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Glucosamine prevents in vitro collagen degradation in chondrocytes by inhibiting advanced lipoxidation reactions and protein oxidation
Moti L Tiku, Haritha Narla, Mohit Jain, Praveen Yalamanchili
Arthritis Research & Therapy , 2007, DOI: 10.1186/ar2274
Abstract: Osteoarthritis (OA) is characterized by the progressive degradation and loss of articular cartilage [1]. OA is the most common arthritic disease and its incidence increases with age. As population demographics changes to include more elderly individuals, this disease will have a serious impact in multiple ways. Along with the cost for health care and lost work time, individuals with OA suffer from pain and disability [2]. Currently, there is no specific treatment to prevent or retard the cartilage degradation in OA. Present treatments used for OA provide only symptomatic relief from the pain. Glucosamine sulfate, which has received attention as a putative agent that may retard cartilage structural degradation in OA, has been investigated in several OA trials [3-5]. The result on applicability of glucosamine in the clinical setting is still controversial [6-8]. Glucosamine in its various salt formulations with or without chondroitin sulfate is available over-the-counter as a nutritional supplement and is consumed by large numbers of osteoarthritic patients.The mechanism of retardation of cartilage degradation by glucosamine is not known. Glucosamine has been shown to have a number of effects in in vitro chondrocyte and explant cultures [9-13]. These effects include stimulation of proteoglycan synthesis, inhibition of the degradation of proteoglycans, and inhibition of matrix metalloproteinase-3 synthesis [14-16]. Glucosamine inhibits aggrecanase activity via suppression of glycosylphosphatidylinositol-linked proteins [17]. Furthermore, glucosamine has been shown to inhibit cytokine (interleukin-1 [IL-1])-induced activation of chondrocytes and nuclear factor-kappa-B activity and to upregulate type II IL-l decoy receptor [18,19]. In vivo, glucosamine helps enhance healing of cartilage injury [20-23]. Glucosamine has been demonstrated to have immunosuppressive and tumor-inhibiting activity [24,25]. All these pleiotropic effects of glucosamine may individually or collect
A natural mineral supplement provides relief from knee osteoarthritis symptoms: a randomized controlled pilot trial
Joy L Frestedt, Melanie Walsh, Michael A Kuskowski, John L Zenk
Nutrition Journal , 2008, DOI: 10.1186/1475-2891-7-9
Abstract: Subjects (n = 70) with moderate to severe osteoarthritis of the knee were randomized to four double-blinded treatments for 12 weeks: (a) Glucosamine sulfate (1500 mg/d); (b) Aquamin (2400 mg/d); (c) Combined treatment composed of Glucosamine sulfate (1500 mg/d) plus Aquamin (2400 mg/d) and (d) Placebo. Primary outcome measures were WOMAC scores and 6 Minute Walking Distances (6 MWD). Laboratory based blood tests were used as safety measures.Fifty subjects completed the study and analysis of the data showed significant differences between the groups for changes in WOMAC pain scores over time (p = 0.009 ANCOVA); however, these data must be reviewed with caution since significant differences were found between the groups at baseline for WOMAC pain and stiffness scores (p = 0.0039 and p = 0.013, respectively, ANOVA). Only the Aquamin and Glucosamine groups demonstrated significant improvements in symptoms over the course of the study. The combination group (like the placebo group) did not show any significant improvements in OA symptoms in this trial. Within group analysis demonstrated significant improvements over time on treatment for the WOMAC pain, activity, composite and stiffness (Aquamin only) scores as well as the 6 minute walking distances for subjects in the Aquamin and Glucosamine treatment groups. The Aquamin and Glucosamine groups walked 101 feet (+7%) and 56 feet (+3.5%) extra respectively. All treatments were well tolerated and the adverse events profiles were not significantly different between the groups.This small preliminary study suggested that a multi mineral supplement (Aquamin) may reduce the pain and stiffness of osteoarthritis of the knee over 12 weeks of treatment and warrants further study.ClinicalTrials.gov number: NCT00452101.Osteoarthritis (OA), also called degenerative joint disease, is a slow destructive process of the joint affecting millions of people worldwide. Although the exact biochemical cause of OA remains unknown, the process usu
Osteoarthritis and Glucosamine
Meral Kozak??o?lu
Romatizma , 2009,
Abstract: Osteoarthritis is the most common form of arthritis and a worldwide health problem. Many institutes and centers have been conducting research studies for years about the advantages of glucosamine sulphate derivatives and chondroitin sulphate on pain and deformities caused by osteoarthritis. The results of the research studies mentioned are discussed in this paper. The controlled, randomized, double blind research studies have shown chondroitin sulphate to have good symptomatic effects on osteoarthritis, although some controversies remain. New research studies have revealed that glucosamine sulphate and chondroitin sulphate both have a suppressor effect on the structural deformities of osteoarthritis.
Critical appraisal of the role of glucosamine and chondroitin in the management of osteoarthritis of the knee  [cached]
Steven J Narvy,C Thomas Vangsness Jr
Nutrition and Dietary Supplements , 2010,
Abstract: Steven J Narvy1, C Thomas Vangsness Jr21Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 2Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USAAbstract: Osteoarthritis (OA) is the most common musculoskeletal disease in the United States, with rising prevalence. Medical management of OA involves acetaminophen, nonsteroidal anti-inflammatory drugs, and other analgesics, all of which are of variable efficacy and are associated with significant side effects and toxicities. The purpose of this review is to critically evaluate the efficacy of glucosamine and chondroitin, both as single agents and in combination, for the treatment of knee OA. Also evaluated were the level of evidence and funding support of the included articles. Almost every included trial of glucosamine sulfate, glucosamine hydrochloride, and chondroitin sulfate has found the safety of these compounds to be equal to that of placebo, though their therapeutic efficacy in decreasing knee OA pain and improving joint function is variable. Additionally, there are data to support a role of these agents in reducing radiographic progression of knee OA. Industry involvement, however, remains prominent. Further, more comprehensive study by independent researchers free of industry ties is necessary to identify a subset of patients in whom the use of glucosamine and/or chondroitin would be most beneficial. These agents may be safely tried as an initial therapy in select OA patients prior to initiating therapy with nonsteroidal anti-inflammatory drugs, acetaminophen, and other traditional medications.Keywords: glucosamine sulfate, glucosamine hydrochloride, chondroitin sulfate, knee osteoarthritis, nutritional supplement, nutraceutical
Pharmacotherapeutic aspects of treating knee osteoarthritis with glucosamine sulfate  [PDF]
Steven Simoens, Gert Laekeman
Health (Health) , 2010, DOI: 10.4236/health.2010.27107
Abstract: Glucosamine sulfate is a natural constituent of cartilage and is used in the treatment of knee osteoarthritis. The aim of this study is to provide a short but comprehensive pharmacotherapeutic update on treating knee osteoarthritis with glucosamine sulfate. A literature search was conducted of PubMed, Centre for Reviews and Dissemination databases, Cochrane Reviews and EconLit up to January 2010. The literature review indicated that the mechanism of action of glucosamine sulfate is based on hypothesis, but its treatment effects in knee osteoarthritis are symptomatic. With steady-state peak concentrations at the 1,500 mg dosage in the range of 10 µM, it is estimated that only 2% of glucosamine is incorporated in the cartilage. A once-daily dosage of 1,500 mg of glucosamine sulfate is licensed for the treatment of symptomatic osteoarthritis and has been shown to reduce pain, improve function and exhibit similar safety to placebo. Glucosamine sulfate is likely to be a cost-effective treatment of knee osteoarthritis. In conclusion, a once-daily dosage of 1,500 mg of glucosamine sulfate is likely to be a safe, effective and cost-effective treatment of knee osteoarthritis as compared to placebo.
Glucosamine hydrochloride for the treatment of osteoarthritis symptoms  [cached]
Beth Anne Fox,Mary M Stephens
Clinical Interventions in Aging , 2007,
Abstract: Beth Anne Fox, Mary M StephensEast Tennessee State University, Family Physicians of Kingsport, Kingsport, TN, USAAbstract: Osteoarthritis is the most common arthritis in the world. It affects millions of people with age being the greatest risk factor for developing the disease. The burden of disease will worsen with the aging of the world’s population. The disease causes pain and functional disability. The direct costs of osteoarthritis include hospital and physician visits, medications, and assistive services. The indirect costs include work absences and lost wages. Many studies have sought to find a therapy to relieve pain and reduce disability. Glucosamine hydrochloride (HCl) is one of these therapies. There are limited studies of glucosamine HCl in humans. Although some subjects do report statistically significant improvement in pain and function from products combining glucosamine HCl and other agents, glucosamine HCl by itself appears to offer little benefit to those suffering from osteoarthritis.Keywords: osteoarthritis, glucosamine HCl, middle aged, aged, humans
Experimental Pharmacology of Glucosamine Sulfate  [PDF]
Riccardo Chiusaroli,Tiziana Piepoli,Tiziano Zanelli,Paola Ballanti,Marco Lanza,Lucio C. Rovati,Gianfranco Caselli
International Journal of Rheumatology , 2011, DOI: 10.1155/2011/939265
Abstract: Several clinical studies demonstrated that glucosamine sulfate (GS) is effective in controlling osteoarthritis (OA), showing a structure-modifying action. However, little is known about the molecular mechanism(s) by which GS exerts such action and about the effects of GS at a tissue level on osteoarthritic cartilage and other joint structures. Here we provide mechanistic evidence suggesting that in vitro GS attenuates NF-κB activation at concentrations in the range of those observed after GS administration to volunteers and patients, thus strengthening previous findings. Furthermore, we describe the effects of GS at a tissue level on the progression of the disease in a relevant model of spontaneous OA, the STR/ort mouse. In this model, the administration of GS at human corresponding doses was associated with a significant decrease of OA scores. Histomorphometry showed that the lesion surface was also significantly decreased, while the number of viable chondrocytes within the matrix was significantly increased. GS improved the course of OA in the STR/Ort mouse, by delaying cartilage breakdown as assessed histologically and histomorphometrically. 1. Introduction Glucosamine sulfate (GS) is used all over the world for the therapy of osteoarthritis. Several clinical studies have shown that it is effective in controlling osteoarthritis (OA) not only in terms of symptoms, but also in reason of its ability to delay the progression of the disease, at least as far as can be assessed with the currently available clinical readouts [1–8]. However, there is still considerable confusion and conflict as to the real effects of glucosamine as an osteoarthritis disease modifying drug—in its heterogeneous preparations and different salts. Outcomes of the clinical trials have not been unanimous in assigning efficacy to glucosamine, due to a number of issues [9, 10]. Nevertheless, GS is recommended in 6/10 existing guidelines for the management of hip or knee OA [10]. Parallel to the clinical, a considerable amount of preclinical, experimental pharmacology studies have been accruing through the years, both by other groups and by ours, that contribute to the understanding of the modes of action of GS, although much certainly is yet to be done. Most of the efforts in this field were accurately reviewed by Block et al. [11]. It appears that the studies on glucosamine were mainly performed along two lines of research, one that employed mostly in vitro and cell biology methods, aimed at shedding light on the molecular mechanism, or mechanisms, through which glucosamine exerts
Relief of osteoarthritis with a herbal-amino acid supplement: A randomized double-blind placebo controlled trial  [PDF]
Mark J.S. Miller, Ross Butler
Advances in Bioscience and Biotechnology (ABB) , 2012, DOI: 10.4236/abb.2012.324066
Abstract: A redox active medicinal plant and L-leucine mixture (HLM) was investigated in subjects with established osteoarthritis of the knee in a multi-center, rando- m-ized, placebo-controlled, double-blind clinical trial. A total of 96 subjects with osteoarthritis were enrolled and randomized to either placebo (n = 38) or HLM treatment group (n = 38). The HLM group re- ceived a combination of Uncaria tomentosa (300 mg), Boswellia serrata (200 mg), Lepidium meyenii (1000 mg) and L-Leucine (700 mg) given as 3 capsules once a day. The placebo group received matching capsules with carboxymethylcellulose. The treatment period was 8 weeks, with assessments made at days 7, 14, 28 and 56. The primary outcome was reduction in total WOMAC score. VAS pain, tolerability, investigator assessments, use of rescue medication (acetominophen), and safety assessments of vital signs and laboratory assessments were included. Subject randomization was effective for age, gender and disease severity. In the placebo group 32/38 subjects completed the trial and for HLM 35/38. WOMAC scores (pain, stiffness, physical performance and total) steadily declined over the course of the 8 week study in both groups, but the magnitude was significantly greater for HLM (P < 0.05). Total WOMAC was reduced 46.5% for HLM and 25.4 % for placebo. VAS pain was reduced 21.8% in the placebo group (p < 0.002) but the changes were significantly greater (37.8% p < 0.03) with HLM treatment. Investigator’s global assessment rating of good-excellent was 24/35 (69%) for HLM and 14/32 (44%) for placebo (P = 0.05). Rescue medication consumption and tolerability were comparable for HLM and placebo. No safety issues were evident with either group. As expected a placebo effect was observed, nevertheless HLM was clearly more effective in relieving the symptoms of osteoarthritis. This HLM represents a safe and effective new approach to the management of osteoarthritis symptoms.
Glucosamine Prescription for Osteoarthritis and its Impact on Patients with Diabetes Prescripción de glucosamina para la osteoartritis y sus efectos en personas con diabetes  [cached]
Levi González Rivero
Finlay : Revista de Enfermedades no Transmisibles , 2012,
Abstract: Glucosamine is a nutritional supplement widely used as a treatment for osteoarthritis. Nevertheless, according to well-designed studies, no solid evidence confirms its clinical effectiveness when treating this disease. It is considered to be a safe product for the general population, but it is an amino monosaccharide that appears to have adverse effects on glucose metabolism in individuals with insulin resistance. Its apparent safety in patients with controlled diabetes lasting for a short period of time can not be extrapolated to all those who suffer from diabetes, least of all to those at potential risk of suffering from it. This paper is aimed at discouraging irrational prescription of glucosamine for osteoarthritis in presence of glucidic disorders, as long as no studies addressing the safety of its use in this particular group of patients are available. La glucosamina es un suplemento nutricional de amplio consumo como tratamiento de la osteoartritis, aunque según estudios bien dise ados no existe evidencia firme de su efectividad clínica sobre esa enfermedad. Se considera un producto seguro en población general, pero es un amino monosacárido que parece tener efectos adversos en el metabolismo glucídico de sujetos con resistencia a insulina. Su aparente inocuidad en personas con diabetes controlada y de corto tiempo de evolución, no puede extrapolarse a toda la población con diabetes, y menos a aquellos en riesgo potencial de padecerla. El enfoque de este trabajo persigue desalentar la prescripción irracional de glucosamina para la osteoartritis en presencia de trastornos glucídicos, hasta tanto no estén disponibles estudios que avalen la seguridad de su consumo en este grupo particular de pacientes.
Early relief of osteoarthritis symptoms with a natural mineral supplement and a herbomineral combination: A randomized controlled trial [ISRCTN38432711]
Mark JS Miller, Komal Mehta, Sameer Kunte, Vidyanand Raut, Jayesh Gala, Ramesh Dhumale, Anil Shukla, Hemant Tupalli, Himanshu Parikh, Paul Bobrowski, Jayesh Chaudhary
Journal of Inflammation , 2005, DOI: 10.1186/1476-9255-2-11
Abstract: Patients (n = 107) with mild to moderate osteoarthritis of the knee were randomly assigned to one of 4 groups; high dose sierrasil (3 g/day), low dose sierrasil (2 g/day), low dose sierrasil (2 g/day) + cat's claw extract (100 mg/day) or placebo, administered for 8 weeks. Treatment was double blinded. Primary efficacy variables were WOMAC scores (A, B, C and total). Visual analog score (VAS) for pain, consumption of rescue medication (paracetamol), and tolerability were secondary variables. Safety measures included vital signs and laboratory-based assays.Ninety-one of the 107 patients successfully completed the protocol. All four groups showed improvement in WOMAC and VAS scores after 8 weeks (p < 0.001), in all 3 groups receiving sierrasil the magnitude of benefits were greater vs. placebo (WOMAC Total 38–43% vs. 27%) but this was not statistically significant. In reference to baseline values sierrasil treated groups had a considerably faster onset of benefits. Placebo-treated individuals failed to show significant benefits at 4 weeks (11% reduction in total WOMAC). In contrast, after 1 or 2 weeks of therapy all the sierrasil groups displayed significant reductions in WOMAC scores (p < 0.05) and at week 4 displayed a 38–43% improvement. VAS was significantly improved at 4 weeks in all groups (p < 0.001) but was significantly greater in all sierrasil groups compared to placebo (p < 0.05). Rescue medication use was 28-23% lower in the herbomineral combination and high dose sierrasil groups although not statistically different from placebo (P = 0.101 and P = 0.193, respectively). Tolerability was good for all groups, no serious adverse events were noted and safety parameters remained unchanged.The natural mineral supplement, sierrasil alone and in combination with a cat's claw extract, improved joint health and function within 1–2 weeks of treatment but significant benefits over placebo were not sustained, possibly due to rescue medication masking. Sierrasil may offer
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