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February 2013

Antioxidants for Alzheimer Disease—Reply

Author Affiliations

Author Affiliations: Department of Neurosciences, University of California, San Diego, La Jolla.

JAMA Neurol. 2013;70(2):270-271. doi:10.1001/jamaneurol.2013.935

In reply

We thank Dr Praticò for his correspondence. The doses of vitamins and coenzyme Q (CoQ) that we used are consistent with studies where plasma levels were monitored.1,2 We evaluated compliance by pill counts at visits at weeks 8 and 16, which indicated more than 90% compliance for subjects analyzed in each treatment arm.3 Subjects and caregivers denied taking additional (nonpermitted) antioxidants during the study. In view of the absence of effects on cerebrospinal fluid (CSF) biomarkers in our study, we did not pursue plasma or CSF measures of CoQ. Although plasma levels of CoQ show proportional increases in relation to dosing,2 the value of plasma or CSF levels to predict brain levels of this highly lipophilic coenzyme are not clear. Equivalent doses of CoQ from different suppliers may result in widely different blood levels,2 and we were not able to explore this important aspect of CoQ bioavailability before designing our study. Attempts to improve the bioavailability of CoQ are underway,4 and further studies of novel preparations with better brain penetration may be worth pursuing in the future. The question of whether dietary or low doses of supplemental vitamins and CoQ that were permitted could have masked changes in oxidative stress responses due to the treatment interventions is potentially interesting, although difficult to test definitively. Comparison groups of patients with Alzheimer disease and healthy control subjects who were not taking any antioxidant supplements at all would be necessary to address this question. The F2-isoprostane assays were run in a single batch; a reference range for F2-isoprostanes in CSF from healthy subjects run by Montine Laboratory during the same period was 15 pg/mL to 40 pg/mL (90% CI).

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