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Folate, vitamin B12, and risk of ischemic and hemorrhagic stroke: a prospective, nested case-referent study of plasma concentrations and dietary intake.

Journal article
Authors Bethany Van Guelpen
Johan Hultdin
Ingegerd Johansson
Birgitta Stegmayr
Göran Hallmans
Torbjörn K Nilsson
Lars Weinehall
Cornelia Witthöft
Richard Palmqvist
Anna Winkvist
Published in Stroke; a journal of cerebral circulation
Volume 36
Issue 7
Pages 1426-31
ISSN 1524-4628
Publication year 2005
Published at Institute of Internal Medicine, Dept of Clinical Nutrition
Pages 1426-31
Language en
Keywords Adult, Aged, Brain Ischemia, etiology, pathology, Case-Control Studies, Cerebrovascular Accident, etiology, pathology, Cohort Studies, Diet, Female, Folic Acid, blood, pharmacology, Hemorrhage, blood, Homocysteine, blood, Humans, Male, Methylenetetrahydrofolate Reductase (NADPH2), genetics, Middle Aged, Multivariate Analysis, Nutritional Status, Odds Ratio, Polymorphism, Genetic, Prospective Studies, Registries, Risk, Sweden, Vitamin B 12, pharmacology
Subject categories Health Care Service and Management, Health Policy and Services and Health Economy, Public Health, Global Health, Social Medicine and Epidemiology


BACKGROUND AND PURPOSE: Folate metabolism has been implicated in stroke. However, the possibility of a role for folate and vitamin B12, independent of their effects on homocysteine status, remains to be explored. The aim of this prospective, nested case-referent study was to relate plasma and dietary intake levels of folate and vitamin B12 to risk of stroke, taking into consideration plasma homocysteine concentrations and methylenetetrahydrofolate reductase polymorphisms. METHODS: Subjects were 334 ischemic and 62 hemorrhagic stroke cases and matched double referents from the population-based Northern Sweden Health and Disease Cohort. RESULTS: Plasma folate was statistically significantly associated with risk of hemorrhagic stroke in an inverse linear manner, both in univariate analysis and after adjustment for conventional risk factors including hypertension (odds ratio [OR] for highest versus lowest quartile 0.21 (95% confidence interval [CI], 0.06 to 0.71; P for trend=0.008)). Risk estimates were attenuated by inclusion of homocysteine in the model (OR, 0.34; 95% CI, 0.08 to 1.40; P for trend=0.088). A similar pattern was observed for increasing folate intake (multivariate OR, 0.07; 95% CI, 0.01 to 0.55; P for trend=0.031 without homocysteine, and OR, 0.16, 95% CI, 0.02 to 1.23; P for trend=0.118 with homocysteine in the analysis). We found little evidence of an association between plasma or dietary folate and risk of ischemic stroke. Neither plasma nor dietary vitamin B12 was associated with risk of either stroke subtype. CONCLUSIONS: The results of this study suggest a protective role for folate, possibly in addition to its effects on homocysteine status, in hemorrhagic but not ischemic stroke.

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