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(Circulation. 2003;108:1059.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Antioxidant Vitamins C and E Improve Endothelial Function in Children With Hyperlipidemia

Endothelial Assessment of Risk from Lipids in Youth (EARLY) Trial

Marguerite M. Engler, PhD; Mary B. Engler, PhD; Mary J. Malloy, MD; Elisa Y. Chiu, RN, MS; Monique C. Schloetter, RD, MS; Steven M. Paul, PhD; Markus Stuehlinger, MD; Ken Y. Lin; John P. Cooke, MD, PhD; Jason D. Morrow, MD; Paul M Ridker, MD; Nader Rifai, PhD; Elizabeth Miller; Joseph L. Witztum, MD; Michele Mietus-Snyder, MD

From the University of California at San Francisco (M.M.E., M.B.E., M.J.M., E.Y.C., M.C.S., S.M.P., M.M.-S.), San Francisco, Calif; University Clinic of Innsbruck (M.S.), Division of Cardiology, Innsbruck, Austria; Stanford University (K.Y.L., J.P.C.), Division of Cardiovascular Medicine, Stanford, Calif; Vanderbilt University Medical Center (J.D.M.), Division of Clinical Pharmacology, Nashville, Tenn; Harvard Medical School (P.M.R., N.R.), Brigham & Women’s Hospital, Boston, Mass; and the University of California at San Diego (E.M., J.L.W.), San Diego, Calif.

Correspondence to Marguerite M. Engler, PhD, Professor and Vice Chair, University of California, San Francisco, 2 Koret Way, Rm N631, San Francisco, CA 94143-0610. E-mail marguerite.engler{at}nursing.ucsf.edu

Received July 11, 2003; de novo received May 9, 2003; accepted June 16, 2003.

Background— Hyperlipidemia is associated with endothelial dysfunction, an early event in atherosclerosis and predictor of risk for future coronary artery disease. Epidemiological studies suggest that increased dietary intake of antioxidants reduces the risk of coronary artery disease. The purpose of this study was to determine whether antioxidant vitamin therapy improves endothelial function and affects surrogate biomarkers for oxidative stress and inflammation in hyperlipidemic children.

Methods and Results— In a randomized, double-blind, placebo-controlled trial, the effects of antioxidant vitamins C (500 mg/d) and E (400 IU/d) for 6 weeks and the National Cholesterol Education Program Step II (NCEP-II) diet for 6 months on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery were examined in 15 children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). Antioxidant vitamin therapy improved FMD of the brachial artery compared with baseline (P<0.001) without an effect on biomarkers for oxidative stress (autoantibodies to epitopes of oxidized LDL, F₂-isoprostanes, 8-hydroxy-2'-deoxyguanosine), inflammation (C-reactive protein), or levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide.

Conclusions— Antioxidant therapy with vitamins C and E restores endothelial function in hyperlipidemic children. Early detection and treatment of endothelial dysfunction in high-risk children may retard the progression of atherosclerosis.

Key Words: lipids • nutrition • pediatrics • prevention

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