Coenzyme Q10

The biological role of coenzyme Q10
     Coenzyme Q10 and cardiovascular disease
     Coenzyme Q10 and muscle disease
     Coenzyme Q10 and periodontal disease
     Coenzyme Q10 and the body's resistance
     Coenzyme Q10 and diabetes
     Coenzyme Q10 and obesity

Coenzyme Q10 and detoxification processes
     Coenzyme Q10 and neurodegenerative
     diseases
     Coenzyme Q10 and aging
     Interaction of coenzyme Q10
     with medications
     Side effects and toxicity of CoQ10

Coenzyme Q10 (CoQ10), which is also called "ubiquinone", is one of the most important factors ensuring the normal course of life processes in the cell. Due to the extremely interesting biological properties, it has recently been the focus of specialists in many fields of medicine. Alzheimer's disease.

CoQ10 is an essential element of the respiratory chain; it participates in the mitochondrial electron transport, ensuring uninterrupted production and use of high-energy phosphorus compounds.

It is also one of the most important lipophilic antioxidants, preventing the formation of free radicals and oxidative modification of proteins, lipids and DNA, as well as contributing to the re-generation of other strong lipophilic antioxidant - alpha-tocopherol.

• Transport of electrons in the mitochondrial respiratory chain and transport of electrons outside the mitochondria;
• Anti-oxidant effect in the lipid phase;
• Regulation of the physic-chemical properties of biological membranes;
• Stabilization of cell membranes, increase their resistance to proteases and phospholipase A;
• Support for the conduction of free ion channels;
• involved in the activation of mitochondrial proteins and signaling protein kinases, as well as in the formation of disulfide bonds (in bacteria);
• Effect on the number of beta-2-integrins on the surface of blood monocytes;
• Prevention of dysfunction of epithelial membranes (by increasing the concentration of NO).

These properties justify the use of CoQ10 in diseases that can be caused by insufficient production of cellular energy, or free radicals action.

Given the high prevalence of ubiquinone in nature (it is contained in almost all foods); it is believed that it is impossible to talk about avitaminosis of CoQ10. Nevertheless, the results of many scientific studies, primarily conducted by Folkers and co-workers show that CoQ10 deficiency can occur in separate organs and body systems.

In disease states, inhibits the function of tissues and organs, local biosynthesis of CoQ10 becomes insufficient and it is required replenishing its deficit by transport through the bloodstream.

Intersystem CoQ10 deficiency can be caused by:

1. The oppression of its synthesis, because of:
   1. Malnutrition;
   2. Genetically determined defects of cells or their damage to by various factors in the disease;
2. Reduced CoQ10 content in the diet;
3. Increased needs.

The main reason for the low efficiency of ubiquinone biosynthesis is deficiency the raw material necessary for its production, in the first place, phenylalanine, tyrosine, and fatty acids.

Synthesis process includes several reactions, for which is required the presence of many coenzymes, including vitamins B2, B6 and B12, acid - folic and pantothenic, some minerals - fluorine, magnesium, calcium. With insufficient intake of substrates and coenzyme, CoQ10 biosynthesis efficiency decreases; that reduces its internal resources. This situation may arise, for example, in diet for weight loss, metabolic diseases (for example, phenylketonuria), as well as when taking certain medications such as A-reductase inhibitors (statins).

Deficiency of coenzyme Q10 in the body can also be a consequence of certain dietary habits (reduced levels of ubiquinone in the menu of vegetarians, in low-fat or too unilateral diets) or disease of the gastrointestinal tract. A special case is a cooking: boiling and frying result a loss of about 50% ubiquinone in the foods, and when the drying and fermentation losses can be even greater.

According to some researchers, CoQ10 deficiency may occur as a result of increased requirement for the substance, for example, during intense exercise (athletes), as well as when accelerated energy metabolism, such as hyperthyroidism - thyroid disease. Its deficiency is diagnosed with diseases such as heart failure, muscle diseases, nervous system or liver.

It was also noted that the content of coenzyme Q10 in various organs and tissues is less in the elderly than in younger people (for example, in people in their forties, the heart contains only 3/4 of the amount of CoQ10, which is available for 19-21 year olds; and in age 70-75 years, the amount thereof is reduced to half its initial value), as well as smokers. Ubiquinone deficiency may also be a consequence of drug therapy or radiation therapy.

The clinical manifestation of CoQ10 deficiency in humans is not clear. Its consequence is energy starvation, which as a result may reduce the effectiveness of the activity of cells, tissues and the whole organism. At first, signs of chronic fatigue syndrome may appear. Then, begin to dominate the symptoms of dysfunction of the organs, in which the depth of the deficit is greatest. This may be, in particular, impaired circulation, metabolism, rehabilitation processes, or the immune system.

CoQ10 is an essential link of the respiratory chain and, thus, extremely important part of the cell cycle of adenosine triphosphate (ATP) production. It is known that the degree of reduction of cardiac contractility is proportional to degree of ATP deficiency in cardiac muscle cells. From the above facts it follows that the lack of CoQ10 in heart muscle may reduce its exercise tolerance.

This was confirmed by the results of many clinical trials in which it was found that the content of CoQ10 in the heart muscle is lower the higher the degree of heart failure. However, it was not possible to find out until the end whether low levels of CoQ10 is primary cause or a consequence of heart disease, but clinical studies have shown a positive effect of CoQ10 on hemodynamic parameters in patients with heart failure.

First clinical results of CoQ10 using in treating cardiovascular disease were obtained in 1967 in Japan. Positive results of observations of Japanese researchers led clinicians from other countries to conduct their own research of suitability CoQ10 in the treatment of cardiovascular diseases.

Here are some examples:

Lengsdzhouin and colleagues compared the effectiveness of ubiquinone and placebo in patients with grades III and IV heart failure by NYHA classification (New York Heart Association). CoQ10 were given orally at a dose of 99 mg/day (3 x 33 mg) for 12 weeks. All examined patients were treated with digitalis and diuretics; 81% of patients were treated at the same time also vasodilators, 30% - antiarrhythmic drugs and 20% - oral anticoagulants.

The following results were obtained:

1. The average content of CoQ10 in the blood of sick people was lower than in healthy persons.
2. After 12 weeks of CoQ10 taking, its content in blood increased significantly.
3. After discontinuation of coenzyme Q10 and 12-week receiving the placebo, ubiquinone content in the blood decreased significantly.
4. During the receiving of CoQ10 there were positive changes, including the borders of the heart, the cardiac output and the left ventricular ejection as well as physical activity.
5. There were no side effects of CoQ10.
6. There were no adverse interactions of CoQ10 with other drugs that are taken at the same time.

Baggio with employees reported the consolidated results of studies on the efficacy and safety of coenzyme Q10 on the material of 2359 patients with congestive heart failure.

Most patients simultaneously receive glycosides, diuretics and/or angiotensin-convertase inhibitors. The therapeutic effect was evaluated at 3 months as a percentage reduction of the main symptoms of the disease, as well as on the NYHA functional scale in comparison with the initial state, that is, before start taking CoQ10.

Undesired symptoms were observed in 1.4% of patients, and most of them were mild. It is possible that they could be linked to conventional therapy, carried simulta-neously. Over 50% of patients reported improvement in quality of life.

According to Mantsoli and staff, in the treatment of heart failure, the best results are obtained by the intake of CoQ10 in a dose of 2 mg per kilogram of body weight.

The mechanism of action of coenzyme Q10 in heart failure has not been fully elucidated. It is assumed that it is associated with:

1. Beneficial effects on the respiratory chain;
2. The improvement of ATP synthesis and use;
3. The neutralization of free radicals;
4. The prevention of oversaturation of heart muscle cells by calcium ions;
5. The decrease in peripheral vascular resistance.

Some authors suggest that CoQ10 may also counteract the effects of elevated levels of aldosterone in patients with heart failure. Kumagai and Masako showed that CoQ10 decreases aldosterone levels in rats as a result of reducing the influx of calcium into the adrenal cells and inhibiting the hydroxylation of steroids.

Kuharskaya with colleagues presented the results of measurements of CoQ10 in heart muscle and blood of 34 patients after successful heart transplant. It was shown that patients who showed any signs of graft rejection, the ubiquinone content was significantly lower than in patients without evidence of rejection.

Based on this, the authors of this study suggest the use of measurement of CoQ10 level in heart muscle biopsy as a good marker of rejection of the transplanted heart. At the same time they pay attention to the fact that the deficit of coenzyme in the transplanted heart can be the cause of a violation of his bio-energy and the development of heart failure.

Confirmation of the validity of the proposals of Kucharskaya are researches of Moravesik who gave CoQ10 to cardiac patients before shunting surgery (bypass) at a dose of 180 mg per day for 21-28 days before surgery and for 3 months after surgery. There was first of all zero postoperative mortality. The conclusion from these studies is obvious - after cardiac surgery, reception of adequate doses of CoQ10 is needed.

The essence of coronary heart disease is the imbalance between the myocardial need for oxygen and its entry into myocardial cells. The lack of oxygen leads to a decrease in the pH of the intracellular medium, slowing ATP synthesis, reduction in the concentration of potassium ions and increase in concentration of sodium and calcium ions.

A major consequence of ischemia is the increased production of free radicals, which oxidize the lipids of cell membranes and other intracellular components, including respiratory enzymes. Violation of the dynamics of exchange processes can be restored by bringing in cardiac tissue substances involved in the respiratory chain of cardiocytes, first and foremost, such necessary for the normal functioning of this complex enzymatic system connection as CoQ10.

Coenzyme Q10, by the activation of energy production in mitochondria, can maintain cellular ATP stores at the appropriate level and to maintain a pH within normal limits. It facilitates the transport of calcium ions into cells, and their interaction with the contractile elements. Stabilizing cell membranes, CoQ10 improves the conductivity of calcium channels. As a result, it prevents the disturbance of function and structure of the myocardium in conditions of oxygen starvation.

Some researchers believe that the beneficial effect of Coenzyme Q10 in patients with coronary heart disease is the result of increased blood rheology, primarily viscosity reduction. R. Singh said that taking CoQ10 120 mg per day in 144 people with acute infarction in the randomized, double-blind study, significantly reduced pain, the number of cardiac arrhythmias and left ventricular dysfunction. In the group receiving ubiquinone, there were fewer sudden deaths during the four weeks of observation.

Coronary heart disease often affects older people. Numerous studies have shown that CoQ10 content in heart muscle in people in this age group decreased. According to Rosenfeld and co-workers, for this reason alone there are grounds for preventive CoQ10 supplementation for elderly people, especially having coronary heart disease.

It was found that CoQ10 facilitates production and utilization of ATP in cardiac muscle when using electrical stimulation. It was also noted that this substance speeds up the elimination of lactic acid and reduces its production in low supply of oxygen to the heart.

It should also be recalled that CoQ10, preventing oxidation of LDL cholesterol, slows the development of atherosclerosis. Interesting data have been obtained as a result of numerous studies conducted by Italian doctors in the therapeutic efficacy of coenzyme Q10 in patients with stable stenocardia. They compared two groups of patients: undergoing conventional treatment and getting extra ubiquinone. It was found that the addition of CoQ10 improved life comfort of patients, reducing the frequency of pain attacks. They also proved to be less need to increase dose of age drugs.

It was noted that the prophylactic intake of CoQ10 patients before surgery of the aortic bypass protects against the effects of free radicals, reduces the risk of arrhythmias and other disorders.

It is found that patients with atherosclerosis and coronary heart disease have a low content of CoQ10 in the blood. According Hanaki, a high ratio of LDL/CoQ10 in plasma may be an important factor that increases the likelihood of developing these diseases.

Ubiquinone inhibits cholesterol biosynthesis in the liver and decreases its blood levels, but its effect on LDL oxidation is most important. Some authors believe that the reduced form of ubiquinone protects LDL against peroxidation more effective than vitamin E and beta-carotene.

CoQ10 is involved in the first line of cellular defense from reactive oxygen forms, preventing free radical reactions with components of the cell membranes and plasma lipids. This may be an important factor in the prevention of atherosclerosis. It should be emphasized that the above-mentioned oil-soluble antioxidants may interact with each other. Ubiquinone restores tocopherol radicals to tocopherol, while alpha-tocopherol recovers beta-carotene.

Digezi with employees given CoQ10 100 mg daily for 10 weeks to patients with hypertension and observed a statistically significant reduction in total blood cholesterol, as well as an increase in HDL fraction. According to these authors, the exogenous ubiquinone may be especially useful in patients with hyperchole-sterolemia, reducing the risk of coronary heart disease and hypertension.

Unusually high CQ10 levels in the blood noted among the Eskimos, which is undoubtedly a consequence of their diet. It should be emphasized that the Eskimos are characterized by low incidence of atherosclerosis and coronary heart disease.

In high blood pressure, peripheral vascular resistance increased. The development of this phenomenon depends on the humoral factors, processes of the nervous regulation and self-regulation mechanisms. Correct dynamics of contraction and relaxation of the blood vessels is determined by bioenergetic processes. Therefore CoQ10 deficiency may turn on mechanisms that lead to increased peripheral resistance and thereby to increased blood pressure.

This was the conclusion of B. Digezi with staff who gave patients with hypertension CoQ10 100 mg daily for 10 weeks. Initially, the ubiquinone content in the blood was 0.64 + - 0.1 mg/ml, but after treatment, it increased to 1.61 + -0.3 mg/ml.

It was found that the decrease in systolic and diastolic blood pressure correlated with the increase in the content of CoQ10 in the blood. Such a reaction is due to a significant decrease in peripheral resistance. At the same time there was noticed a reduction in total blood cholesterol and increase the level of HDL fraction. There has been no change in content of potassium, endothelin and renin in the blood, and aldosterone in the urine.

Interesting results were obtained by Lengsdzhouin with staff who in 109 patients evaluated the efficacy of CoQ10 in conjunction with the previously prescribed treatment with antihypertensive drugs. Ubiquinone was given in an average dose of 225 mg/day for about 13 months. Arterial hypertension was assessed by NYHA functional scale, and systolic and diastolic pressure was recorded also.

The vast majority of patients had a significant reduction in blood pressure, and some of them have managed to reduce the dose of antihypertensive drugs. The authors came to the following conclusions:

• By receiving CoQ10 in patients with idiopathic hypertension, it can be achieved significant improvement in the clinical picture and a significant reduction in blood pressure (both systolic and diastolic), despite the abolition of the majority of patients of all other antihypertensive drugs;
• Exogenous CoQ10, improving the function of the left ventricle in the diastolic phase, reduces the degree of compensatory neurohumoral activation;
• Despite receiving very high doses (average of 225 mg per day) and the achievement of a high concentration of CoQ10 in the blood, there were not noticed any serious side effects as well as interactions with other drugs.

It should be emphasized that in some clinical variants of hypertonic disease, hypo-tensive effect of coenzyme Q10 was continued for some time after taking the drug.

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