RESULTS The meta- analysis of observational studies showed a weaker slope of dose-response relations than the meta- analysis of RCTs .
The obtained dose-response estimate between vitamin B-12 intake and status provides complementary evidence to underpin recommendations for a vitamin B-12 intake of population
BACKGROUND Many r and omized controlled trials ( RCTs ) and observational studies have provided information on the association between vitamin B-12 intake and biomarkers .
The use of these data to estimate dose-response relations provides a useful means to summarize the body of evidence .
OBJECTIVE We systematic ally review ed studies that investigated vitamin B-12 intake and biomarkers of vitamin B-12  status and estimated dose-response relations with the use of a meta- analysis .
Folate, Vitamin B12, and Risk of Ischemic and Hemorrhagic Stroke: A Prospective, Nested Case-Referent Study of Plasma Concentrations and Dietary Intake
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 prospect i ve , 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
RESULTS The meta- analysis of observational studies showed a weaker slope of dose-response relations than the meta- analysis of RCTs .
The obtained dose-response estimate between vitamin B-12 intake and status provides complementary evidence to underpin recommendations for a vitamin B-12 intake of population
BACKGROUND Many r and omized controlled trials ( RCTs ) and observational studies have provided information on the association between vitamin B-12 intake and biomarkers .
The use of these data to estimate dose-response relations provides a useful means to summarize the body of evidence .
OBJECTIVE We systematic ally review ed studies that investigated vitamin B-12 intake and biomarkers of vitamin B-12  status and estimated dose-response relations with the use of a meta- analysis .