Coenzyme Q10

Key Terms: Antioxidant, Chemotherapy, Lipids, Lymphoma, Mitochondria.

Definition

Coenzyme Q10 is a fat-soluble nutrient also known as CoQ10, or ubiquinone. It is primarily found in the mitochondria, which are small bodies within cells that produce energy for the body. Apart from the important process that provides energy, CoQ10 also stabilizes cell membranes and acts as an antioxidant (a substance that reduces damage that results from oxygen, such as is caused by free radicals).

Purpose

Some people believe and anecdotal data suggest that oxygen-derived radicals are involved in the origins and development of cancer. Oxygen-derived radicals may cause damage to membranes, mitochondria, and large molecules, including proteins, lipids, and DNA. Accumulation of DNA damage may contribute to the development of cancer. There may be a relationship between oxidative stress and breast cancer development. People who subscribe to the belief that antioxidants are health-promoting may consume coenzyme Q10 (CoQ10) as one way of maintaining their health. However, as of 2005, this belief has not been conclusively proven by medical institutions.

Increased antioxidant enzyme activities may affect susceptibility of cells to cancer-causing agents and the response of tumor cells to chemotherapy. Administration of coenzyme Q10 by nutrition may induce the protective effect of coenzyme Q10 on breast tissue.

Furthermore, coenzyme Q10 is reputed to reduce the toxicity of some types of chemotherapy. Doxorubicin, a chemotherapeutic agent, is known to sometimes damage the heart. But use with coenzyme Q10 may reduce this toxic effect. People who are considering taking coenzyme Q10 should discuss its possible benefits of with a nutritionally oriented healthcare provider.

Description

Coenzyme Q10 appears to help ignite the cellular power stations that are necessary to maintain healthy cells, enhancing energy at the cellular level. The powerful antioxidant is highly concentrated in heart muscle cells. Coenzyme Q10 is believed by some to be an immune system booster and antioxidant that may help people avoid getting cancer, and it may be useful in treating it. Apart from its important function of providing energy, CoQ10 also stabilizes cell membranes, and as an antioxidant, it destroys free radicals in the body. These unstable molecules can cause damage to normal cells.

CoQ10 occurs naturally in many foods, which provide approximately half of the body's requirement. Cold-water fish such as mackerel, salmon, sardines, and tuna are particularly high in CoQ10. Meats and vegetable oils are also good sources. The human liver manufactures adequate amounts to fulfill the need not met in the diet. Some whole food nutritionists may believe that people who are deficient in B vitamins, selenium, vitamin C, or vitamin E may not be able to make as much coenzyme Q10 as they need since all these nutrients are required in order to produce it. The belief is that liver production and consumption of foods rich in CoQ10 may not provide the amounts needed to treat certain cancers, and for that reason, some people consume the enzyme in supplement form. It can be found formulated as capsules, gel caps, liquids, and tablets. The latter may be the best choice as it generally includes a source of fat that improves absorption. Vitamin E is a helpful stabilizing additive as well.

Coenzyme Q10 was first identified in 1957. Its chemical structure was determined in 1958. Interest in coenzyme Q10 as a potential treatment for cancer began in 1961, when a deficiency of the enzyme was noted in the blood of cancer patients. Low blood levels of coenzyme Q10 have been found in some patients with myeloma (a malignant tumor that develops in the blood-cell-producing cells of the bone marrow), lymphoma (cancer of the lymph nodes), and cancers of the breast, lung, prostate, pancreas, colon, kidney, and head and neck, according to the National Cancer Institute (NCI).

Recommended Dosage

Coenzyme Q10 is usually taken by mouth as a tablet or capsule. It may also be given by injection into a vein. CoQ10 is available in oil-based capsules, powder-filled capsules, tablets, and liquid soft gels. The soft gels are believed to give higher absorption. Therapeutic dosages of CoQ10 for cancer range from 200 to 600 mg per day. As a general nutritional supplement, daily doses of CoQ10 range from 5 to 300 mg. Those who use CoQ10 for periodontal (the tissue around teeth) health may take 100–150 mg daily. The same dose range applies to those who take statin (cholesterol-lowering) drugs for treatment of high cholesterol. CoQ10 is best taken with food. About three weeks of daily dosing are necessary to reach maximum blood concentrations of CoQ10. It comes in the various dosages.

Precautions

Coenzyme Q10 should not be taken by persons who are allergic to it. Symptoms of an allergic reaction include breathing problems or tightness in the throat or chest, chest pain, and skin hives, rash, or itchy or swollen skin. No other known precautions are indicated for normal dosage.

Side Effects

No serious adverse side effects have been reported. Some patients using coenzyme Q10 have experienced mild insomnia, elevated levels of liver enzymes, rashes, nausea, and upper abdominal pain. Other reported side effects have include dizziness, visual sensitivity to light, irritability, headache, heartburn, and fatigue.

Interactions

Patients should talk with their healthcare provider about possible interactions between CoQ10 and prescription drugs they may be taking. Certain drugs, such as those that are used to lower cholesterol or blood sugar levels, may reduce the effects of CoQ10. CoQ10 may also alter the body's response to warfarin, a drug that prevents the blood from clotting, and insulin, used to treat diabetes. The cholesterol-lowering drugs known as statins, such as lovastatin (Mevacor), simvastatin (Zocor), and pravastatin (Pravacol) may decrease CoQ10 levels in humans. It is likely that all statins have this effect. Also, CoQ10 may improve glycemic control in some type II diabetics. If this were to occur, antidiabetic medications might need appropriate adjusting. Some beta-blockers, in particular propanolol, may inhibit some CoQ10-dependent enzymes. Piperine, found in black pepper, may increase levels of CoQ10 in the blood.

—Ken R. Wells

Brand names: Oleomed™ Cell-QPreventive Nutrition® Coenzyme Q-10Q-Gel® ForteUbiQGel®

Drug Forms:
• Co-Enzyme Q-10 (Ubiquinone) Oral capsule (below)
• Co-Enzyme Q-10 (Ubiquinone) Oral capsule, liquid filled
• Co-Enzyme Q-10 (Ubiquinone) Oral disintegrating tablet

Co-Enzyme Q-10 (Ubiquinone) Oral capsule

What is this medicine?

CO-ENZYME Q10 is an herbal or dietary supplement. It is promoted to help many disorders including congestive heart failure, certain mitochondrial diseases, migraine, and high blood pressure. The FDA has not approved this supplement for any medical use.
 
 
This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•an unusual or allergic reaction to co-enzyme Q10, other herbs, plants, medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding
 

How should I use this medicine?

Take this medicine by mouth with a glass of water. Follow the directions on the package labeling, or take as directed by your health care professional. You should take this medicine with a high-fat meal. Do not take this medicine more often than directed.
 
Contact your pediatrician regarding the use of this medicine in children. Special care may be needed.
 
 
Overdosage: If you think you've taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

•medicines for blood pressure
•warfarin

What should I watch for while using this medicine?

See your doctor if your symptoms do not get better or if they get worse.
 
Herbal or dietary supplements are not regulated like medicines. Rigid quality control standards are not required for dietary supplements. The purity and strength of these products can vary. The safety and effect of this dietary supplement for a certain disease or illness is not well known. This product is not intended to diagnose, treat, cure or prevent any disease.
 
The Food and Drug Administration suggests the following to help consumers protect themselves:
•Always read product labels and follow directions.
•Natural does not mean a product is safe for humans to take.
•Look for products that include USP after the ingredient name. This means that the manufacturer followed the standards of the US Pharmacopoeia.
•Supplements made or sold by a nationally known food or drug company are more likely to be made under tight controls. You can write to the company for more information about how the product was made.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
 
Side effects that usually do not require medical attention (Report these to your doctor or health care professional if they continue or are bothersome.):
•diarrhea
•loss of appetite
•nausea
•trouble sleeping
•upset stomach
 
This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.
 
Store at room temperature or as directed on the package label. Throw away any unused medicine after the expiration date.

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

Description

Coenzyme Q₁₀ is a fat-soluble nutrient also known as CoQ₁₀, vitamin Q₁₀, ubidecarenone, or ubiquinone. It is a natural product of the human body that is primarily found in the mitochondria, which are the cellular organelles that produce energy. It occurs in most tissues of the human body; however, the highest concentrations are found in the heart, liver, kidneys, and pancreas. Ubiquinone takes its name from a combination of the word ubiquitous, meaning something that is found everywhere, and quinone 10. Quinones are substances found in all plants and animals. The variety found in humans has a 10-unit side chain in its molecular structure. Apart from the important process that provides energy, CoQ₁₀ also stabilizes cell membranes and acts as an antioxidant. In this capacity, it destroys free radicals, which are unstable molecules that can damage normal cells.

General Use

CoQ₁₀ is used extensively in Canada, Western Europe, Japan, and Russia to treat congestive heart failure. It is available as a prescription medication almost everywhere it is sold, although it is sold over-the-counter as a nutritional supplement in the United States. Some studies have shown it to be effective for as many as 70% of patients with congestive heart failure. It appears to improve patient health and wellbeing, and to increase cardiac efficiency. The dosage generally recommended for this condition is 100–300 mg a day, preferably in divided doses. According to Dr. Karl Folkers in Prevention's Healing with Vitamins, it takes one to three months to achieve desired results from supplementation, and as long as six months to attain maximum benefit.

CoQ₁₀ may also help people with some forms of cardiomyopathy. Patients should consult their physician about the possible benefits of supplementation for this condition.

The usefulness of CoQ₁₀ in lowering blood pressure is not well documented. One study suggests that the supplement is helpful for hypertension, but the results are in question as it was not a double-blind, controlled research project. The dose recommended is 200–250 mg a day, with results taking several months to appear. It is possible that some patients with essential hypertension who are initially low in CoQ₁₀ may eventually be able to decrease the amount of their other blood pressure medications. This must be done under the care of a health care provider.

Oral supplementation of CoQ₁₀ has been shown to improve periodontal disease, as it decreases the size of abnormally deep pockets in the gums, and also reduces the extent of bacterial contamination. Other possible benefits of CoQ₁₀ are to decrease angina symptoms, improve immune function in patients with AIDS and other immune deficiencies, improve control of blood sugar, lower cholesterol, improve physical stamina, and help people with muscular dystrophy and Huntington's disease. A group of researchers at the University of California at San Diego reported in 2002 that coenzyme Q₁₀ appears to slow the progress of Parkinson's disease, Friedreich's ataxia, and other conditions marked by degeneration of the central nervous system. The supplement can also reduce the toxicity of some types of chemotherapy. Doxorubicin, a chemotherapeutic agent, is known to sometimes damage the heart. Concomitant supplementation seems to reduce this toxic effect. The possible benefits of CoQ₁₀ should be discussed with a nutritionally-oriented health care provider.

Since 1961, when it was first noticed that cancer patients in Sweden and the United States had low levels of the enzyme, coenzyme Q₁₀ has been studied as a possible cancer treatment. Researchers believe that coenzyme Q₁₀ may protect against cancer by stimulating the immune system, and functioning as an antioxidant. Although animal studies have been conducted, as of early 2004 no report of a randomized clinical trial involving human subjects whose survival times were lengthened by using coenzyme Q₁₀ in addition to a traditional cancer treatment has been reported in a peer-reviewed medical journal.

Deficiency

Patients with certain conditions tend to have lower levels of CoQ₁₀, and may benefit from supplements. Some diseases that are associated with decreased amounts of this nutrient are AIDS, chronic fatigue, congestive heart failure, cardiomyopathy, and inflammatory gum disease. Levels of CoQ₁₀ tend to decrease with age; tests for its presence in the body are not widely available. Adverse effects from this supplement are rare and mild, so anyone suffering from one of the listed conditions should consider discussing supplementation with a health care provider.

Preparations

Natural Sources

Food products are a good source of CoQ₁₀, and provide approximately half of the body's requirement. Cold-water fish such as mackerel, salmon, sardines, and tuna are particularly high in CoQ₁₀. Vegetable oils and meats also provide good sources. The liver manufactures adequate amounts to fulfill the need not met in the diet. People who are deficient in B vitamins, selenium, vitamin C, and vitamin E may not be able to make as much CoQ₁₀ as they need because these nutrients are required for production. Consumption of foods rich in CoQ₁₀ and production of the nutrient in the liver will not provide the amounts needed to treat heart failure and other conditions that may contribute to a deficiency of this nutrient. In those cases, supplements are required.

Supplemental Sources

Supplements of CoQ₁₀ are widely available; however, its cost varies considerably. As of 2004, it is available in the United States, ranging in price from $7.79 for a bottle of 40 30-mg capsules to $38.95 for a bottle of 60 100-mg capsules. It is found in various forms including capsules, gelcaps, liquids, and tablets. The latter may be the best choice, as this form generally includes a source of fat that improves absorption. Vitamin E is a helpful stabilizing additive as well. Most of the CoQ₁₀ products currently available on the market are manufactured in Japan. Like other supplements, Co₁₀ is best kept in a cool, dry place, out of direct light, and out of the reach of children.

Precautions

As of 2004, the safety of CoQ₁₀ for pregnant or breast-feeding women has not been established, and its use is not recommended under these conditions. It is also not recommended for young children. People diagnosed with heart failure, diabetes, kidney problems, or liver disease should use particular care with this supplement, as the dosage of other medications may require adjustment. These individuals should consult a physician before taking coenzyme Q₁₀.

Side Effects

Reported adverse effects related to supplemental CoQ₁₀ use include diarrhea, irritation of the stomach, poor appetite, and nausea. These effects are rarely reported and are mild. CoQ₁₀ is considered extremely safe for most people. If doses over 300 mg per day are taken, liver enzyme levels may be affected, and may need monitoring.

Interactions

It is possible that CoQ₁₀ decreases the action of sodium warfarin (known by the brand name, Coumadin), which is prescribed to prevent the formation of blood clots in patients at risk of heart attack or stroke. Some oral diabetes medications may also interfere with the action of CoQ₁₀. Cholesterol-lowering drugs in the statin group may have this effect as well.

Resources

Books

Bratman, Steven, and David Kroll. Natural Health Bible. Roseville, CA: Prima Publishing, 2000.

Griffith, H. Winter. Vitamins, Herbs, Minerals & Supplements: The Complete Guide. Tucson, AZ: Fisher Books, 2000.

Pressman, Alan H., and Sheila Buff. The Complete Idiot's Guide to Vitamins and Minerals., 2nd ed. Indianapolis: Macmillan General Reference, 2000.

Therapeutic Research Faculty Staff. Natural Medicines Comprehensive Database. Stockton, CA: Therapeutic Research Faculty, 1999.

Periodicals

Baker, S. K., and M. A. Tarnopolsky. "Targeting Cellular Energy Production in Neurological Disorders." Expert Opinion on Investigational Drugs 12 (October 2003): 1655–79.

Naini, A., V., J. Lewis, M. Hirano, and S. DiMauro. "Primary Coenzyme Q₁₀ and the Brain." Biofactors 18 (2003): 145–52.

Shults, C. W. "Coenzyme Q₁₀ in Neurodegenerative Diseases." Current Medical Chemistry 10 (October 2003): 1917–21.

Shults, C. W., D. Oakes, K. Kieburtz, et al. "Effects of Coenzyme Q₁₀ in Early Parkinson's Disease: Evidence of Slowing of the Functional Decline." Archives of Neurology 59 (October 2002): 1541–50.

Vedanarayanan, V. V. "Mitochondrial Disorders and Ataxia." Seminars in Pediatric Neurology 10 (September 2003): 200–9.

Organizations

Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857. (888) 463-6332. .

National Cancer Institute (NCI). .

National Center for Complementary and Alternative Medicine (NCCAM) Clearinghouse. P. O. Box 7923, Gaithersburg, MD 20898-7923. (888) 644-6226. Fax: (866) 464-3615. .

Other

National Cancer Institute (NCI). Complementary and Alternative Medicine (CAM) Information Summary: Coenzyme Q₁₀. Bethesda, MD: NCI, 2003. [cited June 3, 2004]. .

National Institute of Neurological Disorders and Stroke (NINDS). "Study Suggests Coenzyme Q₁₀ Slows Functional Decline in Parkinson's Disease." NINDS press release, 14 October 2002. [cited June 3, 2004]. .

[Article by: Rebecca J. Frey, PhD]

A coenzyme that functions as part of the electron transport system and as an antioxidant. In patients with congestive heart failure, CoQ₁₀ has been reported to improve cardiac function, including stroke volume and cardiac output. Endurance athletes sometimes use coenzyme Q₁₀ to improve anaerobic and aerobic performance, but scientific studies on the effects of CoQ₁₀ on sport performance are inconclusive. CoQ₁₀ is not on the World Anti-Doping Agency's 2005 Prohibited List.

Coenzyme Q10
IUPAC name	2-[(2E,6E,10E,14E,18E,22E,26E,30E,34E)-3,7,11,15,19,23,27,31,35,39-decamethyltetraconta-2,6,10,14,18,22,26,30,34,38-decaenyl]-5, 6-dimethoxy-3-methylcyclohexa-2,5-diene-1,4-dione
Identifiers
CAS number	303-98-0 Y
PubChem	5281915
SMILES	CC1=C(C(=O)C(=C(C1=O)OC)OC)C/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/ CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CCC=C(C)C
Properties
Molecular formula	C59H90O4
Molar mass	863.34 g mol−1
Related compounds
Related compounds	1,4-Benzoquinone Quinone Plastoquinone
Y (what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Coenzyme Q₁₀ (also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ₁₀ – pronounced like "ko-cue-ten" –, CoQ, Q10, or simply Q) is a 1,4-benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the isoprenyl chemical subunits.

This oil-soluble vitamin-like substance is present in most eukaryotic cells, primarily in the mitochondria. It is a component of the electron transport chain and participates in aerobic cellular respiration, generating energy in the form of ATP. Ninety-five percent of the human body’s energy is generated this way.^[1][2] Therefore, those organs with the highest energy requirements—such as the heart and the liver—have the highest CoQ₁₀ concentrations.^[3][4][5]

Contents 1 History 2 Chemical properties 3 Biochemical role 4 Supplementation 4.1 Mitochondrial disorders 4.2 Heart failure 4.3 Migraine headaches 4.4 Cancer 4.5 Cardiac arrest 4.6 Blood pressure 4.7 Lifespan 5 Biosynthesis 6 Inhibition by statins and beta blockers 7 Absorption and metabolism 7.1 Factors affecting ubiquinone levels 8 Pharmacokinetics and bioavailability 9 Improving the bioavailability of CoQ10 10 Occurrence in nature 11 See also 12 References 13 External links

History

Coenzyme Q was first discovered by professor Fredrick L. Crane and colleagues at the University of Wisconsin–Madison Enzyme Institute in 1957.^[6][7] In 1958, its chemical structure was reported by Dr. Karl Folkers and coworkers at Merck; in 1968, Folkers became a Professor in the Chemistry Department at the University of Texas at Austin.^[7][8]

Chemical properties

The oxidized structure of CoQ10 is shown on the top right. The various kinds of Coenzyme Q can be distinguished by the number of isoprenoid side-chains they have. The most common CoQ in human mitochondria is Q₁₀. The 10 refers to the number of isoprene repeats. The image below has three isoprenoid units and would be called Q₃.

Biochemical role

Electron transport chain ("UQ" visible in green near center.)

CoQ is found in the membranes of many organelles. Since its primary function in cells is in generating energy, the highest concentration is found on the inner membrane of the mitochondrion. Some other organelles that contain CoQ₁₀ include endoplasmic reticulum, peroxisomes, lysosomes, and vesicles.

Supplementation

Because of its ability to transfer electrons and therefore act as an antioxidant, Coenzyme Q is used as a dietary supplement.

According to the Mayo Clinic^[9] "CoQ10 has been used, recommended, or studied for numerous conditions, but remains controversial as a treatment in many areas." Further clinical results are needed to determine whether the supplementation with Coenzyme Q10 is beneficial for healthy people.

Mitochondrial disorders

Supplementation of Coenzyme Q₁₀ is a treatment for some of the very rare and serious mitochondrial disorders and other metabolic disorders, where patients are not capable of producing enough coenzyme Q₁₀ because of their disorder. Coenzyme Q₁₀ is then prescribed by a physician.^[10]

Heart failure

There is some clinical evidence^[11] that supplementation with Coenzyme Q10 is beneficial treatment of patients with congestive heart failure. However, The American College of Cardiology published in 2005 an expert consensus document concluding that the value of coenzyme Q10 in cardiovascular disease has not been clearly established.^[12] The Mayo clinic says that there is not enough scientific evidence to recommend for or against the use of CoQ10 in patients with coronary heart disease.^[9]

Migraine headaches

Supplementation of Coenzyme Q₁₀ has been found to have a beneficial effect on the condition of some sufferers of migraine headaches. So far, three studies have been done, of which two were small, did not have a placebo group, were not randomized, and were open-label,^[13] and one was a double-blind, randomized, placebo-controlled trial, which found statistically significant results despite its small sample size of 42 patients.^[14] Dosages were 150 to 300 mg/day.

Cancer

It is also being investigated as a treatment for cancer, and as relief from cancer treatment side-effects.^[15]

Cardiac arrest

Another recent study shows a survival benefit after cardiac arrest if coenzyme Q₁₀ is administered in addition to commencing active cooling of the body to 90–93 degrees Fahrenheit (32–34 degrees Celsius).^[16]

Blood pressure

There are several reports concerning the effect of CoQ₁₀ on blood pressure in human studies.^[17] In a recent meta-analysis of the clinical trials of CoQ₁₀ for hypertension, a research group led by Professor Frank Rosenfeldt (Director, Cardiac Surgical Research Unit, Alfred Hospital, Melbourne, Australia) reviewed all published trials of Coenzyme Q₁₀ for hypertension, and assessed overall efficacy, consistency of therapeutic action, and side-effect incidence. Meta-analysis was performed in 12 clinical trials (362 patients) comprising three randomized controlled trials, one crossover study, and eight open-label studies. The research group concluded that coenzyme Q₁₀ has the potential in hypertensive patients to lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by up to 10 mm Hg without significant side-effects.^[18]

Lifespan

One study demonstrated that low dosages of coenzyme Q₁₀ reduce oxidation and DNA double-strand breaks, and a combination of a diet rich in polyunsaturated fatty acids and coenzyme Q₁₀ supplementation leads to a longer lifespan in rats.^[19] Coles and Harris demonstrated an extension in the lifespan of rats when they were given coenzyme Q₁₀ supplementation.^[20] Another study demonstrated that coenzyme Q₁₀ extends the lifespan of c. elegans (nematode).^[21]

Biosynthesis

The benzoquinone portion of Coenzyme Q₁₀ is synthesized from tyrosine, whereas the isoprene sidechain is synthesized from acetyl-CoA through the mevalonate pathway. The mevalonate pathway is also used for the first steps of cholesterol biosynthesis.

Inhibition by statins and beta blockers

Coenzyme Q₁₀ shares a common biosynthetic pathway with cholesterol. The synthesis of an intermediary precursor of Coenzyme Q₁₀, mevalonate, is inhibited by some beta blockers, blood pressure-lowering medication,^[22] and statins, a class of cholesterol-lowering drugs.^[23] Statins can reduce serum levels of coenzyme Q₁₀ by up to 40%.^[24] Some research suggests the logical option of supplementation with coenzyme Q₁₀ as a routine adjunct to any treatment that may reduce endogenous production of coenzyme Q₁₀, based on a balance of likely benefit against very small risk.^[25][26]

Absorption and metabolism

CoQ₁₀ is a crystalline powder that is insoluble in water due to its low polarity. It has a relatively high molecular weight (863 g/mol) and its solubility in lipids is also limited so it is very poorly absorbed in the gastrointestinal tract.^[27],[28] Absorption follows the same process as that of lipids and the uptake mechanism appears to be similar to that of vitamin E, another lipid-soluble nutrient. Emulsification and micelle formation is required for the absorption of fats. For CoQ₁₀, this process is chiefly facilitated by secretions from the pancreas and bile salts in the small intestine.^[29] A general rule is that the higher the dose orally administered, the lower the percent of the dose absorbed.^[29]

Data on the metabolism of CoQ₁₀ in animals and humans are limited.^[27] A study with ¹⁴C-labeled CoQ₁₀ in rats showed most of the radioactivity in the liver 2 hours after oral administration when the peak plasma radioactivity was observed, but it should be noted that CoQ₉ is the predominant form of coenzyme Q in rats.^[30] It appears that CoQ₁₀ is metabolised in all tissues, while a major route for its elimination is biliary and fecal excretion. After the withdrawal of CoQ₁₀ supplementation, the levels return to their normal levels within a few days, irrespective of the type of formulation used.^[31]

Factors affecting ubiquinone levels

Use of statins reduce ubiquinone levels.
Aging, in individuals older than 20 years, reduces ubiquinone levels in internal organs.^[32][33]
UV exposure reduces ubiquinone levels in the skin.^[34]

Pharmacokinetics and bioavailability

Some reports have been published on the pharmacokinetics of CoQ10. The plasma peak can be observed 2–6 hours after oral administration, mainly depending on the design of the study. In some studies, a second plasma peak was also observed at about 24 hours after administration, probably due to both enterohepatic recycling and redistribution from the liver to circulation.^[35] Tomono et al. used deuterium-labelled crystalline CoQ10 to investigate pharmacokinetics in human and determined an elimination half-time of 33 hours.^[36]

Improving the bioavailability of CoQ₁₀

The importance of how drugs are formulated for bioavailability is well known. In order to find a principle to boost the bioavailability of CoQ₁₀ after oral administration, several new approaches have been taken and different formulations and forms have been developed and tested on animals or humans.^[27]

Reduction of particle size

The obvious strategy is reduction of the particle size to as low as the micro- and nano-scale. Nanoparticles have been explored as a delivery system for various drugs and an improvement of the oral bioavailability of drugs with poor absorption characteristics has been reported;^[37] the pathways of absorption and the efficiency were affected by reduction of particle size. This protocol has so far not proved to be very successful with CoQ10, although reports have differed widely.^[38],[39] The use of the aqueous suspension of finely powdered CoQ₁₀ in pure water has also only revealed a minor effect.^[31]

Soft-gel capsules with CoQ10 in oil suspension

A successful approach was to use the emulsion system to facilitate absorption from the gastrointestinal tract and to improve bioavailability. Emulsions of soybean oil (lipid microspheres) could be stabilised very effectively by lecithin and were utilised in the preparation of soft gelatine capsules. In one of the first such attempts, Ozawa et al. performed a pharmacokinetic study on beagle dogs in which the emulsion of CoQ₁₀ in soybean oil was investigated; about two times higher plasma CoQ₁₀ level than that of the control tablet preparation was determined during administration of a lipid microsphere.^[31] Although an almost negligible improvement of bioavailability was observed by Kommuru et al. with oil-based soft-gel capsules in a later study on dogs,^[40] the significantly increased bioavailability of CoQ10 was confirmed for several oil-based formulations in most other studies.^[28]

Novel forms of CoQ10 with increased water-solubility

Facilitating drug absorption by increasing its solubility in water is a common pharmaceutical strategy and has also been shown to be successful for Coenzyme Q10. Various approaches have been developed to achieve this goal, with many of them producing significantly better results over oil-based soft-gel capsules in spite of the many attempts to optimize their composition.^[27] Examples of such approaches are use of the aqueous dispersion of solid CoQ10 with tyloxapol polymer,^[41] formulations based on various solubilising agents, i.e. hydrogenated lecithin, ^[42] and complexation with cyclodextrins; among the latter, complex with β-cyclodextrin has been found to have highly increased bioavailability.^[43] and is also used in pharmaceutical and food industry for CoQ10-fortification.^[27] Also some other novel carrier systems like liposomes, nanoparticles, dendrimers etc can be used to increase the bioavailability of Coenzyme Q10.

Occurrence in nature

This article needs reorganization to meet Wikipedia's quality standards. There is good information here, but it is poorly organized; editors are encouraged to be bold and make changes to the overall structure to improve this article. (July 2008)

Fresh tissue samples from both mackerel and herring found the concentration of Coenzyme Q10 to be higher in the heart tissue (105-148 μg/g) compared to concentrations found in the body tissue. The red tissue of mackerel contained a higher concentration (67μg/g) of CoQ10 than the white tissue (15μg/g) whilst in herring tissue the concentration was found to range between 15–24 μg/g. A small seasonal variance in the concentrations of CoQ10 was observed in both fish ^[44].

Cooking by frying reduces Q10 content by 14-32%.^[45]

See also

• Idebenone - synthetic analog with reduced oxidant generating properties
• Ubiquinol

References

1. ^ Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271: 195-204, 1995
2. ^ Dutton PL, Ohnishi T, Darrouzet E, Leonard, MA, Sharp RE, Cibney BR, Daldal F and Moser CC. 4 Coenzyme Q oxidation reduction reactions in mitochondrial electron transport (pp 65-82) in Coenzyme Q: Molecular mechanisms in health and disease edited by Kagan VE and Quinn PJ, CRC Press (2000), Boca Raton
3. ^ Okamoto, T.et al. (1989) Interna.J.Vit.Nutr.Res.,59,288-292
4. ^ Aberg,F.et al. (1992)Archives of Biochemistry and Biophysics, 295, 230-234
5. ^ Shindo, Y., Witt, E., Han, D., Epstein, W., and Packer, L., Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin, Invest. Dermatol., 102 (1994) 122-124.
6. ^ Crane F, Hatefi Y, Lester R, Widmer C (1957). "Isolation of a quinone from beef heart mitochondria". Biochim Biophys Acta 25 (1): 220–1. doi:10.1016/0006-3002(57)90457-2. PMID 13445756. 
7. ^ ^{a b} Peter H. Langsjoen, "Introduction of Coezyme Q10"
8. ^ Wolf DE, Hoffman CH, Trenner NR, Arison BH, Shunk CH, Linn BD, McPherson JF, and Folkers K. Structure studies on the coenzyme Q group. J Am Chem Soc 1958: 80:4752.
9. ^ ^{a b} Mayo Clinic Drugs and Supplements: Coenzyme Q10 (accessed 13 November 2008)
10. ^ Berbel-Garcia, A.; et al. (July 2004). "Coenzyme Q 10 improves lactic acidosis, strokelike episodes, and epilepsy in a patient with MELAS". Clinical Neuropharmacology 27: 187–191. doi:10.1097/01.wnf.0000137862.67131.bf. PMID 15319706. 
11. ^ Peter H. Langsjoen, University of Washington, INTRODUCTION TO COENZYME Q10 (accessed 13 November 2008)
12. ^ ROBERT ALAN BONAKDAR and ERMINIA GUARNERI, American Family Physician page on CoEnzyme Q10 (Sept 2005, accessed 13 November 2008)
13. ^ Rozen T, Oshinsky M, Gebeline C, Bradley K, Young W, Shechter A, Silberstein S (2002). "Open label trial of coenzyme Q10 as a migraine preventive". Cephalalgia 22 (2): 137–41. doi:10.1046/j.1468-2982.2002.00335.x. PMID 11972582. http://www.blackwell-synergy.com/doi/full/10.1046/j.1468-2982.2002.00335.x. 
14. ^ Sándor PS, et al. (2005). "Efficacy of coenzyme Q10 in migraine prophylaxis: A randomized controlled trial". Neurology 64: 713–715. doi:10.1212/01.WNL.0000151975.03598.ED. PMID 15728298. http://www.neurology.org/cgi/content/abstract/64/4/713. 
15. ^ Katsuhisa Sakano, Mami Takahashi, Mitsuaki Kitano, Takashi Sugimura, Keiji Wakabayashi: Suppression of Azoxymethane-induced Colonic Premalignant Lesion Formation by Coenzyme Q10 in Rats. Asian Pacific J Cancer Prev, 7, 599-603, 2006
16. ^ Damian, M. S.; et al. (July 2004). "Coenzyme Q10 Combined With Mild Hypothermia After Cardiac Arrest". Circulation, American Heart Foundation 110: 3011–3016. doi:10.1161/01.CIR.0000146894.45533.C2. PMID 15520321. http://www.circ.ahajournals.org/cgi/content/abstract/110/19/3011. Retrieved 2006-12-01. 
17. ^ Cupp MJ and Tracy TS. Chapter 4: Coenzyme Q10 (Ubiquinone, Ubidecarenone), pp 53-85 in Dietary Supplements edited by Cupp MJ and Tracy TS Humana press, Totowa, New Jersey (2003)
18. ^ Rosenfeldt FL, Haas SJ, Krum H, Hadj A, Ng K, Leong J-Y, Watts GF. Coenzyme Q₁₀ in the treatment of hypertension: a meta-analysis of the clinical trials. J Human Hypertension 21: 297-306, 2007
19. ^ Quiles JL, Ochoa JJ, Huertas JR, Mataix J (2004). "Coenzyme Q supplementation protects from age-related DNA double-strand breaks and increases lifespan in rats fed on a PUFA-rich diet.". Exp Gerontol. 39 (2): 189–94. doi:10.1016/j.exger.2003.10.002. PMID 15036411. 
20. ^ Coles L, Harris S (1996). "Coenzyme Q-10 and Lifespan Extension.". Advances in Anti-Aging Medicine. 1 (1): 205-215. 
21. ^ Ishii N, Senoo-Matsuda N, Miyake K, Yasuda K, Ishii T, Hartman PS, Furukawa S (2004). "Coenzyme Q10 can prolong C. elegans lifespan by lowering oxidative stress.". Mech Ageing Dev. 125 (1): 41-6. PMID 14706236. 
22. ^ Kishi T, Watanabe T, Folkers K (1977). "Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors". Res Commun Chem Pathol Pharmacol 17 (1): 157–64. PMID 17892. 
23. ^ The Synthesis of Cholesterol
24. ^ Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, Greco A, Littarru G (1993). "Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study". J Clin Pharmacol 33 (3): 226–9. PMID 8463436. 
25. ^ Sarter B (2002). "Coenzyme Q10 and cardiovascular disease: a review". J Cardiovasc Nurs 16 (4): 9–20. doi:10.1002/cncr.11242<hr><a (inactive 2008-06-26). PMID 12597259. 
26. ^ Thibault A, Samid D, Tompkins A, Figg W, Cooper M, Hohl R, Trepel J, Liang B, Patronas N, Venzon D, Reed E, Myers C (1996). "Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer". Clin Cancer Res 2 (3): 483–91. PMID 9816194. 
27. ^ ^{a b c d e} Zmitek et al. (2008) Agro Food Ind. Hi Tec. 19, 4, 9. - Improving the bioavailability of CoQ₁₀
28. ^ ^{a b} H. N. Bhagavan and R. K. Chopra, Mitochondrion, 7: S78-S88 (2007).
29. ^ ^{a b} H. N. Bhagavan and R. K. Chopra, Free Radic. Res., 40: 445-453 (2006).
30. ^ H. Kishi, N. Kanamori, S. Nisii, E. Hiraoka, T. Okamoto and T. Kishi, Metabolism and Exogenous Coenzyme Q10 in vivo and Bioavailability of Coenzyme Q10 Preparations in Japan. In Biomedical and Clinical Aspects of Coenzyme Q. pp. 131-142, Elsevier, Amsterdam 1964.
31. ^ ^{a b c} Y. Ozawa, Y. Mizushima, I. Koyama, M. Akimoto, Y. Yamagata, H. Hayashi and H. Murayama, Drug Res., 36-1: 689-690 (1986).
32. ^ Kalén, A.; Appelkvist, E. L.; Dallner, G. (1989). "Age-related changes in the lipid compositions of rat and human tissues". Lipids 24 (7): 579–584. doi:10.1007/BF02535072. PMID 2779364.  edit
33. ^ Söderberg, M. (1990). "Lipid Compositions of Different Regions of the Human Brain During Aging". Journal of Neurochemistry 54: 415–419. doi:10.1111/j.1471-4159.1990.tb01889.x.  edit
34. ^ Shindo, Y; Witt, E; Han, D; Packer, L (Apr 1994). "Dose-response effects of acute ultraviolet irradiation on antioxidants and molecular markers of oxidation in murine epidermis and dermis". The Journal of investigative dermatology 102 (4): 470–5. doi:10.1111/1523-1747.ep12373027. ISSN 0022-202X. PMID 8151122.  edit
35. ^ H. N. Bhagavan and R. K. Chopra, Free Radic. Res., 40: 445-453 (2006)
36. ^ Y. Tomono, J. Hasegawa, T. Seki, K. Motegi and N. Morishita, Int. J. Clin. Pharmacol. Ther., 24: 536-541 (1986).
37. ^ E. Mathiowitz, J. S. Jacob, Y. S. Jong, G. P. Carino, D. E. Chickering, P. Chaturvedi, C. A. Santos, K. Vijayaraghavan, S. Montgomery, M. Bassett and C. Morrell, Nature, 386: 410-414 (1997).
38. ^ C. H. Hsu, Z. Cui, R. J. Mumper and M. Jay, AAPS PharmSciTech., 4: E32 (2003).
39. ^ S. S. Joshi, S. V. Sawant, A. Shedge and A. D. Halpner, Int. J. Clin. Pharmacol. Ther., 41: 42-48 (2003).
40. ^ T. R. Kommuru, M. Ashraf, M. A. Khan and I. K. Reddy, Chemical & Pharmaceutical Bulletin, 47: 1024-1028 (1999).
41. ^ K. Westesen and B. Siekmann. Particles with modified physicochemical properties, their preparation and uses. US6197349. 2001.
42. ^ H. Ohashi, T. Takami, N. Koyama, Y. Kogure and K. Ida. Aqueous solution containing ubidecarenone. US4483873. 1984
43. ^ Zmitek, J. et all (2008) Relative bioavailability of two forms of a novel water soluble CoQ10 Ann. Nutri. Metab. 52:281-287 (2008)
44. ^ Nathalie Soucheta and Serge Laplante, Seasonal variation of Co-enzyme Q10 content in pelagic fish tissues from Eastern Quebec
45. ^ The coenzyme Q10 content of the average Danish die...[Int J Vitam Nutr Res. 1997] - PubMed Result

External links

• A video showing the effects of Coenzyme Q10 on the aging and activity of mice
• Coenzyme Q10: An Antioxidant Drug - from the Huntington's Disease Outreach Project for Education at Stanford
• List of USP Verified CoQ10 Ingredients
• National Cancer Institute page on CoEnzyme Q10
• Robert Alan Bonakdar and Erminia Guarneri, American Family Physician page on CoEnzyme Q10,
• Coenzyme Q10 general details, treatment methods, and side effects
• An Introduction to Coenzyme Q₁₀ at University of Washington
• Possible Health Benefits of Coenzyme Q₁₀ at Oregon State University
• Study Suggests Coenzyme Q₁₀ Slows Functional Decline in Parkinson's Disease at National Institute of Neurological Disorders and Stroke

v • d • e Mitochondrial electron transport chain/oxidative phosphorylation Primary Complex I/NADH dehydrogenase - Complex II/Succinate dehydrogenase - Coenzyme Q - Complex III/Coenzyme Q - cytochrome c reductase - Cytochrome c - Complex IV/Cytochrome c oxidase Other Alternative oxidase - Electron-transferring-flavoprotein dehydrogenase

v • d • e Enzyme cofactors Active Forms vitamins: TPP / ThDP (B1) · FMN, FAD (B2) · NAD+, NADH, NADP+, NADPH (B3) · Coenzyme A (B5) · PLP / P5P (B6) · Biotin (B7) · THFA / H4FA, DHFA / H2FA, MTHF (B9) · AdoCbl, MeCbl (B12) · Ascorbic Acid (C) · Phylloquinone (K1, Menaquinone (K2) · Coenzyme F420 non-vitamins: ATP · CTP · SAMe · PAPS · GSH · Coenzyme B · Coenzyme M · Coenzyme Q · Heme / Haem (A, B, C, O) · Lipoic Acid · Methanofuran · Molybdopterin · PQQ · THB / BH4 · THMPT / H4MPT minerals: Ca2+ · Cu2+ · Fe2+, Fe3+ · Mg2+ · Mn2+ · Mo · Ni2+ · Se · Zn2+ Base Forms vitamins: Thiamine (B1) · Riboflavin (B2) · Niacin, Niacinamide (B3) · Pantothenic Acid (B5) · Pyridoxine, Pyridoxamine, Pyridoxal (B6) · Cyanocobalamin, Hydroxocobalamin (B12) Major families of biochemicals Saccharides/Carbohydrates/Glycosides · Amino acids/Peptides/Proteins/Glycoproteins · Lipids/Terpenes/Steroids/Carotenoids · Alkaloids/Nucleobases/Nucleic acids · Cofactors/Phenylpropanoids/Polyketides/Tetrapyrroles

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