Antioxidant vitamins are being widely discussed as a therapeutic option in Alzheimer's disease (AD). We recently found that supplementation with vitamin C and E over 1 month leads to an increase of their levels in cerebrospinal fluid (CSF) and a reduction of CSF lipid peroxidation. In the present study, we followed-up the biochemical and clinical effect of vitamin C and E supplementation in an open clinical trial over 1 year. Twelve AD patients stably taking a cholinesterase inhibitor were supplemented with vitamin C (1,000 mg/day) and E (400 I.U./day), while 11 patients taking cholinergic medication only served as a control group. Cognition was assessed at baseline, after 6 months and 12 months using the Mini-Mental State Examination; a more detailed testing of cognitive function was performed at baseline and after 12 months. From eight of the vitamin-supplemented patients, CSF was taken at baseline, after 1 month and after 1 year to measure the antioxidant effect of vitamin supplementation on CSF lipids using a recently established in vitro oxidation assay. CSF antioxidant vitamins were significantly increased after 1 month and 1 year of supplementation, while in vitro oxidation of CSF lipids was significantly reduced only after 1 year of the supplementation. The clinical course of AD did not significantly differ between the vitamin and the control group. We conclude that supplementation with vitamins E and C did not have a significant effect on the course of AD over 1 year despite of a limited antioxidant effect that could be observed in CSF.