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New meta-analyses, RCTs and systematic reviews that we monitor daily in PubMed. Independently indexed, not editorially curated.
Expert review of proteomics · 2024
Oral squamous cell carcinoma (OSCC) represents the most prevalent form of oral cancer. Potentially malignant disorders of oral mucosa exhibit an elevated propensity for malignant progression. A substantial proportion of cases are discerned during advanced stages, significantly impacting overall survival. This investigation aims to ascertain salivary metabolites with potential utility in the early detection of OSCC. A search encompassing PubMed, EMBASE, Scopus, Ovid, Science Direct, and Web of Science databases was conducted to identify eligible articles. The search strategy employed precise terms. The quality assessment of the included studies was executed using the QUADAS 2 ROB tool. This was registered with PROSPERO CRD42021278217. Upon removing duplicate articles and publications that didn't satisfy the inclusion criteria, seven articles were included in the current study. The Random Effects Maximum Likelihood (REML) model adopted for quantitative synthesis identified Nacetyl glucosamine as the sole metabolite in two studies included in this metaanalysis. The pathways significantly influenced by these identified metabolites were delineated. This study highlights Nacetyl glucosamine as a distinctive metabolite with the potential to serve as an early diagnostic marker for OSCC. Nevertheless, further research is warranted to validate its clinical utility.
Nutrients · 2024
Various nutritional supplements are available over the counter, yet few have been investigated in randomized controlled trials. The rationale for using the specific mix of nutritional substances including collagen type II, hyaluronic acid, n-acetyl-glucosamine, bamboo extract, L-lysine, and vitamin C is the assumption that combining naturally occurring ingredients of the intervertebral disc would maintain spine function. This double-blinded, placebo-controlled randomized trial aimed to evaluate the efficacy of a nutraceutical supplement mix in the management of lumbar osteochondrosis. Fifty patients were randomly assigned to either the supplement or placebo group in a 1:1 ratio. Patient-Reported Outcome Measures (PROMs) included the Oswestry Disability Index (ODI), the visual analogue scale for pain (pVAS), short form-12 (SF-12) physical and mental component summary subscale scores (PCS and MCS, respectively), and global physical activity questionnaire (GPAQ). Magnetic resonance imaging (MRI) was used to evaluate degenerative changes of intervertebral discs (IVD) including Pfirrmann grades as well as three-dimensional (3D) volume measurements. Data were collected at baseline and after the 3-month intervention. None of the PROMs were significantly different between the supplement and placebo groups. Disc degeneration according to Pfirrmann classifications remained stable during the 3-month intervention in both groups. Despite no significance regarding the distribution of Pfirrmann grade changes (improvement, no change, worsening; p = 0.259), in the supplement group, one patient achieved a three-grade improvement, and worsening of Pfirrmann grades were only detected in the placebo group (9.1%). Furthermore, in-depth evaluations of MRIs showed significantly higher 3D-measured volume changes (increase) in the supplement (+740.3 ± 796.1 mm3) compared to lower 3D-measured volume changes (decrease) in the placebo group (-417.2 ± 875.0 mm3; p < 0.001). In conclusion, this multi-nutrient supplement might not only stabilize the progression of lumbar osteochondrosis, but it might also potentially even increase IVD volumes as detected on MRIs.
Journal of applied physiology (Bethesda, Md. : 1985) · 2024
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 diabetic mice. However, the utilized dietary supplement as a therapeutic strategy to enhance vascular function in individuals with T2D is not efficacious.
Nutrients · 2024
The relationship between gut microbiota composition, lifestyles, and colonic transit time (CTT) remains poorly understood. This study investigated associations among gut microbiota profiles, diet, lifestyles, and CTT in individuals with subjective constipation. We conducted a secondary analysis of data from our randomized clinical trial, examining gut microbiota composition, CTT, and dietary intake in baseline and final assessments of 94 participants with subjective constipation. Participants were categorized into normal-transit (<36 h) and slow-transit (≥36 h) groups based on CTT at baseline. Gut microbiota composition was measured using 16S rRNA sequencing, and dietary patterns were assessed through semi-quantitative food frequency questionnaires. Enterotype analysis, machine learning approaches, and metabolic modeling were employed to investigate microbiota-diet interactions. The constipated participants primarily belonged to Lachnospiraceae (ET-L). The slow-transit group showed higher alpha diversity than the normal-transit group. Butyricicoccus faecihominis was abundant in the normal-transit group, while Neglectibacter timonensis, Intestinimonas massiliensis, and Intestinibacter bartlettii were abundant in the slow-transit group, which also had a higher abundance of mucin-degrading bacteria. Metabolic modeling predicted increased N-acetyl-D-glucosamine (GlcNAc), a mucin-derived metabolite, in the slow-transit group. Network analysis identified two microbial co-abundance groups (CAG3 and CAG9) significantly associated with transit time and dietary patterns. Six mucin-degrading species showed differential correlations with GlcNAc and a plant-based diet, particularly, including rice, bread, fruits and vegetables, and fermented beans. In conclusion, an increased abundance of mucin-degrading bacteria and their predicted metabolic products were associated with delayed CTT. These findings suggest dietary modulation of these bacterial populations as a potential therapeutic strategy for constipation. Moreover, our results reveal a potential immunometabolic mechanism where mucin-degrading bacteria and their metabolic interactions may influence intestinal transit, mucosal barrier function, and immune response.
Age and ageing · 2025
To investigate the effectiveness of formula nutrition supplementation (mainly containing glucosamine sulphate, chondroitin sulphate and rhizoma drynariae) plus supervised exercise versus exercise alone for the treatment of knee osteoarthritis (OA). This was a double-blinded, single-centre, randomised, placebo-controlled trial. The study recruited 65 participants (40-75 years) with knee OA. Participants were randomly allocated to nutrition supplementation plus exercise (N + E) group or placebo plus exercise (P + E) group. The intervention lasted for 6 months. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes included physical function and performance scores, lower extremity strength and serum biomarkers. Among the 65 randomised patients, 56 (86%) completed the trial. At 3 months, more participants in the N + E group than in the P + E group achieved minimum clinically important difference (MCID) in WOMAC total score (19/30 [63.3%] vs 8/26 [30.8%]; P < .01). At 6 months, more participants in the N + E group than in the P + E group achieved MCID in WOMAC stiffness score (19/30 [63.3%] vs 10/26 [38.5%]; P < .05). Meanwhile, at 6 months the decreased percentages of WOMAC stiffness score in the N + E group was greater than in the P + E group (P < .05). The flexor peak torque at 120°/s and 180°/s in the N + E group were significantly higher than those in the P + E group at 3 months (P < .05). Moreover, compared with baseline, improvements in the WOMAC overall and pain score, visual analogue scale pain and 30-second chair stand test were observed in both groups at 6 months. However, these indicators in the N + E group were improved as early as 3 months (P < .05). The improvement effects of nutrition supplementation plus exercise were superior to those of exercise alone, and the improvement occurred earlier. Nutrition supplementation plus exercise would be a more efficient strategy for knee OA.
Medicina (Kaunas, Lithuania) · 2025
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.
Drugs · 2025
Several meta-analyses of phase 3 randomized controlled trials (RCTs) were published in 2019, reassessing the safety of most anti-osteoarthritis (OA) medications, mainly on the basis of data from full safety reports. The current systematic review (SR) intends to provide complementary insights into the safety of anti-OA medications, using evidence from post-marketing safety surveillance studies. The review protocol was registered with PROSPERO database (registration no. CRD42021227872). We followed the Cochrane methodology for SRs of interventions and comprehensively searched the Medline, CENTRAL, Scopus and TOXLINE databases from inception to November 2023, to include all post-marketing safety surveillance studies on any anti-OA medications. The outcomes of this SR were any adverse events (AEs) reported in the included studies. The literature search yielded 16,990 studies, of which 59 articles were ultimately included in the review. Most studies investigated non-steroidal anti-inflammatory drugs (NSAIDs, 27 studies, 28 reports) and intra-articular hyaluronic acid (IAHA, 16 studies). Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) were assessed in seven studies (one of which also assessed NSAIDs), and corticosteroid injections in four studies, while opioids and "herbal mixtures and other compounds" each were investigated respectively in three and two studies. Most of the studies were cohort studies (n = 44), others were case reports or case series (n = 12), RCTs (n = 2 reports of the same trial), or a case-control study (n = 1). The most commonly reported AEs with NSAIDs from cohort (sample sizes varied between 129 and 22,938 patients), RCT (21,645 patients with OA), and case-control (174 cases and 926 control patients with OA) studies were gastrointestinal (GI) and/or cardiovascular (CV) AEs, with specific AEs varying with individual NSAIDs. Where comparisons between NSAIDs were made, the overall literature shows a better or similar safety profile for celecoxib (at a daily dose of 200 mg, where dosage was reported) compared with other NSAIDs in regards to GI, CV and renal events. Other anti-OA medications with most common AEs reported from cohort studies were: IAHA (injection site pain); diacerein (GI AEs and reddish urine); avocado-soybean unsaponifiables (GI AEs); non-pharmaceutical-grade glucosamine and chondroitin (allergic reactions, GI disorders); opioids (hip fracture associated with long-term tramadol use among older adults; GI and nervous system disorders with hydrocodone); corticosteroid injections (increased risk of OA progression); herbal mixtures and other compounds (GI AEs). There were case reports or case series of specific AEs with various anti-OA medications that require further investigations in well-designed cohort studies before any definitive conclusions can be reached. This SR confirms previous evidence on the safety of anti-OA medications from meta-analyses of phase 3 RCTs. Beyond the evidence here reported, the limitations of this research highlight the urgent need of a reporting guideline for post-marketing safety surveillance studies. Importantly, real-life safety surveillance of anti-OA medications should be strengthened with large cohort studies with control groups, and results should be disaggregated by disease populations for drugs common to several conditions.
Frontiers in nutrition · 2025
Knee osteoarthritis (KOA) stands as a prevalent clinical condition that frequently affects individuals. A growing body of research has highlighted the potential advantages of dietary supplements, including glucosamine and chondroitin, in the management of KOA. This study aims to ascertain the most efficacious dietary supplement for KOA, with a specific focus on reducing pain, alleviating stiffness, and enhancing joint function. We conducted an exhaustive search of multiple databases, including PubMed, Web of Science, Embase, and the Cochrane Library, from inception to May 2023. We specifically focused on randomized controlled trials (RCTs) comparing various dietary supplements with the placebo group within the context of KOA. Assessment of outcomes among these groups relied on the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), with weighted mean differences (WMDs) and associated 95% confidence intervals (CIs) computed. Network meta-analyses were employed to compare outcomes across different supplement groups in comparison with the placebo. The surface under the cumulative ranking curve (SUCRA) was utilized to rank these supplements. Our comprehensive analysis included 22 studies with 2,777 participants in total. The outcomes from our network meta-analysis yielded the following key findings: To reduce the total WOMAC score, the top three interventions were E-OA-7, LParActin, and LcS. For reducing the WOMAC score of pain, the most effective interventions were Aflapin, NEM, and PFP. In addressing the reduction of the WOMAC score of stiffness, NEM, Aflapin, and MSM emerged as the optimal interventions. Finally, for diminishing the WOMAC score of physical function, the most effective interventions were E-OA-7, LParActin, and LcS. In comparison to the placebo, NEM (for stiffness), Aflapin (for pain), and E-OA-07 (for knee function and WOMAC total score) were discerned as the most effective interventions for the treatment of KOA. https://www.crd.york.ac.uk/prospero/.
Brain and behavior · 2025
Multiple sclerosis (MS) is a multifaceted neurodegenerative disorder influenced by genetics and lifestyle. This systematic literature review investigates the role of six obesity-associated genes, including fat mass and obesity-associated (FTO), FAS apoptosis inhibitory molecule 2 (FAIM2), Niemann-Pick disease type C1-like 1 (NPC1), glucosamine-6-phosphate deaminase 2 (GNPDA2), melanocortin-4 receptor (MC4R), and brain-derived neurotrophic factor (BDNF) in the context of MS. A literature search was executed using Embase, Scopus, Cochrane, Web of Science, and PubMed databases from inception to July 2024. The related keywords employed during the search process are "fas apoptotic inhibitory molecule 2," "Niemann-Pick disease type C1," "fat mass and obesity-associated," "melanocortin-4 receptor," "brain-derived neurotrophic factor," "glucosamine-6-phosphate deaminase 2," and "multiple sclerosis." Out of 2108 papers, 27 were entered into the present systematic literature review. The FTO gene may affect MS susceptibility through metabolic and inflammatory pathways. FAIM2 and NPC1 genes may contribute to MS pathogenesis, though their precise roles are still being elucidated. The GNPDA2 gene may have some connections with MS but requires further clarification. MC4R has demonstrated significant neuroprotective and anti-inflammatory effects, suggesting its potential impact on MS progression. BDNF plays a complex role in neuronal survival and repair and may influence the risk of MS. Our findings demonstrated that obesity-related genes may have a significant impact on MS risk and disease course, revealing novel insights into the genetic underpinnings of MS.
European journal of clinical investigation · 2025
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. 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. 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. Four-month treatment with GDS may improve endothelial glycocalyx and vascular function after COVID-19 infection. URL: https://www. gov. Unique identifier: NCT05185934.
The Journal of international medical research · 2025
ObjectiveObservational studies on glucosamine supplementation and type 2 diabetes risk have shown inconsistent results, necessitating the use of Mendelian randomization to clarify the true causal relationship.MethodsThe glucosamine supplementation-related genome-wide association study dataset was obtained from the MRC Integrative Epidemiology Unit consortium, whereas type 2 diabetes-related genome-wide association study datasets were obtained from the FinnGen consortium (discovery) and Xue et al.'s meta-analysis (validation). Two-sample Mendelian randomization analyses were performed separately in the discovery and validation datasets, followed by meta-analysis and multivariable Mendelian randomization analyses to verify the robustness of the results of two-sample Mendelian randomization. The estimation of the causal relationship was conducted through the inverse variance weighted method.ResultsGlucosamine supplementation exhibited a significant protective effect against type 2 diabetes, as identified by two-sample Mendelian randomization analysis in the FinnGen consortium (odds ratio: 0.13, 95% confidence interval: 0.02-0.89) and validated in Xue et al.'s meta-analysis (odds ratio: 0.06, 95%; confidence interval: 0.01-0.29). A combined meta-analysis (odds ratio: 0.08, 95%; confidence interval: 0.02-0.27) of the results of two-sample Mendelian randomization confirmed the robustness of these findings. Additionally, multivariable Mendelian randomization analysis (odds ratio: 0.12, 95%; confidence interval: 0.02-0.94), after adjusting for confounding factors, supported the results of two-sample Mendelian randomization. No evidence of heterogeneity or pleiotropy was observed.ConclusionOverall, our results revealed that genetically predicted glucosamine supplementation was inversely associated with the risk of type 2 diabetes, highlighting the potential importance of glucosamine supplementation in preventing type 2 diabetes.
Pakistan journal of pharmaceutical sciences · 2025
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.
Nutrients · 2025
Glucosamine and chondroitin are natural substances often used alone or in combination for conditions affecting the joints. Our objective was to evaluate the efficacy and safety of glucosamine and/or chondroitin supplementation in humans as well as to determine the common dosages used. A systematic review was conducted using PRISMA methodology. Searches were performed in PubMed and Web of Science and uploaded into Covidence where two independent researchers reviewed articles according to inclusion and exclusion criteria. Quality assessment was performed using the Mixed Methods Appraisal Tool (MMAT). Of the 2013 articles screened, 146 studies were included in our review, with nearly 60% being randomized controlled trials and most conducted in Europe, Asia, or the U.S. Most studies focused on osteoarthritis and joint pain, with over 90% of efficacy studies reporting positive outcomes and most safety studies indicating minimal or no adverse effects. Glucosamine and chondroitin were most commonly administered together at daily doses of 1500 mg and 1200 mg, respectively, and often compared to a placebo or celecoxib. Overall, the evidence suggests that glucosamine and chondroitin are generally effective and well-tolerated, particularly for managing osteoarthritis and joint pain. Consistent dosing strategies and favorable safety profiles across a diverse range of studies support their continued use in clinical practice, but further research is needed related to other disease states.
Scientific reports · 2025
Osteoarthritis (OA) is a prevalent degenerative joint disease, often affecting the elderly, characterized by cartilage degradation and bone remodelling, leading to pain, stiffness, and impaired movement. This 12-week, randomized, double-blind, placebo-controlled pilot study investigated the efficacy of a formulation containing collagen type II, glucosamine hydrochloride and chondroitin sulfate, in alleviating knee OA symptoms in subjects with mild to moderate knee pain. Fifty-four participants were enrolled, with 52 completing the study. Participants were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS), performance-based physical function tests and global assessment tests. Results indicated significant improvements in the verum group compared to placebo. KOOS subscales showed improvements in symptoms (8.16%, p < 0.05), sport/recreation (25.25%, p < 0.01), and quality of life (27.66%, p < 0.001). Stiffness improved by 14.68% (p < 0.05) in the verum group. Both groups exhibited significant pain reduction (KOOS pain, p < 0.001 and p < 0.01 for verum and placebo, respectively). Performance-based measures, such as the Chair Stand test, improved significantly in both groups, though other metrics showed no significant differences. The verum group exhibited a linear improvement over 12 weeks, contrasting with the placebo group's initial response and subsequent plateau. SF-36 Physical Component scores improved in both groups (p < 0.05), but mental health scores remained unchanged. Global assessment favoured the verum group, with more participants reporting OA improvement and recommending the product (p < 0.01). Biomarkers hsCRP and COMP showed no significant changes, likely due to sample variability. While the study did not achieve its primary endpoint, the nutritional formulation demonstrated an excellent safety profile and encouraging improvements in patient-reported symptoms and quality of life, warranting larger confirmatory trials.Registration number: DRKS00029563 05/10/2022.
Nutrients · 2025
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.
Journal of drug targeting · 2026
This study aimed to unveil the effect of glucosamine hydrochloride (GAH) and eperisone combined with exercise therapy on inflammatory markers and knee joint function in patients with knee osteoarthritis (KOA). Sixty KOA patients were randomly assigned into two groups. Group A (n = 30) received GAH plus exercise therapy, while Group B (n = 30) received GAH combined with eperisone and exercise therapy. Serum inflammatory factors, knee symptom scores (pain, stiffness, daily function), and functional measures [knee flexion range of motion (ROM), Lysholm score, five-time sit-to-stand test, and 15-meter walking time] were assessed before and after treatment. Clinical efficacy was also evaluated. Post-treatment, both groups showed decreased serum MMP-3, TNF-α, and IL-6 levels, with significantly greater reductions in Group B (p < 0.001). Group B had lower symptom scores (p < 0.05), greater ROM and Lysholm improvements (p < 0.001), and better functional performance (p < 0.001). The effective rate was higher in Group B (100.00%) than in Group A (86.67%) (p = 0.038). GAH combined with eperisone and exercise therapy is more effective than GAH alone in patients with KOA. It significantly reduces inflammatory markers and symptoms, and enhances knee joint function.
Clinical oral investigations · 2025
To evaluate the effectiveness of minimally invasive interventions (arthrocentesis and intra-articular injections) versus conservative therapies for temporomandibular joint osteoarthritis (TMJ OA). This systematic review included randomized controlled and prospective or observational studies involving patients with TMJ OA. A comprehensive search of five databases was conducted up to November 2024. Pain intensity (VAS) and maximum mouth opening (MMO) were analyzed via meta-analysis, with risk of bias assessed using ROB 2 and ROBINS-I tools, and certainty of evidence using GRADE. The significance level adopted for the analysis was set at α = 0.05. Sixteen studies (901 patients) were included. Arthrocentesis, alone or with adjuvants such as PRP, i-PRF, corticosteroids, or NSAIDs, significantly improved pain (MD - 5.50; 95%CI: - 6.61 to - 4.39) and MMO (MD 6.97 mm; 95%CI: 1.96 to 11.98) versus baseline and between groups. Intra-articular hyaluronic acid, with or without glucosamine, showed clinical benefit over time, but its superiority over conservative care was inconsistent. Substantial heterogeneity was observed, mainly in injection-based protocols. GRADE indicated high certainty of evidence for most comparisons, except one (MMO, moderate certainty). Minimally invasive therapies, especially arthrocentesis with biological adjuvants, seems to be effective for TMJ OA management. However, due to heterogeneity and methodological limitations, their superiority over conservative strategies remains uncertain. Minimally invasive therapies, particularly arthrocentesis with or without biological agents, may reduce pain and improve jaw function in TMJ OA, offering a potential alternative to conservative treatments over a 3- to 12-month period.
Phytomedicine : international journal of phytotherapy and phytopharmacology · 2021
Evidence indicates a close association between oxidative stress and the etiopathogenesis of osteopenia. In vitro and animal studies report that Oligopin®, an extract of French maritime pine bark extract, has beneficial effects on oxidative stress. Here, we aimed to determine whether supplementation with Oligopin® affects bone turnover markers, antioxidant enzymes, and oxidative stress markers in these patients. Forty-three postmenopausal women with osteopenia were randomized in a placebo-controlled, double-blind clinical trial to receive either 150 mg/day Oligopin® (n = 22) or placebo (n = 21) for 12 weeks. Plasma levels of bone turnover markers; osteocalcin (OC), type I collagen cross-linked C-telopeptide (CTX-1), OC/CTX1 ratio along with total antioxidant capacity(TAC), malondialdehyde (MDA) concentration, protein carbonyl, and total thiol contents in plasma, activities of manganese superoxide dismutase (MnSOD) and catalase in both peripheral blood mononuclear cells (PBMCs) and plasma as well as mRNA expression of MnSOD, catalase, and Nrf2 in PBMCs were measured at the baseline and the end of the intervention. Oligopin® supplementation significantly increased OC levels and the ratio of OC to CTX1 in women with osteopenia compared to placebo intervention after 12 weeks. Oligopin® significantly decreased plasma protein carbonyl content in postmenopausal women compared with the after placebo treatment. Moreover, Oligopin® intervention significantly increased plasma total thiol content, TAC, plasma activity of both MnSOD and catalase, and the transcript level of Nrf2, MnSOD, and catalase in comparison with the placebo group. Supplementation with 150 mg/day Oligopin® for 12 weeks exerts beneficial effects in postmenopausal osteopenia through improving the antioxidant defense system in the plasma and PBMCs that was accompanied by an increase in indicators of bone turnover.
The Cochrane database of systematic reviews · 2021
Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention or impulsivity or both, and hyperactivity, which affect children, adolescents, and adults. In some countries, methylphenidate is the first option to treat adults with moderate or severe ADHD. However, evidence on the efficacy and adverse events of immediate-release (IR) methylphenidate in the treatment of ADHD in adults is limited and controversial. To evaluate the efficacy and harms (adverse events) of IR methylphenidate for treating ADHD in adults. In January 2020, we searched CENTRAL, MEDLINE, Embase, eight additional databases and three trial registers. We also searched internal reports on the European Medicines Agency and the US Food and Drug Administration websites. We checked citations of included trials to identify additional trials not captured by the electronic searches. Randomized controlled trials (RCTs) comparing IR methylphenidate, at any dose, with placebo or other pharmacological interventions (including extended-release formulations of methylphenidate) for ADHD in adults. Primary outcomes comprised changes in the symptoms of ADHD (efficacy) and harms. Secondary outcomes included changes in the clinical impression of severity and improvement, level of functioning, depression, anxiety and quality of life. Outcomes could have been rated by investigators or participants. Two review authors extracted data independently on the characteristics of the trials, participants, interventions; outcomes and financial conflict of interests. We resolved disagreements by discussion or consulting a third review author. We obtained additional, unpublished information from the authors of one included trial that had reported efficacy data in a graph. We calculated mean differences (MDs) or standardized MDs (SMDs) with 95% confidence intervals (CIs) for continuous data reported on the same or different scales, respectively. We summarized dichotomous variables as risk ratios (RRs) with 95% CI. We included 10 trials published between 2001 and 2016 involving 497 adults with ADHD. Three trials were conducted in Europe and one in Argentina; the remaining trials did not report their location. The RCTs compared IR methylphenidate with placebo, an osmotic-release oral system (OROS) of methylphenidate (an extended-release formulation), an extended-release formulation of bupropion, lithium, and Pycnogenol® (maritime pine bark extract). Participants comprised outpatients, inpatients in addiction treatment, and adults willing to attend an intensive outpatient program for cocaine dependence. The duration of the follow-up ranged from 6 to 18 weeks. IR methylphenidate versus placebo We found very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce symptoms of ADHD when measured with investigator-rated scales (MD -20.70, 95% CI -23.97 to -17.43; 1 trial, 146 participants; end scores; Adult ADHD Investigator Symptom Report Scale (AISRS), scored from 0 to 54), but the evidence is uncertain. The effect of IR methylphenidate on ADHD symptoms when measured with participant-rated scales was moderate, but the certainty of the evidence is very low (SMD -0.59, 95% CI -1.25 to 0.06; I2 = 69%; 2 trials, 138 participants; end scores). There is very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce the clinical impression of the severity of ADHD symptoms (MD -0.57, 95% CI -0.85 to -0.28; 2 trials, 139 participants; I2 = 0%; change and end scores; Clinical Global Impression (CGI)-Severity scale (scored from 1 (very much improved) to 7 (very much worse))). There is low-certainty evidence that, compared with placebo, IR methylphenidate may slightly impact the clinical impression of an improvement in symptoms of ADHD (MD -0.94, 95% CI -1.37 to -0.51; 1 trial, 49 participants; end scores; CGI-Improvement scale (scored from 1 (very much improved) to 7 (very much worse))). There is no clear evidence of an effect on anxiety (MD -0.20, 95% CI -4.84 to 4.44; 1 trial, 19 participants; change scores; Hamilton Anxiety Scale (HAM-A; scored from 0 to 56); very low-certainty evidence) or depression (MD 2.80, 95% CI -0.09 to 5.69; 1 trial, 19 participants; change scores; Hamilton Depression Scale (HAM-D; scored from 0 to 52); very low-certainty evidence) in analyses comparing IR methylphenidate with placebo. IR methylphenidate versus lithium Compared with lithium, it is uncertain whether IR methylphenidate increases or decreases symptoms of ADHD (MD 0.60, 95% CI -3.11 to 4.31; 1 trial, 46 participants; end scores; Conners' Adult ADHD Rating Scale (scored from 0 to 198); very low-certainty evidence); anxiety (MD -0.80, 95% CI -4.49 to 2.89; 1 trial, 46 participants; end scores; HAM-A; very low-certainty evidence); or depression (MD -1.20, 95% CI -3.81 to 1.41, 1 trial, 46 participants; end scores; HAM-D scale; very low-certainty evidence). None of the included trials assessed participant-rated changes in symptoms of ADHD, or clinical impression of severity or improvement in participants treated with IR methylphenidate compared with lithium. Adverse events were poorly assessed and reported. We rated all trials at high risk of bias due to selective outcome reporting of harms and masking of outcome assessors (failure to blind outcome assessor to measure adverse events). Overall, four trials with 203 participants who received IR methylphenidate and 141 participants who received placebo described the occurrence of harms. The use of IR methylphenidate in these trials increased the risk of gastrointestinal complications (RR 1.96, 95% CI 1.13 to 2.95) and loss of appetite (RR 1.77, 95% CI 1.06 to 2.96). Cardiovascular adverse events were reported inconsistently, preventing a comprehensive analysis. One trial comparing IR methylphenidate to lithium reported five and nine adverse events, respectively. We considered four trials to have notable concerns of vested interests influencing the evidence, and authors from two trials omitted information related to the sources of funding and conflicts of interest. We found no certain evidence that IR methylphenidate compared with placebo or lithium can reduce symptoms of ADHD in adults (low- and very low-certainty evidence). Adults treated with IR methylphenidate are at increased risk of gastrointestinal and metabolic-related harms compared with placebo. Clinicians should consider whether it is appropriate to prescribe IR methylphenidate, given its limited efficacy and increased risk of harms. Future RCTs should explore the long-term efficacy and risks of IR methylphenidate, and the influence of conflicts of interest on reported effects.
Phytotherapy research : PTR · 2021
The purpose of this study was to investigate the complementary effects of polyphenolic compounds from pine bark extract (PE) as a strong antioxidative substrate on the symptoms of inattention and impulsivity in children with attention-deficit hyperactivity disorder (ADHD). This was a randomized, double-blind, crossover, placebo-controlled study that included two experimental units (4 weeks with PE supplementation and 4 weeks with placebo supplementation) separated by a 2-week washout period. ADHD participants were supplemented with 25 mg or 50 mg PE. We recruited 20 participants (17 boys and 3 girls) with a mean age of 10.0 ± 2.1 years. PE supplementation caused a significant reduction in the inattention and hyperactivity-impulsivity items of SNAP-IV. During the period of PE supplementation, the item of commissions in the Continuous Performance Test III (CPT III) significantly decreased, which was used to evaluate the symptoms of inattention and impulsivity. In addition, the erythrocytic reduced glutathione/oxidized glutathione ratio significantly increased, and the plasma TBARs level significantly decreased after 4 weeks of PE supplementation. However, there was no significant correlation between CPT III (commission) and antioxidative status indictors. PE supplementation may have potential effects of ameliorating inattention and impulsivity, and elevating the antioxidative status in children with ADHD.