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CLINICAL RESEARCH

long-term effect of combined vitamins e and c on coronary and peripheral endothelial function

Scott Kinlay, MBBS, FACC^*,*, Dominik Behrendt, MD^*, James C. Fang, MD, FACC^*, Danielle Delagrange, MS^*, Jason Morrow, MD, Joseph L. Witztum, MD, Nader Rifai, PhD, Andrew P. Selwyn, MD, FACC^*, Mark A. Creager, MD, FACC^* and Peter Ganz, MD, FACC^*

^* Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Vanderbilt University, Nashville, Tennessee, USA
University of California at San Diego, La Jolla, California, USA
Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA

Manuscript received June 3, 2003; revised manuscript received August 1, 2003, accepted August 6, 2003.

^* Reprint requests and correspondence: Dr. Scott Kinlay, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
skinlay{at}partners.org

OBJECTIVES: We tested whether long-term administration of antioxidant vitamins C and E improves coronary and brachial artery endothelial function in patients with coronary artery disease (CAD).

BACKGROUND: Endothelial function is a sensitive indicator of vascular health. Oxidant stress and oxidized low-density lipoprotein (LDL) impair endothelial function by reducing nitric oxide bioavailability in the artery wall.

METHODS: We randomly assigned 30 subjects with CAD to combined vitamin E (800 IU per day) and C (1,000 mg per day) or to placebos in a double-blind trial. Coronary artery endothelial function was measured as the change in coronary artery diameter to acetylcholine infusions (n = 18 patients), and brachial artery endothelial function was assessed by flow-mediated dilation (n = 25 patients) at baseline and six months. Plasma markers of oxidant stress (oxidized LDL and autoantibodies) were also measured.

RESULTS: Plasma alpha-tocopherol (p < 0.001) and ascorbic acid (p < 0.02) increased with active therapy. Compared to placebo, there was no improvement in coronary and brachial endothelial vasomotor function over six months. Although vitamins C and E tended to reduce F2-isoprostanes (p = 0.065), they failed to alter oxidized LDL or autoantibodies to oxidized LDL.

CONCLUSIONS: Long-term oral vitamins C and E do not improve key mechanisms in the biology of atherosclerosis or endothelial dysfunction, or reduce LDL oxidation in vivo.

Abbreviations and Acronyms   CAD = coronary artery disease   IgG = immunoglobulin G   LDL = low-density lipoprotein

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