US-20260124169-A1 - METHODS USING ADMINISTRATION OF MEDIUM CHAIN TRIGLYCERIDES (MCT) PRIOR TO A MEAL TO INCREASE KETONE PRODUCTION FROM THE MCTS

US20260124169A1US 20260124169 A1US20260124169 A1US 20260124169A1US-20260124169-A1

Abstract

A method increases production of ketones derived from oral consumption of medium chain triglycerides (MCT) by an individual. The method includes orally administering to the individual a composition containing the MCTs and then subsequently orally administering to the individual a meal at least about ten minutes after the oral administration of the composition containing the MCTs and within about one hour of the oral administration of the composition containing the MCTs. For example, the meal can be administered about thirty minutes after the administration of the composition containing the MCTs. The ketone production is increased relative to ketone production from oral administration of the MCTs and the meal at approximately the same time. The meal can be breakfast. The composition containing the MCTs can be a liquid oral nutritional supplement (ONS) providing incomplete nutrition.

Inventors

Bernard Cuenoud

Assignees

SOCIETE DES PRODUITS NESTLE S.A.

Dates

Publication Date: 20260507
Application Date: 20260105

Claims (20)

1 : A method of increasing production of ketones derived from oral consumption of medium chain triglycerides (MCT) by an individual, the method comprising: orally administering to the individual a composition comprising the MCTs; and subsequently orally administering to the individual a meal after the orally administering of the composition comprising the MCTs and within about one hour of the orally administering of the composition comprising the MCTs.
2 : The method of claim 1 wherein the individual is elderly.
3 : The method of claim 1 wherein the composition comprising the MCTs is a liquid.
4 : The method of claim 1 wherein the composition is administered to the individual in a serving comprising at least about 15.0 g of the MCTs up to about 30.0 g of the MCTs.
5 : The method of claim 1 wherein the composition comprises the MCTs emulsified in at least one additional component selected from the group consisting of a protein, a lipid, a carbohydrate, and an emulsifier.
6 : The method of claim 1 wherein the meal is administered between about ten minutes after the administration of the composition comprising the MCTs and about one hour after the administration of the composition comprising the MCTs.
7 : The method of claim 1 wherein the meal is administered about thirty minutes after the administration of the composition comprising the MCTs.
8 : The method of claim 1 wherein the meal is breakfast.
9 : The method of claim 1 wherein at least a portion of the MCTs comprises at least one of octanoic acid or decanoic acid.
10 : The method of claim 1 wherein at least a portion of the ketones are selected from the group consisting of β-hydroxy butyrate, acetone-acetate and mixtures thereof.
11 : The method of claim 1 wherein the production of the ketones in the individual is increased relative to ketone production from oral administration of the composition comprising the MCTs and the meal to the individual at approximately the same time.
12 : The method of claim 1 wherein the composition is a liquid incomplete nutrition oral nutritional supplement (ONS).
13 : The method of claim 1 wherein the individual does not consume any food products other than optional water during a time period starting at the oral administration of the composition comprising the MCTs to the individual and ending at the oral administration of the meal to the individual.
14 : A method of treating or preventing a condition for which increased production of ketones from medium chain triglycerides (MCTs) is beneficial, the method comprising: orally administering, to an individual having the condition or at risk of the condition, a composition comprising the MCTs; and subsequently orally administering to the individual a meal at least about ten minutes after the oral administration of the composition comprising the MCTs and within about one hour of the oral administration of the composition comprising the MCTs.
15 : The method of claim 14 wherein the condition is selected from the group consisting of epilepsy, a neurological disease, a neurodegenerative disease, heart failure, inborn errors of metabolism, obesity, type 2 diabetes, diabetic cardiomyopathy, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), cancer, a brain energy deficiency condition, a migraine, a memory disorder, an age-related memory disorder, a brain injury, a stroke, amyotrophic lateral sclerosis, multiple sclerosis, cognitive impairment, cognitive impairment post-intensive care, age-induced cognition impairment, Alzheimer's disease, Parkinson's disease, Huntington's disease, an inherited metabolic disorder, bipolar disorder, schizophrenia, and combinations thereof.
16 : The method of claim 14 wherein the meal is administered at least about fifteen minutes after the administration of the composition comprising the MCTs and about forty minutes after the administration of the composition comprising the MCTs.
17 : The method of claim 14 wherein the meal is administered about thirty minutes after the administration of the composition comprising the MCTs.
18 : A method of improving or maintaining at least one of neurologic health, cognitive function, or exercise performance, the method comprising: orally administering to an individual a composition comprising medium chain triglycerides (MCTs); and subsequently orally administering to the individual a meal at least about ten minutes after the oral administration of the composition comprising the MCTs and within about one hour of the oral administration of the composition comprising the MCTs.
19 : The method of claim 18 wherein the meal is administered at least about ten minutes after the administration of the composition comprising the MCTs and within about one hour after the administration of the composition comprising the MCTs.
20 : The method of claim 18 wherein the meal is administered at least about fifteen minutes after the administration of the composition comprising the MCTs and within about forty minutes after the administration of the composition comprising the MCTs.

Description

CROSS REFERENCE TO RELATED APPLICATIONS The present application is a continuation of U.S. patent application Ser. No. 17/440,021, filed on Sep. 16, 2021, which is a National Stage of International Application No. PCT/EP2020/057315, filed on Mar. 17, 2020, which claims priority to U.S. Provisional Patent Application No. 62/822,299, filed on Mar. 22, 2019, the entire contents of which are being incorporated herein by reference. BACKGROUND The present disclosure generally relates to administration of medium chain triglycerides (MCTs) before subsequent administration of a meal, for example administration of MCTs about thirty minutes before the meal. The two main ketones, beta-hydroxybutyrate (BHB) and acteto-actetate (AcA), represent an important alternative source of energy for extrahepatic tissues like brain, heart or skeletal muscle. Moreover, accumulating evidence suggests that ketones might also have a signaling role, either direct or indirect. Products aimed at increasing blood ketones have potential therapeutic benefits in several conditions including epilepsy, neurological and neurodegenerative diseases, heart failure, diabetic cardiomyopathy, inborn errors of metabolism, obesity, type 2 diabetes, cancer, exercise performance, and nonalcoholic fatty liver disease (NAFLD) such as nonalcoholic steatohepatitis (NASH). BHB and AcA are actively transported to the brain by the monocarboxylic transporter 1 (MCT1), resulting in brain levels directly proportional to their blood concentrations. Therefore, products that provide a higher and more sustained plasma level of ketones are anticipated to have a stronger and longer effect (higher area under the curve AUC) compared to products that raise blood ketones for a lower and shorter time span (smaller AUC). Hence it is critical to maximize the exposure to blood ketones. However, the factors that drive ketone plasma AUC derived from ketone precursors are not known. Medium-chain triglycerides (MCTs) are efficient ketone precursors when administered by oral bolus. They are rapidly digested, and the resultant free medium chain fatty acids (MCFAs) are absorbed efficiently by the portal vein to reach the liver where they are extensively metabolized to ketones, bypassing the normal long-chain fatty acid digestion and absorption processes. Their specific formulation can affect ketogenesis efficiency and gastrointestinal tolerability. Recently, human pharmacokinetic (PK) characterization of various MCT formulations has been reported, indicating that the intrinsic ketone production efficiency from MCT of various chain lengths varies, and a 8 carbon (C8) MCT being the most effective. Additionally, it was reported in humans that a good emulsion of the MCT oil displayed a much higher ketone production compared to the same non-emulsified oil after oral intake. However, ketone production by oral intake of MCT is variable and not optimum. Moreover, intake of MCT without food often results in gastrointestinal (GI) side effects such as diarrhea. SUMMARY To the best knowledge of the present inventor, the impact of specific timing of a meal on the ketogenic effect of MCT has not been reported before the present patent application. As set forth in greater detail later herein, the inventors conducted a study that surprisingly and unexpectedly showed that an MCT emulsion administered prior to a meal provides the largest amount of blood ketones without GI side effects, compared to administration together with a meal, which both provided less amounts of blood ketones. Specifically, the relative timing of a meal strongly impacted ketone production from an MCT emulsion. Accordingly, in a non-limiting embodiment, the present disclosure provides a method of increasing ketone production from medium chain triglycerides (MCT). The method comprises orally administering a composition comprising the MCTs to an individual and then subsequently orally administering a meal to the individual after the oral administration of the composition comprising the MCTs and within about one hour of the oral administration of the composition comprising the MCTs, for example at least about ten minutes after the oral administration of the composition comprising the MCTs and within about on hour after the oral administration of the composition comprising the MCTs, preferably at least about fifteen minutes after the oral administration of the composition comprising the MCTs and within about forty minutes after the oral administration of the composition comprising the MCTs, most preferably about thirty minutes after the oral administration of the composition comprising the MCTs. In an embodiment, the individual is elderly. For example, the oral administration of the composition comprising the MCTs can be between about ten minutes before the administration of the meal and about one hour before the administration of the meal, preferably at least about fifteen minutes before the administration of the meal and within about