Effects of Vitamins C and E on Oxidative Stress Markers and Endothelial Function in Patients with Systemic Lupus Erythematosus: A Double Blind, Placebo Controlled Pilot Study

LAI S. TAM, EDMUND K. LI, VIVIAN Y.F. LEUNG, JAMES F. GRIFFITH, IRIS F.F. BENZIE, PAK L. LIM, BRUCE WHITNEY, VIVIAN W.Y. LEE, KENNETH K.C. LEE, G. NEIL THOMAS, and BRIAN TOMLINSON

ABSTRACT.

Objective. Patients with systemic lupus erythematosus (SLE) experience excess morbidity and mortality due to coronary artery disease (CAD) that cannot be fully explained by the classical CAD risk factors. Among emerging CAD risk factors, oxidative stress is currently being emphasized. We evaluated the effects of longterm antioxidant vitamins on markers of oxidative stress and antioxidant defense and endothelial function in 39 patients with SLE.

Methods. Patients were randomized to receive either placebo or vitamins (500 mg vitamin C and 800 IU vitamin E daily) for 12 weeks. Markers of oxidative stress included malondialdehyde (MDA) and allantoin. Antioxidants measured included erythrocyte superoxide dismutase and glutathione peroxidase, plasma total antioxidant power (as FRAP value), and ascorbic acid and vitamin E concentrations. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery and plasma concentration of von Willebrand factor (vWF) and plasminogen activator inhibitor type 1 (PAI-1). Primary outcome of the study included the change in lipid peroxidation as revealed by MDA levels. Secondary outcomes included changes in allantoin and antioxidant levels and change in endothelial function.

Results. After treatment, plasma ascorbic acid and a-tocopherol concentrations were significantly (p < 0.05) increased only in the vitamin-treated group, associated with a significant decrease (p < 0.05) in plasma MDA. Other oxidative stress markers and antioxidant levels remained unchanged in both groups. FMD and vWF and PAI-1 levels remained unchanged in both groups.

Conclusion. Combined administration of vitamins C and E was associated with decreased lipid peroxidation, but did not affect endothelial function in patients with SLE after 3 months of therapy. (J Rheumatol 2005;32:275-82)

Key Indexing Terms:

SYSTEMIC LUPUS ERYTHEMATOSUS
OXIDATIVE STRESS
ANTIOXIDANTS
ENDOTHELIAL FUNCTION
CONTROLLED TRIAL

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From the Department of Medicine and Therapeutics, Department of Radiology, and the Clinical Immunology Unit, Hong Kong Cancer Institute; the School of Pharmacy, Chinese University of Hong Kong, Prince of Wales Hospital; the Department of Nursing and Health Sciences, Hong Kong Polytechnic University; and the Department of Community Medicine, Hong Kong University, Hong Kong.

L.S. Tam, MRCP(UK), Rheumatologist; E.K. Li, FRCP(C), Professor; B. Tomlinson, FRCP, Professor, Department of Medicine and Therapeutics; V.Y.F. Leung, PhD, Assistant Professor; J.F. Griffith, FRCR, Professor, Department of Radiology; P.L. Lim, PhD, Professor, Clinical Immunology Unit; B. Whitney, PhD, Scientific Officer, Hong Kong Cancer Institute; I.F.F. Benzie, DPhil, Professor, Department of Nursing and Health Sciences, Hong Kong Polytechnic University; V.W.Y. Lee, PharmD, Professor; K.K.C. Lee, PhD, Professor, School of Pharmacy, Chinese University of Hong Kong; G.N. Thomas, PhD, Research Assistant Professor, Department of Community Medicine, Hong Kong University.

Address reprint requests to Dr. L.S. Tam, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. E-mail: tamls_813@yahoo.com

Submitted November 28, 2003; revision accepted September 8, 2004.

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