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Eggs and beyond: Is dietary cholesterol no longer important?

Authors:
Editorial
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
RECENT GUIDELINES
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.
PUBLIC MESSAGING
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.
cancer.gov/diet/foodsources/cholesterol/table1.html).
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
(P:Ss)
1
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).
NEW META-ANALYSIS
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@
ucdenver.edu.
1
Abbreviations used: CAD, coronary artery disease; CVD, cardiovascular
disease; P:S, ratio of polyunsaturated to saturated fat.
doi: 10.3945/ajcn.115.116905.
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).
TAKE-HOME MESSAGE
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
editorial.
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Nutrition research, in contrast with randomized clinical trials that compare a drug with placebo, is more difficult for many reasons, including complexities in data gathering and changes in human behavior over time. In this issue of JAMA, Zhong and colleagues¹ report new insights about a controversial topic, the association of egg consumption and dietary cholesterol with cardiovascular disease (CVD) incidence and all-cause mortality. Clearly, the topic of this study is important to clinicians, patients, and the public at large because the association of egg consumption and dietary cholesterol with CVD, although debated for decades, has more recently been thought to be less important. Compared with the meta-analyses and reviews previously published, this report is far more comprehensive, with enough data to make a strong statement that eggs and overall dietary cholesterol intake remain important in affecting the risk of CVD and more so the risk of all-cause mortality.
Thesis
This is a summary on the cumulative dissertation. Seeking health information online is a prevalent way to obtain knowledge about any medical issue, as it is low-thresholding, anonymous, and independent from medical appointments. In this sense, seeking online information also goes along with relevant decisions for people’s health. Thus, it is crucial to understand how people assess the accuracy of online information. Since health information seekers are usually incapable to assess the accuracy of information efficiently, they need to identify whom and which information to rely on. At the same time, the relationship between health information seekers and providers is mainly determined by their communicative patterns. Thus, the present dissertation examines providers’ language styles and the contexts of online communication and how both aspects impact people’s evaluations of providers and information. In particular, the dissertation investigates whether providers’ language styles and the context of online communication do not only individually but also reciprocally impact people’s evaluations, as a specific language style might be appropriate within a specific context of online communication. Accordingly, the first study focuses on the extent of medical technical jargon used by providers toward an audience of either medical professionals or laypersons in online health forums. Furthermore, the extent of self-reference used by providers in an online video was examined, and whether the context of video presentation impacts people’s evaluations. The context of video presentation was realized by YouTube’s sidebars that recommend similar or unrelated other videos (Study 2), or by the online platforms YouTube and Moodle (i.e., an academic online platform) (Study 3). Study 1 revealed that the extent of medical technical jargon and the type of online forums impacted participants’ evaluations individually and reciprocally. Participants evaluated providers in forums for medical professionals to be more trustworthy than in forums for laypersons. In addition, they judged providers who used a low instead of a high amount of medical technical jargon to be more trustworthy and ascribed to them more language adaption toward the audience. In addition, participants evaluated the information to be more credible when providers’ medical technical jargon was appropriate toward the intended audience of the online forum. The results of Study 2 and Study 3 revealed ambiguous findings regarding the individual impact of the extent of self-reference by providers, which once impacted and once did not impact participants’ evaluations of providers’ benevolence. Furthermore, both operationalized contexts (YouTube’s sidebars with similar or unrelated videos and YouTube or Moodle) did not individually impact participants’ evaluations of providers and information. However, the extent of self-reference by providers influenced participants’ evaluations of providers’ trustworthiness depending on YouTube’s sidebar (Study 2) as wells as their ascription of language accommodation depending on Moodle and YouTube (Study 3). In sum, the present dissertation gives insights into the role of an appropriate language use given specific online communication contexts. It shows that the consideration of both aspects is also crucial for seeking health information online. Future research should consider various aspects of contexts of online communication to expand the understanding of how people assess online health information. The results of the present dissertation likewise can inform health information seekers and providers.
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Dietary cholesterol has been suggested to increase the risk of cardiovascular disease (CVD), which has led to US recommendations to reduce cholesterol intake. The authors examine the effects of dietary cholesterol on CVD risk in healthy adults by using systematic review and meta-analysis. MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau Abstracts databases were searched through December 2013 for prospective studies that quantified dietary cholesterol. Investigators independently screened citations and verified extracted data on study and participant characteristics, outcomes, and quality. Random-effect models meta-analysis was used when at least 3 studies reported the same CVD outcome. Forty studies (17 cohorts in 19 publications with 361,923 subjects and 19 trials in 21 publications with 632 subjects) published between 1979 and 2013 were eligible for review. Dietary cholesterol was not statistically significantly associated with any coronary artery disease (4 cohorts; no summary RR), ischemic stroke (4 cohorts; summary RR: 1.13; 95% CI: 0.99, 1.28), or hemorrhagic stroke (3 cohorts; summary RR: 1.09; 95% CI: 0.79, 1.50). Dietary cholesterol statistically significantly increased both serum total cholesterol (17 trials; net change: 11.2 mg/dL; 95% CI: 6.4, 15.9) and low-density lipoprotein (LDL) cholesterol (14 trials; net change: 6.7 mg/dL; 95% CI: 1.7, 11.7). Increases in LDL cholesterol were no longer statistically significant when intervention doses exceeded 900 mg/d. Dietary cholesterol also statistically significantly increased serum high-density lipoprotein cholesterol (13 trials; net change: 3.2 mg/dL; 95% CI: 0.9, 9.7) and the LDL to high-density lipoprotein ratio (5 trials; net change: 0.2; 95% CI: 0.0, 0.3). Dietary cholesterol did not statistically significantly change serum triglycerides or very-low-density lipoprotein concentrations. Reviewed studies were heterogeneous and lacked the methodologic rigor to draw any conclusions regarding the effects of dietary cholesterol on CVD risk. Carefully adjusted and well-conducted cohort studies would be useful to identify the relative effects of dietary cholesterol on CVD risk. © 2015 American Society for Nutrition.
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Background: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. Methods: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years. Results: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. Conclusions: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).
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In recent years, the high-density lipoprotein (HDL) hypothesis has been challenged. Several completed randomized clinical trials continue to fall short in demonstrating HDL, or at least HDL-cholesterol (HDL-C) levels, as being a consistent target in the prevention of cardiovascular diseases. However, population studies and findings in lipid modifying trials continue to strongly support HDL-C as a superb risk predictor. It is increasingly evident that the complexity of HDL metabolism confounds the use of HDL-C concentration as a unified target. However, important insights continue to emerge from the post hoc analyses of recently completed (i) fibrate-based FIELD and ACCORD trials, including the unexpected beneficial effect of fibrates in microvascular diseases, (ii) the niacin-based AIM-HIGH and HPS2-THRIVE studies, (iii) recombinant HDL-based as well as (iv) the completed CETP inhibitor-based trials. These together with on-going mechanistic studies on novel pathways, which include the unique roles of microRNAs, post-translational remodeling of HDL and novel pathways related to HDL modulators will provide valuable insights to guide how best to refocus and redesign the conceptual framework for selecting HDL-based targets.
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This study reviewed epidemiological and experimental evidence on the relationship between egg consumption and cardiovascular disease (CVD) risks among type II diabetes mellitus (T2DM) individuals, and T2DM risk in nondiabetic subjects. Four of the six studies that examined CVD and mortality and egg consumption among diabetics found a statistically significant association. Of the eight studies evaluating incident T2DM and egg consumption, four prospective studies found a statistically significant association. Lack of adjustment for dietary confounders was a common study limitation. A small number of experimental studies examined the relationship between egg intake and CVD risk biomarkers among diabetics or individuals with T2DM risk factors. Studies among healthy subjects found suggestive evidence that dietary interventions that include eggs may reduce the risk of T2DM and metabolic syndrome. Differences in study design, T2DM status, exposure measurement, subject age, control for confounders and follow-up time present significant challenges for conducting a meta-analysis. Conflicting results, coupled with small sample sizes, prevent broad interpretation. Given the study limitations, these findings need to be further investigated.
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Early work suggested that dietary cholesterol increased plasma total cholesterol concentrations in humans. Given the relationship between elevated plasma cholesterol concentrations and cardiovascular disease risk, dietary guidelines have consistently recommended limiting food sources of cholesterol. Current intakes are approaching recommended levels. Recently there have been calls to reassess the importance of continuing to recommend limiting dietary cholesterol. Over the past 10 years, there have been a limited number of studies addressing this issue. Striking among these studies is the high degree of variability in background diet, study subject characteristics, and study design. Within the context of current levels of dietary cholesterol intake, the effect on plasma lipid concentrations, with primary interest in LDL cholesterol concentrations, is modest and appears to be limited to population subgroups. In these cases, restrictions in dietary cholesterol intake are likely warranted. The biological determinants of interindividual variability remain a relatively understudied area.
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BACKGROUND: The associations of egg consumption with cardiovascular disease (CVD) and diabetes are still unclear. OBJECTIVE: We aimed to quantitatively summarize the literature on egg consumption and risk of CVD, cardiac mortality, and type 2 diabetes by conducting a meta-analysis of prospective cohort studies. DESIGN: A systematic literature review was conducted for published studies in PubMed and EMBASE through March 2012. Additional information was retrieved through Google or a hand review of the reference from relevant articles. Studies were included if they had a prospective study design, were published in English-language journals, and provided HRs and 95% CIs for the associations of interest. Data were independently extracted by 2 investigators, and the weighted HRs and 95% CIs for the associations of interest were estimated by using a random-effects model. RESULTS: A total of 22 independent cohorts from 16 studies were identified, including participants ranging in number from 1600 to 90,735 and in follow-up time from 5.8 to 20.0 y. Comparison of the highest category (≥1 egg/d) of egg consumption with the lowest (<1 egg/wk or never) resulted in a pooled HR (95% CI) of 0.96 (0.88, 1.05) for overall CVD, 0.97 (0.86, 1.09) for ischemic heart disease, 0.93 (0.81, 1.07) for stroke, 0.98 (0.77, 1.24) for ischemic heart disease mortality, 0.92 (0.56, 1.50) for stroke mortality, and 1.42 (1.09, 1.86) for type 2 diabetes. Of the studies conducted in diabetic patients, the pooled HR (95% CI) was 1.69 (1.09, 2.62) for overall CVD. CONCLUSION: This meta-analysis suggests that egg consumption is not associated with the risk of CVD and cardiac mortality in the general population. However, egg consumption may be associated with an increased incidence of type 2 diabetes among the general population and CVD comorbidity among diabetic patients.
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Context Reduction in egg consumption has been widely recommended to lower blood cholesterol levels and prevent coronary heart disease (CHD). Epidemiologic studies on egg consumption and risk of CHD are sparse. Objective To examine the association between egg consumption and risk of CHD and stroke in men and women. Design and Setting Two prospective cohort studies, the Health Professionals Follow-up Study (1986-1994) and the Nurses' Health Study (1980-1994). Participants A total of 37,851 men aged 40 to 75 years at study outset and 80,082 women aged 34 to 59 years at study outset, free of cardiovascular disease, diabetes, hypercholesterolemia, or cancer. Main Outcome Measures Incident nonfatal myocardial infarction, fatal CHD, and stroke corresponding to daily egg consumption as determined by a food-frequency questionnaire. Results We documented 866 incident cases of CHD and 258 incident cases of stroke in men during 8 years of follow-up and 939 incident cases of CHD and 563 incident cases of stroke in women during 14 years of follow-up. After adjustment for age, smoking, and other potential CHD risk factors, we found no evidence of an overall significant association between egg consumption and risk of CHD or stroke in either men or women. The relative risks (RRs) of CHD across categories of intake were less than 1 per week (1.0), 1 per week (1.06), 2 to 4 per week (1.12), 5 to 6 per week (0.90), and ≥1 per day (1.08) (P for trend=.75) for men; and less than 1 per week (1.0), 1 per week (0.82), 2 to 4 per week (0.99), 5 to 6 per week (0.95), and ≥1 per day (0.82) (P for trend=.95) for women. In subgroup analyses, higher egg consumption appeared to be associated with increased risk of CHD only among diabetic subjects (RR of CHD comparing more than 1 egg per day with less than 1 egg per week among diabetic men, 2.02 [95% confidence interval, 1.05-3.87; P for trend=.04], and among diabetic women, 1.49 [0.88-2.52; P for trend=.008]). Conclusions These findings suggest that consumption of up to 1 egg per day is unlikely to have substantial overall impact on the risk of CHD or stroke among healthy men and women. The apparent increased risk of CHD associated with higher egg consumption among diabetic participants warrants further research.
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Background: Previously published research that examined the effects of high egg consumption in people with type 2 diabetes (T2D) produced conflicting results leading to recommendations to limit egg intake. However, people with T2D may benefit from egg consumption because eggs are a nutritious and convenient way of improving protein and micronutrient contents of the diet, which have importance for satiety and weight management. Objective: In this randomized controlled study, we aimed to determine whether a high-egg diet (2 eggs/d for 6 d/wk) compared with a low-egg diet (<2 eggs/wk) affected circulating lipid profiles, in particular high-density lipoprotein (HDL) cholesterol, in overweight or obese people with prediabetes or T2D. Design: A total of 140 participants were randomly assigned to one of the 2 diets as part of a 3-mo weight maintenance study. Participants attended the clinic monthly and were instructed on the specific types of foods and quantities to be consumed. Results: There was no significant difference in the change in HDL cholesterol from screening to 3 mo between groups; the mean difference (95% CI) between high- and low-egg groups was +0.02 mmol/L (-0.03, 0.08 mmol/L; P = 0.38). No between-group differences were shown for total cholesterol, low-density lipoprotein cholesterol, triglycerides, or glycemic control. Both groups were matched for protein intake, but the high-egg group reported less hunger and greater satiety postbreakfast. Polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) intakes significantly increased from baseline in both groups. Conclusions: High egg consumption did not have an adverse effect on the lipid profile of people with T2D in the context of increased MUFA and PUFA consumption. This study suggests that a high-egg diet can be included safely as part of the dietary management of T2D, and it may provide greater satiety. This trial was registered at the Australia New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) as ACTRN12612001266853.
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