Current Atherosclerosis Reports

, Volume 12, Issue 6, pp 377–383

Revisiting Dietary Cholesterol Recommendations: Does the Evidence Support a Limit of 300 mg/d?

Authors

    • Department of Nutritional Sciencesthe University of Connecticut
  • Mariana Calle
    • Department of Nutritional Sciencesthe University of Connecticut
Article

DOI: 10.1007/s11883-010-0130-7

Cite this article as:
Fernandez, M.L. & Calle, M. Curr Atheroscler Rep (2010) 12: 377. doi:10.1007/s11883-010-0130-7

Abstract

The perceived association between dietary cholesterol (DC) and risk for coronary heart disease (CHD) has resulted in recommendations of no more than 300 mg/d for healthy persons in the United States. These dietary recommendations proposed in the 1960s had little scientific evidence other than the known association between saturated fat and cholesterol and animal studies where cholesterol was fed in amounts far exceeding normal intakes. In contrast, European countries, Asian countries, and Canada do not have an upper limit for DC. Further, current epidemiologic data have clearly demonstrated that increasing concentrations of DC are not correlated with increased risk for CHD. Clinical studies have shown that even if DC may increase plasma low-density lipoprotein (LDL) cholesterol in certain individuals (hyper-responders), this is always accompanied by increases in high-density lipoprotein (HDL) cholesterol, so the LDL/HDL cholesterol ratio is maintained. More importantly, DC reduces circulating levels of small, dense LDL particles, a well-defined risk factor for CHD. This article presents recent evidence from human studies documenting the lack of effect of DC on CHD risk, suggesting that guidelines for DC should be revisited.

Keywords

Dietary cholesterolLDL cholesterolHDL cholesterolLDL sizeClinical studiesEpidemiologic dataEggs

Introduction

The American Heart Association (AHA) recommends no more than 300 mg/d of dietary cholesterol (DC) for healthy persons to prevent increased risk for coronary heart disease (CHD) [1]. These recommendations are mostly based on the presence of both saturated fat and cholesterol in many foods and on data derived from animal studies where supraphysiologic doses of cholesterol, ranging from the equivalent of 1,000 mg to 20,000 mg/d for humans, were fed in order to produce atherosclerosis [2].

It is important to note that many other countries do not have the same guidelines for DC. Canada [3••], Korea [4•], New Zealand [5], and India [6], for example, do not set an upper limit for DC, focusing instead on controlling the intake of saturated fat and trans fat, which are the major determinants of blood cholesterol concentrations. Similarly, the European guidelines on cardiovascular disease prevention have the following recommendations regarding healthy food choices: “consume a wide variety of foods, adjust energy intake to maintain a healthy weight, encourage consumption of fruits and vegetables, replace saturated fat with mono or polyunsaturated fatty acids and reduce salt intake” [7]. In contrast to US policies, Europeans have no dietary guidelines for DC [7]. A summary of the dietary recommendations for DC in different countries, including two recent reports from the AHA, is presented in Table 1.
Table 1

Dietary guidelines for saturated fat and dietary cholesterol in different countries

Author/year

Country/region

Institution/society

Dietary fat guidelines

Cholesterol guidelines

Genest et al. [3••]/2009

Canada

2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult

Limit intake of saturated fat to <10% of energy

No recommendation for dietary cholesterol

Task Force Members [7]/2007

Europe

European guidelines on cardiovascular disease prevention in clinical practice: Fourth Joint Task Force of the European Society of Cardiology and Other societies on cardiovascular disease prevention in clinical practice.

Limit intake of saturated fat to <10% of total energy

No recommendation for dietary cholesterol

National Institute of Nutrition [6]/2010

India

National Institute of Nutrition

Limit saturated fat and total fat

No recommendation for dietary cholesterol

Pai et al. [4•]/2008

Korea

Korean Nutrition Society

Total fat <20%

No recommendation for dietary cholesterol

Ministry of Health [5]/2003

New Zealand

Food and Nutrition Guidelines for Healthy Adults

Limit saturated fat to <12% of total energy

No recommendation for dietary cholesterol

Lichenstein et al. [1]/2006

United States

AHA Scientific Committee

Limit intake of saturated fat to <7%

< 300 mg/d

Lloyd-Jones et al. [16••]/2009

United States

AHA Special Report. Defining and setting National goals for cardiovascular health promotion and disease reduction.

Limit intake of saturated fat and trans fat

Dietary cholesterol not mentioned

Gidding et al. [17••]/2010

United States

AHA Pediatric and Adult Nutrition Guidelines: a scientific statement from the AHA Nutrition Committee

Limit intake of saturated fat and trans fat

Adolescents and children. Dietary cholesterol not mentioned

AHA American Heart Association.

Epidemiologic studies do not support an association between cholesterol intake and CHD [812]. This could partly be explained by the fluctuations in response to dietary cholesterol among all individuals, which varies from no changes to large increases in plasma cholesterol. In addition, it is critical to note that for those individuals who have hypercholesterolemic response to dietary cholesterol (about one third of the population), the rise is typically due to increases in both plasma low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) concentrations, with no alterations in the LDL-C/HDL-C ratio.

Epidemiologic Studies

Extensive research derived from epidemiologic studies, including Framingham [8], the Nurses’ Health study [9], National Health and Nutrition Examination Survey (NHANES) [10], and the Lipid Research Clinics Prevalence Follow-up Study [11], do not support a relationship of increased intake of cholesterol and CHD events [12]. In contrast, Weggermans et al. [13] analyzed 17 clinical studies and concluded that eggs or other cholesterol-rich foods raise the ratio total cholesterol to HDL-C, adversely affecting the associations with CHD risk. However, clinical trials evaluating DC effects from the past three decades show that effects of DC on plasma cholesterol obtained in the short term (eg, 2 weeks) do not reflect the effects of high intakes over longer periods of time [14], and this has led Conti et al. [15•] to caution organizations such as the AHA against publishing clinical guidelines based on a shallow evidence base. In a recent report by the AHA regarding the goals for cardiovascular health promotion, dietary habits with the strongest evidence for causal effects on cardiovascular events were emphasized [16••]. In this report, the Dietary Approaches to Stop Hypertension (DASH) diet was highly recommended, as was a restriction of saturated fat and trans fat, but there was no mention of DC [16••]. Similarly, Gidding et al. [17••], in their recommendations for the AHA Pediatric and Adult Nutrition guidelines, gave no specific guidelines for DC.

A recent article reviewed the epidemiologic data relating egg consumption and CHD. When multiple regression analysis was used, no relationship was found [18••]. Constance [19] discussed the complexity of atherosclerosis development, indicating that LDL is not the only causal factor and that that egg consumption has a low association with atherogenic risk. The relative prohibition of eggs therefore was not considered to be well supported [19]. Nakamura et al. [20] report an inverse association between egg consumption and total cholesterol concentration, possibly due to hypercholesterolemic individuals avoiding eggs. However, they did not find an association between eating eggs and CHD incidence in two cohorts of 90,735 Japanese men and women. Qureshi et al. [21] evaluated egg intake in 9734 adults and divided them into those consuming less than 1 egg per week or more than 6 eggs per week. Egg consumption was not associated with stroke, ischemia, or CHD in these individuals. However, there was an increase in CHD in patients diagnosed with diabetes at the highest level of egg consumption [21]. Other studies also suggest that individuals with diabetes should limit egg intake [22, 23•]. In summary, the preponderance of the epidemiologic evidence from the past 14 years does not support a relationship between dietary cholesterol (or egg intake) and risk for CHD [4•, 814], [15•, 16••, 17••]. Accordingly, neither Europe [7], Canada [3••], nor Asian countries [4•, 5] restrict dietary cholesterol as part of the recommendations for a heart-healthy diet.

Eggs and Dietary Cholesterol

The AHA still recommends limiting other food items high in cholesterol if eggs are to be consumed [1] in spite of recent reports that show no association between egg intake and risk for heart disease [811, 18••, 1921]. In fact, there are no studies with substantial evidence supporting the claims of egg consumption involved in CHD risk. In contrast, a recent analysis in which a risk-apportionment approach was used on the risk factors for CHD revealed that egg intake contributes to less than 1% of the risk, and the authors conclude that AHA dietary guidelines possibly should be revised [18••]. Eggs are the only food that is both rich in cholesterol and low in saturated fat, perhaps explaining why eggs are often used to evaluate the effects of dietary cholesterol on plasma lipids and CHD risk [811, 24, 25]. Other cholesterol-containing foods, such as dairy products, also contain high concentrations of saturated fat, which is a confounder for dietary cholesterol effects. This might be the reason why controversial results exist regarding the effects of dairy products on CHD risk [26].

Clinical trials conducted in children [27], younger adults [24, 25], and the elderly [28, 29] have clearly demonstrated that although dietary cholesterol provided by eggs significantly increases LDL-C in one third of the population, those individuals considered hyper-responders to a cholesterol challenge exhibit increases in both LDL-C and HDL-C, with the result of no changes in the LDL-C/HDL-C ratio, a major predictor of CHD [30•]. These results indicate that individuals with initial plasma cholesterol concentrations that place them at a low risk for CHD do not develop an atherogenic lipoprotein profile following the consumption of additional dietary cholesterol, regardless of their response classification.

It is well established that nutritional interventions aimed at managing plasma lipids are known to be less effective in obese and overweight individuals [31]. During a weight loss intervention, intake of 3 eggs per day for 12 weeks was shown to selectively increase plasma HDL-C without increasing LDL-C in overweight men [32••]. Harman et al. [33•] also reported no changes in LDL-C after consuming 2 eggs per day for 12 weeks in a weight loss intervention study. Intake of only 1 egg per day increased HDL-C without increasing LDL-C in men and women aged 40–60 years, resulting in a lower LDL-C/HDL-C ratio [34]. Similarly, in a study in which 56 participants with a mean age of 35 years were given an additional egg per day during 12 weeks, significant increases were reported for HDL-C with no changes in LDL-C [35•]. A summary of plasma LDL-C and HDL-C concentrations as a response to egg intake in recent clinical studies is presented in Table 2.
Table 2

Changes in LDL-C, HDL-C, LDL size, and HDL size as a response to dietary cholesterol provided by eggs in various populations

Population

Duration

Additional dietary cholesterol

LDL-C

HDL-C

LDL-C/HDL-C ratio

LDL size

HDL size

Children (n = 54) [27]

4 wk

518 mg/d

Increase

Increase

No change

Increase

ND

Women (n = 51) [25]

4 wk

640 mg/d

Increase

Increase

No change

Increase

ND

Men (n = 28) [32••]

12 wk

640 mg/d

No change

Increase

Decrease

Increase

Increase

Men/women (n = 42) [34]

12 wk

215 mg/d

No change

Increase

No change

Increase

Increase

Men/women (n = 34) [28]

4 wk

640 mg/d

Increase

Increase

No change

Increase

Increase

Men/women (n = 56) [35•]

12 wk

250 mg/d

No change

Increase

Decrease

ND

ND

Men/women (n = 45) [33•]

12 wk

400 mg/d

No change

No change

No change

ND

ND

HDL-C high-density lipoprotein cholesterol; LDL-C low-density lipoprotein cholesterol; ND not determined.

To evaluate whether insulin resistance, with or without obesity, influences the response to dietary cholesterol, Knopp et al. [36] recruited 197 healthy individuals into a randomized crossover study in which 0, 2, and 4 eggs per day were fed for 4 weeks with a 1-month washout period in between. The participants were classified as insulin sensitive (n = 65), insulin resistant (n = 75), and obese insulin resistant (OIR, n = 58). Insulin-resistant and insulin-sensitive individuals had significant increases in LDL-C of 7.8% and 3.3%, respectively, after consuming 4 eggs per day, whereas OIR individuals had no changes in LDL-C at any intake level. In contrast, HDL-C was significantly increased for all groups even after the consumption of only 2 eggs per day. These studies suggest that dietary management of OIR individuals need not include restrictions on eggs.

Effects of Eggs on Atherogenic Lipoproteins

The association between elevated LDL-C and an increased risk for CHD has been well documented [37]. However, it is now well established that LDL particles are heterogeneous with regard to size, density, composition, charge, and atherosclerotic potential [38]. These characteristics need to be taken into consideration when we evaluate the effects of any dietary component on plasma lipoprotein levels and atherogenic potential. The Adult Treatment Panel III acknowledged the predominance of small, dense LDL particles as an emerging CHD risk factor [37]. The increase in cardiovascular risk, attributable to plasma lipids, is significantly modulated by variations in LDL particle size and number [39]. Utilizing nuclear magnetic resonance spectroscopy, Blake et al. [40] reported that median baseline values of LDL particle concentration were higher and LDL particle size was lower among women who subsequently experienced a coronary event. In a cohort of men from the Quebec Cardiovascular Study, the association between LDL particle size and the incidence of ischemic heart disease yielded similar results [41]. Thus, concentrations of LDL-C alone do not provide a comprehensive evaluation of CHD in the general population. Egg intake has been shown to increase the number of both large LDL and HDL particles while decreasing the concentrations of small LDL subfractions [42••]. Other studies have also shown a shift of the atherogenic pattern B to pattern A following egg intake in children [27] and in adults [43], and these larger LDL particles showed no increased susceptibility to oxidation. In addition, individuals having a lower number of the large HDL particles as well as increased number of small HDL particles are considered to be at increased risk for heart disease [38], possibly because of the existing relationship between large HDL and more efficient reverse cholesterol transport. Increases in large HDL as measured by nuclear magnetic resonance spectroscopy have been reported in adults consuming 3 eggs per day for 4 weeks [34] and in individuals following a weight loss intervention and consuming 3 eggs per day for 12 weeks [42••].

Other Beneficial Effects of Eggs

The current recommendations for dietary cholesterol pose a challenge to those individuals who might benefit from including eggs in their regular diets. Eggs have numerous nutritional benefits that are often overlooked when eggs are viewed as nothing more than a cholesterol-containing food. Eggs contain lutein and zexanthin, two major carotenoids that are known to protect against macular degeneration [44] and the development of cataracts [45••]. These carotenoids are highly bioavailable in eggs compared with other dietary sources [46], and egg consumption has been associated with increases in macular pigment density [34, 41], which protects against increasing visual range by absorbing blue light and decreasing oxidative stress [47]. Because egg intake results in formation of larger HDL particles [48], the transport of these carotenoids in a larger particle becomes more efficient. Lutein may also protect against inflammation by decreasing C-reactive protein and other inflammatory markers [49]. Eggs are also very good sources of highly bioavailable and affordable protein [50]. Eggs in combination with a low-carbohydrate diet have also been shown to decrease insulin resistance and leptin in overweight individuals [51]. Finally, a recent study that compared two types of breakfasts (bagel based vs egg based) reported consumption of 400 less kcal in the same day after the egg-based compared with the bagel-based breakfast [52•]. In addition, the egg-based breakfast was associated with decreases in ghrelin, the hormone associated with increased appetite, indicating a potential role of eggs in weight loss interventions. In agreement with these observations, more efficient weight loss was seen when egg-based breakfasts were consumed as part of an energy-deficient diet as compared with bagel-based breakfasts [53]. The only cautionary note regarding egg intake is that, as mentioned earlier, diabetic individuals may benefit from limiting egg intake [22]. However, for healthy populations across all ages, eggs can be part of an overall heart-healthy diet, as stated by Eckel [54•].

Conclusions

The epidemiologic studies and clinical trial results reviewed here suggest that compelling evidence is lacking for limiting cholesterol intake to 300 mg/d. Accordingly, the current US dietary guidelines should be re-evaluated. Based on recent evidence, the current restrictions on cholesterol have largely and inappropriately been translated into a reduced consumption of eggs, a highly nutritious food. The fact that most other countries have chosen to not only not limit eggs, but dietary cholesterol itself, indicates that the overall evidence cannot sustain such limitations. Why not follow their example and accept the challenge of modifying these guidelines?

Disclosure

Dr. Fernandez and her institution have received a grant from the American Egg Board. No other potential conflicts of interest relevant to this article were reported.

Copyright information

© Springer Science+Business Media, LLC 2010