Coenzyme Q10

Description

Coenzyme Q10 (CoQ10), also known as ubiquinone, is a lipoidal vitamin-like substance similar in structure to vitamin K. CoQ10 resembles a vitamin but is unique in that it is not only present in many human foods, but also can be biosynthesized within mammalian tissue. Two other vitamins having similar properties, including the ability to be synthesized within mammalian tissue, are nicotinamide and vitamin C.

CoQ6 through CoQ10 are the most common forms of this coenzyme and occur in a wide range of microorganisms. However, CoQ10 is found only in mammals. Studies have shown although other CoQ "homologues" are found in human tissue, only CoQ10 is functional. The homologues are in such trace amounts as to be functionally insignificant.

Coenzyme Q10 has captured the imagination of medical scientists since it was discovered in 1957 and isolated in 1960. Thereafter, researchers found it to be essential in cell respiration, electron transfer and the control of oxidation reactions (redox reactions). What this may mean therapeutically will be discussed later.

Coenzyme Q10 can be found human heart tissue. Its importance to humans is illustrated by the fact the heart may cease to function as coenzyme Q10 levels fall by 75%.

Method of Action

Dr. F.L. Crane and colleagues first isolated and extracted Coenzyme Q10 from mammalian tissue in 1957. Their initial research concluded CoQ10 was able to add or remove oxygen from a biologically active molecule. The importance of this becomes clear when it is realized a lack of oxygen can produce a decline in cellular energy, while an overabundance will result in the formation of toxic elements.

CoQ10 is found in the myocardium, particularly concentrated in the inner membranes of the mitochondria and membranes of the Golgi apparatus. Mitochondria manufacture adenosine triphosphate (ATP).

CoQ10 plays a critical role in pumping protons across the mitochondrial membrane, hence providing the body with enough energy to stay alive.

CoQ10 serves the same function as the cylinders in an automobile engine where the gasoline is ignited and explodes to drive the piston. Without CoQ10 the cell is like a dead engine; there is no spark or ignition. CoQ10 also appears to exert regulatory effects on mitochondrial enzymes. CoQ10 functions in redox reactions in Golgi membranes. The role of CoQ10 as a redox carrier in the respiratory chain is well established based on the evidence of reconstitution data and kinetic evidence.

Research on CoQ10-depleted or replenished submitochondrial particles demonstrates this coenzyme is essential to the redox component between NADH and succinate dehydrogenase and cytochrome. It also has regulatory effects on the succinate dehydrogenase and NADH dehydrogenase and cyctochrome b-C1 complex. More recent investigations confirm these findings.

These findings are important therapeutically, for they provide insight as to how CoQ10 can be of benefit those with congestive heart failure, for example, where correction of deficiencies and improved bioenergetics occur following treatment with CoQ10.

Oral administration elevates plasma CoQ10 levels. CoQ10 passes quickly from plasma into the tissue, reaching levels higher in tissue than would occur solely due to equilibration. CoQ10 is absorbed mainly into the liver and to a lesser degree into other tissues.

A carefully designed study compared CoQ10-containing vesicles with beta-carotene containing vesicles. The study raised the possibility that the observed CoQ10 antioxidant effect could be to scavenge singlet oxygen and to affect the structure of the lipid bilayer so as to inhibit the decomposition of hydrogen peroxide and the release of harmful free radicals.

Therapeutic Approaches

A review of coenzyme Q10's therapeutic benefits suggests that in time CoQ10 therapy may become a standard for prevention and treatment of cardiovascular disease, including angina pectoris; congestive heart failure; thyrotoxic heart failure; symptomatic mitral valve prolapse in children; cardiomyopathy, and cardiotoxicity induced by adriamycin (doxorubicin hydrochloride, a commonly used anti-cancer drug).

CoQ10 may be of benefit in the prevention and treatment of disease and reactions associated with immunodeficiency, gastric ulcers, accelerated weight loss in obesity, and periodontal disease. There is also evidence of enhanced physical and athletic performance and endurance following supplementation with CoQ10. It has received wide acceptance in Japan, where physicians have treated thousands of patients with CoQ10 for many years.

Decreased levels of CoQ10 have been repeatedly found in:
Congestive heart failure, diabetes mellitus, periodontal disease and muscular dystrophy.

There is strong scientific evidence for the efficacy of coenzyme Q10 in the improvement of cardiac function, as measured by monitoring using impedance cardiography of three prime criteria of the pumping performance of the heart. This evidence is on top of all the biochemical, pharmacological, biomedical and other clinical data that shows the essentiality of CoQ10 to the vitality of the human heart.

A review of 25 clinical reports from 110 physicians in 41 medical institutions, including two double-blind placebo trials, suggests therapeutic benefit in about 70% of patients having congestive heart failure. Essential hypertension improved, as did dyspnea, rale, edema and hepatomegaly. These symptomatic findings were supported by EKG, digital plethysmograph, phonocardiogram and carotid sphygmogram data. Dosages reported in these studies generally averaged 30 mg per day, taken orally for several weeks to months.


Adriamycin cardiotoxicity

Adriamycin is a chemotherapeutic agent used in the treatment of certain types of tumors. Some patients develop a serious cardiotoxicity after long term treatment on adriamycin. It has been shown in patients who have been on long-term treatment with adriamycin, CoQ10 levels are significantly lower than in controls. The drug inhibits CoQ10-dependent enzymes, possibly causing the deficiency.


Athletic performance

A limited number of studies have examined the benefits of CoQ10 supplementation in enhancing aerobic capacity, endurance or muscle strength. One such study of 6 healthy sedentary men (mean age 21.5 years), who were tested on a bicycle before and after taking 60 mg a day of CoQ10 for 4 to 8 weeks, showed some benefits as measured by improved cardiac function, oxygen capacity and oxygen transport. No study could be found on the use of CoQ10 in improving the performance or ability of trained athletes.


Cardiomyopathy

Numerous studies have shown benefits in most patients with severe cardiomyopathy. In a recent study, 88 of 115 patients completed a trial of therapy with CoQ10 for cardiomyopathy. Patients were selected on the basis of clinical criteria, x-rays, electrocardiograms, echocardiography and coronary angiography. Clinical responses proved favorable as measured by ejection fractions, cardiac output and improvements in functional classifications (as defined by New York Heart Association criteria).

A deficiency of CoQ10 has been measured in the blood and myocardial tissue of patients with severe cardiomyopathy. CoQ10 cardiac levels increased by 20-85% after 2 to 8 months of treatment with oral CoQ10.

In one double-blind crossover trial, 89% of patients receiving 100 mg of CoQ10 orally per day for 12 weeks experienced increased cardiac ejection fraction and muscle strength, and a decreased frequency of shortness of breath. These improvements continued for up to three years in patients who continued to take CoQ10. In an open trial of 34 patients, 82% reported improvements, as shown by increases in stroke volume, ejection fraction (25% to 40%) and cardiac index. The two year survival rate was 62%, compared to 25% for those treated without CoQ10 but receiving conventional therapies. However, this therapy is not as effective if the congestive heart failure is due to hyperthyroidism.

Hyperthyroid heart failure (thyrotoxic heart failure). Patients with hyperthyroidism have significantly lower CoQ10 levels than healthy controls. Because congestive heart failure can result from either CoQ10 deficiency or hyperthyroidism, one study gave 120 milligrams of CoQ10 daily for one week to 12 hyperthyroid patients. This therapy improved cardiac performance in these patients.

Cholesterol lowering agents
Cholesterol lowering agents (such as Mevacor and Zocor) dramatically inhibit the synthesis of coenzyme Q10. Dr. Alan Gaby considers it reprehensible, even malpractice, to prescribe these medications without providing CoQ10 at the same time.

Hypertension

A study of patients with hypertension found 39% of 59 patients had deficiency of CoQ10 versus 6% of 65 healthy controls. In another study, 25 patients with essential hypertension were given 50 milligrams a day of CoQ10 for 8 weeks. At the end of this period there was a significant decrease in blood pressure in the group as a whole. This study and many others have confirmed the antihypertensive effects of CoQ10. However, results are not immediate. Usually any benefits from CoQ10 are seen after 4 weeks of therapy. This seems to suggest CoQ10 corrects some underlying metabolic abnormality that later has a favorable effect on blood pressure.

Rat studies have demonstrated a decrease in the sodium-retaining effects of aldosterone and angiotensin II following CoQ10 administration. CoQ10 may also prevent some of the common side effects of beta-blockers, such as propranolol.

A small percentage of patients with diabetes mellitus might benefit from CoQ10. In a study of 120 diabetics, 8.3% were deficient in CoQ10, compared to 1.9% of healthy controls. Incidence of CoQ10 deficiency was more than twice as high (20%) in diabetics receiving oral hypoglycemic drugs.

Immune function declines with advancing age

Studies have demonstrated a marked CoQ10 deficiency in thymic tissue and pronounced suppression of immune response in aged mice. Partial improvement in immune response was accomplished with CoQ10 therapy.

The healing and repair of the gastric mucosa are very energy-dependent and presumably would depend upon Coenzyme Q10. Healing of gastric ulcers has been demonstrated in animals but not humans. Further work is in progress.

Mitral valve prolapse

In a study of children with symptomatic mitral valve prolapse, 85% showed marked cardiac improvement, after taking 2 mg/kg/day of CoQ10 for 8 weeks as compared to children taking the placebo. Relapse of symptoms occurred in those children who stopped taking CoQ10 within 12-17 months, but rarely in those who continued to take it for more than 18 months.

Muscular dystrophy

A series of studies demonstrated a marked biochemical deficiency of coenzyme Q10 in the cardiac and skeletal muscles of animals with hereditary muscular dystrophy. Therapy with CoQ10 and its analogs improved survival, performance and function in mice, rabbits and monkeys. These animals experienced significant gains in weight, improvement in righting reflexes and reduction of creatinuria.

Obesity

CoQ10 is important in cellular respiration. Data from morbidly obese subjects show an abnormally low level of CoQ10 in approximately half of those tested. To examine whether CoQ10 would help such obese patients loss weight, a study involving 9 subjects (5 with low CoQ10 levels) were given 100 milligrams of CoQ10 a day along with a measured 650 kilocalorie diet. After nearly 9 weeks, mean weight loss in the CoQ-deficient group was 13.5 kilograms (kg), compared to only 5.8 kg in those subjects with initially normal CoQ10 levels. This single study suggests CoQ10 might be of benefit in a weight management program employing very low calorie diets.

Periodontal disease

Periodontal disease affects 60% of young adults and over 80% of individuals over the age of 65. For many sufferers proper oral hygiene with brushing and flossing produces negligible results necessitating surgery. CoQ10 deficiency has been reported in 60 to 96% of patients with gingivitis.

Numerous studies have demonstrated significant benefits from CoQ10 therapy in the treatment of peridontitis. In one 3 week double-blind study, 18 patients with periodontal disease received either 50 milligrams a day of CoQ10 or placebo. All 8 patients receiving CoQ10 had less swelling, bleeding, redness, pain, exudate, loss of teeth and gingival pocket depth, than controls taking placebo. One of the study's dental specialists, who was blind to the nature of the study, commented the results seen in 3 weeks normally would be seen only after 6 months of conventional therapy.

In post-surgical treatment of experimentally-induced periodontal disease in dogs, CoQ10 accelerated the post-surgical healing time by 2-3 times the normal rate. CoQ10 may be beneficial in periodontal disease because it seems to correct abnormal citrate metabolism, found in many patients with periodontitis, a factor that appears to contribute to the disease.

Cells of the immune system are highly energy-dependent and therefore require an adequate supply of CoQ10 for optimal function. A number of experimental animal studies have shown CoQ10 enhances immune function. Increased serum immunoglobulin levels have been reported in humans with cardiovascular disease, diabetes or cancer after 27 to 98 days of taking CoQ10 at a dosage of 60 milligrams per day. However, it is not clear from these studies if the CoQ10 therapy improved immunocompetence or corrected immunodeficiency.

Psychotrophic drug-induced cardiotoxicity

All phenothiazines and tricyclic antidepressants, drugs commonly used in the treatment of psychiatric disorders, inhibit coenzyme Q10-dependent enzymes in vitro. Findings have important implications in drug-induced cardiotoxicities, since heart arrhythmias, heart failure, and myocardial infarction and sudden death from ischemia, have been associated with the use of these psychotrophic drugs. Histochemical studies have demonstrated the mechanism of such cardiotoxicity is probably related to inhibition of cellular respiration in myocardial tissue. Supplementation with CoQ10 resulted in positive electrocardiographic changes in psychiatric patients taking psychotropic drugs.

There is the possibility that CoQ10 might be useful topically, based on a recent study of skin penetration of CoQ10 in the rat. The coenzyme was suspended in olive oil and administered at two different concentrations. Coenzyme levels in the skin were directly related to the concentrations employed and the contact time allowed.

An excellent review of these and other studies on the therapeutic effects of coenzyme Q10 up through 1985 has been provided by Professor Yuichi Yamamura of Osaka University, Japan. He presents a comprehensive review of every clinical study reported in the literature on CoQ10 and heart disease, drug-induced cardiac disturbances, hypertension and cerbrovascular disturbances, with information on the investigators, experimental conditions, sample size, method of administration, statistical methods and outcome. His review is particularly noteworthy since the majority of clinical trials with CoQ10 have been conducted in Japan and published in Japanese.

Toxicity Factors

No serious side effects have been reported with long-term clinical use of CoQ10. In one study of 5,143 patients treated with 30 milligrams of CoQ10 per day, the incidence of side effects reported were epigastric discomfort (0.39%), loss of appetite (0.23%), nausea (0.16%), and diarrhea (0.12%).

Larger amounts (150 mg/day) are recommended.

No studies have been carried out on pregnant or lactating mother, suggesting such groups should take CoQ10 only under the advice and guidance of their physician.

No deaths or allergic reactions to CoQ10 have been reported in the literature.

Coenzyme Q10 is contraindicated in cases of known hypersensitivity.

There may be clinical decline and relapse of cardiac patients following CoQ10 withdrawal. It has been recommended CoQ10 be considered a lifelong therapy for patients classified in the most severe functional classes of heart disease (Class III and IV). Caution should be used in withdrawing this therapy from such patients. Severe clinical and hemodynamic rebound events may occur within a few weeks, but such patients again show clinical improvement upon resumption of CoQ10 treatment.

Overall, the safety of coenzyme Q10 has been studied thoroughly in Japan, where several million patients have used it for many years with few cases showing any signs of toxicity. The few side effects observed by Japanese physicians are common to many therapies for the conditions under treatment and were not proven to result from the administration of CoQ10.

Pharmaceutical interactions:

CoQ10 appears to be reduced, significantly (up to 40%) during use of cholesterol-lowering drugs (e.g. pravastatin or simvastatin ).

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