Role of dietary cholesterol in the optimal diet for the treatment of hypercholesterolemia.

OBJECTIVE: This paper discusses studies in which the effects of dietary cholesterol on the plasma concentrations of lipids and lipoproteins have been evaluated in adult human subjects including patients with hypo- and hypercholesterolemia. DESIGN: The dietary studies were conducted on an outpatient basis in the Clinical Research Center. Each dietary period was four weeks in duration and an adequate washout period was interposed between each dietary phase. SETTING: A university medical centre. PATIENTS: The participants in these studies were adult men or women with hypocholesterolemia, normal volunteers or patients with primary hypercholesterolemia. INTERVENTIONS: The dietary periods consisted of three separate dietary phases in which dietary cholesterol was a single variable. The diets contained 50 mg/day of cholesterol for the low cholesterol diet, 350 mg/day for the moderate cholesterol diet and 650 mg/day for the high cholesterol diet. RESULTS: Concentrations of total and low density lipoprotein (LDL) cholesterol increased in all three patient groups from the low cholesterol to the moderate cholesterol to the high cholesterol diet but the magnitude of increase in LDL cholesterol concentrations was greater in the patients with pre-existent hypercholesterolemia and least in the patients with hypocholesterolemia. In all three patients groups an increased intake of dietary cholesterol was associated with suppression of endogenous cholesterol biosynthesis as assessed by the urinary excretion of mevalonic acid. CONCLUSIONS: An increased intake of dietary cholesterol results in increases in the plasma concentrations of total and LDL cholesterol in patients with inherently low, normal or high concentrations of LDL cholesterol but the magnitude of increase is greatest in those patients with pre-existent hypercholesterolemia. These results support the view that restriction of dietary cholesterol leads to a reduction in the plasma concentrations of total and LDL cholesterol and is an appropriate recommendation for patients with known hypercholesterolemia or patients in whom medical recommendations call for a reduction in the plasma concentrations of total and LDL cholesterol.

Individual effects of dietary saturated fatty acids and fish oil on plasma lipids and lipoproteins in normal men.

Fish ingestion is associated with lower mortality from coronary heart disease (CHD). However, in some Western populations whose diets are rich in saturated fatty acids (SFAs), CHD mortality is consistently high despite high fish consumption. To study this paradox, we fed six healthy men diets with two amounts of SFA (5% and 19% of energy) that also differed in total fat (25% and 39% of energy). Each fat amount was given with and without n-3 fatty acids (FAs) (2% of energy) for 3 wk. On both the low and high SFA diets the presence of n-3 FAs significantly lowered plasma total cholesterol, very-low-density-lipoprotein cholesterol, (high-density-lipoprotein cholesterol (HDL-C), total triglyceride, and very-low-density-lipoprotein triglyceride. Compared with the high SFA diet, the low SFA diet decreased total cholesterol, low-density-lipoprotein cholesterol, and HDL-C. No interaction of SFA and n-3 FA was found. These results indicate that dietary SFAs and n-3 FAs have independent mechanisms of actions on the plasma lipids and lipoproteins. Optimal plasma lipids were produced by the diet low in SFA and high in n-3 FA.

Will a high-carbohydrate, low-fat diet lower plasma lipids and lipoproteins without producing hypertriglyceridemia?

A sudden increase in dietary carbohydrate invariably increases the plasma levels of very low density lipoprotein (VLDL) and triglyceride. The present studies were designed to test the hypothesis that dietary carbohydrate-induced hypertriglyceridemia need not occur. In the first study we fed gradually increasing amounts of carbohydrate and gradually decreasing amounts of fat to eight subjects. The usual American diet (40% fat, 45% carbohydrate, and 15% protein) was followed in sequence by four diets in a phased regimen, the carbohydrate increasing by 5% of total calories and the fat content decreasing by 5% for each dietary period. In the last dietary period (phase 4), 20% of the energy was in the form of fat and 65% in the form of carbohydrates; the cholesterol content was 100 mg/day. Throughout the study, plasma triglyceride and VLDL triglyceride levels did not change significantly. The plasma total and low density lipoprotein (LDL) cholesterol levels were greatly reduced, by 15% and 22%, respectively (p = 0.004). Plasma high density lipoprotein (HDL) cholesterol levels decreased concomitantly. In the second study, after a washout period six of the subjects were initially fed the phase 4 high-carbohydrate diet for a 10-day period. The plasma triglyceride concentration increased over baseline levels by 47%, and VLDL triglyceride levels increased by 73%. We conclude that although a sudden increase in dietary carbohydrate increases the plasma triglyceride level, patients gradually introduced to a high-carbohydrate, low-fat diet may achieve a significant reduction of plasma total and LDL cholesterol without developing carbohydrate-induced hypertriglyceridemia.

Amount and distribution of dietary protein affects clinical response to levodopa in Parkinson's disease.

Reducing dietary protein improves the effectiveness of levodopa (LD) but the most effective distribution of a low-protein diet (0.8 g/kg) is unclear. We compared a 1.6 g/kg protein diet, a 0.8 g/kg diet with protein evenly distributed between meals, and a 0.8 g/kg diet with protein restricted to the evening meal in 5 parkinsonian patients with motor fluctuations. We monitored clinical response, plasma LD, and plasma large amino acids (LNAAs) hourly throughout the day. Mean "on" times were 51% (1.6 g/kg diet), 67% (0.8 g/kg evenly distributed), and 77% (0.8 g/kg restricted). Hourly averages of plasma LD did not differ between the diets. The mean plasma LNAAs were 732 nmol/ml (1.6 g/kg diet), 640 (0.8 g/kg distributed), and 542 (0.8 g/kg restricted), and the diurnal pattern reflected the distribution of protein intake. In conclusion, the amount and distribution of dietary protein affect clinical response to LD. These effects are not related to LD absorption but are explained by the variation in plasma LNAAs.

Hypolipidaemic effects of n-3 fatty acids in primary hyperlipoproteinaemia.

The influence of fish oils rich in n-3 fatty acids on plasma lipid and lipoprotein concentrations in patients with primary hyperlipoproteinaemia is reviewed. When used as a dietary supplement, n-3 fatty acids exert their greatest effect on the concentrations of triglyceride-rich lipoproteins and these effects are dose dependent. Low doses of n-3 fatty acids reduce plasma triglyceride concentrations in patients with phenotypic type IV, type V and type IIB hyperlipoproteinaemia, but concurrently result in modest increases in the plasma concentrations of low density lipoprotein (LDL). With very high doses plasma concentrations of LDL cholesterol decrease in patients with the type IIB phenotype. At low doses n-3 fatty acids do not significantly lower concentrations of LDL cholesterol in patients with primary hypercholesterolaemia whereas at higher doses a modest LDL lowering effect is achieved. The results indicate that the therapeutic potential of n-3 fatty acids as hypolipidaemic agents is greatest in patients with hypertriglyceridaemia.

The cholesterol/saturated-fat index: an indication of the hypercholesterolaemic and atherogenic potential of food.

A food's hypercholesterolaemic-atherogenic potential lies in its cholesterol and saturated-fat content. To help understand the contribution of these two factors a cholesterol/saturated-fat index (CSI) has been calculated. This index is based on a modification of a regression equation computed from metabolic studies designed to lower plasma lipids. A low CSI indicates low saturated fat and cholesterol content and low atherogenicity. The CSI may be used to compare different foods and recipes and to evaluate daily intake quickly and easily.