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Glucosamine HCL References

1: Arthritis Rheum. 2007 May;56(5):1537-48.

The effects of glucosamine hydrochloride on subchondral bone changes in an animal model of osteoarthritis.

Wang SX, Laverty S, Dumitriu M, Plaas A, Grynpas MD. University of Toronto, Toronto, Ontario, Canada.

OBJECTIVE: To quantify periarticular subchondral bone changes in a rabbit model of experimental osteoarthritis (OA), and to determine the effects of continuous administration of a clinically relevant dose of glucosamine HCl on subchondral bone changes in this model. METHODS: Anterior cruciate ligament transection (ACLT) was performed on the left femorotibial joints of 16 rabbits to induce OA. Ten rabbits that did not undergo ACLT served as unoperated controls. Eight rabbits that underwent ACLT and 6 control rabbits were treated with 100 mg of glucosamine daily, and the others were given a placebo. The articular cartilage was evaluated macroscopically and graded at the time of necropsy, 8 weeks after ACLT. Bone mineral density (BMD) was measured using dual-energy x-ray absorptiometry on the dissected distal femur and proximal tibia. Subchondral trabecular bone turnover, architecture, and connectivity, as well as subchondral plate thickness and mineralization were studied on the undecalcified tibia sections from each animal. RESULTS: Eight weeks after ACLT, most of the operated joints had various degrees of cartilage damage and fibrillation. Compared with the control group, the ACLT group had significantly increased subchondral bone turnover and lower BMD, bone volume, connectivity, and bone mineralization. The high bone turnover was significantly reduced in glucosamine-treated animals that underwent ACLT. In fact, there were no significant differences between the ACLT/glucosamine group and the control/glucosamine group in most of the bone parameters studied. CONCLUSION: This study shows that subchondral bone turnover, structure, and mineralization are significantly altered in the early stages of experimental OA, and that these changes are attenuated by glucosamine treatment.

2: Mil Med. 1999 Feb;164(2):85-91.

Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study.

Leffler CT, Philippi AF, Leffler SG, Mosure JC, Kim PD. Medical Department, Naval Special Warfare Group Two, Naval Amphibious Base Little Creek, Norfolk, VA 23521, USA. This e-mail address is being protected from spambots. You need JavaScript enabled to view it

OBJECTIVE: A 16-week randomized, double-blind, placebo-controlled crossover trial of a combination of glucosamine HCl (1,500 mg/day), chondroitin sulfate (1,200 mg/day), and manganese ascorbate (228 mg/day) in degenerative joint disease (DJD) of the knee or low back was conducted. METHODS: Thirty-four males from the U.S. Navy diving and special warfare community with chronic pain and radiographic DJD of the knee or low back were randomized. A summary disease score incorporated results of pain and functional questionnaires, physical examination scores, and running times. Changes were presented as a percentage of the patient's average score. RESULTS: Knee osteoarthritis symptoms were relieved as demonstrated by the summary disease score (-16.3%; p = 0.05), patient assessment of treatment effect (p = 0.02), visual analog scale for pain recorded at clinic visits (-26.6%; p = 0.05) and in a diary (-28.6%; p = 0.02), and physical examination score (-43.3%; p = 0.01). Running times did not change. The study neither demonstrated, nor excluded, a benefit for spinal DJD. Side effect frequency was similar to that at baseline. There were no hematologic effects.

CONCLUSIONS: The combination therapy relieves symptoms of knee osteoarthritis. A larger data set is needed to determine the value of this therapy for spinal DJD. Short-term combination therapy appears safe in this setting. 3: Clin Interv Aging. 2007;2(4):599-604.

Glucosamine hydrochloride for the treatment of osteoarthritis symptoms.

Fox BA, Stephens MM. East Tennessee State University, Family Physicians of Kingsport, 201 Cassel Drive, Kingsport,Tennessee 37660, USA. This e-mail address is being protected from spambots. You need JavaScript enabled to view it 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.

4: J Biol Chem. 2007 Sep 21;282(38):27622-32. Epub 2007 Jul 16.

Glucosamine hydrochloride specifically inhibits COX-2 by preventing COX-2 N-glycosylation and by increasing COX-2 protein turnover in a proteasome-dependent manner.

Jang BC, Sung SH, Park JG, Park JW, Bae JH, Shin DH, Park GY, Han SB, Suh SI. Chronic Disease Research Center and Institute for Medical Science, Keimyung University School of Medicine, Daegu, South Korea. This e-mail address is being protected from spambots. You need JavaScript enabled to view it COX-2 and its products, including prostaglandin E(2), are involved in many inflammatory processes. Glucosamine (GS) is an amino monosaccharide and has been widely used for alternative regimen of (osteo) arthritis. However, the mechanism of action of GS on COX-2 expression remains unclear. Here we describe a new action mechanism of glucosamine hydrochloride (GS-HCl) to tackle endogenous and agonist-driven COX-2 at protein level. GS-HCl (but not GS sulfate, N-acetyl GS, or galactosamine HCl) resulted in a shift in the molecular mass of COX-2 from 72-74 to 66-70 kDa and concomitant inhibition of prostaglandin E(2) production in a concentration-dependent manner in interleukin (IL)-1beta-treated A549 human lung epithelial cells. Remarkably, GS-HCl-mediated decrease in COX-2 molecular mass was associated with inhibition of COX-2 N-glycosylation during translation, as assessed by the effect of tunicamycin, the protein N-glycosylation inhibitor, or of cycloheximide, the translation inhibitor, on COX-2 modification. Specifically, the effect of low concentration of GS-HCl (1 mM) or of tunicamycin (0.1 microg/ml) to produce the aglycosylated COX-2 was rescued by the proteasomal inhibitor MG132 but not by the lysosomal or caspase inhibitors. However, the proteasomal inhibitors did not show an effect at 5 mM GS-HCl, which produced the aglycosylated or completely deglycosylated form of COX-2. Notably, GS-HCl (5 mM) also facilitated degradation of the higher molecular species of COX-2 in IL-1beta-treated A549 cells that was retarded by MG132. GS-HCl (5 mM) was also able to decrease the molecular mass of endogenous and IL-1beta- or tumor necrosis factor-alpha-driven COX-2 in different human cell lines, including Hep2 (bronchial) and H292 (laryngeal). However, GS-HCl did not affect COX-1 protein expression. These results demonstrate for the first time that GS-HCl inhibits COX-2 activity by preventing COX-2 co-translational N-glycosylation and by facilitating COX-2 protein turnover during translation in a proteasome-dependent manner.

5: J Cell Biochem. 2008 May 1;104(1):38-50.

Disease-modifying effects of glucosamine HCl involving regulation of metalloproteinases and chemokines activated by interleukin-1beta in human primary synovial fibroblasts.

Lu HT, Liang YC, Sheu MT, Ho HO, Lin YT, Hsieh MS, Chen CH.

Department of Orthopedics and Traumatology, Taipei Medical University Hospital,

Taipei, Taiwan, ROC.

The purpose of this study was to investigate the possible involvement of synovium in cartilage destruction in osteoarthritis (OA) patients. Using human primary synovial fibroblasts (HPSFs), we examined the effects of glucosamine (GLN) on the regulation of the expression of matrix metalloproteinases (MMP-1, -2, and -13) and chemokines (IL-8, MCP-1, and RANTES) as well as the involvement of MAPK signal pathways (JNK, ERK, and p-38) and the transcription factor of NF-kappaB on the present or absence of interleukin (IL)-1beta. Our experiments showed that protein production and mRNA expressions of MMP-1, MMP-3, MMP-13, IL-8, MCP-1, and RANTES were down regulated by treatment with glucosamine in HPSFs. The results further showed that GLN could inhibit IkappaBalpha phosphorylation and IkappaBalpha degradation leading to inhibition of the translocation of NF-kappaB to nuclei. However, GLN upregulated MAPKs pathways in HPSFs cells with or without IL-1beta. The results suggest that the inhibition of MMP-1, -3, and -13 expressions as well as IL-8, MCP-1, and RANTES productions by GLN might mediate suppression of NF-kappaB signal pathways, and HPSFs seem to have a potential functions as an alternative source of MMPs and chemokines for inducing the degradation of cartilage in OA. 6: Osteoarthritis Cartilage.

2000 Sep;8(5):343-50.

Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis.

Das A Jr, Hammad TA.

Hendersonville Orthopedics Associates, Hendersonville, North Carolina 28739, USA. OBJECTIVES: The objective of this study was to evaluate the oral combination of glucosamine HCl, sodium chondroitin sulfate and manganese ascorbate for the treatment of osteoarthritis (OA) of the knee. DESIGN: A randomized placebo-controlled study design was implemented. We recruited 93 patients with OA of the knee from a single center. The intervention group received 1000 mg FCHG49 glucosamine HCl, 800 mg TRH122 low molecular weight sodium chondroitin sulfate and 152 mg manganese ascorbate twice daily (Cosamin DS). Patients were evaluated initially and then every 2 months for 6 months. The primary outcome was the Lesquene Index of severity of osteoarthritis of the knee (ISK). RESULTS: Patients with radiographically mild or moderate OA (N=72) in the intervention group showed significant improvement in the ISK at 4 and 6 months (P=0.003 and P=0.04, respectively). The response rate to the medication was 52% vs a 28% response rate to placebo. Patients with radiographically severe osteoarthritis (N=21) did not show significant improvements in the ISK. There was a 17% incidence of adverse events in the intervention group and 19% in the placebo group. CONCLUSIONS: The studied combination of glucosamine HCl, sodium chondroitin sulfate and manganese ascorbate was found to be effective for the treatment of radiographically mild to moderate OA of the knee as measured by the ISK. This is the first U.S. study of these agents. Copyright 2000 OsteoArthritis Research Society International.

7: Osteoarthritis Cartilage. 2000 Jul;8(4):258-65.

Glucosamine HCl reduces equine articular cartilage degradation in explant culture.

Fenton JI, Chlebek-Brown KA, Peters TL, Caron JP, Orth MW.

Department of Animal Science, Michigan State University, East Lansing, Michigan

48824, USA.

Objective: To determine whether glucosamine inhibits experimentally induced degradation of equine articular cartilage explants. Methods Articular cartilage was obtained from the antebrachio-carpal and middle joints of horses (2-8 years old) killed for reasons unrelated to lameness. Cartilage discs were harvested from the weight-bearing region of the articular surface and cultured. Media were exchanged daily and the recovered media stored at 4 degrees C. Explants were maintained in basal media 2 days prior to the start of four treatment days. On days 1-4 lipopolysaccharide (LPS, 10 microg/ml) or recombinant human interleukin-1 (rhIL-1, 50 ng/ml) were added to induce cartilage degradation. To test the potential protective effects of glucosamine, the compound was added in three concentrations (0.25, 2.5, or 25 mg/ml) and treatments were performed in triplicate. Controls included wells without LPS, rhIL-1beta, or glucosamine. Nitric oxide, proteoglycan and matrix metalloproteinases (MMP) released into conditioned media and tissue proteoglycan synthesis were measured as indicators of cartilage metabolism. Results Maximal nitric oxide production, proteoglycan release, and MMP activity were detected 1 day after the addition of LPS or rhIL-1beta to the media. The addition of 25 mg/ml of glucosamine prevented the increase in nitric oxide production, proteoglycan release and MMP activity induced by LPS or rhIL-1. Conclusions These data indicate that glucosamine can prevent experimentally induced cartilage degradation in vitro.

8: BR J Sports Med 2003; 37:45-49.

The effect of glucosamine supplementation on people experiencing regular knee pain.

Braham R, Dawson B, Goodman C.

Department of Human Movement and Exercise Science, University of Western Australia, Crawley, Western Australia 6009. Reprint Request: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

OBJECTIVE: The purpose of this study was to examine the effects of oral glucosamine supplementation on the functional ability and degree of pain felt by individuals who had regular knee pain, most likely due to previous articular cartilage damage, and possibly osteoarthritis. METHODS: Subjects were randomly supplemented with either glucosamine (G) (n=24) or placebo (P) (lactose) (n=22) for 12 weeks at a dose of 2,000 mg per day. Over this period, four testing sessions were conducted, with changes in knee pain and function assessed by clinical and functional tests, (joint line palpation, a 3 meter "duck walk" and a repeated, walking stair climb), two questionnaires (the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Knee Pain Scale (KPS)) and participant subjective evaluations. RESULTS: The clinical and functional test scores improved with time (main effects: p<0.05, p<0.01) but there were no significant differences between the two groups. The questionnaire results also recorded a significant main effect for time (p<0.05), but the glucosamine group was found to have significantly better KOOS quality of life scores at week eight and 12 (p<0.05), and lower KPS scores (p<0.05) at week eight than the placebo group. On self report evaluations of changes across the 12 week supplementation period, 88% (n=21) of the glucosamine group reported some degree of improvement in their knee pain versus only 17% (n=3) in the placebo group. CONCLUSIONS: These results suggest that glucosamine supplementation can provide some degree of pain relief and improved function in persons who experience regular knee pain, which may be caused by prior cartilage injury and/or osteoarthritis. The trends in the results also suggest that, at a dosage of 2,000 mg per day, the majority of improvements are present after eight weeks. 9: Journal of Rheumatology 1999; 26:2423-2430. Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. Houpt JB, McMillan R, Wein C, Paget-Dellio SD. Mount Sinai Hospital Rheumatic Disease Unit, University of Toronto, Ontario, Canada. Reprint Request: This e-mail address is being protected from spambots. You need JavaScript enabled to view it OBJECTIVE: Glucosamine products have been used extensively for the management of pain in osteoarthritis (OA). We investigated the efficacy of the hydrochloride salt of glucosamine on pain and disability in knee OA. METHODS: At Week -2, subjects were examined, randomized, and instructed to take only prescribed acetaminophen for pain. At Week 0 patients were examined, prescribed acetaminophen, and either placebo or glucosamine hydrochloride (glucosamine). At Week 4 the prescriptions for acetaminophen and placebo or glucosamine were renewed. At Weeks 4 and 8, patients returned diaries and unused medications, and were examined. The WOMAC questionnaire was administered at Weeks -2, 0, and 8. After completing the randomized 8 week trial, subjects were offered known glucosamine hydrochloride capsules in an 8 week open label trial, with follow-up telephone survey after the 8 week open label trial. RESULTS: The primary endpoint (statistically significant difference in WOMAC pain score between Week 0 and Week 8) was not met. However, positive trends were noted for the glucosamine group in 23 of 24 WOMAC questions. A significant difference was noted from Week 5 through Week 8 in the knee examination (p = 0.026) and in the response to a daily diary pain question (p = 0.018). However, responding to the question, "Are you better than at the start of the trial?", 40% of placebo and only 49% of glucosamine subjects answered in the affirmative (p = 0.58). At the end of the randomized trial, 34% of placebo and 47% of glucosamine subjects believed that they had been given glucosamine. After the end of the 8 week open label trial, 77% of the subjects were still taking glucosamine, although now obliged to pay for commercially available products. CONCLUSION: There was no significant difference in pain reduction between the glucosamine hydrochloride and placebo groups as measured by WOMAC. However, the secondary endpoints of cumulative pain reduction as measured by daily diary and knee examination were favorable, suggesting that glucosamine hydrochloride benefits some patients with knee OA. 10: Paper #180 presented at the 66th annual meeting, American Academy of Orthopedic Surgeons, Anaheim, CA, February 6, 1999. Accepted for publication in Osteoarthritis & Cartilage. Efficacy of a new class of agents (glucosamine hydrochloride and chondroitin sulfate) in the treatment of osteoarthritis of the knee.

Das AK, Eitel J, Hammad TA.

11: Military Medicine February 1999; 164:2:85-91.

Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double blind, placebo-controlled pilot study.

Leffler CT, Philippi AF, Leffler SG, Mosure JC, Kim PD.

Medical Department, Naval Special Warfare Group Two, Naval Amphibious Base Little Creek, Norfolk, VA 23521, USA. Reprint Request: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

OBJECTIVE: A 16-week randomized, double-blind, placebo-controlled crossover trial of a combination of glucosamine HCl (1,500 mg/day), chondroitin sulfate (1,200 mg/day), and manganese ascorbate (228 mg/day) in degenerative joint disease (DJD) of the knee or low back was conducted. METHODS: Thirty-four males from the U.S. Navy diving and special warfare community with chronic pain and radiographic DJD of the knee or low back were randomized. A summary disease score incorporated results of pain and functional questionnaires, physical examination scores, and running times. Changes were presented as a percentage of the patient's average score. RESULTS: Knee osteoarthritis symptoms were relieved as demonstrated by the summary disease score (-16.3%; p = 0.05), patient assessment of treatment effect (p = 0.02), visual analog scale for pain recorded at clinic visits (-26.6%; p = 0.05) and in a diary (-28.6%; p = 0.02), and physical examination score (-43.3%; p = 0.01). Running times did not change. The study neither demonstrated, nor excluded, a benefit for spinal DJD. Side effect frequency was similar to that at baseline. There were no hematologic effects. CONCLUSIONS: The combination therapy relieves symptoms of knee osteoarthritis. A larger data set is needed to determine the value of this therapy for spinal DJD. Short-term combination therapy appears safe in this setting.

12: Accepted for publication in the Proceedings of the Society for Experimental Biology and Medicine, 2000.

The therapeutic effect of glucosamine HCl/chondroitin sulfate combination of type II collagen-induced arthritis in D/A rats.

Beren J, Hiss S, Hammad T, Rose N.

13: Paper presented at the 67th annual meeting of the American Academy of Orthopedic Surgeons, Orlando, FL, 2000; Vol.3, No. 1:23-27.

Dose response and synergistic effect of glucosamine HCl and chondroitin sulfate on in-vitro proteoglycan synthesis by bovine and human chondrocytes.

Lippiello L, Hammad T.

14: Arch Intern Med. 2003 Jul 14;163(13):1587-90.

The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial.

Scroggie DA, Albright A, Harris MD Department of Rheumatology, 59th Medical Wing, Wilford Hall Medical Center, Lackland Air Force Base, Lackland, TX 78236, USA.

This e-mail address is being protected from spambots. You need JavaScript enabled to view it

BACKGROUND: With increasing use of glucosamine-containing supplements for the treatment of osteoarthritis, there is increasing concern in the medical community about possible toxic effects. The present study was undertaken to determine whether glucosamine supplementation altered hemoglobin A1c concentrations in patients with well-controlled diabetes mellitus.

OBJECTIVE: To evaluate possible effects of glucosamine supplementation on glycemic control in a selected population of patients with type 2 diabetes mellitus. DESIGN: Placebo-controlled, double-blinded, randomized clinical trial.

SETTING: Outpatient, diabetes monitoring clinic.

PATIENTS: Patients were typically elderly patients, evenly divided between men and women. Most of the patients were being treated with 1 or 2 drugs for glycemic control.

INTERVENTION: In daily doses for 90 days, patients received either placebo or a combination of 1500 mg of glucosamine hydrochloride with 1200 mg of chondroitin sulfate (Cosamin DS; Nutramax Laboratories Inc, Edgewood, Md).Main Outcome Measure Hemoglobin A1c levels before and after 90 days of therapy.

RESULTS: There were 4 withdrawals from the glucosamine-treated group. Three were related to comorbidities (myocardial infarction, congestive heart failure, and atrial fibrillation) and 1 to a possible adverse reaction (excessive flatus). No other patient reported any adverse effects of glucosamine therapy, and no patient had any change in their diabetes management. Mean hemoglobin A1c concentrations were not significantly different between groups prior to glucosamine therapy. Post treatment hemoglobin A1c concentrations were not significantly different between groups, nor were there any significant differences within groups before and after treatment.

CONCLUSION: This study demonstrates that oral glucosamine supplementation does not result in clinically significant alterations in glucose metabolism in patients with type 2 diabetes mellitus.