Dietary Fat and High-Density Lipoprotein (HDL) Metabolism-Effect of Carbohydrate and Fat Intake

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01399632
Recruitment Status : Completed
First Posted : July 22, 2011
Last Update Posted : July 6, 2016
Information provided by (Responsible Party):
Frank M. Sacks, Brigham and Women's Hospital

Brief Summary:
Generally, people with low levels of high-density lipoprotein (HDL) in blood are more likely to get heart disease than those who have normal or high levels. Dietary fat, whether the harmful type (saturated) or beneficial type (unsaturated) raises HDL levels. Dietary carbohydrate lowers HDL. The investigators are doing this research study to find out why the amount of HDL in a person's blood is affected by dietary unsaturated fat and carbohydrate. The investigators will trace the ability of the HDL in a person's blood to take up cholesterol, get bigger, and then leave the blood by passing into the liver. The investigators want to know if dietary unsaturated fat improves the ability of HDL to do this compared to dietary carbohydrate.

Condition or disease Intervention/treatment Phase
Overweight Cardiovascular Diseases Behavioral: Low Fat and High Carbohydrate Diet Behavioral: High Fat and Low Carbohydrate Diet Not Applicable

Detailed Description:
The investigators will study the kinetics of multiple types of high-density lipoprotein (HDL) in humans under two strictly controlled dietary conditions, high unsaturated fat and high carbohydrate, in 20 individuals with low HDL cholesterol and overweight or obesity. The participants will be given the controlled diets for 4 weeks in a randomized crossover design. They will be admitted to the Brigham & Women's Hospital Center for Clinical Investigation (CCI) the morning of Day 28 when they will be infused intravenously with a stable isotope tracer, trideuterated (D3), leucine for 10 minutes as a bolus. Blood will be sampled in the hospital through 24 hours, and thereafter at the ambulatory clinical center throughout 94 hours. HDL subtypes will be prepared in Dr. Sacks's laboratory at Harvard School of Public Health (HSPH) and analyzed for content of lipids and proteins, and for incorporation of the tracer into apolipoprotein A-I, the principal protein of HDL. These data will be studied by interactive modeling to a multi-compartment model of human HDL physiology that best fits the observed data. The model will yield HDL metabolic rates during unsaturated fat and carbohydrate-rich diets which will be tested for statistical significance.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Dietary Fat and High-Density Lipoprotein (HDL) Metabolism-Effect of Carbohydrate and Fat Intake
Study Start Date : August 2010
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dietary Fats

Arm Intervention/treatment
Experimental: High Fat and Low Carbohydrate Diet Behavioral: High Fat and Low Carbohydrate Diet
High Fat and Low Carbohydrate Diet
Other Name: Diet and HDL Metabolism

Experimental: Low Fat and High Carbohydrate Diet Behavioral: Low Fat and High Carbohydrate Diet
Low Fat and High Carbohydrate Diet
Other Name: Diet and HDL Metabolism

Primary Outcome Measures :
  1. high-density lipoprotein (HDL) cholesterol [ Time Frame: Diet Periods I and II-Days 28-32 ]
    To determine how dietary unsaturated fat when it replaces carbohydrate affects HDL metabolism.

Secondary Outcome Measures :
  1. To study HDL with apoE [ Time Frame: Diet Periods I and II-Days 28-32 ]

Other Outcome Measures:
  1. Provide guidance for interpreting effects of unsaturated fats on reverse cholesterol transport [ Time Frame: Diet Periods I and II-Days 28-32 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Only accepting participants in the Boston, Massachusetts area
  • Age 21 to 75, male or female
  • Willingness to eat prescribed diet for 4 weeks prior to infusion date, and 3.5 days after the infusion date
  • Willingness to participate in an infusion protocol, which will require them to stay at the Center for Clinical Investigation (CCI) for one night and return for blood draws every day for the next 3 days.
  • Body Mass Index (BMI) 25-35 Kg/m2
  • HDL<45 mg/dL for men, <55 mg/dL for women

Exclusion Criteria:

  • Hematocrit <33
  • Low-density Lipoprotein (LDL) cholesterol >190 mg/dl
  • HDL cholesterol <20 mg/dl, to exclude those with rare genetic HDL deficiency syndromes
  • Fasting Triglycerides >500 mg/dl to exclude those with risk of pancreatitis
  • ApoE genotypes, E2E2, E2E4, and E4E4.
  • Lipid lowering medications
  • Hormone replacement therapy
  • Other medicines that affect plasma lipid levels: e.g. beta blockers, certain psychiatric medicines including Alprazolam, Chlordiazepoxide, Clonazepam, Diazepam, Lorazepam, Oxazepam, Prazepam, Aripiprazole, Chlorpromazine, Chlorprothixene, Clozapine, Flupenthixol, Fluphenazine, Haloperidol, Loxapine, Mesoridazine, Methotrimeprazine, Molindone, Olanzapine, Perphenazine, Pimozide, Pipotiazine, Prochlorperazine, Promazine, Promethazine, Quetiapine, Risperidone, Sulpiride, Thioridazine, Thiothixene, Trifluoperazine, Ziprasidone.
  • Thyrotrophin-stimulating hormone: <0.5 or >5.0
  • alanine aminotransferase : 1.5 x uln or 60 IU/L
  • Aspartate transaminase: 1.5 x uln or 60 IU/L
  • Bilirubin: outside upper limit. (>1.2 mg/dL)
  • Creatinine: outside upper limit (>1.00 mg/dL)
  • Diabetes by history
  • Diabetes by fasting or post-challenge glycemia according to ADA guidelines:

    • Fasting hyperglycemia (glucose >126 mg/dl).
    • Post-challenge glucose by standard oral glucose tolerance test, >200 mg/dl
  • Will not eat the provided diet and abstain from alcoholic beverages.
  • Women who are pregnant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01399632

United States, Massachusetts
Harvard T. H. Chan School of Public Health
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Brigham and Women's Hospital
Principal Investigator: Frank M Sacks, MD Harvard University

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Frank M. Sacks, MD, Brigham and Women's Hospital Identifier: NCT01399632     History of Changes
Other Study ID Numbers: HL095964
First Posted: July 22, 2011    Key Record Dates
Last Update Posted: July 6, 2016
Last Verified: July 2016

Additional relevant MeSH terms:
Cardiovascular Diseases
Body Weight
Signs and Symptoms