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Effects of flavonoid rich fruits on hypertension in adults: a systematic review.

OBJECTIVE
The objective of this systematic review was to synthesize the best available research evidence on the effectiveness of flavonoid rich fruits in the treatment of hypertension.


INTRODUCTION
Hypertension is a serious public health concern as it contributes to a significant burden of disease, attributable for millions of deaths globally. Complementary therapies including flavonoids have generated interest in assisting the treatment of hypertension. Flavonoids are a type of polyphenol abundant in fruits and a growing body of evidence suggests antihypertensive effects of the flavonoids due to its antioxidant properties. To date, no systematic review has been performed to collate the evidence on the effects of flavonoid rich fruits on hypertension in adults.


INCLUSION CRITERIA
This systematic review included only randomized controlled trials (RCTs) that compared the administration of any type of flavonoid rich fruit or equivalent supplement with a placebo or other intervention in adults with hypertension. Trials that measured blood pressure using objective outcome measures such as a manual mercury sphygmomanometer were included. Studies that did not specify the flavonoid component of the fruit or fruit supplement were excluded in the review. Secondary outcomes, including change in weight, blood glucose level, triglycerides and total blood cholesterol levels were also assessed.


METHODS
A three-step search was undertaken, including a comprehensive search of the MEDLINE, Embase, Cochrane Trials (CENTRAL) and CINAHL databases, in September 2018. We also searched Dissertation Abstracts International, ProQuest Dissertations and Theses, MedNar and ClinicalTrials.gov to identify unpublished studies. The title and abstracts of the studies were reviewed by two independent reviewers against the inclusion/exclusion criteria. The methodological quality of the potential studies for inclusion were assessed using the critical appraisal checklist for randomized controlled trials as recommended by the Joanna Briggs Institute. Data were pooled in a statistical meta-analysis model. Subgroup-analysis according to type of intervention and length of intervention period was performed. Where statistical pooling was not possible, the findings have been presented in a narrative form.


RESULTS
Fifteen randomized controlled trials involving 572 participants were included in the review. The subclasses of flavonoids assessed included: anthocyanins, naringin, narirutin and flavan-3-ols. The overall methodological quality of the trials was high. Six trials investigated the effect of the flavonoid intervention on blood pressure within four weeks. Meta-analysis of five of the trials demonstrated evidence of no effect of flavonoids on systolic or diastolic blood pressure when compared to placebo (systolic mean difference = -1.02, 95% CI -3.12, 1.07; p = 0.34, I = 0%; diastolic mean difference = -0.90, 95% CI -2.10, 0.31; p = 0.15, I = 0%). Similarly, pooled results from two cross-over RCTs with two-timed dosed interventions in a 24-hour period demonstrated evidence of no effect on a reduction in diastolic blood pressure (p = 0.38) but did reveal evidence of a reduction in systolic blood pressure (p = 0). Six trials that assessed blood pressure following the flavonoid intervention at more than four weeks follow-up demonstrated evidence of no effect on either systolic (mean difference = -0.95, 95%CI -3.58, 1.68; p = 0.478, I = 0%) or diastolic blood pressure (mean difference = 0.86, 95%CI -1.11, 2.82; p = 0.393, I = 0%).


CONCLUSIONS
The findings from this systematic review should be interpreted with caution, given that the results are obtained from single-center trials with small sample sizes. Given the results provided in this review, there is evidence of no effect of flavonoids on systolic and diastolic blood pressure. Further robust randomized controlled trials using sample sizes based on power calculations are needed to provide evidence for the use of flavonoid rich fruits for the management of hypertension.