Double-duty energy/antioxidant compound can
now be made more bioavailable and less costly
When’s the last time you changed your spark plugs? Even those who know nothing about automotive technology are probably aware that good spark plugs are essential for making a car run well. They produce the spark that ignites the gas-air mixture that drives the pistons that turn the crankshaft that … well, you get the picture. Without spark plugs, your car would be like a Chevy Nova in Latin America, where many years ago an ad campaign for that car bombed, because no va in Spanish means “doesn’t go.” Oops!
But what makes you go? Just as your car runs on gasoline, your body’s cells run on a chemical fuel, glucose, and it too burns—albeit in a very different and vastly more complicated way than what happens in an engine cylinder. And you too have “spark plugs,” as it turns out—zillions of them. You’ll see what they are in a moment.
ATP—Lifes Master Energy Molecule
In your cells, glucose molecules undergo a slow, controlled “burn” with oxygen, via a complex series of biochemical reactions that are collectively called cellular energy metabolism, or cellular respiration; the central feature of this process is a cycle of reactions called the Krebs cycle. Ultimately, the process yields carbon dioxide and water … and energy—the energy that was contained in the chemical bonds that initially held the glucose molecules together.
When the biochemical smoke clears, so to speak, much of that energy is found to have been stored in newly formed chemical bonds of a molecule called adenosine triphosphate, or ATP. This versatile compound participates in a host of other biochemical reactions, driving them forward by giving up the energy contained in its high-energy pyrophosphate bonds when they break. ATP’s chemical energy is what powers the various kinds of work performed by living cells, such as the contraction of muscles, the production of secretions, the activities of the nervous system, and the synthesis of cell constituents from nutrients in our food.
That’s why ATP is called life’s master energy molecule. As we have just seen, its energy comes from glucose, which is an end product of the digestion of our food. And all the food we eat, whether animal or vegetable in origin, gets its energy, ultimately, from the sun, via photosynthesis. Thus, all the energy for all life forms, including us, comes from the thermonuclear reactions that power the sun, via a long chain of well-understood processes governed by the laws of physics and chemistry (quantum mechanics, electromagnetism, thermodynamics, chemical kinetics, etc.). There is no mystical “life force” involved.
CoQ10 Sparks the Production of ATP
But there are spark plugs, in a sense, and life would grind to a halt without them, just as surely as your car would stop running if its spark plugs burned out. As you’ve probably guessed, our spark plugs consist of a certain kind of molecule, and it’s ubiquitous throughout the body’s cells—it has to be, in order to keep life going. This molecule belongs to a class of compounds called ubiquinones (from the word ubiquitous), and it’s the most important one in that class: it’s called coenzyme Q10, or CoQ10 for short. CoQ10 is found in virtually all aerobic organisms, from bacteria to plants to animals and humans. (For some basics on coenzymes, see the sidebar “What Does a Coenzyme Do?”)
What Does a Coenzyme Do?
Coenzymes are not enzymes, but enzyme helpers. Let’s see how they do that. All enzymes are proteins (but not all proteins are enzymes). Their function is to catalyze biochemical reactions, i.e., to make the reactions proceed much faster than they would otherwise—typically about 1 billion (109) times faster, but it can be up to 100 quintillion (1020, or 100 billion billion) times faster. A catalyst changes only the rate of a reaction, not its direction or equilibrium, and it remains unchanged by the reaction.
A coenzyme (white) attached to an enzyme
In order to function, some enzymes depend critically on a cofactor—a nonprotein chemical entity that alters the enzyme in such a way as to activate it; often this occurs through molecular interactions that cause subtle but essential changes in the enzyme’s protein structure. There are two kinds of cofactors: certain metal ions (such as zinc, copper, and iron) and certain organic compounds, called coenzymes (such as coenzyme Q10, choline, and lipoic acid).
Because enzymes are catalysts, not reactants, the body needs them only in very small amounts. The same is therefore true of coenzymes. This explains why vitamins, even though they’re essential for life, are needed only in very small amounts: it’s because they function primarily as precursors of coenzymes. And it explains why the trace minerals required for life are only “trace”: it’s because they serve as enzyme cofactors, usually as components of organic molecules that are acting as coenzymes.
CoQ10 can be viewed as the body’s cellular spark plug because of the key role it plays in the biosynthesis of ATP. It’s found in the highest amounts in the mitochondria of our cells, the tiny “powerhouses” where energy metabolism occurs, and it’s particularly abundant in the mitochondria of the hardest-working tissues of the body, notably the heart, brain, kidneys, and liver. That adds significance to the fact that CoQ10 is a strong antioxidant, because antioxidant protection is needed most in those hardest-working tissues, where cellular energy metabolism runs the “hottest” and produces the most free radicals. Is this dual role of energy booster and antioxidant a coincidence? Perhaps not. (Thank you, Mother Nature, in any case.)
CoQ10 Helps Power Your Heart
As is true of many other important compounds, our CoQ10 levels decline markedly as we age—almost certainly to our detriment on both of the counts mentioned above. Age-related deterioration is believed to be caused in part by free radical damage to a host of bodily organs and systems. Such damage is strongly implicated in many of the chronic disorders of aging, such as cardiovascular disease, cancer, diabetes, and Alzheimer’s disease.
An obvious countermeasure is the use of antioxidants, of which CoQ10 is among the most vital. It’s one component of the body’s uniquely efficient, five-member antioxidant network (the other four members being vitamin C, vitamin E, lipoic acid, and glutathione). Its role is not only that of an antioxidant per se, but also that of a chemical regenerator of vitamin E (to which it’s closely related), an even stronger antioxidant.1
Owing to its effectiveness as an energy booster for the heart muscle, CoQ10 has for several decades been widely prescribed by physicians in Europe and Japan for patients with cardiovascular disease—especially congestive heart failure, a weakened condition of the heart in which its ability to pump blood is severely impaired.1,2 Substantial improvement is often seen when the heart cells’ ability to produce more ATP is sparked by the supplemental CoQ10. There is also evidence to show that CoQ10 is helpful in treating isolated systolic hypertension, a type of high blood pressure that’s common in the elderly.
CoQ10 May Also Help Your Brain and Muscles—Even Your Gums!
The great American biochemist Karl Folkers, a pioneer in CoQ10 research, was the first to suggest that the age-related decline in this compound was probably a contributing factor in many of the chronic diseases of aging. Since CoQ10 is critical for the production of ATP, he reasoned, a decline in CoQ10 levels would impair the body’s energy metabolism and would be felt by every system: cardiovascular, neurological, immune, reproductive, etc.
Not coincidentally, perhaps, it has been found that serious CoQ10 deficiency is commonly seen in patients with heart disease, and below-normal levels have also been noted in patients with cancer and, of all things, gingivitis.1 There is preliminary evidence that CoQ10 may be of benefit for some cancer patients, as well as for patients with neurological diseases, and it is widely used in Japan as a treatment for gum disease (it’s even included in some toothpastes and mouthwashes there).
Indeed, it has been pointed out, by researchers at the Cincinnati Children’s Hospital Medical Center and University of Cincinnati, that:3
. . . CoQ10
differs from many other dietary supplements because its use is advocated by many physicians for many indications. … A review of numerous clinical trials of CoQ10
showed the drug to be remarkably free of serious and minor side effects. As such, it is attractive to consider its use as an adjunctive therapy.
These authors discuss several conditions for which CoQ10 appears to be useful, including early Parkinson’s disease. They also discuss the possibility that CoQ10therapy might be useful in combating certain myopathies (diseases of muscle tissue) that, in rare cases, are caused by statin drugs.
CoQ10 Is, Alas, Expensive …
CoQ10 is manufactured in the body (so it’s not a vitamin, despite some misconceptions on that score), and it shares a biosynthetic pathway with cholesterol. For that reason, the statin drugs, which are highly effective inhibitors of cholesterol biosynthesis, also inhibit the production of CoQ10. This suggests the advisability of making up for the loss through supplementation. It could be especially important in patients who suffer from congestive heart failure, for whom a CoQ10 deficiency is hazardous.2 (As always, however, consult with your doctor first!)
In patients with cardiovascular
disease, substantial improvement is
often seen when the heart cells’
ability to produce more ATP is
sparked by the supplemental CoQ10.
Dietary CoQ10 comes mainly from foods such as salmon, liver, and other organ meats, but it’s nearly impossible to get enough from food alone. Fortunately, CoQ10 is readily available in capsule form, and daily servings in the range of 30 to 300 mg are common. Unfortunately, however, its bioavailability is poor: well over 60% of an oral dose is excreted via the feces, and absorption of the remainder is highly variable (it’s best taken with fatty foods, because it’s fat-soluble). Worse yet, CoQ10 is expensive to make, and the cost has skyrocketed during the past year, owing to serious production shortages in Japan, the principal source of this compound.
. . . But New Delivery Technology May Reduce the Cost to Consumers
All this has led some supplement manufacturers to seek more efficient means of delivery than capsules, so that CoQ10 can be taken in smaller amounts—while maintaining or even increasing the amount that winds up in the bloodstream. In other words, if the bioavailability can be increased through a better delivery method, then the amount taken can be decreased, and the cost to the consumer can be decreased as well (although not necessarily in direct proportion to the decreased amount, because the increased cost of the delivery technology must be factored into the equation).
The most promising method for achieving this goal is via a technology in which the CoQ10 is delivered transmucosally (through a mucous membrane), in the form of a gel-like material consisting of manmade cells called liposomes, which contain the CoQ10within them. This is a well-established and extremely safe method; it can be augmented by a clever technique called PEGylation, which enhances the effectiveness of the liposomes.4 (See the sidebar “PEGylation—Molecular Stealth Technology.”)
PEGylation—Molecular Stealth Technology
No, PEGylation is not the thrill you feel when you meet PEG, the girl of your dreams. Compared to that, it’s pretty dull—but let’s have a look anyway. We’ll start with your car’s radiator, which probably contains antifreeze, the principal component of which is ethylene glycol, a colorless, syrupy liquid. Chemically, it’s an alcohol, but it’s toxic (so don’t drink it!).
Chemists can make a polymer—a long-chain molecule consisting of repeating units of a small molecule—out of ethylene glycol. The polymer is a colorless liquid called polyethylene glycol, or PEG, and it’s soluble both in water and in many organic solvents. PEG is an important industrial compound, used in detergents and as an emulsifier and plasticizer in a variety of products. It shows so little toxicity that the FDA has approved it for use as a vehicle or base in foods, pharmaceuticals, and cosmetics.1
PEGs consisting of dozens to hundreds of ethylene glycol links in the polymer chain are used in the pharmaceutical industry in an ingenious way: they’re chemically attached (a process called PEGylation) to drug molecules of various kinds in order to improve the drugs’ ability to be absorbed, distributed, and metabolized in the body.1PEGylation creates a kind of biologically inactive molecular shield around the drug molecule, greatly reducing the likelihood that the drug will be recognized and attacked as an outside agent by the body’s defense systems before it has a chance to reach its destination and do its job. Pharmaceutical chemists call this trick “stealth technology.”
A similar stealth role is performed by PEGs attached to liposomes, which are artificial cells created as delivery vehicles for drugs or supplements.2 Like a biological cell, a liposome consists of a lipid membrane surrounding an aqueous interior. Whereas the interior of a real cell is enormously complex, however, the interior of a liposome is simple: it contains just a drug or supplement, either dissolved or suspended (as fine particles) in water. The drug or supplement remains trapped inside until the liposome breaks down and spills its contents.*
*One supplement that benefits greatly from this kind of delivery vehicle is the female hormone progesterone. For more detailed discussions of liposomes, see “A Better Way to Take Progesterone” (October 2004 issue) and “Natural Hormone Replacement Update” (an interview with Dr. Jonathan Wright in the November 2004 issue); the latter also describes the advantages of taking vitamin B12 and folic acid in liposomal form.
Liposomes are gel-like and are generally administered parenterally, i.e., by some route other than the digestive tract. They can be injected, or they can be applied to the skin (transdermal delivery) or to mucous membranes, such as those of the cheeks, the vagina, or the inner labia (transmucosal delivery). In this way, they bypass the chemically harsh digestive tract and deliver their “payload” more efficiently, with less loss. In a word, the payload is made more bioavailable. For some substances, such as certain B-vitamins, this can be an extremely important factor, especially as we age and our bodies gradually lose the ability to absorb these substances efficiently.
Liposomes are PEGylated to prolong the time they survive in the bloodstream without being attacked by hostile proteins or phagocytes (cell-eating cells, whose role is to devour anything that doesn’t “smell” right, in a biochemical sense). Extending the liposomes’ lifetime with this stealth technology extends the useful lifetime of the payload as well—which is the whole idea—and increases the chances of its being taken up by those tissues that need it the most. The leftover PEG molecules, by the way, are excreted harmlessly via the urine or feces.
- Harris JM, Chess RB. Effect of pegylation on pharmaceuticals. Nature Rev/Drug Disc 2003;2:214-21.
- Lian T, Ho RJY. Trends and developments in liposome drug delivery systems. J Pharm Sci 2001;90:667-80.
CoQ10 for Cruise Control
Just as you wouldn’t allow your car to fall apart for lack of proper maintenance, it’s unwise to neglect the maintenance of your own body, which is, after all, rather more precious than any car. If you want to keep cruising down the road of life for a long time to come, you should make sure that your body is supplied daily with all the “parts” it needs, in optimal quantities. One of those vital parts is coenzyme Q10, the spark plug of life.
- Packer L, Colman C. The Antioxidant Miracle. John Wiley & Sons, New York, 1999.
- Hendler SS, Rorvik D, eds. PDR for Nutritional Supplements. Medical Economics Co., Montvale, NJ, 2001.
- Steele PE, Tang PH, DeGrauw AJ, Miles MV. Clinical laboratory monitoring of coenzyme Q10 use in neurologic and muscular diseases. Am J Clin Pathol2004;121(Suppl 1):S113-20.
- Stone WL, Smith M. Therapeutic uses of antioxidant liposomes. Molec Biotech2004;27:217-30.