Intra-individual Real Life Effects of Cocoa Flavanols on Blood Pressure and Arterial Stiffness
Condition: Blood Pressure; Stiffness, Vascular; Sleep
Study type: Interventional

Summary: 
      Very controlled dietary intervention studies support that individual polyphenol rich foods
      and isolated polyphenols can increase endothelial function and HDL cholesterol and decrease
      blood pressure, arterial stiffness, and LDL cholesterol even in healthy subjects. The intake
      of (-)-epicatechin, the major polyphenol in cocoa, was previously mechanistically linked with
      acute improvements in endothelial function and nitric oxide availability. A profound
      understanding of inter- and intra-individual variability of responses in real life are an
      important area of research in a world that aims at personalized nutrition and medicine.
      N-of-1 trials are a powerful tool allowing to study small effects even in fewer subjects and
      help account for intra-individual variations in responses. The overall aim of the present
      pilot study is to evaluate intra-and inter-individual variability of responses to cocoa
      flavanols in everyday life using the N-of-1 paradigm. In this pilot study, young healthy
      humans will monitor blood pressure, pulse wave velocity, heart rate, diet, and physical
      activity on 8 days using a personal and wearable devices. Each subject will undergo the 8
      study days; 4 days with cocoa flavanol capsules (CF; containing 750 mg (1500 mg per day)) and
      4 days with calorically matched placebo capsules (P; 0 mg cocoa flavanols) taken at the same
      time in the morning with breakfast and at night before going to bed. The subjects will be
      randomized to different treatment allocation sequences to allow blinding of volunteers and
      investigator; either CF-P-CF-P-CF-P-CF-P or P-CF-P-CF-P-CF-P-CF.
    

Detailed description: 
      Background: Very controlled dietary intervention studies support that individual polyphenol
      rich foods and isolated polyphenols can increase endothelial function and HDL cholesterol and
      decrease blood pressure, arterial stiffness, and LDL cholesterol even in healthy subjects.
      The intake of (-)-epicatechin, the major polyphenol in cocoa, was previously mechanistically
      linked with acute improvements in endothelial function and nitric oxide availability.
      However, the clinical intervention studies were performed in tightly controlled experimental
      settings and variability of individual responses were not investigated. A profound
      understanding of inter- and intra-individual variability of responses in real life are an
      important area of research in a world that aims at personalized nutrition and medicine.
      N-of-1 trials are a powerful tool allowing to study small effects even in fewer subjects and
      help account for intra-individual variations in responses. N-of-1 trials in clinical medicine
      are multiple crossover trials, usually randomized and often blinded, conducted in a single
      patient.

      Aim, hypothesis, objectives: The overall aim of the present pilot study is to evaluate
      intra-and inter-individual variability of responses to cocoa flavanols in everyday life using
      the N-of-1 paradigm. It is the hypothesis that cocoa flavanols decrease blood pressure and
      arterial stiffness in everyday life of healthy individuals. The objectives to investigate the
      aim are (1) to test the effect of CF using wearable devices repeatedly measuring blood
      pressure, arterial stiffness, and heart rate in healthy individuals participating in in every
      days life, (2) to explore intra-and inter-individual variability in responses by repeatedly
      testing responses in the same individuals, and (3) to test different statistical models
      taking repeated measurements in the same subject into account.

      Methods: In this pilot study, young healthy humans will monitor blood pressure, pulse wave
      velocity, heart rate, diet, and physical activity on 8 days using a personal and wearable
      devices. Each subject will undergo the 8 study days; 4 days with cocoa flavanol capsules (CF;
      containing 750 mg (1500 mg per day)) and 4 days with calorically matched placebo capsules (P;
      0 mg cocoa flavanols) taken at the same time in the morning with breakfast and at night
      before going to bed. The subjects will be randomized to different treatment allocation
      sequences to allow blinding of volunteers and investigator; either CF-P-CF-P-CF-P-CF-P or
      P-CF-P-CF-P-CF-P-CF. Blood pressure and heart rate will be measured by a standard upper arm
      blood pressure cuff and estimated by a fitness wristband and pulse wave velocity via a finger
      device in 30 min intervals for 3 h starting after morning treatment ingestion followed by
      hourly intervals until going to bed.
    

Intervention name(s): Cocoa flavanol (CF); Placebo (P)
Intervention type(s): Dietary Supplement; Other
Intervention description(s): 2 times per day 750 mg cocoa flavanols (each delivered in 6 CocoaVia capsules); 2 times per day 0 mg cocoa flavanols calorically matched control (delivered in 6 identical capsules)
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Series of Repeated Cross-over Randomized Controlled Double-blind N-of-1 Pilot Studies; each subject receives 4 times treatment and 4 times placebo
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science