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Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures


Galasko, Douglas R, Peskind, Elaine, Clark, Christopher M., Quinn, Joseph F., Ringman, John M., Jicha, Gregory A., Cotman, Carl, Cottrell, Barbara, Montine, Thomas J., Thomas, Ronald G., Aisen, Paul


Archives Of Neurology, Volume: 69, No.: 7, Pages.: 836-841

Year of Publication



Objective: To evaluate whether antioxidant supplements presumed to target specific cellular compartments affected cerebrospinal fluid (CSF) biomarkers.; Design: Double-blind, placebo-controlled clinical trial.; Setting: Academic medical centers.; Participants: Subjects with mild to moderate Alzheimer disease.; Intervention: Random assignment to treatment for 16 weeks with 800 IU/d of vitamin E (α-tocopherol) plus 500 mg/d of vitamin C plus 900 mg/d of α-lipoic acid (E/C/ALA); 400 mg of coenzyme Q 3 times/d; or placebo.; Main Outcome Measures: Changes from baseline to 16 weeks in CSF biomarkers related to Alzheimer disease and oxidative stress, cognition (Mini-Mental State Examination), and function (Alzheimer’s Disease Cooperative Study Activities of Daily Living Scale).; Results: Seventy-eight subjects were randomized; 66 provided serial CSF specimens adequate for biochemical analyses. Study drugs were well tolerated, but accelerated decline in Mini-Mental State Examination scores occurred in the E/C/ALA group, a potential safety concern. Changes in CSF Aβ42, tau, and P-tau(181) levels did not differ between the 3 groups. Cerebrospinal fluid F2-isoprostane levels, an oxidative stress biomarker, decreased on average by 19% from baseline to week 16 in the E/C/ALA group but were unchanged in the other groups.; Conclusions: Antioxidants did not influence CSF biomarkers related to amyloid or tau pathology. Lowering of CSF F2-isoprostane levels in the E/C/ALA group suggests reduction of oxidative stress in the brain. However, this treatment raised the caution of faster cognitive decline, which would need careful assessment if longer-term clinical trials are conducted.; Trial Registration: Identifier: NCT00117403.;


acid, activities of daily living, administration & dosage, aged, aged, 80 and over, alzheimer disease, analogs derivatives, antioxidants, ascorbic acid, biological markers, c, cerebrospinal, cerebrospinal fluid, cholinesterase inhibitors, coenzyme, csf, dietary supplements, double-blind method, drug therapy, e, female, fluid, humans, levels, male, memantine, mental status schedule, middle aged, peptide fragments, q, retrospective studies, tau proteins, therapeutic use, thioctic acid, ubiquinone, vitamin

Countries of Study


Types of Dementia

Alzheimer’s Disease

Types of Study

Randomised Controlled Trial

Type of Outcomes

ADLs/IADLs, Cognition, Other

Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions