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Exercise and Inflammation

You ever feel like you live in Opposite World?  Well, I do sometimes as I read about the world of health, medicine and longevity.  I'll explain what I mean below, but first consider this proposition:

MODERATE EXERCISE = POWERFUL ANTI-INFLAMMATORY

Not only is the above true, but I will show below that moderate exercise is nearly as powerful as any anti-inflammatory drug.  The effects are both profound and long-lasting. The best example of this from the research is probably from a study that put the participants in two groups doing 30 minute bike rides.  One group did "regular" bike riding and the other the same but with a lot of braking.  What was the purpose of the braking?  Basically, to inflict greater muscle damage.

As you may have guessed, the partipants doing just normal cardio on the bike without all the braking achieved the powerful anti-inflammatory effects:  their IL-6 levels rose a little bit post-exercise - maybe 50% - and then dropped 50% below baseline values on days 2-7! [8] (IL-6 is your body's Inflammation Increaser.) Yes, it looks like you can cut your IL-6 levels in half by simply sticking with moderate exercise rather long duration or intense exercise protocols that do significant muscle damage even though they are relatively equal as to how hard they push your cardiovascular system. 

The title of this study was "Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage"  and I highly recommend that you pull up the full study online and read through it here.

Keep in mind that this study is not the only one to show that moderate exercise, i.e. exercise such as a brisk walk, swimming or easier cardio style biking like the above, dramatically decreases inflammatory levels in the body.  There are also studies that show that moderate exercise decreases TNF alpha for days after, and TNF is your body's other big Inflammation Increaser.

Again, why have I never read an article in any fitness or health magazine or blog on this subject?!  I believe this is underplayed by the health press because moderate exercise does not sell.  Nobody wants to hear about moderate exercise, because it is considered boring and time consuming.  But the fact is that there is no pill that can do what moderate exercise can do for you.  Don't forget that it also boost baseline nitric oxide levels and is a powerful anti-depressant.  But to get these benefits, you have to be willing to let your body rest and forego all the muscle (and I sure tendon/ligament) damage.  Don't believe me?  Check out this:

DOES INTENSE AND/OR LONG EXERCISE RAISE INFLAMMATION?  Let me answer that question with a question:  do you know what Overtraining Syndrome (OTS) is?  If so, you know you know that OTS is a nasty condition that afflicts men that have trained too intensely for too long.  Not surprisingly, recent evidence shows that inflammation is the root cause of Overtraining Sydnrome (OTS).  Check out this summary:

 "A number of hypotheses have been proposed to explain various symptoms associated with OTS, yet none have sufficiently accounted for all the manifestations of the syndrome. A recent article in Medicine and Science in Sport and Exercise presents an all-encompassing hypothesis focused on the role of cytokines in initiating and perpetuating OTS. The Cytokine Hypothesis suggests that exercise-induced muscle and connective tissue microtrauma triggers the release of pro-inflammatory cytokines (e.g. IL-1 beta, IL-6 and TNF-alpha), which when sufficient rest is allowed, can aid in the healing process. The acute inflammation that results from excessive exercise with inadequate rest, however, evolves into a chronic response resulting in a systemic immune response involving the central nervous system (CNS), liver, and immune system (see Figure 1)." [11]

In other words, overexercising can do the polar opposite of all that you want to do as a guy.  Instead of de-aging yourself, you can actually put your foot on the accelerator to the grave.  Instead of avoiding all the chronic disease that you see all around you, you are actually embracing it.

 SO WHEN DOES INTENSE AND/OR LONG EXERCISE RAISE INFLAMMATION?  To understand the discussion, I need to explain that there are two primary inflammatory "messengers" in the body:  IL-6 and TNF alpha.  These messengers are called "cytokines" in the research, and, if you read health stuff, you will see them crop up all the time, because they are so fundamentally associated with the chronic disease that you see in modern societies - more on that below.

So at what point does exercise increase inflammation rather than lower it?  Here are a few key principles:

a)  If you are overweight or obese, this will increase TNF alpha levels and TNF alpha is arguably the prime player in inflammation.  Exercise, by increasing metabolism and burning calories, can help with weight loss.

b) Exercise increases transiently IL-6  and IL-6, in turn, dampens TNF alpha.  This is one of the ways that exercise can lower inflammation in a positive way. [12] That said, exercise, if overdone, can actually lead to runaway inflammation.

c) Exercise (if done right) can lower both baseline TNF alpha and IL-6 levels.  However, if done for too long or with too much intensity or volume can increase inflammation. 

Here are some example from the research of "over-exercising" and how it can dramatically raise inflammation for days afterward:

1. Equivalent to Trauma.  Participants were put on a 2.5 hour treadmill run at 75% VO2max- pretty serious exercise indeed.  Researchers observed the following:

"The plasma concentration of IL-6 increased after 30 min of running, and peaked at the end of running with a 25-fold increase compared with the pre-exercise value. IL-1ra increased only after running, and peaked after 2 h of rest with an 18-fold increase compared with the pre-exercise value...The results suggest that very early events in exercise trigger the release of IL-6, and that the cytokine response to exercise has similarities to that observed after trauma." [1]

2. IL-6 @ 2 Hours Post-Exercise. Another earlier study put particpants on a mere 30 minute bike ride but added in a lot of braking, which of course would tend to really work the muscles.  What they found was that two hours after exercis IL-6 levels were 4.75 X baseline values.  Again, just 30 minutes of exercise spiked IL-6 for hours after exercise. [8]

3. IL-6 Elevated for At Least 3 Days.  This same study found that IL-6 was elevated between 2.0 and 2.5 X baseline IL-6 before the study.  In other words, just 30 minutes of exercise doubled inflammation for days afterward.

4. IL-6 Levels Increase a 100 Fold Post-Marathon.  This astonishing increase is hard to argue as being good from the longevity and anti-aging perspective if you ask me much as I admire anyone who does a marathon.  It's fun and impressive, but it is hard to believe these levels of inflammation are going to play out well in the long term if done regularly. [10]

REBUTTAL:  Anti-Inflammatory Molecules May Save the Day?  Some may argue that a trained individual will secrete a barrage of anti-inflammatories that compensate for the astronomical increases in IL-6. 

"Thus, the increase in TNF-alpha and IL-1beta levels is accompanied by a dramatic increase in IL-6. This release is balanced by the release of cytokine inhibitors (IL-1ra and TNF receptors (TNF-R)) and the anti-inflammatory cytokine IL-10. In addition, the concentrations of the chemokines IL-8, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta are elevated after a marathon (K Ostrowski and BK Pedersen, unpubl. data, 2000). These findings suggest that cytokine inhibitors and anti-inflammatory cytokines restrict the magnitude and duration of the inflammatory response to exercise." [10]

SO WHO CARES ABOUT IL-6 and TNF ALPHA?  Let's look at just IL-6. Elevated levels of IL-6 has been associated with just about every nasty chronic disease you can think of:

a. Atherosclerosis (Arterial Plaque). "...the interleukin-6 (IL-6) cytokines and their signalling events have been shown to contribute to both, atherosclerotic plaque development and plaque destabilisation via a variety of mechanisms." [3]

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b.  Alzheimer's. "We investigated whether interleukin-6 could be detected in plaques of Alzheimer's disease patients prior to the onset of neuritic degeneration. We found interleukin-6 mostly in plaques where neuritic pathology has not yet developed. This indicates that the appearance of interleukin-6 may precede neuritic changes and is not just a consequence of neuritic degeneration." [4]

c. Crohn's. "Increased levels of IL-6 and sIL-6R have been demonstrated in both serum and intestinal tissues of the patients with active Crohn's disease. In animal model studies, anti-IL-6R monoclonal antibody (mAb) successfully prevented intestinal inflammation and systemic wasting disease by suppressing adhesion molecule expression by vascular endothelium." [5]

d.  Irritable Bowel Syndrome.  "IBS patients showed significantly (P < .017) higher baseline TNF-alpha, IL-1beta, IL-6, and LPS-induced IL-6 levels compared with HCs." [6]

e. Rheumatoid Arthritis.  "Interleukin 6 (IL-6) is a pleiotropic cytokine with a pivotal role in the pathophysiology of rheumatoid arthritis (RA). It is found in abundance in the synovial fluid and serum of patients with RA and the level correlates with the disease activity and joint destruction." [7]

Okay, I could go on and on with this, but you get the idea:  elevated levels of IL-6 for an extended is just not going to be a good idea.  The research on elevated TNF alpha is just as bad.

So bottom line for you guys 40+:  be careful.  If you can afford it, pull some of these values and see how you are doing.  You generally don't want elevated IL-6 or TNF alpha.

 

REFERENCES::

1)  J of Physiology, Dec 1998, 513(3):889–894, "A trauma-like elevation of plasma cytokines in humans in response to treadmill running"

2) International Journal of Obesity, 2000, 24:1207-1211, "Moderate-intensity regular exercise decreases serum tumor necrosis factor-a and HbA1c levels in healthy women"

3) Thromb Haemost, 2009 Aug, 102(2):215-22, "How much is too much? Interleukin-6 and its signalling in atherosclerosis"

4) Neurobiol Aging, 1996 Sep-Oct, 17(5):795-800, "Interleukin-6-associated inflammatory processes in Alzheimer's disease: new therapeutic options"

5) Curr Drug Targets Inflamm Allergy, 2003 Jun;2(2):125-30, "IL-6 and Crohn's disease"

6) Gastroenterology, 2007 Mar, 132(3):913-20, "Immune activation in patients with irritable bowel syndrome"

7) Ther Adv Musculoskelet Dis, 2010 Oct, 2(5):247–256, "The Role of Interleukin 6 in the Pathophysiology of Rheumatoid Arthritis"

8) Journal of Physiology, 1997, 499(3):833-841, "Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage"

9) J Am Coll Cardiol, Dec 2004, 44(12), "Effects of prior moderate exercise on postprandial metabolism and vascular function in lean and centrally obese men"

10) Immunology and Cell Biology, 2000, 78:532–535;, "Special Feature for the Olympics: Effects of Excercise on the Immune System"

11) https://www.rndsystems.com/resources/articles/cytokines-and-overtraining

12) Journal of Applied Physiology, Apr 1 2005, 8(4):1154-1162, "The anti-inflammatory effect of exercise"

 

 

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