Effect of Curcuma longa extract on serum inflammatory markers and MRI-based synovitis in knee osteoarthritis: secondary analyses from the CurKOA randomised trial.

BACKGROUND: Curcuma longa (CL) extract is modestly effective for relieving knee symptoms in knee osteoarthritis (OA) patients; however, its mechanism of action is unclear. PURPOSE: We aimed to determine the effects of CL treatment on serum inflammatory markers over 12 weeks and to explore its potential effects on synovitis assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of the knee. METHODS: Secondary analyses were conducted on the CL for knee OA (CurKOA) trial, which compared CL (n = 36) and placebo (n = 34) over 12 weeks for the treatment of knee OA. Systemic inflammatory markers (TNFα, IL6, and hsCRP) and a cartilage extracellular matrix degradative enzyme (MMP-3) were measured. A subgroup of participants (CL, n = 7; placebo, n = 5) underwent CE-MRI at baseline and a 12-week follow-up. RESULTS: Over 12 weeks, there were no between-group differences in change in hsCRP, IL-6, and TNFα levels. MMP-3 levels decreased in both CL (-1.31 ng/ml [95%CI: -1.89 to -0.73]) and placebo (-2.34 ng/ml [95%CI: -2.95 to -1.73]) groups, with the placebo group having a slightly greater decrease (1.03 ng/ml [95%CI: 0.19 to 1.88]). Most (10 of 12) sub-study participants had normal synovial thickness scores at baseline. One participant had mild synovitis in each of the placebo and CL groups. Synovitis status was stable for all except two participants, one each in the CL and placebo group, whose synovitis score increased. CONCLUSION: This is the first study that explored the effect of CL treatment on local and systemic inflammation using biochemical markers and CE-MRI outcomes on knee OA patients. Secondary analyses from this pilot study suggest that CL is unlikely to have clinically significant effects on systemic (inflammatory and cartilage) or local synovitis (CE-MRI) biomarkers compared to placebo. The mechanism of action for CL effect on pain remains unclear.

A Randomised Controlled Trial of YOGa and Strengthening Exercise for Knee OsteoArthritis: Protocol for a Comparative Effectiveness Trial (YOGA Trial).

Osteoarthritis (OA) is a common joint disorder for which there is no cure. Current treatments are suboptimal. Exercise is a core treatment for knee OA, with muscle strengthening exercise commonly recommended. Yoga is a mind-body exercise intervention that can improve flexibility, muscle strength, balance, and fitness and potentially reduce symptoms of OA. However, there is a scarcity of robust, high-quality conclusive evidence on the efficacy of yoga in knee OA. We are currently conducting the first randomised comparative effectiveness and cost-effectiveness trial of a yoga program compared with a strengthening exercise program in patients with symptomatic knee OA. This study protocol describes the design and conduct of this trial. The YOGA study is a phase III, single-centre, parallel, superiority, randomised, active-controlled trial which will be conducted in Hobart, Australia. One hundred and twenty-six participants (63 in each arm) aged over 40 years with symptomatic knee OA will be recruited from the community and randomly allocated to receive either a 24-week yoga program (3×/week) or a strengthening exercise program (3×/week). The primary outcome will be change in knee pain over 12 weeks, assessed using a 100 mm visual analogue scale (VAS). The secondary outcomes include change in knee pain, patient global assessment, physical function, quality of life, gait speed, biomarkers, and others over 12 and 24 weeks. We will also assess whether the presence of neuropathic pain moderates the effects of yoga compared to strengthening exercise. Additional data, such as cost and resource utilization, will be collected for the cost-effectiveness analysis. The primary analysis will be conducted using an intention-to-treat approach. Adverse events will be monitored throughout the study. Once completed, this trial will contribute to the knowledge of whether yoga can be used as a simple, effective, low-cost option for the management of knee OA, thus saving economic costs in the healthcare system.

Efficacy and Safety of Turmeric Extracts for the Treatment of Knee Osteoarthritis: a Systematic Review and Meta-analysis of Randomised Controlled Trials.

PURPOSE OF THE REVIEW: Finding appropriate pharmacological options to treat osteoarthritis (OA) remain challenging. We aimed to determine the efficacy and safety of all types of turmeric extracts for the management of knee OA. RECENT FINDINGS: Sixteen RCTs of up to 16 weeks duration including 1810 adults with knee OA were included. Eleven RCTs compared the efficacy of turmeric extracts with placebo and five with active comparators (NSAIDs). The overall risk bias of included RCTs was moderate. Turmeric extracts significantly reduced knee pain (SMD - 0.82, 95% CI - 1.17 to - 0.47, I2 = 86.23%) and improved physical function (SMD - 0.75, 95% CI - 1.18 to - 0.33, I2 = 90.05%) compared to placebo but had similar effects compared to NSAIDs. BMI was the major contributor to heterogeneity in the placebo-controlled studies (explained 37.68% and 67.24%, respectively, in the models) and modified the effects of the turmeric on pain and physical function with less improvement with higher BMI (SMD 0.26 95% CI 0.04 to 0.48; SMD 0.48 95% CI 0.21 to 0.74). No significant between-group differences were reported for either biochemical markers or imaging outcomes. Turmeric extracts had 12% fewer adverse events than NSAIDs and similar rates to placebo. Turmeric extract is a safe and effective option for the symptomatic management of knee OA, compared to placebo or NSAIDs. However, current evidence from short-term studies is heterogeneous and has moderate risk of bias leading to some uncertainty about the true effect.

Nicotinamide Therapy in Dialysis Patients: A Systematic Review of Randomized Controlled Trials.

Randomized controlled trials (RCTs) have presented variable findings concerning the reduction of phosphorous level by nicotinamide. This systematic review is aimed to explore the safety and efficacy of nicotinamide in hemodialysis patients and was conducted by adhering to the PRISMA guidelines. Studies for inclusion were identified by running the suitable keywords in PubMed, Embase, and Cochrane Central till June 13, 2018. Cochrane risk of bias tool was used to judge the quality of the included RCTs. The primary outcome was change in serum phosphorus, calcium, and calcium-phosphorus product levels. Change in other biochemical parameters including serum calcium, parathormone, platelets, lipid profile parameters, and the safety profile was considered under secondary outcomes. Review Manager (RevMan v5.3) was used for the risk of bias estimate. A total of 12 articles were qualified for inclusion in this study. All the included RCTs showed a statistically significant reduction in mean serum phosphorous and calcium-phosphorus product levels in the treatment arm as compared to the placebo group. Among several biochemical parameters analyzed, only high-density lipoprotein (HDL) was found to be significantly increased from baseline to the endpoint of the study in the nicotinamide group, while the placebo group showed no significant difference. Flushing and diarrhea, followed by thrombocytopenia, were the most commonly reported adverse events in the treatment group. Nicotinamide was found to be effective in reducing the phosphorous level and calcium-phosphorus product level and increasing the HDL cholesterol level in dialysis patients. The safety profile was found to be satisfactory.

Effectiveness of Curcuma longa Extract for the Treatment of Symptoms and Effusion-Synovitis of Knee Osteoarthritis : A Randomized Trial.

BACKGROUND: Current pharmacologic therapies for patients with osteoarthritis are suboptimal. OBJECTIVE: To determine the efficacy of Curcuma longa extract (CL) for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee osteoarthritis and knee effusion-synovitis. DESIGN: Randomized, double-blind, placebo-controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000080224). SETTING: Single-center study with patients from southern Tasmania, Australia. PARTICIPANTS: 70 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis. INTERVENTION: 2 capsules of CL (n = 36) or matched placebo (n = 34) per day for 12 weeks. MEASUREMENTS: The 2 primary outcomes were changes in knee pain on a visual analogue scale (VAS) and effusion-synovitis volume on magnetic resonance imaging (MRI). The key secondary outcomes were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and cartilage composition values. Outcomes were assessed over 12 weeks. RESULTS: CL improved VAS pain compared with placebo by -9.1 mm (95% CI, -17.8 to -0.4 mm [P = 0.039]) but did not change effusion-synovitis volume (3.2 mL [CI, -0.3 to 6.8 mL]). CL also improved WOMAC knee pain (-47.2 mm [CI, -81.2 to -13.2 mm]; P = 0.006) but not lateral femoral cartilage T2 relaxation time (-0.4 ms [CI, -1.1 to 0.3 ms]). The incidence of adverse events was similar in the CL (n = 14 [39%]) and placebo (n = 18 [53%]) groups (P = 0.16); 2 events in the CL group and 5 in the placebo group may have been treatment related. LIMITATION: Modest sample size and short duration. CONCLUSION: CL was more effective than placebo for knee pain but did not affect knee effusion-synovitis or cartilage composition. Multicenter trials with larger sample sizes are needed to assess the clinical significance of these findings. PRIMARY FUNDING SOURCE: University of Tasmania and Natural Remedies Private Limited.

Effects of walnut intake on blood pressure: A systematic review and meta-analysis of randomized controlled trials.

The impact of walnuts on blood pressure (BP) is not a well-established fact. Although several studies have assessed the effects of walnut consumption on BP, results are conflicting. Thus, we examined the effects of walnut doses and length of supplementation on BP. Biomedical databases were searched for published trials that compared walnut-enhanced diet to control diet. Eighteen trials met eligibility criteria (n = 1,799). Overall, walnut consumption neither did alter SBP (weighted mean difference [WMD]: 0.08 mmHg; 95% CI: -0.69, 0.85) nor DBP (WMD: 0.08 CI: -0.26, 0.42). In subgroup analyses, walnut ingestion ≤40 g was statistically correlated with reduction in SBP (WMD: -0.53 mmHg, 95% CI: -0.79, -0.26) and DBP (WMD: -0.191 mmHg, 95% CI: -0.384, -0.034). Moreover, the length of intervention ≥8 weeks was linked to a significant reduction in SBP (WMD: -1.18 mmHg, 95% CI: -1.30, -1.06). Following dose-response evaluation, walnut intake significantly changed SBP (p = .015) and DBP (p = .026) through a nonlinear fashion at walnut dose up to 40 g/d. Nevertheless, these statistical results cannot be translated into clinical practice, once the changes expressed as WMD are slight taking into consideration the absolute values of BP categories. In conclusion, this meta-analysis does not support walnut consumption as a BP-lowering strategy.

Vitamin D supplementation for the management of knee osteoarthritis: a systematic review of randomized controlled trials.

Conflicting evidence exists concerning the supplementation of vitamin D in knee osteoarthritis condition. This systematic literature review was done to explore the effects of vitamin D supplementation in the management of knee osteoarthritis. Electronic literature search was done in databases like PubMed®, Embase®, and Cochrane CENTRAL from inception to 6th July 2016. The quality of included Randomized Controlled Trials (RCTs) was assessed using Cochrane risk of bias tool. We considered change in Western Ontario and McMaster Universities (WOMAC) index, Visual Analog Scale (VAS) and Functional Pain Score (FPS) as the primary outcome measure. Change in tibial cartilage thickness, joint space width and safety profile was considered as secondary outcomes. Participants were randomized either to treatment or placebo group. Participants received cholecalciferol as an intervention through oral route in the dose range of 800-60,000 IU except in the one study where participants received ergocalciferol. All included RCTs showed a significant increase in serum vitamin D level in the treatment group compared to the placebo group at the end point. No significant reduction in pain and function was reported on WOMAC scale except in one study. No significant difference was reported for WOMAC stiffness in any study. VAS was assessed in three studies in which two showed statistically significant improvement in knee pain. Three of the RCTs reported safety data with one incidence of calculus ureteric and hip fracture found to be related to the drug. The study found evidence from RCTs to be insufficient to support the use of vitamin D supplementation for patients with knee osteoarthritis.