The Effects of Fat and Theobromine on apoA-I
Condition: Cardiovascular Diseases
MeSH terms: Cardiovascular Diseases
Study type: Interventional

Summary: 
      Rationale: Despite successful efforts to lower atherogenic serum low-density lipoprotein
      (LDL) cholesterol concentrations, a substantial residual cardiovascular risk is still
      present. An additive strategy to further lower this residual risk may be via raising
      high-density lipoprotein (HDL) cholesterol concentrations, and in particular those of its
      major protein constituent apolipoprotein A-I (apoA-I). However, recent evidence shows that
      raising HDL cholesterol (HDL-C) concentrations not always causes a reduction in
      cardiovascular disease (CVD) risk. To understand this it is important to know what are the
      targets and molecular mechanisms that underlie a shift to a HDL fraction with
      cardioprotective activities. There is increasing evidence that particularly the apoA-I
      proteins in the HDL fractions are atheroprotective. It is important to verify whether the
      effect of an intervention actually increases apoA-I production since that results in the
      formation of de-novo small pre-beta HDL particles that have full capacity to resorb
      cholesterol from the arterial wall and return this to the liver for secretion (reverse
      cholesterol transport). The investigators here propose to evaluate, in a double-blind human
      intervention study, the difference in intestinal apoA-I gene expression, of healthy subjects,
      after consumption of a high fat (HF) or low fat (LF) meal. Additionally the investigators
      propose to evaluate the effect of theobromine on intestinal apoA-I expression. Based on
      several studies, theobromine improved cardiovascular risk parameters among which an elevation
      in apoA-I and HDL cholesterol concentrations. It is however unknown whether this effect of
      theobromine originates from elevated apoA-I production, which suggest improved functionality,
      or decreased clearance, suggesting reduced functionality. The investigators therefore propose
      to also evaluate if the usage of theobromine is a better way to increase intestinal apoA-I
      mRNA and protein expression, than consumption of a HF meal. The investigators will do this in
      the same double-blind human intervention study. The theobromine will be added in a third arm
      in a LF condition.

      Study design: The proposed study will have a randomized, double-blind cross-over design. The
      total study duration will be 17 days, consisting of 3 experimental days with postprandial
      tests, each separated by a 1 week wash-out period.

      Study population: Ten apparently healthy male subjects, aged 18-60 years, without a history
      of any gastrointestinal disorders or complaints.

      Intervention: During the three experimental days, subjects will consume a milkshake: one HF
      milkshake, one LF milkshake and one LF milkshake supplemented with 850 mg theobromine. Total
      follow-up during each of the postprandial tests is 5 hours.
    


Intervention name(s): Fat milkshake; Theobromine
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention MeSH terms: Theobromine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Cardiovascular Diseases; HDL metabolism; ApoA-I; High fat; Theobromine