Effects of turmeric (Curcuma longa) supplementation on glucose metabolism in diabetes mellitus and metabolic syndrome: An umbrella review and updated meta-analysis.

AIMS: This study aims to comprehensively review the existing evidence and conduct analysis of updated randomized controlled trials (RCTs) of turmeric (Curcuma longa, CL) and its related bioactive compounds on glycemic and metabolic parameters in patients with type 2 diabetes (T2DM), prediabetes, and metabolic syndrome (MetS) together with a sub-group analysis of different CL preparation forms. METHODS: An umbrella review (UR) and updated systematic reviews and meta-analyses (SRMAs) were conducted to evaluate the effects of CL compared with a placebo/standard treatment in adult T2DM, prediabetes, and MetS. The MEDLINE, Embase, The Cochrane Central Register of Control Trials, and Scopus databases were searched from inception to September 2022. The primary efficacy outcomes were hemoglobin A1C (HbA1C) and fasting blood glucose (FBG). The corrected covered area (CCA) was used to assess overlap. Mean differences were pooled across individual RCTs using a random-effects model. Subgroup and sensitivity analyses were performed for various CL preparation forms. RESULTS: Fourteen SRMAs of 61 individual RCTs were included in the UR. The updated SRMA included 28 studies. The CCA was 11.54%, indicating high overlap across SRMAs. The updated SRMA revealed significant reduction in FBG and HbA1C with CL supplementation, obtaining a mean difference (95% confidence interval [CI]) of -8.129 (-12.175, -4.084) mg/dL and -0.134 (-0.304, -0.037) %, respectively. FBG and HbA1C levels decreased with all CL preparation forms as did other metabolic parameters levels. The results of the sensitivity and subgroup analyses were consistent with those of the main analysis. CONCLUSION: CL supplementation can significantly reduce FBG and HbA1C levels and other metabolic parameters in T2DM and mitigate related conditions, including prediabetes and MetS. TRIAL REGISTRATION: PROSPERO (CRD42016042131).

Effect of tomato, lycopene and related products on blood pressure: A systematic review and network meta-analysis.

BACKGROUND: A number of randomized controlled trials (RCTs) have been conducted to evaluate the hypotensive effects of tomato, lycopene, and related products. However, the findings were conflicting, partly due to differences in the types of products investigated. Therefore, this study aimed to assess and compare the hypotensive effects of different tomato-related preparations through a network meta-analysis based on randomized controlled trials. STUDY DESIGN: A systematic review and network meta-analysis. METHODS: A network meta-analysis based on a systematic review of RCTs comparing the effect of various tomato, lycopene and related products versus placebo on blood pressure in adults was performed. PubMed, EMBASE, SCOPUS, and Clinicaltrial.gov databases were searched up to October 2020 without language restrictions. The primary outcomes were systolic and diastolic blood pressure. Mean differences (MDs) along with 95% confidence intervals (CIs) were estimated and pooled using a random-effects model. Heterogeneity was assessed using the global inconsistency test. RESULTS: A total of 11 studies including six forms of tomato, lycopene and related products met the inclusion criteria. Among these trials, eight (N = 617) and seven trials (N = 501) were included in the analysis of systolic (SBP) and diastolic blood pressure (DBP) outcomes, respectively. The standardized tomato extract (STE) significantly decreased SBP compared to placebo, with a pooled MD (95% CI) of -5.89 (-9.13 to -2.64) mmHg. The effect on DBP was not significant, with a pooled MD (95% CI) of -3.51 (-7.39 to 0.38) mmHg. Subgroup analysis in hypertensive patients showed that STE significantly reduced both SBP and DBP with pooled MDs (95% CIs) of -8.09 (-11.52 to -4.67) and -4.25 (-6.97 to -1.53) mmHg, respectively, compared to placebo. Other forms of tomato, including other dose ranges of standardized tomato extract, tomato-containing diet, lycopene-free preparation, and synthetic lycopene, did not show consistent and significant effects on either SBP or DBP in all analyses. CONCLUSION: Standardized tomato extract (STE) significantly decreased SBP compared to placebo in a mixed population of healthy volunteers and hypertensive patients. The BP-lowering effect was more pronounced among hypertensive patients. No significant BP effects were seen with other forms of tomato, lycopene and related products in the overall population or any subgroup of the population.

Efficacy and safety of chemopreventive agents on colorectal cancer incidence and mortality: systematic review and network meta-analysis.

BACKGROUND: Various interventions have been tested as primary prevention of colorectal cancers (CRC), but comprehensive evidence comparing them is absent. We examined the effects of various chemopreventive agents (CPAs) on CRC incidence and mortality. METHODS: We did a network meta-analysis based on a systematic review of randomized controlled trials (RCTs) that compared at least one CPA (aspirin, antioxidants, folic acid, vitamin B6, vitamin B12, calcium, vitamin D, alone or in combination) to placebo or other CPA in persons without history of CRC. Several databases were searched from inception up to March 2017. Primary outcomes were early and long-term CRC incidence and mortality. RESULTS: Twenty-one RCTs comprising 281,063 participants, 9 RCTS comprising 160,101 participants, and 7 RCTs comprising 24,001 participants were included in the network meta-analysis for early risk of CRC incidence, long-term risk of CRC incidence and mortality, respectively. For early CRC incidence, no CPAs were found to be effective. For long-term CRC incidence and mortality, aspirin was the only intervention that showed protective effects with potential dose-dependent effects (risk ratio [RR], 0.74 [95% CI, 0.57-0.97] for high-dose [≥325 mg/day] and RR, 0.81 [95% CI, 0.67-0.98] for very-low-dose [≤100 mg/day]). Similar trend was found for mortality (RR, 0.43 [95% CI, 0.23-0.81] for low-dose [>100-325 mg/day] and RR, 0.65 [95% CI, 0.45-0.94] for very-low-dose). However, in net clinical benefit analysis, when combining risk estimates on mortality from CRC, cardiovascular disease, and pooled risk estimates of major gastrointestinal bleeding, low-dose aspirin provided the highest net survival gain (%) of 1.736 [95% CI, 1.010-2.434]. CONCLUSION: Aspirin at the dose range of 75-325 mg/day is a safe and effective primary prevention for long-term CRC among people at average risk. None of the other CPAs were found to be effective. There may potentially be differential effects among various doses of aspirin that needs further investigation.

Comparative performance of pharmacogenetics-based warfarin dosing algorithms derived from Caucasian, Asian, and mixed races in Thai population.

AIM: This study was conducted to compare predictive accuracy of the available pharmacogenetics (PGx)-guided warfarin dosing algorithms derived from Caucasian, Asian, and mixed population to identify a suitable algorithm for Thai population. METHODS: Ten warfarin dosing algorithms derived from different population including Caucasian, East Asian, South-East Asian, and mixed races were selected and tested with clinical and genetic data of Thai patients. Comparative performances of these algorithms were tested using mean dose error (MDE) between actual warfarin maintenance dose (AWMD) and predicted dose generated by each dosing algorithm, and percentage of ideal dose prediction (IDP). Sensitivity analysis for predictive accuracy was also conducted by stratifying patients into low (AWMD ≤21 mg/wk), intermediate (AWMD >21 to <49 mg/wk), and high maintenance dose (AWMD ≥49 mg/wk) groups. RESULTS: Data of 165 patients were included for the analyses. Mean actual warfarin dose of the study population was 25.03 ± 10.53 mg/wk. Large variability of MDE, ranging from -12.11 to 11.24 mg/wk, among algorithms was observed. International Warfarin Pharmacogenetics Consortium, Gage et al, and Ohno et al algorithms had comparable performances to Sangviroon et al algorithm, as observed by MDE of <1 mg/wk with percentage of IDP ≥40%. Further sensitivity analyses among patients requiring low and intermediate maintenance doses confirmed such findings with IDP percentage ranging from 37.8% to 59.2%. Among high-dose group, only Ohno et al and Sarapakdi et al algorithms had acceptable performance. CONCLUSIONS: Warfarin PGx-guided dosing algorithms derived from large, mixed population performed comparably to Sangviroon et al algorithm. Certain algorithms should be avoided due to significant dose prediction error.

Assessing evidence of interaction between smoking and warfarin: a systematic review and meta-analysis.

BACKGROUND: Chronic smoking, theoretically, can interfere with warfarin metabolism through enzyme-inducing effects of polycyclic aromatic hydrocarbons. However, clinical evidence of interactions between warfarin and smoking are inconclusive. This study aimed to systematically review all relevant clinical evidence of this interaction. METHODS: We performed a systematic search using computerized databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, CINAHL, Allied and Complementary Medicine, PsycINFO, International Pharmaceutical Abstracts, and ClinicalTrials.gov from 1966 to December 2008. Keywords included "warfarin" with "smoking," "tobacco," "cigarette," and "polycyclic aromatic hydrocarbons." Original articles reporting interaction between warfarin and smoking were included. All articles were reviewed independently by two investigators for study design, population, outcomes, and quality of evidence. RESULTS: Of the 1,240 studies retrieved, one experimental pharmacokinetic study and 12 cross-sectional studies were included. The pooled analyses of multivariate studies suggested that smoking was associated with a 12.13% (95% CI, 6.999-17.265; P < .001) increase in warfarin dosage requirement and an additional 2.26 mg (95% CI, 2.529-7.042; P = .355) per week compared with nonsmoking. Additional sensitivity analysis of four multivariate studies with adjustment for pharmacogenomic factors suggested that smoking was associated with a 13.21% (95% CI, 8.59%-17.83%; P < .001) increase in warfarin dosage requirement compared with nonsmokers. Results of an experimental pharmacokinetic study lend theoretical support to the findings. CONCLUSIONS: Evidence suggests that smoking may potentially cause significant interaction with warfarin by increasing warfarin clearance, which leads to reduced warfarin effects. Close monitoring of warfarin therapy should be instituted when there is a change in smoking status of patients requiring warfarin therapy.