The effect of an apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers on brachial artery flow-mediated vasodilatory function in volunteers with elevated blood pressure

Maria Saarenhovi, Pia Salo, Mika Scheinin, Jussi Lehto, Zsófia Lovró, Kirsti Tiihonen, Markus J Lehtinen, Jouni Junnila, Oliver Hasselwander, Anneli Tarpila, Olli T Raitakari, Maria Saarenhovi, Pia Salo, Mika Scheinin, Jussi Lehto, Zsófia Lovró, Kirsti Tiihonen, Markus J Lehtinen, Jouni Junnila, Oliver Hasselwander, Anneli Tarpila, Olli T Raitakari

Abstract

Background: The primary aim of this study was to test the hypothesis that an orally ingested apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers improves endothelium-dependent brachial artery flow-mediated vasodilatation (FMD) in volunteers with borderline hypertension. The secondary aim of the study was to test whether the investigational product would improve endothelium-independent nitrate-mediated vasodilatation (NMD).

Methods: This was a single centre, repeated-dose, double-blind, placebo-controlled, crossover study in 60 otherwise healthy subjects (26 men, 34 women; aged 40-65 years) with borderline hypertension (blood pressure 130-139/85-89 mmHg) or unmedicated mild hypertension (blood pressure 140-165/90-95 mmHg). The subjects were randomised to receive placebo or the apple polyphenol extract to provide a daily dose of 100 mg epicatechin for 4 weeks, followed by a four to five-week wash-out period, and then 4 weeks intake of the product that they did not receive during the first treatment period. FMD and NMD of the left brachial artery were investigated with ultrasonography at the start and end of both treatment periods, and the per cent increase of the arterial diameter (FMD% and NMD%) was calculated.

Results: With the apple extract treatment, a significant acute improvement was detected in the mean change of maximum FMD% at the first visit 1.16 (p = 0.04, 95% CI: 0.04; 2.28), last visit 1.37 (p = 0.02, 95% CI: 0.22; 2.52) and for both visits combined 1.29 (p < 0.01, 95% CI: 0.40; 2.18). However, such improvement was not statistically significant when apple extract was compared with placebo. The overall long-term effect of apple extract on FMD% was not different from placebo. No statistically significant differences between the apple extract and placebo treatments were observed for endothelium-independent NMD.

Conclusions: A significant acute improvement in maximum FMD% with apple extract administration was found. However, superiority of apple extract over placebo was not statistically significant in our study subjects with borderline hypertension or mild hypertension. The study raised no safety concerns regarding the daily administration of an apple polyphenol extract rich in epicatechin.

Trial registration: The trial is registered at https://ichgcp.net/clinical-trials-registry/NCT01690676" title="See in ClinicalTrials.gov">NCT01690676 ). Registered 25th May 2012.

Keywords: Endothelial function; Epicatechin; Flavanol-3-ols; Flavonoids; Vasodilatory function.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Ethics Committee of Southwest Finland Hospital District, Turku, Finland and the study was conducted in accordance with the Declaration of Helsinki. All participants gave their written informed consent.

Consent for publication

Not applicaple.

Competing interests

OH, KT, MJL and AT are or have been employed by DuPont. The authors declare no other competing interest regarding this study.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study flow diagram
Fig. 2
Fig. 2
Study design. Screening visit was conducted within 30 days prior to the first study product administration. FMD, flow-mediated dilatation. Sequence: apple extract – placebo, sequence: placebo – apple extract
Fig. 3
Fig. 3
The maximal FMD% by the treatment periods after apple extract and placebo administration. The figure shows the mean values and S.E. for each FMD measurements that were taken before and after the dosing during the first and last treatment visits. FMD, flow-mediated dilatation
Fig. 4
Fig. 4
The acute changes from baseline in maximal FMD% within visits and for the visits combined. The figure shows mean change in FMD% from baseline. The error bars represent 95% CI. *p < 0.05 and **p < 005. FMD, flow-mediated dilatation. Test for difference between groups in combined visits p = 0.181. Test for difference epicatechin vs baseline: 1. visits p = 0.043, 2. visits p = 0.02, combined p = 0.005

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