Published Online
on June 6, 2005

A more recent version of this article appeared on June 14, 2005

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Submitted on September 10, 2004
Revised on February 22, 2005
Accepted on February 28, 2005

Cholesterol Feeding Increases C-Reactive Protein and Serum Amyloid A Levels in Lean Insulin-Sensitive Subjects

Lisa R. Tannock MD, Kevin D. O’Brien MD, Robert H. Knopp MD, Barbara Retzlaff MPH, Brian Fish AB, Mark H. Wener MD, Steven E. Kahn MB, ChB, and Alan Chait MD^*

From the Department of Medicine (L.R.T., K.D.O., R.H.K., B.R., B.F., M.H.W., S.E.K., A.C.), University of Washington, Seattle, and the Veterans Administration Puget Sound Health Care System (S.E.K.), Seattle, Wash. L.R.T. is currently at the Department of Medicine, University of Kentucky, Lexington.

^* To whom correspondence should be addressed. E-mail: achait{at}u.washington.edu.

Background--Inflammatory markers associated with elevated cardiovascular risk are increased by cholesterol feeding in animal models. However, whether dietary cholesterol increases inflammatory marker levels in humans is not known.

Methods and Results--C-reactive protein (CRP), serum amyloid A (SAA), and lipoprotein levels were compared in 201 healthy subjects on an American Heart Association-National Cholesterol Education Program step 1 diet at baseline and after addition of 4 eggs per day for 4 weeks. Subjects were classified a priori into 3 groups based on their body mass index (BMI) and insulin sensitivity index (S_I): lean insulin sensitive (LIS), mean±SEM BMI, 23.2±0.3 kg/m², and S_I, 6.7±0.3x10^-4min^-1/(µU/mL), n=66; lean insulin resistant (LIR), BMI, 24.5±0.2 kg/m² and S_I, 2.9±0.1x10^-4min^-1/(µU/mL), n=76; or obese insulin resistant (OIR), BMI, 31.4±0.5 kg/m² and S_I, 2.1±0.1x10^-4min^-1/(µU/mL), n=59. Insulin resistance and obesity each were associated with increased baseline levels of both CRP (P for trend, <0.001) and SAA (P for trend=0.015). Egg feeding was associated with significant increases in both CRP and SAA in the LIS group (both P<0.01) but not in the LIR or OIR groups. Egg feeding also was associated with a significant increase in non-HDL cholesterol (P<0.001) in LIS subjects; however, there was no correlation between the change in non-HDL cholesterol or changes in either CRP or SAA in this group.

Conclusions--A high-cholesterol diet leads to significant increases in both inflammatory markers and non-HDL cholesterol levels in insulin-sensitive individuals but not in lean or obese insulin-resistant subjects.

Key words: cholesterol • C-reactive protein • insulin resistance • lipoproteins • serum amyloid A

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