Juvenon Health Journal volume 2 number 5 – May 2003
Acetyl-L-Carnitine: The Lesser Known Cousin Acetyl-L-carnitine (ALC) is the powerful but lesser known cousin of L-carnitine (LC), a natural cellular amino acid synthesized by the body. LC is required for the conversion of fat, one of three types of cellular fuel, to chemical energy. LC functions as a vehicle to transport subunits of fat, fatty acids, into the specialized cellular structures, the mitochondria, for conversion to a chemical form of energy. A deficiency in LC, common in vegetarians (vegans), aging, and those who use certain prescribed drugs, results in a tired physical and mental state.
How is it different?
Structurally, the difference between the acetyl-L-carnitine (ALC) and L-carnitine (LC) is that ALC is an LC molecule that also contains an attached acetic acid group. This structural difference is small, but it produces a considerable difference in the biochemical properties of the molecule and, consequently, in its effects on metabolism. Acetyl-L-carnitine can substitute for L-carnitine in fat metabolism; however, as described below, recent studies have resulted in identification of several biological characteristics that are unique to acetyl-L-carnitine .
- The acetyl group on acetyl-L-carnitine can be donated to a specific acceptor molecule, choline, to form the neurotransmitter acetylcholine, which helps restore nerve function. This activity is believed to be at least partly responsible for the improved mental function that results from acetyl-L-carnitine supplementation in patients with cognitive disorders, including Alzheimer’s disease, Parkinson’s disease, Chronic Fatigue Syndrome, and other disorders of the nervous system. Additional studies supporting a neuroprotective role for acetyl-L-carnitine are those demonstrating an improvement in symptoms of peripheral nerve damage common to diabetic patients.
- The acetyl group can also be utilized for the production of energy in the Krebs cycle. This donation increases the availability of an important cofactor (CoA) required for the conversion of carbohydrates to energy. Sufficient amounts of carnitine, derived from acetyl-L-carnitine, are necessary to transport, toxic, non-metabolizable, short-chain fatty acids, out of the mitochondria, and thus to free up the cofactor, CoA. A deficiency in acetyl-L-carnitine promotes a corresponding decrease in this cofactor, and consequently impaired energy production from both fats and carbohydrates, thus affecting energy levels in all cells of the body.
- ALC, but not LC, has been demonstrated to protect the nervous system, partly because it more readily is transported into the nervous system. Recent studies with humans have indicated many of the age-associated disorders involving the nervous system, such as depression, impaired cognition, and decreased mental alertness, may be at least partially a response to a deficiency in ALC.
- ALC, but not LC, protects the mitochondria. A recent finding demonstrated that a deficiency in ALC affects the structure and energy-producing capacity of the mitochondria. The mitochondria are responsible for producing virtually all the energy required by the cell. Therefore any subtle change in their structure can have a tremendous effect on the cell’s energy reserves. ALC has been demonstrated to revitalize mitochondria by restoring levels of a key mitochondrial component, a phospholipid known as cardiolipin, which is susceptible to age-associated reduction in levels. Cardiolipin can be envisioned as the glue that secures and organizes, or better yet, orchestrates, the energy-producing machinery of the mitochondria.
- The acetic acid group on ALC allows it to enter the mitochondria more readily than LC and consequently more rapidly perform its beneficial effects An additional enzyme must act on LC before it can enter the mitochondria.
How can it affect physical and mental state?
These characteristics raise some questions. First, why would a deficiency in a fat-burning chemical affect our physical as well as mental state? The two systems of the body requiring the most energy are the muscular and nervous systems. It has been estimated that for normal function and health, the brain requires every day the amount of energy present in a quarter pound of sugar. A lack of energy in brain and muscle tissues will be exhibited as impaired physical and mental activity. If the deficiency persists for a sufficient period of time, it can lead to disease.
Although the brain normally does not use fat for energy, (it prefers glucose from carbohydrates), except under conditions of fasting or starvation, it nevertheless can be adversely affected by a deficiency in ALC, because of all 5 of the numbered items described above.
Where does it come from?
Although the cells of the body do produce this important chemical, it is widely believed that the major source of the compound is derived from the diet. Meat, lamb especially, is the major dietary source of ALC, and the basis for why vegans can be deficient in ALC, since plants contain insignificant amounts.
Studies with animals have recently demonstrated a gradual decline in plasma levels of ALC with age, which correlates with age-associated energy decline. Additional studies with humans have indicated a steady decline in ALC, beginning with the fourth decade of life. This too is correlated with energy decline. This decline in plasma ALC may be a reflection of inefficient absorption from the diet and/or reduced synthesis. Both are believed to be responsible for the lower levels of ALC as we age. In view of the age-associated decline in the ability of the body to synthesize and absorb ALC, use of dietary supplements to ensure adequate ALC is a growing trend in healthy aging.
For years, scientists have theorized that, in view of the biochemical properties of acetyl-L-carnitine (ALC; also abbreviated as ALCAR), it should have a beneficial effect on brain function. Many clinical trials in the U.S. and Europe have looked into the ability of ALC to slow the progression of natural cognitive impairment associated with old age. Studies have varied in length from 3 to 12 months, and doses from 1.5 to 3 grams/day.
Because of different study parameters, interpretation of the combined results is a challenging endeavor. However, in a recently published study, a group at Imperial College University in London has conducted a “meta-analysis,” which gathers data from a large number of studies and uses statistical techniques to reach overall conclusions. The result demonstrated a beneficial effect of ALC, compared to placebo, in protecting against age-related cognitive impairment. In addition, ALC was well tolerated.
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This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.
Dr. Treadwell answers your questions about Juvenon™ Cellular Health Supplement
QUESTION: What is the difference between acetyl-L-carnitine and L-carnitine? Which is more effective in combination with alpha lipoic acid?
R.B., via email
ANSWER: Significant evidence indicates that acetyl-L-carnitine (ALC) is more effective than L-carnitine in stimulating energy production and cognitive function. See nearby article for details on the structural and biochemical advantages of ALC.
ALC works especially well with alpha lipoic acid. For example, lipoic acid stimulates the enzyme involved in the transfer of the acetyl group on ALC to the acceptor choline, to form the neurotransmitter, acetylcholine. The two compounds complement one another in the production of energy, with alpha lipoic acid serving as a key cofactor in the Krebs cycle, and ALC feeding the cycle energy by supplying subunits in the form of acetyl moieties to be converted to energy. In developing the Juvenon Energy Formula, Juvenon scientists experimented with other anti-oxidants and found that alpha lipoic acid gave the best results.
For more questions and answers, go to juvenon.com/product/qa.htm.
Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor and member of Juvenon’s Scientific Advisory Board.