Vitamin E May Help Slow Alzheimer’s Progression in Combination with Drugs, JAMA Study Says

A high dose of vitamin E (alpha-tocopherol) may help slow cognitive decline in those with mild to moderate Alzheimer’s disease (AD), according to a new study published in the Journal of the American Medical Association (JAMA). Researchers tested vitamin E supplementation in those simultaneously taking an acetylcholinesterase inhibitor drug for AD.

The double-blind, placebo-controlled, parallel-group, randomized clinical trial tested 613 mild-to-moderate AD patients (mainly older male veterans). Subjects were given either 2000 IU/day of alpha-tocopherol; 20 mg/day of AD drug memantine; a combination of alpha-tocopherol and memantine; or placebo. Cognitive decline was measured using the Alzheimer’s Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score.

Those given alpha-tocopherol alone exhibited slower functional decline compared to placebo. “This change in the alpha-tocopherol group translates into a delay in clinical progression of 19% per year compared with placebo or a delay of approximately 6.2 months over the follow-up period,” the researchers said.

By contrast, patients receiving memantine alone or memantine plus alpha-tocopherol did not show significant difference in cognitive decline compared to placebo.

Researchers say this study is important for several reasons. First, while studies have shown that vitamin E and memantine have benefits for those with severe AD, this study provides more evidence in those with mild to moderate AD. Secondly, the study subjects showed no severe adverse effects from the alpha-tocopherol treatment. In an editorial by D Evans et al. commenting on the study in the same issue of JAMA, the authors said that alpha-tocopherol’s lack of adverse side effects may make its combination with other treatments promising for AD.

“The results seem especially pertinent to the use of combinations of agents to treat AD,” they wrote. “Combination therapy for AD has substantial appeal because agents currently available for treating AD offer on average only modest therapeutic benefit, and some have bothersome adverse effects. Achieving greater benefit without more adverse effects by using medications in combinations, especially agents with different presumed mechanisms of action, is a reasonable goal.”

Dietary supplement association the Council for Responsible Nutrition (CRN; Washington, DC) commented favorably on the study, noting that it is one of the largest and longest treatments in patients with mild to moderate AD.

“This study is significant as it presents strong data on the safety of vitamin E, at high doses, and dismisses previous questions raised about the safety of this essential nutrient. The authors’ stated ‘In contrast to the conclusion drawn from a 2005 meta-analysis of vitamin E, which showed that high-dose vitamin E (≥400 IU/d) may increase the risk of all-cause mortality, we found no significant increase in mortality with vitamin E,’” said Duffy MacKay, ND, CRN’s vice president of scientific and regulatory affairs, in a press release. (The 2005 meta-analysis MacKay referenced is Miller ER III et al., “Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality,” Annals of Internal Medicine, January 4, 2005 (vol. 142, no. 1): 37-46.)

MacKay also pointed out that the vitamin E dose in the study was high and reminded industry members that dietary supplements cannot be marketed to treat disease.