Clinical trial NCT00895141: Effect of Saturated Fat on Large Low-density Lipoprotein (LDL) and High-density Lipoprotein (HDL)
Official title: Changes in LDL and HDL With Increased Intake of Saturated Fat From Dairy Foods in Individuals With Atherogenic Dyslipidemia and LDL Subclass Pattern B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dyslipidemia
Keywords: Saturated fat
LDL size
Large LDL
Large HDL
Lead sponsor: UCSF Benioff Children's Hospital Oakland
Sponsor class: OTHER
Collaborators: name: Dairy Management Inc.
First posted: 2009-05-08
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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).

Eligibility criteria: 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)

Primary outcomes:
measure: Large LDL (LDL I + 2a) (mg/dl)
timeFrame: 3 wk, 6 wk
measure: Large HDL (HDL2b) (mg/dl)
timeFrame: 3 wk, 6 wk
measure: LDL peak particle size
timeFrame: 3 wk, 6 wk
Secondary outcomes:
measure: Triglycerides (mg/dl)
timeFrame: 3 wk, 6 wk
measure: Total Cholesterol (mg/dl)
timeFrame: 3 wk, 6 wk
measure: LDL cholesterol (mg/dl)
timeFrame: 3 wk, 6 wk
measure: HDL cholesterol (mg/dl)
timeFrame: 3 wk, 6 wk
measure: Apolipoprotein AI (mg/dl)
timeFrame: 3 wk, 6 wk
measure: Apolipoprotein B (mg/dl)
timeFrame: 3 wk, 6 wk
measure: Medium LDL (LDL2b) (mg/dl)
timeFrame: 3 wk, 6 wk
measure: Small LDL (LDL3a) (mg/dl)
timeFrame: 3 wk, 6 wk
measure: Hepatic Lipase Activity
timeFrame: 3 wk, 6 wk
measure: Lipoprotein Lipase Activity
timeFrame: 3 wk, 6 wk
measure: Cholesteryl Ester Transfer Protein Activity
timeFrame: 3 wk, 6 wk
measure: Very Small LDL (LDL3b, 4a, 4b) (mg/dl)
timeFrame: 3 wk, 6 wk
Other outcomes:
Locations:
city: Berkeley
country: United States
facility: Cholesterol Research Center
state: California
Study officials:
affiliation: UCSF Benioff Children's Hospital Oakland
name: Ronald M Krauss, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.