Berberine for the treatment of hypertension: A systematic review

Abstract

Background: Hypertension is the highest risk factor for disease globally. When prescription of drug therapy is recommended, patients might decline treatment due to hypertension asymptomatic nature, sometimes turning to alternative therapies. One popular therapy is berberine, a plant alkaloid that has been used in eastern medicine for millennia to treat several ailments, including cardiovascular diseases and their risk factors.

Aims: Through a transparent and pragmatic approach towards searching, synthesising, assessing, and reporting the available clinical evidence, the present review aimed to investigate berberine effect on blood pressure and cardiovascular disease risk. It also intended to provide guidance for clinician when advising their patients, and to highlight gaps in the research along offering suggestions to fill them.

Methods: The review was conducted following the protocol PRISMA-P, and reported according to the related PRISMA statement. The PICO framework was used to define the scope of the review, and to arrive at a database search strategy. The strategy was run on the databases Medline, CINAHL, AMED, Embase, and Cochrane Library through the platforms EBSCOhost and Ovid. Citations were exported to Mendeley citation manger for screening. Relevant studies were selected based on specified inclusion and exclusion criteria. Data from included studies was extracted in the form of a detailed table of characteristics of studies, and summarised in an evidence table. Quality of studies was assessed using the SIGN methodology checklist for controlled trials. The results from the quality assessment were summarised through an adaptation of the Robvis tool software package output. Effect estimates and their precision were calculated with RevMan 5 computer program from the extracted study outcomes.

Results: Five randomised controlled trials and two non-randomised controlled trials were included with 614 participants. All provided data on blood pressure, but none measured cardiovascular events or long-term adverse events. The group of studies was highly heterogeneous in terms of experimental intervention, comparator intervention, length to follow-up, participants' diagnosis, and setting. The heterogeneity prevented a meaningful meta-analysis. Berberine plus amlodipine was not significantly better than amlodipine alone at reducing systolic and diastolic blood pressure. Compared to metformin, berberine provided a statistically significant moderate reduction effect on systolic blood pressure (-11.87 [-16.64, -7.10] mmHg). A proprietary nutraceutical containing berberine as one of its ingredients was in one study significantly effective at reducing blood pressure compared to placebo (-11.80 [-18.73, -4.87] mmHg systolic, and -11.10 [-15.17, -7.43] mmHg diastolic), and also effective in another study compared to dietary advice (-3.40 [-5.48, -1.32] mmHg for systolic 24 h ambulatory blood pressure), although effects could not be reliably attributed to berberine alone. The herbal extract Chunghyul-dan, which contains berberine, showed a significant beneficial moderate effect compared to no treatment on systolic 24 h ambulatory blood pressure (-7.34 [-13.14, -1.54] mmHg) in one study, but in another study employing higher dose and longer treatment duration, no effects were detected. Again, the effects could not be attributed to berberine alone. The quality of the body of evidence was low, especially due to lack of trial design details and presence of outcome reporting bias.

Conclusions: The evidence around berberine effect on blood pressure is limited, of low quality, and ultimately inconclusive. Clinicians should be aware that the evidence from randomised trials is not sufficient to establish berberine effectiveness and safety in the treatment of hypertension, and they should balance these findings with the long history of berberine use in the Eastern world. Researchers should aim at improving quality of studies, by raising the standard of designing and reporting them, e.g., by following the CONSORT guidelines, and strive to measure meaningful clinical endpoints, such as cardiovascular events, mortality, and adverse outcomes.

Keywords: Barberry; Berberine; Berberis; Herbal medicine; Hypertension.