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Intake of Glucosinolates and Risk of Coronary Heart Disease in Three Large Prospective Cohorts of US Men and Women

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Intake of Glucosinolates and Risk of Coronary Heart Disease in Three Large Prospective Cohorts of US Men and Women Journal name: Clinical Epidemiology Article Designation: ORIGINAL RESEARCH Year: 2018 Volume: 10 Clinical Epidemiology Dovepress Running head verso: Ma et al Running head recto: Glucosinolates and CHD open access to scientific and medical research DOI: http://dx.doi.org/10.2147/CLEP.S164497 Open Access Full Text Article ORIGINAL RESEARCH Intake of glucosinolates and risk of coronary heart disease in three large prospective cohorts of US men and women Le Ma1,2 Importance: Glucosinolates, a group of phytochemicals abundant in cruciferous vegetables, Gang Liu1 may have cardioprotective properties. However, no prospective study has evaluated the associa- Geng Zong1 tion of intake of glucosinolates with the risk of coronary heart disease (CHD). Laura Sampson1 Objective: The objective of the study was to evaluate the association between the intake of Frank B Hu1,3,4 glucosinolates and incident CHD in US men and women. Prospective longitudinal cohort study. Walter C Willett1,3,4 Design: Setting: Health professionals in the USA. Eric B Rimm1,3,4 We followed 74,241 women in the Nurses’ Health Study (NHS; 1984–2012), 3,5,6 Participants: JoAnn E Manson 94,163 women in the NHSII (1991–2013), and 42,170 men in the Health Professionals Follow- Kathryn M Rexrode6 For personal use only. Up Study (1986–2012), who were free of cardiovascular disease and cancer at baseline. 1,4 Qi Sun Exposure: Glucosinolate intake was assessed using validated semi-quantitative food frequency 1Department of Nutrition, Harvard questionnaires at baseline and updated every 2–4 years during follow-up. T.H. Chan School of Public Health, Main outcome measures: Incident cases of CHD were confirmed by medical record review. Boston, MA, USA; 2Department of Maternal, School of Public Health, Results: During 4,824,001 person-years of follow-up, 8,010 cases of CHD were identified in Xi’an Jiaotong University Health the three cohorts. After adjustment for major lifestyle and dietary risk factors of CHD, weak but Science Center, Xi’an, China; significantly positive associations were observed for glucosinolates with CHD risk when com- 3Department of Epidemiology, Harvard T.H. Chan School of Public paring the top with bottom quintiles (hazard ratio [HR]:1.09; 95% CI: 1.01, 1.17; Ptrend<0.001). Health, 4Channing Division of Higher intakes of three major subtypes of glucosinolates were consistently associated with a Network Medicine, Department of higher CHD risk, although the association for indolylglucosinolate did not achieve statistical Medicine, 5Department of Medicine, 6 Clinical Epidemiology downloaded from https://www.dovepress.com/ by 54.70.40.11 on 16-Dec-2018 Division of Preventive Medicine, significance. Regarding cruciferous vegetable intake, participants who consumed one or more Department of Medicine, Brigham and servings per week of Brussels sprouts (HR: 1.16; 95% CI: 1.06, 1.26; P<0.001) and cabbage Women’s Hospital, Boston, MA, USA (HR: 1.09; 95% CI: 1.02, 1.17; P=0.009) had a significantly higher CHD risk than those who consumed these cruciferous vegetables less than once per month. Conclusion and relevance: In these three prospective cohort studies, dietary glucosinolate intake was associated with a slightly higher risk of CHD in US adults. These results warrant replications in further studies including biomarker-based studies. Further studies are needed to confirm these findings and elucidate mechanistic pathways that may underlie these associations. Keywords: coronary heart disease, glucosinolate, cruciferous vegetable, diet Introduction Correspondence: Qi Sun The American Heart Association guidelines underscore the importance of increas- Department of Nutrition, Harvard ing consumption of vegetables for the prevention of heart disease and other chronic T.H. Chan School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA conditions, and a variety of vegetables in a healthy diet has been recently emphasized Tel +1 617 432 7490 by the US Department of Agriculture Dietary Guidelines for Americans as well.1,2 Fax +1 617 432 3435 Email [email protected] Growing evidence indicates that specific types of vegetables may have distinct effects submit your manuscript | www.dovepress.com Clinical Epidemiology 2018:10 749–762 749 Dovepress © 2018 Ma et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work http://dx.doi.org/10.2147/CLEP.S164497 you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Powered by TCPDF (www.tcpdf.org) 1 / 1 Ma et al Dovepress on the risk for coronary heart disease (CHD), which may be boards of Brigham and Women’s Hospital and Harvard T.H. due to the heterogeneous composition of nutrients and other Chan School of Public Health. The completion of the self- constituents in vegetables.3,4 administered questionnaire was considered to imply written Glucosinolates are a class of secondary plant metabo- informed consent. lites that are particularly rich in cruciferous vegetables.5,6 Dietary glucosinolates can be hydrolyzed to biologically Assessment of glucosinolate intake active compounds, such as isothiocyanates (ITCs), which In each cohort, the intake of glucosinolates was assessed are able to modulate cellular redox status and protect against using validated FFQs every 2–4 years. The FFQs inquired carcinogenesis in animal experiements.6,7 Emerging evidence about the consumption of selected foods (with a prespecified from experimental studies has shown that glucosinolate serving size) during the past year with nine categories of metabolites can reduce oxidative stress, inflammation, endo- intake frequency. The Harvard University Food Composi- thelial dysfunction, and cardiomyocyte death,8–10 indicating tion Database was primarily used to calculate the nutrient that these compounds may also have beneficial effects on values, complemented by published data.16 Intake of indi- the cardiovascular system. Despite the evidence from basic vidual glucosinolates was calculated by multiplying the science research, human data regarding glucosinolates intake glucosinolate levels in a prespecified portion size with the and CHD risk are limited. A couple of epidemiologic studies consumption frequency for each contributing food item and investigated cruciferous vegetable intake in relation to risk then summing the intake levels across all contributing food of CHD, and mixed results were observed.11,12 Furthermore, items. Intake of total and subgroups of glucosinolates was existing evidence from relatively small clinical trials regard- derived by summing up individual glucosinolates in each ing the effects of glucosinolates or glucosinolate-rich foods category. Glucosinolate intakes were energy-adjusted using on the development of coronary intermediate endpoints the residual method. Reasonable validity and reproduc- remains limited and inconclusive.13,14 ibility of the assessments of food sources of glucosinolates, In the current investigation, we aimed to evaluate the including broccoli, cabbage, and Brussels sprouts, have been For personal use only. hypothesis that higher glucosinolate intake is associated with demonstrated in validation studies.17–19 lower risk of CHD. To test this hypothesis, we prospectively examined dietary glucosinolate intake, as well as major Assessment of covariates dietary glucosinolate sources, in relation to the risk of CHD. In all three cohorts, information on age, body weight, medical history, smoking status, physical activity, parental history of Subjects and methods myocardial infarction (MI) before age 65 years, medical his- Study population tory, menopausal status and use of hormone therapy (women Participants in this analysis were US men and women from only), and medication use was collected and updated in bien- three prospective cohort studies: Nurses’ Health Study nial validated questionnaires. Alcohol intake was assessed Clinical Epidemiology downloaded from https://www.dovepress.com/ by 54.70.40.11 on 16-Dec-2018 (NHS; n=121,700 female registered nurses enrolled in and updated by validated FFQs. Detailed descriptions on 1976), NHSII (n=116,686 younger female registered nurses the validity and reproducibility of these assessments have enrolled in 1989), and Health Professionals Follow-Up been published elsewhere.20–22 We calculated an Alternative Study (HPFS; n=51,529 male health professionals enrolled Healthy Eating Index (AHEI) score to quantify the overall in 1986). Detailed descriptions of the cohorts are provided diet quality of the participants.23 The AHEI score summarizes elsewhere.15 For this analysis, we excluded participants who the intake of 11 foods or nutrients that are most predictive of had diagnoses of cardiovascular disease (CVD) or cancer at chronic diseases: vegetables, fruits, whole grains, nuts and baseline, left 70 or more items blank on the food frequency legumes, long-chain n-3 fats, polyunsaturated fats, sugar- questionnaire (FFQ), reported implausible energy intake sweetened beverages and fruit juice, red and processed meat, (<3,347 or >17,573 kJ/day for men and <2,510
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