As of the early 1970's, a reduction in consumption of eggs, a concentrated source of cholesterol (one yolk provides ~215 mg of cholesterol), had been widely recommended in an effort to lower blood cholesterol and reduce the risk of heart disease1. In 1973, the American Heart Association (AHA) guidelines specifically advocated exclusion of eggs from the diet, accompanying the advised cholesterol restriction2. More recent AHA guidelines no longer advise for or against egg or egg yolk consumption, admitting that there is a lack of scientific evidence for selecting a target level for dietary cholesterol3. This is partially due to individual differences in serum cholesterol responses to dietary cholesterol. The recommended intake of daily dietary cholesterol continues to be 300 mg/day or less for healthy adults and less than 200 mg/day for persons with elevated cholesterol or heart disease3. Given the widespread nature of this recommendation, there is surprisingly little evidence that egg consumption increases blood cholesterol levels, thereby increasing cardiovascular risk 4.

Data from recent studies show that consumption of one or two eggs per day, when part of a low fat diet, does not adversely affect the lipid profile56. In fact, the preclusion of eggs from the diet may represent a potential reduction in overall dietary quality. As an inexpensive functional food with an exceptional nutritional profile78, eggs are an excellent natural source of folate, riboflavin, selenium, choline, vitamin B12, and fat-soluble vitamins A, D, E, and K. Eggs also provide high-quality, bioavailable protein910 with little total fat. Compared to other animal protein sources, eggs contain proportionately less saturated fat, which has generally been recognized as a strong dietary determinant of elevated low-density lipoprotein (LDL) levels and increased risk of coronary heart disease (CHD) 11 although this topic is not without controversy 12.

As a dietary substitute for eggs, egg substitute is comprised of 99% egg whites and provide 12 key vitamins and nutrients, including riboflavin, B12, folate, and pantothenic acid, while excluding the cholesterol contribution of the egg yolk13. Although nutritionally similar to eggs, egg substitute contains emulsifiers, stabilizers, and artificial color and are on average three times as expensive as regular eggs.

Endothelial function refers to arterial vasomotor responses mediated predominantly by the release of nitric oxide (vasodilating), and endothelin (vasoconstricting) from the vascular endothelium1415, and plays an important role in the pathogenesis of atherosclerosis, hypertension, cardiovascular disease, and diabetes151617. Endothelial dysfunction correlates strongly with both coronary disease and its risk factors1819 and reverses in response to risk modification efforts152021222324252627. Endothelial dysfunction has increasingly been viewed as an indicator of coronary risk19, and its amelioration as an indicator of risk reduction2023.

The relationship of egg consumption to coronary outcomes depends not only on the cholesterol content of eggs themselves, but on the composition of the total diet. It is a common misconception that dietary cholesterol increases serum cholesterol which increases CHD risk2829; however, research has failed to provide substantial evidence of this assumed relationship30. In our previous trial, daily ingestion of eggs did not produce adverse effects on cardiac risk, as indicated by endothelial function and lipid profile, in healthy adults31. To the best of our knowledge, no study has ever compared the effects of egg versus egg substitute consumption on cardiovascular risk. Therefore, we performed a randomized cross-over trial to assess the effects of egg or egg substitute consumption on endothelial function and lipid panel in hyperlipidemic adults.

Forty hyperlipidemic participants participated in this study. Sixty percent of the participants were female. Participants ranged in age from 35 to 77 years, with a mean age of 60 years (Table 2). Four participants dropped out of the study after the acute phase. One participant dropped out because the participant was unwilling to consume eggs or egg substitute daily for six weeks, another dropped out because of relocation to another state, and two dropped out because they started using lipid lowering medication (statin).

Our findings in this study expand on existing evidence that short-term egg consumption does not adversely affect endothelial function, in a population not previously examined: hyperlipidemic adults. Moreover, we observed that consuming eggs daily did not unfavorably influence serum cholesterol or other measures of the lipid profile. While the subjects demonstrated impaired endothelial function at baseline (i.e. relative to healthy endothelial function), the acute induction of endothelial dysfunction by the test meal high in saturated fat was not observed. Egg substitute, which is made from 99% egg whites, is lower in calories relative to whole eggs, lacks cholesterol and fat, and is fortified with vitamins, also lowered cholesterol and triglyceride levels. In addition, egg substitute led to a decrease in LDL and significantly improved endothelial function, as compared to sustained egg consumption. To the best of our knowledge, this is the first study to provide evidence that egg or egg substitute consumption does not adversely affect endothelial function in hyperlipidemic adults.

The acute phase findings were consistent with those of the sustained phase. Single, acute doses of egg did not adversely affect endothelial function. The sausage and cheese breakfast sandwich, designed to demonstrate acute dysfunction in the endothelium, surprisingly also did not adversely affect endothelial function. This finding is consistent with the prior study of egg ingestion in healthy adults conducted at our lab31, but is at odds with the reported literature. This may be explained by differences in gastric transit times for different types of food 31. Future studies should evaluate postprandial brachial artery dilation at different time points to assess the effect of time. Several studies have examined FMD serially over time following meal ingestion4041.

While rich in cholesterol, eggs are also nutritious. Data from NHANES III reveal that egg consumption is an important nutritional contribution to the average American diet, providing a relatively inexpensive source of amino acids and essential fatty acids9. Eggs provide arginine, a precursor to nitric oxide, which in turn plays a central role in endothelial function42. Endothelial function is an arterial vasomotor response mediated predominantly by the release of nitric oxide (vasodilating), and endothelin (vasoconstricting) from the vascular endothelium26. This system plays an important role in the pathogenesis of atherosclerosis, cardiovascular disease, and other chronic diseases1943.

The relative importance of dietary cholesterol to cardiovascular risk, and the association between dietary and serum cholesterol, are both subject to ongoing debate444546. The association between dietary cholesterol and coronary events and mortality is generally positive but rather weak, and derived largely from ecological and prospective cohort studies with variable follow-up47484950. In most of these studies, it is difficult to determine the effects of cholesterol independent of dietary fat. One large prospective cohort followed U.S. male physicians for over 20 years. The study monitored egg consumption and documented new cases of heart failure during follow-up. Results failed to find a correlation between occasional egg consumption and heart failure, although an increased risk of heart failure was related to participants who reported consuming more than one egg per day49. Another study found no impact of egg intake on cardiovascular risk, specifically stroke, ischemic stroke, and coronary artery disease. However, Nakamura et al demonstrated significant correlation with serum cholesterol concentrations in women consuming more than two eggs per day 51. In a recent study by Djoussé et al, egg consumption was associated with increased risk of diabetes 52. Djoussé et al also linked egg consumption to increased mortality and even more so in diabetics 53. Overall, scientific studies of the relationship between egg consumption, cardiovascular disease and mortality3054, have thus been somewhat inconsistent.

Little, if any, epidemiological evidence exists supporting a direct link between egg consumption and cardiovascular disease or mortality risk. Previous studies have shown weak positive associations between intake of dietary cholesterol and serum cholesterol, while others failed to find any association30. Hu and colleagues analyzed data from two large cohorts, the Health Professional Follow-Up Study and the Nurses' Health Study, to assess the effect of egg consumption on cardiovascular events and deaths47. After a mean of 8 years of follow-up, no overall significant association was observed between egg consumption and risk of CHD in both males and females. Hu et al 47 also reported that the relative risk of CHD was the same whether the participants consumed less than, or more than, one egg per week.

While our study provides valuable data regarding egg ingestion in hyperlipidemic adults, it is not without limitations. The study's small sample size almost entirely derived from one community in Southwestern Connecticut may limit the generalization these of results. Furthermore, the duration of egg consumption during this study limits the ability to predict the long-term effects. Variables potentially confounding the correlation between nutrient intakes and endothelial responses included physical activity, vasoactive medication use, and genetic factors. Unmeasured or inaccurately measured dietary intake data could also have confounded results. Three-day food diaries, used to track dietary intake, did not indicate any significant unintended changes in overall dietary pattern, although changes in diet or behavior that were not captured may have impacted findings. Adjustment for potential confounders was managed through application of strict eligibility criteria, randomization, and crossover design. Also of note, the intended provocation of endothelial dysfunction by a single meal high in saturated fat failed to demonstrate a deleterious effect. Finally, endothelial function was measured only one time after treatment assignments and not monitored for a prolonged time.

In light of the persistent uncertainties and lack of observational evidence regarding the effects of egg consumption on serum cholesterol and cardiac risk, the application of this methodology and technology in further studies is appropriate, and very much needed. Short of a randomized controlled trial of egg consumption and cardiovascular events, endothelial function testing offers one of the best available means to evaluate the role of egg ingestion on cardiac risk. To date, the evidence generally mitigates against an association between moderate egg consumption and increased cardiac risk. Further testing in at-risk samples, including individuals with established coronary disease, is now justified to clarify the place of eggs in a judicious and heart-healthy diet.

The authors declare that they have no competing interests.

The authors contributions are as follows: DLK served as the Principal Investigator and is responsible for oversight of all study related activities, data analysis and manuscript preparation. VYN was responsible for the protocol development, data analysis, interpretation, manuscript preparation, and critical review of the paper. ZF was responsible for study management, ultrasound reading, data collection, and manuscript preparation. SD contributed to manuscript preparation. AGS contributed to manuscript preparation. All Authors have read and approved the final manuscript.