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.

Nutr J. 2017 Oct 27;16(1):73. doi: 10.1186/s12937-017-0291-0. Saarenhovi M1,2, Salo P3, Scheinin M4, Lehto J4, Lovró Z4, Tiihonen K5, Lehtinen MJ5, Junnila J6, Hasselwander O7, Tarpila A5, Raitakari OT3,8. Author information 1 Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. marwen@utu.fi. 2 Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, P.O. Box 52, FI-20521, Turku, Finland. marwen@utu.fi. 3 Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. 4 Clinical Research Services Turku (CRST), University of Turku, and Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland. 5 DuPont, Nutrition and Health, Kantvik, Finland. 6 4Pharma Ltd, Turku, Finland. 7 DuPont, Nutrition and Health, Reigate, UK. 8 Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, P.O. Box 52, FI-20521, Turku, Finland. 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 http://clinicaltrials.gov (identifier: NCT01690676 ). Registered 25th May 2012. KEYWORDS: Endothelial function; Epicatechin; Flavanol-3-ols; Flavonoids; Vasodilatory function PMID: 29078780 PMCID: PMC5660451 DOI: 10.1186/s12937-017-0291-0 Free PMC Article