© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Influence of Folic Acid on Postprandial Endothelial Dysfunction
From the Divisions of Internal Medicine (H.W.M., W.D.E., J.-D.B.) and Nephrology and Hypertension (E.S.G.S., T.J.R.), University Hospital Utrecht; the Department of Clinical Chemistry, Sint Antonius Hospital Nieuwegein (W.B.G.); and the Department of Clinical Chemistry, University Hospital Utrecht (R.W.).
Correspondence to Prof Dr T.J. Rabelink, Department of Nephrology and Vascular Medicine, F 03.226, University Hospital Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands. E-mail t.rabelink{at}digd.azu.nl
Abstract—Triglyceride-rich lipoproteins that circulate postprandially are increasingly being recognized as potentially atherogenic. These particles also have been shown to cause endothelial dysfunction. We recently demonstrated that acute parenteral administration of folic acid restores endothelial function in vivo in patients with increased LDL cholesterol levels. In vitro data suggested 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 administration (10 mg/d for 2 weeks) on basal endothelial function as well as endothelial function on an acute fat load in 20 healthy volunteers 18 to 33 years old. Endothelial function was assessed as flow-mediated dilatation (FMD). Endothelium-independent dilatation was measured after sublingual nitroglycerin spray. Oxygen radical stress was assessed by measurement of the urinary excretion of the stable radical-damage end product malondialdehyde. During administration of placebo, FMD decreased significantly after an acute oral 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 load, 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 was also prevented during folic acid administration (absolute increase after an acute fat load during placebo, 0.11±0.1 µmol/L versus folic acid, 0.02±0.1 µmol/L, P<0.05). The response to the endothelium-independent vasodilator nitroglycerin remained unaltered throughout the study. Pretreatment with oral folic acid prevents the lipid-induced decrease in FMD as well as the lipid-induced increase in urinary radical-damage end products. Because these observations were made in healthy volunteers with normal folate and homocysteine levels, it is suggested that a higher folate intake in the general population may have vasculoprotective effects.
Key Words: endothelial function • malondialdehyde • triglyceride-rich lipoproteins • folic acid
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