Acetyl-L-Carnitine Protects Cellular Function

Acetyl-L-Carnitine Strikes Again

Protects Cellular Function

It boosts cellular energy metabolism and activates
genes that control internal defense mechanisms
By Hyla Cass, M.D.

Rules of war: the laws that make it illegal to hit below the toes.
— Leo Rosten

o rational person wants war, but it’s sometimes unavoidable, as 9/11 proved so tragically. It’s always unavoidable, alas, within our own bodies, where two microscopic armies—the Good Molecules and the Bad Molecules—are perpetually at each others’ atoms, in a civil war that rages from our scalp to our toes. The only rules in this war are the laws of chemistry. In the myriad and often amazingly ingenious ways in which the molecular “soldiers” in our inborn armies seek to carry out their life-and-death missions, they put us mere humans—their host organisms—to shame. Their “special ops” are as complex as biochemistry and molecular biology are complex, which is to say: very.

We Ingest Good Molecules So that . . .

In the pages of this magazine, we have encountered many good molecules. Some, such as all the vitamins and certain minerals, are those that we must ingest for our health and well-being, because they’re essential for life, and we can’t produce them on our own. Others, such as galantamine, resveratrol, quercetin, curcumin, EGCG, and procyanidins (type A), are those that we also do not produce on our own but that are beneficial to our health, even though we don’t need them to sustain life.

A third category of good molecules consists of compounds that we do produce on our own but that we should ingest more of, because we don’t produce them in optimal quantities, especially as we grow older. Some examples in this category are lipoic acid, coenzyme Q10, the omega-3 fatty acids, 5-HTP, and DHEA. Another is the amino acid derivative acetyl-L-carnitine (ALC), a supplement best known for its role in enhancing cellular energy metabolism (also known as cellular respiration). This article is about ALC. Before we get to that, however, let’s review some of the bad molecules we have to contend with.

. . . We Can Better Deal with Bad Molecules

The worst molecule in our bodies, arguably, is the amino acid homocysteine, whose negative effects on almost every aspect of our health and well-being are notorious. Other molecular species that can do us great harm—if they get out of the proper physiological balance—are the sugar glucose, the catecholamine adrenaline (aka epinephrine), the corticosteroid cortisol (aka hydrocortisone), and the electrolytes sodium and potassium. Although they all play essential roles in our health (as does homocysteine), they can also kill us if our internal regulatory mechanisms are sufficiently disrupted.

A true molecular monster, apparently lacking any redeeming qualities, is amyloid-beta, the protein that attacks and destroys our brains in Alzheimer’s disease. A fascinating and unusual aspect of amyloid-beta is that it is both a partial effect of and a partial cause of oxidative stress, which is believed to be a major factor in the aging process.

Oxidative Stress—A Major Factor in Aging

Oxidative stress is the cumulative, negative physiological effects of reactive oxygen species (ROS) in our bodies. And just what are ROS? They’re short-lived, oxygen-containing molecular intermediates (many of them very small) that are formed in chemical reactions, mainly those involved in the energy-generating process of cellular respiration, which occurs in the mitochondria of our cells. Mitochondria, our cellular “powerhouses,” are thus the primary source of ROS, and they are also their primary victim.

Most ROS are free radicals, such as the hydroxyl radical, •OH, whose unstable electronic structures (the spatial distribution and quantum-mechanical properties of electrons in the molecule) make them highly reactive, in mostly destructive ways, toward almost any other kind of molecule they encounter.* Those molecules include proteins, nucleic acids (DNA and RNA), lipids, and carbohydrates—in other words, all the major kinds of molecules upon which life processes depend.

*Not all ROS are free radicals, and not all free radicals contain oxygen atoms. Also, some free radicals, such as nitric oxide, can be either harmful or beneficial, depending on the circumstances.

Acetyl-L-Carnitine for Peyronie’s Penis

If you know 100 men, chances are that 2.3 of them have a pathologically curved penis, but none of them (not even the 0.3 guy) wants to talk about it. The condition, called Peyronie’s disease, has an estimated 2.3% incidence among adult men, according to a recent review, and about 70% of cases occur in men aged 50–70.1 The disease is characterized by the deposition of a fibrous, often calcified plaque on the top side (usually) of the penis, resulting in pain, curvature that can reach an astounding 90°, difficulty or impossibility of having intercourse, and, sometimes, impotence.

Yikes! Something that bad ought to be rare! Although the disease is probably as old as mankind, it’s still somewhat of a mystery. Only very recently was it concluded that the primary cause is not coital trauma or infection, as had been thought, but that Peyronie’s is probably both an inflammatory disorder and an autoimmune disorder.1 That’s no comfort to its victims, who probably couldn’t care less what causes it, as long as there’s a way to cure it.

Unfortunately, there isn’t, although a great variety of medical therapies have been tried, with varying degrees of success (the last resort, when medical options have failed, is surgery). Among the more successful agents in alleviating the pain of Peyronie’s, and even diminishing the penile curvature to a significant degree, is acetyl-L-carnitine (ALC), as we reported in October 2001 (“Acetyl L-Carnitine Can Help Straighten Your Penis”).

In the study in question, conducted in Italy, ALC was tested not against a placebo but against the breast-cancer drug tamoxifen, which was one of the agents being used to treat Peyronie’s disease at the time.2 ALC proved to be substantially better than tamoxifen. Since then, it has been determined independently that tamoxifen is ineffective against Peyronie’s, so it was, for all practical purposes, acting as a placebo in that study.3

The same group that did the ALC study subsequently did a similar study using propionyl-L- carnitine (PLC), a close relative of ALC, but the results were inconclusive owing to the study’s poor design. PLC did, however, prove effective, in combination with ALC, in some other studies that we reported on in June 2006 ( “Carnitines—Better Than Testosterone for Impotence”). Here the affliction was impotence, not Peyronie’s disease, and the PLC/ALC combination (2 g of each, daily) provided significant improvements, vs. testosterone therapy, in various aspects of sexual function and satisfaction.

When the researchers tested PLC together with the drug sildenafil (Viagra®), the combination proved significantly better than sildenafil alone in alleviating the symptoms of impotence in diabetic men. It’s worth noting that lipoic acid has also been shown to be helpful in treating diabetic men with this condition (see “Can Lipoic Acid Fight Diabetes-Induced Impotence?” in the April 2006 issue).


  1. Cavallini G. Towards an evidence-based understanding of Peyronie’s disease. Int J STD AIDS 2005;16:187-95.
  2. Biagiotti G, Cavallini G. Acetyl-L-carnitine vs. tamoxifen in the oral therapy of Peyronie’s disease: a preliminary report. BJU Int 2001; 88:63-7.
  3. Hauck EW, Diemer T, Schmelz HU, Weidner W. A critical analysis of nonsurgical treatment of Peyronie’s disease. Eur Urol 2006;49:987-97.

The continuous assault, from within, by ROS on our mitochondria—particularly the mitochondrial DNA—causes a gradual, lifelong deterioration of mitochondrial function that is believed to be a major factor in the aging process. Mitochondrial decay is particularly harmful in the brain and heart, which are exceptionally demanding of energy input and, therefore, exceptionally prolific in the production of free radicals as byproducts of their energy output. (The input is mainly in the form of glucose and fatty acids from our food, and the output is mainly in the form of ATP, the energy-storage compound that powers most of life’s biochemical processes.)

Glutathione—Antioxidant Champion

It’s ironic that oxygen, a quintessential life-giving molecule, is also the source of reactive oxygen species, which attack and damage almost everything they encounter, thereby hastening our demise. How dangerous are ROS? Consider this: if it were not for our bodies’ built-in antioxidant defenses, the torrents of ROS produced constantly in our cells (about 20 billion per cell per day) would kill us in roughly 100 minutes!

Fortunately, evolution has given us an array of inborn antioxidants, of which glutathione is by far the most important. They “mop up” free radicals almost as fast as they’re formed, neutralizing them before they can do too much damage to vital molecules. Because this defensive system is not perfect, however, some damage inevitably occurs, and it tends to accumulate throughout our lives, resulting in chronic disease, aging, and, ultimately, death. The more we can augment our antioxidant defenses with supplements, many scientists believe, the better our chances of staving off the chronic degenerative diseases of aging and of slowing the aging process itself.

Two Ways to Boost Glutathione Levels

So we take antioxidant supplements, such as vitamins C and E, lipoic acid, coenzyme Q10, carotenoids (lycopene, lutein, zeaxanthin, etc.), and polyphenolics (resveratrol, quercetin, curcumin, EGCG, etc.). We do not, however, take glutathione, because it’s a tripeptide (three linked amino acids), and such compounds are degraded in the digestive tract. Fortunately, there are ways to boost our glutathione levels from within. The best way, probably, is by taking lipoic acid, which is called “the antioxidant’s antioxidant” because it’s so effective not only as an antioxidant in its own right but also in facilitating the chemical regeneration of certain other antioxidants, notably glutathione.

Another way is by taking acetyl-L-carnitine, which boosts glutathione levels via a more indirect route—in rats, at least, and presumably in humans as well. As rats grow old, their glutathione levels decline, to the detriment of their health. At the same time, their levels of oxidized glutathione (the molecular form that results from neutralizing a free radical) are elevated. Smart old rats who understood something about the role of oxidative stress in disease and aging would surely wish that their glutathione levels could be restored to those of their younger years.

ALC Upregulates Rats’ Glutathione Levels

Recently a team of Italian and American scientists obligingly tried to do that for a group of senescent (very old—28 months) rats, by adding some ALC to their chow daily for 4 months.1 In order to see whether the experiment was successful, the researchers had to kill the rats and examine their brains, which was probably not what the rats had in mind when they wished for more glutathione (they should have remembered the old saying, “Be careful what you wish for—you might get it.) As it turned out, the experiment was successful. ALC supplementation (150 mg per kg of body weight) upregulated glutathione levels in the rats’ brains to those of normal adult (12-month-old) rats, and their oxidized glutathione was brought down to normal adult levels.

ALC Upregulates Heat-Shock Proteins

ALC’s ability to restore glutathione levels has broad implications beyond the obvious antioxidant benefit. Our bodies’ glutathione status is intimately connected with the production of a special class of proteins whose function is to protect the structural and functional integrity of countless other proteins (which constitute most of the cellular machinery of life) from damage caused by such factors as excessive heat or cold, infection, inflammation, oxygen deprivation, cellular trauma, and toxic agents. The special proteins also protect against disruptions of redox homeostasis, the delicate balance between the oxidative and reductive (antioxidative) forces within our cells.

These extremely tough, versatile protein guardians of other proteins and of our redox status are called heat-shock proteins (HSPs), although their functions, as we have just seen, encompass far more than just protection from heat shock. (In recognition of that, they’re also called stress proteins.) One HSP of particular interest is heme oxygenase-1 (HO-1, also known as HSP32), an enzyme that appears to play a central role in stress tolerance in the brain, where it helps protect against oxidative injury and neurodegenerative processes. Production of HO-1 is triggered by, among other things, the presence of free radicals as well as the depletion of glutathione.

ALC inhibited the formation of
neurotoxic compounds resulting
from the oxidative degradation of
lipids and proteins.

Vitagenes Control Longevity Assurance Processes

Increasingly, scientists are viewing the heat-shock response, as exemplified by HO-1 (and other HSPs, including a crucial one called HSP70), as being of fundamental importance in protecting our cells from damage associated with a variety of metabolic disturbances and injuries, including the aging process. Such protection is part of a complex network of so-called longevity assurance processes, which are under the control of a number of genes that some scientists have termed vitagenes. These genes include the ones that code for heat-shock proteins and for certain critical antioxidants, such as superoxide dismutase-2 (SOD-2).

ALC Provides Neuroprotection

Naturally, there is a strong incentive to find molecular agents that can activate this comprehensive defense mechanism, which is critical for maintaining optimal brain function. In the study mentioned above, the researchers found that ALC stimulated the heat-shock response in the brains of senescent rats—as they suspected it would, based on the glutathione results. They also found (again not to their surprise) that ALC inhibited the formation of neurotoxic compounds resulting from the oxidative degradation of lipids and proteins. This protective action was most pronounced in the hippocampus, the region of the brain most closely associated with memory and learning.

These results seem to support those of previous studies demonstrating the therapeutic role of ALC in various neurodegenerative diseases (see “Acetyl L-Carnitine Protects Memory and Intellectual Functions” in the August 2005 issue). In summarizing their results, the authors stated,

… we found that treatment of rats with acetyl-L-carnitine resulted in upregulation of protective antioxidant genes, such as HSP70, HO-1, and SOD-2, as well as prevention of age-dependent changes in mitochondrial chain respiratory complex expression. … The results from our study show for the first time that ALC treatment of aging rats induces HO-1 and HSP70 heat-shock proteins in the brain. … The data presented here are consistent with the notion that ALC plays a crucial role in the regulation of critical vitagenes (HO-1, HSPs, and SOD) …

Can We Be Civil . . . Please?

It’s noteworthy that numerous health and antiaging benefits have been ascribed both to ALC and to lipoic acid (see “Can Acetyl L-Carnitine and Lipoic Acid Slow the Aging Process?” in the October 2004 issue). Lipoic acid is an antioxidant, but ALC is not. In fact, ALC can have pro-oxidant effects (when given to old rats in large doses). Although it tends to diminish oxidative stress by stimulating antioxidant defense mechanisms, ALC also contributes to the production of reactive oxygen species by boosting cellular energy metabolism. Because of the potential for a net pro-oxidant effect, it’s advisable to take ALC together with lipoic acid, whose powerful antioxidant action can offset this effect.

It’s reassuring, in any case, to know that we have two such stalwart soldiers on the side of the Good Guys in our bodies’ internal civil war. Which, however, brings to mind George Carlin’s disarming question, “How is it possible to have a civil war?”


  1. Calabrese V, Colombrita C, Sultana R, Scapagnini G, Calvani M, Butterfield DA, Giuffrida Stella AM. Redox modulation of heat shock protein expression by acetylcarnitine in aging rat brain: relationship to antioxidant status and mitochondrial function. Antioxid Redox Signal 2006;8:404-16.

Dr. Hyla Cass is a nationally recognized expert in integrative medicine, an assistant clinical professor of psychiatry at the UCLA School of Medicine, and the author or coauthor of several popular books, including Natural Highs: Supplements, Nutrition, and Mind-Body Techniques to Help You Feel Good All the Time and 8 Weeks to Vibrant Health: A Woman’s Take-Charge Program to Correct Imbalances, Reclaim Energy, and Restore Well-Being.

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