How exercise and a special ketone supplement may improve heart health, metabolism, and brain function

Approved 25/06/2025, Sub-Panel on Biomedical Science & Engineering Research Ethics of Panel on Research Ethics the Research Committee of the University of Macau (Room 5011 Administration Building University of Macau, N6 Avenida da Universidade Taipa, Macau, 519000, China; +853 8822 4399; rskto.ethics@um.edu.mo), ref: BSE-0213-2025

Study 1
1. Cognitive function is measured using Stroop Test, N-Back, and Delay Discounting Task at baseline and post-intervention
2. Perceived fatigue is measured using Rate of Perceived Exertion (RPE) at pre-exercise, during exercise, and post-exercise
3. Food motivation is measured using Food Craving Questionnaire-State (FCQ-S) at baseline and post-intervention
4. Prefrontal cortex activation patterns are measured using functional Near-Infrared Spectroscopy (fNIRS) during cognitive tasks at baseline and post-intervention
5. Blood glucose, lactate, and beta-hydroxybutyrate are measured using capillary blood sampling analyzed with portable biochemical analyzers at baseline, 45 minutes after the supplement, 60 minutes after the supplement, post-exercise, 1 hour post-exercise, and 2 hours post-exercise
6. Aerobic fitness level is measured using submaximal VO₂ kinetics test with CORTEX METAMAX 3B at baseline, 1 hour post-exercise, 2 hours post-exercise, and 24 hours post-exercise
7. Intervention adherence is measured using blood beta-hydroxybutyrate and lactate concentrations via capillary blood sampling analyzed with portable biochemical analyzers at baseline, 45 minutes after the supplement, 60 minutes after the supplement, post-exercise, 1 hour post-exercise, and 2 hours post-exercise

Study 2
8. Cardiorespiratory fitness is measured using graded exercise test on a cycle ergometer with metabolic cart and heart rate monitoring at baseline and post-intervention
9. Body composition is measured using Dual-energy X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA) at baseline and post-intervention
10. Blood biomarkers of metabolism and appetite are measured using venous blood sampling analyzed via standard clinical chemistry assays at baseline and post-intervention
11. Cognitive function and prefrontal cortex activation patterns are measured using Stroop Test, N-Back, Delay Discounting Task, and fNIRS monitoring during cognitive tasks at baseline, mid-test, and post-intervention
12. Glucose tolerance is measured using 2-hour Oral Glucose Tolerance Test (OGTT) with venous blood sampling at baseline and post-intervention

Study 3
13. Cognitive function is measured using Stroop Task, N-Back Task, and Go/No-Go Task at baseline and 0, 30, and 60 minutes after intervention
14. Prefrontal cortex activation patterns are measured using fNIRS monitoring during cognitive tasks at baseline and 0, 30, and 60 minutes after intervention
15. Blood glucose is measured using finger-prick with portable glucometer at baseline, pre-exercise, 1 hour post-exercise, 90 minutes post-exercise, and 2 hours post-exercise
16. Blood beta-hydroxybutyrate is measured using finger-prick with portable ketone meter at baseline, pre-exercise, 1 hour post-exercise, 90 minutes post-exercise, and 2 hours post-exercise
17. Anxiety is measured using Zung Self-Rating Anxiety Scale (SAS) at pre-test
18. Impulsiveness is measured using Barratt Impulsiveness Scale (BIS-11) at baseline and post-intervention
19. Mobile phone addiction tendency is measured using Mobile Phone Addiction Tendency Scale at baseline and post-intervention
20. Short-form video addiction is measured using short version of social networking sites addictive tendency scale at baseline and post-intervention
21. Smartphone addiction is measured using Smartphone Addiction Scale – Short Version (SAS-SV) at baseline and post-intervention
22. Affective responses are measured using visual analog scale (VAS), Feeling Scale (FS), Physical Activity Enjoyment Scale (PACES), and Empirical Valence Scale (EVS) over the whole intervention
23. Heart rate is measured using Polar heart rate monitor (Polar H10) over the whole intervention
24. Step count is measured using ActiGraph accelerometer over the whole intervention

Study 1
1. Body composition distribution is measured using Dual-energy X-ray absorptiometry (DEXA) and anthropometric measurements at baseline
2. Side effects are measured using oral enquiry after supplementation and exercise sessions at after each intervention session
3. Appetite is measured using Food Craving Questionnaire-State (FCQ-S) at baseline and after intervention
4. Dietary behaviors are measured using 24-hour dietary recall, Three-Factor Eating Questionnaire, and Eating Behavior Scale at baseline and after intervention
5. Anxiety is measured using Generalized Anxiety Scale at baseline and after intervention
6. Ratings of perceived exertion (RPE) are measured using Borg Rating of Perceived Exertion Scale at before, during, and after each exercise session
7. Enjoyment is measured using Physical Activity Enjoyment Scale (PACES), Exercise Enjoyment Scale (EES), and Exercise-induced Feeling Inventory (EFI) at immediately after exercise sessions
8. Heart rate is measured using Polar heart rate monitor (Polar H10) at continuously during intervention sessions
9. Blood pressure is measured using automated sphygmomanometer at baseline, 45 minutes after the supplement, 60 minutes after the supplement, post-exercise, 1 hour post-exercise, and 2 hours post-exercise
10. Peripheral oxygen saturation (SpO₂) is measured using pulse oximeter at during intervention sessions

Study 2
11. Dietary compliance is measured using 3-day food diaries and 24-hour dietary recalls analyzed using the “bohejiankang (薄荷健康)” app at one week before the intervention (lead-in period) as baseline and during the 4-week intervention (e.g., weekly)

Study 3
12. Aerobic fitness is measured using maximal oxygen uptake test with Cortex MetaMax 3B metabolic cart during graded exercise test at baseline
13. Smartphone addiction is measured using proposed diagnostic criteria for smartphone addiction at baseline

All studies
14. Background information is measured using oral enquiry including major, age, origin, and date of birth at baseline for Study 1 and 3 and baseline, during, and after the intervention for Study 2
15. Physical activity is measured using International Physical Activity Questionnaire at baseline for Study 1 and 3 and baseline, during, and after the intervention for Study 2
16. Stature is measured using stadiometer at baseline for Study 1 and 3 and baseline, during, and after the intervention for Study 2