Eggs and beyond: is dietary cholesterol no longer important?
Robert H Eckel*
Divisions of Endocrinology, Metabolism, and Diabetes and Cardiology, University of Colorado School of Medicine, University of Colorado, Aurora, CO
Within the past 18 mo, 2 sets of nutritional guidelines, the 2013
American College of Cardiology/American Heart Association Life-
style Guideline for the Reduction of Cardiovascular Disease (1) and
the 2015 USDA Dietary Guidelines for Americans (http://www.
health.gov/dietaryguidelines/2015.asp), have indicated that the ev-
idence for dietary cholesterol restriction to lower total and LDL
cholesterol is insufﬁcient. In fact, the USDA guidelines state that
“cholesterol is not considered a nutrient of concern for overcon-
sumption.” These statements about dietary cholesterol have pro-
voked considerable reaction.
Related news coverage has been ﬁlled with mixed messages,
many of which have been and continue to be misinterpreted. On
10 February 2015, a Washington Post headline stated, “The U.S.
government is poised to withdraw longstanding warnings about
cholesterol.” CNN went on to report on 19 February 2015 that
“Cholesterol in Food Not a Concern, New Report Says.” And
although the 10 June 2015 issue of the Health Hub from the
Cleveland Clinic posed “Do Your Cholesterol Numbers Really
Matter?” they went on to say “yes—just because the emphasis on
cholesterol in food is less—it does not mean that your blood
cholesterol does not matter.” Nevertheless, can the public or even
the health care professional distinguish between the relative dis-
tinction and importance between dietary cholesterol and saturated
or even trans fat? In fact, confusion lies in the fact that ;60%
of cholesterol intake is from foods that also contain a moderate
amount of saturated fat such as beef/beef dishes, burgers, sausage,
bacon, and cheese, with the other ;40% mostly from eggs (;25%
of total cholesterol intake), chicken and chicken dishes (;12%),
and foods such as shellﬁsh, which contain very little or a much
smaller percentage of total fat as saturated fat (http://appliedresearch.
VARIABLE HISTORICAL SCIENCE IN TERMS OF
EXPERIMENTAL DESIGN, QUALITY, AND SUBGROUPS
Studies to document the independent effect of dietary cholesterol
on total serum cholesterol and LDL cholesterol have suffered from
methodologic ﬂaws, including the absence of data that distinguish
the distribution of cholesterol among lipoprotein fractions, the use
of extreme ranges of cholesterol intake, and identifying subgroups
post hoc that respond differentially (2–4). Yet, a few very well-done
studies that support this independent effect of dietary cholesterol are
worth noting. In 1982, Schonfeld et al. (5) examined the impact of
750 compared with 1500 mg dietary cholesterol daily consumed in
the form of eggs on plasma lipoproteins in 20 young men in the
setting of diets with a range of polyunsaturated to saturated fat ratios
of 0.25, 0.4, 0.8, or 2.5. The addition of 750 mg cholesterol/
d to the diet with a P:S of 0.25–0.4 increased LDL cholesterol by 16
614 mg/dL, whereas the addition of 1500 mg increased LDL
cholesterol by 25 619 mg/dL (both P,0.01). When consumed
in the diet with a P:S of 0.8, only 1500 mg cholesterol/d increased
LDL cholesterol by17 622 mg/dL (P,0.02), whereas with the
diet with a P:S of 2.5, neither amount of cholesterol intake pro-
duced signiﬁcant changes in LDL cholesterol. Thus, both the
cholesterol content and P:S of diets were important in determin-
ing LDL-cholesterol concentrations. In the mid-1990s, Ginsberg
et al. (6) studied healthy young men using a randomized, 4-way
crossover design to examine the impact of 0, 1, 2, or 4 eggs/d for
8 wk, with a daily cholesterol intake ranging from 128 to 858 mg,
on plasma lipids and lipoproteins, which were consumed while
following a step 1 American Heart Association diet. On average,
plasma total cholesterol increased by 1.5 mg/dL for every 100
mg dietary cholesterol added to the diet (P,0.001) and LDL
cholesterol increased in parallel. A similar study examined the
effects of the addition of 0, 1, or 3 eggs/d with dietary cholesterol
intakes ranging from 108 to 667 mg/d in healthy young women (7).
In the women, LDL cholesterol increased by 2.1 mg/dL per 100
mg dietary cholesterol/d (P¼0.003), which accounted for ;75%
of the increase in total cholesterol. HDL cholesterol also increased
by 0.57 mg/dL per 100 mg dietary cholesterol/d (P,0.04).
The meta-analysis by Berger et al. (8) published in this issue of the
Journal documents the heterogeneous nature of the clinical trials that
support a relation between dietary cholesterol and cardiovascular dis-
ease (CVD) risk. When extrapolating data shown in their Figure 3,
wherein subjects showed an increase in cholesterol intake from a mean
* To whom correspondence should be addressed. E-mail: robert.eckel@
Abbreviations used: CAD, coronary artery disease; CVD, cardiovascular
disease; P:S, ratio of polyunsaturated to saturated fat.
Am J Clin Nutr doi: 10.3945/ajcn.115.116905. Printed in USA. ÓAmerican Society for Nutrition 1of2
AJCN. First published ahead of print July 15, 2015 as doi: 10.3945/ajcn.115.116905.
Copyright (C) 2015 by the American Society for Nutrition
of 214 to 821 mg, or ;3 eggs daily, the mean increase in LDL
cholesterol was 7 mg/dL and in HDL cholesterol was ;3–4 mg/dL.
This increase in HDL cholesterol with increases in dietary choles-
terol is very similar to the effect of saturated fat on HDL cholesterol
and should not be inferred as neutralizing. In general, we live in an
age wherein increases in HDL cholesterol should be interpreted
cautiously in comparison to changes in LDL cholesterol (9).
REDUCTION IN CORONARY ARTERY DISEASE
INCIDENCE FOLLOWING RECOMMENDATIONS FOR
<300 OR <200 mg CHOLESTEROL DAILY
Of interest without adequate documentation is the fact that the
decrease in coronary artery disease (CAD) incidence began after
recommendations for restrictions of total/saturated fat and dietary
cholesterol occurred (10) and before reductions in tobacco use and
risk factor modiﬁcations such as reductions in blood pressure and
LDL cholesterol with medications. Although the basis for ,300
or ,200 mg dietary cholesterol/d may have been questionable at
the time, this translated to ;1.5 or 1 egg/d in the absence of any
other dietary cholesterol intake. Because eggs remain the most
abundant source of dietary cholesterol and could be the most easily
assessed change in the low-fat, low-cholesterol diet, the decline
in egg consumption since 1945 ensued a bit earlier and paral-
leled CAD/stroke mortality since ;1950. Although such com-
parisons can be questioned for many reasons, the association is of
interest. Nevertheless, updated data show no consistent relation
between egg consumption and CVD (11).
IS DIABETES DIFFERENT?
Despite modest effects of dietary cholesterol on LDL cholesterol,
there is some evidence that patients with diabetes may be subject to
more harm. Most cholesterol absorption in the intestine is not from
the diet but from hepatobiliary sources (12). However, patients with
diabetes show increases in Niemann-Pick-like-1 protein, a molecule
that facilitates intestinal cholesterol transport, and microsomal
transfer protein, which couples triglycerides to apo B-48 dur-
ing chylomicron assembly; moreover, patients with diabetes show
reductions in the ATP-binding cassette gene (ABCG5G8) hetero-
dimer that promotes the re-excretion of enterocyte cholesterol
back into the intestinal lumen (13). Overall, these alterations
support increases in intestinal cholesterol absorption in patients
with diabetes. Although some studies indicate that more egg con-
sumption in patients with diabetes results in more CAD events (11,
14, 15), this relation has been questioned (16). Moreover, in a ran-
domized controlled 3-mo trial of 2 eggs/d for 6 d/wk in patients with
type 2 diabetes there was no adverse effect on lipid proﬁle when the
diet included a higher content of MUFAs and PUFAs (17). Of in-
terest, however, are the results from the recent IMProved Reduction
of Outcomes: Vytorin Efﬁcacy International Trial, which showed in
patients with diabetes a particularly pronounced beneﬁcial effect of
ezetimibe (a drug that inhibits intestinal absorption of cholesterol) 1
simvastatin compared with simvastatin alone on CVD events (18).
Overall, some reservation is appropriate when claiming that di-
etary cholesterol is unimportant in modifying LDL cholesterol and
the risk of CVD. Yet, the primary emphasis should be placed on
dietary patterns wherein the overall diet is heart healthy (1), a set-
ting in which more egg consumption is likely not harmful. De-
spite .50 y of science, a few better-done crossover studies to
address the independent effect of dietary cholesterol in the setting
of a heart-healthy lifestyle would be timely, with or without statin
therapy on board. Nevertheless, when ordering an omelet, why
not order an egg white omelet with plenty of vegetables, lean meat,
and spices rather than one with 600 mg cholesterol?
The author had no personal or ﬁnancial conﬂicts of interest related to this
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