Alzheimer's biomarkers unaffected by antioxidants

Adding antioxidant supplements such as vitamin E and vitamin C to the diet does not appear to affect some cerebrospinal fluid (CSF) biomarkers linked to Alzheimer's disease, according to the results of a randomized controlled trial that were published online in Archives of Neurology on Monday. First author Dr Douglas R. Galasko, from the Department of Neuroscience at the University of California San Diego, and colleagues describe how they tested for the effects of a combination of vitamin E, vitamin C and alpha-lipoic acid (E/C/ALA) on levels of CSF biomarkers. Alzheimer's disease is characterized by an abundance of beta-amyloid protein plaques that clog up the spaces between brain cells and tau-based neurofibrillary tangles that clog up the insides of brain cells. Certain proteins in spinal fluid relate to this amyloid and tau pathology and serve as reliable biomarkers for the disease. Metabolic reactions in the body produce free radicals that interact with other molecules to cause oxidative damage to proteins, membranes and genes. This influences the aging process and is also linked to disease, including cancer and Alzheimer's. In fact, oxidative damage in the brain is widespread among people with Alzheimer's disease. The body defends against oxidative damage by producing antioxidants to mop up free radicals. Genes, environment and lifestyle (eg diet, smoking, exercise) determine how well it does this. Increasing intake of antioxidants can boost the body's ability to defend itself against oxidative damage, and Galasko and colleagues write that some observational studies have suggested that a diet rich in antioxidants can reduce the risk of Alzheimer's disease, but randomized clinical trials have shown mixed results. For their study, Galasko and colleagues looked at changes in CSF biomarkers related to Alzheimer's disease and oxidative stress, cognition and function in 78 patients from the Alzheimer's Disease Cooperative Study (ADCS) Antioxidant Biomarker study. The patients were placed in three groups. One group took 800 IU per day of vitamin E (alpha-tocopherol), plus 500 mg per day of vitamin C, plus 900 mg per day of alpha -lipoic acid (E/C/ALA). Another group took 400 mg of the popular antioxidant coenzyme Q (CoQ) three times a day, while the third group was given a placebo. 66 of the patients provided serial CSF samples that were adequate for analysis during the trial, which lasted for 16 weeks. The results showed that changes in the CSF biomarkers for the amyloid and tau proteins that are related to Alzheimer's disease (alpha-beta, tau, and P-tau proteins) did not differ among the three groups. The E/C/ALA group did show a 19% reduction in the oxidative stress CSF biomarker F2-isoprostane, but the authors expressed concern at the rapid decline in cognitive function in this group, as assessed using the Mini-Mental State Examination (MMSE). "It is unclear whether the relatively small reduction in CSF F2-isoprostane level seen in this study may lead to clinical benefits in AD. The more rapid MMSE score decline raises a caution and indicates that cognitive performance would need to be assessed if a longer-term clinical trial of this antioxidant combination is considered," they conclude. They also note that while the findings suggest CoQ was safe and well tolerated, the absence of any impact on the CSF biomarkers would suggest that at the dose tested in this trail, CoQ does not affect oxidative stress or the progress of neurodegeneration.