Glucosamine

Purported Benefits, Side Effects & More
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Glucosamine

Purported Benefits, Side Effects & More
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Glucosamine

Common Names

  • Glucosamine sulphate
  • Glucosamine hydrochloride
  • Chitosamine

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For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.

What is it?

Glucosamine is a chemical found in your body that helps make cartilage (the protective tissue at the ends of bones). When cartilage breaks down in people with osteoarthritis (joint pain in your hands, neck, lower back, knees, or hips), glucosamine may help slow this down.

You can take glucosamine supplements as pills, tablets, capsules, or powder that can be made into a drink by dissolving it in water. You can also rub a glucosamine gel or lotion onto your skin.

What are the potential uses and benefits?

Glucosamine is used to:

  • Decrease swelling in joints
  • Treat osteoarthritis
  • Treat temporomandibular joint disorder (TMJ). TMJ is pain and difficulty moving the jaw joint and muscles around it.

Glucosamine also has other uses that haven’t been studied by doctors to see if they work.

Talk with your healthcare provider before taking glucosamine supplements. They can interact with some prescription medications and affect how they work.

For more information, read the “What else do I need to know?” section below.

What are the side effects?

Side effects of glucosamine may include:

  • Nausea (feeling like you’re going to throw up)
  • Diarrhea (loose or watery bowel movements)
  • Abdominal (belly) pain
  • Heartburn
  • Itching
  • Skin rash
  • Temporary memory loss
  • Low blood pressure
  • Sleepiness
  • Trouble breathing
What else do I need to know?
  • Talk with your healthcare provider before taking glucosamine supplements if you have liver disease. Glucosamine may worsen your condition.
  • Talk with your healthcare provider before taking glucosamine supplements if you’re taking blood thinners such as warfarin (Coumadin®). Taking both may cause side effects.
  • Talk with your healthcare provider if you have diabetes or glaucoma (an eye condition that may lead to blindness). Glucosamine may worsen your condition.
  • Talk with your healthcare provider if you’re allergic to shellfish. You may have an allergic reaction to glucosamine supplements.
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For Healthcare Professionals

Scientific Name
2-Amino-2-deoxyglucose
Clinical Summary

Glucosamine is an aminomonosaccharide synthesized from glucose. It is found in the cartilage and fluid around the joints as well as in marine invertebrate exoskeletons. Glucosamine has anti-inflammatory effects, and is marketed as a dietary supplement and often paired with chondroitin sulfate for joint health.

Glucosamine has been mostly studied for osteoarthritis (OA). Although glucosamine/chondroitin supplementation was comparable to celecoxib in a large multicenter trial of patients with severe knee OA pain (2), and reduced circulating inflammatory cytokine IL-6 (47), other studies have not found benefit with glucosamine, chondroitin, or the combination for knee or hip OA (3) (4) (5) (6) (7) (8) (9) (10) (53). Data on chondroitin alone also suggest no significant benefit (10) (11). In addition, no efficacy was seen with glucosamine for back pain (12) (13), degenerative lumbar OA (13), or improving glucose metabolism in type 2 diabetes (14). Any benefits with glucosamine may be limited to older patients who have arthritis that is more severe (15) or for longer periods of time (16).

Meta-analyses of glucosamine trials are also mixed (35) (36) (37) (38) (39) (54). The American College of Rheumatology conditionally recommends that patients avoid glucosamine for OA (45). In contrast, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis treatment guidelines (40) recommend a prescription glucosamine formulation as being superior to other forms, but this product is not available in the US (40). It is further suggested that these differences in availability and formulas have contributed to the lack of significant effect across studies and pooled analyses (46). Additionally, interindividual differences in the absorption and elimination of glucosamine may cause variable clinical outcomes in OA according to a study of healthy adults (48).

Clinical trials on whether glucosamine can improve temporomandibular joint symptoms are limited, providing low or no evidence of this effect (1) (41) (55) (60) although one study of oral glucosamine adjunctive to hyaluronic acid injection suggests long-term benefit (42). Preliminary studies of other combination treatments with glucosamine for various types of OA suggest improvements in pain and function (49) (52), but more studies are needed to confirm these effects.

Glucosamine has been assessed for its potential role against depression. Although preclinical studies suggested antidepressive effects, a clinical investigation failed to find any benefit (50).

Exploratory findings suggest glucosamine may benefit gut health (56). Larger studies are needed to confirm these effects.

Glucosamine/chondroitin supplementation has been correlated with reduction in cancer risk and mortality, although limitations such as bias could not be ruled out and confirmatory studies are needed (17) (18) (19) (57) (58) (59).

Glucosamine use has been associated with a higher risk for cardiovascular diseases in patients with osteoarthritis (61) along with case reports of liver injury/toxicity (20) (21).  Patients on antiplatelet or anticoagulant therapies should be monitored for interactions or increased INR levels (22) (23). Patients with poorly controlled diabetes or glucose intolerance should be monitored as glucosamine could worsen insulin resistance (24) (25).

Purported Uses and Benefits
  • Inflammation
  • Osteoarthritis
  • Temporomandibular joint disorders
Mechanism of Action

Progressive degeneration of cartilage glycosaminoglycans is evident in osteoarthritis. Glucosamine is the first step in glycosaminoglycan biosynthesis. In vitro, it increased production of monomeric proteoglycans capable of assembling into high molecular weight aggregates (26). Glucosamine can protect cartilage from metabolic impairment by NSAIDs, corticosteroids, and by exerting anti-inflammatory effects (27). It may promote cartilage repair by inducing tissue TGFβ1 and CTGF expression that regulates chondrocyte proliferation (28). Long-term reductions in TMJ symptoms with adjunctive oral glucosamine may be due to TGF-beta stimulation and IL-1beta / IL-6 suppression (42). Reduced systemic inflammation and cytokine activity found in a small randomized crossover study may explain potential reductions in mortality or cancer risk (30).

Although glucosamine is slow to act (31), its effects may persist after treatment cessation (26).

The rise in intraocular pressure associated with older patients in one study may relate to exogenous glycosaminoglycans effects on accumulations of extracellular matrix and thickening of the basement membrane, thereby compromising function of the trabecular meshwork (29).

Warnings
  • Patients with liver disease should avoid taking glucosamine, as it is extensively metabolized in the liver and there are case reports of liver injury/toxicity (20) (21).
  • Patients who are taking anticoagulants or antiplatelet drugs or who have glaucoma or diabetes should be monitored, as there is some preliminary evidence for potential side effects (22) (23) (24) (25) (29).
  • Individuals should consult their doctor if allergic to shellfish (32).
Adverse Reactions

Glucosamine tends to be safe and well tolerated (43), but caution should be exercised in certain populations (see Warnings and Interactions).

Rare reactions include gastrointestinal complaints (33) (41) and allergic reactions (20) (62).

Case Reports 
Chronic tubulointerstitial nephropathy: In a 67-year-old patient who took glucosamine daily for 3 years for OA knee pain (44).
Increased intraocular pressure: In a randomized double-blind trial, glucosamine sulfate supplementation significantly increased intraocular pressure in older patients with OA (29). The implication of this finding needs further evaluation.
Liver injury/hepatotoxicity and elevated aminotransferase values: In patients with liver disease (20) (21).
Reduced glucose tolerance: From infusion and oral forms of glucosamine (34).

Analysis of 366 adverse drug reactions to glucosamine and chondroitin preparations showed 263 cases had hypersensitivity reactions (51):

  • Mild: Pruritus, urticaria, lip edema
  • Moderate: Dyspnea, nausea, abdominal pain
  • Severe: Amnesia, gait disturbance, somnolence, hypotension
Herb-Drug Interactions
  • Warfarin: Although more information is needed to define this interaction, glucosamine-chondroitin may potentiate warfarin effects and increase INR levels (22).
  • Anticoagulants/Antiplatelets: Use of glucosamine may inhibit platelet aggregation (23).
Herb Lab Interactions
  • Blood glucose levels: May be affected by glucosamine (34).
  • Increased International Normalized Ratio (INR): Glucosamine was associated with increased INR that return to normal levels when discontinued (22).
  • Elevated aminotransferase values: In patients with liver disease (20).
Dosage (OneMSK Only)
References
  1. Nguyen P, Mohamed SE, Gardiner D, et al. A randomized double-blind clinical trial of the effect of chondroitin sulfate and glucosamine hydrochloride on temporomandibular joint disorders: a pilot study. Cranio. Apr 2001;19(2):130-139.
  2. Hochberg MC, Martel-Pelletier J, Monfort J, et al. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis. Jan 2016;75(1):37-44.
  3. Roman-Blas JA, Castaneda S, Sanchez-Pernaute O, et al. 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. Jan 2017;69(1):77-85.
  4. Fransen M, Agaliotis M, Nairn L, et al. Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis. May 2015;74(5):851-858.
  5. Kwoh CK, Roemer FW, Hannon MJ, et al. Effect of oral glucosamine on joint structure in individuals with chronic knee pain: a randomized, placebo-controlled clinical trial. Arthritis Rheumatol. Apr 2014;66(4):930-939.
  6. Cibere J, Kopec JA, Thorne A, et al. Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis. Arthritis Rheum. Oct 15 2004;51(5):738-745.
  7. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. Feb 23 2006;354(8):795-808.
  8. 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. Feb 2007;56(2):555-567.
  9. 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. Oct 2008;58(10):3183-3191.
  10. Wandel S, Juni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ. Sep 16 2010;341:c4675.
  11. Reichenbach S, Sterchi R, Scherer M, et al. Meta-analysis: chondroitin for osteoarthritis of the knee or hip. Ann Intern Med. Apr 17 2007;146(8):580-590.
  12. Leffler CT, Philippi AF, Leffler SG, et al. Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study. Mil Med. Feb 1999;164(2):85-91.
  13. Wilkens P, Scheel IB, Grundnes O, et al. Effect of glucosamine on pain-related disability in patients with chronic low back pain and degenerative lumbar osteoarthritis: a randomized controlled trial. JAMA. Jul 7 2010;304(1):45-52.
  14. Scroggie DA, Albright A, Harris MD. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Arch Intern Med. Jul 14 2003;163(13):1587-1590.
  15. Hughes R, Carr A. A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee. Rheumatology (Oxford). Mar 2002;41(3):279-284.
  16. Rindone JP, Hiller D, Collacott E, et al. Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee. West J Med. Feb 2000;172(2):91-94.
  17. Bell GA, Kantor ED, Lampe JW, et al. Use of glucosamine and chondroitin in relation to mortality. Eur J Epidemiol. Aug 2012;27(8):593-603.
  18. Pocobelli G, Kristal AR, Patterson RE, et al. Total mortality risk in relation to use of less-common dietary supplements. Am J Clin Nutr. Jun 2010;91(6):1791-1800.
  19. Satia JA, Littman A, Slatore CG, et al. Associations of herbal and specialty supplements with lung and colorectal cancer risk in the VITamins and Lifestyle study. Cancer Epidemiol Biomarkers Prev. May 2009;18(5):1419-1428.
  20. Cerda C, Bruguera M, Pares A. Hepatotoxicity associated with glucosamine and chondroitin sulfate in patients with chronic liver disease. World J Gastroenterol. Aug 28 2013;19(32):5381-5384.
  21. Smith A, Dillon J. Acute liver injury associated with the use of herbal preparations containing glucosamine: three case studies. BMJ Case Rep. 2009;2009.
  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. Apr 2008;28(4):540-548.
  23. Lin PC, Jones SO, McGlasson DL. Effects of glucosamine and Celadrin on platelet function. Clin Lab Sci. Winter 2010;23(1):32-36.
  24. Marshall PD, Poddar S, Tweed EM, et al. Clinical inquiries: Do glucosamine and chondroitin worsen blood sugar control in diabetes? J Fam Pract. Dec 2006;55(12):1091-1093.
  25. Pham T, Cornea A, Blick KE, et al. Oral glucosamine in doses used to treat osteoarthritis worsens insulin resistance. Am J Med Sci. Jun 2007;333(6):333-339.
  26. Bassleer C, Rovati L, Franchimont P. Stimulation of proteoglycan production by glucosamine sulfate in chondrocytes isolated from human osteoarthritic articular cartilage in vitro. Osteoarthritis Cartilage. Nov 1998;6(6):427-434.
  27. Runkel DR, Cupp MJ. Glucosamine sulfate use in osteoarthritis. Am J Health Syst Pharm. Feb 1 1999;56(3):267-269.
  28. Ali AA, Lewis SM, Badgley HL, et al. Oral glucosamine increases expression of transforming growth factor beta1 (TGFbeta1) and connective tissue growth factor (CTGF) mRNA in rat cartilage and kidney: implications for human efficacy and toxicity. Arch Biochem Biophys. Jun 1 2011;510(1):11-18.
  29. Esfandiari H, Pakravan M, Zakeri Z, et al. Effect of glucosamine on intraocular pressure: a randomized clinical trial. Eye (Lond). Mar 2017;31(3):389-394.
  30. Navarro SL, White E, Kantor ED, et al. Randomized trial of glucosamine and chondroitin supplementation on inflammation and oxidative stress biomarkers and plasma proteomics profiles in healthy humans. PLoS One. 2015;10(2):e0117534.
  31. Muller-Fassbender H, Bach GL, Haase W, et al. Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis Cartilage. Mar 1994;2(1):61-69.
  32. Dahmer S, Schiller RM. Glucosamine. Am Fam Physician. Aug 15 2008;78(4):471-476.
  33. Towheed TE, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. Apr 18 2005(2):Cd002946.
  34. Monauni T, Zenti MG, Cretti A, et al. Effects of glucosamine infusion on insulin secretion and insulin action in humans. Diabetes. Jun 2000;49(6):926-935.
  35. Gregori D, Giacovelli G, Minto C, et al. Association of Pharmacological Treatments With Long-term Pain Control in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis. JAMA. Dec 25 2018;320(24):2564-2579.
  36. Liu X, Machado GC, Eyles JP, et al. Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Br J Sports Med. Feb 2018;52(3):167-175.
  37. Ogata T, Ideno Y, Akai M, et al. Effects of glucosamine in patients with osteoarthritis of the knee: a systematic review and meta-analysis. Clin Rheumatol. Sep 2018;37(9):2479-2487.
  38. Zhu X, Sang L, Wu D, et al. Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials. J Orthop Surg Res. Jul 6 2018;13(1):170.
  39. Simental-Mendia M, Sanchez-Garcia A, Vilchez-Cavazos F, et al. Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials. Rheumatol Int. Aug 2018;38(8):1413-1428.
  40. Bruyere O, Altman RD, Reginster JY. Efficacy and safety of glucosamine sulfate in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. Feb 2016;45(4 Suppl):S12-17.
  41. Melo G, Casett E, Stuginski-Barbosa J, et al. Effects of glucosamine supplements on painful temporomandibular joint osteoarthritis: A systematic review. J Oral Rehabil. May 2018;45(5):414-422.
  42. Cen X, Liu Y, Wang S, et al. Glucosamine oral administration as an adjunct to hyaluronic acid injection in treating temporomandibular joint osteoarthritis. Oral Dis. Apr 2018;24(3):404-411.
  43. 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. Apr 2019;36(Suppl 1):65-99.
  44. Gueye S, Saint-Cricq M, Coulibaly M, et al. Chronic tubulointerstitial nephropathy induced by glucosamine: a case report and literature review. Clin Nephrol. Aug 2016;86(2):106-110.
  45. Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). Apr 2012;64(4):465-474. Full article available at https://www.aafp.org/afp/2013/0401/p515.html and https://www.aafp.org/afp/2013/0401/p515.pdf.
  46. Reginster JY, Cooper C, Hochberg M, et al. Comments on the discordant recommendations for the use of symptomatic slow-acting drugs in knee osteoarthritis. Curr Med Res Opin. May 2015;31(5):1041-1045.
  47. Navarro SL, Herrero M, Martinez H, et al. Differences in Serum Biomarkers Between Combined Glucosamine and Chondroitin Versus Celecoxib in a Randomized, Double-blind Trial in Osteoarthritis Patients. Antiinflamm Antiallergy Agents Med Chem. 2020;19(2):190-201.
  48. Asthana C, Peterson GM, Shastri MD, Patel RP. Variation in the pharmacokinetics of glucosamine in healthy individuals. Rheumatology (Oxford). 2020 Sep 9:keaa418.
  49. Tenti S, Giordano N, Mondanelli N, et al. A retrospective observational study of glucosamine sulfate in addition to conventional therapy in hand osteoarthritis patients compared to conventional treatment alone. Aging Clin Exp Res. 2020 Jun;32(6):1161-1172.
  50. Kumar PNS, Sharma A, Andrade C. A pilot, open-label investigation of the efficacy of glucosamine for the treatment of major depression.Asian J Psychiatr. 2020 Aug;52:102113.
  51. 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 Apr;96(1134):190-193.
  52. Wang SJ, Wang YH, Huang LC. The effect of oral low molecular weight liquid hyaluronic acid combination with glucosamine and chondroitin on knee osteoarthritis patients with mild knee pain: An 8-week randomized double-blind placebo-controlled trial. Medicine (Baltimore). Feb 5 2021;100(5):e24252.
  53. Wang SJ, Wang YH, Huang LC. Liquid combination of hyaluronan, glucosamine, and chondroitin as a dietary supplement for knee osteoarthritis patients with moderate knee pain: A randomized controlled study. Medicine (Baltimore). 2021 Oct 8;100(40):e27405.
  54. Wang Z, Wang R, Yao H, et al. Clinical Efficacy and Safety of Chondroitin Combined with Glucosamine in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-Analysis. Comput Math Methods Med. 2022 Jul 25;2022:5285244.
  55. Cömert Kılıç S. Does glucosamine, chondroitin sulfate, and methylsulfonylmethane supplementation improve the outcome of temporomandibular joint osteoarthritis management with arthrocentesis plus intraarticular hyaluronic acid injection. A randomized clinical trial. J Craniomaxillofac Surg. 2021 Aug;49(8):711-718.
  56. Moon JM, Finnegan P, Stecker RA,et al. Impact of Glucosamine Supplementation on Gut Health. Nutrients. 2021 Jun 24;13(7):2180.
  57. Kantor ED, O’Connell K, Liang PS, Navarro SL, Giovannucci EL, Du M. Glucosamine Use and Risk of Colorectal Cancer: Results from UK Biobank. Cancer Epidemiol Biomarkers Prev. 2022 Mar 1;31(3):647-653.
  58. Li G, Zhang X, Liu Y, et al. Relationship between glucosamine use and the risk of lung cancer: data from a nationwide prospective cohort study. Eur Respir J. 2022 Mar 10;59(3):2101399.
  59. Zhou J, Wu Z, Lin Z, et al. Association between glucosamine use and cancer mortality: A large prospective cohort study. Front Nutr. 2022 Nov 2;9:947818.
  60. Derwich M, Górski B, Amm E, Pawłowska E. Oral Glucosamine in the Treatment of Temporomandibular Joint Osteoarthritis: A Systematic Review.  Int J Mol Sci. 2023 Mar 3;24(5):4925. 
  61. Yu H, Wu J, Chen H, et al. Glucosamine Use Is Associated with a Higher Risk of Cardiovascular Diseases in Patients with Osteoarthritis: Results from a Large Study in 685,778 Subjects. Nutrients. 2022 Sep 7;14(18):3694.
  62. Chu EC, Huang KHK, Cheung G, Ng G, Lin A. Delayed Skin Allergy to Glucosamine Chondroitin Supplement.  Cureus. 2023 Mar 17;15(3):e36310.
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