NSAID ingestion augments training‐induced muscle hypertrophy and differentially affects muscle mRNA expression, but not strength gains, in trained men

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely overused in sports. The temporal effects of combined NSAID consumption and resistance exercise training (RET) on muscle cross-sectional area (CSA), volume and targeted mRNA transcripts (n = 93) were quantified. Seventeen trained males (24.5 ± 1.1 years, body mass index (BMI) 24.2 ± 0.7 kg/m²) consumed either placebo (PLA; n = 8) or diclofenac (75 mg, NSAID; n = 9) daily for 12 weeks and performed 3×30 maximal, isokinetic knee extensions in the non-dominant leg (90°/s) thrice each week. Quadriceps muscle CSA and volume were measured at baseline, 28 days and 84 days (3T MRI). Vastus lateralis biopsies were obtained at baseline, 24 h, 7 days, 28 days and 84 days for mRNA abundance measurements (RT-PCR microfluidic cards). Work output throughout RET was no different between groups. Muscle CSA was increased from baseline in both groups at 28 days (PLA 4.3 ± 2.5%, P = 0.039; NSAID 4.6 ± 3.7%, P = 0.011), but only in the NSAID group at 84 days (PLA 3.9 ± 0.8%, NSAID 8.6 ± 5.3%; P < 0.001; NSAID vs. PLA, P = 0.038), and was paralleled by muscle volume changes. RET increased isometric strength (∼40%-50%), but gains were no different between groups. Based on mRNA expression changes several cellular functions associated with muscle mass and metabolic regulation were altered in both groups throughout RET and were greater in NSAID at 28 and 84 days. NSAID intervention produced greater muscle hypertrophy than PLA, which occurred between 28 and 84 days of RET and was paralleled by more pronounced muscle mRNA changes. These collective events were not accompanied by greater strength gains, suggesting that using NSAIDs alongside RET may not be optimal for enhancing sports performance. KEY POINTS: Non-steroidal anti-inflammatory drug (NSAID) ingestion over 84 days of resistance exercise training increased muscle cross-sectional area and volume gains compared to placebo ingestion in young, trained male volunteers, and this occurred predominantly from day 28 to day 84 of training. In parallel with this, alterations in gene networks associated with a number of cellular functions linked to regulation of muscle mass and muscle metabolism were detected in the NSAID group relative to placebo. This greater resistance training-induced hypertrophy associated with NSAID ingestion was not accompanied by greater gains in isometric knee extensor strength or isokinetic work output during training compared to resistance training alone.