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L-Folic Acid Supplementation in Healthy Postmenopausal Women: Effect on Homocysteine and Glycolipid Metabolism

Department of Obstetrics and Gynecology (P.V., C.P., R.S., F.C., A.L.), and Institute of Biological Chemistry (M.R., C.M.), Catholic University of Sacred Heart, 00168 Rome, Italy; and National Research Center, Institute for System Analysis and Informatics Biomatlab (S.P.), 00168 Rome, Italy

Address all correspondence and requests for reprints to: Dr. Antonio Lanzone, Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, L. go Gemelli 8, 00168 Rome, Italy. E-mail: alanzone{at}rm.unicatt.it.

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

Objective: The aim of this study was to examine the effect of L-folic acid supplementation on homocysteine (Hcy) and related thiols, such as cysteine (Cys) and Cys-glycine (Cys-Glyc) pathways and their relationship to glucose, insulin, and lipidic metabolism in normoinsulinemic postmenopausal women.

Design: This study was a randomized placebo, not double-blind, trial.

Setting: The study was performed in an academic research center.

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

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

Main Outcome Measure(s): Hcy, Cys, and Cys-Glyc, basally and after a methionine loading test, were measured. Basal insulin, glucose, and peptide C levels as well as area under the curve for insulin, area under the curve for peptide, hepatic insulin extraction, and metabolic index were assayed. The total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels and the cholesterol/HDL and LDL/HDL ratios were also measured.

Results: The total basal Hcy concentration and the plasma postmethionine loading Hcy values were significantly decreased (P < 0.01) in L-folic acid-treated patients, whereas postmethionine loading Cys-Glyc levels were markedly increased (P < 0.02). Furthermore, L-folic acid intake induced a significant improvement in carbohydrate metabolism through an increase in fractional hepatic insulin extraction (P < 0.05) and peripheral insulin sensitivity (P < 0.02) in normoinsulinemic women. HDL levels considerably increased, inducing an improvement in other atherosclerotic indexes, such as cholesterol/HDL and LDL/HDL ratios (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.