Rejuvenating Effects of ALC (Acetyl-L-Carnitine)
Ward Dean, MD
One of the most common characteristics of aging is a loss of energy. I am reminded of this dry scientific fact every day as I try to keep up with my two sons — seemingly perpetual-motion dynamos. It is widely believed that one cause of this age-related decline in energy metabolism is due to loss of mitochondrial function. The mitochondria are the cellular ‘powerhouses.’ In fact, it has been hypothesized that aging could be due entirely to mitochondrial dysfunction. (2,3) Mitochondria produce metabolic energy by a process known as oxidative phosphorylation, which results in the production of adenosine triphosphate (ATP), the key energy source in the body.
Mitochondrial membranes are considered by many scientists to be the likely subcellular site of the age-related decline in mitochondrial function. Many mitochondrial tasks are believed to depend on the lipid composition and content, as well as lipid-protein interactions, of the mitochondrial membrane. It is believed that the decreased energy production with aging is due to alterations of the lipid composition and content of this membrane. These alterations and methods of reversing them have not, until recently, been clearly identified.
ALC Restores Enzyme Activity in Old Rats
Cytochrome c oxidase is an enzyme complex in mitochondria which is a vital component of cellular energy processes and is responsible for virtually all oxygen consumption in mammals. A team of Italian scientists found that the maximal activity of cytochrome c oxidase was markedly reduced (about 30%) in mitochondria from aged rats compared to mitochondria from young rats. (5) This reduction in activity of this critical enzyme appears to be one explanation for the reduction in formation of ATP (and reduced energy) with age. After treating aged rats with ALC, the scientists were gratified to find that the activity of this enzyme system was restored to the activity level of young rats. (1) (Fig. 1)
ALC Restores ADP Activity in Old Rats
These same Italian scientists also found that the activity of another enzyme, adenine nucleotidetranslocase (ANT), also decreases with age. ANT is a carrier protein which translocates (exchanges) ATP for ADP across the inner mitochondrial membrane from inside the mitochondrion to the cytosol (outside of the mitochondrion, but inside the cell) (Fig 2). This decreased activity of ANT results in reduced ATP available for cellular energy production. Again, after treatment of aged rats with ALC, the scientists found that ADP transport of rat heart mitochondria was restored to the level of young rats (Fig 3).
ALC Restores Changes in Cardiolipin Levels
Cardiolipin (diphosphatidyl glycerol) is a phospholipid that is biosynthesized and concentrated almost exclusively in the inner mitochondrial membrane. When the Italians analyzed and compared the phospholipid content of the mitochondrial membranes of young and old rats, they found no changes in the relative concentrations of (1) phosphatidylethanolamine, (2) phosphatidylinositol, (3) phosphatidylserine, or (4) phosphatidylcholine. However, they did find a 30% drop in cardiolipin concentrations (Fig 4). Significantly, maximal activity of cytochrome c oxidase appears to depend upon cardiolipin levels.
The scientists again found that treatment of aged rats with acetyl-L-carnitine restored cardiolipin in mitochondrial membranes to youthful levels. They also found that restoration of mitochondrial membrane cardiolipin content to youthful levels was associated with parallel restoration of the functional activity of the mitochondria themselves.
They drew the conclusion that restoration of the juvenile lipid microenvironment (i.e., restoration of inner mitochondrial membrane cardiolipin levels) by ALC is the most obvious explanation of ALC’s rejuvenating effect on cytochrome c oxidase activity as well. They concluded that restoration of these functions to youthful levels should allow more efficient oxidative phosphorylation, thereby improving performance in aged animals.
ALC Dose for Humans
The doses administered to the rats in these studies were massive — 300 mg/kg of body weight! In human terms, this equates to 21 grams! Does this mean that in order to obtain the same mitochondrial-rejuvenating benefits the rats gained we would have to consume 21 grams of acetyl-L-carnitine each day? I don’t believe so. First, because of the differences in metabolism, animal doses are seldom directly proportional to bio-equivalent human doses. Second, ALC is well-documented to be effective in many conditions, including:
- Treating Alzheimer’s and Parkinson’s diseases;
- Enhancing cerebro- and cardiovascular blood flow;
- Alleviating depression;
- Improving memory and mental performance in normal humans and those suffering from Aging Associated Memory Impairment (AAMI);
- Improving immune function;
- Resolving lipofuscin deposits in humans (‘aging spots’). (1)
Since, all these effects occurred using doses ranging from 1,000-3,000 mg daily, it is likely that 1 to 3 grams daily will result in enhanced mitochondrial function in humans.
Finally, it is not altogether clear that the relatively expensive acetylated form of L-carnitine must be used. Some scientists believe that there are no advantages to taking the pricey ALC, over the more-economical unacetylated version. Dr. Brian Leibovitz, author of Carnitine, Vitamin BT believes that because the Sigma Tau pharmaceutical corporation owns the patents on the acetylated form of carnitine for pharmaceutical use, and has conducted all its research with ALC, they have concocted a myth that only ALC is clinically effective in many conditions. Steven Fowkes, Executive Director of the Cognitive Enhancement Research Institute (CERI) concedes that Leibovitz might be right, but hedges his bets by splitting his doses of Carnitine, and takes half his daily dose as L-carnitine and half as acetyl-L-carnitine. Like Steve, I’m in the middle, and will continue to split my doses — at least until the price of ALC becomes more affordable.
1. Dean, W., Morgenthaler, J., and Fowkes, S.W. Smart Drugs II-The Next Generation. Vol 2 in the Smart Drug Series. Smart Publications, Petaluma, 1993.
2. Harman, D. The biological clock: The Mitochondria? J Am Geriatr Soc. 1972, 20: 145-147.
3. Miquel, J., Economos, A.C., Fleming, J., and Johnson, J.E., Jr. Mitochondrial role in cell aging. Exp Gerontol. 1980, 15: 575-591.
4. Murray, R.K., Granner, D.K., Mayes, P.A., and Rodwell, V.W. Harper’s Biochemistry. 21st Edition, 1988, Appleton & Lange, New York.
5. Paradies, G., Ruggiero, F.M., Petrosillo, M.N., et al. The effect of aging and acetyl-L-carnitine on the function and on the lipid composition of rat heart mitochondria. In: Pharmacology of Aging Processes-Methods of Assessment and Potential Interventions, Annals of the New York Academy of Sciences. Volume 717, by Zs.-Nagy, I., Harman, D., and Kitani, K. (Eds), New York, 1994, 233-243.