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

Overweight and Obesity Clinical Trial

Official title:

The Effect of Ketone Ester Supplementation and Ketogenic Diet on Brain Plasticity in Overweight/Obese Adults: A Neurophysiological and Resting Functional Magnetic Resonance Study (rfMRI)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06368297
• Other study ID #: BSERE22-APP007-FED
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 2024
• Est. completion date: August 2024

Study information

• Verified date: April 2024
• Source: University of Macau
• Contact: Zhaowei Kong, PhD
• Phone: 8822 8730
• Email: zwkong[@]um.edu.mo
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The study initially makes a bold attempt to explore whether the ketone supplementation would induce improvements in the overweight/ obese population's brain health via altering motor cortex plasticity, brain function and structure, and metabolic and neuroendocrine pathways. The study's aims include:

• assessing changes in brain plasticity associated with excessive body weight and/or obesity.

• evaluating the potential of ketone monoester supplementation in enhancing brain plasticity.

• evaluating the potential of ketone monoester supplementation in correcting impaired brain plasticity due to excessive body weight.

• evaluating the impact of short-term ketogenic dieting and ketone monoester supplementation on brain plasticity.

• investigating structural and functional brain adaptations to short-term ketogenic dieting and ketone supplementation.

• assessing 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Cognitive Change
• Overweight
• Overweight and Obesity
• Psychophysiologic Reaction

Intervention

Dietary Supplement:
• Ketone Monoester Supplementation
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, ß-hydroxybutyrate [ß-HB], and acetone).
• Ketogenic diet
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Macau

References & Publications (4)

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. — View Citation

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. — View Citation

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 — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	Blood Glucose	The measurement name is "blood glucose". It will be assessed by a glucometer in laboratory settings. The unit of measurement is millimoles per liter (mmol/L).	6 weeks
Secondary	Blood Beta-Hydroxybutyrate	The measurement name is "blood beta-hydroxybutyrate". It will be assessed by specific ketone meters designed for beta-hydroxybutyrate measurement. The unit of measurement is millimoles per liter (mmol/L).	6 weeks
Secondary	Blood Insulin	The measurement name is "blood insulin". It will be assessed by immunoassay system (chemiluminescence immunoassay analyzer) using blood samples. The unit of measurement is microunits per milliliter (µU/mL).	6 weeks
Secondary	Leptin	The measurement name is "leptin". It will be assessed by immunoassay system (chemiluminescence immunoassay analyzer) using blood samples. The unit of measurement is nanograms per milliliter (ng/mL).	6 weeks
Secondary	Ghrelin	The measurement name is "ghrelin". It will be assessed by immunoassay system (chemiluminescence immunoassay analyzer) using blood samples. The unit of measurement is picograms per milliliter (pg/mL).	6 weeks
Secondary	Brain-Derived Neurotrophic Factor	The measurement name is "brain-derived neurotrophic factor". It will be assessed by immunoassay system (chemiluminescence immunoassay analyzer) using blood samples. The unit of measurement is nanograms per milliliter (ng/mL).	6 weeks
Secondary	Reaction Time of Attention Network Test	The measurement name is "reaction time of Attention Network Test". The measurement will be assessed by psychological paradigm named Attention Network Test. The unit of measurement is milliseconds (ms).	2 weeks
Secondary	Accuracy of Attention Network Test	The measurement name is "accuracy of attention network test". The measurement will be assessed by psychological paradigm named Attention Network Test. Accuracy is generally measured as a percentage (%).	2 weeks
Secondary	Reaction Time of Stroop Task	The measurement name is "reaction time of stroop task". The measurement will be assessed by psychological paradigm named Stroop Task. The unit of measurement is milliseconds (ms).	2 weeks
Secondary	Accuracy of Stroop Task	The measurement name is "accuracy of stroop task". The measurement will be assessed by psychological paradigm named Stroop Task. Accuracy is generally measured as a percentage (%).	2 weeks
Secondary	Reaction Time of N-back Task	The measurement name is "reaction time of n-back task". The measurement will be assessed by psychological paradigm named N-back task. The unit of measurement is milliseconds (ms).	2 weeks
Secondary	Accuracy of N-back Task	The measurement name is "accuracy of n-back task". The measurement will be assessed by psychological paradigm named N-back task. Accuracy is generally measured as a percentage (%).	2 weeks
Secondary	Cerebral Hemoglobin Concentration	The measurement name is "cerebral hemoglobin concentration". The measurement will be assessed by functional near-infrared spectroscopy (fNIRS). The unit of measurement is micromoles per liter (µM).	2 weeks
Secondary	Height in Kilograms	The measurement name is "height in kilograms". It will be assessed by a stadiometer. The unit of measurement is meters (m).	2 weeks
Secondary	Weight in Meters	The measurement name is "weight in meters". It will be assessed by a scale. The unit of measurement is kilograms (kg).	2 weeks
Secondary	Body Fat Percentage	The measurement name is "body fat percentage". It will be assessed by a bioelectrical impedance analysis device. The unit of measurement is percentage (%).	2 weeks
Secondary	Fat Mass	The measurement name is "fat mass". It will be assessed by a bioelectrical impedance analysis device. The unit of measurement is kilograms (kg).	2 weeks
Secondary	Muscle Mass	The measurement name is "muscle mass". It will be assessed by a bioelectrical impedance analysis device. The unit of measurement is kilograms (kg).	2 weeks
Secondary	Body Water	The measurement name is "body water". It will be assessed by a bioelectrical impedance analysis device. The unit of measurement is liters (L).	2 weeks
Secondary	Body Mass Index	The measurement name is "body mass index (BMI)". It will be assessed by calculating BMI using height and weight measurements obtained from a stadiometer and a scale, respectively. The unit of measurement is kilograms per square meter (kg/m²).	2 weeks
Secondary	Skinfold Thickness	The measurement name is "skinfold thickness". It will be assessed by skinfold calipers. The unit of measurement is millimeters (mm).	2 weeks
Secondary	Maximal Oxygen Uptake	The measurement name is "maximal oxygen uptake". It will be assessed by cardiopulmonary exercise testing (CPET) equipment, such as cycle ergometers, along with a metabolic cart for measuring oxygen consumption. The unit of measurement is milliliters of oxygen per kilogram per minute (mL/kg/min).	2 weeks