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(Stroke. 2005;36:1426.)
© 2005 American Heart Association, Inc.

Original Contributions

Folate, Vitamin B₁₂, and Risk of Ischemic and Hemorrhagic Stroke

A Prospective, Nested Case-Referent Study of Plasma Concentrations and Dietary Intake

Bethany Van Guelpen, MSSc; Johan Hultdin, MD; Ingegerd Johansson, DDS, PhD; Birgitta Stegmayr, PhD; Göran Hallmans, MD, PhD; Torbjörn K. Nilsson, MD, PhD; Lars Weinehall, MD, PhD; Cornelia Witthöft, PhD; Richard Palmqvist, MD, PhD Anna Winkvist, PhD

From the Departments of Medical Biosciences, Pathology (B.V.G., R.P.) and Clinical Chemistry (J.H.), Odontology, Cariology (I.J.), Public Health and Clinical Medicine, Medicine (B.S.), Nutrition Research (G.H.), and Epidemiology (L.W.), Umeå University Hospital, Umeå, Sweden; Clinical Chemistry (T.K.N.), Örebro University Hospital, Örebro, Sweden; Food Science (C.W.), Swedish University of Agricultural Sciences, Uppsala, Sweden; and Clinical Nutrition (A.W.), The Sahlgrenska Academy, Göteborg University, Gothenburg, Sweden.

Correspondence to Bethany Van Guelpen, Department of Medical Biosciences, Pathology, Building 6M, 2nd Floor, Umeå University, SE-901 85 Umeå, Sweden. E-mail Bethany.Van.Guelpen{at}nutrires.umu.se

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.

Key Words: cerebral infarct • intracerebral hemorrhage • folate • vitamin B₁₂ • risk factors • Sweden

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