This is the fourth installment of the series NSAIDs and athletes. This article will address the question of why athletes use NSAIDs so often and if the intended benefits are supported by clinical research. The first article in this series dealt with the mechanism of action of NSAIDs and the prevalence of use of these medications. The second article dealt with potential adverse effects of NSAIDs. The third article dealt with demonstrated adverse effects of NSAIDs in athletes participating in endurance sports.
Given the important adverse effects of NSAIDs as discussed in the second and third articles in this series, it is reasonable to ask: “why would any athlete take NSAIDs?” There appear to be a number of reasons, all of which are underpinned by the observation that most athletes are unaware of the full potential for harm from NSAIDs. An example of this lack of awareness is given in a study of the 2010 Bonn Marathon, in which approximately one half of participants (who responded to a survey) took NSAIDs, and 93% stated that they were unaware of the negative consequences of the use of NSAIDs in connection with endurance sports.
One reason athletes may take NSAIDs before and during exercise is to reduce pain. For example, an injured, but fit, athlete may want to use an NSAID as a crutch to allow him or her to train for or participate in an event without being limited by pain from a pre-existing injury. Another example is using NSAIDs to prevent pain that is anticipated to arise naturally during the course of an event. In this sense, NSAIDs can be considered to be ergogenic aids: preventing pain that would distract an athlete or otherwise degrade performance. Finally, NSAIDs may be used with the intention of preventing pain or soreness that may arise after exercise, such as delayed-onset muscle soreness (DOMS).
Since NSAIDs reduce the production of prostaglandins, and since prostaglandins help mediate inflammation, many athletes also use NSAIDs before, during, and after exercise to prevent inflammation. The rationale may be that inflammation from exercise may cause injury and prevent or prolong the healing process. Therefore, since NSAIDs are anti-inflammatory medications, the use of these medications would promote recovery.
Are these suppositions about pain and inflammation and the effects of NSAIDs substantiated? Let’s look at the clinical data.
In a study published in March, 2015, 20 male endurance runners, average age 18.8 years, were divided into two equal groups. Both groups performed running trials of time until self-reported fatigue 48 hours before a muscle-damaging activity called isokinetic dynamometry. 48 hours after this muscle-damaging activity, participants again performed running trials of time until self-reported fatigue. One group received 1.2 grams of ibuprofen 1 hour before the second time trial, whereas the other group received placebo. The researchers found that both groups had more muscle pain and decreased performance with the second time trial, but that there was no difference between the groups. The authors conclude:
“Ibuprofen did not reduce the effect of muscle damage and pain on performance. Prophylactic use of nonsteroidal anti-inflammatory drugs did not have an ergogenic effect on running performance after exercise-induced muscle damage in male long-distance runners.”
Similar findings were reported in another study of runners. 32 subjects participated in a two-period crossover trial in which ibuprofen was compared to placebo for its effectiveness in reducing muscle soreness and laboratory measures of muscle damage after two trials of downhill running. While the downhill runs led to muscle soreness, reduced muscle strength, and reduced isometric endurance time at 50% of maximum strength, there was no difference between the ibuprofen and placebo groups. With regard to laboratory measures of muscle damage, serum creatine kinase and urea levels were higher in the ibuprofen group after both runs. This indicates that ibuprofen does not improve performance or reduce soreness and may worsen muscle damage when taken before exercise.
There were somewhat different findings in another study of the effects of ibuprofen on muscles. In this small study, 10 volunteers performed one-arm eccentric bouts of exercise on opposite arms separated by three weeks. The volunteers received 2400 mg of ibuprofen (a high dose) or placebo for 5 days before exercise and for 10 days after exercise. The investigators found that isometric strength, soreness, tenderness, and arm angles were similar between the groups who received ibuprofen vs placebo. Laboratory measurements were made, at 7 different points in time, of neutrophil counts, neutrophil O2* production, and creatine kinase. The only significant difference in these measures between the ibuprofen and placebo groups was at 3 days post-exercise. At this point, creatine kinase levels were lower in the ibuprofen group relative to placebo. This indicates that ibuprofen taken before exercise, even in high doses, does not improve strength, reduce soreness, or significantly reduce muscle damage.
One of the most important studies on this subject was done with 54 ultramarathoners who participated in the Western States Endurance Run. 29 of the participants in this study took 600 mg of ibuprofen on the day before the race and 1200 mg of ibuprofen on race day. These participants were compared to 25 ultramarathoners who did not consume ibuprofen or any other medications before the race. The study found that finishing time and ratings of perceived exertion did not differ significantly between the ibuprofen and control groups. Furthermore, muscle soreness in the week following the race (DOMS) did not differ significantly between the two groups. The main difference between the two groups was in indicators of endotoxemia and inflammation, which was worse (not better!) in the ibuprofen takers. For example, plasma levels of lipopolysaccharide, C-reactive protein, interleukin (IL)-6, IL-8, IL-10, IL-1ra, granulocyte colony-stimulating factor, monocyte chemotactic protein 1, and macrophage inflammatory protein 1 beta, but not tumor necrosis factor alpha, were elevated in the ibuprofen group relative to the control group. Therefore, and very importantly, the authors concluded that:
“Ibuprofen use compared to nonuse by athletes competing in a 160-km race did not alter muscle damage or soreness, and was related to elevated indicators of endotoxemia and inflammation.”
These studies demonstrate that taking NSAIDs before exercise to reduce pain and inflammation and to enhance performance is ineffective. Why does this approach fail? A large part of the reason for the failure of this approach is the underlying mechanism of sports-related injuries. While NSAIDs have undeniable anti-inflammatory properties, histopathological studies have shown that the mechanism of many sports-related injuries is degenerative rather than inflammatory. One way to visualize this concept of injury is to consider muscles as ropes: ropes become frayed, not swollen, from overuse.
I sincerely hope you have learned a lot from reading all four parts of this series about NSAIDs and athletes. This is important information that can impact the health of the athletic community. Please help me spread the word!
Da Silva E, Pinto RS, Cadore EL, et al. Nonsteroidal anti-inflammatory drug use and endurance during running in male long-distance runners. J Athl Train. 2015 Mar;50(3):295-302.
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Küster M, Renner B, Oppel P, et al. Consumption of analgesics before a marathon and the incidence of cardiovascular, gastrointestinal and renal problems: a cohort study. BMJ Open 2013;3:e002090.
Nieman DC, Henson DA, Dumke CL, et al. Ibuprofen use, endotoxemia, inflammation, and plasma cytokines during ultramarathon competition. Brain, Behavior, and Immunity 2006 Nov;20(6):578-584.
Pizza FX, Cavender D, Stockard A, et al. Anti-inflammatory doses of ibuprofen: effect on neutrophils and exercise-induced muscle injury. Int J Sports Med. 1999 Feb;20(2):98-102.
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