Alpha Lipoic Acid, Acetyl-L-Carnitine May Aid Cognitive Health

BERKELEY, Calif.--Two chemicals produced in the body and available as dietary supplements may rejuvenate an aging brain. In the Feb. 19 Proceedings of the National Academy of Sciences (www.pnas.org), Bruce Ames, M.D., from the University of California, Berkeley, and his colleagues reported that acetyl-L-carnitine, an ester of the amino acid L-carnitine, and the antioxidant alpha lipoic acid may reverse the effects aging has on the brain.

Reportedly, an accumulation of oxidative damage on the brain's mitochondria, protein and nucleic acid may lead to neuronal and cognitive dysfunction. In fact, Ames calls mitochondria the "weak link in aging." In the first study (99, 4:2356-61, 2002), Ames and his colleagues found that these two supplements (mitochondrial metabolites) may improve memory tasks by reducing oxidative damage and improving mitochondrial function. Scientists fed old rats acetyl-L-carnitine and/or alpha lipoic acid and then assessed the animals' spatial and temporal memories. Based on these results, the researchers found that supplemented rats experienced improved memory. In addition, both metabolites reduced oxidative damage to nucleic acid, especially when given together. And in microscopic studies of the hippocampus (a region of the brain important for memory), the supplements reversed age-associated mitochondrial structural decay.

In the second study (99, 4:1876-81, 2002), the researchers found that feeding old rats high levels of acetyl-L-carnitine and/or alpha lipoic acid ameliorated destructive cognitive events such as oxidative damage and mitochondrial dysfunction.

In the third study, (99, 4:1870-5, 2002) researchers reported that feeding rats acetyl-L-carnitine together with alpha lipoic acid increased mitochondrial-supported cellular metabolism and lowered oxidative stress more than either compound alone. Because decreased cellular metabolism and increased oxidative stress are associated with getting older, this finding may prove to be significant in the fight to retain cognitive health.

Not only did the older rats do better on memory tests after taking supplements, the researchers reported, they also had more "pep." "With the two supplements together, these old rats got up and did the Macarena," Ames stated. "The brain looks better, they are full of energy--everything we looked at looks more like a young animal."

According to the researchers, alpha lipoic acid targets mitochondria to get rid of destructive free radicals while acetyl-L-carnitine boosts the activity of a damaged enzyme (carnitine acetyltransferase) that plays a key role in burning fuel for mitochondria. "Each chemical solves a different problem--the two together are better than either one alone," Ames said.

The university has already patented the use of this combo to rejuvenate cells based on earlier studies. In 1999, Ames co-founded the company Juvenon (www.juvenon.com) to license the patent from the university; the company is currently engaged in human clinical trials using the combination.