Effects of anti-inflammatory drugs on human skeletal muscle adaptations to resistance training

Previous studies in young adults suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may impair early skeletal muscle responses to exercise. Whether chronic use of NSAIDs affects skeletal muscle adaptations to resistance training in young adults remains uncertain.

A randomized experimental study was conducted to investigate the effects of maximum over-the-counter doses of ibuprofen compared with low doses of acetylsalicylic acid on muscle responses and adaptations to acute and chronic resistance training in young adults. Thirty-one young (aged 18 to 35 years) healthy men (n = 17) and women (n = 14) were randomly assigned to either an experimental group receiving 1200 mg ibuprofen (IBU; 3 × 400 mg/day; n = 15) or a control group that received an active but low dose of 75 mg acetylsalicylic acid (ASA; 1 × 75 mg/day; n = 16) while participating in knee extension training for 8 weeks. Before and after training, muscle volume (magnetic resonance imaging) was assessed, and muscle biopsies were taken before training, 3 hours after an acute exercise session, and 48 hours after the 8-week intervention. Tissue analysis included acute and chronic markers of hypertrophy regulation and mitochondrial function. In addition, immunohistochemistry together with whole-muscle image analyses were used to examine the relationship between muscle fiber cross-sectional area and whole muscle size. The results showed an attenuation in muscle volume with ibuprofen intake where ASA (7.5%) increased more than IBU (3.7%) after 8-weeks of resistance training. In parallel, a significant group interaction in an ibuprofen-induced downregulation was found in IL-6 mRNA in comparison to an increase in ASA (Paper I). After 8-weeks of resistance training, mitochondrial function (CI+IIP) decreased in both IBU (23%) and ASA (29%) with no difference across medical treatments. Citrate synthase activity (a marker of mitochondrial content) increased with resistance training, with no interactions with medical treatment (Paper II). Several training effects were noted in acute and chronic markers of hypertrophy regulation, including mTOR signaling, ribosome biogenesis, satellite cell content, myonuclear accretion, and angiogenesis, but only two treatment × time interactions in atrogin-1 and MuRF1 mRNA 3 hours after acute exercise were found (Paper III). Moderate correlation (R = 0.47-0.50) was found between the fiber size and whole muscle size. No correlation was found between changes in fiber size and changes in quadriceps size (R = 0.22) and vastus lateralis size (R = 0.28) (Paper IV).

Collectively, these results suggest that 1) resistance training with concomitant ibuprofen intake impairs muscle hypertrophy in young adults, 2) resistance training-induced decreases in mitochondrial function together with increases in mitochondrial content is likely unaffected by concomitant NSAIDs intake, 3) selected established acute and chronic markers of hypertrophy regulation were generally not differentially altered between groups and do not explain the negative effects of ibuprofen on muscle hypertrophy in young adults, and finally, 4) changes in muscle fiber size is an unreliable marker of whole-muscle hypertrophy in response to longitudinal interventions.

List of scientific papers

I. Lilja M, Mandić M, Apró W, Melin M, Olsson K, Rosenborg S, Gustafsson T, Lundberg TR. High doses of anti-inflammatory drugs compromise muscle strength and hypertrophic adaptations to resistance training in young adults. Acta Physiol (Oxf). 2018 Feb;222(2).
https://doi.org/10.1111/apha.12948

II. Cardinale DA, Lilja M, Mandić M, Gustafsson T, Larsen FJ, Lundberg TR. Resistance Training with Co-ingestion of Anti-inflammatory Drugs Attenuates Mitochondrial Function. Front Physiol. 2017 Dec 19;8:1074.
https://doi.org/10.3389/fphys.2017.01074

III. Lilja M, Moberg M, Apró W, Martínez-Aranda LM, Rundqvist H, Langlet B, Gustafsson T, Lundberg TR. Limited effect of over-the-counter doses of ibuprofen on mechanisms regulating muscle hypertrophy during resistance training in young adults. J Appl Physiol. 2023.
https://doi.org/10.1152/japplphysiol.00698.2022

IV. Lilja M, Petrovic G, Rundqvist H, Gustafsson T, Lundberg TR. (2023). Changes in myofiber cross-sectional area are a limited predictor of whole-muscle hypertrophy. [Manuscript]