scienceThere a huge volumes of research that span over 3 decades investigating the role of oral glucosamine sulphate and chondroitin sulphate

1. Aghazadeh-Habashi A, Jamali F. The glucosamine controversy; a pharmacokinetic issue. J Pharm Pharm Sci. 2011;14(2):264-73.
This research highlights the essential requirement for high-quality bioavailable actives and correlates this whether or not specific research yields positive result…in summary consistent high quality product is essential when deciding which product to use.
2. Bottegoni C, Muzzarelli RA, Giovannini F, Busilacchi A, Gigante A. Oral chondroprotection with nutraceuticals made of chondroitin sulphate plus glucosamine sulphate in osteoarthritis. Carbohydr Polym. 2014 Aug 30;109:126-38.

This paper reports that oral supplementation of chondroitin sulphate plus glucosamine sulphate helps repair the articular surface in osteoarthritis. Chondroitin sulphate reduces the concentration of the pro-inflammatory cytokines and transcription factor involved in inflammation. Glucosamine sulphate enhances cartilage specific matrix components and prevents collagen degeneration in chondrocytes by inhibiting hydrolytic enzymes, and preventing the oxidation of lipids and proteins. Chondroitin sulphate plus glucosamine sulphate are slow-acting drugs that alleviate pain and partly restore joint function in osteoarthritis patients. Orally administered pharmaceutical-grade chondroitin sulphate plus glucosamine sulphate stabilize the joint space narrowing and significantly decrease the number of patients with new erosive osteoarthritis. They are safe and no adverse events have ever been reported. The synergistic association of these two world-widely preferred nutraceuticals is a step forward in the management of oestoarthritis.

3. Comblain F, Serisier S, Barthelemy N, Balligand M, Henrotin Y. Review of dietary supplements for the management of osteoarthritis in dogs in studies from 2004 to 2014. J Vet Pharmacol Ther. 2015 Jul 23.

Osteoarthritis (OA) is a chronic, painful, degenerative and inflammatory disease that affects the synovial joints and leads finally to the loss of mobility. It is highly prevalent in dogs. Nowadays, no cure exists, and the pharmacological treatment is limited to clinical signs alleviation. Some positive beneficial effects have been highlighted with dietary supplements in the course of dog OA. Chondroitin sulphate, and glucosamine sulphate showed anticatabolic and anti-inflammatory effects and should be considered in osteoarthritis management in dogs.

4. Damlar I, Esen E, Tatli U. Effects of glucosamine-chondroitin combination on synovial fluid IL-1β, IL-6, TNF-α and PGE2 levels in internal derangements of temporomandibular joint. Med Oral Patol Oral Cir Bucal. 2015 May 1;20(3):e278-83.

The results in this study suggest that glucosamine-chondroitin combination may significantly increases the MMO and decreases the synovial fluid IL1β and IL6 levels in internal derangements of TMJ compared to tramadol. This glucosamine-chondroitin combination also provides efficient pain relief in similar level with tramadol, a narcotic analgesic.

5. Dechant JE, Baxter GM, Frisbie DD, Trotter GW, McIlwraith CW. Effects of glucosamine hydrochloride and chondroitin sulphate, alone and in combination, on normal and interleukin-1 conditioned equine articular cartilage explant metabolism. Equine Vet J. 2005 May;37(3):227-31.

The combination of Glucosamine and chondroitin may be more effective in preventing or treating osteoarthritis in horses than either glucosamine or chondroitin alone.

6. Fenton JI, Chlebek-Brown KA, Peters TL, Caron JP, Orth MW. The effects of glucosamine derivatives on equine articular cartilage degradation in explant culture. Osteoarthritis Cartilage. 2000 Nov;8(6):444-51.

This research indicates that glucosamine sulfate also has the potential to prevent or reduce articular cartilage degradation in vitro. Furthermore this research suggests the effectiveness of the glucosamine derivative relates to the additional molecule (in glucosamine sulphate) located on the group at the carbon-2.

7. Forsyth RK, Brigden CV, Northrop AJ. Double blind investigation of the effects of oral supplementation of combined glucosamine hydrochloride (GHCL) and chondroitin sulphate (CS) on stride characteristics of veteran horses. Equine Vet J Suppl. 2006 Aug.

This paper reports that oral chondroprotectives offered symptomatic relief to veteran horses, evidenced by improved stride characteristics. More specifically that oral glucosamine and chondroitin supplementation may improve welfare by alleviating symptoms of degenerative joint disease.

8. Fox BA, Stephens MM. Glucosamine/chondroitin/primorine combination therapy for osteoarthritis. Drugs Today (Barc). 2009 Jan;45(1):21-31.

This paper looks at the use of oral supplementation to help osteoarthritis sufferers. This paper highlights that the use of a combination product of glucosamine sulfate and chondroitin sulfate seems to have the greatest potential as a therapeutic intervention for patients that suffer the side effects profiles of other therapies such as NSAIDs (gastric irritation/ulceration and bleeding).

9. Hanson RR, Brawner WR, Blaik MA, Hammad TA, Kincaid SA, et al. Oral treatment with a nutraceutical for ameliorating signs of navicular syndrome in horses. Vet Ther. 2001 Spring;2(2):148-59.

This paper highlights that there is role for combination therapy of Glucosamine and Chondroitin in the context of navicular syndrome

10. Harvey WF, Hunter DJ. The role of analgesics and intra-articular injections in disease management. Med Clin North Am. 2009 Jan;93(1):201-11, xii.

This paper discusses the importance of a multimodal approach to managing pain in the context of the disease state. What does this mean? Essentially there is not one simple fix to the management of osteoarthritis; using combined therapy with good management is the key to improving not only pain but disease progression. In horses this can mean using oral glucosamine and chondroitin but also realizing there is role for short-term NSAID, shoeing, weight management, correct shoeing and correct training.

11. Hathcock JN, Shao A. Risk assessment for glucosamine and chondroitin sulfate. Regul Toxicol Pharmacol. 2007 Feb;47(1):78-83.

This paper demonstrates the safety of glucosamine and chondroitin when compared to many other oral therapies. There are essentially now long term side effects.

12. Henrotin Y, Marty M, Mobasheri A. What is the current status of chondroitin sulfate and glucosamine for the treatment of knee osteoarthritis?. Maturitas. 2014 Jul;78(3):184-7.

Chondroitin sulfate and glucosamine sulphate are recommended by several guidelines from international societies for the management of osteoarthritis. This comprehensive review clarifies that their is a role for Chondroitin sulfate and glucosamine sulphate compounds in the therapeutic arsenal for patients osteoarthritis.

13. Hoffer LJ, Kaplan LN, Hamadeh MJ, Grigoriu AC, Baron M. Sulfate could mediate the therapeutic effect of glucosamine sulfate. Metabolism. 2001 Jul;50(7):767-70.

This paper reports that that it is not simply glucosamine itself that stimulates articular cartilage glycosaminoglycan synthesis and repair. The paper reports that it is sulfate that mediates the clinical benefit attributed to this treatment. Sulfate is required for glycosaminoglycan synthesis, and unlike glucosamine, its serum level can be modified by dietary and other factors. In this study, oral glucosamine sulfate increases the sulfate concentration in the synovial fluid. Whilst the mechanism is not clearly understood, this paper suggests that sulphation of glucosamine is an important consideration for oral joint supplements.

14. Homandberg GA, Guo D, Ray LM, Ding L. Mixtures of glucosamine and chondroitin sulfate reverse fibronectin fragment mediated damage to cartilage more effectively than either agent alone. Osteoarthritis Cartilage. 2006 Aug;14(8):793-806.

Glucosamine and Chondroitin act synergistically in reversing damage and promoting repair at concentrations found in plasma after oral ingestion of these agents. Reversal of prostaglandin synthesis suppression (inflammatory pathway) also correlates with the use of these actives. Meaning these actives both repair and provide anti-inflammatory benefit.

15. Kamarul T, Ab-Rahim S, Tumin M, Selvaratnam L, Ahmad TS. A preliminary study of the effects of glucosamine sulphate and chondroitin sulphate on surgically treated and untreated focal cartilage damage. Eur Cell Mater. 2011 Mar 15;21:259-71; discussion 270-1.

This is an animal model study that used Histological examination to demonstrate a typical hyaline cartilage structure; with proteoglycans, type II collagen and GAGs being highly expressed in repair areas. Further the rate of repair was 6 x faster when treated with oral glucosamine sulphate and even faster with a combination of glucosamine sulphate + chondroitin sulphate when compared to the untreated (without pharmacotherapy) group. Essentially this paper demonstrates that a combination of glucosamine sulphate alone/ or with chondroitin sulphate may prove beneficial for healing of damaged cartilage, particularly in relation to focal cartilage defects.

16. Kanzaki N, Ono Y, Shibata H, Moritani T. Glucosamine-containing supplement improves locomotor functions in subjects with knee pain: a randomized, double-blind, placebo-controlled study. Clin Interv Aging. 2015;10:1743-53.
Whilst human research (as with all oral osteoarthritis actives) subjects with knee pain, where given oral combination of glucosamine sulphate + chondroitin sulphate supplementation which demonstrated effective for relieving knee pain and improving locomotor functions.

17. Kanzaki N, Saito K, Maeda A, Kitagawa Y, Kiso Y, et al. Effect of a dietary supplement containing glucosamine hydrochloride, chondroitin sulfate and quercetin glycosides on symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled study. J Sci Food Agric. 2012 Mar 15;92(4):862-9.

The conclusion in this paper was that oral combination of glucosamine sulphate + chondroitin sulphate was thought to be more effective than placebo in decreasing the intensity of knee OA-associated clinical symptoms.

18. Lenox CE, Lunn KF. Effects of glucosamine-chondroitin sulfate supplementation on serum fructosamine concentration in healthy dogs. J Am Vet Med Assoc. 2010 Jan 15;236(2):183-6.

This paper demonstrates the safety of oral combination of glucosamine sulphate + chondroitin sulphate in diabetic dogs

19. McCarthy G, O’Donovan J, Jones B, McAllister H, Seed M, et al. Randomised double-blind, positive-controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis. Vet J. 2007 Jul;174(1):54-61.

Thirty-five dogs were included in a randomised, double-blind, positive controlled, multi-centre trial to assess the efficacy of an orally-administered glucosamine and chondroitin sulfate (Glu/CS) combination for the treatment of confirmed osteoarthritis of hips or elbows. Carprofen was used as a positive control. Dogs were re-examined on days 14, 42 and 70 after initiation of treatment. Medication was then withdrawn and dogs were re-assessed on day 98Dogs treated with Glu/CS showed statistically significant improvements in scores for pain, weight-bearing and severity of the condition by day 70 (P<0.001). Onset of significant response was slower for Glu/CS than for carprofen-treated dogs, though longer lasting. The results show that Glu/CS has a positive clinical effect in dogs with osteoarthritis.

20. Phitak T, Pothacharoen P, Kongtawelert P. Comparison of glucose derivatives effects on cartilage degradation. BMC Musculoskelet Disord. 2010 Jul 15;11:162.

This study shows that different types of glucosamine (HCl vs Sulphate) can alter anabolic and catabolic processes in chondrocytes (cells present in cartilage). This chondroprotective study showed that glucosamine sulphate had the strongest effect.

21. Sawitzke AD, Shi H, Finco MF, Dunlop DD, Harris CL, 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 Aug;69(8):1459-64.

Over 2 years, glucosamine sulphate showed comparable benefit to celecoxib (NSAID).

22. Scholtissen S, Bruyère O, Neuprez A, Severens JL, Herrero-Beaumont G, et al. Glucosamine sulphate in the treatment of knee osteoarthritis: cost-effectiveness comparison with paracetamol. Int J Clin Pract. 2010 May;64(6):756-62.

This is review of randomized trials of mostly low quality reveals that chondroitin (alone or in combination with glucosamine) was better than placebo in improving pain in participants with osteoarthritis in short-term studies

23. Taşkesen A, Ataoğlu B, Özer M, Demirkale İ, Turanli S. Glucosamine-chondroitin sulphate accelerates tendon-to-bone healing in rabbits. Eklem Hastalik Cerrahisi. 2015;26(2):77-83.

Glucosamine-chondroitin sulphate treatment enhances tendon-to-bone healing by increasing hyaline cartilage formation and decreasing formation of capillary vessels.

24. Tsuji T, Yoon J, Kitano N, Okura T, Tanaka K. Effects of N-acetyl glucosamine and chondroitin sulfate supplementation on knee pain and self-reported knee function in middle-aged and older Japanese adults: a randomized, double-blind, placebo-controlled trial. Aging Clin Exp Res. 2015 Jul 16.

These results suggest that consumption of glucosamine and chondroitin sulfate for 12 weeks or longer has a positive effect on self-reported knee function and household physical activity in middle-aged and older Japanese adults with knee pain and/or stiffness.

25. Vangsness CT Jr, Spiker W, Erickson J. A review of evidence-based medicine for glucosamine and chondroitin sulfate use in knee osteoarthritis. Arthroscopy. 2009 Jan;25(1):86-94.

This study confirmed OA pain relief with glucosamine and chondroitin sulfate use. The excellent safety profile of glucosamine and chondroitin sulfate therapy should be discussed with patients, and these supplements may serve a role as an initial treatment modality for many OA patients

26. Wen ZH, Tang CC, Chang YC, Huang SY, Hsieh SP, et al. Glucosamine sulfate reduces experimental osteoarthritis and nociception in rats: association with changes of mitogen-activated protein kinase in chondrocytes. Osteoarthritis Cartilage. 2010 Sep;18(9):1192-202.

The results from this study indicates that treatment with oral glucosamine sulfate in an animal model (1) attenuates/slows the development of osteoarthritis, (2) reduces nociception/pain, and (3) modulates chondrocyte metabolism/repair.