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Assessing Variability in Vascular Response to Cocoa With Personal Devices: A Series of Double-Blind Randomized Crossover n-of-1 Trials

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Mariam Bapir, Paola Campagnolo, Ana Rodriguez-Mateos, Simon S. Skene, Christian Heiss

Original languageEnglish
Article number886597
JournalFrontiers in Nutrition
Published13 Jun 2022

Bibliographical note

Funding Information: MB was funded by an institutional grant of Health Education England to CH. This study was funded by the University of Surrey as part of the Biomedical Science final year Bachelor of Science research project (BMS3049). CH and SS have received funding from the Economic and Social Research Council (ES/V00980X/1). Publisher Copyright: Copyright © 2022 Bapir, Campagnolo, Rodriguez-Mateos, Skene and Heiss.

King's Authors


Controlled clinical intervention studies have demonstrated that cocoa flavanols (CF) can decrease blood pressure and arterial stiffness in healthy humans, although a large variability in the effect size across trials has been reported. In this study, we evaluated the intra- and inter-individual variability of responses to CF in everyday life using a series of n-of-1 trials in healthy free-living individuals with normal blood pressure carrying personal devices. In total, eleven healthy young humans participated in a repeated crossover randomized controlled double-blind n-of-1 trial. On 8 consecutive days, each volunteer consumed on alternating days 6 CF capsules (862 mg CF) on 4 days and 6 matched placebo capsules (P, 0 mg CF/day) on another 4 days in one of the two randomized sequences (CF-P-CF-P-CF-P-CF-P or P-CF-P-CF-P-CF-P-CF). On each day, the capsules were taken at the same time in the morning with breakfast after baseline measurements. Each subject was provided with an upper arm blood pressure monitor and a finger clip that measures pulse wave velocity (PWV). Measurements of blood pressure, heart rate, and PWV were taken at least hourly over 12 h during the day by the participants. On the first 2 days, measurements were performed under supervision to provide training. The overall mixed model analysis showed that CF significantly decreased 12-h systolic blood pressure and PWV by −1.4 ± 0.3 mmHg and −0.11 ± 0.03 m/s, respectively. Peak effects were observed within the first 3 h (1.5 h SBP: −4.9 ± 2.2 mmHg, PWV: −0.32 ± 0.17 m/s) and again after 8 h post-ingestion. Large inter-individual variation in responses was found [intra-cluster correlation coefficients (ICC): 0.41, 0.41]. When analyzing single individuals’ datasets, there was also considerable between-day variation in individual responses that varied greatly between subjects (ICC: 0–0.30, 0–0.22, 0–0.45). Effect sizes inversely correlated with baseline blood pressure values both between- and within-subjects. The data confirm that cocoa can decrease blood pressure and arterial stiffness in everyday life when elevated within the normal range. The large inter- and intra-individual variation in responses calls for more personalized nutritional intervention strategies.

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