misinflammation sullivan

8/22/2019 Misinflammation Sullivan

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Stopping the Spread o

Misinfammation

by

Jonathon Sullivan

StartingStrength.com 2012 Te Aasgaard Company

Starting Strength

INTRODUCTION: LOTS OF HEAT, LITTLE LIGHT

Teres an idea foating around out there, in that ill-dened nebula that we could call the FitnessCommunity, that seems to be picking up steam. Its an idea whose proponents pride themselves onbeing iconoclastic and cutting edge, on slaying sacred cows, on bashing the longstanding conventionalwisdom o clueless doctors and uddy-duddy ironheads o the Old Guard. A recent and apparentlyvirulent exposition o the idea can be ound in this video, a presentation that will allegedly blow yourmind.

As expounded in this video and other sources (see, or example, here,here, here, and here) theidea is this: infammation is how we heal, how we get huge, and how we get strong. Tereore, thingsthat suppress infammation are bad or you. From which it ollows directly that acetaminophen, aspirin,nonsteroidal anti-infammatory drugs and cryotherapy (cold therapy; ice and other such interventions)are no-nos. We Were Wrongabout ice and NSAIDs, the daring iconoclasts tell us, charitably includingthemselves among those who once cleaved to superstition, and thereby underscoring the dierencebetween themselves and those benighted souls who still wont see the light. So Wrong.

o be air, the idea that interering with the infammation o injury or training would slowyour healing or hold back your gains is not new. For example, Abadjiev and other exponents o theBulgarian method seem to think so.1 Questions about the eect o anti-infammatory interventions onhealing, hypertrophy and adaptation have been bandied about in the biomedical literature or quite

a while, as well see. What seems to have changed, at least rom where Im standing, is how condentand vocierous the proponents o these ideas have become. Watching the video (which racked up about35,000 hits on Youube inside o ten days), youd think the question was settled: ice and NSAIDs willscrew up your training. Te science says so. At 11:05, Kelly Starrett and Gary Reinl suggest that theliterature oers us a scientic consensus on this issue. So it must be true.

Right?
http://startingstrength.com/http://aasgaardco.com/http://www.youtube.com/watch?v=0UmJVgEWZu4&list=PL28F7B1F419028525&index=1&feature=plpp_videohttp://www.mobilitywod.com/2012/08/people-weve-got-to-stop-icing-we-were-wrong-sooo-wrong.htmlhttps://vimeo.com/20446573http://www.yourbodymechanic.com/Community/index.php?option=com_content&view=article&id=131:inflammation-friend-or-foe&catid=1:latest-news&Itemid=70http://sanfranciscocrossfit.blogspot.com/2009/06/get-off-ibuprofen-peoples.htmlhttp://startingstrength.com/articles/bulgarian_training_moser.pdfhttp://startingstrength.com/articles/bulgarian_training_moser.pdfhttp://sanfranciscocrossfit.blogspot.com/2009/06/get-off-ibuprofen-peoples.htmlhttp://www.yourbodymechanic.com/Community/index.php?option=com_content&view=article&id=131:inflammation-friend-or-foe&catid=1:latest-news&Itemid=70https://vimeo.com/20446573http://www.mobilitywod.com/2012/08/people-weve-got-to-stop-icing-we-were-wrong-sooo-wrong.htmlhttp://www.youtube.com/watch?v=0UmJVgEWZu4&list=PL28F7B1F419028525&index=1&feature=plpp_videohttp://aasgaardco.com/http://startingstrength.com/


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2 StartingStrength.com 2012 Te Aasgaard Company

Welllets put a pin in that. Lets step back, and take a look at where all this is coming rom.From where I sit, the anti-anti-infammation (AAI) guys seem to be coalescing around the ollowingarguments:

1. Infammation is the bodys naturaland therefore correctresponse to injury. Your

body knows what its doing, so interering with the infammatory response is ill-consideredrom the git-go.

2. Without infammation, the body would never heal. You want to heal, dont you? So whyin the world would you intervene in the infammatory process?

3. Without infammation, muscles cannot adapt to training stress with protein synthesisand hypertrophy. Tereore, interering with training-induced infammation (i.e.,delayed-onset muscle soreness (DOMS)) will stunt your gains.

4. e scientic literature overwhelmingly supports all o these contentions, and the

issue is essentially settled or Tose In Te Know. In particular, many AAI exponentspoint to the literature review on cryotherapy published in the Emergency Medicine Journalby Collins in 20082; a 2001 study by rappe showing that ibuproen and acetaminophendampen post-exercise muscle protein synthesis,3 a study by Mikkelson published in 20084

concluding that anti-infammatories block the activation o satellite cells in skeletal muscleater injury, and Novaks 2009 study o skeletal muscle hypertrophy in mice.5

Tis isnt inoil Hat stu. Right or wrong, these claims are not irrational, and they deserve tobe considered. So lets consider them, shall we?

I hope youre Getting Your Nerd On.

INFLAMMATION: A GEEKY REVIEW FOR INTERESTED ATHLETES

Infammation is an ancient, primitive and nevertheless highly elaborate response to insult orinjuryjust about anyinsult or injury.6 Infammation is involved when you sprain an ankle, sustain aburn, catch pneumonia, go into anaphylactic shock rom a bee sting, deteriorate rom a wheezing tto status asthmaticus,7,8 do a high volume o heavy squats, get appendicitis, have an ischemic stroke,9go into septic shock,10 or start raising antibodies against yoursel, as in the autoimmune diseases.Infammation is horribly complex in the particularsit remains a vibrant eld o investigation. Butthe broad scope o the process is well-understood and easily apprehended, even by doctors and uddy-

duddies.Infammation begins when injury, inection or some other insult exposes the tissue to pro-

infammatory substances. Such substances constitute a diverse range o biomolecules and toxins,including environmental irritants and antigens, bacterial and viral products, and infammatorymediators produced by our own cells. Tese substances engage in a complex web o interactions withtissue and the immune system to trigger proound changes in the injured area, which maniest as theclassic clinical signs o infammation: tumor, dolor, ruborand calor. Tats swelling, pain, redness andheat, or those o you who, like me, are a bit rusty on your Latin.
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Tats the big picture. Lets ll it in by doing what people like me always do when conrontedwith the task o explaining complex physiology: put up some geeky cartoons with lots o arrows andtell a story.

First, lets introduce the major players:

Our story has a cast o thousands11, but some o the major players are pictured above. Plateletsare tiny, non-nucleated cell ragments that, as Im sure you know, play an important role in hemostasis(suppressing bleeding). But their role in infammation is also crucial, and there are importantinteractions between the hemostatic and infammatory cascades. Platelets catalyze a number o relevantbiochemical reactions on their surace membranes.12,13White blood cells (WBCs, neutrophils,polymorphonuclear leukocytes (PMNs), granulocytes) normally hang out in the vascular space, like

shock troops playing poker in the barracks, until an insult puts them on alert. Teir granules are lledwith digestive enzymes and other antibiotic goodies.11Immunocytes (L) are a large and diverse amilyo immune system cells with complex interactions and unctions that participate in cell-mediatedimmunity, antibody production, and infammatory responses. Monocytes (Mo) are a class o immunecells which, under the right circumstances, grow up to be macrophages. Macrophages (Mp)are, likeWBCs,phagocyticcells, meaning they gobble up bacteria, oreign matter and cellular debris. But theyalso elaborate an array o signaling molecules, including cytokines and growth actors, important ininfammation and healing.11 Like neutrophils, mast cells (MC)and other specialized granulocytes

Figure 1. Te major players.


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contain packets o enzymes and signaling substances. Mast cell granules are stued with histamine,serotonin, and proteases (enzymes that eat protein). Granule release is triggered by antibody-antigeninteractions. Mast cells hang out in tissue, close to neurovascular structures, waiting or somethingto piss them o so they can spill their guts and Unleash Hell.11Fibroblasts (F)are the progenitorso scar tissue, and critical to wound healing. Satellite cells (S) are specialized stem cells that reside

within muscle bers and, when activated, participate directly in the repair o damaged muscle tissue.14

Bacteria arewell, nasty, and we have given them an appropriately ecal hue in our little cartoon.Depending on the species, they exude specic toxins and immunogens that can trigger a range oimmune responses rom local infammation to ull-blown systemic syndromessome o them quitecolorul and devastating.11,15Endothelial cells (E)and their basement membrane orm the lining oblood vessels. Capillaries are little more than a single layer o epithelium surrounded by the basementmembrane.16

Molecular players include arachidonic acid (AA), a product o damage to cell membrane lipid.Arachidonate is rapidly converted to various species o signaling molecules called eicosanoids, the mostimportant or our discussion beingprostaglandins (PG) but also including prostacyclins, leukotrienes,thromboxanes, and other potent chemical messengers, with diverse physiologic eects in both health

and disease.11,17 A vast array o peptide molecules also participate in infammation and repair, includingan entire bestiary ocytokines (interleukins, intererons, and other immunomodulators), cell adhesionmolecules, enzymes, growth actors, and antibodies.11

Now, as in any good story, lets put the players in a setting; namely, the tissue.

In this idyllic tableau, theres a place or everything, and everything in its place. White cellsare in their barracks, in the vascular space. Blood vessel integrity is high, blood cells and plasma arein the bloodstream where they belong, mast cells keep it in their pants, lymphocytes and monocytesare garrisoned away in the bone marrow and lymphatic system, and the tissue is sterile (no bacteriaaround). issue pressure and pH are normal, and the molecular environment is stable. Everything iskind o boring, really.

Figure 2. Normal tissue in homeostasis.

MUSCLE TISSUE

OTHER TISSUE

WBCP

INTERSTITIAL SPACE

ROS, norm pH, norm Temp, norm Press, norm pO2MC

S


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Te stage is set. Lets introduce a confict, and watch as Hijinks Ensue. Tis is where the storyreally gets underway.

Looks like a war zone, doesnt it? Virtually any insult to the tissue can quicklyset o a goatrodeo like the one pictured here. A very early response to the insult is vasoconstriction, which rapidlydiminishes blood fow to the area, ollowed soon by vasodilation, which leads to tissue congestion,redness and heat.

Bacteria elaborate secreted toxins, or substances rom their cell walls such as lipopolysaccharide(LPS), which trigger an infammatory response. Some o these substances act as chemoattractants(CA) that draw WBCs to the action, as a silent alarm attracts SWA to a bank robbery. Bacteria and

their vile products can also attract the attention o antibodies. Binding o these immunoglobulinstobacterial suraces act as additional triggers to the complex infammatory cascade, including activationo the complementsystem (not pictured).11

Any kind o trauma, rom penetrating to crush to your basic sprain, disrupts tissue andvascular integrity, resulting in the exposure o tissue actors, the activation o platelets, and therelease o arachidonate and ree atty acids. Tese are converted by enzymes called cyclooxygenasesandlipoxygenasesto prostaglandins, leukotrienes and other eicosanoids, sending powerul signals to theimmune system, vascular structures, nerve endings, white blood cells, you name it. Some o these

Figure 3. Insult and early infammatory processes.


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signals are pro-infammatory, while others are anti-infammatory, a good point to keep in mind.18,19Among other things, pro-infammatory prostaglandins can attract white blood cells to the area andprooundly aect cellular unctions.11 All o these processes result in the elaboration o more cytokines,which urther drive and modulate the infammatory response,20 and induce many more white bloodcells to storm into the tissue,21 a process called demargination.11 White blood cells release digestive

enzymes and reactive oxygen species (ree radicals), all o which promote the degradation o damagedtissueand, alas, some undamaged tissue, too. Here we see a recurring theme: infammation is anaggressive, scorched-earth, shock-and-awe response to injury. Teres always collateral damage.21

Te unique stress imposed on skeletal muscle by eccentric exercise is not yet completelyunderstood. One model holds that eccentric contractions result in the overstretching o some sarcomeres,leading to actomyosin dissociation, direct damage to myolaments, tearing o the sarcoplasmic reticulum(SR, the muscle cell membrane) and connective tissue, and the release o calcium rom the SR.18,22 Tiscalcium release triggers the activation o calcium-dependent lipases, which eat membrane lipids andproduce arachidonate, and o calcium-dependent proteases (calpains) which indiscriminately chew upstructural proteins, ribosome-associated proteins, enzymes and the like.23 Damaged muscle probablyreleases some cytokines (myokines),24,25 and within a short time ater injury or strain the muscle

tissue is invaded by WBCs.18 Damaged muscle leaks the pigment myoglobin (Mb) and the enzymecreatine kinase (CK) into the serum, which is why the latter is the most commonly used laboratorymarker o rhabdomyolysis. Tis kind o myositis almost always precedes recovery and adaptationbut is it the causeo that adaptation? Most exercise scientists assume it is, but this belie has not goneunquestioned.26

In all o these infammatory scenarios, cytokines are released into the bloodstream and thetissue, driving the infammatory process and attracting the attention o various breeds o immunocytes.Lymphocytes, cells, killer cells, monocytes and their kin normally hang in the Rear with Gear, butnow they deploy to the Front with the Grunts. Te capillaries get leaky, and plasma fuid leaks intothe interstitium, causing the tissue to swell (edema). In some cases, this swelling can cause the tissuehydrostatic pressure to exceed capillary perusion pressure, resulting in a total loss o blood fow to theaected tissue (ischemia). Te resultant muscle compartment syndromemay lead to muscle necrosis(death) and permanent loss o unction. Tis phenomenon is well-described in the setting o severerhabdomyolysis and other orms o acute muscle injury.27

Te oregoing is a gross oversimplication o the infammatory response, but a serviceable oneor our purposes. Te picture that emerges is like what youd see downtown ater Jason Bourne blowsup a CIA oce and trashes a city block. Flashing lights and sirens everywhere. Local cops, sheris,state troopers, eds, spooks, reporters, EMS, re department, local pols, helicopters, SWA, gawkers,looters, barricades, smoke, broken glass, body parts, martial law, whos-in-charge-here, civil rightsviolations, and all the screaming and the running and the biting and the scratching. As the late, great

Lewis Tomas says in his indispensable book, Te Lives o a Cell,28

it is a shambles. Infammation is thebest rst step to getting back to normal that evolution has come up with so ar, and there is an awul,implacable, sledgehammer logic to it. But its also a Hot Mess, and, rom the perspective o the wholecity (i.e.,you, the suering athlete), its damn inconvenient.

By 12-24 hours, we nd that the situation is getting a bit more orderly. Gross or capillarybleeding has been dealt with by hemostasis and the ormation o platelet plugs and brin clots. WBCscontinue to eat up invading pathogens, oreign matter and cellular debris. Immunocytes have begun topopulate the area, and the complex signaling milieu (cytokines, eicosanoids, stress hormones) spurs the


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transormation o some o these cells to macrophages, who will presently climb out o the vasculatureto assume jurisdiction over the crisis. Like white blood cells, they engage in avid phagocytosis, butthey also release growth actors, an early step in the process o rebuilding and repair.18,20,21 But its stilla disaster area. Nerve endings are sensitized and screaming, tissue pH and oxygen tension may still bedecreased, tissue oxidative stress is high, and tissue temperature and hydrostatic pressure are still wayup. umor, dolor, rubor, calor.

Like all good stories, the tale o infammation needs a resolution. Later in infammation (about24 hours and out, to weeks or even months later), macrophages have supplanted the WBC shocktroops. Macrophages continue to mop up the area, gobbling die-hard pathogens and removing debris.Tey continue to release growth actors and participate in immunomodulation. Te cytokine milieuhas attracted stem cells and/or broblasts, to replace or reconstruct damaged tissue or ll in the craters

with scar. Growth actors trigger the activation o muscle satellite cells,18

which in turn participate in therepair, regeneration and adaptation o muscle bers. Vascular integrity returns, and tissue hydrostaticpressure, temperature, redox state, oxygenation, and pH gradually normalize. Depending on the initialinsult and extent o damageincluding damage induced by the infammatory response itselthishealing process can be brie or it can take a very long time indeed. And the potential outcomes o thisprocess (again, depending on the particulars) are legion, ranging rom complete healing to unctionalor dysunctional scarring to chronic infammation, abscess, tissue loss, anaphylaxis, septic shock,cardiovascular collapse, and even death.6,29,30

Figure 4. Developed infammatory response (12-24 hours).


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ANTI-INFLAMMATORY INTERVENTIONS & EXERCISE:BLINDING US WITH SCIENCE

Te one thing everybody knows about infammation, even your dog, is that it sucks. Yourinjured paw (or whatever) is hot, swollen, tender, and throbbing, and it doesnt work so well. Chasingthat squirrel just isnt as interesting as it was a minute ago. Infammation is natures way o saying:You just *cked up. Maybe you should stop and limp on home.

Because infammation is both ubiquitous and uncomortable, the relie o its more unpleasanteects has been a prime ocus o medicine or millennia. Compression, cooling, elevation and rest arevenerable approaches to relieving the discomort o infammation, reinorced in the late 19th centuryby the advent o modern anti-infammatory drugs. Te AAI guys seem to reserve their ire or ice andNSAIDs, so thats what well ocus on here.

NSAIDs Nonsteroidal anti-infammatory drugs have, as the name implies, a mechanism oaction that is distinct rom corticosteroids. Most steroid receptors are transcription actors that interactdirectly with DNA and eect gene expression. NSAIDs, by contrast, infuence the activity o cellularenzymes to suppress the release o signaling molecules.

Te NSAID class o drugs is airly broad, and includes salicylates like aspirin, propionicacid derivatives or proens such as ibuproen, ketoproen and naproxen, acetate derivatives likeindomethacin and ketoralac, and the coxibs, which includes celecoxib (Celebrex) and a plethorao withdrawn and discontinued medications. I we consider the mechanism o action, we can extend

Figure 5. Late infammation (24+ hours).


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the NSAID classication to the very common analgesic and antipyretic acetaminophen (ylenol),although doing so elicits much brow-urrowing among pharmacologists.31

Tese drugs exert their anti-infammatory eect by inhibiting cyclooxygenase (COX), a amilyo enzymes ound in most mammalian cells, including platelets and endothelium.32 We have seenthat arachidonic acid is released rom cell membranes early ater injury or insult. Cyclooxygenase

converts arachidonic acid into prostaglandins and other eicosanoid signaling molecules, which in turnsignal a wide range o pro-infammatory, anti-infammatory, vasoactive and cellular processes.33 COXis thought to come in 3 favors, or isoorms, although the role o COX3 is as yet unclear. ClassicalNSAIDs target both COX1 and COX2 indiscriminately, with the potential or side eects, particularlygastrointestinal problems. Renal and cardiovascular eects have also been described or NSAIDs, aswell as a number o drug interactions.34, 35, 36 Te coxib NSAIDs target only COX2. Tis reduces theinstance o GI side eects, but may increase the potential or other problems, including pro-thromboticcomplications. Much has been made o the side eects o NSAIDs and acetaminophen, which arevery realand oten overblown. Te human/clinical experience with these medicines encompassesliterally billions o doses every year and a low incidence o adverse events. In general they are well-tolerated when used as directed in OC doses.31 Acetaminophen, in particular, has an excellent saety

prole.37 Prophylactic use o these medications (i.e., beore injury or soreness occur) is probably to bediscouraged.38

Now, i you have any experience with NSAIDs, and/or you have meditated upon Figure 3above, you may have made the ollowing observation: NSAIDs can antagonize infammation, but theycannot and do not obliterate it. Although direct action o NSAIDs on targets beside COX have not beenruled out, their primary mechanism is clearly the suppression o prostaglandin synthesis. And whileprostaglandin production is certainly both upstream and important, weve seen that its neverthelessjust one component o this intricate biological clusteruck. For example, while NSAIDs can inhibitCOX production o prostaglandins, they have little or no eect on the production o leukotrienes bylipooxygenase,32 which is also an important pro-infammatory process. Such observations comportnicely with the common experience that an NSAID can relieve pain and swelling, but it doesnteliminatethem, nor does it cause our boo-boos to persist and never heal.

Even so, many have put orward the hypothesis that NSAIDs, by moderating the all-out urbanwarare response o infammation, might somehow delay the return to peace and prosperityi.e.,healing and adaptation. As noted earlier, the AAI crowd has seized on some studies that have addressedthis hypothesis. Tree o the most requently cited are studies by Novak, Mikkelson, and rappe,which we will consider now.

In 2009, Novak published a study o the eect o a COX2 inhibitor on skeletal musclehypertrophy in mice5. Since its tough to get mice to do their squats, the investigator used asynergistablation technique to induce muscular stress and adaptation. And what, you might ask, is synergistablation? Simple: you completely resect (i.e., cut out) the soleus and gastrocnemius muscles at surgery,

leaving only the plantaris intact to perorm the unction o the cal. Te idea is that, let all alone inthe mangled leg, those plantaris muscles will have to get big and strong. A COX2 inhibitor, NS-398,was administered to these hobbled mice intraperitonealy (i.e., they were shot up with the drug in theabdominal cavity) just beore the surgery (when they presumably were neither infamed nor sore, nothaving worked out yet) and every day thereater until tissue collection. Ater two weeks, the mice weresacriced, the plantaris muscles removed, and the tissue weighed and assayed. Te investigators reportblunted compensatory hypertrophy and muscle protein synthesis in NSAID-treated mice comparedto untreated mice, along with decreased macrophage accumulation and cell prolieration. Interestingly,


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the drug had no impact on expression o IGF-1 or phosphorylation o Akt, mOR, or p70S6k, whichappear to be criticalevents in growth actor signaling and hypertrophy.39,40

Te study is well-done as ar as it goes, and must be o considerable interest to those workingon the role o cyclooxygenase in tissue repair and healing. Te investigators concludecorrectly, in myopinionthat their results suggesta requirement o COX2 activity or skeletal muscle hypertrophy.

Tey wave their hands about exactly why this is so, and go on to issue concerns about the use oNSAIDs or exercise-induced muscle pain. One should certainly take these misgivings to heartione is a mutilated, quasi-amputated rodent who takes abdominal injections o experimental COX2inhibitors, even beore he gets sore, eats rodent chow, and hobbles around a cage ull o wood shavingsand mouse turds.Te scientic implications o this paper may be quite important. Te clinical andpractical implications o this paper are exactly zippo, because it demonstrates absolutely nothing aboutthe chronic eect o commercially available NSAIDs takenper osby intact human athletes engaged inprogrammed strength training.

Te Mikkelson paper is a small study, in which 8 young men were tted or microdialysisinusion o the vastus lateralis o each leg prior to the onset o the experiment. 4 One side (chosen atrandom) was inused with a placebo, while the other was inused with indomethacin. In other words,

these poor bros had a nonsteroidal delivered directly into their muscle by a catheter. And the medicationwas started beore exerciseagain, beore they had even evoked an infammatory response(aside rom thelocal infammatory response o having a oreign body rammed into their thigh). Muscle biopsies werecollected beore and eight days ater exercise. Satellite cells were assayed by immunohistochemistry.Te methods section does not tell us who counted the cells, whether the cells were counted by morethan one investigator or, i so, the magnitude o agreement between counters. Such methodologicalcontrols are crucial to a study like this, and their absence undermines our condence in the results.Be that as it may, the study reports a decreased number o muscle satellite cells in tissue biopsies romtreated muscles.

Tis is indeed interesting. Also interesting is that the number o infammatory cells was unaectedby the inusion. Tis nding raises pesky questions which I leave the reader to ponder. Te eect o theinusion on soreness was minimal at best, and there was no impact o NSAIDs on maximal isometricstrength immediately ater exercise. Finally, the investigators undertook no assay o the eect o theirstrange intramuscular inusions on adaptationno measurements o strength, power, unction orhypertrophy are reported. Even so, these authors, like those o the previous study, elt ree to issuegrave warnings about the use o NSAIDS. But again, the clinical relevance o this paper, i any, is entirelyspeculative.

Finally, the paper by rappe3looked at the eect o acetaminophen and ibuproen on muscleprotein synthesis in 24 men ater 10-14 sets o 10 eccentric knee extensor repetitions at 120% oconcentric 1RM. Lets set aside the ner points o the methodology and take the results at ace value.Muscle protein ractional synthetic rate (FSR) appeared to increase in all three groups (placebo,

acetaminophen, ibuproen), but only reached statisticalsignicance in the placebo group (who seemedto have a slightly lower FSR at baseline). Te clinicalsignicance o these increases is unclear at best,and the experiment did not identiy changes in particular proteins, which immediately raises the questiono whether the decreased FSR in the NSAID group was due to decreased production o infammatoryproteins in muscle(cytokines and other infammatory cell products)rather than decreased productiono structural proteins. Most importantly, the paper undertakes no assay o practical outcomethere isno data here on adaptation, strength, power, hypertrophy or any other training-associated measure.So once again, the practical implications o this work to trainees and coaches isbupkis. In act,
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rappe went on to conduct a clinical study showing that acetaminophen and ibuproen enhancedhypertrophy and strength gains in older adults.41

My orays into the literature reveal no shortage o basic science papers like these on the role othe infammatory system in healing and adaptation. Tey all have one thing in common: theyre basicscience papers, and we make assumptions about the translation o their ndings rom the lab bench to

the bar at our peril.A number o studies in humans have addressed more practical outcomes, including somesystematic reviews and meta-analyses. Tey are o varying clinical relevance, and most o them are notwhat I would call high quality. I have presented a selection o such papers rom the last twenty years inable 1 (appendix below). A cursory look at this table will reveal that the conclusions o these studiesare all over the map. In other words, or any study that says NSAIDs will stunt your growth, you cannd another that says they dont, or even that they help.

So much or a scientic consensus.

CRYOTHERAPY Te mechanism o cryotherapy as an anti-infammatory is not asstraightorward as that o the NSAIDs. Cryotherapy certainly seems to prolong the vasoconstriction

that occurs ater injury, delaying (but not ablating) the development o vasodilation and increasedcapillary permeability. Cryotherapy decreases the rate o biochemical reactions, blunts the elaborationo reactive oxygen species, and slows cell migration into the injured area. And o course cryotherapydecreases pain, probably through multiple pathways, including pain gating, suppression o substanceP and bradykinin release, and inhibition o pain ber transmission.

Teres no shortage o basic science data on cryotherapy, healing and hypertrophy.42,43,44 Again,some such studies could be odder or the anti-icing, anti-anti-infammation crowd. Others wouldsuggest that icing is salutary. But again, they all have one thing in common: theyre basic sciencestudies, and their relevance to actual training practice is unclear at best.

Clinical studies also abound, and as with NSAIDs, they are generally o middling-to-lowquality. But a meta-analysis o such studies, published in 2007 by Collins2 in the Emergency MedicineJournal, has drawn the attention oanti-icingexponents. Lets look at it.

Tis paper is not a true meta-analysis, and Im not sure it even meets the threshold or asystematic review. It seems rather to be an implicit literature review. Te author included both humanstudies and animal studies, which is a bit odd, and his review excluded studies o exercise-inducedinjury (see page 2 o the paper, Methods section).

Let me say that again: this review, a major data point cited by the AAI guys, excluded study oexercise-induced injury.

Te author identied our animal studies, all o which suggested that excessive or prolongedcooling is damaging. As is usually the case with animal studies, the clinical relevance o such data isunclear. Te author reports that, ater applying his exclusion criteria, he identied our human studies

worthy o his consideration. wo o these were randomized controlled clinical trials. One showed apositive eect o cryotherapy (cooling gel) and the other did not. wo systematic reviews o human datawere reviewed. One was inconclusive and the other suggested that ice may hasten return to participation.

So ar, so what? Except the author then concludes that there is insucient evidence to suggestthat cryotherapy improves clinical outcome in the management o sot tissue injuries.But the authors ownresultsshow that at least two papers meeting his inclusion criteria do suggest that cryotherapy has apositive clinical eect. Tis is an example o a requently-encountered phenomenon in the literature:conclusions that do not refect, or even contradict, the ndings o the study.
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Te study was criticizedin the same journal in which it was publishedor importantmethodological faws, including the omission o several studies that met the authors inclusion criteria,serious issues with the authors quality scores, a lack o structured assessment o the two includedsystematic reviews, subjective evaluation o included studies, and the inevitable heterogeneity oincorporating data rom both human and animal studies.

In short, Collins paper is not a particularly comprehensive, well-done, or revealing analysis othe available data. But thats not really the point I want to make right now, because, although this paperis brandished by the anti-icing crowd, its really just one study. (Less charitably, it may be considered animplicit review o cherry-picked studies. And an irrelevant one, at that.) And so, again, I have prepareda table presenting the results o many investigations o cryotherapy in humans over the last twentyyears (able 2, appen). And again, we nd that the literature ishow shall we put it?Discordant. Temuch ballyhooed scientic consensus on ice seems to be just as elusive as the one or NSAIDs.

O course, the inconsistency o clinical studies o anti-infammatory interventions (both iceand NSAIDs) shouldnt surprise us. Nor should the ailure o clinical studies to consistently bearout the concerns raised by basic science research on cryotherapy and nonsteroidals. Again, icing andnonsteroidals cant obliterate infammation, they can only inhibit certain parts o the infammatory

response. And their long-term clinical eect on healing and adaptation in people who train seriouslywill inevitably be conoundedand dilutedby diverse other actors: programming, diet, trainingcompliance, mood, motivation, pain threshold, genetics, training history, return to unction, natureand extent o injury, coaching, and a plethora o other variables that could never be denitivelycontrolled. Here we have an example o the critical distinction between physiologic outcome measuresand practical, patient-oriented outcome measures. Te real question isnt what happens to yoursatellite cells or your prostaglandins when you pop a pill or rub an ice pack on your throbbing knee.Te real question is how the use o anti-infammatory therapies aect your perormance and healthover a training career. We just dont have good data on that yet. And I wouldnt hold my breath waitingor it.

BACK TO THE ARGUMENT

So, with all o the oregoing in mind, lets circle around and get to cases. I you can rememberback that ar, I told you that the AAI guys seem to be making the ollowing arguments:

1. Infammation is the bodys naturaland therefore correctresponse to injury.Your body knows what its doing, and interering with the infammatory response isthereore ill-considered. Tis is the easiest argument to dispense with, because its justsillynot to mention selectively applied. For example, in the video it is made clear that iceand NSAIDs are bad because they interere with infammation, but compression, which

suppresses post-infammatory edema, is not. In any event, this argument proceeds rom theassumption that pristine natural processes are always optimal to the realization o humanends, which is clearly not the case; and that the human body is a perect machine, whichis just so much bullshit.

Heres a reality check: Mother Nature doesnt give a rats ass about your program,your WOD time, your 1RM bench press, or even your survival as an individual. 45Shedesigned you to make new primate gene replicators, and then croak. Lets not even talkabout the design o the low back, the exquisite suicidal sensitivity o neural and cardiac


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tissue to brie ischemia, or the deplorable shortcomings o cartilage. Infammation is notanideal adaptation just because its the natural response to insult. Pain, scarring, unctionalimpairment, tissue loss and cancer are also natural responses to insultand all can resultrom infammation. On the logic o the AAI crowd, analgesia, wound repair by primaryintention, tissue debridement, abscess drainage and tissue salvage are also bad ideas. I

thats what you really think, its unlikely were going to have a meeting o the minds. Godhelp you i you ever get anaphylaxis or appendicitis.

2. Without infammation, the body would never heal. You want to heal, dont you? Sowhy in the world would you intervene in the infammatory process? As we have seen,infammation is indeed the de acto initial stage o healing. But weve also seen that neitherice nor NSAIDs are capable o obliterating the infammatory response, and that there isno scientic consensus that anti-infammatory interventions retard wound healing, stuntadaptation, or delay return to unction to any practically relevant degree. Next!

3. Without infammation, muscles and other tissues cannot respond to training stress

with protein synthesis and hypertrophy. ereore, interering with training-inducedinfammation (eg, DOMS) will stunt your gains. Again, there is no consensus in theclinical literature, such as it is, to support this contention. Tere is data suggesting thatyou can screw up muscle protein synthesis or satellite cell activation or hypertrophy i youpump NSAIDs into mutilated mice or inuse them directly into the thigh muscles o brosdoing leg presses. Tats just not the same thing as regular human beings popping ibuproenor DOMS, and tells us nothing about the actual practical impact o such therapy onperormance, healing or adaptation.

4. e scientic literature overwhelmingly supports all o these contentions, and theissue is essentially settled. I think we all know by now that this simply isnt true.46,47 Despitedecades o work and dozens o clinical studies and systematic reviews, the issue remainsmost decidedlyunsettled.

STOP SPREADING MISINFLAMMATION

Point # 4 above deserves a little extra unpacking, because it raises two important issues.Te rst is this: in one sense, the anti-anti-infammatory guys might be right. I we had an

inallible window into ruth (which, by the way, would notbe called Science), we might very wellobserve that athletes who ice or pop ibuproens are slightlystunting their gains or slightlydelaying theirhealing. Or we might nd that the AAI guys are wrong, and that athletes who keep infammation on

a short leash actually heal a bitaster and/or get back under the bar alittlesooner.But either way, the AAI guys wouldnt be very right or verywrong. By which I mean that

i anti-infammatory interventions delay healing or blunt gains, they dont do it by very damn much.Conversely, i they aid return to unction or actually promote gains, again, its not by very damnmuch. Because the one thing we can take rom the available evidence is that the eect size o anti-infammatory medications on healing and adaptation is probably small. I NSAIDs or cryotherapy hada robust eect on healing or adaptation, I believe wed know it by now, because these issues have drawnconsiderable scientic attention, and large, robust eect sizes are easy to detect, easy to replicate, and


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hard to argue with. When it comes to healing and hypertrophy in the setting o anti-infammatorytreatment, were probably making a mountain out o a molehill.

From a practical perspective, this means that the critical deciding actor in whether to takeNSAIDs or cryotherapy or training-associated pain is whether they make you eel better. And thatsgood news, because when it comes to the science oyou, an N=1 observation is practical and relevant.

Its dicult i not impossible to tell whether NSAIDs reduceyourtime to heal. (Unless youre willingto infict exactly the same injury on yoursel at least twice. Please dont.) You cant tell whether icingyour aching hamstrings ater squats or a sprain changesyourmuscle protein synthesis or impactsyourstrength gains over time. (rust me. You cant.) But you can tell, to a reasonable and practical extent,whether cryotherapy or NSAIDs makeyou eel better whenyourehurting.

And i they make you eel better, and i youre hurting, and i you have no contraindications,then or heavens sake just use them. Lie is painul enough without suering through a bad case oDOMS or a jacked-up knee because some grad student in a lab cut up a premedicated mouse, orbecause some Big Name Coach has decreed that Icing Aint Natural. Use medicines as directed, use icejudiciously, use compression and elevation i they make you eel better. ake care o your pain and keepyour infammation shock troops under civilian control. Get some rest, maintain mobility, use good

judgment, and recover, so you can get on with your lie and ease back into your training.Te second and larger point raised by #4 above is the unortunate human propensity to seize

on a piece o scientic data that aligns with our own world view and take that as an indication thatScience is On Our Side. It demonstrates a complete misapprehension o the way science works, a lacko critical thinking, and a woeul ignorance o the act that even peer-reviewed scientic literature is,on average, about 95% shit by weight.

Tis has wider implications than one might imagine, because BroScience, like any other toxin,can extravasate into the wider culture, with untoward results. In particular, misinormation aboutNSAIDs has the potential to do real harm. Tese are inexpensive, well-tolerated and eective drugs,indispensable not only as anti-infammatories but as antipyretics, analgesics, and antithromboticagents.36,37 Teir use relieves untold suering and can even save lives. Its a Big Deal. Some o you maythink Ive been a bit contentious in this article. But the rst time one o my patients with chronicpain, acute trauma or coronary syndrome looks at me like Im a monster or giving her ylenol ,MotrinM or aspirin because Crystal Te Crosst Coach or Brendan the Bodybuilder told her theywere poisonwell. Ten Ill reallygo all Braveheart on somebody.

BroScience, like poverty and taxes, will always be with us, but we can suppress it by learningand teaching the proper approach to the literature, cool it down by avoiding rigid, categorical orpremature conclusions based on minimal data, and limit the damage and suering with judiciousdoses o both skepticism and curiosity toward all ideas, old and new.

So, to the AAI guys I say this: anti-infammatory therapy may slow adaptation and healing.Or it may not. I really just dont know. And neither do you. You certainly dont have enough good

scientic data or consensus backing you up to be as categorical in your opinions about ice and NSAIDsas you are, nor to withhold them rom athletes in pain. When and i convincing evidence demonstratesa meaningul negative eect o these interventions on our training, Ill be the rst to say you guys wereright. But or now, i the science tells us anything at all, its that the minimal practical eect o thistherapy on our healing and adaptation just doesnt justiy getting all infamedabout it.

Maybe you guys should take a chill pill.


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Jonathon Sullivan MD, PhD, FACEP, SSC is Attending Physician at Detroit Receiving HospitalEmergency Department, and Associate Director o the Cerebral Resuscitation Laboratory atWayne State University. His research is ocused on molecular mechanisms o brain injury andrepair ater cardiac arrest. He is a Starting Strength Coach, aKrav MagaPractitioner, and a 3d Dan

and certied instructor o ang Soo Do. Hes old and creaky, but hes still trying to get stronger,and buys his acetaminophen and aspirin by the crate. He can be contacted at GreySteel.org.

Dr. Sullivan has no commercial relationships with drug manuacturers, cryotherapy devicemanuactures, the Ice Fairy, or any other confict o interest to disclose. People with medical questionsor issues should see their doctor. Tis article is oered or educational purposes only, does not representthe opinions o the Detroit Medical Center or Wayne State University, and does not constitute medicaladvice or any specic patient, disease, injury or condition. So dont get any big ideas.

Te author wishes to thank amara Cohen, ever the agitator, or instigating this article, and MarilynFuller, whose comments and suggestions were, as usual, incisive and invaluable.

Illustrations were prepared by the author.

Starting Strength : Resources : Articles : Forums : Discuss Tis Article
http://startingstrength.com/http://aasgaardco.com/http://www.greysteel.org/http://startingstrength.com/http://startingstrength.com/index.php/site/resources/http://startingstrength.com/index.php/site/articleshttp://startingstrength.com/resources/forum/forum.phphttp://startingstrength.com/resources/forum/showthread.php?t=33520http://startingstrength.com/resources/forum/showthread.php?t=33520http://startingstrength.com/resources/forum/forum.phphttp://startingstrength.com/index.php/site/articleshttp://startingstrength.com/index.php/site/resources/http://startingstrength.com/http://www.greysteel.org/http://aasgaardco.com/http://startingstrength.com/


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APPENDIX: HUMAN STUDIES OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS,ACETAMINOPHEN AND CRYOTHERAPY.

A note on the tables: Papers were identied by multiple-iteration searches o relevant terms(cryotherapy, NSAIDs, DOMS, hypertrophy, sot tissue injury, etc), on Pub Med and Google

Scholar, ollowed by searches o related and reerenced articles. Basic science and animal studies werenot tabulated, nor were clearly irrelevant studies. I reviewed and included papers only i the ull textwas reasonably accessible and they were published in the last 20 years. ( I have a lie and a job andeverything.) I made no attempt to grade the quality o the studies. Te purpose o the exercise wasnot to conduct an exhaustive survey nor to rate the evidence, but rather to evaluate the claim that theliterature has reached a consensus on the use o NSAIDs and cryotherapy in the setting o traininginjury and soreness.

o this end, I include a summary column indicating whether the paper could be reasonablyinterpreted as supporting the use o the therapy. Tis was an entirely implicit assignment, basedon my own understanding o the paper, and made solely by me, without the use o any objectivedecision instrument or scoring system. Te assignment was guided based on the assumption

that the reader derives some relief from the therapy in question, unless the paper substantiallychallenged the palliative ecacy of that therapy. For example, i the paper oered strong evidenceo a robust maladaptive impact o the therapy, this would override the palliative assumption, andthe recommendation assigned would be No (N). I the paper oered no evidence o maladaptiveimpact, or evidence o a positive impact, the palliative assumption would take precedence, andthe recommendation assigned would be Yes (Y). I the paper oered weak evidence o adaptive ormaladaptive impact, the assignment would be Maybe (M), Maybe Yes (MY), or Maybe No (MN),depending on my own implicit evaluation o the paper and the reliability o its ndings. I the papersubstantially challenged the palliative ecacy o the the therapy and identied no other robust adaptivebenet, this overrode the palliative assumption, and the recommendation was No. (Te reader mayobviously have dierent ideas i she gets relie rom the therapy, but this assignment decision was madeto err on the side of the AAI argument).

Just be perectly clear: this is all very presumptuous on my part; this scoring was completelyimplicit, unscientic and loosey-goosey; and it was done onlyto highlight the diverse conclusions andlack o consensus in the literature, while making the tables more accessible to the truncated attentionspan o North American readers. Te reader is strongly advised to take all o this with a shaker o salt,and is invited to read the articles tabulated here and make his or her own conclusionsalways a GoodIdea.


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CITATIONSTUDY

TYPECONCLUSIONS

NSAIDs:

Y,N,M?

1990s

Various treatment

techniques on signs

and symptoms of de-

layed onset muscle

soreness. Gulick

DT et al.J Athlet rain1996;31(2):145-52.

RCT

The authors report no benet of an NSAID (oxapro-

zin), ice, stretching, high velocity concentric exercise,

or sublingual or topicalA. montanaextract on DOMSinduced by eccentric forearm contractions. In fact,

NSAID andA. montanaappeared to impede recov-ery. No long-term practically relevant outcomes were

assessed.

N

Anti-inammatory

doses of ibuprofen:effect on neutrophils

and exercise-in-

duced muscle injury.

Pizza FX, Cavendar

D, Stockard A. Int JSports Med1999; 20(2):98-102.

RPCT

Anti-inammatory doses of ibuprofen reduced CK

activity but not the neutrophil response or other in-

direct markers of muscle injury during recovery from

eccentric arm exercise. There was no impact on iso-

metric strength or soreness. No long-term variables

were studied.

Y

2000s

Effect of ketoprofen

on muscle function

and sEMG activ-

ity after eccentricexercise. Sayers SP,

Knight CA, Clarkson

PM, et al.Med Sci SportsExerc2001; 33(5): 702-10.

RTKetoprofen had no impact on reducing post-exerciseincreases in myoelectric activity. It improved sore-

ness compared with placebo.

Y

Managing delayed-

onset muscle sore-

ness: Lack of effect

of selected oral

systemic analgesis.

Barlas et al, PhysMedRe-

habil2000;81:966-72.

DBPCRT

No benecial effect of aspirin, codeine (?) or

paracetamol in reducing DOMS induced in nondomi-

nant elbow exors by repeated eccentric contrac-

tions. No study of impact on adaptation or healing.

N

Nonsteroidal anti-

inammatory therapy

after eccentric exer-

cise in healthy older

individuals. Baldwin

AC.J Gerontol Med Sci2001;56A(8)M510-13.

DBCT

Naproxen sodium decreased muscle injury, strength

loss and soreness after eccentric knee extensions in

15 elderly (aged approx 60 years) men and women.

The authors conclude that this therapy may be

benecial in older patients during the early stages of

increased physical activity. No assays of long-term

adaptation were undertaken.

Y

TABLE 1: HUMAN STUDIES OF NSAIDs AND RELATED DRUGS FOR SOFT-TISSUE INJURIES AND

MUSCLE SORENESS. DB=double blind. R=randomized. PC=placebo-controlled. RCT=randomized

controlled trial. CxT= crossover trial. MA = meta-analysis. For information on the recommendation

assignments in the right-hand column, see the Appendix Notes.
http://startingstrength.com/http://aasgaardco.com/http://startingstrength.com/articles/bulgarian_training_moser.pdfhttp://startingstrength.com/articles/bulgarian_training_moser.pdfhttp://startingstrength.com/articles/bulgarian_training_moser.pdfhttp://startingstrength.com/articles/bulgarian_training_moser.pdfhttp://startingstrength.com/articles/bulgarian_training_moser.pdfhttp://startingstrength.com/articles/bulgarian_training_moser.pdfhttp://startingstrength.com/articles/bulgarian_training_moser.pdfhttp://startingstrength.com/articles/bulgarian_training_moser.pdfhttp://aasgaardco.com/http://startingstrength.com/


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CITATIONSTUDY

TYPECONCLUSIONS

NSAIDs:

Y,N,M?

The effects of ibu-

profen on delayed

onset muscle sore-

ness and muscular

performance aftereccentric exercise.

Tokmakidis SP,et al.

JSCR2003;17(1):53-59.

RPCT

Nineteen subjects performed eccentric leg curls

and got sore hamstrings. They were randomized to

ibuprofen or placebo. The ibuprofen group had less

soreness and lower CK release and peripheral WBC

count, but no differences in maximal strength, verticaljump performance, or knee ROM. The results of this

study reveal that intake of ibuprofen can decrease

muscle soreness induced after eccentric exercise but

cannot assist in restoring muscle function.

Y

2010s

The effect of nonste-

roidal anti-inamma-

tory drug administra-

tion on acute-phasefracture-healing:

a review. Kurmis et

al.J Bone Joint Surg2012;94:815-23.

SR

The authors conducted a review of 316 relevant

studies. The available clinical evidence does not

substantiate the concern raised by animal studies,

and suggests that NSAIDs are safe and effective for

pain control after fracture, without an adverse effect

on fracture healing. Although increasing evidence

from animal studies suggests that COX-2 inhibitionsuppresses early fracture healing, in vivo studies

involving human subjects have not substantiated

this concern.balance of evidence in the available

literature appears to suggest thatNSAID(s are)

safe and effective supplement to post-fracture pain

control, withoutincreased risk ofdisrupted heal-

ing.

Y

Effect of ibuprofen

and acetaminophenon post-exercise

muscle protein syn-

thesis. Trappe et al.

Am J Phyiol EndocrinolMetab 2001; 282:E551-6.

RPCT

24 males received a maximal doseof medicine orplacebo after 10 eccentric reps at 120% 1RM.

Postexercise fractional synthesis rate appeared to be

increased in all three groups, but reached statistical

signicance only in the placebo group. Differenceswere of unclear practical signicance. Muscle break-

down was not effected by any regimen. Te authorsdid not investigate which proteins were aected(i.e.,muscle protein, inammatory protein, etc), and no

functional assessments (strength, pain control, time

to return to function etc) were undertaken. The long-

term inuence of this acute response after resistance

exercise for individuals who chronically consume

these (or similar) drugs cannot be determined from

this study.

MN

Inuence of acet-

aminophen and

ibuprofen on skeletalmuscle adaptations

to resistance exer-

cise in older adults.

Trappe et al.Am JPhysiol Regul Integr CompPhysiol2011;300:R655-62.

RDBPCT

Drug consumption unexpectedly increased musclevolume and muscle strength to a greater extent than

placebo. No change in muscle protein content, water

content or myosin heavy chain distributions were ob-

served on muscle biopsy. Medication did not inhibit,

and in fact appeared to enhance, muscle hypertrophyand strength gains in older adults.

Y


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Misinammation


CITATIONSTUDY

TYPECONCLUSIONS

NSAIDs:

Y,N,M?

Ingestion of low-

dose ibuprofen

following resistance

exercise in post-

menopausal women.Candow et al.J Ca-chexia Sarcopenia Muscle2012 DOI 10.1007/

s13539-012-0077-3

RCT

Postmenopausal women demonstrated no signicant

difference in strength gain or lean body mass wheth-er they took ibuprofen or placebo after resistance

exercise. Analgesic efcacy was not assessed.

M

The effect of nonste-

roidal anti-inamma-

tory drugs on tissue

healing. Chen and

Dragoo. Knee Surg Sportsraumatol Arthrosc2012;

DOI 10.1007/s00167-012-2095-2

SR

Short-term, low-dose use of NSAIDs and

COX-2 inhibitors does not appear to have a detri-

mental effect following soft tissue injury, but is inhibi-

tory in cases involving bony healing.Clinically, the

prudent use of anti-inammatory medications follow-

ing sports medicine injuries and surgeries appears

to be a reasonable option in clinical practice unlessbone healing is required.

MY

The effects of ibu-

profen on muscle hy-

pertrophy, strength,

and soreness during

resistance train-

ing. Krentz et al.

Appl Physiol Nutr Metab2008;33:470-75.

RDBPCT

Ibuprofen did not impair muscle hypertrophy or

strength in young men and women after resistance

training.

Y

A COX-2 inhibitor

reduces muscle

soreness, but doesnot inuence re-

covery and adapta-

tion after eccentric

exercise. Paulsen et

al. Scan J Med Sci Sports2010;20:e195-207.

DBPCT

Subjects who took celecoxib had less sorenessthan the placebo group, but no difference in serum

creatine kinase levels or tissue levels of radiolabled

leukocytes (WBCs), monocytes, macrophages or

satellite cells.

Y

Inuence of acet-

aminophen and

ibuprofen on in

vivo patellar tendon

adaptations to kneeextensor resistance

exercise in older

adults. Carroll CC

et al.J Appl Physiol2011;111:508-15.

RDBPCT

Patellar tendon anatomical and biophysical proper-

ties were assessed with MRI and ultrasound coupled

with force measurements before and after training in

older adults training with knee extensor exercises.

Patellar cross-sectional area (CSA) was unchanged

in the placebo and ibuprofen groups and increased inthe acetaminophen group. However, tendon defor-

mation and strain, while unaffected except in the

placebo and ibuprofen groups, increased in the ac-

etaminophen group. No long-term practical outcome

measures were assessed.

MY (Ibu-

prof)

MN

(Acet)


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Misinammation


CITATIONSTUDY

TYPECONCLUSIONS

NSAIDs:

Y,N,M?

Nonsteroidal anti-

inammatory drug

or glucosamine

reduced pain and

improved musclestrength with resis-

tance training in a

randomized con-

trolled trial of knee

osteoarthritis pa-

tients. Peterson SG et

al.Arch Phys Med Rehabil2011;92:1185-93.

DBRCT

36 men and women with knee osteoarthritis, 50-70

yo, were randomly assigned to ibuprofen, glucos-

amine or placebo during 12 weeks of quad train-

ing. The authors report that In patients with kneeOA, NSAID or glucosamine administration during a

12-week strength-training programdid not improve

muscle mass gain, but improved maximal muscle

strength gain in comparison with treatment with

placebo. However, we do not nd that the benets

are large enough to justify taking NSAIDs or glucos-

amine.

MY


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Misinammation


CITATIONSTUDY

TYPE

CONCLUSIONS

LOCAL

CRYOTX:

Y,N,M?1990s

Various treatment

techniques on signs

and symptoms of de-

layed onset muscle

soreness. Gulick

DT et al.J Athlet rain1996;31(2):145-52.

RCT

The authors report no benet of an NSAID (oxapro-

zin), ice, stretching, high velocity concentric exer-

cise, or sublingual or topicalA. montanaextract onDOMS induced by eccentric forearm contractions.

No long-term practically relevant outcomes were

assessed.

N

Effect of cryotherapy

on muscle soreness

and strength follow-

ing eccentric exer-cise. Paddon-Jones

DJ, Quigly BM. Int JSports Med1997; 18(8):588-93.

CT

After performing 64 eccentric elbow exions with

each arm, 8 resistance trained males did ve 20

minute immersions in a cold-water bath (1 deg C)

interspersed with 60 minute rests. No signicant dif-ference between cryo-treated or control arms were

noted for soreness, limb volume, isometric torque,

isokinetic torque, or any other variable. No long-term

assay of adaptive response was undertaken.

MN

2000s

The use of ice in the

treatment of acute

soft-tissue injury: a

systematic review of

randomized con-

trolled trials. Bleakley

et al.Am J Sports Med2004; 32(1)251-61

MA

Analysis of twenty-two studies meeting inclusion

criteria yielded marginal evidence that ice plus

exercise was most effective after acute ankle injury

or surgery. Ice appeared to add little to compression,

but this nding was restricted to hospitalized (post-

operative) patients. Data on ice after closed soft-

tissue injury was sparse. Many more high-qualitytrials are needed.

MY

Ice-water immersion

and delayed-onset

muscle soreness:

a randomised con-

trolled trial. Sellwood

et al. Br J Sports Med2007;41:392-7.

DBPCRT

The protocol ofice-water immersion*used in thisstudy was innefectual in minimising markers of

DOMS in untrained individuals.This study challeng-

es the use of this intervention as a recovery strategy

by athletes. Te study did not address local cryotherapyfor injury or DOMS.

MN*

Efcacy of cold gel

for soft tissue inju-

ries: a prospective

randomized double-

blinded trial.Airak-senen, et al.Am J SportsMed2003;31(5)680-4.

DBPCRT

Cold gel therapy was safe and effective at reducing

pain, compared to placebo, when applied to patients

with sports-related soft-tissue injuries.

Y

Does cryotherapy

improve outcomes

with soft tissue

injury? Hubbard and

Denegar.J Athlet rain-ing2004;39(3):278-79.

SR

A systematic review of 22 RCTs, all of relatively low

quality, suggested that cryotherapy was effective

in reducing pain. Its effectiveness relative to other

therapies and its impact on patient-oriented out-

comes remains somewhat unclear.

MY

TABLE 2: HUMAN STUDIES OF CRYOTHERAPY. DB=double blind. R=randomized. PC=placebo-

controlled. RCT=randomized controlled trial. CxT= crossover trial. MA = meta-analysis.For informa-

tion on the recommendation assignments in the right-hand column, see the Appendix Notes.


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Misinammation


CITATIONSTUDY

TYPECONCLUSIONS

LOCAL

CRYOTX:

Y,N,M?

Ice therapy: how

good is the evi-

dence? MacAuley DC.

Int J Sports Med2001;22(5):379-84.

SR

This systematic review suggests that intermittent

application of ice is effective, but notes decreased

motor function and reex activity after ice is applied.

M

The efccy of ice

massage in the treat-

ment of exercise-in-

duced muscle dam-

age. Howatson G, et

al. Scand J. Med Sci Sports2005;15:416-422.

PCCT

Compared to a sham ultrasound therapy (the

placebo) ice demonstrated no difference in reduc-

tion of discomfort, indirect serum markers of muscle

damage (CK, Mb), or enhancement of function. No

long-term outcome variables were assessed.

MY

Is ice right? Does

cryotherapy improve

outcome for acute

soft tissue injury.Collins NC, Emerg MedJournal2008;25:65-68.

SR,

sorta.

This implicit review of both human and animal stud-

ies concludedcontrary to its own ndingsthat the

literature contains insufcient evidence to suggest

that cryotherapy is useful. See detailed analysis in

the main body of the article.

N

The effects of vari-

ous therapeutic mea-

sures on shoulder

strength and muscle

soreness after base-

ball pitching. Yanagi-

sawa O, Miyanaga Y,

Shiraki H et al.J SportsMed Phys Fitness2003;43(2):189-201.

RCT

Participants were randomized to one of 4 groups af-

ter throwing 98 pitches: ice (IT), light exercise (LSE),

ice + light exercise (ILSE), and control (CON). The

investigators report that both IT and ILSE had a

positive effect, and that ILSE (ice + light exercise)

was the optimal therapy.

Y

2010s

A comparison of

topical menthol to

ice on pain, evoked

tetanic and voluntary

force during delayed

onset muscle sore-

ness. Johar et al.

Int J Sports Phys Ter2012;7(3):314-22.

RT

A topical menthol preparation displayed better an-

algesia and permitted greater force generation than

ice. No placebo (non-treatment) group was incorpo-

rated into the study, so we know nothing about how

these two therapies compared with no therapy at all.

Investigators were blinded, but obviously patients

could not be. No long-term end-points were studied.

M


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Misinammation


REFERENCES

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