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Feature Article

Lab studies yield mixed results on alpha-lipoic acid, a potential memory booster

Alpha-lipoic acid is a fatty acid that's found in every body cell. The body uses this acid to convert glucose (blood sugar) into energy. Alpha-lipoic acid is also a potent antioxidant, neutralizing potentially harmful chemicals called free radicals—and the acid has been shown to increase the production of acetylcholine, a brain chemical that is a key component of memory.

Small amounts of alpha-lipoic acid can be found in foods such as spinach, broccoli, peas, brussels sprouts, and organ meats. Supplements of the acid can be found at health food stores, drug stores, and on the Internet—and many people take these supplements in hopes of warding off the effects of Alzheimer's disease on memory.

In a paper published online in the Journal of Alzheimer's Disease in July 2012 a team of VA researchers and their colleagues looked at the effects of administering alpha-lipoic acid to mice—not only on their memories, but also on their oxidative processes and on their longevity. i Their results offered some hope for those with Alzheimer's and their families—and also some cautionary information.

"Our results indicate that alpha-lipoic acid improves memory and reverses indications of oxidative stress in extremely old mice, but decreases lifespan," says Susan A. Farr, PhD, of the St. Louis VA Medical Center and the St. Louis University School of Medicine, the study's lead author.

Farr and her colleagues used a specially bred strain of mice called SAMP8 (the acronym stands for senescence-accelerated mouse prone). These mice tend to have the same kinds of age-related learning and memory deficits many humans do, and are used to investigate those mechanisms.

The team conducted two types of studies with SAMP8 mice. The first type was designed to see if the behavior of the mice changed after receiving daily dosages of alpha-lipoic acid; the second attempted to determine whether their lifespan was either shortened or lengthened after receiving doses of the acid over longer periods of time.

Mice tend to spend more time exploring new objects than familiar ones, so the mice in the behavior study were exposed to two similar objects (plastic frogs) for five minutes. Twenty-four hours later, one of the frogs was replaced with a novel object (a plastic bird). The 10 mice that had been given alpha-lipoic acid before the test spent more time exploring the new object than 10 others who had not been given the drug.

These mice also were given a test using a maze, to see if the mice could learn the location of an escape chamber. In this test, the mice that were administered alpha-lipoic acid learned the location of the "target area" more quickly than those who had not received the acid, especially during the first few days of testing. Since all 20 of the mice in the study were extremely old for the species (18 months), the study indicated that even more advanced dementia can be reversed by alpha-lipoic acid.

Autopsies of the mice's brain tissue, conducted after the tests were completed, indicated that oxidative stress had been reversed in the group that had been given alpha-lipoic acid; a likely reason the ability to learn had improved in those mice. Oxidative stress describes the level of damage in a cell, tissue, or organ, caused by the body's reaction to oxygen as it breathes and produces energy. Failure to keep up with the harmful chemicals oxidative stress produces has been implicated in many diseases, including Alzheimer's, and has an impact on the body's aging process.

The lifespan study, however, provided less encouraging results. In this study, 50 11-month old SAMP8 mice were given alpha-lipoic acid every day until the day they died. Their longevity was compared with a control group of 50 SAMP8 mice that were not given the drug. The team found that mice receiving the drug lived for an average of 20 weeks after the drug was first administered, and those who did not receive the drug lived an average of 34 weeks from the beginning of the test—a significant difference.

"The reason for the increased mortality with alpha-lipoic acid in this species remains to be determined," says Farr. "However, these studies have confirmed the potent effect of alpha-lipoic acid on memory and oxidative stress in SAMP8 mice."

"The findings on longevity," she adds, "are similar to those of studies using other types of antioxidants."

Alzheimer's disease is a type of dementia that causes problems with memory, thinking and behavior. The symptoms of Alzheimer's usually develop slowly and get worse over time, eventually becoming severe enough to interfere with daily tasks.

VA provides a full range of care for Veterans with Alzheimer's disease, including home-based primary care; homemakers and home health aides; respite care; adult day care; and impatient hospital, nursing home or hospice care. VA's 20 Geriatric Research Education and Clinical Centers, or GRECCs, conduct laboratory and clinical research on the origins of aging and the diseases commonly associated with aging, including Alzheimer's. Research on Alzheimer's and other conditions associated with aging is ongoing at other VA sites, as well.



i SA Farr, TO Price, WA Banks, N Ercal, JE Morley, "Effect of Alpha-Lipoic Acid on Memory, Oxidation, and Lifespan in SAMP8 Mice". Journal of Alzheimer's Disease, DOI 10.3233/JAD-2012-120130.

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