Eggs Should Be Included in a ‘Heart-Healthy’ Diet

It is often thought that eggs should not form part of a ‘heart-healthy’ diet due to their high cholesterol content. However, research has disproven this by suggesting their consumption favourably modifies lipoprotein concentration and particle profile. A recent study by DiMarco et al. concluded that egg consumption may also improve HDL function, enhancing reverse cholesterol transport, and increase carotenoid concentration, offering antioxidant effects [1]. From discussing these findings within wider research, it could be stated that regularly consuming eggs as part of a balanced diet may offer cardioprotective effects and reduce risk of CVD.

In the UK it is estimated that 34.5 million eggs are consumed every day, creating a market that is worth £947m [2]. As low energy density and nutrient rich foods, eggs provide only 3% of daily caloric intake but all nine essential and nine non-essential amino acids, 70mg of long chain omega-3 polynsaturated fatty acids, primarily in the form of docosahexaenoic acid, and a wide range of vitamins and minerals including vitamins A, D, K, B12, riboflavin, folate, selenium, iodine, calcium, iron and zinc. Despite the numerous health benefits of regularly consuming eggs as part of a balanced diet, they are often believed to be associated with high cholesterol. Although egg yolks contain approximately 200mg cholesterol [3], there is only a weak correlation between dietary and plasma cholesterol levels in the general population [4]. It has instead been reported that eggs have favourable effects on high density lipoprotein (HDL) cholesterol, and consequently risk of cardiovascular disease (CVD), without adversely affecting other risk markers such as total cholesterol and triacylglycerol concentration [5]

HDL particles contain an outer layer of phospholipids and apolipoproteins, mainly apoAI, apoAII, apoCI and apoCII, with a central core of triacylglycerols and cholesterol esters. ApoAI comprises 70% of HDL proteins [6], and is primarily responsible for the initial stage in reverse cholesterol transport by facilitating the interaction of HDL with cellular cholesterol efflux transporters [1]. Free cholesterol taken up by HDL is esterified by lecithin-cholesterol acyltransferase (LCAT), stabilising it within the core, then returned to the liver for catabolism [7]. Removal of cholesterol from macrophages and a reduction in cellular cholesterol in the subintimal space characterises the anti-atherosclerotic effect of HDL [6]. Further to this, it also has antioxidant and anti-inflammatory activity as it contains paraoxonase-1 (PON1), which prevents oxidative modification [6] and transports xanthophyll carotenoids [1], which are lipophilic antioxidants.

For the reasons previously described, high HDL is associated with reduced risk of CVD [4]. However, HDL is heterogeneous in nature, differing in structure, composition and biological function due to variation in the apolipoprotein and lipid content of particles [8]. This means that particle size, as well as LCAT activity and both apolipoprotein and carotenoid concentrations, may affect risk of CVD in addition to HDL level. A recent intervention study by DiMarco et al. investigated whether frequent intake of eggs affects lipoprotein composition and function [1]. This review will discuss their findings in relation to wider research to determine whether the consumption of eggs may adversely affect CVD risk or should, in fact, be promoted due to cardioprotective effects.


Method

Study design

A 14 week crossover dietary intervention study was completed with a 2 week wash-out period, during which 0 eggs/day were consumed, followed by three 4 week periods of egg consumption at 1, 2 and 3 eggs/day, sequentially. Fasting plasma was taken at the end of each dietary period, and serum after the 1, 2 and 3 eggs/day intervention blocks.

Lipoprotein, enzyme and carotenoid measurements

Lipoprotein particles were classed as small, medium and large, and mean VLDL, LDL and HDL particle size was determined. Apolipoproteins apoAI, apoAII, apoCII, apoCIII and apoE were quantified. CETP and LCAT activity in plasma were assessed, as was PON1. Lutein and zeaxanthin were extracted from plasma and concentrations analysed. A standard cure was generated to determine carotenoid recovery efficiency.

Statistical analysis

Analysis was conducted on all variables measured to assess the association with varying egg intake.


Results

Subject characteristics

37 healthy men and women, mean age 24.1 years, participated in the intervention. No change was observed in BMI, waist circumference, systolic blood pressure (BP), fasting plasma glucose or fasting plasma TG with egg intake, but diastolic BP decreased.

Results of statistical analysis

Intake of 1 egg/day resulted in lower plasma LDL than the other intakes, although there was no difference between 0, 2 and 3 eggs/day. LDL particle concentration increased with egg intake in a dose-dependent manner resulting from an increase in concentration of large-LDL particles. HDL increased with egg intake, and similarly there was a dose-dependent increase in large-HDL particle concentration. There was no change in VLDL particle size or concentration.

Compared to a lower intake, apoAI concentration increased with intake of 1-3 eggs/day and apoAII with 2-3 eggs/day, but there was no change in apo CII, apoCIII and apoE. There was a positive correlation between apoAI and large-HDL concentration.

There was no change in CETP yet LCAT activity increased with egg intake in a dose-dependent manner. PON1 activity was higher with 3 eggs/day compared to 1-2 eggs/day, and a positive correlation was observed with both apoAIII concentration and LCAT activity.


There was no change observed in lutein and zeaxanthin intake but plasma concentrations increased following intake of 2-3 eggs/day compared to 0-1 eggs/day.


Discussion

The study by DiMarco et al. found increases in LDL and HDL concentration with higher egg intake [1], which is a conclusion that is common within much of the literature [9][10]. Although the increase in LDL cholesterol may suggest that there may be a consequential elevated risk of CVD due to its role in atherosclerosis, the increase in HDL has been shown to be such that the HDL/LDL ratio is maintained [11]; a shift in this ratio towards a greater proportion of LDL would be associated with higher risk of CVD [12]. It is, however, significant to note that in less healthy individuals the beneficial effects of HDL may be attenuated by oxidative modification by myeloperoxidase in response to inflammation [13], forming a proinflammatory molecule. This limits the generalisability of the results by DiMarco et al..

In addition to the concentration of lipoproteins, the heterogeneity of HDL has been deemed of importance in determining its capacity to facilitate cholesterol efflux [14]. DiMarco et al. found that there was an increase in large-HDL particles in a dose-dependent manner with egg consumption [1], as was also observed in the intervention study by Missimer et al. where consumption of 2 eggs/day for breakfast increased mean particle size to larger HDL compared to oatmeal [15]. It is generally reported that large HDL particles reduce risk of CHD due to a greater cholesterol efflux ability [16], although this may rely on the function of LCAT to stabilise transferred cholesterol by esterification [14] else HDL may have the potential to become pro-atherogenic due to the bidirectional nature of cholesterol transfer with peripheral cells [17]. However, the increase in LCAT activity in the study by DiMarco et al., again in a dose-dependent manner [1], could suggest that the larger HDL particles may be able perform their anti-atherosclerotic role. However, the link between large HDL particles and CHD risk should not be taken as certain as it could be that the large HDL particle size observed within participants may be a marker of a generally healthy cardiometabolic risk profile rather than reflecting direct cardioprotective effects. This is speculated due to Arsenault et al. observing that the association between HDL and CHD was mostly explained by traditional CHD risk factors such as HDL concentration [16]. Despite this, the increase in large LDL particles with egg intake reported by DiMarco et al., [1] suggests a further anti-atherosclerotic role due to larger LDL particles being less susceptible to oxidative modification and scavenging by macrophages in the arterial wall to form atherosclerotic lesions. A higher concentration of small LDL is often observed in those with metabolic syndrome despite no difference in LDL concentration [18], suggesting this change in lipoprotein particle size in response to egg consumption may be of greater significance than any change in concentration.

An increase in apoAI concentration was also observed following consumption of 1-3 eggs/day [1], a conclusion comparable to findings from the intervention study by Missimer et al. [15]. High apoAI concentration has a protective role similar to that of HDL [17] due to interaction of apoAI with cholesterol efflux transports [1], as well as its ability to dissociate from HDL and acquire cholesterol and phospholipids from cell membranes and other lipoproteins to form new nascent HDL particles [19]. Low concentrations of apoAI have been associated with increased risk of CHD irrespective of HDL size [16], suggesting it to also be a key marker for chronic disease risk.

Finally, DiMarco et al. reported that there was an increase in plasma concentration of lutein and zeaxanthin with intake of 2-3 eggs/day compared to 0-1 eggs/day [1]. This has been frequently observed within research [15][20][11] due to the high bioavailability of these carotenoids from eggs where its incorporation in the lipid egg yolk facilitates absorption [12]. This increase suggests that greater egg consumption may reduce oxidative stress and hence risk of atherosclerosis and CVD [11]. Additionally, Greene et al. observed a significant correlation between HDL size and plasma lutein and zeaxanthin [12], and Blesso et al. also found 3 eggs/day to increase the proportion of each carried by HDL [20]. This indicates the potential for carotenoids to act directly as antioxidants in lipoprotein particles to prevent oxidative modification and conversion to proinflammatory molecules [16].


Impacts

The overall conclusion by DiMarco et al., that intake of >1 egg/day improves HDL function, offers a favourable LDL particle profile and increases plasma antioxidants [1], suggests that the health benefits of eggs extend beyond their amino acid, vitamin and mineral contents. Discussing this finding within wider research, it has been found that, although eggs affect cholesterol concentration by increasing LDL and HDL, the lack of change in LDL/HDL ratio results in no increase in risk of CVD. This contrasts the supposition that eggs should not be included in a ‘heart-healthy’ diet. Moreover, the associated  increase in apoAI concentration in HDL, hence greater ability to accumulate free cholesterol for reverse cholesterol transport, as well as the increased size of LDL and HDL particles, reflects an anti-atherosclerotic effect of egg consumption, as does the increased plasma and lipoprotein concentration of lutein and zeaxanthin.

Considering the factors discussed, it could be recommended that eggs should not be avoided and that regular consumption as part of a balanced diet may offer cardioprotective effects and reduce risk of CVD due to the improvements in HDL function and lipoprotein profile. Additionally, the carotenoids lutein and zeaxanthin are more bioavailable from eggs than fruit and vegetables [1], despite their lower presence, making eggs an optimum source for such compounds. There is, however, a significant amount of variation in the responsiveness of an individual to dietary cholesterol [4], with ‘hyper-responders’ observing a greater increase in HDL and LDL cholesterol concentration, larger LDL and HDL particles, and a higher carotenoid concentration following egg intake compared to ‘hypo-responders’ [12]. This suggests that a proportion of the population may experience enhanced cardioprotective effects from consuming eggs. Nonetheless, those with a lessened response should not be discouraged from consuming eggs due to the considerable number of additional health benefits they provide.



[1] DiMarco, D.M., Norris, G.H., Millar, C.L., Blesso, C.N., Luz Fernandez, M.L. (2017) Intake of up to 3 eggs per day is associated with changes in HDL function and increased plasma antioxidants in healthy, young adults. The Journal of Nutrition, jn241877.
[2] Egg info (2017?) Industry data. URL: https://www.egginfo.co.uk/egg-facts-and-figures/industry-information/data [18th June 2016]
[3] Harvard University (2017?) The Nutrition Source. URL: https://www.hsph.harvard.edu/nutritionsource/eggs/ [18th March 2016]
[4] Griffin, J.D., Lichtenstein, A.H. (2013) Dietary cholesterol and plasma lipoprotein profiles: Randomized-controlled trials. Current Nutrition Reports, 2(4), 274-282.
[5] Melough, M.M., Chung, S-J., Luz Fernandez, M.L., Chun, O.K. (2017) Impact of eggs on dietary nutrient adequacy and cardiovascular risk in U.S. adults. The FASEB Journal, 31(1), Supplement 789.18.
[6] Navab, M., Reddy, S.T., Van Lenten, B.J., Fogelman, A.M. (2011) HDL and cardiovascular disease: Atherogenic and atheroprotective mechanisms. Nature Reviews: Cardiology, 8, 222-232.
[7] Boisvert, W.A., Black, A.S., Cutriss, L.K. (1998) ApoAI reduces free cholesterol accumulation in atherosclerotic lesions of apoE-deficient mice transplanted with apoE-expressing macrophages. Arteriosclerosis, thrombosis and vascular biology, 19(3), 525-530.
[8] Camont, L., Chapman, M.J., Kontush, A. (2011) Biological activities of HDL subpopulations and their relevance to cardiovascular disease. ITrends in Molecular Medicine, 17(10), 594-603.
[9] Lemos, B.S., DiMarco, D.M., Missimer, A., Murillo, A>G., Malysheva, O.V., Caudill, M.A., Blesso, C.N., Luz Fernandez, M.L. (2017) Consumption of up to three eggs per day increases dietary cholesterol and choline while plasma LDL cholesterol and trimethylamine N-oxide concentrations are not increased in a young, healthy population. The FASEB Journal, 31(1), Supplement 447.3.
[10] Mutungi, G., Ratliff, J., Puglisi, M., Torres-Gonzalez, M., Vaishnav, U., Leite, J.O., Quann, E., Volek, J.S., Luz Fernandez, M.L. (2007) Dietary cholesterol from eggs increases plasma HDL cholesterol in overweight men consuming a carbohydrate-restricted diet. The Journal of Nutrition, 138(2), 272-276.
[11] Ballesteros, M.N., Cabrera, R.M., Saucedo, S., Luz Fernandez, M.L. (2013) Two eggs per day increase plasma lutein and zeaxanthin in a pediatric population characterized by low intake of fruits and vegetables. British Journal of Medicine & Medical Research, 3(4), 2203-2213.
[12] Greene, C.M., Waters, D., Clark, R.M., Contois, J.H., Luz Fernandez, M.L. (2006) Plasma LDL and HDL characteristics and carotenoid content are positively influenced by egg consumption in an elderly population. Nutrition & Metabolism, 3(6).
[13] Undurti, A., Huang, Y., Lupica, J.A., Smith, J.D., DiDonato, J.A., Hazen, S.L. (2009) Modification of high density lipoprotein by myeloperoxidase generates a pro-inflammatory particle. The Journal of Biological Chemistry, 284, 30825-30835.
[14] Andersen, C.J., Blesso, C.N., Lee, J., Barona, J., Shah, D., Thomas, M.J., Luz Fernandez, M. (2013) Egg consumption modulates HDL lipid composition and increases the cholesterol-accepting capacity of serum in metabolic syndrome. Lipids, 48, 557-567.
[15] Missimer, A.C., DiMarco, D.M., Murillo, A.G., Millar, C.L., Blesso, C.N., Luz Fernandez, M. (2017) Consumption of 2 eggs per day as compared to an oatmeal breakfast increases plasma carotenoids and markers associated with reverse cholesterol transport in young, healthy individuals. The FASEB Journal, 31(1), Supplement 431.7.
[16] Arsenault, B.J., Lemieux, I., Després, J-P., Gagnon, P., Wareham, N.J., Stroes, E.S.G., Kastelein, J.J.P., Khaw, K-T., Boekholdt, M. (2009) HDL particle size and the risk of coronary heart disease in apparently healthy men and women: The EPIC-Norfolk prospective population study. Atherosclerosis,206(1), 276-281.
[17] Van der Steeg, W.A., Holme, I., Boekholdt, S.M., Larsen, M.L., Lindahl, C., Stroes, E.S.G., Tikkanen, M.J., Wareham, N.J., Faergeman, O., Olsson, A.G., Pedersen, T.R., Khaw, K-T., Kastelein, J.J.P. (2008) High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: Significant for cardiovascular risk: The IDEAL and EPIC-Norfolk studies. Journal of the American College of Cardiology, 51(6), 634-642.
[18] Kathiresan, S., Otvos, J.D., Sullivan, L.M., Keyes, M.J., Schaefer, E.J., Wilson, P.W.F., D’Agostino, R..B., Vasan, R.S., Robins, S.J. (2006) Increased small low-density lipoprotein particle number: A prominent feature of the metabolic syndrome in the Framingham Heart Study. Circulatio, 113, 20-29.
[19] Lieberman, M., Marks, A., Smith, C. (2007) Mark’s Essentials of medical biochemisty: A clinical approach. Maryland: Lippincott Williams & Williams.
[20] Blesso, C.N., Andersen, C.J., Bolling, B.W., Luz Fernandez, M. (2013) Egg intake improves carotenoid status by increasing plasma HDL cholesterol in adults with metabolic syndrome. Food & Function, 2.

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