ORIGINAL ARTICLE The effect of ginseng (genus Panax) on blood pressure: a systematic review and meta-analysis of randomized controlled clinical trials AM Komishon 1,2 , E Shishtar 1,2 , V Ha 1,2 , JL Sievenpiper 1,3,4 , RJ de Souza 1,5 , E Jovanovski 1,2,6 , HVT Ho 1,2 , LS Duvnjak 7 and V Vuksan 1,2,6,8 Pre-clinical evidence indicates the potential for ginseng to reduce cardiovascular disease risk and acutely aid in blood pressure (BP) control. Clinical evidence evaluating repeated ginseng exposure, however, is controversial, triggering consumer and clinician concern. A systematic review and meta-analysis were conducted to assess whether ginseng has an effect on BP. MEDLINE, EMBASE, Cochrane and CINAHL were searched for relevant randomized controlled trials X 4 weeks that compared the effect of ginseng on systolic (SBP), diastolic (DBP) and/or mean arterial (MAP) BPs to control. Two independent reviewers extracted data and assessed methodological quality and risk of bias. Data were pooled using random-effects models and expressed as mean differences (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed and quantified. Seventeen studies satisfied eligibility criteria (n = 1381). No significant effect of ginseng on SBP, DBP and MAP was found. Stratified analysis, although not significant, appears to favour systolic BP improvement in diabetes, metabolic syndrome and obesity (MD =  2.76 mm Hg (95% CI =  6.40, 0.87); P = 0.14). A priori subgroup analyses revealed significant association between body mass index and treatment differences (β =  0.95 mm Hg (95% CI =  1.56,  0.34); P = 0.007). Ginseng appears to have neutral vascular affects; therefore, should not be discouraged for concern of increased BP. More high-quality, randomized, controlled trials assessing BP as a primary end point, and use of standardized ginseng root or extracts are warranted to limit evidence of heterogeneity in ginseng research and to better understand its cardiovascular health potential. Journal of Human Hypertension advance online publication, 14 April 2016; doi:10.1038/jhh.2016.18 INTRODUCTION Hypertension (HTN) remains a significant risk factor for cardiovas- cular disease, affecting more than 1 billion individuals world- wide and accounting for ~ 9.4 million deaths per year. 1 Despite improvement in detection and treatment strategies, blood pressure (BP) control remains elusive. With pursuit for more effective management strategies, there has been growing interest in the use of medicinal herbs, with ginseng emerging as a serious contender. The herb ginseng has long-been considered by Asian pharma- copeia as a ‘cure-all’ tonic and valued for its exceptional therapeutic properties. Consequently, ginseng has been studied extensively, with growing evidence attributing its pharmacological effects to the presence of triterpenoid saponins, known as ginsenosides. Despite its therapeutic promise, ginseng is often unwarrantedly avoided by consumers and practitioners, because of clinically unproven concerns from an early observational study suggesting it may adversely affect BP. 2 Pre-clinical research has consistently contradicted these findings, suggesting ginseng and its individual ginsenosides have the potential to acutely reduce BP. 3–6 Clinical evidence to support these findings, however, remains controversial. 7–14 To clarify uncertainty and to assess whether ginseng has an effect on systolic (SBP), diastolic (DBP) and mean arterial (MAP) BPs, a systematic review and meta- analysis of randomized controlled trials (RCTs) were conducted. MATERIALS AND METHODS The Cochrane Handbook for Systematic Reviews of Interventions was used as a guideline for this meta-analysis and reporting of results followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. 15 The review protocol is available at the ClinicalTrials.gov (registration no. NCT01913210). Study selection Relevant RCTs were identified using MEDLINE, EMBASE, Cochrane Central and CINAHL, through 28 April 2014, with the search strategy: Panax OR ginseng OR ninjin OR renshen OR shinseng OR jen shen OR schinseng OR quinquefolius OR ginsenosides AND Blood Pressure OR BP OR diastolic pressure OR systolic pressure OR SBP OR DBP OR MAP OR mean arterial pressure. Manual searches of references cited by published studies supplemented the electronic search. Eligible RCTs were those that investigated the effect of ginseng of the genus Panax on SBP, DBP and/ or MAP, for minimum 4 weeks. Trials less than 4 weeks in duration, lacked suitable control, had no viable end point data and where ginseng was part of a multi-herbal treatment were excluded. Duration of 4 weeks was chosen as it is suggested to be a minimal recommended period to 1 Clinical Nutrition and Risk Factor Modification Centre, St Michael’s Hospital, Toronto, Ontario, Canada; 2 Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; 3 Department of Pathology, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada; 4 Department of Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada; 5 Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; 6 Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada; 7 School of Medicine University of Zagreb, University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Zagreb, Croatia and 8 Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Correspondence: Professor V Vuksan, Clinical Nutrition and Risk Factor Modification Centre, St Michael’s Hospital, 193 Yonge Street, Toronto, Ontario, Canada M5B 1M8. E-mail: v.vuksan@utoronto.ca Received 6 September 2015; revised 3 March 2016; accepted 14 March 2016 Journal of Human Hypertension (2016), 1 – 8 © 2016 Macmillan Publishers Limited All rights reserved 0950-9240/16 www.nature.com/jhh