Acetyl L-Carnitine and Lipoic Acid Are Good for What Ages You
An instant classic in aging research indicates that damaged mitochondrial DNA causes aging
By Edward R. Rosick
It is autumn; not without
but within me is the cold.
Youth and spring are all about;
It is I that have grown old.
— Henry Wadsworth Longfellow
Poets and philosophers, princes and peasants, men and women of every persuasion and walk of life—all are bound by one currently immutable fate: aging and death. An age-old question is: why do we age, and what, if anything, can we do about it? To both parts of this question, modern science is providing answers that become clearer every year. This article is about an important new discovery regarding the causes of aging.
Gerontologists (scientists who study aging) generally agree that the aging process and the reasons why some people age well while others don’t are probably the result of complex interactions among three factors: heredity, environment, and lifestyle. Although you can’t change your genetic makeup (at least not yet, but that day is not far off), you can change your environment, to a degree, and you most certainly can change your lifestyle, through diet, exercise, etc.
Diet includes nutritional supplements, of course, and research has shown that certain supplements, such as acetyl-L-carnitine and lipoic acid, may be able to slow the aging process because of the manner in which they affect your energy metabolism. We’ll get to that shortly.
Oxidative Damage Causes Aging
One of the prevailing theories of aging is that it’s due in part to the cumulative oxidative damage caused by free radicals. These unstable, highly reactive molecular species are generated constantly in all our cells during cellular respiration, the process in which the oxygen we breathe is used to “burn” the glucose and fatty acids derived from the foods we eat. Much of the chemical energy thus produced is stored in the form of molecules of ATP (adenosine triphosphate), which subsequently give up that energy when they participate in myriad metabolic reactions. Meanwhile, however, the free radicals produced through cellular respiration attack and degrade the lipids and proteins of our cells—and the DNA as well.
Among the leading proponents of the oxidative damage (free radical) theory of aging is Dr. Bruce Ames, a world-renowned biochemist at the University of California, Berkeley. In two classic papers, Ames and his colleagues argued, based on a number of animal and human studies, that “… oxidation is a major contributor to cellular aging and the degenerative diseases that accompany aging, such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts.” Ames also postulated that antioxidant supplements, such as vitamin C, vitamin E, and carotenoids, could provide protection against these pathological hallmarks of aging.
Damage to Mitochondria Is Cumulative
In those same papers, Ames highlighted the role that free radicals play in damaging the mitochondria of our cells. Thousands of these tiny organelles are found inside every cell of the body. They serve as the “powerhouses” where cellular respiration occurs, producing torrents of beneficial ATP molecules and harmful free radicals. Most, but not all, of the latter are quickly neutralized by the body’s own antioxidants, especially glutathione, the most important one of all. Four others play vital roles as well: lipoic acid, vitamin C, vitamin E, and coenzyme Q10.
The free radicals that survive cause damage to all major cell components, including the mitochondria themselves—and some of that damage is cumulative. Quoting Ames again, “… age-associated accumulation of mitochondrial deficits due to oxidative damage is likely to be a major contributor to cellular, tissue, and organismal aging.” In a more recent paper, Ames presents intriguing evidence from laboratory studies that certain micronutrients, such as zinc, biotin, vitamin B6, and pantothenic acid (vitamin B5) may help prevent mitochondrial decay due to oxidative damage.
Mitochondria Have Their Own DNA
A fascinating aspect of mitochondria is the widely held belief that, early in the evolution of life on earth, they were free-living bacteria that became incorporated into the cells of larger (but very primitive) organisms in a symbiotic relationship—the larger organisms providing vital nutrients, and the mitochondria providing ATP. Scientists base this theory in part on the fact that mitochondria have their own separate DNA molecules (called mitochondrial DNA), which replicate independently of the chromosomal DNA residing in the nuclei of the host cells. Mitochondrial DNA molecules are small, containing a mere 13 genes that code for the synthesis of enzymes involved in cellular respiration.
Does Washing Your Face Cause Aging?
A characteristic feature of mitochondrial DNA (mtDNA) is the fact that it gradually becomes degraded as we age, owing to mutations (molecular changes in genes) and deletions (loss of portions of the genetic material). These effects are believed to be caused in part by oxidative damage. As we age, all sorts of other things happen to our bodies, most of which are unseen and unfelt, but many of which are all too obvious. The question is: is the degradation of mtDNA merely correlated with the symptoms of aging, or does it actually cause them?
Some scientists have espoused the latter idea as the mitochondrial theory of aging, but many have rejected it for various theoretical reasons and for one practical reason: there’s no proof. Remember that a cardinal principle of science (as well as of economics and many other areas of human endeavor) is: correlation is not causation. To establish cause and effect, you need more than a mere correlation, which could mean little or nothing (e.g., you wash your face every day, and your face ages—does washing cause aging?). You need proof that the one thing leads inevitably to the other.
Mitochondrial DNA Damage Causes Aging
Since proof for the mitochondrial theory of aging had been conspicuously lacking, a group of researchers at Sweden’s renowned Karolinska Institute decided to tackle this problem head-on. In concept (but not in execution), their experiment was simple: genetically engineer a strain of mice in which the degradation of mtDNA occurs at an accelerated pace, and see whether the symptoms of aging follow suit. If they do, that would be strong evidence that mtDNA damage causes aging.
Guess what? Although the mice bred to be susceptible to accelerated mtDNA damage appeared normal at birth, they did, in fact, age faster and die younger than normal mice. At about 25 weeks of age (young adulthood), they began to show premature signs of aging, such as weight loss, hair loss, anemia, infertility, osteoporosis, and heart enlargement—all of which are features of aging also seen in humans. Here was compelling experimental evidence (which may or may not constitute proof—that’s another question) to support the mitochondrial theory of aging. The experiment has been hailed as an instant classic in aging research.
Dietary Interventions for Aging
The mitochondrial theory is consistent with the oxidative damage theory; it seems clearer than ever, in fact, that the two mechanisms are linked. (Let’s not forget, however, that there are other credible theories of aging, which probably has multiple causes.) Because mitochondrial function can be enhanced and free radicals can be combated, there is the possibility of finding effective nutritional strategies (among others) for fighting the aging process. In the Swedish researchers’ words,
The mtDNA-mutator mice will thus be a valuable tool for future experiments to determine whether the consequences of increased somatic mtDNA mutation can be counteracted by genetic, pharmacological, or dietary interventions … Such approaches may allow us to design strategies to antagonize or delay deleterious consequences of naturally occurring somatic mtDNA mutations in human aging.
Acetyl L-Carnitine Is a Good Candidate
The Swedish research gives new credence to the idea that dietary supplements having a positive or protective effect on mitochondrial function—such as acetyl-L-carnitine and lipoic acid—may be able to slow the aging process. Acetyl-L-carnitine (ALC) is a derivative of L-carnitine, an unusual type of amino acid found naturally throughout the human body. L-Carnitine facilitates the transport of fatty acids—which, like glucose, are fuels for cellular respiration—into our mitochondria, thus playing an important role in cellular energy production.
ALC is used as a supplement rather than L-carnitine itself because it is better able than L-carnitine to pass through cell walls; ALC thus serves as a vehicle for getting L-carnitine into our cells, where the L-carnitine (once liberated from the acetyl group) can then deliver fatty acids into the mitochondria.
A recent review article by scientists at the Linus Pauling Institute in Oregon cites numerous studies on aged rats (which typically have declining L-carnitine levels) showing that supplemental ALC can slow or reverse a variety of processes involved in mitochondrial decay in many different tissues. ALC thus serves in a number of ways to increase the capacity of the mitochondria to generate ATP—a particularly beneficial feature for heart-muscle cells, whose incessant demand for chemical energy to keep on going must be met.
Unfortunately, however, ALC has no antioxidant capacity, so it’s ineffective in reducing the oxidative stress on mtDNA (as well as the other components of the mitochondria) caused by all the free radicals being generated.
Lipoic Acid Complements Acetyl L-Carnitine
Enter lipoic acid, “the antioxidant’s antioxidant.” This remarkable fatty acid is not only a potent antioxidant in its own right but serves as the linchpin in the body’s antioxidant network by regenerating the other major antioxidants. By far the most important of these, as mentioned earlier, is glutathione (which cannot be taken as a supplement because it’s destroyed in the digestive tract). Glutathione is the mitochondria’s number one defender, and lipoic acid is glutathione’s number one regenerator.
The Oregon researchers also cite numerous studies on the use of lipoic acid as therapy for diseases associated with impaired energy utilization or increased oxidative stress, such as type 2 diabetes and heart disease. They emphasize that there is a significant age-related mitochondrial decay in heart cells and that either ALC or lipoic acid can ameliorate this decay independently. Because of the complementary nature of the effects of these two agents on mitochondria, however, some scientists—most notably Bruce Ames—recommend that they be taken together.*
A Recipe for Better Vision
Age-related macular degeneration (AMD) is the number one cause of legal blindness in people over 60 and is thought to affect some 10 million Americans. In AMD, the macula—a small yellow spot on the retina responsible for sharp central vision—deteriorates, leading to visual impairment or blindness. Although limited medical treatment is possible in some cases, certain supplements, notably lutein and zeaxanthin, have been recommended for their ability to help prevent the retinal damage (see “Protect and Improve Your Vision with Carotenoids” in the March 2003 issue).
Now a study has been published showing that a mixture of acetyl-L-carnitine, omega-3 fatty acids, vitamin E, and coenzyme Q10—all chosen because they are believed to improve mitochondrial function—may provide some hope for victims of this devastating disease. In this pilot study, 14 patients with early AMD were treated with the supplement mixture, while an equal number of age- and sex-matched AMD controls were treated with vitamin E alone. Visual testing was done in both groups at 3, 6, 9, 12, and 24 months.
The patients receiving the supplement mixture showed slight visual improvement at 3 months and slightly more at 9 months; the improvement then remained unchanged for the duration of the study. By contrast, the patients receiving vitamin E alone suffered gradual worsening of their visual symptoms. Although the differences between the treatment and control groups were not statistically significant at any point during the study, the trend observed is suggestive of a possible long-term benefit. Further research is needed to pursue this tantalizing prospect.
- Feher J, Papale A, Mannino G, Gualdi L, Gabrieli CB. Mitotropic compounds for the treatment of age-related macular degeneration. Ophthalmologica2003;217:351-7.
What’s in the Fountain of Youth?
Could acetyl-L-carnitine and lipoic acid be ingredients in the proverbial fountain of youth? It’s too early to say that, but we can say that these two supplements, already well known for their many health benefits, are looking better than ever. Cutting-edge research has given us a clearer look at the age-old mystery of aging by revealing how our mitochondria, those ancient powerhouses of our cells, seem to cause the symptoms of aging when their DNA suffers damage—damage that may be preventable to some degree with acetyl-L-carnitine and lipoic acid.
- Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci 1993;90:7915-22.
- Shigenaga MK, Hagen TM, Ames BN. Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci 1994;91:10771-8.
- Ames BN. Delaying the mitochondrial decay of aging. Ann NY Acad Sci2004;1019:406-11.
- Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly-Y M, Gidlöf S, Oldfors A, Wibom R, Törnell , Jacobs HT, Larsson N-G. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 2004;429:417-23.
- Travis J. Dying before their time: studies of prematurely old mice hint that DNA mutations underlie aging. Science News, July 10, 2004, pp 26-8.
- Martin GM, Loeb LA. Mice and mitochondria. Nature 2004;429:357-9.
- Hagen TM, Moreau R, Suh JH, Visioli F. Mitochondrial decay in the aging rat heart. Ann NY Acad Sci 2002;959:491-507.
Dr. Rosick is an attending physician and clinical assistant professor of medicine at Pennsylvania State University, where he specializes in preventive and alternative medicine. He also holds a master’s degree in healthcare administration.