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The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability

Lea, Roda c; Colson, Nataliea; Quinlan, Sharona; Macmillan, Johnb; Griffiths, Lyna

Pharmacogenetics and Genomics: June 2009 - Volume 19 - Issue 6 - p 422-428
doi: 10.1097/FPC.0b013e32832af5a3

Background Migraine is a prevalent and debilitating disease that may, in part, arise because of disruption in neurovascular endothelia caused by elevated homocysteine. This study examined the homocysteine-lowering effects of vitamin supplementation on migraine disability, frequency and severity and whether MTHFRC677T genotype influenced treatment response.

Methods This was a randomized, double-blind placebo, controlled trial of 6 months of daily vitamin supplementation (i.e. 2 mg of folic acid, 25 mg vitamin B6, and 400 μg of vitamin B12) in 52 patients diagnosed with migraine with aura.

Findings Vitamin supplementation reduced homocysteine by 39% (approximately 4 μmol/l) compared with baseline, a reduction that was greater then placebo (P=0.001). Vitamin supplementation also reduced the prevalence of migraine disability from 60% at baseline to 30% after 6 months (P=0.01), whereas no reduction was observed for the placebo group (P>0.1). Headache frequency and pain severity were also reduced (P<0.05), whereas there was no reduction in the placebo group (P>0.1). In this patient group the treatment effect on both homocysteine levels and migraine disability was associated with MTHFRC677T genotype whereby carriers of the C allele experienced a greater response compared with TT genotypes (P<0.05).

Interpretation This study provides some early evidence that lowering homocysteine through vitamin supplementation reduces migraine disability in a subgroup of patients. Larger trials are now warranted to establish whether vitamin therapy is a safe, inexpensive and effective prophylactic option for treatment of migraine and whether efficacy is dependant on MTHFRC677T genotype.

aGenomics Research Centre, School of Health Science, Griffith University,Gold Coast

bQueensland Clinical Genetics Service, Royal Children's Hospital Health Service District, Brisbane, Queensland, Australia

cThe Institute of Environmental Science and Research Limited, Wellington, New Zealand

Correspondence to Professor Lyn Griffiths, PhD, School of Medical Science, Griffith University, Queensland 4222, Australia

Tel/fax: +61 755528664; e-mail:

Received 13 August 2008 Accepted 26 February 2009

© 2009 Lippincott Williams & Wilkins, Inc.