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A Greater Flavonoid Intake Is Associated with Lower Total and Cause-Specific Mortality: A Meta-Analysis of Cohort Studies.
Mazidi, M, Katsiki, N, Banach, M
Nutrients. 2020;(8)
Abstract
Introduction: The links between flavonoid intake and mortality were previously evaluated in epidemiological studies. The aim of the present study was to perform a systematic review and meta-analysis of cohort studies evaluating the link of flavonoid consumption with total and cause-specific mortality. Methods: Prospective cohort studies reporting flavonoid intake and mortality data published up to 30th April 2019 (without language restriction) were searched using PubMed, Scopus and EMBASE database. Generic inverse variance methods and random effects models were used to synthesize pooled and quantitative data. Sensitivity analysis was also performed by a leave-one-out method. Results: Overall, 16 articles met the inclusion criteria (nine studies were performed in Europe, five in the USA, one in Asia and one in Oceania); a total of 462,194 participants (all adults aged >19 years) with 23,473 mortality cases were included in the final analysis. The duration of follow-up ranged from 4.8 to 28 years. Most of the studies assessed flavonoid intake using food frequency questionnaires, whereas four studies used interviews and 1 study used 4-day food records. The meta-analysis showed that flavonoid consumption was inversely and significantly associated with total (relative risk (RR): 0.87, 95% confidence interval (CI) = 0.77-0.99) and cardiovascular disease mortality risk (RR: 0.85, 95%CI = 0.75-0.97), but not cancer (0.86, 95%CI = 0.65-1.14) mortality risk. These findings remained robust in sensitivity analyses. Conclusions: The present findings highlight the potential protective role of flavonoids against total and cause-specific mortality. These results support the recommendations for flavonoid-rich foods intake to prevent chronic diseases.
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Pine bark (Pinus spp.) extract for treating chronic disorders.
Robertson, NU, Schoonees, A, Brand, A, Visser, J
The Cochrane database of systematic reviews. 2020;(9):CD008294
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Abstract
BACKGROUND Pine bark (Pinus spp.) extract is rich in bioflavonoids, predominantly proanthocyanidins, which are antioxidants. Commercially-available extract supplements are marketed for preventing or treating various chronic conditions associated with oxidative stress. This is an update of a previously published review. OBJECTIVES To assess the efficacy and safety of pine bark extract supplements for treating chronic disorders. SEARCH METHODS We searched three databases and three trial registries; latest search: 30 September 2019. We contacted the manufacturers of pine bark extracts to identify additional studies and hand-searched bibliographies of included studies. SELECTION CRITERIA Randomised controlled trials (RCTs) evaluating pine bark extract supplements in adults or children with any chronic disorder. DATA COLLECTION AND ANALYSIS Two authors independently assessed trial eligibility, extracted data and assessed risk of bias. Where possible, we pooled data in meta-analyses. We used GRADE to evaluate the certainty of evidence. Primary outcomes were participant- and investigator-reported clinical outcomes directly related to each disorder and all-cause mortality. We also assessed adverse events and biomarkers of oxidative stress. MAIN RESULTS This review included 27 RCTs (22 parallel and five cross-over designs; 1641 participants) evaluating pine bark extract supplements across 10 chronic disorders: asthma (two studies; 86 participants); attention deficit hyperactivity disorder (ADHD) (one study; 61 participants), cardiovascular disease (CVD) and risk factors (seven studies; 338 participants), chronic venous insufficiency (CVI) (two studies; 60 participants), diabetes mellitus (DM) (six studies; 339 participants), erectile dysfunction (three studies; 277 participants), female sexual dysfunction (one study; 83 participants), osteoarthritis (three studies; 293 participants), osteopenia (one study; 44 participants) and traumatic brain injury (one study; 60 participants). Two studies exclusively recruited children; the remainder recruited adults. Trials lasted between four weeks and six months. Placebo was the control in 24 studies. Overall risk of bias was low for four, high for one and unclear for 22 studies. In adults with asthma, we do not know whether pine bark extract increases change in forced expiratory volume in one second (FEV1) % predicted/forced vital capacity (FVC) (mean difference (MD) 7.70, 95% confidence interval (CI) 3.19 to 12.21; one study; 44 participants; very low-certainty evidence), increases change in FEV1 % predicted (MD 7.00, 95% CI 0.10 to 13.90; one study; 44 participants; very low-certainty evidence), improves asthma symptoms (risk ratio (RR) 1.85, 95% CI 1.32 to 2.58; one study; 60 participants; very low-certainty evidence) or increases the number of people able to stop using albuterol inhalers (RR 6.00, 95% CI 1.97 to 18.25; one study; 60 participants; very low-certainty evidence). In children with ADHD, we do not know whether pine bark extract decreases inattention and hyperactivity assessed by parent- and teacher-rating scales (narrative synthesis; one study; 57 participants; very low-certainty evidence) or increases the change in visual-motoric coordination and concentration (MD 3.37, 95% CI 2.41 to 4.33; one study; 57 participants; very low-certainty evidence). In participants with CVD, we do not know whether pine bark extract decreases diastolic blood pressure (MD -3.00 mm Hg, 95% CI -4.51 to -1.49; one study; 61 participants; very low-certainty evidence); increases HDL cholesterol (MD 0.05 mmol/L, 95% CI -0.01 to 0.11; one study; 61 participants; very low-certainty evidence) or decreases LDL cholesterol (MD -0.03 mmol/L, 95% CI -0.05 to 0.00; one study; 61 participants; very low-certainty evidence). In participants with CVI, we do not know whether pine bark extract decreases pain scores (MD -0.59, 95% CI -1.02 to -0.16; one study; 40 participants; very low-certainty evidence), increases the disappearance of pain (RR 25.0, 95% CI 1.58 to 395.48; one study; 40 participants; very low-certainty evidence) or increases physician-judged treatment efficacy (RR 4.75, 95% CI 1.97 to 11.48; 1 study; 40 participants; very low-certainty evidence). In type 2 DM, we do not know whether pine bark extract leads to a greater reduction in fasting blood glucose (MD 1.0 mmol/L, 95% CI 0.91 to 1.09; one study; 48 participants;very low-certainty evidence) or decreases HbA1c (MD -0.90 %, 95% CI -1.78 to -0.02; 1 study; 48 participants; very low-certainty evidence). In a mixed group of participants with type 1 and type 2 DM we do not know whether pine bark extract decreases HbA1c (MD -0.20 %, 95% CI -1.83 to 1.43; one study; 67 participants; very low-certainty evidence). In men with erectile dysfunction, we do not know whether pine bark extract supplements increase International Index of Erectile Function-5 scores (not pooled; two studies; 147 participants; very low-certainty evidence). In women with sexual dysfunction, we do not know whether pine bark extract increases satisfaction as measured by the Female Sexual Function Index (MD 5.10, 95% CI 3.49 to 6.71; one study; 75 participants; very low-certainty evidence) or leads to a greater reduction of pain scores (MD 4.30, 95% CI 2.69 to 5.91; one study; 75 participants; very low-certainty evidence). In adults with osteoarthritis of the knee, we do not know whether pine bark extract decreases composite Western Ontario and McMaster Universities Osteoarthritis Index scores (MD -730.00, 95% CI -1011.95 to -448.05; one study; 37 participants; very low-certainty evidence) or the use of non-steroidal anti-inflammatory medication (MD -18.30, 95% CI -25.14 to -11.46; one study; 35 participants; very low-certainty evidence). We do not know whether pine bark extract increases bone alkaline phosphatase in post-menopausal women with osteopenia (MD 1.16 ug/L, 95% CI -2.37 to 4.69; one study; 40 participants; very low-certainty evidence). In individuals with traumatic brain injury, we do not know whether pine bark extract decreases cognitive failure scores (MD -2.24, 95% CI -11.17 to 6.69; one study; 56 participants; very low-certainty evidence) or post-concussion symptoms (MD -0.76, 95% CI -5.39 to 3.87; one study; 56 participants; very low-certainty evidence). For most comparisons, studies did not report outcomes of hospital admissions or serious adverse events. AUTHORS' CONCLUSIONS Small sample sizes, limited numbers of RCTs per condition, variation in outcome measures, and poor reporting of the included RCTs mean no definitive conclusions regarding the efficacy or safety of pine bark extract supplements are possible.
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Effect of Pycnogenol on Blood Pressure: Findings From a PRISMA Compliant Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled, Clinical Studies.
Fogacci, F, Tocci, G, Sahebkar, A, Presta, V, Banach, M, Cicero, AFG
Angiology. 2020;(3):217-225
Abstract
Results of previous clinical trials evaluating the effect of pycnogenol supplementation on blood pressure (BP) are controversial. Therefore, we aimed to assess the impact of pycnogenol on BP through a systematic review of literature and meta-analysis of available randomized, double-blind, placebo-controlled clinical studies (randomized clinical trials [RCTs]). Literature search included SCOPUS, PubMed-Medline, ISI Web of Science, and Google Scholar databases up to January 10, 2019 to identify RCTs investigating the impact of pycnogenol on BP. Two investigators independently extracted data on study characteristics, methods, and outcomes. This systematic review and meta-analysis is registered in International Prospective Register of Systematic Reviews (PROSPERO) under number CRD42018112172. Overall, the impact of pycnogenol on BP was reported in 7 trials involving 626 participants. Meta-analysis did not suggest any significant improvement in systolic BP (weighted mean difference [WMD]: -0.028 mm Hg; 95% confidence interval [CI]: -0.182 to 0.127; P = .726; I2 = 46%), diastolic BP (WMD: -0.144 mm Hg; 95% CI: -0.299 to 0.010; P = .067; I2 = 0%), mean arterial pressure (WMD: -0.091 mm Hg; 95% CI: -0.246 to 0.063; P = .246; I2 = 0%), and pulse pressure (WMD: -0.003 mm Hg; 95% CI: -0.151 to 0.158; P = .966; I2 = 0%) following pycnogenol treatment. Results persisted in the leave-one-out sensitivity analysis. Therefore, the present meta-analysis does not suggest any significant effect of pycnogenol on BP.
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Dietary intakes of flavan-3-ols and cardiometabolic health: systematic review and meta-analysis of randomized trials and prospective cohort studies.
Raman, G, Avendano, EE, Chen, S, Wang, J, Matson, J, Gayer, B, Novotny, JA, Cassidy, A
The American journal of clinical nutrition. 2019;(5):1067-1078
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BACKGROUND Although available data suggest that some dietary flavan-3-ol sources reduce cardiometabolic risk, to our knowledge no review has systematically synthesized their specific contribution. OBJECTIVE We aimed to examine, for the first time, if there is consistent evidence that higher flavan-3-ol intake, irrespective of dietary source, reduces cardiometabolic risk. METHODS MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau abstracts were searched for prospective cohorts and randomized controlled trials (RCTs) published from 1946 to March 2019 on flavan-3-ol intake and cardiovascular disease (CVD) risk. Random-effects models meta-analysis was used. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach assessed the strength of evidence. RESULTS Of 15 prospective cohorts (23 publications), 4 found highest compared with lowest habitual intakes of flavan-3-ols were associated with a 13% reduction in risk of CVD mortality and 2 found a 19% reduction in risk of chronic heart disease (CHD) incidence. Highest compared with lowest habitual intakes of monomers were associated with a reduction in risk of type 2 diabetes mellitus (T2DM) (n = 5) and stroke (n = 4) (10% and 18%, respectively). No association was found for hypertension. Of 156 RCTs, flavan-3-ol intervention resulted in significant improvements in acute/chronic flow-mediated dilation (FMD), systolic (SBP) and diastolic blood pressure (DBP), total cholesterol (TC), LDL and HDL cholesterol, triglycerides (TGs), hemoglobin A1c (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR). All analyses, except HbA1c, were associated with moderate/high heterogeneity. When analyses were limited to good methodological quality studies, improvements in TC, HDL cholesterol, SBP, DBP, HOMA-IR, and acute/chronic FMD remained significant. In GRADE evaluations, there was moderate evidence in cohort studies that flavan-3-ol and monomer intakes were associated with reduced risk of CVD mortality, CHD, stroke, and T2DM, whereas RCTs reported improved TC, HDL cholesterol, SBP, and HOMA-IR. CONCLUSIONS Available evidence supports a beneficial effect of flavan-3-ol intake on cardiometabolic outcomes, but there was considerable heterogeneity in the meta-analysis. Future research should focus on an integrated intake/biomarker approach in cohorts and high-quality dose-response RCTs. This review was registered at www.crd.york.ac.uk/PROSPERO/ as CRD42018035782.
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Effects of pycnogenol on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials.
Malekahmadi, M, Moradi Moghaddam, O, Firouzi, S, Daryabeygi-Khotbehsara, R, Shariful Islam, SM, Norouzy, A, Soltani, S
Pharmacological research. 2019;:104472
Abstract
AIM: Clinical trials on the effect of pycnogenol supplementation on cardiometabolic health have been controversial. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the potential effect of pycnogenol supplementation on cardiometabolic profile. METHODS PubMed, Scopus, and ISI Web of Science databases were searched until October 2018. RCTs that evaluated the effects of pycnogenol on cardiometabolic parameters were included. DerSimonian and Laird random-effect models were used to compute the weighted mean differences (WMDs) and 95% confidence intervals (CIs). RESULTS Twenty-four RCTs including 1594 participants were included in the meta-analysis. Pycnogenol significantly reduced fasting blood glucose (WMD: -5.86 mg/dl; 95% CI: -9.56, -2.15), glycated hemoglobin (WMD = -0.29%, 95%CI: -0.56, -0.01), systolic blood pressure (WMD: -2.54 mmhg; 95% CI: -4.08, -0.99), diastolic blood pressure (WMD: -1.76 mmhg; 95% CI: -3.12, -0.41), body mass index (WMD: -0.47 kg/m2; 95% CI: -0.90, -0.03), LDL cholesterol (WMD: -7.12 mg/dl; 95% CI: -13.66, -0.58) and increased HDL cholesterol (WMD: 3.27 mg/dl; 95% CI: 0.87, 5.66). CONCLUSION This meta-analysis suggests that pycnogenol may have a role in preventing cardiometabolic disease. However, further well-designed RCTs are recommended to evaluate its long-term effects and explore the optimal duration of use and dosage.
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Flavonoid subclasses and type 2 diabetes mellitus risk: a meta-analysis of prospective cohort studies.
Guo, XF, Ruan, Y, Li, ZH, Li, D
Critical reviews in food science and nutrition. 2019;(17):2850-2862
Abstract
Epidemiological studies have suggested controversial associations between flavonoid subclasses and type 2 diabetes mellitus (T2DM) risk. The aim of the present meta-analysis was to quantitatively estimate these associations with prospective cohort study. A systematic literature search in PubMed and Scopus databases was performed up to May 2018. Multivariate-adjust relative risks (RRs) with corresponding 95% confidence intervals (CIs) for the highest versus the lowest category were pooled by using a random-effects model. Using restricted cubic spline regression model, non-linear dose-response analysis was estimated. Nine independent prospective cohort studies with 172,058 participants and 16910 events were included. Dietary intakes of flavanols, flavonols, flavan-3-ols and isoflavones were inversely associated with T2DM risk, and the summary RRs were 0.86 (95%CI: 0.77, 0.97), 0.91 (95%CI: 0.85, 0.98), 0.90 (95%: 0.82, 0.99) and 0.91 (95%CI: 0.84, 0.98), respectively. Dose-response analysis showed that 135 mg/day increment of flavanols (95%CI: 0.92, 0.96; P for trend <0.001), 50 mg/day increment of flavonols (95%CI: 0.88, 0.99, P for trend = 0.021), 68 mg/day increment of flavan-3-ols (95%CI: 0.92, 0.96, P for trend <0.001), or 1.8 mg/day increment of isoflavones (95%CI: 0.92, 0.97, P for trend <0.001) were associated with 6% reduction in T2DM risk. Non-significant association was observed with respect to flavanones and flavones. The present meta-analysis provides substantial evidence that dietary intakes of flavanols, flavonols, flavan-3-ols and isoflavones were inversely associated with T2DM risk, respectively. Higher dietary intakes of flavanol-, flavonol-, flavan-3-ol- and isoflavone-foods would have beneficial effects for protection against T2DM.
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Flavonoids intake and risk of type 2 diabetes mellitus: A meta-analysis of prospective cohort studies.
Xu, H, Luo, J, Huang, J, Wen, Q
Medicine. 2018;(19):e0686
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Epidemiological studies exploring the role of flavonoids intake in preventing type 2 diabetes mellitus (T2DM) showed inconsistent results. Therefore, we performed a meta-analysis of relevant studies to examine the relationship between flavonoids intake and risk of T2DM. We hypothesized that flavonoids intake may decrease the risk of developing T2DM.A systematical search in PubMed and Embase until September 2017 was performed to identify eligible prospective cohort studies. The summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effect models. Dose-response pattern between total flavonoids intake and T2DM risk was also estimated.Eight prospective studies were included with 312,015 participants, of whom 19,953 developed T2DM during the follow-up periods of 4 to 28 years. Compared with lower consumption, high intake of total flavonoids was associated with a decreased risk of T2DM (RR: 0.89, 95% CI: 0.82-0.96). Among flavonoid subclasses, inverse correlations with T2DM were achieved for intakes of anthocyanidins, flavan-3-ols, flavonols, and isoflavones. Dose-response meta-analysis indicated a curvilinear relationship between total flavonoids intake and incident T2DM (P for nonlinearity = .042), with a significant risk reduction at an intake of ≥550 mg/day. When assuming a linear pattern, the risk of T2DM was decreased by 5% for each 300-mg/day increment in total flavonoids intake (RR: 0.95, 95% CI: 0.93-0.97).Our study suggests that higher intakes of total flavonoids and subclasses (anthocyanidins, flavan-3-ols, flavonols, and isoflavones) are associated with lower risk of T2DM.
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Dietary Flavonoids and the Risk of Colorectal Cancer: An Updated Meta-Analysis of Epidemiological Studies.
Chang, H, Lei, L, Zhou, Y, Ye, F, Zhao, G
Nutrients. 2018;(7)
Abstract
Aim: The aim of this study was to perform an up-to-date meta-analysis of the association between the intake of dietary flavonoids and the risk of colorectal cancer. Methods: The PubMed and EMBASE databases were searched to identify eligible studies. The risk of colorectal cancer for the highest versus the lowest categories of flavonoids intake were assessed. Results: A total of 12 studies (5 cohort and 7 case-control studies) involving 17,481 cases and 740,859 controls were eligible for meta-analysis. High intake of dietary flavonols, flavones and anthocyanidins may decrease the risk of colorectal cancer; the pooled odds ratio (OR) for the highest intake compared with the lowest was 0.70 (0.54⁻0.90), 0.79 (0.83⁻0.99) and 0.78 (0.64⁻0.95), respectively. No association between the intake of total flavonoids, flavanones or flavan-3-ols and the risk of colorectal cancer was observed. Furthermore, the data showed that high intake of flavonols may decrease the risk of colon cancer [0.80 (0.68⁻0.94)] but not rectal cancer [0.93 (0.74⁻1.18)], while on the contrary, the intake of flavones may decrease rectal cancer risk [0.82 (0.70⁻0.97)] but not colon cancer risk [0.88 (0.69⁻1.13)]. Conclusions: The present study suggested that high intake of flavonols (such as quercetin) may reduce the risk of colon cancer, and high intake of flavones (such as apigenin) may reduce the risk of rectal cancer.
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Dietary total flavonoids intake and risk of mortality from all causes and cardiovascular disease in the general population: A systematic review and meta-analysis of cohort studies.
Liu, XM, Liu, YJ, Huang, Y, Yu, HJ, Yuan, S, Tang, BW, Wang, PG, He, QQ
Molecular nutrition & food research. 2017;(6)
Abstract
SCOPE Epidemiologic studies assessing the association between dietary total flavonoids intake and the risk of mortality from cardiovascular disease (CVD) and all causes have yielded inconsistent results. Therefore, we conducted a dose-response meta-analysis to investigate this association. METHOD AND RESULTS We searched PubMed and Embase databases from January 1966 through May 2016 and examined the references of retrieved articles to identify relevant prospective cohort studies. The random-effect model was used to calculate the summary risk estimates and dose-response analysis was performed. Ten studies were included in the present meta-analysis. The relative risk (RR) of all-cause mortality for the highest versus lowest category of total flavonoids intake was 0.82 (95% confidence interval (CI): 0.72-0.92). Dose-response analysis showed that those consuming 200 mg/day of total flavonoids had the lowest risk of all-cause mortality. Furthermore, a marginally significant association was found between dietary total flavonoids consumption and risk of death from CVD (summary RR: 0.85; 95% CI: 0.70-1.03; P = 0.099) and coronary heart diseases (summary RR: 0.74; 95% CI: 0.54-1.02; P = 0.069), respectively. CONCLUSION The meta-analysis provides strong evidence for the recommendation of consuming flavonoids-rich food to reduce risks of mortality from all causes as part of a healthy diet among general adults.
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Dietary Flavonoid and Lignan Intake and Mortality in Prospective Cohort Studies: Systematic Review and Dose-Response Meta-Analysis.
Grosso, G, Micek, A, Godos, J, Pajak, A, Sciacca, S, Galvano, F, Giovannucci, EL
American journal of epidemiology. 2017;(12):1304-1316
Abstract
Recent evidence has suggested that flavonoid and lignan intake may be associated with decreased risk of chronic and degenerative diseases. The aim of this meta-analysis was to assess the association between dietary flavonoid and lignan intake and all-cause and cardiovascular disease (CVD) mortality in prospective cohort studies. A systematic search was conducted in electronic databases to identify studies published from January 1996 to December 2015 that satisfied inclusion/exclusion criteria. Risk ratios and 95% confidence intervals were extracted and analyzed using a random-effects model. Nonlinear dose-response analysis was modeled by using restricted cubic splines. The inclusion criteria were met by 22 prospective studies exploring various flavonoid and lignan classes. Compared with lower intake, high consumption of total flavonoids was associated with decreased risk of all-cause mortality (risk ratio = 0.74, 95% confidence intervals: 0.55, 0.99), while a 100-mg/day increment in intake led to a (linear) decreased risk of 6% and 4% of all-cause and CVD mortality, respectively. Among flavonoid classes, significant results were obtained for intakes of flavonols, flavones, flavanones, anthocyanidins, and proanthocyanidins. Only limited evidence was available on flavonoid classes and lignans and all-cause mortality. Findings from this meta-analysis indicated that dietary flavonoids are associated with decreased risk of all-cause and CVD mortality.