US Pharm. 2011;36(2):HS21-HS-26.

Coenzyme Q10 (CoQ10) is a fat-soluble, vitamin-like compound that is also known as ubiquinone. It is produced by the human body (endogenous) and is necessary for the basic functioning of all cells. Of the 10 forms of coenzyme Q found in nature, only CoQ10 is synthesized in humans. CoQ10 levels are reported to decrease with age and to be low in patients with some chronic diseases such as heart conditions, muscular dystrophies, Parkinson's disease, cancer, and diabetes.1 It is also reported that some prescription drugs may lower CoQ10 levels.1

CoQ10 occurs naturally in the energy-producing center of the cell known as the mitochondria and is involved in making an important molecule, known as adenosine triphosphate (ATP). ATP serves as the cell's major energy source and drives a number of biological processes, including muscle contraction and the production of protein.2

The heart contains the largest amount of mitochondria (cell powerhouse) of any muscle in the body, so it is not surprising that CoQ10 has been proven effective for treatment of heart disease. It is claimed that it is beneficial as a cardiotonic in a variety of cardiovascular diseases, including angina, congestive heart failure (CHF), and hypertension. In addition, CoQ10 may be of value in musculoskeletal disorders, periodontal disease, diabetes, and obesity. CoQ10 is also involved in prevention of atherosclerosis, abnormal protein synthesis, and age-related degenerative diseases, and is a cell-membrane stabilizer.3 It also works as a powerful antioxidant due to its role in electron-transfer processes.

CoQ10 is used as a supplement, and it should be noted that the dosing of dietary supplements is highly dependent on a variety of factors, such as quality of raw materials, manufacturing process, and packaging. Since no official standards have been established to date to regulate the production of dietary supplements in the United States, dosage ranges must be employed as guidelines only.

CoQ10 Indications

CoQ10 is well documented as a potentially efficacious and adjunctive agent for the treatment of CHF and cardiomyopathy. Several open and placebo-controlled studies have demonstrated some benefit in patients having cardiovascular surgery, such as cardiac valve replacement, coronary artery bypass grafting, and repair of abdominal aortic aneurysms. CoQ10 prophylaxis has been associated with decreased serum markers of peroxidative damage and with myocardial preservation.4 Reported evidence to date does not currently justify its routine use in any of the cited conditions. CoQ10 has not consistently improved athletic performance. The FDA has granted orphan drug status to CoQ10 for the treatment of mitochondrial cytopathies.

Although the most common clinical use of CoQ10 is in heart disease, hypertension, and immunodepression, it is a powerful antioxidant. Depending on the clinical presentation, a common oral dosage for CoQ10 begins at 30 mg daily for general wellness and prevention and can be as high as 400 mg daily for heart disease and angina.5 Higher doses have not been substantiated in clinical trials. As an essential component of mitochondria, CoQ10 is vital for energy production and function, but further studies are needed to warrant its use for performance enhancement. Though CoQ10 appears safe and relatively nontoxic, high doses should be avoided until further studies prove its safety. One advantage of CoQ10 is its apparent very low order of toxicity. In addition to the need for well-controlled trials in other indications, further studies are needed to investigate the pharmacokinetics of CoQ10 and its potential for drug interactions, and to determine optimal dosing regimens for various conditions.3 CoQ10 is available as a dietary supplement in the United States under the Dietary Supplement Health and Education Act of 1994.

Mode of Action

CoQ10 is synthesized intracellularly and participates in a variety of essential cellular processes. It is primarily found in the inner mitochondrial membrane, and the highest concentrations in the human body are in the heart, liver, kidneys, and pancreas. The total body content ranges from 0.5 to 1.5 g. CoQ10 is an essential coenzyme and has vitamin-like characteristics; it is structurally similar to vitamin K.6

Cardiotonic Effects

Several potential therapeutic mechanisms for CoQ10 in treating cardiovascular diseases have been suggested (TABLE 1). In vitro and animal studies have indicated the ability of CoQ10 to protect the myocardium against functional and structural changes induced by ischemia and reperfusion. Results of other experimental data suggest that the coenzyme may have a role in protecting the heart from functional damage elicited by doxorubicin.



In a study of 15 healthy nonsmoking subjects with no history of bleeding disorders or medication use, administration of 200 mg CoQ10 daily for 20 days significantly increased plasma CoQ10 levels, caused a significant inhibition of vitronectin-receptor expression, and reduced platelet size. These could affect the final common pathway of platelet aggregation, which may explain some of the observed beneficial effects of CoQ10 in patients with cardiomyopathy, ischemic heart disease, and other vascular disorders.8

As some migraine sufferers display dysfunction in mitochondrial energy metabolism, it is believed that CoQ10 reduces migraine frequency by improving mitochondrial oxidative phosphorylation.9

CoQ10 is absorbed slowly from the gastrointestinal tract, due to its high molecular weight and low water solubility. At a daily dose of 90 mg/day in adults, about 3% of the administered dose was found in the blood. It is better absorbed when taken with food, especially with peanut butter.10
Antioxidant Effects

Antioxidants are substances that scavenge free radicals, damage compounds in the body that alter cell membranes, interact with DNA, and even cause cell death. Free radicals occur naturally in the body, but environmental toxins (including ultraviolet light, radiation, cigarette smoking, and air pollution) can also increase the number of these damaging particles. Researchers believe free radicals contribute to the aging process, as well as the development of a number of health problems, including heart disease and cancer. Endogenous antioxidants, such as glutathione and CoQ10, can neutralize free radicals and may reduce or even help prevent some of the damage they cause.11

In most people over 30 years old, CoQ10 levels begin to drop, leaving the body more vulnerable to free radical damage. CoQ10 supplements may help increase collagen and elastin in the skin, and help repair damaged skin cells.

Fish such as mackerel and tuna, red meat, and vegetable oils are good sources of CoQ10, but it is hard to acquire medicinal amounts of CoQ10 from dietary sources. CoQ10 supplements are extremely safe and are available in many forms, including capsules, tablets, skin creams, and combination products marketed as energy boosters or antiaging supplements.  
Drug Interactions

Drugs such as hydralazine, thiazide diuretics, fibric acid derivatives, sulfonylureas, beta-blockers, tricyclic antidepressants, chlorpromazine, clonidine, methyldopa, diazoxide, biguanides, and haloperidol cause depletion of CoQ10 from the body. On the other hand, CoQ10 may reduce corticosteroids needed to control asthma symptoms. CoQ10 may also help reduce the toxic effects of chemotherapy agents such as daunorubicin and doxorubicin.12

Levels of CoQ10 tend to be lower in people with high cholesterol compared to healthy individuals of the same age. In addition, certain cholesterol-lowering drugs called statins (such as atorvastatin, cerivastatin, lovastatin, pravastatin, simvastatin) appear to deplete natural levels of CoQ10 in the body. Taking CoQ10 supplements can correct the deficiency caused by statin medications without affecting the medication's positive effects on cholesterol levels. Plus, it is reported that CoQ10 supplementation may decrease the muscle pain associated with statin treatment.13,14

There have been reports that CoQ10 may decrease the effectiveness of blood-thinning medications such as warfarin (Coumadin) or clopidogrel (Plavix), leading to the need for increased doses. Therefore, given that these medications must be monitored very closely for maintenance of appropriate levels and steady blood thinning, CoQ10 should be used with warfarin only under careful supervision by a health care provider.15

REFERENCES

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11. Reiter M, Rupp K, Baumeister P, et al. Antioxidant effects of quercetin and coenzyme Q10 mini organ cultures of human nasal mucosa cells. Anticancer Research. 2009;29(1):33-39.
12. Coenzyme Q-10. www.nlm.nih.gov/medlineplus/druginfo/natural/938.html.
13. Caso G, Kelly P, McNurlan MA, et al. Effect of coenzyme Q10 on myopathyic symptoms in patients treated with statins. Am J Cardiol. 2007;99(10):1409-1412.
14. Langsjoen PH, Langsjoen JO, Langsjoen AM, et al. Treatment of statin adverse effects with supplemental Coenzyme Q10 and statin drug discontinuation. Biofactors. 2005;25(1-4):147-152.
15. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health-System Pharm. 2000;57(13):1221-1227.

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