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doi: 10.1097/01.NNN.0000451329.36281.09
Departments: Living Well

Promising But Preliminary: Study shows modest benefit of vitamin E for mild-to-moderate Alzheimer's disease.

Stephens, Stephanie

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Go to bit.ly/1iCT85y for a podcast interview with Dr. Maurice Dysken about vitamin E for Alzheimer's disease.


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For some of the 5 million Americans living with Alzheimer's disease (AD) and their families, vitamin E may be back on the table for discussion with their neurologists. The results of a study published in the Jan. 1 issue of the Journal of the American Medical Association (JAMA) suggest that a synthetic form of vitamin E (alpha-tocopherol) may improve some symptoms of the disease. The researchers found that in patients with mild-to-moderate AD, a daily dose of the commonly used antioxidant slowed functional decline and decreased the amount of time caregivers needed to assist them with tasks of daily living. Functional decline is defined as deterioration in self-care skills such as bathing, dressing, and eating with utensils.

However, while the study found a reduction in functional decline, it did not find cognitive benefits. People who took vitamin E did not see an improvement in memory, for example. In addition, the research did not shed light on how vitamin E might slow functional decline in AD.

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THE STUDY

“Our interest and efforts were mainly driven by previous reports of the effectiveness of vitamin E,” says Maurice W. Dysken, M.D., one of the authors and a psychiatrist with the Minneapolis Veterans Affairs (VA) Health Care System. Dr. Dysken cites a 1997 study led by Mary Sano, Ph.D., which found that vitamin E slowed progression of AD in patients with moderately severe symptoms.

When reviewing previous work on the subject, Dr. Dysken's team also considered results of a 2005 treatment trial led by Ronald Petersen, M.D., Ph.D., member of the American Academy of Neurology (AAN), Cadieux director of the Mayo Alzheimer's Disease Research Center, and director of the Advisory Council on Alzheimer's Research, Care and Services for the National Alzheimer's Project Act. That report found vitamin E showed no benefit in slowing the rate of conversion from mild cognitive impairment to AD.

Dr. Dysken and colleagues also considered three previous trials with memantine (brand name Namenda) that suggested little benefit in mild AD.

This latest five-year randomized, double-blind clinical trial followed more than 600 veterans—with an average age of 79—for a minimum of six months to a maximum of four years. (See box, “The Best Medical Evidence.”)

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THE BEST MEDICAL EVIDENCE

Medical evidence should be based on large studies that include many people. When appropriate, the studies should be “double-blinded,” which means neither the researchers nor the participants know who is receiving the actual treatment and who is receiving a placebo. In addition, studies should be “randomized,” which means that participants are assigned randomly (in a sense, by coin toss) to receive either the treatment or a placebo, a treatment that looks just like the new therapy but has no active ingredients. The effects of the treatment should be clearly measured and not left to interpretation by the researchers. If more than one study produces similar results, the treatment recommendation is considered more reliable.

Researchers in the vitamin E study evaluated four groups: one taking vitamin E alone, another taking memantine alone, a third taking vitamin E and memantine in combination, and a placebo group. The authors sought to determine whether vitamin E, medication, or a combination of the two slowed progression of mild to moderate AD in those patients who were also taking an acetylcholinesterase inhibitor. Acetylcholinesterase inhibitors are medications (brand names include Aricept, Exelon, and Razadyne) that work by inhibiting the enzyme acetylcholinesterase. This class of drugs is approved by the U.S. Food and Drug Administration for improving cognitive function in people with AD. (Memantine, which is not an acetylcholinesterase inhibitor, works by blocking activity of a chemical messenger called glutamate.)

The authors of the JAMA study found no improvement in patients who took memantine or memantine with vitamin E when they compared both to the study's placebo group. However, they did discover something else.

“We found that using 2,000 international units per day of vitamin E slowed functional decline by about six months over the average follow-up period of two years,” Dr. Dysken says. The amount of time caregivers spent helping patients with tasks of daily living also increased least in the vitamin E group.

The researchers found no significant difference in the risk of death in any of their groups when compared to placebo. When asked whether he might increase the vitamin E dose in a future study, Dr. Dysken says, “We don't really know what the upper limit should be. We will need to consider that dosages above 2,000 international units per day could increase the risk of bleeding events because of vitamin E's effect on platelet aggregation [the clumping together of platelets in the blood].” In fact, people should not take vitamin E supplements without telling their doctor. The vitamin can interact with blood-thinners, cholesterol medications, chemotherapy, and medications that suppress the immune system.

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MEDICAL PRACTICE SHOULD NOT CHANGE

“It is a well done study by a solid research group. The results are positive enough to warrant more research, and we await independent review to determine if changes in current practice should be considered,” says Maria Carrillo, Ph.D., Alzheimer's Association vice president of medical and scientific relations, and member of the AAN. “No one should take vitamin E for Alzheimer's disease except under the supervision of a physician.”

People should exercise caution when interpreting the study results, according to Dr. Carrillo. For one thing, 97 percent of the participants were male, which is not representative of the general population.

The lack of cognitive benefit also raises important questions. “It's unclear why there were functional but not cognitive benefits. This emphasizes the need for confirming the results before considering this as a treatment strategy,” says Dr. Carrillo.

In addition, participants who received vitamin E and memantine did not show the benefit that the vitamin E only group did, Dr. Carrillo notes.

According to Rachelle S. Doody, M.D., Ph.D., Fellow of the American Academy of Neurology, and director of the Alzheimer's Disease and Memory Disorders Center at Baylor College of Medicine's department of neurology, memantine may not have been the best drug to use with some of the patients in the VA study. “This study tested memantine in patients with milder AD, but the drug is approved for use in those with moderate and severe Alzheimer's disease.”

The Alzheimer's Association has funded several studies to examine how vitamin E might have an effect on people with AD, including a 2011 grant to Ramit Ravona-Springer, M.D., to study “Dietary Factors, Inflammation and Cognitive Decline in Diabetic Elderly” (bit.ly/1j7zV8C).

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THE QUESTION OF PREVENTION

A JAMA editorial accompanying the study suggests that when it comes to AD, “shifting to more emphasis on prevention seems warranted.” As the baby boomers get older, the number of people with AD is expected to rise dramatically, experts say. According to the Alzheimer's Association, up to 16 million will have AD by 2050, and care for those people will cost the United States more than $1 trillion.

However, taking vitamin E to prevent AD may be wasted money. “In terms of vitamin E for preventing AD, studies have not shown a benefit of high doses for healthy people who don't have the disease,” says Dr. Doody, who was not connected to the VA study. “We've been trying high doses of vitamin E for diagnosed AD patients since 1996 in hopes it would slow down functional progression,” she says. “But there's no evidence that taking it for prevention is helpful.”

Still, calling the VA study “well done,” Mayo's Dr. Petersen is optimistic that more can and should be done. “The take-home message is that vitamin E has a modest effect on people with mild-to-moderate AD,” he says. “Of course, vitamin E needs to be weighed against potential side effects, but I don't think there's a high risk of death.” However, as Dr. Petersen notes, a 2005 study found that doses of vitamin E above 400 international units showed a small increased risk of death.

“We know none of these supplements are completely benign, but I think this puts vitamin E back on the table for discussions that physicians, patients, and families can have,” Dr. Petersen says.


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What to Ask Your Doctor

Rachelle S. Doody, M.D., Ph.D., of the Baylor College of Medicine, recommends asking your doctor the following questions if you are a caregiver for someone who has dementia and want to know whether that person should try vitamin E:

  • 1. Is the person's dementia due to Alzheimer's disease (AD)? The benefits have only been shown for people with AD as opposed to other forms of dementia.
  • 2. Given the person's medical history, is there a substantial risk in taking vitamin E?
  • 3. Should the person discontinue any other supplements he or she is taking?
  • 4. What are the possible side effects? Are any of these side effects reason to discontinue taking vitamin E?
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FOR MORE INFORMATION

  • ▸ For more Neurology Now articles on Alzheimer's disease (AD) and dementia, go to bit.ly/IQiH4U
  • ▸ For articles on AD and dementia in Neurology Today, go to bit.ly/1hk7WRJ
  • ▸ For a Neurology Patient Page on the possibility of preventing AD with exercise, go to bit.ly/1noDAmm

© 2014 American Academy of Neurology

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