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Glucosamine and Chondroitin: The Unbiased Scientific Truth, Evidenced-Based Health Benefits, Risks, & Side Effects

Glucosamine and Chondroitin: The Unbiased Scientific Truth, Evidenced-Based Health Benefits, Risks, & Side Effects

A scientific look at glucosamine and chondroitin, including their background, benefits, risks and side effects, considerations and more.

Glucosamine and Chondroitin

KYIV /KIEV, UKRAINE - July 19, 2019: Plastic bottle of 120 pills of Glucosamine, Chondroitin with MSM prodused by CVS Health (Source: Shutterstock)

Over the last 20 years, throughout the world, chondroitin and glucosamine supplementation have been increasingly recommended in guidelines, prescribed by general practitioners and rheumatologists, and used by patients as over-the-counter medications to modify the clinical and radiological course of osteoarthritis, a common type of arthritis that destroys cartilage in the joints, especially in the knees, hips, spine, and hands[1][3].

Background of Glucosamine and Chondroitin

Glucosamine and chondroitin are natural substances found in and around the cells of cartilage, the tissue that cushions the joints and gives them strength and resilience.

They are the principal substrates in the biosynthesis of proteoglycans, a group of large protein molecules that make up the ground substance of cartilage and is essential for maintaining cartilage integrity[4][5].

Within cartilage, glucosamine is most important for the formation of hyaluronic acid, chondroitin sulfate, as well as keratan sulfate, which are some of the most important components of the extracellular matrix of the articular cartilage and the synovial fluid, which is the fluid that lubricates the joints[6].

In general, chondroitin sulfate inhibits cartilage destruction processes & stimulates the anabolic processes involved in new cartilage formation; and it has been found to exert anti-inflammatory activity.[6][7]

Glucosamine and chondroitin were also developed as prescription drugs for osteoarthritis in Europe and Asia.

In the United States and Australia, they are available as over-the-counter supplements and are not pharmaceutical grade[4][5].

Glucosamine and chondroitin can also be given topically or through an injection, however, supplementation is the most common form of delivery.

Glucosamine is commonly used as either glucosamine hydrochloride or glucosamine sulfate, while chondroitin supplements are typically used in the form of chondroitin sulfate.

Evidenced-Based Health Benefits

Major studies have had conflicting results regarding glucosamine and chondroitin, however, supplementation may be beneficial, especially when there is a disturbed balance between catabolic and anabolic processes, such as in osteoarthritis.

In fact, there is significant evidence in the published literature to support the promising disease-modifying osteoarthritis drug potencies of both glucosamine and chondroitin sulfate.

Several studies have shown benefit in the treatment of osteoarthritis with regards to:

  • Pain relief

    • In the GAIT (Glucosamine/Chondroitin Arthritis Intervention Trial) study, a large-scale, multicenter clinical trial in the United States, glucosamine combined with chondroitin sulfate supplemented for 8 weeks provided statistically significant pain relief compared with placebo for a subset of participants with moderate-to-severe pain[4][8].
    • Findings from in vitro and in vivo studies, clinical trials and meta-analyses show that chondroitin sulfate reduces pain due to its structure-modifying effects.[6][9][10][7]
  • Reduction in joint space narrowing/reduces osteoarthritis progression

    • In one systematic review looking at the clinical effectiveness of glucosamine and chondroitin supplements, a reduction in joint space narrowing was consistently observed, however, the effect size was small[11].
    • Results from a double-blind randomized placebo-controlled clinical trial also suggested that taking glucosamine sulfate (1,500 mg) in combination with low molecular weight chondroitin sulfate (800 mg) daily for 2 years provided a meaningful reduction in joint space narrowing in people with knee osteoarthritis and evidence of mostly mild radiographic disease[5].
    • Another study, called the LEGS study, demonstrated that the combination of glucosamine sulfate and chondroitin sulfate achieved a meaningful reduction in tibio-femoral joint space narrowing over 2 years, compared with placebo[5].
    • Findings from many types of studies show that chondroitin sulfate reduces the progression of osteoarthritis by its structure-modifying effects.[6][9][7]
  • Better joint functioning overall

    • In several European studies, participants reported that their knees felt and functioned better after taking a large, once-a-day dose of glucosamine sulfate[1].
    • One double-blind trial also found that the combination of glucosamine hydrochloride and chondroitin sulfate was as effective as celecoxib (a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain or inflammation) in patients with osteoarthritis of the knee[7].
    • Chondroitin sulfate has also been shown to improve the function/mobility of the joint by its structure-modifying effects[6][7].

Results of many studies, including in vivo and in vitro, suggest that both glucosamine and chondroitin sulfate may enhance each other’s efficacy.[6][7][12][21]

Positive results from these studies were found when glucosamine was supplemented as glucosamine sulfate at 1,500 mg per day and chondroitin sulfate was supplemented at 800-1,200 mg per day[7].

Glucosamine and chondroitin may be beneficial for other conditions, however, more research is needed to determine their efficacy. These conditions include, but are not limited to[22][24]:

  • Cataracts (specifically chondroitin)
  • Interstitial cystitis (painful bladder syndrome)
  • Joint pain
  • Kashin-Beck Disease
  • Multiple Sclerosis (specifically glucosamine)
  • Osteoporosis
  • Temporomandibular joint (TMJ) (specifically glucosamine)
  • Urinary tract infections (specifically chondroitin)

Risks and Side Effects

While several studies have had beneficial results with glucosamine & chondroitin sulfate supplementation, many studies have come to mixed conclusions and found no benefit whatsoever.

A 2010 analysis of multiple studies (meta-analysis)[2] found that among more than 3,800 people with osteoarthritis of the knee or hip, treatment with glucosamine, chondroitin, or the combination was no better than placebo.

Two other studies, including the GAIT study, did not find a reduction in joint space narrowing, reduction in knee pain or improvement in knee function in participants who received glucosamine and chondroitin supplements either together or alone versus placebo[1][5].

In fact, a 2016 study that used glucosamine and chondroitin supplementation had to stop early as those taking the supplement reported worse symptoms than those taking a placebo[25][26].

In general, glucosamine and chondroitin are thought to be safe and no serious side effects have been reported in large, well-conducted studies of people taking glucosamine, chondroitin, or both for up to 3 years[1].

In most trials, dosages of 1,500 mg per day of glucosamine were used and the dose was as safe as a placebo and tolerated better than NSAIDs. Results were similar with chondroitin sulfate as well.

However, as with any medication, there are potential risks and side effects.

Listed below are some of the side effects reported:

Some other potential risks listed below have been reported from studies but cannot be concluded as more research is needed:

  • Glucosamine may increase the risk of glaucoma[27].
  • A study in rats showed that long-term use of moderately large doses of glucosamine might damage the kidneys[1][28].
  • Glucosamine might affect the way your body handles sugar, especially if you have diabetes or other blood sugar problems, such as insulin resistance or impaired glucose tolerance, however further research is required.[3][7][10][30][34]
  • Avoid taking chondroitin sulfate and glucosamine if you are taking anticoagulants (blood-thinners) or daily aspirin, as it is chemically similar to the blood-thinner heparin[23].
  • Do not use if you are pregnant or nursing and do not use in children[1][23].

As with all supplements and medications, check with your doctor or pharmacist before taking glucosamine & chondroitin.

Many doctors warn patients that the FDA does not regulate supplements such as glucosamine & chondroitin, so they may not contain the amounts stated on the label or there could be contaminants in them.

Some dietary supplements may interact with medications or pose risks if you have medical problems or are going to have surgery.

It is also important to note that health insurance usually does not cover these supplements.

Considerations to the Research

Results from randomized trials about the effectiveness of chondroitin and glucosamine are conflicting.

Trials that have reported large effects on joint pain were often hampered by poor study quality and small sample sizes,[2][9][35][38] whereas large methodologically sound trials often found only small or no effects[2][36][37].

It is uncertain why the results of large, well-done studies differ. It may be because of difference in the types of glucosamine used (glucosamine hydrochloride in the NIH study vs. glucosamine sulfate in the European studies), difference in the way they were administered (one large daily dose in European studies vs. three smaller ones in the NIH study), other differences in the way the studies were done, or chance.[1][5][7][39][40]

The participants themselves may also play a role in the conflicting results as some patients included in trials were too ill and others were not ill enough. Research bias may also come into play and influence results in studies and should be taken into consideration.

Conclusion

Chondroitin and glucosamine are natural substances in the body, and they are available over the counter as supplements.

They appear to be well-tolerated with no major safety issues and their efficacy seems to range from small to medium treatment effects when it comes to osteoarthritis. However, more research is needed for various conditions.

Results from these supplements are dependent on the individual and therefore glucosamine and chondroitin sulfate supplementation should not be disregarded in treatment.

People with osteoarthritis should work with their health care provider to develop a comprehensive plan for managing their arthritis pain and determine whether glucosamine and chondroitin sulfate is an appropriate treatment option as they are more favorable than the use of NSAIDs, analgesics, and narcotics, especially in elderly individuals with comorbidities.

If you take warfarin or have blood sugar problems, make sure to talk to your doctor about the potential side effects if you are considering or taking glucosamine or chondroitin.

Based on research findings, if you plan on using glucosamine and chondroitin, the dosing recommendation is glucosamine sulfate at 1,500 mg per day in combination with chondroitin sulfate at 800-1,200 mg per day.

Feedback:

References

1. Glucosamine and Chondroitin for Osteoarthritis. National Center for Complementary and Integrative Health. https://nccih.nih.gov/https://nccih.nih.gov/health/glucosaminechondroitin. Published September 24, 2017. Accessed January 20, 2020.
2. Wandel S, Jüni P, Tendal B, Nüesch E, Villiger PM, Welton NJ, Reichenbach S, Trelle S. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ. 2010;341:c4675. doi:10.1136/bmj.c4675
3. Annual nutrition industry overview. Nutrition Business J 2005;X:6-7.
4. Questions and Answers: NIH Glucosamine/Chondroitin Arthritis Intervention Trial Primary Study. National Center for Complementary and Integrative Health. https://nccih.nih.gov/research/results/gait/qa.htm. Published September 24, 2017. Accessed January 20, 2020.
5. Fransen M, Agaliotis M, Nairn L, Votrubec M, Bridgett L, Su S, Jan S, March L, Edmonds J, Norton R, Woodward M, Day R. Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis. 2014:0:1-8. doi:10.1136/annrheumdis-2013-203954
6. Jerosch J. Effects of glucosamine and chondroitin sulfate on cartilage metabolism in OA: outlook on other nutrient partners especially omega-3 fatty acids. International Journal of Rheumatology. 2011;2011:1-17. doi:10.1155/2011/969012
7. Gaby AR. Rheumatology and connective tissue disorders. Nutritional Medicine. Second Edition. Concord, NH: Fritz Perlberg Publishing; 2017:623-625,628. 8. Axe J. The Body-Healing Supplement. Dr. Axe. https://draxe.com/nutrition/glucosamine/. Published August 19, 2019. Accessed January 20, 2020.
9. Singh JA, Noorbaloochi S, MacDonald R, Maxwell LJ. Chondroitin for osteoarthritis. Cochrane Database Syst Rev. 2016;1-264. doi: 10.1002/14651858.CD005614.pub2.
10. 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 & Rheumatism. 2011;63(11):3383-3391. doi:10.1002/art.30574
11. Black C, Clar C, Henderson R, MacEachern C, McNamee P, Quayyum Z, Royle P, Thomas S. The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation. Health Technology Assessment. 2009;13(52):1-4. doi:10.3310/hta13520
12. Huskisson EC. Glucosamine and chondroitin for osteoarthritis. J Int Med Res. 2008;36:1161–79.
13. Bruyere O, Reginster JY. Glucosamine and chondroitin sulfate as therapeutic agents for knee and hip osteoarthritis. Drugs & Aging. 2007;24(7):573-580.
14. 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 & Rheumatism. 2008;58(10):3183-3191.
15. Das Jr. A, Hammad TA. Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis. Osteoarthritis and Cartilage. 2000;8(5):343-350.
16. Hochberg MC, Clegg DO. Potential effects of chondroitin sulfate on joint swelling: a GAIT report. Osteoarthritis and Cartilage. 2008;16(3):S22-S24.
17. Lippiello L. Collagen synthesis in tenocytes, ligament cells and chondrocytes exposed to a combination of glucosamine HCl and chondroitin sulfate. Evidence-Based Complementary and Alternative Medicine. 2007;4(2):219-224.
18. Collier S, Ghosh P. Evaluation of the effects of antiarthritic drugs on the secretion of proteoglycans by lapine chondrocytes using a novel assay procedure. Annals of the Rheumatic Diseases. 1989;48(5):372-381.
19. Lippiello L. Glucosamine and chondroitin sulfate: biological response modifiers of chondrocytes under simulated conditions of joint stress. Osteoarthritis and Cartilage. 2003;11(5):335-342.
20. Orth MW, Peters TL, Hawkins JN. Inhibition of articular cartilage degradation by glucosamine-HCl and chondroitin sulphate. Equine Veterinary Journal Supplement. 2002;34:224-229.
21. McCarty MF, Russell AL, Seed MP. Sulfated glycosaminsglycan and glucosamine may synergize in promoting synovial hyaluronic acid synthesis. Medical Hypotheses. 2000;54(5):798-802.
22. Balch PA. Natural food supplements. Prescription for Nutritional Healing: A Practical A-to-Z Reference to Drug-Free Remedies Using Vitamins, Minerals, Herbs & Food Supplements. Fifth Ed. New York, NY: Penguin Group; 2010:85.
23. Chondroitin Sulfate: MedlinePlus Supplements. MedlinePlus. NIH U.S. National Library of Medicine. https://medlineplus.gov/druginfo/natural/744.html. Revised August 14, 2019. Accessed January 23, 2020.
24. Glucosamine Sulfate: MedlinePlus Supplements. MedlinePlus. NIH U.S. National Library of Medicine. https://medlineplus.gov/druginfo/natural/807.html. Revised June 17, 2019. Accessed January 23, 2020.
25. Shmerling RH. The latest on glucosamine/chondroitin supplements. Harvard Health Blog. https://www.health.harvard.edu/blog/the-latest-on-glucosaminechondroitin-supplements-2016101710391. Published September 16, 2019. Accessed January 20, 2020.
26. 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 & Rheumatology. 2016;69(1):77-85. doi:10.1002/art.39819
27. Murphy RK, Ketzler L, Rice RDE, et. al. Oral glucosamine supplements as a possible ocular hypertensive agent. JAMA Opthalmol. 2013;131(7):995-957. doi:10.1001/jamaophthalmol.2013.227
28. 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. doi:10.1592/phco.28.4.540.
29. Dostrovsky NR., Towheed TE., Hudson RW., Anastassiades TP. The effect of glucosamine on glucose metabolism in humans: a systematic review of the literature. Osteoarthritis and Cartilage. 2011;19:375-380. doi:10.1016/j.joca.2011.01.007
30. Hussain MA. A case for glucosamine. Eur J Endocrinol. 1998;139:472e5.
31. Tannis AJ, Barban J, Conquer JA. Effect of glucosamine supplementation on fasting and non-fasting plasma glucose and serum insulin concentrations in healthy individuals. Osteoarthritis Cartilage. 2004;12:506e11. doi:10.1016/j.joca.2004.03.001
32. Kaneto H, Xu G, Song KH, Suzuma K, Bonner-Weir S, Sharma A, et al. Activation of the hexosamine pathway leads to deterioration of pancreatic beta-cell function through the induction of oxidative stress. J Biol Chem. 2001;276:31099e104.
33. Cooksey RC, Pusuluri S, Hazel M, McClain DA. Hexosamines regulate sensitivity of glucose-stimulated insulin secretion in beta-cells. Am J Physiol Endocrinol Metab. 2006;290:e334-340. doi:10.1152/ajpendo.00265.2005
34. Anderson JW, Nicolosi RJ, Borzelleca JF. Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy. Food Chem Toxicol. 2005;43(2):187-201. doi:10.1016/j.fct.2004.11.006
35. Jüni P, Reichenbach S, Dieppe P. Osteoarthritis: rational approach to treating the individual. Best Pract Res Clin Rheumatol. 2006;20:721-40. doi:10.1016/j.berh.2006.05.002
36. Reichenbach S, Sterchi R, Scherer M, Trelle S, Burgi E, Burgi U, et al. Meta-analysis: chondroitin for osteoarthritis of the knee or hip. Ann Intern Med. 2007;146:580-90. doi:10.7326/0003-4819-146-8-200704170-00009
37. Vlad SC, LaValleyMP, McAlindon TE, Felson DT. Glucosamine for pain in osteoarthritis: why do trial results differ? Arthritis Rheum. 2007;56(7):2267-77. doi:10.1002/art.22728
38. Nüesch E, Trelle S, Reichenbach S, Rutjes AW, Bürgi E, Scherer M, et al. The effects of the exclusion of patients from the analysis in randomised controlled trials: meta-epidemiological study. BMJ. 2009;339:b3244. doi:10.1136/bmj.b3244
39. Henroitin Y, Marty M, Mobasheri A. What is the current status of chondroitin sulfate and glucosamine for the treatment of knee osteoarthritis? Maturitas. 2014;78(3):184-187. https://doi.org/10.1016/j.maturitas.2014.04.015
40. Altman RD. Glucosamine therapy for knee osteoarthritis: pharmacokinetic considerations. Expert Rev Clin Pharmacol. 2009;2:359–71.
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Meghan Rittmaster, MS, RDN, LD

Meghan is a registered dietitian nutritionist in private practice in Minneapolis, Minnesota. Her areas of expertise include functional ...

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