Lipoprotein metabolism

Natural Cholesterol Guide

Beat Cholesterol By Scott Davis

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In the mid-1980s, investigators began to debate the question of the ideal substitute for SFA calories: carbohydrate or unsaturated fatty acids, specifically MUFAs under stable weight conditions. The results of two similar studies conducted by Grundy (1986) and Mensink and Katan (1987) reported a similar total cholesterol-lowering effect of both a high-fat diet (40% of energy) rich in MUFA and low in SFAs and a low-fat/carbohydrate-rich diet. Although both diets lowered total and LDL cholesterol, the high-MUFA diet did not lower high-density lipoprotein (HDL) cholesterol or increase triglycerides, as did the carbohydrate-rich diet. The carbohydrate-rich diet lowered HDL cholesterol by 14-22% and markedly elevated triglycerides (22-39%).

Since these pioneering studies, a number of subsequent studies have reported similar results (Grundy et al., 1988; Ginsberg et al., 1990). More recently, the DELTA Study reported that a Step 1 diet and a high-MUFA diet low in SFA and cholesterol, both lowered total and LDL cholesterol levels by 5.5% and 7%, respectively, compared with an average American diet (AAD) rich in SFA in subjects with a low HDL cholesterol level, moderately elevated triglycerides, or elevated insulin levels (Ginsberg et al., 1998). Triglycerides increased by 12% and 7% on the Step 1 diet compared with the high-MUFA diet and the AAD, respectively. Interestingly, plasma triglycerides were lower on the high-MUFA diet (by 4%) than on the AAD. Although HDL cholesterol decreased on both cholesterol-lowering diets compared with the AAD, the decrease in HDL cholesterol was less on the high-MUFA diet (4.3%) than on the Step 1 diet (7.2%). When MUFA substitutes SFA, the most important effect is a decrease in LDL cholesterol at a level comparable to low-fat diets, with up to 30% of total calories provided by fat and 55-60% of total calories as CHO. An additional benefit is that the HDL cholesterol is maintained at higher levels when SFA rather than PUFA or CHO is replaced by MUFA in the diet (Mensink et al., 1989; Mata et al., 1992; Gardner and Kraemer, 1995; Perez-Jimenez et al., 1995) (Table 4.1). Thus, the high-MUFA Mediterranean diet may be a better nutritional option than the low-fat, high-CHO diet, for substituting a Westernized diet enriched in SFA, considering that low levels of HDL cholesterol are frequent in populations with low total fat consumption.

A well-designed study performed in healthy subjects by Kris-Etherton et al. (1999) is illustrative of both the assortment of MUFA-rich foods that can be incorporated into a healthy diet and the beneficial effect of MUFA diets on serum triglycerides when substituted for CHO. These investigators compared the average American diet with four cholesterol-lowering diets: the NCEP Step II diet and three different MUFA diets. The four diets had a similar cholesterol-lowering effect but, compared with those in the average American diet, triglycerides concentrations were 11% higher with the Step II diet and were 13% lower with the MUFA diets. The HDL cholesterol level was preserved with the high-MUFA, while it was 4% lower with the Step II diet (Kris-Etherton et al., 1999).

Table 4.1 Expected healthy effects with the replacement of dietary monounsaturated fat for saturated fat. CHO: carbohydrates

Level of evidence Type of effect

Demonstrated by dietary intervention trials in different populations subjects fed with MUFA-rich diets 3. Improvement of glucose metabolism in normal subjects and type 2 diabetic patients. MUFAs result in a lower insulin requirement and plasma glucose concentration compared with the replacement by CHO

1. A more favourable lipid profile, with a decrease m LDL cholesterol plasma levels. Moreover, HDL cholesterol is higher than with the replacement by CHO

2. Reduction in vitro oxidation of LDL obtained from

Suggested by few dietary intervention trials or with in vitro experiments

1. Reduced activation of monocytes by oxidized LDL obtained from subjects fed with MUFA-rich diets.

2. A 3-10% reduction in systolic and diastolic blood pressure, in normotensive and hypertensive subjects.

3. Changes in arterial wall components (Table 4.2).

4. The promotion of a less prothrombotic environment, influencing different thrombogenic factors (Tables 4.3 and 4.4)

In comparison with low-fat diets, modest triglyceride reductions and/or HDL cholesterol increases have been observed as well after consumption of diets containing MUFA-rich nuts, such as macadamia nuts (Curb et al., 2000) and pecans (Rajaram et al., 2001). Thus, both in diabetic and in healthy subjects, natural food-based MUFA regimes may be preferable to a low-fat diet because of more favourable effects on TAG-rich lipoproteins and HDL cholesterol, with an attendant decrease of the cardiovascular risk profile. However, there exists no evidence that the reduction of HDL cholesterol, related with low-fat diets, favours the onset of coronary heart disease (Knuiman et al., 1982).

Both Keys (1965) and Hegsted et al. (1965) analysed data from controlled feeding studies and developed similar blood cholesterol predictive equations. MUFAs did not affect total cholesterol levels, but SFA raised them. PUFAs lowered total cholesterol half as much as SFA raised it. More recent analyses confirmed these findings, although there is some suggestion that MUFAs elicit a cholesterol-lowering effect that is less than that observed for PUFAs (Mensink and Katan, 1992; Yu et al., 1995). In support of these findings, Howard et al. (1995) found greater reductions in total cholesterol levels with PUFAs versus MUFAs (p < 0.05) in a controlled-feeding study. However, other controlled-feeding studies, as well as a study with free-living subjects, observed comparable total and LDL cholesterol-lowering effects of these fatty acids (Ginsberg et al., 1994; Gardner and Kraemer, 1995) when 4-14% of energy of each fatty acid class was substituted for the other. Likewise, in a meta-analysis of results of 14 studies published between 1983 and 1994, diets high in oils enriched in

MUFAs versus PUFA elicited similar effects on total, LDL and HDL cholesterol, whereas the PUFA-enriched oil had a slight triglyceride-lowering effect (Gardner and Kraemer, 1995). Thus, the cholesterolaemic effects of MUFA versus PUFA substitution for dietary SFA are comparable.

In addition, in patients with diabetes mellitus, Garg's meta-analysis of ten studies (Garg, 1998) showed that the net changes in fasting plasma concentrations of TAG, VLDL cholesterol, HDL cholesterol and LDL cholesterol with consumption of a high-MUFA diet were a 19% reduction, a 22.5% reduction, a 4% increase and a 0% change, respectively.

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