Glucosamine / Chondroitin Sulfate

Effects of diet type and supplementation of glucosamine, chondroitin, and MSM on body composition, functional status, and markers of health in women with knee osteoarthritis initiating a resistance-based exercise and weight loss program.
Magrans-Courtney T, Wilborn C, Rasmussen C, Ferreira M, Greenwood L, Campbell B, Kerksick CM, Nassar E, Li R, Iosia M, Cooke M, Dugan K, Willoughby D, Soliah L, Kreider RB.
J Int Soc Sports Nutr. 2011 Jun 20;8(1):8

 The purpose of this study was to determine whether sedentary obese women with knee OA initiating an exercise and weight loss program may experience more beneficial changes in body composition, functional capacity, and/or markers of health following a higher protein diet compared to a higher carbohydrate diet with or without GCM supplementation. Thirty sedentary women (54+/-9 yrs, 163+/-6 cm, 88.6+/-13 kg, 46.1+/-3 % fat, 33.3+/-5 kg/m2) with clinically diagnosed knee OA participated in a 14-week exercise and weight loss program. Participants followed an isoenergenic low fat higher carbohydrate (HC) or higher protein (HP) diet while participating in a supervised 30-minute circuit resistance-training program three times per week for 14-weeks. In a randomized and double blind manner, participants ingested supplements containing 1,500 mg/d of glucosamine (as d-glucosamine HCL), 1,200 mg/d of chondroitin sulfate (fromchondroitin sulfate sodium), and 900 mg/d of methylsulfonylmethane or a placebo. At 0, 10, and 14-weeks, participants completed a battery of assessments. Data were analyzed by MANOVA with repeated measures. Participants in both groups experienced significant reductions in body mass (-2.4+/-3%), fat mass (-6.0+/-6%), and body fat (-3.5+/-4%) with no significant changes in fat free mass or resting energy expenditure. Perception of knee pain (-49+/-39%) and knee stiffness (-42+/-37%) was decreased while maximal strength (12%), muscular endurance (20%), balance indices (7% to 20%), lipid levels (-8% to -12%), homeostasis model assessment for estimating insulin resistance (-17%), leptin (-30%), and measures of physical functioning (59%), vitality (120%), and social function (66%) were improved in both groups with no differences among groups. Functional aerobic capacity was increased to a greater degree for those in the HP and GCM groups while there were some trends suggesting that supplementation affected perceptions of knee pain (p < 0.08).  Circuit style resistance-training and weight loss improved functional capacity in women with knee OA. The type of diet and dietary supplementation of GCM provided marginal additive benefits.
PMID: 21689421

  Effects of chondroitin sulfate and glucosamine in adult patients with Kaschin-Beck disease.
Zhang YX, Dong W, Liu H, Cicuttini F, de Courten M, Yang JB.
Clin Rheumatol. 2010 Apr;29(4):357-62

 The purpose is to investigate the effects of chondroitin sulfate and glucosamine on adult patients with Kaschin-Beck disease (KBD). A total of 80 patients, aged over 40 years, were randomized into two groups receiving either 1,600 mg oral mixture of chondroitin sulfate and glucosamine or placebo twice daily for 8 months. Posteroanterior radiographs of bilateral knee in full extension were taken at enrollment and after 8 months. Mean joint-space width of the assigned six points on the tibiofemoral joint compartment was measured by a graduated magnifying lens. The mean joint space decreased significantly in the placebo group (4.3 +/- 1.09 versus 4.1 +/- 1.07 mm, P < 0.0001) after 8 months and was unchanged in the experimental group (P = 0.51). There was no statistical significance in the mean joint space between two groups at baseline and follow-up (P = 0.65 and P = 0.84, respectively). But the overall mean change in joint space was significant between the two groups (P < 0.0001). Knee joint space of the experimental group narrowed slowly compared to the control group. Therefore, chondroitin sulfate and glucosamine might play a protective role in preserving articular cartilage and provide evidence for therapeutic drugs in adult patients with KBD. PMID: 20108108

  Effect of glucosamine or chondroitin sulfate on the osteoarthritis progression: a meta-analysis.
Lee YH, Woo JH, Choi SJ, Ji JD, Song GG.
Rheumatol Int. 2010 Jan;30(3):357-63

 The aim of this study was to assess the structural efficacies of daily glucosamine sulfate and chondroitin sulfate in patients with knee osteoarthritis (OA). The authors surveyed randomized controlled studies that examined the effects of long-term daily glucosamine sulfate and chondroitin sulfate on joint space narrowing (JSN) in knee OA patients using the Medline and the Cochrane Controlled Trials Register, and by performing manual searches. Meta-analysis was performed using a fixed effect model because no between-study heterogeneity was evident. Six studies involving 1,502 cases were included in this meta-analysis, which consisted of two studies on glucosamine sulfate and four studies on chondroitin sulfate. Glucosamine sulfate did not show a significant effect versus controls on minimum JSN over the first year of treatment (SMD 0.078, 95% CI -0.116 to -0.273, P = 0.429). However, after 3 years of treatment, glucosamine sulfate revealed a small to moderate protective effect on minimum JSN (SMD 0.432, 95% CI 0.235-0.628, P < 0.001). The same was observed for chondroitin sulfate, which had a small but significant protective effect on minimum JSN after 2 years (SMD 0.261, 95% CI 0.131-0.392, P < 0.001). This meta-analysis of available data shows that glucosamine and chondroitin sulfate may delay radiological progression of OA of the knee after daily administration for over 2 or 3 years.
PMID: 19544061

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

 The effects of Glucosamine Sulphate (GS) and Chondroitin Sulphate (CS) on the healing of damaged and repaired articular cartilage were investigated. This study was conducted using 18 New Zealand white rabbits as experimental models. Focal cartilage defects, surgically created in the medial femoral condyle, were either treated by means of autologous chondrocyte implantation (ACI) or left untreated as controls. Rabbits were then divided into groups which received either GS+/-CS or no pharmacotherapy. Three rabbits from each group were sacrificed at 12 and 24 weeks post-surgery. Knees dissected from rabbits were then evaluated using gross quantification of repair tissue, glycosaminoglycan (GAG) assays, immunoassays and histological assessments. It was observed that, in contrast to untreated sites, surfaces of the ACI-repaired sites appeared smooth and continuous with the surrounding native cartilage. Histological examination demonstrated a typical hyaline cartilage structure; with proteoglycans, type II collagen and GAGs being highly expressed in repair areas. The improved regeneration of these repair sites was also noted to be significant over time (6 months vs. 3 months) and in GS and GS+CS groups compared to the untreated (without pharmacotherapy) group. Combination of ACI and pharmacotherapy (with glucosamine sulphate alone/ or with chondroitin sulphate) may prove beneficial for healing of damaged cartilage, particularly in relation to focal cartilage defects. PMID: 21409755

  Effects of glucosamine and chondroitin sulfate on bovine cartilage explants under long-term culture conditions.
Chan PS, Caron JP, Orth MW.
Am J Vet Res. 2007 Jul;68(7):709-15.

 To determine effects of glucosamine (GLN) and chondroitin sulfate (CS) on expression of genes encoding putative mediators of osteoarthritis in bovine cartilage explants cultured for 2 weeks. Articular cartilage explants harvested from carpal joints of 4 Holstein steers after slaughter. Cartilage disks were treated as follows: fetal bovine serum only (control treatment), human recombinant interleukin (IL)-1beta (50 ng/mL; IL-1 treatment), GLN (5 microg/mL) with addition of CS (20 microg/mL; GLN-CS treatment), and human recombinant IL-1beta (50 ng/mL) with addition of GLN and CS (IL-1-GLN-CS treatment). Media were analyzed for nitric oxide and prostaglandin E(2) (PGE(2)) release. Explants were subjected to quantitative real-time PCR analysis; expressions of mRNA for inducible nitric oxide synthase, cyclooxygenase-2, microsomal prostaglandin E synthase 1, matrix metalloproteinase (MMP)-3 and -13, aggrecanase-1 and -2, tissue inhibitor of metalloproteinase (TIMP)-3, type II collagen, and aggrecan were assessed. IL-1-GLN-CS and GLN-CS treatments decreased nitrite release, compared with IL-1 treatment; IL-1-GLN-CS treatment decreased IL-1-induced PGE(2) release. Expressions of inducible nitric oxide synthase, cyclooxygenase-2, and microsomal prostaglandin E synthase 1 mRNA were abrogated by GLN-CS and IL-1-GLN-CS treatments. Interleukin-1-induced mRNA expressions of proteolytic enzymes were diminished by IL-1-GLN-CS treatment. Compared with control treatment, GLN-CS treatment decreased MMP-3 and aggrecanase-2 mRNA expression. Transcripts of TIMP-3 were increased by IL-1-GLN-CS treatment, compared with IL-1 treatment. Genes encoding type II collagen and aggrecan on day 14 were upregulated by GLN-CS and IL-1-GLN-CS treatments, compared with control treatment. Treatment with GLN and CS consistently downregulated mRNA expression for inflammatory mediators and matrix degrading enzymes while increasing TIMP-3 transcripts. PMID: 17605605

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

 To test the effectiveness of glucosamine (GluNH(2))-HCl, chondroitin sulfate (CS) and mixtures in protecting cartilage exposed to fibronectin fragments (Fn-fs), an exposure known to enhance catabolic cytokines and matrix metalloproteinases (MMPs). Pharmacologic formulations of GluNH(2) (FCHG49) and CS (TRH122) (Nutramax Laboratories, Inc.) were added at 1, 10 or 100 microg/ml singly or in mixtures to bovine cartilage cultures in serum or serum-free conditions with or without Fn-f. Proteoglycan (PG) release into media and remaining cartilage PG content were measured by dye binding analysis and effects on PG synthesis by assays of 35-sulfate incorporation. Effects on MMP-3 and -13 expression were measured by Western blotting of conditioned media. In serum-free conditions, the agents singly or as mixtures did not block Fn-f mediated matrix degradation. In serum, single agents were weakly effective at 100 microg/ml, while the mixture of each agent at 0.1 microg/ml decreased PG loss by about 50% by day 7 and at 1 microg/ml restored nearly 50% of the PG after 7 days in Fn-f pretreated cartilage. However, both agents singly and as mixtures at 0.1-100 microg/ml decreased MMP release. In serum, the single agents at 1-10 microg/ml weakly reversed Fn-f mediated PG synthesis suppression, while the mixtures were 100% effective at 1 microg/ml. GluNH(2) and CS act synergistically in reversing damage and promoting repair at concentrations found in plasma after oral ingestion of these agents. Reversal of PG synthesis suppression correlates more with these activities than suppression of MMP-3 or -13 expression. PMID: 16581272

  Recent advances in glucosamine and chondroitin supplementation.
Owens S, Wagner P, Vangsness CT Jr.
J Knee Surg. 2004 Oct;17(4):185-93.

 Glucosamine and chondroitin are alternative solutions to previous pharmaceutical options for the treatment of osteoarthritis. This article describes the mechanisms of action, pharmacokinetics, recent findings, and upcoming studies of these two natural remedies. The majority of studies on the mechanisms behind glucosamine and chondroitin have been performed in vitro or on animal models; however, the results have shown favorable effects on the balance between cartilage matrix synthesis and degradation. The pharmacokinetics of the three main forms of glucosamine were compared, andglucosamine hydrochloride displayed the greatest compound purity, despite the compounds having equal oral absorption rates of 90%. Chondroitin sulfate has been the principal clinical formulation with a slightly lower oral absorption of 70%. Clinical trials were evaluated based on two categories-radiographic changes and symptom improvement of pain and function. Although adverse effects of these two remedies were minor, the quality and labeled quantity of these relatively unregulated products must be considered. More randomized controlled studies on humans in vivo need to evaluate the efficacy, long-term effects, and quality of these compounds. PMID: 15553585

  Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis.
McAlindon TE, LaValley MP, Gulin JP, Felson DT.
JAMA. 2000 Mar 15;283(11):1469-75.

 Glucosamine and chondroitin preparations are widely touted in the lay press as remedies for osteoarthritis (OA), but uncertainty about their efficacy exists among the medical community. To evaluate benefit of glucosamine and chondroitin preparations for OA symptoms using meta-analysis combined with systematic quality assessment of clinical trials of these preparations in knee and/or hip OA. We searched for human clinical trials in MEDLINE (1966 to June 1999) and the Cochrane Controlled Trials Register using the terms osteoarthritis, osteoarthrosis, degenerative arthritis, glucosamine, chondroitin, and glycosaminoglycans. We also manually searched review articles, manuscripts, and supplements from rheumatology and OA journals and sought unpublished data by contacting content experts, study authors, and manufacturers of glucosamine or  chondroitin. Studies were included if they were published or unpublished double-blind, randomized, placebo-controlled trials of 4 or more weeks’ duration that tested glucosamine or chondroitinfor knee or hip OA and reported extractable data on the effect of treatment on symptoms. Fifteen of 37 studies were included in the analysis. Reviewers performed data extraction and scored each trial using a quality assessment instrument. We computed an effect size from the intergroup difference in mean outcome values at trial end, divided by the SD of the outcome value in the placebo group (0.2, small effect; 0.5, moderate; 0.8, large), and applied a correction factor to reduce bias. We tested for trial heterogeneity and publication bias and stratified for trial quality and size. We pooled effect sizes using a random effects model. Quality scores ranged from 12.3% to 55.4% of the maximum, with a mean (SD) of 35.5% (12%). Only 1 study described adequate allocation concealment and 2 reported an intent-to-treat analysis. Most were supported or performed by a manufacturer. Funnel plots showed significant asymmetry (P< or =.01) compatible with publication bias. Tests for heterogeneity were nonsignificant after removing 1 outlier trial. The aggregated effect sizes were 0.44 (95% confidence interval [CI], 0.24-0.64) for glucosamine and 0.78 (95% CI, 0.60-0.95) for chondroitin, but they were diminished when only high-quality or large trials were considered. The effect sizes were relatively consistent for pain and functional outcomes. Trials of glucosamine and chondroitin preparations for OA symptoms demonstrate moderate to large effects, but quality issues and likely publication bias suggest that these effects are exaggerated. Nevertheless, some degree of efficacy appears probable for these preparations. PMID: 10732937

  Inhibition of articular cartilage degradation by glucosamine-HCl and chondroitin sulphate.
Orth MW, Peters TL, Hawkins JN.
Equine Vet J Suppl. 2002 Sep;(34):224-9.

 Glucosamine and chondroitin sulphate in many animal and human trials has improved joint health. In vitro studies are beginning to clarify their mode of action. The objective of this research was to: 1) determine at what concentrations glucosamine-HCl (GLN) and/or chondroitin sulphate (CS) would inhibit the cytokine-induced catabolic response in equine articular cartilage explants and 2) to determine if a combination of the 2 was more effective at inhibiting the catabolic response than the individual compounds. Articular cartilage was obtained from carpal joints of horses (age 1-4 years). Cartilage discs (3.5 mm) were biopsied and cultured. Explants were incubated with lipopolysaccharide (LPS) in the presence of varying concentrations of GLN, CS, or both. Control treatments included explants with no LPS and LPS without GLN or CS. Media were analysed for nitric oxide (NO), prostaglandin E2 (PGE2) and keratan sulphate. Cartilage was extracted for analysis of metalloproteinases (MMP). Four experiments were conducted. In all experiments, GLN at concentrations as low as 1 mg/ml decreased NO production relative to LPS stimulated cartilage without GLN over the 4 day period. In general, CS at either 0.25 or 0.5 mg/ml did not inhibit NO production. The addition of CS to GLN containing media did not further inhibit NO production. GLN at concentrations as low as 0.5 mg/ml decreased PGE2 production, whereas CS did not effect on PGE2. The combination of GLN/CS decreased MMP-9 gelatinolytic activity but had no effect on MMP-2 activity. The combination in 2 experiments tended to decrease MMP-13 protein concentrations and decreased keratan sulphate levels in media. Overall, the combination of GLN (1 mg/ml) and CS (0.25 mg/ml) inhibited the synthesis of several mediators of cartilagedegradation. These results further support the effort to understand the role of GLN and CS in preserving articular cartilage in athletic horses. PMID: 12405691

  Glucosamine and chondroitin sulfate as therapeutic agents for knee and hip osteoarthritis.
Bruyere O, Reginster JY.
Drugs Aging. 2007;24(7):573-80.

 Osteoarthritis (OA), the most common form of arthritis, is a public health problem throughout the world. Several entities have been carefully investigated for the symptomatic and structural management of OA. This review evaluates published studies of the effect of glucosamine salts and chondroitin sulfate preparations on the progression of knee or hip OA. Despite multiple double-blind, controlled clinical trials of the use of glucosamine and chondroitin sulfate in OA, controversy regarding the efficacy of these agents with respect to symptomatic improvement remains. Several potential confounders, including placebo response, use of prescription medicines versus over-the-counter pills or food supplements, or use of glucosamine sulfate versus glucosamine hydrochloride, may have relevance when attempting to interpret the seemingly contradictory results of different clinical trials. The National Institutes of Health-sponsored GAIT (Glucosamine/chondroitin Arthritis Intervention Trial) compared placebo, glucosamine hydrochloride, chondroitin sulfate, a combination of glucosamine and chondroitin sulfate and celecoxib in a parallel, blinded 6-month multicentre study of patients with knee OA. This trial showed that glucosamine hydrochloride and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with OA of the knee. However, exploratory analyses suggest that the combination of glucosamine hydrochloride and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain. For decades, the traditional pharmacological management of OA has been mainly symptomatic. However, in recent years, several randomised controlled studies have assessed the structure-modifying effect of glucosamine sulfate and chondroitin sulfate using plain radiography to measure joint space narrowing over years. There is some evidence to suggest a structure-modifying effect of glucosamine sulfate and chondroitin sulfate. On the basis of the results of recent randomised controlled trials and meta-analyses, we can conclude that glucosamine sulfate (but not glucosamine hydrochloride) and chondroitin sulfate have small-to-moderate symptomatic efficacy in OA, although this is still debated. With respect to the structure-modifying effect, there is compelling evidence that glucosamine sulfate and chondroitin sulfate may interfere with progression of OA. PMID: 17658908

  Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis.
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 HJ.
N Engl J Med. 2006 Feb 23;354(8):795-808.

 Glucosamine and chondroitin sulfate are used to treat osteoarthritis. The multicenter, double-blind, placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis. We randomly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, both glucosamine and chondroitin sulfate, 200 mg of celecoxib daily, or placebo for 24 weeks. Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia. Assignment was stratified according to the severity of knee pain (mild [N=1229] vs. moderate to severe [N=354]). The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24. The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent. As compared with the rate of response to placebo (60.1 percent), the rate of response to glucosamine was 3.9 percentage points higher (P=0.30), the rate of response to chondroitin sulfate was 5.3 percentage points higher (P=0.17), and the rate of response to combined treatment was 6.5 percentage points higher (P=0.09). The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group (P=0.008). For patients with moderate-to-severe pain at baseline, the rate of response was significantly higher with combined therapy than with placebo (79.2 percent vs. 54.3 percent, P=0.002). Adverse events were mild, infrequent, and evenly distributed among the groups. Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee. Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain. PMID: 16495392 Copyright 2006 Massachusetts Medical Society.