Influence of hydrogenated fat and butter on CVD risk factors: remnant-like particles, glucose and insulin, blood pressure and C-reactive protein

Abstract

Dietary trans fatty acids/partially-hydrogenated fat has been associated with increased risk of developing cardiovascular disease (CVD), possibly greater than predicted from changes in lipoprotein levels. To explore this issue further potential risk factors were assessed in subjects provided with each of six diets in randomized order containing as the major source of fat: soybean oil, semi-liquid margarine, soft margarine, shortening, traditional stick margarine or butter. Plasma fatty acid profiles reflected diet, with triglyceride and phospholipid subfractions affected to a greater extent than cholesteryl ester. Non-fasting LDL-cholesterol levels were 144±27, 141±27, 146±26, 148±30, 151±29 and 165±31 mg/dl (P<0.001) and total cholesterol/HDL-cholesterol ratios were 5.50±1.25, 5.54±1.50, 5.69±1.29, 5.82±1.40, 6.11±1.30 and 5.94±1.43 (P=0.011), respectively, whereas other lipoprotein levels were not significantly different. Remnant-like particles levels were unaffected by dietary fat, either in the fasting or non-fasting state. Differences in fasting insulin and glucose levels were small and would not be predicted to have a large impact on glucose homeostasis. There was no significant effect of dietary fat type on C-reactive protein levels or blood pressure. These data suggest that, as previously demonstrated, the major CVD risk factor adversely affected by dietary trans fatty acids/partially-hydrogenated fat is LDL-cholesterol levels and total cholesterol/HDL-cholesterol ratios.

Introduction

The relationship between diet and chronic disease risk is complex and multi-factorial. There are a number of biological factors that are altered by diet. In turn, some of these factors may independently or in combination alter cardiovascular disease (CVD) risk. Data on the relationship between both saturated and trans fatty acid intake, and plasma lipid levels are relatively consistent. When either saturated and trans fatty acids are substituted for cis unsaturated fatty acids, total and LDL cholesterol levels are higher [1], [2], [3]. When trans fatty acids are substituted for saturated fatty acids, HDL cholesterol levels are lower, triglyceride levels are higher and the total cholesterol to HDL cholesterol ratio is less favorable.

The results of some large-scale epidemiological studies suggest that trans fatty acid intake is associated with an increased risk of developing CVD, potentially greater than would be predicted from changes in plasma lipid levels alone [4], [5], [6]. It has further been reported that trans fatty acid intake is associated with an increased risk of developing Type 2 diabetes [7]. In contrast, data from smaller studies suggested that trans fatty acid intake is not associated with markers of insulin resistance [8], [9], [10]. Saturated fat intake is positively associated with increased LDL cholesterol levels and CVD risk and has been associated with a deterioration of glucose control [11], [12], [13].

C-reactive protein (CRP) is a marker of low to moderate systemic inflammation. In cross-sectional and prospective studies elevated levels of CRP have been positively associated with risk of future events in both healthy subjects and subjects who have had a previous myocardial infarction or with stable and unstable angina [14], [15]. Little is known about the effect of diet on CRP levels [16], [17], [18], especially with respect to trans and saturated fatty acids.

High levels of plasma triglyceride have been observed in patients with heart disease and have been associated with increased risk of developing CVD [19], [20]. Plasma triglyceride is carried on a variety of particles from both intestinal and hepatic origin, collectively referred to as remnant-like particles (RLP). For the most part, these particles represent a broad spectrum of partially hydrolyzed lipoprotein remnants. Emerging data suggest that elevated levels of RLPs in circulation are associated with increased CVD risk [21], [22]. Trans fatty acids have been reported to increase triglyceride levels [1], [2], [3]. However, little is known about the type of particle on which this triglyceride is carried.

The objective of this report was to assess the effect of a wide range of commonly available partially-hydrogenated fats, varying primarily in the levels of trans fatty acids and polyunsaturated fatty acids, as well as saturated fatty acids in the form of butter, on CVD risk factors, including RLP, glucose and insulin and CRP levels, and blood pressure. The study subjects, moderately hypercholesterolemic middle aged and older female and male subjects, were chosen because they represent a group of individuals to whom dietary modification is particularly targeted.