For over 50 years, restriction of dietary cholesterol has been part of dietary recommendations for heart health. Now the focus of cardiovascular nutrition research is shifting. In considering whether specific limits on cholesterol consumption make sense as part of dietary assessment and education, two questions are relevant: 1) does evidence support dietary cholesterol as harmful to cardiovascular risk as assessed by today's standards; 2) how does setting limits on cholesterol intake fit with today's efforts to express dietary recommendations within the context of dietary patterns?

Background

The complexity of the relationship between dietary cholesterol and cardiovascular disease (CVD) has become more apparent because of advances in identifying biomarkers of cardiovascular risk and in understanding that a wide range of dietary factors may influence atherosclerotic disease. Several panels creating dietary recommendations in recent years have concluded that evidence is insufficient to support a recommendation to limit dietary cholesterol.^1-3 These panels concluded that limiting saturated fat within the context of a healthful dietary pattern is a more effective approach to reduce atherogenic lipids. Some cardiovascular nutrition guidelines, however, do include a recommendation to limit dietary cholesterol to less than 200 mg per day.^4,5

Since cholesterol is vital as a component of cell membranes and for production of vitamin D, steroid hormones, and bile acids, body regulatory systems ensure that a pool remains available. Changes in endogenous cholesterol synthesis and intestinal absorption can offset increased or decreased dietary cholesterol. Total cholesterol reaching the intestinal lumen and available for absorption has been estimated at 1,000 to 2,000 mg per day,⁶ including 800 to 1,400 mg of endogenous cholesterol found within bile acids plus dietary cholesterol, which currently averages 282 mg per day in U.S. adults.⁷ About 50-60% of cholesterol within the intestinal lumen is absorbed, although this can vary from 20-80%.^6,8

Research Gaps and Emerging Perspectives

The rationale for restricting dietary cholesterol originated when research focused on total circulating cholesterol as a biomarker of risk. When dietary cholesterol increases, despite a reduced percentage of intestinal cholesterol absorbed, absolute amount of cholesterol absorbed does increase. A recent meta-analysis of intervention trials shows dietary cholesterol challenges that ranged from approximately 500 to 1,400 mg per day increased total blood cholesterol, though with significant heterogeneity.⁹

Looking at average response can mask individual variation. In several clinical trials, the majority of subjects given a cholesterol challenge exhibited little or no increase in total circulating cholesterol, apparently due to the additional influence of decreased endogenous cholesterol synthesis.^8,10 Plasma cholesterol did increase in approximately 25-30% of subjects, dubbed hyper-responders or noncompensators. Individual variation in plasma or serum cholesterol responsiveness to dietary cholesterol appears independent of, and thus can't be predicted based on, baseline circulating cholesterol level.^8,10

It is also important to consider how dietary cholesterol affects different classes of circulating cholesterol and the fractionated subclasses considered as emerging biomarkers of risk. Clinical trials involving 600 to 900 mg dietary cholesterol increased low-density lipoprotein cholesterol (LDL-C). However, high-density lipoprotein cholesterol (HDL-C) generally also increased, and total:HDL-C or LDL-C:HDL-C ratio showed little, if any, change.^8-11 Moreover, dietary cholesterol may influence lipoprotein subclasses. Cardiovascular risk related to elevated LDL-C may stem primarily from small dense LDL particles that easily penetrate into artery walls.^12,13 Likewise, some research suggests that it is not HDL number but HDL size and function (such as efflux capacity) that is most associated with reduced CVD risk.^11,14 Limited evidence suggests that when increased dietary cholesterol raises circulating cholesterol, it may be in the form of increased particle size of LDL and HDL. If this is substantiated, then it could be as part of a less atherogenic pattern (pattern A) even if dietary cholesterol intake raises total blood cholesterol.^10,11

Data is lacking to answer the more practical question of the effects of dietary cholesterol corresponding to the upper levels of U.S. adult intake (300 to 500 mg per day), especially since short-term trials don't reflect effects of longer-term adaptations. Overall, observational prospective cohort studies are not sufficient to support a link between dietary cholesterol and cardiovascular risk or mortality.^15,16 Most do not show an association. Regardless of whether an association is shown, most of these studies have not controlled for potential diet-related confounders. In considering implications of observational studies, it's important to consider food choices typically made in conjunction with high-cholesterol foods. For example, in the U.S., eggs are often accompanied by foods high in saturated fat, such as bacon or sausage. Similarly, dietary choices that characterize lower-cholesterol comparison diets may include higher intake of vegetables and high-fiber foods that likely offer cardioprotective benefits. This makes it hard to distinguish how much high or low intake of dietary cholesterol is associated with CVD or its biomarkers, and how much it relates to other dietary factors.

Practically Speaking

The question of whether to recommend specific limits on dietary cholesterol may be considered by looking at more than its physiological effects. There are also practical implications for creating and communicating strategies for heart-healthy eating.

Given the sources of cholesterol in the diet, limiting consumption of saturated fat automatically tends to limit dietary cholesterol. Even if aiming to keep cholesterol consumption within the maximum limits of 200 or 300 mg per day included in some guidelines, the only foods that most people need to focus on restricting beyond what is necessary to meet recommended saturated fat limits are eggs (and for some people, shrimp).

Table: Cholesterol, Saturated Fat, and Calorie Content of Food Choice Comparisons

Food	Cholesterol (mg)	Saturated Fat (g)	Calories (kcals)
Egg (1 whole large)	186	1.6	72
Bacon (3 slices panfried, approx. 1 oz)	33	4.1	162
Shrimp (3 oz cooked without added fat)	179	0.4	101
Salmon (3 oz canned pink, no skin or bones)	71	0.6	116
Cheese (1 oz regular Cheddar)	29	5.5	115
Ground Beef (3 oz, 80% lean, pan-broiled)	71	5.1	209
Beef, Top Round (3 oz, exterior fat removed, roasted)	65	1.2	138
Chicken Breast (3 oz, skin removed, roasted)	72	0.85	140

Shrimp is the most consumed form of seafood in the U.S.,¹⁷ so if Americans follow recommendations to increase seafood consumption, cholesterol intake could modestly increase for some. Although this choice of seafood does not provide as high a level of omega-3 fatty acids as several other options, it can reduce saturated fat intake by replacing high-fat meats if prepared in a healthful manner. Thus, its cholesterol content should not lead to discouragement of its use. For practical reasons, however, the food choice most affected by limiting both dietary cholesterol and saturated fat is eggs.

Each large egg contains about 186 mg of cholesterol. Therefore, someone who averages one egg daily and consumes additional meat, fish, poultry, or dairy products cannot meet the 200 mg per day cap recommended in those guidelines that currently include cholesterol limits. Since cholesterol content does not decrease proportionately with fat content, this is true even if additional animal-based foods are lean. Overall, prospective cohort studies do not support a link between egg consumption and risk of cardiovascular events or mortality.^18,19 Moreover, a controlled interventional trial showed no effect of daily egg consumption on endothelial function in adults with coronary artery disease.²⁰ Thus, although setting a limit on dietary cholesterol requires a limit on egg consumption, evidence showing benefit of reduced consumption of eggs appears lacking.

People with diabetes may represent a special population for whom attention to dietary cholesterol intake and egg consumption does make sense, at least until further research provides more clarity. Meta-analyses of prospective cohort studies show that among subjects with diabetes, daily consumption of one or more eggs is linked with about 50-70% increased risk of cardiovascular events compared to risk in those who seldom eat eggs.^18,19,21 As with observational studies noted above, lack of adjustment for dietary confounders was a common study limitation. Hypothesized changes in cholesterol metabolism in people with diabetes could lead to greater CVD risk related to dietary cholesterol. However, greater egg consumption by people with diabetes is not consistently associated with changes in biomarkers of CHD risk.^21,22 Although greatest consumption of eggs resulted in only moderately increased dietary cholesterol (344.5 mg/day) in the NHLBI Family Heart Study, it was significantly higher than in those who rarely ate eggs, and there was no association with prevalence of coronary-artery calcium (CAC), even in patients with diabetes.²³

Focus on the Big Message

A variety of healthful eating patterns provide dietary fiber and a wide range of nutrients and phytochemicals that may promote cardiovascular health, potentially acting through effects on circulating lipids, endothelial function, inflammation, insulin resistance, and even intestinal microbiota.^1,2,24 It seems likely that greater overall benefit comes from moving beyond a narrow focus on food's cholesterol content to helping people see their eating choices within a larger vision of cardioprotective eating habits.

People who enjoy foods like shrimp and eggs that are somewhat high in cholesterol but not excessive in saturated fat can include them within overall healthful eating habits by making smart choices regarding their preparation (e.g., eggs poached, hardboiled or in a vegetable omelet vs. eggs fried with bacon or in a rich quiche) and the foods that accompany them. By emphasizing healthful preparation and appropriate portion sizes, recommendations can remain consistent that those who consume meat, fish, and poultry make them a small side element of meals, with focus shifted to a variety and abundance of vegetables, whole grains, legumes, fruits, nuts, and seeds as meals' mainstays, which is consistent with the focus on such a dietary pattern in the recent American College of Cardiology/American Heart Association guideline on lifestyle management.¹

Additional research is needed to determine whether certain people may benefit from including specific restrictions of dietary cholesterol. Until then, it seems that research using today's enhanced range of cardiovascular health biomarkers is not sufficient to support cholesterol restriction in of itself as a priority message. This allows focus on efforts to replace foods high in saturated fat, trans fat, or refined carbohydrates with alternatives that offer much more to support cardiovascular health.

References

1. Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2960-84.
2. U.S. Department of Health and Human Services, Office of Disease Prevention and Health Promotion. Scientific Report of the 2015 Dietary Guidelines Advisory Committee (health.gov website). 2015. Available at: http://health.gov/dietaryguidelines/2015-scientific-report/. Accessed on 7/10/15.
3. Agostoni C, Bresson J-L, Fairweather-Tait S, et al., on behalf of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on Dietary Reference Values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol. EFSA J 2010;8:1461
4. Expert Dyslipidemia Panel, Grundy SM. An International Atherosclerosis Society Position Paper: global recommendations for the management of dyslipidemia. J Clin Lipidol 2014;8:29-60.
5. Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1--full report. J Clin Lipidol 2015;9:129-69.
6. Lecerf JM, de Lorgeril M. Dietary cholesterol: from physiology to cardiovascular risk. Br J Nutr 2011;106:6-14.
7. What We Eat in America, NHANES 2011-2012, individuals 2 years and over (excluding breast-fed children), day 1 (USDA website). 2011-2012. Available at: http://www.ars.usda.gov/SP2UserFiles/Place/80400530/pdf/1112/Table_13_BRK_GEN_11.pdf. Accessed 7/10/15.
8. McNamara DJ, Kolb R, Parker TS, et al. Heterogeneity of cholesterol homeostasis in man. Response to changes in dietary fat quality and cholesterol quantity. J Clin Invest 1987;79:1729-39.
9. Berger S, Raman G, Vishwanathan R, Jacques PF, Johnson EJ. Dietary cholesterol and cardiovascular disease: a systematic review and meta-analysis. Am J Clin Nutr 2015;102:276-94.
10. Greene CM, Waters D, Clark RM, Contois JH, Fernandez ML. Plasma LDL and HDL characteristics and carotenoid content are positively influenced by egg consumption in an elderly population. Nutr Metab (Lond) 2006;3:6.
11. Barona J, Fernandez ML. Dietary cholesterol affects plasma lipid levels, the intravascular processing of lipoproteins and reverse cholesterol transport without increasing the risk for heart disease. Nutrients 2012;4:1015-25.
12. Williams PT, Zhao XQ, Marcovina SM, Brown BG, Krauss RM. Levels of cholesterol in small LDL particles predict atherosclerosis progression and incident CHD in the HDL-Atherosclerosis Treatment Study (HATS). PLoS One 2013;8:e56782.
13. St-Pierre AC, Cantin B, Dagenais GR, et al. Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Quebec Cardiovascular Study. Arterioscler Thromb Vasc Biol 2005;25:553-9.
14. Fisher EA, Feig JE, Hewing B, Hazen SL, Smith JD. High-density lipoprotein function, dysfunction, and reverse cholesterol transport. Arterioscler Thromb Vasc Biol 2012;32:2813-2820.
15. Houston DK, Ding J, Lee JS, et al. Dietary fat and cholesterol and risk of cardiovascular disease in older adults: the Health ABC Study. Nutr Metab Cardiovasc Dis 2011;21:430-7.
16. Fernandez ML, Calle M. Revisiting dietary cholesterol recommendations: does the evidence support a limit of 300 mg/d? Curr Atheroscler Rep 2010;12:377-83.
17. National Fisheries Institute. Top 10 Consumed Seafoods. 2015; Available at: https://www.aboutseafood.com/about/about-seafood/top-10-consumed-seafoods. Accessed on 7/10/2015.
18. Shin JY, Xun P, Nakamura Y, He K. Egg consumption in relation to risk of cardiovascular disease and diabetes: a systematic review and meta-analysis. Am J Clin Nutr 2013;98:146-59.
19. Rong Y, Chen L, Zhu T, et al. Egg consumption and risk of coronary heart disease and stroke: dose-response meta-analysis of prospective cohort studies. BMJ 2013;346:e8539.
20. Katz DL, Gnanaraj J, Treu JA, Ma Y, Kavak Y, Njike VY. Effects of egg ingestion on endothelial function in adults with coronary artery disease: a randomized, controlled, crossover trial. Am Heart J 2015;169:162-9.
21. Tran NL, Barraj LM, Heilman JM, Scrafford CG. Egg consumption and cardiovascular disease among diabetic individuals: a systematic review of the literature. Diabetes Metab Syndr Obes 2014;7:121-37.
22. Fuller NR, Caterson ID, Sainsbury A, et al. The effect of a high-egg diet on cardiovascular risk factors in people with type 2 diabetes: the Diabetes and Egg (DIABEGG) study-a 3-mo randomized controlled trial. Am J Clin Nutr 2015;101:705-13.
23. Robbins JM, Petrone AB, Ellison RC, et al. Association of egg consumption and calcified atherosclerotic plaque in the coronary arteries: the NHLBI Family Heart Study. Espen J 2014;9:e131-5.
24. Mozaffarian D, Appel LJ, Van Horn L. Components of a cardioprotective diet: new insights. Circulation 2011;123:2870-91.

Keywords: Adult, American Heart Association, Antineoplastic Combined Chemotherapy Protocols, Arteries, Bile Acids and Salts, Biomarkers, Bleomycin, Calcium, Cardiovascular Diseases, Cell Membrane, Cholesterol, Cholesterol, Dietary, Cholesterol, LDL, Cholesterol, HDL, Coronary Artery Disease, Cyclophosphamide, Cytarabine, Diabetes Mellitus, Doxorubicin, Fatty Acids, Omega-3, Inflammation, Insulin Resistance, Intestinal Absorption, Life Style, Lipids, Lipoproteins, HDL, Lipoproteins, LDL, Lomustine, Mechlorethamine, Microbiota, Phytochemicals, Prednisone, Prevalence, Risk Factors, Vincristine, Vitamin D

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