Context. Hyperhomocisteinemia as well as alterations of the glycemic and lipidic metabolism are recognized as risk factors for cardiovascular diseases.

Objective. To study the effect of L-folic acid supplementation on homocysteine (Hcy) and related thiols such as cysteine (Cys) and cysteinil-glicine (Cys-Glyc) pathways and their relationship with glucose, insulin and lipidic metabolism in normoinsulinemic postmenopausal women.

Design. Randomized placebo not double blind trial.

Setting. Accademic research center.

Patients or Other Partecopants. Twenty healthy postmenopausal women were selected. No patient was taking drugs known to affect the lipid or glucose metabolism.

Intervention (s). Patients underwent two hospitalizations before and after 8 weeks of L-acid folic (7.5 mg/d) or placebo administration. The glycemic metabolism was studied by an oral glucose tolerance test (OGTT) and a hyperinsulinemic euglycemic clamp. The homocysteine metabolism was studied by a standardized oral methionine loading test.

Main Outcome Measure (s). Homocysteine, cysteine (Cys) and cysteinil-glicine (Cys-Glyc) basal and post metionine loading test were measured. Basal insulin, glucose, Pep-C levels as well as AUC-I, AUC -pep, FHIE, M were assayed. The total Col, HDL LDL levels and the Cholesterol/HDL and LDL/HDL ratio were also measured

Results. Total basal homocysteine (tHcy) concentration and plasma post-methionine loading Hcy values significantly decreased (P < 0.01) in L-folic acid treated patients whereas post methionine loading Cys-Glyc levels markedly increased (P < 0.02). Furthermore L-folic acid intake induced a significant improvement of the carbohydrate metabolism through an increase of fractional hepatic insulin extraction (P < 0.05) and peripheral insulin sensitivity (P < 0.02) in normoinsulinemic women. HDL levels considerably increased inducing an improvement of other atherosclerotic indexes such as Cholesterol/HDL and LDL/HDL ratio (P < 0.03).

Conclusions. These results show that folic acid supplementation lowers plasma Hcy levels and improves insulin and lipid metabolism reducing the risk of cardiovascular disease.