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{{DISPLAYTITLE: NSAIDs (Ibuprofen, Naproxen, Aspirin) and Acetaminophen/Paracetamol for runners, impairs healing and interferes with hydration}}
[[File:Extra Strength Tylenol and Tylenol PM.jpg|right|thumb|200px|Acetaminophen (brand names Tylenol, aspirin-free Anacin, Excedrin, and numerous cold medicines)]]
NSAIDs are generally unhelpful for runners, masking the symptoms while impairing healing, interfering with hydration and can be life threatening. Risks include kidney failure, heart attacks, strokes, intestinal damage, and liver failure. The most common NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) are Ibuprofen (Advil, Motrin), Naproxen (Aleve, Naprosyn), and Aspirin. They work by inhibiting a particular enzyme ([http://en.wikipedia.org/wiki/Cyclooxygenase Cyclooxygenase]) which reduces pain, fever and inflammation. Ibuprofen use is so common among runners that it is sometimes called "Vitamin I"<ref name="VitaminI"/>, with one study finding about 60% of runners using NSAIDs during training<ref name="JoslinLloyd2013"/>. This is unsurprising given the estimates of injury rates in runners varying between 20% and 80%<ref name="van GentvanGent-2007"/>. This article also covers Acetaminophen (also called Paracetamol), though it's not technically an NSAID. ==NSAIDs and Healing==
The inflammation response of our bodies is a key part of the healing process. Using NSAIDs to reduce the inflammation has been shown to impair healing in different tissue types:
* '''Muscles'''<ref name="MuscleTrappe"/>. A 2001 study showed that Ibuprofen and Acetaminophen reduce [[Muscle|muscle]] growth after eccentric exercise. Another study<ref name="muscle"/> on muscle damage and NSAIDs showed impaired recovery in the early stages of healing. There was some increased [[Protein]] synthesis with NSAIDs in latter stages of healing, but the muscles were still weaker 28 days after injury. Other studies<ref name="muscle2"/><ref name="muscle3"/> have shown that four days after injury, NSAIDs resulted in very little muscle regeneration compared with no drugs.
* '''Cartilage. ''' NSAIDs have been shown<ref name="CartilageRabbit"/> to impair the healing of bone and cartilage in rabbits.
* '''Bone fractures.''' Tests on rats shows that a NSAID (Celecoxib) in the early stages of bone healing impaired healing, producing a weaker repair.<ref name="bone"/> A study <ref name="BoneLaurence "/> in 2004 declared " Nonsteroidal anti-inflammatory drugs continue to be prescribed as analgesics for patients with healing fractures even though these drugs diminish bone formation, healing, and remodeling".
While there is extensive experimental evidence for NSAIDs impairing healing, there are also some studies that show no change with NSAID use, and a few that indicated improved healing. For instance, one study<ref name="LigamentImprovement"/> showed that using an NSAID for 6 days after injury resulted in a 42% increased ligament strength at day 14, though there was no change by day 21. Another study<ref name="LigamentUninjuredImprovement"/> showed that an NSAID did not change ligament healing, but did improve the strength of the uninjured ligaments. However, my reading indicates that the preponderance of evidence shows NSAIDs impair healing.
If NSAIDs are bad for healing, should we treat with ice? So far I have found no definitive studies, but ice has a different mechanism of action from NSAIDs. By cooling the tissues, ice temporarily reduces swelling, thereby flushing the wound. If applied for a longer period of time, ice will produce a periodic increase in blood supply that creates a further flushing effect. I have found that ice can produce dramatic improvements in healing speed. See [[Cryotherapy - Ice for Healing]] for more details. There is no evidence that ice reduces any of the inflammation processes.
=Turmeric as an NSAID=
Turmeric is an anti-inflammatory<ref name="Sahebkar2014"/><ref name="PanahiSahebkar2012"/> that is often considered an alternative to more common NSAIDs. Turmeric has been medicinally used for 1000s of years<ref name="Benzie-"/> and even in large doses turmeric shows low toxicity<ref name="Hsu-2007"/><ref name="Cheng-2001"/><ref name="Chandran-2012"/><ref name="GanigerMalleshappa2007"/> with only a few studies finding nausea and diarrhea<ref name="Hsu-2007"/> or abdominal pain<ref name="Kuptniratsaikul-2014"/>. Turmeric has poor bioavailability<ref name="Anand-2010"/><ref name="AnandKunnumakkara2007"/>, but versions with improved bioavailability are being developed such as Flexofytol<ref name="AppelboomMaes2014"/> or Meriva<ref name="Drobnic-2014"/>. Like other NSAIDs, Turmeric is an effective pain reliever (analgesic)<ref name="Agarwal-2011"/><ref name="Panahi-2014"/><ref name="Kuptniratsaikul-2009"/><ref name="Zhu-2014"/> and it may be effective in treating [[Delayed Onset Muscle Soreness]]<ref name="Nicol-2015"/><ref name="Drobnic-2014"/><ref name="McFarlinVenable2016"/><ref name="TanabeMaeda2015"/><ref name="Davis-2007"/><ref name="Kawanishi-2013"/>. Studies of Turmeric and turmeric derivatives as treatments for osteoarthritis<ref name="Henrotin-2014"/><ref name="Kuptniratsaikul-2014"/> and rheumatoid arthritis<ref name="Chandran-2012"/> show promising results. Digestive problems, a common side effect of NSAIDs, are believed to be because most NSAIDs inhibit both COX-1 and COX-2 enzymes<ref name="Bertolini-2002"/>. COX-2 is predominantly responsible for inflammation where COX-1 helps maintain the digestive system<ref name="Hawkey-2001"/>. Selectively inhibiting just COX-2 may have the benefits of NSAIDS without the digestive issues<ref name="FutakiTakahashi1994"/><ref name="Hawkey1999"/><ref name="Hawkey-2001"/>. Studies have found that Turmeric is a COX-2 inhibitor<ref name="Moini Zanjani-2014"/><ref name="Moriyuki-2010"/><ref name="Ireson-2001"/><ref name="Lev-Ari-2006"/><ref name="Plummer-1999"/>, and turmeric preferentially inhibits COX-2 over COX-1<ref name="RamsewakDeWitt2000"/>. Turmeric has ~36% COX-1 inhibition and ~77% COX-2 inhibition, while aspirin, ibuprofen and naproxen had 41-52% COX-1 inhibition and ~30-40% COX-2 inhibition<ref name="RamsewakDeWitt2000"/>. Diferuloylmethane (Curcumin) is the main active ingredient in turmeric<ref name="Anand-2010"/><ref name="Henrotin-2010"/>, though it also includes monodemethoxycurcumin (curcumin II) and bisdemethoxycurcumin (curcumin III)<ref name="RamsewakDeWitt2000"/>. Concentrations of Diferuloylmethane typically peak 1-2 hours after consumption and decline within 12 hours<ref name="Cheng-2001"/><ref name="Agarwal-2011"/>.
=NSAIDs and Acute kidney failure=
Kidney failure while running is extremely rare, and seems to require multiple factors to come together. Looking at the [http://en.wikipedia.org/wiki/Comrades_Marathon Comrades Marathon], a 90 Km/56 Mile ultramarathon in South Africa, there have only been 19 cases of kidney failure between 1969 and 1986, it even though thousands of people participate each year<ref name="rhabdo1"/>. The following are considered factors in acute kidney failure related to running.
* The most common NSAIDs (Ibuprofen, Acetaminophen (Paracetamol), and Aspirin) are unlikely to help with DOMS.
* There is some evidence that Naproxen may be more effective than the common NSAIDs. There is not enough evidence to reach a conclusion on Diclofenac, Codeine, Rofecoxib, Ketoprofen, or Bromelain.
* There is also some evidence that Turmeric may help with DOMS.
* If an NSAID is taken for DOMS, it should probably be taken immediately after the damaging exercise rather than waiting until the soreness develops.
* It seems likely that taking an NSAID for DOMS will reduce the muscular growth that would normally occur as part of the recovery.** In one study, rabbits treated with flurbiprofen after DOMS inducing exercise regained more strength after 3-7 days, but between days 7 and 28 days the treated rabbits became weaker while the controls became stronger<ref name="Mishra-1995"/>. This is only one study, and on animals, but it is rather troubling as none of the human studies look at the results over this time period.
==A Summary of the Research on NSAIDs and DOMS==
The table below summarizes the research I located on the effect of NSAIDs on DOMS in humans. I've only considered the primary DOMS markers of soreness (pain) and weakness, rather than including things like blood enzymes. For each NSAID I've shown how many studies show an improvement and how many studies show no effect.
| 1xNo Effect<ref name="Stone-2002"/>
|
|-
| Turmeric
| 2xImproved<ref name="Nicol-2015"/><ref name="Drobnic-2014"/>
2xNo Effect<ref name="McFarlinVenable2016"/><ref name="TanabeMaeda2015"/>
| 2xImproved<ref name="TanabeMaeda2015"/><ref name="Davis-2007"/>
|}
=NSAIDs and Intestinal Damage=
=References=
<references>
<ref name="Hawkey1999">CJ Hawkey, COX-2 inhibitors, The Lancet, volume 353, issue 9149, 1999, pages 307–314, ISSN [http://www.worldcat.org/issn/01406736 01406736], doi [http://dx.doi.org/10.1016/S0140-6736(98)12154-2 10.1016/S0140-6736(98)12154-2]</ref>
<ref name="FutakiTakahashi1994">N. Futaki, S. Takahashi, M. Yokoyama, I. Arai, S. Higuchi, S. Otomo, NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity in vitro, Prostaglandins, volume 47, issue 1, 1994, pages 55–59, ISSN [http://www.worldcat.org/issn/00906980 00906980], doi [http://dx.doi.org/10.1016/0090-6980(94)90074-4 10.1016/0090-6980(94)90074-4]</ref>
<ref name="Bertolini-2002">A. Bertolini, A. Ottani, M. Sandrini, Selective COX-2 inhibitors and dual acting anti-inflammatory drugs: critical remarks., Curr Med Chem, volume 9, issue 10, pages 1033-43, May 2002, PMID [http://www.ncbi.nlm.nih.gov/pubmed/12733982 12733982]</ref>
<ref name="Zhu-2014">X. Zhu, Q. Li, R. Chang, D. Yang, Z. Song, Q. Guo, C. Huang, Curcumin alleviates neuropathic pain by inhibiting p300/CBP histone acetyltransferase activity-regulated expression of BDNF and cox-2 in a rat model., PLoS One, volume 9, issue 3, pages e91303, 2014, doi [http://dx.doi.org/10.1371/journal.pone.0091303 10.1371/journal.pone.0091303], PMID [http://www.ncbi.nlm.nih.gov/pubmed/24603592 24603592]</ref>
<ref name="Plummer-1999">SM. Plummer, KA. Holloway, MM. Manson, RJ. Munks, A. Kaptein, S. Farrow, L. Howells, Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex., Oncogene, volume 18, issue 44, pages 6013-20, Oct 1999, doi [http://dx.doi.org/10.1038/sj.onc.1202980 10.1038/sj.onc.1202980], PMID [http://www.ncbi.nlm.nih.gov/pubmed/10557090 10557090]</ref>
<ref name="Lev-Ari-2006">S. Lev-Ari, A. Starr, A. Vexler, V. Karaush, V. Loew, J. Greif, E. Fenig, D. Aderka, R. Ben-Yosef, Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is associated with increased apoptosis, down-regulation of COX-2 and EGFR and inhibition of Erk1/2 activity., Anticancer Res, volume 26, issue 6B, pages 4423-30, PMID [http://www.ncbi.nlm.nih.gov/pubmed/17201164 17201164]</ref>
<ref name="RamsewakDeWitt2000">R.S. Ramsewak, D.L. DeWitt, M.G. Nair, Cytotoxicity, antioxidant and anti-inflammatory activities of Curcumins I–III from Curcuma longa, Phytomedicine, volume 7, issue 4, 2000, pages 303–308, ISSN [http://www.worldcat.org/issn/09447113 09447113], doi [http://dx.doi.org/10.1016/S0944-7113(00)80048-3 10.1016/S0944-7113(00)80048-3]</ref>
<ref name="Ireson-2001">C. Ireson, S. Orr, DJ. Jones, R. Verschoyle, CK. Lim, JL. Luo, L. Howells, S. Plummer, R. Jukes, Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production., Cancer Res, volume 61, issue 3, pages 1058-64, Feb 2001, PMID [http://www.ncbi.nlm.nih.gov/pubmed/11221833 11221833]</ref>
<ref name="Moriyuki-2010">K. Moriyuki, F. Sekiguchi, K. Matsubara, H. Nishikawa, A. Kawabata, Curcumin Inhibits the proteinase-activated receptor-2-triggered prostaglandin E2 production by suppressing cyclooxygenase-2 upregulation and Akt-dependent activation of nuclear factor-κB in human lung epithelial cells., J Pharmacol Sci, volume 114, issue 2, pages 225-9, 2010, PMID [http://www.ncbi.nlm.nih.gov/pubmed/20838026 20838026]</ref>
<ref name="Kawanishi-2013">N. Kawanishi, K. Kato, M. Takahashi, T. Mizokami, Y. Otsuka, A. Imaizumi, D. Shiva, H. Yano, K. Suzuki, Curcumin attenuates oxidative stress following downhill running-induced muscle damage., Biochem Biophys Res Commun, volume 441, issue 3, pages 573-8, Nov 2013, doi [http://dx.doi.org/10.1016/j.bbrc.2013.10.119 10.1016/j.bbrc.2013.10.119], PMID [http://www.ncbi.nlm.nih.gov/pubmed/24184481 24184481]</ref>
<ref name="Davis-2007">JM. Davis, EA. Murphy, MD. Carmichael, MR. Zielinski, CM. Groschwitz, AS. Brown, JD. Gangemi, A. Ghaffar, EP. Mayer, Curcumin effects on inflammation and performance recovery following eccentric exercise-induced muscle damage., Am J Physiol Regul Integr Comp Physiol, volume 292, issue 6, pages R2168-73, Jun 2007, doi [http://dx.doi.org/10.1152/ajpregu.00858.2006 10.1152/ajpregu.00858.2006], PMID [http://www.ncbi.nlm.nih.gov/pubmed/17332159 17332159]</ref>
<ref name="TanabeMaeda2015">Yoko Tanabe, Seiji Maeda, Nobuhiko Akazawa, Asako Zempo-Miyaki, Youngju Choi, Song-Gyu Ra, Atsushi Imaizumi, Yoshihiko Otsuka, Kazunori Nosaka, Attenuation of indirect markers of eccentric exercise-induced muscle damage by curcumin, European Journal of Applied Physiology, volume 115, issue 9, 2015, pages 1949–1957, ISSN [http://www.worldcat.org/issn/1439-6319 1439-6319], doi [http://dx.doi.org/10.1007/s00421-015-3170-4 10.1007/s00421-015-3170-4]</ref>
<ref name="McFarlinVenable2016">Brian K. McFarlin, Adam S. Venable, Andrea L. Henning, Jill N. Best Sampson, Kathryn Pennel, Jakob L. Vingren, David W. Hill, Reduced Inflammatory and Muscle Damage Biomarkers following Oral Supplementation with Bioavailable Curcumin, BBA Clinical, 2016, ISSN [http://www.worldcat.org/issn/22146474 22146474], doi [http://dx.doi.org/10.1016/j.bbacli.2016.02.003 10.1016/j.bbacli.2016.02.003]</ref>
<ref name="Kuptniratsaikul-2014">V. Kuptniratsaikul, P. Dajpratham, W. Taechaarpornkul, M. Buntragulpoontawee, P. Lukkanapichonchut, C. Chootip, J. Saengsuwan, K. Tantayakom, S. Laongpech, Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study., Clin Interv Aging, volume 9, pages 451-8, 2014, doi [http://dx.doi.org/10.2147/CIA.S58535 10.2147/CIA.S58535], PMID [http://www.ncbi.nlm.nih.gov/pubmed/24672232 24672232]</ref>
<ref name="Drobnic-2014">F. Drobnic, J. Riera, G. Appendino, S. Togni, F. Franceschi, X. Valle, A. Pons, J. Tur, Reduction of delayed onset muscle soreness by a novel curcumin delivery system (Meriva): a randomised, placebo-controlled trial., J Int Soc Sports Nutr, volume 11, pages 31, 2014, doi [http://dx.doi.org/10.1186/1550-2783-11-31 10.1186/1550-2783-11-31], PMID [http://www.ncbi.nlm.nih.gov/pubmed/24982601 24982601]</ref>
<ref name="Nicol-2015">LM. Nicol, DS. Rowlands, R. Fazakerly, J. Kellett, Curcumin supplementation likely attenuates delayed onset muscle soreness (DOMS)., Eur J Appl Physiol, volume 115, issue 8, pages 1769-77, Aug 2015, doi [http://dx.doi.org/10.1007/s00421-015-3152-6 10.1007/s00421-015-3152-6], PMID [http://www.ncbi.nlm.nih.gov/pubmed/25795285 25795285]</ref>
<ref name="Henrotin-2014">Y. Henrotin, M. Gharbi, Y. Dierckxsens, F. Priem, M. Marty, L. Seidel, A. Albert, E. Heuse, V. Bonnet, Decrease of a specific biomarker of collagen degradation in osteoarthritis, Coll2-1, by treatment with highly bioavailable curcumin during an exploratory clinical trial., BMC Complement Altern Med, volume 14, pages 159, 2014, doi [http://dx.doi.org/10.1186/1472-6882-14-159 10.1186/1472-6882-14-159], PMID [http://www.ncbi.nlm.nih.gov/pubmed/24886572 24886572]</ref>
<ref name="Chandran-2012">B. Chandran, A. Goel, A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis., Phytother Res, volume 26, issue 11, pages 1719-25, Nov 2012, doi [http://dx.doi.org/10.1002/ptr.4639 10.1002/ptr.4639], PMID [http://www.ncbi.nlm.nih.gov/pubmed/22407780 22407780]</ref>
<ref name="Moini Zanjani-2014">T. Moini Zanjani, H. Ameli, F. Labibi, K. Sedaghat, M. Sabetkasaei, The Attenuation of Pain Behavior and Serum COX-2 Concentration by Curcumin in a Rat Model of Neuropathic Pain., Korean J Pain, volume 27, issue 3, pages 246-52, Jul 2014, doi [http://dx.doi.org/10.3344/kjp.2014.27.3.246 10.3344/kjp.2014.27.3.246], PMID [http://www.ncbi.nlm.nih.gov/pubmed/25031810 25031810]</ref>
<ref name="AppelboomMaes2014">Thierry Appelboom, Nathalie Maes, Adelin Albert, A New Curcuma Extract (Flexofytol®) in Osteoarthritis: Results from a Belgian Real-Life Experience, The Open Rheumatology Journal, volume 8, issue 1, 2014, pages 77–81, ISSN [http://www.worldcat.org/issn/18743129 18743129], doi [http://dx.doi.org/10.2174/1874312901408010077 10.2174/1874312901408010077]</ref>
<ref name="Kuptniratsaikul-2009">V. Kuptniratsaikul, S. Thanakhumtorn, P. Chinswangwatanakul, L. Wattanamongkonsil, V. Thamlikitkul, Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis., J Altern Complement Med, volume 15, issue 8, pages 891-7, Aug 2009, doi [http://dx.doi.org/10.1089/acm.2008.0186 10.1089/acm.2008.0186], PMID [http://www.ncbi.nlm.nih.gov/pubmed/19678780 19678780]</ref>
<ref name="Panahi-2014">Y. Panahi, AR. Rahimnia, M. Sharafi, G. Alishiri, A. Saburi, A. Sahebkar, Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo-controlled trial., Phytother Res, volume 28, issue 11, pages 1625-31, Nov 2014, doi [http://dx.doi.org/10.1002/ptr.5174 10.1002/ptr.5174], PMID [http://www.ncbi.nlm.nih.gov/pubmed/24853120 24853120]</ref>
<ref name="Agarwal-2011">KA. Agarwal, CD. Tripathi, BB. Agarwal, S. Saluja, Efficacy of turmeric (curcumin) in pain and postoperative fatigue after laparoscopic cholecystectomy: a double-blind, randomized placebo-controlled study., Surg Endosc, volume 25, issue 12, pages 3805-10, Dec 2011, doi [http://dx.doi.org/10.1007/s00464-011-1793-z 10.1007/s00464-011-1793-z], PMID [http://www.ncbi.nlm.nih.gov/pubmed/21671126 21671126]</ref>
<ref name="AnandKunnumakkara2007">Preetha Anand, Ajaikumar B. Kunnumakkara, Robert A. Newman, Bharat B. Aggarwal, Bioavailability of Curcumin: Problems and Promises, Molecular Pharmaceutics, volume 4, issue 6, 2007, pages 807–818, ISSN [http://www.worldcat.org/issn/1543-8384 1543-8384], doi [http://dx.doi.org/10.1021/mp700113r 10.1021/mp700113r]</ref>
<ref name="Cheng-2001">AL. Cheng, CH. Hsu, JK. Lin, MM. Hsu, YF. Ho, TS. Shen, JY. Ko, JT. Lin, BR. Lin, Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions., Anticancer Res, volume 21, issue 4B, pages 2895-900, PMID [http://www.ncbi.nlm.nih.gov/pubmed/11712783 11712783]</ref>
<ref name="Hsu-2007">CH. Hsu, AL. Cheng, Clinical studies with curcumin., Adv Exp Med Biol, volume 595, pages 471-80, 2007, doi [http://dx.doi.org/10.1007/978-0-387-46401-5_21 10.1007/978-0-387-46401-5_21], PMID [http://www.ncbi.nlm.nih.gov/pubmed/17569225 17569225]</ref>
<ref name="Henrotin-2010">Y. Henrotin, AL. Clutterbuck, D. Allaway, EM. Lodwig, P. Harris, M. Mathy-Hartert, M. Shakibaei, A. Mobasheri, Biological actions of curcumin on articular chondrocytes., Osteoarthritis Cartilage, volume 18, issue 2, pages 141-9, Feb 2010, doi [http://dx.doi.org/10.1016/j.joca.2009.10.002 10.1016/j.joca.2009.10.002], PMID [http://www.ncbi.nlm.nih.gov/pubmed/19836480 19836480]</ref>
<ref name="Anand-2010">P. Anand, HB. Nair, B. Sung, AB. Kunnumakkara, VR. Yadav, RR. Tekmal, BB. Aggarwal, Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo., Biochem Pharmacol, volume 79, issue 3, pages 330-8, Feb 2010, doi [http://dx.doi.org/10.1016/j.bcp.2009.09.003 10.1016/j.bcp.2009.09.003], PMID [http://www.ncbi.nlm.nih.gov/pubmed/19735646 19735646]</ref>
<ref name="PanahiSahebkar2012">Y. Panahi, A. Sahebkar, S. Parvin, A. Saadat, A randomized controlled trial on the anti-inflammatory effects of curcumin in patients with chronic sulphur mustard-induced cutaneous complications, Annals of Clinical Biochemistry, volume 49, issue 6, 2012, pages 580–588, ISSN [http://www.worldcat.org/issn/0004-5632 0004-5632], doi [http://dx.doi.org/10.1258/acb.2012.012040 10.1258/acb.2012.012040]</ref>
<ref name="Sahebkar2014">Amirhossein Sahebkar, Are Curcuminoids Effective C-Reactive Protein-Lowering Agents in Clinical Practice? Evidence from a Meta-Analysis, Phytotherapy Research, volume 28, issue 5, 2014, pages 633–642, ISSN [http://www.worldcat.org/issn/0951418X 0951418X], doi [http://dx.doi.org/10.1002/ptr.5045 10.1002/ptr.5045]</ref>
<ref name="bone">JBJS | Dose and Time-Dependent Effects of Cyclooxygenase-2 Inhibition on Fracture-Healing http://www.jbjs.org/article.aspx?Volume=89&page=500</ref>
<ref name="tendon">NSAIDs Inhibit Tendon-to-Bone Healing in Rotator Cuff Repair http://www.shoulderdoc.co.uk/article.asp?article=295</ref>
<ref name="ToussaintYang2010">K. Toussaint, X. C. Yang, M. A. Zielinski, K. L. Reigle, S. D. Sacavage, S. Nagar, R. B. Raffa, What do we (not) know about how paracetamol (acetaminophen) works?, Journal of Clinical Pharmacy and Therapeutics, volume 35, issue 6, 2010, pages 617–638, ISSN [http://www.worldcat.org/issn/02694727 02694727], doi [http://dx.doi.org/10.1111/j.1365-2710.2009.01143.x 10.1111/j.1365-2710.2009.01143.x]</ref>
<ref name="www.fda.gov">FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes, http://www.fda.gov/Drugs/DrugSafety/ucm451800.htm, Accessed on 25 January 2016</ref>
<ref name="JoslinLloyd2013">Jeremy D Joslin, Jarem B Lloyd, Timur Kotlyar, Susan M Wojcik, NSAID and other analgesic use by endurance runners during training, competition and recovery, South African Journal of Sports Medicine, volume 25, issue 4, 2013, pages 101, ISSN [http://www.worldcat.org/issn/2078-516X 2078-516X], doi [http://dx.doi.org/10.7196/sajsm.495 10.7196/sajsm.495]</ref></references><ref name="van GentvanGent-2007">RN. van Gent, D. Siem, M. van Middelkoop, AG. van Os, SM. Bierma-Zeinstra, BW. Koes, Incidence and determinants of lower extremity running injuries in long distance runners: a systematic review., Br J Sports Med, volume 41, issue 8, pages 469-80; discussion 480, Aug 2007, doi [http://dx.doi.org/10.1136/bjsm.2006.033548 10.1136/bjsm.2006.033548], PMID [http://www.ncbi.nlm.nih.gov/pubmed/17473005 17473005]</ref><ref name="Benzie-">IFF. Benzie, S. Wachtel-Galor, S. Prasad, BB. Aggarwal, Turmeric, the Golden Spice: From Traditional Medicine to Modern Medicine, PMID [http://www.ncbi.nlm.nih.gov/pubmed/22593922 22593922]</ref><ref name="GanigerMalleshappa2007">S. Ganiger, H.N. Malleshappa, H. Krishnappa, Geetha Rajashekhar, V. Ramakrishna Rao, Frank Sullivan, A two generation reproductive toxicity study with curcumin, turmeric yellow, in Wistar rats, Food and Chemical Toxicology, volume 45, issue 1, 2007, pages 64–69, ISSN [http://www.worldcat.org/issn/02786915 02786915], doi [http://dx.doi.org/10.1016/j.fct.2006.07.016 10.1016/j.fct.2006.07.016]</ref><ref name="Hawkey-2001">CJ. Hawkey, COX-1 and COX-2 inhibitors., Best Pract Res Clin Gastroenterol, volume 15, issue 5, pages 801-20, Oct 2001, doi [http://dx.doi.org/10.1053/bega.2001.0236 10.1053/bega.2001.0236], PMID [http://www.ncbi.nlm.nih.gov/pubmed/11566042 11566042]</ref></references>
[[Category:Training]]
[[Category:Injury]]
[[Category:Science]]
