Effect of high-dose alpha-tocopherol supplementation on biomarkers of oxidative stress and inflammation and carotid atherosclerosis in patients with coronary artery disease.
BACKGROUND
Oxidative stress and inflammation are crucial in atherogenesis. alpha-Tocopherol is both an antioxidant and an antiinflammatory agent.


OBJECTIVE
We evaluated the effect of RRR-alpha-tocopherol supplementation on carotid atherosclerosis in patients with stable coronary artery disease (CAD) on drug therapy.


METHODS
Randomized, controlled, double-blind trial compared RRR-alpha-tocopherol (1200 IU/d for 2 y) with placebo in 90 patients with CAD. Intimal medial thickness (IMT) of both carotid arteries was measured by high-resolution B-mode ultrasonography at 0, 1, 1.5, and 2 y. At 6-mo intervals, plasma alpha-tocopherol concentrations, C-reactive protein (CRP), LDL oxidation, monocyte function (superoxide anion release, cytokine release, and adhesion to endothelium), and urinary F(2)-isoprostanes were measured.


RESULTS
alpha-Tocopherol concentrations were significantly higher in the alpha-tocopherol group but not in the placebo group. High-sensitivity CRP concentrations were significantly lowered with alpha-tocopherol supplementation than with placebo (32%; P < 0.001). alpha-Tocopherol supplementation significantly reduced urinary F(2)-isoprostanes (P < 0.001) and monocyte superoxide anion and tumor necrosis factor release compared with baseline and placebo (P < 0.001). No significant difference was observed in the mean change in total carotid IMT in the placebo and alpha-tocopherol groups. In addition, no significant difference in cardiovascular events was observed (P = 0.21).


CONCLUSIONS
High-dose RRR-alpha-tocopherol supplementation in patients with CAD was safe and significantly reduced plasma biomarkers of oxidative stress and inflammation but had no significant effect on carotid IMT during 2 y.
Devaraj
Sridevi
S
University of Texas Southwestern Medical Center, Dallas, TX, USA.
Tang
Rong
R
Adams-Huet
Beverley
B
Harris
Andrea
A
Seenivasan
Thanalakshmi
T
de Lemos
James A
JA
Jialal
Ishwarlal
I
D000368:Aged; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D002340:Carotid Artery Diseases / Q000517:prevention & control*; D003324:Coronary Artery Disease / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D019587:Dietary Supplements; D004311:Double-Blind Method; D028441:F2-Isoprostanes / Q000652:urine; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011446:Prospective Studies; D024502:alpha-Tocopherol / Q000008:administration & dosage*
D015415:Biomarkers; D016207:Cytokines; D028441:F2-Isoprostanes; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein; D024502:alpha-Tocopherol