Nutrient Combo Boosts Memory—At Least in Rats

Can a combination of two nutrient supplements counter the benign memory loss that often comes with aging? Possibly, a new rodent study suggests.

The study was conducted by Bruce Ames, Ph.D., a professor of molecular and cell biology at the University of California at Berkeley, and his colleagues and is reported in the February 19 Proceedings of the National Academy of Sciences.

The two supplements that were tested are called lipoic acid and acetyl-L-carnitine. Lipoic acid is a potent antioxidant that is able to keep cells from getting damaged by unstable oxygen molecules called free radicals. Lipoic acid can also be found in foods such as spinach, liver, and brewer’s yeast. Acetyl-L-carnitine, in contrast, consists of L carnitine (an amino acid involved in fatty-acid transport into cells’ mitochondria) plus an acetyl group. Although L-carnitine is amply available in diets containing beef and pork, it is more accessible to both brain and body when an acetyl group is added to it.

Ames and his colleagues used some 300 “old” rats in their experiments, that is, rats a little over two years old. During a seven-week period, some of the rats served as controls, while others received lipoic acid, acetyl-L-carnitine, or a combination of both. All of the rats were then given spatial memory and temporal memory tests. The rats receiving lipoic acid alone or acetyl-L-carnitine alone did a little better on these tests than the control rats did. But the rats receiving lipoic acid plus acetyl-L-carnitine did significantly better on the tests than the controls did.

Ames and his coworkers then examined the hippocampus—that area of the brain that is so crucial to memory—in some animals from the control group and from the treatment groups to see whether they could find any differences between the groups. They could, they found.

Damage Less Pronounced

First, the control animals showed oxidative damage to RNA molecules in cells from their hippocampi—damage that had been brought about by the aging process. However, there was less age-induced oxidative damage to hippocampal-cell RNA molecules from animals that had received either lipoic acid or acetyl-L-carnitine than there was in the control animals. What’s more, the damage was even less pronounced in the animals that had gotten the combination of supplements than in the animals that had gotten only one of them.

Second, mitochondria in hippocampal cells from the control animals were deteriorated—a phenomenon that results from the aging process. However, there was less age-provoked deterioration of these mitochondria in animals that had received lipoic acid, acetyl-L-carnitine, or both than there was in the control animals.

“These results,” Ames and his team concluded in their study report, “suggest that feeding acetyl-L-carnitine and lipoic acid to old rats improves performance on memory tasks,” and that it does so “by lowering oxidative damage and improving mitochondrial function.”

“I think it is a great study,” Hyla Cass, M.D., a Pacific Palisades, Calif., psychiatrist who has written several books on nutrient supplements, told Psychiatric News. The reason, she explained, is because it reinforces some of her own clinical experiences using the two compounds in older patients.

Specifically, she has been advising some of her middle-aged and older patients who have “senior moments” —say, when they forget where they placed their keys—to take acetyl-L-carnitine and lipoic acid, and the patients have reported back to her that the nutrients have helped them.

Applicability to Humans

However, Neal Barnard, M.D., a psychiatrist, nutrition researcher, and president of the Physicians’ Committee for Responsible Medicine in Washington, D.C., is not so enthusiastic about the study.

“I find the results very difficult to apply to people for several reasons,” he said in an interview with Psychiatric News. “First, there are substantial neurological differences between rats and humans. Second, there are also other physiological differences between them, say, in the absorption of drugs. And third, the memory tests used in the study were crude.”

If the study’s results are found to apply to humans, however, the results lead to a more provocative question: Might acetyl-L-carnitine and lipoic acid be able to counter not only benign senior memory problems, but perhaps even protect people from Alzheimer’s disease?

This possibility is certainly not lost on Ames and his colleagues. As they concluded in their study report, consuming large amounts of acetyl-L-carnitine and lipoic acid “may be an efficient intervention in humans for delaying brain aging and age-associated neurodegenerative diseases.”

How does Barnard regard this notion? “I think there is reason to be optimistic about nutrient use in Alzheimer’s disease,” he said. However, he stressed, “the studies that are going to nail that down are clinical trials, not rat studies.”

So are any trials being done to learn whether a combination of acetyl-L-carnitine and lipoic acid supplements might be able to fend off Alzheimer’s?

The answer is yes, Tory Hagen, Ph.D., an assistant professor at Oregon State University’s Linus Pauling Institute and one of the scientists involved in this rodent study, told Psychiatric News.

He, Ames, and other researchers are giving acetyl-L-carnitine and lipoic acid supplements to men who are over age 65 and have no discernible health problems to establish which doses might confer memory protection and whether such doses might have undesirable side effects. They then plan to conduct a trial to see whether the supplements can retard progression of mild cognitive impairment—a first sign of Alzheimer’s—in healthy volunteers.

The rodent study conducted by Ames and his team was supported by grants from the Ellison Foundation, the National Institute on Aging, the Wheeler Fund of the Dean of Biology, and the National Institute of Environmental Health Sciences Center. Their clinical trials are being conducted at Juvenon, a company that Ames and Hagen founded in 1999.

An abstract of the study, “Memory Loss in Old Rats Is Associated With Brain Mitochondrial Decay and RNA/DNA Oxidation: Partial Reversal by Feeding Acetyl-L-carnitine and/or R-alpha-lipoic Acid,” is posted on the Web at www.pnas.org/cgi/content/abstract/99/4/2356?. ▪