Dr. Dean is the Research Director of Vitamin Research Products and this article is reprinted from VRP’s Nutritional News with their kind permission. To avail yourself of good nutritional information on a regular basis call VRP in Carson City, Nevada, USA on 800 877 2447.
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 aged 9 and 10!
It is widely believed that one cause of this age-related decline in energy metabolism is due to loss of mitochondrial function. The mitochondria, remember, are the cellular “powerhouses.”. In fact, it has been hypothesized that aging could be due entirely to mitochondrial dysfunction (Harman, 1972; Miguel, et al, 1980). Mitochondrial produce metabolic energy by a process known as oxidative phophorylation, 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 alteration of the lipid composition and content of mitochondrial membranes. These alterations and methods of reversing them have not, until recently, been clearly identified.
ALC – restores age-related alterations of Cytochrome C 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 (Paradies, et al, 1994) recently 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. 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 Acetyl-L-Carnitine (ALC), the scientists were gratified to find that the activity of this enzyme system was restored to the activity level of young rats.
ALC – Restores ADP carrier protein activity in old rats
These same Italian scientists also found that the activity of another enzyme- adenine nucleotide tanslocase (ANT)- also decreases with age. ANT is a carrier protein that 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). 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.
ALC – Restores age related changes in mitochondrial membrane 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) phosphatidyl enthanolamine, (2) phosphatidyl inositol, (3) phosphatidyl serine, or (4) phosphatidyl choline. However, they did find a 30% drop in cardiolipin concentrations. Significantly, maximal activity of cytochrome C oxidase appears to depend upon cardiolipin levels.
The scientists again found that treatment of aged rats with ALC 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 cardolipin 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 phophorylation, thereby improving performance in aged animals.
ALC – Doses for humans
The doses administered to the rats in these studies were massive- 300mg/ Kg of body weight! In human terms, this would equate directly 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 ALC 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, since ALC is well documented to be effective in many conditions, including;
(1) treating Alzheimer’s and Parkinson’s disease;
(2) enhancing cerebro- and cardiovascular blood flow;
(3) alleviating depression;
(4) improving memory and mental performance in normal humans and those suffering from Aging Associated Memory Impairment (AAMI);
(5) improving immune function and
(6) resolving lipofuscin deposits in humans (“aging spots”), (Dean, et al, 1993)- and all these effects occurred using doses ranging from 1,000mg to 3,000mg daily.
It is likely that one to three grams daily will result in enhanced mitochondrial function in humans.
ALC – The references
1. Dean W, Morgenthaler J, 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 AC, Fleming J, Johnson JE, Jr. Mitochondrial role in cell aging. Exp Gerontol, 1980, 15: 575-591.
4. Murray RK, Granner DK, Mayes PA,, Rodwell VW, Harper’s Biochemistry, 21st edition, 1988, Appleton & Lange, New York.
5. Paradies G, Ruggiero FM, Petrosillo MN, 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.