Influence of folic acid on postprandial endothelial dysfunction

Triglyceride-rich lipoproteins that circulate postprandially are increasing ly being recognized as potentially atherogenic. These particles also have b een shown to cause endothelial dysfunction. We recently demonstrated that a cute parenteral administration of folic acid restores endothelial function in vivo in patients with increased LDL cholesterol levels. In vitro data su ggested that this effect could be mediated by a reduction of radical stress . In the present study, therefore, we evaluated the effect of an acute oral fat load on both endothelial function and oxygen radical production. Next, we studied whether 2 weeks of pretreatment with 10 mg folic acid PO could prevent these fat-induced changes. We conducted a prospective, randomized, placebo-controlled study to evaluate the effect of oral folic acid administ ration (10 mg/d for 2 weeks) on basal endothelial function as well as endot helial function on an acute fat load in 20 healthy volunteers 18 to 33 year s old. Endothelial function was assessed as flow-mediated dilatation (FMD). Endothelium-independent dilatation was measured after sublingual nitroglyc erin spray. Oxygen radical stress was assessed by measurement of the urinar y excretion of the stable radical-damage end product malondialdehyde. Durin g administration of placebo, FMD decreased significantly after an acute ora l fat load, with a median from 10.6% (8.3% to 12.2%) to 5.8% (3.0% to 10.2% ), P<0.05. During folic acid administration, FMD was unaffected by a fat lo ad, with a median from 9.6% (7.1% to 12.8%) to 9.9% (7.5% to 14.1%), P=NS, The increase in malondialdehyde excretion in the urine after fat loading wa s also prevented during folic acid administration (absolute increase after an acute fat load during placebo, 0.11+/-0.1 mu mol/L versus folic acid, 0. 02+/-0.1 mu mol/L, P<0.05), The response to the endothelium-independent vas odilator nitroglycerin remained unaltered throughout the study. Pretreatmen t with oral folic acid prevents the lipid-induced decrease in FMD as well a s the lipid-induced increase in urinary radical-damage end products. Becaus e these observations were made in healthy volunteers with normal folate and homocysteine levels, it is suggested that a higher folate intake in the ge neral population may have vasculoprotective effects.