METFORMIN INCREASES TOTAL SERUM HOMOCYSTEINE LEVELS IN NONDIABETIC MALE-PATIENTS WITH CORONARY HEART-DISEASE

It is known that the metabolism of homocysteine (Hey) depends on the v itamins B-6, B-12, and folate, and furthermore that metformin reduces serum vitamin B-12 levels. In order to investigate whether metformin t reatment affects serum total Hey (tHcy) levels we performed an open, p rospective, randomised study in 60 non-diabetic male patients with car diovascular disease. After a 4-week run-in period with lovastatin 40 m g day(-1), and diet and lifestyle advice, patients were randomised int o two groups, both continuing the run-in treatment. One group received metformin up to 2000 mg day(-1), whereas the control group got no add itional treatment. After 12 and 40 weeks of metformin treatment, tHcy levels increased moderately but significantly by 7.2% (p<0.05) and 13. 8% (p<0.05) in the metformin group relative to the control group, wher eas serum vitamin B-12 levels decreased by 13.4% (p<0.0005) and 17.7% (p<0.0005), respectively. Serum folate levels did not change after 12 weeks, but decreased by 8.0% after 40 weeks (p=0.061) relative to the control group. Serum levels of total cysteine and methylmalonic acid ( MMA) did not change. In conclusion, metformin treatment increased tHcy levels and decreased levels of vitamin B-12 and folate. Since MMA Sev ers were unchanged, it remains an open question whether the increase i n tHcy levels is secondary to reduced vitamin B-12 levels, folate leve ls or a combination of both.