In this large prospective cohort of apparently healthy men at baseline, we found no evidence for an association between nut consumption and the risk of total or ischemic stroke after an average follow up of 21.1 years. For hemorrhagic stroke, we observed suggestive evidence for a J-shaped relation with nut consumption. Despite advances in medical and surgical treatment, stroke is still associated with major disability and is the 3rd
leading cause of death. This underscores the importance of preventive measures for this disease. Several dietary factors have shown beneficial effects on stroke predictors. Data from the PREDIMED trial showed that compared with a low-fat diet, Mediterranean diets supplemented with 30 g/d of nuts (almonds, hazelnuts, and walnuts) and olive oil were associated with 7.1 and 5.9 mm Hg reduction in systolic blood pressure after 3 months of intervention, respectively, among ~257 adult men and women per intervention group13
. In that study, corresponding effects for diastolic blood pressure were 2.6 and 1.6 mm Hg for Mediterranean diet with nuts and olive oil13
, respectively. Nut consumption may lower the risk of stroke via its beneficial effects on blood pressure or other predictors of stroke. Nut consumption has been associated with improved lipid profile24–28
, insulin sensitivity12,29
, and reduced inflammation6,13,30
. However, our data on total and ischemic stroke do not support this hypothesis.
The J-shaped relation observed between nut consumption and hemorrhagic stroke merits some comments. We had limited number of stroke in the higher categories of nut consumption. Consequently our data should be interpreted with caution. However, it is possible that omega-3 fatty acids contained in nuts may be partially responsible for the observed increased risk of hemorrhagic stroke with consumption of nuts 5 or more times per week. Previous studies have demonstrated that polyunsaturated fatty acids found in nuts may inhibit platelet aggregation 15,16
. This may increase the propensity to bleeding. In a necropsy study in Greenland, the concentration of total n-3 polyunsaturated fatty acids in perirenal adipose tissue was higher (2.3 units) in 4 cases of fatal hemorrhagic stroke than in 26 subjects without cerebral pathology (1.5 units)31
. In contrast, the Cardiovascular Health Study32
and the Health Professional Follow-up Study33
did not find a statistically significant association between fish intake and hemorrhagic stroke. Of note is that n-3 fatty acids only affect bleeding times at higher concentrations (3–15 g/d)34,35
. The lower intake of fish in the Western diet compared with Greenland Inuit may partially account for the inconsistency in these findings. Lastly, it is possible that people with a lifestyle considered healthy for ischemic stroke may be at increased risk for hemorrhagic stroke36
. For example, subjects with low body mass index and low LDL-cholesterol have been reported to have a higher risk of hemorrhagic stroke37
Strengths of the present paper are the large sample size, large number of outcomes events, the long duration of follow up, and the ascertainment of stroke through review of medical records. However, our study has some limitations. While the number of stroke events is large, the number of stroke subtypes according to nut consumption categories is relatively small. Thus, the statistically significant results for hemorrhagic stroke should be interpreted with caution. The generalizability of our findings is limited by the fact that all participants were male physicians who may have different behaviors or lifestyle habits than the general population. Nut consumption was assessed only once (12 months post-randomization) and since subjects may have changed their dietary habits, we were not able to account for such changes in our analyses. Such misclassification may bias the results towards the null and may partially explain the lack of an association between nuts and ischemic stroke in this study. However, the fact that we have shown an inverse relation between nuts assessed at one single time point and incident hypertension14
in the same cohort does not support the hypothesis of a large misclassification of nuts over time in this population. In addition, our findings on ischemic stroke did not change when we restricted the follow-up time to 5 or 10 years (a period within which one could assume little change in nut consumption). Since we used a simple questionnaire to assess nut consumption, we were unable to adjust for total energy intake and other nutrients consumed by study subjects. In addition, we did not have data on types of nuts consumed; their preparation including salted, spiced, roasted, or raw nuts to examine the influence of types of nuts or preparation method on the risk of total stroke and stroke subtype. The prevalence of atrial fibrillation was higher in stroke cases than in non-cases, suggesting that the use of warfarin might have been more prevalent in people with stroke. Such use of anticoagulant may have confounded the association between nut consumption and hemorrhagic stroke. Although we did not have information on warfarin use for further evaluation, we did adjust for atrial fibrillation (more likely to be correlated with warfarin use during follow up). Lastly, given the observational design of the present study, we can not exclude unmeasured or residual confounding as a possible explanation for observed findings.
In conclusion, our data suggest no association between nut consumption and total or ischemic stroke. However, there is suggestive J-shaped relation between nut consumption and hemorrhagic stroke. Since we had limited number of hemorrhagic strokes in the highest categories of nut consumption, replication of our findings is other populations along with assessment of types of nuts consumed and underlying physiologic mechanisms are warranted.