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Research · Medication

NSAIDs

After muscle injury, NSAIDs reduced strength loss, soreness and creatine kinase by a small to medium amount. Training trials split three ways. Ibuprofen raised, did not change, or blunted muscle and strength gains, depending on age and dose. High-dose ibuprofen and diclofenac raised coronary events. All NSAIDs raised gastrointestinal bleeding and kidney injury risk.

Add to Bio HackChecked 2026-11-09
Status
FDA-approved drugs in the US. Ibuprofen and naproxen are sold over the counter at lower strengths and by prescription at higher strengths. Prescription labels carry a boxed warning on serious cardiovascular and gastrointestinal events.
Also called
ibuprofen, Advil, Motrin, naproxen, Aleve, Naprosyn, diclofenac, celecoxib, Celebrex, nonsteroidal anti-inflammatory drugs, anti-inflammatories, painkillers
Taken for
muscle soreness, pain relief, joint pain, recovery, inflammation, training through injury, muscle growth, heavy periods, period pain, endometriosis pain

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help5

Reported risks6

What people take it for, and what was found

Shown to help5

Moderate

Soreness and strength loss after muscle injury

Shown to reduce strength loss, soreness and creatine kinase modestly after acute muscle injury, more for lower body muscles, in studies including animals.

The numbers and sources
Effect
Across injury markers combined, NSAIDs produced a small to medium decrease (standardized effect size +0.34) in strength loss, soreness and blood creatine kinase after acute muscle injury. The effect was larger when lower body muscles were injured [1].
Population
41 studies of acute skeletal muscle injury, human and animal, including exercise-induced damage [1].
Sources
[1]
Caveats
Heterogeneity was moderate (I² 57%). The pooled result includes animal studies, and in animals the effect fell with longer use and longer follow-up [1].
Strong

Joint pain in knee or hip osteoarthritis

Shown to ease knee osteoarthritis pain and stiffness over placebo, including topical diclofenac. Pain relief was similar to exercise therapy.

The numbers and sources
Effect
Pain relief did not differ between exercise therapy and oral NSAIDs or paracetamol at about 4 weeks (SMD -0.12, 95% CrI -1.74 to 1.50), 8 weeks or 24 weeks. Function also did not differ at any time point [2]. Against placebo in knee osteoarthritis, etoricoxib improved WOMAC pain (MD -0.44, 95% CI -0.61 to -0.26), naproxen WOMAC function (MD -0.43, 95% CI -0.82 to -0.04) and diclofenac WOMAC stiffness (MD -0.40, 95% CI -0.67 to -0.13) [3]. Topical diclofenac gel, solution and patch each lowered knee pain and improved function against placebo. The patch gave the largest relief at 1 to 2 weeks (SMD -0.64, 95% CI -0.90 to -0.39), and skin and whole-body side effects stayed low [4].
Population
152 RCTs with 17,431 people with knee or hip osteoarthritis [2]; 31 RCTs with 68,539 people with knee osteoarthritis comparing 16 treatments [3]; 12 RCTs of topical diclofenac in knee osteoarthritis [4].
Sources
[2], [3], [4]
Caveats
The comparison with exercise is mostly indirect, and NSAIDs were pooled with paracetamol. Few trials reported 8- and 24-week results [2]. The network estimates in [3] compare drugs indirectly. [4] covered up to 12 weeks.
Moderate

Low back pain

Shown to lower acute low back pain slightly with diclofenac, with other NSAIDs unconfirmed or showing no benefit.

The numbers and sources
Effect
Against placebo, diclofenac lowered pain intensity in acute low back pain. Ibuprofen in acute low back pain without nerve root pain and naproxen in acute low back pain with nerve root pain showed results the authors rated as needing confirmation. Celecoxib, etoricoxib and ketoprofen showed no evidence of benefit. The authors judged every effect small [5].
Population
11 RCTs with 3,784 people, 1,642 with acute and 2,142 with chronic low back pain [5].
Sources
[5]
Caveats
5 of the 11 trials were at high risk of bias for pain, and more than half used the NSAID as a comparator for another treatment [5].
ModerateStudied in women

Heavy menstrual bleeding

Shown to lower menstrual blood loss more than placebo in women with heavy periods. Tranexamic acid, danazol and the hormonal IUD lowered it more.

Compared with placebo, tranexamic acid, danazol, the levonorgestrel IUD, oral luteal progestogen, ethamsylate, the combined pill, an older progesterone IUD and other NSAIDs [23]

The numbers and sources
Effect
As a group, NSAIDs reduced heavy menstrual bleeding more than placebo and less than tranexamic acid, danazol or the levonorgestrel IUD. In one trial of 11 women, blood loss was 124 mL a cycle lower on mefenamic acid than on placebo (MD -124 mL, 95% CI -186 to -62). In a crossover trial, median loss was 146 mL a cycle on placebo, 123 mL on ibuprofen 600 mg and 110 mL on ibuprofen 1,200 mg. Against tranexamic acid, loss was 73 mL a cycle higher on mefenamic acid (95% CI 22 to 124, 48 women). Naproxen and mefenamic acid did not differ, and no clear difference was found against oral luteal progestogen, ethamsylate, the combined pill or an older progesterone IUD [23].
Population
759 women with regular heavy periods not caused by a disease or treatment, in 19 randomized trials, 9 of them pooled [23].
Sources
[23]
Caveats
The reviewers rated the evidence low to moderate quality, and most trials were small and underpowered. Women whose bleeding had a disease or treatment cause, such as fibroids, were not included, so these trials do not test bleeding from fibroids [23].
StrongStudied in womenVery common

Period pain

Shown to relieve period pain more than placebo, with moderate or excellent relief in 45% to 53% of women against 18% on placebo.

Compared with placebo [24][25]; paracetamol [24]; other NSAIDs and aspirin [24][25]

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In primary dysmenorrhea, NSAIDs gave more pain relief than placebo (OR 4.37, 95% CI 3.76 to 5.09, 35 RCTs, low-quality evidence). If 18% of women on placebo got moderate or excellent relief, 45% to 53% on NSAIDs would. NSAIDs also relieved pain more than paracetamol (OR 1.89, 95% CI 1.05 to 3.43, 3 RCTs). No single NSAID was shown to relieve pain more or cause fewer side effects than another [24]. A network meta-analysis of 13 drugs found most gave more pain relief than aspirin, and ketoprofen, naproxen, rofecoxib and ibuprofen scored higher than placebo on overall assessment [25].
Population
80 RCTs with 5,820 women with primary dysmenorrhea, comparing 20 NSAIDs [24]; 72 RCTs with 5,723 patients [25].
Sources
[24], [25]
Caveats
The Cochrane authors rated most evidence low quality because study methods were poorly reported. 59% of trials were commercially funded and 31% did not state funding [24].

Mixed results1

Limited

Muscle growth and strength with resistance training

Small trials found mixed results: ibuprofen raised muscle gains in older adults, lowered them in young adults against aspirin, and made no difference in another.

The numbers and sources
Effect
Results differ by trial. In older adults training for 12 weeks, ibuprofen 1.2 g a day increased quadriceps volume 10.9% against 8.6% on placebo, and strength 19 kg against 15 kg [6]. In young adults training for 8 weeks, ibuprofen 1,200 mg a day increased quadriceps volume 3.7% against 7.5% on low-dose aspirin, and strength gains on the maximal-effort leg were smaller [7]. In young adults training for 6 weeks, ibuprofen 400 mg after each session did not change biceps thickness or strength against placebo [8]. A systematic review of 7 athlete trials found NSAIDs did not raise collagen synthesis or satellite cell activity after exercise [9].
Population
36 adults aged about 64 to 67 [6]; 31 adults aged 18 to 35 [7]; 18 adults aged about 24, each arm its own control [8]; 346 athletes in 7 RCTs [9].
Sources
[6], [7], [8], [9]
Caveats
Small trials with different doses, ages and comparators. [7] compared ibuprofen with 75 mg aspirin, not placebo. No meta-analysis of training adaptations was sourced.

Not shown to help1

LimitedStudied in women

Endometriosis pain

One small trial found naproxen did not clearly relieve endometriosis pain more than placebo, in very low-quality evidence.

Compared with placebo [26]

The numbers and sources
Effect
Pain relief on naproxen did not differ clearly from placebo (OR 3.27, 95% CI 0.61 to 17.69, 24 women). The need for extra pain medicine (OR 0.12, 95% CI 0.01 to 1.29) and side effects (OR 0.46, 95% CI 0.09 to 2.47) were inconclusive [26].
Population
24 women with endometriosis in one crossover trial, the only one of two included trials that could be analyzed [26].
Sources
[26]
Caveats
One small trial with unclear risk of bias. The review found no new trials in its 2016 update, and no data on quality of life or daily activities [26].

Doses studied

The training trials used ibuprofen 1.2 g a day for 12 weeks [6], 1,200 mg a day for 8 weeks [7] and 400 mg after each session for 6 weeks [8].

Risks

Reported risks6

ModerateStudied in womenVery common

Side effects when taken for period pain

Shown to raise side effects in women taking NSAIDs for period pain, from 10% on placebo to between 11% and 14%, mostly gut and nervous system effects.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Against placebo, overall adverse effects rose (OR 1.29, 95% CI 1.11 to 1.51, 25 RCTs, low-quality evidence), as did gastrointestinal effects (OR 1.58, 95% CI 1.12 to 2.23, 14 RCTs) and neurological effects (OR 2.74, 95% CI 1.66 to 4.53, 7 RCTs). If 10% of women on placebo had side effects, 11% to 14% on NSAIDs would [24].
Population
Women with primary dysmenorrhea in RCTs of NSAIDs against placebo [24].
Sources
[24]
Caveats
Short courses taken during periods. Evidence quality was low [24].
StrongCommon

Heart attack, stroke and heart failure

Shown to raise major vascular events with coxibs and diclofenac, mostly at high doses, about 3 more per 1,000 people a year. Heart failure roughly doubled.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Against placebo, a coxib raised major vascular events by a rate ratio of 1.37 and diclofenac by 1.41. Ibuprofen raised major coronary events (RR 2.22, 95% CI 1.10 to 4.48), while naproxen did not raise major vascular events (RR 0.93). Of 1,000 people on a coxib or diclofenac for a year, 3 more had a major vascular event, 1 of them fatal. Heart failure risk was roughly doubled by all NSAIDs [10]. In people with arthritis at raised cardiovascular risk, the primary cardiovascular outcome occurred in 2.3% on celecoxib, 2.5% on naproxen and 2.7% on ibuprofen [11]. The prescription label states the risk may occur early in treatment and may increase with duration of use [12].
Population
280 placebo-controlled trials with 124,513 participants and 474 head-to-head trials with 229,296 participants [10]; 24,081 adults with osteoarthritis or rheumatoid arthritis on mean daily doses of 2,045 mg ibuprofen, 852 mg naproxen or 209 mg celecoxib, mean follow-up 34.1 months [11].
Sources
[10], [11], [12]
Caveats
The meta-analysis mostly reflects high doses [10]. In [11], 68.8% stopped the study drug and 27.4% left follow-up, and the trial was funded by Pfizer, maker of celecoxib.
StrongHow often is not known

Stomach and intestinal bleeding

Shown to raise stomach and intestinal bleeding with all NSAIDs, about 2 to 4 times, rising with dose and age. Celecoxib had fewer events.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
All NSAID regimens raised upper gastrointestinal complications (perforation, obstruction or bleeding): coxibs RR 1.81, diclofenac 1.89, ibuprofen 3.97 (95% CI 2.22 to 7.10) and naproxen 4.22 (95% CI 2.71 to 6.56) [10]. Gastrointestinal events were less frequent with celecoxib than with naproxen or ibuprofen [11]. The label states these events can occur at any time without warning symptoms, with higher risk in older people [12]. Across 25 studies, odds of gastrointestinal bleeding were 1.16 (95% CI 0.84 to 1.61) for celecoxib, 2.28 (95% CI 1.71 to 3.03) for ibuprofen and 20.67 (95% CI 14.56 to 29.34) for ketorolac [13]. Against non-users, ibuprofen had an odds ratio for upper gastrointestinal bleeding of 2.51 (95% CI 1.33 to 4.74). Against paracetamol, at mostly 1,200 to 1,800 mg a day for a median 1.5 weeks, it did not differ (OR 0.96, 95% CI 0.36 to 2.59) [14]. In trials of celecoxib for up to 10 days for acute pain, gastrointestinal adverse events did not differ from placebo (RR 0.96, 95% CI 0.64 to 1.43) [15].
Population
As above [10][11]; 25 studies [13]; 7 RCTs and 10 observational studies with 89,522 participants [14]; 50 RCTs with 10,693 participants [15].
Sources
[10], [11], [12], [13], [14], [15]
Caveats
Rates rise with dose and age. [13] reported substantial heterogeneity. [14] rated its certainty very low, and [15] rated most outcomes very low certainty.
ModerateHow often is not known

Acute kidney injury

Linked to acute kidney injury about 1.6 to 2 times as often with traditional NSAIDs, including in people with chronic kidney disease.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In cohort studies, risk ratios for acute kidney injury with individual traditional NSAIDs ranged from 1.58 to 2.11 [16]. In the general population, current NSAID use carried an odds ratio of 1.73 (95% CI 1.44 to 2.07), and 1.63 in people with chronic kidney disease [17]. In an 80 km desert race, acute kidney injury occurred in 52% on ibuprofen 400 mg every 4 hours and 34% on placebo (OR 2.1, 95% CI 0.9 to 5.1), one extra case for every 5.5 runners [18]. Renal events were less frequent with celecoxib than ibuprofen in the arthritis trial [11]. In a crossover trial, 600 mg of ibuprofen before 1 hour of running in the heat did not raise kidney or gut injury markers above placebo, though serum IL-8 was higher [19]. Topical diclofenac produced little to no change in creatinine in general populations, with smaller kidney effects than oral diclofenac. In people at raised kidney risk, one cohort found more acute kidney injury in topical NSAID users, mostly of other NSAIDs, and less than with oral NSAIDs [20].
Population
5 cohort studies [16]; 10 population studies [17]; 89 ultramarathon runners [18]; 11 active adults [19]; 18 studies with more than 500,000 participants [20].
Sources
[16], [17], [18], [11], [19], [20]
Caveats
[16] and [17] are observational. [18] was small and did not reach significance. [19] was small and measured markers, not diagnosed kidney injury. [20] did not pool its studies.
ModerateHow often is not known

Use in later pregnancy

The label warns use from about 20 weeks of pregnancy may cause fetal kidney problems, and from 30 weeks early closure of the ductus arteriosus.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The prescription ibuprofen label states that use at about 20 weeks of pregnancy or later may cause fetal kidney problems leading to low amniotic fluid, and that from about 30 weeks NSAIDs raise the risk of premature closure of the fetal ductus arteriosus [12]. In a meta-analysis of observational studies, NSAID use in pregnancy was associated with kidney disease in the child (OR 1.36, 95% CI 1.14 to 1.62), including in the second trimester (OR 1.17) and third trimester (OR 1.10) [21].
Population
Postmarketing reports and studies summarized in the label [12]; 7 studies with 4,159,617 participants [21].
Sources
[12], [21]
Caveats
The label statement is not a trial rate. The authors of [21] state their observational data cannot settle whether the link is causal.
LimitedHow often is not known

Allergic acute coronary syndrome (Kounis syndrome) with diclofenac

Case reports: 27 people had allergic acute coronary events after diclofenac, mostly coronary spasm, and all survived to discharge.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
A review of 27 published cases described acute coronary events with allergic features after diclofenac, most often coronary spasm without underlying coronary disease. Hypotension occurred in 70.4%, hives in 66.7% and chest pain in 85.2%, and all patients survived to discharge. The FDA adverse event database showed a positive reporting signal from 137 reports [22].
Population
27 case patients, 81.5% male; FAERS reports [22].
Sources
[22]
Caveats
Case reports and reporting signals cannot give a rate.

Claims tested and not found

  1. That NSAIDs improve athletic performance. A systematic review of 7 RCTs in athletes found the pooled data did not show performance or other ergogenic gains [9].

Sources

  1. Morelli KM, Brown LB, Warren GL. Effect of NSAIDs on Recovery From Acute Skeletal Muscle Injury: A Systematic Review and Meta-analysis. The American Journal of Sports Medicine. 2017. https://doi.org/10.1177/0363546517697957
  2. Weng Q, Goh SL, Wu J, et al. Comparative efficacy of exercise therapy and oral non-steroidal anti-inflammatory drugs and paracetamol for knee or hip osteoarthritis: a network meta-analysis of randomised controlled trials. British Journal of Sports Medicine. 2023. https://doi.org/10.1136/bjsports-2022-105898
  3. JiaoYi P, YongQi S, KeChun G, et al. Assessing the efficacy and safety of different nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis: A systematic review and network meta-analysis based on RCT trials. PLOS One. 2025. https://doi.org/10.1371/journal.pone.0320379
  4. Chen ZR, Chen BK, Li P, Feng K. Efficacy and safety of different topical diclofenac formulations for the treatment of knee osteoarthritis: a meta-analysis of short-term and long-term treatment comparisons. BMC Musculoskeletal Disorders. 2025. https://doi.org/10.1186/s12891-025-08465-7
  5. Alfieri P, Landry M, Boussageon R. Efficacité du célécoxib, du diclofénac, de l'étoricoxib, de l'ibuprofène, du kétoprofène et du naproxène dans les lombalgies avec ou sans radiculalgie : revue systématique et méta-analyse des essais comparatifs randomisés. Thérapies. 2026. https://doi.org/10.1016/j.therap.2026.04.003
  6. Trappe TA, Carroll CC, Dickinson JM, et al. Influence of acetaminophen and ibuprofen on skeletal muscle adaptations to resistance exercise in older adults. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2011. https://doi.org/10.1152/ajpregu.00611.2010
  7. Lilja M, Mandić M, Apró W, et al. High doses of anti-inflammatory drugs compromise muscle strength and hypertrophic adaptations to resistance training in young adults. Acta Physiologica. 2017. https://doi.org/10.1111/apha.12948
  8. Krentz JR, Quest B, Farthing JP, et al. The effects of ibuprofen on muscle hypertrophy, strength, and soreness during resistance training. Applied Physiology, Nutrition, and Metabolism. 2008. https://doi.org/10.1139/h08-019
  9. Pham H, Spaniol F. The Efficacy of Non-Steroidal Anti-Inflammatory Drugs in Athletes for Injury Management, Training Response, and Athletic Performance: A Systematic Review. Sports. 2024. https://doi.org/10.3390/sports12110302
  10. Coxib and traditional NSAID Trialists' (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. The Lancet. 2013. https://doi.org/10.1016/S0140-6736(13)60900-9
  11. Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. New England Journal of Medicine. 2016. https://doi.org/10.1056/NEJMoa1611593
  12. U.S. Food and Drug Administration. Ibuprofen tablets, prescribing information. 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00872852-680a-41b3-901b-b991b12a176d
  13. Tawfik AG, Gomez-Lumbreras A, Del Fiol G, et al. Nonsteroidal Anti-Inflammatory Drugs and Risk of Gastrointestinal Bleeding: A Systematic Review and Meta-Analysis. Clinical Pharmacology & Therapeutics. 2026. https://doi.org/10.1002/cpt.70054
  14. Gkiouras K, Myrogiannis I, Kouvelas D. Is ibuprofen associated with upper gastrointestinal bleeding? A systematic review and meta-analysis. Inflammopharmacology. 2025. https://doi.org/10.1007/s10787-025-01856-1
  15. Mesa-Castrillon C, Tian Y, Hughes J, et al. Safety Profile of the Non-steroidal Anti-inflammatory Drug Celecoxib in the Short-Term Management of Acute Non-cancer Pain: A Systematic Review with Meta-analysis of Randomised Controlled Trials. Drugs. 2026. https://doi.org/10.1007/s40265-026-02377-z
  16. Ungprasert P, Cheungpasitporn W, Crowson CS, Matteson EL. Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury: A systematic review and meta-analysis of observational studies. European Journal of Internal Medicine. 2015. https://doi.org/10.1016/j.ejim.2015.03.008
  17. Zhang X, Donnan PT, Bell S, Guthrie B. Non-steroidal anti-inflammatory drug induced acute kidney injury in the community dwelling general population and people with chronic kidney disease: systematic review and meta-analysis. BMC Nephrology. 2017. https://doi.org/10.1186/s12882-017-0673-8
  18. Lipman GS, Shea K, Christensen M, et al. Ibuprofen versus placebo effect on acute kidney injury in ultramarathons: a randomised controlled trial. Emergency Medicine Journal. 2017. https://doi.org/10.1136/emermed-2016-206353
  19. Specht JW, Bailly AR, Garcia S, et al. Effect of Ibuprofen on Markers of Acute Kidney Injury, Intestinal Injury, and Endotoxemia after Running in the Heat. Medicine & Science in Sports & Exercise. 2025. https://doi.org/10.1249/mss.0000000000003659
  20. Coșovanu EO, Coșovanu ET, Balan TA, et al. Renal Safety of Topical Diclofenac in Adults with Increased Renal Risk: A Systematic Review. Medicina. 2026. https://doi.org/10.3390/medicina62081606
  21. Cui X, Feng R, Song B, et al. Prenatal NSAIDs exposure and childhood kidney disease: a systematic review and meta-analysis. Frontiers in Pediatrics. 2026. https://doi.org/10.3389/fped.2026.1808919
  22. Abraham B, Sridharan K. Diclofenac-Associated Kounis Syndrome: A Systematic Review and Disproportionality Analysis of FAERS Database. Hospital Pharmacy. 2026. https://doi.org/10.1177/00185787261465849
  23. Bofill Rodriguez M, Lethaby A, Farquhar C. Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding. Cochrane Database of Systematic Reviews. 2019. https://doi.org/10.1002/14651858.cd000400.pub4
  24. Marjoribanks J, Ayeleke RO, Farquhar C, Proctor M. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database of Systematic Reviews. 2015. https://doi.org/10.1002/14651858.cd001751.pub3
  25. Feng X, Wang X. Comparison of the efficacy and safety of non-steroidal anti-inflammatory drugs for patients with primary dysmenorrhea: A network meta-analysis. Molecular Pain. 2018. https://doi.org/10.1177/1744806918770320
  26. Brown J, Crawford TJ, Allen C, et al. Nonsteroidal anti-inflammatory drugs for pain in women with endometriosis. Cochrane Database of Systematic Reviews. 2017. https://doi.org/10.1002/14651858.cd004753.pub4

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