Dietary Cholesterol and Plasma Cholesterol: Recent Studies
Clinical studies of the effects of dietary cholesterol on plasma cholesterol levels are complicated by many factors, not the least of which is the wide range of dietary cholesterol levels fed to study subjects. Other factors include the type and amount of dietary fat and whether the studies use a controlled feeding environment or are carried out in free-living subjects. The following outline summarizes the methodology and results of dietary cholesterol – plasma cholesterol studies published between 1994 and 1996. In order to more accurately compare the various cholesterol feeding studies carried out over the past two years, the plasma cholesterol changes (mg/dl) have been normalized per 100 mg per day change in dietary cholesterol to give a dose adjusted value as mg/dl per 100 mg/day.
1994
Ginsberg et al. 1994. A dose-response study of the effects of dietary cholesterol on fasting and postprandial lipid and lipoprotein metabolism in healthy young men. Arterioscler. Thrombosis 14:576-586.
For these controlled feeding studies twenty-four young men were fed 30% fat diets (NCEP Step I) with addition of zero (128 mg cholesterol/day), one (283 mg/day), two (468 mg/day) or four (858 mg/day) eggs per day to the basal diet. Each diet was fed for eight weeks. Average plasma cholesterol levels in the twenty-four subjects were 155, 161, 162, and 166 mg/dl for the zero, one, two and four eggs per day feeding periods. Plasma total cholesterol increased 1.5 mg/dl per 100 mg/day added dietary cholesterol. There was no evidence that changes in dietary cholesterol intakes altered the postprandial plasma lipoprotein profile (lipoproteins thought to be involved in the development of atherosclerosis) and thus did not alter the atherogenic potential of the plasma lipoproteins. The data indicate that in the majority of healthy young men addition of two eggs per day to a low-fat diet has little effect on plasma cholesterol levels.
Schnohr et al. 1994. Egg consumption and high-density-lipoprotein cholesterol. J. Intern. Med. 235:249-251.
To determine the effects of egg consumption on plasma HDL cholesterol levels, twenty-four adults added two eggs per day to their usual diets for six weeks. Total cholesterol levels were increased by 4% while HDL cholesterol levels increased 10%. The dose adjusted response to the change in dietary cholesterol was 2.4 mg/dl per 100 mg/day. The authors concluded that “a moderate egg intake should not be rigorously restricted in healthy individuals.”
McComb et al. 1994. Attenuated hypercholesterolemic response to a high-cholesterol diet in subjects heterozygous for the apolipoprotein A-IV-2 allele.N. Engl. J. Med. 331:706-710.
Genetic factors contribute to the variability of the plasma lipid responses to dietary cholesterol and in this study it was shown that subjects with the apolipoprotein A-IV-2 allele have an attenuated response to a dietary cholesterol challenge. Subjects were fed a low-cholesterol diet and one with 1100 mg/day added cholesterol. The change in plasma cholesterol in subjects without the apo A-IV-2 allele (n=12) was 22 mg/dl (dose adjusted: 2.3 mg/dl per 100 mg/day) while for those with the apo A-IV-2 allele (n=11) the change was 6 mg/dl (dose adjusted: 0.7 mg/dl per 100 mg/day). It is estimated that one in every seven individuals in the United States has the apo A-IV-2 allele and, based on the data from this study, has a genetic resistance to the plasma cholesterol raising effects of very high intakes of dietary cholesterol. These findings are a breakthrough in beginning to understand the role of genetic factors in the variability of plasma lipid responses to dietary cholesterol.
Vuoristo & Miettinen. 1994. Absorption, metabolism, and serum concentrations of cholesterol in vegetarians: effects of cholesterol feeding. Am. J. Clin. Nutr. 59:1325-1331.
Dietary cholesterol feeding studies were carried out in five vegetarians to determine if there were any differences in responses as compared to non-vegetarians. Addition of three egg yolks per day (690 mg cholesterol) to the diet for two months increased the average plasma cholesterol level by 23 mg/dl (dose adjusted: 3.4 mg/dl per 100 mg/day). Surprisingly, HDL cholesterol levels were increased by 10 mg/dl with addition of egg yolks to the diet and the LDL:HDL ratio was unaffected by cholesterol feeding. The authors concluded that the metabolic responses to dietary cholesterol are similar for vegetarians and non-vegetarian subjects.
Kern. 1994. Effects of dietary cholesterol on cholesterol and bile acid homeostasis in patients with cholesterol gallstones. J. Clin. Invest. 93:1186-1194.
Sixteen women, eight controls and eight with cholesterol gallstones, were fed moderate- and high-cholesterol (5 eggs/day = 939 mg/day cholesterol) diets for 15-18 days and various parameters of cholesterol metabolism were measured. In control subjects the plasma cholesterol level increased by 6 mg/dl with cholesterol feeding (0.7 mg/dl per 100 mg/day) while in the gallstone subjects the plasma total cholesterol level was decreased by 8 mg/dl with intake of the high cholesterol diet. The study also found that in both groups cholesterol absorption and cholesterol synthesis were decreased on the high cholesterol diet. In both groups of patients, the body’s response to a large increase in dietary cholesterol was sufficient to compensate for the increase resulting in little or no increase in plasma cholesterol levels.
Lichtenstein et al. 1994. Hypercholesterolemic effect of dietary cholesterol in diets enriched in polyunsaturated and saturated fat. Dietary cholesterol, fat saturation, and plasma lipids. Arterioscler. Thromb. 14:168-175.
Studies in fourteen men (n=8) and women (n=6) fed either corn oil (polyunsaturated fat) or beef tallow (saturated fat) with or without addition of 197-226 mg cholesterol per 1000 kcal, documented little effect of dietary fat saturation on the plasma cholesterol response to dietary cholesterol. In the corn oil fed group the addition of cholesterol increased plasma cholesterol 11 mg/dl (dose adjusted: 3.9 mg/dl per 100 mg/day) and in the beef tallow group the increase was the same, 11 mg/dl (dose adjusted: 3.8 mg/dl per 100 mg/day). The findings are consistent with other studies which indicate that with a 30% fat diet, the plasma cholesterol response to dietary cholesterol is independent of the fatty acid composition of the diet. The study also provides evidence which suggests that resistance to the effects of dietary cholesterol occurs in older men and women and is not limited to only young, healthy volunteers.
Jones et al. 1994. Interaction of dietary fat saturation and cholesterol level on cholesterol synthesis measured using deuterium incorporation. J. Lipid Res. 35:1093-1101.
These investigators tested the effects of dietary fat and cholesterol on the regulation of cholesterol synthesis in older men (n=6) and women (n=8). The study subjects were fed diets high in either polyunsaturated fat, corn oil, or saturated fat, beef tallow, with and without addition of 120 mg cholesterol per 1000 kcal. Dietary cholesterol increased plasma cholesterol levels by 12 mg/dl (dose adjusted response = 4.1 mg/dl per 100 mg/day change in dietary cholesterol) and there was no difference between the dietary polyunsaturated and saturated fat groups. The results from this study provide evidence that one effect of an increase in dietary cholesterol is a decease in cholesterol synthesis by the body to compensate for the change. The precision of this mechanisms helps maintain plasma cholesterol levels constant.
1995
Ginsberg et al. 1995. Increases in dietary cholesterol are associated with modest increases in both LDL and HDL cholesterol in healthy young women. Arterioscler. Thromb. Vasc. Biol. 15:169-178.
A controlled dietary cholesterol feeding study in thirteen young women tested the effects of feeding zero, one, or three eggs per day on plasma lipids and lipoproteins. The data indicated that the dose adjusted plasma cholesterol response was 2.8 mg/dl per 100 mg/day dietary cholesterol (a value higher than that obtained in males in the 1994 study). In women, however, the increase in total plasma cholesterol with dietary cholesterol occurred in both the atherogenic LDL cholesterol (2.1 mg/dl per 100 mg/day) and the anti-atherogenic HDL cholesterol (0.6 mg/dl per 100 mg/day). As found in the previous study in healthy young men, young women have the ability to compensate for an increased intake of cholesterol by adjusting the way cholesterol is handled by the body. The data show that addition of two eggs per day to the diet of healthy young women has little effect on plasma cholesterol levels in the majority of study subjects.
Ferrier et al. 1995. Alpha-linolenic acid- and docosahexanaenoic acid-enriched eggs from hens fed flaxseed: influence on blood lipids and platelet phospholipid fatty acids in humans. Am. J. Clin. Nutr. 62:81-86.
This study compared the effects of feeding four regular or omega-3 fatty acid enriched eggs per day for two weeks on plasma lipids in twenty-eight males. Eggs were obtained from hens fed either zero, ten or twenty percent flax seed diets. Addition of four eggs per day (720 mg of cholesterol) to the diet increased plasma total cholesterol levels an average of 13 mg/dl and there were no differences between the sources of eggs tested. The dose adjusted change in plasma cholesterol levels was 1.9 mg/dl per 100 mg/day change in dietary cholesterol. HDL cholesterol levels were increased 2 mg/dl with the addition of eggs. It would appear from this study that the fatty acid composition of the egg has no relationship to the effects of dietary cholesterol on plasma cholesterol levels.
1996
Knopp et al. 1996. A double-blind, randomized trial of the effects of two eggs per day in moderately hypercholesterolemic and combined hyperlipidemic subjects consuming the NCEP Step I diet. (Reported in abstract at the November 1995 American Heart Association meeting in Anaheim, CA)
Studies in middle-aged men and women with either moderate hypercholesterolemia (n=44) or combined hyperlipidemia (elevated plasma cholesterol and triglyceride, n=31) were fed either no eggs or two eggs per day as part of a NCEP Step I diet. Subjects with moderate hypercholesterolemia were found to have a dose adjusted plasma cholesterol response to added dietary cholesterol of 1.6 mg/dl per 100 mg/day whereas combined hyperlipidemic individuals are more sensitive to dietary cholesterol and have an average dose response factor of 3.2 mg/dl per 100 mg/day change in dietary cholesterol. The authors concluded that middle aged men and women with elevated plasma cholesterol levels were not more sensitive to dietary cholesterol compared to subjects with normal cholesterol levels. In contrast, middle aged patients with combined hyperlipidemia appear to be more sensitive to dietary cholesterol and in their case dietary cholesterol restrictions appear more appropriate.
DATA SUMMARY:
STUDY | PLASMA CHOLESTEROL [mg/dl per 100 mg/day] |
Ginsberg et al. 1994 | 1.5 |
Schnohr et al. 1994 | 2.4 |
McComb et al. 1994 | 2.3; 0.7 |
Vuoristo & Miettinen 1994 | 3.4 |
Kern 1994 | 0.7; 0.0 |
Lichtenstein et al. 1994 | 3.9; 3.8 |
Jones et al. 1994 | 4.1 |
Ginsberg et al. 1995 | 2.8 |
Ferrier et al. 1995 | 1.9 |
Knopp et al. 1996 | 1.6, 3.2 |
AVERAGE | 2.3 |
1960-96 (n=142) | 2.5 |
SUMMARY
The dietary cholesterol feeding studies carried out during the past two years add to a growing body of evidence demonstrating that the majority of study subjects have relatively small plasma cholesterol changes in response to changes in dietary cholesterol intake. These findings are consistent with data from over thirty years of clinical investigations on this question and indicate that the average response to a 100 mg/day change in dietary cholesterol intake is a 2.5 mg/dl change in plasma cholesterol levels. While some individuals are more sensitive to the effects of dietary cholesterol (15-20% of the population), the dose adjusted response factor in this group is still relatively small (3.2 vs 1.6 for sensitive vs resistant study subjects). For example, it can be estimated that reducing dietary cholesterol intake from 400 mg/day to 300 mg/day results in a plasma cholesterol reduction of 3.2 mg/dl in cholesterol sensitive individuals and as little as 1.6 mg/dl in cholesterol insensitive individuals. What becomes essential for effective dietary interventions to lower an elevated plasma cholesterol level is an understanding of the extensive variability of individual responses to dietary changes and the need to determine the most effective dietary intervention for the high risk patient.