Abstract
Chocolate is a rich dietary source of various bioactive flavonoid compounds. Despite being one of the most popular foods worldwide, the association between chocolate consumption and long-term mortality remains unclear. The objective of this study is to determine the associations between chocolate consumption and long-term overall and cause-specific mortality, to evaluate dose–response and potential mediators, and to conduct an updated meta-analysis based on prospective cohort studies. We performed a prospective analysis in the Alpha-Tocopherol, Beta-Carotene cancer prevention (ATBC) Study with a total of 27,111 men who were recruited between 1985 and 1988 and followed through 2015. Exposure data of daily chocolate consumption was obtained from validated baseline food frequency questionnaire. Hazard ratios (HRs) and 30-year absolute risk differences (ARDs) including 95% confidence intervals (CI) for overall and cause-specific mortality were estimated using multivariable-adjusted Cox proportional hazards regression models. An updated meta-analysis of cohort studies was also conducted. During 482,807 person-years of follow-up, a total of 22,064 men died. The multivariable analyses showed a statistically significant inverse association between chocolate consumption and risk of overall mortality, with HRs of 0.91, 0.89, 0.89, and 0.88 for the increasing categories 2–5 as compared with those in the lowest category (Ptrend < 0.0001, and P for nonlinearity < 0.0001). We observed significantly lower mortality from cardiovascular disease (CVD), heart disease and cancer, representing 13%, 16% and 12% risk reductions for the highest compared to lowest chocolate category, respectively (all Ptrend ≤ 0.002; all P for nonlinearity < 0.0001). The inverse associations of chocolate consumption with risk of overall, CVD and heart disease mortality were generally consistent across cohort subgroups (e.g., body mass index and serum cholesterol). Mediation analysis showed that 4.3% of the inverse association of chocolate and overall mortality was mediated through reducing blood pressure. Within the updated meta-analysis of cohort studies (21 risk estimates, 908,390 participants and 65,407 events), greater consumption of chocolate (per 5 g/day) was associated with a lower risk of CVD incidence and mortality (pooled relative risk = 0.98, P value < 0.001; P for nonlinearity < 0.001). The predefined subgroup analyses generally revealed consistent inverse chocolate-CVD risk associations. In this prospective study, calorie-balanced greater consumption of chocolate was inversely associated with lower overall, CVD, heart disease and cancer mortality. The systematic review and meta-analysis provide support for the inverse chocolate-CVD association. Our findings may provide evidence to partially allay concerns regarding adverse health outcomes from low-to-moderate chocolate consumption.
Similar content being viewed by others
References
Gong F, Yao S, Wan J, Gan X. Chocolate consumption and risk of heart failure: a meta-analysis of prospective studies. Nutrients. 2017;9(4). https://doi.org/10.3390/nu9040402
Lee KW, Kim YJ, Lee HJ, Lee CY. Cocoa has more phenolic phytochemicals and a higher antioxidant capacity than teas and red wine. J Agric Food Chem. 2003;51(25):7292–5. https://doi.org/10.1021/jf0344385.
Buijsse B, Weikert C, Drogan D, Bergmann M, Boeing H. Chocolate consumption in relation to blood pressure and risk of cardiovascular disease in German adults. Eur Heart J. 2010;31(13):1616–23. https://doi.org/10.1093/eurheartj/ehq068.
Faridi Z, Njike VY, Dutta S, Ali A, Katz DL. Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial. Am J Clin Nutr. 2008;88(1):58–63. https://doi.org/10.1093/ajcn/88.1.58.
Hooper L, Kay C, Abdelhamid A, et al. Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. Am J Clin Nutr. 2012;95(3):740–51. https://doi.org/10.3945/ajcn.111.023457.
Shrime MG, Bauer SR, McDonald AC, Chowdhury NH, Coltart CE, Ding EL. Flavonoid-rich cocoa consumption affects multiple cardiovascular risk factors in a meta-analysis of short-term studies. J Nutr. 2011;141(11):1982–8. https://doi.org/10.3945/jn.111.145482.
https://efsa.onlinelibrary.wiley.com/doi/abs/10.2903/j.efsa.2012.2809
Morze J, Schwedhelm C, Bencic A, et al. Chocolate and risk of chronic disease: a systematic review and dose-response meta-analysis. Eur J Nutr. 2020;59(1):389–97. https://doi.org/10.1007/s00394-019-01914-9.
U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015–2020 dietary guidelines for Americans. 8th Edition. December 2015. https://health.gov/our-work/food-nutrition/previous-dietary-guidelines/2015
Krittanawong C, Narasimhan B, Wang Z, et al. Association between chocolate consumption and risk of coronary artery disease: a systematic review and meta-analysis. Eur J Prev Cardiol. 2020;2047487320936787. https://doi.org/10.1177/2047487320936787
Ren Y, Liu Y, Sun XZ, et al. Chocolate consumption and risk of cardiovascular diseases: a meta-analysis of prospective studies. Heart. 2019;105(1):49–55. https://doi.org/10.1136/heartjnl-2018-313131.
Veronese N, Demurtas J, Celotto S, et al. Is chocolate consumption associated with health outcomes? An umbrella review of systematic reviews and meta-analyses. Clin Nutr. 2019;38(3):1101–8. https://doi.org/10.1016/j.clnu.2018.05.019.
Kwok CS, Gulati M, Michos ED, et al. Dietary components and risk of cardiovascular disease and all-cause mortality: a review of evidence from meta-analyses. Eur J Prev Cardiol. 2019;26(13):1415–29. https://doi.org/10.1177/2047487319843667.
Greenberg JA, Manson JE, Neuhouser ML, et al. Chocolate intake and heart disease and stroke in the Women’s Health Initiative: a prospective analysis. Am J Clin Nutr. 2018;108(1):41–8. https://doi.org/10.1093/ajcn/nqy073.
Larsson SC, Drca N, Jensen-Urstad M, Wolk A. Chocolate consumption and risk of atrial fibrillation: two cohort studies and a meta-analysis. Am Heart J. 2018;195:86–90. https://doi.org/10.1016/j.ahj.2017.09.013.
Kwok CS, Boekholdt SM, Lentjes MA, et al. Habitual chocolate consumption and risk of cardiovascular disease among healthy men and women. Heart. 2015;101(16):1279–87. https://doi.org/10.1136/heartjnl-2014-307050.
Petrone AB, Gaziano JM, Djousse L. Chocolate consumption and risk of heart failure in the Physicians’ Health Study. Eur J Heart Fail. 2014;16(12):1372–6. https://doi.org/10.1002/ejhf.180.
The ATBC Cancer Prevention Study Group. The alpha-tocopherol, beta-carotene lung cancer prevention study: design, methods, participant characteristics, and compliance. Ann Epidemiol. 1994;4(1):1–10.
Pietinen P, Hartman AM, Haapa E, et al. Reproducibility and validity of dietary assessment instruments. II. A qualitative food frequency questionnaire. Am J Epidemiol. 1988;128(3):667–76. https://doi.org/10.1093/oxfordjournals.aje.a115014
Pietinen P, Hartman AM, Haapa E, et al. Reproducibility and validity of dietary assessment instruments. I. A self-administered food use questionnaire with a portion size picture booklet. Am J Epidemiol. 1988;128(3):655–66. https://doi.org/10.1093/oxfordjournals.aje.a115013
Hertzmark E, Pazaris M, Spiegelman D. The SAS MEDIATE Macro. MA: Harvard T.H. Chan School of Public Health; 2012.
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097
Greenland S, Longnecker MP. Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol. 1992;135(11):1301–9. https://doi.org/10.1093/oxfordjournals.aje.a116237.
Janszky I, Mukamal KJ, Ljung R, Ahnve S, Ahlbom A, Hallqvist J. Chocolate consumption and mortality following a first acute myocardial infarction: the Stockholm Heart Epidemiology Program. J Intern Med. 2009;266(3):248–57. https://doi.org/10.1111/j.1365-2796.2009.02088.x.
Kwok CS, Loke YK, Welch AA, et al. Habitual chocolate consumption and the risk of incident heart failure among healthy men and women. Nutr Metab Cardiovasc Dis. 2016;26(8):722–34. https://doi.org/10.1016/j.numecd.2016.01.003.
Lewis JR, Prince RL, Zhu K, Devine A, Thompson PL, Hodgson JM. Habitual chocolate intake and vascular disease: a prospective study of clinical outcomes in older women. Arch Intern Med. 2010;170(20):1857–8. https://doi.org/10.1001/archinternmed.2010.396.
Zhong GC, Hu TY, Yang PF, et al. Chocolate consumption and all-cause and cause-specific mortality in a US population: a post hoc analysis of the PLCO cancer screening trial. Aging. 2021;13(14):18564–85. https://doi.org/10.18632/aging.203302.
Orsini N, Li R, Wolk A, Khudyakov P, Spiegelman D. Meta-analysis for linear and nonlinear dose-response relations: examples, an evaluation of approximations, and software. Am J Epidemiol. 2012;175(1):66–73. https://doi.org/10.1093/aje/kwr265.
Buijsse B, Feskens EJ, Kok FJ, Kromhout D. Cocoa intake, blood pressure, and cardiovascular mortality: the Zutphen Elderly Study. Arch Intern Med. 2006;166(4):411–7. https://doi.org/10.1001/archinte.166.4.411.
Dong JY, Iso H, Yamagishi K, Sawada N, Tsugane S, Japan Public Health Center-based Prospective Study G. Chocolate consumption and risk of stroke among men and women: A large population-based, prospective cohort study. Atherosclerosis. 2017;260:8–12. doi:https://doi.org/10.1016/j.atherosclerosis.2017.03.004
Khawaja O, Petrone AB, Kanjwal Y, Gaziano JM, Djousse L. Chocolate consumption and risk of atrial fibrillation (from the Physicians’ Health Study). Am J Cardiol. 2015;116(4):563–6. https://doi.org/10.1016/j.amjcard.2015.05.009.
Larsson SC, Virtamo J, Wolk A. Chocolate consumption and risk of stroke in women. J Am Coll Cardiol. 2011;58(17):1828–9. https://doi.org/10.1016/j.jacc.2011.07.023.
Larsson SC, Virtamo J, Wolk A. Chocolate consumption and risk of stroke: a prospective cohort of men and meta-analysis. Neurology. 2012;79(12):1223–9. https://doi.org/10.1212/WNL.0b013e31826aacfa.
Larsson SC, Akesson A, Gigante B, Wolk A. Chocolate consumption and risk of myocardial infarction: a prospective study and meta-analysis. Heart. 2016;102(13):1017–22. https://doi.org/10.1136/heartjnl-2015-309203.
Mostofsky E, Levitan EB, Wolk A, Mittleman MA. Chocolate intake and incidence of heart failure: a population-based prospective study of middle-aged and elderly women. Circ Heart Fail. 2010;3(5):612–6. https://doi.org/10.1161/CIRCHEARTFAILURE.110.944025.
Mostofsky E, Berg Johansen M, Tjonneland A, Chahal HS, Mittleman MA, Overvad K. Chocolate intake and risk of clinically apparent atrial fibrillation: the Danish Diet, Cancer, and Health Study. Heart. 2017;103(15):1163–7. https://doi.org/10.1136/heartjnl-2016-310357.
Steinhaus DA, Mostofsky E, Levitan EB, et al. Chocolate intake and incidence of heart failure: findings from the Cohort of Swedish Men. Am Heart J. 2017;183:18–23. https://doi.org/10.1016/j.ahj.2016.10.002.
Ho YL, Nguyen XT, Yan JQ, et al. Chocolate consumption and risk of coronary artery disease: the Million Veteran Program. Am J Clin Nutr. 2021;113(5):1137–44. https://doi.org/10.1093/ajcn/nqaa427.
Paganini-Hill A, Kawas CH, Corrada MM. Non-alcoholic beverage and caffeine consumption and mortality: the Leisure World Cohort Study. Prev Med. 2007;44(4):305–10. https://doi.org/10.1016/j.ypmed.2006.12.011.
Greenberg JA, Neuhouser ML, Tinker LF, et al. Chocolate candy and incident invasive cancer risk in the women’s health initiative: an observational prospective analysis. J Acad Nutr Diet. 2020. https://doi.org/10.1016/j.jand.2020.06.014.
Bondonno NP, Dalgaard F, Kyro C, et al. Flavonoid intake is associated with lower mortality in the Danish Diet Cancer and Health Cohort. Nat Commun. 2019;10(1):3651. https://doi.org/10.1038/s41467-019-11622-x.
Clark JL, Zahradka P, Taylor CG. Efficacy of flavonoids in the management of high blood pressure. Nutr Rev. 2015;73(12):799–822. https://doi.org/10.1093/nutrit/nuv048.
Bondonno CP, Croft KD, Ward N, Considine MJ, Hodgson JM. Dietary flavonoids and nitrate: effects on nitric oxide and vascular function. Nutr Rev. 2015;73(4):216–35. https://doi.org/10.1093/nutrit/nuu014.
Heptinstall S, May J, Fox S, Kwik-Uribe C, Zhao L. Cocoa flavanols and platelet and leukocyte function: recent in vitro and ex vivo studies in healthy adults. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S197–205 (discussion S6–9). https://doi.org/10.1097/00005344-200606001-00015
Hermann F, Spieker LE, Ruschitzka F, et al. Dark chocolate improves endothelial and platelet function. Heart. 2006;92(1):119–20. https://doi.org/10.1136/hrt.2005.063362.
Rein D, Paglieroni TG, Wun T, et al. Cocoa inhibits platelet activation and function. Am J Clin Nutr. 2000;72(1):30–5. https://doi.org/10.1093/ajcn/72.1.30.
Pearson DA, Paglieroni TG, Rein D, et al. The effects of flavanol-rich cocoa and aspirin on ex vivo platelet function. Thromb Res. 2002;106(4–5):191–7. https://doi.org/10.1016/s0049-3848(02)00128-7.
Corti R, Flammer AJ, Hollenberg NK, Luscher TF. Cocoa and cardiovascular health. Circulation. 2009;119(10):1433–41. https://doi.org/10.1161/CIRCULATIONAHA.108.827022.
Croft KD. Dietary polyphenols: antioxidants or not? Arch Biochem Biophys. 2016;595:120–4. https://doi.org/10.1016/j.abb.2015.11.014.
Ramirez-Sanchez I, Maya L, Ceballos G, Villarreal F. (-)-epicatechin activation of endothelial cell endothelial nitric oxide synthase, nitric oxide, and related signaling pathways. Hypertension. 2010;55(6):1398–405. https://doi.org/10.1161/HYPERTENSIONAHA.109.147892.
Mozaffarian D, Wu JHY. Flavonoids, dairy foods, and cardiovascular and metabolic health: a review of emerging biologic pathways. Circ Res. 2018;122(2):369–84. https://doi.org/10.1161/CIRCRESAHA.117.309008.
Lv D, Cheng X, Tang L, Jiang M. The cardioprotective effect of total flavonoids on myocardial ischemia/reperfusion in rats. Biomed Pharmacother. 2017;88:277–84. https://doi.org/10.1016/j.biopha.2017.01.060.
Prince PD, Fischerman L, Toblli JE, Fraga CG, Galleano M. LPS-induced renal inflammation is prevented by (-)-epicatechin in rats. Redox Biol. 2017;11:342–9. https://doi.org/10.1016/j.redox.2016.12.023.
Martinez-Pinilla E, Onatibia-Astibia A, Franco R. The relevance of theobromine for the beneficial effects of cocoa consumption. Front Pharmacol. 2015;6:30. https://doi.org/10.3389/fphar.2015.00030.
Neufingerl N, Zebregs YE, Schuring EA, Trautwein EA. Effect of cocoa and theobromine consumption on serum HDL-cholesterol concentrations: a randomized controlled trial. Am J Clin Nutr. 2013;97(6):1201–9. https://doi.org/10.3945/ajcn.112.047373.
Taubert D, Berkels R, Roesen R, Klaus W. Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA. 2003;290(8):1029–30. https://doi.org/10.1001/jama.290.8.1029.
Acknowledgements
We thank participants of the ATBC Study cohort for their contributions to this research.
Funding
The ATBC Study is supported by the Intramural Research Program of the U.S. National Cancer Institute, National Institutes of Health.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Zhao, B., Gan, L., Yu, K. et al. Relationship between chocolate consumption and overall and cause-specific mortality, systematic review and updated meta-analysis. Eur J Epidemiol 37, 321–333 (2022). https://doi.org/10.1007/s10654-022-00858-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10654-022-00858-5