Lowering high levels of fasting total homocysteine with folic acid and vitamins B in patients with venous thromboembolism: relationship between response and the C677T methylenetetrahydrofolate reductase (MTHFR) genotype

BACKGROUND: High levels of plasma total homocysteine (tHcy) are involved in arterial or venous occlusive diseases. It esentially depends on the nutrit ional status of folic acid (FA) and vitamins B-12 or B-6, but also on the m ethylenetetrahydrofolate reductase (MTHFR) enzymatic activity. We aim to ev aluate the response of the hyperhomocysteinemia (HHcy) to a standard schedu le of vitamin supplementation, according with the MTHFR genotype. PATIENTS AND METHODS: 227 patients, diagnosed with venous thromboembolism ( VTE) were analysed for tHcy (in fasting conditions), and for the MTHFR-C677 T gene polymorphism. When the tHcy exceeded the cut-off point (men = 16, wo men = 15 mu mol/l), the patients were supplemented with a dose equivalent t o 1 mg FA, 0.2 mg B-12 and 100 mg of B-6, daily by 6 weeks. Afterwards they were reanalysed and the reduction was stratified by MTHFR genotype, lookin g for any difference in the response. RESULTS: The mean fasting tHcy was 12.3 mu mol/l (SD = 8). The 51 hyperhomo cysteinemic patients (22%) were older (65.1 y) than the normal ones (55.0 y ) (p = 0.0001). The treatment was carried out properly in 46 patients (90%) . The pre-treatment mean Hcy was 23.2 (SD = 10.5) mu mol/l, and it was redu ced to 13.0 (SD = 5.9) (p = 0.0001) (mean reduction = 42.1%). By genotype, the C/C reduced from 21.0 to 13.2 mu mol/l (37%) (n = 18), the C/T from 25. 0 to 12.6 mu mol/l (46%) (n = 24), and the abnormal homozygotes T/T from 22 .7 to 14.5 umol/l (39%) (n = 4), although no statistical significant differ ences were found. In 80% of cases (37/46), tHcy values normalised. A negati ve correlation (r = -0.471) (p = 0.005) was observed between age and respon se. CONCLUSIONS: The FA/B-6/B-12 based therapy reduces in a simple, quick and e ffective way (> 40% in 6 weeks) the pathologic tHcy levels on a VTE populat ion and this is not influenced by the MTHFR genotype. As HHcy seems related with recurrences of venous thrombosis, we could speculate if it would be u seful to analyse routinely the tHcy, attempting reduction in selected cases .