NUTRITION EPIDEMIOLOGY HIGHLIGHTS ORIGINAL ARTICLE The association between nut consumption and the risk of total and ischemic stroke in a German cohort study R di Giuseppe 1,7 , MK Fjeld 2,7 , J Dierkes 2 , D Theoflylaktopoulou 3,4 , M Arregui 1 , H Boeing 5 and C Weikert 1,6 BACKGROUND/OBJECTIVES: Nuts have beneficial effects on coronary heart disease and many cardiovascular risk factors. However, their effect on stroke is less established, and no studies on the topic are available in Northern and Central European populations. Therefore, we aimed at investigating the association between nut consumption and the risk of stroke in a German population. SUBJECTS/METHODS: We used data from a prospective cohort of 26 285 participants of the European Prospective Investigation into the Cancer and Nutrition Potsdam Study. During a median follow-up time of 8.3 years (interquartile range: 7.5–9.2), 288 incident cases of stroke occurred. Nut consumption (standard portion size of 50 g) was assessed at baseline with a semiquantitative food-frequency questionnaire. RESULTS: The median nut intake was 0.82 g per day, interquartile range: 0.41–4.11. In the multivariable model, an increased risk of stroke was observed among participants who never consumed nuts (hazard ratio (HR): 1.56, 95% confidence interval: 1.17–2.08), compared with those consuming o½ portion/week. However, there was no evidence of a dose–response relationship between nut consumption and stroke. Compared with those who consumed o½ portion/week, the multivariable HR for total stroke was 1.06 (0.75–1.52) among those who consumed ½ to 1 portion/week and 1.37 (0.92–2.05) for those who consumed 41 portion/week. Similar nonsignificant associations were observed in stratified analysis for gender, or for fatal and nonfatal stroke. CONCLUSIONS: We could not observe an association between nut consumption and the risk of developing stroke (fatal/nonfatal) in a population with low habitual nut consumption. European Journal of Clinical Nutrition (2015) 69, 431–435; doi:10.1038/ejcn.2014.212; published online 8 October 2014 INTRODUCTION Stroke is a major public health issue, with limited treatment options. Therefore, prevention strategies are highly warranted. Nuts are a good source of unsaturated fatty acids, protein, vitamins, fiber and minerals. 1 They are an important component of the Mediterranean diet, 2 and nut intake was recently found to be inversely associated with total mortality and death from cancer, heart disease and respiratory disease. 3 In addition, a protective role of nuts against coronary heart disease is well established. 4–8 The latter is possibly explained by the beneficial effect of nuts on risk factors for coronary heart disease, such as blood pressure, 9,10 lipids 11,12 and insulin sensitivity. 13,14 Although those risk factors, and especially hypertension, are also important for stroke, the association between nut consumption and stroke remains unclear. A pooled analysis of the Health Professionals Follow-Up Study and Nurses’ Health Study found no significant relationships between nut consumption and stroke. 15 In the US male physicians study, a J-shaped relationship was observed between nut consumption and the risk of hemorrhagic stroke, but not of total or ischemic stroke (IS). 9 However, the generalizability of these findings to a general European population may be questionable, especially in populations with low habitual nut consumption. Therefore, also the findings from the PREDIMED trial suggesting a protective effect of a Mediterranean diet with high nut consumption, in particular for stroke, cannot easily be generalized to these populations. 2,16 Furthermore, three recently published meta-analyses of either randomized controlled trials or observa- tional studies have shown nonsignificant pooled risk estimates for stroke. 17–19 In the present study, we investigated the possible relationships between consumption of nuts and incident fatal and nonfatal total and IS in middle-aged German men and women, in the framework of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. SUBJECTS AND METHODS Study population The EPIC is an ongoing multicenter prospective cohort study that is designed to investigate the relationships between diet, metabolic characteristics, various lifestyle factors and the risk of cancer, as well as other chronic diseases. 20,21 Co-ordinated by the International Agency for Research on Cancer of the World Health Organisation (WHO) in Lyon, France, the EPIC study started in 1992 and it currently includes 519 978 participants who were recruited until 2000 in 10 European countries, for a total of 23 centers. Among them, Potsdam represents one of the two German cohorts within the EPIC project. 22 Between 1994 and 1998, 27 548 participants (16 644 women and 10 904 men with a mean age of, respectively, 49.2 years and 52.5 years) were recruited from the general population of the Potsdam area. Biennially, self-administered 1 Research Group Cardiovascular Epidemiology, Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany; 2 Department of Clinical Medicine, University of Bergen, Bergen, Norway; 3 Department of Clinical Science, University of Bergen, Bergen, Norway; 4 Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; 5 Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany and 6 Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, Berlin, Germany. Correspondence: Dr R di Giuseppe, Research Group Cardiovascular Epidemiology, Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, Nuthetal D-14558, Germany. E-mail: romina.digiuseppe@dife.de 7 These authors contributed equally to this work. Received 21 May 2014; revised 28 August 2014; accepted 29 August 2014; published online 8 October 2014 European Journal of Clinical Nutrition (2015) 69, 431 – 435 © 2015 Macmillan Publishers Limited All rights reserved 0954-3007/15 www.nature.com/ejcn