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The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis

Kathleen Potter1*, Graeme J Hankey12, Daniel J Green34, John Eikelboom5, Konrad Jamrozik6 and Leonard F Arnolda17

Author affiliations

1 School of Medicine and Pharmacology, University of Western Australia, Perth, Australia

2 Department of Neurology, Royal Perth Hospital, Perth, Australia

3 School of Sport Science, Exercise and Health, University of Western Australia, Perth, Australia

4 Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, UK

5 Department of Medicine, McMaster University, Hamilton, Canada

6 School of Population Health and Clinical Practice, University of Adelaide, Adelaide, Australia

7 Department of Cardiology, Royal Perth Hospital, Perth, Australia

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Citation and License

BMC Cardiovascular Disorders 2008, 8:24  doi:10.1186/1471-2261-8-24

Published: 20 September 2008



Experimental and epidemiological evidence suggests that homocysteine (tHcy) may be a causal risk factor for atherosclerosis. B-vitamin supplements reduce tHcy and improve endothelial function in short term trials, but the long-term effects of the treatment on vascular structure and function are unknown.


We conducted a sub-study of VITATOPS, a randomised, double-blind, placebo-controlled intervention trial designed to test the efficacy of long term B-vitamin supplementation (folic acid 2 mg, vitamin B6 25 mg and vitamin B12 0.5 mg) in the prevention of vascular events in patients with a history of stroke. We measured carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD) at least two years after randomisation in 162 VITATOPS participants. We also conducted a systematic review and meta-analysis of studies designed to test the effect of B-vitamin treatment on CIMT and FMD.


After a mean treatment period of 3.9 ± 0.9 years, the vitamin-treated group had a significantly lower mean plasma homocysteine concentration than the placebo-treated group (7.9 μmol/L, 95% CI 7.5 to 8.4 versus 11.8 μmol/L, 95% CI 10.9 to 12.8, p < 0.001). Post-treatment CIMT (0.84 ± 0.17 mm vitamins versus 0.83 ± 0.18 mm placebo, p = 0.74) and FMD (median of 4.0%, IQR 0.9 to 7.2 vitamins versus 3.0%, IQR 0.6 to 6.6 placebo, p = 0.48) did not differ significantly between groups. A meta-analysis of published randomised data, including those from the current study, suggested that B-vitamin supplements should reduce CIMT (-0.10 mm, 95% CI -0.20 to -0.01 mm) and increase FMD (1.4%, 95% CI 0.7 to 2.1%). However, the improvement in endothelial function associated with homocysteine-lowering treatment was significant in short-term studies but not in longer trials.


Although short-term treatment with B-vitamins is associated with increased FMD, long-term homocysteine-lowering did not significantly improve FMD or CIMT in people with a history of stroke.

Trial Registration

Clinical Trial Registration URL: webcite

Trial Registration number: 12605000005651