Dietary Lipids and Plasma Lipoproteins: 
A Meta-Analysis

ABSTRACT: Quantitative relations between dietary fat and cholesterol and plasma lipid concentrations have been the subject of much study and some controversy during the past 40 y. Previous meta-analyses have focused on the most tightly controlled, highest- quality experiments. To test whether the findings of these investigations are generalizable to broader experimental settings and to the design of practical dietary education interventions, data from 224 published studies on 8143 subjects in 366 independent groups including 878 diet-blood lipid comparisons were subjected to weighted multiple-regression analysis. Inclusion criteria specified intervention studies published in English between 1966 and 1994 reporting quantitative data on changes in dietary cholesterol and fat and corresponding changes in serum cholesterol, triacyl- glycerol, and lipoprotein cholesterol concentrations. Regression models are reported for serum total cholesterol, triacylglycerol, and low-density- high-density-, and very-low- density-lipoprotein cholesterol, with multiple correlations of 0.74, 0.65, 0.41, 0.14, and 0.34, respectively. Interactions of dietary factors, initial dietary intakes and serum concentrations, and study and subject characteristics had little effect on these models. Predictions indicated that compliance with current dietary recommendations (30% of energy from fat, < 10% from saturated fat, and < 300 mg cholesterol/d) will reduce plasma total and low-density-lipoprotein-cholesterol concentrations by -5% compared with amounts associated with the average American diet.

COMMENTARY

The report by Howell et al. [Am J Clin Nutr 1997;65: in press] provides a better derstanding of the effects of dietary lipids on plasma lipids and lipoproteins, and gives a quantitative perspective on the relative effects of dietary fatty acid saturation versus dietary cholesterol on plasma lipids and lipoproteins. Based on a very large data-base, Howell et al. used meta-analytic procedures to estimate the average effects of dietary lipids on plasma lipids and the potential interactions between dietary factors and study subject characteristics. Interestingly, the results of this analysis, as well as many others done over the years, reach pretty much the same conclusions. Simply stated, the data demonstrate that the major dietary lipid determinant of plasma cholesterol is saturated fat, followed by polyunsaturated fat and then dietary cholesterol.

Ever since the initial publication of the predictive equations for dietary lipid effects on plasma lipids, there has been a debate over the dietary cholesterol response factor. Ancel Keys did not include a dietary cholesterol component in his original equation published in 1957. In 1965 and 66 Keys and Mark Hegsted independently published predictive equations which differed on the importance of dietary cholesterol. The Hegsted 1965 equation had a much larger dietary cholesterol factor than the 1966 Keys equation. Over the years, with an ever expanding data base for analysis, the dietary cholesterol factor has gotten smaller and smaller such that in the 90s the most recent equations have listed factors ranging from 0.02 to 0.03 mg/dl per mg dietary cholesterol. What the data indicate is that for every 100 mg/day decrease in the average daily dietary cholesterol intake there will be, on average, a 2 - 3 mg/dl fall in the plasma cholesterol level.

Using the most recent equations one can estimate the effects of shifting from the average American diet to the widely recommended diet lower in fat and cholesterol. If the average American diet has 37% of calories from fat [13% saturated fat, 17% monounsaturated fat and 7% polyunsaturated fat] and 385 mg/day cholesterol, and the population shifts to a 30% fat diet [10% saturated, 10% monounsaturated and 10% polyunsaturated] with 300 mg of cholesterol, it can be predicted that the average plasma cholesterol level will decrease by 12 mg/dl. This decrease is equal to a 5.7% drop in the average plasma cholesterol value in the population. This decrease is the sum of the effects of the decrease in saturated fat [6.6 mg/dl, 56%], the increase in polyunsaturated fat [3.1 mg/dl, 26%], and the decrease in dietary cholesterol [2.2 g/dl, 18%].

In a recent interview in Eating Light magazine, Dr. Ancel Keys was quoted as saying "... there's no connection whatsoever between cholesterol in food and cholesterol in the blood. None. And we've known that all along." Forty years after the publication of the first Keys equation we are back where we started with regard to dietary cholesterol, except that instead of saying it has no effect on plasma cholesterol levels we now state that it has little effect based on the large amount of data which can document a statistically significant, but probably biologically insignificant, effect of dietary cholesterol on plasma cholesterol.

The report by Howell et al. provides additional evidence to an ever growing body of research findings that come to the same conclusions: first, restrictions on dietary cholesterol intake have little effect on plasma cholesterol levels; second, specific quantitative restrictions on egg consumption have little, if any, scientific justification and fosters continued confusion for the consumer regarding the importance of saturated fat versus dietary cholesterol; and finally, undue restriction limit the valuable contributions eggs can make to the balance and variety of the diet, while keeping many in the population (the elderly, children, low-income families) from an readily affordable, nutrient dense source of high quality protein and 13 vitamins and minerals.