Effect of Saturated Fat on Large Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL)

Study Overview
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Brief Summary
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The purpose of the study is to test whether increased saturated fat intake results in increased levels of larger LDL and HDL particles in individuals with LDL Pattern B.

Detailed Description
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Increased saturated fat intake is known to elevate plasma levels of both low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), however, less is know regarding the effect of saturated fat on lipoprotein subclasses. We previously showed that, in the context of a reduced carbohydrate diet, saturated fat induced increases in LDL cholesterol were apparently due to increases in large, more buoyant LDL without increases in small, dense LDL. This finding was supported by a previous dietary intervention study showing a correlation between saturated fat intake and large LDL. In both cases, this increase in large LDL was correlated with an increase in large HDL. In this study, we will test the following specific hypotheses regarding changes in plasma lipoproteins induced by a diet high in myristic acid and other saturated fats derived primarily from dairy sources in individuals with LDL subclass pattern B: 1) there will be a coordinate increase in levels of large HDL particles that are considered anti-atherogenic and large LDL particles that are less strongly associated with increased CVD risk than smaller LDL; 2) this change in lipoprotein profile will result in a higher proportion of pattern B individuals converting to LDL subclass pattern A (predominance of larger LDL); and 3) the coordinate increase in large HDL and LDL is due to a common underlying pathway. The latter hypothesis will be addressed by assaying cholesterol ester transfer protein (CETP), hepatic lipase (HL), and lipoprotein lipase (LPL).

Official Title
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Changes in LDL and HDL With Increased Intake of Saturated Fat From Dairy Foods in Individuals With Atherogenic Dyslipidemia and LDL Subclass Pattern B

Conditions
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Dyslipidemia

Intervention / Treatment
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* Dietary Supplement: Saturated Fat Diet
* Dietary Supplement: Saturated Fat Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or postmenopausal woman between 18-70 yrs Body Mass Index between 25-35 Blood pressure <150/90 Non smoking Agrees to consume no alcohol or dietary supplements during the study LDL Subclass Pattern B Total cholesterol and LDLC ≤95th percentile for sex and age Fasting triglycerides ≤ 500mg/dl Fasting blood sugar < 126 mg/dl At least 3 months weight stable Exclusion Criteria: History of coronary heart disease, cerebrovascular disease, peripheral vascular disease, bleeding disorder, liver or renal disease, diabetes, lung disease, HIV, or cancer (other than skin) in the last 5 years Taking drugs known to affect lipid metabolism or hormones Abnormal thyroid stimulating hormone (TSH)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low saturated fat diet<br>Moderate carbohydrate (35%E), moderate protein (25%E), high fat (40%E) diet with 8%E saturated fat | Dietary Supplement: Saturated Fat Diet<br>* Moderate carbohydrate (35%E), moderate protein (25%E), high fat diet (40%E) with 8%E saturated fat<br>|
| Experimental: High saturated fat diet<br>Moderate carbohydrate (35%E), moderate protein (25%E), high fat (40%E) diet with 20%E saturated fat | Dietary Supplement: Saturated Fat Diet<br>* Moderate carbohydrate (35%E), moderate protein (25%E), high fat (40%E) diet with 20%E saturated fat<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Large LDL (LDL I + 2a) (mg/dl) |  | 3 wk, 6 wk | 
| Large HDL (HDL2b) (mg/dl) |  | 3 wk, 6 wk | 
| LDL peak particle size |  | 3 wk, 6 wk | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Triglycerides (mg/dl) |  | 3 wk, 6 wk | 
| Total Cholesterol (mg/dl) |  | 3 wk, 6 wk | 
| LDL cholesterol (mg/dl) |  | 3 wk, 6 wk | 
| HDL cholesterol (mg/dl) |  | 3 wk, 6 wk | 
| Apolipoprotein AI (mg/dl) |  | 3 wk, 6 wk | 
| Apolipoprotein B (mg/dl) |  | 3 wk, 6 wk | 
| Medium LDL (LDL2b) (mg/dl) |  | 3 wk, 6 wk | 
| Small LDL (LDL3a) (mg/dl) |  | 3 wk, 6 wk | 
| Hepatic Lipase Activity |  | 3 wk, 6 wk | 
| Lipoprotein Lipase Activity |  | 3 wk, 6 wk | 
| Cholesteryl Ester Transfer Protein Activity |  | 3 wk, 6 wk | 
| Very Small LDL (LDL3b, 4a, 4b) (mg/dl) |  | 3 wk, 6 wk | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Saturated fat, LDL size, Large LDL, Large HDL