1. Introduction
Inflammation is a normal, adaptive physiological response to pathogenic insult, including microbial infection and tissue injury; however the incidence of chronic low-grade, systemic inflammation underlying multiple highly prevalent chronic metabolic diseases has warranted the evaluation of inflammatory processes in disease pathogenesis [1,2]. Acute inflammatory responses mediated by immune system cells are considered beneficial if executed in a local, controlled manner, as they function to rapidly and effectively eliminate pathogenic stimuli and return the affected tissue to a normal, homeostatic state through coordinated activation and resolution of pro-inflammatory leukocyte activity [1]. However, failure of the body to appropriately execute and resolve acute inflammatory responses can lead to a detrimental chronic inflammatory tissue state, characterized by pathological tissue remodeling, fibrosis, and impaired functioning due to persistent inflammatory cell infiltration, activation, and leukocyte-mediated tissue damage [3,4]. These detrimental effects are observed in cases of inappropriate activation of the immune system, such as autoimmune conditions and allergic responses [5–7].
Given its significant role in the pathophysiology of many chronic diseases, inflammation has become a primary target for nutritional intervention. Various dietary patterns, functional foods, nutrients, and bioactive components have been shown to modulate inflammatory processes within the context of disease risk and progression [12–15]. Within this category, eggs are one of the most complex and controversial foods [16]. Eggs contain a variety of essential nutrients and bioactive components, but are most often recognized as a relatively rich source of high-quality protein and dietary cholesterol [17–19].
This had led to discrepancy in dietary recommendations across populations, where egg consumption has traditionally been considered more advisable to young, healthy populations and/or athletes (e.g., those with greater protein needs that can withstand a dietary cholesterol “challenge”), whereas egg intake by individuals at risk for CVD has been discouraged [20,21]. These recommendations have held, despite numerous epidemiological studies finding no association between egg intake and risk of coronary heart disease (CHD) mortality or stroke in the general U.S. population [22–25].
These findings indicate that healthy individuals often have greater pro-inflammatory responses to egg intake [30,31], whereas egg consumption by individuals who are overweight [32], classified with metabolic syndrome [33–37], or type 2 diabetic [38] is associated with a reduction in inflammatory markers.
2. Composition and Bioavailability of Egg Components
Eggs contain a wide variety of essential nutrients and bioactive compounds that can impact human health [17,39]. At only 72 kilocalories/large egg, eggs are a good source of high quality protein, fat-soluble and B vitamins, minerals, and choline, while providing relatively less saturated fat per gram compared to other animal protein sources [17,40].
2.1. Phospholipids
Eggs—particularly the yolk fractions—are one of the richest dietary sources of phospholipids [41,42]. On average, one large egg contains approximately 1.3 g of phospholipids [43,44], which represent approximately 28%–30% of total lipids by weight [45]. The predominate phospholipid class found in eggs is the glycerophospholipid phosphatidylcholine, representing approximately ~72% of phospholipids.
The majority of egg-derived phospholipids are highly bioavailable, with glycerophospholipid classes such as phosphatidylcholine being absorbed at >90% efficiency [49,50].
In general, phospholipids are known to influence plasma lipids and preferentially raise HDL-cholesterol [51,52], making them the likely egg component attributable to increases in HDL-cholesterol observed from egg intake [34,53].
2.2. Cholesterol
Eggs are one of the richest sources of dietary cholesterol, with an average large egg providing approximately 186 mg cholesterol [17].
2.3. Lutein and Zeaxanthin
In addition to phospholipids and cholesterol, egg yolks contain various antioxidant carotenoids [69].
Compared to plant sources, eggs contain a relatively low amount of lutein and zeaxanthin; however, egg-derived carotenoids have been shown to be significantly more bioavailable [76].
Increases in plasma lutein, zeaxanthin, and -carotene were observed in subjects with metabolic syndrome who consumed 3 eggs per day for 3 weeks. These changes corresponded to enrichment of HDL (+20%, +57%) and low-density lipoproteins (LDL) (+9%, +46%) fractions with lutein and zeaxanthin, respectively [69].
In older adults (60 years +), consumption or 2 or 4 eggs per day for 5 weeks increased serum lutein and zeaxanthin, in addition to increasing macular pigment optical density [85]. Serum zeaxanthin and macular pigment density was additionally increased in adult women (age 24–59) who consumed 6 eggs/week for 12 weeks [86].
2.4. Egg Proteins
Eggs are a good source of high-quality protein that promote protein synthesis and maintenance of skeletal muscle mass [91–93]. On average, one large egg provides ~6.3 g protein that is rich in essential amino acids [17,94]. Eggs also contain a variety of bioactive proteins that possess antimicrobial and immunoprotective properties—that majority of which can be found in the egg white fraction [54,95–97].
The predominant egg white proteins that can impact inflammation include ovalbumin (54% of egg white protein by weight), ovotransferrin (12%), ovomucin (3.5%), lysozyme (3.4%), and avidin (0.5%) [54].
Egg white additionally contains ovoinhibitor, a serine proteinase inhibitor that can reduce enzymatic digestion by trypsin and chymotrypsin, and it has been demonstrated that certain egg proteins can be absorbed intact [98–100].
The absorption of intact egg proteins has been implicated in mediating allergic responses to egg proteins, whereas heating and digestion of egg proteins can lower allergenicity [99–101].
3. Pro- and Anti-Inflammatory Properties of Egg Components: Mechanisms of Action
The components of eggs highlighted above each possess unique pro- and/or anti-inflammatory properties that likely contribute to the effects that egg intake has on inflammation in human populations [30–32,36,54,72,103].
3.1. Phospholipids
In Caco-2 cells, phosphatidylcholine (200 mol) has been shown to inhibit TNF
-induced alterations of plasma membrane architecture required for receptor-mediated signaling, activation of the pro-inflammatory mitogen-activated protein kinases (MAPKs), extracellular-signal-regulated kinase (ERK) and p38, nuclear factor B (NF-B) subunit translocation to the nucleus, and up-regulation of pro-inflammatory cytokines, such as tumor necrosis factor (TNF), interleukin (IL)-8, intercellular adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1, interferon -induced protein (IP)-10, and matrix metalloproteinase (MMP)-1 [104,105].
Despite the evidence to suggest that phosphatidylcholine is anti-inflammatory, egg phospholipids have recently been implicated in the promotion of inflammation and atherosclerosis due formation of trimethylamine-N-oxide (TMAO) [31,111]. Production of TMAO is dependent upon intestinal microbiota-induced conversion of phosphatidylcholine to trimethylamine (TMA), followed by oxidation of TMA by hepatic flavin-containing monooxygenase 3 (FMO3).
Variation between individuals may be attributable to differences in FMO3 expression and/or intestinal microbiota composition [114]. However, intake of more than one egg per day has been associated with lower atherosclerotic burden, as determined by coronary angiography [115].
3.2. Cholesterol
Dietary cholesterol is known to be pro-atherogenic and pro-inflammatory in animal studies [116,117]; however, these studies are often not representative of egg consumption, as cholesterol is provided in high doses as an isolated form, thus failing to take into account the phospholipid matrix, realistic dose provided by eggs, and the variability in cholesterol absorption across populations [17,43,55,57].
In line with its atheroprotective properties, HDL and its related lipid transporter, ATP-binding cassette transport A 1 (ABCA1), have been shown to exert direct and indirect anti-inflammatory activity by reducing cellular cholesterol levels, lipid raft formation, and mitigating leukocyte inflammation [120,121,126–128]. This may have significant implications for egg consumption, which is known to favorably modulate HDL metabolism, as discussed in greater detail below [33,34,36,46].
3.3. Lutein and Zeaxanthin
Supplementation with lutein alone or in combination with zeaxanthin has been shown to have anti-inflammatory effects in a variety of experimental models.
However, in a study conducted in healthy adults by Graydon et al. [141],
lutein (10 mg/day) and zeaxanthin (5 mg/day) supplementation for 8 weeks did not affect serum ICAM-1, VCAM-1 or CRP levels [141]. These results may be indicative of a lower bioavailability of lutein and zeaxanthin from supplements, or perhaps a lack of an anti-inflammatory effect in healthy individuals who do not exhibit physiological stress and tissue dysfunction [8,76].
3.4. Egg Proteins
These proteins possess antibacterial and immunoprotective properties, yet are also capable of inducing unfavorable pro-inflammatory responses in individuals allergic to egg proteins [99–101]. Egg white-derived lysozyme naturally exerts antimicrobial activity against Gram-positive and Gram-negative bacteria through hydrolysis of structural peptidoglycans in the bacterial cell walls, in addition to giving rise to antibacterial peptides from within its complete protein structure through enzymatic hydrolysis [142,143].
Ovotransferrin, an iron-binding glycoprotein with antibacterial activity, has additionally been shown reduce inflammatory colitis pathology in a DSS-induced mouse model of colitis [95,144]. Oral administration of egg ovotransferrin reduced inflammatory cytokines, while additionally mitigating clinical markers of colitis, including weight loss and histological scores of the colon [95].
Ovokinin, a biologically active peptide derivative of ovalbumin, has been shown to lower blood pressure in spontaneously hypertensive rats when provided via oral administration [146].
In addition to the bioactive proteins above, utilization of immunoglobulin Y (IgY) in medicine has additionally shown promising results in promoting passive immunity against a variety of pathogens in the treatment of conditions such as colitis, influenza, and infection of Clostridium botulinum, Staphylococcus aureus, Candida albicans, and Helicobacter pylori [96,147].
4. Effects of Egg Intake on Inflammation in Human Populations
As outlined above, eggs contain a variety of bioactive components that possess pro- and/or anti-inflammatory properties. Each of these components likely contribute to the overall response observed in human subjects following egg consumption; however, evidence suggests that the effects of egg intake on inflammatory markers differs across populations, based on body weight and health status [30–33,35,36].
4.1. Healthy Populations
A number of intervention trials conducted in healthy adults have demonstrated a pro-inflammatory response to egg intake.
Increased susceptibility to plasma and LDL oxidation was additionally observed by Levy et al. [153] in subjects consuming 2 eggs per day for 3 weeks. These subjects additionally exhibited minor increases in plasma glucose [153], contributing to the controversial body of research regarding the effects of egg intake on T2DM risk [26,27]. Similarly, healthy subjects who consumed a 2-egg meal exhibited increased plasma levels of pro-inflammatory TMAO postprandially; however, these increases were dependent upon the presence of normal intestinal microbiota, as administration of an oral broad-spectrum antibiotic suppressed the egg-induced increase in TMAO [31].
4.2. Overweight
In contrast to what is observed in most healthy populations, egg consumption in overweight populations shows beneficial anti-inflammatory effects. In a study by Ratliff et al. [32], overweight men consuming 3 eggs per day for 12 weeks while following an ad libitum carbohydrate-restricted diet showed reductions in plasma CRP, that were not observed in overweight men consuming a carbohydrate restriction diet with yolk-free egg substitute.
Consumption of eggs for breakfast has additionally been shown to increased satiety in overweight/obese women [154] and healthy men [155] when compared to a bagel breakfast, while also promoting weight loss and reductions in daily caloric intake [155,156].
4.3. Metabolic Syndrome
In men and women classified with metabolic syndrome following a moderate carbohydrate-restricted diet, consumption of either 3 eggs per day or the equivalent amount of yolk-free egg substitute for 12 weeks lowered oxLDL [34].
4.4. T2DM
Of all populations, the recommendation of egg intake in T2DM is one of the most controversial, given the results of some epidemiological studies that found a positive association between egg intake and T2DM risk [26,27]. However, similar to what has been observed in obese and metabolic syndrome populations, egg intake in T2DM appears to reduce markers of inflammation. In a randomized, crossover study conducted in patients with well-controlled T2DM, intake of 1 whole egg per day breakfast for 5 weeks significantly reduced AST and TNF when compared to an oatmeal-based breakfast [38].
4.6. Implications from Human Studies
As presented above, the majority of research suggests that egg intake promotes a pro-inflammatory response in healthy adults [30,31], whereas the consumption of eggs in conditions of overweight [32], insulin resistance [30], metabolic syndrome [35,36], and T2DM [38,151] have either an anti-inflammatory or neutral effect.
Referência :
Nutrients. 2015;7(9):7889-7913.