This is the third part in a series about NSAIDs and athletes. This article will explore the effects of NSAIDs on athletes during endurance events. The first part of this series examined the mechanism of action of NSAIDs and the prevalence of use of these medications by athletes. The second part explored the adverse effects of NSAIDs for anybody, but especially athletes.
As described in the first article in this series, an amazingly high proportion of athletes use NSAIDs before and during events. This is so commonplace that may be hard to imagine that these athletes could be doing harm to themselves. But they may be doing just that. A number of studies address this issue in great detail.
One such study, by Kuster et al, was conducted as a survey of approximately 4000 of the 7000 participants in the 2010 Bonn Marathon and Half-Marathon. Overall, the researchers found no difference in the rate of withdrawal from the race between the NSAID consumers and non-consumers. However, withdrawal because of gastrointestinal adverse events was significantly higher in the consumer group, while withdrawal because of muscle cramping was higher in the non-consumer group. More remarkably, in this study there was almost a 5x higher incidence of adverse events, overall, in the consumer group compared to the non-consumer group. This incidence also increased significantly with increasing dose of NSAIDs. Of the analgesic users, there were nine who reported hospital admittance: three (who had taken ibuprofen) were admitted for kidney failure, four (who had taken aspirin) for GI bleeds, and two (who had taken aspirin) for heart attacks. There were no non-users of NSAIDs who required hospital admittance. Note that the NSAIDs taken by 90% of participants in this study were either diclofenac or ibuprofen. Also the rate of adverse events in the NSAID-taking group was almost three times higher for the marathon participants than the half-marathon participants, so duration of exercise does appear to have an effect.
In 2005, there was a widely-publicized paper in the New England Journal Medicine that reported that 13% of finishers of the Boston Marathon in 2002 had hyponatremia (low blood sodium). Furthermore, 0.6% had critical levels of hyponatremia. Mechanistically, since NSAIDs reduce the removal of water by the kidneys, it is a realistic concern that the use of NSAIDs could independently raise the rate of hyponatremia (since sodium is diluted by retained water). However, in this study, while 50-60% of participants reported having taken NSAIDs in the week before the race (this was a survey study), there was no linkage between the use of NSAIDs and the incidence of hyponatremia.
In contrast, a study of participants in the 2004 Ironman triathlon in New Zealand did demonstrate such a linkage. Overall, 30% of athletes used NSAIDs and the rate of hyponatremia was 1.8%. Statistically, there was a highly significant association in this study between having taken NSAIDs and developing hyponatremia.
In yet another study of endurance athletes, having taken NSAIDs was found to be statistically associated the the development of hyponatremia. This study was of the Kepler Challenge 60 km mountain run in New Zealand in 2003. Of note is that 20% of participants in the study had used NSAIDs within 24 hours of the start of the event, whereas 15% had used selective COX-2 enzyme inhibitors, called COXIBs (although these are also NSAIDs) within 24 hours of the start of the race.
After the 2009 Western States Endurance Run, which is an ultra-marathon of 161 km, 5 out of 400 participants were hospitalized with rhabdomyolysis (severe muscle damage) and hyponatremia. The authors of the scientific report about these adverse events stated that “these individuals tended to be younger, faster, more likely to have had an injury that interfered with training, and more likely to have used NSAIDs during the race.”
Abdominal complaints are very common in distance runners (including me). In a study of participants in the 1996 Chicago Marathon, researchers assessed the effects of prolonged exercise and NSAID ingestion on gastric and intestinal permeability during the first five hours following completion of the race (side note: anyone who has completed this race will remember that most of that first hour post-race is spent limping through huge crowds of people to get out of the finish area, then additional limping through downtown Chicago to finally arrive at a parking deck or CTA station- not a good time to have intestinal cramping!). Remarkably, 75% of participants reported having taken aspirin or ibuprofen before or during the race (the highest percentage I have seen in researching this subject area). Those runners who took ibuprofen, but not those runners who took aspirin, had significant elevations in measures of small intestinal permeability. This study only had 34 participants. Of the 26 participants in the study who had taken NSAIDs, 13 reported GI complaints whereas 4 out of the 8 participants who had not taken NSAIDs also reported GI complaints (no difference between these two groups).
In another study of the effects of exercise and NSAIDs on the function of the gut, nine healthy, trained male cyclists were studied on four occasions. These occasions were as follows: after having received 400 mg of ibuprofen twice before cycling, cycling without having taken ibuprofen, 400 mg of ibuprofen twice taken at rest, rest without having taken ibuprofen. The researchers reported that both having taken ibuprofen and cycling independently led to evidence of injury to the small intestine. The greatest injury was associated with the first test, in which ibuprofen was taken before cycling.
As alluded to above, most of the studies used in this article were based on survey information and have inherent weaknesses. The study of participants in the Chicago Marathon was unfortunately very small. But the last study, of cyclists, was more scientifically rigorous. Taken together, however, the scientific evidence appears to be strong that the use of NSAIDs before or during endurance events can lead to dangerous, potentially life-threatening, conditions including hyponatremia and intestinal injury. This potential for harm appears to be true even at more routine doses, such as the 800 mg of ibuprofen that was used in the cycling study.
The final installment in this series about NSAIDs and athletes will explore why athletes rely on NSAIDs and if these intended beneficial effects are scientifically-supported.
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Almond CS, Shin AY, Fortescue EB, et al. Hyponatremia among runners in the Boston Marathon. N Engl J Med. 2005 Apr 14;352(15):1550-1556.
Bruso JR, Hoffman MD, Rogers IR, et al. Rhabdomyolysis and hyponatremia: a cluster of five cases at the 161-km 2009 Western States Endurance Run. Wilderness Environ Med. 2010 Dec;21(4):303-308.
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.
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Wharam PC, Speedy DB, Noakes TD, et al. NSAID use increases the risk of developing hyponatremia during an Ironman triathlon. Med Sci Sports Exerc. 2006 Apr;38(4):618-622.