Glucosamine Sulfate

OBJECTIVE: To assess the structural and symptomatic efficacy of oral glucosamine sulfate and chondroitin sulfate in knee osteoarthritis through independent meta-analyses of their effects on joint space narrowing, Lequesne Index, Western Ontario MacMaster University Osteoarthritis Index (WOMAC), visual analog scale for pain, mobility, safety, and response to treatment. METHODS: An exhaustive systematic research of randomized, placebo-controlled clinical trials published or performed between January 1980 and March 2002 that assessed the efficacy of oral glucosamine or chondroitin on gonarthrosis was performed using MEDLINE, PREMEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Contents, BIOSIS Previews, HealthSTAR, EBM Reviews, manual review of the literature and congressional abstracts, and direct contact with the authors and manufacturers of glucosamine and chondroitin. Inclusion, quality scoring, and data abstraction were performed systematically by 2 independent reviewers who were blinded to sources and authors. Conservative approaches were used for clear assessment of potential efficacy. RESULTS: Our results demonstrated a highly significant efficacy of glucosamine on all outcomes, including joint space narrowing and WOMAC. Chondroitin was found to be effective on Lequesne Index, visual analog scale pain, mobility, and responding status. Safety was excellent for both compounds. CONCLUSIONS: Our study demonstrates the structural efficacy of glucosamine and indistinguishable symptomatic efficacies for both compounds. Regarding the relatively sparse data on glucosamine and joint space narrowing and the absence of data on structural effects of chondroitin, further studies are needed to investigate the relationship among time, dose, patient baseline characteristics, and structural efficacy for an accurate, disease-modifying characterization of these 2 compounds.

Background: Crystalline glucosamine sulfate (cGS) claims to be a stabilized form of glucosamine sulfate with a defined crystalline structure intended to enhance chemical stability. It is proposed to offer pharmacokinetic advantages over regular glucosamine sulfate (rGS) which is stabilized with potassium or sodium chloride. However, comparative human bioavailability data are limited. Since both forms dissociate in gastric fluid into constituent ions, the impact of cGS formulation on absorption remains uncertain. This pilot study aimed to compare the bioavailability of cGS and rGS using a randomized, double-blind, crossover design. Methods: Ten healthy adults received a single 1500 mg oral dose of either cGS or rGS with a 7-day washout between interventions. Capillary blood samples were collected over 24 h. Glucosamine and its metabolite concentrations were quantified by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS), and pharmacokinetic parameters-including maximum concentration (Cmax), time to reach Cmax (Tmax), and area under the curve (AUC)-were calculated. Results: Mean AUC0-24, Cmax, Tmax, and T½ values for glucosamine and glucosamine-6-sulfate (GlcN-6-S) were comparable between cGS and rGS. Although the AUC0-24 for glucosamine was modestly higher with rGS (18,300 ng·h/mL) than with cGS (12,900 ng·h/mL), the difference was not statistically significant (p = 0.136). GlcN-6-S exposure was also similar between formulations (rGS: 50,700 ng·h/mL; cGS: 50,600 ng·h/mL), with a geometric mean ratio of 1.39, a delayed Tmax (6-8 h) and longer half-life, consistent with its role as a downstream metabolite. N-acetylglucosamine levels remained stable, indicating potential homeostatic regulation. Conclusions: This pilot study found no significant pharmacokinetic advantage of cGS over rGS. These preliminary findings challenge claims of cGS' pharmacokinetic superiority, although the small sample size limits definitive conclusions. Larger, adequately powered studies are needed to confirm these results.

This study focused on the difference in efficacy between glucosamine sulfate capsules and Huoxue Xiaozhong recipe in the treatment of knee osteoarthritis, as well as their effects on knee joint function recovery. A total of 128 patients with knee osteoarthritis who met the criteria were prospectively enrolled and randomly divided into a glucosamine sulfate group (n = 64) and a traditional Chinese medicine group (n = 64). The total effective rate, visual analogue score (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), degree of joint swelling, range of motion (ROM), serum inflammatory factor levels, degree of articular cartilage wear, knee joint function recovery and adverse reactions were observed from multiple dimensions. In this study, independent sample t-test and repeated measures analysis of variance were used to statistically evaluate the data. The results showed that the traditional Chinese medicine group had significant advantages in total effective rate, improvement of WOMAC score, relief of joint swelling, improvement of ROM, control of articular cartilage wear and knee joint function recovery; the glucosamine sulfate group performed outstandingly in reducing VAS scores and regulating serum inflammatory factor levels and the incidence of adverse reactions in the traditional Chinese medicine group was lower. In summary, for patients who urgently need to relieve pain, glucosamine sulfate capsules can be used as an initial option; while for patients who hope to comprehensively improve joint function, the blood circulation and swelling reduction formula is more valuable.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been associated with impaired endothelial and vascular function. We investigated whether intervention with glycocalyx dietary supplement (GDS), containing glucosamine sulfate and fucoidan, improves endothelial glycocalyx and vascular function after COVID-19 infection. METHODS: Fifty-seven convalescent patients 14 days after mild-to-moderate COVID-19 infection managed in an outpatient setting were randomized to receive GDS (n = 29) or placebo (n = 28) for 4 consecutive months. We measured at baseline and at 4 months: (a) perfused boundary region (PBR) of the sublingual microvessels with a diameter range of 4-25 μm, as a marker of endothelial glycocalyx integrity, (b) pulse wave velocity and augmentation index, (c) coronary flow reserve using Doppler echocardiography, and (d) malondialdehyde and protein carbonyls as oxidative stress markers. RESULTS: Four months after treatment, patients who received GDS showed a greater reduction in PBR 4-25 μm (-6.8% vs. -1.3%), pulse wave velocity (-13.2% vs. -3%), augmentation index (-28.5% vs. -2.5%), malondialdehyde (-26% vs. -2.9%), protein carbonyls (-31.3% vs. -1%) and a greater increase in coronary flow reserve (12.9% vs. 1.6%) compared to placebo (p < .05). In the GDS group, the reduction in PBR 4-25 μm was associated with the corresponding decrease in pulse wave velocity (r = .31, p = .047), malondialdehyde, and protein carbonyls, as well as with the increase in coronary flow reserve (r = -.59, p = .008) at follow-up. Post-treatment, none of the patients under GDS reported post-COVID symptoms compared to 21.4% of the patients under placebo. CONCLUSION: Four-month treatment with GDS may improve endothelial glycocalyx and vascular function after COVID-19 infection. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT05185934. © 2025 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

Degradation of the endothelial glycocalyx in type 2 diabetes (T2D) is thought to contribute to impaired shear stress mechanotransduction, leading to endothelial dysfunction and the development of cardiovascular disease. Herein, we tested the hypothesis that restoration of the endothelial glycocalyx with dietary supplementation of glycocalyx precursors (DSGPs, containing glucosamine sulfate, fucoidan, superoxide dismutase, and high-molecular weight hyaluronan) improves endothelial function and other indices of vascular function in T2D. First, in db/db mice, we showed that treatment with DSGP (100 mg/kg/day) for 4 wk restored endothelial glycocalyx length, as assessed via atomic force microscopy in aortic explants. Restoration of the glycocalyx with DSGP was accompanied by improved flow-mediated dilation (FMD) and reduced arterial stiffness in isolated mesenteric arteries. Further corroborating these findings, the treatment of cultured endothelial cells with that same mixture of glycocalyx precursors promoted glycocalyx growth. Next, as an initial step to investigate the translatability of these findings, we conducted a pilot (n = 22) double-blinded randomized placebo-controlled clinical trial to assess the effects of DSGP (3,712.5 mg/day) for 8 wk on endothelial glycocalyx integrity and indices of vascular function, including FMD, in Veterans with T2D. Contrary to the hypothesis, DSGP neither enhanced endothelial glycocalyx integrity nor improved vascular function indices relative to placebo. Together, these findings conceptually support the notion that restoration of the endothelial glycocalyx can lead to improvements in vascular function in a mouse model of T2D; however, DSGP as a therapeutic strategy to enhance vascular function in individuals with T2D does not appear to be efficacious.NEW & NOTEWORTHY Endothelial glycocalyx degradation in type 2 diabetes (T2D) is thought to contribute to impaired shear stress mechanotransduction, leading to vascular dysfunction. The findings of this study support the notion that restoration of the endothelial glycocalyx using a dietary supplementation of glycocalyx precursors can lead to improvements in vascular function in d

BACKGROUND: Piascledine is a potential treatment for osteoarthritis; however, current evidence regarding its efficacy in patients with knee osteoarthritis remains limited. OBJECTIVE: To evaluate the efficacy of Piascledine in improving symptoms and its impact on blood lipid levels and body mass index in patients with knee osteoarthritis. METHODS: A randomized, controlled, single-blind clinical trial. The odd-numbered group was treated with Piascledine at a dose of 300mg/day, while the even-numbered group was treated with glucosamine sulfate at a dose of 1,500mg/day. Outcomes were assessed at 4 weeks and 8 weeks. RESULTS: A total of 200 patients were included in the study, with a mean age of 58.5 ± 11.3 years, of whom 42.0% were male. Obesity (OR=2.83; 95% CI: 1.88-4.26; p<0.001) and hypertriglyceridemia (OR=2.07; 95% CI: 1.17-3.67; p<0.05) were identified as factors significantly increasing the risk of severe osteoarthritis. At 4 weeks and 8 weeks, the Piascledine group showed a reduction in VAS scores from 49.3 ± 19.6mm to 37.6 ± 14.2mm and 25.3 ± 10.2mm, respectively. At 4 weeks, the VAS and WOMAC scores showed greater improvement in the GCS group compared to the Piascledine group. However, at 8 weeks, there was no significant difference in efficacy between the two groups. Treatment with Piascledine slightly increased triglyceride levels from 2.3 ± 1.4mmol/L to 2.7 ± 1.4mmol/L. Side effects were observed in 16.0% of patients during treatment, with the most common being nausea (10.0%). CONCLUSION: The study indicates that obesity and hypertriglyceridemia are risk factors for severe knee osteoarthritis. Treatment with Piascledine improves symptoms and knee joint function, without impacting body mass index or lipid metabolism. The majority of side effects were mild and primarily gastrointestinal. © 2024 Hoang Minh Phan, Cang Trung Huynh, Phu Van La, Khanh Hoang Pham, Phuong Minh Vo, Trang Huynh Vo.

Glucosamine and chondroitin sulfate have been used as nutritional supplementation for joint tissues and osteoarthritis (OA). Biofermented glucosamine is of great interest in the supplement industry as an alternative source of glucosamine. The purpose of this study is to compare the pharmacokinetics of chitosan-derived glucosamine and biofermentation-derived glucosamine as nutritional supplementation. In a randomized, double-blind and cross-over study design, we recruited subjects of healthy men and women. The pharmacokinetics of glucosamine were examined after a single dose of glucosamine sulfate 2KCl (1500 mg) with two different sources of glucosamine (chitosan-derived glucosamine and biofermentation-derived glucosamine) to male and female subjects fitted with intravenous (iv) catheters for repeated blood sampling up to 8 h. According to plasma concentration-time curve of glucosamine after an oral administration of 1500 mg of glucosamine sulfate 2KCl, AUC0-8h and AUC0-∞ values of glucosamine following oral administration of chitosan-derived and biofermentation-derived glucosamine formulations were within the bioequivalence criteria (90% CI of ratios are within 0.8-1.25). The mean Cmax ratios for these two formulations (90% CI of 0.892-1.342) did not meet bioequivalence criteria due to high within-subject variability. There were no statistically significant effects of sequence, period, origin of glucosamine on pharmacokinetic parameters of glucosamine such as AUC0-8h, AUC0-∞, Cmax. Our findings suggest that biofermentation-derived glucosamine could be a sustainable source of raw materials for glucosamine supplement.

BACKGROUND AND AIM: To determine the efficacy of the synergistic use of High Power Laser Therapy (HPLT) with glucosamine sulfate (GS) in knee osteoarthritis. METHODS: This 2-arm randomized controlled trial (RCT) enrolled 90 subjects (M=53, F=37, y= 55±11.2) and randomly allocated using a stratified sampling method in experimental group (A) with HPLT+GS 1500mg (GS - Dona®, Rottapharm, Monza, Italy) (n=45) or in a control group (B) with HPLT + placebo (n=45). Results: VAS score in Activities of day Living (ADL), Standardized stair climb test (SSCT), Zohlen's sign (RASPING) and Rabot test were used, to evaluate patients at the beginning of the study (T0), at 2 months (T1) and at 6 months (T2). In the mean scores for VAS in ADL, SSCT, RABOT and RASPING at T1, no significant differences were found between the experimental and the control group with paired T and ANOVA test. But significant differences between groups (p<0.05) in all outcomes were observed at 6 months (T2). CONCLUSIONS: HPLT is useful in treating knee osteoarthritis, but when combined with Glucosamine Sulfate, thanks to the synergy of two interventions, can achieve a long-term effect up to 6 months after treatment.

BACKGROUND: The aim of this study was to identify modifiable clinical factors associated with radiographic osteoarthritis progression over 1 to 2 years in people with painful medial knee osteoarthritis. METHODS: A longitudinal study was conducted within a randomised controlled trial, the "Long-term Evaluation of Glucosamine Sulfate" (LEGS study). Recruitment occurred in 2007-2009, with 1- and 2-year follow-up assessments by blinded assessors. Community-dwelling people with chronic knee pain (≥4/10) and medial tibiofemoral narrowing (but retaining >2mm medial joint space width) on radiographs were recruited. From 605 participants, follow-up data were available for 498 (82%, mean [sd] age 60 [8] years). Risk factors evaluated at baseline were pain, physical function, use of non-steroidal anti-inflammatory drugs (NSAIDs), statin use, not meeting physical activity guidelines, presence of Heberden's nodes, history of knee surgery/trauma, and manual occupation. Multivariable logistic regression analysis was conducted adjusting for age, sex, obesity, high blood pressure, allocation to glucosamine and chondroitin treatment, and baseline structural disease severity (Kellgren and Lawrence grade, joint space width, and varus alignment). Radiographic osteoarthritis progression was defined as joint space narrowing ≥0.5mm over 1 to 2 years (latest follow-up used where available). RESULTS: Radiographic osteoarthritis progression occurred in 58 participants (12%). Clinical factors independently associated with radiographic progression were the use of NSAIDs, adjusted odds ratios (OR) and 95% confidence intervals (CI) 2.05 (95% CI 1.1 to 3.8), and not meeting physical activity guidelines, OR 2.07 (95% CI 0.9 to 4.7). CONCLUSIONS: Among people with mild radiographic knee osteoarthritis, people who use NSAIDs and/or do not meet physical activity guidelines have a greater risk of radiographic osteoarthritis progression. TRIAL REGISTRATION: ClinicalTrials.gov , NCT00513422 . This original study trial was registered a priori, on August 8, 2007. The current study hypothesis arose before inspection of the data.

Osteoarthritis is the most common chronic joint disorder especially during aging. Although with controversies, glucosamine, both in its forms of sulfate and hydrochloride, and chondroitin sulfate are commonly employed to treat osteoarthritis. Due to the modest improve in the symptoms observed in patients treated with these drugs alone, a formulation combining both agents has been considered. The discrepant results achieved for pain control or structural improvement in osteoarthritis patients has been attributed to the quality of chemical formulations or different bias in clinical studies. The current study has been designed to test the effects of two different combined formulations with adequate pharmaceutical grade of these drugs in osteoarthritic joints, and to explore the underlying mechanisms modulated by both formulations in different osteoarthritis target tissues. Knee osteoarthritis was surgically induced in experimental rabbits. Some animals received the combined therapy (CT)1, (chondroitin sulfate 1200mg/day + glucosamine sulfate 1500mg/day), or the CT2 ((chondroitin sulfate 1200mg/day + glucosamine hydrochloride 1500mg/day). Neither CT1 nor CT2 significantly modified the cartilage damage or the synovial inflammation observed in osteoarthritic animals. Treatments were also unable to modify the presence of pro-inflammatory mediators, and the synthesis of metalloproteinases in the cartilage or in the synovium of osteoarthritic animals. Combined therapies did not modify the decrease in the subchondral bone mineral density observed in osteoarthritic rabbits. Therapies of chondroitin sulfate plus glucosamine sulfate or chondroitin sulfate plus glucosamine hydrochloride failed to improve structural damage or to ameliorate the inflammatory profile of joint tissues during experimental osteoarthritis. Published by Elsevier B.V.

Overproduction of reactive oxygen species and impaired antioxidant defence accompanied by chronic inflammatory processes may impair joint health. Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) stimulate the expression of metalloproteinases which degrade the extracellular matrix. Little is known regarding the potential synergistic effects of natural compounds such as alpha-tocopherol (alpha-toc), ascorbic acid (AA) and selenium (Se) on oxidant induced cell death. Furthermore studies regarding the metalloproteinase-3 inhibitory activity of glucosamine sulfate (GS) and chondroitin sulfate (CS) are scarce. Therefore we have studied the effect of alpha-toc (0.1-2.5 micromol/L), AA (10-50 micromol/L) and Se (1-50 nmol/L) on t-butyl hydroperoxide (t-BHP, 100-500 micromol/L)-induced cell death in SW1353 chondrocytes. Furthermore we have determined the effect of GS and CS alone (100-500 micromol/L each) and in combination on MMP3 mRNA levels and MMP3 secretion in IL-1beta stimulated chondrocytes. A combination of alpha-toc, AA, and Se was more potent in counteracting t-BHP-induced cytotoxicity as compared to the single compounds. Similarly a combination of CS and GS was more effective in inhibiting MMP3 gene expression and secretion than the single components. The inhibition of MMP3 secretion due to GS plus CS was accompanied by a decrease in TNF-alpha production. Combining natural compounds such as alpha-toc, AA, and Se as well as GS and CS seems to be a promising strategy to combat oxidative stress and cytokine induced matrix degradation in chondrocytes.

Protein binding of [14C]glucosamine (400, 1000 and 4000 ng/ml) was evaluated in human and mouse plasma and in human synovial fluid. Blood cell/plasma partitioning in human and mouse was also determined. There was no measurable protein binding of [14C]glucosamine. Its association with human and mouse blood cells ranged from 43-47% and from 27-29%, respectively. Therefore, the unbound (pharmacologically active) fraction of glucosamine in plasma and at the site of action (the joint) is the same. Protein binding displacement drug-drug interactions are unlikely during the clinical use of crystalline glucosamine sulfate. No corrections are needed, either for unbound fraction when comparing human and mouse pharmacokinetic data or for blood cell/plasma partitioning to assess glucosamine total blood clearance from plasma data in these two species.

Early in the pathological process of osteoarthritis (OA), subchondral bone remodelling, which is related to altered osteoblast metabolism, takes place. In the present study, we explored in human OA subchondral bone whether chondroitin sulfate (CS), glucosamine sulfate (GS), or both together affect the major bone biomarkers, osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B ligand (RANKL), and the pro-resorptive activity of OA osteoblasts. The effect of CS (200 mug/mL), GS (50 and 200 mug/mL), or both together on human OA subchondral bone osteoblasts, in the presence or absence of 1,25(OH)2D3 (vitamin D3) (50 nM), was determined on the bone biomarkers alkaline phosphatase and osteocalcin, on the expression (mRNA) and production (enzyme-linked immunosorbent assay) of bone remodelling factors OPG and RANKL, and on the pro-resorptive activity of these cells. For the latter experiments, human OA osteoblasts were incubated with differentiated peripheral blood mononuclear cells on a sub-micron synthetic calcium phosphate thin film. Data showed that CS and GS affected neither basal nor vitamin D3-induced alkaline phosphatase or osteocalcin release. Interestingly, OPG expression and production under basal conditions or vitamin D3 treatment were upregulated by CS and by both CS and GS incubated together. Under basal conditions, RANKL expression was significantly reduced by CS and by both drugs incubated together. Under vitamin D3, these drugs also showed a decrease in RANKL level, which, however, did not reach statistical significance. Importantly, under basal conditions, CS and both compounds combined significantly upregulated the expression ratio of OPG/RANKL. Vitamin D3 decreased this ratio, and GS further decreased it. Both drugs reduced the resorption activity, and statistical significance was reached for GS and when CS and GS were incubated together. Our data indicate that CS and GS do not overly affect cell integrity or bone biomarkers. Yet CS and both compounds together increase the expression ratio of OPG/RANKL, suggesting a positive effect on OA subchondral bone structural changes. This was confirmed by the decreased resorptive activity for the

Glucosamine is an amine-containing sugar that exhibits immunosuppressive effects in vitro and in vivo, although its mechanism of action is unknown. We investigated whether glucosamine sulfate (GS) modulates the proinflammatory cytokine interleukin (IL)-1beta-induced expression and production of intercellular adhesion molecule (ICAM)-1, the mechanism responsible for this effect, and whether GS inhibits leukocyte adhesion to the monolayer of retinal pigment epithelial (RPE) cells stimulated with various cytokines. We used flow cytometry and an ARPE-19 cell model to determine the effect of GS on the production of ICAM-1 in response to IL-1beta, IL-6, tumor necrosis factor (TNF)-alpha plus IL-1beta, TNF-alpha plus IL-6, and TNF-alpha plus interferon (IFN)-gamma. We also used semiquantitative RT-PCR to determine the effect of GS on IL-1beta-induced expression of the ICAM-1 gene, and immunocytochemistry and western blotting to measure the effect of GS on the activation and nuclear translocation of the nuclear factor NF-kappaB and the degradation of cytoplasmic IkappaB. The functionality of GS-modulated ICAM-1 on leukocyte adhesion was demonstrated in an RPE cell-neutrophil adherence assay. IL-1beta increased the expression of ICAM-1 at the mRNA and protein levels in ARPE-19 cells. GS downregulated the production of ICAM-1 induced by IL-1beta, IL-6, TNF-alpha, and IFN-gamma at the protein level in a dose-dependent manner. GS also inhibited the nuclear translocation of NF-kappaB subunit p65 and partially prevented the degradation of cytoplasmic IkappaB in IL-1beta-stimulated ARPE-19 cells. GS significantly decreased the number of neutrophils adhering to the RPE monolayer in response to cytokines IL-1beta, IL-6, TNF-alpha, and IFN-gamma. GS inhibits the expression of the ICAM-1 gene in ARPE-19 cells stimulated with IL-1beta by blocking NF-kappaB subunit p65 translocation and by partially preventing IkappaB degradation. GS also decreases leukocyte adhesion to the monolayer of ARPE-19 cells stimulated with various cytokines by decreasing ICAM-1 production. Our study demonstrates a potentially important property of GS in reducing ICAM-1-mediated inflammatory mechanisms in t

The interactions of natural products with drugs are discussed. Interactions between natural products and drugs are based on the same pharmacokinetic and pharmacodynamic principles as drug-drug interactions. Clinically important interactions appear to involve effects on drug metabolism via cytochrome P-450 isoenzymes, impairment of hepatic or renal function, and other possible mechanisms. Natural products that have been reported to interact with drugs in humans include coenzyme Q10, dong quai, ephedra, Ginkgo biloba, ginseng, glucosamine sulfate, ipriflavone, melatonin, and St. John's wort. In many cases, more research is needed to confirm these interactions and to determine whether other natural products may also interact with drugs. To effectively counsel patients about interactions involving natural products, pharmacists should be familiar with the most commonly used products and have access to information on more obscure products. In view of the less than stringent provisions of the Dietary Supplement Health and Education Act, pharmacists should consult reliable, independent sources of information on natural products rather than rely on literature provided by manufacturers. Pharmacists should recommend only those products that are manufactured to high quality-control standards. Natural products can interact with drugs and with other natural products by the same mechanisms as drugs.

88. Posit Health News. 1998 Fall;(No 17):7-11. Anecdotal reports: elderberry extract plus chondroitin and glucosamine sulfate and Thy-mate reduces viral load to non-detectable levels in 10 days. [No authors listed] AIDS: Several HIV patients offer anecdotal reports in which they attribute significant viral load reductions to taking elderberry extract. Thy-Mate was also used. Case studies from six patients are presented. In an interview, Steven Rahn describes his self-imposed treatment and its effect on his viral load. Another case discusses reports of dicalcium phosphate, a binding agent found in some dietary supplements such as glucosamine, inhibiting absorption of the supplements. Other cases are described, and contact information is included.

BACKGROUND: Glucosamine sulfate is used for the treatment of arthrosis, especially osteoarthritis of the knee joint. The available evidence suggests differences in its pharmacokinetics in Chinese subjects compared with non-Chinese subjects. OBJECTIVE: The aim of this study was to compare the pharmacokinetics and relative bioavailability of a test and reference formulation of glucosamine sulfate 500 mg after single oral administration in healthy Chinese volunteers. METHODS: This open-label, randomized-sequence, single-dose, 2-way crossover study was performed at the First Hospital of Nanjing Medical University, Nanjing, China. Eligible subjects were healthy male volunteers who were randomly assigned at a 1:1 ratio to receive a single 500-mg dose of the test or reference capsule formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Glucosamine sulfate was assayed using a liquid-chromatography tandem mass spectrometry method. For analysis of pharmacokinetic properties, including C(max), AUC(0-t), and AUC(0-infinity)), blood samples were obtained at intervals over a 14-hour period after study drug administration. The formulations were considered bioequivalent if the log-transformed ratios of C(max) and AUC were within the predetermined equivalence range (70%-143% for C(max) and 80%-125% for AUC) as established by the State Food and Drug Administration (SFDA) of China. Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis), and by questioning subjects about adverse events (AEs). RESULTS: Twenty-two healthy male Chinese subjects were enrolled (mean [range] age, 24 [22-26] years; weight, 63.9 [58.5-69.3] kg; height, 172 [167-177] cm); all completed the study. No period or sequence effect was observed. The 90% CIs for the log-transformed ratios of C(max), AUC(0-t), and AUC(0-infinity)) were 93.4 to 127.3, 92.4 to 114.5, and 92.7 to 114.6, respectively (all, P = NS). The AUC(0-infinity) of the test and reference formulations was 1.83 (0.66) and 1.77 ( 0.72) microg/h/mL, respectiv

OBJECTIVE: To compare the efficacy, safety and tolerability of different therapies in Caucasian patients with osteoarthritis (QA) of the knee. METHODS: Seventy-five cases (90 knee joints) of osteoarthritis were randomly divided into 3 groups, western medicine group, traditional Chinese medicine (TCM) group, integrated Chinese and western medicine group. The western medicine group were treated with oral administration of Glucosamine Sulfate, oral administration and external application of non-steroid anti-inflammatory agent, ultrasound physiotherapy, etc. The TCM group were treated with oral administration of J uanbi Decoction, acupuncture and moxibustion, cupping, massage of acupoint and ear acupuncture. The integrated Chinese and western medicine group were treated with oral administration of Glucosamine Sulfate, oral administration and external application of non-steroid anti-inflammatory agent, acupuncture and moxibustion, cupping, massage of acupoint and ear acupuncture. The intensity of knee joint pain on walking, resting and standing, the nocturnal pain, stiffness, the maximum walking distance and the daily living ability were monitored after 30 days, 60 days and 90 days of treatment. RESULTS: After 90 days of treatment, the integrated Chinese and western medicine group was better than other two groups in improvement of percentages in self pain assessment with visual analog scale (VAS), pain and stiffness measured by WOMAC scale, pain and maximum walking distance measured by Lequesne scale (P < 0.05 or P < 0.01). There were no significant differences in the therapeutic effects between the TCM group and the western medicine group. All of these three treatments were well tolerated, and no severe adverse events were found. CONCLUSION: Combined TCM and western medicine treatment has rapid and definite therapeutic effect in reducing pain and improving mobility of knee joints and daily living ability in Caucasian patients of knee osteoarthritis.

OBJECTIVE: To characterize the usefulness of glucosamine sulfate in the treatment of patients with osteoarthritis (OA). DATA SOURCES AND STUDY SELECTION: Pertinent citations were identified via a MEDLINE search (January 1975-March 1997). Only trials available in the English language involving human subjects, OA, and glucosamine sulfate were selected for review. DATA SYNTHESIS: OA is the most common form of arthritis and represents a major cause of morbidity and disability in the elderly. The main symptom of OA is pain and most of the commonly prescribed medications (e.g. acetaminophen, nonsteroidal antiinflammatory drugs) have been targeted at relieving the pain. Some of these medications have serious adverse effects and do not necessarily change the natural course of the disease. Glucosamine sulfate, a nutritional supplement, has recently emerged as an alternative treatment option for patients with OA. The beneficial effects of this chondroprotective agent have been reported to reverse or at least stop the progression of the disease without inducing serious adverse effects. Limited data from short-term human trials suggest that glucosamine sulfate administered orally, intravenously, intramuscularly, and intraarticularly may produce a gradual and progressive reduction in joint pain and tenderness, as well as improved range of motion and walking speed. Results of the trials have also shown that glucosamine has produced consistent benefits (> 50% overall improvement in symptom scores) in patients with OA and that, in some cases, it may be equal or superior to ibuprofen in controlling symptoms. CONCLUSIONS: There is evidence that glucosamine sulfate may provide pain relief, reduce tenderness, and improve mobility in patients with OA. Most of the current data, however, are derived from the European and Asian literature and there are no studies supporting the use of this agent in the US. The studies published to date have been done in small numbers of patients; adequate long-term trials examining the safety, efficacy, and optimal dosage requirements of glucosamine sulfate are lacking. Most of the available clinical data are difficult to interpret due to serious defic

Background and Objective: According to international guidelines, glucosamine and chondroitin, regarded as slow-acting drugs for osteoarthritis (SYSADOAs), have been first-line treatments for knee osteoarthritis (OA); however, their efficacies remain controversial. Additionally, the efficacies of plant extract cocktails, SKI306X, and its newer formulation, SKCPT, have not been well investigated. To evaluate the effectiveness and safety of symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) in patients with knee OA. Materials and Methods: Electronic databases were systematically searched to identify randomized controlled trials (RCTs) assessing the effectiveness and safety of SYSADOAs, including chondroitin sulfate, glucosamine sulfate, and SKCPT/SKI306X. The outcomes included pain relief, functional improvements, and safety profiles. The outcome measurements were compared between the treatment and control groups, including placebo and non-placebo groups, within and after 3 months of follow-up. Results: Analysis of 21 RCTs showed significantly greater improvement in pain relief in the treatment group compared with the placebo group both within (standard mean difference [SMD], 0.38; 95% confidence interval [CI], 0.18-0.57; p < 0.001) and after 3 months of follow-up (SMD, 0.22; 95%CI, 0.03-0.42 p = 0.023). The treatment group also showed significantly greater functional improvements regardless of follow-up. Pain and functional improvement did not differ significantly between the treatment and non-placebo groups. Regarding the safety profile, the risk ratios did not differ significantly between the treatment and control groups, including the placebo and non-placebo subgroups. Conclusions: Glucosamine, chondroitin, and SKCPT/SKI306X improved the pain and function and were non-inferior to pharmacologic drugs for up to 12 months. These findings support the clinical use of these SYSADOAs to treat knee OA. Level of Evidence: Therapeutic Level II.

AIM: This study was aimed to assess the efficacy and safety of two oral Symptomatic Slow Acting Drugs for Osteoarthritis (SYSADOAs)-Glucosamine Sulfate, Chondroitin Sulfate, and their combination regimen in the management of knee osteoarthritis (KOA). METHODS: This systematic review was conducted according to PRISMA 2020 guidelines. A detailed literature search was performed from 03/1994 to 31/12/2022 using various electronic databases including PubMed, Embase, Cochrane Library, and Google Scholar, using the search terms-Glucosamine sulfate (GS), Chondroitin sulfate (CS), Knee osteoarthritis, Joint pain, Joint disease, and Joint structure, for literature concerning glucosamine, chondroitin, and their combination in knee osteoarthritis treatment. Cochrane Collaboration's Risk assessment tool (version 5.4.1) was used for assessing the risk of bias and the quality of the literature. The data was extracted from the included studies and subjected to statistical analysis to determine the beneficial effect of Glucosamine Sulfate, Chondroitin Sulfate, and their combination. RESULTS: Twenty-five randomized controlled trials (RCTs) were included in this systematic review. In short, exclusively 9 RCTs for GS, 13 RCTs for CS, and 3 RCTs for the combination of GS and CS. All these studies had their treatment groups compared with placebo. In the meta-analysis, CS showed a significant reduction in pain intensity, and improved physical function compared to the placebo; GS showed a significant reduction in tibiofemoral joint space narrowing. While the combination of GS and CS showed neither a reduction in pain intensity, nor any improvement in the physical function. However, the combination exhibited a non-significant reduction in joint space narrowing. In the safety evaluation, both CS and GS have shown good safety profile and were well tolerated. CONCLUSION: This meta-analysis revealed that the CS (with decreased pain intensity and improvement in the physical function), and GS (with significant reduction in the joint space narrowing) have significant therapeutic benefits. However, their combination did not significantly improve the symptoms or modify the disease. This may be d

INTRODUCTION: Several pharmacological treatments aiming at a better symptomatic control of osteoarthritis (OA) are used in daily practice but their efficacy is often disputed. The purpose of this network meta-analysis (NMA) is to assess the efficacy on pain and function of the drugs that are most widely prescribed against knee OA. METHODS: Medline, Scopus, and Cochrane database of systematic reviews were searched for randomized controlled trials published up to August 2019 and assessing the efficacy of knee OA treatments using a 6-month time horizon. Pain and function changes from baseline were the primary outcomes. A Bayesian network meta-analysis was run and standardized mean differences (SMDs) with 95% credibility intervals (95% CrIs) were calculated. RESULTS: 9697 references were identified and 80 RCTs were concordant with our inclusion criteria (79 studies involving 15,609 individuals reported pain outcomes and 55 studies involving 13,655 individuals reported function outcomes). A significant decrease in pain was observed for the intra-articular (IA) combination of hyaluronic acid (HA) and triamcinolone (SMD - 0.49, 95% CrI - 0.78; - 0.19), vitamin D (SMD - 0.31, 95% CrI - 0.56; - 0.06), IA HA (SMD - 0.29, 95% CrI - 0.40; - 0.17), prescription-grade crystalline glucosamine sulfate (pCGS) (SMD - 0.29, 95% CrI - 0.58; - 0.004), and prescription-grade chondroitin sulfate (pCS) (SMD - 0.26, 95% CrI - 0.44; - 0.08). Significant improvements in physical function were found with pCGS (SMD - 0.44, 95% CrI - 0.66; - 0.21), vitamin D (SMD - 0.30, 95% CrIs - 0.49; - 0.11) and IA HA (SMD - 0.21, 95% CrIs - 0.31; - 0.11). CONCLUSION: Six months of treatment with IA HA, pCGS, pCS, vitamin D and the combination of IA HA and triamcinolone improve pain and/or physical function in patients suffering from knee OA.

BACKGROUND: Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA). OBJECTIVE: We aimed to re-assess the safety of various SYSADOAs in a comprehensive meta-analysis of randomized placebo-controlled trials, using, as much as possible, data from full safety reports. METHODS: We performed a systematic review and random-effects meta-analyses of randomized, double-blind, placebo-controlled trials that assessed adverse events (AEs) with various SYSADOAs in patients with OA. The databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus were searched. The primary outcomes were overall severe and serious AEs, as well as AEs involving the following Medical Dictionary for Regulatory Activities (MedDRA) system organ classes (SOCs): gastrointestinal, cardiac, vascular, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue, renal and urinary system. RESULTS: Database searches initially identified 3815 records. After exclusions according to the selection criteria, 25 studies on various SYSADOAs were included in the qualitative synthesis, and 13 studies with adequate data were included in the meta-analyses. Next, from the studies previously excluded according to the protocol, 37 with mainly oral nonsteroidal anti-inflammatory drugs (NSAIDs) permitted as concomitant medication were included in a parallel qualitative synthesis, from which 18 studies on various SYSADOAs were included in parallel meta-analyses. This post hoc parallel inclusion was conducted because of the high number of studies allowing concomitant anti-OA medications. Indeed, primarily excluding studies with concomitant anti-OA medications was crucial for a meta-analysis on safety. The decision for parallel inclusion was made for the purpose of comparative analyses. Glucosamine sulfate (GS), chondroitin sulfate (CS) and avocado soybean unsaponifiables (ASU; Piascledine®) were not associated with increased odds for any type of AEs compared with placebo. Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of tot

Oral glucosamine sulfate (GS) and chondroitin sulfate (CS), while widely marketed as joint-protective supplements, have limited intestinal absorption and are predominantly utilized by gut microbiota. Hence the effects of these supplements on the gut microbiome are of great interest, and may clarify their mode of action, or explain heterogeneity in therapeutic responses. We conducted a systematic review of animal and human studies reporting the effects of GS or CS on gut microbial composition. We searched MEDLINE, EMBASE, and Scopus databases for journal articles in English from database inception until July 2018, using search terms microbiome, microflora, intestinal microbiota/flora, gut microbiota/flora and glucosamine or chondroitin. Eight original articles reported the effects of GS or CS on microbiome composition in adult humans (four articles) or animals (four articles). Studies varied significantly in design, supplementation protocols, and microbiome assessment methods. There was moderate-quality evidence for an association between CS exposure and increased abundance of genus Bacteroides in the murine and human gut, and low-quality evidence for an association between CS exposure and an increase in Desulfovibrio piger species, an increase in Bacteroidales S24-7 family, and a decrease in Lactobacillus. We discuss the possible metabolic implications of these changes for the host. For GS, evidence of effects on gut microbiome was limited to one low-quality study. This review highlights the importance of considering the potential influence of oral CS supplements on gut microbiota when evaluating their effects and safety for the host.

Comment in doi: 10.1001/jama.2018.0899. doi: 10.1001/jama.2017.5283. IMPORTANCE: Even though osteoarthritis is a chronic and progressive disease, pharmacological agents are mainly studied over short-term periods, resulting in unclear recommendations for long-term disease management. OBJECTIVE: To search, review, and analyze long-term (≥12 months) outcomes (symptoms, joint structure) from randomized clinical trials (RCTs) of medications for knee osteoarthritis. DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE, Scopus, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched until June 30, 2018 (MEDLINE alerts through August 31, 2018) for RCTs of patients with knee osteoarthritis that had treatment and follow-up lasting 1 year or longer. DATA EXTRACTION AND SYNTHESIS: Data at baseline and at the longest available treatment and follow-up of 12 months' duration or longer (or the change from baseline) were extracted. A Bayesian random-effects network meta-analysis was performed. MAIN OUTCOMES AND MEASURES: The primary outcome was the mean change from baseline in knee pain. Secondary outcomes were physical function and joint structure (the latter was measured radiologically as joint space narrowing). Standardized mean differences (SMDs) and mean differences with 95% credibility intervals (95% CrIs) were calculated. Findings were interpreted as associations when the 95% CrIs excluded the null value. RESULTS: Forty-seven RCTs (22 037 patients; mean age range, mostly 55-70 years; and a higher mean proportion of women than men, around 70%) included the following medication categories: analgesics; antioxidants; bone-acting agents such as bisphosphonates and strontium ranelate; nonsteroidal anti-inflammatory drugs; intra-articular injection medications such as hyaluronic acid and corticosteroids; symptomatic slow-acting drugs in osteoarthritis such as glucosamine and chondroitin sulfate; and putative disease-modifying agents such as cindunistat and sprifermin. Thirty-one interventions were studied for pain, 13 for physical function, and 16 for joint structure. Trial duration ranged from 1 to 4 years. Associations with decreases

BACKGROUND: Osteoarthritis (OA) is a disorder involving deterioration of articular cartilage and underlying bone and is associated with symptoms of pain and disability. Glucosamine is a component of articular cartilage naturally synthesized in the body from glucose and incorporated into substances contained in the cartilage. It has been suggested that consumption of glucosamine may reduce the pain of OA and may have favorable effects on structural changes in the cartilage. This article presents a systematic review and meta-analysis of the effectiveness of orally consumed glucosamine sulfate (GS) on OA-related pain and joint structural changes. METHODS: PubMed and Ovid Embase were searched using specific search terms to find randomized, double-blinded, placebo-controlled trials on the effects of GS on pain and/or joint-space narrowing. The outcome measure was the standardized mean difference (SMD), which was the improvement in the placebo groups minus the improvement in the GS groups divided by the pooled standard deviation. RESULTS: There were 17 studies meeting the review criteria for pain, and the summary SMD was -0.35, with a 95% confidence interval (95% CI) = -0.54 to -0.16 (negative SMD is in favor of GS). Of the 17 studies, 7 showed a statistically significant reduction in pain from GS use. Four studies met the review criteria for joint space narrowing with a summary SMD = -0.10 (95% CI = -0.23 to +0.04). Studies without involvement of the commercial glucosamine industry had a lower (but still significant) pain reduction efficacy (summary SMD = -0.19, 95% CI = -0.39 to -0.02) than those with industry involvement. Several smaller dosages throughout the day had larger pain reduction effects than a single daily large dose (1500 mg). CONCLUSION: These data indicate that GS may have a small to moderate effect in reducing OA-related pain but little effect on joint-space narrowing. Until there is more definitive evidence, healthcare providers should be cautious in recommending use of GS to their patients. Because GS dosages used in studies to date resulted in mild and transient adverse effects, and these were similar to that experienced by patients receiving plac

BACKGROUND: Symptomatic knee osteoarthritis (OA) involves millions of adults around the world. PURPOSE: To analyze the effectiveness and tolerability of topical therapies and their contemporary placement in knee OA management criteria. METHODS: A Cochrane Library and PubMed (MEDLINE) search related to the role of topical therapies in knee OA was carried out. RESULTS: Many types of local therapy have been reported, including nonsteroidal anti-inflammatory drugs (NSAIDs) like diclofenac and ketoprofen; capsaicin, cream containing glucosamine sulfate, chondroitin sulfate, and camphor; nimesulide; civamide cream 0.075%; menthol; drug-free gel containing ultra-deformable phospholipid vesicles (TDT 064); 4Jointz utilizing Acteev technology; herbal therapies; gel of medical leech (Hirudo medicinalis) saliva extract; and gel prepared using Lake Urmia mud. One systematic review showed that topical diclofenac and topical ketoprofen can alleviate pain. However, another systematic review found that topical diclofenac and ketoprofen had limited efficacy in knee OA at 6 to 12 weeks. Many studies with a low level of evidence have reported some pain mitigation using the rest of aforementioned topical therapies. CONCLUSIONS: Although some controversy exists on the role of topical NSAIDs, current management guidelines advise topical NSAIDs as an option and even first-line therapy for knee OA treatment, particularly among elderly patients. Topical NSAIDs may be contemplated as similar options to oral NSAIDs and are associated with fewer gastrointestinal complications when compared with oral NSAIDs. Caution should be taken with the use of both topical and oral NSAIDs, including close adherence to dosing regimens and monitoring, especially for patients with previous complications of NSAIDs. The role of other topical therapies needs further research.

OBJECTIVES: Systematic review of outcomes of three treatments for osteoarthritis (OA) of the knee: intra-articular viscosupplementation; oral glucosamine, chondroitin or the combination; and arthroscopic lavage or debridement. DATA SOURCES: We abstracted data from: 42 randomized, controlled trials (RCTs) of viscosupplementation, all but one synthesized among six meta-analyses; 21 RCTs of glucosamine/chondroitin, 16 synthesized among 6 meta-analyses; and 23 articles on arthroscopy. The search included foreign-language studies and relevant conference proceedings. REVIEW METHODS: The review methods were defined prospectively in a written protocol. We sought systematic reviews, meta-analyses, and RCTs published in full or in abstract. Where randomized trials were few, we sought other study designs. We independently assessed the quality of all primary studies. RESULTS: Viscosupplementation trials generally report positive effects on pain and function scores compared to placebo, but the evidence on clinical benefit is uncertain, due to variable trial quality, potential publication bias, and unclear clinical significance of the changes reported. The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), a large (n=1,583), high-quality, National Institutes of Health-funded, multicenter RCT showed no significant difference compared to placebo. Glucosamine sulfate has been reported to be more effective than glucosamine hydrochloride, which was used in GAIT, but the evidence is not sufficient to draw conclusions. Clinical studies of glucosamine effect on glucose metabolism are short term, or if longer (e.g., 3 years), excluded patients with metabolic disorders. The best available evidence for arthroscopy, a single sham-controlled RCT (n=180), showed that arthroscopic lavage with or without debridement was equivalent to placebo. The main limitations of this trial are the use of a single surgeon and enrollment of patients at a single Veterans Affairs Medical Center. No studies reported separately on patients with secondary OA of the knee. The only comparative study was an underpowered, poor-quality trial comparing viscosupplementation to arthroscopy with debridement. C

OBJECTIVE: To investigate the structural and symptomatic efficacy and safety of glucosamine in knee osteoarthritis (OA). DATA SOURCES: Clinical trials of glucosamine were identified through electronic searches (MEDLINE, EMBASE, BIOSIS, EMB review, the Cochrane Library) using the key words glucosamine, osteoarthritis, degenerative joint disease, degenerative arthritis, osteoarthrosis, gonarthrosis, knee, disease progression, and clinical trial. The bibliographic databases were searched from their respective inception dates to August 2004. We also hand-searched reference lists of relevant articles. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they were double-blind, randomized, controlled trials that evaluated oral glucosamine long-term treatment in knee OA; lasting at least one year; and reporting as outcome measures the symptom severity and disease progression as assessed by joint space narrowing. Two authors interpreted data independently. Disagreements were resolved through discussion. DATA SYNTHESIS: Glucosamine sulfate was more effective than placebo in delaying structural progression in knee OA. The risk of disease progression was reduced by 54% (pooled RR 0.46; 95% CI 0.28 to 0.73; p = 0.0011). The number-needed-to-treat was 9 (95% CI 6 to 20). The pooled effect sizes for pain reduction and improvement in physical function were 0.41 (95% CI 0.21 to 0.60; p < 0.0001) and 0.46 (95% CI 0.27 to 0.66; p < 0.0001), respectively, in favor of glucosamine sulfate. Glucosamine sulfate caused no more adverse effects than placebo. CONCLUSIONS: The available evidence suggests that glucosamine sulfate may be effective and safe in delaying the progression and improving the symptoms of knee OA. Due to the sparse data on structural efficacy and safety, further studies are warranted.