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Does Glucosamine Work? Glucosamine & Chondroitin for Knee Pain

Glucosamine and chondroitin are the best-selling joint supplements in the world, and they have been studied more thoroughly than almost any other. That is exactly why the answer is clearer than the marketing suggests: in large, independent trials, the average benefit for knee pain is small or indistinguishable from placebo, and neither supplement has been shown to rebuild cartilage. Yet some trials of one prescription European product were positive, and a European expert group still recommends pharmaceutical-grade forms, while U.S. and UK guidelines advise against them. This page goes deeper than our supplements overview: what they are, sulfate versus hydrochloride, the key trials (GAIT, LEGS, MOVES and others), the meta-analyses, the joint-space claims, why guidelines disagree, safety, cost, and how to run a fair, time-limited trial if you and your clinician decide to try.

Important: This page is general educational information, not medical advice. Osteoarthritis should be diagnosed and managed with a qualified clinician. Always consult a doctor or pharmacist before starting glucosamine or chondroitin, especially if you take warfarin or other blood thinners, have diabetes, asthma or a shellfish allergy, and never stop or change a prescribed medication, including pain relievers or NSAIDs, without speaking to the prescriber.

Key takeaways

  • In GAIT, the largest independent U.S. trial (1,583 people), neither glucosamine, chondroitin nor the combination beat placebo overall for knee pain at 24 weeks; placebo response was 60%.1 Strong
  • A 2010 BMJ network meta-analysis of 10 large trials (3,803 people) found pain reductions of 0.3–0.5 cm on a 10 cm scale, below the 0.9 cm patients notice, and smaller effects in industry-independent trials.13 Strong
  • Brand and formulation explain much of the disagreement: trials of one prescription crystalline glucosamine sulfate product were far more positive than others, but its low-bias trials show only a small effect.16 Contested
  • Cartilage: a few trials reported tenths of a millimetre less joint space narrowing on X-ray; independent trials largely did not. Neither supplement regrows cartilage.213 Contested
  • Guidelines split: ACR 2019 strongly recommends against glucosamine (knee, hip, hand) and chondroitin (knee, hip), with a conditional recommendation for chondroitin in hand OA; ESCEO recommends pharmaceutical-grade forms.1720 Strong
  • Both are generally well tolerated, but glucosamine can raise INR with warfarin, most is shellfish-derived, and it may affect blood sugar in some people.2227 Strong (warfarin signal)

What glucosamine and chondroitin are Strong

Glucosamine is an amino sugar the body uses to build glycosaminoglycans, the long sugar chains that help cartilage hold water and resist compression. Supplement glucosamine is usually made from the shells of shrimp, crab and other shellfish, although some products are made by fermentation from non-shellfish sources. Chondroitin sulfate is one of those glycosaminoglycans itself; it is extracted from animal cartilage such as cow, pig, chicken or shark.

Mechanism: the theory

The idea is intuitive: swallow the building blocks of cartilage and the joint will use them for repair. In lab studies, both molecules also dampen some inflammatory and cartilage-degrading signals in cartilage cells. The weak link is the step in between: oral doses are partly absorbed and broken down, and there is little direct evidence that supplement molecules reach worn cartilage in amounts that change its behavior in people. So the mechanism is plausible but unproven, and only clinical trials can settle whether it matters. Emerging (lab)

In trials, the usual daily doses have been glucosamine 1,500 mg (once daily or as 500 mg three times daily) and chondroitin 800–1,200 mg.1410 In the United States they are sold as dietary supplements; in parts of Europe specific pharmaceutical-grade products are sold as medicines and are grouped with other "symptomatic slow-acting drugs for osteoarthritis" (SYSADOAs).26

Sulfate vs. hydrochloride & prescription glucosamine Contested

Glucosamine comes mainly as glucosamine sulfate or glucosamine hydrochloride (HCl). Much of the positive evidence comes from one product: a prescription crystalline glucosamine sulfate developed by the Italian company Rottapharm (later Rottapharm/Madaus), taken as 1,500 mg once daily. Several European trials of that product reported benefit; GAIT, the main U.S. trial, used glucosamine hydrochloride and found none.114

Glucosamine and chondroitin products are not interchangeable
ProductWhere it is usedWhat trials showEvidence
Prescription crystalline glucosamine sulfate (1,500 mg once daily)Licensed medicine in many European countriesMost positive trials; 12 trials pooled SMD −1.07 for pain, but only −0.27 (small) in the 3 trials at low risk of bias16Contested
Other glucosamine sulfate productsSupplements worldwide13 non-Rottapharm trials pooled showed no significant pain reduction (SMD −0.11)16Strong (no benefit)
Glucosamine hydrochlorideCommon U.S. supplement form; used in GAIT and MOVESNo significant benefit over placebo in GAIT1Strong (no benefit)
Pharmaceutical-grade chondroitin sulfate (800 mg/day)Licensed medicine in parts of EuropePositive industry-linked trials vs. placebo and similar to celecoxib (CONCEPT)11Contested
Supplement chondroitinSupplements worldwide, often combined with glucosamineQuality and purity vary; Cochrane benefits uncertain once restricted to high-quality, non-industry trials15Contested

Supporters of the prescription product argue that the sulfate salt, the crystalline formulation and the single 1,500 mg daily dose produce higher, more consistent blood levels than supplement forms. Skeptics point out that the most positive trials were sponsored by or involved the manufacturer, and that an independent Australian trial of glucosamine sulfate (LEGS) also found no pain benefit.4 Either way, a result for one product does not automatically transfer to the glucosamine on a supermarket shelf.

The key trials: GAIT, LEGS, MOVES and more Strong

These are the trials you will hear cited most often, on both sides of the argument.

1,583People with knee OA in GAIT, the largest independent trial
60.1%Placebo response rate in GAIT at 24 weeks
+6.5Percentage points more responders with the combination vs. placebo (not significant)
Major randomized trials of glucosamine and/or chondroitin in osteoarthritis
TrialDesignMain findingCaveats
GAIT, Clegg 2006 (NEJM)11,583 people with knee OA; glucosamine HCl 1,500 mg, chondroitin 1,200 mg, both, celecoxib 200 mg or placebo; 24 weeksNo supplement beat placebo for a 20% pain reduction (glucosamine +3.9, chondroitin +5.3, combination +6.5 percentage points); celecoxib +10.0 (significant)In a smaller moderate-to-severe pain subgroup, the combination appeared to help (79.2% vs. 54.3%), but this was exploratory
GAIT 2-year, Sawitzke 20103662 GAIT participants continued their assigned treatment for 24 monthsNo treatment, including celecoxib, achieved a clinically important difference in pain or function vs. placeboGlucosamine and celecoxib showed non-significant trends
LEGS, Fransen 2015 (Australia)4605 people with knee pain; glucosamine sulfate 1,500 mg, chondroitin 800 mg, both, or placebo; 2 yearsAll groups improved, with no significant pain difference between any treatment and placeboThe combination showed slightly less joint space narrowing (0.10 mm; p=0.046); see below
MOVES, Hochberg 20165606 people with knee OA and moderate-to-severe pain; chondroitin 400 mg + glucosamine HCl 500 mg three times daily vs. celecoxib 200 mg; 6 monthsPain fell about 50% in both groups; the combination was non-inferior to celecoxibNo placebo arm. With placebo responses as large as GAIT's (60%), it cannot show the combination beats placebo
GUIDE, Herrero-Beaumont 20077318 people; prescription glucosamine sulfate 1,500 mg vs. acetaminophen 3 g vs. placebo; 6 monthsGlucosamine sulfate improved the Lequesne index by 1.2 points more than placebo; responders 39.6% vs. 21.2%Product-specific; modest absolute difference on a 24-point scale
Roman-Blas 20176164 people with moderate-to-severe knee pain; chondroitin 1,200 mg + glucosamine sulfate 1,500 mg vs. placebo; 6 monthsCombination was not superior to placebo; in the main analysis placebo reduced pain more (33% vs. 19%)Small trial; led by investigators who had previously reported positive glucosamine sulfate results
CONCEPT, Reginster 201711604 people; pharmaceutical-grade chondroitin 800 mg vs. celecoxib vs. placebo; 6 monthsChondroitin (−42.6 mm) and celecoxib (−39.5 mm) reduced pain more than placebo (−33.3 mm)Difference vs. placebo about 9 mm on a 100 mm scale; product-specific
Gabay 2011 (hand OA)12162 people with hand OA; chondroitin 800 mg vs. placebo; 6 months; investigator-initiatedHand pain 8.7 mm lower and function better than placeboSingle center; consistent with the ACR's conditional recommendation for hand OA

How to read this: trials that compared supplements with an active drug and no placebo (such as MOVES) tell you the two groups felt similar, not that the supplement worked; in GAIT, even celecoxib beat placebo by only 10 percentage points. Placebo-controlled trials that were independent of manufacturers have generally been negative, while positive results cluster around specific branded products.

Meta-analyses: Wandel 2010 and Cochrane Strong

Pooling trials helps, but only if you look at which trials drive the result.

  • Wandel et al., BMJ 2010 (network meta-analysis): included only large trials (more than 200 patients each): 10 trials, 3,803 people with knee or hip OA. Compared with placebo, pain on a 10 cm scale fell by just 0.4 cm with glucosamine, 0.3 cm with chondroitin and 0.5 cm with the combination, all short of the prespecified minimal clinically important difference of 0.9 cm. Industry-independent trials showed smaller effects than commercially funded ones. The authors concluded that health authorities and insurers should not cover these products and new prescriptions should be discouraged.13
  • Cochrane review of glucosamine (Towheed 2005): 20 trials, 2,570 people. Trials of the Rotta prescription product favored glucosamine for pain (SMD −1.31), but non-Rotta preparations showed no significant benefit (SMD −0.15), and the 8 trials with adequate allocation concealment failed to show benefit for pain or WOMAC function.14 This review has not been updated since 2005.
  • Cochrane review of chondroitin (Singh 2015): 43 trials, mostly of low quality. Chondroitin improved pain by about 8 points on a 100-point scale in short-term studies and had fewer serious adverse events than control, but the benefit became uncertain when the analysis was limited to trials with proper allocation concealment, large samples, or no pharmaceutical funding.15
  • Eriksen et al., 2014: 25 placebo-controlled glucosamine trials (3,458 people). Brand was the single biggest explanation for inconsistent results, ahead of risk of bias. The prescription product's trials averaged a large effect (SMD −1.07), shrinking to a small one (−0.27) in its 3 low-bias trials; other products showed no significant effect (−0.11).16
Translating "SMD": a standardized mean difference around 0.2 is usually considered small, 0.5 moderate and 0.8 large. The pattern across reviews is that the higher-quality and more independent the evidence, the closer the effect gets to small or zero.

Can they slow joint damage? Contested

The most ambitious claim is that these supplements are "disease-modifying": that they slow the loss of cartilage, measured on knee X-rays as joint space narrowing.

Trials measuring joint space width (JSW) on knee X-rays
TrialTreatmentJSW changeContext
Reginster 2001 (Lancet)8Prescription glucosamine sulfate, 3 years, 212 people−0.06 mm vs. −0.31 mm with placeboPositive; prescription-product trial
Pavelká 20029Prescription glucosamine sulfate, 3 years, 202 people+0.04 mm vs. −0.19 mm with placebo; severe narrowing 5% vs. 14%Positive; prescription-product trial
STOPP, Kahan 200910Chondroitin 800 mg, 2 years, 622 people−0.07 mm vs. −0.31 mm with placebo; progression ≥0.25 mm in 28% vs. 41%Positive
GAIT ancillary, Sawitzke 20082Glucosamine HCl, chondroitin, both, or celecoxib; 2 years, 572 peopleNo significant difference from placebo for any groupIndependent; placebo lost only 0.166 mm, limiting power
LEGS, Fransen 20154Glucosamine sulfate, chondroitin, both; 2 years, 605 peopleCombination 0.10 mm less narrowing (p=0.046); single agents no effectIndependent; borderline result and no pain benefit

The Wandel network meta-analysis found the differences in joint space width "all minute", with credible intervals overlapping zero,13 while the Cochrane chondroitin review found a small reduction in joint space loss in two low-bias trials.15 Several caveats apply: joint space width on an X-ray is an indirect stand-in for cartilage, the differences are tenths of a millimetre, and none of these trials showed cartilage regrowth. Whether such small differences mean fewer knee replacements has not been established in independent trials. Our page on whether arthritis can be reversed explains why cartilage rarely regrows and what does change the course of OA.

What the guidelines say Strong

Major guideline positions on glucosamine and chondroitin
GuidelineGlucosamineChondroitin
ACR/Arthritis Foundation 2019 (U.S.)17Strongly recommended against for knee, hip and hand OAStrongly recommended against for knee and hip OA; conditionally recommended for hand OA
OARSI 2019 (international)1820Strongly recommended against, including all formulationsStrongly recommended against, including all formulations
NICE NG226, 2022 (England)21"Do not offer glucosamine"; explain there is no strong evidence of benefitNot specifically addressed in the 2022 recommendations
ESCEO 2019 (European expert society)1920Recommends prescription crystalline glucosamine sulfate as a pharmacological option alongside core non-drug care; the recommendation is limited to pharmaceutical-grade productsRecommends pharmaceutical-grade chondroitin sulfate

A 2021 comparison written jointly by OARSI and ESCEO authors summarized the split plainly: both groups agree on education, exercise and weight loss as core treatment, but ESCEO recommends pharmaceutical-grade glucosamine and chondroitin sulfate, whereas OARSI strongly recommends against all glucosamine and chondroitin formulations.20 These positions are consistent with what we report on our osteoarthritis page.

Why the experts disagree Contested

Reasonable experts reading the same literature reach different conclusions. The main reasons:

The case for (ESCEO view)

  • Formulation matters: negative trials often used hydrochloride or supplement-grade products, so they say little about the prescription crystalline sulfate or pharmaceutical-grade chondroitin.16
  • Positive placebo-controlled trials of those products exist for both symptoms and joint space narrowing.7811
  • Their safety record is good, which matters in older people for whom NSAIDs carry real risks.26

The case against (ACR, OARSI, NICE view)

  • Industry funding: commercially funded trials show larger effects than independent ones,13 and several ESCEO authors were investigators on the positive branded-product trials.819
  • Bias: when analysis is restricted to well-concealed, low-bias trials, the benefit shrinks to small or nothing.1416
  • Placebo response: OA pain responds strongly to placebo (60% in GAIT), so small trials easily mistake that for a drug effect.1
  • Clinical relevance: pooled effects fall short of the difference patients notice.13

It is also worth noting that a 2017 trial of a chondroitin-plus-glucosamine-sulfate combination, led by researchers who had previously reported positive glucosamine sulfate results, found it no better than placebo,6 which shows the field self-correcting rather than one side simply being right. For our general approach to weighing this kind of evidence, see how to read the grades.

Safety: shellfish, warfarin, blood sugar Strong

In trials, both supplements are well tolerated. In GAIT, adverse events were mild, infrequent and evenly spread across groups, including placebo,1 and a systematic review by the ESCEO group found glucosamine sulfate and chondroitin sulfate were not associated with more adverse events than placebo.26 The issues below are uncommon but matter for specific people.

Warfarin and other blood thinners Strong (safety signal)

NCCIH notes that glucosamine and chondroitin have been associated with an increased risk of bleeding in people taking warfarin.27 An FDA review described a 71-year-old man whose stable INR rose to 3.9 and then 4.7 after he increased his glucosamine-chondroitin dose, and identified 20 FDA MedWatch reports of altered coagulation (raised INR, bleeding or bruising) with glucosamine and warfarin, including one serious brain bleed. The WHO database held 21 reports of raised INR, 17 of which resolved when glucosamine was stopped.22 If you take warfarin, do not start, stop or change glucosamine without talking to the clinician who manages your anticoagulation, who may want to check your INR more often.

Shellfish allergy and hypersensitivity Emerging

Most glucosamine is made from shellfish shells. Shellfish allergy is usually triggered by proteins in the flesh rather than the shell-derived sugar, but labeling and purity vary. An analysis of 366 spontaneous adverse-reaction reports to Australia's regulator (2000–2011) found that 72% were hypersensitivity reactions, 43 of them classified as severe, although it was unclear whether those people had a shellfish allergy.25 If you have a shellfish allergy or asthma, ask a clinician first or choose a product clearly labeled and verified as made from a non-shellfish source.

Blood sugar and diabetes Emerging

Because glucosamine is an amino sugar, there has long been concern that it could worsen glucose control. A systematic review of 11 human studies found mixed results: 4 found lower insulin sensitivity or higher fasting glucose, especially in people who already had impaired glucose tolerance.23 Reassuringly, in a randomized trial of 407 overweight women, 2.5 years of crystalline glucosamine sulfate did not change HbA1c or new-onset diabetes over 6.5 years.24 If you have diabetes or prediabetes, monitor your blood sugar and tell your clinician.

Who should talk to a doctor or pharmacist before taking glucosamine or chondroitin
If you…WhyEvidence
Take warfarin or another anticoagulant or antiplateletRaised INR and bleeding reportedStrong
Have a shellfish allergy, asthma or other allergiesShellfish-derived products; hypersensitivity reportsEmerging
Have diabetes or prediabetesPossible effect on glucose in some peopleEmerging
Are pregnant or breastfeedingSafety not establishedEmerging
Take several other supplements or medicinesCombination products may contain extra ingredients; check for overlapsEmerging

Our supplement safety table lists interactions for other joint supplements, and the medications page covers the risks of the NSAIDs these supplements are often compared with.

Cost vs. benefit Emerging

Glucosamine and chondroitin are not expensive per bottle, but people often take them for years, and combination or "premium" products cost more. The value question is simple: are you paying for an effect you can actually feel? On the best independent evidence, the average effect is below what most patients notice,13 which is why the Wandel authors recommended that health systems not pay for them and NICE advises clinicians not to offer glucosamine.21

Arguments for a short trial

  • Low risk for most people without the cautions above.
  • Some individuals report benefit, and averages can hide responders.
  • A defined trial costs little and gives you your own answer.

Arguments against open-ended use

  • Ongoing cost with no proven average benefit.
  • Placebo response can make it look effective when it is not.
  • Money and effort may be better spent on exercise therapy and weight management, which have strong evidence.

The treatments with the strongest evidence in knee OA are exercise, weight loss if relevant, and education; see evidence-graded OA interventions and exercise and movement. If you are comparing supplements, our turmeric guide covers curcumin, which has a different (also modest) evidence base.

If you want to try it: a fair 3-month trial Emerging

Many people want to find out for themselves, and that is reasonable when done safely and honestly. This is a framework to discuss with your doctor or pharmacist, not a dosing recommendation.

  1. Check safety first. Ask a pharmacist if you take warfarin or other blood thinners, have diabetes, asthma or a shellfish allergy, or are pregnant.
  2. Choose one product that matches a studied form. For glucosamine, that usually means glucosamine sulfate 1,500 mg daily (the form and dose used in the more positive trials); for chondroitin, 800–1,200 mg daily. Prefer a third-party-tested product (see quality and testing).
  3. Record a baseline. Log pain, stiffness and a function measure you care about (stairs, walking distance) for 1–2 weeks before starting, using our flare tracker.
  4. Keep everything else stable. Avoid starting a new exercise program, injection or medicine at the same time, or you will not know what helped.
  5. Give it about 12 weeks. Trials measured benefit over 3–6 months, so judging after a week or two is too early.17
  6. Decide honestly and stop if there is no clear benefit. Compare your log with the baseline. Because placebo responses are large, a vague or small improvement is not strong evidence; if you are unsure, a supervised pause can help you tell.
Stop and contact a clinician if you notice unusual bleeding or bruising, signs of an allergic reaction (rash, swelling of the lips or face, wheeze), or rising blood sugar readings.
Dietary & supplement note: Statements here about dietary supplements have not been evaluated by the U.S. Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure, or prevent any disease.

When to see a doctor Strong

Seek prompt medical care if you:
  • have a hot, red, swollen joint with fever, which needs same-day assessment to rule out infection or gout;
  • notice unusual bleeding or bruising, blood in urine or stool, or black stools, especially if you take warfarin;
  • develop hives, facial or throat swelling, or difficulty breathing after taking a supplement;
  • cannot bear weight after an injury, or have sudden severe joint pain.

Book a routine appointment or pharmacist review if you:

  • have new joint swelling, morning stiffness lasting more than an hour, or several swollen joints, which can signal inflammatory arthritis such as rheumatoid arthritis that supplements will not control;
  • have taken glucosamine or chondroitin for about 3 months without clear benefit;
  • take prescription medicines, especially blood thinners or diabetes medication, and want to try a supplement;
  • are considering using a supplement in place of a prescribed treatment; please discuss this first rather than stopping anything on your own.

Frequently asked questions

Does glucosamine actually work for knee pain?

For most people, probably not by much. The large NIH-funded GAIT trial found no significant overall benefit over placebo after 24 weeks, and a 2010 BMJ network meta-analysis of 10 large trials found pain differences well below what patients notice. Some trials of a prescription crystalline glucosamine sulfate product were more positive, which is why some European experts still recommend it, while the American College of Rheumatology strongly recommends against glucosamine for knee, hip and hand osteoarthritis. This is educational information, not medical advice.

Is glucosamine sulfate better than glucosamine hydrochloride?

Possibly, but it is unproven. Positive trials mostly used one prescription crystalline glucosamine sulfate product, and meta-analyses find that brand explains much of the difference between trials. However, when only the trials of that product at low risk of bias are pooled, the effect is small, and an independent Australian trial of glucosamine sulfate (LEGS) found no pain benefit over placebo. Glucosamine hydrochloride, the form used in GAIT, has not outperformed placebo in large trials.

Can glucosamine or chondroitin rebuild cartilage?

No supplement has been shown to rebuild cartilage. A few industry-linked trials reported slightly less joint space narrowing on X-ray over two to three years, measured in tenths of a millimetre, but independent trials and a network meta-analysis found differences that were minute or absent, and none showed regrowth. Guidelines do not recommend either supplement for slowing osteoarthritis.

Is glucosamine safe with warfarin or a shellfish allergy?

Check with your prescriber or pharmacist first. Glucosamine, with or without chondroitin, has been linked to a raised INR and bleeding in people taking warfarin, including more than 20 spontaneous reports in FDA and WHO databases. Most glucosamine is made from shellfish shells, and Australian regulators received hundreds of reports of allergic-type reactions to these products, so people with shellfish allergy or asthma should get advice before using them. People with diabetes should monitor their blood sugar.

How long should I try glucosamine before deciding if it works?

Trials usually measured benefit at about 3 to 6 months, so if you and your clinician decide to try it, a fixed trial of around 12 weeks with a symptom log is reasonable. Record pain and function for a week or two before starting, keep other treatments stable, and stop if you cannot see a clear benefit by the end. Remember that placebo responses in these trials were large, so a modest improvement may not be due to the supplement.

References

  1. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006;354(8):795–808. PubMed 16495392
  2. Sawitzke AD, Shi H, Finco MF, et al. The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: a report from the glucosamine/chondroitin arthritis intervention trial. Arthritis Rheum. 2008;58(10):3183–3191. PubMed 18821708
  3. Sawitzke AD, Shi H, Finco MF, et al. Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT. Ann Rheum Dis. 2010;69(8):1459–1464. PubMed 20525840
  4. Fransen M, Agaliotis M, Nairn L, et al; LEGS study collaborative group. Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis. 2015;74(5):851–858. PubMed 24395557
  5. Hochberg MC, Martel-Pelletier J, Monfort J, et al; MOVES Investigation Group. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis. 2016;75(1):37–44. PubMed 25589511
  6. Roman-Blas JA, Castañeda S, Sánchez-Pernaute O, Largo R, Herrero-Beaumont G; CS/GS Combined Therapy Study Group. Combined treatment with chondroitin sulfate and glucosamine sulfate shows no superiority over placebo for reduction of joint pain and functional impairment in patients with knee osteoarthritis: a six-month multicenter, randomized, double-blind, placebo-controlled clinical trial. Arthritis Rheumatol. 2017;69(1):77–85. PubMed 27477804
  7. Herrero-Beaumont G, Ivorra JA, Del Carmen Trabado M, et al. Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis Rheum. 2007;56(2):555–567. PubMed 17265490
  8. Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. 2001;357(9252):251–256. PubMed 11214126
  9. Pavelká K, Gatterová J, Olejarová M, Machacek S, Giacovelli G, Rovati LC. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med. 2002;162(18):2113–2123. PubMed 12374520
  10. Kahan A, Uebelhart D, De Vathaire F, Delmas PD, Reginster JY. Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: the study on osteoarthritis progression prevention, a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2009;60(2):524–533. PubMed 19180484
  11. Reginster JY, Dudler J, Blicharski T, Pavelka K. Pharmaceutical-grade chondroitin sulfate is as effective as celecoxib and superior to placebo in symptomatic knee osteoarthritis: the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT). Ann Rheum Dis. 2017;76(9):1537–1543. PubMed 28533290
  12. Gabay C, Medinger-Sadowski C, Gascon D, Kolo F, Finckh A. Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate on hand osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial at a single center. Arthritis Rheum. 2011;63(11):3383–3391. PubMed 21898340
  13. Wandel S, Jüni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ. 2010;341:c4675. PubMed 20847017
  14. Towheed TE, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2005;(2):CD002946. PubMed 15846645
  15. Singh JA, Noorbaloochi S, MacDonald R, Maxwell LJ. Chondroitin for osteoarthritis. Cochrane Database Syst Rev. 2015;1:CD005614. PubMed 25629804
  16. Eriksen P, Bartels EM, Altman RD, Bliddal H, Juhl C, Christensen R. Risk of bias and brand explain the observed inconsistency in trials on glucosamine for symptomatic relief of osteoarthritis: a meta-analysis of placebo-controlled trials. Arthritis Care Res (Hoboken). 2014;66(12):1844–1855. PubMed 24905534
  17. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res (Hoboken). 2020;72(2):149–162. PubMed 31908149
  18. Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27(11):1578–1589. PubMed 31278997
  19. Bruyère O, Honvo G, Veronese N, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum. 2019;49(3):337–350. PubMed 31126594
  20. Arden NK, Perry TA, Bannuru RR, et al. Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nat Rev Rheumatol. 2021;17(1):59–66. PubMed 33116279
  21. Osteoarthritis in over 16s: diagnosis and management (NG226). National Institute for Health and Care Excellence; 2022. nice.org.uk/guidance/ng226
  22. Knudsen JF, Sokol GH. Potential glucosamine-warfarin interaction resulting in increased international normalized ratio: case report and review of the literature and MedWatch database. Pharmacotherapy. 2008;28(4):540–548. PubMed 18363538
  23. Dostrovsky NR, Towheed TE, Hudson RW, Anastassiades TP. The effect of glucosamine on glucose metabolism in humans: a systematic review of the literature. Osteoarthritis Cartilage. 2011;19(4):375–380. PubMed 21251987
  24. Gommans YMM, Runhaar J, Jacobs ML, Bierma-Zeinstra SMA. The effect of prolonged glucosamine usage on HbA1c levels and new-onset diabetes mellitus in overweight and obese middle-aged women. Am J Med. 2017;130(6):731–737.e6. PubMed 28011309
  25. Hoban C, Byard R, Musgrave I. Hypersensitive adverse drug reactions to glucosamine and chondroitin preparations in Australia between 2000 and 2011. Postgrad Med J. 2020;96(1134):190–193. PubMed 31597786
  26. Honvo G, Reginster JY, Rabenda V, et al. Safety of symptomatic slow-acting drugs for osteoarthritis: outcomes of a systematic review and meta-analysis. Drugs Aging. 2019;36(Suppl 1):65–99. PubMed 31073924
  27. Glucosamine and Chondroitin for Osteoarthritis — National Center for Complementary and Integrative Health (NCCIH), NIH. nccih.nih.gov/health/glucosamine-and-chondroitin-for-osteoarthritis