Refresh Your Brain with ALC

Acetyl-L-Carnitine & Coenzyme Q10 Benefit the Entire Body

Refresh Your Brain with ALC
Acetyl-L-carnitine promotes mitochondrial function and
may protect against Alzheimer’s neurotoxicity
By Will Block

Give your brain as much attention as you do
your hair, and you’ll be a thousand times better off.

— Malcolm X

boat made of sugar will dissolve. A sundial made of butter will melt. A furnace made of wood will burn up. … Oops—back to the ol’ drawing board! But consider the following statement, made on page 25 of this issue of Life Enhancement: “The mitochondria, however, are vulnerable to attack by the free radical byproducts of the oxidation reactions occurring within them—it’s as though they were tiny furnaces made of combustible material.”

Bingo! That analogy neatly summarizes a central problem with cellular respiration (aka cellular energy metabolism): our mitochondria, the tiny cellular “furnaces” where nutrient fuels are “burned” to produce energy, are highly vulnerable to attack from within. The danger is greatest in our brains, where the mitochondrial “flames” burn more intensely than anywhere else in our bodies. And because our own built-in chemical “flame retardants” are not perfect, our mitochondria suffer gradual dysfunction and decay as we age.

Or is it that we age because of mitochondrial dysfunction and decay? Many scientists believe that that process is largely to blame for aging as we know it—especially in the brain, where it’s believed to play a major role in the development of neurodegenerative diseases, such as Alzheimer’s. They call this the mitochondrial theory of aging. The bad news is that mitochondrial decay has far-reaching effects—none of them good—on the body’s systems and functions. The good news is that there are nutritional supplements that can help protect our mitochondria, with potential antiaging benefits. (See “Acetyl L-Carnitine Protects Memory and Intellectual Functions” in the August 2005 issue.)

Reactive Oxygen Species Could Be the Death of You …

There are anywhere from hundreds to thousands of mitochondria—tiny, sausage-shaped organelles—in every cell of your body. The nutrient fuels they burn are mainly glucose and long-chain fatty acids, whose chemical energy can be released by reaction with the oxygen in the air we breathe. Among the byproducts of the “flames” are reactive oxygen species (ROS), including free radicals. These are highly destructive to the “wooden” mitochondrial membrane (which is actually composed of chemically vulnerable phospholipids and cholesterol) and to the DNA and proteins contained within the mitochondria. The “flame retardants” our bodies use to protect the mitochondrial membranes and their contents are antioxidants, compounds that neutralize ROS before they can wreak havoc.

Got the picture? It’s reasonably accurate except for one thing: there are no real flames—the “burning” occurs slowly, at body temperature, in a watery environment (to see how that’s possible, read the sidebar “Where’s the Fire?”). The damage—including mutations in our DNA and functional degradation of cellular proteins, not to mention degradation of the phospholipids in the mitochondrial membrane (the “wooden furnace”)—accumulates slowly over the years of our lives. It gradually erodes the mitochondria’s ability to provide their host cells with the chemical energy needed to maintain their structural and functional integrity. The result: aging and death.

Where’s the Fire?

In describing cellular respiration, we speak of our cells’ “burning” fuel to produce the energy upon which all life processes depend. It’s an oxidation process like that occurring when wood burns, with the same end products: water, carbon dioxide, and energy. But wait a minute—the temperature inside our cells is our own comfortable body temperature, and besides, everything in there is, well, wet. How could anything burn? Where are the flames?

There are no flames, of course. In a nutshell, here’s how it works. Most combustion reactions (there are exceptions) require an ignition source, such as a spark or a lit match, to get them started. This provides the activation energy (a physicochemical characteristic of each molecular system) for the combustion to begin; without it, there’s no combustion.* Once the fire starts, the heat generated by the chemical reactions keeps the flame going until the fuel is exhausted. The reactions are very fast, and they usually generate light as well as heat.


*So where does the activation energy for a lit match come from? From the kinetic energy of the strike, which is dissipated as friction, which generates the heat necessary to light the match. The energy input and output of all chemical processes can be accounted for—there are no mysteries here.


To start and propagate a similar combustion reaction at low temperature without an ignition source, one must lower the activation energy of the system sufficiently to allow this to occur (even in a wet environment). That is what catalysts do, via intermolecular forces acting on the reactants—without participating in the reactions themselves. They merely facilitate reactions that would not otherwise occur to any appreciable extent at the temperature in question—in this case, body temperature.

The other thing a catalyst does is increase the rate of the reaction, making it proceed much faster than it would otherwise at that temperature. Although biochemical oxidation reactions are much slower than those of conventional combustion in flames, they still proceed billions of times faster, typically, than they would without the catalyst, at body temperature.

The catalysts for biochemical reactions are enzymes (all enzymes are proteins, but not all proteins are enzymes). Sometimes things are more complicated than described above, and the enzyme can’t function without the assistance of a nonprotein compound, called a coenzyme or cofactor, which activates the enzyme. Two well-known coenzymes that play important roles in cellular respiration are coenzyme Q10 and acetyl-coenzyme A.

The physicochemical principles underlying all biochemical reactions have been well understood for many decades.* Thus there is no need to invoke any mysterious “life force” to explain the existence of life processes and the evolution of living things. That quaint notion was discredited over half a century ago.


*The reactions can be explained (and often predicted) with mathematical precision through two branches of physical chemistry: (1) chemical thermodynamics, the science of the interconversion of thermal energy and chemical energy, and (2) chemical kinetics, the science of the rates at which chemical reactions proceed.


… Unless You Fight Back with Antioxidants

Our brains are particularly susceptible to mitochondrial decay because their energy output is extraordinarily high, accounting for about 20% of all the glucose and oxygen we take in. (Unlike other bodily tissues, the brain uses no fatty acids as fuel—just glucose.) The more fuel there is to burn, the more oxygen is required to burn it—and the more reactive oxygen species (ROS) are produced. That’s one reason why brain mitochondria are so vulnerable to oxidative stress, the cumulative damage, both direct and indirect, caused by ROS. (The mitochondria use about 95% of all the oxygen taken in by brain cells, by the way.)

Thus, through oxygen—the giver and the taker of life—mitochondria are the instruments of their own destruction. All that stands between them and their fate is antioxidants, such as vitamins C and E, lipoic acid, glutathione, and coenzyme Q10 (CoQ10). The last of these plays a dual role in our mitochondria: in addition to its antioxidant function, it serves as a kind of molecular “spark plug” in facilitating the reactions by which ATP, life’s master energy molecule, is produced during cellular respiration. (For more on this process, see the sidebar “How Does Cellular Respiration Work?” See also the article “Coenzyme Q10 Sparks the Life Within You” in the May 2005 issue.)

How Does Cellular Respiration Work?

ATP
It sounds simple enough: cellular respiration is the process by which a nutrient fuel—glucose or long-chain fatty acids—is converted to carbon dioxide (CO2) and water (H2O), with the release of energy. In reality, it’s a very complicated process. Unlike the combustion of wood, which produces a lot of heat and light in addition to gaseous CO2 and H2O, cellular respiration produces a little heat (which goes toward maintaining body temperature), no light, some CO2 and H2O, and a lot of chemical energy stored in the form of ATP molecules, the body’s energy “currency.”

The usable energy in ATP (adenosine triphosphate) exists in the form of one particular chemical bond, called the high-energy phosphate bond. When that bond breaks in a biochemical reaction, ATP becomes ADP (adenosine diphosphate), with the release of energy. In cellular respiration, most of the energy from the oxidation of glucose is used to convert ADP back to ATP so that the cycle can continue.

Using glucose as the example, the process of cellular respiration begins with glycolysis, the enzyme-catalyzed conversion of glucose to pyruvic acid. The pyruvic acid molecules then participate in a complex series of enzyme-catalyzed oxidative reactions collectively called the Krebs cycle, in which they are broken down, stepwise, to carbon dioxide and water.

Integrally tied to the Krebs cycle is a process called oxidative phosphorylation, aka the electron-transport chain. In this process, ATP molecules are produced through a cascade of reactions in which electrons are transferred from one molecule to another, losing energy to ATP as they go, until they finally reach oxygen molecules, which then react with hydrogen ions to form water. Ultimately, as many as 38 ATP molecules could be produced from the oxidative breakdown of one glucose molecule, but for various reasons, the actual number probably seldom exceeds 30.

The above description pertains to aerobic respiration, which occurs when oxygen is present in the cells. When oxygen is not present for whatever reason, cellular respiration can still occur, but via an anaerobic pathway, which is very different from the above, and much less efficient in terms of energy production.

ALC Is an Antioxidant, and More

A great variety of other molecules have antioxidant effects in our bodies, in different ways and at different levels. It is more the rule than the exception that these compounds play multiple roles in human physiology, just as CoQ10 does. Take, e.g., acetyl-L-carnitine (ALC), a derivative of the amino acid L-carnitine. For some time, ALC’s role as an antioxidant was in doubt, because under certain circumstances (i.e., when administered in very large amounts to aged rats), it acts as a prooxidant rather than an antioxidant.

Accumulating evidence has shown, however, that when ALC is administered in lower, therapeutic amounts, it is indeed an antioxidant, like its close chemical relative propionyl-L-carnitine (PLC). Just to be safe, though, ALC is generally taken along with the powerful antioxidant lipoic acid, which eliminates any concerns on this score. (See “Can Acetyl L-Carnitine and Lipoic Acid Slow the Aging Process?” in the October 2004 issue.)

ALC’s primary function is as a precursor to its parent compound, L-carnitine, which plays a key role in cellular respiration: L-carnitine transports long-chain fatty acids from the cell’s cytoplasm (the watery interior) into the mitochondria, where they are used as fuel (it also transports unwanted metabolic byproducts out of the mitochondria into the cytoplasm, whence they are disposed of by other means).*


*By increasing intracellular levels of L-carnitine, ALC supplementation (PLC too) indirectly promotes the increased transport of fatty acids into the mitochondria. That boosts cellular respiration, which, ironically, results in more ROS, the nasties that cause all the trouble. Cellular antioxidants thus have that much more to contend with—but the tradeoff seems to be worth it, owing to the overriding importance of maintaining healthy energy metabolism.


This vital transport function of L-carnitine occurs almost everywhere except the brain, which, as noted above, does not use fatty acids as fuel—just glucose. That does not mean, however, that ALC has no role to play in the brain. On the contrary, it acts as a donor of acetyl groups for two important compounds: the neurotransmitter acetylcholine and the enzyme cofactor (“enzyme helper”) acetyl-coenzyme A (acetyl-CoA), which is a crucial chemical intermediate in cellular respiration in brain mitochondria, just as it is in mitochondria throughout the rest of the body.

Amyloid-Beta Reduces ATP Production and Destroys Brain Cells


A highly simplified schematic of cellular respiration, which begins in the cytoplasm, with glycolysis, and is completed in the mitochondria, with the Krebs cycle and the electron transport chain. Altogether, about 3 dozen different chemical entities are involved in the process.
ALC’s role doesn’t stop there, though, as we will now see. Researchers at the University of Massachusetts studied the effects of ALC on a strain of human cells from a neuroblastoma (a malignant tumor of infants and children), characterized by immature nerve cells of embryonic type.1 Their tragic origin notwithstanding, these cells have properties that make them useful for studies of neuronal development and responses to neuronal trauma.

The researchers treated the cell cultures with amyloid-beta, the protein notorious as neuron-destroying plaques in the brains of Alzheimer’s victims. Amyloid-beta is formed in part through the effects of oxidative stress on the brain, and it creates a vicious cycle by generating more oxidative stress in the form of ROS. This leads to a gradual cellular degeneration, which is partly attributable to interference with the cells’ ability to generate normal amounts of ATP through cellular respiration. As ATP goes, so goes everything that depends on it—which is just about everything. Gradually, the cellular home fires flicker and die—and so, ultimately, do we.

ALC Protects Against Amyloid-Beta and Preserves ATP Levels

When the researchers treated the amyloid-beta-afflicted neurons with ALC, they observed dramatic reductions in the rate of neuronal death. This suggested that ALC was scavenging ROS, and further experiments gave strong evidence to support that conclusion. Additional experiments indicated that ALC was also providing neuroprotection by preventing the oxidative stress-induced decline in neuronal ATP production. The latter finding jibes with the fact that ALC is known to increase plasma levels of ATP in patients with peripheral artery disease, in which blood flow to the legs is impaired by atherosclerosis (for information on how to treat this disease, see the article on page 23 of this issue).

Acetyl-L-carnitine’s apparent ability to maintain normal ATP levels in cells afflicted by the neurotoxic amyloid-beta suggests that it may have an indirect as well as a direct antioxidant effect. ATP is required for the biosynthesis of the cells’ own endogenous antioxidants, of which glutathione is by far the most important (lipoic acid is also vital). Thus, by boosting not only the cells’ energy reserves but also their capacity to defend themselves against ROS, ALC provides a dual benefit. (For more on how ALC maintains neuronal glutathione levels, see “Acetyl-L-Carnitine Protects Cellular Function” in the August 2006 issue.)

The authors pointed out that their laboratory experiments were short-term and used cells that, aside from being subjected to amyloid-beta, were “otherwise healthy” (which seems an odd way to characterize cancer cells). They recommended that further studies be done with cell cultures that are at greater risk for Alzheimer’s-type neurodegeneration and in which amyloid-beta neurotoxicity would be exacerbated by such factors as vitamin deficiencies or elevated levels of the harmful amino acid homocysteine.

Fight Fire with Supplements

Both L-carnitine and CoQ10 levels decline with age. That impairs mitochondrial function throughout the body, including the brain, which can ill afford this burden—it’s already subject to aggressive assault by reactive oxygen species. Although we may not be able to change the figurative material of our mitochondrial furnaces from wood to iron, we can apply ever more antioxidant “flame retardants” and other mitochondria-friendly substances to help protect them from harm.

Reference

  1. Dhitavat S, Ortiz D, Shea TB, Rivera ER. Acetyl-L-carnitine protects against amyloid-beta neurotoxicity: roles of oxidative buffering and ATP levels. Neurochem Res 2002;27:501-5.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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