Garcia Garcia MA1*, Rosero Arenas MA2, Martinez Cornejo A1 and Perez Lluna L3
1UCI Hospital Sagunto, Valencia, Spain 2C Salud Cheste, Valencia, Spain 3Servicio M. Interna Hospital Sagunto, Valencia, Spain
Received: 10 March, 2016; Accepted: 11 April, 2016; Published: 12 April, 2016
Miguel Angel Garcia Garcia, Avenida Doctor Peset Aleixandre No. 81 gate 21 , 46009 Valencia , SPAIN, Intensive Care Unit, Hospital de Sagunto, 46520 Puerto de Sagunto / Valencia, SPAIN, Tel: 03699743390; E-mail:
Garcia Garcia MA, Rosero Arenas MA, Martinez CA, Perez LL (2016) Usefullness of Phytoestrogens in Treatment of Arterial Hypertension. Systematic Review and Meta-Analysis: Un Update. Arch Clin Hypertens 2(1): 013-018.
© 2016 Garcia Garcia MA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Phytoestrogens, Isoflavones; Soy protein; Blood pressure; Meta-analysis
Background: It has been suggested that phytoestrogens may have utility in the control of arterial hypertension.
Methods: We performed a systematic review and meta-analysis of randomized controlled trials, and the main outcome was the decrease of blood pressure.
Results: Decrease in systolic (- 0,15 mmHg, CI 95% from -0,24 to -0,05) and diastolic (-0,14 mmHg, CI 95% from -0,25 to -0,03) blood pressure were observed in patients taking phytoestrogens, but this difference was not clinically relevant. There can be a little greater decrease in Asian patients and in patients with higher baseline blood pressure values.
Conclusion: The global effect of phytoestrogens seems of small amount in reducing blood pressure. Nevertheless, it has not been realized a clinical trials about the efficacy of these products in no mild hypertensive patients, similar to real life.
Introduction and Background
Soy is a legume of Asian origin that contains 2 main components, phytoestrogens (PHE) and soy protein (SP), whose beneficial effects on the cardiovascular system (among other) have been studied over the last 30 years. It has been described its benefits to improve lipid and glycemic profiles, as well as to reduce the harmful effects of cardiovascular (CV) risk factors. Other benefits attributed to soy and its derivate (PHE and SP) are: reduce the symptoms associated with menopause, osteoporosis fractures and progression of metastatic cancers (prostate, breast, lung, stomach, etc).
It has been suggested that PHE may have utility in the control of arterial hypertension. This disease affects 1000 millions of people all around the world and is a modifiable cardiovascular risk factor . Its prevalence in adults is elevated (26,4%) , with an improbable control . An increase of BP (20/10 mmHg) is associated with doubling the risk of CV disease, and on the other side, reductions of 4-5/2-3 mmHg are associated with lower risk of CV disease [4,5]. Adecuate dietary intervention with proper medical therapy are important in controlling blood pressure (BP) according to American Heart Association (AHA) and the Seventh Report of the Joint National Committee (JNC 7) [4,6].
The Food and Drug Administration (FDA) has recommended intake of 25 g of SP , to leverage its cardio protective effects, which could be related to its agonist action on estrogenic receptor. The main described PHE are isoflavones (IF) and their active principles daidzein and genistein. They could produce arterial vasodilatation, improvement of endothelial function and decrease of BP in animals, all these effects mediated by nitric oxide mechanisms . Previous clinical trials and meta-analysis [9-11], have previously shown inconsistent results: results without statistical significance or with little clinical impact , statistically significant reduction of systolic BP (SBP) , or statistically significant reduction of SBP and diastolic BP (DBP) ; these differences could be due to the different trials included in the numerical analysis, and different aspects of it (length of intervention, parallel vs cross-over design, amount of used active principle –IF or SP-, etc).
To clarify the usefulness of PHE in reducing BP, we performed a new systematic review and meta-analysis. It has been considered this time aspects such as: age of participants, the fact that BP is –or isn´t- the primary outcome in the design of the study, country, etc. In addition, several metaregresions have been performed to assess the mathematical relationship between BP reduction achieved and the initial BP, the dose of active principles, etc.
Material and Methods
Our systematic review is aimed at randomized clinical trials involving adult patients (older than 18 years), hypertensive and non-hypertensive, and the main objective of the study were controlling BP, cholesterol and other lipids levels, symptoms associated with menopause, osteoporosis, diabetes mellitus (including chronic complications), metastatic breast and lung cancer, etc.
The intervention in these studies was the addition of PHE, in capsule form or dietary supplement. The estimated IF (mg) or SP (g) daily amount was noted. The control treatment was placebo or an inactive derivate (milk protein, casseinate, etc). The measured result was the decrease in systolic and diastolic blood pressure during the study period.
This systematic review was registered on the web PROSPERO.
We have also made searching several databases such as PubMed, Embase, ClinicalTrials.gov, Trip Database and CENTRAL data base of Cochrane collaboration. The search strategy PUBMED was: “Phytoestrogens” (Mesh) OR “Isoflavones”(Mesh) OR “Soy Foods”(Mesh) OR “Soybeans”(Mesh) OR “daidzein” (Supplementary concept); filters: Clinical Trial Phase III; Clinical Trial Phase IV; Systematic Reviews; Humans. We obtained 197 studies (clinical trials and meta-analysis). The other search strategies were similar (Table A, Appendix).
We also looked for systematic reviews and meta-analysis reviews obtained through searches in PUBMED and Trip Database, although the primary outcome may or may not be the control of BP. We have not included in this search works published only in Chinese or Japanese language.
The analysis of the original works and data collection was carried out by pairs (MAG and MAR); in case of differences of opinion, the point of view of a third researcher (LPL) was required. The manuscript was translated into English by another researcher (AMC). The final review of the work was done by the four authors.
We have made an estimation of decrease in systolic and diastolic BP between the end of the active period and the initial moment. In all studies assessed, it has been measured BP at the start and at the end of intervention, in each treatment arm. The variables retrieved from the original work has been the variation of BP and standard deviation (SD). In those works where these data are described, they are incorporated directly into the estimation; in those works that didn´t include these data, calculations are made as described in Appendix. We performed a meta-analysis with a weighted mean difference according to the random effects model (Der Simonian and Laird) assessing the possible statistical heterogeneity between estimated effect in the included studies.
Study quality was estimated by Jadad´s scale , and with the risk of bias tool of the Cochrane collaboration. Finally, we have considered the Impact Factor of the journal where the work was published.
We valued the presence of publication bias using the funnel plot, and calculating the number of unpublished studies (Glesser-Olkin method). The presence of statistical heterogeneity was assessed using the Cochran - Q index and I 2 index. Finally we assessed the effect of small studies in the overall estimate with the Egger´s graphical method.
Statistical calculators and graphics were performed by STATA v.14 and REVMAN v.5.3 (Cochrane collaboration).
Flow-chart of evaluated and excluded studies are shown in Figure 1. After removing duplicate works and leaving out systematic reviews and observational studies, we finally left 346 clinical trials. Most of them (246) were not included because no BP was measured in them. Finally our work includes 100 clinical trials, and 71 were included in the mathematical elaboration (meta-analysis).