Journal Name:
Arteriosclerosis & Thrombosis
Article Title:
Effect of dietary fat selection on plasma cholesterol synthesis in older, moderately hypercholesterolemic humans.
Date Written:
1994
Volume:
14
Number:
4
Page:
542
Author(s):
Jones, P.J.H.; Lichtenstein, A.H.; Schaefer, E.J.; Namchuk, G L.
Article:
Evidence indicates that cholesterol levels are raised with saturated fatty acids (SFAs) and reduced with monounsaturated (MUFA) and polyunsaturated fatty acid (PUFA). The mechanism by which dietary fats influence circulating cholesterol levels is not well understood. In animals, higher rates of both the removal of cholesterol from the circulating compartment and cholesterogenesis have been reported with PUFA consumption. In humans, the consumption of PUFA appears to lead to enhanced fecal sterol excretion with resultant negative sterol balance. The objectives of this study were to examine (1) the influence of the ratio of MUFA to PUFA on circulating cholesterol levels and plasma cholesterol synthesis rates in moderately hypercholesterolemic subjects and (2) associations between fatty acid and plant sterol contents of the oils consumed and plasma cholesterol synthesis rate. Cholesterol synthesis was determined as the fractional synthesis rate (FSR) of the rapid-turnover body cholesterol pool and as a calculated estimate of absolute synthesis rate (ASR).
Diets were fed to 15 hypercholesterolemic subjects (low-density lipoprotein [LDL] cholesterol > 130 mg/dL) over a period of 32 days: (1) a baseline diet (36% kcal as fat: 15% SFA, 15% MUFA, and 6% PUFA; 180 mg cholesterol/1000 kcal) and diets meeting National Cholesterol Education Program step 2 criteria (30% kcal as fat, 7% SFA, 80 to 85 mg cholesterol/Meal), where two thirds of the fat was either (2) olive, (3) corn, or (4) canola oil. Plasma total, LDL, and high-density lipoprotein (HDL) cholesterol and triglyceride levels were determined at the end of each period. Cholesterol fractional synthesis rate (FSR) was measured as the deuterium (D) incorporation into plasma total cholesterol relative to body D2O level (1.2 g D2O.kg estimated body water) over 24 hours. Absolute synthesis rates (ASRs) were determined as the product of FSR and rapid turnover cholesterol pool size. The results showed that plasma total and LDL cholesterol levels declined significantly on all plant-oil diets compared with the baseline diet; however, triglyceride levels were not different. FSRs were significantly higher for the corn oil compared with baseline and olive oil but not canola oil. Mean ASR for the corn oil diet was significantly elevated relative to baseline and olive oil but not canola oil.
The enhanced cholesterol synthesis which resulted following consuming corn relative to olive and canola oils, suggests a difference in the mechanism by which these plant oils elicit their cholesterol-lowering effects. Positive correlations were observed between the 18:2n-6 (linoleic LA) and plant sterol of the three plant oils tested but not with other oil constituents. These associations suggest that fatty acids or plant sterol levels may play a role in the regulation of cholesterogenesis. Whereas plant oils containing MUFAs and PUFAs lower total circulating cholesterol concentrations in comparison with SFAs, lipoprotein distribution may differ with the type of plant oil consumed. Dietary fat-dependent variations in both lipoprotein clearance and cholesterol synthesis rates have been reported. Elevated LDL removal, associated with enhanced hepatic elimination, may reduce circulating cholesterol levels and result in an enhancement in synthesis.
Differing levels of fatty acids in the oils may directly alter cholesterol synthesis rates in a structure-specific manner. Evidence shows that PUFAs are preferentially used for oxidation versus retention in vivo. Beta-oxidation of PUFA could result in greater availability of acetyl coenzyme A as a substrate for cholesterol synthesis. Plant sterols may also upregulate cholesterogenesis indirectly by reducing cholesterol absorption directly or by serving as a synthesis precursor. Sitosterol and total plant sterol concentrations in the three oils tested varied directly with cholesterol synthesis, suggesting an interference with cholesterol absorption.
The canola oil tested was intermediate between corn and olive oil in its PUFA-to-MUFA ratio and in sitosterol and total plant sterol content. The intermediate effect of addition of canola oil on cholesterol synthesis rate may be attributable to its plant sterol and/or fatty acid composition.
In conclusion, differences were found in cholesterol synthesis in response to dietary fats in middle-aged, moderately hypercholesterolemic subjects consuming diets relatively low in fat content. The findings suggest that there is a more rapid flux of central-pool cholesterol associated with enhanced synthesis following corn versus olive oil feeding. The authors postulate that, although other factors not presently identified may be responsible for this association, LA and plant sterol content of oils may be contributing factors.
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