Review of literature: Joint Support ingredients

Review of scientific literature to demonstrate efficacy of ingredients used in JOINT SUPPORT:

“Urinary glycosaminoglycans in horse osteoarthritis. Effects of chondroitin sulphate and glucosamine”. Baccarin. R.Y.A, Machado. T.S.L, Lopes-Mores. A.P, Vieira. F.A.C, Michelacci. Y.M. Research in Veterinary Science 93 (2012) 88-96.

ABSTRACT:
Our objectives were to characterize the urinary excretion of glycosaminoglycans (GAGs) in horse osteoarthritis, and to investigate the effects of chondroitin sulphate (CS) and glucosamine (GlcN) upon the disease. Urinary GAGs were measured in 47 athletic horses, 20 healthy and 27 with osteoarthritis. The effects of CS and GlcN were investigated in mild osteoarthritis. In comparison to normal, urinary GAGs were increased in osteoarthritis, including mild osteoarthritis affecting only one joint. Treatment with CS+GlcN led to long lasting increase in urinary CS and keratin sulphate (KS), and significant improvement in flexion test of tarsocrural and metacarpophalangeal joints was observed. In conclusion, urinary CS and KS seems to reflect the turnover rates of cartilage matrix proteoglycans, and the measurement of these compounds could provide objective means of evaluating and monitoring joint diseases.

Extracts of interest from paper:

“Upon treatment with CS+GlcN, there was a significant improvement in flexion test of tarsocrural and metacarpophalangeal joints. There was also a decrease in joint volume, and the scores assigned to lameness and pain in different joints also improved.”.

“Concering CS, many authors have shown anti-inflammatory activities for CS in cultured chondrocytes or cartilage explants from different mammalian species (reviews in du Souich et al., 2009; Lovu et al., 2008). Also, there are evidences suggesting that the combination of GlcN and CS may be more effective in preventing cartilage degradation (Dechant et al., 2005).”

“A critical review of neutraceutical use for osteoarthritis in the horse”, Shelia Laverty, Prof, MVB, Dipl ACVS & ECVS, University of Montreal. Proceedings of the 15th European Society of Veterinary Orthopaedics and Traumatology, Sept 15-18, 2010 Bologna, Italy.

Extracts:

“Glucosamine is an aminosaccharide that is synthesized and incorporated into many molecules in the body including the proteoglycan matrix components of articular cartilage...glucosamine could potentially improve aggrecan synthesis and have anti inflammatory effects (reduce COX-2, PGE2 and reduce cartilage degrading enzymes). Novel intriguing data from a study of a mouse model of cartilage destruction has shown that glucosamine administration can alster the acute phase response in the liver and reduce circulating cytokines...Recent in vitro work on equine cartilage explants has shown that glucosamine, at physiologically relevant doses prevents proteoglycan degrading effects of corticosteroids (MAP)”.

“Chondroitin sulphate is a component of the extracellular matrix of cartilage, bone, ligaments and tendons...In vitro effects detected by the addition of chondroitin sulphate to stressed joint cells or cartlage explants include induction of production of proteoglycans and reduction of chondrocyte apoptosis [cell death], matrix metalloprotease

production and bone resorption...The administration of chondroitin sulphate to animals with experimental osteoarthritis has been reported to reduce inflammation, synovitis and proinflammatory cytokines”

“Three clinical trials evaluating the combination of glucosamine hydrochloride and chondroitin sulphate have been performed in horses and all reported beneficial effects on symptoms of joint disease. The most recent study which was blinded and randomized assessed their effects on lameness and joint motion in older horses and significant improvements in range of motion, increased stride length and swing duration were observed at 8 weeks suggesting that the combination offered symptomatic relief”.

“Double blind investigation of the effects of oral supplementation of combined glucosamine hydrochloride (GHCL) and chondroitin sulphate (CS) on stride characteristics of veteran horses”, Forsyth RK, Brigden CV, Northrop AJ. Equine Vet J Suppl. 2006 Aug;(36):622-5.

REASONS FOR PERFORMING STUDY: Oral chondroprotective supplements are commercially popular for veteran (and other athletic or arthritic) horses prone to joint degradation, yet lack conclusive scientific support.
OBJECTIVES: To quantify the effects of an oral joint supplement (combination glucosamine hydrochloride (GHCL), chondroitin sulphate (CS) and N-acetyl-D-glucosamine) in vivo on stride parameters of veteran horses.
METHODS: 20 veteran horses were randomly assigned to a treatment or placebo group. Pre-treatment gait characteristics were recorded at trot using digital video footage. The range of joint otion, stride length, and swing and stance duration were assessed using 2 dimensional motion analysis. Treatment was administered daily for 12 weeks. Double blind procedure was implemented throughout.
RESULTS: Differences occurred in the treated horses by week 8. Range of joint motion increased significantly in the elbow, stifle and hind fetlock. Stride length increased significantly with treatment. Swing duration was significantly increased at week 12.
CONCLUSION: The oral chondroprotective offered symptomatic relief to veteran horses, evidenced by improved stride characteristics.
POTENTIAL RELEVANCE: Oral GHCL and CS supplementation may improve welfare by alleviating symptoms of degenerative joint disease.

Research paper that demonstrated glucosamine and chondroitin sulphate combined can protect against arthritis developing, using guinea pig test subjects:

“Effects of cartilage protective agents on histopathological, histochemical features of articular cartilage and serum level of aggrecan in Hartley guinea pigs”, Xiao P, Dong M, Hong X, Wang N, et al., Wei Sheng Yan Jiu, 2008 Mar;37(2):171-4.

OBJECTIVE: To observe the effect of glucosamine (GS) and chondroitin sulphate (CS) on histopathological, histochemical features of articular cartilage and on the agrecan serum level in Hartly guinea pigs: a kind og primary OA animal model.
METHODS: 120 female Hartley guinea pigs aged 2 months were randomly divided into 3 test groups and a control group, 30 animals for each group. The 3 test groups refer to GS group, CS group and combined group. Before dosing and after each monthly treatment during the five months, knee joint cartilage from 5 guinea pigs each group were examined through histopathological method (H.E stain) and histopathological method (Alcain Blue, PAS and Mallory stain) and the serum levels of aggrecan were detected synchronously.
RESULTS: During the entire 5 months period, distinct pathological lesions appeared just after the first month in the control group. And the distinct pathological lesions didn’t appear until the 3rd month ended in the GS group. In the CS group, moderate pathological lesions were observed in the fourth month, while there were almost no obviously pathological changes in the combined group during the whole test period. The serum levels of aggrecan in all three test groups were all decreased slower after 4 months treatment than those in the control group.

CONCLUSION: GS and CS can postpone and inhibit the pathological changes of articular cartilage, as well as serum aggrecan levels decrease in Hartly guinea pigs. The effects of GS and CS used in combination was stronger than individual GS and CS, showing a repair property.

MSM (METHYL-SULFONYL-METHANE):  research papers demonstrating the efficacy of this substance in symptomatic relief of joint problems have mainly been carried out in human clinic trials.

“METHYL-SULFONYL-METHANE (M.S.M.). A DOUBLE BLIND STUDY OF ITS USE IN DEGENERATIVE ARTHRITIS”, By Ronald M. Lawrence, M.D., Ph.D. Assistant Clinical Professor U.C.L.A. School of Medicine, Los Angeles, California

Study Design
M.S.M. was provided in a crystalline form (LIGNISULmsm) which we encapsulated in a clear gelatin capsule providing 750 mgms of LIGNISUL MSM per capsule. The placebo substance, which was also placed in clear gelatin capsules, consisted of sugar (sucrose) to which a small amount of quinine sulfate was added to create a slightly bitter taste. This was done in case the capsule was opened and tasted, Since M.S.M. also has a slightly bitter taste.
A total of sixteen patients were studied over a period of four months. Initially twelve patients were admitted to the study and subsequently (two months later) additional four patients were added to the study group. The initial twelve patients were divided as follows. Eight were given the M.S.M., while four received the placebo. Later, the additional four patients were divided into two on M.S.M. and two on placebo. Totally, therefore, we had ten patients on M.S.M. and six patients on placebo.

RESULTS
At the four week visit, the patients on the LIGNISULmsm, showed a 60 percent improvement on average, while at the six week V.A.S. evaluation the patients showed an 82 percent improvement in pain on average. Those on the placebo showed an improvement of 20 percent on average at four weeks and an 18 percent improvement on average at six weeks.

“msm may offer a significant new nutritional substance for the control of arthritic pain as a safe, non-toxic method.”

“Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in Osteoarthritis”, DR P.R. Usha, M.U.R. Naidu, Clinical Drug Investigation
June 2004, Volume 24, Issue 6, pp 353-363.

Objective: Glucosamine, classified as a slow-acting drug in osteoarthritis (SADOA), is an efficacious chondroprotective agent. Methylsulfonylmethane (MSM), the isoxidised form of dimethyl-sulfoxide (DSMO), is an effective natural analgesic and anti-inflammatory agent. The aim of this study was to compare the efficacy and safety of oral glucosamine (Glu), methylsulfonylmethane (MSM), their combination and placebo in osteoarthritis of the knee.
Results: Glu, MSM and their combination significantly improved signs and symptoms of osteoarthritis compared with placebo. There was a statistically significant decrease in mean pain index at week 12 with Glu. MSM significantly decreased the mean pain index, and combination treatment resulted in a more significant decrease in the mean pain index. After 12 weeks, the mean swelling index significantly decreased with Glu and MSM, while the decrease in swelling index with combination therapy was greater after 12 weeks. The combination produced a statistically significant decrease in the Lequesne index. All treatments were well tolerated.
Conclusion: Glu, MSM and their combination produced an analgesic and anti-inflammatory effect in osteoarthritis. Combination therapy showed better efficacy in reducing pain and swelling and in improving the functional ability of joints than the individual agents. All the treatments were well tolerated. The onset of analgesic and anti-inflammatory activity was found to be more rapid with the combination than with Glu. It can be concluded that the combination of MSM with Glu provides better and more rapid improvement in patients with osteoarthritis.