Egg and cholesterol consumption and mortality from cardiovascular and different causes in the United States: A population-based cohort study

Pan Zhuang, Fei Wu, Lei Mao, Fanghuan Zhu, Yiju Zhang, Xiaoqian Chen, Jingjing Jiao, Yu Zhang, Pan Zhuang, Fei Wu, Lei Mao, Fanghuan Zhu, Yiju Zhang, Xiaoqian Chen, Jingjing Jiao, Yu Zhang

Abstract

Background: Whether consumption of egg and cholesterol is detrimental to cardiovascular health and longevity is highly debated. Data from large-scale cohort studies are scarce. This study aimed to examine the associations of egg and cholesterol intakes with mortality from all causes, cardiovascular disease (CVD), and other causes in a US population.

Methods and findings: Overall, 521,120 participants (aged 50-71 years, mean age = 62.2 years, 41.2% women, and 91.8% non-Hispanic white) were recruited from 6 states and 2 additional cities in the US between 1995 and 1996 and prospectively followed up until the end of 2011. Intakes of whole eggs, egg whites/substitutes, and cholesterol were assessed by a validated food frequency questionnaire. Cause-specific hazard models considering competing risks were used, with the lowest quintile of energy-adjusted intake (per 2,000 kcal per day) as the reference. There were 129,328 deaths including 38,747 deaths from CVD during a median follow-up of 16 years. Whole egg and cholesterol intakes were both positively associated with all-cause, CVD, and cancer mortality. In multivariable-adjusted models, the hazard ratios (95% confidence intervals) associated with each intake of an additional half of a whole egg per day were 1.07 (1.06-1.08) for all-cause mortality, 1.07 (1.06-1.09) for CVD mortality, and 1.07 (1.06-1.09) for cancer mortality. Each intake of an additional 300 mg of dietary cholesterol per day was associated with 19%, 16%, and 24% higher all-cause, CVD, and cancer mortality, respectively. Mediation models estimated that cholesterol intake contributed to 63.2% (95% CI 49.6%-75.0%), 62.3% (95% CI 39.5%-80.7%), and 49.6% (95% CI 31.9%-67.4%) of all-cause, CVD, and cancer mortality associated with whole egg consumption, respectively. Egg white/substitute consumers had lower all-cause mortality and mortality from stroke, cancer, respiratory disease, and Alzheimer disease compared with non-consumers. Hypothetically, replacing half a whole egg with equivalent amounts of egg whites/substitutes, poultry, fish, dairy products, or nuts/legumes was related to lower all-cause, CVD, cancer, and respiratory disease mortality. Study limitations include its observational nature, reliance on participant self-report, and residual confounding despite extensive adjustment for acknowledged dietary and lifestyle risk factors.

Conclusions: In this study, intakes of eggs and cholesterol were associated with higher all-cause, CVD, and cancer mortality. The increased mortality associated with egg consumption was largely influenced by cholesterol intake. Our findings suggest limiting cholesterol intake and replacing whole eggs with egg whites/substitutes or other alternative protein sources for facilitating cardiovascular health and long-term survival.

Trial registration: ClinicalTrials.gov NCT00340015.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Multivariable-adjusted HRs of all-cause and…
Fig 1. Multivariable-adjusted HRs of all-cause and cause-specific mortality for whole egg, egg white/substitute, and cholesterol consumption.
Forest plots show the multivariable HRs of total and cause-specific mortality associated with each additional half a whole egg/day, egg white/substitute consumption (consumers versus non-consumers), or each additional 300 mg of cholesterol/day. HRs were adjusted for model 6 covariates for whole eggs, egg whites/substitutes, and cholesterol. Horizontal lines represent 95% CIs. CI, confidence interval; HR, hazard ratio.
Fig 2. Multivariable-adjusted hazard ratios of all-cause…
Fig 2. Multivariable-adjusted hazard ratios of all-cause and cause-specific mortality by replacing 1 whole egg with equivalent amounts of other protein sources.
Forest plots show the multivariable HRs of (A) total, (B) CVD, (C) cancer, (D) respiratory disease, (E) Alzheimer disease, and (F) diabetes mortality associated with replacing half a whole egg/day with an equivalent amount of egg whites/substitutes, poultry, fish, dairy products, nuts, or legumes. HRs were adjusted for age; sex; BMI; race; education; marital status; household income; smoking; alcohol; vigorous physical activity; usual activity at work; history of hypertension, hypercholesteremia, heart disease, stroke, diabetes, and cancer at baseline; total energy intake; and intakes of fruit, vegetables, potatoes, whole grains, refined grains, coffee, and sugar-sweetened beverages. Horizontal lines represent 95% CIs. CI, confidence interval; CVD, cardiovascular disease; HR, hazard ratio.

References

    1. Andersen CJ. Bioactive egg components and inflammation. Nutrients. 2015;7(9):7889–913. 10.3390/nu7095372
    1. US Department of Health and Human Services. 2015–2020 dietary guidelines for Americans. 8th edition Washington (DC): US Department of Health and Human Services; 2015. [cited 2021 Jan 8]. Available from: .
    1. Shekelle RB, Stamler J. Dietary cholesterol and ischaemic heart disease. Lancet. 1989;1(8648):1177–9. 10.1016/s0140-6736(89)92759-1
    1. Zhong VW, Van Horn L, Cornelis MC, Wilkins JT, Ning H, Carnethon MR, et al. Associations of dietary cholesterol or egg consumption with incident cardiovascular disease and mortality. JAMA. 2019;321(11):1081–95. 10.1001/jama.2019.1572
    1. Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, et al. AHA Dietary Guidelines: Revision 2000: a statement for healthcare professionals from the nutrition committee of the American Heart Association. Circulation. 2000;102(18):2284–99. 10.1161/01.cir.102.18.2284
    1. 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(2):276–94. 10.3945/ajcn.114.100305
    1. Eckel RH, Jakicic JM, Ard JD, de Jesus JM, Miller NH, Hubbard VS, 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. Circulation. 2014;129(25 Suppl 2):S76–99. 10.1161/01.cir.0000437740.48606.d1
    1. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1046–81. 10.1161/CIR.0000000000000624
    1. Millen BE, Abrams S, Adams-Campbell L, Anderson CA, Brenna JT, Campbell WW, et al. The 2015 Dietary Guidelines Advisory Committee Scientific Report: development and major conclusions. Adv Nutr. 2016;7(3):438–44. 10.3945/an.116.012120
    1. Li Y, Zhou C, Zhou X, Li L. Egg consumption and risk of cardiovascular diseases and diabetes: a meta-analysis. Atherosclerosis. 2013;229(2):524–30. 10.1016/j.atherosclerosis.2013.04.003
    1. Rong Y, Chen L, Zhu T, Song Y, Yu M, Shan Z, et al. Egg consumption and risk of coronary heart disease and stroke: dose-response meta-analysis of prospective cohort studies. BMJ. 2013;346:e8539 10.1136/bmj.e8539
    1. 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(1):146–59. 10.3945/ajcn.112.051318
    1. Mazidi M, Katsiki N, Mikhailidis DP, Pencina MJ, Banach M. Egg consumption and risk of total and cause-specific mortality: an individual-based cohort study and pooling prospective studies on Behalf of the Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group. J Am Coll Nutr. 2019;38(6):552–63. 10.1080/07315724.2018.1534620
    1. Xu L, Lam TH, Jiang CQ, Zhang WS, Zhu F, Jin YL, et al. Egg consumption and the risk of cardiovascular disease and all-cause mortality: Guangzhou Biobank Cohort Study and meta-analyses. Eur J Nutr. 2019;58(2):785–96. 10.1007/s00394-018-1692-3
    1. Schatzkin A, Subar AF, Thompson FE, Harlan LC, Tangrea J, Hollenbeck AR, et al. Design and serendipity in establishing a large cohort with wide dietary intake distributions: the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Am J Epidemiol. 2001;154(12):1119–25. 10.1093/aje/154.12.1119
    1. Midthune D, Schatzkin A, Subar AF, Thompson FE, Freedman LS, Carroll RJ, et al. Validating an FFQ for intake of episodically consumed foods: application to the National Institutes of Health-AARP Diet and Health Study. Public Health Nutr. 2011;14(7):1212–21. 10.1017/S1368980011000632
    1. Subar AF, Midthune D, Kulldorff M, Brown CC, Thompson FE, Kipnis V, et al. Evaluation of alternative approaches to assign nutrient values to food groups in food frequency questionnaires. Am J Epidemiol. 2000;152(3):279–86. 10.1093/aje/152.3.279
    1. Thompson FE, Kipnis V, Midthune D, Freedman LS, Carroll RJ, Subar AF, et al. Performance of a food-frequency questionnaire in the US NIH-AARP (National Institutes of Health-American Association of Retired Persons) Diet and Health Study. Public Health Nutr. 2008;11(2):183–95. 10.1017/S1368980007000419
    1. Panizza CE, Shvetsov YB, Harmon BE, Wilkens LR, Le Marchand L, Haiman C, et al. Testing the predictive validity of the Healthy Eating Index-2015 in the multiethnic cohort: is the score associated with a reduced risk of all-cause and cause-specific mortality? Nutrients. 2018;10(4):452 10.3390/nu10040452
    1. Willett WC. Nutritional epidemiology. 3rd edition Oxford: Oxford University Press; 2012. 10.1097/EDE.0b013e31825afb0b
    1. Lau B, Cole SR, Gange SJ. Competing risk regression models for epidemiologic data. Am J Epidemiol. 2009;170(2):244–56. 10.1093/aje/kwp107
    1. Austin PC, Lee DS, Fine JP. Introduction to the analysis of survival data in the presence of competing risks. Circulation. 2016;133(6):601–9. 10.1161/CIRCULATIONAHA.115.017719
    1. Etemadi A, Sinha R, Ward MH, Graubard BI, Inoue-Choi M, Dawsey SM, et al. Mortality from different causes associated with meat, heme iron, nitrates, and nitrites in the NIH-AARP Diet and Health Study: population based cohort study. BMJ. 2017;357:j1957 10.1136/bmj.j1957
    1. Zhuang P, Zhang Y, He W, Chen X, Chen J, He L, et al. Dietary fats in relation to total and cause-specific mortality in a prospective cohort of 521 120 Individuals with 16 years of follow-up. Circ Res. 2019;124(5):757–68. 10.1161/CIRCRESAHA.118.314038
    1. Xu Z, McClure ST, Appel LJ. Dietary cholesterol intake and sources among U.S adults: results from National Health and Nutrition Examination Surveys (NHANES), 2001–2014. Nutrients. 2018;10(6):771 10.3390/nu10060771
    1. Lin DY, Fleming TR, De Gruttola V. Estimating the proportion of treatment effect explained by a surrogate marker. Stat Med. 1997;16(13):1515–27. 10.1002/(sici)1097-0258(19970715)16:13<1515::aid-sim572>;2-1
    1. Guasch-Ferre M, Hruby A, Salas-Salvado J, Martinez-Gonzalez MA, Sun Q, Willett WC, et al. Olive oil consumption and risk of type 2 diabetes in US women. Am J Clin Nutr. 2015;102(2):479–86. 10.3945/ajcn.115.112029
    1. D’Agostino RB Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17(19):2265–81. 10.1002/(sici)1097-0258(19981015)17:19<2265::aid-sim918>;2-b
    1. Alexander DD, Miller PE, Vargas AJ, Weed DL, Cohen SS. Meta-analysis of egg consumption and risk of coronary heart disease and stroke. J Am Coll Nutr. 2016;35(8):704–16. 10.1080/07315724.2016.1152928
    1. Khawaja O, Singh H, Luni F, Kabour A, Ali SS, Taleb M, et al. Egg consumption and incidence of heart failure: a meta-analysis of prospective cohort studies. Front Nutr. 2017;4:10 10.3389/fnut.2017.00010
    1. Hu FB, Stampfer MJ, Rimm EB, Manson JE, Ascherio A, Colditz GA, et al. A prospective study of egg consumption and risk of cardiovascular disease in men and women. JAMA. 1999;281(15):1387–94. 10.1001/jama.281.15.1387
    1. Clarke R, Frost C, Collins R, Appleby P, Peto R. Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies. BMJ. 1997;314(7074):112–7. 10.1136/bmj.314.7074.112
    1. Li MY, Chen JH, Chen C, Kang YN. Association between egg consumption and cholesterol concentration: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2020;12(7):1995 10.3390/nu12071995
    1. Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459–72. 10.1093/eurheartj/ehx144
    1. Carson JAS, Lichtenstein AH, Anderson CAM, Appel LJ, Kris-Etherton PM, Meyer KA, et al. Dietary cholesterol and cardiovascular risk: a science advisory from the American Heart Association. Circulation. 2020;141(3):e39–53. 10.1161/CIR.0000000000000743
    1. Rouhani MH, Rashidi-Pourfard N, Salehi-Abargouei A, Karimi M, Haghighatdoost F. Effects of egg consumption on blood lipids: a systematic review and meta-analysis of randomized cinical trials. J Am Coll Nutr. 2018;37(2):99–110. 10.1080/07315724.2017.1366878
    1. Li C, Yang L, Zhang D, Jiang W. Systematic review and meta-analysis suggest that dietary cholesterol intake increases risk of breast cancer. Nutr Res. 2016;36(7):627–35. 10.1016/j.nutres.2016.04.009
    1. Wang J, Wang WJ, Zhai L, Zhang DF. Association of cholesterol with risk of pancreatic cancer: a meta-analysis. World J Gastroenterol. 2015;21(12):3711–9. 10.3748/wjg.v21.i12.3711
    1. Zeng ST, Guo L, Liu SK, Wang DH, Xi J, Huang P, et al. Egg consumption is associated with increased risk of ovarian cancer: Evidence from a meta-analysis of observational studies. Clin Nutr. 2015;34(4):635–41. 10.1016/j.clnu.2014.07.009
    1. Haddy N. IL-6, TNF-α and atherosclerosis risk indicators in a healthy family population: the STANISLAS cohort. Atherosclerosis. 2003;170(2):277–83. 10.1016/s0021-9150(03)00287-9
    1. Kimura Y, Sumiyoshi M. High-fat, high-sucrose, and high-cholesterol diets accelerate tumor growth and metastasis in tumor-bearing mice. Nutr Cancer. 2007;59(2):207–16. 10.1080/01635580701499537
    1. Sakaguchi M, Minoura T, Hiramatsu Y, Takada H, Yamamura M, Hioki K, et al. Effects of dietary saturated and unsaturated fatty acids on fecal bile acids and colon carcinogenesis induced by azoxymethane in rats. Cancer Res. 1986;46(1):61–5.
    1. Djousse L, Khawaja OA, Gaziano JM. Egg consumption and risk of type 2 diabetes: a meta-analysis of prospective studies. Am J Clin Nutr. 2016;103(2):474–80. 10.3945/ajcn.115.119933
    1. Rafie S, Moitra S, Brashier BB. Association between the serum metabolic profile and lung function in chronic obstructive pulmonary disease. Turk Thorac J. 2018;19(1):13–18. 10.5152/TurkThoracJ.2017.17043
    1. Yeh YF, Huang SL. Dietary cholesterol enhances pulmonary eosinophilic inflammation in a murine model of asthma. Int Arch Allergy Immunol. 2001;125(4):329–34. 10.1159/000053834
    1. Zamora-Ros R, Cayssials V, Cleries R, Redondo ML, Sanchez MJ, Rodriguez-Barranco M, et al. Moderate egg consumption and all-cause and specific-cause mortality in the Spanish European Prospective into Cancer and Nutrition (EPIC-Spain) study. Eur J Nutr. 2019;58(5):2003–10. 10.1007/s00394-018-1754-6
    1. Ylilauri MP, Voutilainen S, Lonnroos E, Mursu J, Virtanen HE, Koskinen TT, et al. Association of dietary cholesterol and egg intakes with the risk of incident dementia or Alzheimer disease: the Kuopio Ischaemic Heart Disease Risk Factor Study. Am J Clin Nutr. 2017;105(2):476–84. 10.3945/ajcn.116.146753
    1. Zeisel SH, Mar MH, Howe JC, Holden JM. Concentrations of choline-containing compounds and betaine in common foods. J Nutr. 2003;133(5):1302–7. 10.1093/jn/133.5.1302
    1. Goodrow EF, Wilson TA, Houde SC, Vishwanathan R, Scollin PA, Handelman G, et al. Consumption of one egg per day increases serum lutein and zeaxanthin concentrations in older adults without altering serum lipid and lipoprotein cholesterol concentrations. J Nutr. 2006;136(10):2519–24. 10.1093/jn/136.10.2519
    1. Wallace TC. A comprehensive review of eggs, choline, and lutein on cognition across the life-span. J Am Coll Nutr. 2018;37(4):269–85. 10.1080/07315724.2017.1423248
    1. Enjoji M, Nakamuta M. Is the control of dietary cholesterol intake sufficiently effective to ameliorate nonalcoholic fatty liver disease? World J Gastroenterol. 2010;16(7):800–3. 10.3748/wjg.v16.i7.800
    1. Abeyrathne E, Huang X, Ahn DU. Antioxidant, angiotensin-converting enzyme inhibitory activity and other functional properties of egg white proteins and their derived peptides—a review. Poult Sci. 2018;97(4):1462–68. 10.3382/ps/pex399
    1. Phelps T, Snyder E, Rodriguez E, Child H, Harvey P. The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis. Biol Sex Differ. 2019;10(1):52 10.1186/s13293-019-0265-3
    1. Wakabayashi I. Difference in sensitivities of blood HDL cholesterol and LDL cholesterol levels to alcohol in middle-aged Japanese men. Alcohol. 2018;67:45–50. 10.1016/j.alcohol.2017.08.011
    1. Nakamura K, Barzi F, Huxley R, Lam TH, Suh I, Woo J, et al. Does cigarette smoking exacerbate the effect of total cholesterol and high-density lipoprotein cholesterol on the risk of cardiovascular diseases? Heart. 2009;95(11):909–16. 10.1136/hrt.2008.147066
    1. Wu F, Mao L, Zhuang P, Chen X, Jiao J, Zhang Y. Plant-sourced cooking oil consumption is associated with lower total mortality in a longitudinal nationwide cohort study. Clin Nutr. 2020. 10.1016/j.clnu.2020.03.031

Source: PubMed

3
購読する