplements also caused significant elevation of blood ?HB levels and changed blood glucose levels.

Abstract: Compositions and methods for inducing weight loss, fat loss, maintaining weight or fat loss, suppressing appetite, reducing calorie intake, reducing weight gain, decreasing feed efficiency, increasing metabolic inefficiency, increasing energy expenditure, increasing thermogenesis and/or resetting metabolic set are disclosed. The compositions have a therapeutically effective amount of a ketogenic supplement, e.g., a ketone diesters, such as R,S 1,3-butanediol diacetoacetate. Compositions of one or more beta-hydroxy butyrate, beta-hydroxybutyrate salt, and medium chain triglycerides are also disclosed.

Abstract: Methods and compositions for preventing, reducing, delaying, or reversing effects due to aging or preventing, treating, or reducing time to recovery from a disease associated with aging, as well as anemia, hypoalbuminemia, hypoc-holesterolemia, malnutrition/anorexia/starvation, and/or splenomegaly in a subject in need thereof are disclosed. The method can include administering a therapeutically effective amount of a ketogenic supplement to the subject, wherein the subject is fed ad libitum. The ketogenic supplement can include R, S 1,3-butanediol acetoacetate diester or derivatives thereof.

Abstract: Compositions and methods for inducing weight loss, fat loss, maintaining weight or fat loss, suppressing appetite, reducing calorie intake, reducing weight gain, decreasing feed efficiency, increasing metabolic inefficiency, increasing energy expenditure, increasing thermogenesis and/or resetting metabolic set are disclosed. The compositions have a therapeutically effective amount of a ketogenic supplement, e.g., a ketone diesters, such as R,S 1,3-butanediol diacetoacetate. Compositions of one or more beta-hydroxybutyrate, beta-hydroxybutyrate salt, and medium chain triglycerides are also disclosed.

Abstract: Methods and compositions for treating or preventing muscle wasting resulting from an underlying disease or disorder, such as cancer cachexia. A therapeutically effective amount of a ketogenic supplement—such as R,S 1,3 butanediol diacetoacetate, R,S 1,3-butanediol acetoacetate diester, derivatives thereof, or combinations thereof—is administered to a patient or subject in need. The ketogenic supplement may further include a medium chain triglyceride in combination with the ketone ester.

Abstract: Disclosed herein are compositions and methods for treating nervous system injury in a subject.

Abstract: Methods of treating anxiety disorders or reducing anxiety-related behaviors. The methods include administering a therapeutically effective amount of ketone supplementation, such as butanediol, ketone esters (e.g., 1,3-butanediol-acetoacetate diester) and/or ketone salts (e.g., beta-hydroxybutyrate-mineral salt), chronically, sub-chronically, or acutely, with or without admixture with a medium chain triglyceride or in combination. It was determined herein that ketone supplementation reduced anxiety in rats on elevated plus maze as measured by less entries to closed arms, more time spent in open arms, more distance travelled in open arms, and delayed latency to entrance to closed arms, when compared to control. Along with reducing anxiety-related behavior, the chronic, sub-chronic, and acute ketone supplements also caused significant elevation of blood ?HB levels and changed blood glucose levels.

Abstract: Methods and compositions for treating or preventing muscle wasting resulting from an underlying disease or disorder, such as cancer cachexia. A therapeutically effective amount of a ketogenic supplement—such as R,S 1,3 butanediol diacetoacetate, R,S 1,3-butanediol acetoacetate diester, derivatives thereof, or combinations thereof—is administered to a patient or subject in need. The ketogenic supplement may further include a medium chain triglyceride in combination with the ketone ester.

Abstract: The present invention demonstrates the therapeutic use of ketone esters for seizure disorders, Alzheimer's disease and malignant brain cancer, which are associated with metabolic dysregulation. The administration of ketone esters resulted therapeutic ketosis and neuroprotection against seizures resulting from CNS oxygen toxicity. Supplemental ketones were also found to reduce superoxide production in cultured cortex neurons exposed to hyperbaric oxygen and A?-42, and to decrease proliferation and viability in U87 glioma cells. These observations support the therapeutic effect of ketones for seizure disorders, Alzheimer's disease and malignant brain cancer. The ketone esters may be derived from acetoacetate and can include R,S-1,3-butanediol acetoacetate monoester, R,S-1,3-butanediol acetoacetate diester, or a combination of the two.

Abstract: Methods of treating anxiety disorders or reducing anxiety-related behaviors. The methods include administering a therapeutically effective amount of ketone supplementation, such as butanediol, ketone esters (e.g., 1,3-butanediol-acetoacetate diester) and/or ketone salts (e.g., beta-hydroxybutyrate-mineral salt), chronically, sub-chronically, or acutely, with or without admixture with a medium chain triglyceride or in combination. It was determined herein that ketone supplementation reduced anxiety in rats on elevated plus maze as measured by less entries to closed arms, more time spent in open arms, more distance travelled in open arms, and delayed latency to entrance to closed arms, when compared to control. Along with reducing anxiety-related behavior, the chronic, sub-chronic, and acute ketone supplements also caused significant elevation of blood ?HB levels and changed blood glucose levels.

Abstract: The ketogenic diet (KD) has therapeutic implications in many disease states. It was hypothesized ketone precursor supplementation would elevate blood ketone levels to therapeutic ranges (2-7 mM) without need for dietary restriction. The effects of ketogenic agents were tested on blood glucose, ketones, and lipids with a 28-day dose escalation study in male Sprague-Dawley rats: R,S-1,3-Butandiol (BD), acetoacetate ketone ester (KE), and control (H2O) (n?8). Days 1-28, rats received a daily 5g/kg intragastric gavage, based on previous toxicology studies. Once weekly, whole blood samples (10 ?l) were acquired for analysis of glucose and ?HB at 0, 0.5, 1, 4, 8, and 12 hours after test substance administration, or until ?HB returned to baseline. At day 1 and 28, 10 ?L of whole blood were collected to measure triglycerides, total cholesterol, and HDL concentration. Significant elevation of blood ketone was observed with a significant inverse relationship with blood glucose for the duration of the experiment.

Abstract: Ketone supplementation, such as through use of precursors of beta-hydroxybutyrate (BHB) and acetoacetate (AcAc), increased blood levels of ketone bodies, increases blood flow and wound closure in ischemic young and aged fisher rats significantly earlier compared to standard diet in aged rats. In vitro experiments with ketone bodies demonstrate decreased mitochondrial and cytosolic ROS in young and aged primary human dermal fibroblasts (PHDF). Ketone bodies increased migration in young and aged PHDFs.

Abstract: Provided herein are compositions and methods for preventing central nervous system oxygen toxicity in a subject.

Abstract: Compositions and methods for inducing weight loss, fat loss, maintaining weight or fat loss, suppressing appetite, reducing calorie intake, reducing weight gain, decreasing feed efficiency, increasing metabolic inefficiency, increasing energy expenditure, increasing thermogenesis and/or resetting metabolic set are disclosed. The compositions have a therapeutically effective amount of a ketogenic supplement, e.g., a ketone diesters, such as R,S 1,3-butanediol diacetoacetate. Compositions of one or more beta-hydroxybutyrate, beta-hydroxybutyrate salt, and medium chain triglycerides are also disclosed.

Abstract: Ketone supplementation, such as through use of precursors of beta-hydroxybutyrate (BHB) and acetoacetate (AcAc), increased blood levels of ketone bodies, increases blood flow and wound closure in ischemic young and aged fisher rats significantly earlier compared to standard diet in aged rats. In vitro experiments with ketone bodies demonstrate decreased mitochondrial and cytosolic ROS in young and aged primary human dermal fibroblasts (PHDF). Ketone bodies increased migration in young and aged PHDFs.

Abstract: The present invention demonstrates the therapeutic use of ketone esters for seizure disorders, Alzheimer's disease and malignant brain cancer, which are associated with metabolic dysregulation. The administration of ketone esters resulted therapeutic ketosis and neuroprotection against seizures resulting from CNS oxygen toxicity. Supplemental ketones were also found to reduce superoxide production in cultured cortex neurons exposed to hyperbaric oxygen and A?-42, and to decrease proliferation and viability in U87 glioma cells. These observations support the therapeutic effect of ketones for seizure disorders, Alzheimer's disease and malignant brain cancer. The ketone esters may be derived from acetoacetate and can include R,S-1,3-butanediol acetoacetate monoester, R,S-1,3-butanediol acetoacetate diester, or a combination of the two.

Abstract: The ketogenic diet (KD) has therapeutic implications in many disease states. It was hypothesized ketone precursor supplementation would elevate blood ketone levels to therapeutic ranges (2-7 mM) without need for dietary restriction. The effects of ketogenic agents were tested on blood glucose, ketones, and lipids with a 28-day dose escalation study in male Sprague-Dawley rats: R,S-1,3-Butandiol (BD), acetoacetate ketone ester (KE), and control (H2O) (n?8). Days 1-28, rats received a daily 5 g/kg intragastric gavage, based on previous toxicology studies. Once weekly, whole blood samples (10 ?l) were acquired for analysis of glucose and ?HB at 0, 0.5, 1, 4, 8, and 12 hours after test substance administration, or until ?HB returned to baseline. At day 1 and 28, 10 ?L of whole blood were collected to measure triglycerides, total cholesterol, and HDL concentration. Significant elevation of blood ketone was observed with a significant inverse relationship with blood glucose for the duration of the experiment.

Abstract: Beta-hydroxybutyrate mineral salts in combination with medium chain fatty acids or an ester thereof such as medium chain triglycerides were used to induce ketosis, achieving blood ketone levels of (2-7 mmol/L), with or without dietary restriction. The combination results in substantial improvements in metabolic biomarkers related to insulin resistance, diabetes, weight loss, and physical performance in a short period of time. Further, use of these supplements to achieve ketosis yields a significant elevation of blood ketones and reduction of blood glucose levels. Use of these substances does not adversely affect lipid profiles. By initiating rapid ketosis and accelerating the rate of ketoadaptation, this invention is useful for the avoidance of glucose withdrawal symptoms commonly experienced by individuals initiating a ketogenic diet, and minimizes the loss of lean body mass during dietary restriction.

Abstract: Beta-hydroxybutyrate mineral salts in combination with medium chain fatty acids or an ester thereof such as medium chain triglycerides were used to induce ketosis, achieving blood ketone levels of (2-7 mmol/L), with or without dietary restriction. The combination results in substantial improvements in metabolic biomarkers related to insulin resistance, diabetes, weight loss, and physical performance in a short period of time. Further, use of these supplements to achieve ketosis yields a significant elevation of blood ketones and reduction of blood glucose levels. Use of these substances does not adversely affect lipid profiles. By initiating rapid ketosis and accelerating the rate of ketoadaptation, this invention is useful for the avoidance of glucose withdrawal symptoms commonly experienced by individuals initiating a ketogenic diet, and minimizes the loss of lean body mass during dietary restriction.