Low-dose aspirin and COX inhibition in human skeletal muscle

Abstract

Skeletal muscle health has been shown to benefit from regular consumption of cyclooxygenase (COX) inhibiting drugs. Aspirin, especially at low doses, is one of the most commonly consumed COX inhibitors, yet investigations of low dose aspirin effects on skeletal muscle are nonexistent. The goal of this study was to examine the efficacy of low dose aspirin on skeletal muscle COX production of the inflammatory regulator prostaglandin (PG) E2 at rest and following exercise. Skeletal muscle biopsies (vastus lateralis) were taken from eight individuals (4M, 4W; 25±1y; 81.4±3.4kg; VO2max: 3.33±0.21L/min) before and 3.5 hours after 40 minutes of cycling at 70% of VO2max for the measurement of ex vivo PGE2 production. Muscle strips were incubated in Krebs-Henseleit buffer (control) or supplemented with one of two aspirin concentrations that reflected blood levels following a low (10µM; typical oral dose: 75-325mg) or standard (100µM; typical oral dose: 975-1000mg) dose. Low (-22±5%) and standard (-28±5%) dose aspirin concentrations both reduced skeletal muscle PGE2 production, independent of exercise (P<0.05). There was no difference in PGE2suppression between the two doses (P>0.05). In summary, low dose aspirin levels are sufficient to inhibit the COX enzyme in skeletal muscle and significantly reduce production of PGE2, a known regulator of skeletal muscle health. Aerobic exercise does not appear to alter the inhibitory efficacy of aspirin. These findings may have implications for the tens of millions of individuals that chronically consume low dose aspirin.

Influence of low‐dose aspirin, resistance exercise, and sex on human skeletal muscle PGE2/COX pathway activity

“…The postexercise timepoint was chosen because of the increased metabolic and molecular activity related to exercise adaptation (Sanford et al, 2020) and the increased COX activity and PG production (Carroll et al, 2013; Trappe & Liu, 2013; Vella et al, 2019). In addition, this timepoint coincided with our previous study on aspirin and aerobic exercise (Fountain et al, 2020).…”

“…Subject characteristics of the individuals (4 M/2 W) included in this investigation are presented in Table 1. Subjects also completed resistance exercise familiarization prior to an acute resistance exercise trial with muscle biopsies (Fountain et al, 2020; Sanford et al, 2020). Specific pretrial controls were in place for COX inhibitor consumption, diet, physical activity, and menstrual cycle timing for the women.…”

“…Aspirin is a potent cyclooxygenase (COX) inhibitor that is commonly consumed for its anti‐inflammatory and cardioprotective effects (O'Brien et al, 2019; Stuntz & Bernstein, 2017; Zhou et al, 2014). Recent investigations have shown that aspirin inhibits COX production of the inflammatory regulator prostaglandin E 2 (PGE 2 ) in resting human skeletal muscle under in vivo and ex vivo conditions (Fountain et al, 2020; Ratchford et al, 2017). Considering that aspirin is consumed chronically at low doses by an estimated 65 million adults in the United States, it is noteworthy that low‐dose aspirin significantly reduces skeletal muscle PGE 2 production (Fountain et al, 2020).…”

“…Specifically, absorption and clearance appear to be influenced, but these studies do not provide skeletal muscle‐specific information. As there are few investigations into the effects of aspirin on skeletal muscle (Fountain et al, 2020; Ratchford et al, 2017), any potential sex‐specific effects are unknown. Lack of sex‐specific information is not uncommon in drug development, and there are likely more differences in drug responsiveness between men and women than has been previously appreciated (Zucker & Prendergast, 2020).…”

“…We hypothesized that low‐dose aspirin concentrations would suppress skeletal muscle PGE 2 production and that low‐dose aspirin efficacy would be reduced following resistance exercise. An additional exploratory objective was to examine potential sex‐specific effects of aspirin on skeletal muscle by combining the data from the current and previous (Fountain et al, 2020; Ratchford et al, 2017) investigations, which used the same methodologies to examine the PGE 2 /COX pathway activity in skeletal muscle.…”