Effects of Medium-Chain Triglyceride and Medium-Chain Fatty Acid Supplementation on Skeletal Muscle Morphology, Metabolism, and Function in Adult Humans and Animals: A Protocol for a Systematic Review and Meta-Analysis
Abstract
Background. Medium-chain triglycerides (MCT) and medium-chain fatty acids (MCFA) have distinct metabolic properties and may influence skeletal muscle metabolism and function; however, evidence is fragmented and inconsistent.
Aim. The aim of this systematic review and meta-analysis is to evaluate the clinically relevant and mechanistic effects of MCFA/MCT supplementation on skeletal muscle morphology, metabolism, and function in adult humans and adult animal models.
Data Sources. Peer-reviewed studies will be identified through systematic searches of major electronic databases, and reference lists of included studies will be screened to identify additional relevant publications.
Participants and Interventions. Eligible studies will include randomised controlled trials conducted in adult human and adult animal models, comparing the effects of oral MCFA/MCT supplementation with placebo oils, usual diet, or calorie-matched controls.
Study Appraisal and Synthesis Methods. Risk of bias will be assessed using RoB 2 for human studies and the SYRCLE tool for animal studies. Where appropriate, random-effects meta-analyses will be conducted; otherwise, findings will be synthesised narratively. The certainty of evidence will be evaluated using the GRADE framework. Human and animal studies will be synthesised and analysed separately to distinguish clinically relevant outcomes from mechanistic evidence and to avoid inappropriate cross-species inference.
Conclusions. This protocol outlines a transparent and rigorous approach to synthesising current evidence on MCFA/MCT supplementation and skeletal muscle-related outcomes. The findings are expected to clarify existing evidence gaps and inform future research in nutrition and muscle health.
Keywords: Medium-chain fatty acids; skeletal muscle; muscle metabolism; muscle function; randomised controlled trials
References
1. Abe, T., Hirasaka, K., Kohno, S., Tomida, C., Haruna, M., Uchida, T., Ohno, A., Oarada, M., Teshima-Kondo, S., Okumura, Y., Choi, I., Aoyama, T., Terao, J., & Nikawa, T. (2016). Capric acid up-regulates UCP3 expression without PDK4 induction in mouse C2C12 myotubes. Journal of Nutritional Science and Vitaminology, 62(1), 32–39. https://doi.org/10.3177/jnsv.62.32
2. Bach, A. C., & Babayan, V. K. (1982). Medium-chain triglycerides: An update. The American Journal of Clinical Nutrition, 36(5), 950–962. https://doi.org/10.1093/ajcn/36.5.950
3. Chapman-Lopez, T. J., & Koh, Y. (2022). The effects of medium-chain triglyceride oil supplementation on endurance performance and substrate utilization in healthy populations: A systematic review. Journal of Obesity & Metabolic Syndrome, 31(3), 217–229. https://doi.org/10.7570/jomes22028
4. Charlot, A., Morel, L., Bringolf, A., Georg, I., Charles, A.-L., Goupilleau, F., Geny, B., & Zoll, J. (2022). Octanoic acid-enrichment diet improves endurance capacity and reprograms mitochondrial biogenesis in skeletal muscle of mice. Nutrients, 14(13), 2721. https://doi.org/10.3390/nu14132721
5. Ishizawa, R., Masuda, K., Sakata, S., & Nakatani, A. (2015). Effects of different fatty acid chain lengths on fatty acid oxidation-related protein expression levels in rat skeletal muscles. Journal of Oleo Science, 64(4), 415–421. https://doi.org/10.5650/jos.ess14199
6. Kojima, K., Ishikawa, H., Watanabe, S., Nosaka, N., & Mutoh, T. (2023). A randomized, double-blind, controlled trial assessing if medium-chain triglycerides in combination with moderate-intensity exercise increase muscle strength in healthy middle-aged and older adults. Nutrients, 15(14), 3275. https://doi.org/10.3390/nu15143275
7. Mastavičiūtė, A., Kilaitė, J., Petroška, D., Laurinavičius, A., Tamulaitienė, M., & Alekna, V. (2021). Associations between physical function, bone density, muscle mass and muscle morphology in older men with sarcopenia: A pilot study. Medicina, 57(2), 156. https://doi.org/10.3390/medicina57020156
8. Moher, D., Shamseer, L., Clarke, M., Ghersi, D., Liberati, A., Petticrew, M., Shekelle, P., & Stewart, L. A., & PRISMA-P Group. (2015). Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic Reviews, 4, 1. https://doi.org/10.1186/2046-4053-4-1
9. Mumme, K., & Stonehouse, W. (2015). Effects of medium-chain triglycerides on weight loss and body composition: A meta-analysis of randomized controlled trials. Journal of the Academy of Nutrition and Dietetics, 115(2), 249–263. https://doi.org/10.1016/j.jand.2014.10.022
10. Mutoh, T., Kataoka, H., Tatewaki, Y., & Taki, Y. (2025). Medium-chain triglyceride dietary supplements reduce glucose metabolism of gait-related skeletal muscle in older adults: A longitudinal 18F-FDG PET/CT analysis. Nutrients, 17(10), 1707. https://doi.org/10.3390/nu17101707
11. Nishi, Y., Hiejima, H., Hosoda, H., Kaiya, H., Mori, K., Fukue, Y., Yanase, T., Nawata, H., Kangawa, K., & Kojima, M. (2005). Ingested medium-chain fatty acids are directly utilized for the acyl modification of ghrelin. Endocrinology, 146(5), 2255–2264. https://doi.org/10.1210/en.2004-0695
12. Nosaka, N., Suzuki, Y., Suemitsu, H., Kasai, M., Kato, K., & Taguchi, M. (2018). Medium-chain triglycerides with maltodextrin increase fat oxidation during moderate-intensity exercise and extend the duration of subsequent high-intensity exercise. Journal of Oleo Science, 67(11), 1455–1462. https://doi.org/10.5650/jos.ess18112
13. Nosaka, N., Tsujino, S., Honda, K., Suemitsu, H., & Kato, K. (2020). Enhancement of fat oxidation during submaximal exercise in sedentary persons: Variations by medium-chain fatty acid composition and age group. Lipids, 55(2), 173–183. https://doi.org/10.1002/lipd.12222
14. Nosaka, N., Tsujino, S., Honda, K., Suemitsu, H., Kato, K., & Kondo, K. (2020). Effect of ingestion of medium-chain triglycerides on substrate oxidation during aerobic exercise could depend on sex difference in middle-aged sedentary persons. Nutrients, 13(1), 36. https://doi.org/10.3390/nu13010036
15. Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., Chou, R., Glanville, J., Grimshaw, J. M., Hróbjartsson, A., Lalu, M. M., Li, T., Loder, E. W., Mayo-Wilson, E., McDonald, S., … Moher, D. (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ, 372, n71. https://doi.org/10.1136/bmj.n71
16. Papamandjaris, A. A., MacDougall, D. E., & Jones, P. J. (1998). Medium chain fatty acid metabolism and energy expenditure: Obesity treatment implications. Life Sciences, 62(14), 1203–1215. https://doi.org/10.1016/S0024-3205(97)01143-0
17. Shamseer, L., Moher, D., Clarke, M., Ghersi, D., Liberati, A., Petticrew, M., Shekelle, P., & Stewart, L. A., & PRISMA-P Group. (2015). Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: Elaboration and explanation. BMJ, 349. https://doi.org/10.1136/bmj.g7647
18. St-Onge, M. P., Bourque, C., Jones, P. J., Ross, R., & Parsons, W. E. (2003). Medium- versus long-chain triglycerides for 27 days increases fat oxidation and energy expenditure without resulting in changes in body composition in overweight women. International Journal of Obesity and Related Metabolic Disorders, 27(1), 95–102. https://doi.org/10.1038/sj.ijo.0802169
19. Takada, S., Sabe, H., & Kinugawa, S. (2022). Treatments for skeletal muscle abnormalities in heart failure: Sodium-glucose transporter 2 and ketone bodies. American Journal of Physiology-Heart and Circulatory Physiology, 322(2), H117–H128. https://doi.org/10.1152/ajpheart.00100.2021
20. Takeuchi, H., Sekine, S., Kojima, K., & Aoyama, T. (2008). The application of medium-chain fatty acids: Edible oil with a suppressing effect on body fat accumulation. Asia Pacific Journal of Clinical Nutrition, 17(Suppl 1), 320–323.
21. Watanabe, S., & Tsujino, S. (2022). Applications of medium-chain triglycerides in foods. Frontiers in Nutrition, 9, 802805. https://doi.org/10.3389/fnut.2022.802805
22. Yakupova, E. I., Bocharnikov, A. D., & Plotnikov, E. Y. (2022). Effects of ketogenic diet on muscle metabolism in health and disease. Nutrients, 14(18), 3842. https://doi.org/10.3390/nu14183842
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