The Effect of Ketone Ester Supplementation and Ketogenic Diet on Brain Plasticity in Overweight/Obese Adults

NCT06368297 | Not Yet Recruiting DMC

• 1 other identifier: BSERE22-APP007-FED
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

This project comprises an initial crossover placebo-controlled neurophysiological study to ascertain the effect of acute ketone ester ingestion on motor cortex plasticity, followed by a second 2-week intervention study aimed to compare the effect of a ketogenic diet versus ketone ester supplementation on motor cortex plasticity, resting brain function and structure, and metabolic and neuroendocrine responses.

Conditions

Overweight and Obesity; Cognitive Change; Psychophysiologic Reaction

Keywords

Overweight; Obesity; Ketone; Neurocognition

Outcome Measures

Primary Outcomes (4)

• Brain Plasticity

  This measurement is "brain plasticity". Brain plasticity, also known as neuroplasticity, refers to the brain's remarkable ability to change and adapt in response to experience. The brain plasticity will be measured by transcranial magnetic stimulation (TMS) system. When assessing brain plasticity using TMS through the measurement of Motor Evoked Potentials (MEPs), the primary unit of measurement is typically in millivolts (mV) for the amplitude of the MEPs. MEPs are electrical signals recorded from muscles after stimulation of the motor cortex with TMS, reflecting the excitability of the corticospinal pathway and, indirectly, cortical plasticity.

  2 weeks

• Grey Matter Volume

  The measurement name is "grey matter volume", which belongs to brain structure. The grey matter volume will be assessed by the magnetic resonance imaging system. Grey matter volume is generally measured in cubic centimeters (cm³) or milliliters (mL), as both units are equivalent in volume measurement (1 cm³ = 1 mL). This measure reflects the volume of grey matter regions in the brain, which include areas dense with neuronal cell bodies, dendrites, axon terminals, and glial cells.

  2 weeks

• Cortical Thickness

  The measurement name is "cortical thickness", which belongs to brain structure. The cortical thickness will be assessed by the magnetic resonance imaging system. Cortical thickness is measured in millimeters (mm). It refers to the average thickness of the grey matter cortex across various regions of the brain. Cortical thickness can vary significantly across different parts of the cortex, typically ranging from around 1 mm to 4 mm, depending on the specific brain region and individual differences.

  2 weeks

• Blood-Oxygen-Level-Dependent (BOLD) Signal Changes

  The measurement name is "Blood-Oxygen-Level-Dependent (BOLD) Signal Changes", which belongs to brain function. The cortical thickness will be assessed by the magnetic resonance imaging system (MRI). The unit of BOLD signal changes measured by MRI is typically expressed as a percentage change (%). The BOLD signal reflects changes in the magnetic properties of blood due to variations in oxygenation levels that occur in response to neural activity.

  2 weeks

Secondary Outcomes (22)

• Blood Glucose

  6 weeks

• Blood Beta-Hydroxybutyrate

  6 weeks

• Blood Insulin

  6 weeks

• Leptin

  6 weeks

• Ghrelin

  6 weeks

Study Arms (2)

Acute effect of ketone monoester supplementation

EXPERIMENTAL

To investigate the acute effect of ketone monoester ingestion on brain cortical plasticity using high-frequency rTMS.

Dietary Supplement: Ketone Monoester Supplementation

Effects of a 2-week ketogenic diet or ketone monoester supplementation

EXPERIMENTAL

To evaluate the impact of short-term ketogenic dieting and ketone monoester supplementation on brain plasticity. To investigate structural and functional brain adaptations to short-term ketogenic dieting and ketone supplementation. To assess the relationship between changes in brain plasticity and the brain's structural and functional adaptations and changes in circulating levels of brain-derived neurotrophic factors and key central acting hormones (i.e., insulin and leptin) due to ketogenic dieting and ketone monoester supplementation.

Dietary Supplement: Ketone Monoester Supplementation; Dietary Supplement: Ketogenic diet

Interventions

Ketone Monoester Supplementation DIETARY_SUPPLEMENT

Exogenous ketones are a class of ketone bodies that are ingested using nutritional supplements or foods. This class of ketone bodies refers to the three water-soluble ketones (acetoacetate, β-hydroxybutyrate \[β-HB\], and acetone).

Acute effect of ketone monoester supplementation; Effects of a 2-week ketogenic diet or ketone monoester supplementation

Ketogenic diet DIETARY_SUPPLEMENT

The ketogenic diet typically reduces total carbohydrate intake to less than 50 grams a day-less than the amount found in a medium plain bagel-and can be as low as 20 grams a day. Generally, popular ketogenic resources suggest an average of 70-80% fat from total daily calories, 5-10% carbohydrate, and 10-20% protein.

Effects of a 2-week ketogenic diet or ketone monoester supplementation

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body mass index (BMI) \> 25 and \< 35 kg/m2 (overweight/obese group) or BMI \> 18.5 and \< 25 kg/m2 (healthy weight group);
• Right-handed.

You may not qualify if:

• Presenting any established counter indication for transcranial magnetic stimulation;
• Currently taking any medication affecting the central or the peripheral nervous system;
• Suffering from any psychiatric, neurologic, cardiovascular, or metabolic disease, including type 1 and type 2 diabetes mellitus;
• Undertaking surgery in the past six months;
• Engaged in resistance training.
• Pregnancy;
• Breastfeeding;
• Being amenorrhea.

Sponsors & Collaborators

• University of Macau: lead

Related Publications (5)

• Falkenhain K, Daraei A, Forbes SC, Little JP. Effects of Exogenous Ketone Supplementation on Blood Glucose: A Systematic Review and Meta-analysis. Adv Nutr. 2022 Oct 2;13(5):1697-1714. doi: 10.1093/advances/nmac036.

  PMID: 35380602 BACKGROUND

• Evans M, McClure TS, Koutnik AP, Egan B. Exogenous Ketone Supplements in Athletic Contexts: Past, Present, and Future. Sports Med. 2022 Dec;52(Suppl 1):25-67. doi: 10.1007/s40279-022-01756-2. Epub 2022 Oct 10.

  PMID: 36214993 BACKGROUND

• Kesl SL, Poff AM, Ward NP, Fiorelli TN, Ari C, Van Putten AJ, Sherwood JW, Arnold P, D'Agostino DP. Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats. Nutr Metab (Lond). 2016 Feb 4;13:9. doi: 10.1186/s12986-016-0069-y. eCollection 2016.

  PMID: 26855664 RESULT

• Walsh JJ, Neudorf H, Little JP. 14-Day Ketone Supplementation Lowers Glucose and Improves Vascular Function in Obesity: A Randomized Crossover Trial. J Clin Endocrinol Metab. 2021 Mar 25;106(4):e1738-e1754. doi: 10.1210/clinem/dgaa925.

  PMID: 33367782 RESULT

• Yu Q, Wong KK, Lei OK, Armada-da-Silva PAS, Wu Z, Nie J, Shi Q, Kong Z. Acute ketone monoester supplementation in young adults: modulating metabolic and neurocognitive functions across body weights. Appl Physiol Nutr Metab. 2025 Jan 1;50:1-12. doi: 10.1139/apnm-2024-0229. Epub 2024 Oct 17.

  PMID: 39418669 DERIVED

MeSH Terms

Conditions

Overweight; Obesity; Ketosis

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Acidosis; Acid-Base Imbalance; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Zhaowei Kong, PhD

  University of Macau

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhaowei Kong, PhD

CONTACT

8822 8730; zwkong@um.edu.mo

Zhen Yuan, PhD

CONTACT

8822 2314; zhenyuan@um.edu.mo

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: April 16, 2024
• Study Start: April 1, 2024
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: April 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 01/09/2026-01/09/2028
• Access Criteria: The data will be shared by request two years after the completion. The data will be available for two years.