FOLATE ADMINISTRATION REDUCES CIRCULATING HOMOCYSTEINE LEVELS IN NIDDM PATIENTS ON LONG-TERM METFORMIN TREATMENT

Objectives. Metformin treatment increases circulating homocysteine lev els. We studied whether administration of folate reduces serum total h omocysteine levels in patients on long-term metformin treatment. Desig n. A prospective, randomized, double-blind, placebo-controlled study l asting for 12 weeks and taking place in a university hospital setting. Subjects. Thirty patients treated with a metformin dose of at least 1 000 mg day(-1) for a minimum of 1 year were included. At baseline seru m total homocysteine levels were within the reference range. One patie nt who withdrew and one who died were excluded from the statistical ev aluation. Twenty-six of the remaining patients suffered from NIDDM, th e other two from hyperlipidaemia. Intervention. Patients were randomiz ed into two groups at week 0. The folate group received 0.25 mg day(-1 ) of folate in addition to 60 mg day(-1) of Fe2+, while the placebo gr oup received only 60 mg da(y-)1 of Fe2+. Main outcome measures. Eastin g homocysteine, cysteine, cysteinylglycine, vitamin B-12 and folate we re measured at week 0, 4 and 12. Changes from week 0 to week 4 and fro m week 0 to week 12 were calculated. Results, Folate administration re duced serum levels of total homocysteine in the folate group as compar ed with the placebo group by 13.9% (P < 0.01) and 21.7% (P < 0.001) at week 4 and 12, respectively. In the folate group versus the placebo g roup serum levels of vitamin B-12 increased by 9.9% (P = 0.010) and 9. 6% (P = 0.043) while folate levels increased by 96.9 and 89.9% at week 4 and 12, respectively. Conclusion. The present study indicates that the homocysteine-increasing effect of metformin can be counteracted by folate administration.