Published: Sep 18, 2013 | Updated: Sep 19, 2013
By Crystal Phend, Senior Staff Writer, MedPage Today

Vitamin B supplementation may modestly help reduce stroke risk, though largely for patients who don’t fit the typical U.S. stroke prevention profile, a meta-analysis showed.

The risk of stroke was 7% lower overall with B vitamin supplements due to reduction in homocysteine levels (P=0.04), Yuming Xu, MD, of First Affiliated Hospital of China’s Zhengzhou University, and colleagues found.

The effect appeared of borderline significance in the absence of folate (vitamin B9) fortification of grain products but wasn’t significant for populations already getting the vitamin in their food supply, the researchers reported online inNeurology.

Other factors associated with modest benefit included high blood pressure and low antiplatelet usage.

“All three of these factors do not apply to the typical stroke-prone patient seen in the U.S. clinic,” commented James Meschia, MD, chair of neurology at the Mayo Clinic in Jacksonville, Fla.

He also cautioned about some surprising findings: How much B vitamin was given, baseline homocysteine levels, and how much homocysteine subsequently dropped didn’t seem to have an impact on stroke. That was unexpected, given that the proposed mechanism of stroke reduction is homocysteine lowering.

“Until we can understand why these particular subgroups do not seem to matter, it does call into question how compelling the finding is that B vitamin supplementation lowers stroke risk,” Meschia said.

Regardless, a 7% relative reduction of patients’ typically 1% to 2% annual stroke risk probably wouldn’t be enough to influence practice, he told MedPage Today.

A string of prior trials and meta-analyses cast doubt on folic acid benefits in cardiovascular prevention overall.

It was reassuring, though, that the meta-analysis didn’t turn up a cancer risk of vitamin B supplements (pooled RR 1.05, P=0.17), which had been a concern based on some prior studies, Meschia noted.

“Clinicians do not necessarily feel compelled to recommend stopping vitamin supplementation,” he said.

The meta-analysis included 14 randomized controlled trials with a total of 54,913 participants.

Vitamin B supplementation drove down homocysteine levels by 1.3 to 10.4 mmol/L across the trials, as expected from the various doses given.

No effect was seen on transient ischemic attack risk in the pooled analysis (relative risk 0.93, 95% CI 0.80–1.10) or on myocardial infarction (RR 1.00, 95% CI 0.94-1.07).

For stroke, subgroup analyses showed the following borderline and significant associations with B vitamins:

• With 3 or more years of follow-up, an 8% reduction in risk (RR 0.92, 95% CI 0.84-1.00)
• With no folate fortification, a 9% reduction in risk (RR 0.91, 95% CI 0.83-1.00)
• With systolic blood pressure above 130 mm Hg, a 14% reduction in risk (RR 0.86, 95% CI 0.76-0.97)
• With an antiplatelet agent use rate below 50%, a 16% reduction in risk (RR 0.84, 95% CI 0.70-1.00)

Results were not significant for primary or secondary prevention individually, for hemorrhagic or ischemic stroke individually, for fatal or disabling stroke, for any individual dose level of folic acid, for any baseline homocysteine level group, for higher or lower homocysteine reduction, or for those with or without chronic kidney disease.

Vitamin B12 had no impact on stroke risk in the analysis either overall or in folate-fortified populations.

The researchers pointed out that they excluded several studies because of “small samples, zero rates of outcome events, ill-defined endpoint events, and inappropriate control group design,” which could have led to a greater estimate of B vitamin benefit than in prior analyses.

Other limitations were inability to entirely exclude the possibility of publication bias and inevitable bias from the differences in patient populations included, treatment duration and intensity, expertise of event adjudicators, and other variables in study design.

• Guidelines for the Primary Prevention of Stroke
• Stroke: Efficacy of Homocysteine-Lowering Therapy With Folic Acid in Stroke Prevention: A Meta-Analysis

Primary source: Neurology