WO2025194080A1

WO2025194080A1 - Combination of β-hydroxybutyrate and allulose for weight loss and kidney disease management

Info

Publication number: WO2025194080A1
Application number: PCT/US2025/020008
Authority: WO
Inventors: Thomas Weimbs
Original assignee: Santa Barbara Nutrients Inc
Current assignee: Santa Barbara Nutrients Inc
Priority date: 2024-03-15
Filing date: 2025-03-14
Publication date: 2025-09-18
Anticipated expiration: 2026-09-15

Abstract

The present specification relates to a composition, such as, a medical food, a conventional food, a dietary supplement, or a therapeutic drug, and methods of treatment for weight loss and management of kidney disease, based on a combination of β-hydroxybutyrate and allulose that results in an unexpected improvement in weight loss outcomes. The disclosed composition is designed to induce ketosis, reduce caloric intake, and improve metabolic health, thereby facilitating weight loss, enhancing overall well-being, and supporting kidney health.

Description

COMBINATION OF BETA-HYDROXYBUTYRATE AND ALLULOSE FOR WEIGHT LOSS AND KIDNEY DISEASE MANAGEMENT

BACKGROUND

[0001] This application is an international patent application that claims the benefit of priority and is entitled to the filing date pursuant to Article 8 of the Patent Cooperation Treaty (PCT) of U.S. Provisional Patent Application 63/565,841 , filed March 15, 2024, the content of which is hereby incorporated by reference in its entirety.

[0002] The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.

[0003] The present specification relates to compositions such as medical foods, conventional foods, dietary supplements, or therapeutic drugs, and weight management, and more specifically to compositions and methods for promoting weight loss and kidney disease management and in particular management of polycystic kidney disease or PKD, through the administration of |3- hydroxybutyrate and allulose.

[0004] Obesity and being overweight, conditions associated with excessive fat deposits, result from an imbalance of energy intake (diet) and energy expenditure (physical activity). Increasing to epidemic proportions worldwide, obesity is a chronic complex disease that poses significant health risks and has become a leading cause of morbidity. A prevalent condition caused by poor metabolic health, obesity and being overweight can be considered a metabolism syndrome. For example, obesity and being overweight has been associated with other metabolic disorders such as type 2 diabetes, dyslipidemia, and cardiovascular diseases, reproductive disfunctions, cancer, and inflammation. Another common complication of poor metabolic health, and one associated with obesity and being overweight, is chronic kidney disease (CKD). Even the rate of progression of genetic forms of CKD, such as autosomal-dominant polycystic kidney disease (PKD), is associated with obesity and overweight.

[0005] Often, obesity results from inherited, physiological and environmental factors, combined with diet, physical activity and exercise choices. The obvious treatment of obesity and being overweight is to lose weight. While a straight-forward solution, there are many reasons why some people have trouble losing weight. Various interventions, including education on healthy lifestyle choices and dietary supplements, have been explored to facilitate weight loss and improve metabolic health. Although attaining success to various degrees, there is still an urgent need to develop compositions and methods to treat obesity and being overweight and achieving meaningful and sustainable weight loss.

[0006] The present specification provides a composition such as a medical food, a conventional food, a dietary supplement, or a therapeutic drug containing p-hydroxybutyrate, or salt or ester thereof, and allulose, a combination that surprisingly enhances weight loss and improves metabolic health. The present specification also encompasses an improved method for weight loss in an individual by administering an effective amount of the composition. The BHB, or salt or ester thereof, and allulose combination offers a novel approach to weight management that is both effective and safe for long-term use. These and other advantages will be discussed in the present specification.

SUMMARY

[0007] Aspects of the present specification disclose a composition comprising an effective amount of p-hydroxybutyric acid, one or more p-hydroxybutyrate salts or esters, and/or one or more p-hydroxybutyrate precursors, and an effective amount of an allulose. A disclosed composition can be a medical food, a conventional food, a dietary supplement, or a therapeutic drug. A disclosed p-hydroxybutyrate can be a D-p-hydroxybutyrate, a L-p-hydroxybutyrate, or both. A disclosed p-hydroxybutyrate salt can include a calcium p-hydroxybutyrate salt, a magnesium p-hydroxybutyrate salt, a potassium p-hydroxybutyrate salt, a sodium p- hydroxybutyrate salt, or any combination thereof. A disclosed composition can further comprise citric acid or a citrate, one or more electrolytes, a dietary fiber, one or more flavorings, or any combination thereof.

[0008] Aspects of the present specification disclose a method of promoting or enhancing weight loss in an individual. A method disclosed herein comprises administering an effective amount of a composition disclosed herein to an individual seeking weight loss. Other aspects of the present specification disclose a composition disclosed herein for use in promoting or enhancing weight loss in an individual. A disclosed use comprises administering an effective amount of a composition disclosed herein to an individual seeking weight loss. Yet other aspects of the present specification disclose use of a composition disclosed herein in promoting or enhancing weight loss in an individual. A disclosed use comprises administering an effective amount of a composition disclosed herein to an individual seeking weight loss. Still of aspects of the present specification disclose use of a composition disclosed herein as a medicament use in promoting or enhancing weight loss in an individual. A disclosed use comprises administering an effective amount of a medicament disclosed herein to an individual seeking weight loss.

[0009] Aspects of the present specification disclose a method of treating or managing a metabolic disease in an individual. A disclosed method comprises administering an effective amount of a composition disclosed herein to an individual suffering from a metabolic disease. Other aspects of the present specification disclose a composition disclosed herein for use in treating or managing a metabolic disease in an individual. A disclosed use comprises administering an effective amount of a composition disclosed herein to an individual suffering from a metabolic disease. Yet other aspects of the present specification disclose use of a composition disclosed herein in treating or managing a metabolic disease in an individual. A disclosed use comprises administering an effective amount of a composition disclosed herein to an individual suffering from a metabolic disease. Still of aspects of the present specification disclose use of a composition disclosed herein as a medicament use in treating or managing a metabolic disease in an individual. A disclosed use comprises administering an effective amount of a medicament disclosed herein to an individual suffering from a metabolic disease. A disclosed metabolic disease can be a kidney disease including a polycystic kidney disease.

BRIEF DESCRIPTION OF DRAWINGS

[0010] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate aspects of the disclosed subject matter in at least one of its exemplary embodiments, which are further defined in detail in the following description. Features, elements, and aspects of the disclosure are referenced by numerals with like numerals in different drawings representing the same, equivalent, or similar features, elements, or aspects, in accordance with one or more embodiments. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles herein described and provided by exemplary embodiments of the invention. More generally, those skilled in the art will appreciate that the drawings are schematic in nature and are not to be taken literally or to scale in terms of material configurations, sizes, thicknesses, and other attributes of an apparatus according to aspects of the present invention and its components or features unless specifically set forth herein. In such drawings:

[0011] FIG. 1 is a graph showing the weight loss percentage of subjects administered a composition disclosed herein over the course of a 30-day study; and

[0012] FIG. 2 is a graph comparing the weight loss percentages of subjects disclosed in the study described in Example 1 with the weight loss percentages of subject treated with semaglutide reported in Garvey et al, “Two-Year Effects of Semaglutide in Adults with Overweight or Obesity: The STEP 5 Trial.” Nature Medicine 28(10): 2083-2091 (2022).

DETAILED DESCRIPTION

[0013] p-hydroxybutyrate has been used with modest success as a supplement to promote weight loss in an individual. Allulose is a non-caloric sweetener and is used as a replacement for table sugar. Although allulose is metabolized poorly by the human body, its impact on weight loss has been minimal. For example, in one study both low and high doses of allulose resulted in a minimal weight loss of about 1 pound over the course of the study (Han, et al., Nutrients 10, 160; doi:10.3390/nu10020160). Surprisingly, the present specification discloses that combining allulose with p-hydroxybutyrate results in robust weight loss in individuals that was simply not expected. This robust weight loss was significantly better than either p-hydroxybutyrate or allulose alone.

[0014] The present specification discloses in part a medical food, conventional food, dietary supplement, or therapeutic drug (collectively referred to herein as a “composition”) comprising p- hydroxybutyrate (BHB), or salts or esters thereof, or one of more BHB precursors, and allulose in a ratio that maximizes weight loss efficacy while minimizing potential side effects. The composition may be formulated as a powder, pill, liquid, or any suitable delivery form for oral consumption. A composition disclosed herein may optionally comprise additional components, including without limitation, one or more inorganic electrolytes, one or more vitamins and other nutritional supplements, one or more stabilizers, and one or more flavorings. In some embodiments, composition disclosed herein is an ionic mixture comprising BHB, or salts or esters thereof, or one of more BHB precursors, allulose, citrate, and inorganic electrolytes of potassium, calcium, and magnesium.

[0015] The present specification discloses a composition comprising a p-hydroxybutyrate (BHB). BHB, also known as 3-hydroxybutyric acid, is a ketone body with a chemical formula CH3CH(OH)CH2CC>2H and serves as an alternative energy source during carbohydrate restriction or deprivation, aiding in weight loss and metabolic efficiency. It is one of the three ketone bodies, the other two being acetoacetate and acetone, making up about 78% of the total ketones in the blood. In humans, BHB can be synthesized in the liver via the metabolism of fatty acids (e.g., butyrate), p-hydroxy p-methylbutyrate, and ketogenic amino acids through a series of reactions that metabolize these compounds into acetoacetate, which is the first ketone body that is produced in a carbohydrate deprivation state. BHB is a chiral compound with two enantiomers: D-P-hydroxybutyrate and L-p-hydroxybutyrate. The concentration of BHB in human blood plasma, as with other ketone bodies, increases through ketosis. BHB can be used as an energy source by the brain and skeletal muscle when blood glucose is low. BHB is described in more detail in US Patent 11 ,013,705 which is hereby incorporated by reference.

[0016] In some embodiments, a composition comprises one or more salt forms of BHB. The use of a BHB salt has an added benefit of providing one or more electrolytes to a composition disclosed herein upon the addition of a solute. Non-limiting examples of a BHB salt include a sodium BHB salt, a potassium BHB salt, a calcium BHB salt, and a magnesium BHB salt. In aspects of these embodiments, a composition disclosed herein may comprise, e.g., one to two BHB salts, one to three BHB salts, one to four BHB salts, one to five BHB salts, two to three BHB salts, two to four BHB salts, two to five BHB salts, three to four BHB salts, three to five BHB salts, or four to five BHB salts.

[0017] In some embodiments, a composition comprises one or more ester forms of BHB. The use of a BHB ester has an added benefit of liberating further ketones in the digestive system for absorption and induce acute ketosis. Non-limiting examples of a BHB ester include a 3- hydroxybutyl and a 3-hydroxybutyrate. In aspects of these embodiments, a composition disclosed herein may comprise, e.g. , one to two BHB esters, one to three BHB esters, one to four BHB esters, one to five BHB esters, two to three BHB esters, two to four BHB esters, two to five BHB esters, three to four BHB esters, three to five BHB esters, or four to five BHB esters.

[0018] In some embodiments, a composition comprises one or more precursors of BHB. Nonlimiting examples of a BHB precursor include acetoacetate and butane-diol. In aspects of these embodiments, a composition disclosed herein may comprise, e.g., one to two BHB precursors, one to three BHB precursors, one to four BHB precursors, one to five BHB precursors, two to three BHB precursors, two to four BHB precursors, two to five BHB precursors, three to four BHB precursors, three to five BHB precursors, or four to five BHB precursors.

[0019] A composition disclosed herein has an effective amount of one of more BHBs, or salts or esters thereof, or one of more BHB precursors. An effective amount of one of more BHBs, or salts or esters thereof, or one of more BHB precursors, is an amount that is sufficient, in combination with allulose, to affect the metabolism of an individual to promote weight loss in a healthy manner. In aspects of this embodiment, a composition disclosed herein comprises one of more BHBs, or salts or esters thereof, or one of more BHB precursors, in a combined amount of, e.g., about 5% to about 25%, about 7.5% to about 22.5%, about 12.5% to about 22.5%, about 15% to about 25%, about 10% to about 20%, about 10.5% to about 19%, about 11% to about 18%, about 12% to about 17%, about 13% to about 16%, or about 14% to about 15%, by weight of the composition.

[0020] In other aspects of this embodiment, a composition disclosed herein comprises one of more BHBs, or salts or esters thereof, or one of more BHB precursors where each BHB, or salt or ester thereof, or BHB precursor, is present in an amount of, e.g., about 0.5% to about 10%, about 1% to about 9%, about 2% to about 8%, about 2.5% to about 7.5%, about 3% to about 7%, about 3.5% to about 6.5%, or about 4% to about 6%, by weight of the composition. In other aspects of this embodiment, a composition disclosed herein comprises one of more BHBs, or salts or esters thereof, or one of more BHB precursors where each BHB, or salt or ester thereof, or BHB precursor, is present in an amount of, e.g., about 0.5% to about 10%, about 1% to about 9%, about 1.5% to about 8,5%, about 2% to about 8%, about 2.5% to about 7.5%, about 3% to about 7%, or about 3.5% to about 6.5%, by weight of the composition.

[0021] The present specification discloses a composition comprising an allulose. Allulose, also known as D-allulose, D-psicose or D-ribo-2-hexulose, is a rare, naturally-occurring monosaccharide with a chemical formula of C₆H₁₂O₆ and is a C3 epimer of fructose. A ketohexose, the sweetness of allulose is estimated to be 70% of the sweetness of sucrose (/.e., common or white sugar) but a low caloric value. For example, in humans, allulose has a caloric value of about 0.2 kcal/g to 0.4 kcal/g, relative to a caloric value of about 4 kcal/g for typical carbohydrates like sucrose, fructose and glucose. The biosynthesis of allulose from fructose is catalyzed by D-tagatose 3-epimerase and/or D-psicose 3-epimerase which has allowed for mass production of allulose from corn and sugar beet. The compound is found naturally in trace amounts in wheat, figs, raisins, maple syrup, and molasses. Besides naturally-occurring allulose, two proprietary allulose variants exist, ALLSWEET® (Anderson Global Group, LLC) and Dolcia Prima allulose (Tate & Lyle, PLC). Allulose is described in more detail in US Patent Publication 2024/0041060 which is hereby incorporated by reference.

[0022] A composition disclosed herein has an effective amount of an allulose disclosed herein. An effective amount of an allulose disclosed herein is an amount that is sufficient, in combination with BHB, to affect the metabolism of an individual to promote weight loss in a healthy manner. In aspects of this embodiment, a composition disclosed herein comprises an allulose disclosed herein in an amount of, e.g., about 60% to about 90%, about 65% to about 85%, about 80% to about 90%, about 75% to about 85%, about 70% to about 80%, about 71% to about 79%, about 72% to about 78%, about 73% to about 77%, about 74% to about 76%, by weight of the composition. [0023] A composition disclosed herein has an effective amount of one of more BHBs, or salts or esters thereof, or one of more BHB precursors, and an effective amount of allulose disclosed herein in a ratio necessary to affect the metabolism of an individual to promote wight loss in a healthy manner. In aspects of this embodiment, a composition disclosed herein has one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and an allulose disclosed herein in a ratio of, e.g. , about 1 :3 to 1 :7 BHB to allulose, about 1 :4 to 1 :6 BHB to allulose, about 1 :4.5 to 1 :5.5 BHB to allulose, about 1 :5.0 to about 1 :5.4 BHB to allulose, about 1 :5.1 to about 1 :5.3 BHB to allulose, or about 1 :5.2 BHB to allulose.

[0024] A composition disclosed herein can, optionally, comprise additional ingredients, including, without limitation, citric acid or a citrate, one or more electrolytes, one or more dietary fibers, and one or more flavorings. Citric acid is a weak organic acid with the formula C₆H₇O7. Citrate is an acid salt of citric acid and serves as an intermediate in the citric acid cycle. As a conjugate base of citric acid, citrate can perform as a buffering agent or acidity regulator, resisting changes in pH. Citrate is also used as an antioxidant and as a sequestrant or preservative. An electrolyte is a substance that conducts electricity through the movement of ions, but not through the movement of electrons, and in some embodiments, electrolytes are provided using salt forms of BHB. A dietary fiber is a plant-derived food that is miscible in water and cannot be completely broken down by human digestive system. A flavoring is typically used as an additive to improve the taste or smell of a food by changing the perceptual impression of the food, for example, by causing the food to become sweet, sour, tangy, or spicey. Flavorings can be divided into three principal types: "natural flavorings", "nature-identical flavorings", and "artificial flavorings". Non-limiting examples of a flavoring disclosed herein include lemon, lime, orange, cherry, strawberry, grape, apple, watermelon, blueberry, chocolate, mint, and peanut butter.

[0025] In some embodiments, a composition disclosed herein comprises an effective amount of one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and an effective amount of an allulose. In aspects of these embodiments, a composition disclosed herein comprises about 5% to about 25% by weight of the composition of one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and about 60% to about 90% by weight of the composition of an allulose. In other aspects of these embodiments, a composition disclosed herein comprises about 7.5% to about 22.5% by weight of the composition of one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and about 65% to about 85% by weight of the composition of an allulose. In yet other aspects of these embodiments, a composition disclosed herein comprises about 12.5% to about 22.5% by weight of the composition of one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and about 75% to about 85% by weight of the composition of an allulose. In still other aspects of these embodiments, a composition disclosed herein comprises about 15% to about 25% by weight of the composition of one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and about 80% to about 90% by weight of the composition of an allulose. In all aspects of the above embodiments, a composition disclosed herein can further comprise citric acid or citrate, one or more dietary fibers, one or more flavorings, or any combination thereof. In all aspects of the above embodiments, the percent weight of the one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and the allulose in the composition are in a ratio of about 1 :3 to 1 :7 BHB to allulose, about 1 :4 to 1 :6 BHB to allulose, about 1 :4.5 to 1 :5.5 BHB to allulose, about 1 :5.0 to about 1 :5.4 BHB to allulose, about 1 :5.1 to about 1 :5.3 BHB to allulose, or about 1 :5.2 BHB to allulose.

[0026] In aspects of these embodiments, a composition disclosed herein comprises about 10% to about 20% by weight of the composition of one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and about 70% to about 80% by weight of the composition of an allulose. In other aspects of these embodiments, a composition disclosed herein comprises about 1 1% to about 18% by weight of the composition of one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and about 71 % to about 79% by weight of the composition of an allulose. In yet other aspects of these embodiments, a composition disclosed herein comprises about 12% to about 17% by weight of the composition of one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and about 72% to about 78% by weight of the composition of an allulose. In still other aspects of these embodiments, a composition disclosed herein comprises about 13% to about 16% by weight of the composition of one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and about 73% to about 77% by weight of the composition of an allulose. In further other aspects of these embodiments, a composition disclosed herein comprises about 14% to about 15% by weight of the composition of one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and about 74% to about 76% by weight of the composition of an allulose. In all aspects of the above embodiments, a composition disclosed herein can further comprise citric acid or citrate, one or more dietary fibers, one or more flavorings, or any combination thereof. In all aspects of the above embodiments, the percent weight of the one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and the allulose in the composition are in a ratio of about 1 :3 to 1 :7 BHB to allulose, about 1 :4 to 1 :6 BHB to allulose, about 1 :4.5 to 1 :5.5 BHB to allulose, about 1 :5.0 to about 1 :5.4 BHB to allulose, about 1 :5.1 to about 1 :5.3 BHB to allulose, or about 1 :5.2 BHB to allulose.

[0027] In some embodiments, a composition disclosed herein comprises an effective amount of one or more BHB salts and an effective amount of an allulose. In aspects of these embodiments, a composition disclosed herein comprises about 5% to about 25% by weight of the composition of one or more BHB salts and about 60% to about 90% by weight of the composition of an allulose. In other aspects of these embodiments, a composition disclosed herein comprises about 7.5% to about 22.5% by weight of the composition of one or more BHB salts and about 65% to about 85% by weight of the composition of an allulose. In yet other aspects of these embodiments, a composition disclosed herein comprises about 12.5% to about 22.5% by weight of the composition of one or more BHB salts and about 75% to about 85% by weight of the composition of an allulose. In still other aspects of these embodiments, a composition disclosed herein comprises about 15% to about 25% by weight of the composition of one or more BHB salts and about 80% to about 90% by weight of the composition of an allulose. In all aspects of the above embodiments, a composition disclosed herein can further comprise citric acid or citrate, one or more dietary fibers, one or more flavorings, or any combination thereof. In all aspects of the above embodiments, the percent weight of the one or more BHB salts and the allulose in the composition are in a ratio of about 1 :3 to 1 :7 BHB to allulose, about 1 :4 to 1 :6 BHB to allulose, about 1 :4.5 to 1 :5.5 BHB to allulose, about 1 :5.0 to about 1 :5.4 BHB to allulose, about 1 :5.1 to about 1 :5.3 BHB to allulose, or about 1 :5.2 BHB to allulose.

[0028] In aspects of these embodiments, a composition disclosed herein comprises about 10% to about 20% by weight of the composition of one or more BHB salts and about 70% to about 80% by weight of the composition of an allulose. In other aspects of these embodiments, a composition disclosed herein comprises about 1 1 % to about 18% by weight of the composition of one or more BHBs salts and about 71 % to about 79% by weight of the composition of an allulose. In yet other aspects of these embodiments, a composition disclosed herein comprises about 12% to about 17% by weight of the composition of one or more BHB salts and about 73% to about 77% by weight of the composition of an allulose. In still other aspects of these embodiments, a composition disclosed herein comprises about 13% to about 16% by weight of the composition of one or more BHB salts and about 73% to about 77% by weight of the composition of an allulose. In further other aspects of these embodiments, a composition disclosed herein comprises about 14% to about 15% by weight of the composition of one or more BHB salts and about 74% to about 76% by weight of the composition of an allulose. In all aspects of the above embodiments, a composition disclosed herein can further comprise citric acid or citrate, one or more dietary fibers, one or more flavorings, or any combination thereof. In all aspects of the above embodiments, the percent weight of the one or more BHB salts and the allulose in the composition are in a ratio of about 1 :3 to 1 :7 BHB to allulose, about 1 :4 to 1 :6 BHB to allulose, about 1 :4.5 to 1 :5.5 BHB to allulose, about 1 :5.0 to about 1 :5.4 BHB to allulose, about 1 :5.1 to about 1 :5.3 BHB to allulose, or about 1 :5.2 BHB to allulose. [0029] In some embodiments, a composition disclosed herein comprises an effective amount of a magnesium BHB salt, a potassium BHB salt and a calcium BHB salt and an effective amount of an allulose. In aspects of these embodiments, a composition disclosed herein comprises about 5% to about 25% by weight of the composition of a magnesium BHB salt, a potassium BHB salt and a calcium BHB salt and about 60% to about 90% by weight of the composition of an allulose. In other aspects of these embodiments, a composition disclosed herein comprises about 7.5% to about 22.5% by weight of the composition of a magnesium BHB salt, a potassium BHB salt and a calcium BHB salt and about 65% to about 85% by weight of the composition of an allulose. In yet other aspects of these embodiments, a composition disclosed herein comprises about 12.5% to about 22.5% by weight of the composition of a magnesium BHB salt, a potassium BHB salt and a calcium BHB salt and about 75% to about 85% by weight of the composition of an allulose. In still other aspects of these embodiments, a composition disclosed herein comprises about 15% to about 25% by weight of the composition of a magnesium BHB salt, a potassium BHB salt and a calcium BHB salt and about 80% to about 90% by weight of the composition of an allulose. In all aspects of the above embodiments, a composition disclosed herein can further comprise citric acid or citrate, one or more dietary fibers, one or more flavorings, or any combination thereof. In all aspects of the above embodiments, the combined percent weight of the one or more BHB salts and the allulose in the composition are in a ratio of about 1 :3 to 1 :7 BHB to allulose, about 1 :4 to 1 :6 BHB to allulose, about 1 :4.5 to 1 :5.5 BHB to allulose, about 1 :5.0 to about 1 :5.4 BHB to allulose, about 1 :5.1 to about 1 :5.3 BHB to allulose, or about 1 :5.2 BHB to allulose.

[0030] In aspects of these embodiments, a composition disclosed herein comprises about 10% to about 20% by weight of the composition of a magnesium BHB salt, a potassium BHB salt and a calcium BHB salt and about 70% to about 80% by weight of the composition of an allulose. In other aspects of these embodiments, a composition disclosed herein comprises about 1 1 % to about 19% by weight of the composition of a magnesium BHB salt, a potassium BHB salt and a calcium BHB salt and about 71% to about 79% by weight of the composition of an allulose. In yet other aspects of these embodiments, a composition disclosed herein comprises about 12% to about 18% by weight of the composition of a magnesium BHB salt, a potassium BHB salt and a calcium BHB salt and about 72% to about 78% by weight of the composition of an allulose. In still other aspects of these embodiments, a composition disclosed herein comprises about 13% to about 16% by weight of the composition of a magnesium BHB salt, a potassium BHB salt and a calcium BHB salt and about 73% to about 77% by weight of the composition of an allulose. In further other aspects of these embodiments, a composition disclosed herein comprises about 14% to about 15% by weight of the composition of a magnesium BHB salt, a potassium BHB salt and a calcium BHB salt and about 74% to about 76% by weight of the composition of an allulose. In all aspects of the above embodiments, a composition disclosed herein can further comprise citric acid or citrate, one or more dietary fibers, one or more flavorings, or any combination thereof. In all aspects of the above embodiments, the combined percent weight of the one or more BHB salts and the allulose in the composition are in a ratio of about 1 :3 to 1 :7 BHB to allulose, about 1 :4 to 1 :6 BHB to allulose, about 1 :4.5 to 1 :5.5 BHB to allulose, about 1 :5.0 to about 1 :5.4 BHB to allulose, about 1 :5.1 to about 1 :5.3 BHB to allulose, or about 1 :5.2 BHB to allulose.

[0031] In some embodiments, a composition disclosed herein comprises an effective amount of a magnesium BHB salt, an effective amount of a potassium BHB salt, an effective amount of a calcium BHB salt and an effective amount of an allulose. In aspects of these embodiments, a composition disclosed herein comprises about 2.5% to about 8.5% by weight of the composition of a magnesium BHB salt, about 2% to about 8% by weight of the composition of a potassium BHB salt, about 1.5% to about 7.5% by weight of the composition of a calcium BHB salt and about 60% to about 90% by weight of the composition of an allulose. In other aspects of these embodiments, a composition disclosed herein comprises about 2.5% to about 8.5% by weight of the composition of a magnesium BHB salt, about 2% to about 8% by weight of the composition of a potassium BHB salt, about 1 .5% to about 7.5% by weight of the composition of a calcium BHB salt and about 65% to about 85% by weight of the composition of an allulose. In yet other aspects of these embodiments, a composition disclosed herein comprises about 2.5% to about 8.5% by weight of the composition of a magnesium BHB salt, about 2% to about 8% by weight of the composition of a potassium BHB salt, about 1 .5% to about 7.5% by weight of the composition of a calcium BHB salt and about 75% to about 85% by weight of the composition of an allulose. In still other aspects of these embodiments, a composition disclosed herein comprises about 2.5% to about 8.5% by weight of the composition of a magnesium BHB salt, about 2% to about 8% by weight of the composition of a potassium BHB salt, about 1.5% to about 7.5% by weight of the composition of a calcium BHB salt and about 80% to about 90% by weight of the composition of an allulose. In all aspects of the above embodiments, a composition disclosed herein can further comprise citric acid or citrate, one or more dietary fibers, one or more flavorings, or any combination thereof. In all aspects of the above embodiments, the combined percent weight of the BHB salts and the allulose in the composition are in a ratio of about 1 :3 to 1 :7 BHB to allulose, about 1 :4 to 1 :6 BHB to allulose, about 1 :4.5 to 1 :5.5 BHB to allulose, about 1 :5.0 to about 1 :5.4 BHB to allulose, about 1 :5.1 to about 1 :5.3 BHB to allulose, or about 1 :5.2 BHB to allulose.

[0032] In aspects of these embodiments, a composition disclosed herein comprises about 2.5% to about 8.5% by weight of the composition of a magnesium BHB salt, about 2% to about 8% by weight of the composition of a potassium BHB salt, about 1.5% to about 7.5% by weight of the composition of a calcium BHB salt and about 70% to about 80% by weight of the composition of an allulose. In other aspects of these embodiments, a composition disclosed herein comprises about 3% to about 8% by weight of the composition of a magnesium BHB salt, about 2.5% to about 7.5% by weight of the composition of a potassium BHB salt, about 2% to about 7% by weight of the composition of a calcium BHB salt and about 71% to about 79% by weight of the composition of an allulose. In yet other aspects of these embodiments, a composition disclosed herein comprises about 3.5% to about 7.5% by weight of the composition of a magnesium BHB salt, about 3% to about 7% by weight of the composition of a potassium BHB salt, about 2.5% to about 6.5% by weight of the composition of a calcium BHB salt and about 72% to about 78% by weight of the composition of an allulose. In still other aspects of these embodiments, a composition disclosed herein comprises about 4% to about 7% by weight of the composition of a magnesium BHB salt, about 3.5% to about 6.5% by weight of the composition of a potassium BHB salt, about 3% to about 6% by weight of the composition of a calcium BHB salt and about 73% to about 77% by weight of the composition of an allulose. In further other aspects of these embodiments, a composition disclosed herein comprises about 4.5% to about 6.5% by weight of the composition of a magnesium BHB salt, about 4% to about 6% by weight of the composition of a potassium BHB salt, about 3.5% to about 5.5% by weight of the composition of a calcium BHB salt and about 74% to about 76% by weight of the composition of an allulose. In all aspects of the above embodiments, a composition disclosed herein can further comprise citric acid or citrate, one or more dietary fibers, one or more flavorings, or any combination thereof. In all aspects of the above embodiments, the combined percent weight of the BHB salts and the allulose in the composition are in a ratio of about 1 :3 to 1 :7 BHB to allulose, about 1 :4 to 1 :6 BHB to allulose, about 1 :4.5 to 1 :5.5 BHB to allulose, about 1 :5.0 to about 1 :5.4 BHB to allulose, about 1 :5.1 to about 1 :5.3 BHB to allulose, or about 1 :5.2 BHB to allulose.

[0033] In some embodiments, a composition disclosed herein comprises an effective amount of a magnesium BHB salt, an effective amount of a potassium BHB salt, an effective amount of a calcium BHB salt and an effective amount of an allulose. In aspects of these embodiments, a composition disclosed herein comprises about 1.5% to about 8.5% by weight of the composition of a magnesium BHB salt, about 1 .5% to about 8.5% by weight of the composition of a potassium BHB salt, about 1.5% to about 8.5% by weight of the composition of a calcium BHB salt and about 60% to about 90% by weight of the composition of an allulose. In other aspects of these embodiments, a composition disclosed herein comprises about 1.5% to about 8.5% by weight of the composition of a magnesium BHB salt, about 1 .5% to about 8.5% by weight of the composition of a potassium BHB salt, about 1 .5% to about 8.5% by weight of the composition of a calcium BHB salt and about 65% to about 85% by weight of the composition of an allulose. In yet other aspects of these embodiments, a composition disclosed herein comprises about 1 .5% to about 8.5% by weight of the composition of a magnesium BHB salt, about 1.5% to about 8.5% by weight of the composition of a potassium BHB salt, about 1.5% to about 8.5% by weight of the composition of a calcium BHB salt and about 75% to about 85% by weight of the composition of an allulose. In still other aspects of these embodiments, a composition disclosed herein comprises about 1.5% to about 8.5% by weight of the composition of a magnesium BHB salt, about 1 .5% to about 8.5% by weight of the composition of a potassium BHB salt, about 1 .5% to about 8.5% by weight of the composition of a calcium BHB salt and about 80% to about 90% by weight of the composition of an allulose. In all aspects of the above embodiments, a composition disclosed herein can further comprise citric acid or citrate, one or more dietary fibers, one or more flavorings, or any combination thereof. In all aspects of the above embodiments, he combined percent weight of the BHB salts and the allulose in the composition are in a ratio of about 1 :3 to 1 :7 BHB to allulose, about 1 :4 to 1 :6 BHB to allulose, about 1 :4.5 to 1 :5.5 BHB to allulose, about 1 :5.0 to about 1 :5.4 BHB to allulose, about 1 :5.1 to about 1 :5.3 BHB to allulose, or about 1 :5.2 BHB to allulose.

[0034] In aspects of these embodiments, a composition disclosed herein comprises about 1.5% to about 8.5% by weight of the composition of a magnesium BHB salt, about 1 .5% to about 8.5% by weight of the composition of a potassium BHB salt, about 1 .5% to about 8.5% by weight of the composition of a calcium BHB salt and about 70% to about 80% by weight of the composition of an allulose. In other aspects of these embodiments, a composition disclosed herein comprises about 2% to about 8% by weight of the composition of a magnesium BHB salt, about 2% to about 8% by weight of the composition of a potassium BHB salt, about 2% to about 8% by weight of the composition of a calcium BHB salt and about 71 % to about 79% by weight of the composition of an allulose. In yet other aspects of these embodiments, a composition disclosed herein comprises about 2.5% to about 7.5% by weight of the composition of a magnesium BHB salt, about 2.5% to about 7.5% by weight of the composition of a potassium BHB salt, about 2.5% to about 7.5% by weight of the composition of a calcium BHB salt and about 72% to about 78% by weight of the composition of an allulose. In still other aspects of these embodiments, a composition disclosed herein comprises about 3% to about 7% by weight of the composition of a magnesium BHB salt, about 3% to about 7% by weight of the composition of a potassium BHB salt, about 3% to about 7% by weight of the composition of a calcium BHB salt and about 73% to about 77% by weight of the composition of an allulose. In further other aspects of these embodiments, a composition disclosed herein comprises about 3.5% to about 6.5% by weight of the composition of a magnesium BHB salt, about 3.5% to about 6.5% by weight of the composition of a potassium BHB salt, about 3.5% to about 6.5% by weight of the composition of a calcium BHB salt and about 74% to about 76% by weight of the composition of an allulose. In all aspects of the above embodiments, a composition disclosed herein can further comprise citric acid or citrate, one or more dietary fibers, one or more flavorings, or any combination thereof. In all aspects of the above embodiments, he combined percent weight of the BHB salts and the allulose in the composition are in a ratio of about 1 :3 to 1 :7 BHB to allulose, about 1 :4 to 1 :6 BHB to allulose, about 1 :4.5 to 1 :5.5 BHB to allulose, about 1 :5.0 to about 1 :5.4 BHB to allulose, about 1 :5.1 to about 1 :5.3 BHB to allulose, or about 1 :5.2 BHB to allulose.

[0035] Aspects of the present specification disclose a method of promoting or enhancing weight loss in an individual. A method disclosed herein comprises administering an effective amount of a composition disclosed herein to an individual seeking weight loss. In some embodiments, a composition disclosed herein is formulated as a pill, tablet, capsule, or other orally administrable form. In some embodiments, a composition disclosed herein is formulated as a liquid. In some embodiments, a composition disclosed herein is a dry powder formulation and a method disclosed herein comprises admixing a dry powdered composition disclosed herein with a solvent to form a liquid composition. Non-limiting examples of a solvent include still water and carbonated water.

[0036] Other aspects of the present specification disclose a composition disclosed herein for use in promoting or enhancing weight loss in an individual. A use disclosed herein comprises administering an effective amount of a composition disclosed herein to an individual seeking weight loss. In some embodiments, a composition disclosed herein is formulated as a pill, tablet, capsule, or other orally administrable form. In some embodiments, a composition disclosed herein is formulated as a liquid. In some embodiments, a composition disclosed herein is a dry powder formulation and a use disclosed herein comprises admixing a dry powdered composition disclosed herein with a solvent to form a liquid composition. Non-limiting examples of a solvent include still water and carbonated water.

[0037] Yet other aspects of the present specification disclose use of a composition disclosed herein in promoting or enhancing weight loss in an individual. A use disclosed herein comprises administering an effective amount of a composition disclosed herein to an individual seeking weight loss. In some embodiments, a composition disclosed herein is formulated as a pill, tablet, capsule, or other orally administrable form. In some embodiments, a composition disclosed herein is formulated as a liquid. In some embodiments, a composition disclosed herein is a dry powder formulation and a use disclosed herein comprises admixing a dry powdered composition disclosed herein with a solvent to form a liquid composition. Non-limiting examples of a solvent include still water and carbonated water.

[0038] Still of aspects of the present specification disclose use of a composition disclosed herein as a medicament use in promoting or enhancing weight loss in an individual. A use disclosed herein comprises administering an effective amount of a medicament disclosed herein to an individual seeking weight loss. In some embodiments, a medicament disclosed herein is formulated as a pill, tablet, capsule, or other orally administrable form. In some embodiments, a medicament disclosed herein is formulated as a liquid. In some embodiments, a medicament disclosed herein is a dry powder formulation and a use disclosed herein comprises admixing a dry powdered medicament disclosed herein with a solvent to form a liquid composition. Nonlimiting examples of a solvent include still water and carbonated water.

[0039] Aspects of the present specification disclose a method of treating or managing a metabolic disease in an individual. A method disclosed herein comprises administering an effective amount of a composition disclosed herein to an individual suffering from a metabolic disease. In some embodiments, a composition disclosed herein is formulated as a pill, tablet, capsule, or other orally administrable form. In some embodiments, a composition disclosed herein is formulated as a liquid. In some embodiments, a composition disclosed herein is a dry powder formulation and a method disclosed herein comprises admixing a dry powdered composition disclosed herein with a solvent to form a liquid composition. Non-limiting examples of a solvent include still water and carbonated water.

[0040] Other aspects of the present specification disclose a composition disclosed herein for use in treating or managing a metabolic disease in an individual. A use disclosed herein comprises administering an effective amount of a composition disclosed herein to an individual suffering from a metabolic disease. In some embodiments, a composition disclosed herein is formulated as a pill, tablet, capsule, or other orally administrable form. In some embodiments, a composition disclosed herein is formulated as a liquid. In some embodiments, a composition disclosed herein is a dry powder formulation and a use disclosed herein comprises admixing a dry powdered composition disclosed herein with a solvent to form a liquid composition. Non-limiting examples of a solvent include still water and carbonated water.

[0041] Yet other aspects of the present specification disclose use of a composition disclosed herein in treating or managing a metabolic disease in an individual. A use disclosed herein comprises administering an effective amount of a composition disclosed herein to an individual suffering from a metabolic disease. In some embodiments, a composition disclosed herein is formulated as a pill, tablet, capsule, or other orally administrable form. In some embodiments, a composition disclosed herein is formulated as a liquid. In some embodiments, a composition disclosed herein is a dry powder formulation and a use disclosed herein comprises admixing a dry powdered composition disclosed herein with a solvent to form a liquid composition. Nonlimiting examples of a solvent include still water and carbonated water. [0042] Still of aspects of the present specification disclose use of a composition disclosed herein as a medicament use in treating or managing a metabolic disease in an individual. A use disclosed herein comprises administering an effective amount of a medicament disclosed herein to an individual suffering from a metabolic disease. In some embodiments, a medicament disclosed herein is formulated as a pill, tablet, capsule, or other orally administrable form. In some embodiments, a medicament disclosed herein is formulated as a liquid. In some embodiments, a medicament disclosed herein is a dry powder formulation and a use disclosed herein comprises admixing a dry powdered medicament disclosed herein with a solvent to form a liquid composition. Non-limiting examples of a solvent include still water and carbonated water.

[0043] A composition or medicament disclosed herein is typically administered in a therapeutically effective amount. As used herein, the term “therapeutically effective amount’’ is synonymous with “effective amount”, “effective dose”, or “therapeutically effective dose”. In some embodiments, therapeutically effective amount is the minimum dose of one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and allulose disclosed herein necessary to achieve the desired therapeutic effect in a weight loss treatment and includes a dose sufficient to reduce the desired weight of an individual in the desired time period. The effectiveness of a composition or medicament disclosed herein can be determined by observing an improvement in an individual based upon one or more clinical symptoms, and/or physiological indicators associated with losing weight in an individual.

[0044] The appropriate effective amount of a composition or medicament disclosed herein to be administered to an individual undergoing a weight loss method disclosed herein can be determined by a person of ordinary skill in the art by taking into account factors, including, without limitation, the amount of weight loss desired, the particular physiological conditions or symptoms associated with the individual being obese or overweight, the cause of the obesity or being overweight, the severity of the obesity or being overweight, the particular one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and allulose disclosed herein being used, the pharmacokinetic characteristics of the particular one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and allulose disclosed herein used including liberation, absorption, distribution, metabolism, and excretion, the pharmacodynamic characteristics of the particular one or more BHBs, or salts or esters thereof, or one of more BHB precursors, and allulose disclosed herein used including mechanism of action, dose-response relationship, desired activity, undesirable side effects, treatment window and duration of action, the frequency of administration, the particular route of administration used, the use and type of concurrent therapy, the use and type of other weight loss drugs, the particular characteristics, history and risk factors of the individual, such as, e.g., age, weight, general health and the like, or any combination thereof. It is known by a person of ordinary skill in the art that an effective amount of a composition or medicament disclosed herein can be extrapolated from in-vitro assays and in-vivo administration studies using animal models prior to administration to humans. Variations in these dosage levels can be adjusted using standard empirical routines of optimization, which are well-known to a person of ordinary skill in the art. One skilled in the art will also recognize that the condition of the individual can be monitored throughout the course of a method or use disclosed herein and that the effective amount of a composition or medicament disclosed herein that is administered can be adjusted accordingly. Thus, the precise therapeutically effective dosage levels and patterns are preferably determined by the attending healthcare professional in consideration of the above-identified factors.

[0045] In some embodiments, an effective amount of one or more BHBs, or salts or esters thereof, or one of more BHB precursors, present in a composition or medicament disclosed herein that is administered to an individual is an amount that is sufficient to affect the metabolism of an individual to promote wight loss in a healthy manner. In aspects of these embodiments, an effective amount of one or more BHBs, or salts or esters thereof, or one of more BHB precursors, present in a composition or medicament disclosed herein that is administered to an individual can be, e.g., about 2 g/day to about 5 g/day, about 2 g/day to about 7.5 g/day, about 2 g/day to about 10 g/day, about 2 g/day to about 15 g/day, about 2 g/day to about 20 g/day, about 1 g/day to about 25 g/day, about 1 g/day to about 30 g/day, about 2.5 g/day to about 5 g/day, about 2.5 g/day to about 7.5 g/day, about 2.5 g/day to about 10 g/day, about 2.5 g/day to about 15 g/day, about 2.5 g/day to about 20 g/day, about 2.5 g/day to about 25 g/day, about 2.5 g/day to about 30 g/day, about 5 g/day to about 7.5 g/day, about 5 g/day to about 10 g/day, about 5 g/day to about 15 g/day, about 5 g/day to about 20 g/day, about 5 g/day to about 25 g/day, about 5 g/day to about 30 g/day, about 7.5 g/day to about 10 g/day, about 7.5 g/day to about 15 g/day, about 7.5 g/day to about 20 g/day, about 7.5 g/day to about 25 g/day, about 7.5 g/day to about 30 g/day, about 10 g/day to about 15 g/day, about 10 g/day to about 20 g/day, about 10 g/day to about 25 g/day, about 10 g/day to about 30 g/day, about 15 g/day to about 20 g/day, about 15 g/day to about 25 g/day, about 15 g/day to about 30 g/day, about 20 g/day to about 25 g/day, about 20 g/day to about 30 g/day, or about 25 g/day to about 30 g/day.

[0046] In some embodiments, an effective amount of one or more BHB salts present in a composition or medicament disclosed herein that is administered to an individual is an amount that is sufficient to affect the metabolism of an individual to promote wight loss in a healthy manner. In aspects of these embodiments, an effective amount of one or more BHB salts present in a composition or medicament disclosed herein that is administered to an individual can be, e.g., about 2 g/day to about 5 g/day, about 2 g/day to about 7.5 g/day, about 2 g/day to about 10 g/day, about 2 g/day to about 15 g/day, about 2 g/day to about 20 g/day, about 1 g/day to about 25 g/day, about 1 g/day to about 30 g/day, about 2.5 g/day to about 5 g/day, about 2.5 g/day to about 7.5 g/day, about 2.5 g/day to about 10 g/day, about 2.5 g/day to about 15 g/day, about 2.5 g/day to about 20 g/day, about 2.5 g/day to about 25 g/day, about 2.5 g/day to about 30 g/day, about 5 g/day to about 7.5 g/day, about 5 g/day to about 10 g/day, about 5 g/day to about 15 g/day, about 5 g/day to about 20 g/day, about 5 g/day to about 25 g/day, about 5 g/day to about 30 g/day, about 7.5 g/day to about 10 g/day, about 7.5 g/day to about 15 g/day, about 7.5 g/day to about 20 g/day, about 7.5 g/day to about 25 g/day, about 7.5 g/day to about 30 g/day, about 10 g/day to about 15 g/day, about 10 g/day to about 20 g/day, about 10 g/day to about 25 g/day, about 10 g/day to about 30 g/day, about 15 g/day to about 20 g/day, about 15 g/day to about 25 g/day, about 15 g/day to about 30 g/day, about 20 g/day to about 25 g/day, about 20 g/day to about 30 g/day, or about 25 g/day to about 30 g/day.

[0047] In some embodiments, a therapeutically effective amount of an allulose present in a composition or medicament disclosed herein that is administered to an individual is an amount that is sufficient to affect the metabolism of an individual to promote wight loss in a healthy manner. In aspects of these embodiments, an effective amount of an allulose present in a composition or medicament disclosed herein that is administered to an individual can be, e.g., about 10 g/day to about 30 g/day, about 10 g/day to about 35 g/day, about 10 g/day to about 40 g/day, about 10 g/day to about 45 g/day, about 10 g/day to about 50 g/day, about 10 g/day to about 55 g/day, about 10 g/day to about 60 g/day, about 10 g/day to about 65 g/day, about 10 g/day to about 70 g/day, about 10 g/day to about 75 g/day, about 10 g/day to about 80 g/day, about 15 g/day to about 30 g/day, about 15 g/day to about 35 g/day, about 15 g/day to about 40 g/day, about 15 g/day to about 45 g/day, about 15 g/day to about 50 g/day, about 15 g/day to about 55 g/day, about 15 g/day to about 60 g/day, about 15 g/day to about 65 g/day, about 15 g/day to about 70 g/day, about 15 g/day to about 75 g/day, about 15 g/day to about 80 g/day, about 20 g/day to about 30 g/day, about 20 g/day to about 35 g/day, about 20 g/day to about 40 g/day, about 20 g/day to about 45 g/day, about 20 g/day to about 50 g/day, about 20 g/day to about 55 g/day, about 20 g/day to about 60 g/day, about 20 g/day to about 65 g/day, about 20 g/day to about 70 g/day, about 20 g/day to about 75 g/day, about 20 g/day to about 80 g/day, about 25 g/day to about 30 g/day, about 25 g/day to about 35 g/day, about 25 g/day to about 40 g/day, about 25 g/day to about 45 g/day, about 25 g/day to about 50 g/day, about 25 g/day to about 55 g/day, about 25 g/day to about 60 g/day, about 25 g/day to about 65 g/day, about 25 g/day to about 70 g/day, about 25 g/day to about 75 g/day, about 25 g/day to about 80 g/day, about 30 g/day to about 35 g/day, about 30 g/day to about 40 g/day, about 30 g/day to about 45 g/day, about 30 g/day to about 50 g/day, about 30 g/day to about 55 g/day, about 30 g/day to about 60 g/day, about 30 g/day to about 65 g/day, about 30 g/day to about 70 g/day, about 30 g/day to about 75 g/day, about 30 g/day to about 80 g/day, about 35 g/day to about 40 g/day, about 35 g/day to about 45 g/day, about 35 g/day to about 50 g/day, about 35 g/day to about 55 g/day, about 35 g/day to about 60 g/day, about 35 g/day to about 65 g/day, about 35 g/day to about 70 g/day, about 35 g/day to about 75 g/day, about 35 g/day to about 80 g/day, about 40 g/day to about 45 g/day, about 40 g/day to about 50 g/day, about 40 g/day to about 55 g/day, about 40 g/day to about 60 g/day, about 40 g/day to about 65 g/day, about 40 g/day to about 70 g/day, about 40 g/day to about 75 g/day, or about 40 g/day to about 80 g/day.

[0048] Dosing can be single dosage or cumulative (serial dosing), and can be readily determined by one skilled in the art. For instance, treatment of weight loss may comprise a one-time administration of an effective dose of a composition or medicament disclosed herein. Alternatively, treatment of weight loss may comprise multiple administrations of an effective dose of a composition or medicament disclosed herein carried out over a range of time periods, such as, e.g., once daily, twice daily, thrice daily, once every few days, or once weekly. The timing of administration can vary from individual to individual, depending upon such factors as the severity of an individual's symptoms. For example, an effective dose of a composition or medicament disclosed herein can be administered to an individual once daily for an indefinite period of time, or until the individual no longer requires weight loss treatment. A person of ordinary skill in the art will recognize that the condition of the individual can be monitored throughout the course of treatment and that the effective amount of a composition or medicament disclosed herein that is administered can be adjusted accordingly.

[0049] A method or use disclosed herein administers a composition disclosed herein to an individual. An individual refers to any mammal including a human, a horse, a cow, a sheep, a dog, and a cat. As such, a method disclosed herein is for human use as well as veterinarian use.

[0050] In some embodiments, a method or use disclosed herein promotes or enhances weight loss in an individual. In an embodiment, an individual in need of weight loss is an overweight individual. In another embodiment, an individual in need of weight loss is obese or suffers from obesity. Overweight is a condition of excessive fat deposits while obesity is a chronic complex disease defined by excessive fat deposits that can impair health. The diagnosis of overweight and obesity is made by measuring an individual’s weight and height and by calculating the body mass index (BMI): weight (kg)Zheight² (m²). The body mass index is a surrogate marker of fatness and additional measurements, such as the waist circumference, can help the diagnosis of obesity. The BMI categories for defining obesity vary by age and gender in infants, children and adolescents. For adults, the World Health Organization (WHO) defines an overweight adult individual as an individual having a BMI greater than or equal to 25, an overweight child individual between 5 to 18 years of age as an individual having a BMI greater than 1 standard deviation above the WHO Growth Reference median, and an overweight child under 5 years of age as an individual having a BMI greater than 2 standard deviations above the WHO Growth Reference median. For adults, the WHO defines an obese adult individual as an individual having a BMI greaterthan or equal to 30, an obese child individual between 5 to 18 years of age as an individual having a BMI greater than 2 standard deviations above the WHO Growth Reference median, and an obese child under 5 years of age as an individual having a BMI greater than 3 standard deviations above the WHO Growth Reference median.

[0051] In some embodiments, a method or use disclosed herein treats or manages a metabolic disease. A metabolic disease is any disease or disorder that disrupts normal sum of the chemical reactions that take place within each cell of an individual necessary for life, including providing energy for vital processes and synthesizing new organic material. Nonlimiting examples of a metabolic disease include a kidney disease. A kidney disease includes a polycystic kidney disease.

[0052] Aspects of the present specification can also be described by the following embodiments:

1 . A composition comprising about 5% to about 25% by weight of the composition of one or more P-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors, and about 60% to about 90% by weight of the composition of an allulose.

2. The composition of embodiment 1 , wherein the one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors, are present in an amount of about 7.5% to about 22.5%, about 12.5% to about 22.5%, about 15% to about 25%, about 10% to about 20%, about 10.5% to about 19%, about 1 1 % to about 18%, about 12% to about 17%, about 13% to about 16%, or about 14% to about 15%, by weight of the composition.

3. The composition of embodiment 1 or 2, wherein the one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors, are each present in an amount of about 0.5% to about 10%, about 1 % to about 9%, about 1 .5% to about 8,5%, about 2% to about 8%, about 2.5% to about 7.5%, about 3% to about 7%, or about 3.5% to about 6.5%, by weight of the composition.

4. The composition of any one of embodiment 1 -3, wherein the allulose is present in an amount of about 65% to about 85%, about 80% to about 90%, about 75% to about 85%, about 70% to about 80%, about 71% to about 79%, about 72% to about 78%, about 73% to about 77%, about 74% to about 76%, by weight of the composition.

5. The composition of any one of embodiment 1 -4, wherein the one of more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors, and the allulose are in a ratio of about 1 :3 to 1 :7 BHB to allulose, about 1 :4 to 1 :6 BHB to allulose, about 1 :4.5 to 1 :5.5 BHB to allulose, about 1 :5.0 to about 1 :5.4 BHB to allulose, about 1 :5.1 to about 1 :5.3 BHB to allulose, or about 1 :5.2 BHB to allulose. The composition of any one of embodiment 1 -5, wherein the one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors, include a D-p-hydroxybutyrate, or a salt or ester thereof, a L-p-hydroxybutyrate, or a salt or ester thereof, or any combination thereof. The composition of any one of embodiment 1-6, wherein the one or more p-hydroxybutyrate salts include a magnesium p-hydroxybutyrate salt, a potassium p-hydroxybutyrate salt, a calcium p-hydroxybutyrate salt, a sodium p-hydroxybutyrate salt, or any combination thereof. The composition of embodiment 7, wherein the magnesium p-hydroxybutyrate salt is present in an amount of about 1.5% to about 8.5% by weight of the composition, the potassium p- hydroxybutyrate salt is present in an amount of about 1 .5% to about 8.5% by weight of the composition, the calcium p-hydroxybutyrate salt is present in an amount of about 1.5% to about 8.5% by weight of the composition, and the sodium p-hydroxybutyrate salt is present in an amount of about 1.5% to about 8.5% by weight of the composition. The composition of embodiment 8, wherein the magnesium p-hydroxybutyrate salt is present in an amount of about 2% to about 8%, about 2.5% to about 7.5%, about 3% to about 7%, or about 3.5% to about 6.5% by weight of the composition, the potassium p-hydroxybutyrate salt is present in an amount of about 2% to about 8%, about 2.5% to about 7.5%, about 3% to about 7%, or about 3.5% to about 6.5% by weight of the composition, the calcium p- hydroxybutyrate salt is present in an amount of about 2% to about 8%, about 2.5% to about 7.5%, about 3% to about 7%, or about 3.5% to about 6.5% by weight of the composition, and the sodium p-hydroxybutyrate salt is present in an amount of about 2% to about 8%, about 2.5% to about 7.5%, about 3% to about 7%, or about 3.5% to about 6.5% by weight of the composition. The composition of embodiment 7, wherein the magnesium p-hydroxybutyrate salt is present in an amount of about 2.5% to about 8.5% by weight of the composition, the potassium p- hydroxybutyrate salt is present in an amount of about 2% to about 8% by weight of the composition, the calcium p-hydroxybutyrate salt is present in an amount of about 1.5% to about 7.5% by weight of the composition, and the sodium p-hydroxybutyrate salt is present in an amount of about 1.5% to about 8.5% by weight of the composition. The composition of embodiment 10, wherein the magnesium p-hydroxybutyrate salt is present in an amount of about 3% to about 8%, about 3.5% to about 7.5%, about 4% to about 7%, or about 4.5% to about 6.5% by weight of the composition, the potassium p-hydroxybutyrate salt is present in an amount of about 2.5% to about 7.5%, about 3% to about 7%, about 3.5% to about 6.5%, or about 4% to about 6% by weight of the composition, the calcium p- hydroxybutyrate salt is present in an amount of about 2% to about 7%, about 2.5% to about 6.5%, about 3% to about 6%, or about 3.5% to about 5.5% by weight of the composition, and the sodium p-hydroxybutyrate salt is present in an amount of about 2% to about 8%, about 2.5% to about 7.5%, about 3% to about 7%, or about 3.5% to about 6.5% by weight of the composition. The composition of any one of embodiment 1-11 further comprising citric acid or a citrate, a dietary fiber, one or more flavorings, or any combination thereof. The composition of any one of embodiment 1-12, wherein the composition is formulated as a dry powdered composition. The composition of any one of embodiment 1-13, wherein the composition is a medical food, a conventional food, a dietary supplement, or a therapeutic drug. The composition of any one of embodiment 1-14, wherein the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors, and the allulose are in a synergistic combination. A method of promoting or enhancing weight loss in an individual, the method comprising administering an effective amount of a composition according to any one of embodiments 1- 15, wherein the effective amount of the composition is about 15 g/day to 80 g/day of an allulose and about 2.5 g/day to 30 g/day of one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors,. The method of embodiment 16, wherein the effective amount of the composition is about 20 g/day to 60 g/day of the allulose and about 3 g/day to 20 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The method of embodiment 17, wherein the effective amount of the composition is about 35 g to about 45 g/day of the allulose and about 5 g/day to about 10 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The method of any one of embodiment 16-18, wherein the individual is obese or overweight. A composition according to any one of embodiments 1-15 for use in promoting or enhancing weight loss in an individual, wherein the effective amount of the composition is about 15 g/day to 80 g/day of an allulose and about 2.5 g/day to 30 g/day of one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors,. The composition of embodiment 20, wherein the effective amount of the composition is about 20 g/day to 60 g/day of the allulose and about 3 g/day to 20 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The composition of embodiment 21 , wherein the effective amount of the composition is about 35 g to about 45 g/day of the allulose and about 5 g/day to about 10 g/day of the one or more P-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The composition of any one of embodiment 20-22, wherein the individual is obese or overweight. Use of a composition according to any one of embodiments 1-15 in promoting or enhancing weight loss in an individual, wherein the effective amount of the composition is about 15 g/day to 80 g/day of an allulose and about 2.5 g/day to 30 g/day of one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors,. The use of embodiment 24, wherein the effective amount of the composition is about 20 g/day to 60 g/day of the allulose and about 3 g/day to 20 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The use of embodiment 25, wherein the effective amount of the composition is about 35 g to about 45 g/day of the allulose and about 5 g/day to about 10 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The use of any one of embodiment 24-26, wherein the individual is obese or overweight. Use of a composition according to any one of embodiments 1-15 15 in the manufacture of a medicament for promoting or enhancing weight loss in an individual, wherein the effective amount of the composition is about 15 g/day to 80 g/day of an allulose and about 2.5 g/day to 30 g/day of one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors,. The use of embodiment 28, wherein the effective amount of the composition is about 20 g/day to 60 g/day of the allulose and about 3 g/day to 20 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The use of embodiment 29, wherein the effective amount of the composition is about 35 g to about 45 g/day of the allulose and about 5 g/day to about 10 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The use of any one of embodiment 28-30, wherein the individual is obese or overweight. A method of treating or managing a metabolic disease in an individual, the method comprising administering an effective amount of a composition according to any one of embodiments 1- 15, wherein the effective amount of the composition is about 15 g/day to 80 g/day of an allulose and about 2.5 g/day to 30 g/day of one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors,. The method of embodiment 32, wherein the effective amount of the composition is about 20 g/day to 60 g/day of the allulose and about 3 g/day to 20 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The method of embodiment 33, wherein the effective amount of the composition is about 35 g to about 45 g/day of the allulose and about 5 g/day to about 10 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The method of any one of embodiments 32-34, wherein the metabolic disease is a kidney disease. The method of embodiment 35, wherein the kidney disease is a polycystic kidney disease. A composition according to any one of embodiments 1-15 for use in treating or managing a metabolic disease in an individual, wherein the effective amount of the composition is about 15 g/day to 80 g/day of an allulose and about 2.5 g/day to 30 g/day of one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors,. The composition of embodiment 37, wherein the effective amount of the composition is about 20 g/day to 60 g/day of the allulose and about 3 g/day to 20 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The composition of embodiment 38, wherein the effective amount of the composition is about 35 g to about 45 g/day of the allulose and about 5 g/day to about 10 g/day of the one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The composition of any one of embodiments 37-39, wherein the metabolic disease is a kidney disease. The composition of embodiment 40, wherein the kidney disease is a polycystic kidney disease. Use of a composition according to any one of embodiments 1-15 in treating or managing a metabolic disease in an individual, wherein the effective amount of the composition is about 15 g/day to 80 g/day of an allulose and about 2.5 g/day to 30 g/day of one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors,. The use of embodiment 42, wherein the effective amount of the composition is about 20 g/day to 60 g/day of the allulose and about 3 g/day to 20 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The use of embodiment 43, wherein the effective amount of the composition is about 35 g to about 45 g/day of the allulose and about 5 g/day to about 10 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The use of any one of embodiments 42-44, wherein the metabolic disease is a kidney disease. The use of embodiment 45, wherein the kidney disease is a polycystic kidney disease. Use of a composition according to any one of embodiments 1-15 in the manufacture of a medicament for treating or managing a metabolic disease in an individual, wherein the effective amount of the composition is about 15 g/day to 80 g/day of an allulose and about 2.5 g/day to 30 g/day of one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors,. The use of embodiment 47, wherein the effective amount of the composition is about 20 g/day to 60 g/day of the allulose and about 3 g/day to 20 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. The use of embodiment 48, wherein the effective amount of the composition is about 35 g to about 45 g/day of the allulose and about 5 g/day to about 10 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors. 50. The use of any one of embodiments 47-49, wherein the metabolic disease is a kidney disease.

51 . The use of embodiment 50, wherein the kidney disease is a polycystic kidney disease.

EXAMPLES

[0053] The following non-limiting examples are provided for illustrative purposes only in order to facilitate a more complete understanding of representative embodiments now contemplated. These examples should not be construed to limit any of the embodiments described in the present specification, including those pertaining to the compounds, pharmaceutical compositions, or methods and uses disclosed herein.

Example 1 Weight Loss Study

[0054] A study was conducted to evaluate the weight loss effectiveness of a composition disclosed herein by recruiting five volunteers to participate in a 30-day evaluation. Each participant received a supply of a composition disclosed herein formulated as ready-to-mix dry powder product (see Table 1) with instructions to prepare 1 L (or about 32 oz) of a composition disclosed herein by mixing 26.4 g (3/4 scoop) of ready-to-mix dry powder product into water contained in a hydration bottle. For each day of the study, participants were instructed to drink 2 liters (about 64 oz) of the study composition by sipping the composition throughout the morning and afternoon. Participants were advised to maintain their regular diet but eat only when hungry and stop when comfortably full. Each participant weighed themselves daily at a consistent time, such as in the morning or evening, and recorded their weight on an evaluation form. At the end of the evaluation period, participants submitted their forms, which included daily weight records and responses to questions assessing the product’s effectiveness for weight loss, tolerability, impact on daily life, and satisfaction with various aspects such as taste and ease of use. [0055] The results of the study indicated that, on average, participants who used the study composition for 30 days experienced a significant decrease of 2.7% body weight (P<0.05). For Example, as shown in FIG. 1 , except for Subject 3, all subjects lost at least 2.4% of body weight over the 30 day evaluation period with Subject 2 losing 2.4% body weight, Subject 1 losing 2.8% body weight, Subject 5 losing 3.1% body weight, and Subject 4 losing 3.6% body weight. Subject 3 lost 1 .7% body weight overthe course of the study. Interestingly, Subject 3 reported not drinking the test composition on Day 17 through Day 21 , and this 3-day interruption in the treatment could explain why less weight loss was observed in this subject relative to the other four participants. Besides showing statistically significant weight loss efficacy, the study composition was generally well-tolerated, though one tester reported minor discomfort, such as body itchiness. Questionnaire feedback indicated that the study composition helped with satiety and snacking, and most participants expressed a willingness to continue using it to achieve their weight loss goals. The main challenges were increased hydration requirements and difficulties incorporating the study composition into social or weekend activities. These results are surprising, and simply not expected, given that studies have shown that BHB, or salt or ester thereof, or a BHB precursor, alone has modest effects on weight loss and allulose alone have minimal efficacy in promoting weight loss. Thus, allulose surprisingly and unexpectedly enhanced the weight loss properties of BHB, or salt or ester thereof, or a BHB precursor. As such, the study revealed that a composition disclosed herein results in robust weight loss in individuals that is significantly better than using BHB, or salt or ester thereof, or allulose alone in achieving substantial weight loss in an individual.

[0056] Furthermore, when compared to a publication on a large study group on body weight loss, the test composition disclosed herein achieved better results than semaglutide. As shown in FIG. 2, the reported body weight loss percentage of a group receiving semaglutide was 2.3% with the placebo group reported a weight loss percentage of only 1.0%. However, the data obtained from the disclosed study of five participants demonstrated an average weight loss percentage of 2.7%. These results reveal that a composition disclosed herein results in robust weight loss in individuals that appears to be on par with the effect of semaglutide in achieving substantial weight loss in an individual.

[0057] In closing, foregoing descriptions of embodiments of the present invention have been presented for the purposes of illustration and description. It is to be understood that, although aspects of the present invention are highlighted by referring to specific embodiments, one skilled in the art will readily appreciate that these described embodiments are only illustrative of the principles comprising the present invention and such examples are not limiting thereto. As such, the specific embodiments are not intended to be exhaustive or to limit the invention to the precise forms disclosed. The use of any and all examples or exemplary language (e.g., “such as”) provided herein is intended merely to better illuminate the present invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the present specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[0058] In addition, groupings of alternative embodiments, elements, steps and/or limitations of the present invention are not to be construed as limitations. Each such grouping may be referred to and claimed individually or in any combination with other groupings disclosed herein. It is anticipated that one or more alternative embodiments, elements, steps and/or limitations of a grouping may be included in, or deleted from, the grouping for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the grouping as modified, thus fulfilling the written description of all Markush groups used in the appended claims. In addition, all methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. Therefore, it should be understood that embodiments of the disclosed subject matter are in no way limited to a particular element, compound, composition, component, article, apparatus, methodology, use, protocol, step, and/or limitation described herein, unless expressly stated as such.

[0059] While aspects of the inventive subject matter have been described with reference to at least one exemplary embodiment, it is to be clearly understood by those skilled in the art that the inventive subject matter is not limited thereto. For example, although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus, if one embodiment comprises elements A, B, and C, and a second embodiment comprises elements B and D, then the inventive subject matter is also considered to include other remaining combinations of A, B, C, or D, even if not explicitly disclosed. Furthermore, those of ordinary skill in the art will recognize that certain changes, modifications, permutations, alterations, additions, subtractions, and subcombinations thereof can be made in accordance with the teachings herein without departing from the spirit of the present inventive subject matter. Thus, while the inventive subject matter is susceptible of various modifications and alternative embodiments, certain illustrated embodiments thereof are shown in the drawings and will be described below in detail. It should be understood, however, that there is no intention to limit the inventive subject matter to any specific form disclosed, but on the contrary, the inventive subject matter is to cover all modifications, alternative embodiments, and equivalents falling within the scope of the claims. It is intended that the following appended claims and claims hereafter introduced are interpreted to include all such changes, modifications, permutations, alterations, additions, subtractions, and sub-combinations as are within their true spirit and scope. Accordingly, the scope of the present inventive subject matter is not to be limited to that precisely as shown and described by this specification. Rather, the scope of the inventive subject matter is to be interpreted only in conjunction with the appended claims and it is made clear, here, that the inventor(s) believe that the claimed subject matter is the inventive subject matter.

[0060] Certain embodiments of the present inventive subject matter are described herein, including the best mode known to the inventors for conducting the inventive subject matter. Of course, variations on these described embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventor expects skilled artisans to employ such variations as appropriate, and the inventors intend for the present inventive subject matter to be practiced otherwise than specifically described herein. Accordingly, this inventive subject matter includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the abovedescribed embodiments in all possible variations thereof is encompassed by the inventive subject matter unless otherwise indicated herein or otherwise clearly contradicted by context.

[0061] The words, language, and terminology used in this specification is for the purpose of describing particular embodiments, elements, steps and/or limitations only and is not intended to limit the scope of the present inventive subject matter, which is defined solely by the claims. In addition, such words, language, and terminology are to be understood not only in the sense of their commonly defined meanings, but to include by special definition in this specification structure, material or acts beyond the scope of the commonly defined meanings. Thus, if an element, step or limitation can be understood in the context of this specification as including more than one meaning, then its use in a claim must be understood as being generic to all possible meanings supported by the specification and by the word itself.

[0062] The definitions and meanings of the elements, steps or limitations recited in a claim set forth below are, therefore, defined in this specification to include not only the combination of elements, steps or limitations which are literally set forth, but all equivalent structure, material or acts for performing substantially the same function in substantially the same way to obtain substantially the same result. In this sense it is therefore contemplated that an equivalent substitution of two or more elements, steps and/or limitations may be made for any one of the elements, steps or limitations in a claim set forth below or that a single element, step, or limitation may be substituted for two or more elements, steps and/or limitations in such a claim. Although elements, steps or limitations may be described above as acting in certain combinations and even initially claimed as such, it is to be expressly understood that one or more elements, steps and/or limitations from a claimed combination can in some cases be excised from the combination and that the claimed combination may be directed to a sub-combination or variation of a subcombination. As such, notwithstanding the fact that the elements, steps and/or limitations of a claim are set forth below in a certain combination, it must be expressly understood that the inventive subject matter includes other combinations of fewer, more, or different elements, steps and/or limitations, which are disclosed in above combination even when not initially claimed in such combinations. Furthermore, insubstantial changes from the claimed subject matter as viewed by a person with ordinary skill in the art, now known or later devised, are expressly contemplated as being equivalently within the scope of the claims. Therefore, obvious substitutions now or later known to one with ordinary skill in the art are defined to be within the scope of the defined elements. Accordingly, the claims are thus to be understood to include what is specifically illustrated and described above, what is conceptually equivalent, what can be obviously substituted and also what essentially incorporates the essential idea of the inventive subject matter.

[0063] Unless otherwise indicated, all numbers expressing a characteristic, item, quantity, parameter, property, term, and so forth used in the present specification and claims are to be understood as being modified in all instances by the term “about.” As used herein, the term “about” means that the characteristic, item, quantity, parameter, property, or term so qualified encompasses a range of plus or minus ten percent above and below the value of the stated characteristic, item, quantity, parameter, property, or term. Similarly, as used herein, unless indicated to the contrary, the term “substantially” is a term of degree intended to indicate an approximation of the characteristic, item, quantity, parameter, property, or term so qualified, encompassing a range that can be understood and construed by those of ordinary skill in the art. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical indication should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0064] Notwithstanding that the numerical ranges and values setting forth the broad scope of the inventive subject matter are approximations, the numerical ranges and values set forth in the specific examples are reported as precisely as possible. Any numerical range or value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Unless the context dictates the contrary, all ranges set forth herein should be interpreted as being inclusive of their endpoints and open-ended ranges should be interpreted to include only commercially practical values. Recitation of numerical ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate numerical value falling within the range. Unless otherwise indicated herein, each individual value of a numerical range is incorporated into the present specification as if it were individually recited herein. Similarly, all lists of values should be considered as inclusive of intermediate values unless the context indicates the contrary.

[0065] Use of the terms “may” or “can” in reference to an embodiment or aspect of an embodiment also carries with it the alternative meaning of “may not” or “cannot.” As such, if the present specification discloses that an embodiment or an aspect of an embodiment may be or can be included as part of the inventive subject matter, then the negative limitation or exclusionary proviso is also explicitly meant, meaning that an embodiment or an aspect of an embodiment may not be or cannot be included as part of the inventive subject matter. In a comparable manner, use of the term “optionally” in reference to an embodiment or aspect of an embodiment means that such embodiment or aspect of the embodiment may be included as part of the inventive subject matter or may not be included as part of the inventive subject matter. Whether such a negative limitation or exclusionary proviso applies will be based on whether the negative limitation or exclusionary proviso is recited in the claimed subject matter.

[0066] The terms “a,” “an,” “the” and similar references used in the context of describing the present inventive subject matter (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Further, ordinal indicators - such as, e.g., “first,” “second,” “third,” etc. - for identified elements are used to distinguish between the elements, and do not indicate or imply a required or limited number of such elements, and do not indicate a particular position or order of such elements unless otherwise specifically stated.

[0067] When used in the claims, whether as filed or added per amendment, the open-ended transitional term “comprising”, variations thereof such as, e.g., “comprise” and “comprises”, and equivalent open-ended transitional phrases thereof like “including”, “containing” and “having”, encompass all the expressly recited elements, limitations, steps, integers, and/or features alone or in combination with unrecited subject matter; the named elements, limitations, steps, integers, and/or features are essential, but other unnamed elements, limitations, steps, integers, and/or features may be added and still form a construct within the scope of the claim. Specific embodiments disclosed herein may be further limited in the claims using the closed-ended transitional phrases “consisting of’ or “consisting essentially of’ (or variations thereof such as, e.g., “consist of’, “consists of’, “consist essentially of’, and “consists essentially of’) in lieu of or as an amendment for “comprising.” When used in the claims, whether as filed or added per amendment, the closed-ended transitional phrase “consisting of’ excludes any element, limitation, step, integer, or feature not expressly recited in the claims. The closed-ended transitional phrase “consisting essentially of’ limits the scope of a claim to the expressly recited elements, limitations, steps, integers, and/or features and any other elements, limitations, steps, integers, and/or features that do not materially affect the basic and novel characteristic(s) of the claimed subject matter. Thus, the meaning of the open-ended transitional phrase “comprising” is being defined as encompassing all the specifically recited elements, limitations, steps and/or features as well as any optional, additional unspecified ones. The meaning of the closed-ended transitional phrase “consisting of’ is being defined as only including those elements, limitations, steps, integers, and/or features specifically recited in the claim, whereas the meaning of the closed- ended transitional phrase “consisting essentially of’ is being defined as only including those elements, limitations, steps, integers, and/or features specifically recited in the claim and those elements, limitations, steps, integers, and/or features that do not materially affect the basic and novel characteristic(s) of the claimed subject matter. Therefore, the open-ended transitional phrase “comprising” (and equivalent open-ended transitional phrases thereof) includes within its meaning, as a limiting case, claimed subject matter specified by the closed-ended transitional phrases “consisting of’ or “consisting essentially of.” As such, the embodiments described herein or so claimed with the phrase “comprising” expressly and unambiguously provide description, enablement, and support for the phrases “consisting essentially of’ and “consisting of.”

[0068] It should be apparent to those skilled in the art that many more modifications besides those already described are possible without departing from the inventive concepts herein. The inventive subject matter, therefore, is not to be restricted except in the spirit of the appended claims. Moreover, in interpreting both the specification and the claims, all terms should be interpreted in the broadest possible manner consistent with the context. In particular, the terms “comprises” and “comprising” should be interpreted as referring to elements, components, or steps in a non-exclusive manner, indicating that the referenced elements, components, or steps may be present, or utilized, or combined with other elements, components, or steps that are not expressly referenced. Where the specification claims refers to at least one of something selected from the group consisting of A, B, C .... and N, the text should be interpreted as requiring only one element from the group, not A plus N, or B plus N, etc.

[0069] Any claims intended to be treated under 35 U.S.C. §112(f) will begin with the words “means for,” but use of the term “for” in any other context is not intended to invoke treatment under 35 U.S.C. §112(f). Accordingly, Applicant reserves the right to pursue additional claims after filing this application, in either this application or in a continuing application. [0070] It should be understood that the methods and the order in which the respective elements of each method are performed are purely exemplary. Depending on the implementation, they may be performed in any order or in parallel, unless indicated otherwise in the present disclosure.

[0071] Finally, all patents, patent publications, and other references cited and identified in the present specification are individually and expressly incorporated herein by reference in their entirety to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. These publications are provided solely for their disclosure prior to the filing date of the present application. The reference to any prior art in this specification is not, and should not be taken as, an acknowledgement or any form of suggestion that the prior art forms part of the common general knowledge from any country. In addition, where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply. Lastly, nothing in this regard is or should be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention or for any other reason. All statements as to the date or representation as to the contents of these documents are based on the information available to the applicant and do not constitute any admission as to the correctness of the dates or contents of these documents.

Claims

2. The composition of claim 1 , wherein the one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors, are present in an amount of about 7.5% to about 22.5%, about 12.5% to about 22.5%, about 15% to about 25%, about 10% to about 20%, about 10.5% to about 19%, about 1 1% to about 18%, about 12% to about 17%, about 13% to about 16%, or about 14% to about 15%, by weight of the composition.

3. The composition of claim 1 or 2, wherein the one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors, are each present in an amount of about 0.5% to about 10%, about 1% to about 9%, about 1 .5% to about 8,5%, about 2% to about 8%, about 2.5% to about 7.5%, about 3% to about 7%, or about 3.5% to about 6.5%, by weight of the composition.

4. The composition of any one of claim 1-3, wherein the allulose is present in an amount of about 65% to about 85%, about 80% to about 90%, about 75% to about 85%, about 70% to about 80%, about 71 % to about 79%, about 72% to about 78%, about 73% to about 77%, about 74% to about 76%, by weight of the composition.

5. The composition of any one of claim 1 -4, wherein the one of more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors, and the allulose are in a ratio of about 1 :3 to 1 :7 BHB to allulose, about 1 :4 to 1 :6 BHB to allulose, about 1 :4.5 to 1 :5.5 BHB to allulose, about 1 :5.0 to about 1 :5.4 BHB to allulose, about 1 :5.1 to about 1 :5.3 BHB to allulose, or about 1 :5.2 BHB to allulose.

6. The composition of any one of claim 1 -5, wherein the one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors, include a D-p-hydroxybutyrate, or a salt or ester thereof, a L-p-hydroxybutyrate, or a salt or ester thereof, or any combination thereof.

7. The composition of any one of claim 1-6, wherein the one or more p-hydroxybutyrate salts include a magnesium p-hydroxybutyrate salt, a potassium p-hydroxybutyrate salt, a calcium P-hydroxybutyrate salt, a sodium p-hydroxybutyrate salt, or any combination thereof.

8. The composition of claim 7, wherein the magnesium p-hydroxybutyrate salt is present in an amount of about 1.5% to about 8.5% by weight of the composition, the potassium p- hydroxybutyrate salt is present in an amount of about 1 .5% to about 8.5% by weight of the composition, the calcium p-hydroxybutyrate salt is present in an amount of about 1.5% to about 8.5% by weight of the composition, and the sodium p-hydroxybutyrate salt is present in an amount of about 1 .5% to about 8.5% by weight of the composition.

9 The composition of claim 8, wherein the magnesium p-hydroxybutyrate salt is present in an amount of about 2% to about 8%, about 2.5% to about 7.5%, about 3% to about 7%, or about 3.5% to about 6.5% by weight of the composition, the potassium p-hydroxybutyrate salt is present in an amount of about 2% to about 8%, about 2.5% to about 7.5%, about 3% to about 7%, or about 3.5% to about 6.5% by weight of the composition, the calcium p-hydroxybutyrate salt is present in an amount of about 2% to about 8%, about 2.5% to about 7.5%, about 3% to about 7%, or about 3.5% to about 6.5% by weight of the composition, and the sodium p- hydroxybutyrate salt is present in an amount of about 2% to about 8%, about 2.5% to about 7.5%, about 3% to about 7%, or about 3.5% to about 6.5% by weight of the composition.

10. The composition of claim 7, wherein the magnesium p-hydroxybutyrate salt is present in an amount of about 2.5% to about 8.5% by weight of the composition, the potassium p- hydroxybutyrate salt is present in an amount of about 2% to about 8% by weight of the composition, the calcium p-hydroxybutyrate salt is present in an amount of about 1.5% to about 7.5% by weight of the composition, and the sodium p-hydroxybutyrate salt is present in an amount of about 1 .5% to about 8.5% by weight of the composition.

1 1 The composition of claim 10, wherein the magnesium p-hydroxybutyrate salt is present in an amount of about 3% to about 8%, about 3.5% to about 7.5%, about 4% to about 7%, or about 4.5% to about 6.5% by weight of the composition, the potassium p-hydroxybutyrate salt is present in an amount of about 2.5% to about 7.5%, about 3% to about 7%, about 3.5% to about 6.5%, or about 4% to about 6% by weight of the composition, the calcium p- hydroxybutyrate salt is present in an amount of about 2% to about 7%, about 2.5% to about 6.5%, about 3% to about 6%, or about 3.5% to about 5.5% by weight of the composition, and the sodium p-hydroxybutyrate salt is present in an amount of about 2% to about 8%, about 2.5% to about 7.5%, about 3% to about 7%, or about 3.5% to about 6.5% by weight of the composition.

12. The composition of any one of claim 1-1 1 further comprising citric acid or a citrate, a dietary fiber, one or more flavorings, or any combination thereof.

13. The composition of any one of claim 1-12, wherein the composition is formulated as a dry powdered composition.

14. The composition of any one of claim 1-13, wherein the composition is a medical food, a conventional food, a dietary supplement, or a therapeutic drug.

15. The composition of any one of claim 1-14, wherein the one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors, and the allulose are in a synergistic combination.

16. A method of promoting or enhancing weight loss in an individual, the method comprising administering an effective amount of a composition according to any one of claims 1-15, wherein the effective amount of the composition is about 15 g/day to 80 g/day of an allulose and about 2.5 g/day to 30 g/day of one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors,.

17. The method of claim 16, wherein the effective amount of the composition is about 20 g/day to 60 g/day of the allulose and about 3 g/day to 20 g/day of the one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors.

18. The method of claim 17, wherein the effective amount of the composition is about 35 g to about 45 g/day of the allulose and about 5 g/day to about 10 g/day of the one or more p- hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors.

19. The method of any one of claim 16-18, wherein the individual is obese or overweight.

20. A method of treating or managing a metabolic disease in an individual, the method comprising administering an effective amount of a composition according to any one of claims 1-15, wherein the effective amount of the composition is about 15 g/day to 80 g/day of an allulose and about 2.5 g/day to 30 g/day of one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors,.

21. The method of claim 20, wherein the effective amount of the composition is about 20 g/day to 60 g/day of the allulose and about 3 g/day to 20 g/day of the one or more p-hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors.

22. The method of claim 21 , wherein the effective amount of the composition is about 35 g to about 45 g/day of the allulose and about 5 g/day to about 10 g/day of the one or more - hydroxybutyrates, or salts or esters thereof, or one of more BHB precursors.

23. The method of any one of claims 20-22, wherein the metabolic disease is a kidney disease.

24. The method of claim 23, wherein the kidney disease is a polycystic kidney disease.