Exercise is anti-inflammatory medicine for injuries (Member Post)

Many people ironically overuse an overuse injury while trying to recover from it, pushing back towards normal too hard, too soon. Overdoing it is the most common of all training and rehab errors, I suspect. Thanks to a strong cultural predilection to believe that there is no gain without pain, the need for rest in the early stages of rehab is often underestimated.

Another irony: the same culture that celebrates intensity in rehab also fears wear and tear out of proportion to the danger. Some people are afraid to push even a little! And that’s also a problem. Overuse can go very badly, which understandably makes some people shy of using their body at all. No one wants another stress fracture!

But tissues clearly thrive on stimulation, and it’s hard to damage them. For instance, we know — from many studies — that even quite a lot of running does not destroy knees with premature arthritis. And here are a whole bunch of citations for that statement, a collection I’ve been curating for about a decade.123456789

Exercise doesn’t wreck joints because it probably does the opposite: at the right dosage, exercise is probably anti-inflammatory. It probably protects joints and promotes healing.

But getting the dosage right? That’s the hard part! People often go to the extremes during rehab: too much too soon, or too little too late.

Every overuse injury must eventually once again be used. No cartilage, bone, tendon, or muscle can get healthy — or stay healthy — without some action. But when and how much? And if we get it right, can exercise actually be therapeutic for RSIs? Can it rush recovery?

Tendinitis is actually inflamed — it’s just subtle.10 And exercise probably is actually anti-inflammatory — more than most things that are supposedly anti-inflammatory, like ibuprofen or turmeric. Indeed, it may be the only effective way to manage inflammation long-term. We’ve known for at least twenty years that this was probably the major mechanism for how exercise prevents cardiovascular disease: muscle is an endocrine organ that secretes molecules with anti-inflammatory effects … mainly when you use them.11 And that anti-inflammatory magic probably has effects on musculoskeletal health as well.

For instance, in a 2019 experiment, scientists mechanically stressed samples of excised cartilage and cartilage cells, and the loading actually reduced inflammatory signals produced by these cells.12 Cool.

Another good example: weightlifting is good for brain health via an anti-inflammatory effect.13

And so on. There are mountains of indirect evidence like this, many good clues that “load management” matters for preventing and treating injury.14 For instance, when a couple dozen Norwegian students spent the summer doing “progressive and individualized” training, they got hurt quite a bit less in the fall than students who didn’t prepare.15

We clearly do get in trouble with both too much and too little loading, but mechanical loading in the Goldilocks zone probably does the opposite by easing inflammation: a specific and substantive reason why “exercise is medicine” for distressed tendons as well as heart disease.

Is there direct evidence to confirm this? Yes-ish …

I keep talking about “exercise,” but I specifically and mainly mean resistance training, weightlifting — because it’s probably the best way to load specific tissues precisely.

The science of using overused tissue to calm it down

Sports medicine suffers from its usual bizarre shortage of exactly the evidence it most needs, but there are some examples that come close …

• A good quality trial that clearly showed “good, lasting clinical results” for two kinds of exercise for Achilles tendinitis.16
• Another respectable trial of heel lifts also reported good results for plantar fasciitis.17
• The encouraging body of evidence that “exercise therapy benefits patients with patellofemoral pain.”18
• And much the same consensus about strengthening for tennis elbow: “Strengthening … is effective in reducing pain and improving function for lateral epicondylosis but optimal dosing is not defined.”19

But “optimal dosing is not defined” is a problem with all of the evidence, and might be why there are also a bunch of discouraging studies. Dosing alone can probably make or break exercise-as-medicine for an overuse injury, and yet it’s just impossible to know exactly what the just-right dose is. It’s a moving target and a function of many variables, many of them unknowable in practice. For instance, we can easily think they we slept better than we actually did. Or a minor infection draining our physiological resources, undetectable except for feeling a little extra tired or slightly oogy.

We have good reasons to try to get the dose right, though — by backing off a bit on those “off” days, even though we really have no idea what's going on or exactly how much to adjust our load. Those guesses are going to be wrong sometimes, but, if you grok the principle, you can probably improve your accuracy.

And if you get it wrong, if you fail to do good, or if you even make a tendon a bit worse for a couple days? Fortunately, exercise (as always) has its great consolation prize: truly major general health benefits. If you’re going to fail … fail fitter!

Resistance training is a terrific rehab tool not because strength is inherently therapeutic (though it might be), but specifically because it’s a great way to regulate exercise dosage. It can be tidy and precise, and you really want that when you’re doing your best to get the dosage right — you can’t control a lot of other variables, but you can at least control that.

Common anti-inflammatory medications are probably not biologically relevant to the rather subtle, chronic inflammation that characterizes repetitive strain injuries. But exercise is, presumably, highly relevant: it gives the body the only medicine that was possible for millions of years of evolution. Our job is just to tinker with the dosage — which probably means being more patient in the early stages than most of us want to be. And some need to be a bit braver.

All my evidence-inspired speculation about exercise being “anti-inflammatory” for tendinitis and other overuse injuries could be wrong, and it would still be a great idea to try — because it’s an extremely healthy activity otherwise.

Notes

1. Luke AC, Stehling C, Stahl R, et al. High-Field Magnetic Resonance Imaging Assessment of Articular Cartilage Before and After Marathon Running: Does Long-Distance Running Lead to Cartilage Damage? Am J Sports Med. 2010 Jul. PubMed 20631252 ❐

   Studies (like Weng) have shown that runners probably do not get more knee osteoarthritis than anyone else, which is a bit surprising: surely regular pounding wears out joints? Researchers took a bunch of fancy pictures of the insides of knees before and after a marathon, using a new MRI technique that can detect early cartilage degeneration: “Runners showed elevated T1rho and T2 values after a marathon, suggesting biochemical changes in articular cartilage” and “the patellofemoral joint and medial compartment of the knee show the highest signal changes, suggesting they are at higher risk for degeneration.” Sounds bad, doesn’t it? Also, perhaps some biomarkers of trouble “remain elevated after 3 months of reduced activity” — but it’s arguable that those results were not actually statistically significant.

   It’s also an open question whether any of this is clinically significant: it’s not clear that signs of stress actually mean anything in and of themselves. And this data also shows that the effect is surprisingly minor, and that most of the knees recovered, either mostly or completely, within three months … even from a very large dose of running. That harmonizes nicely with other evidence showing that the average runner is nowhere close to having a "wear and tear" problem.

   (See more detailed commentary on this paper.)

2. Williams PT. Effects of running and walking on osteoarthritis and hip replacement risk. Med Sci Sports Exerc. 2013 Jul;45(7):1292–7. PubMed 23377837 ❐

   This analysis of about a zillion runners versus walkers found that “running significantly reduced arthritis and hip replacement risk”… but due in large part to the fact that runners were typically skinnier. So weight was a trump factor here.

   This data flies in the face of the common assumption that running is much harder on the joints. Instead, what it clearly shows is that running is either neutral or helpful, and weight is a much more important factor regardless of whether you walk or run.

3. Lefèvre-Colau MM, Nguyen C, Haddad R, et al. Is physical activity, practiced as recommended for health benefit, a risk factor for osteoarthritis? Ann Phys Rehabil Med. 2016 Jun;59(3):196–206. PubMed 27103057 ❐

   This review of the scientific literature on arthritis risk focused specifically on the role of injury in driving arthritis in people who are active and athletic. They reported that moderate activities/sports are “not a consistent risk factor for clinical or radiographic knee/hip OA.” Signs of arthritis visible on x-ray increased with volume of activity and injury risk, but modestly even up to the elite level, and former athletes actually had fewer symptoms despite those signs. Finally, the “risk of injury in different sports may be the key factor to understanding the risk of oseoarthritis related to sport.”

   About the review not being “systematic”: it was just experts choosing papers, as opposed to using a reproducible method that anyone, in theory, could use to produce the same list of papers to read.

4. Alentorn-Geli E, Samuelsson K, Musahl V, et al. The Association of Recreational and Competitive Running With Hip and Knee Osteoarthritis: A Systematic Review and Meta-analysis. J Orthop Sports Phys Ther. 2017 Jun;47(6):373–390. PubMed 28504066 ❐

   This study reports that long-term prevalence of hip and knee osteoarthritis was lowest in recreational runners, and much higher in both sedentary people and competitive runners. They did not control well for confounders, and there are lots of possible ones, but the results were consistent with the predictable wisdom of “moderation in all things,” and that typical walking and running is, if anything, actually inversely correlated with OA progression in both hip and knee. And that conclusion is support by plenty of other evidence (e.g. Voinier, Weng).

5. Lo GH, Musa SM, Driban JB, et al. Running does not increase symptoms or structural progression in people with knee osteoarthritis: data from the osteoarthritis initiative. Clin Rheumatol. 2018 May. PubMed 29728929 ❐

   This study looked at the relationship between running and arthritis in 1200 aging runners with at least some arthritis, selected from the Osteoarthritis Initiative (a 10-year study of about 5000 arthritis patients). No data is ever perfect or complete, and Lo et al. had to fill in the blanks (imputation) for 8% of the runners. The runners-with-arthritis were divided into groups who got worse or better signs or symptoms over two years, adjusting for factors like age, weight, and sex.

   They did not get worse. In fact, the runners — normal people, mostly just a bunch of aging amateur athletes who consider themselves runners — actually had less pain than the non-runners, and the state of their joints (on x-ray) were stable. Conclusion:

   self-selected running is associated with improved knee pain and not with worsening knee pain or radiographically defined structural progression.

6. Ponzio DY, Syed UAM, Purcell K, et al. Low Prevalence of Hip and Knee Arthritis in Active Marathon Runners. J Bone Joint Surg Am. 2018 Jan;100(2):131–137. PubMed 29342063 ❐

   In this survey of 675 marathoners, there was no link between current arthritis symptoms and their running history, and they had a lower rate of arthritis than the general population. That is, no matter how much they ran, they had the same low rate of arthritis: about 9%, compared to 18% in non-runners.

   This is good-news evidence that challenges the assumption that relentless “pounding” on the road is hard on joints, as many other studies have. But we’re still far from “proof.” For something closer, see Chakravarty — the best single study on this topic that I’m aware of to date.

7. Voinier D, White DK. Walking, running, and recreational sports for knee osteoarthritis: An overview of the evidence. Eur J Rheumatol. 2022 Aug. PubMed 35943452 ❐

   Voiner and White reviewed a lot of reviews of the relationship between exercise and arthritis — an “overview of narrative reviews, systematic reviews, and meta-analyses,” twenty of them. They also threw a dozen original trials into the mix. Their clear conclusion, based on “consistent evidence,” is that arthritis just has nothing to do with common kinds of physical activity and exercise, like walking and running and playing softball. Specifically, the “structural progression” is unrelated to physical activity in the general population.

8. Weng Q, Goh SL, Wu J, et al. Comparative efficacy of exercise therapy and oral non-steroidal anti-inflammatory drugs and paracetamol for knee or hip osteoarthritis: a network meta-analysis of randomised controlled trials. Br J Sports Med. 2023 Jan;57(15):990–996. PubMed 36593092 ❐ PainSci Bibliography 51421 ❐

   This enormous meta-analysis concludes that exercise is a modestly effective treatment for hip/knee arthritis in the short term:

   Exercise has similar effects on pain and function to that of oral NSAIDs and paracetamol. Given its excellent safety profile, exercise should be given more prominence in clinical care, especially in older people with comorbidity or at higher risk of adverse events related to NSAIDs and paracetamol.

   The data also shows diminishing returns over time, dwindling to a trivial benefit.

   But this data shows that exercise is quite safe and somewhat helpful — and therefore also obviously not harmful.

9. Chakravarty EF, Hubert HB, Lingala VB, Zatarain E, Fries JF. Long distance running and knee osteoarthritis. A prospective study. Am J Prev Med. 2008 Aug;35(2):133–8. PubMed 18550323 ❐ PainSci Bibliography 49918 ❐

   Chakravarty et al. tracked a few dozen older runners and non-runners for many years — most for more than a decade, some as long as twenty years — and 32% of the non-runners ended up with severe arthritis versus only 20% of the runners. And the runners started with 7%! And therefore…

   “Severe OA may not be more common among runners.”

   Indeed, it was clearly less common in this study.

   This was a good quality prospective trial, which is exactly what this research question needed, but it was also tiny (among other acknowledged limitations). You might well see different results in another few dozen runners just by fluke.

   “Much larger studies involving hundreds to thousands of healthy older adults followed for several decades are needed to determine if long-distance running may be associated with a modest decrease in incidence or severity of radiographic OA.”

10. Dakin SG, Newton J, Martinez FO, et al. Chronic inflammation is a feature of Achilles tendinopathy and rupture. Br J Sports Med. 2017 Nov. PubMed 29118051 ❐

    This paper now stands as the best available evidence so far that rumours of inflammation’s demise in tendinopathy are exaggerated/oversimplified. There are no other important sources I’m aware of so far (as of early 2020), and Dakin et al. cite only their own evidence on this.

    This evidence and related ideas are explored in detail in my repetitive strain injury guide, a couple thousand words about whether and how these injuries are "inflamed." It’s complicated (duh) and the truth is in the middle. But this is best single citation to date to support statement “Tendinitis is actually inflamed — it’s just subtle.”

11. Pedersen BK. The anti-inflammatory effect of exercise: its role in diabetes and cardiovascular disease control. Essays Biochem. 2006;42:105–17. PubMed 17144883 ❐

    This paper is one of dozens by exercise physiologist Dr. Bente K. Pedersen, who has studied exercise as medicine for non-communicable disease for thirty years, and especially “the myokine concept.” This explores the early (mid-2000s) evidence for the hypothesis that “skeletal muscle is a endocrine organ with the capacity to produce so called ‘myokines,’ i.e. cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either autocrine, paracrine or endocrine effects” (as summarized here), and those molecules mediate "beneficial health effects against chronic diseases associated with low-grade inflammation such as diabetes and cardiovascular diseases.”

    That hypothesis has generally been confirmed over years. For Dr. Pedersen’s 2023 update (concise and readable), see “From the discovery of myokines to exercise as medicine.”

12. Fu S, Thompson CL, Ali A, et al. Mechanical loading inhibits cartilage inflammatory signalling via an HDAC6 and IFT-dependent mechanism regulating primary cilia elongation. Osteoarthritis Cartilage. 2019 Jul;27(7):1064–1074. PubMed 30922983 ❐ PainSci Bibliography 52660 ❐

    This is a highly technical petri-dish study of the effect of “exercise” (mechanical loading) on the inflammation signalling of cartilage cells. Basically, they mechanically stressed samples of excised cartilage and cartilage cells. The surprising, good-news result was that the researchers reported that moderate loading actually reduced inflammation. That is, fewer inflammatory signals were produced by the cells.

13. Liu Y, Chu JMT, Yan T, et al. Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer's disease mice. Journal of neuroinflammation. 2020 01;17(1):4––4. PubMed 31900170 ❐ PainSci Bibliography 52495 ❐

    Lifting weights: good for Alzheimer’s? Good chance. This study clearly showed a neuroprotective effect from resistance training in mice. Compared to mice who were not given cute little barbells! Specifically, they found:

    “improved cognitive performance and reduced neuropathological and neuroinflammatory changes in the frontal cortex and hippocampus of mice… [and] inhibition of pro-inflammatory intracellular pathways.”

    Obviously a human study would be more persuasive (always), but it’s still early days for studying neuroinflammation. Lots of what we now know about exercise physiology we learned from mice initially. It’s likely (or at least highly plausible) that the effect will be confirmed in humans as well, despite the fact that “mice lie and monkeys exaggerate” in research.

    It has been clear for many years now that exercise in general is neuroprotective — that is, it has an anti-inflammatory effect in the brain and slows down Alzheimer’s disease progression — but that insight mostly comes from studies of aerobic exercise. This study extends that effect to resistance training, which is why the conclusion isn't much of a reach: we already know that another kind of exercise does this, and we already know that resistance training is an excellent way to exercise.

    And now, just for fun… how exactly do you strength train mice? A ladder with a treat at the top, and teensy weights attached to their tails! I am not even joking: that really is how they did this. “The mice were motivated to climb up the ladder to a total of 15 times, with progressively heavier weights attached to their tails and a 2-minute rest in between each climb.” Sounds like more fun than my gym visits.

14. Soligard T, Schwellnus M, Alonso JM, et al. How much is too much? (Part 1) International Olympic Committee consensus statement on load in sport and risk of injury. Br J Sports Med. 2016 Sep;50(17):1030–41. PubMed 27535989 ❐

    This is the first of a pair of papers (with Schwellnus) about the risks of athletic training and competition intensity (load). Is load a risk for injury and illness? How much is too much? Is too little a problem? These papers were prepared by a panel of experts for the International Olympic Committee, and both them use many words to say the same things formally — but they are good points. Here they are in plain English:

    • There’s not enough research, surprise surprise, and what we do know is mostly from limited data about a few specific sports. But there’s enough to be confident that “load management” overall is definitely important.
    • Both illness and injury seem to have a similar relationship to load — lots of overlap.
    • Too much and not enough load probably increase the risk of both injury and illness. You want to be in the goldilocks zone! But the devil is in the details …
    • Not everyone is vulnerable to high load, and elite athletes are the most notable exception: they are relatively immune to the risks of overload, probably because of genetic gifts. Everyone else gets weeded out!
    • Big load changes — dialing intensity up or down too fast — are much bigger risks than absolute load. If you methodically work your way up to a high load, it may even be protective.
    • “Load” can also refer to non-sport stressors and “internal” loads, which are legion. Psychology, for instance, probably does matter: anything from daily hassles to major emotional challenges, as well as stresses related to sport itself.
15. Nyhus Hagum C, Tønnessen E, Hisdal J, Shalfawi SAI. The effect of progressive and individualised sport-specific training on the prevalence of injury in football and handball student athletes: a randomised controlled trial. Front Sports Act Living. 2023;5:1106404. PubMed 37346384 ❐ PainSci Bibliography 49671 ❐

    Forty-two Norwegian students were divided into two groups before entry into a sports academy. Half didn’t prepare, and the other half did “weekly progressive, individualized sport-specific training programs.” Each student had their own plan for “increasing the training load gradually when the athlete had adapted to a specific training load or stimuli.” Baby steps, tested.

    In their first three months of play, the students who prepared suffered far fewer injuries, a rate of just 11% compared to 19% for any injury, and 7% versus 10% for more serious ones. That’s a 1.8× greater risk of injury for the unprepared, which is quite dramatic.

    This is a clear and plausible result, but the small sample of convenience reduces its power quite a bit, and they didn't account for previous injuries. The strength of the result could be a fluke.

16. Beyer R, Kongsgaard M, Hougs Kjær B, et al. Heavy Slow Resistance Versus Eccentric Training as Treatment for Achilles Tendinopathy: A Randomized Controlled Trial. Am J Sports Med. 2015 Jul;43(7):1704–11. PubMed 26018970 ❐

    Trials have shown promise for eccentric training (contracting while elongating) for Achilles tendinitis (and other tendinitises), but … does it really have to be “eccentric”? Maybe any resistance training will do the job. This trial was designed to test that by comparing eccentric training to a more conventional weightlifting style of heavy slow resistance training.

    They tested both approaches for three months in a few dozen people with chronic midportion Achilles tendinitis. The tendons changed! “Significant reduction in tendon thickness and neovascularization”! But …

    None of these robust clinical and structural improvements differed between the ECC and HSR groups.

    Eccentric wasn’t better. It was actually a little worse in one way: amusingly, people were more satisfied doing the regular exercises — probably because they’re less tedious!

17. Rathleff MS, Mølgaard CM, Fredberg U, et al. High-load strength training improves outcome in patients with plantar fasciitis: A randomized controlled trial with 12-month follow-up. Scand J Med Sci Sports. 2015 Jun;25(3):e292–300. PubMed 25145882 ❐

    Raise a little heel 🎶 raise a little heel 🎶 raise a little heel! If you don’t like what you got, why don’t you change it? If you know there’s something wrong why don’t you right it?

    Trooper, from the classic song, “Raise a Little Heel”

    In 48 plantar fasciitis patients, Rathleff et al. compared the effect of stretching to heel raises (AKA repeatedly standing up on your tip-toes). A towel was inserted under the toes for a little extra angle. When patients were able to comfortable manage a dozen slow lifts every other day, they added weight: a backpack full of books. Elegant simplicity! They kept this regimen up for several months … but it didn’t take long to help. Although everybody got better eventually, the heel raisers got better a lot quicker than the stretchers. They were already much better off after three months.

    This isn’t proof that heel raises are going to work … but it’s more than good enough to justify trying it. Obviously we’ll hope to see replication by other researchers.

18. Van Der Heijden RA, Lankhorst NE, Van Linschoten R, Bierma-Zeinstra SM, Van Middelkoop M. Exercise for treating patellofemoral pain syndrome: an abridged version of Cochrane systematic review. Eur J Phys Rehabil Med. 2016 Feb;52(1):110–33. PubMed 26158920 ❐

    This paper is the abridged version of a 2015 Cochrane review of exercise for patellofemoral pain, mainly strengthening. It reports on 31 trials including 1690 participants; it’s not the most recent review (as of 2024), but probably still the most credible. It’s not like the evidence situation has improved all that much! It likely remains “very low quality but consistent,” with nearly all of them being “at high risk of performance bias and detection bias due to lack of blinding.”

    Despite that, the consistency does suggest that “exercise therapy benefits patients with PFP” — and it also seems clear that we still don’t know the best kind of exercise, and “it is unknown whether this result would apply to all people with PFPS.”

19. Raman J, MacDermid JC, Grewal R. Effectiveness of different methods of resistance exercises in lateral epicondylosis—a systematic review. J Hand Ther. 2012;25(1):5–25; quiz 26. PubMed 22075055 ❐

    This systematic review of studies for tennis elbow considered just twelve experiments, selected from several hundred candidates. The quality of the trials was generally poor, with only two that would have gotten better than about a C+ grade in school, so it’s got a bit of the “garbage in, garbage out” like most reviews in this field. Good news, though: all of them came to the same plausible conclusion that “resistance exercise resulted in substantial improvement in pain and grip strength.”

    The authors note that “optimal dosing is not defined” — that would take a lot more research, and even the research summarize here isn’t adequate. But it is consistent, at least. It also harmonizes with data on strengthening for other repetitive strain injuries.