BioFactors 24 (2005) 265–274 265 IOS Press Effects of vitamin C and aspirin in ischemic stroke-related lipid peroxidation: Results of the AVASAS (Aspirin Versus Ascorbic acid plus Aspirin in Stroke) Study M. Cristina Polidori a,1 , Domenico Pratic ´ o b,1 , Tiziana Ingegni c , Elena Mariani c , Liana Spazzafumo d , Paola Del Sindaco e , Roberta Cecchetti c , Yuemang Yao b , Stefano Ricci f , Antonio Cherubini c , Wilhelm Stahl a , Helmut Sies a , Umberto Senin c and, Patrizia Mecocci c,∗ for the AVASASStudy Group 2 a Institute of Biochemistry and Molecular Biology I, Heinrich-Heine University, D ¨ usseldorf, Germany b Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA c Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy d INRCA (National Institute for Research and Cure for the Elderly), Ancona, Italy e Department of Internal Medicine, Hospital of Todi (Perugia), Italy f Stroke Service, ASL 2, Perugia, Italy Abstract. A condition of oxidative stress is known to occur in ischemic stroke, the current therapeutic intervention of which is largely limited to thrombolysis. To assess the effect of vitamin C – in conjunction to aspirin – in ischemic stroke-related lipid peroxidation, we measured plasma levels of ascorbate, of 8,12-isoprostanes F 2α-VI (8,12-iPF2α-VI) and activities and levels of a broad spectrum of antioxidant enzymes and micronutrients in stroke patients randomized to receive, from stroke onset and up to three months, either vitamin C (200 mg/day) plus aspirin (300 mg/day) or only aspirin (300 mg/day). By the end of the first week, patients treated with vitamin C plus aspirin had higher vitamin C levels (p =0.02) and lower 8,12-iPF2α-VI levels (p =0.01) than patients treated with aspirin alone. The significance was maintained for the increase of vitamin C after three months of therapy (p< 0.01). The clinical functional outcome for both groups of patients similarly ameliorated after three months of treatment. We conclude that vitamin C, at the dose of 200 mg/day and in conjunction with aspirin, significantly decreases ischemic stroke-related lipid peroxidation in humans. Further studies are warranted to clarify whether the use of vitamin C may add clinical long-term beneficial effects in patients with stroke. Keywords: Aspirin, ischemic stroke, isoprostanes, oxidative stress, vitamin C Abbreviations: 8,12-iPF2α-VI: 8,12-isoprostanes F2α-VI; ASA: acetylsalicilic acid; BI: Barthel Index; GPx: glutathione peroxidase; HPLC: high-performance liquid chromatography; RBC: red blood cells; SOD: superoxide dismutase 1 M.C.P. and D.P. contributed equally to this research project. 2 C. Denbech, Department of Internal Medicine, Hospital of Castiglion del Lago (Perugia), Italy; M.G. Celani, E. Righetti, Department of Internal Medicine, Hospital of Citt´ a della Pieve (Perugia), Italy; B. Biscottini, Department of Internal Medicine, Hospital of Todi (Perugia), Italy. * Address for correspondence: Patrizia Mecocci, MD PhD, Institute of Gerontology and Geriatrics, Department of Clinical 0951-6433/05/$17.00  2005 – IOS Press and the authors. All rights reserved