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

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

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.

Study Overview

• Status: Completed
• Conditions: Dyslipidemia
• Intervention / Treatment: Dietary supplement: Saturated Fat Diet; Dietary supplement: Saturated Fat Diet

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Berkeley, California, United States, 94705
      • Cholesterol Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low saturated fat diet; Moderate carbohydrate (35%E), moderate protein (25%E), high fat (40%E) diet with 8%E saturated fat	Dietary supplement: Saturated Fat Diet; Moderate carbohydrate (35%E), moderate protein (25%E), high fat diet (40%E) with 8%E saturated fat; Dietary supplement: Saturated Fat Diet; Moderate carbohydrate (35%E), moderate protein (25%E), high fat (40%E) diet with 20%E saturated fat
Experimental: High saturated fat diet; Moderate carbohydrate (35%E), moderate protein (25%E), high fat (40%E) diet with 20%E saturated fat	Dietary supplement: Saturated Fat Diet; Moderate carbohydrate (35%E), moderate protein (25%E), high fat diet (40%E) with 8%E saturated fat; Dietary supplement: Saturated Fat Diet; Moderate carbohydrate (35%E), moderate protein (25%E), high fat (40%E) diet with 20%E saturated fat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: UCSF Benioff Children's Hospital Oakland
• Collaborators: Dairy Management Inc.

Publications and helpful links

General Publications

• Chiu S, Williams PT, Krauss RM. Effects of a very high saturated fat diet on LDL particles in adults with atherogenic dyslipidemia: A randomized controlled trial. PLoS One. 2017 Feb 6;12(2):e0170664. doi: 10.1371/journal.pone.0170664. eCollection 2017.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: May 7, 2009
• First Submitted That Met QC Criteria: May 7, 2009
• First Posted (Estimate): May 8, 2009

Study Record Updates

• Last Update Posted (Estimate): January 14, 2013
• Last Update Submitted That Met QC Criteria: January 10, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Saturated fat; LDL size; Large LDL; Large HDL
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias
• Other Study ID Numbers: MM3355