Vitamin B Supplements May Lower Stroke Risk

Pauline Anderson

September 18, 2013

Unlike other similar reports that failed to find a significant effect of vitamin B supplementation on stroke risk, an updated meta-analysis has shown that taking these vitamins to lower homocysteine levels significantly reduces the stroke rate.

Folate (vitamin B9) and vitamin B12 are important regulators of homocysteine metabolism. In several jurisdictions, cereals are fortified with folate. Folic acid is a supplemental form of folate.

Several biological factors may affect whether vitamin B supplements will affect stroke risk, the study showed.

"Based on our results, the ability of vitamin B to reduce stroke risk may be influenced by a number of other factors, such as the body's absorption rate, the amount of folic acid or vitamin B12 concentration in the blood, and whether a person has kidney disease or high blood pressure," said Yuming Xu, MD, Department of Neurology, The First Affiliated Hospital of Zhengzhou University, China, in a press release.

The study is published online September 18 in Neurology.

Updated Analysis

Researchers searched for randomized controlled trials published before August 2012 that compared vitamin B supplementation with placebo, very-low-dose B vitamins, or usual care; had a minimum follow-up of 6 months; and included stroke events as a study endpoint.

Since 2010, several important meta-analyses have been published on the effects of therapy to lower homocysteine levels with B vitamin supplementation on vascular disease risk. The new meta-analysis included studies that were omitted from previous reports and adopted stricter inclusion criteria (it excluded several studies because of small samples, zero rates of outcome events, ill-defined endpoints events, and inappropriate control group design).

The updated analysis included 14 trials, all double-blind, with a mean age ranging from 52 to 68.9 years, and involving a total of 54,913 participants. Study follow-up ranged from 24 months to 87 months. One study, the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST), had just folic acid as the intervention, while the rest adopted combined intervention with B vitamins.

In these 14 reports, there were 2471 stroke events. The researchers noted a reduction in overall stroke events resulting from lowered homocysteine levels following B vitamin supplementation (risk ratio, 0.93; 95% confidence interval, 0.86 - 1.00; P = .04).

However, several strictly designed trials reported increased stroke events even with B vitamin supplementation.

In a subgroup analysis, the researchers found no significant differences between intervention and control groups regarding primary or secondary stroke prevention, stroke type (hemorrhagic, ischemic), or stroke severity.

Results were also not significant in a subgroup analysis for changes of stroke risks in response to various doses of folic acid supplementation or various baseline blood homocysteine concentrations. Previous studies had shown that 0.4 or 0.8 mg of folic acid is beneficial for lowering homocysteine levels and improving vascular endothelial function.

The researchers did find a benefit in the subgroup with 3 or more years of follow-up.

Subgroups of patients with chronic kidney disease were included in 5 of the 14 studies and 1 subanalysis. Some trials reported decreased glomerular filtration rate with B vitamin supplements.

As for analyses specific to vitamin B12, the report did not find significant benefit for reduction of stroke events in subgroups according to intervention dose, reduction of homocysteine level, or baseline blood vitamin B12 concentration. An analysis of populations with folate fortification of cereal products also failed to obtain significant results regarding B12 dose. Other research had reported that 1 mg of B12 is beneficial.

Vitamin B12 Deficiency

The authors explored the issue of pre-existing metabolic B12 deficiency. A subanalysis of the Vitamin Intervention for Stroke Prevention (VISP) trial that excluded participants with low baseline B12 concentrations due to malabsorption and high B12 levels following B12 injection found beneficial results of B vitamin supplementation for reduction of stroke risk. The current analysis showed a beneficial trend although not a significant benefit in the group with baseline median B12 concentrations of 322 to 400 pmol/L.

"Our clinical implication is that metabolic B12 deficiency should be more thoroughly followed and treated, so that such deficiencies are found and treated appropriately with B vitamin intervention," the authors write. "In future, we should consider adoption of specific administration routes rather than a single oral route, e.g. oral route in populations with inadequate dietary intake or injection route in populations with B12 malabsorption to obtain effective intervention results."

As for baseline blood pressure levels, the meta-analysis identified a benefit of B vitamins in study participants with baseline high blood pressure. Hyperhomocysteinemia is known to promote hypertension. In China, guidelines for hypertension recommend reducing homocysteine levels to manage blood pressure.

The analysis did not find a significant increase in cancer incidence.

Asked to comment, Ralph L. Sacco, MD, professor and Olemberg Chair of Neurology, executive director, McKnight Brain Institute, and chief of neurology, Jackson Memorial Miller School of Medicine, University of Miami, Florida, said he found the meta-analysis interesting but that the reduction in stroke events among those treated with vitamin B is only slight, albeit significant.

"The effects are quite small and greatest among those with elevated Hcy [homocysteine] over 20 and among subjects who do not have a diet with folate supplementation," Dr. Sacco told Medscape Medical News.

The addition of some new studies since the last meta-analysis explains the different findings, said Dr. Sacco, adding that the change is not sufficient to alter current guidelines.

"When one examines the largest clinical trials individually, there is no significant effect of vitamin B supplementation for primary or secondary stroke prevention, so it's difficult to use a meta-analysis to change evidence-based guidelines. There may be some subgroups of patients who could benefit from vitamin B supplementation, but unfortunately the effects are small and limited."

Dr. Xu serves as an editorial board member for the Chinese Journal of Neurology and Life Science Journal and on the Scientific Advisory Board for the Chinese Medical Association and the Neural Immune Professional Committee of Hunan Province.

Neurology. Published online September 18, 2013. Abstract

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