Effect of Apple Flavanols on Risk of Cardiovascular Disease
Condition: Cardiovascular Disease
MeSH terms: Cardiovascular Diseases
Study type: Interventional

Summary: 
      A randomised three period cross over trial will be carried out in adults (19-64 years) to
      assess the acute and chronic effects of a large dose of apple procyanidin (PA) compared with
      a low dose of apple PA (negative control) and aspirin (positive control), on platelet
      function and other risk factors of cardiovascular disease. Platelet function will be assessed
      prior to a run in diet and at the start and end of each intervention. Volunteers will be
      assigned at random to consume 230grams of low PA apple puree or high PA apple puree or
      aspirin (75mg) each day for 2 weeks followed by a minimum 14 day wash out.

      Hypothesis: Consuming apple PA reduces platelet function consistent with reduced risk of
      cardiovascular disease.
    

Detailed description: 
      A randomised 3-period cross-over trial will be carried out to assess the acute and chronic
      effects of a large dose of apple PA compared with a low dose of apple PA (negative control)
      and aspirin (positive control), on platelet function (flow cytometry) and other risk factors
      of CVD (endothelial function, plasma antioxidants, inflammatory markers, lipid profile). Once
      recruited, volunteers will be assigned at random to consume 230g of low PA apple puree or
      high PA apple puree or aspirin (75mg) each day for 14 days in period 1. Following a minimum
      14 day wash-out volunteers will then be crossed over for period 2 and after another 14-day
      wash-out volunteers will be crossed over to complete period 3 of the intervention (flow chart
      I). The acute effect of each treatment will be investigated on day 15 of each period. A
      fasting blood sample will be obtained prior to consumption of a standard breakfast and the
      apple puree or aspirin. Further blood samples will then be obtained at 2, 6 and 24 hours
      post-dosing. The chronic effect of all three treatments will be determined by measuring CVD
      risk factors in fasting blood samples obtained on day 1, 15 and 29. Flow chart II provides a
      more detailed overview of the design of each period which is identical for the apple puree
      treatments and differs only in the omission of urine collections and PWV measurements for the
      aspirin period. During the apple puree interventions phenolic acids will be analysed in
      24-hour urine pools collected on the day prior to the start of each period, as well as on day
      14, 15, and 28. PWV measurements will be carried on day 15 and 29 after a 12-hour overnight
      fast for each of the 2 apple intervention periods.

      For the intervention to be successful it is necessary to exclude some food sources that
      contribute significantly to total PA intake (e.g. cocoa, berries, grapes, red wine, apples,
      legumes) and limit other PA food sources (tea/coffee) to levels that support compliance and
      are unlikely to mask any effects of the intervention. Because of its well documented effect
      on platelet function alcohol will be restricted to a maximum of 2 units per day and excluded
      completely for the 48 hours prior to blood sampling appointments. Oily fish consumption will
      be limited to 2 portions per week and will not be allowed for 48 hours prior to blood
      sampling. These dietary restrictions may have significant effects on platelet function in
      individuals that consume these foods regularly. Therefore, dietary restrictions will apply
      during a 14-day run-in diet prior to and for the duration of each intervention period.
      Platelet function will be assessed prior to the start of the run-in diet as well as at the
      start and end of each PA/aspirin intervention (flow chart II).

      Male and female volunteers aged 19 to 64 will be recruited and screened for eligibility for
      up to 2 months prior to the start of the intervention. Those meeting the study criteria will
      be randomly assigned to one out of the six possible treatment orders, i.e. ABC, ACB, BAC,
      CAB, BCA, CBA. Randomisation will be stratified by sex.

      Volunteers will be given a user friendly booklet (Run-in diet/Apple/Aspirin diary) for each
      intervention period to record apple puree/aspirin consumption and volunteers will also be
      prompted to record their alcohol, tea/coffee and oily fish intake (Annex 2). Foods not
      allowed during each intervention period are listed. Volunteers will be reminded not to
      consume oily fish (as listed), alcohol, coffee and tea 48 hours prior to a blood sampling
      appointment.
    

Intervention name(s): Low PA apple puree; High PA apple puree; Aspirin
Intervention type(s): Dietary Supplement; Dietary Supplement; Drug
Intervention description(s): Golden Delicious apple puree 230grams consumed daily for 14 days; High PA apple puree (Mitchalin) consumed daily for 14 days; 75mg dispersable aspirin taken daily for 14 days
Intervention MeSH terms: Aspirin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: Apples; Dietary intervention; Procyanidins