Effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability – Source: Pharmacogenetics and Genomics, Apr 20, 2009

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[Note: Homocysteine is a protein in the blood, strongly influenced by genetic factors, that at elevated levels appears to damage the lining of vessels & capillaries (endothelium), and is changed by B vitamins to the useful compound SAM.]

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 [B9], 25 mg vitamin B6, and 400 mug of vitamin B12) in 52 patients diagnosed with migraine with aura.

Findings:
• Vitamin supplementation reduced homocysteine by 39% (approximately 4 mumol/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.

Source: Pharmacogenetics and Genomics, Apr 20. 2009, PMID: 19384265, by Lea R, Colson N, Quinlan S, Macmillan J, Griffiths L. Genomics Research Centre, School of Health Science, Griffith University, Gold Coast; Queensland Clinical Genetics Service, Royal Children's Hospital Health Service District, Brisbane, Queensland, Australia; The Institute of Environmental Science and Research Limited, Wellington, New Zealand.

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