Can acetyl-L-carnitine and alpha-lipoic acid really turn back the clock?

Throughout the ages, people have searched for magical potions to reverse the aging process. Ponce de León was searching for the Fountain of Youth when he discovered Florida. And the 19th century was rife with anti-aging potions.

In 1889, for example, a French scientist called Charles Edouard Brown-Séquard claimed that drinking an extract of crushed dog testicle could restore youth and vigor to old men.

Acetyl-L-carnitine and alpha-lipoic acid are the latest in a long line of supplements promising to turn back the clock.

Acetyl-L-carnitine and alpha-lipoic acid

The interest started when researchers in the Linus Pauling Institute at Oregon State University and the University of California at Berkeley found that they improved both the activity, energy level and cognitive function of old rats [2, 3, 4].

"After just a month, older rats whose diet was supplemented with these two compounds were about twice as active as our control rats, which remained largely inactive," says Tory Hagen, an assistant professor in Oregon State University's Linus Pauling Institute.

"With the two supplements together, these old rats got up and did the Macarena," says Bruce Ames, a professor of biochemistry at the University of California at Berkeley. "The brain looks better, they are full of energy — everything we looked at looks more like a young animal."

There are scores of different theories about aging. Some believe that aging is due to the normal wear and tear resulting from daily living. Others think that it's the result of a pre-programmed genetic plan, a process that begins at birth and continues until your "biological clock" runs down.

Ames falls in the wear and tear camp. He thinks that aging is at least partly due to a process called oxidative stress.

One particularly vulnerable area appears to be the mitochondria (pronounced my-toe-kon-dree-a).

Your body is made up of millions of tiny cells. Think of each cell like a miniature city. Inside each city, you'll find the power stations of the cell. They're called mitochondria. Of the oxygen consumed by an average cell, the mitochondria use most of it to help turn food into energy.

Unfortunately, mitochondria also appear to have a major design flaw — they leak electron electricity. This, in turn, leads to an increase in the production of free radicals.

The antioxidant defenses of your body are usually adequate to prevent substantial tissue damage. However, an overproduction of free radicals (caused, for example, by intense exercise) or a drop in the level of the antioxidant defenses will lead to an imbalance between free radical generation and antioxidant protection.

This imbalance is known as oxidative stress.

Mitochondria are right in the neighborhood of the free radicals they just created. This means they're often the first victims.

It's ironic that the thing we most need to live — oxygen — is the very thing contributing to aging and some of the other problems associated with it, such as cancer and heart disease.

"Oxygen is a double-edged sword," says Tory Hagen. "We need it to live and it’s essential to cell function. But oxygen can be converted into what we call reactive radical oxygen species, or free radicals."

Bruce Ames and Tory Hagen have long had an interest in mitochondria as they relate to aging. They were intrigued by Italian research showing that acetyl-L-carnitine improved mitochondrial activity in older rats [5].

When Ames and Hagen tried the same experiment, there was a problem [1]. The carnitine did improve mitochondrial health. But it also appeared to increase the level of free radicals. So, they decided to pair it with alpha-lipoic acid.

In one of the studies, Hagen, Ames and colleagues compared old rats to young rats, all fed acetyl-L-carnitine in their water and alpha-lipoic acid in their chow [2].

"We significantly reversed the decline in overall activity typical of aged rats to what you see in a middle-aged to young adult rat 7 to 10 months of age," Hagen says. "This is equivalent to making a 75- to 80-year-old person act middle-aged. We've only shown short-term effects, but the results give us the rationale for looking at these things long term."

Supplementation has also been shown to improve both spatial and temporal memory. Pictures of brain cells show less decay in old rats fed a supplemented diet [3].

"It appears that some compounds, including carnitine and lipoic acid, can mask the metabolic problems caused by cellular aging and the natural oxidative process," Hagen says. "If we can better understand the process of aging and how to influence it, we may be able to give people a way to maintain human health for as long as possible."

The University of California has patented the use of acetyl-L-carnitine and alpha-lipoic acid (US Patent #5,916,912) as a way of "enhancing metabolism and alleviating oxidative stress."

Juvenon, a company founded by Ames and Hagen, has licensed the patent from the university. Their first product — Juvenon Energy Formula — contains both alpha-lipoic acid and acetyl-L-carnitine.

The bottom line

Of course, the big problem is the lack of reliable research to show that these compounds benefit humans in the same way as rats.

Under certain circumstances, large doses of the popular antioxidants vitamin C and CoQ10 have been shown to increase oxidative stress. Whether alpha-lipoic acid and carnitine have any negative effects is a question that can only be answered by more human research.

Aging is a complex process. Different tissues may have fundamentally different mechanisms underlying their maintenance and repair. And most scientists believe that mitochondrial health is only one cog in the aging wheel.

Ames acknowledges he has not discovered the Fountain of Youth. But he does lay claim to a Fountain of Middle Age. "I don't want to over-hype it," he cautions. "If you're an old rat, it looks very good. But we still have to wait for the results from the human trials. There's every reason to think it's going to work in people. I'm very optimistic."

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About the Author

Christian Finn holds a master's degree in exercise science, is a certified personal trainer and has been featured on BBC TV and radio, as well as in Men's Health, Men's Fitness, Muscle & Fitness, Fit Pro, Zest and other popular fitness magazines.

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References
1. Hagen, T.M., Ingersoll, R.T., Wehr, C.M., Lykkesfeldt, J., Vinarsky, V., Bartholomew, J.C., Song, M.H., & Ames, B.N. (1998). Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proceedings of the National Academy of Sciences, 95, 9562-9566
2. Hagen, T.M., Liu, J., Lykkesfeldt, J., Wehr, C.M., Ingersoll, R.T., Vinarsky, V., Bartholomew, J.C., & Ames, B.N. (2002). Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proceedings of the National Academy of Sciences, 99, 1870-1875
3. Liu, J., Head, E., Gharib, A.M., Yuan, W., Ingersoll, R.T., Hagen, T.M., Cotman, C.W., & Ames, B.N. (2002). 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 Proceedings of the National Academy of Sciences, 99, 2356-2361
4. Liu, J., Killilea, D.W., & Ames, B.N. (2002). Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. Proceedings of the National Academy of Sciences, 99, 1876-1881
5. Paradies, G., Ruggiero, F.M., Petrosillo, G., Gadaleta, M.N., & Quagliariello, E. (1995). Carnitine-acylcarnitine translocase activity in cardiac mitochondria from aged rats: the effect of acetyl-L-carnitine. Mechanisms of Ageing and Development, 84, 103-112