This site uses cookies to measure how you use the website so it can be updated and improved based on your needs and also uses cookies to help remember the notifications you’ve seen, like this one, so that we don’t show them to you again. If you could also tell us a little bit about yourself, this information will help us understand how we can support you better and make this site even easier for you to use and navigate.

Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis


Hankey, Graeme J., Ford, Andrew H., Yi, Qilong, Eikelboom, John W., Lees, Kennedy R., Chen, Christopher, Xavier, Denis, Navarro, Jose C., Ranawaka, Udaya K., Uddin, Wasim, Ricci, Stefano, Gommans, John, Schmidt, Reinhold, Almeida, Osvaldo P., van Bockxmeer, Frank M.


Stroke; A Journal Of Cerebral Circulation, Volume: 44, No.: 8, Pages.: 2232-2239

Year of Publication



Background and Purpose: High plasma total homocysteine (tHcy) has been associated with cognitive impairment but lowering tHcy with B-vitamins has produced equivocal results. We aimed to determine whether B-vitamin supplementation would reduce tHcy and the incidence of new cognitive impairment among individuals with stroke or transient ischemic attack≥6 months previously.; Methods: A total of 8164 patients with stroke or transient ischemic attack were randomly allocated to double-blind treatment with one tablet daily of B-vitamins (folic acid, 2 mg; vitamin B6, 25 mg; vitamin B12, 500 μg) or placebo and followed up for 3.4 years (median) in the VITAmins TO Prevent Stroke (VITATOPS) trial. For this prespecified secondary analysis of VITATOPS, the primary outcome was a new diagnosis of cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score<24 on ≥2 follow-up visits. Secondary outcomes were cognitive decline, and the mean tHcy and MMSE at final follow-up.; Results: A total of 3089 participants (38%) voluntarily undertook the MMSE>6 months after the qualifying stroke; 2608 participants were cognitively unimpaired (MMSE≥24), of whom 2214 participants (1110 B-vitamins versus 1104 placebo) had follow-up MMSEs during 2.8 years (median). At final follow-up, allocation to B-vitamins, compared with placebo, was associated with a reduction in mean tHcy (10.2 μmol/L versus 14.2 μmol/L; P<0.001) but no change from baseline in the mean MMSE score (-0.22 points versus -0.25 points; difference, 0.03; 95% confidence interval, -0.13 to 0.19; P=0.726) and no difference in the incidence of cognitive impairment (5.51% versus 5.47%; risk ratio, 1.01; 95% confidence interval, 0.69-1.48; P=0.976), cognitive decline (9.1% versus 10.3%; risk ratio, 0.89; 0.67-1.18; P=0.414), or cognitive impairment or decline (11.0% versus 11.3%; risk ratio, 0.98; 0.75-1.27; P=0.855).; Conclusions: Daily supplementation with folic acid, vitamin B6, and vitamin B12 to a self-selected clinical trial cohort of cognitively unimpaired patients with previous stroke or transient ischemic attack lowered mean tHcy but had no effect on the incidence of cognitive impairment or cognitive decline, as measured by the MMSE, during a median of 2.8 years.; Clinical Trial Registration: URL: Unique identifier: ISRCTN74743444; URL: Unique identifier: NCT00097669.;

Bibtex Citation

@article{Hankey_2013, doi = {10.1161/strokeaha.113.001886}, url = {}, year = 2013, month = {jun}, publisher = {Ovid Technologies (Wolters Kluwer Health)}, volume = {44}, number = {8}, pages = {2232--2239}, author = {G. J. Hankey and A. H. Ford and Q. Yi and J. W. Eikelboom and K. R. Lees and C. Chen and D. Xavier and J. C. Navarro and U. K. Ranawaka and W. Uddin and S. Ricci and J. Gommans and R. Schmidt and O. P. Almeida and F. M. van Bockxmeer}, title = {Effect of B Vitamins and Lowering Homocysteine on Cognitive Impairment in Patients With Previous Stroke or Transient Ischemic Attack: A Prespecified Secondary Analysis of a Randomized, Placebo-Controlled Trial and Meta-Analysis}, journal = {Stroke} }


acid, administration & dosage, aged, antagonists inhibitors, b12, b6, blood, bvitamins, clinical trial, cognition disorders, cognitive impairment, complications, double-blind method, drug therapy, etiology, female, folic, homocysteine, humans, ischemic attack transient, male, middle aged, of, pharmacology, physiology, placebos, prevention & control, recurrence, stroke, treatment outcome, use, vitamin b 12, vitamin b complex

Countries of Study


Types of Study

Randomised Controlled Trial

Type of Outcomes


Type of Interventions

Risk Factor Modification

Risk Factor Modifications

At risk population