A method using pre-meal administration of medium-chain triglycerides (MCTs) to increase ketone production from MCTs.

Abstract

This invention provides a method for increasing ketone production induced by oral intake of medium-chain triglycerides (MCTs) by an individual. [Solution] The method involves orally administering a composition containing MCT to an individual, followed by orally administering a meal to the individual at least about 10 minutes after the oral administration of the MCT-containing composition and within about 1 hour after the oral administration of the MCT-containing composition. For example, the meal may be administered about 30 minutes after the administration of the MCT-containing composition. Ketone production is increased compared to ketone production by orally administering MCT and the meal almost simultaneously. The meal may be breakfast. The MCT-containing composition can be an oral nutritional supplement (ONS) solution that provides near-complete nutrition.

Description

Background Art

[0001]

[0001] The present disclosure generally relates to administering medium-chain triglycerides (MCTs) prior to administering a meal, for example, administering MCTs about 30 minutes before a meal.

[0002]

[0002] The two major ketones, beta-hydroxybutyrate (BHB) and acetoacetate (AcA), are important alternative energy sources for extrahepatic tissues such as the brain, heart or skeletal muscle. Furthermore, there is increasing evidence suggesting that ketones may also have a direct or indirect role in signaling. Products aimed at increasing blood ketones may have a therapeutic effect in several conditions including epilepsy, neurological and neurodegenerative diseases, heart failure, diabetic cardiomyopathy, inborn errors of metabolism, obesity, type 2 diabetes, cancer, athletic performance, and non-alcoholic fatty liver disease (NAFLD), such as non-alcoholic steatohepatitis (NASH).

[0003]

[0003] BHB and AcA are actively transported into the brain by monocarboxylate transporter 1 (MCT1), and as a result, the brain concentration is directly proportional to the blood concentration. Therefore, products that provide high and sustained plasma ketone concentrations are expected to have a stronger and longer-lasting (larger area under the AUC curve) effect compared to products with a smaller and shorter increase in plasma ketones (smaller area under the AUC curve). Thus, it is important to maximize exposure to blood ketones. However, factors involved in driving the increase in plasma AUC of ketones from ketone precursors are not known.

[0004]

[0004] Medium-chain triglycerides (MCTs) are efficient ketone precursors when administered orally as a bolus. MCTs are rapidly digested, and the free medium-chain fatty acids (MCFAs) produced by digestion are efficiently absorbed by the portal vein without going through the normal digestion and absorption process of long-chain fatty acids, and are transported to the liver where most of them are metabolized into ketones. These specific formulations may affect the efficiency of ketone body production and gastrointestinal tolerability.

[0005]

[0005] In recent years, the pharmacokinetic (PK) characteristics of various MCT formulations in humans have been reported, showing that the efficiency of endogenous ketone production obtained from MCTs of various chain lengths is diverse, and that MCTs with 8 carbon atoms (C8) are the most effective. In addition, it has been reported that in humans, a good emulsion of MCT oil shows much higher ketone production after oral ingestion compared to unemulsified MCT oil.

[0006]

[0006] However, ketone production from oral intake of MCTs is varied and not optimal. Furthermore, when MCTs are taken without accompanying food, gastrointestinal (GI) side effects such as diarrhea often occur. [Overview of the Initiative]

[0007]

[0007] To the best of the inventors' knowledge, it has not been previously reported that the timing of meals affects the ketone production effect of MCTs. Surprisingly and unexpectedly, as described in more detail below herein, our tests showed that administering the MCT emulsion before meals provided the largest amount of blood ketones without causing GI side effects compared to administering it with meals (the amount of blood ketones provided was less when administered with meals or with meals alone). Specifically, the relative timing of meals strongly influenced ketone production from the MCT emulsion.

[0008]

[0008] Accordingly, in non-limiting embodiments, the present disclosure provides a method for increasing ketone production from medium-chain triglycerides (MCTs). The method includes orally administering a composition comprising MCTs to an individual, and subsequently orally administering a meal to the individual after oral administration of the MCT-containing composition and within about one hour thereafter, for example, at least about 10 minutes and within about one hour thereafter, preferably at least about 15 minutes and within about 40 minutes thereafter, most preferably about 30 minutes thereafter. In one embodiment, the individual is elderly.

[0009]

[0009] For example, oral administration of the composition containing MCT may take place between about 10 minutes before and about 1 hour before the administration of a meal, preferably at least about 15 minutes before and within about 40 minutes before the administration of a meal, and most preferably about 30 minutes before the administration of a meal. Preferably, the individual does not ingest any food products other than any hydration during the period starting with the administration of the composition containing MCT and ending with the administration of a meal.

[0010]

[0010] The composition can be administered to an individual in servings that provide up to about 30 g of MCT per serving, for example, about 5 g to about 30 g of MCT, about 10 g to about 30 g of MCT, or about 15 g to about 30 g of MCT. At least a portion of the MCT may consist of at least one of octanoic acid or decanoic acid. At least a portion of the ketones produced from the MCT can be selected from the group consisting of β-hydroxybutyrate, acetoacetate and mixtures thereof.

[0011]

[0011] In one embodiment, ketone production achieved by administering a composition containing MCT before a meal (for example, administering MCT about 30 minutes before a meal) is greater than ketone production achieved by administering the same composition containing MCT at approximately the same time as the meal. The composition containing MCT may be an oral nutritional supplement (ONS) that provides near-complete nutrition. Optionally, the composition may contain, in addition to MCT, one or more formulation components, for example, optional additional components selected from the group consisting of proteins, carbohydrates, lipids, vitamins, minerals, excipients, emulsifiers, stabilizers, and mixtures thereof. The final formulation may be in liquid form that can be ingested immediately, or in powder form that is reconstituted with water before use.

[0012]

[0012] In another embodiment, a composition comprising MCT is used in a method for treating or preventing a condition in which increased ketone production by MCT is beneficial. The method comprises orally administering the composition comprising MCT to an individual in need of or at risk of administration, and subsequently orally administering a meal to the individual after the oral administration of the composition comprising MCT and within about one hour thereafter, for example, at least about 10 minutes and within about one hour thereafter, preferably at least about 15 minutes and within about 40 minutes thereafter, most preferably about 30 minutes thereafter.

[0013]

[0013] In some embodiments, compositions comprising MCT are used to treat or prevent conditions selected from the group consisting of epilepsy, neurological disorders, neurodegenerative diseases, heart failure, diabetic cardiomyopathy, congenital metabolic disorders, obesity, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cancer, cerebral energy deficiency, migraines, memory impairment, age-related memory impairment, brain injury, stroke, amyloid lateral sclerosis, multiple sclerosis, cognitive impairment, post-intensive care cognitive impairment, age-related cognitive impairment, Alzheimer's disease, Parkinson's disease, Huntington's disease, hereditary metabolic disorders, bipolar disorder, schizophrenia, and combinations thereof.

[0014]

[0014] In another embodiment, the composition comprising MCT is used in a method for improving or maintaining at least one of neurological health, cognitive function, or motor ability. The method comprises orally administering the composition comprising MCT to an individual, and subsequently orally administering a meal to the individual after the oral administration of the composition comprising MCT and within about one hour thereafter, for example, at least about 10 minutes and within about one hour thereafter, preferably at least about 15 minutes and within about 40 minutes thereafter, most preferably about 30 minutes thereafter.

[0015]

[0015] Additional features and advantages will be described in the following detailed description of the invention and in the drawings, and will become apparent therefrom. [Brief explanation of the drawing]

[0016] [Figure 1] This graph shows the change in mean total plasma ketone concentration over 4 hours in relation to the metabolic studies disclosed herein. T0 corresponds to the intake of the MCT product, and the large symbols correspond to the timing of breakfast intake. [Modes for carrying out the invention]

[0017]

[0017] Definition

[0018] The following are some definitions. However, definitions may also be found in the "Embodiments" section below, and the above heading "Definitions" does not mean that such disclosures in the "Embodiments" section are not definitions.

[0018]

[0019] All percentages are expressed by weight relative to the total weight of the composition unless otherwise specified. Similarly, all ratios are expressed by weight unless otherwise specified. As used herein, “about,” “approximately,” and “substantially” are understood to refer to numbers within a numerical range, for example, within -10% to +10% of the reference figure, preferably within -5% to +5%, more preferably within -1% to +1%, and most preferably within -0.1% to +0.1% of the reference figure.

[0019]

[0020] Furthermore, all numerical ranges in this specification should be understood to include all integers, integers, or fractions within that range. Moreover, these numerical ranges should be interpreted as supporting claims that cover any number or subset of a number within that range. For example, a disclosure of 1 to 10 should be interpreted as supporting ranges such as 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, etc. Ranges defined using "between" include the referenced endpoint.

[0020]

[0021] Where used herein and in the appended claims, singular words include plural forms unless the context clearly indicates otherwise. Thus, references to “one,” “a,” and “the” (“a,” “an,” and “the”) generally include the plural forms of the respective terms. For example, when referring to “an ingredient” or “a method,” there are multiple such “ingredients” or “methods.” The term “and / or” used in the context of “X and / or Y” should be interpreted as “X” or “Y” or “X and Y.” Similarly, “at least one of X or Y” should be interpreted as “X” or “Y” or “both X and Y.”

[0021]

[0022] Similarly, the terms “comprise,” “comprises,” and “comprising” should be interpreted inclusively, not exclusively. Likewise, the terms “include,” “including,” and “or” should all be interpreted as encompassing the others unless such interpretation is clearly prevented by the context. However, embodiments provided by this disclosure may not include any elements not specifically disclosed herein. Thus, disclosures of embodiments defined using the term “comprising” are also disclosures of embodiments that “essentially consist of” the disclosed components and embodiments that “consist of.” “Essentially consist of” means that an embodiment or its components contain more than 50% by weight of the individually identified components, preferably at least 75% by weight of the individually identified components, more preferably at least 85% by weight of the individually identified components, and most preferably at least 95% by weight of the individually identified components, for example, at least 99% by weight of the individually identified components.

[0022]

[0023] As used herein, the term “example,” especially when followed by a list of terms, is merely illustrative and descriptive, and should not be considered exclusive or comprehensive. All embodiments disclosed herein can be combined with any other embodiments disclosed herein unless otherwise expressly indicated.

[0023]

[0024] "Animals" include, but are not limited to, rodents, aquatic mammals, domestic animals such as dogs and cats, livestock such as sheep, pigs, cattle and horses, and mammals including, but not limited to, humans. Where "animals" or "mammals," or their plural forms, are used, these terms also apply to any animals that can obtain the effects indicated or intended to be indicated by the context of that section, for example, animals that benefit from ketones. The terms "individual" or "subject" are often used herein to refer to humans, but this disclosure is not limited in that way. Accordingly, the terms "individual" or "subject" refer to any animal, mammal or human that can benefit from the methods and compositions disclosed herein.

[0024]

[0025] Relative terms such as “improved,” “increased,” and “enhanced” refer to the effects of the methods disclosed herein, in particular to the effects of administering the MCT-containing composition before a meal (e.g., about 30 minutes before a meal) compared to administering the same composition containing MCT with or after a meal (e.g., about 30 minutes after a meal). The terms “maintained” and “sustained” mean that individual characteristics such as neurological health, cognitive function, or motor ability are approximately the same as the average level of the previous week, the average level of the previous month, or the average level of the previous year.

[0025]

[0026] As used herein, the terms "treat" and "treatment" mean administering a composition disclosed herein to a subject having a condition, for the purpose of attenuating, reducing or ameliorating at least one symptom associated with the condition and / or for the purpose of delaying, decreasing or preventing the progression of the condition. The terms "treatment" and "treat" include both prophylactic or preventive treatment (treatment that prevents and / or delays the onset of a targeted pathological condition or disorder) and curative, therapeutic or disease-modifying treatment, for example, therapeutic means for curing, delaying, alleviating symptoms, and / or halting the progression of a diagnosed pathological condition or disorder, as well as treatment of patients at risk of developing a disease, or suspected of having a disease, and patients with ill health, or diagnosed with a disease or medical condition. The terms "treatment" and "treat" do not necessarily mean treating the subject until complete recovery. The terms "treatment" and "treat" also refer to maintaining and / or promoting the health of an individual who is not suffering from a disease but is likely to develop an unhealthy condition. The terms "treatment" and "treat" are also intended to include synergistic effects or otherwise enhancement of one or more primary prophylactic or therapeutic means. By way of non-limiting example, treatment can be effected by a patient, caregiver, physician, nurse, or other medical professional.

[0026]

[0027] The terms "prevent" and "prevention" mean administering a composition disclosed herein to a subject that does not exhibit any symptoms of the condition, for the purpose of reducing or preventing the onset of at least one symptom associated with the condition. Further, "prevention" includes reducing the risk, incidence, and / or severity of a condition or disorder. As used herein, an "effective amount" is an amount that treats or prevents a deficiency, treats or prevents a disease or medical condition, or more generally, alleviates symptoms, manages the progression of a disease, or provides nutritional, physiological or medical benefits to an individual.

[0027]

[0028] As used herein, "administering" includes another person providing the composition to an individual such that the individual can ingest the referenced composition, and also includes only the act of the individual himself or herself ingesting the referenced composition.

[0028]

[0029] The terms "food", "food product", and "food composition" are intended for ingestion by an individual such as a human, and mean a composition that provides at least one nutrient to the individual. "Food" and related terms include any food, diet, snack, dietary supplement, treat, meal replacement, or substitute meal for humans or other animals. Animal food includes food or diet for any domesticated or wild species of animal. In a preferred embodiment, the animal food represents extruded pet food such as extruded food for dogs and cats, which is pelleted, extruded, or dried.

[0029]

[0030] As used herein, the terms "serving" or "unit dosage form" are interchangeable and refer to physically discrete units suitable as unit dosages for the intended humans and animals, each unit preferably containing a predetermined amount of a composition comprising MCT disclosed herein in an amount sufficient to provide the desired effect in association with a pharmaceutically acceptable diluent, carrier, or vehicle. The specification of the unit dosage form is determined by the specific compound used, the effect to be achieved, and the pharmacodynamics associated with each compound in the host body. In one embodiment, the unit dosage form can be a predetermined amount of liquid contained within a container such as a bottle.

[0030]

[0031] An “oral nutritional supplement” or “ONS” is a composition comprising at least one major nutrient and / or at least one micronutrient, for example, in the form of a sterile liquid, semi-solid, or powder, and is intended to supplement other nutritional intake, such as from food. Non-limiting examples of commercially available ONS products include MERITENE®, BOOST®, NUTREN®, and SUSTAGEN®. In some embodiments, ONS can be a liquid beverage that can be consumed without further liquid addition, for example, with a liquid volume of one serving of the composition.

[0031]

[0032] As used herein, “incomplete nutrition” preferably refers to a nutritional product in which the major nutrients (proteins, fats, and carbohydrates) or micronutrients contained in the nutritional product are not in sufficient levels to serve as the sole source of nutrition for the animal to which the nutritional product is administered.

[0032]

[0033] The term “kit” means that the components of a kit, in or with one or more containers, are physically related and can be considered as a single unit for manufacture, delivery, sale, or use. Containers include, but are not limited to, bags, boxes, cartons, bottles, packaging of any kind, design, or material, top packaging, shrink wrap, attached components (e.g., stapled or glued), or combinations thereof.

[0033]

[0034] Triglycerides (also known as triacylglycerols or triacylglycerides) are esters derived from glycerol and three fatty acids. The fatty acids may be unsaturated or saturated. Fatty acids that are not bound to other molecules are called free fatty acids (FFAs).

[0034]

[0035] Medium-chain triglycerides (MCTs) are triglycerides in which all three fatty acid portions of the molecule are medium-chain fatty acids. As defined herein, medium-chain fatty acids (MCFAs) are fatty acids having 6 to 12 carbon atoms. Medium-chain fatty acids having 8 carbon atoms may be referred to herein as "C8 fatty acids" or "C8". Medium-chain fatty acids having 10 carbon atoms may be referred to herein as "C10 fatty acids" or "C10".

[0035]

[0036] The term "fatty acid portion" refers to the MCT portion derived from fatty acids in the esterification reaction with glycerol. As a non-limiting example, the esterification reaction between glycerol and octanoic acid alone produces MCT containing the octanoic acid portion. Another non-limiting example is the esterification reaction between glycerol and decanoic acid alone, which produces MCT containing the decanoic acid portion.

[0036]

[0037] Octanoic acid (also known as caprylic acid) is a saturated fatty acid with the formula CH3(CH2)6COOH.

[0037]

[0038] Decanoic acid (also known as capric acid) is a saturated fatty acid with the formula CH3(CH2)8COOH.

[0038]

[0039] Embodiment

[0040] Aspects of this disclosure provide a method for increasing ketone production from medium-chain triglycerides (MCTs). The method includes orally administering a composition comprising MCTs to an individual, and subsequently orally administering a food to the individual after oral administration of the MCT-containing composition and within about one hour thereafter, for example, at least about 10 minutes after oral administration of the MCT-containing composition and within about one hour thereafter, preferably at least about 15 minutes after oral administration of the MCT-containing composition and within about 40 minutes thereafter, most preferably about 30 minutes after oral administration of the MCT-containing composition. As used herein, “subsequently” means at least about 5 minutes, preferably 10 minutes, more preferably at least about 15 minutes, even more preferably at least about 20 minutes, even more preferably at least about 25 minutes, and most preferably about 30 minutes.

[0039]

[0041] As used herein, “meal” refers to one or more food products, each consumed substantially simultaneously, and preferably, as a result, at least one major nutrient and at least one micronutrient are provided by consuming the meal; more preferably, as a result, one or more proteins, one or more carbohydrates, one or more lipids, one or more vitamins and one or more minerals are provided by consuming the meal. Preferably, a meal comprises multiple food products. In one embodiment, the meal provides 200 kcal to 1,000 kcal, preferably 250 kcal to 900 kcal, more preferably 300 kcal to 850 kcal, and most preferably 350 kcal to 800 kcal. In one embodiment, the meal is substantially MCT-free (i.e., less than 2.5% by weight, preferably less than 2.0% by weight, more preferably less than 1.0% by weight, and most preferably less than 0.5% by weight of MCT), or completely MCT-free.

[0040]

[0042] The composition containing MCT may be administered between approximately 10 minutes before and approximately 1 hour before the administration of a meal, preferably between at least approximately 15 minutes before and approximately 40 minutes before the administration of a meal, for example, approximately 30 minutes before the administration of a meal. Preferably, the individual does not consume any food products other than any hydration during the period between the administration of the composition containing MCT and the administration of a meal.

[0041]

[0043] In some embodiments, the meal is breakfast. For example, the composition containing MCTs can be administered to the individual before breakfast, followed by breakfast after the administration of the composition containing MCTs. For example, breakfast may be given between about 10 minutes after the administration of the composition containing MCTs and about 1 hour after the administration of the composition containing MCTs, preferably at least about 15 minutes after the oral administration of the composition containing MCTs and within about 40 minutes after the oral administration of the composition containing MCTs, and most preferably about 30 minutes after the administration of the composition containing MCTs.

[0042]

[0044] As used herein, “breakfast” refers to the first meal consumed by an individual on any given day. For example, breakfast may be consumed before noon according to the individual’s local time, preferably before 11:00 a.m. according to the individual’s local time, more preferably before 10:00 a.m. according to the individual’s local time, and most preferably before 9:00 a.m. according to the individual’s local time, but may also be consumed after the individual has woken from sleep and / or after 4:00 a.m. according to the individual’s local time, preferably after 5:00 a.m. according to the individual’s local time, more preferably after 6:00 a.m. according to the individual’s local time, and most preferably after 7:00 a.m. according to the individual’s local time.

[0043]

[0045] In one embodiment, a serving of composition providing at least about 5 g of MCT, for example, at least about 10 g of MCT, for example, at least about 15 g of MCT, is administered to an individual. In some embodiments, up to 30 g of MCT is administered per serving of composition.

[0044]

[0046] MCT contains three fatty acid moieties, each independently having 6-12, 6-11, 6-10, 7-12, 7-11, 7-10, 8-12, 8-11, or 8-10 carbon atoms. In one embodiment, at least a portion of the MCT contains one or more octanoic acid moieties. In one embodiment, at least a portion of the MCT contains one or more decanoic acid moieties.

[0045]

[0047] Preferably, the composition contains one or more natural materials that yield at least a portion of the MCT. Non-limiting examples of suitable natural materials for MCT include plant materials, such as coconut, coconut oil, palm kernel, and palm kernel oil, as well as animal materials, such as milk. For example, decanoic acid and octanoic acid account for about 5-8% and 4-10% of the fatty acid composition of coconut oil, respectively.

[0046]

[0048] Additionally or alternatively, at least a portion of MCTs can be synthesized by esterifying glycerol with one or more medium-chain fatty acids (MCFAs) having a tail consisting of 6 to 12 carbon atoms. For example, a homotriglyceride containing three fatty acid moieties, each having 8 carbon atoms, can be synthesized by esterifying glycerol with a C8 fatty acid (e.g., octanoic acid), and a homotriglyceride containing three fatty acid moieties, each having 10 carbon atoms, can be synthesized by esterifying glycerol with a C10 fatty acid (e.g., decanoic acid).

[0047]

[0049] In one embodiment, the composition comprises MCT containing at least one octanoic acid moiety or decanoic acid moiety, and the composition is free from or substantially free from any other triglycerides. As used herein, the term "free from any other triglycerides" means that the composition contains no triglycerides that do not contain at least one octanoic acid moiety or decanoic acid moiety. As used herein, the term "substantially free from any other triglycerides" means that the composition may contain trace amounts of other triglycerides, i.e., less than 5 mol%, preferably less than 3 mol%, more preferably less than 2 mol%, even more preferably less than 1 mol%, or most preferably less than 0.5 mol% of other triglycerides.

[0048]

[0050] In some embodiments, the composition containing MCT may be in the form of a nutritional composition or a nutritional supplement. The term “nutritional supplement” refers to a product intended to supplement the subject’s normal diet. For example, the composition containing MCT may be an oral nutritional supplement (ONS) that provides near-complete nutrition. However, an ONS may include, in addition to MCT, one or more formulations, such as additional components selected from the group consisting of proteins, carbohydrates, lipids, vitamins, minerals, and mixtures thereof. Furthermore, in alternative embodiments, the composition containing MCT may be in the form of a complete nutritional product. The term “complete nutritional product” refers to a product that can be the sole source of nutrition for the subject.

[0049]

[0051] In preferred embodiments, the composition comprises MCT emulsified with a mixture of one or more proteins, lipids, or carbohydrates, and optionally further comprises a food flavoring (e.g., vanilla).

[0050]

[0052] Non-limiting examples of suitable proteins include animal proteins, e.g., milk proteins, meat proteins, and egg proteins; or plant proteins, e.g., soy protein, wheat protein, rice protein, pea protein, corn protein, canola protein, oat protein, potato protein, peanut protein, and any protein derived from beans, buckwheat, or lentils. Milk proteins, e.g., casein and whey, and soy protein may be preferred in some applications. When the protein is a milk protein or milk protein fraction, the protein may be, for example, sweet whey, acidic whey, α-lactalbumin, β-lactoglobulin, bovine serum albumin, acidic casein, caseinate, α-casein, β-casein, and / or γ-casein.

[0051]

[0053] Non-limiting examples of suitable carbohydrates include monosaccharides and / or disaccharides, fully caloric carbohydrates, oligosaccharides, or mixtures thereof. Specific non-limiting examples include maltodextrin, maltose, high-maltose corn syrup, fructose, galactose, sucrose, lactose, or mixtures thereof.

[0052]

[0054] Non-limiting examples of suitable lipids to be added to MCTs include monoacylglycerols (MAGs), diacylglycerols (DAGs), long-chain triglycerides (LCTs), short-chain fatty acids (SCFAs), branched-chain fatty acids (BCFAs), structured MAGs, structured DAGs, fatty acids (free and / or conjugated, e.g., fatty acids esterified to glycerol or ethyl esters), phospholipids, lysophospholipids, sphingomyelin, gangliosides, specific anti-inflammatory mediators (SPMs), or mixtures thereof. Free and / or bound fatty acids may include one or more of the following: linoleic acid (18:2n-6), alpha-linolenic acid (18:3n-3), dihomo-gamma-linolenic acid (20:3n-6), gamma-linolenic acid (GLA, 18:3n-6), stearidonic acid (18:4n-3), docosapentaenoic acid (DPA, 22:5n-3), or mixtures thereof. The lipid source may be one or more of the following: animal, plant, fermentation, microalgae, GMO, non-GMO, or mixtures thereof.

[0053]

[0055] One embodiment of a composition containing MCT is a near-complete nutritional ONS solution that may further contain a protein, such as a milk protein concentrate. In one embodiment of this near-complete nutritional ONS solution, the composition may essentially consist of water, MCT and protein (e.g., milk protein concentrate) and optionally a flavoring. Preferably, the near-complete nutritional ONS solution is a "shot" having a volume of, for example, about 40 mL to about 400 mL, more preferably about 50 mL to about 300 mL, and most preferably about 70 mL. Preferably, the near-complete nutritional ONS solution is a unit dosage form that provides at least about 5 g of MCT, more preferably at least about 10 g of MCT, most preferably at least about 15 g of MCT, and in some embodiments, 30 g or less of MCT. In a particularly preferred embodiment, the near-complete nutritional ONS solution is an MCT emulsion.

[0054]

[0056] The protein can be 0% to about 50% by weight of the composition, preferably about 0.1% to about 20% by weight, more preferably about 1.0% to about 10.0% by weight, and most preferably about 5.0% by weight. The protein can be 0g to about 30g per serving of the composition, preferably about 5g to about 30g per serving of the composition.

[0055]

[0057] Another embodiment of the composition containing MCT is a complete nutritional replacement liquid food that may further contain protein (e.g., one or more of whey, casein, and milk protein concentrate), additional lipids (e.g., long-chain triglycerides (LCTs)), and carbohydrates (lactose and / or glucose).

[0056]

[0058] In this embodiment of the complete nutritional replacement liquid food, the composition may essentially consist of water, MCT, protein, additional lipids, carbohydrates, and optionally flavorings. Preferably, the complete nutritional replacement liquid food is a "shot" having a volume of, for example, about 40 mL to about 400 mL, more preferably about 50 mL to about 300 mL, and most preferably about 70 mL. Preferably, the complete nutritional replacement liquid food is a unit dosage form providing at least about 5 g of MCT, more preferably at least about 10 g of MCT, most preferably at least about 15 g of MCT, and in some embodiments, 30 g or less of MCT. In a particularly preferred embodiment, the complete nutritional replacement liquid food is an MCT emulsion.

[0057]

[0059] The MCT product format may contain excipients, emulsifiers, stabilizers, and mixtures thereof, and the final formulation may be a liquid or gel ready for immediate consumption, or a powder that is reconstituted with water before use.

[0058]

[0060] MCT can be present in an amount of about 10 to about 120 g / L of the composition. Protein can be present in an amount of 0 to about 200 g / L of the composition, preferably about 10 g / L to about 200 g / L of the composition. Additional lipids can be present in an amount of 0 to about 120 g / L of the composition, preferably about 10 g / L to about 200 g / L of the composition. Carbohydrates can be present in an amount of 0 to about 200 g / L of the composition, preferably about 10 g / L to about 200 g / L of the composition.

[0059]

[0061] In some embodiments, the MCT-containing composition is provided in a kit that also provides at least a portion of a meal. For example, the MCT-containing composition and at least a portion of a meal can be prepared in separate containers, and both of these separate containers can be placed in a larger container.

[0060]

[0062] After oral absorption, MCTs are metabolized into free fatty acids, and then further into ketones. Free fatty acids are first metabolized to β-hydroxybutyrate (BHB), and then to acetacetate (AcA). Depending on the MCTs utilized, MCFAs and ketones are produced in body fluids in varying amounts, and these molecules can be used as an alternative energy source to glucose, or to supplement energy derived from glucose.

[0061]

[0063] Ketones can be transported to the brain, for example, by monocarboxylic acid transporter 1 (MCT1), where they are primarily metabolized by neurons. Free fatty acids, such as C8 and C10 free fatty acids, can reach the brain by diffusion, where they are primarily metabolized by astrocytes.

[0062]

[0064] In one embodiment, oral administration of the composition to a subject provides one or more of ketones, C8 fatty acids, or C10 fatty acids to the subject's body fluids. Preferably, the ketone is β-hydroxybutyrate and / or acetacetate. In one embodiment, ketone production achieved by pre-meal administration of the MCT-containing composition (e.g., about 30 minutes before a meal) is greater than ketone production by the same formulation of MCT-containing composition administered approximately simultaneously with a meal. The subject's exposure to ketones can be quantified, for example, by measuring the level of ketones in the subject's plasma over 4 hours after oral administration. The subject's exposure to ketones can be calculated by determining the area under the curve (AUC) on a plot of ketone concentrations in body fluids, e.g., plasma, over time (e.g., a 4-hour period). In one embodiment, the biological fluid is treated with an organic solvent to precipitate proteins before analysis and reconstituted with a solvent suitable for enzyme assay or mass spectrometry (MS). Ketone levels can be evaluated using liquid chromatography in combination with a standard enzyme assay or high-resolution mass spectrometry (LC-MS). In particular, the concentrations of β-hydroxybutyrate (BHB) and acetacetate (AcA) can be quantitatively measured using the external calibration method.

[0063]

[0065] A composition containing MCT may further contain one or more additional components, such as minerals; vitamins; salts; or one or more functional additives, such as palatants, colorants, emulsifiers, antimicrobial agents, or other preservatives. Non-limiting examples of minerals suitable for the compositions disclosed herein include calcium, phosphorus, potassium, sodium, iron, chloride, boron, copper, zinc, magnesium, manganese, iodine, selenium, chromium, molybdenum, fluoride, and any combination thereof. Examples of vitamins suitable for the compositions disclosed herein include water-soluble vitamins (such as thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), pantothenic acid (vitamin B5), pyridoxine (vitamin B6), biotin (vitamin B7), myo-inositol (vitamin B8), folic acid (vitamin B9), cobalamin (vitamin B12), and vitamin C) and fat-soluble vitamins (such as vitamins A, D, E, and K), as well as salts, esters, or derivatives thereof. Inulin, taurine, carnitine, amino acids, enzymes, coenzymes, and any combination thereof may be included in various embodiments.

[0064]

[0066] The composition may further contain one or more active ingredients that promote or maintain the overall health of the nervous system or further enhance cognitive function. Examples of such ingredients include choline, phosphatidylserine, alpha-lipoic acid, CoQ10, acetyl-L-carnitine, herbal extracts (e.g., Ginkgo biloba, Bacopa monniera, Convolvulus pluricaulis, and Leucojum aestivum), omega-3 or omega-6 polyunsaturated fatty acids (e.g., eicosapentaenoic acid, docosapentaenoic acid, or docosahexaenoic acid as free fatty acids), aliphatic esters (e.g., ethyl esters, triglycerides, or monoglycerides), and fish oil extracts.

[0065]

[0067] The subject may be a human, dog, cat, horse, goat, cow, sheep, pig, deer, or mammal such as a primate. Preferably, the subject is a human. In one embodiment, the subject is an infant. The infant may be a human, such as a newborn (i.e., an infant less than 28 days old) or a premature infant (i.e., an infant born before the completion of a 37-week gestation period).

[0066]

[0068] In one embodiment, the subjects are aged subjects. For example, the subjects may be aged subjects who have reached 40, 50, 60, 66, 70, 75, or 80% of their estimated lifespan. The determination of lifespan may be based on actuarial tables, calculations, or estimates, and may take into account past, present, and future influences, or factors known to have a positive or negative effect on lifespan. When determining lifespan, species, sex, size, genetic factors, environmental and stress factors, current and past health status, past and present nutritional status, and stress factors may be taken into consideration. Aged subjects may be, for example, human subjects who are over 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 years of age.

[0067]

[0069] Furthermore, in this regard, the term "elderly" in relation to humans means a postnatal age of at least 60 years, preferably over 63 years, more preferably over 65 years, and most preferably over 70 years. The term "older adult" in a human context means a postnatal age of 45 years or older, preferably over 50 years, and more preferably over 55 years, and includes older individuals.

[0068]

[0070] All references herein to treatment include curative, palliative, and prophylactic treatments. Treatment may also include inhibiting the progression of disease severity. Treatments in both humans and animals are within the scope of this disclosure. Preferably, a composition comprising MCTs is administered as a single serving or unit dosage form that provides a therapeutically effective or prophylactically effective amount of MCTs and / or an amount of MCTs that is metabolized to a therapeutically effective or prophylactically effective amount of ketones.

[0069]

[0071] The free fatty acids and ketones produced from MCTs provide an alternative energy source to glucose, supplementing or replacing the energy of cells such as astrocytes, muscle cells, cardiomyocytes, or nerve cells.

[0070]

[0072] Brain tissue consumes a large amount of energy relative to its volume. In the average healthy individual, the brain obtains most of its energy from oxygen-dependent glucose metabolism. Typically, most of the brain's energy is used to assist in signal transduction by neurons or nerve cells, while the remaining energy is used to maintain cellular health. For example, energy deficiency in the brain caused by impaired glucose utilization can lead to increased neuronal activity, seizures, and cognitive impairment.

[0071]

[0073] Examples of brain energy deficiency states or diseases include migraines, memory impairment, age-related memory impairment, brain injury, neurorehabilitation, stroke and post-stroke, amyloid lateral sclerosis, multiple sclerosis, cognitive impairment, post-intensive care cognitive impairment, age-related cognitive impairment, Alzheimer's disease, Parkinson's disease, Huntington's disease, congenital metabolic disorders (such as glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase complex deficiency), bipolar disorder, schizophrenia, and / or epilepsy.

[0072]

[0074] As used herein, the term “neurological condition” refers to a disorder of the nervous system. A neurological condition may result from damage to the brain, spine, or nerves caused by illness or trauma. Non-limiting examples of symptoms of a neurological condition include paralysis, weakness, poor coordination, loss of sensation, seizures, confusion, pain, and altered levels of consciousness. Assessment of responses to touch, pressure, vibration, limb position, heat, cold, pain, and reflexes can determine whether a subject has a nervous system disorder.

[0073]

[0075] Some neurological conditions are lifelong, and their onset can occur at any point in life. Other neurological conditions, such as cerebral palsy, are present from birth. Some neurological conditions, such as Duchenne muscular dystrophy, generally manifest in early childhood, while other neurological conditions, such as Alzheimer's disease and Parkinson's disease, primarily affect older adults. Some neurological conditions develop suddenly due to trauma or disease, such as head injury, stroke, or cancer of the brain and spine.

[0074]

[0076] In one embodiment, the neurological condition is a result of traumatic brain injury. Additionally or alternatively, the neurological condition is a result of energy deficiency in the brain or muscles.

[0075]

[0077] Examples of neurological conditions include migraines, memory impairment, age-related memory impairment, brain injury, neurorehabilitation, stroke and post-stroke, amyloid lateral sclerosis, multiple sclerosis, cognitive impairment, post-intensive care cognitive impairment, age-related cognitive impairment, Alzheimer's disease, Parkinson's disease, Huntington's disease, congenital metabolic disorders (such as glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase complex deficiency), bipolar disorder, schizophrenia, and / or epilepsy.

[0076]

[0078] Migraine is a severe headache accompanied by other symptoms such as nausea, visual disturbances, and increased sensitivity to light or sound. Migraine may be preceded by an aura; the main symptoms of the aura are visual disturbances such as blurred vision (difficulty focusing), scotoma, flashes of light, or a zigzag pattern moving from the central field of vision to the edges.

[0077]

[0079] Stroke (also known as cerebrovascular disease (CVA) and cerebrovascular injury (CVI)) occurs when blood flow to the brain becomes insufficient, resulting in cell death. There are two main types of stroke: ischemic (caused by insufficient blood flow) and hemorrhagic (caused by bleeding). A stroke causes a part of the brain to stop functioning normally. Signs and symptoms of a stroke may include inability to move one side of the body, loss of sensation on one side of the body, difficulty understanding or speaking, a feeling that the world is spinning, or a loss of vision on one side. Signs and symptoms often appear immediately after a stroke.

[0078]

[0080] Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, Charcot's disease, and motor neuron disease, is characterized by the death of neurons that control voluntary muscles. ALS is characterized by progressively worsening weakness due to muscle stiffness, simple muscle contractions, and muscle wasting; this leads to difficulty speaking, swallowing, and ultimately breathing.

[0079]

[0081] Multiple sclerosis affects the nerves of the brain and spinal cord, causing a wide range of symptoms including problems with muscle movement, motor function and balance, numbness and tingling, blurred vision (typically unilateral visual field defects), and fatigue.

[0080]

[0082] Parkinson's disease is a degenerative disorder of the central nervous system that primarily affects the motor system. In the early stages of the disease, the most prominent symptoms are motor-related; these include resting tremor, rigidity, bradykinesia, and difficulty walking and gaiting. Later in the course of the disease, cognitive and behavioral problems may develop, and dementia generally occurs in the advanced stages of the disease. Other symptoms include depressive symptoms and sensory, sleep, and emotional problems.

[0081]

[0083] Alzheimer's disease is a progressive neurodegenerative disease. It is the most common cause of dementia. Symptoms include memory loss and difficulties with thinking, problem-solving, or language. The Mini-Mental State Examination (MMSE) is one example of a test used to diagnose Alzheimer's disease.

[0082]

[0084] Huntington's disease is a genetic condition that damages specific nerve cells in the brain. It affects muscle coordination, leading to mental decline and behavioral symptoms. Early symptoms often include minor mood or cognitive issues. This is followed by a general lack of coordination and unsteady gait. As the disease progresses, jerky, convulsive movements become more pronounced, along with a decline in mental capacity and behavioral symptoms. Physical abilities gradually deteriorate to the point where coordination becomes difficult. Mental abilities generally decline to the point of dementia.

[0083]

[0085] Congenital metabolic disorders are a variety of diseases caused by defective genes. Typically, the defective gene(s) result in a deficiency of an enzyme or transport protein, leading to inhibition by a mechanism that causes the body to process the compound, resulting in the accumulation of its toxicity. Congenital metabolic disorders can affect any organ, and usually two or more organs are affected. Symptoms tend to be nonspecific in many cases and are usually related to dysfunction or failure of major organs. The onset and severity of metabolic disorders may be exacerbated by environmental factors such as diet and co-existing diseases.

[0084]

[0086] Glucose transporter 1 (Glut1) deficiency syndrome is a genetic metabolic disorder involving the GLUT1 protein, which transports glucose across the blood-brain barrier, the boundary separating small blood vessels from brain tissue. The most common symptom is seizures (epilepsy), which usually begin within the first few months of life. Further possible symptoms include varying degrees of cognitive impairment, as well as motor disorders characterized by ataxia, dystonia, and chorea. Glut1 deficiency syndrome can be caused by mutations in the SLC2A1 gene, which produces the GLUT1 protein.

[0085]

[0087] Pyruvate dehydrogenase complex deficiency (PDCD) is a neurodegenerative disease associated with mitochondrial metabolic abnormalities and impaired carbohydrate metabolism. PDCD is characterized by lactic acid buildup and various neurological disorders. The signs and symptoms of this condition usually first appear shortly after birth, but can vary considerably among affected individuals. The most common feature is lactic acidosis, a potentially life-threatening buildup of lactic acid that can cause nausea, vomiting, severe respiratory distress, and abnormal heartbeat. Other symptoms include neurological problems; delayed development of mental abilities and motor skills such as sitting and walking; intellectual disability; seizures; hypotonia; poor coordination; and difficulty walking. Some affected individuals may have abnormal brain structures, such as underdeveloped corpus callosum (the tissue connecting the left and right hemispheres of the brain), atrophy of the lateral part of the brain known as the cerebral cortex, or multiple damaged tissue areas (lesions) in parts of the brain.

[0086]

[0088] In PDCD, one of the proteins in the pyruvate dehydrogenase complex (PDC) is deficient. The pyruvate dehydrogenase complex contains three enzymes identified as E1, E2, and E3; the E1 enzyme contains subunits identified as α and β. The most common form of PDCD is caused by an abnormal gene in the E1α subunit (PDHA1 gene) located on the X chromosome. Some cases of PDCD are caused by genetic mutations in other pyruvate dehydrogenase complex subunits, such as the PDHX, PDHB, DLAT, PDP1, and DLD genes.

[0087]

[0089] Bipolar disorder is a brain disorder characterized by abnormal shifts in mood, energy levels, activity levels, and ability to perform daily tasks. It is characterized by periods of elevated mood and periods of depression. Bipolar disorder can be diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM) or the World Health Organization's International Statistical Classification of Diseases and Related Health Problems.

[0088]

[0090] Schizophrenia is a chronic and serious illness characterized by abnormal interpretations of reality and brain damage. It can result in a combination of hallucinations, auditory hallucinations, delusions, and highly confused thoughts and behaviors. Schizophrenia can be diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM) or the World Health Organization's International Statistical Classification of Diseases and Related Health Problems.

[0089]

[0091] Epilepsy is a neurological disorder characterized by disruption of nerve cell activity in the brain, resulting in seizures or abnormal behaviors, sensations, and sometimes periods of loss of consciousness.

[0090]

[0092] Diabetic cardiomyopathy (DCM) is a disorder of the heart muscle in people with diabetes. Fluid accumulation in the lungs or legs can prevent the heart from effectively circulating blood throughout the body, leading to a condition known as heart failure.

[0091]

[0093] The terms "cognitive impairment" and "cognitive disorder" refer to disorders that cause impairment in cognition, particularly those that primarily affect learning, memory, perception, and / or problem-solving.

[0092]

[0094] Cognitive impairment can occur in patients after intensive care. It can also occur as part of the aging process.

[0093]

[0095] The term “cognition” refers to the entire set of mental abilities and processes, including knowledge, attention, long-term and working memory, judgment and evaluation, reasoning and “calculation,” problem-solving and decision-making, language comprehension and language creation. The level and improvement of cognition can be readily assessed by those skilled in the art using any suitable neurological and cognitive tests known in the art, including cognitive tests designed to assess information processing speed, executive function and memory. Suitable tests include the Mini-Mental State Examination (MMSE), the Cambridge Neuropsychological Assessment Battery (CANTAB), the Alzheimer's Disease Assessment Scale Cognitive Test (ADAScog), the Wisconsin Card Classification Task, verbal and visual fluency tests and trail-making tests, the Wechsler Memory Scale (WMS), immediate and delayed visual recall tests (complete liquid diet) (Trahan et al. Neuropsychology, 1988 19(3) p.173-89), the Ray Auditory Language Learning Test (RAVLT) (Ivnik, RJ. et al. Psychological Assessment: A Journal of Consulting and Clinical Psychology, 1990(2): p.304-312), electroencephalography (EEG), magnetoencephalography (MEG), positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), computed tomography, and long-term potentiation.

[0094]

[0096] EEG, the measurement of electrical activity in the brain, is achieved by placing electrodes on the scalp at various landmarks and amplifying and recording brain signals. MEG is similar to EEG in that it measures magnetic fields, which are related to electric fields. MEG is used to measure spontaneous brain activity, including synchronization waves, in the nervous system.

[0095]

[0097] PET provides measurement of oxygen utilization and glucose metabolism. In this technique, a radioactive positron-emitting tracer is administered, and the brain's uptake of the tracer correlates with brain activity. These tracers emit gamma rays, which are detected by sensors surrounding the head, thereby obtaining a 3D map of brain activity. Radioactivity is detected as soon as the tracer is taken up by the brain, corresponding to local cerebral blood flow. During activation, an increase in cerebral blood flow and neuronal glucose metabolism can be detected within seconds.

[0096]

[0098] A more suitable analysis may also be based on neuropsychological tests, clinical examinations, and individual complaints of cognitive decline (e.g., subjective memory loss). A more suitable examination may be based on assessments of motor skills, memory and attention, seizure susceptibility, and social engagement and / or social cognition.

[0097]

[0099] Memory impairment is the result of nerve damage to brain structures that impairs the storage, retention, and retrieval of memories. Memory impairment can progress with age (e.g., Alzheimer's disease) or it can result directly from, for example, head injury. The level and improvement of memory impairment can be readily assessed by those skilled in the art using any suitable tests known in the art, such as the Alzheimer's Disease Rating Scale Cognitive Test (ADAScog), the Mini-Mental State Examination (MMSE), computed tomography (CT) scans, magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and electroencephalography (EEG).

[0098]

[0100] In view of the above disclosure, embodiments provided herein are methods for increasing ketone production induced by oral ingestion of medium-chain triglycerides (MCTs) by an individual, the methods comprising: orally administering a composition comprising MCTs to an individual; and subsequently orally administering a meal to the individual after oral administration of the composition comprising MCTs and within about one hour thereafter, for example, at least about 10 minutes after oral administration of the composition comprising MCTs and within about one hour thereafter, preferably at least about 15 minutes after oral administration of the composition comprising MCTs and within about 40 minutes thereafter, most preferably about 30 minutes after oral administration of the composition comprising MCTs.

[0099]

[0101] Ketone production in an individual is preferably increased compared to ketone production obtained by orally administering a composition containing MCTs and a diet to the individual almost simultaneously.

[0100]

[0102] The individual may be elderly. The composition containing MCT may be liquid. The composition can be administered to the individual containing at least about 15.0 g to a maximum of about 30.0 g of MCT per serving. The composition may contain MCT emulsified with at least one additional component selected from the group consisting of proteins, lipids, and carbohydrates.

[0101]

[0103] At least a portion of the MCT may be at least one of octanoic acid or decanoic acid. At least a portion of the ketone may be selected from the group consisting of β-hydroxybutyrate, acetoacetate, and mixtures thereof.

[0102]

[0104] The meal could be breakfast. The composition could be a near-complete nutritional oral nutritional supplement (ONS) solution.

[0103]

[0105] Preferably, the individual does not experience gastrointestinal side effects from MCTs. Preferably, the individual does not ingest any food products other than any hydration during the period, which begins with oral administration of the composition containing MCTs to the individual and ends with oral administration of a meal to the individual.

[0104]

[0106] Another embodiment provided herein is a method for treating or preventing a condition in which increased production of ketones from medium-chain triglycerides (MCTs) is beneficial, the method comprising: orally administering a composition comprising MCTs to an individual in need of or at risk of such treatment; and subsequently orally administering a meal to the individual after oral administration of the composition comprising MCTs and within about one hour thereafter, for example, at least about 10 minutes after oral administration of the composition comprising MCTs and within about one hour thereafter, preferably at least about 15 minutes after oral administration of the composition comprising MCTs and within about 40 minutes thereafter, most preferably within about 30 minutes thereafter.

[0105]

[0107] The aforementioned conditions may be selected from the group consisting of epilepsy, neurological disorders, neurodegenerative diseases, heart failure, congenital metabolic disorders, obesity, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cancer, cerebral energy deficiency, migraine, memory impairment, age-related memory impairment, brain injury, stroke, amyloid lateral sclerosis, multiple sclerosis, cognitive impairment, post-intensive care cognitive impairment, age-related cognitive impairment, Alzheimer's disease, Parkinson's disease, Huntington's disease, hereditary metabolic disorders, bipolar disorder, schizophrenia, and combinations thereof.

[0106]

[0108] Another embodiment provided herein is a method for improving or maintaining at least one of neurological health, cognitive function, or motor ability, the method comprising: orally administering to an individual a composition comprising medium-chain triglycerides (MCTs); and subsequently orally administering a meal to the individual after oral administration of the composition comprising MCTs and within about one hour thereafter, for example, at least about 10 minutes after oral administration of the composition comprising MCTs and within about one hour thereafter, preferably at least about 15 minutes after oral administration of the composition comprising MCTs and within about 40 minutes thereafter, most preferably about 30 minutes after oral administration of the composition comprising MCTs.

[0107]

[0109] Another embodiment provided herein is a kit for providing nutrition, the kit comprising: an orally administrative composition comprising MCT; at least a portion of a meal stored separately in the kit from the orally administrative composition comprising MCT; and instructions, the instructions for orally administering the composition comprising medium-chain triglycerides (MCT) to an individual, and subsequently orally administering a meal to the individual after the oral administration of the composition comprising MCT and within about one hour thereafter, for example, at least about 10 minutes and within about one hour thereafter, preferably at least about 15 minutes and within about 40 minutes thereafter, most preferably about 30 minutes thereafter. [Examples]

[0108]

[0111] The following non-limiting examples present clinical data that further develops and supports the concepts of this disclosure.

[0109]

[0112] A metabolic study was conducted in healthy volunteers. A standard breakfast was administered orally, either during (Group B) or 30 minutes after (Group A) intake of an MCT emulsion (15 g of MCT in 70 mL of 5% aqueous protein solution). Plasma ketone concentrations were measured at various time points using a standard enzyme assay. Control group C received breakfast only.

[0110]

[0113] Figure 1 shows the time course of mean plasma ketone concentrations for groups A, B, and C, each consisting of 15 patients. Time 0 corresponds to oral intake of the MCT product. Large symbols correspond to breakfast intake time.

[0111] [Table 1]

[0112]

[0114] Table 1 shows the incremental AUC obtained for each group. A statistically significant difference was found between group A and group B (p<0.05).

[0113]

[0115] These results indicate that administering the MCT product before a meal results in significantly higher ketone production compared to administering the same amount of MCT during a meal.

[0114]

[0116] It should be understood that various changes and modifications to the current preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the subject matter of the invention and without impairing the intended advantages. Therefore, such changes and modifications are intended to be covered by the appended claims.

Claims

1. A method for increasing ketone production induced by oral intake of medium-chain triglycerides (MCTs) by an individual, The composition containing the aforementioned MCT is administered orally to the individual, A method further comprising administering a food to the individual orally after the oral administration of the composition containing the MCT, and within approximately one hour of the oral administration of the composition containing the MCT.

2. The method according to claim 1, wherein the individual is elderly.

3. The method according to claim 1, wherein the composition containing the MCT is a liquid.

4. The method according to claim 1, wherein the composition comprises at least about 15.0 g to a maximum of about 30.0 g of the MCTs per serving and is administered to the individual.

5. The method according to claim 1, wherein the composition comprises the MCT emulsified with at least one additional component selected from the group consisting of proteins, lipids, carbohydrates, and emulsifiers.

6. The method according to claim 1, wherein the meal is administered between approximately 10 minutes after the administration of the composition containing the MCT and approximately 1 hour after the administration of the composition containing the MCT.

7. The method according to claim 1, wherein the meal is administered between approximately 15 minutes after the administration of the composition containing the MCT and approximately 40 minutes after the administration of the composition containing the MCT.

8. The method according to claim 1, wherein the meal is administered about 30 minutes after the administration of the composition containing the MCT.

9. The method according to claim 1, wherein the meal is breakfast.

10. The method according to claim 1, wherein at least a portion of the MCT comprises at least one of octanoic acid or decanoic acid.

11. The method according to claim 1, wherein at least a portion of the ketone is selected from the group consisting of β-hydroxybutyrate, acetone acetate, and mixtures thereof.

12. The method according to claim 1, wherein the production of the ketone in the individual is increased compared to the production of ketones obtained by orally administering the composition containing the MCT and the diet to the individual at approximately the same time.

13. The method according to claim 1, wherein the composition is a liquid for oral nutritional support (ONS) that provides near-complete nutrition.

14. The method according to claim 1, wherein the individual does not experience gastrointestinal side effects due to the MCT.

15. The method according to claim 1, wherein the individual does not ingest any food products other than any hydration during a period beginning with the oral administration of the composition containing the MCT to the individual and ending with the oral administration of the meal to the individual.

16. A method for treating or preventing a condition in which increased ketone production from medium-chain triglycerides (MCTs) is beneficial, Oral administration of the composition containing the MCT to an individual in the aforementioned condition or at risk of the aforementioned condition, A method comprising subsequently administering a meal orally to the individual at least about 10 minutes after the oral administration of the composition containing the MCT and within about 1 hour after the oral administration of the composition containing the MCT.

17. The method according to claim 16, wherein the condition is selected from the group consisting of epilepsy, neurological disorders, neurodegenerative diseases, heart failure, congenital metabolic disorders, obesity, type 2 diabetes, diabetic cardiomyopathy, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cancer, cerebral energy deficiency state, migraine, memory impairment, age-related memory impairment, brain injury, stroke, amyloid lateral sclerosis, multiple sclerosis, cognitive impairment, post-intensive care cognitive impairment, age-related cognitive impairment, Alzheimer's disease, Parkinson's disease, Huntington's disease, hereditary metabolic disorders, bipolar disorder, schizophrenia, and combinations thereof.

18. The method according to claim 16, wherein the meal is administered at least about 10 minutes after the administration of the composition containing the MCT and within about 1 hour after the administration of the composition containing the MCT.

19. The method according to claim 16, wherein the meal is administered at least about 15 minutes after the administration of the composition containing the MCT and about 40 minutes after the administration of the composition containing the MCT.

20. The method according to claim 16, wherein the meal is administered about 30 minutes after the administration of the composition containing the MCT.

21. A method for improving or maintaining at least one of neurological health, cognitive function, or motor skills, Oral administration of a composition containing medium-chain triglycerides (MCTs) to an individual, A method comprising subsequently administering a meal orally to the individual at least about 10 minutes after the oral administration of the composition containing the MCT and within about 1 hour after the oral administration of the composition containing the MCT.

22. The method according to claim 21, wherein the meal is administered at least about 10 minutes after the administration of the composition containing the MCT and within about 1 hour after the administration of the composition containing the MCT.

23. The method according to claim 21, wherein the meal is administered at least about 15 minutes after the administration of the composition containing the MCT and within about 40 minutes after the administration of the composition containing the MCT.

24. The method according to claim 21, wherein the meal is administered about 30 minutes after the administration of the composition containing the MCT.

25. It is a kit for providing nutrition, An orally administrative composition comprising the aforementioned medium-chain triglycerides (MCTs), In the kit, at least a portion of a meal is stored separately from the orally administrative composition containing the MCT, Includes the instruction manual, A kit comprising instructions for orally administering a composition containing MCT to an individual, and subsequently orally administering a meal to the individual at least about 10 minutes after the oral administration of the composition containing MCT and within about 1 hour after the oral administration of the composition containing MCT.

26. A composition for use in increasing the production of ketones induced from oral intake of medium-chain triglycerides (MCTs) in an individual by orally administering a composition containing medium-chain triglycerides (MCTs) to the individual, and subsequently orally administering a meal to the individual after the oral administration of the composition containing MCTs and within approximately one hour thereafter.

27. A composition for use in the treatment or prevention of a condition in which increased production of ketones from medium-chain triglycerides (MCTs) is beneficial, wherein the composition is administered orally to an individual having the condition or at risk of the condition, wherein the composition comprises MCTs, and subsequently, a meal is administered orally to the individual after the oral administration of the MCT-containing composition and within approximately one hour thereafter.

28. A composition for use in improving or maintaining at least one of neurological health, cognitive function, or motor ability, by orally administering a composition containing medium-chain triglycerides (MCTs) to an individual, and subsequently orally administering a meal to the individual after the oral administration of the composition containing MCTs and within about one hour thereafter.

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