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Joints and tendons

Everything in the library studied for it, medical and holistic together. Within each kind, what was shown to help comes first, strongest evidence first. What was tested and not shown to help stays on the list.

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

Medication13 Peptides and SARMs4 Supplements24 Therapies25 Practices8 Lab markers1

Medication

AcetaminophenStrong

Knee and hip osteoarthritis pain

Shown to lower knee and hip osteoarthritis pain by about 3 points on a 100-point scale, below the 9 points the reviewers set as clinically important.

The numbers and sources

Effect: In 10 placebo-controlled trials, pain fell 23 points on a 0 to 100 scale on placebo and 3.23 points more on paracetamol (95% CI 1.02 to 5.43), against a minimal clinically important difference of 9. Physical function improved 2.9 points more than on placebo (95% CI 0.95 to 4.89). Effects did not differ between 3.0 g a day or less and 3.9 g or more [8]. An earlier meta-analysis found a similar effect on pain (-3.7 points, 95% CI -5.5 to -1.9) and disability (-2.9, 95% CI -4.9 to -0.9) [9]. An overview of systematic reviews put the pain effect at 0.3 points on a 0 to 10 scale (95% CI 0.1 to 0.6) [5].
Population: 3,541 people with hip or knee osteoarthritis in 10 trials at 1.95 to 4 g a day, most followed for 3 months [8]; 13 randomized trials in spinal pain and osteoarthritis [9].
Sources: [8], [9], [5]
Caveats: The reviews share trials and authors. No trial reported quality of life [8].

NSAIDsStrong

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.

Opioid pain relieversStrong

Knee and hip osteoarthritis pain

Shown to lower knee and hip osteoarthritis pain by small amounts against placebo, about 0.7 points of 10 for oxycodone-type opioids and 4% for tramadol.

The numbers and sources

Effect: In 22 trials, 10 of them of oral oxycodone, opioids lowered pain by 0.7 cm on a 10 cm scale against placebo (SMD -0.28, 95% CI -0.35 to -0.20), a number needed to treat of 10, and improved function by 0.6 units on a 0 to 10 scale. Effects were larger in trials of 4 weeks or less. Dropouts over adverse events were 6.4% against 1.7% [9]. In 22 trials of tramadol, pain improved 4% more than on placebo (95% CI 3% to 5%), and 15 of 100 against 10 of 100 improved by 20%. Physical function improved 4% more (95% CI 2% to 6%). The authors judged neither an important benefit [10].
Population: 8,275 people with knee or hip osteoarthritis in 22 trials [9]; 22 trials with 3,871 participants randomized to tramadol alone or with acetaminophen and 2,625 to placebo or an active control, mean duration 2 months [10].
Sources: [9], [10]
Caveats: Most tramadol trials were funded by industry, and 10 of 22 had incomplete outcome data [10]. The first review found signs of small-study bias [9].

Oral corticosteroidsStrong

Rheumatoid arthritis

Shown to ease joint tenderness and pain in rheumatoid arthritis more than placebo or NSAIDs, and to slow joint damage on X-ray over 1 to 2 years.

The numbers and sources

Effect: Low-dose prednisolone, at no more than 15 mg a day, improved joint tenderness against placebo by 12 tender joints (95% CI 6 to 18) and improved pain (SMD 1.75, 95% CI 0.87 to 2.64) and grip strength. Against NSAIDs it improved joint tenderness by 9 joints (95% CI 5 to 12) and pain (SMD 1.25, 95% CI 0.26 to 2.24) [4]. Across 15 studies, mostly in early disease and added to other disease-modifying drugs, glucocorticoids slowed X-ray progression (SMD 0.40, 95% CI 0.27 to 0.54), with a similar effect at 2 years (0.42, 95% CI 0.30 to 0.55) [5]. In a 2-year trial of prednisone 10 mg a day, clinical improvement over placebo was seen mainly in the first 6 months and X-ray progression was lower after month 6, with more osteoporotic fractures in the prednisone group [6].
Population: 320 people with rheumatoid arthritis in 10 short-term studies [4]; 1,414 people in 15 studies [5]; people with early active rheumatoid arthritis not yet on disease-modifying drugs [6].
Sources: [4], [5], [6]
Caveats: The short-term review covers small trials [4]. The mean cumulative dose in the X-ray studies was 2,300 mg of prednisone equivalent in the first year [5].

AllopurinolModerateVery common

Lowering uric acid in gout

Shown to lower blood uric acid, with 25 of 26 people on 300 mg a day reaching the target within 30 days against none of 25 on placebo.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: In the one placebo-controlled trial in a Cochrane review, 25 of 26 people on allopurinol 300 mg a day reached the target serum urate over 30 days against 0 of 25 on placebo [1]. At a fixed 300 mg a day for 52 weeks, 21% had urate below 6.0 mg/dL at the last three monthly measurements [2]. When the dose was raised step by step, 69% had urate below 6 mg/dL at 12 months against 32% of those left on their starting dose, with mean changes of -1.5 and -0.34 mg/dL [3]. In a 72-week trial that raised doses toward a urate target, 80% reached it on allopurinol or febuxostat with no difference between them [4].
Population: 4,531 participants in 11 trials, 2 of them placebo-controlled [1]; 760 people with gout and urate of at least 8.0 mg/dL [2]; 183 people with gout already on allopurinol, 52% with reduced kidney function [3]; 940 people with gout, at least a third with stage 3 chronic kidney disease [4].
Sources: [1], [2], [3], [4]
Caveats: The placebo comparison rests on one trial of 57 people [1]. The share reaching target depended on whether the dose was fixed or raised [2][3].

SGLT2 inhibitorsModerate

Gout

Shown to lower gout events by about 45% against placebo in adults with type 2 diabetes or heart failure, in one meta-analysis of five trials.

The numbers and sources

Effect: Across five randomized trials with 1,052 gout-related events, SGLT2 inhibitors were associated with fewer gout outcomes than placebo (HR 0.55, 95% CI 0.45 to 0.67). The effect was smaller with empagliflozin (HR 0.68, 95% CI 0.57 to 0.81) than in the other trials (HR 0.46, 95% CI 0.39 to 0.55), and was not explained by how far uric acid fell [18].
Population: 29,776 patients in five trials, 23,780 with type 2 diabetes [18].
Sources: [18]
Caveats: Not an approved use. Gout was not a primary outcome of the trials, and heterogeneity was moderate (I² 61%) [18].

SNRIsModerate

Chronic back pain and osteoarthritis pain

Shown to lower back pain by about 5 points on a 100-point scale, which reviewers called not clinically important, and osteoarthritis pain by about 10 points.

The numbers and sources

Effect: On a scale from 0 to 100, SNRIs lowered back pain by 5.30 points more than placebo at 3 to 13 weeks (95% CI 3.30 to 7.31) and osteoarthritis pain by 9.72 points (95% CI 6.69 to 12.75). Back pain disability fell by 3.55 points. The authors judged the back pain effect small and not clinically important, and could not exclude a clinically important effect in osteoarthritis [17]. Across chronic pain conditions, duloxetine 60 mg lowered pain intensity against placebo (SMD -0.31, 95% CI -0.39 to -0.24) [15].
Population: 5,318 participants with back pain, sciatica or osteoarthritis in 33 trials [17]; 4,959 participants in 18 studies for pain intensity [15].
Sources: [17], [15], [18]
Caveats: Certainty was moderate for back pain and low for osteoarthritis [17]. Duloxetine is the only SNRI with a chronic musculoskeletal pain approval [18]. Most trials were short and excluded people with low mood [15].

Ezetimibe and fenofibrateLimited

Fenofibrate: uric acid and gout

One trial's later analysis found fenofibrate lowered uric acid about 20% and nearly halved first gout attacks over 5 years in type 2 diabetes, 2% against 3%.

Compared with placebo [15]

The numbers and sources

Effect: Uric acid fell 20.2% during the fenofibrate run-in and stayed 20.1% lower than placebo at 1 year. First gout events were 81 (2%) on fenofibrate and 151 (3%) on placebo over 5 years (HR 0.54, 95% CI 0.41 to 0.70), and all gout events halved (HR 0.48) [15].
Population: 9,795 adults aged 50 to 75 with type 2 diabetes [15].
Sources: [15]
Caveats: A post hoc analysis of a heart trial, not a gout trial.
Why limited: This rests on one trial, of 9,795 people. Strength counts independent studies that agree, so one trial is limited at any size.

RetatrutideGrey marketLimited

Knee osteoarthritis pain

One trial found knee pain scores fell about 1.5 points more than placebo in people with knee osteoarthritis. The placebo group also improved.

The numbers and sources

Effect: In people with knee osteoarthritis, the WOMAC pain score changed by -3.4, -3.9 and -4.1 on 4, 9 and 12 mg, against -2.5 on placebo by intention to treat, differences of -1.4 and -1.6 points for 9 mg and 12 mg [1].
Population: 574 participants with knee osteoarthritis within TRIUMPH-1 [1].
Sources: [1]
Caveats: A subgroup of one trial. The placebo group also improved by 2.5 points.

AllopurinolModerate

Gout flares

Mixed results: no fewer gout attacks than placebo over 30 days in one small trial, and flares became less frequent with continued treatment in longer trials.

The numbers and sources

Effect: Over 30 days, gout attacks occurred in 2 of 26 people on allopurinol 300 mg and 3 of 25 on placebo (RR 0.64, 95% CI 0.12 to 3.52) [1]. Over weeks 9 to 52 of a year-long trial, 64% on allopurinol had a flare, and the incidence fell with continued treatment [2]. In the final 24 weeks of a 72-week trial, 36.5% on allopurinol had one or more flares against 43.5% on febuxostat, meeting the test for noninferiority [4]. The label states that gout attacks usually become shorter and less severe after several months of treatment [5].
Population: 51 people in the placebo-controlled trial [1]; 760 people with gout [2]; 940 people with gout [4].
Sources: [1], [2], [4], [5]
Caveats: The longer trials had no placebo group, so the fall in flares over time has no untreated comparison [2][4].

AllopurinolModerate

Compared with febuxostat

Not shown to differ from febuxostat in gout flares or major cardiovascular events. One trial found fewer deaths on allopurinol.

The numbers and sources

Effect: Across 3 trials, gout attacks over 8 to 24 weeks occurred in 21% on allopurinol up to 300 mg and 23% on febuxostat 80 mg (RR 0.89, 95% CI 0.71 to 1.1) [1]. At fixed doses, 21% on allopurinol 300 mg reached the urate target against 53% and 62% on febuxostat 80 and 120 mg, with flares over weeks 9 to 52 in 64%, 64% and 70% [2]. With doses raised to target, flares in the last phase were 36.5% on allopurinol and 43.5% on febuxostat [4]. In people with gout and cardiovascular disease, the main cardiovascular outcome occurred in 10.4% on allopurinol and 10.8% on febuxostat (HR 1.03), and death from any cause was more frequent on febuxostat (HR 1.22, 95% CI 1.01 to 1.47), as was cardiovascular death (HR 1.34, 95% CI 1.03 to 1.73) [6].
Population: 1,136 participants in 3 trials [1]; 760 people with gout [2]; 940 people with gout [4]; 6,190 people with gout and cardiovascular disease followed a median of 32 months [6].
Sources: [1], [2], [4], [6]
Caveats: In the cardiovascular trial 56.6% stopped the study drug and 45.0% left follow-up [6].

Low-dose naltrexoneModerate

Chronic pain across conditions

Not shown to improve pain or quality of life across chronic pain conditions, with less pain than placebo only in fibromyalgia in one analysis.

The numbers and sources

Effect: In a meta-analysis of 7 RCTs, pain response did not differ from control overall (d -0.11, 95% CI -0.96 to 0.74). Against placebo in fibromyalgia, pain was lower (d -0.34, 95% CI -0.62 to -0.06). Against active drugs, there was no difference [6]. A systematic review of 7 RCTs (406 patients) at 2 to 4.5 mg a day found no improvement in pain or quality of life across chronic pain conditions [7]. In 23 people with osteoarthritis or inflammatory arthritis, 8 weeks of 4.5 mg did not change pain interference (-23 points against -22 on placebo, p 0.90), pain severity or fatigue [8].
Population: Adults with chronic pain conditions, including fibromyalgia [6][7], and 17 people with osteoarthritis and 6 with inflammatory arthritis [8].
Sources: [6], [7], [8]
Caveats: The arthritis trial was a pilot too small to rule out a modest effect [8].

Oral corticosteroidsModerate

Gout flares, compared with NSAIDs

Not shown to differ from indomethacin or naproxen in pain relief for a gout flare in two randomized trials.

The numbers and sources

Effect: In emergency departments, pain fell by about 25 mm at rest and 45 mm with activity on a 100 mm scale over 14 days on both prednisolone and indomethacin. Minor adverse events in the emergency department were less frequent on prednisolone (6% against 19%) and equal over 14 days (37% each) [7]. In primary care, pain at 90 hours had fallen 44.7 mm on prednisolone and 46.0 mm on naproxen (difference 1.3 mm, 95% CI -9.8 to 7.1), with similar adverse effects [8].
Population: 416 adults with acute gout in 4 Hong Kong emergency departments, 376 completing [7]; 120 primary care patients with crystal-confirmed gout, given prednisolone 35 mg or naproxen 500 mg twice a day for 5 days [8].
Sources: [7], [8]
Caveats: Neither trial had a placebo group. In the larger trial gout was usually diagnosed on clinical criteria [7].

Peptides and SARMs

BPC-157Grey marketLimited

Knee pain

One small uncontrolled study found 14 of 16 patients reported knee pain relief after BPC-157 injections, some combined with thymosin beta-4.

Compared with the same patients' recall of their pain before the injection, with no other group [14]

The numbers and sources

Effect: A chart review at one US clinic reached 16 patients by phone 6 months to 1 year after a knee injection. Of 12 who received BPC-157 alone, 11 reported significant improvement in knee pain. Of 4 who received BPC-157 with thymosin beta-4, 3 reported significant improvement. Overall, 14 of 16 (87.5%) reported relief. No tools were used to measure function, stiffness, quality of life or daily activities [14]. A 2026 systematic review judged the study of poor methodological quality and rated the certainty of evidence very low [9].
Population: 16 patients with knee pain of several causes, from a chart review covering 2019 to 2020 [14].
Sources: [14], [9], [10]
Caveats: Retrospective, uncontrolled and unblinded, with pain recalled in a phone survey [14]. With no comparison group, the study cannot separate an effect of the injection from placebo response or natural recovery. A 2026 review describes human musculoskeletal evidence for BPC-157 as limited to this one small case series without validated outcome measures [10].

BPC-157Grey marketUntested

Tendon and ligament healing

Not studied in people. Animal studies found faster healing of cut tendons and ligaments in rats, from a handful of research groups.

No study in people. This rests on animal studies, lab studies.

The numbers and sources

Effect: A 2019 review found that studies of BPC-157 reported consistent healing effects on tendon, ligament and skeletal muscle, mostly in small rodent models, from a handful of research groups [15]. A 2025 systematic review included 35 preclinical studies and found that BPC-157 improved functional, structural and biomechanical outcomes in tendon, ligament, muscle and bone injuries in those models [16]. After the medial collateral ligament of the knee was cut in rats, BPC-157 given by injection, in drinking water or as a cream improved functional, biomechanical, macroscopic and microscopic healing over 90 days [17]. In the lab, it sped the outgrowth of fibroblasts from rat Achilles tendon tissue, raised their survival under oxidative stress and increased their migration, without directly changing how fast they multiplied [18]. In a 2026 study, rats given BPC-157 after Achilles tendon repair had a higher load to failure and lower tendon damage scores than controls at 4 weeks, but neither difference was statistically significant [19].
Population: Rats, and tendon cells from rats in the lab [15][16][17][18]. 32 rats in the 2026 study [19].
Sources: [15], [16], [17], [18], [19]
Caveats: The 2019 review notes that efficacy has not been confirmed in humans [15]. Surgically cut tendons and ligaments in rats do not show what happens in people. A 2026 review found no controlled human orthopaedic evidence for BPC-157 [10].

TB-500Grey marketUntested

Tendon healing

Not studied in people. One rat study found stronger repaired Achilles tendons and better tissue scores after 4 weeks of TB-500.

No study in people. This rests on animal studies.

The numbers and sources

Effect: In rats whose Achilles tendon was cut and repaired, those given TB-500 for 4 weeks had a higher maximum load to failure than controls, a statistically significant difference, and lower total tendon damage scores on two microscopic scoring scales. Adding BPC-157 to TB-500 gave no further benefit over either alone [15]. A 2026 review found that direct musculoskeletal evidence for full-length thymosin beta-4 is limited to lab and rodent studies, and that TB-500 has no validated equivalence with it [9].
Population: 32 male rats, 8 in each of four groups [15].
Sources: [15], [9]
Caveats: One small study, which its authors describe as exploratory and preliminary [15]. Surgically cut tendons in rats do not show what happens in people. FDA found no clinical studies of TB-500 by any route [3].

TB-500Grey marketNo research yet

Flexibility

We haven't sourced research on this yet.

Supplements

BoswelliaStrong

Knee osteoarthritis pain and function

Shown to lower knee osteoarthritis pain and stiffness and improve function against control in adults, in mostly small, low-quality trials.

The numbers and sources

Effect: In 7 trials (545 patients), boswellia lowered VAS pain (WMD -8.33, 95% CI -11.19 to -5.46) and WOMAC pain (WMD -14.22), stiffness (WMD -10.04) and function scores (WMD -10.75) against control [1]. A meta-analysis of 11 RCTs (1,009 patients) of curcuminoids and boswellia found both improved pain and function more than placebo [2]. A 2026 network meta-analysis of 20 RCTs (1,633 participants) found modified boswellia formulations improved WOMAC pain, stiffness and function [3].
Population: Adults with knee osteoarthritis, mostly mild to moderate [1][2][3].
Sources: [1], [2], [3]
Caveats: Study quality was low overall, and most trials had fewer than 100 participants. No RCT compared boswellia with approved NSAIDs [2]. The abstracts do not report trial funding.

CollagenStrong

Tendon size and stiffness with training

Shown to improve tendon size alongside training in healthy adults, with stiffness gains at 15 to 30 g a day, though certainty was very low.

The numbers and sources

Effect: Across 19 RCTs (768 healthy adults) training for 8 weeks or more, collagen peptides improved tendon morphology (SMD 0.67) [1]. In a systematic review of 8 RCTs (257 people, 246 of them men) with resistance or plyometric training for 3 to 15 weeks, tendon cross-sectional area grew more on collagen than placebo in 3 of 4 studies. Tendon stiffness rose more on collagen in the 2 studies using 15 to 30 g a day, and the studies using about 5 g a day showed within-group changes only [2].
Population: Healthy adults over 17 in exercise programs [1]; trained adults aged 18 to 52 [2].
Sources: [1], [2]
Caveats: GRADE certainty for tendon outcomes was very low [1]. Trials were small and short, and nearly all participants were men [2]. The second review did not pool results [2].

CollagenStrong

Joint pain and function

Shown to ease joint pain and improve joint function in recreational athletes and others, in reviews that did not pool results.

The numbers and sources

Effect: A systematic review of 15 RCTs, 12 in recreational athletes, reported the most consistent benefit for joint function and joint pain [3]. A systematic review of 36 RCTs of type I collagen hydrolysate found joint studies reported less pain, better clinical scores, more mobility and better ankle function [4].
Population: Recreational athletes, older adults and premenopausal women [3]; RCTs of type I collagen alone, with varied populations and health conditions [4].
Sources: [3], [4]
Caveats: Both reviews are narrative, without pooled effect sizes, and heterogeneity among trials limits generalization [4]. In a 2026 trial in 74 healthy people with joint discomfort during activity, 40 mg a day of undenatured type II collagen for 180 days improved joint scores, but so did placebo, and between-group differences appeared only in subgroups [5].

Thunder god vineCautionStrong

Rheumatoid arthritis

Shown to improve joint swelling, stiffness and grip in adults with rheumatoid arthritis, matching or beating standard drugs, in trials mostly from China.

The numbers and sources

Effect: Across 14 RCTs, TwHF extracts improved grip strength, swollen joint count and morning stiffness against placebo (P < 0.001). Against DMARDs, grip strength, morning stiffness, CRP and tender joint count differed (P < 0.05), and ESR and swollen joint count did not [1]. Across 40 RCTs (3,092 patients), tripterygium glycosides added to DMARDs lowered morning stiffness, tender and swollen joint counts, pain scores, CRP, ESR and rheumatoid factor against DMARDs alone (all p < .001) [2]. A network meta-analysis of 21 trials (5,039 participants) ranked TwHF with methotrexate first and TwHF alone second for ACR20 response among the conventional DMARDs compared [3]. In 207 patients, ACR50 response at 24 weeks was 46.4% on methotrexate, 55.1% on TwHF (p 0.014) and 76.8% on both (p < 0.001) [4]. In 121 US patients, 65.0% on TwHF extract and 32.8% on sulfasalazine met ACR20 at 24 weeks (P 0.001) [5].
Population: Adults with active rheumatoid arthritis, mostly in China [1][2][3][4]. 121 patients at US centers [5].
Sources: [1], [2], [3], [4], [5]
Caveats: The methotrexate trial was open label, with blinded assessors [4]. In the sulfasalazine trial only 62 patients had outcome data at 24 weeks, and 62% and 41% stayed on treatment [5]. Most pooled trials were small and Chinese.

TurmericStrong

Knee osteoarthritis pain and function

Shown to lower knee pain and improve function more than placebo in adults with knee osteoarthritis, similar to NSAIDs, in short trials and low-quality reviews.

The numbers and sources

Effect: Across 16 RCTs (1,810 adults, up to 16 weeks), turmeric extracts reduced knee pain (SMD -0.82, 95% CI -1.17 to -0.47, I² 86.23%) and improved function (SMD -0.75, 95% CI -1.18 to -0.33) against placebo, with effects similar to NSAIDs. Higher BMI was linked to less improvement [1]. A second meta-analysis of 15 RCTs (1,621 participants) also reported lower VAS and WOMAC pain, function and stiffness scores than placebo and similar effects to NSAIDs [2]. A network meta-analysis of 17 RCTs found every turmeric preparation reduced WOMAC pain against placebo, by MD -3.17 (95% CI -5.50 to -0.83) for conventional curcuminoids and -2.47 (95% CI -3.27 to -1.67) for bioavailability-enhanced forms [3]. Another network meta-analysis of 20 RCTs (1,633 participants) found lower VAS pain against placebo only with modified Curcuma longa formulations (SMD -2.82, 95% CI -5.30 to -0.33) [4].
Population: Adults with knee osteoarthritis [1][2][3][4].
Sources: [1], [2], [3], [4], [5]
Caveats: Heterogeneity was high, trials were short, and risk of bias was moderate [1]. Imaging and biochemical markers did not differ [1]. Certainty was low in the 17-trial network analysis [3]. A review of 7 earlier systematic reviews rated their methods extremely low in quality, with heavy overlap of trials and 37 of 48 outcomes at extremely low evidence quality [5].

TurmericStrong

Rheumatoid arthritis

Shown to lower disease activity, joint counts and inflammation markers in adults with rheumatoid arthritis, in few small trials with very low certainty.

The numbers and sources

Effect: Across 6 publications (539 patients), curcumin lowered DAS28 (MD -1.20, 95% CI -1.85 to -0.55), ESR (MD -29.47), swollen joint count (MD -5.33) and tender joint count (MD -6.33) against controls [19]. Across 7 RCTs, DAS28 fell by 1.47 (95% CI -1.68 to -1.26), with lower rheumatoid factor, ESR and CRP [20]. Across 6 placebo-controlled trials (244 participants), ACR20 response, DAS28, ESR, CRP, pain and joint counts all improved, with very low certainty for most outcomes [21].
Population: Adults with rheumatoid arthritis [19][20][21].
Sources: [19], [20], [21]
Caveats: The trials were few and small, heterogeneity was substantial [20], and the certainty of evidence was very low [21].

Vitamin DStrong

Rheumatoid arthritis disease activity

Shown to lower disease activity modestly in adults with rheumatoid arthritis. Reviews disagree on CRP, ESR and pain.

The numbers and sources

Effect: Across 6 studies (438 patients), vitamin D lowered DAS28 (WMD -0.41, 95% CI -0.59 to -0.23), ESR (WMD -3.40) and tender joint count (WMD -1.44) against control [6]. Across 11 RCTs, it lowered pain scores (WMD -1.30) and DAS28-CRP (WMD -0.58, 95% CI -0.86 to -0.31), while CRP, ESR and HAQ did not change [7]. A third meta-analysis of 11 studies found lower DAS28 (WMD -0.83, 95% CI -1.38 to -0.28), CRP and ESR, with no change in HAQ or pain scores [8].
Population: Adults with rheumatoid arthritis in RCTs [6][7][8].
Sources: [6], [7], [8]
Caveats: The reviews disagree on CRP, ESR and pain, and heterogeneity was high [7].

CollagenModerate

Osteoarthritis symptoms

Shown to lower total osteoarthritis scores by about 8 points and lower pain ratings, though the WOMAC pain subscore did not change.

The numbers and sources

Effect: In placebo-controlled trials, collagen lowered total WOMAC score by 8.00 points (95% CI -13.04 to -2.95) and VAS pain by 16.57 points (95% CI -26.24 to -6.89). Within WOMAC, stiffness fell (-0.41) but the pain (-0.22, 95% CI -1.58 to 1.13) and function subscores did not change [9].
Population: Adults with osteoarthritis [9].
Sources: [9]
Caveats: The pain subscore and the separate VAS pain score point in different directions. The abstract does not report the number of trials or their funding.

GingerModerate

Osteoarthritis pain

Shown to reduce osteoarthritis pain and disability modestly in adults over placebo.

The numbers and sources

Effect: In 5 placebo-controlled trials (593 patients), ginger reduced pain (SMD -0.30, 95% CI -0.50 to -0.09, I² 27%) and disability (SMD -0.22, 95% CI -0.39 to -0.04) [6].
Population: Adults with osteoarthritis [6].
Sources: [6]
Caveats: The authors rated the evidence moderate quality because trials were small and lacked proper intention-to-treat analysis [6].

Glucosamine and chondroitinModerateVery common

Chondroitin and pain in shorter trials

Shown to lower pain about 10% in trials under 6 months in people with osteoarthritis, mostly of the knee. Reviews disagree on whether this is meaningful.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: Across 43 RCTs, chondroitin lowered pain by an absolute 10% (95% CI 6 to 15%) in studies under 6 months, with I² 70% and low-quality evidence. A 20% reduction in knee pain was reached by 53 per 100 on chondroitin and 47 per 100 on placebo (RR 1.12, 95% CI 1.01 to 1.24, 2 trials, high-quality evidence) [4].
Population: 4,962 participants on chondroitin and 4,148 controls, mostly knee osteoarthritis, 1 month to 3 years [4].
Sources: [4]
Caveats: This review and the network meta-analysis disagree on whether chondroitin's pain effect is clinically meaningful [1][4]. High heterogeneity was not explained by bias or sample size [4].

MSMModerate

Knee osteoarthritis pain and function

Shown to improve knee osteoarthritis physical function scores over placebo in adults, with pain results mixed and gains called small.

The numbers and sources

Effect: On 6 g a day for 12 weeks, WOMAC pain and physical function improved against placebo (P < 0.05). Stiffness and total symptom scores did not change [1]. On 3.4 g a day for 12 weeks, WOMAC physical function (14.6 mm, P = 0.04) and total score (15.0 mm, P = 0.03) improved. WOMAC pain did not reach significance (P = 0.08) [2]. On 1.5 g a day, the pain index fell from 1.53 to 0.74, and more with glucosamine added [3]. A 2008 review called the MSM trials positive but not definitive [4].
Population: 50 adults aged 40 to 76 [1]; 49 adults aged 45 to 90 [2]; 118 people with mild to moderate knee osteoarthritis [3]; 168 people in 2 MSM trials [4].
Sources: [1], [2], [3], [4]
Caveats: The authors of [2] call the improvements small and of uncertain clinical significance. The review raised concerns about dose and treatment length [4].

BoronLimited

Joint pain and arthritis

Small trials found boron supplements eased knee discomfort over 2 weeks and lowered inflammation markers in arthritis. Several were short, and one was run by the maker.

The numbers and sources

Effect: In 60 adults with self-reported knee discomfort, calcium fructoborate 110 mg twice a day lowered McGill Pain Questionnaire scores by 8.9 points and WOMAC scores by 13.73 points more than placebo at day 14 (both p < 0.0001), with no change on placebo [10]. In 60 adults with knee osteoarthritis, 15 days of calcium fructoborate improved C-reactive protein, fibrinogen and sedimentation rate against placebo, with no serious adverse events [11]. In 72 people with rheumatoid arthritis on etanercept, calcium fructoborate or borax (6 mg of boron a day) for 60 days improved disease activity scores and lowered ESR, hsCRP, IL-1α, IL-6 and TNF-α against placebo [12]. A 1994 review reported a 20-person trial in osteoarthritis in which 50% improved on 6 mg of boron a day against 10% on placebo [13].
Population: 60 adults aged 35 to 65 with knee discomfort in Mexico [10]. 60 middle-aged adults with knee osteoarthritis [11]. 72 adults with rheumatoid arthritis in Iraq [12]. 20 adults with osteoarthritis [13].
Sources: [10], [11], [12], [13]
Caveats: Trials ran 2 weeks to 2 months. The knee discomfort trial was designed by FutureCeuticals, which supplied the calcium fructoborate and employed most authors [10]. The 20-person trial is known only from its author's review [13]. No meta-analysis was located.

CollagenLimited

Collagen synthesis and tendon or ligament injury

Limited evidence: 15 g of vitamin C-enriched gelatin doubled a blood marker of collagen synthesis in 8 men. Injury studies were sparse and low certainty.

The numbers and sources

Effect: In 8 healthy men, 15 g of vitamin C-enriched gelatin taken 1 hour before 6 minutes of rope skipping doubled a blood marker of collagen synthesis (amino-terminal propeptide of collagen I). The abstract reports this doubling for the 15 g dose, not the 5 g dose [11]. A systematic review of 15 RCTs reported collagen synthesis rates were raised with 15 g a day [3]. A 2026 review of 6 studies in tendon and ligament tears, repairs and related conditions found collagen-based treatments associated with better pain, function, analgesic use or imaging results [12].
Population: 8 healthy men, crossover [11]; 15 RCTs, mostly recreational athletes [3]; people with tendon or ligament tears, after ACL reconstruction or rotator cuff repair, and with tendinopathy or ankle instability [12].
Sources: [3], [11], [12]
Caveats: Blood markers and engineered ligaments in a lab, not injury rates [11]. In the injury review, most oral products contained several ingredients besides collagen, and its authors rated the evidence sparse and low certainty [12].

Fish oilModerate

Rheumatoid arthritis

Mixed results: one review found better disease activity markers in rheumatoid arthritis, while others found small or no effects on pain and swollen joints.

The numbers and sources

Effect: Across 20 RCTs (1,252 patients), omega-3 improved eight disease activity markers. Of five inflammatory markers, only leukotriene B4 fell (SMD -0.440, 95% CI -0.676 to -0.205) [11]. Across 23 placebo-controlled trials, pooled effects on pain (SMD -0.16, 95% CI -0.40 to 0.09), tender joints (SMD -0.20, 95% CI -0.46 to 0.05) and swollen joints (SMD -0.10, 95% CI -0.28 to 0.07) were small, with intervals that include no effect [12]. Across 18 RCTs (1,018 patients), tender joint count fell (SMD -0.59, 95% CI -0.79 to -0.39), while ESR, CRP and DAS28 did not change significantly [13].
Population: Adults with rheumatoid arthritis in RCTs [11][12][13].
Sources: [11], [12], [13]
Caveats: The certainty of the evidence was mostly very low or low [12]. The authors of [12] note that earlier findings of lower NSAID use may reflect inadequate blinding.

Fish oilModerate

Chronic pain and knee osteoarthritis

Mixed results: omega-3 lowered chronic pain but not osteoarthritis pain in one review, while krill oil reviews found better knee osteoarthritis pain scores.

The numbers and sources

Effect: Across 41 RCTs (3,759 participants), omega-3 lowered chronic pain intensity (SMD -0.55, 95% CI -0.76 to -0.34, I² 87%), from -0.27 at 1 month to -0.83 at 6 months. Effects were significant in rheumatoid arthritis, migraine and mixed chronic pain, and not in osteoarthritis or breast pain [27]. In knee osteoarthritis, krill oil improved WOMAC pain (SMD -0.60, 95% CI -0.99 to -0.21), stiffness and function across 5 RCTs (730 participants), with no change on a visual analog pain scale [28]. A 2026 review of 6 RCTs (971 participants) also found better WOMAC pain and function at week 4 [29].
Population: Adults with chronic pain conditions [27]; adults with knee osteoarthritis [28][29].
Sources: [27], [28], [29]
Caveats: Heterogeneity was high in [27]. The reviews disagree on osteoarthritis, though the krill reviews tested one product type. Lower doses (1.35 g a day or less) did as well as higher doses [27].

Glucosamine and chondroitinModerate

Glucosamine product type

Mixed results: trials of the Rotta preparation showed larger pain relief, while other preparations and well-concealed trials found no benefit.

The numbers and sources

Effect: Across 20 RCTs, glucosamine improved pain (SMD -0.61, 95% CI -0.95 to -0.28), but analyses limited to 8 trials with adequate allocation concealment found no benefit. Trials of the Rotta preparation showed pain SMD -1.31, while non-Rotta preparations showed SMD -0.15 (95% CI -0.35 to 0.05) [5].
Population: 2,570 patients in 20 RCTs [5].
Sources: [5]
Caveats: WOMAC pain, function and stiffness did not differ from placebo in this review. The 2005 search predates the large independent trials [2][3].

Glucosamine and chondroitinModerate

Joint space narrowing

Mixed results: one review found minute differences in joint space width, while others found slightly less narrowing with chondroitin or Rotta glucosamine.

The numbers and sources

Effect: Differences in joint space width were minute, with credible intervals overlapping zero for all three preparations [1]. In 2 trials, loss of minimum joint space width was 4.7% less with chondroitin (95% CI 1.6% to 7.8%) [4]. Two Rotta glucosamine trials found slower radiological progression over 3 years (SMD 0.24) [5].
Population: Adults with knee osteoarthritis followed up to 3 years [1][4][5].
Sources: [1], [4], [5]
Caveats: Reviews disagree. Joint space width is a structural measure and was not tied to symptoms in these abstracts.

ProbioticsModerate

Rheumatoid arthritis

Mixed results: reviews agree probiotics lower CRP or IL-6 in rheumatoid arthritis, but disagree on disease activity.

The numbers and sources

Effect: Across 9 studies (361 patients), probiotics lowered IL-6 (SMD -0.708) and did not change disease activity scores (MD 0.023, 95% CI -0.584 to 0.631) [8]. Across 4 RCTs (153 participants), DAS fell (SMD -0.58, 95% CI -0.97 to -0.19), CRP fell borderline (SMD -0.32, 95% CI -0.65 to 0.00), and ESR and cytokines did not change [9]. A review of 8 RA trials (344 patients) found CRP 3.04 mg/L lower (95% CI -4.47 to -1.62). With high risk-of-bias trials excluded, DAS28 did not differ from placebo (SMD -0.54, 95% CI -1.94 to 0.85) [10].
Population: Adults with rheumatoid arthritis, mostly women, over 8 weeks to 1 year [8][9][10].
Sources: [8], [9], [10]
Caveats: The reviews agree on lower CRP or IL-6 and disagree on disease activity. Strains, doses and durations varied [10].

BromelainLimited

Joint pain and osteoarthritis

Limited evidence: one trial found no change in knee osteoarthritis scores against placebo, and pooled studies across conditions found slightly lower pain.

The numbers and sources

Effect: In 47 adults with moderate to severe knee osteoarthritis, 800 mg a day for 12 weeks did not change the total WOMAC score against placebo (coefficient 11.16, 95% CI -8.86 to 31.18, p 0.27) [6]. In 40 adults with mild to moderate knee osteoarthritis, 500 mg a day did not differ from diclofenac 100 mg a day at 4 weeks [7]. Across 9 studies of oral bromelain in various conditions, pain scores were slightly lower than in controls (MD -0.27, 95% CI -0.45 to -0.08, I² 29%) [8]. An earlier review found that all trials before 2004 were uncontrolled or comparative [9].
Population: Adults with knee osteoarthritis [6][7]. Mixed conditions [8].
Sources: [6], [7], [8], [9]
Caveats: Only 31 of 47 finished the placebo trial [6]. The diclofenac trial was single-blind with no placebo [7]. The pooled pain estimate mixes conditions [8].

Glucosamine and chondroitinStrong

Knee and hip osteoarthritis pain

Not shown to lower osteoarthritis pain by a clinically important amount: about 0.3 to 0.5 cm on a 10 cm scale, and independent trials found no difference.

The numbers and sources

Effect: Across 10 trials (3,803 patients), pain on a 10 cm scale differed from placebo by -0.4 cm for glucosamine (95% credible interval -0.7 to -0.1), -0.3 cm for chondroitin and -0.5 cm for the combination. None reached the prespecified minimal clinically important difference of -0.9 cm [1]. In 1,583 patients over 24 weeks, response rates did not differ significantly from placebo (60.1%): 3.9 points higher with glucosamine, 5.3 with chondroitin and 6.5 with both. Celecoxib was 10.0 points higher [2]. Individual patient data from 5 industry-independent trials (1,625 people) found glucosamine no different from placebo at 3 and 24 months, in every predefined subgroup [3].
Population: Adults with knee or hip osteoarthritis [1][2][3].
Sources: [1], [2], [3]
Caveats: Industry-independent trials showed smaller effects than commercially funded trials (P = 0.02 for interaction) [1]. In GAIT, an exploratory subgroup with moderate to severe pain responded more to the combination (79.2% versus 54.3%) [2].

SAM-eModerate

Osteoarthritis pain and function

Not shown to lower pain or improve function more than placebo in adults with knee or hip osteoarthritis.

The numbers and sources

Effect: In 4 trials (656 patients), pain was slightly lower than placebo, but not significantly (SMD -0.17, 95% CI -0.34 to 0.01), equal to 0.4 cm on a 10 cm scale. Function did not differ (SMD 0.02, 95% CI -0.68 to 0.71) [6].
Population: Adults with knee or hip osteoarthritis [6].
Sources: [6]
Caveats: The review rated trial quality and reporting as poor and called itself inconclusive [6].

Deer antler velvetLimited

Arthritis

One trial found elk velvet antler did not differ from placebo over 6 months in 168 adults with rheumatoid arthritis.

The numbers and sources

Effect: In 168 people with rheumatoid arthritis on standard treatment, 6 months of elk velvet antler did not differ from placebo on joint pain and swelling, disease activity, function, quality of life or CRP [4]. A systematic review identified 2 rheumatoid arthritis trials and 1 osteoarthritis trial, and its authors wrote that the osteoarthritis findings may have some promise [5].
Population: Adults with stage 2 to 3 rheumatoid arthritis [4]; RCTs [5].
Sources: [4], [5]
Caveats: One osteoarthritis trial.

Tart cherryLimited

Knee osteoarthritis pain

One trial found knee pain scores did not differ significantly from placebo in adults with knee osteoarthritis, though CRP fell.

The numbers and sources

Effect: In 58 patients drinking two 8 oz bottles a day for 6 weeks, WOMAC scores fell during cherry juice but the difference from placebo was not significant (P = 0.16). hsCRP fell compared with placebo [14].
Population: Non-diabetic adults with Kellgren grade 2 to 3 knee osteoarthritis, crossover [14].
Sources: [14]
Caveats: One trial.

TurmericLimited

Hand osteoarthritis

One small pilot found hand pain fell from baseline over 3 months in adults over 50, but differences from placebo at 1 month were not significant.

The numbers and sources

Effect: In 27 adults over 50, 170 mg of curcumin a day for 3 months lowered VAS pain from baseline by 1.37 at rest and 1.74 during activity, and improved DASH scores by 11.84. Differences against placebo at 1 month were not significant [41].
Population: 27 adults with hand osteoarthritis, 13 on curcumin [41].
Sources: [41]
Caveats: A pilot trial. The month 3 changes are reported against baseline [41].

Therapies

AcupunctureStrong

Chronic pain across conditions

Shown to ease chronic pain about 0.5 standard deviations more than no acupuncture and about 0.2 more than sham acupuncture, with effects lasting a year.

Compared with sham acupuncture [2][3]; no acupuncture [2][3]

The numbers and sources

Effect: In individual patient data from 39 trials, acupuncture was superior to both sham and no acupuncture for each pain condition (all P < .001). The difference was close to 0.5 standard deviations against no acupuncture and close to 0.2 against sham, and about 15% of the effect was lost at 1 year. Effects were smaller in trials whose sham used a penetrating needle [2]. The earlier analysis of 29 trials found pain scores lower than sham by 0.23 SD for back and neck pain, 0.16 SD for osteoarthritis and 0.15 SD for chronic headache, and lower than no acupuncture by 0.55, 0.57 and 0.42 SD [3].
Population: 20,827 patients with nonspecific musculoskeletal pain, osteoarthritis, chronic headache or shoulder pain in 39 trials [2]. 17,922 patients in 29 trials [3].
Sources: [2], [3]
Caveats: The two analyses come from the same collaboration and the later one contains the earlier trials. Patients and acupuncturists cannot be blinded when the comparison is no acupuncture, so the larger effect includes expectation. The authors say factors beyond needling contribute to the effect [3].

AcupunctureStrong

Knee osteoarthritis, compared with no acupuncture or a waiting list

Shown to ease osteoarthritis pain 14.5 points on a 100-point scale more than a waiting list in the short term. One later trial found no gain at 1 year.

Compared with waiting list [8]; no acupuncture [3][9]

The numbers and sources

Effect: Against a waiting list, pain improved by 14.5 points more on a 100-point scale (SMD -0.96, 95% CI -1.19 to -0.72, 4 trials, 884 participants) and function by 13.0 points (SMD -0.89) [8]. Individual patient data put the difference from no acupuncture at 0.57 SD for osteoarthritis [3]. Against no acupuncture, needle acupuncture lowered knee pain by 1.1 units on a 0 to 10 scale at 12 weeks (95% CI -1.8 to -0.4), and not at 1 year [9].
Population: People with knee or hip osteoarthritis in 4 waiting-list trials [8]. 282 adults aged 50 or older [9].
Sources: [8], [3], [9]
Caveats: None of these comparisons could blind participants, so expectation and attention are part of the effect. The 1-point change at 12 weeks was below that trial's 1.8-unit threshold for clinical importance [9].

Dry needlingModerate

Shoulder pain

Shown to ease nontraumatic shoulder pain by a small amount, about half a point, and disability by a larger amount, in the short term only.

Compared with comparison groups the review abstract does not describe [10]

The numbers and sources

Effect: Trigger point dry needling, alone or added to other treatment, lowered shoulder pain (mean difference -0.49 points, 95% CI -0.84 to -0.13, SMD -0.25) and pain-related disability (mean difference -9.99 points, 95% CI -15.97 to -4.01, SMD -1.14) more than the comparison groups. The effect on pain was found only in the short term [10].
Population: 6 trials of nontraumatic shoulder pain [10].
Sources: [10]
Caveats: Evidence was moderate in quality for pain and low for disability, downgraded for heterogeneity [10].

Dry needlingModerate

Tennis elbow

Shown to ease tennis elbow pain and disability with large effects in the short term, and grip strength with a small effect.

Compared with comparison groups the review abstract does not describe [15]

The numbers and sources

Effect: Dry needling, alone or with other treatment, lowered pain (SMD -1.13, 95% CI -1.64 to -0.62) and related disability (SMD -2.17, 95% CI -3.34 to -1.01), and raised pressure pain thresholds (SMD 0.98) and grip strength (SMD 0.48, 95% CI 0.16 to 0.81). The largest effects were in the short term [15].
Population: 320 people with lateral epicondylalgia in 7 trials [15].
Sources: [15]
Caveats: Evidence was low to moderate, downgraded for heterogeneity [15].

Physical therapy and exercise therapyModerate

Knee osteoarthritis, compared with no exercise

Shown to ease knee osteoarthritis pain about 12 points on a 100-point scale and improve function about 10 points against no exercise, right after treatment.

Compared with non-exercise or no-treatment control groups [4]

The numbers and sources

Effect: Exercise reduced pain (SMD -0.49, 44 trials, 3,537 participants), equal to 12 points on a 0 to 100 scale, and improved physical function by 10 points (SMD -0.52), both immediately after treatment. Quality of life improved by 4 points. Two to six months after treatment ended, pain was 6 points lower and function 3 points better [4].
Population: 54 trials of people with knee osteoarthritis [4].
Sources: [4]
Caveats: Only 4 trials blinded participants, and pain and function were self-reported [4].

Physical therapy and exercise therapyModerate

Hip osteoarthritis, compared with no exercise

Shown to ease hip osteoarthritis pain and improve function about 8 and 7 points on a 100-point scale against no exercise, sustained 3 to 6 months later.

Compared with non-exercise control groups [5]

The numbers and sources

Effect: Exercise reduced pain (SMD -0.38, 9 trials, 549 participants), equal to 8 points on a 0 to 100 scale, and improved function by 7 points, with a number needed to treat of 6 for both. The pain reduction held 3 to 6 months after supervised treatment ended. Quality of life did not change (3 small studies) [5].
Population: 10 trials of people with hip osteoarthritis [5].
Sources: [5]
Caveats: No trial could blind participants, and outcomes were self-reported [5].

Physical therapy and exercise therapyModerate

Recovery after knee replacement

Shown to improve function and pain modestly 3 to 4 months after knee replacement, compared with minimal physiotherapy. No long-term benefit was found.

Compared with minimal physiotherapy [13]; home-based physiotherapy [13]

The numbers and sources

Effect: Against minimal physiotherapy, physiotherapy exercise improved function (SMD -0.37, 95% CI -0.62 to -0.12) and pain (SMD -0.45, 95% CI -0.85 to -0.06) at 3 to 4 months. Outpatient and home-based programs did not differ for function or pain, and adding balance or cycling made no difference [13].
Population: 1,739 patients with recent total knee replacement in 18 trials [13].
Sources: [13]
Caveats: Studies were small and underpowered individually and combined [13].

PRP injectionsModerate

Knee osteoarthritis, compared with hyaluronic acid

Shown in pooled trials to give better knee pain, function and WOMAC scores after injection than hyaluronic acid injections.

Compared with hyaluronic acid injections [5]

The numbers and sources

Effect: Across 27 randomized trials, scores after injection were better with PRP than with hyaluronic acid for WOMAC (P < .001), pain on the visual analog scale (P < .01) and the Subjective IKDC knee score (P < .001) [5].
Population: 1,042 patients given PRP and 1,128 given hyaluronic acid, mean age 57.7 and 59.0, mean follow-up about 14 months [5].
Sources: [5]
Caveats: Hyaluronic acid is an active injection, not a placebo. The abstract gives P values without effect sizes [5].

PRP injectionsModerate

Rotator cuff repair, added during surgery

Shown to lower repair failure after rotator cuff surgery, 15.9% against 29.0%, with function gains below the clinically important threshold.

Compared with rotator cuff repair without PRP [12]

The numbers and sources

Effect: Leukocyte-poor PRP injected during arthroscopic repair lowered repair failure to 34 of 213 (15.9%) from 63 of 217 (29.0%) (RR 0.55, 95% CI 0.38 to 0.79). Constant, UCLA and other function scores were higher at 6 to 24 months, by amounts below the minimal clinically important difference. Complications were 9.4% and 7.7% (P = .508) [12].
Population: 470 patients in 5 randomized trials [12].
Sources: [12]
Caveats: Applies to PRP given during surgery, not to injections for tendon pain without surgery.

Dry needlingLimited

Knee osteoarthritis, other comparisons

Limited evidence: pooled small trials found less osteoarthritis pain and better function in the short term, with no difference at medium or long term.

Compared with non-drug treatments, sham techniques or no added treatment, pooled together [13]; control, sham or placebo treatment [14]

The numbers and sources

Effect: Across 7 trials, dry needling lowered pain (SMD -0.76, 95% CI -1.24 to -0.29, I² 74%) and improved physical function (SMD -0.98, 95% CI -1.54 to -0.42, I² 75%) in the short term, with no difference at medium or long term [13]. A review of 9 trials found contradictory results for trigger point needling. Periosteal stimulation improved pain and function right after treatment, and intramuscular electrical stimulation lowered pain with marked heterogeneity [14].
Population: 291 people with hip or knee osteoarthritis in 7 trials [13]. 9 trials of knee osteoarthritis [14].
Sources: [13], [14]
Caveats: Evidence was rated very low quality for risk of bias, heterogeneity and imprecision [13]. Sham and no-treatment comparisons were pooled together.

Massage therapyLimited

Knee osteoarthritis

One trial of 222 adults found weekly massage improved knee osteoarthritis scores more than light touch or usual care at 8 weeks, with no difference at 52 weeks.

Compared with light touch [7]; usual care [7]

The numbers and sources

Effect: At 8 weeks, WOMAC global scores improved by 8.16 points more than light touch (95% CI -13.50 to -2.81) and 9.55 points more than usual care (95% CI -14.66 to -4.45), with gains in pain, stiffness and function. At 52 weeks, change did not differ across groups (P = 0.707) [7].
Population: 222 adults with knee osteoarthritis [7].
Sources: [7]
Caveats: One trial. Light touch was the closest thing to a sham, and participants knew which hands-on treatment they had.

Ozone therapyLimited

Knee osteoarthritis, compared with placebo

Limited evidence: one double-blind trial and three reviews found less knee osteoarthritis pain than placebo, and an umbrella review rated every review critically low in confidence.

Compared with placebo injections [6][7]

The numbers and sources

Effect: After 8 weeks of injections, pain was 2.16 points lower than placebo on the visual analog scale (95% CI 0.42 to 3.89), and the Lequesne index, WOMAC scores and several quality of life scores improved more. The Timed Up and Go test did not differ [6]. An umbrella review of 8 reviews covering 15 trials found 3 reporting significant pain reduction against placebo, while 5 found ozone no better than other therapies, with less consistent effects on joint function [7].
Population: 98 adults with symptomatic knee osteoarthritis in Brazil [6]. 8 systematic reviews of 15 trials with 3,685 patients [7].
Sources: [6], [7]
Caveats: All 8 reviews had critically low confidence ratings on AMSTAR 2 [7]. The placebo trial lasted 8 weeks [6].

Physical therapy and exercise therapyLimited

Knee osteoarthritis, compared with a steroid injection

One trial of 156 adults found less knee pain and disability at 1 year with physical therapy than with a glucocorticoid injection.

Compared with intra-articular glucocorticoid injection [8]

The numbers and sources

Effect: At 1 year, WOMAC scores (0 to 240) were 37.0 with physical therapy and 55.8 with injection, a difference of 18.8 points (95% CI 5.0 to 32.6) [8].
Population: 156 patients with knee osteoarthritis, mean age 56, in the US Military Health System [8].
Sources: [8]
Caveats: One trial, without blinding of participants.

AcupunctureStrong

Knee osteoarthritis, compared with sham acupuncture

Mixed results: pooled trials found a small edge over sham acupuncture that reviewers judged below clinical relevance, and a 282-person trial found no difference from sham.

Compared with sham acupuncture [3][8][9][10]; sham laser [9]

The numbers and sources

Effect: Against sham, pain improved by 0.9 points more on a 20-point scale (SMD -0.28, 95% CI -0.45 to -0.11, 9 trials, 1,835 participants), below the reviewers' 1.3-point threshold for clinical relevance. With the shams most likely to blind participants, the benefit was smaller and not significant, and at 6 months it was borderline (SMD -0.10) [8]. Individual patient data put the edge over sham at 0.16 SD for osteoarthritis [3]. In people over 50 with chronic knee pain, needle acupuncture did not differ from sham for pain (-0.4 units on a 0 to 10 scale, 95% CI -1.2 to 0.4) or function at 12 weeks [9]. In a 480-person trial, 60.3% responded to electroacupuncture, 58.6% to manual acupuncture and 47.3% to sham at 8 weeks. Electroacupuncture differed from sham (P = 0.0234) and manual acupuncture narrowly did not (P = 0.0507) [10].
Population: 16 trials with 3,498 people with knee or hip osteoarthritis [8]. 282 adults aged 50 or older in Australia [9]. 480 adults in China [10].
Sources: [8], [3], [9], [10]
Caveats: Heterogeneity was substantial across sham-controlled trials [8]. The trials used different shams, from non-penetrating needles to inactive lasers.

Ozone therapyModerate

Joint and muscle pain, compared with corticosteroid injections

Mixed results: across musculoskeletal conditions, steroid injections eased pain more in the short term, while in knee osteoarthritis alone ozone eased pain more.

Compared with corticosteroid injections [8][9]

The numbers and sources

Effect: Across 11 studies of musculoskeletal pain of several kinds, short-term pain fell more with corticosteroid injections (d 0.31, 95% CI 0.01 to 0.60), and medium-term pain did not differ (d -0.17, 95% CI -0.42 to 0.07) [8]. In 7 knee osteoarthritis trials, ozone injections reduced pain more than corticosteroid injections in the short and medium term and improved function in the medium term [9].
Population: 534 people with musculoskeletal pain in 11 studies [8]. 409 people with knee osteoarthritis in 7 trials [9].
Sources: [8], [9]
Caveats: Both reviews describe the included trials as limited in quality [8][9]. The knee review abstract gives no effect sizes [9].

Physical therapy and exercise therapyModerate

Compared with surgery

Mixed results: trials found outcomes similar to surgery for degenerative meniscus tears, spinal stenosis and ACL tears, and smaller gains than knee replacement.

Compared with arthroscopic partial meniscectomy [9]; surgical decompression [10]; early ACL reconstruction [11]; total knee replacement followed by nonsurgical treatment [12]

The numbers and sources

Effect: For degenerative meniscus tears, knee scores at 2 years differed by 0.9 points between 12 weeks of supervised exercise and surgery (95% CI -4.3 to 6.1), and 19% of the exercise group crossed over to surgery [9]. For lumbar spinal stenosis, physical function improved by 19.2 points with physical therapy and 22.4 with surgery, with no difference at 2 years, and 57% crossed over from therapy to surgery [10]. For acute ACL tears, knee scores rose 39.4 points with rehabilitation plus optional later reconstruction and 39.2 with rehabilitation plus early reconstruction, and 36 of 59 never had surgery [11]. For knee osteoarthritis, knee replacement plus nonsurgical treatment improved scores by 32.5 points against 16.0 with nonsurgical treatment alone, and had more serious adverse events (24 against 6) [12].
Population: 140 adults aged 35 to 60 with degenerative meniscal tears [9]. 169 surgical candidates aged 50 or older with lumbar spinal stenosis [10]. 121 young, active adults with acute ACL tears [11]. 100 patients eligible for knee replacement [12].
Sources: [9], [10], [11], [12]
Caveats: Each condition rests on one trial, and crossover to surgery was common [9][10]. The spinal stenosis trial had no untreated group [10].

PRP injectionsModerate

Knee osteoarthritis, compared with saline placebo

Mixed results: pooled placebo-controlled trials found less knee pain up to 6 months, while the largest trial, of 288 people, found no difference from saline at 12 months.

Compared with saline placebo injections [2][3][4]

The numbers and sources

Effect: In 288 adults aged 50 or older, knee pain changed by -2.1 points with PRP and -1.8 with saline at 12 months (difference -0.4, 95% CI -0.9 to 0.2, on a 0 to 10 scale with a clinically important difference of 1.8). Cartilage volume did not differ, and 29 of 31 secondary outcomes did not differ [2]. Across 11 trials, pain was lower than placebo at 3 months (MD -1.1, 95% CI -1.8 to -0.4) and 6 months (MD -2.0, 95% CI -2.8 to -1.2), and not at 12 months. WOMAC scores improved at 3 months only [3]. A review of 20 placebo-controlled studies found better function and pain at 6 and 12 months, at very low certainty [4].
Population: 288 adults with mild to moderate medial knee osteoarthritis in Australia [2]. 1,616 patients in 11 trials, mean age 56.9 [3]. 1,774 PRP and 1,518 placebo participants in 20 studies [4].
Sources: [2], [3], [4]
Caveats: Heterogeneity was high in the pooled pain results [3], and certainty very low [4]. The largest trial, blinded for participants, injectors and assessors, found no difference [2].

PRP injectionsModerate

Rotator cuff tendinopathy, injection

Mixed results: a pooled review reported short-term pain relief against placebo and corticosteroids, while a placebo-controlled trial found no difference from saline at one year.

Compared with placebo or corticosteroid injections [10]; saline injection, both groups exercising [11]

The numbers and sources

Effect: Across 30 randomized trials, PRP reduced pain and improved function in the short term against placebo and corticosteroids, with no greater benefit beyond 12 months [10]. In 40 patients, WORC, SPADI and pain scores did not differ from saline at any time point through one year (P = .174, .314 and .904 at one year), and both groups improved [11].
Population: About 2,500 participants in 30 trials [10]. 40 adults aged 18 to 70 with chronic rotator cuff tendinopathy [11].
Sources: [10], [11]
Caveats: The review abstract gives no effect sizes and does not separate placebo from corticosteroid comparisons [10].

Reiki and therapeutic touchLimited

Pain, compared with sham Reiki

Mixed results: a fibromyalgia trial found Reiki no different from sham given by actors, and a knee pain trial found more people improved with Reiki than with sham.

Compared with sham Reiki given by actors, with or without touch [7]; sham Reiki and a waiting list [8]

The numbers and sources

Effect: In 100 adults with fibromyalgia treated twice weekly for 8 weeks, pain and every secondary outcome were nearly identical whether a Reiki master or an actor gave the treatment, with touch or at a distance [7]. In 164 adults with knee osteoarthritis, symptoms improved more with Reiki than with a waiting list (P = .02), and a reduction of more than 30% was reported by 55% given Reiki, 20% given sham Reiki and 13% on the waiting list [8].
Population: 100 adults with fibromyalgia in Seattle [7]. 164 adults with knee osteoarthritis [8].
Sources: [7], [8]
Caveats: The knee trial abstract does not report a direct test of Reiki against sham [8].

Lymphatic drainage massageStrong

Swelling after knee replacement

Not shown to reduce leg swelling, pain or stiffness after knee replacement, in two meta-analyses of randomized trials.

Compared with no drainage [6]; no drainage or other physiotherapy [7]

The numbers and sources

Effect: Across 4 trials, knee flexion, pain and the circumference of the thigh, knee, calf and ankle did not differ with drainage [6]. Across 7 trials, knee flexion (SMD 0.03, 95% CI -0.22 to 0.28), knee extension, leg circumference (SMD -0.09, 95% CI -0.27 to 0.09) and pain (SMD -0.33, 95% CI -0.71 to 0.04) did not differ [7].
Population: 197 knee replacements, mean age 69.6, followed about 7 weeks [6]. 285 patients in 7 trials [7].
Sources: [6], [7]
Caveats: The two reviews share trials. Trials were small.

CuppingModerate

Chronic pain, compared with sham cupping

Not shown to ease chronic pain more than sham cupping, in two meta-analyses and three later trials of back pain, knee osteoarthritis and fibromyalgia.

Compared with sham cupping [2][3][4][5][6]

The numbers and sources

Effect: Against sham cupping, pain did not differ significantly (SMD -0.27, 95% CI -0.58 to 0.05) and neither did disability (SMD -0.26) [2]. In 5 trials of dry against placebo cupping, the short-term pain difference was -9.9 points on a 100-point scale (95% CI -30.5 to 10.7), very uncertain at every time point [3]. In 90 people with chronic low back pain, pain differed by 0.0 to 0.6 points on a 0 to 10 scale over 8 weeks [4]. In 62 women with knee osteoarthritis, no outcome differed from sham at any time point [5]. In 141 people with fibromyalgia, pain at day 18 differed from sham by -3.0 points (95% CI -9.9 to 3.9) [6].
Population: 1,172 people with chronic pain in 18 trials [2]. 281 adults with musculoskeletal complaints in 5 trials [3]. 90 adults [4]. 62 women aged 50 to 75 [5]. 141 patients, 139 of them women [6].
Sources: [2], [3], [4], [5], [6]
Caveats: Few sham-controlled trials exist and most are small. The second meta-analysis rated certainty very low and four of its trials at high risk of bias [3].

PRP injectionsModerate

Tennis elbow

Not shown to ease tennis elbow pain or function more than placebo injection at 3, 6 or 12 months, for PRP or whole-blood injections, in a Cochrane review.

Compared with placebo injection [6]

The numbers and sources

Effect: At 3 months, mean pain was 3.7 out of 10 with placebo and 0.16 points better with autologous blood or PRP (95% CI 0.60 better to 0.29 worse, 8 studies, 523 participants). Function was 1.86 points better on a 100-point scale (95% CI 4.9 better to 1.25 worse), and treatment success was 67% against 65% (RR 1.00, 95% CI 0.83 to 1.19). No clinically important benefit appeared at 6 or 12 months [6].
Population: 32 trials with 2,337 people with lateral elbow pain, 10 of them placebo-controlled [6].
Sources: [6]
Caveats: Evidence was moderate in certainty, downgraded for bias [6].

PRP injectionsModerate

Achilles tendinopathy

Not shown to improve chronic Achilles tendinopathy more than a sham or saline injection, in three placebo-controlled trials through one year.

Compared with sham injection, a dry needle under the skin not entering the tendon [7]; saline injection, both groups doing eccentric exercises [8][9]

The numbers and sources

Effect: At 6 months, VISA-A scores were 54.4 with PRP and 53.4 with sham (adjusted difference -2.7, 95% CI -8.8 to 3.3, clinically important difference 12) [7]. With eccentric exercise, VISA-A improved 21.7 points with PRP and 20.5 with saline at 24 weeks (difference -0.9, 95% CI -12.4 to 10.6) [8]. At one year the difference was 5.5 points (95% CI -4.9 to 15.8), and 59% in both groups were satisfied [9].
Population: 240 adults at 24 UK sites, mean age 52 [7]. 54 adults aged 18 to 70 in the Netherlands, followed for 24 weeks [8] and one year [9].
Sources: [7], [8], [9]
Caveats: The two smaller reports are the same trial at two time points [8][9].

Dry needlingLimited

Knee osteoarthritis, compared with sham needling

Small trials found adding dry needling to exercise did not ease knee osteoarthritis pain or disability more than sham dry needling, through one year.

Compared with sham dry needling, both groups exercising [11][12]

The numbers and sources

Effect: At one year, pain differed from sham by 0.32 points (95% CI -1.12 to 1.18, P = 0.92) and WOMAC score by 0.29 points (95% CI -6.16 to 6.74). Both groups improved over time. In the dry needling group 90.3% reduced their medication, against 26.3% with sham [11]. In a 20-person pilot, pain and WOMAC scores improved in both groups with no group difference [12].
Population: 62 adults with knee osteoarthritis in a multicenter trial [11]. 20 adults aged 65 or older with thigh trigger points [12].
Sources: [11], [12]
Caveats: Two small trials from the same group, both adding needling to exercise.

Physical therapy and exercise therapyLimited

Hip and knee osteoarthritis, compared with sham treatment

Two small trials found physical therapy programs did not ease hip or knee osteoarthritis pain more than sham ultrasound with inert gel.

Compared with sham ultrasound and inert gel [6][7]

The numbers and sources

Effect: In hip osteoarthritis, pain at week 13 fell from 58.8 to 40.1 mm with physical therapy and from 58.0 to 35.2 mm with sham, a difference of 6.9 mm favoring sham (95% CI -3.9 to 17.7). Function did not differ [6]. In knee osteoarthritis, pain fell by 2.2 cm with physiotherapy and 2.0 cm with placebo at 12 weeks, and global improvement was reported by 70% and 72% [7].
Population: 102 adults with painful hip osteoarthritis [6]. 140 adults with knee osteoarthritis, 119 completing [7].
Sources: [6], [7]
Caveats: The sham involved regular contact with a therapist, so both groups received attention. The authors of [7] wrote that the program did no more than regular contact with a therapist.

Practices

Red light therapyStrong

Knee osteoarthritis pain

Shown to reduce knee osteoarthritis pain compared with placebo, by about 14 mm on a 100 mm scale in one meta-analysis. A later review rated certainty very low.

The numbers and sources

Effect: Across 22 placebo-controlled trials (1,063 participants), low-level laser reduced pain by 14.23 mm on a 100 mm visual analogue scale at the end of therapy (95% CI 7.31 to 21.14) and by 15.92 mm at follow-ups 1 to 12 weeks later (95% CI 6.47 to 25.37). At the doses advised by the World Association for Laser Therapy, the reduction was 18.71 mm. Disability was also reduced [6]. Across 10 placebo-controlled studies (542 participants), pain at rest was lower with photobiomodulation (-0.7, 95% CI -1.1 to -0.2), and the Timed Up and Go test did not differ [7].
Population: 1,063 people with knee osteoarthritis in 22 trials [6]. 542 people in 10 trials [7].
Sources: [6], [7]
Caveats: The later review judged every study at unclear to high risk of bias and the certainty of evidence very low [7]. The first review states that major knee osteoarthritis treatment guidelines do not endorse low-level laser [6]. These trials used clinic lasers applied to the joint, not consumer light panels.

Red light therapyModerate

Tendon pain and plantar fasciitis

Shown to reduce pain in lower-limb tendinopathy and plantar fasciitis by about 13 mm on a 100 mm scale in one meta-analysis, with wide intervals.

The numbers and sources

Effect: Across randomized trials, low-level laser reduced pain by 13.15 mm on a 100 mm scale at the end of therapy (95% CI 7.82 to 18.48) and 12.56 mm at 4 to 12 weeks (95% CI 5.69 to 19.42). Disability improved (SMD 0.39, 95% CI 0.09 to 0.7). Added to exercise at the doses advised by the World Association for Laser Therapy, it reduced pain 18.15 mm more than exercise alone [9].
Population: People with lower extremity tendinopathy or plantar fasciitis in 18 trials, 10 of them against placebo [9].
Sources: [9]
Caveats: The authors note wide confidence intervals, no large trials and no long-term data [9].

Tai chi and qigongModerate

Knee osteoarthritis, against no program or attention control

Shown to ease knee osteoarthritis pain and stiffness and improve function in one meta-analysis of 16 trials. A small trial found more relief than wellness education and stretching.

Compared with control groups the source abstract does not describe [8]; wellness education and stretching, as an attention control [9]

The numbers and sources

Effect: Tai chi improved pain (SMD -0.69, 95% CI -0.95 to -0.44), stiffness (SMD -0.59), physical function (SMD -0.92, 95% CI -1.16 to -0.69), dynamic balance (SMD 0.69) and physical and mental quality of life [8]. In 40 adults, WOMAC pain improved more with tai chi than with the attention control at 12 weeks (mean difference -118.80 mm, 95% CI -183.66 to -53.94), along with function, chair stand time and depression scores [9].
Population: 986 patients with knee osteoarthritis in 16 trials [8]. 40 adults with symptomatic knee osteoarthritis, mean age 65 [9].
Sources: [8], [9]
Caveats: Strength of evidence for the main outcomes was low or moderate [8]. Patients knew their group [9].

Whole-body cryotherapyModerate

Ankylosing spondylitis

Shown to improve pain, function and disease activity scores in people with ankylosing spondylitis in a meta-analysis of 5 studies. C-reactive protein did not change.

The numbers and sources

Effect: Across 5 studies (310 patients), cryotherapy improved the BASDAI disease activity index (p < 0.001), ASDAS (p = 0.015), BASFI function index (p = 0.006) and pain scores (p = 0.005). C-reactive protein did not change (p = 0.684) [11].
Population: 310 people with ankylosing spondylitis in 5 studies with varied temperatures and session lengths of 80 seconds to 3 minutes [11].
Sources: [11]
Caveats: Five studies, with protocols that varied. The abstract gives p values without effect sizes, and the authors call for studies of tolerance and long-term results.

Whole-body cryotherapyLimited

Frozen shoulder

One trial found greater gains in pain and shoulder movement when cryotherapy was added to physical therapy in 30 people with adhesive capsulitis.

The numbers and sources

Effect: Pain, active range of motion in four directions and a shoulder function score improved more in the group that added whole-body cryotherapy to physical therapy and joint mobilization (P < .01) [16].
Population: 30 patients with adhesive capsulitis of the shoulder, randomized to two groups [16].
Sources: [16]
Caveats: Thirty people, no sham, and the abstract gives no sizes.

Infrared saunaLimited

Rheumatoid arthritis and ankylosing spondylitis

Mixed results: pain and stiffness eased during infrared sessions in 34 patients, while changes across the 4-week course did not reach significance.

The numbers and sources

Effect: Pain and stiffness decreased significantly during a session (p < 0.05 in rheumatoid arthritis and p < 0.001 in ankylosing spondylitis). Over 4 weeks and 8 sessions, improvements in pain, stiffness and fatigue did not reach statistical significance. Disease activity scores did not change [27].
Population: 17 people with rheumatoid arthritis and 17 with ankylosing spondylitis, no control group [27].
Sources: [27]
Caveats: A pilot study with no control group.

Tai chi and qigongLimited

Knee osteoarthritis, against physical therapy

One trial of 204 adults found tai chi and physical therapy eased knee osteoarthritis symptoms by similar amounts at 12 weeks, maintained to 52 weeks.

Compared with standard physical therapy twice a week for 6 weeks, then 6 weeks of monitored home exercise [10]

The numbers and sources

Effect: WOMAC scores fell 167 points with tai chi and 143 points with physical therapy at 12 weeks, a difference of 24 points (95% CI -10 to 58) that was not significant. Tai chi produced greater improvement in depression and in the physical component of quality of life [10].
Population: 204 adults with symptomatic knee osteoarthritis, mean age 60, 70% women [10].
Sources: [10]
Caveats: Patients knew their group. One urban academic hospital [10].

Whole-body cryotherapyLimited

Rheumatoid arthritis

One study found people with rheumatoid arthritis improved about equally with whole-body cryotherapy and with traditional rehabilitation over 2 weeks.

The numbers and sources

Effect: Pain, disease activity, fatigue and walking measures improved similarly in both groups, as did interleukin-6 and TNF-alpha. The Health Assessment Questionnaire result was better in the traditional rehabilitation group (p < 0.05) [19].
Population: 25 patients given cryotherapy at -110°C and 19 given traditional rehabilitation [19].
Sources: [19]
Caveats: A comparison of two active programs, not described as randomized, with no untreated group.

Lab markers

Uric acid (serum urate)Strong

Gout

Linked to gout in a graded way: 15-year incidence ran from 1.1% below 6 mg/dL to 49% at 10 mg/dL or above.

The numbers and sources

Effect: In pooled individual data from four US cohorts, the 15-year cumulative incidence of gout was 1.1% (95% CI 0.9 to 1.4) at a baseline serum urate below 6 mg/dL and 49% (31 to 67) at 10 mg/dL or above. Against below 6 mg/dL, adjusted hazard ratios were 2.7 at 6.0 to 6.9 mg/dL, 6.6 at 7.0 to 7.9, 15 at 8.0 to 8.9, 30 at 9.0 to 9.9 and 64 at 10 or above [9]. In 2,046 initially healthy men followed for 14.9 years, the annual incidence of gouty arthritis was 4.9% at 9 mg/dL or more, 0.5% at 7.0 to 8.9 mg/dL and 0.1% below 7.0 mg/dL [10]. In a Mendelian randomization study, a genetically higher serum urate of 1 standard deviation went with an odds ratio for gout of 5.84 (95% CI 4.56 to 7.49) [11]. An umbrella review of 136 health outcomes found convincing evidence of a clear role for serum uric acid only for gout and kidney stones [12].
Population: 18,889 gout-free participants followed for a mean of 11.2 years [9]. 2,046 men in the Normative Aging Study [10]. 3,151 gout cases and 68,350 controls [11].
Sources: [9], [10], [11], [12]
Caveats: About half of the people at 10 mg/dL or above did not develop gout within 15 years, which the authors read as a role for other factors and for how long the level stays high [9].