Ketone Esters for Appetite, Cognition, and Cardiovascular Function in Individuals With Obesity and Insulin Resistance

Non-pharmacological Treatments for Obesity: Leveraging the Appetite Suppressive Effects of Hyperketonemia Through Exogenous Ketone Ingestion to Treat Obesity, Insulin Resistance, and Cognition

The goal of this single-blind randomized placebo-controlled trial is to test the effects of an oral ketone supplement on appetite, cognition, metabolism, and cardiovascular function in individuals with obesity and insulin resistance.

The main question[s] it aims to answer are:

• Does taking the ketone supplement reduce appetite and improve cognition?
• How does the ketone supplement alter metabolism and cardiovascular function?

Participants will be asked to consume a randomly assigned ketone ester supplement or a placebo and testing will be done to see how the supplement affects the following compared to a placebo:

• appetite,
• cognition,
• metabolism
• cardiovascular function

Researchers will compare individuals with obesity and insulin resistance to individuals with normal weight and no insulin resistance to see if the ketone supplement affects groups differently.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Dietary supplement: Ketone Ester Supplement; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39406
      • University of Southern Mississippi - School of Kinesiology and Nutrition

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults between the ages of 18-50 years of age.
• Presence of metabolic sydnrome

Control Participant Eligibility:

• A waist circumference of < 102 cm for males and < 88 cm for females, and
• No indication of metabolic syndrome

Exclusion Criteria:

• Pregnant
• Breastfeeding or lactating
• Missing any limbs or part of a limb
• Having a substantial amount of metal implants (metal plates or complete joint replacements)
• Having a pacemaker or any other electrical implant
• Type I diabetes
• Gestational diabetes
• Taking insulin
• Any history of severe traumatic brain injury or mild traumatic brain injury within the last two years
• Kidney disease
• Liver disease
• Thyroid disease
• Any diagnosed neurological or neurodegenerative diseases
• Any surgeries that would impact swallowing and/or digestion
• Being on a ketogenic diet or having been on a ketogenic diet in the last 6 months
• Having received ionizing radiation from a medical procedure within the last 30 days
• Being on a medically prescribed diet

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketone Ester; Oral ketone ester supplement	Dietary supplement: Ketone Ester Supplement; Oral ingestion of a ketone supplement combined with a flavoring agent and diluted in water
Placebo Comparator: Placebo; Taste and viscosity matched placebo	Other: Placebo; Oral ingestion of cellulose combined with a flavoring agent and diluted in water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	Blood pressure responses (systolic and diastolic) to sympathoexcitation	Baseline (pre-ingestion)
Blood pressure	Blood pressure responses (systolic and diastolic) to sympathoexcitation	30 minutes post ingestion
Blood pressure	Blood pressure responses (systolic and diastolic) to sympathoexcitation	45 minutes post ingestion
Blood pressure	Blood pressure responses (systolic and diastolic) to sympathoexcitation	60 minutes post ingestion
Blood pressure	Blood pressure responses (systolic and diastolic) to sympathoexcitation	75 minutes post ingestion
Blood pressure	Blood pressure responses (systolic and diastolic) to sympathoexcitation	90 minutes post ingestion
Blood pressure	Blood pressure responses (systolic and diastolic) to sympathoexcitation	105 minutes post ingestion
Heart Rate	Heart rate responses to sympathoexcitation	Baseline (pre-ingestion)
Heart Rate	Heart rate responses to sympathoexcitation	30 minutes post ingestion
Heart Rate	Heart rate responses to sympathoexcitation	45 minutes post ingestion
Heart Rate	Heart rate responses to sympathoexcitation	60 minutes post ingestion
Heart Rate	Heart rate responses to sympathoexcitation	75 minutes post ingestion
Heart Rate	Heart rate responses to sympathoexcitation	90 minutes post ingestion
Heart Rate	Heart rate responses to sympathoexcitation	105 minutes post ingestion
Heart Rate Variability	Index of cardiac autonomic control	Baseline (pre-ingestion)
Heart Rate Variability	Index of cardiac autonomic control	45 post ingestion
Cardiac Baroreflex Sensitivity	Changes in cardiac interval relative to changes in systolic blood pressure	105 minutes post ingestion
Hunger - Visual Digital Analog Scale (0-100)	Changes in subjective rating of hunger	Baseline, 30, 45, 60, 75, 90, 105, 120 minutes post ingestion
Fullness - Visual Digital Analog Scale (0-100)	Changes in subjective rating of fullness	Baseline, 30, 45, 60, 75, 90, 105, 120 minutes post ingestion
Desire to eat - Visual Digital Analog Scale (0-100)	Changes in subjective rating of desire to eat	Baseline, 30, 45, 60, 75, 90, 105, 120 minutes post ingestion
Prospective consumption of food - Visual Digital Analog Scale (0-100)	Changes in subjective rating of prospective consumption of food	Baseline, 30, 45, 60, 75, 90, 105, 120 minutes post ingestion
Thirst - Visual Digital Analog Scale (0-100)	Changes in subjective rating of thirst	Baseline, 30, 45, 60, 75, 90, 105, 120 minutes post ingestion
Stroop Test - Digital Cognitive Function Test	Changes in Stroop score	Baseline, 75 minutes
Go/No-go Test - Digital Cognitive Function Test	Changes in Go/No-go score	Baseline, 75 minutes
Task Switching Task - Digital Cognitive Function Test	Changes in Task Switching Task score	Baseline, 75 minutes
Number Back Test - Digital Cognitive Function Test	Changes in Number Back Test score	Baseline, 75 minutes
Digit Span Test - Digital Cognitive Function Test	Changes in Digit Span Test score	Baseline, 75 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prefrontal Cortex Oxygenation	Near-infrared spectroscopy	Baseline, 90 minutes post ingestion
Peripheral Blood Flow	Doppler Ultrasound of Femoral Artery	Baseline, 30, 60 and 90 minutes post ingestion
Peripheral Vascular Conductance	Blood flow normalized to blood pressure (mL/min/mmHg)	Baseline, 30, 60 and 90 minutes post ingestion
Blood ketones	Ketone body level from capillary blood	Baseline, 30, 60, 90, 120 minutes post ingestion
Blood glucose	Blood glucose level from capillary blood	Baseline, 30, 60, 90, 120 minutes post ingestion
Oxygen Consumption from Respiratory Gases	Amount of oxygen consumed using indirect calorimetry	Baseline and continuous for 120 minutes
Carbon Dioxide Produced from Respiratory Gases	Amount of carbon dioxide produced using indirect calorimetry	Baseline and continuous for 120 minutes

Collaborators and Investigators

• Sponsor: University of Southern Mississippi
• Investigators: Principal Investigator: Austin J Graybeal, PhD, University of Southern Mississippi

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2022
• Primary Completion (Actual): December 29, 2023
• Study Completion (Actual): December 29, 2023

Study Registration Dates

• First Submitted: November 3, 2022
• First Submitted That Met QC Criteria: December 6, 2022
• First Posted (Actual): December 14, 2022

Study Record Updates

• Last Update Posted (Actual): May 22, 2024
• Last Update Submitted That Met QC Criteria: May 20, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperinsulinism; Obesity; Metabolic Syndrome; Insulin Resistance
• Other Study ID Numbers: 22-877

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No