Every 5 years, the Dietary Guidelines Advisory Committee of the United States releases a scientific report on nutrition policy. In February 2015, the latest report garnered special attention with a new stance on dietary cholesterol. Although the report introduced some critically important and evidence-based dietary recommendations, such as lowering sugar, sodium, and red meat intake, the committee’s conclusion that “cholesterol is not considered a nutrient of concern for overconsumption” received widespread attention and drew concern that it could be overly broad as it did not acknowledge some of the uncertainties of conflicting literature and regarding cardiovascular risk in some important populations.

There is mounting evidence that for many subjects moderate intake of dietary cholesterol, most often studied as egg consumption, is not likely to be a major contributor to coronary risk factors or cardiovascular events. However, the findings of published studies raise concerns about high egg consumption, and by proxy, cholesterol intake, in the development of diabetes, cardiovascular disease in those with diabetes, and worsening coronary risk factors in a significant proportion of the population who are “hyper-responders” to dietary cholesterol.

Much of the conflict relates to ingestion of dietary cholesterol and the risk of developing diabetes. One study cited in the 2015 Dietary Guidelines report looked at egg consumption and risk of cardiovascular disease, cardiac mortality, and diabetes. This was a meta-analysis of 22 independent cohorts from 16 prospective studies, ranging in size from 1,600 to 90,735 participants and in follow-up time from 6 to 20 years. Egg consumption was determined by food frequency questionnaires, comparing the highest category of egg consumption (≥1 egg/day) with the lowest category (<1 egg/week or never). Comparison of these 2 categories showed no association between egg consumption and cardiovascular disease, stroke, or cardiac mortality in nondiabetic patients. However, the analysis revealed a 42% increase (i.e., a hazard ratio 1.42) in the incidence of type 2 diabetes in the high egg consumption. More importantly, there was a 69% increase in overall cardiovascular disease among the subgroup of existing diabetic patients in the high egg consumption group during the follow-up period.

A more recent report, albeit limited in relative size, came to the opposite conclusion, finding a 38% reduced risk of type 2 diabetes in those with high versus low egg intake. This study was in a much smaller population of 2,332 middle-aged and older men followed for 19 years. This suggests that there may be unrecognized age and gender differences that may play an unrecognized role. Similarly, reverse causality, in this case, eggs being chosen as a food in subjects less likely to develop diabetes for genetic, morphologic, or other lifestyle reasons, cannot be ruled out.

There are 2 prospective cohort studies that have examined this question as well, the Health Professional Follow-up Study (1986 to 1994) and the Nurses’ Health Study (1980 to 1994). Together, they enrolled 37,851 men aged 40 to 75 years and 80,082 women aged 34 to 59 years, respectively. They included healthy subjects with no known cardiovascular disease, diabetes, hypercholesterolemia, or cancer at study onset. They sought an association between egg consumption on food frequency questionnaire and the development of nonfatal myocardial infarction, fatal coronary heart disease (CHD), and stroke. After adjusting for age, smoking, and CHD risk factors, no association was found between egg consumption and risk of CHD or stroke in men or women. The authors note that this result may be skewed by intake of other foods. However, in subgroup analyses, diabetic subjects consuming >1 egg per day had an increased relative risk of CHD, 2.02 for men and 1.49 for women, similar to the findings of Shin et al quoted by the Dietary Guidelines Advisory Committee. The consistency of this finding in these 3 study groups is concerning and should be acknowledged, considering that 29.1 million Americans are diabetic. Frequent egg consumption puts this growing population at high risk for cardiovascular events.

Another group of subjects in whom special concern may be warranted are “hyper-responders” to dietary cholesterol, a sizable group comprising 25% of the population. Hyper-responders experience an unusual increase in circulating low-density and high-density lipoprotein levels in response to dietary cholesterol, likely because of variances in cholesterol absorption and/or endogenous synthesis. The prognostic implications of this response have not been well defined. However, egg consumption may increase serum cholesterol in some subjects.

A weakness of existing publications on this subject is that the trial designs are usually retrospective and observational and do not control for the confounding variable of item substitution and competing risks. The impetus to reduce egg consumption may range from health concern to personal taste or egg allergy. For example, if studied subjects change their typical breakfast of 2 eggs and 2 strips of bacon, by replacing the eggs with more bacon, those subjects may be in the low egg consumption group but be at higher mortality risk than patients in the higher egg consumption group. A randomized prospective trial is needed to inform useful guidelines in this regard.

Based on the current knowledge, we believe that dietary cholesterol should not be given a free pass to be consumed in unlimited quantities. Food items containing cholesterol are generally ingested with other substances that have been found to increase cardiovascular risk, such as phosphorus, insulin-like growth factor 1, heme iron, and phosphatidyl choline with metabolism to trimethyl-N-amine oxide, leaving any independent deleterious effects of cholesterol difficult to ascertain. However, extra caution is certainly warranted in diabetic patients and those at risk for developing diabetes. Increased awareness is needed of hyper-responders who experience a greater than average increase in blood cholesterol with frequent egg consumption.

Rather than a full green light approach, we suggest a more nuanced, yellow light recommendation for dietary cholesterol.