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Impaired NO-dependent vasodilation in patients with Type II (non-insulin-dependent) diabetes mellitus is restored by acute administration of folate Folate supplements may help protect type 2 diabetics from cardiovascular damage associated with endothelial nitric oxide synthase uncoupling.
Endothelium-derived nitric oxide protects against vascular damage associated with atherosclerosis, report researchers at the University Medical Centre in Utrecht, in the Netherlands. Hyperglycemia, which causes oxygen radical stress, has been associated with endothelial nitric oxide synthase uncoupling – both of which can decrease the availability of nitric oxide.
The researchers, R. W. van Etten and colleagues, previously showed that folate can boost nitric oxide levels in vitro by reversing endothelial nitric oxide synthase uncoupling. They now report similar findings from a clinical study involving 23 patients with type 2 diabetes and 21 control subjects.
The researchers evaluated the effect of local, intra-arterial administration of the active form of folic acid, 5-methyltetrahydrofolate (5-MTHF), on forearm blood flow in patients and controls, who were matched for age, sex, blood pressure, body mass index, weight and smoking habits. They then infused the patients and controls with serotonin, to stimulate nitric oxide-dependent vasodilation, and sodium nitroprusside, to stimulate endothelium-independent vasodilation.
Serotonin-induced vasodilation was blunted and nitroprusside-induced vasodilation was mildly reduced in the diabetic patients, compared with control subjects, the researchers reported. While 5-MTHF improved nitric oxide-mediated vasodilation in the patients, it had no effect on forearm blood flow in the control subjects.
These findings suggest that folate can be used to improve nitric oxide status and to restore endothelial function in patients with type 2 diabetes. "Our results provide a strong rationale for the initiation of studies that investigate whether supplementation with folic acid prevents future cardiovascular events in this patient group," the researchers concluded. Diabetologia (2002) 45: 1004-1010