Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment.
OBJECTIVE
Metformin treatment increases circulating homocysteine levels. We studied whether administration of folate reduces serum total homocysteine levels in patients on long-term metformin treatment.


METHODS
A prospective, randomized, double-blind, placebo-controlled study lasting for 12 weeks and taking place in a university hospital setting.


METHODS
Thirty patients treated with a metformin dose of at least 1000 mg day-1 for a minimum of 1 year were included. At baseline serum total homocysteine levels were within the reference range. One patient who withdrew and one who died were excluded from the statistical evaluation. Twenty-six of the remaining patients suffered from NIDDM, the other two from hyperlipidaemia.


METHODS
Patients were randomized 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 group received only 60 mg day-1 of Fe2+.


METHODS
Fasting homocysteine, cysteine, cysteinylglycine, vitamin B12 and folate were measured at week 0, 4 and 12. Changes from week 0 to week 4 and from week 0 to week 12 were calculated.


RESULTS
Folate administration reduced serum levels of total homocysteine in the folate group as compared 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 group serum levels of vitamin B12 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.


CONCLUSIONS
The present study indicates that the homocysteine-increasing effect of metformin can be counteracted by folate administration.
Aarsand
A K
AK
Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Carlsen
S M
SM
D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004151:Dipeptides / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006397:Hematinics / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood* / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000097:blood
D004151:Dipeptides; D006397:Hematinics; D007004:Hypoglycemic Agents; D006710:Homocysteine; C028505:cysteinylglycine; D008687:Metformin; D005492:Folic Acid; D014805:Vitamin B 12