Italian Study Demonstrates that Acetyl L-Carnitine
Restores Youthful Mitochodrial and Energy Levels
By 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 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.
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 the 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 restored to the activity level of young rats.
These same Italian scientist found that the activity of a enzyme-
adenine nucleotide translocase (ANT) also decreases with age. ANT is a
carrier protein 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 acetyl-L-carnitine,
the scientists found that ADP transport of rat heart mitochondria was
restored to the level of young rats .
Cardiolipin (diphosphatidyl glycerol) is a phospholipid that is bio
sized 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 changes in the
relative concentrations of (1) phosphatidyl ethanolamine, (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 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
cardolipin levels) by acetyl-L-carnitine is the most obvious explanation
of acetyl-L-carnitine'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.
The doses administered to the rats in these studies were massive- 300mg/
Kg of bodyweight! 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 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, since acetyl-L-carnitine
is well documented to be effective in many conditions, including: (1)
treating Alzheimer's and Parkinson's disease; (2) enhancing cerebro- and
cardio-vascular 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.
1. Dean W, Morgenthaler J, Fowkes SW, 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.. 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
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 71 Zs.-Nagy I, Harman D, and Kitani K (Eds), New
York, 1994, 233-243.
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