Published on: March 19, 2012
by Crystal Phend for Medpage Today
Antioxidant supplements don’t appear to have an impact on cerebrospinal fluid (CSF) biomarkers related to Alzheimer’s disease, a clinical trial determined.
The combination of vitamin E, vitamin C, and alpha-lipoic acid did not lower levels of the amyloid and tau proteins that make up the plaques and tangles seen in the brain with Alzheimer’s disease, Douglas R. Galasko, MD, of the University of California San Diego, and colleagues found.
The combination did reduce CSF levels of the oxidative stress biomarker F2-isoprostane by 19% but raised a safety concern with faster decline in cognitive scores, they reported online in the Archives of Neurology.
The popular antioxidant coenzyme Q (CoQ) had no significant impact on any CSF measures in the Alzheimer’s Disease Cooperative Study antioxidant biomarker trial. Oxidative damage is widespread in the brain in Alzheimer’s disease and contributes to neuronal damage, Galasko’s group explained.
Some prior observational evidence has pointed to lower Alzheimer’s risk with an antioxidant-rich diet, although prevention trials with supplements have had mixed results, they noted.
Their study included 78 adults with mild to moderate Alzheimer’s randomly assigned to double-blind treatment over 16 weeks with the combination of 800 IU vitamin E, 500 mg vitamin C, and 900 mg of alpha-lipoic acid once a day; CoQ alone at a dose of 400 mg three times a day; or placebo.
Vitamins C and E act as antioxidants by controlling dangerous free radicals produced when oxygen reacts with certain molecules, while alpha-lipoic acid spurs production of many antioxidant enzymes in the body. CoQ is an antioxidant that helps protect mitochondria from oxidation.
Serial CSF specimens collected from 66 of the participants showed only small changes from baseline.
Beta-amyloid 42, which accumulates to forms plaques in the Alzheimer’s brain, declined by 8 pg/mL from a baseline of 190 pg/mL with the antioxidant combination and by 15 pg/mL from a baseline of 185 in the CoQ group, but neither was a significant difference from placebo.
Tau protein, which forms neurofibrillary tangles in the brain with Alzheimer’s, fell by 23 pg/mL with the antioxidant combination from a baseline of 123 and by 9 pg/mL from a baseline of 109 in the CoQ group, but again neither differed from changes with placebo.
Levels of tau phosphorylated at a specific site (P-tau181) likewise declined slightly over the study period for the two antioxidant groups but without a significant difference from placebo.
The one significant change was in CSF levels of the oxidative marker F2-isoprostane, which is stable oxidized arachidonic acid.
The vitamin C and E plus alpha-lipoic acid group saw a 7 pg/mL reduction in F2-isoprostane from a baseline of 38 over the 16 weeks of treatment (P=0.04). The other groups showed no change.
“It is unclear whether the relatively small reduction in CSF F2-isoprostane level seen in this study may lead to clinical benefits in Alzheimer disease,” the group cautioned.
Cognition, measured with the Mini-Mental State Examination, didn’t improve in any of the groups. In fact, the decline in scores appeared accelerated in the antioxidant combination group, with a change of -4.6 points over the 16 weeks compared with -2.3 to -2.4 in the other two groups.
The researchers highlighted that as a potential safety concern that needs further careful assessment if longer-term trials are considered. The antioxidants were otherwise well tolerated.
Function, as measured on the Alzheimer’s Disease Cooperative Study Activities of Daily Living Scale, didn’t change in any group.
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Two blood markers, phosphorylated tau 217 (p-tau217) and phosphorylated tau 181 (p-tau181), showed strong diagnostic performances for Alzheimer’s disease and discriminated Alzheimer’s from frontotemporal lobar denervation (FTLD) syndromes and normal cognition, a retrospective study...
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