Glucosamine is an amino monosaccharide (a sugar molecule with a nitrogen group attached) that occurs naturally in almost all human tissues, but is highly concentrated in connective tissues (joints) and cartilage.
The body uses glucosamine to synthesize glycoproteins and glycosaminoglycans. Notably, glycosaminoglycans are structural components present in both cartilage and joints, playing a crucial role in providing these tissues with elasticity, strength, and flexibility.
Although glucosamine is not an FDA-approved treatment, glucosamine supplements are commonly used as adjunct therapy for the management of osteoarthritis. Nevertheless, studies investigating the effectiveness of glucosamine have produced conflicting results.
Glucosamine is a popular supplement for osteoarthritis, a disease characterized by excessive collagen degradation. However, the evidence supporting its effectiveness is not robust, and study results vary. One trial, known as the Glucosamine Unum In Die Efficacy (GUIDE) trial, which compared supplementation with a glucosamine sulfate-sodium chloride complex to placebo and to acetaminophen (the reference drug for osteoarthritis), found that the glucosamine preparation outperformed both placebo and acetaminophen at reducing knee arthritis severity scores. Although it was well-designed, this trial has been criticized as it was sponsored by the same company that manufactured the glucosamine salt used, who not only provided funding but also carried out the statistical analysis. In contrast, a larger trial of interventions for knee osteoarthritis found that glucosamine had no significant effect on pain. Finally, one meta-analysis of interventions for hip and knee arthritis found that glucosamine may improve stiffness but does not significantly affect pain or physical function, whether used alone or in combination with chondroitin (another supplement often used for osteoarthritis and joint health). It’s also important to note that studies suggesting a positive impact of glucosamine on osteoarthritis indicate that it might slow down the disease progression rather than reverse it.
Research on soccer players and bicycle racers has found that in these athletic participants, glucosamine supplementation, particularly at a dose of 3 grams, was able to reduce levels of a biomarker associated with collagen breakdown, CPX-II. While collagen synthesis was not affected, these results suggest that glucosamine may help prevent collagen degradation. Another study involving participants with knee osteoarthritis who underwent a 12-week strength training program compared glucosamine (1500 mg) to a non-steroidal anti-inflammatory drug (NSAID) (1200 mg of ibuprofen) and found that glucosamine reduced exercise-related pain but did not impact muscle growth or power.
There are also potential uses for glucosamine sulfate in temporomandibular joint disorder (TMD). Glucosamine appears to reduce pain associated with TMD and increase mouth opening, but only when taken for over 3 months. However, as with osteoarthritis, there isn’t enough scientific evidence to support the use of glucosamine sulfate for symptomatic relief of TMD or as a modifier of the disease’s progression.
Glucosamine appears to be overall safe and with minimal side effects at its most common dosage of 1500 mg a day. One systematic review of randomized controlled trials found no significant difference in the frequency of reported side effects between participants taking glucosamine and those in the placebo group. Although no serious side effects were reported, most adverse events associated with glucosamine supplementation affect the gastrointestinal tract (e.g., diarrhea, abdominal pain, nausea).
There are no known interactions between glucosamine and medications. However, there was one reported case where glucosamine appeared to enhance the anticoagulant effect of warfarin, therefore increasing the risk of bleeding and bruising. It’s important to note that this was an isolated case, and the person involved was taking a combination of glucosamine and chondroitin, which may also have been responsible for the interaction.
Additionally, animal studies observed an increase in insulin resistance after the administration of glucosamine. Clinical studies administering glucosamine intravenously have confirmed these results. However, this effect occurs at plasma concentrations higher than those achieved with oral supplementation, and to a lesser degree than observed in rat studies. Other clinical studies have concluded that glucosamine supplementation does not impact insulin sensitivity, so more research is needed to clarify these potential effects.
Although glucosamine was initially thought to act as a substrate of collagen, this theory has since been discredited. Instead, it appears that glucosamine interferes with the inflammatory cascade involved in the degradation of collagen in arthritic tissues by downregulating the collagen-deteriorating effects of pro-inflammatory molecules, such as interleukin 1 (IL-1).
Another proposed mechanism observed in vitro is that glucosamine sulfate increases collagen expression by promoting the synthesis of glycosaminoglycans. However, it’s important to specify that the concentrations used in this research were high and may not be directly applicable to human oral consumption. Additionally, clinical studies attempting to measure a serum biomarker of collagen synthesis, type II collagen synthesis (CPII), did not observe a significant effect from glucosamine treatment.
- Glucosamine sulfate
- Glucosamine hydrochloride
Glucosamine sulfate is typically taken as a 500 mg dose three times a day with food.
The benefits of glucosamine are dose-dependent, and some studies on athletes used up to 2,000–3,000 mg a day, taken in divided doses.
Glucosamine sulfate salts are usually taken as a one-a-day dose of 1500 mg glucosamine.
- ^Williams C, Ampat GGlucosamine SulfateStatPearls.(2023-01)
- ^Momomura R, Naito K, Igarashi M, Watari T, Terakado A, Oike S, Sakamoto K, Nagaoka I, Kaneko KEvaluation of the effect of glucosamine administration on biomarkers of cartilage and bone metabolism in bicycle racersMol Med Report.(2013 Jan 25)
- ^Herrero-Beaumont G, Ivorra JA, Del Carmen Trabado M, Blanco FJ, Benito P, Martín-Mola E, Paulino J, Marenco JL, Porto A, Laffon A, Araújo D, Figueroa M, Branco JGlucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparatorArthritis Rheum.(2007 Feb)
- ^Dahmer S, Schiller RMGlucosamine.Am Fam Physician.(2008-Aug-15)
- ^Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, Bradley JD, Bingham CO 3rd, Weisman MH, Jackson CG, Lane NE, Cush JJ, Moreland LW, Schumacher HR Jr, Oddis CV, Wolfe F, Molitor JA, Yocum DE, Schnitzer TJ, Furst DE, Sawitzke AD, Shi H, Brandt KD, Moskowitz RW, Williams HJGlucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritisN Engl J Med.(2006 Feb 23)
- ^Zhu X, Sang L, Wu D, Rong J, Jiang LEffectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials.J Orthop Surg Res.(2018-Jul-06)
- ^Yoshimura M, Sakamoto K, Tsuruta A, Yamamoto T, Ishida K, Yamaguchi H, Nagaoka IEvaluation of the effect of glucosamine administration on biomarkers for cartilage and bone metabolism in soccer playersInt J Mol Med.(2009 Oct)
- ^Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, Kjaer MNonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients.Arch Phys Med Rehabil.(2011-Aug)
- ^Derwich M, Górski B, Amm E, Pawłowska EOral Glucosamine in the Treatment of Temporomandibular Joint Osteoarthritis: A Systematic Review.Int J Mol Sci.(2023-Mar-03)
- ^Vo NX, Le NNH, Chu TDP, Pham HL, Dinh KXA, Che UTT, Ngo TTT, Bui TTEffectiveness and Safety of Glucosamine in Osteoarthritis: A Systematic Review.Pharmacy (Basel).(2023-Jul-14)
- ^Knudsen JF, Sokol GHPotential glucosamine-warfarin interaction resulting in increased international normalized ratio: case report and review of the literature and MedWatch database.Pharmacotherapy.(2008-Apr)
- ^Baron AD, Zhu JS, Zhu JH, Weldon H, Maianu L, Garvey WTGlucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity.J Clin Invest.(1995-Dec)
- ^Herrero-Beaumont G, Rovati LC, Castañeda S, Alvarez-Soria MA, Largo RThe reverse glucosamine sulfate pathway: application in knee osteoarthritis.Expert Opin Pharmacother.(2007-Feb)
- ^Block JA, Oegema TR, Sandy JD, Plaas AThe effects of oral glucosamine on joint health: is a change in research approach needed?Osteoarthritis Cartilage.(2010-Jan)
- ^Vlad SC, LaValley MP, McAlindon TE, Felson DTGlucosamine for pain in osteoarthritis: why do trial results differArthritis Rheum.(2007 Jul)
- ^Henrotin Y, Mobasheri A, Marty MIs there any scientific evidence for the use of glucosamine in the management of human osteoarthritis?Arthritis Res Ther.(2012-Jan-30)
- ^Meulyzer M, Vachon P, Beaudry F, Vinardell T, Richard H, Beauchamp G, Laverty SComparison of pharmacokinetics of glucosamine and synovial fluid levels following administration of glucosamine sulphate or glucosamine hydrochloride.Osteoarthritis Cartilage.(2008-Sep)
- ^Chhavi Asthana, Gregory M Peterson, Madhur D Shastri, Rahul P PatelVariation in the pharmacokinetics of glucosamine in healthy individualsRheumatology (Oxford).(2021 Mar 2)
- ^Heather C Gray, Patricia S Hutcheson, Raymond G SlavinIs glucosamine safe in patients with seafood allergy?J Allergy Clin Immunol.(2004 Aug)
- ^Liu W, Liu G, Pei F, Liu Y, Zhou Z, Li J, Shen B, Kang P, Xie Q, Ma XKashin-Beck disease in Sichuan, China: report of a pilot open therapeutic trialJ Clin Rheumatol.(2012 Jan)
- ^Singh S, Khajuria A, Taneja SC, Khajuria RK, Singh J, Qazi GNBoswellic acids and glucosamine show synergistic effect in preclinical anti-inflammatory study in rats.Bioorg Med Chem Lett.(2007-Jul-01)
- ^Gruenwald J, Petzold E, Busch R, Petzold HP, Graubaum HJEffect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis.Adv Ther.(2009-Sep)
- ^Zhu X, Wu D, Sang L, Wang Y, Shen Y, Zhuang X, Chu M, Jiang LComparative effectiveness of glucosamine, chondroitin, acetaminophen or celecoxib for the treatment of knee and/or hip osteoarthritis: a network meta-analysis.Clin Exp Rheumatol.(2018)
- ^Selvan T, Rajiah K, Nainar MS, Mathew EMA clinical study on glucosamine sulfate versus combination of glucosamine sulfate and NSAIDs in mild to moderate knee osteoarthritis.ScientificWorldJournal.(2012)
- Osteoarthritis Symptoms - Chopra A, Saluja M, Tillu G, Sarmukkaddam S, Venugopalan A, Narsimulu G, Handa R, Sumantran V, Raut A, Bichile L, Joshi K, Patwardhan BAyurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trialRheumatology (Oxford).(2013 Jan 30)
- Osteoarthritis Symptoms - Vlad SC, LaValley MP, McAlindon TE, Felson DTGlucosamine for pain in osteoarthritis: why do trial results differArthritis Rheum.(2007 Jul)
- Osteoarthritis Symptoms - Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster JYStructural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysisArch Intern Med.(2003 Jul 14)
- Osteoarthritis Symptoms - Yongsak Wangroongsub, Aree Tanavalee, Vajara Wilairatana, Srihatach NgarmukosComparable clinical outcomes between glucosamine sulfate-potassium chloride and glucosamine sulfate sodium chloride in patients with mild and moderate knee osteoarthritis: a randomized, double-blind studyJ Med Assoc Thai.(2010 Jul)
- Osteoarthritis Symptoms - Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, Bradley JD, Bingham CO 3rd, Weisman MH, Jackson CG, Lane NE, Cush JJ, Moreland LW, Schumacher HR Jr, Oddis CV, Wolfe F, Molitor JA, Yocum DE, Schnitzer TJ, Furst DE, Sawitzke AD, Shi H, Brandt KD, Moskowitz RW, Williams HJGlucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritisN Engl J Med.(2006 Feb 23)
- Osteoarthritis Symptoms - Wandel S, Jüni P, Tendal B, Nüesch E, Villiger PM, Welton NJ, Reichenbach S, Trelle SEffects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysisBMJ.(2010 Sep 16)
- Osteoarthritis Symptoms - Houpt JB, McMillan R, Wein C, Paget-Dellio SDEffect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the kneeJ Rheumatol.(1999 Nov)
- Osteoarthritis Symptoms - Towheed TE, Anastassiades TP, Shea B, Houpt J, Welch V, Hochberg MCGlucosamine therapy for treating osteoarthritisCochrane Database Syst Rev.(2001)
- Osteoarthritis Symptoms - McAlindon TE, LaValley MP, Gulin JP, Felson DTGlucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysisJAMA.(2000 Mar 15)
- Osteoarthritis Symptoms - Pujalte JM, Llavore EP, Ylescupidez FRDouble-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosisCurr Med Res Opin.(1980)
- Osteoarthritis Symptoms - McAlindon T, Formica M, LaValley M, Lehmer M, Kabbara KEffectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trialAm J Med.(2004 Nov 1)
- Osteoarthritis Symptoms - Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, Giacovelli G, Henrotin Y, Dacre JE, Gossett CLong-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trialLancet.(2001 Jan 27)
- Osteoarthritis Symptoms - Herrero-Beaumont G, Ivorra JA, Del Carmen Trabado M, Blanco FJ, Benito P, Martín-Mola E, Paulino J, Marenco JL, Porto A, Laffon A, Araújo D, Figueroa M, Branco JGlucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparatorArthritis Rheum.(2007 Feb)
- Osteoarthritis Symptoms - Pavelká K, Gatterová J, Olejarová M, Machacek S, Giacovelli G, Rovati LCGlucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind studyArch Intern Med.(2002 Oct 14)
- Osteoarthritis Symptoms - Hughes R, Carr AA randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the kneeRheumatology (Oxford).(2002 Mar)
- Osteoarthritis Symptoms - Rindone JP, Hiller D, Collacott E, Nordhaugen N, Arriola GRandomized, controlled trial of glucosamine for treating osteoarthritis of the kneeWest J Med.(2000 Feb)
- Osteoarthritis Symptoms - Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, Hochberg MC, Wells GGlucosamine therapy for treating osteoarthritisCochrane Database Syst Rev.(2005 Apr 18)
- Pain - Noack W, Fischer M, Förster KK, Rovati LC, Setnikar IGlucosamine sulfate in osteoarthritis of the kneeOsteoarthritis Cartilage.(1994 Mar)
- Temporomandibular Disorder (TMD) Symptoms - Thie NM, Prasad NG, Major PWEvaluation of glucosamine sulfate compared to ibuprofen for the treatment of temporomandibular joint osteoarthritis: a randomized double blind controlled 3 month clinical trialJ Rheumatol.(2001 Jun)
- Temporomandibular Disorder (TMD) Symptoms - Cahlin BJ, Dahlström LNo effect of glucosamine sulfate on osteoarthritis in the temporomandibular joints--a randomized, controlled, short-term studyOral Surg Oral Med Oral Pathol Oral Radiol Endod.(2011 Dec)
- Lower Back Pain - Wilkens P, Scheel IB, Grundnes O, Hellum C, Storheim KEffect of glucosamine on pain-related disability in patients with chronic low back pain and degenerative lumbar osteoarthritis: a randomized controlled trialJAMA.(2010 Jul 7)
- Kashin-Beck Disease Symptoms - Liu W, Liu G, Pei F, Liu Y, Zhou Z, Li J, Shen B, Kang P, Xie Q, Ma XKashin-Beck disease in Sichuan, China: report of a pilot open therapeutic trialJ Clin Rheumatol.(2012 Jan)
- Kashin-Beck Disease Symptoms - Yue J, Yang M, Yi S, Dong B, Li W, Yang Z, Lu J, Zhang R, Yong JChondroitin sulfate and/or glucosamine hydrochloride for Kashin-Beck disease: a cluster-randomized, placebo-controlled studyOsteoarthritis Cartilage.(2012 Jul)
- Range of Motion - Ostojic SM, Arsic M, Prodanovic S, Vukovic J, Zlatanovic MGlucosamine administration in athletes: effects on recovery of acute knee injuryRes Sports Med.(2007 Apr-Jun)
- CTX-II - Yoshimura M, Sakamoto K, Tsuruta A, Yamamoto T, Ishida K, Yamaguchi H, Nagaoka IEvaluation of the effect of glucosamine administration on biomarkers for cartilage and bone metabolism in soccer playersInt J Mol Med.(2009 Oct)