Investigation of the Relationship Between Gray and White Matter Volumes, Walking Exercise, and Body Fat Percentage in Adults With a Body Mass Index Above 25

This study examines the relationship between walking exercise, body fat percentage changes, and brain gray and white matter volumes in overweight and obese adults with headache complaints. Participants with a Body Mass Index (BMI) of 25 or above will be divided into two groups: one receiving a diet program combined with a 12-week walking exercise regimen, and a control group receiving diet alone. Both groups will undergo brain MRI scans and body composition measurements at baseline and after 12 weeks. The study aims to determine whether exercise-induced reductions in body fat percentage have a measurable impact on brain structure, specifically gray and white matter volumes. Blood tests will monitor metabolic markers throughout the intervention. This research may contribute to understanding how different types of exercise affect brain health and inform the development of more effective treatments for obesity-related neurological changes.

Study Overview

• Status: Completed
• Conditions: Sedentary Lifestyle; Headache; Obesity & Overweight; Body Fat Percentage; Brain Grey Matter; Brain White Matter
• Intervention / Treatment: Behavioral: Walking Exercise Program; Behavioral: Dietary Intervention; Diagnostic test: Brain MRI Morphometry; Diagnostic test: Body Composition Analysis; Diagnostic test: Blood Biomarker Analysis

Detailed Description

Background:

Obesity has become a major public health concern over the past 40 years, with increasing evidence linking elevated BMI to numerous physical and mental health problems. Neuroimaging studies demonstrate that obesity negatively affects brain function and structure, particularly within the fronto-mesolimbic circuit. Structural MRI studies have revealed associations between obesity and reduced gray/white matter volumes, altered cortical morphometry, and impaired white matter integrity. Research highlights obesity's impact on cognitive functions including decision-making, inhibition control, learning/memory, and attention.

Study Design:

This is a 12-week prospective experimental study with a control group design. The study will recruit 22 adults (11 per group) with BMI ≥25 who present with headache complaints to the neurosurgery department between January-March 2024.

Inclusion Criteria:

Adults aged 19-65 years with headache complaints BMI ≥25 kg/m² Brain MRI performed between 01.01.2024-01.03.2024 Baseline blood tests completed (fasting glucose, lipid profile, liver enzymes, thyroid function, vitamin B12, hemogram, HbA1c) Scheduled for routine 6-month follow-up blood work Willing to undergo follow-up brain MRI at 12 weeks (funded by researchers) Able to attend 6 biweekly nutrition counseling sessions over 12 weeks Able to attend 6 biweekly body composition measurements No diagnosed chronic conditions (hypertension, diabetes) Proficient with smartphone heart rate and step counter applications

Exclusion Criteria:

Chronic diseases (hypertension, diabetes) Physical disabilities Use of antidepressant medications Regular exercise practitioners History of cerebrovascular disease Epilepsy diagnosis Multiple sclerosis or Alzheimer's disease Conditions affecting brain ventricular volume (e.g., hydrocephalus) Pregnancy or breastfeeding

Intervention:

Exercise Protocol (Experimental Group):

Exercise intensity will be determined using the Karvonen method to establish target heart rate. Walking exercise will be prescribed 5 days per week, with progressive intensity increases from 50% to 70% maximum heart rate over 12 weeks. Session duration will gradually increase from 20 minutes initially to 60 minutes by week 12 to support adaptation and achieve maximum heart rate targets. Heart rate will be monitored every 20 minutes during exercise using smartphone applications.

Diet Protocol (Both Groups):

Individual energy needs will be calculated using Mifflin-St. Jeor equations based on current weight. Physical activity level (PAL) will be determined, and total energy expenditure calculated. Diet prescriptions will create a 500-750 kcal/day deficit targeting 0.5-1 kg weekly weight loss, with a goal of 5% weight reduction over 12 weeks. Macronutrient distribution will be 50-60% carbohydrates, 15-20% protein, and 25-30% fat.

Measurements:

Baseline and 12-Week Assessments:

Sociodemographic Data: Personal interview form Anthropometrics: Height measured with SECA 216 stadiometer; BMI calculated Body Composition: InBody 370 bioelectrical impedance analysis under standardized conditions (light clothing, barefoot, fasted ≥2 hours, post-void 30 minutes) Blood Samples: Fasting (12 hours) venous blood collected at 09:00 AM to minimize circadian variation. Analysis includes fasting glucose, lipid profile, liver enzymes (ALT, AST, GGT), thyroid function (T3, T4, TSH), vitamin B12, complete blood count, and HbA1c Brain MRI: Performed using 1.5T Siemens Magnetom Avanto scanner with standard head coil. T2-weighted axial images using 3D SPGR sequence (TR=800ms, TE=26ms, FOV=230mm, resolution=192x256, slice thickness=5mm). T1-weighted axial images (FOV=420mm, FOV Phase=81.3%, slice thickness=6mm, TR=170ms, TE=2.38ms)

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Amasya, Turkey (Türkiye), 05100
    • Amasya Sabuncuoglu Serefeddin Training and Research Hospital
  • Amasya, Turkey (Türkiye), 05100
    • Kolmed Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults aged 19-65 years
2. Body Mass Index (BMI) ≥25 kg/m²
3. Presented to the neurosurgery department with headache complaints between January 1, 2024 and March 1, 2024
4. Underwent brain magnetic resonance imaging (MRI) between January 1, 2024 and March 1, 2024

5. Completed baseline blood tests between January 1, 2024 and March 1, 2024, including:

   • Fasting blood glucose
   • Lipid profile (total cholesterol, LDL, HDL, triglycerides)
   • Liver enzymes (ALT, AST, GGT)
   • Thyroid function tests (T3, T4, TSH)
   • Vitamin B12
   • Complete blood count (hemogram)
   • Hemoglobin A1c (HbA1c)
6. Scheduled for routine 6-month follow-up blood work based on initial test results
7. Willing to undergo follow-up brain MRI at 12 weeks (costs covered by research team)
8. Willing and able to attend 6 biweekly nutrition counseling sessions over 12 weeks with the study dietitian
9. Willing and able to attend 6 biweekly body composition measurement appointments over 12 weeks
10. No diagnosed chronic conditions including hypertension or diabetes
11. Owns a smartphone and is proficient in using smartphone applications for heart rate monitoring and step counting

Exclusion Criteria:

1. Did not present to the neurosurgery department with headache complaints between January 1, 2024 and March 1, 2024
2. Did not undergo brain MRI between January 1, 2024 and March 1, 2024
3. Did not complete required baseline blood tests (fasting glucose, lipid profile, liver enzymes, thyroid function, vitamin B12, hemogram, HbA1c) between January 1, 2024 and March 1, 2024
4. BMI <25 kg/m²
5. Unable or unwilling to attend 6 biweekly nutrition counseling sessions over 12 weeks
6. Unable or unwilling to attend 6 biweekly body composition measurement appointments over 12 weeks
7. Diagnosed chronic diseases including hypertension or diabetes
8. Unable to use smartphone applications for heart rate monitoring and step counting, or does not own a smartphone
9. Physical disabilities that would prevent walking exercise
10. Current use of antidepressant medications
11. Currently engaged in regular exercise programs
12. History of cerebrovascular disease (stroke, transient ischemic attack)
13. Diagnosis of epilepsy
14. Diagnosis of Multiple Sclerosis or Alzheimer's disease
15. Conditions affecting brain ventricular volume (e.g., hydrocephalus)
16. Pregnancy
17. Currently breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Walking Exercise + Diet; Participants in this arm will receive a personalized diet program combined with a 12-week supervised walking exercise intervention. Exercise intensity will be determined using the Karvonen method to establish target heart rate, with progressive increases from 50% to 70% maximum heart rate. Walking will be performed 5 days per week, with duration gradually increasing from 20 minutes to 60 minutes over 12 weeks. Heart rate will be monitored every 20 minutes using smartphone applications. Diet will create a 500-750 kcal/day deficit with macronutrient distribution of 50-60% carbohydrates, 15-20% protein, and 25-30% fat. Participants will attend 6 biweekly nutrition counseling sessions and 6 biweekly body composition measurements over the 12-week period.	Behavioral: Walking Exercise Program; Supervised 12-week progressive walking exercise program performed 5 days per week. Exercise intensity is determined using the Karvonen method to calculate target heart rate zones, starting at 50% and progressively increasing to 70% of maximum heart rate. Session duration begins at 20 minutes and gradually increases to 60 minutes by week 12 to support cardiovascular adaptation. Heart rate is monitored every 20 minutes during exercise using smartphone applications with integrated pulse measurement capabilities. Participants receive individualized heart rate targets and step count goals based on their baseline fitness level and age.; Behavioral: Dietary Intervention; Individualized calorie-restricted diet program calculated using the Mifflin-St. Jeor equation based on participants' current weight, height, age, and physical activity level. Diet creates a 500-750 kcal/day energy deficit targeting 0.5-1 kg weekly weight loss with a goal of 5% body weight reduction over 12 weeks. Macronutrient distribution: 50-60% carbohydrates, 15-20% protein, 25-30% fat, following Turkish Ministry of Health dietary guidelines. Participants attend 6 biweekly individual nutrition counseling sessions with a registered dietitian over the 12-week intervention period to review progress, adjust meal plans, and provide ongoing support and education.; Diagnostic test: Brain MRI Morphometry; Brain magnetic resonance imaging performed at baseline and 12 weeks using 1.5 Tesla Siemens Magnetom Avanto scanner with standard head coil. Imaging protocol includes: (1) T2-weighted axial images using 3D Spoiled Gradient (SPGR) sequence (TR=800ms, TE=26ms, FOV=230mm, matrix=192x256, slice thickness=5mm) for volumetric analysis; (2) T1-weighted axial images (FOV=420mm, FOV Phase=81.3%, slice thickness=6mm, TR=170ms, TE=2.38ms). Images will be analyzed for gray matter and white matter volumes using standardized morphometric techniques. The 12-week follow-up MRI is funded by the research team.; Diagnostic test: Body Composition Analysis; Body composition measurements performed at baseline and biweekly throughout the 12-week intervention (6 total assessments) using InBody 370 bioelectrical impedance analysis device. Measurements are standardized with participants wearing light clothing, barefoot, in a fasted state (minimum 2 hours), and 30 minutes post-void to ensure accuracy. Parameters assessed include body fat percentage, skeletal muscle mass, total body water, and segmental body composition. A fixed 0.50 kg clothing allowance is applied to all measurements for consistency.; Diagnostic test: Blood Biomarker Analysis; Fasting venous blood samples (approximately 5 mL) collected at baseline and 12 weeks after minimum 12-hour fast, standardized to 09:00 AM collection time to minimize circadian variation. Metabolic parameters analyzed include: fasting glucose, lipid profile (total cholesterol, LDL, HDL, triglycerides), liver enzymes (ALT, AST, GGT), thyroid function (T3, T4, TSH), vitamin B12, complete blood count (hemogram), and HbA1c. Blood samples are analyzed using standardized laboratory equipment: Beckman Coulter for glucose and lipids, Siemens Advia Centaur XP for hormones, Sysmex XN-1000 for hematology, and Premier Hb9210 for HbA1c.
Active Comparator: Active Comparator: Diet Only; Participants in this arm will receive the same personalized diet program as the experimental group but without the walking exercise component. Diet will create a 500-750 kcal/day deficit with macronutrient distribution of 50-60% carbohydrates, 15-20% protein, and 25-30% fat. Participants will attend 6 biweekly nutrition counseling sessions and 6 biweekly body composition measurements over the 12-week period. This group serves as an active control to isolate the specific effects of exercise on brain structure beyond those achieved through dietary weight loss alone.	Behavioral: Dietary Intervention; Individualized calorie-restricted diet program calculated using the Mifflin-St. Jeor equation based on participants' current weight, height, age, and physical activity level. Diet creates a 500-750 kcal/day energy deficit targeting 0.5-1 kg weekly weight loss with a goal of 5% body weight reduction over 12 weeks. Macronutrient distribution: 50-60% carbohydrates, 15-20% protein, 25-30% fat, following Turkish Ministry of Health dietary guidelines. Participants attend 6 biweekly individual nutrition counseling sessions with a registered dietitian over the 12-week intervention period to review progress, adjust meal plans, and provide ongoing support and education.; Diagnostic test: Brain MRI Morphometry; Brain magnetic resonance imaging performed at baseline and 12 weeks using 1.5 Tesla Siemens Magnetom Avanto scanner with standard head coil. Imaging protocol includes: (1) T2-weighted axial images using 3D Spoiled Gradient (SPGR) sequence (TR=800ms, TE=26ms, FOV=230mm, matrix=192x256, slice thickness=5mm) for volumetric analysis; (2) T1-weighted axial images (FOV=420mm, FOV Phase=81.3%, slice thickness=6mm, TR=170ms, TE=2.38ms). Images will be analyzed for gray matter and white matter volumes using standardized morphometric techniques. The 12-week follow-up MRI is funded by the research team.; Diagnostic test: Body Composition Analysis; Body composition measurements performed at baseline and biweekly throughout the 12-week intervention (6 total assessments) using InBody 370 bioelectrical impedance analysis device. Measurements are standardized with participants wearing light clothing, barefoot, in a fasted state (minimum 2 hours), and 30 minutes post-void to ensure accuracy. Parameters assessed include body fat percentage, skeletal muscle mass, total body water, and segmental body composition. A fixed 0.50 kg clothing allowance is applied to all measurements for consistency.; Diagnostic test: Blood Biomarker Analysis; Fasting venous blood samples (approximately 5 mL) collected at baseline and 12 weeks after minimum 12-hour fast, standardized to 09:00 AM collection time to minimize circadian variation. Metabolic parameters analyzed include: fasting glucose, lipid profile (total cholesterol, LDL, HDL, triglycerides), liver enzymes (ALT, AST, GGT), thyroid function (T3, T4, TSH), vitamin B12, complete blood count (hemogram), and HbA1c. Blood samples are analyzed using standardized laboratory equipment: Beckman Coulter for glucose and lipids, Siemens Advia Centaur XP for hormones, Sysmex XN-1000 for hematology, and Premier Hb9210 for HbA1c.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brain Gray Matter Volume	Change in total cerebral gray matter volume measured by structural MRI morphometry using 1.5T Siemens Magnetom Avanto scanner. Volumetric analysis performed using T2-weighted 3D SPGR sequences (TR=800ms, TE=26ms, slice thickness=5mm) and T1-weighted axial images. Gray matter volume quantified in cubic centimeters (cm³) or milliliters (mL). Change calculated as: (12-week volume) - (baseline volume).	Baseline and 12 weeks
Change in Brain White Matter Volume	Change in total cerebral white matter volume measured by structural MRI morphometry using 1.5T Siemens Magnetom Avanto scanner. Volumetric analysis performed using T2-weighted 3D SPGR sequences (TR=800ms, TE=26ms, slice thickness=5mm) and T1-weighted axial images. White matter volume quantified in cubic centimeters (cm³) or milliliters (mL). Change calculated as: (12-week volume) - (baseline volume).	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Fat Percentage	Change in body fat percentage measured by bioelectrical impedance analysis using InBody 370 device. Measurements performed under standardized conditions (fasted ≥2 hours, post-void 30 minutes, light clothing, barefoot). Body fat percentage expressed as percentage of total body weight. Change calculated as: (12-week percentage) - (baseline percentage).	Baseline, weeks 2, 4, 6, 8, 10, and 12 (7 total assessments)
Change in Body Weight	Change in body weight measured in kilograms using InBody 370 bioelectrical impedance analysis device with standardized 0.50 kg clothing allowance. Change calculated as: (12-week weight) - (baseline weight). Percent weight change also calculated as: [(12-week weight - baseline weight) / baseline weight] × 100.	Baseline, weeks 2, 4, 6, 8, 10, and 12 (7 total assessments)
Change in Body Mass Index (BMI)	Change in Body Mass Index calculated as weight (kg) divided by height squared (m²). Height measured using SECA 216 stadiometer at baseline. BMI expressed in kg/m². Change calculated as: (12-week BMI) - (baseline BMI).	Baseline and 12 weeks
Change in Fasting Blood Glucose	Change in fasting blood glucose concentration measured in mg/dL from venous blood samples collected after minimum 12-hour fast at standardized time (09:00 AM). Analyzed using Beckman Coulter automated analyzer. Change calculated as: (12-week glucose) - (baseline glucose).	Baseline and 12 weeks
Change in Lipid Profile	Change in lipid panel including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, all measured in mg/dL from fasting venous blood samples. Analyzed using Beckman Coulter automated analyzer. Changes calculated as: (12-week values) - (baseline values) for each lipid parameter.	Baseline and 12 weeks
Change in Liver Enzymes	Change in liver function markers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT), measured in U/L from fasting venous blood samples. Analyzed using Beckman Coulter automated analyzer. Changes calculated as: (12-week values) - (baseline values) for each enzyme.	Baseline and 12 weeks
Change in Hemoglobin A1c (HbA1c)	Change in glycated hemoglobin (HbA1c) measured as percentage of total hemoglobin from venous blood samples. Analyzed using Premier Hb9210 automated analyzer. Change calculated as: (12-week HbA1c) - (baseline HbA1c).	Baseline and 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between Body Fat Percentage Change and Gray Matter Volume Change	Pearson or Spearman correlation coefficient examining the relationship between changes in body fat percentage and changes in gray matter volume over the 12-week intervention period. Correlation analysis will assess whether greater reductions in body fat are associated with changes (positive or negative) in gray matter volume.	12 weeks (correlation of changes from baseline to week 12)
Correlation Between Body Fat Percentage Change and White Matter Volume Change	Pearson or Spearman correlation coefficient examining the relationship between changes in body fat percentage and changes in white matter volume over the 12-week intervention period. Correlation analysis will assess whether greater reductions in body fat are associated with changes (positive or negative) in white matter volume.	12 weeks (correlation of changes from baseline to week 12)
Change in Thyroid Function Markers	Change in thyroid function markers including triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) measured from fasting venous blood samples. Analyzed using Siemens Advia Centaur XP automated analyzer. Changes calculated as: (12-week values) - (baseline values) for each marker.	Baseline and 12 weeks
Change in Vitamin B12 Level	Change in serum vitamin B12 concentration measured in pg/mL from fasting venous blood samples. Analyzed using Siemens Advia Centaur XP automated analyzer. Change calculated as: (12-week B12) - (baseline B12).	Baseline and 12 weeks
Change in Skeletal Muscle Mass	Change in total skeletal muscle mass measured in kilograms using InBody 370 bioelectrical impedance analysis. Measurements performed under standardized conditions. Change calculated as: (12-week muscle mass) - (baseline muscle mass).	Baseline, weeks 2, 4, 6, 8, 10, and 12 (7 total assessments)

Collaborators and Investigators

• Sponsor: Amasya University

Publications and helpful links

General Publications

• Kullmann S, Callaghan MF, Heni M, Weiskopf N, Scheffler K, Haring HU, Fritsche A, Veit R, Preissl H. Specific white matter tissue microstructure changes associated with obesity. Neuroimage. 2016 Jan 15;125:36-44. doi: 10.1016/j.neuroimage.2015.10.006. Epub 2015 Oct 13.
• Jaacks LM, Vandevijvere S, Pan A, McGowan CJ, Wallace C, Imamura F, Mozaffarian D, Swinburn B, Ezzati M. The obesity transition: stages of the global epidemic. Lancet Diabetes Endocrinol. 2019 Mar;7(3):231-240. doi: 10.1016/S2213-8587(19)30026-9. Epub 2019 Jan 28.

Helpful Links

• Official website of Amasya University, host institution for the ethics committee that approved this study (approval number: 2024/42)

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Actual): March 1, 2024
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: February 15, 2026
• First Submitted That Met QC Criteria: February 15, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 15, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: physical activity; body mass index; obesity; aerobic exercise; weight loss; diet intervention; brain grey matter; brain white matter; mri brain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nutrition Disorders; Overnutrition; Body Weight; Body Weight Changes; Pathological Conditions, Signs and Symptoms; Behavior; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Weight Loss; Headache; Motor Activity; Sedentary Behavior; Therapeutics; Nutrition Therapy; Diet Therapy
• Other Study ID Numbers: 050.04-190521

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