Specialty Corner: Dietary Cholesterol: Does it Still Matter for Managing Dyslipidemia?

Introduction

Recent conflicting messages have left some practitioners wondering whether patients with dyslipidemia should limit dietary cholesterol. In 2015, the National Lipid Association (NLA) Recommendations for Patient-Centered Management of Dyslipidemia-Part 2 recommended <200 mg/day of dietary cholesterol for patients managing elevated levels of blood cholesterol.1 The 2015-2020 Dietary Guidelines for Americans (DGA) did not limit dietary cholesterol to 300 mg per day for healthy adults as they had in the 2010 DGA. However, the 2015-2020 DGA did state that “this change does not suggest that dietary cholesterol is no longer important to consider when building healthy eating patterns” and “individuals should eat as little dietary cholesterol as possible while consuming a healthy eating pattern.”2 Unfortunately, some journalists misinterpreted the DGA message and suggested that restricting dietary cholesterol is not necessary,3,4 although others interpreted the message correctly and encouraged restriction of dietary cholesterol.5

Table 1 shows the most recent NLA evidence-based nutrition recommendations regarding intake of dietary cholesterol for the management of dyslipidemia, along with the quality and grade of evidence. These include consuming <200 mg/day in all patients with dyslipidemia, and for known or suspected hyper-responders, consuming as little dietary cholesterol as possible.

Review of Evidence to Support Dietary Cholesterol Restriction

Clinical Studies

Griffin and Lichtenstein conducted a systematic review of 12 randomized controlled trials (RCT) published between 2003 and 2013 that examined the effect of increased dietary cholesterol on blood cholesterol level. Results suggested that a dietary cholesterol challenge of at least 200 mg per day and up to 640 mg per day from three whole eggs or 794 mg per day from cold water prawns did not increase lowdensity lipoprotein cholesterol (LDL-C) in participants with or without dyslipidemia, except in those who were insulin-sensitive, had the ABCG5 C/C allele, or were hyperresponders to dietary cholesterol.6

 Furthermore, six meta-analyses based on 438 studies7–12 examined the effects of dietary cholesterol on serum total cholesterol (total-C) and LDL-C; four of the meta-analyses included studies on participants with dyslipidemia.7,8,10,11 Five of the six meta-analyses7–11 predicted that an increased cholesterol intake can modestly increase total-C and LDLC. Using multiple-regression analysis, prediction equations were developed with dietary cholesterol and fatty acid intakes. Three of the meta-analyses reported that a 100 mg/day increase in dietary cholesterol increased total-C approximately 2 mg/ dL7,8 to 3 mg/dL.11 Additionally, Hegsted9 concluded that an increase in dietary cholesterol of 100 mg/1000 kilocalories would increase serum total-C by 6.7 mg/ dL. Clarke11 reported that a 100 mg/ day increase in dietary cholesterol would result in a 2.0 mg/dL increase in LDL-C. Three meta-analyses that examined the influence of type and amount of fatty acids in addition to dietary cholesterol on serum total-C and LDL-C found that plasma LDL-C concentrations were more strongly determined by the change in saturated fatty acid intake rather than the change in cholesterol intake.8,9,11

Howell8 suggested that there are dietsensitive and diet-insensitive individuals regarding the response of dietary cholesterol on serum total-C, and concluded that the total-C response to dietary cholesterol would be lower in individuals with hypercholesterolemia (> 6.21 mmol/L or 240 mg/dL). Hopkins10 determined that baseline cholesterol intake was a stronger predictor of change in serum total-C compared to added dietary cholesterol (P <0.0005, r= 0.617) between observed and predicted points. When baseline dietary cholesterol was higher, the effect of adding dietary cholesterol on serum total-C was less pronounced.

The evidence reviewed above6–12 suggests dietary cholesterol modestly increases total-C and LDL-C. There are individuals who do not respond to a dietary cholesterol challenge, even if they have hyperlipidemia;6–8 however, there clearly are individuals who are hyper-responders and experience an elevation in serum total-C and LDL-C with an increase in dietary cholesterol.6 Additionally, an individual’s baseline cholesterol intake may influence the extent of total-C and LDL-C lowering that is achieved with decreasing dietary cholesterol.10

Epidemiological Studies

Berger and colleagues13 recently conducted a systematic review and meta-analysis of 17 cohort studies with 361,923 subjects and reported that dietary cholesterol significantly increased both serum total-C and LDL-C. However, dietary cholesterol was not significantly associated with incidence of coronary artery disease, ischemic stroke, or hemorrhagic stroke. Limitations noted by the authors were that the cohorts were heterogeneous and many of the studies lacked methodological rigor, which limited definitive conclusions about dietary cholesterol and atherosclerotic cardiovascular disease (ASCVD) outcomes.13

A review of eight large prospective cohort studies (17 reports, including nine for coronary heart disease [CHD] and eight for stroke) and a meta-analysis (3,081,269 person years and 5,847 cases of incident CHD) reported an increased risk of CHD in a sub-group analysis of individuals with diabetes when comparing highest with lowest categories of egg consumption of 1.54 (1.14 to 2.09; P= .01).14

Shin15 compared egg consumption by highest category (≥ 1 egg/d) versus lowest (<1 egg/wk or never) in 22 independent cohorts identified from 16 studies that included from 1,600 to 90,735 subjects with a follow-up period from 5.8 to 20 years. The authors noted that egg consumption was not associated with the risk of CVD and cardiac mortality in the general population. However, egg consumption may be associated with an increased incidence of type 2 diabetes among the general population and CVD comorbidity among patients with diabetes.15

The Nurses’ Health Study examined 5,672 women with diabetes and noted that each increase of 200 mg cholesterol/1000 kcal was associated with a 37 percent increased risk of CVD, which was a composite of fatal CHD, nonfatal myocardial infarction, and stroke.16

In a prospective cohort of 37,851 men (Health Professionals Follow-up Study) and 80,842 women (Nurses’ Health Study), a higher egg consumption was associated with increased risk of CHD only among subjects with diabetes.17 Men with diabetes who consumed one egg or more daily doubled their risk of CHD versus those consuming less than one egg per week. Women with diabetes who consumed one egg or more daily had 1.49 times the risk of CHD versus women who consumed less than one egg per week.17 The results of the studies reviewed above13–17 suggest egg consumption was not associated with the risk of CVD and cardiac mortality in the general, healthy population. However, in people with diabetes, egg consumption and dietary cholesterol significantly increased the risk of CVD. Currently, 29.1 million people, or 9.3 percent of the U.S. population, have diabetes.18 Table 2 illustrates that the average dietary cholesterol intake in the U.S. general population between 2013– 2014 was 293 mg/day.19

What Should Clinicians Tell Patients with Dyslipidemia?

Scientific evidence supports the NLA 2015 recommendation for <200 mg/ day of dietary cholesterol for individuals with elevated blood cholesterol while recognizing that other dietary factors (i.e., saturated fatty acids, trans fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids) more reliably and predictably influence levels of atherogenic cholesterol.1 Even a small reduction in LDL-C appears to reduce CVD risk if maintained over an extended period.20

 For most individuals, restricting saturated fat intake to <7 percent of total daily energy while following a cardio-protective dietary pattern will result in lower dietary cholesterol, because saturated fats and cholesterol are present together in many foods (e.g., fatty cuts of meats, processed meats, full-fat dairy foods). The primary sources of dietary cholesterol in the U.S. dietary pattern are shown in Figure 1.21 Dietary cholesterol is found only in animal products, such as egg yolks, red meat, poultry, shellfish, and dairy foods. Egg yolks, shrimp, and other shellfish are examples of foods that are higher in dietary cholesterol, but low in saturated fatty acids. Therefore, patients with dyslipidemia could be counseled to consume eggs, shrimp, or other shellfish in limited amounts as part of an overall cardio-protective dietary pattern.1,2,21–24

A cardio-protective dietary pattern emphasizes a variety of vegetables, fruits and whole grain foods; low-fat (1 percent) or fat-free dairy products; lean protein foods; fatty fish at least twice a week; and non-tropical vegetable oils, nuts, legumes, and seeds. It limits the intake of sweets, sugar-sweetened beverages, and high-fat meat and dairy products.1,2,21–24 For known or suspected hyper-responders, the NLA recommends as little intake of dietary cholesterol as possible.1

 Referral to a registered dietitian nutritionist for nutrition education/ medical nutrition therapy with follow-up and monitoring are recommended to individualize a patient’s cardio-protective dietary pattern and promote successful lifestyle modification.1

Conclusions

Although popular press has contributed to the confusion surrounding dietary cholesterol, the scientific evidence is clear on its impact on atherogenic lipids.

1. Well-controlled RCTs show that dietary cholesterol has modest effects in raising LDL-C. For every 100 mg/day of dietary cholesterol, LDL-C increases ≈2 mg/dL.11

2. The increase in total-C is also related to baseline cholesterol intake. The lower the baseline intake, the greater the effect of dietary cholesterol on raising total-C.10

3. There is marked variability in the response to dietary cholesterol. There are hyper- and hypo-responders to dietary cholesterol.6 For known or suspected hyper-responders, the NLA recommends as little intake of dietary cholesterol as possible.1 Inexpensive methods to identify hyper- or hyporesponders are currently not available.

4. Observational evidence has consistently reported no association between dietary cholesterol or egg consumption and ASCVD risk in the general population, but suggests an increased risk in people with diabetes.15–17

For additional patient counseling tips, please see page 37 for the tear sheet titled “Heart-Healthy Eating — Why Cholesterol in Food Matters” or go to the NLA Clinician’s Lifestyle Modification Toolbox website at lipid.org/CLMT.   

Disclosure statement: Carol Kirkpatrick has no disclosures to report. Geeta Sikand has no disclosures to report.