Lipoprotein Turnover on Low- and High-MUFA Portfolio Diets

Cardiovascular Diseases Clinical Trial

Official title: Lipoprotein Turnover on Low- and High-MUFA Portfolio Diets

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Diet Therapy
• Hyperlipidemia
• Hyperlipidemias

• NCT number: NCT00430430
• Study type: Interventional
• Source: University of Toronto
• Status: Completed
• Phase: Phase 2
• Start date: April 2007
• Completion date: April 2009