Consumption of Different Egg-Based Diets Alters Clinical Metabolic and Hematological Parameters in Young, Healthy Men and Women.

Eggs-particularly egg yolks-are a rich source of bioactive nutrients and dietary compounds that influence metabolic health, lipid metabolism, immune function, and hematopoiesis. We investigated the effects of consuming an egg-free diet, three egg whites per day, and three whole eggs per day for 4 weeks on comprehensive clinical metabolic, immune, and hematologic profiles in young, healthy adults (18-35 y, BMI < 30 kg/m2 or <30% body fat for men and <40% body fat for women, n = 26) in a 16-week randomized, crossover intervention trial. We observed that average daily macro- and micronutrient intake significantly differed across egg diet periods, including greater intake of choline during the whole egg diet period, which corresponded to increased serum choline and betaine without altering trimethylamine N-oxide. Egg white and whole egg intake increased serum isoleucine while whole egg intake reduced serum glycine-markers of increased and decreased risk of insulin resistance, respectively-without altering other markers of glucose sensitivity or inflammation. Whole egg intake increased a subset of large HDL particles (H6P, 10.8 nm) and decreased the total cholesterol:HDL-cholesterol ratio and % monocytes in female participants using combined oral contraceptive (COC) medication (n = 11) as compared to female non-users (n = 10). Whole egg intake further increased blood hematocrit whereas egg white and whole egg intake reduced blood platelet counts. Changes in clinical immune cell counts between egg white and whole egg diet periods were negatively correlated with several HDL parameters yet positively correlated with measures of triglyceride-rich lipoproteins and insulin sensitivity. Overall, the intake of whole eggs led to greater overall improvements in micronutrient diet quality, choline status, and HDL and hematologic profiles while minimally-yet potentially less adversely-affecting markers of insulin resistance as compared to egg whites.

The Role of Lipids in the Regulation of Immune Responses.

Lipid metabolism plays a major role in the regulation of the immune system. Exogenous (dietary and microbial-derived) and endogenous (non-microbial-derived) lipids play a direct role in regulating immune cell activation, differentiation and expansion, and inflammatory phenotypes. Understanding the complexities of lipid-immune interactions may have important implications for human health, as certain lipids or immune pathways may be beneficial in circumstances of acute infection yet detrimental in chronic inflammatory diseases. Further, there are key differences in the lipid effects between specific immune cell types and location (e.g., gut mucosal vs. systemic immune cells), suggesting that the immunomodulatory properties of lipids may be tissue-compartment-specific, although the direct effect of dietary lipids on the mucosal immune system warrants further investigation. Importantly, there is recent evidence to suggest that lipid-immune interactions are dependent on sex, metabolic status, and the gut microbiome in preclinical models. While the lipid-immune relationship has not been adequately established in/translated to humans, research is warranted to evaluate the differences in lipid-immune interactions across individuals and whether the optimization of lipid-immune interactions requires precision nutrition approaches to mitigate or manage disease. In this review, we discuss the mechanisms by which lipids regulate immune responses and the influence of dietary lipids on these processes, highlighting compelling areas for future research.

Sex-Specific Associations Between Serum Lipids, Antinuclear Antibodies, and Statin Use in National Health and Nutrition Examination Surveys 1999-2004.

Lipid metabolism contributes to the regulation of leukocyte activity and immune responses, and may serve as a therapeutic target in the pathophysiology and clinical management of autoimmune disorders. In addition to lipid-lowering properties, statins have been shown to exert anti-inflammatory and immunomodulatory effects within the context of autoimmunity. Importantly, autoimmune incidence and lipid markers differ between men and women, suggesting that the relationship between lipid metabolism and immune function may vary by sex. Therefore, we investigated whether a predictive, sex-specific relationship exists between serum lipids, statin use, and antinuclear antibodies (ANA)-a routine clinical marker of autoimmunity and immune dysfunction-in U.S. men and women (>20 years old; n = 1,526) from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Within this population, a greater proportion of women were positive for ANA (ANA+) and had higher ANA titers, as compared to men. While we did not observe statistical differences in average total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), or triglyceride levels in ANA positive (ANA+) vs. ANA negative (ANA-) men or women, we observed that a greater proportion of ANA+ women had high total cholesterol levels (>240 mg/dL) when compared to ANA+ men (13.0 vs. 9.0%), and that a greater percentage of ANA+ women had low HDL-C as compared to ANA+ men (29.2 vs. 19.6%). However, in logistic regression models, total cholesterol, LDL-C, and HDL-C levels were not able to predict ANA status, whereas elevated serum triglycerides (150 to < 200 mg/dL) were significantly less likely to be ANA+ vs. ANA- (OR 0.33; 95% CI 0.11-0.92) in men only. Interestingly, women who reported taking statins have significantly lower odds of being ANA+ (OR 0.25; 95% CI 0.09-0.76), whereas no significant association between statin use and ANA status was observed in men. Together, our findings provide novel insight into the relationship between lipid metabolism and autoimmunity by elucidating the limited, albeit sex-specific utility of routine clinical serum lipid levels to predict ANA status at the population level, while further identifying a sex-specific and protective role for statins in predicting ANA status in women.

Lipid Metabolism in Inflammation and Immune Function.

Lipid metabolism plays an essential role in modulating inflammation within the context of acute and chronic diseases [...].

Low-Density Lipoproteins, High-Density Lipoproteins (HDL), and HDL-Associated Proteins Differentially Modulate Chronic Myelogenous Leukemia Cell Viability.

Cellular lipid metabolism, lipoprotein interactions, and liver X receptor (LXR) activation have been implicated in the pathophysiology and treatment of cancer, although findings vary across cancer models and by lipoprotein profiles. In this study, we investigated the effects of human-derived low-density lipoproteins (LDL), high-density lipoproteins (HDL), and HDL-associated proteins apolipoprotein A1 (apoA1) and serum amyloid A (SAA) on markers of viability, cholesterol flux, and differentiation in K562 cells-a bone marrow-derived, stem-like erythroleukemia cell model of chronic myelogenous leukemia (CML). We further evaluated whether lipoprotein-mediated effects were altered by concomitant LXR activation. We observed that LDL promoted higher K562 cell viability in a dose- and time-dependent manner and increased cellular cholesterol concentrations, while LXR activation by the agonist TO901317 ablated these effects. LXR activation in the presence of HDL, apoA1 and SAA-rich HDL suppressed K562 cell viability, while robustly inducing mRNA expression of ATP-binding cassette transporter A1 (ABCA1). HDL and its associated proteins additionally suppressed mRNA expression of anti-apoptotic B-cell lymphoma-extra large (BCL-xL), and the erythroid lineage marker 5'-aminolevulinate synthase 2 (ALAS2), while SAA-rich HDL induced mRNA expression of the megakaryocytic lineage marker integrin subunit alpha 2b (ITGA2B). Together, these findings suggest that lipoproteins and LXR may impact the viability and characteristics of CML cells.

Corrigendum to "Assessment of Dietary Patterns Represents a Potential, Yet Variable, Measure of Inflammatory Status: A Review and Update".

[This corrects the article DOI: 10.1155/2019/3102870.].

Gender Dictates the Relationship between Serum Lipids and Leukocyte Counts in the National Health and Nutrition Examination Survey 1999⁻2004.

Dyslipidemias and leukocytosis are associated with cardiovascular disease and immune disorders. Mechanistic studies have shown lipoprotein metabolism to play a significant role in the regulation of atherosclerosis development and leukocyte activation, whereas lipid-lowering treatments have been shown to exert beneficial anti-inflammatory and immunomodulatory effects in clinical trials. However, the relationship between clinical markers of lipid metabolism and leukocyte counts has not been extensively evaluated at the population level. We aimed to determine whether clinical blood lipid measures are associated with leukocyte counts in the general U.S. population represented in the National Health and Nutrition Examination Survey (NHANES) 1999⁻2004, and whether differences exist between men and women (n = 5647). We observed a strong positive linear trend between serum triglycerides vs. blood lymphocyte and basophil counts in both men and women, whereas a positive trend between monocytes vs. triglycerides and lymphocytes vs. total cholesterol and LDL-cholesterol (LDL-C) was only detected in women. Conversely, HDL-C was inversely associated with a greater number of leukocyte subsets in men, whereas inverse trends between HDL-C vs. lymphocytes were observed in both men and women. In multiple regression models, a 10% increase in total cholesterol, LDL-C, and triglycerides was associated with a predicted 1.6%, 0.6%, and 1.4% increase in blood lymphocyte counts in women, respectively, whereas no relationship was observed in men. In both men and women, a 10% increase in triglycerides was additionally associated with higher lymphocyte, neutrophil, and basophil counts, whereas 10% increases in HDL-cholesterol were associated with significantly lower lymphocyte, neutrophil, eosinophil, and basophil counts in men, in addition to lower lymphocyte and monocyte counts in women. These findings suggest that clinical lipid markers may be used to predict blood leukocyte distributions, and that a gender-specific relationship exists between distinct classes of serum lipids and immune cell subsets.

Assessment of Dietary Patterns Represents a Potential, Yet Variable, Measure of Inflammatory Status: A Review and Update.

Chronic low-grade, systemic inflammation is a well-characterized risk factor in the development of chronic metabolic diseases, such as cardiovascular disease, type 2 diabetes, and metabolic syndrome. Diet could be an effective strategy for reducing inflammation associated with chronic disease. While anti-inflammatory properties of isolated dietary bioactive and functional foods have been routinely studied, the evaluation of dietary patterns on inflammation warrants further review-especially given the recent inclusion of dietary pattern recommendations into dietary guidelines and policies. Therefore, the objective of this narrative review is to examine current evidence linking diet to low-grade, systemic inflammation within the context of chronic disease. Specifically, we provide an update on the findings from human trials that have characterized anti-inflammatory properties of dietary patterns, defined by various methods and indexes. Given the complexity of interpreting results from dietary pattern analysis, we further present recent evidence on the anti-inflammatory roles of isolated bioactive nutrients and functional foods that are common components of distinct dietary patterns, in addition to considerations for interpreting dietary pattern research, population-specific dietary recommendations, and future studies. Overall, we observe a vast range of variability in the evidence from observational studies that have evaluated the relationships between healthy dietary patterns and inflammatory markers. These studies highlight the need for additional intervention studies with study designs that account for metabolic status, diversity in populations, breadth of inflammatory measurements, fasting vs. postprandial effects of diet, and control of confounding factors (e.g., genotype, microbiome profiles, and dietary adherence) in order to better understand the effect that diet has, as a whole, on inflammation. These strategies will help to strengthen diet recommendations aimed at reducing inflammation and chronic disease risk.

Impact of Dietary Cholesterol on the Pathophysiology of Infectious and Autoimmune Disease.

Cellular cholesterol metabolism, lipid raft formation, and lipoprotein interactions contribute to the regulation of immune-mediated inflammation and response to pathogens. Lipid pathways have been implicated in the pathogenesis of bacterial and viral infections, whereas altered lipid metabolism may contribute to immune dysfunction in autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. Interestingly, dietary cholesterol may exert protective or detrimental effects on risk, progression, and treatment of different infectious and autoimmune diseases, although current findings suggest that these effects are variable across populations and different diseases. Research evaluating the effects of dietary cholesterol, often provided by eggs or as a component of Western-style diets, demonstrates that cholesterol-rich dietary patterns affect markers of immune inflammation and cellular cholesterol metabolism, while additionally modulating lipoprotein profiles and functional properties of HDL. Further, cholesterol-rich diets appear to differentially impact immunomodulatory lipid pathways across human populations of variable metabolic status, suggesting that these complex mechanisms may underlie the relationship between dietary cholesterol and immunity. Given the Dietary Guidelines for Americans 2015⁻2020 revision to no longer include limitations on dietary cholesterol, evaluation of dietary cholesterol recommendations beyond the context of cardiovascular disease risk is particularly timely. This review provides a comprehensive and comparative analysis of significant and controversial studies on the role of dietary cholesterol and lipid metabolism in the pathophysiology of infectious disease and autoimmune disorders, highlighting the need for further investigation in this developing area of research.

Consuming Two Eggs per Day, as Compared to an Oatmeal Breakfast, Decreases Plasma Ghrelin while Maintaining the LDL/HDL Ratio.

Eggs contain high quality protein, vitamins, minerals and antioxidants, yet regular consumption is still met with uncertainty. Therefore, the purpose of this study was to compare the effects of consuming two eggs per day or a heart-healthy oatmeal breakfast on biomarkers of cardiovascular disease (CVD) risk and satiety measures in a young, healthy population. Fifty subjects participated in a randomized crossover clinical intervention; subjects were randomly allocated to consume either two eggs or one packet of oatmeal per day for breakfast for four weeks. After a three-week washout period, participants were allocated to the alternative breakfast. Fasting blood samples were collected at the end of each intervention period to assess plasma lipids and plasma ghrelin. Subjects completed visual analog scales (VAS) concurrent to dietary records to assess satiety and hunger. Along with an increase in cholesterol intake, there were significant increases in both low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol following the egg consumption period (p < 0.01). However, there was no difference in the LDL/HDL ratio, a recognized biomarker of CVD risk, nor in the plasma glucose, triglycerides or liver enzymes, between diet periods. Several self-reported satiety measures were increased following the consumption of eggs, which were associated with lower plasma ghrelin concentrations (p < 0.05). These results demonstrate that compared to an oatmeal breakfast, two eggs per day do not adversely affect the biomarkers associated with CVD risk, but increase satiety throughout the day in a young healthy population.

Impact of Obesity and Metabolic Syndrome on Immunity.

Obesity is associated with metabolic disturbances that cause tissue stress and dysfunction. Obese individuals are at a greater risk for chronic disease and often present with clinical parameters of metabolic syndrome (MetS), insulin resistance, and systemic markers of chronic low-grade inflammation. It has been well established that cells of the immune system play an important role in the pathogenesis of obesity- and MetS-related chronic diseases, as evidenced by leukocyte activation and dysfunction in metabolic tissues such as adipose tissue, liver, pancreas, and the vasculature. However, recent findings have highlighted the substantial impact that obesity and MetS parameters have on immunity and pathogen defense, including the disruption of lymphoid tissue integrity; alterations in leukocyte development, phenotypes, and activity; and the coordination of innate and adaptive immune responses. These changes are associated with an overall negative impact on chronic disease progression, immunity from infection, and vaccine efficacy. This review presents an overview of the impact that obesity and MetS parameters have on immune system function.

A Larger Body Mass Index is Associated with Increased Atherogenic Dyslipidemia, Insulin Resistance, and Low-Grade Inflammation in Individuals with Metabolic Syndrome.

BACKGROUND: The consequences of increased body mass index (BMI) on the metabolic disorders associated with metabolic syndrome (MetS) have not been thoroughly examined. METHODS: We analyzed data from 262 individuals, 97 men and 165 women (aged 18-70 years), classified with MetS to investigate whether variations in BMI could be associated with parameters of dyslipidemia, insulin resistance, or low-grade inflammation. We hypothesized that increases in BMI would positively correlate with the major dysregulations in metabolism that define MetS. For this purpose, individuals were separated into four subgroups based on their BMI: normal weight (<25 kg/m(2)), overweight (≥25 to <30 kg/m(2)), obese (≥30 to <40 kg/m(2)), and morbidly obese (≥40 kg/m(2)). RESULTS: As expected, body weight and waist circumference increased significantly as BMI increased (P < 0.0001). Both systolic and diastolic blood pressure were lower in the normal BMI group compared with the other three BMI groups (P = 0.001). Markers of HDL metabolism were adversely impacted in elevated BMI groups, as both high-density lipoprotein cholesterol (HDL-C) and large HDL decreased as BMI increased (P = 0.01). BMI was negatively correlated with HDL-C (r = -0.193, P = 0.002), HDL size (r = (-)0.227, P = 0.002), and large HDL (r = -0.147, P = 0.037). In addition, plasma insulin was highest in subjects classified as morbidly obese (P < 0.0001). There was also a strong positive correlation between BMI and plasma insulin (r = 0.413, P < 0.0001), whereas adiponectin, a marker of insulin sensitivity, was negatively correlated with BMI (r = -0.288, P = 0.001). Finally, BMI was positively correlated with proinflammatory C-reactive protein (r = 0.312, P = 0.0001) and interleukin-6 (r = 0.238, P = 0.001). CONCLUSIONS: The data from this study suggest that the physiological factors associated with increased BMI exacerbate the metabolic abnormalities characteristic of MetS.

Bioactive Egg Components and Inflammation.

Inflammation is a normal acute response of the immune system to pathogens and tissue injury. However, chronic inflammation is known to play a significant role in the pathophysiology of numerous chronic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and cancer. Thus, the impact of dietary factors on inflammation may provide key insight into mitigating chronic disease risk. Eggs are recognized as a functional food that contain a variety of bioactive compounds that can influence pro- and anti-inflammatory pathways. Interestingly, the effects of egg consumption on inflammation varies across different populations, including those that are classified as healthy, overweight, metabolic syndrome, and type 2 diabetic. The following review will discuss the pro- and anti-inflammatory properties of egg components, with a focus on egg phospholipids, cholesterol, the carotenoids lutein and zeaxanthin, and bioactive proteins. The effects of egg consumption of inflammation across human populations will additionally be presented. Together, these findings have implications for population-specific dietary recommendations and chronic disease risk.

One Egg per Day Improves Inflammation when Compared to an Oatmeal-Based Breakfast without Increasing Other Cardiometabolic Risk Factors in Diabetic Patients.

There is concern that egg intake may increase blood glucose in patients with type 2 diabetes mellitus (T2DM). However, we have previously shown that eggs reduce inflammation in patients at risk for T2DM, including obese subjects and those with metabolic syndrome. Thus, we hypothesized that egg intake would not alter plasma glucose in T2DM patients when compared to oatmeal intake. Our primary endpoints for this clinical intervention were plasma glucose and the inflammatory markers tumor necrosis factor (TNF)-α and interleukin 6 (IL-6). As secondary endpoints, we evaluated additional parameters of glucose metabolism, dyslipidemias, oxidative stress and inflammation. Twenty-nine subjects, 35-65 years with glycosylated hemoglobin (HbA1c) values <9% were recruited and randomly allocated to consume isocaloric breakfasts containing either one egg/day or 40 g of oatmeal with 472 mL of lactose-free milk/day for five weeks. Following a three-week washout period, subjects were assigned to the alternate breakfast. At the end of each period, we measured all primary and secondary endpoints. Subjects completed four-day dietary recalls and one exercise questionnaire for each breakfast period. There were no significant differences in plasma glucose, our primary endpoint, plasma lipids, lipoprotein size or subfraction concentrations, insulin, HbA1c, apolipoprotein B, oxidized LDL or C-reactive protein. However, after adjusting for gender, age and body mass index, aspartate amino-transferase (AST) (p < 0.05) and tumor necrosis factor (TNF)-α (p < 0.01), one of our primary endpoints were significantly reduced during the egg period. These results suggest that compared to an oatmeal-based breakfast, eggs do not have any detrimental effects on lipoprotein or glucose metabolism in T2DM. In contrast, eggs reduce AST and TNF-α in this population characterized by chronic low-grade inflammation.

Egg intake during carbohydrate restriction alters peripheral blood mononuclear cell inflammation and cholesterol homeostasis in metabolic syndrome.

Egg yolk contains bioactive components that improve plasma inflammatory markers and HDL profiles in metabolic syndrome (MetS) under carbohydrate restriction. We further sought to determine whether egg yolk intake affects peripheral blood mononuclear cell (PBMC) inflammation and cholesterol homeostasis in MetS, as HDL and its associated lipid transporter ATP-binding cassette transporter A1 (ABCA1) reduce the inflammatory potential of leukocytes through modulation of cellular cholesterol content and distribution. Thirty-seven men and women classified with MetS consumed a moderate carbohydrate-restricted diet (25%-30% of energy) for 12 weeks, in addition to consuming either three whole eggs per day (EGG) or the equivalent amount of yolk-free egg substitute (SUB). Interestingly, lipopolysaccharide-induced PBMC IL-1ß and TNFα secretion increased from baseline to week 12 in the SUB group only, despite increases in PBMC toll-like receptor 4 (TLR4) mRNA expression in the EGG group. Compared to baseline, ABCA1 and 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase mRNA expression increased by week 12 in the EGG group only, whereas changes in PBMC total cholesterol positively correlated with changes in lipid raft content. Together, these findings suggest that intake of whole eggs during carbohydrate restriction alters PBMC inflammation and cholesterol homeostasis in MetS.

Effects of carbohydrate restriction and dietary cholesterol provided by eggs on clinical risk factors in metabolic syndrome.

BACKGROUND: There are a limited number of clinical interventions evaluating the effects of dietary cholesterol in individuals at elevated risk for type 2 diabetes and cardiovascular disease. OBJECTIVE: To investigate the effects of whole egg intake in adults with metabolic syndrome (MetS). METHODS: Men (n = 12) and women (n = 25) with MetS were instructed to follow a moderate carbohydrate-restricted diet (<30% energy) and randomly assigned to consume either three whole eggs (EGG, n = 20) or egg substitute (SUB, n = 17)/d for 12 weeks. Dietary intake, MetS parameters, and body composition were assessed at baseline and post-intervention. RESULTS: Total carbohydrate (P < .001) intake decreased in all participants over time. The EGG group consumed more dietary cholesterol (P < .001) and choline (P < .001) than the SUB group. MetS was reduced in both groups, with improvements noted in dyslipidemia and decreases in waist circumference (P < .01), weight (P < .001), and percent body fat (P < .001). Reductions in plasma tumor necrosis factor-α (P < .001) and serum amyloid A (P < .05) were seen in the EGG group only. Notably, increases in dietary cholesterol were associated with reductions in plasma tumor necrosis factor-α (r = -0.340, P = .04). Plasma C-reactive protein, adiponectin, interleukin-6 interleukin-10, and cell adhesion molecules were unaffected by the intervention. CONCLUSIONS: These results demonstrate that on a moderate carbohydrate background diet, accompanied by weight loss, the inclusion of whole eggs improves inflammation to a greater extent than yolk-free egg substitute in those with MetS.

Dietary strategies to reduce metabolic syndrome.

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities characterized by central obesity, dyslipidemias, hypertension, high fasting glucose, chronic low-grade inflammation and oxidative stress. This condition has become an increasing problem in our society where about 34 % of adults are diagnosed with MetS. In parallel with the adult situation, a significant number of children present lipid abnormalities and insulin resistance, which can be used as markers of MetS in the pediatric population. Changes in lifestyle including healthy dietary regimens and increased physical activity should be the first lines of therapy to decrease MetS. In this article, we present the most recent information on successful dietary modifications that can reduce the parameters associated with MetS. Successful dietary strategies include energy restriction and weight loss, manipulation of dietary macronutrients--either through restriction of carbohydrates, fat, or enrichment in beneficial fatty acids, incorporation of functional foods and bioactive nutrients, and adherence to dietary and lifestyle patterns such the Mediterranean diet and diet/exercise regimens. Together, the recent findings presented in this review serve as evidence to support the therapeutic treatment of MetS through diet.

Dietary approaches to improving atheroprotective HDL functions.

High-density lipoproteins (HDL) are known to protect against cardiovascular disease (CVD). In addition to facilitating reverse cholesterol transport to remove excess lipids from the body - including atherosclerotic plaques - HDL exhibits antioxidant, anti-inflammatory, vasodilatory, and antithrombotic activities. Together, these properties contribute to the overall atheroprotective nature of HDL. However, similar to many other physiological pathways, these HDL parameters are known to become dysregulated in conditions of metabolic disease. Further, research suggests these alternative HDL properties may be regulated independently of blood HDL-cholesterol (HDL-C) levels, and must therefore be considered when designing HDL-targeted therapies. To date, a number of dietary strategies have been investigated to assess the effect of dietary components on functional properties of HDL beyond HDL-C. This review will highlight the bioactive nutrients, functional foods, and dietary programs known to modulate HDL function as a means of reducing CVD.

Egg consumption modulates HDL lipid composition and increases the cholesterol-accepting capacity of serum in metabolic syndrome.

We recently demonstrated that daily whole egg consumption during moderate carbohydrate restriction leads to greater increases in plasma HDL-cholesterol (HDL-C) and improvements in HDL profiles in metabolic syndrome (MetS) when compared to intake of a yolk-free egg substitute. We further investigated the effects of this intervention on HDL composition and function, hypothesizing that the phospholipid species present in egg yolk modulate HDL lipid composition to increase the cholesterol-accepting capacity of subject serum. Men and women classified with MetS were randomly assigned to consume either three whole eggs (EGG, n = 20) per day or the equivalent amount of egg substitute (SUB, n = 17) throughout a 12-week moderate carbohydrate-restricted (25-30 % of energy) diet. Relative to other HDL lipids, HDL-cholesteryl ester content increased in all subjects, with greater increases in the SUB group. Further, HDL-triacylglycerol content was reduced in EGG group subjects with normal baseline plasma HDL-C, resulting in increases in HDL-CE/TAG ratios in both groups. Phospholipid analysis by mass spectrometry revealed that HDL became enriched in phosphatidylethanolamine in the EGG group, and that EGG group HDL better reflected sphingomyelin species present in the whole egg product at week 12 compared to baseline. Further, macrophage cholesterol efflux to EGG subject serum increased from baseline to week 12, whereas no changes were observed in the SUB group. Together, these findings suggest that daily egg consumption promotes favorable shifts in HDL lipid composition and function beyond increasing plasma HDL-C in MetS.