Vitamin E Outpaces Memantine in Mild-to-Moderate Alzheimer Disease

Summary and Comment |
January 7, 2014

Vitamin E Outpaces Memantine in Mild-to-Moderate Alzheimer Disease

  1. Brandy R. Matthews, MD

High-dose vitamin E modestly slows functional decline without associated increase in mortality, but clinical relevance is unclear.

  1. Brandy R. Matthews, MD

Both memantine and vitamin E have demonstrated benefits in patients with moderate-to-severe Alzheimer disease (AD). However, multiple studies of memantine in mild AD revealed no clear benefit, and vitamin E used in normal cognition and mild cognitive impairment does not affect progression to AD. Now, researchers have tested the effects of vitamin E and memantine in more than 600 veterans (97% men; 86% white) diagnosed with mild-to-moderate AD (Mini Mental State Examination score range, 12–26) already treated with stable doses of acetylcholinesterase inhibitor therapy (donepezil, 65%; galantamine, 32%; rivastigmine, 3%). Participants were randomized to receive 2000 IU vitamin E, 20 mg memantine, 2000 IU vitamin E plus 20 mg memantine, or placebo daily. The primary outcome measure was functional decline, measured with the Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) Inventory; secondary outcomes were measures of cognition and behavior.

During a mean follow-up of 2.27 years, the vitamin E group had a statistically significant 19% annual slowing of functional decline (3.15 units on the ADCS-ADL Inventory) compared with the placebo group. Memantine had no significant benefit on any of the preselected outcome measures. No treatment group had significant benefits on any secondary outcome measures. The vitamin E group had no greater mortality or adverse-event rate than the other groups.


The safety outcomes with high-dose vitamin E (2000 IU daily) in this particular patient population (white male veterans with mild-to-moderate Alzheimer disease) are encouraging. Unfortunately, the clinical relevance of the reported slowing of functional decline with vitamin E is difficult to interpret, given the absence of effect in patients treated with both vitamin E and memantine and the lack of supporting findings in the numerous cognitive, behavioral, and functional secondary outcomes. I will continue to advise my patients with mild-to-moderate AD to take no more than 400 IU of vitamin E daily and to refrain from initiating memantine until later disease stages.

  • Disclosures for Brandy R. Matthews, MD at time of publication Grant / research support National Institute on Aging


Reader Comments (2)

patrick malone Physician, Family Medicine/General Practice, Sneem, Co. Kerry, Ireland

I would have concerns re long-term effects of high dose vitamin E e.g. GI malignancy

CHAO JIANG Physician, Internal Medicine, Guangzhou No. 12 Hospital, Guangzhou 510620, China

Hope to receive the good article on internal medicine

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