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

Randomized clinical trial at 12 centers in the United States enrolling ambulatory adults with probable Alzheimer disease and mild-to-moderate cognitive impairment. Participants had caregiver supervision, imaging consistent with Alzheimer disease without significant vascular disease, and stable anti-Alzheimer treatment; allocation was 28:25:25 across E/C/ALA, CoQ, and placebo.

This 16-week, multicenter, placebo-controlled trial tested two oral antioxidant regimens in probable Alzheimer disease. One active arm received vitamin E 800 IU/day, vitamin C 500 mg/day, and alpha-lipoic acid 900 mg/day, each given 3 times/day in encapsulated form; the other received coenzyme Q 400 mg 3 times/day as chewable wafers.

Coenzyme Q was safe and well tolerated but did not improve cerebrospinal fluid biomarkers or clinical outcomes. The vitamin E plus vitamin C plus alpha-lipoic acid regimen did not change CSF Aβ42, total tau, or phosphorylated tau 181, but it reduced CSF F2-isoprostanes by about 19%, suggesting an antioxidant effect. That biomarker change did not translate into benefit: MMSE declined more with E/C/ALA than with placebo (−2.8 vs −1.0 and −0.9), and ADCS-ADL also declined more (−4.6 vs −2.4 and −2.3). No significant differences in adverse events were reported, but the findings do not support further development of CoQ and raise caution about E/C/ALA because of possible adverse cognitive effects.

Small active-arm sample sizes and short 16-week follow-up limit power to detect clinical benefit or safety signals. Baseline CSF biomarker values were not provided, and the study included concomitant supplement use in a substantial minority of participants, which may add variability. The single biomarker improvement seen with E/C/ALA did not correspond to functional benefit, limiting clinical interpretability.