The long run to inflammation

inflammationEvery competitive runner is familiar with the soreness and fatigue that follow a hard race effort. You ran fast, or far, or both, and now behind the scenes your body is retaliating appropriately, sending your immune system into overdrive to repair your traumatized muscles. But what exactly triggers a post-race inflammatory response, and determines how severe or lasting it will be? Building on prior research showing that exercise intensity is related with inflammation 1,2, a recent study by Reihmane and colleagues 3 asked whether this inflammatory reaction also depends on running duration.

Watch that inflammation, marathoners!

To test this, the researchers collected blood samples from half-marathon and marathon runners two days before, 15 minutes after, and 28 hours after, race completion. At each time-point they measured various molecular markers of inflammation. Immediately after racing, two of those markers (IL-6 and TNF-α) were elevated in the marathoners only, and one (MMP-9) was elevated in all runners, but to a greater extent in the marathoners (see Figure). The three measures all returned to normal levels 28 hours after racing. This indicated that some aspect of the immediate exercise-induced inflammatory response depends on how long one runs. They also found that the increases in the three biomarkers were correlated, suggesting that the biochemical processes in which the three molecules act might not be independent, but possibly involve integrated mechanisms.

From Reihmane et al, 2012.White bars = pre-race; Striped bars = 15 min post-race; Black bars = 28 h post-race

From Reihmane et al, 2012.
White bars = pre-race; Striped bars = 15 min post-race; Black bars = 28 h post-race

Wait, not so fast …

This seems straightforward enough, but a closer look at the methods raises a few questions.

Of major concern, only 65% of the original 40 subjects were tested at the 28-hour time-point, leaving 18 runners in the half marathon and only 8 in the full marathon group. The authors acknowledge this limitation and accordingly analyze the pre-race versus 28-hour post-race data on this smaller follow-up subgroup. However, the reduced sample raises concern about the reliability of this time-point, and any comparison with the 15-minute time-point. How confident can we be that any of the inflammatory markers returned to normal or remained elevated over the long-term? The above figure somewhat misleadingly plots data for the full groups at pre-race and 15-minutes post-race against those for the subgroups at 28-hours post-race. It would have been more informative to see these averages plotted in separate figures, one for all participants, and a second for the subgroup. At the very least, it would help if these group averages and full stats (not just p values) had been reported in the text.

Second, the study aims to evaluate effects of running duration, independent of intensity. This might be an issue of semantics, but their quantification of “intensity” seems imprecise. Intensity is equated between groups by matching runners based on average speed. However, on what do they base the assumption that the same pace translates to the same intensity at different race distances? Is a 7:40 min/mile pace the same intensity during a 5k as during a marathon? It certainly doesn’t feel like it! So while they demonstrate that increases in inflammatory markers are related to race duration, independent of pace, it’s not entirely convincing that these effects are fully independent of running intensity. A more direct measure of intensity, such as VO2-max, could strengthen support for this claim.

Third, inflammation is known to be regulated by a variety of factors, including exercise, drugs, or diet 4. They control for some of these, by asking runners not to consume alcohol, nicotine or medication the day before testing. However, if any of those athletes have eating habits similar to my own, I suspect their pre- and post-race diets weren’t exactly matched for nutritional value. Take for example, a predominantly anti-inflammatory pre-race diet of veggies, lean meats and fish, and healthy fats, compared to a celebratory post-race meal feasibly comprising many pro-inflammatory fried, refined and processed treats. The study makes no effort to control, or even assess, such potential dietary confounds. In all fairness, this issue would be less relevant to the 15-minute than the 28-hour post-race measure … unless of course marathoners were fueling with deep-fried Twinkies at mile 20.

If distance = inflammation, does distance = unhealthy?

Looking beyond these potential concerns, the study provides valuable insight into the body’s exercise-induced inflammatory response. So what can we take home from these findings? Early signs of inflammation appear to depend on how many miles you log, but this dependence on distance is only transient, dissipating within a day. It would be interesting to see whether these effects hold up over a broader range of distances, with more precise control over exercise intensity. For example, is there a measurable dose-response curve for inflammatory biomarkers from sprints to 5-ks to marathons to ultras?

Given the general consensus that inflammation is an unhealthy process which should be controlled and dampened, these findings might indicate that the longer you run, the more detrimental the effects. However, there’s mounting evidence that moderate inflammation can in fact confer long-term benefits by promoting healthy physiological adaptation, and that interfering with this natural reparative process may be harmful 5,6. If this is the case, then an elevated inflammatory response with increasing distance might feasibly contribute to the strength and endurance gains reaped from distance training.

Until further research addresses these questions, I certainly won’t be cutting my runs short!


  1. Peake JM et al. 2005. Plasma cytokine changes in relation to exercise intensity and muscle damage. Eur J Appl Physiol 95:514-21.
  2. Akimoto T et al. 2002. Increased plasma concentrations of intercellular adhesion molecule-1 after strenuous exercise associated with muscle damage. Eur J Appl Physiol 86:185–90.
  3. Reihmane D et al. 2012. Increase in IL-6, TNF-α, and MMP-9, but not sICAM-1, concentrations depends on exercise duration. Eur J Appl Physiol.
  4. Myers JL & Allen JC. 2012. Nutrition and Inflammation Insights on Dietary Pattern, Obesity, and Asthma. Am J Lifestyle Med 6:14-7.
  5. Yamane M et al. 2006. Post-exercise leg and forearm flexor muscle cooling in humans attenuates endurance and resistance training effects on muscle performance and on circulatory adaptation. Eur J Appl Physiol 96:572-80.
  6. Trappe TA et al. 2002. Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis. Am J Physiol Endocrinol Metab 282:E551–6.
Reihmane, D., Jurka, A., Tretjakovs, P., & Dela, F. (2012). Increase in IL-6, TNF-α, and MMP-9, but not sICAM-1, concentrations depends on exercise duration European Journal of Applied Physiology DOI: 10.1007/s00421-012-2491-9


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