Sport Physiology

Sport Physiology

The Impact of High Intensity Functional Training and MCT Consumption on Brain Neurometabolites through Magnetic Resonance Spectroscopy in Overweight and Obese Healthy Adults

Document Type : Research Paper

Authors
Maryam Nourshahi 1
Kimia Rahimi pour 1
Sina Sanaei 2
Atiye sadat Mirahmadian baba ahmadi 2
1 Department of Biological Sciences in Sport, Faculty of Sport and Health Sciences, Shahid Beheshti University, Tehran, Iran
2 Dpartment of Exercise Physiology, Faculty of Physical Education, Islamic Azad University of Tehran, East Tehran Branch, Tehran, Iran
10.22089/spj.2025.18236.2382
Abstract
Background and Purpose
Obesity and overweight, in addition to being associated with metabolic and cardiovascular diseases, can also affect brain health and accelerate neuronal degeneration and cognitive impairment. Systemic inflammation and oxidative stress caused by obesity can impair the function of various brain regions (including the hippocampus and prefrontal cortex) and disrupt energy metabolism and neurotransmission. N-acetyl aspartate (NAA) is an indicator of neuronal health and density. Choline (Cho) is also an indicator of membrane metabolism. Myo-inositol (mI) is a sensitive indicator of neuronal health, glial activity, and neuroinflammation, and its increase indicates neuronal damage. Increased NAA, cho, and decreased ml are markers of health. Since the importance of nutrition and exercise in neuronal studies has received much attention in recent years, this study was designed to investigate the simultaneous effect of high-intensity functional training and a ketogenic diet with MCT supplementation on NAA, Cho, and mI levels in overweight or obese individuals.
Materials and Methods
The present study is a randomized, quasi-experimental clinical trial. Thirty adults (aged 25 to 45 years) with overweight and grade 1 obesity (BMI between 25 and 34.9) volunteered for this study, of which 9 were excluded from the study due to non-compliance with diet and exercise. These subjects were divided into three groups: control group (C), extreme functional training (EX), and extreme functional training with ketogenic diet and MCT supplementation (EX+KD). The training program (except for the control group) consisted of three sessions per week for six weeks, and each session consisted of 30 to 40 minutes of high-intensity multi-joint functional training (HIFT) including a combination of aerobic and resistance exercises (including squats, swimming, lunges, chest press, butterfly, plank). In the first two weeks, 3 sets were performed at an intensity of 65%-75% of maximum heart rate, in the second two weeks 4 sets at an intensity of 85% to 95% of maximum heart rate, and in the third two weeks at the same intensity and 5 sets of exercises. The ketogenic diet was adjusted by a nutritionist with a specific ratio of 20% protein, 10% carbohydrate, and 70% fat, including 15 mL of MCT daily based on each individual's BMR, and was consumed by the EX+KD group for six weeks. After 6 weeks (a study without pretest due to ethical considerations and restrictions), neural metabolites were measured using single-voxel hydrogen magnetic resonance spectroscopy (1H-MRS) from the cerebellar vermis and analyzed with Osprey software. Sample size was estimated using G*Power 3.1 software for a three-group design. Data were described as mean and standard deviation. Normality of distribution was checked with the Shapiro-Wilk test and homogeneity of variance was checked with the Levene test. One-way analysis of variance (ANOVA) was used for between-group comparisons, and a significance level of P≥0.05 was considered in all analyses. Effect sizes were also calculated using the Cohen's d test. All statistical analyses were performed using SPSS version 25 software.
Results
Statistical analysis showed that high-intensity functional training combined with a ketogenic diet with MCT supplementation produced significant changes in the levels of key brain neurometabolites. All values are reported in ppm. NAA levels were significantly different between groups (F(2,18) = 96.228, P < 0.001). The EX group had a 91% increase in NAA compared to the C group (2.623 ± 0.05 → 1.368 ± 0.04, P < 0.001), while the EX+KD group showed a 38% increase (9.5 ± 0.4 → 10.8 ± 0.5, P < 0.05). However, NAA levels in the EX+KD group were only 27% lower than in the EX group (1.891 ± 0.05 → 2.623 ± 0.05, P < 0.001). These results indicate a positive effect of high-intensity functional training on neuronal health. These findings suggest that high-intensity functional training can improve neuronal health by improving mitochondrial oxidative capacity, promoting myelin synthesis, and enhancing neuron-glia function. Cho levels also differed significantly between groups (F(2,18) = 36.410, P < 0.001). The EX group showed a 97% increase (1.8 ± 0.1 → 2.2 ± 0.1, P < 0.05) and the EX+KD group showed a 193% increase compared to C (2.984 ± 0.05 → 1.010 ± 0.03, P < 0.001). The increase in Cho reflects the promotion of neuronal membrane phospholipid synthesis and remodeling, synaptic plasticity, and neurotrophic activity, and is associated with an increase in brain-derived neurotrophic factor (BDNF) and other neurotrophic factors. These results indicate that the combination of exercise and a ketogenic diet has an enhancing effect on neuronal membrane synthesis. mI levels also showed a significant difference between groups (F(2,18) = 205.112, P < 0.001). Both intervention groups had a significant decrease in mI compared to control: EX 12% (5.2 ± 0.3 → 4.6 ± 0.2, P < 0.05) and EX+KD 57% (5.3 ± 0.3 → 4.2 ± 0.2, P < 0.01). The decrease in mI is indicative of reduced glial activity and reduced neuroinflammation, and is likely related to increased ketone body (BHB) utilization and improved redox balance. Overall, increases in NAA and Cho and decreases in mI indicate improved neuronal health, increased mitochondrial oxidative capacity, and reduced glial inflammation. These changes may lead to improved cognitive and motor functions, and protection of neurons from obesity-induced damage. The findings suggest that high-intensity functional training and a ketogenic diet combined with MCTs have strong synergistic interactive effects on metabolism and neuroprotection in addition to their independent effects.
Conclusion
The results of this study demonstrated that high intensity functional training combined with a ketogenic diet and MCT supplementation significantly altered key brain neurometabolites. Increases in N-acetylaspartate and choline, along with decreased myoinositol, indicate improved neuronal health, enhanced mitochondrial oxidative capacity, increased myelin synthesis, and reduced glial activity and neuroinflammation. These metabolic changes likely enhance cognitive and motor functions, support neural plasticity, and protect neurons from the adverse effects of overweight and obesity. The combination of exercise and diet produced synergistic effects, with the greatest improvements observed in the group receiving both interventions, although each intervention alone also positively influenced brain metabolism. These findings underscore the importance of combined lifestyle interventions in promoting neural function and reducing the risk of obesity-related neuropsychological disorders, suggesting that vigorous exercise paired with a ketogenic diet can serve as an effective, practical approach to enhance brain health and prevent obesity-associated neurological damage in adults.
Article Message
Overweight and obesity are associated with decreased N-acetyl aspartate and choline and increased myo-inositol in the brain, which can lead to neurological disorders. MRS findings suggest that functional training, alone or in combination with a ketogenic diet, increases these beneficial neurometabolites and decreases myo-inositol. Combining high-intensity exercise with a ketogenic diet containing MCTs is an effective strategy for promoting brain health in overweight and obese individuals by improving neurometabolism and reducing markers of neurodegeneration.
Ethical Considerations
This study was approved by the ethics code IR.IUMS.REC.1402.057 at Iran University of Medical Sciences
Authors’ Contributions
Conceptualization: Kimia Rahimi Pour, Maryam Nourshahi
Data Collection: Kimia Rahimi Pour, Sina Sanaei
Data Analysis: Kimia Rahimi Pour,
Manuscript Writing: Atiye Sadat Mirahmadian Baba Ahmadi
Review and Editing: Maryam Nourshahi
Responsible For Funding: Maryam Nourshahi
Literature Review: Maryam Nourshahi
Project Manager: Maryam Nourshahi
Conflict of Interest
According to the authors, this article has no conflict of interest.
Keywords
Intense Functional Training, Ketogenic Diet, MCT, Proton Magnetic Resonance Spectroscopy, Neurometabolite

Subjects

 
 
1. Ibrahim S, Akram Z, Noreen A, Baig MT, Sheikh S, Huma A, et al. Overweight and obesity prevalence and predictors in people living in Karachi. J Pharm Res Int. 2021;33(31B):194-202. https://doi.org/10.9734/jpri/2021/v33i31B31708/
2. Gómez-Apo E, Mondragón-Maya A, Ferrari-Díaz M, Silva-Pereyra J. Structural brain changes associated with overweight and obesity. Journal of Obesity. 2021;2021(1):6613385. https://doi.org/10.1155/2021/6613385/
3. Mueller K, Sacher J, Arelin K, Holiga Š, Kratzsch J, Villringer A, et al. Overweight and obesity are associated with neuronal injury in the human cerebellum and hippocampus in young adults: a combined MRI, serum marker and gene expression study. Translational Psychiatry. 2012;2(12):e200-e. https://doi.org/10.1038/tp.2012.121 
4. Hwang JJ, Jiang L, Hamza M, Rangel ES, Dai F, Belfort-DeAguiar R, et al. Blunted rise in brain glucose levels during hyperglycemia in adults with obesity and T2DM. JCI Insight. 2017;2(20):e95913. https://doi.org/10.1172/jci.insight.95913/
5. Ledreux A, Håkansson K, Carlsson R, Kidane M, Columbo L, Terjestam Y, et al. Differential effects of physical exercise, cognitive training, and mindfulness practice on serum BDNF levels in healthy older adults: a randomized controlled intervention study. Journal of Alzheimer’s Disease. 2019;71(4):1245-61. https://doi.org/10.3233/JAD-190756/
6. Hashimoto T, Tsukamoto H, Ando S, Ogoh S. Effect of exercise on brain health: the potential role of lactate as a myokine. Metabolites. 2021;11(12):813. https://doi.org/10.3390/metabo11120813/
7. Rivas-Campo Y, Garcia-Garro PA, Aibar-Almazan A, Martinez-Amat A, Vega-Avila GC, Afanador-Restrepo DF, et al. The effects of high-intensity functional training on cognition in older adults with cognitive impairment: a systematic review. Healthcare. 2022;10(4):670. https://doi.org/10.3390/healthcare10040670/
8. Storoni M, Plant GT. The therapeutic potential of the ketogenic diet in treating progressive multiple sclerosis. Multiple Sclerosis International. 2015;2015(1):681289  https://doi.org/681289/2015/10/1155
9. Paoli A. Ketogenic diet for obesity: friend or foe? International Journal of Environmental Research and Public Health. 2014;11(2):2092-107. https://doi.org/10.3390/ijerph110202092/
10. Westman EC, Tondt J, Maguire E, Yancy Jr WS. Implementing a low-carbohydrate, ketogenic diet to manage type 2 diabetes mellitus. Expert Review of Endocrinology & Metabolism. 2018;13(5):263-72. https://doi.org/10.1080/17446651.2018.1523713/
11. Zilberter Y, Zilberter M. The vicious circle of hypometabolism in neurodegenerative diseases: ways and mechanisms of metabolic correction. Journal of Neuroscience Research. 2017;95(11):2217-35. https://doi.org/10.1002/jnr.24064/
12. Avgerinos KI, Egan JM, Mattson MP, Kapogiannis D. Medium Chain Triglycerides induce mild ketosis and may improve cognition in Alzheimer’s disease: a systematic review and meta-analysis of human studies. Ageing Research Reviews. 2020;58:101001. https://doi.org/10.1016/j.arr.2019.101001./
13. Xu Q, Zhang Y, Zhang X, Liu L, Zhou B, Mo R, et al. Medium-chain triglycerides improved cognition and lipid metabolomics in mild to moderate Alzheimer's disease patients with APOE4−/−: a double-blind, randomized, placebo-controlled crossover trial. Clinical Nutrition. 2020;39(7):2092-105. https://doi.org/10.1016/j.clnu.2019.10.017/
14. Juby AG, Blackburn TE, Mager DR. Use of medium chain triglyceride (MCT) oil in subjects with Alzheimer's disease: a randomized, double‐blind, placebo‐controlled, crossover study, with an open‐label extension. Alzheimer's & Dementia: Translational Research & Clinical Interventions. 2022;8(1):e12259.
15. Grochowska K, Przeliorz A. The effect of the ketogenic diet on the therapy of neurodegenerative diseases and its impact on improving cognitive functions. Dementia and geriatric Cognitive Disorders Extra. 2022;12(2):100-6. https://doi.org/10.1159/000524331/
16. Croteau E, Castellano C-A, Richard MA, Fortier M, Nugent S, Lepage M, et al. Ketogenic medium chain triglycerides increase brain energy metabolism in Alzheimer’s disease. Journal of Alzheimer's Disease. 2018;64(2):551-61. https://doi.org/10.3233/JAD-180202/
17. Taheri H, Elahifar MA, Bighamian A. Magnetic Resonance Spectroscopy in Neurological Disorders. Iranian Journal of Radiology (30th Iranian Congress of Radiology). 2014;11. https://doi.org/10.5812/iranjradiol.21326/
18. Zhao X, Han Q, Gang X, Wang G. Altered brain metabolites in patients with diabetes mellitus and related complications–evidence from 1H MRS study. Bioscience Reports. 2018;38(5):BSR20180660. https://doi.org/10.1042/BSR20180660/
19. Robatjazi M PA, Hassan Karimi H, Assadi M. Molecular imaging with Magnetic Resonance Spectroscopy (MRS). Iran South Med. 2015;18(1):210-21. [In Persian].
20. Pawlosky RJ, Kemper MF, Kashiwaya Y, King MT, Mattson MP, Veech RL. Effects of a dietary ketone ester on hippocampal glycolytic and tricarboxylic acid cycle intermediates and amino acids in a 3xTg AD mouse model of Alzheimer's disease. Journal of Neurochemistry. 2017;141(2):195-207.
21. Pawlosky RJ, Kashiwaya Y, King MT, Veech RL. A dietary ketone ester normalizes abnormal behavior in a mouse model of Alzheimer’s disease. International Journal of Molecular Sciences. 2020;21(3):1044.
22. Zhang F, Wu H, Jin Y, Zhang X. Proton magnetic resonance spectroscopy (H1-MRS) study of the ketogenic diet on repetitive mild traumatic brain injury in adolescent rats and its effect on neurodegeneration. World Neurosurg. 2018;120:e1193-e1202. https://doi.org/101016/j.wneu.2018.09.037
23.   Erickson KI, Weinstein AM, Sutton BP, Prakash RS, Voss MW, Chaddock L, et al. Beyond vascularization: aerobic fitness is associated with N‐acetylaspartate and working memory. Brain and Behavior. 2012;2(1):32-41. https://doi.org/10.1002/brb3.30/
24. Wright J, Saneto R, Friedman S. β-Hydroxybutyrate detection with proton MR spectroscopy in children with drug-resistant epilepsy on the ketogenic diet. American Journal of Neuroradiology. 2018;39(7):1336-40.
25. Gonzales MM, Tarumi T, Kaur S, Nualnim N, Fallow BA, Pyron M, et al. Aerobic fitness and the brain: increased N-acetyl-aspartate and choline concentrations in endurance-trained middle-aged adults. Brain Topography. 2013;26:126-34. https://doi.org/10.1007/s10548-012-0248-8/
26. Maddock RJ, Buonocore MH. MR spectroscopic studies of the brain in psychiatric disorders. Brain Imaging in Behavioral Neuroscience. 2012:199-251. https://doi.org/10.1007/7854_2011_197/
27. Sporn L, MacMillan EL, Ge R, Greenway K, Vila‐Rodriguez F, Laule C. Longer repetition time proton MR spectroscopy shows increasing hippocampal and parahippocampal metabolite concentrations with aging. Journal of Neuroimaging. 2019;29(5):592-7. https://doi.org/10.1111/jon.12648/
28. Sleiman SF, Henry J, Al-Haddad R, El Hayek L, Abou Haidar E, Stringer T, et al. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate. Elife. 2016;5:e15092. https://doi.org/10.7554/eLife.15092/
29. Rae CD. A guide to the metabolic pathways and function of metabolites observed in human brain 1 H magnetic resonance spectra. Neurochemical Research. 2014;39:1-36. https://doi.org/10.1007/s11064-013-1199-5/
30. Cleeland C, Pipingas A, Scholey A, White D. Neurochemical changes in the aging brain: a systematic review. Neuroscience & Biobehavioral Reviews. 2019;98:306-19. https://doi.org/10.1016/j.neubiorev.2019.01.003/
31. Yin J, Han P, Tang Z, Liu Q, Shi J. Sirtuin 3 mediates neuroprotection of ketones against ischemic stroke. Journal of Cerebral Blood Flow & Metabolism. 2015;35(11):1783-9. https://doi.org/10.1038/jcbfm.2015.123/
32. Ding X-Q, Maudsley AA, Schweiger U, Schmitz B, Lichtinghagen R, Bleich S, et al. Effects of a 72 hours fasting on brain metabolism in healthy women studied in vivo with magnetic resonance spectroscopic imaging. Journal of Cerebral Blood Flow & Metabolism. 2018;38(3):469-78. https://doi.org/10.1177/0271678X17697721/
33. Göschel L, Fillmer A, Dell'Orco A, Melin J, Aydin S, Kurz L, et al. Associations between the glial marker myo‐inositol measured by 7T MRS and other AD‐relevant measures. Alzheimer's & Dementia. 2022;18:e069340. https://doi.org/10.1002/alz.069340/
34. Warepam M, Mishra AK, Sharma GS, Kumari K, Krishna S, Khan MSA, et al. Brain metabolite, N-acetylaspartate is a potent protein aggregation inhibitor. Frontiers in Cellular Neuroscience. 2021;15:617308. https://doi.org/10.3389/fncel.2021.617308/
35. Zhu H, Bi D, Zhang Y, Kong C, Du J, Wu X, et al. Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations. Signal Transduction and Targeted Therapy. 2022;7(1):11. https://doi.org/10.1038/s41392-021-00831-w/
36. Mutoh T, Kunitoki K, Tatewaki Y, Yamamoto S, Thyreau B, Matsudaira I, et al. Impact of medium-chain triglycerides on gait performance and brain metabolic network in healthy older adults: a double-blind, randomized controlled study. GeroScience. 2022;44(3):1325-38. https://doi.org/10.1007/s11357-022-00553-z/
37. Rojas-Morales P, Pedraza-Chaverri J, Tapia E. Ketone bodies, stress response, and redox homeostasis. Redox Biology. 2020;29:101395.
Sport Physiology
Volume 17, Issue 68
Winter 2026
Pages 17-34

  • Receive Date 19 August 2025
  • Revise Date 26 November 2025
  • Accept Date 05 December 2025