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(Circulation. 2002;106:1453.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Alpha-Tocopherol Supplementation in Healthy Individuals Reduces Low-Density Lipoprotein Oxidation but Not Atherosclerosis

The Vitamin E Atherosclerosis Prevention Study (VEAPS)

Howard N. Hodis, MD; Wendy J. Mack, PhD; Laurie LaBree, MS; Peter R. Mahrer, MD; Alex Sevanian, PhD; Chao-ran Liu, MD; Ci-hua Liu, MD; Juliana Hwang, PharmD; Robert H. Selzer, MS; Stanley P. Azen, PhD, for the VEAPS Research Group^*

From the Departments of Medicine (H.N.H.) and Preventive Medicine (H.N.H., W.J.M., L.L., S.P.A.) and the Atherosclerosis Research Unit (H.N.H., W.J.M., L.L., A.S., C.-r. Liu, C.-h. Liu, J.H., R.H.S., S.P.A.), University of Southern California Keck School of Medicine; Department of Molecular Pharmacology and Toxicology (H.N.H., A.S., J.H.), University of Southern California School of Pharmacy; and Kaiser Permanente Medical Center (P.R.M.), Los Angeles, Calif; and Jet Propulsion Laboratory, California Institute of Technology (R.H.S.), Pasadena, Calif.

Correspondence to Howard N. Hodis, MD, Atherosclerosis Research Unit, 2250 Alcazar St, CSC132, Los Angeles, CA 90033. E-mail watcher{at}usc.edu

Background— Epidemiological studies have demonstrated an inverse relationship between vitamin E intake and cardiovascular disease (CVD) risk. In contrast, randomized controlled trials have reported conflicting results as to whether vitamin E supplementation reduces atherosclerosis progression and CVD events.

Methods and Results— The study population consisted of men and women 40 years old with an LDL cholesterol level 3.37 mmol/L (130 mg/dL) and no clinical signs or symptoms of CVD. Eligible participants were randomized to DL--tocopherol 400 IU per day or placebo and followed every 3 months for an average of 3 years. The primary trial end point was the rate of change in the common carotid artery far-wall intima-media thickness (IMT) assessed by computer image-processed B-mode ultrasonograms. A mixed effects model using all determinations of IMT was used to test the hypothesis of treatment differences in IMT change rates. Compared with placebo, -tocopherol supplementation significantly raised plasma vitamin E levels (P<0.0001), reduced circulating oxidized LDL (P=0.03), and reduced LDL oxidative susceptibility (P<0.01). However, vitamin E supplementation did not reduce the progression of IMT over a 3-year period compared with subjects randomized to placebo.

Conclusions— The results are consistent with previous randomized controlled trials and extend the null results of vitamin E supplementation to the progression of IMT in healthy men and women at low risk for CVD.

Key Words: coronary disease • atherosclerosis • antioxidants • trials

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