Trappe TA, Carroll CC, Dickinson JM, LeMoine JK, Haus JM, Sullivan BE, Lee JD, Jemiolo B, Weinheimer EM, Hollon CJ. Influence of acetaminophen and ibuprofen on skeletal muscle adaptations to resistance exercise in older adults. Am J Physiol Regul Integr Comp Physiol 300: R655-R662, 2011. First published December 15, 2010; doi:10.1152/ajpregu.00611.2010.-Evidence suggests that consumption of over-the-counter cyclooxygenase (COX) inhibitors may interfere with the positive effects that resistance exercise training has on reversing sarcopenia in older adults. This study examined the influence of acetaminophen or ibuprofen consumption on muscle mass and strength during 12 wk of knee extensor progressive resistance exercise training in older adults. Thirty-six individuals were randomly assigned to one of three groups and consumed the COX-inhibiting drugs in double-blind placebo-controlled fashion: placebo (67 Ϯ 2 yr; n ϭ 12), acetaminophen (64 Ϯ 1 yr; n ϭ 11; 4 g/day), and ibuprofen (64 Ϯ 1 yr; n ϭ 13; 1.2 g/day). Compliance with the resistance training program (100%) and drug consumption (via digital video observation, 94%), and resistance training intensity were similar (P Ͼ 0.05) for all three groups. Drug consumption unexpectedly increased muscle volume (acetaminophen: 109 Ϯ 14 cm 3 , 12.5%; ibuprofen: 84 Ϯ 10 cm 3 , 10.9%) and muscle strength (acetaminophen: 19 Ϯ 2 kg; ibuprofen: 19 Ϯ 2 kg) to a greater extent (P Ͻ 0.05) than placebo (muscle volume: 69 Ϯ 12 cm 3 , 8.6%; muscle strength: 15 Ϯ 2 kg), when controlling for initial muscle size and strength. Follow-up analysis of muscle biopsies taken from the vastus lateralis before and after training showed muscle protein content, muscle water content, and myosin heavy chain distribution were not influenced (P Ͼ 0.05) by drug consumption. Similarly, muscle content of the two known enzymes potentially targeted by the drugs, COX-1 and -2, was not influenced (P Ͼ 0.05) by drug consumption, although resistance training did result in a drug-independent increase in COX-1 (32 Ϯ 8%; P Ͻ 0.05). Drug consumption did not influence the size of the nonresistance-trained hamstring muscles (P Ͼ 0.05). Over-thecounter doses of acetaminophen or ibuprofen, when consumed in combination with resistance training, do not inhibit and appear to enhance muscle hypertrophy and strength gains in older adults. The present findings coupled with previous short-term exercise studies provide convincing evidence that the COX pathway(s) are involved in the regulation of muscle protein turnover and muscle mass in humans.cyclooxygenase; prostaglandin; sarcopenia SARCOPENIA, DEFINED AS THE loss of skeletal muscle mass, is a debilitating clinical condition associated with old age (13,40). This age-related loss of muscle mass is associated with a loss of muscle strength and function, a reduced functional independence, and a financial burden to the US healthcare system estimated at $20 billion per year (19,23,24,51). One of the most proven treatments for sarcopenia is resistance exercise training, which in...