Effects of Nonsteroidal Anti-Inflammatory Drugs on Muscle Hypertrophy, Connective Tissue Remodeling and Exercise Adaptation: A Narrative Review
DOI:
https://doi.org/10.12775/QS.2026.59.72817Keywords
NSAIDs, exercise adaption, muscle hypertrophy, skeletal muscle regeneration, mTOR, satellite cells, connective tissue remodeling, tendons, sports medicine, gut-muscle axisAbstract
Introduction and Purpose
Exercise-induced inflammation plays an important role in skeletal muscle regeneration and adaptation to training. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in sports medicine to reduce pain and inflammation; however, chronic suppression of inflammatory pathways may interfere with adaptive responses to exercise. The aim of this review was to analyze current evidence regarding the effects of NSAIDs on muscle hypertrophy, connective tissue remodeling, and exercise adaptation.
Materials and Methods
A narrative review was conducted using PubMed, Scopus, and Web of Science databases. Publications related to NSAIDs, exercise physiology, muscle hypertrophy, satellite cells, mTOR signaling, tendon remodeling, and gut-muscle axis interactions were analyzed. Particular attention was given to experimental studies, systematic reviews, and meta-analyses.
Results
Available evidence indicates that prolonged NSAID use may affect mechanisms involved in muscle regeneration and connective tissue remodeling. Chronic cyclooxygenase inhibition may influence prostaglandin synthesis, satellite cell activity, mTORC1 signaling, collagen turnover, and intestinal barrier integrity. The magnitude of these effects appears to depend on dosage, duration of use, timing of administration, age, and training characteristics. Young individuals exposed to high training loads may be particularly susceptible to altered adaptive responses.
Conclusions
NSAIDs remain valuable agents in short-term pain management; however, routine long-term use as a recovery strategy should be approached with caution. Current evidence suggests that chronic suppression of exercise-induced inflammation may influence physiological mechanisms responsible for muscle and connective tissue adaptation. Further long-term studies are required to determine the clinical significance of these effects in athletic populations.
References
1. Brennan R, Wazaify M, Shawabkeh H, Boardley I, McVeigh J, Van Hout MC. A scoping review of non-medical and extra-medical use of non-steroidal anti-inflammatory drugs (NSAIDs). Drug Saf. 2021;44(9):937-953.
2. Machado GC, Underwood M, Abdel Shaheed C. Non-steroidal anti-inflammatory drugs for musculoskeletal pain. BMJ. 2021;372:n104.
3. Larsen AC, Pedersen JR, Møller M, Storm LK, Koes B, Thorlund JB. The impact of injuries on sports-related analgesic use in Danish youth elite athletes: a 4-week prospective cohort study. J Sci Med Sport. 2025;28(1):40-46.
4. Er Y, Faki A. Different chemical structures and physiological roles of cyclooxygenases. Rambam Maimonides Med J. 2021;12(3):e0021.
5. Sinniah A, Yazid S, Flower RJ. From NSAIDs to glucocorticoids and beyond. Cells. 2021;10(12):3524.
6. Tso J, Hollowed C, Liu C, Alkhoder A, Dommisse M, Gowani Z, et al. Nonsteroidal anti-inflammatory drugs and cardiovascular risk in American football. Med Sci Sports Exerc. 2020;52(12):2522-2528.
7. Warden SJ. Prophylactic use of NSAIDs by athletes: a risk/benefit assessment. Phys Sportsmed. 2010;38(1):132-138.
8. Pham H, Spaniol F. The efficacy of non-steroidal anti-inflammatory drugs in athletes for injury management, training response, and athletic performance: a systematic review. Sports. 2024;12(11):302.
9. Pedersen JR, Andreucci A, Thorlund JB, Koes B, Møller M, Storm LK, et al. Prevalence, frequency, adverse events, and reasons for analgesic use in youth athletes: a systematic review and meta-analysis of 44,381 athletes. J Sci Med Sport. 2022;25(10):810-819.
10. Lilja M, Mandić M, Apró W, Melin M, Olsson K, Rosenborg S, et al. High doses of anti-inflammatory drugs compromise muscle strength and hypertrophic adaptations to resistance training in young adults. Acta Physiol (Oxf). 2018;222(2):e12948.
11. Mackey AL, Mikkelsen UR, Magnusson SP, Kjaer M. Rehabilitation of muscle after injury: the role of anti-inflammatory drugs. Scand J Med Sci Sports. 2012;22(4):e8-e14.
12. Schoenfeld BJ. The use of nonsteroidal anti-inflammatory drugs for exercise-induced muscle damage: implications for skeletal muscle development. Sports Med. 2012;42(12):1017-1028.
13. Lundberg TR, Howatson G. Analgesic and anti-inflammatory drugs in sports: implications for exercise performance and training adaptations. Scand J Med Sci Sports. 2018;28(11):2252-2262.
14. Markworth JF, Vella LD, Figueiredo VC, Cameron-Smith D. Ibuprofen treatment blunts early translational signaling responses in human skeletal muscle following resistance exercise. J Appl Physiol (1985). 2014;117(1):20-28.
15. Careccia G, Saclier M, Tirone M, Heigwer F, Secombe J, Schwörer S, et al. Regulation of satellite cell functions during skeletal muscle regeneration. Int J Mol Sci. 2024;25(1):512.
16. Grgic J. No pain, no gain? Examining the influence of ibuprofen consumption on muscle hypertrophy. Strength Cond J. 2023;45(4):481-485.
17. Roberts BM, Geddis AV, Sczuroski CE, Staab JS. NSAIDs do not prevent exercise-induced performance decrements or muscle soreness following plyometric exercise. J Sci Med Sport. 2024;27(6):402-407.
18. Krentz JR, Quest B, Farthing JP, Quest DW, Chilibeck PD. The effects of ibuprofen on muscle hypertrophy, strength, and soreness during resistance training. Appl Physiol Nutr Metab. 2008;33(3):470-475.
19. Trappe TA, Carroll CC, Dickinson JM, LeMoine JK, Haus JM, Sullivan BE, et al. Influence of acetaminophen and ibuprofen on skeletal muscle adaptations to resistance exercise in older adults. Am J Physiol Regul Integr Comp Physiol. 2011;300(3):R655-R662.
20. Urso ML. Anti-inflammatory interventions and skeletal muscle injury: benefit or detriment? J Appl Physiol (1985). 2013;115(6):920-928.
21. Almekinders LC. Anti-inflammatory treatment of muscular injuries in sport. Sports Med. 1999;28(6):383-388.
22. Bateman LS, McSwain R, Bouffard J. Effects of ibuprofen on muscle hypertrophy and inflammation: a review. Cureus. 2023;15(3):e36735.
23. Duchman KR, Lemmex DB, Patel SH, Ledbetter L, Garrigues GE, Riboh JC. The effect of non-steroidal anti-inflammatory drugs on tendon-to-bone healing: a systematic review. Orthop J Sports Med. 2019;7(4):2325967119838873.
24. Christensen B, Dandanell S, Kjaer M, Langberg H. Effect of anti-inflammatory medication on the running-induced rise in patella tendon collagen synthesis in humans. J Appl Physiol (1985). 2011;110(1):137-141.
25. Tsai WC, Hsu CC, Chou SW, Chung CY, Chen J, Pang JH. Effects of celecoxib on migration, proliferation and collagen expression of tendon cells. Connect Tissue Res. 2007;48(1):46-51.
26. Solaiman RH, Dirnberger J, Kennedy NI, DePhillipo NN, Tagliero AJ, Malinowski K, et al. The effect of nonsteroidal anti-inflammatory drug use on soft tissue and bone healing in the knee: a systematic review. Ann Joint. 2024;9:4.
27. Przewłócka K, Folwarski M, Kaźmierczak-Siedlecka K, Skonieczna-Żydecka K, Kaczor JJ. Gut-muscle axis exists and may affect skeletal muscle adaptation to training. Nutrients. 2020;12(5):1451.
28. Lim YJ, Yang CH. Non-steroidal anti-inflammatory drug-induced enteropathy. Clin Endosc. 2012;45(2):138-144.
29. Shin SJ, Noh CK, Lim SG, Lee KM, Lee KJ. Non-steroidal anti-inflammatory drug-induced enteropathy. Intest Res. 2017;15(4):446-455.
30. Clark A, Mach N. Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes. J Int Soc Sports Nutr. 2016;13:43.
31. Trappe TA, Standley RA, Jemiolo B, Carroll CC, Trappe SW. Prostaglandin and myokine involvement in the cyclooxygenase-inhibiting drug enhancement of skeletal muscle adaptations to resistance exercise in older adults. Am J Physiol Regul Integr Comp Physiol. 2013;304(3):R198-R205.
32. Roberts BM, Geddis AV, Sczuroski CE, Staab JS. A single, maximal dose of celecoxib, ibuprofen, or flurbiprofen does not reduce the muscle signalling response to plyometric exercise in young healthy adults. Eur J Appl Physiol. 2024;124(11):3421-3432.
33. Mishra DK, Fridén J, Schmitz MC, Lieber RL. Anti-inflammatory medication after muscle injury: a treatment resulting in short-term improvement but subsequent loss of muscle function. J Bone Joint Surg Am. 1995;77(10):1510-1519.
34. Dubois B, Esculier JF. Soft-tissue injuries simply need PEACE and LOVE. Br J Sports Med. 2020;54(2):72-73.
35. Lisowska B, Kosson D, Domaracka K. Positives and negatives of NSAIDs in bone healing: the effects on repair. Drug Des Devel Ther. 2018;12:3267-3274.
36. Cohen DB, Kawamura S, Ehteshami JR, Rodeo SA. Indomethacin and celecoxib impair rotator cuff tendon-to-bone healing. Am J Sports Med. 2006;34(3):362-369.
37. Papantoniou K, Michailides C, Bali M, Papantoniou P, Thomopoulos K. Gastrointestinal bleeding in athletes. Ann Gastroenterol. 2023;36(3):267-274.
38. Saponaro F, Sestito S, Runfola M, Rapposelli S, Chiellini G. New perspectives in the endocrine muscle-gut axis. Nutrients. 2024;16(23):4032.
39. Dupuy O, Douzi W, Theurot D, Bosquet L, Dugué B. An evidence-based approach for choosing post-exercise recovery techniques to reduce markers of muscle damage, soreness, fatigue, and inflammation: a systematic review with meta-analysis. Front Physiol. 2018;9:403.
40. Bonilla DA, Pérez-Idárraga A, Odriozola-Martínez A, Kreider RB. The 4R’s framework of nutritional strategies for post-exercise recovery: a review with emphasis on new generation carbohydrates. Int J Environ Res Public Health. 2020;18(1):103.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Ewa Kala-Kaziszyn, Julia Smagowska, Agata Wnęk, Alicja Biskup
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 0
Number of citations: 0
