Ried Karin, Sullivan Thomas R, Fakler Peter, Frank Oliver R, Stocks Nigel P
National Institute of IntegrativeMedicine,Melbourne, Australia.
Cochrane Database Syst Rev. 2012 Aug 15(8):CD008893. doi: 10.1002/14651858.CD008893.pub2.
High blood pressure is an important risk factor for cardiovascular disease attributing to about 50% of cardiovascular events worldwide and 37% of cardiovascular related deaths in Western populations. Epidemiological studies suggest that cocoa rich products reduce the risk of cardiovascular disease. Flavanols found in cocoa have been shown to increase the formation of endothelial nitric oxide which promotes vasodilation and therefore blood pressure reduction. Previous meta-analyses have shown that cocoa-rich foods may reduce blood pressure. Recently additional trials had conflicting results.
To determine the effect of flavanol-rich chocolate or cocoa products on blood pressure in people with or without hypertension.
We searched the following electronic databases from inception to November 2011: Cochrane Hypertension Group Specialised Register, CENTRAL, MEDLINE and EMBASE. In addition we searched international trial registries, and the reference lists of review articles and included trials.
Randomised controlled trials (RCT) investigating the effects of chocolate or cocoa products on systolic and diastolic blood pressure in adults for a minimum of two weeks duration.
Two authors independently extracted data and assessed the risk of bias in each trial in consultation with a third author. Random effects meta-analyses on all studies fitting the inclusion criteria were conducted using Review Manager version 5.1 and Stata version 12. Heterogeneity was explored by subgroup analyses and univariate meta-regression analysis of several variables including dosage of flavanol content (total or monomers) in chocolate or cocoa products, blinding, baseline blood pressure, theobromine content, sugar content, body-mass-index (BMI), duration and age.
Twenty studies met the inclusion criteria. Meta-analyses of the 20 studies involving 856 mainly healthy participants revealed a statistically significant blood pressure reducing effect of flavanol-rich cocoa products compared with control in short-term trials of 2-18 weeks duration: Mean difference SBP (95%CI): -2.77 (-4.72, -0.82) mm Hg, p=0.005, n=20; mean difference DBP (95%CI): - 2.20 (-3.46, -0.93) mm Hg, p=0.006, n=19 available for DBP.Trials provided participants with 30-1080 mg of flavanols (mean=545.5 mg) in 3.6-105 g of cocoa products per day in the active intervention group. In half of the trials (n=10) the active group consumed 500-750 mg of flavanols per day. The control group received either a flavanol-free product (n=12) or a low-flavanol containing cocoa powder (6.4 and 41 mg flavanols, n=8). Subgroup meta-analysis of trials with a flavanol-free control group revealed a significant blood pressure reducing effect, in contrast to trials using a low-flavanol product in the control group. This analysis may have been confounded by trial duration and the level of blinding of participants.Trial duration was short (mean 4.4 weeks, range 2-8 weeks, n=19, and one trial of 18 weeks). A significant blood pressure reducing effect was evident in trials of 2 weeks duration (n=9), but not in trials of >2 weeks duration (n=11). It is important to note that seven out of the nine trials (78%) of 2 weeks duration also had a flavanol-free control group. Therefore, subgroup analysis by duration might be confounded by flavanol dosage used in the control groups, and the level of blinding of participants.Adverse effects including gastrointestinal complaints and distaste of the trial product were reported by 5% of patients in the active cocoa intervention group and 1% of patients in the control groups.
AUTHORS' CONCLUSIONS: Flavanol-rich chocolate and cocoa products may have a small but statistically significant effect in lowering blood pressure by 2-3 mm Hg in the short term.Our findings are limited by the heterogeneity between trials, which was explored by univariate meta-regression and subgroup analyses. Subgroup meta-analysis of trials using a flavanol-free control group revealed a significant blood pressure reducing effect of cocoa, whereas analysis of trials using a low-flavanol control product did not. While it appears that shorter trials of 2 weeks duration were more effective, analysis may be confounded by type of control and unblinding of participants, as the majority of 2-week trials also used a flavanol-free control and unblinding of participants. Results of these and other subgroup analyses based on, for example, age of participants, should be interpreted with caution and need to be confirmed or refuted in trials using direct randomized comparison.Long-term trials investigating the effect of cocoa products are needed to determine whether or not blood pressure is reduced on a chronic basis by daily ingestion of cocoa. Furthermore, long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events and to assess potential adverse effects associated with chronic ingestion of cocoa products.
高血压是心血管疾病的重要危险因素,全球约50%的心血管事件以及西方人群中37%的心血管相关死亡都归因于高血压。流行病学研究表明,富含可可的产品可降低心血管疾病风险。可可中含有的黄烷醇已被证明可增加内皮一氧化氮的生成,从而促进血管舒张,进而降低血压。以往的荟萃分析表明,富含可可的食物可能会降低血压。最近的其他试验结果相互矛盾。
确定富含黄烷醇的巧克力或可可产品对有或无高血压人群血压的影响。
我们检索了以下电子数据库,从建库至2011年11月:Cochrane高血压组专业注册库、Cochrane系统评价数据库、医学期刊数据库和荷兰医学文摘数据库。此外,我们还检索了国际试验注册库以及综述文章和纳入试验的参考文献列表。
随机对照试验(RCT),研究巧克力或可可产品对成年人收缩压和舒张压的影响,持续时间至少为两周。
两位作者独立提取数据,并与第三位作者协商评估每个试验的偏倚风险。使用Review Manager 5.1版和Stata 12版对所有符合纳入标准的研究进行随机效应荟萃分析。通过亚组分析和对几个变量的单变量荟萃回归分析来探讨异质性,这些变量包括巧克力或可可产品中黄烷醇含量(总量或单体)的剂量、盲法、基线血压、可可碱含量、糖含量、体重指数(BMI)、持续时间和年龄。
20项研究符合纳入标准。对涉及856名主要为健康参与者的20项研究进行的荟萃分析显示,在为期2 - 18周的短期试验中,与对照组相比,富含黄烷醇的可可产品具有统计学上显著的降血压效果:收缩压平均差异(95%CI):-2.77(-4.72,-0.82)mmHg,p = 0.005,n = 20;舒张压平均差异(95%CI):-2.20(-3.46,-0.93)mmHg,p = 0.006,有19项研究可用于舒张压分析。在活性干预组中,试验每天为参与者提供3.6 - 105克可可产品,其中含有30 - 1080毫克黄烷醇(平均 = 545.5毫克)。在一半的试验(n = 10)中,活性组每天摄入500 - 750毫克黄烷醇。对照组接受无黄烷醇产品(n = 12)或含低黄烷醇可可粉(6.4和41毫克黄烷醇,n = 8)。对使用无黄烷醇对照组的试验进行亚组荟萃分析显示有显著的降血压效果,而使用低黄烷醇产品作为对照组的试验则不然。该分析可能因试验持续时间和参与者的盲法水平而受到混淆。试验持续时间较短(平均4.4周,范围2 - 8周,n = 19,还有一项18周的试验)。在为期2周的试验(n = 9)中有显著的降血压效果,但在持续时间>2周的试验(n = 11)中则没有。需要注意的是,9项为期2周的试验中有7项(78%)也使用了无黄烷醇对照组。因此,按持续时间进行的亚组分析可能会因对照组中使用的黄烷醇剂量以及参与者的盲法水平而受到混淆。活性可可干预组中有5%的患者报告了包括胃肠道不适和对试验产品厌恶在内的不良反应,对照组中有1%的患者报告了此类不良反应。
富含黄烷醇的巧克力和可可产品在短期内可能有微小但在统计学上显著的降血压效果,可使血压降低2 - 3 mmHg。我们的研究结果受到试验间异质性的限制,通过单变量荟萃回归和亚组分析对此进行了探讨。对使用无黄烷醇对照组的试验进行亚组荟萃分析显示可可有显著的降血压效果,而对使用低黄烷醇对照产品的试验分析则未显示。虽然似乎为期2周的较短试验更有效,但分析可能会因对照类型和参与者的非盲法而受到混淆,因为大多数为期2周的试验也使用了无黄烷醇对照且参与者未设盲。基于例如参与者年龄等因素的这些及其他亚组分析结果应谨慎解读,并且需要在使用直接随机对照的试验中得到证实或反驳。需要进行长期试验来研究可可产品的效果,以确定每日摄入可可是否能长期降低血压。此外,还需要进行长期试验来研究可可对临床结局的影响,以评估可可是否对心血管事件有影响,并评估与长期摄入可可产品相关的潜在不良反应。