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

Not Applicable
Not yet recruiting
Conditions
Cognitive Change
Overweight and Obesity
Psychophysiologic Reaction
Interventions
Dietary Supplement: Ketone Monoester Supplementation
Dietary Supplement: Ketogenic diet
Registration Number
NCT06368297
Lead Sponsor
University of Macau
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.

Detailed 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 & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
40
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Acute effect of ketone monoester supplementationKetone Monoester SupplementationTo investigate the acute effect of ketone monoester ingestion on brain cortical plasticity using high-frequency rTMS.
Effects of a 2-week ketogenic diet or ketone monoester supplementationKetone Monoester SupplementationTo 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.
Effects of a 2-week ketogenic diet or ketone monoester supplementationKetogenic dietTo 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.
Primary Outcome Measures
NameTimeMethod
Grey Matter Volume2 weeks

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.

Brain Plasticity2 weeks

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.

Cortical Thickness2 weeks

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.

Blood-Oxygen-Level-Dependent (BOLD) Signal Changes2 weeks

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.

Secondary Outcome Measures
NameTimeMethod
Blood Insulin6 weeks

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).

Brain-Derived Neurotrophic Factor6 weeks

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).

Blood Glucose6 weeks

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).

Reaction Time of Stroop Task2 weeks

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).

Blood Beta-Hydroxybutyrate6 weeks

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).

Leptin6 weeks

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).

Accuracy of Attention Network Test2 weeks

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 (%).

Height in Kilograms2 weeks

The measurement name is "height in kilograms". It will be assessed by a stadiometer. The unit of measurement is meters (m).

Ghrelin6 weeks

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).

Reaction Time of N-back Task2 weeks

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).

Skinfold Thickness2 weeks

The measurement name is "skinfold thickness". It will be assessed by skinfold calipers. The unit of measurement is millimeters (mm).

Reaction Time of Attention Network Test2 weeks

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).

Accuracy of N-back Task2 weeks

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 (%).

Cerebral Hemoglobin Concentration2 weeks

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).

Body Fat Percentage2 weeks

The measurement name is "body fat percentage". It will be assessed by a bioelectrical impedance analysis device. The unit of measurement is percentage (%).

Body Mass Index2 weeks

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).

Muscle Mass2 weeks

The measurement name is "muscle mass". It will be assessed by a bioelectrical impedance analysis device. The unit of measurement is kilograms (kg).

Maximal Oxygen Uptake2 weeks

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).

Accuracy of Stroop Task2 weeks

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 (%).

Weight in Meters2 weeks

The measurement name is "weight in meters". It will be assessed by a scale. The unit of measurement is kilograms (kg).

Fat Mass2 weeks

The measurement name is "fat mass". It will be assessed by a bioelectrical impedance analysis device. The unit of measurement is kilograms (kg).

Body Water2 weeks

The measurement name is "body water". It will be assessed by a bioelectrical impedance analysis device. The unit of measurement is liters (L).

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