Eating a diet high in antioxidants may protect against ischemic stroke, an Italian cohort study showed.
People who had a diet high in total antioxidant capacity — an index that takes into account several different antioxidants and their interactions — had a 59% reduced relative risk of ischemic stroke (HR 0.41, 95% CI 0.23 to 0.74), according to Nicoletta Pellegrini, PhD, of the University of Parma in Italy, and colleagues. But there was no such relationship with hemorrhagic stroke, they reported in the January issue of the Journal of Nutrition. In fact, the highest intake of the antioxidant vitamin E was associated with a greater risk of hemorrhagic stroke (HR 2.94, 95% CI 1.13 to 7.62).
Considering evidence suggesting that oxidative stress and systemic inflammation are involved in the pathogenesis of ischemic stroke, the researchers noted that “a high-total antioxidant capacity diet could be protective as a consequence of its ability to deliver compounds with antioxidant activity and with a demonstrated anti-inflammatory effect.” But, they acknowledged that the mechanism for such activity was unclear may “go beyond the antioxidant activity of the numerous total antioxidant capacity contributors present in foods and beverages.”
Pellegrini and her colleagues set out to explore the relationship between dietary total antioxidant capacity and the risk of stroke among 41,620 people participating in EPICOR, the Italian segment of the European Prospective Investigation into Cancer and Nutrition (EPIC). None had a history of stroke or MI at baseline. Dietary intake was assessed with a food frequency questionnaire. In the study population, more than half of the total antioxidants consumed came from coffee, wine, and fruit. Through a mean follow-up of 7.9 years, there were 112 ischemic strokes, 48 hemorrhagic strokes, and 34 other types of strokes. After adjustment for energy intake, hypertension, smoking status, education, nonalcoholic energy intake at recruitment, alcohol intake, waist circumference, body mass index, and total physical activity, individuals eating a diet in the highest tertile of total antioxidant capacity had a reduced risk of ischemic — but not hemorrhagic — stroke.
Looking at individual antioxidants, the researchers found that participants consuming the highest amounts of vitamin C had a reduced risk of ischemic stroke (HR 0.58, 95% CI 0.34 to 0.99). Controlling for vitamin C intake did not negate the overall association between antioxidants and ischemic stroke, which ruled out the nutrient as the sole driver of the relationship. High intake of vitamin E, on the other hand, was associated with nearly triple the relative risk of hemorrhagic stroke. However, “it must be stressed that the small number of cases observed in this population strongly limits the validity of statistical observations on hemorrhagic stroke,” noted the researchers, who called for further studies.
Aside from anti-inflammatory effects, it is possible that the association between antioxidants and ischemic stroke risk can be explained by the interaction between polyphenols — the major contributors to total antioxidant capacity — and the generation of nitric oxide from the vascular endothelium. That interaction leads to the vasodilation and expression of genes that may be protective for the vascular system, according to the researchers. In addition, coffee — the main source of antioxidants in the study population — reduces blood pressure, which is a recognized risk factor for ischemic stroke, the researchers wrote.
They noted some limitations of the study, including the low numbers of cases when different types of stroke were analyzed, the measurement of total antioxidant capacity at baseline only, and the inability to rule out confounding effects of other dietary components, like sodium and potassium.
Source: Del Rio D, et al “Total antioxidant capacity of the diet is associated with lower risk of ischemic stroke in a large Italian cohort” J Nutr 2011; 141: 118-123.
A baseline questionnaire about medical history and health practices was completed and then repeated every 2 years through 2006. Self-reported symptoms of depression, use of antidepressant medication, and physician-diagnosed depression were used as measures of depression. Depressed mood was assessed using the 5-item Mental Health Index, with a score of 52 or less indicating severe depression.
Those who reported a diagnosis of type 2 diabetes mellitus had the diagnosis confirmed by means of a supplementary questionnaire validated by medical record review.
During the 10-year follow-up, 2844 women were diagnosed as having type 2 diabetes and 7415 developed depression.
The relative risk of developing type 2 diabetes among women who were depressed was 1.17 (95% confidence interval [CI], 1.05 – 1.30). Study participants using antidepressants had a relative risk of 1.25 (95% CI, 1.10 – 1.41).
After controlling for all covariates, the investigators found women with diabetes had a relative risk of 1.29 (95% CI, 1.18 – 1.40) of developing clinical depression.
In addition, the relative risk for depression in diabetic subjects taking no diabetic medication, oral hypoglycemic agents, and insulin was 1.25 (95% CI, 1.09 – 1.42), 1.24 (95% CI, 1.09 – 1.41), and 1.53 (95% CI, 1.26 – 1.85), respectively.
The results also showed that compared with their nondiabetic counterparts, women with diabetes were more likely to have a higher body mass index and less likely to be physically active, a finding that suggests these 2 risk factors could be “major mediating factors.”
Nevertheless, they note the association remained significant after controlling for body mass index and lifestyle factors, which suggests “depression has effects on incident diabetes independent of adiposity and inactivity.”
The finding that women taking antidepressant medications were at higher risk of developing type 2 diabetes compared with those with severe depressive symptoms or physician-diagnosed depression has at least 2 possible explanations — antidepressant medications may be a marker of more severe, chronic, or recurrent depression or the medications themselves may increase diabetes risk.
“Although antidepressant medication use might be a marker of severe depression, its specific association with elevated risk of diabetes warrants further scrutiny,” they write.
In addition, the study authors note that these findings reinforce the hypothesis that diabetes may be related to stress: “Depression may result from the biochemical changes directly caused by diabetes or its treatment, or from the stresses and strains associated with living with diabetes and its often debilitating consequences.”
“This large, well-established cohort study provides evidence that the association between depression and diabetes is bidirectional and this association is partially explained by, but independent of, other known risk factors such as adiposity and lifestyle variables. Future studies are needed to confirm our findings in different populations and to investigate the potential mechanisms underlying this association,” the investigators conclude.
The study was funded by the National Institutes of Health and the National Alliance for Research on Schizophrenia and Depression. The study authors have disclosed no relevant financial relationships.
Arch Intern Med. 2010;170:1884-1891.