Lipoprotein Turnover on Low- and High-MUFA Portfolio Diets
Condition: Hyperlipidemia; Cardiovascular Diseases; Diet Therapy
MeSH terms: Cardiovascular Diseases; Hyperlipidemias
Study type: Interventional
Phase: Phase 2

Summary: 
      Low and very low carbohydrate diets, such as the Atkins' Diet, have recently gained attention
      for their potential health benefits from weight loss and have gained some scientific support
      from a growing number of studies. Benefits have been noted in relation to raised "good"
      cholesterol, lower "bad" cholesterol and triglycerides. Other studies have shown an advantage
      in substituting vegetable fat for carbohydrate in insulin resistant individuals and in some
      instances in type 2 diabetes where improvements were seen in "good" cholesterol and blood
      sugars. At the same time, our research have been exploring diets containing less processed
      carbohydrates and other components which in combination (portfolio diet) have a similar
      cholesterol lowering effect to drug therapy.

      Therefore we wish to determine whether our cholesterol-lowering components (portfolio diet)
      should be incorporated into lower carbohydrate diets especially to preserve "good"
      cholesterol and lower "bad" cholesterol for decreasing the risk of heart disease.
    

Detailed description: 
      All subjects will undergo two parallel 2-phase treatments. On one treatment, subjects will be
      placed on a low fat diet for one month (control run-in diet) and then for the second month
      will continue on the low- fat diet (i.e. low-MUFA) with the addition of the portfolio
      components. The order of these two phases will not be randomized. The other treatment will be
      similar to the above except that the background diet of the portfolio phase will be high in
      monounsaturated fat (high-MUFA). Subjects will be allocated randomly to either treatment.
      Diets will be metabolically controlled and all food will be provided at weekly intervals.

      Subjects will come after a 12h overnight fast to the Risk Factor Modification Center at St.
      Michael's Hospital or the Department of Nutritional Sciences, University of Toronto
      immediately prior to commencement of each treatment phase and at weekly intervals during the
      course of each study period. Prior to the start of the study, subjects will be instructed on
      details of the study diet protocol. They will also be asked to maintain a constant level of
      physical activity throughout the course of the study. At all visits, body weight (in kg) will
      be obtained in indoor clothing, without shoes, and blood pressure will be taken twice in the
      dominant arm after subjects have been seated for at least 20 minutes. Height (in cm) will be
      recorded at the first visit. Throughout the study period, subjects will maintain the diet
      prescribed on their initial visit. At every other visit of each treatment phase, subjects
      will provide a fasting blood sample. The kinetic tests of lipoprotein metabolism will be
      performed during the 4th and 8th week of the study. At baseline and during the last week of
      each study phase, 24h urine collection and 12h breath hydrogen collections will be completed.

      The measurement of apolipoprotein in vivo kinetics will be carried out using a
      primed-constant infusion of [D3]L-leucine. This protocol allows for the determination of the
      kinetics of all apolipoproteins simultaneously. Kinetics studies will be conducted in the
      constantly fed state where participants receive 1/30th of their daily energy requirements
      every half-hour for the whole duration of the test (15 hours). These methods are described in
      detail in previous publications from our group. Briefly, at 7am on the morning of the study,
      after a 12-hour overnight fast, participants will be admitted to the Toronto General Hospital
      Clinical Investigation Unit and two intravenous catheters (IV's) will be inserted, one into
      each forearm vein. One IV will be for infusion of the stable isotope described below and one
      for withdrawal of blood samples. After achieving a steady state (3hrs after the small
      half-hourly meals), subjects will first receive a bolus injection of 10 µmol/kg of body
      weight of [D3]L-leucine ([D3]L-leucine 98%, C/D/N Isotopes) dissolved in physiological saline
      (0.9% NaCl) and then a constant infusion of 10 µmol/kg/h of [D3]L-leucine for 12 hours via an
      intravenous line inserted into a left forearm vein. Blood samples will be collected at
      regular intervals (0, 1/2, 1, 2, 4, 6, 8, 10, 11, 12hrs). All lipoprotein subfractions will
      be separated by sequential ultracentrifugation and frozen thereafter at -80oC until they are
      processed for analysis.
    

Intervention name(s): High MUFA dietary portfolio; Low MUFA dietary portfolio
Intervention type(s): Procedure; Procedure
Intervention description(s): high monounsaturated fat background diet to dietary portfolio; low monounsaturated fat background diet to dietary portfolio
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment