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NSAIDs and Running

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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=
[[File:Curcuma longa roots.jpg|right|thumb|300px|Turmeric rhizome and powder (By Simon A. Eugster - Own work, CC BY-SA 3.0).]]Turmeric is an anti-inflammatory<ref name="Sahebkar2014"/><ref name="PanahiSahebkar2012"/> that is often considered an alternative to more common NSAIDs. 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"/>, rheumatoid arthritis<ref name="Chandran-2012"/>, and cancer<ref name="Cheng-2001"/><ref name="RaoDinkar2013"/><ref name="Gupta-2013"/> show potentially promising results. However, there are concerns that most of the human studies on Turmeric are of poor quality and should be treated with caution<ref name="Mancuso-2009"/>.==Turmeric Safety==Turmeric has been medicinally used for 1000s of years<ref name="Benzie-"/> and even in large doses turmeric shows low acute 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"/>. However, there are concerns that many studies on Turmeric are in vitro (isolated tissues) at dose levels that are hard to replicate in humans<ref name="Burgos-MorónCalderón-Montaño2010"/>. Doses as high as 12g of curcumin produce negligible levels in the blood<ref name="VareedKakarala2008"/>. At therapeutic levels there is evidence that Turmeric (curcumin) may be carcinogenic<ref name="GoodpastureArrighi1976"/><ref name="Giri-1990"/><ref name="Ahsan-1998"/><ref name="Sakano-2002"/><ref name="Nair-2005"/><ref name="Blasiak-1999"/><ref name="Kelly-2001"/><ref name="Cao-2006"/><ref name="Urbina-Cano-2006"/>, though it can exhibit both anticancer and carcinogenic properties<ref name="López-Lázaro-2008"/>. Curcumin can inhibit liver function, including the drug-metabolizing P450 enzymes<ref name="Hayeshi-2007"/><ref name="Basu-2004"/><ref name="Oetari-1996"/><ref name="Appiah-Opong-2007"/><ref name="Volak-2008"/>. (This could cause problematic drug interactions.) Turmeric has poor bioavailabilitymay bind to iron, resulting in iron deficiency<ref name="AnandJiao-20102009"/><ref name="AnandKunnumakkara2007Baum-2004"/>, but versions with improved bioavailability though it has been suggested that some of the benefits of Turmeric are being developed such from this iron binding<ref name="Means2008"/>. It should be remembered that other common constituents of normal diet have shown to be toxic when used as Flexofytoldietary supplements<ref name="Goodman-2004"/>==Turmeric Doses==It's been estimated people in India consuming high culinary intakes of Turmeric obtain about 150mg/day of curcumin<ref name="AppelboomMaes2014Sharma-2005"/> or Meriva, and average intake is probably 60-100mg/day<ref name="DrobnicShah-20141999"/>. Like other NSAIDsHowever, must studies use much higher levels, and culinary levels (~2g/day) Turmeric is probably ineffective as an effective pain reliever (analgesic)NSAID<ref name="AgarwalNiemanCialdella-2011Kam2012"/>. Turmeric has poor bioavailability<ref name="PanahiAnand-20142010"/><ref name="AnandKunnumakkara2007"/>due to poor absorption and rapid metabolism<ref name="KuptniratsaikulAnandKunnumakkara2007"/>. The curcumin level in Turmeric powder can vary dramatically, with one study finding levels between 0.6 and 3.1% dry weight, a more than five-2009fold variation<ref name="TayyemHeath2006"/>. This makes it hard to use the raw powder, as the actual dose could vary enormously and a high dose of curcumin such as 8g would potentially require the consumption of 1.3Kg/2.8 pounds of Turmeric powder. It's been shown that 3.6 g curcumin produces effective levels in the digestive system, but negligible levels outside the gut<ref name="ZhuGarcea-20142005"/> , and even 12g of curcumin produce negligible levels in the blood<ref name="VareedKakarala2008"/>. This is compounded by the rapid removal, with concentrations of curcumin typically peak 1-2 hours after consumption and declining within 12 hours<ref name="Cheng-2001"/><ref name="Agarwal-2011"/>. At this point, it may 's hard to define a dose of Turmeric or curcumin beyond saying that it's safe at culinary levels (~2g/day of Turmeric powder).==Turmeric Enhancers==The levels of Turmeric can be effective enhanced by taking it with piperine, a constituent of black pepper. One study that gave subjects 2g of curcumin found extremely low levels in treating [[Delayed Onset Muscle Soreness]]the blood, but adding 20mg of piperine boosted blood levels by 2000%<ref name="NicolShoba-20151998"/>. Another animal study using intravenous administration found piperine enhanced the effectiveness of curcumin<ref name="BhutaniBishnoi2009"/>. However, an animal study found that low levels (20 mg/kg) of piperine did not enhance the effectiveness of curcumin, and higher levels (40 mg/kg) actually negated the curcumin benefits<ref name="DrobnicArcaro-2014"/>. Piperine increases the absorption of curcumin<ref name="McFarlinVenable2016Suresh-2010"/>and reduces the metabolism of curcumin by the liver<ref name="TanabeMaeda2015Shoba-1998"/><ref name="DavisVolak-20072008"/>. However, the reduced metabolism is because like curcumin, piperine is a powerful inhibitor of liver function<ref name="KawanishiAtal-20131985"/>. Studies of Turmeric and turmeric derivatives as treatments for osteoarthritis<ref name="HenrotinBhardwaj-20142002"/><ref name="KuptniratsaikulSingh-20141986"/>. Personally, I am cautious about boosting the levels of curcumin by impairing the liver. There are also versions of curcumin with improved bioavailability are being developed such as Flexofytol<ref name="AppelboomMaes2014"/> and rheumatoid arthritisor Meriva<ref name="ChandranDrobnic-20122014"/> show promising results. However, it should be noted that the bulk of the current research does not use enhancers, so caution may be appropriate. ==Turmeric as a selective COX-2 Inhibitor==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.
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</references>
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