Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia.
OBJECTIVE
The purpose of this study was (a) to study whether a folate and vitamin B12 treatment, aimed at decreasing homocysteine levels, might ameliorate insulin resistance and endothelial dysfunction in patients with metabolic syndrome according to the National Cholesterol Education Program-Adult Treatment Panel-III criteria and (b) to evaluate whether, under these metabolic conditions, there is a relationship between hyperhomocysteinemia and insulin resistance.


METHODS
A double-blind, parallel, identical placebo-drug, randomized study was performed for 2 months in 50 patients. Patients were randomly allocated to two groups. In group 1, patients were treated with diet plus placebo for 2 months. In group 2, patients were treated with diet plus placebo for 1 month, followed by diet plus folic acid (5 mg/day) plus vitamin B12 (500 microg/day) for another month.


RESULTS
In group 2, folate treatment significantly decreased homocysteine levels by 27.8% (12.2+/-1.2 vs 8.8+/-0.7 micromol/l; P<0.01). A significant decrement was observed for insulin levels (19.9+/-1.7 vs 14.8+/-1.6 microU/ml; P<0.01) accompanied by a 27% reduction in the homeostasis model assessment levels. A positive relationship was found between the decrement of homocysteine and insulin levels (r=0.60; P<0.002). In parallel, endothelial dysfunction significantly improved in the treated group, since post-ischemic maximal hyperemic vasodilation increased by 29.8% and cGMP by 13.6% while asymmetrical dimethylarginine levels decreased by 21.7%. On the contrary, in group 1 patients, treated with placebo, no changes were shown in any of the variables.


CONCLUSIONS
Folate and vitamin B12 treatment improved insulin resistance and endothelial dysfunction, along with decreasing homocysteine levels, in patients with metabolic syndrome, suggesting that folic acid has several beneficial effects on cardiovascular disease risk factors.
Cardiovascular and Metabolic Rehabilitation Unit, Rehabilitation and Functional Reeducation Division, Scientific Institute H. San Raffaele, Italy.
Emanuela
E
Setola
Lucilla Domenica
LD
Monti
Elena
E
Galluccio
Altin
A
Palloshi
Gabriele
G
Fragasso
Rita
R
Paroni
Fulvio
F
Magni
Emilia Paola
EP
Sandoli
Pietro
P
Lucotti
Sabrina
S
Costa
Isabella
I
Fermo
Marzia
M
Galli-Kienle
Anna
A
Origgi
Alberto
A
Margonato
Piermarco
P
Piatti
D000368:Aged; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006397:Hematinics / Q000008:administration & dosage*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D012307:Risk Factors; D014805:Vitamin B 12 / Q000008:administration & dosage*
D006397:Hematinics; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12