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{{DISPLAYTITLE: NSAIDs (Ibuprofen, Acetaminophen/Paracetamol) for runners, impairs healing and interferes with hydration}}
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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)]]
 
[[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 Non-Steroidal Anti-Inflammatory Drugs, the most common are Ibuprofen (Advil, Motrin), Acetaminophen/Paracetamol (Tylenol, aspirin-free Anacin, Excedrin, and numerous cold medicines) and Aspirin. They work by inhibiting a particular enzyme ([http://en.wikipedia.org/wiki/Cyclooxygenase Cyclooxygenase]) which reduces pain, fever and inflammation. NSAIDs are generally bad for runners, impairing healing, masking symptoms, interfering with hydration and in extreme situations can be life threatening. Ibuprofen use is so common among runners that it is sometimes called "Vitamin I"<ref name="VitaminI"/>.
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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="vanGent-2007"/>. This article also covers Acetaminophen (also called Paracetamol), though it's not technically an NSAID.  
==NSAIDs and Healing==
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=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:
 
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 Acetaminiaphen reduce 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.
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* '''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.
* '''''Tendons'''''. A primate study<ref name="TendonPrimates"/> showed "a marked decrease in the breaking strength of tendons at four and six weeks in the ibuprofen-treated animals". Another animal study<ref name="TendonCOX2"/> showed treated tendons were 32% weaker than their untested counterparts.  
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* '''Tendons'''. A primate study<ref name="TendonPrimates"/> showed "a marked decrease in the breaking strength of tendons at four and six weeks in the ibuprofen-treated animals". Another animal study<ref name="TendonCOX2"/> showed treated tendons were 32% weaker than their untested counterparts. A study of older adults showed a weakening of tendons with acetaminophen (but not ibuprofen) use<ref name="CarrollDickinson2011"/>.
* '''''Bone-Tendon Junctions'''''. An animal study<ref name="tendon"/> of rotator cuff injuries shows that NSAID usage resulted in injuries that did not heal, and those that did heal were weaker than those without NSAID. To quote from the study "Given that NSAID administration was discontinued after 14 days yet affected load-to-failure eight weeks following repair, it appears that inhibition of the early events in the inflammatory cascade has a lasting negative effect on tendon-to-bone healing," Dr. Rodeo said.  
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* '''Bone-Tendon Junctions'''. An animal study<ref name="tendon"/> of rotator cuff injuries shows that NSAID usage resulted in injuries that did not heal, and those that did heal were weaker than those without NSAID. To quote from the study "Given that NSAID administration was discontinued after 14 days yet affected load-to-failure eight weeks following repair, it appears that inhibition of the early events in the inflammatory cascade has a lasting negative effect on tendon-to-bone healing," Dr. Rodeo said.
* '''''Cartilage. ''''' NSAIDs have been shown<ref name="CartilageRabbit"/> to impair the healing of bone and cartilage in rabbits.  
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* '''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".
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* '''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".
===Counterpoint===
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==Counterpoint==
 
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.  
 
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.  
===Ice, Inflammation and Healing===
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==Ice, Inflammation and Healing==
If NSAIDs are bad for healing, should we treat with ice? So far I have found no definitive studies, but ice has a difference mechanism of action from NSAIDs. By cooling the tissues, ice temporarily reduces inflammation, thereby flushing the wound. It does not directly impact any of the body's enzymes or other processes. 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.  
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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.
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=Turmeric as an NSAID=
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[[File:Curcuma longa roots.jpg|right|thumb|300px|Turmeric rhizome and powder (By Simon A. Eugster - Own work, CC BY-SA 3.0).]]
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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"/>.
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==Turmeric Safety==
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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 may bind to iron, resulting in iron deficiency<ref name="Jiao-2009"/><ref name="Baum-2004"/>, though it has been suggested that some of the benefits of Turmeric are 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 dietary supplements<ref name="Goodman-2004"/>
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==Turmeric Doses==
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It's been estimated people in India consuming high culinary intakes of Turmeric obtain about 150mg/day of curcumin<ref name="Sharma-2005"/>, and average intake is probably 60-100mg/day<ref name="Shah-1999"/>. However, must studies use much higher levels, and culinary levels (~2g/day) Turmeric is probably ineffective as an NSAID<ref name="NiemanCialdella-Kam2012"/>. Turmeric has poor bioavailability<ref name="Anand-2010"/><ref name="AnandKunnumakkara2007"/> due to poor absorption and rapid metabolism<ref name="AnandKunnumakkara2007"/>. 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-fold 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="Garcea-2005"/>, 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's hard to define a dose of Turmeric or curcumin beyond saying that it's safe at culinary levels (~2g/day of Turmeric powder).
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==Turmeric Enhancers==
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The levels of Turmeric can be enhanced by taking it with piperine, a constituent of black pepper. One study that gave subjects 2g of curcumin found extremely low levels in the blood, but adding 20mg of piperine boosted blood levels by 2000%<ref name="Shoba-1998"/>. 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="Arcaro-2014"/>. Piperine increases the absorption of curcumin<ref name="Suresh-2010"/> and reduces the metabolism of curcumin by the liver<ref name="Shoba-1998"/><ref name="Volak-2008"/>. However, the reduced metabolism is because like curcumin, piperine is a powerful inhibitor of liver function<ref name="Atal-1985"/><ref name="Bhardwaj-2002"/><ref name="Singh-1986"/>. 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"/> or Meriva<ref name="Drobnic-2014"/>. However, it should be noted that the bulk of the current research does not use enhancers, so caution may be appropriate.
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==Turmeric as a selective COX-2 Inhibitor==
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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"/>.  
 
=NSAIDs and Acute kidney failure=
 
=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.
 
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.
 
* '''Dehydration'''. Exercise reduces blood flow to the kidneys and dehydration makes this worse.
 
* '''Dehydration'''. Exercise reduces blood flow to the kidneys and dehydration makes this worse.
* '''NSAIDs'''. NSAIDs also reduce blood flow to the kidneys<ref name="coxibs"/>. NSAIDs reduce prostaglandin production, and prostaglandins are vital to maintaining blood flow to the kidneys. While NSAIDs are considered safe drugs, NSAIDs are associated with a relatively high incidence of adverse drug reactions involving the kidneys. Generally NSAID side effects are restricted to individuals with predisposition to kidney problems, so extra care should be taken if you have a history of kidney problems. However, athletes push their bodies to extremes, so what applies to the general population may not be valid for runners. One runner was told<ref name="Anecdote"/> by doctors that 2400mg Ibuprofen in an ultramarathon was a contributing factor to his kidney failure.  
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* '''NSAIDs'''. NSAIDs also reduce blood flow to the kidneys<ref name="coxibs"/>. NSAIDs reduce prostaglandin production, and prostaglandins are vital to maintaining blood flow to the kidneys. While NSAIDs are considered safe drugs, NSAIDs are associated with a relatively high incidence of adverse drug reactions involving the kidneys. Generally, NSAID side effects are restricted to individuals with predisposition to kidney problems, so extra care should be taken if you have a history of kidney problems. However, athletes push their bodies to extremes, so what applies to the general population may not be valid for runners. One runner was told<ref name="Anecdote"/> by doctors that 2400mg Ibuprofen in an ultramarathon was a contributing factor to his kidney failure.
* '''Rhabdomyolysis'''. All strenuous exercise causes some muscle damage, but this is generally resolved without a problem. However large amounts of a protein called myoglobin from damaged muscle can cause a condition called [http://en.wikipedia.org/wiki/Rhabdomyolysis rhabdomyolysis] (AKA 'rhabdo'). While serious rhabdomyolysis is rare, it is worth understanding one key symptom, which is low volume, dark urine, often likened to 'coca-cola'. The other symptoms include severe, incapacitating muscle pain and elevated levels of creatine kinase (CK) in the blood (which requires a specialist test). Some individuals<ref name="rhabdoGenes"/> have a genetic condition that makes rhabdomyolysis possible after relatively moderate exercise. Rhabdomyolysis is also more likely after eccentric exercise, such as [[Downhill Running]].
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* '''Rhabdomyolysis'''. All strenuous exercise causes some muscle damage, but this is generally resolved without a problem. However large amounts of a [[Protein]] called myoglobin from damaged muscle can cause a condition called [http://en.wikipedia.org/wiki/Rhabdomyolysis rhabdomyolysis] (AKA 'rhabdo'). While serious rhabdomyolysis is rare, it is worth understanding one key symptom, which is low volume, dark urine, often likened to 'coca-cola'. The other symptoms include severe, incapacitating muscle pain and elevated levels of creatine kinase (CK) in the blood (which requires a specialist test). Some individuals<ref name="rhabdoGenes"/> have a genetic condition that makes rhabdomyolysis possible after relatively moderate exercise. Rhabdomyolysis is also more likely after eccentric exercise, such as [[Downhill Running]].
 
* '''Sickness'''. A viral or bacterial infection is often a factor in exercise related kidney failure.
 
* '''Sickness'''. A viral or bacterial infection is often a factor in exercise related kidney failure.
 
Looking at the analysis<ref name="coxibs"/> of nine cases of continued kidney failure in Comrades Marathon, seven had taken NSAIDs, four may have had a viral or bacterial infection. The combination of dehydration, rhabdomyolysis, infection and NSAIDs are a perfect storm for the kidneys.
 
Looking at the analysis<ref name="coxibs"/> of nine cases of continued kidney failure in Comrades Marathon, seven had taken NSAIDs, four may have had a viral or bacterial infection. The combination of dehydration, rhabdomyolysis, infection and NSAIDs are a perfect storm for the kidneys.
 
=NSAIDs and Hyponatremia=
 
=NSAIDs and Hyponatremia=
 
The kidneys are responsible for removing excess fluid from the blood as well as excreting or withholding sodium. If kidney function is compromised, then this can result in [[Hyponatremia]], which can be fatal. Some studies<ref name="hypo"/><ref name="hypo2"/><ref name="siadh"/> have shown a correlation between NSAID use in races and [[Hyponatremia]], but others<ref name="nohypo"/><ref name="Dumke-2007"/> have not. Using NSAIDs when hydration is a concern increases the risk of problems occuring.  
 
The kidneys are responsible for removing excess fluid from the blood as well as excreting or withholding sodium. If kidney function is compromised, then this can result in [[Hyponatremia]], which can be fatal. Some studies<ref name="hypo"/><ref name="hypo2"/><ref name="siadh"/> have shown a correlation between NSAID use in races and [[Hyponatremia]], but others<ref name="nohypo"/><ref name="Dumke-2007"/> have not. Using NSAIDs when hydration is a concern increases the risk of problems occuring.  
=NSAIDs and Sickness=
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=NSAIDs causing Heart Attacks or Strokes=
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The U.S. Food and Drug Administration (FDA) warnings that non-aspirin NSAIDs increase the risk of a heart attack or stroke<ref name="www.fda.gov"/>. The risk appears to be related to ongoing usage rather than single doses, with the risk increasing in the first weeks of usage and the risk may increase with prolonged usage. The increased risk is dose dependent (taking more has a greater risk), and the includes those without heart disease or risk factors for heart disease. Not surprisingly, those already with a higher risk of heart disease or stroke have a proportionately higher risk with NSAID usage.
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=NSAIDs and Infection=
 
Because a bacterial or viral infection puts more stress on the body, including the kidneys, taking NSAIDs and continuing to run increases your risk of complications. If the sickness is too bad to run without NSAIDs, you probably shouldn't run.  
 
Because a bacterial or viral infection puts more stress on the body, including the kidneys, taking NSAIDs and continuing to run increases your risk of complications. If the sickness is too bad to run without NSAIDs, you probably shouldn't run.  
 
=NSAIDs for Pain Reduction=
 
=NSAIDs for Pain Reduction=
 
The primary purpose of NSAIDs is generally for reducing pain, and they are remarkably effective at achieving this. If you need a painkiller, acetaminophen is probably a better choice than ibuprofen, though be careful as it's easy to overdose on Acetaminophen (see below). Acetaminophen has limited anti-inflammatory properties, so it shouldn't impair healing as much as ibuprofen, but it is still good as a painkiller. Combining acetaminophen or other NSAIDs with [[Caffeine]] further improves their painkilling effectiveness. After a major race I can sometimes have so much leg pain that I can't [[Zeo Sleep Monitor|sleep]] and a little acetaminophen can make all the difference. While the acetaminophen may impair healing somewhat I believe the trade-off in improved [[Zeo Sleep Monitor|sleep]] is worthwhile. After all, the lack of [[Zeo Sleep Monitor|sleep]] itself will impair healing, so it's a reasonable compromise.  
 
The primary purpose of NSAIDs is generally for reducing pain, and they are remarkably effective at achieving this. If you need a painkiller, acetaminophen is probably a better choice than ibuprofen, though be careful as it's easy to overdose on Acetaminophen (see below). Acetaminophen has limited anti-inflammatory properties, so it shouldn't impair healing as much as ibuprofen, but it is still good as a painkiller. Combining acetaminophen or other NSAIDs with [[Caffeine]] further improves their painkilling effectiveness. After a major race I can sometimes have so much leg pain that I can't [[Zeo Sleep Monitor|sleep]] and a little acetaminophen can make all the difference. While the acetaminophen may impair healing somewhat I believe the trade-off in improved [[Zeo Sleep Monitor|sleep]] is worthwhile. After all, the lack of [[Zeo Sleep Monitor|sleep]] itself will impair healing, so it's a reasonable compromise.  
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=NSAIDs and DOMS=
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''Main article: [[Delayed Onset Muscle Soreness]]''
  
=NSAIDs and DOMS=
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[[Delayed Onset Muscle Soreness]] (DOMS) generally occurs between 24 and 72 hours after unusual or severe exercise, such as racing a marathon or [[Downhill Running]]. The use of NSAIDs to prevent or treat DOMS has been widely researched, with somewhat mixed results. Even scholarly reviews of the research have differing conclusions<ref name="Cheung-2003"/> <ref name="Smith-1992"/> <ref name="Baldwin Lanier-2003"/><ref name="Howatson-2008"/>. My conclusions based on the available research are:
Delayed Onset Muscle Soreness (DOMS) generally occurs between 24 and 72 hours after unusual or severe exercise, such as racing a marathon or downhill running. The use of NSAIDs to prevent or treat DOMS has been widely researched, with somewhat mixed results. Even scholarly reviews of the research have differing conclusions<ref name="Cheung-2003"/> <ref name="Smith-1992"/> <ref name="Baldwin Lanier-2003"/><ref name="Howatson-2008"/>. My conclusions based on the available research are:
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* The most common NSAIDs (Ibuprofen, Acetaminophen (Paracetamol), and Aspirin) are unlikely to help with DOMS.
* 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 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.
* If an NSAID is taken for DOMS, it should probably be taken immediately after the damaging exercise rather than waiting until the soreness develops.  
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* There is also some evidence that Turmeric may help with DOMS.
* It seems likely that taking an NSAID for DOMS will reduce the muscular growth that would normally occur as part of the recovery.  
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* If an NSAID is taken for DOMS, it should probably be taken immediately after the damaging exercise rather than waiting until the soreness develops.
** 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.  
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* 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==
 
==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.  
 
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.  
{| class="wikitable"
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{| class="wikitable"  
!NSAID!!Soreness!!Weakness
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! NSAID
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! Soreness
 +
! Weakness
 
|-
 
|-
|Ibuprofen
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| Ibuprofen
|2xImproved<ref name="Hasson-1993"/><ref name="pmid12580656"/>
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| 2xImproved<ref name="Hasson-1993"/><ref name="pmid12580656"/>
 
7xNo Effect<ref name="Grossman-1995"/><ref name="Pizza-1999"/><ref name="RahnamaRahmani-Nia2005"/> <ref name="KrentzQuest2008"/><ref name="Arendt-NielsenWeidner2007"/><ref name="Donnelly-1990"/><ref name="Stone-2002"/>  
 
7xNo Effect<ref name="Grossman-1995"/><ref name="Pizza-1999"/><ref name="RahnamaRahmani-Nia2005"/> <ref name="KrentzQuest2008"/><ref name="Arendt-NielsenWeidner2007"/><ref name="Donnelly-1990"/><ref name="Stone-2002"/>  
|1xMaybe<ref name="Hasson-1993"/>
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| 1xMaybe<ref name="Hasson-1993"/>
 
8xNo Effect<ref name="Grossman-1995"/><ref name="Pizza-1999"/><ref name="RahnamaRahmani-Nia2005"/> <ref name="KrentzQuest2008"/><ref name="Arendt-NielsenWeidner2007"/><ref name="Donnelly-1990"/><ref name="pmid12580656"/><ref name="Stone-2002"/>  
 
8xNo Effect<ref name="Grossman-1995"/><ref name="Pizza-1999"/><ref name="RahnamaRahmani-Nia2005"/> <ref name="KrentzQuest2008"/><ref name="Arendt-NielsenWeidner2007"/><ref name="Donnelly-1990"/><ref name="pmid12580656"/><ref name="Stone-2002"/>  
 
|-
 
|-
|Ibuprofen Gel
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| Ibuprofen Gel
|1xNo Effect<ref name="HyldahlKeadle2010"/>
+
| 1xNo Effect<ref name="HyldahlKeadle2010"/>
|
+
|  
 
|-
 
|-
|Acetaminophen (Paracetamol)
+
| Acetaminophen (Paracetamol)
|2xNo Effect<ref name="Barlas-2000"/><ref name="SmithGeorge1995"/>
+
| 2xNo Effect<ref name="Barlas-2000"/><ref name="SmithGeorge1995"/>
|
+
|  
 
|-
 
|-
|Aspirin
+
| Aspirin
|2xImproved<ref name="Riasata-2010"/><ref name="Francis-1987"/>
+
| 2xImproved<ref name="Riasata-2010"/><ref name="Francis-1987"/>
 
2xNo Effect<ref name="Barlas-2000"/><ref name="SmithGeorge1995"/>
 
2xNo Effect<ref name="Barlas-2000"/><ref name="SmithGeorge1995"/>
|2xNo Effect<ref name="Riasata-2010"/><ref name="Francis-1987"/>
+
| 2xNo Effect<ref name="Riasata-2010"/><ref name="Francis-1987"/>
 
|-
 
|-
|Naproxen   
+
| Naproxen   
|4xImproved<ref name="Dudley-1997"/><ref name="Baldwin-2001"/><ref name="Lecomte-1998"/><ref name="journals.ut.ac.ir"/>
+
| 4xImproved<ref name="Dudley-1997"/><ref name="Baldwin-2001"/><ref name="Lecomte-1998"/><ref name="journals.ut.ac.ir"/>
 
1xNo Effect<ref name="Bourgeois-1999"/>
 
1xNo Effect<ref name="Bourgeois-1999"/>
|3xImproved<ref name="Dudley-1997"/><ref name="Baldwin-2001"/><ref name="Lecomte-1998"/>
+
| 3xImproved<ref name="Dudley-1997"/><ref name="Baldwin-2001"/><ref name="Lecomte-1998"/>
 
1xNo Effect<ref name="Bourgeois-1999"/>
 
1xNo Effect<ref name="Bourgeois-1999"/>
 
|-
 
|-
|Diclofenac   
+
| Diclofenac   
|Possible slight reduction<ref name="DonnellyMcCormick1988"/>
+
| Possible slight reduction<ref name="DonnellyMcCormick1988"/>
|
+
|  
 
|-
 
|-
|Codeine
+
| Codeine
|1xNo Effect<ref name="Barlas-2000"/>  
+
| 1xNo Effect<ref name="Barlas-2000"/>  
|
+
|  
 
|-
 
|-
|Rofecoxib  
+
| Rofecoxib  
|1xNo Effect<ref name="LoramMitchell2005"/>  
+
| 1xNo Effect<ref name="LoramMitchell2005"/>  
|
+
|  
 
|-
 
|-
|Ketoprofen  
+
| Ketoprofen  
|1xImproved<ref name="Sayers-2001"/>
+
| 1xImproved<ref name="Sayers-2001"/>
|1xImproved<ref name="Sayers-2001"/>
+
| 1xImproved<ref name="Sayers-2001"/>
 
|-
 
|-
|Bromelain  
+
| Bromelain  
|1xNo Effect<ref name="Stone-2002"/>
+
| 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=
 
=NSAIDs and Intestinal Damage=
As little as one hour of intense cycling can result in indications of small intestinal damage<ref name="van Wijck-2011"/>. This is believed to be due to the redirection of blood away from the digestive system and towards the active muscles. These markers are significantly higher if 400mg ibuprofen (the standard single adult dose) is taken before the exercise<ref name="VAN Wijck-2012"/>. The marker used is Plasma Intestinal Fatty Acid Binding Protein which is an early marker of intestinal necrosis<ref name="Vermeulen Windsant-2012"/>.
+
As little as one hour of intense cycling can result in indications of small intestinal damage<ref name="van Wijck-2011"/>. This is believed to be due to the redirection of blood away from the digestive system and towards the active muscles. These markers are significantly higher if 400mg ibuprofen (the standard single adult dose) is taken before the exercise<ref name="VAN Wijck-2012"/>. The marker used is Plasma Intestinal Fatty Acid Binding [[Protein]] which is an early marker of intestinal necrosis<ref name="Vermeulen Windsant-2012"/>.
 
[[File:Ibuprofen and GI damage.jpg|none|thumb|500px|The level of a marker of intestinal damage during and after 60 minutes of cycling at 70% [[VO2max|V̇O<sub>2</sub>max]].]]
 
[[File:Ibuprofen and GI damage.jpg|none|thumb|500px|The level of a marker of intestinal damage during and after 60 minutes of cycling at 70% [[VO2max|V̇O<sub>2</sub>max]].]]
 +
=NSAIDs and Wound Healing=
 +
''Main article: [[Popping Blisters]]''
 +
 +
Ibuprofen, and possibly other NSAIDs, impair wound healing and should be avoided<ref name="StadelmannDigenis1998"/><ref name="GuoDiPietro2010"/>.
 
=NSAIDs and Racing=
 
=NSAIDs and Racing=
 
Taking NSAIDs in ultramarathon events can improve performance by reducing pain and acute inflammation, but doing so represents a significant risk. There is some evidence<ref name="wser1"/> <ref name="wser2"/> that many runners taking NSAIDs have the same level of pain and greater damage markers compared with non-users. This may be because the runners push themselves to a similar level of pain, with the NSAIDs allowing them to do more damage.  
 
Taking NSAIDs in ultramarathon events can improve performance by reducing pain and acute inflammation, but doing so represents a significant risk. There is some evidence<ref name="wser1"/> <ref name="wser2"/> that many runners taking NSAIDs have the same level of pain and greater damage markers compared with non-users. This may be because the runners push themselves to a similar level of pain, with the NSAIDs allowing them to do more damage.  
* It seems likely that NSAIDs will increase the risk of injury rather than reducing it, as the symptoms of damage will be masked.  
+
* It seems likely that NSAIDs will increase the risk of injury rather than reducing it, as the symptoms of damage will be masked.
* The most common NSAID for racing seems to be ibuprofen. I've not seen any evidence of the relative effectiveness of different NSAIDs on performance.  
+
* The most common NSAID for racing seems to be ibuprofen. I've not seen any evidence of the relative effectiveness of different NSAIDs on performance.
* It is better to take liquid ibuprofen than tablets or capsules. The tablets and capsules take longer to dissolve and if you have a digestive problem they may not be fully absorbed. You can chew the tablets, but this is unpleasant and ibuprofen can irritate your mouth and throat slightly, so the liquid form is best. It's obviously harder to transport, but you can fill an old film canister with a dose.  
+
* It is better to take liquid ibuprofen than tablets or capsules. The tablets and capsules take longer to dissolve and if you have a digestive problem they may not be fully absorbed. You can chew the tablets, but this is unpleasant and ibuprofen can irritate your mouth and throat slightly, so the liquid form is best. It's obviously harder to transport, but you can fill an old film canister with a dose.
 
* Before an ultramarathon race, you should think through under what circumstances you will consider using NSAIDs and what dosage. Make sure your crew knows that you're taking NSAIDs in case anything happens.
 
* Before an ultramarathon race, you should think through under what circumstances you will consider using NSAIDs and what dosage. Make sure your crew knows that you're taking NSAIDs in case anything happens.
 
* Extra care should be taken when NSAIDs are used in combination with dehydration, sickness or running the causes serious muscle damage.
 
* Extra care should be taken when NSAIDs are used in combination with dehydration, sickness or running the causes serious muscle damage.
* Taking NSAIDs in marathon or shorter races is probably ineffective as the level of damage seen is not as great as in ultramarathon events.  
+
* Taking NSAIDs in marathon or shorter races is probably ineffective as the level of damage seen is not as great as in ultramarathon events.
 
* If you need NSAIDs to start a race, you probably should not compete.
 
* If you need NSAIDs to start a race, you probably should not compete.
 
=Longer Term NSAID usage=
 
=Longer Term NSAID usage=
Line 101: Line 125:
 
=Acetaminophen Overdose Danger (AKA Paracetamol, Tylenol)=
 
=Acetaminophen Overdose Danger (AKA Paracetamol, Tylenol)=
 
Acetaminophen does not have the same risk of ulcers, but it is linked to liver damage, especially in those who drink alcohol. Acetaminophen is the leading cause of acute liver failure<ref name="AcetaAcuteLiver"/><ref name="Staggered"/>. There are concerns<ref name="AcetaNormalDoseLiver"/> that even the standard dose can cause changes in liver function. Acetaminophen can cause delayed symptoms<ref name="Staggered"/>, with people seeking medical help up to 5 days after the overdose (20% < 12 hours, 35% 12-24 hours, 45% 24 hours+). Overdoses of Acetaminophen can be caused by taking slightly too much over several days, with the toxicity building up<ref name="Staggered"/>. This problem is again exacerbated by those taking alcohol with Acetaminophen<ref name="Staggered"/>. (One factor that increases the risk is that some common medications, such as cold remedies, include Acetaminophen. If people do not add in the dose of Acetaminophen from these other sources, it is easy to unwittingly exceed the safe dosage.)  
 
Acetaminophen does not have the same risk of ulcers, but it is linked to liver damage, especially in those who drink alcohol. Acetaminophen is the leading cause of acute liver failure<ref name="AcetaAcuteLiver"/><ref name="Staggered"/>. There are concerns<ref name="AcetaNormalDoseLiver"/> that even the standard dose can cause changes in liver function. Acetaminophen can cause delayed symptoms<ref name="Staggered"/>, with people seeking medical help up to 5 days after the overdose (20% < 12 hours, 35% 12-24 hours, 45% 24 hours+). Overdoses of Acetaminophen can be caused by taking slightly too much over several days, with the toxicity building up<ref name="Staggered"/>. This problem is again exacerbated by those taking alcohol with Acetaminophen<ref name="Staggered"/>. (One factor that increases the risk is that some common medications, such as cold remedies, include Acetaminophen. If people do not add in the dose of Acetaminophen from these other sources, it is easy to unwittingly exceed the safe dosage.)  
=Tangent - Is Acetaminophen really an NSAID?=
+
=Is Acetaminophen an NSAID?=
There are differing opinions around the classification of Acetaminophen as an NSAID with some resources<ref name="NotAnNsaid"/> stating it is not an NSAID. While Acetaminophen has limited anti-inflammatory properties, it shares the same mechanism of action with most NSAIDs of inhibiting the COX enzyme and the inhibition of prostaglandin synthesis. It is therefore reasonable and useful to classify Acetaminophen as an NSAID.  
+
Acetaminophen (also called paracetamol) is generally not classified as an NSAID<ref name="NotAnNsaid"/>. While Acetaminophen has limited anti-inflammatory properties, it shares the same mechanism of action with most NSAIDs of inhibiting the COX enzyme and the inhibition of prostaglandin synthesis<ref name="Graham-2005"/><ref name="BottingAyoub2005"/><ref name="ToussaintYang2010"/><ref name="Anderson2008"/>. Therefore, this article includes Acetaminophen in with NSAIDs.  
 
=References=
 
=References=
 
<references>
 
<references>
 +
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<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="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="tendon">NSAIDs Inhibit Tendon-to-Bone Healing in Rotator Cuff Repair http://www.shoulderdoc.co.uk/article.asp?article=295</ref>
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</references>
 
</references>
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[[Category:Training]]
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[[Category:Injury]]
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[[Category:Science]]

Latest revision as of 13:40, 22 December 2016

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 (Cyclooxygenase) which reduces pain, fever and inflammation. Ibuprofen use is so common among runners that it is sometimes called "Vitamin I"[1], with one study finding about 60% of runners using NSAIDs during training[2]. This is unsurprising given the estimates of injury rates in runners varying between 20% and 80%[3]. This article also covers Acetaminophen (also called Paracetamol), though it's not technically an NSAID.

1 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[4]. A 2001 study showed that Ibuprofen and Acetaminophen reduce muscle growth after eccentric exercise. Another study[5] 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[6][7] have shown that four days after injury, NSAIDs resulted in very little muscle regeneration compared with no drugs.
  • Tendons. A primate study[8] showed "a marked decrease in the breaking strength of tendons at four and six weeks in the ibuprofen-treated animals". Another animal study[9] showed treated tendons were 32% weaker than their untested counterparts. A study of older adults showed a weakening of tendons with acetaminophen (but not ibuprofen) use[10].
  • Bone-Tendon Junctions. An animal study[11] of rotator cuff injuries shows that NSAID usage resulted in injuries that did not heal, and those that did heal were weaker than those without NSAID. To quote from the study "Given that NSAID administration was discontinued after 14 days yet affected load-to-failure eight weeks following repair, it appears that inhibition of the early events in the inflammatory cascade has a lasting negative effect on tendon-to-bone healing," Dr. Rodeo said.
  • Cartilage. NSAIDs have been shown[12] 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.[13] A study [14] 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".

1.1 Counterpoint

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[15] 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[16] 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.

1.2 Ice, Inflammation and 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.

2 Turmeric as an NSAID

Turmeric rhizome and powder (By Simon A. Eugster - Own work, CC BY-SA 3.0).

Turmeric is an anti-inflammatory[17][18] that is often considered an alternative to more common NSAIDs. Like other NSAIDs, Turmeric is an effective pain reliever (analgesic)[19][20][21][22] and it may be effective in treating Delayed Onset Muscle Soreness[23][24][25][26][27][28]. Studies of Turmeric and turmeric derivatives as treatments for osteoarthritis[29][30], rheumatoid arthritis[31], and cancer[32][33][34] 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[35].

2.1 Turmeric Safety

Turmeric has been medicinally used for 1000s of years[36] and even in large doses turmeric shows low acute toxicity[37][32][31][38] with only a few studies finding nausea and diarrhea[37] or abdominal pain[30]. However, there are concerns that many studies on Turmeric are in vitro (isolated tissues) at dose levels that are hard to replicate in humans[39]. Doses as high as 12g of curcumin produce negligible levels in the blood[40]. At therapeutic levels there is evidence that Turmeric (curcumin) may be carcinogenic[41][42][43][44][45][46][47][48][49], though it can exhibit both anticancer and carcinogenic properties[50]. Curcumin can inhibit liver function, including the drug-metabolizing P450 enzymes[51][52][53][54][55]. (This could cause problematic drug interactions.) Turmeric may bind to iron, resulting in iron deficiency[56][57], though it has been suggested that some of the benefits of Turmeric are from this iron binding[58]. It should be remembered that other common constituents of normal diet have shown to be toxic when used as dietary supplements[59]

2.2 Turmeric Doses

It's been estimated people in India consuming high culinary intakes of Turmeric obtain about 150mg/day of curcumin[60], and average intake is probably 60-100mg/day[61]. However, must studies use much higher levels, and culinary levels (~2g/day) Turmeric is probably ineffective as an NSAID[62]. Turmeric has poor bioavailability[63][64] due to poor absorption and rapid metabolism[64]. 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-fold variation[65]. 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[66], and even 12g of curcumin produce negligible levels in the blood[40]. This is compounded by the rapid removal, with concentrations of curcumin typically peak 1-2 hours after consumption and declining within 12 hours[32][19]. At this point, it's hard to define a dose of Turmeric or curcumin beyond saying that it's safe at culinary levels (~2g/day of Turmeric powder).

2.3 Turmeric Enhancers

The levels of Turmeric can be enhanced by taking it with piperine, a constituent of black pepper. One study that gave subjects 2g of curcumin found extremely low levels in the blood, but adding 20mg of piperine boosted blood levels by 2000%[67]. Another animal study using intravenous administration found piperine enhanced the effectiveness of curcumin[68]. 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[69]. Piperine increases the absorption of curcumin[70] and reduces the metabolism of curcumin by the liver[67][55]. However, the reduced metabolism is because like curcumin, piperine is a powerful inhibitor of liver function[71][72][73]. 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[74] or Meriva[24]. However, it should be noted that the bulk of the current research does not use enhancers, so caution may be appropriate.

2.4 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[75]. COX-2 is predominantly responsible for inflammation where COX-1 helps maintain the digestive system[76]. Selectively inhibiting just COX-2 may have the benefits of NSAIDS without the digestive issues[77][78][76]. Studies have found that Turmeric is a COX-2 inhibitor[79][80][81][82][83], and turmeric preferentially inhibits COX-2 over COX-1[84]. 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[84]. Diferuloylmethane (Curcumin) is the main active ingredient in turmeric[63][85], though it also includes monodemethoxycurcumin (curcumin II) and bisdemethoxycurcumin (curcumin III)[84].

3 NSAIDs and Acute kidney failure

Kidney failure while running is extremely rare, and seems to require multiple factors to come together. Looking at the 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[86]. The following are considered factors in acute kidney failure related to running.

  • Dehydration. Exercise reduces blood flow to the kidneys and dehydration makes this worse.
  • NSAIDs. NSAIDs also reduce blood flow to the kidneys[87]. NSAIDs reduce prostaglandin production, and prostaglandins are vital to maintaining blood flow to the kidneys. While NSAIDs are considered safe drugs, NSAIDs are associated with a relatively high incidence of adverse drug reactions involving the kidneys. Generally, NSAID side effects are restricted to individuals with predisposition to kidney problems, so extra care should be taken if you have a history of kidney problems. However, athletes push their bodies to extremes, so what applies to the general population may not be valid for runners. One runner was told[88] by doctors that 2400mg Ibuprofen in an ultramarathon was a contributing factor to his kidney failure.
  • Rhabdomyolysis. All strenuous exercise causes some muscle damage, but this is generally resolved without a problem. However large amounts of a Protein called myoglobin from damaged muscle can cause a condition called rhabdomyolysis (AKA 'rhabdo'). While serious rhabdomyolysis is rare, it is worth understanding one key symptom, which is low volume, dark urine, often likened to 'coca-cola'. The other symptoms include severe, incapacitating muscle pain and elevated levels of creatine kinase (CK) in the blood (which requires a specialist test). Some individuals[89] have a genetic condition that makes rhabdomyolysis possible after relatively moderate exercise. Rhabdomyolysis is also more likely after eccentric exercise, such as Downhill Running.
  • Sickness. A viral or bacterial infection is often a factor in exercise related kidney failure.

Looking at the analysis[87] of nine cases of continued kidney failure in Comrades Marathon, seven had taken NSAIDs, four may have had a viral or bacterial infection. The combination of dehydration, rhabdomyolysis, infection and NSAIDs are a perfect storm for the kidneys.

4 NSAIDs and Hyponatremia

The kidneys are responsible for removing excess fluid from the blood as well as excreting or withholding sodium. If kidney function is compromised, then this can result in Hyponatremia, which can be fatal. Some studies[90][91][92] have shown a correlation between NSAID use in races and Hyponatremia, but others[93][94] have not. Using NSAIDs when hydration is a concern increases the risk of problems occuring.

5 NSAIDs causing Heart Attacks or Strokes

The U.S. Food and Drug Administration (FDA) warnings that non-aspirin NSAIDs increase the risk of a heart attack or stroke[95]. The risk appears to be related to ongoing usage rather than single doses, with the risk increasing in the first weeks of usage and the risk may increase with prolonged usage. The increased risk is dose dependent (taking more has a greater risk), and the includes those without heart disease or risk factors for heart disease. Not surprisingly, those already with a higher risk of heart disease or stroke have a proportionately higher risk with NSAID usage.

6 NSAIDs and Infection

Because a bacterial or viral infection puts more stress on the body, including the kidneys, taking NSAIDs and continuing to run increases your risk of complications. If the sickness is too bad to run without NSAIDs, you probably shouldn't run.

7 NSAIDs for Pain Reduction

The primary purpose of NSAIDs is generally for reducing pain, and they are remarkably effective at achieving this. If you need a painkiller, acetaminophen is probably a better choice than ibuprofen, though be careful as it's easy to overdose on Acetaminophen (see below). Acetaminophen has limited anti-inflammatory properties, so it shouldn't impair healing as much as ibuprofen, but it is still good as a painkiller. Combining acetaminophen or other NSAIDs with Caffeine further improves their painkilling effectiveness. After a major race I can sometimes have so much leg pain that I can't sleep and a little acetaminophen can make all the difference. While the acetaminophen may impair healing somewhat I believe the trade-off in improved sleep is worthwhile. After all, the lack of sleep itself will impair healing, so it's a reasonable compromise.

8 NSAIDs and DOMS

Main article: Delayed Onset Muscle Soreness

Delayed Onset Muscle Soreness (DOMS) generally occurs between 24 and 72 hours after unusual or severe exercise, such as racing a marathon or Downhill Running. The use of NSAIDs to prevent or treat DOMS has been widely researched, with somewhat mixed results. Even scholarly reviews of the research have differing conclusions[96] [97] [98][99]. My conclusions based on the available research are:

  • 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[100]. 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.

8.1 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.

NSAID Soreness Weakness
Ibuprofen 2xImproved[101][102]

7xNo Effect[103][104][105] [106][107][108][109]

1xMaybe[101]

8xNo Effect[103][104][105] [106][107][108][102][109]

Ibuprofen Gel 1xNo Effect[110]
Acetaminophen (Paracetamol) 2xNo Effect[111][112]
Aspirin 2xImproved[113][114]

2xNo Effect[111][112]

2xNo Effect[113][114]
Naproxen 4xImproved[115][116][117][118]

1xNo Effect[119]

3xImproved[115][116][117]

1xNo Effect[119]

Diclofenac Possible slight reduction[120]
Codeine 1xNo Effect[111]
Rofecoxib 1xNo Effect[121]
Ketoprofen 1xImproved[122] 1xImproved[122]
Bromelain 1xNo Effect[109]
Turmeric 2xImproved[23][24]

2xNo Effect[25][26]

2xImproved[26][27]

9 NSAIDs and Intestinal Damage

As little as one hour of intense cycling can result in indications of small intestinal damage[123]. This is believed to be due to the redirection of blood away from the digestive system and towards the active muscles. These markers are significantly higher if 400mg ibuprofen (the standard single adult dose) is taken before the exercise[124]. The marker used is Plasma Intestinal Fatty Acid Binding Protein which is an early marker of intestinal necrosis[125].

The level of a marker of intestinal damage during and after 60 minutes of cycling at 70% V̇O2max.

10 NSAIDs and Wound Healing

Main article: Popping Blisters

Ibuprofen, and possibly other NSAIDs, impair wound healing and should be avoided[126][127].

11 NSAIDs and Racing

Taking NSAIDs in ultramarathon events can improve performance by reducing pain and acute inflammation, but doing so represents a significant risk. There is some evidence[128] [129] that many runners taking NSAIDs have the same level of pain and greater damage markers compared with non-users. This may be because the runners push themselves to a similar level of pain, with the NSAIDs allowing them to do more damage.

  • It seems likely that NSAIDs will increase the risk of injury rather than reducing it, as the symptoms of damage will be masked.
  • The most common NSAID for racing seems to be ibuprofen. I've not seen any evidence of the relative effectiveness of different NSAIDs on performance.
  • It is better to take liquid ibuprofen than tablets or capsules. The tablets and capsules take longer to dissolve and if you have a digestive problem they may not be fully absorbed. You can chew the tablets, but this is unpleasant and ibuprofen can irritate your mouth and throat slightly, so the liquid form is best. It's obviously harder to transport, but you can fill an old film canister with a dose.
  • Before an ultramarathon race, you should think through under what circumstances you will consider using NSAIDs and what dosage. Make sure your crew knows that you're taking NSAIDs in case anything happens.
  • Extra care should be taken when NSAIDs are used in combination with dehydration, sickness or running the causes serious muscle damage.
  • Taking NSAIDs in marathon or shorter races is probably ineffective as the level of damage seen is not as great as in ultramarathon events.
  • If you need NSAIDs to start a race, you probably should not compete.

12 Longer Term NSAID usage

Using NSAIDs for longer periods of time can lead to serious health problems and can be fatal. I have a running friend who had a bleeding ulcer from using Ibuprofen, which is a known[130] side effect. The likelihood of a bleeding or perforated ulcer goes up with time, from 1% after 3-6 months, to 2-4% after 12 months. 35% of long term Ibuprofen users get an ulcer[131], which are grim odds.

13 Acetaminophen Overdose Danger (AKA Paracetamol, Tylenol)

Acetaminophen does not have the same risk of ulcers, but it is linked to liver damage, especially in those who drink alcohol. Acetaminophen is the leading cause of acute liver failure[132][133]. There are concerns[134] that even the standard dose can cause changes in liver function. Acetaminophen can cause delayed symptoms[133], with people seeking medical help up to 5 days after the overdose (20% < 12 hours, 35% 12-24 hours, 45% 24 hours+). Overdoses of Acetaminophen can be caused by taking slightly too much over several days, with the toxicity building up[133]. This problem is again exacerbated by those taking alcohol with Acetaminophen[133]. (One factor that increases the risk is that some common medications, such as cold remedies, include Acetaminophen. If people do not add in the dose of Acetaminophen from these other sources, it is easy to unwittingly exceed the safe dosage.)

14 Is Acetaminophen an NSAID?

Acetaminophen (also called paracetamol) is generally not classified as an NSAID[135]. While Acetaminophen has limited anti-inflammatory properties, it shares the same mechanism of action with most NSAIDs of inhibiting the COX enzyme and the inhibition of prostaglandin synthesis[136][137][138][139]. Therefore, this article includes Acetaminophen in with NSAIDs.

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