ROLE OF COENZYME Q10 IN MODERN MEDICINE

Coenzyme Q10 (CoQ10), also referred to as ubiquinone is one of the important ensuring factors proper course of life processes cells. Due to the remarkable biological properties, it finds itself in the spotlight more and more specialists from many fields of medicine.

THE BIOLOGICAL ROLE OF COQ10

CoQ10 is an essential element of the respiratory chain – taking part in the mitochondrial transport of electrons, it conditions the proper production of and the use of high-energy phosphorus compounds. It is also one of the more important lipophilic antioxidants, which prevents the generation of free radicals, oxidative modifications of proteins, lipids and DNA and contributes to the regeneration of another strong antioxidant lipophilic – alpha-tocopherol (Tab. 1).

Table 1. Biological functions of CoQ10 [1]

Electron transfer in: • the mitochondrial respiratory chain • extra-mitochondrial electron transport

Antioxidant activity in the lipid phase

Regulating the physicochemical properties of biological membranes: • stabilization of cell membranes, making them resistant to proteases and phospholipase A • influencing the integrity of free ion channels

Participation in the activation of mitochondrial coupling proteins and signaling kinases proteins, as well as in the production of disulfide bridges (in bacteria)

Influencing the amount of beta 2-integrins on the surface of blood monocytes

Prevention of epithelial dysfunction (by increasing NO concentration)

These properties justify the use CoQ10 in diseases that may result from insufficient energy production or performance free radicals.

CAUSES OF COQ10 DEFICIENCY IN THE BODY

Due to the fact that they occur everywhere ubiquinone in nature (it contains it practically each food – Table 2) it was believed that you cannot talk about avitaminosis Q10. However, the results of many research, carried out primarily by Folkers et al. confirm that the shortage CoQ10 may only affect specific organs. In disease states that impair function organs and tissues, local biosynthesis is insufficient and requires redistribution through the bloodstream to complete its content.

Table 2. CoQ10 content in selected subjects food products [1].

Food product	CoQ10 [μg / g]
reindeer meat	157.9
canola oil	63.5
beef	36.5
pork liver	22.7
pork ham	20.0
tuna	15.9
Herring	15.9
chicken	14.0
trout	8.5
black currant	3.4
cauliflower	2.7
pea	2.7
yoghurt	2.4
beans	1.8
carrot	1.7
strawberries	1.4
orange	1.4

Intracorporeal CoQ10 deficiencies can be caused [4]:
1.impaired synthesis due to:
a. malnutrition
b. genetically determined defects cells or their damage by various factors pathogenic
2. a reduced content of ubiquinones in the diet
3. Increased demand.

The main reason for the low biosynthesis efficiency ubiquinone is deficient in basic substrates. needed for its course, above all phenylalanine, tyrosine and fatty acids. The synthesis process includes several reactions demanding for their smooth running, presence many coenzymes, including vitamins B2, B6 and B12, folic and pantothenic acids, and some minerals – fluorine, magnesium, calcium. Substrate and coenzyme deficiencies make CoQ10 biosynthesis less efficient, which reduces its endogenous resources. For such a situation may occur during slimming treatments, metabolic diseases (e.g. phenylketonuria) or taking certain medications, such as reductase inhibitors HMG-CoA.

CoQ10 deficiency in the body can also be a result specific eating habits (lower Wife content of ubiquinones in a vegetarian diet, too low fat, too one-sided) or gastrointestinal diseases. A separate cause is food processing – cooking or burning leads to a loss of the order of ubiquinones 50%, while drying and fermenting the losses can be even greater.

According to some researchers [4] CoQ10 deficit it may result from increased demand on this substance, e.g. during intense exercise towards the physical (athletes) and in the states that is accompanied by an accelerated transformation of energy, e.g. in overactive thyroid gland. Its deficiency is noted in the course of diseases such as failure diseases of the muscles, nervous system or liver. It was also observed that the content of CoQ10 is less in various tissues and organs in older people than in young people (eg in the heart at the age of around 40, there is only 3/4 of that coenzyme compared to the group of 19-21-year-olds, and by the age of 70-75, its quantity drops to half original value) and in smokers. Ubiquinone deficiencies can also be a consequence pharmacotherapy or radiotherapy used.

Clinical picture of coenzyme Q10 deficiency in humans, it is ambiguous. His aftermath there is an energy deficit, which in consequence may disturb the efficiency of a cell, tissue or the whole organism. In the initial period, they may the appearance of the features of chronic fatigue syndrome. The symptoms of the part then begin to dominate those organs in which the greatest occurs deficit of this compound; this is especially true of the layout circulation, metabolism, repair processes, the immune system [1].

COENZYME Q10 AND DISEASES CARDIOVASCULAR

General aspects

CoQ10 is an essential component of the chain respiratory system, and therefore extremely important link in the cycle of reactions leading to production adenosine triphosphate (ATP). It is known that the degree the reduction in heart rate is proportional to the degree of ATP deficiency in cardiocytes. From the above facts, therefore, we can draw the following confirmation of conclusion: Myocardial CoQ10 Deficiency it can reduce its efficiency. This has been confirmed by the results of many clinical trials, in which it was found that the contents CoQ10 in the heart muscle was lower with them the degree of heart failure was higher [4]. Admittedly, it has not been fully clarified whether the low levels are CoQ10 are either a primary cause or a consequence heart disease, however, are some attempts clinical findings indicate a beneficial effect of CoQ10 on haemodynamic parameters in patients with failure hearts.

Circulatory failure

First application clinical trials CoQ10 in the treatment of heart failure, performed in Japan in 1967. Positive the observations of Japanese researchers encouraged clinicians from other countries to gain your own experience over the usefulness of CoQ10 in therapy cardiovascular diseases.

Here are some examples:

• Langsjoen et al. [3] compared the efficacy of ubiquinone and placebo in class III and IV patients circulatory failure according to the NYHA. CoQ10 was administered orally at a dose of 99 mg / day (3 x 33 mg) for a period of 12 weeks. All the examined patients were treated with digitalis and medications diuretics, 81% of patients received vasodilating drugs at the same time, 30% antiarrhythmic drugs and 20% oral anticoagulants. The following results were obtained:

1. the average concentration of CoQ10 in the blood of patients it was lower than in healthy subjects2. After 12 weeks of using CoQ10, its concentration in the blood increased statistically significantly
3. after discontinuation of CoQ10 and after 12 weeks after taking a placebo the concentration of ubiquinone in the blood dropped statistically significantly
4. During the use of CoQ10 it was found favorable change, incl. in terms of: dimensions heart rate, stroke and ejection fraction left ventricle and physical activity,
5. No side effects were observed CoQ10
6. no adverse interaction effects were found CoQ10 with other concurrently administered drugs drugs.

• Baggio et al. [4] presented the results multi-center effectiveness research and the safety of CoQ10 in 2359 patients with congestive heart failure. Most people were treated concurrently digitalis, diuretics and / or inhibitors angiotensin converting enzyme. Therapeutic effects evaluated after 3 months as a percentage resolution of basic symptoms and by class performance in relation to the study output, ie before starting CoQ10 administration. Some of the obtained the results are shown in Table 3. Symptoms side effects were found in 1.4% of patients, they were usually mild. It cannot be ruled out that they were related with parallel therapy conventional. The quality of life improved in over 50% of patients.

Table 3. Effect of CoQ10 on some symptoms
in patients with heart failure [4]

Symptom of the diseas	Resolution of symptoms in percentage of the number of the assessed group
Cyanosis	78,7
Swelling	78,1
Enlarged liver	49,3
Dyspnoea	52,8
Irritability	63,4
Insomnia	62,9
Dizziness	73,1

CoQ10 at a dose of 2 mg / kg body weight.

Mechanism of Action of CoQ10 in Failure the heart is not fully explained [3]. I suppose that it is associated with:

1. a beneficial effect on functioning Respiratory chain
2. improving the synthesis and utilization of ATP
3. neutralizing free radicals
4. prevention of cell overload of the heart muscle with calcium ions
5. reduction of vascular resistance perimeter.

Some authors believe CoQ10 can also counteract the consequences of the increased concentration Of aldosterone in patients with cardiac insufficiency Wives. Masaka and Kumagai showed that CoQ10 decreased the concentration of aldosterone in the blood of rats as a result reduce the influx of calcium into the adrenal gland cells and inhibiting the hydroxylation of steroids.

Kucharska and  others presented the measurement results CoQ10 levels in the heart muscle and blood of 34 patients after a heart transplant. They indicate they, that in patients with diagnosed eggs transplant rejection symptoms, concentration ubiquinone was significantly lower than in the group people with no evidence of transplant rejection. On this basis the authors of this study propose to use CoQ10 concentration measurement in meat biopsies Heartburn as a good rejection marker a transplanted heart. They pay off simultaneously attention that deficiency of coenzyme in the transplanted the heart may disrupt its bioenergetics and development of heart failure [10].

Confirmation of the correctness of Kucharska’s suggestion and others are the results of the research by Moravesik, who gave CoQ10 to patients prior to cardiac surgery (bypass grafts) in a dose 180 mg daily 21-28 days before surgery and for 3 months after the procedure. It was found mainly all have zero post-operative mortality.

The conclusion from these studies seems obvious – after supplementation should be included in cardiac surgery procedures appropriate CoQ10 dosages.

Ischemic heart disease

The essence of ischemic heart disease is lack balance between oxygen requirements and its quantity delivered to this organ. Ischemia the myocardium leads to a depression intracellular pH, reduce synthesis ATP and potassium levels and increases sodium and calcium. A serious consequence of ischemia is to increase the production of free radicals, which oxidize cell membrane lipids and other intracellular components, incl respiratory chain enzymes. Disturbed dynamics metabolic processes can be improved, by delivering substances that act in the respiratory chain cardiocytes, and therefore above all crucial for the proper functioning of this complex enzyme system the compound as is CoQ10.

CoQ10 by activating energy production in the mitochondria it can support the cells stocks ATP and keep pH within normal range. It allows for an appropriate flow of ions calcium into cells and their interaction with the elements contractile. By stabilizing the cell membrane, it has a positive effect on free calcium channels. In effect prevents sudden functional disturbances and myocardial structure in ischemic conditions. Some researchers consider it beneficial the effect of CoQ10 in patients with ischemic disease the heart is the result of rheological improvement the properties of the blood. It consists in reducing its viscosity [3].

Singh R. showed that administration of CoQ10 at a dose 120 mg daily in 144 people with acute myocardial infarction randomized, double-blind trials it significantly reduced the frequency of pain attacks and disorders rhythm and dysfunction of the left ventricle. In a group the recipient of ubiquinone was also smaller number of sudden deaths in a four-week period observation.

Ischemic heart disease is more common in elderly people. The results of numerous studies indicate that the content of CoQ10 in the heart muscle in people in this age group it is reduced. According to Rosenfeldt et al., At least for this reason there are justifications for prophylactic supplementation CoQ10, especially in elderly people with the disease ischemic heart disease.

CoQ10 has been found to facilitate production and use ATP through the heart muscle undergoes electrical stimulation. Moreover, it was noted that this compound accelerates the consumption of lactate or even reduces their production in an ischemic heart. It is also worth recalling at this point that CoQ10 slows down the process by blocking the oxidation of LDL atherosclerotic [3].

Interesting data was collected at multi-center time tests carried out by Italian doctors over the therapeutic efficacy of CoQ10 in patients with stable angina. Two large groups were compared: those receiving treatment in the usual manner and receiving supplements ubiquinone. It was found that joining CoQ10 has improved the quality of life of patients by reducing the frequency of pain episodes. It is also less There is a need to increase the doses of coronary drugs. It has been observed that the prophylactic use of CoQ10 in patients before bypass surgery coronary artery disease, protects against the effects of the action free radicals, reduces the risk of their occurrence symptoms of low relapse and heart rhythm disturbances.

Atherosclerosis

It is postulated that patients with atherosclerosis and disease patients with ischemic heart disease have a low concentration of CoQ10 in the blood. According to Hanaki, a high concentration ratio Plasma LDL / CoQ10 may be an important factor increasing the likelihood of development these diseases.

Ubiquinone inhibits the biosynthesis of cholesterol in the liver and lowers its concentration in the blood [Krishnaiak et al.], however the most important is its influence on LDL oxidation. Some authors believe that it is reduced the ubiquinone form protects LDL from peroxidation more effective than vitamin E or beta-carotene. This is because CoQ10 is in the front line defense of cells against reactive oxygen species, preventing the reaction of free radicals with components of cell membranes and plasma lipids [3]. It can be one of the important factors in the prevention of atherosclerosis. It should be emphasized that the mentioned above, hydrophobic antioxidants they can interact with each other. Ubihydroquinone reduces the tocopherol radical to tocopherol, and alpha-tocopherol regenerates beta-carotene.

Digiesi et al. Administered CoQ10 at a dose of 100 mg per day for 10 weeks in hypertensive patients and found significant statistical values ​​in the blood reduction of total cholesterol, a increasing the HDL fraction. According to these authors, exogenous ubiquinone may have a particularly beneficial effect effect in people with hypercholesterolaemia, reducing the risk of coronary heart disease and hypertension.

An unusually high concentration of CQ10 is found in Inuit blood, which is undoubtedly a reflection their diets. It should be emphasized that the Inuit it is characterized by a low incidence of atherosclerosis and ischemic heart disease.

Hypertension

In the course of arterial hypertension, the peripheral increases vascular resistance. In inducing it the symptom is played by humoral factors, system nervous and autoregulatory mechanisms. Dynamics vasoconstriction and relaxation is determined by properly running bioenergetic processes. The CoQ10 deficit may, therefore, intensify the mechanisms that which lead to an increase in the peripheral resistance, thereby increasing the blood pressure blood.

Digiesi V. et al. [3] who in patients with arterial hypertension they used CoQ10 at a dose of 100 mg per day for 10 weeks. Initial ubiquinone concentration in blood was 0.64 ± 0.1 µg / ml, and after treatment it rose to 1.61 ± 0.3 μg / ml. It was found that Complaints of systolic and diastolic blood pressure correlated with an increase in blood CoQ10 concentration. This reaction was caused by a significant reduction peripheral resistance. It was recorded simultaneously reduction of total cholesterol and increasing the HDL fraction in the blood. Not observed while changes in the content of potassium and endothelin and renin in the blood and in the excretion of aldosterone with urine.

Interesting are the observations of Langsjoen et al. [4], who evaluated effectiveness in 109 patients CoQ10, provided with previously used medications hypotensive. Ubiquinone was administered at a dose An average of 225 mg / day for approximately 13 months. Hypertension was assessed according to the functional class NYHA and the systolic pressure values ​​were determined and diastolic.

In the vast majority of patients it was obtained significant reduction in blood pressure, and for some it was possible to reduce the number of used antihypertensive drugs. The authors of the work came to the following conclusions:

• by administering CoQ10 to patients with hypertension intrinsic can be significantly improved clinical and significant blood pressure lowering blood pressure (both systolic and and diastolic) despite interruption in most patients using all other medications antihypertensive;
• exogenous CoQ10 improving left function ventricles in the diastolic range reduces the degree compensatory neurohumoral activation;
• despite administering very large doses (Average 225 mg per day) and get high blood levels of CoQ10 have not been observed no more serious side effects or interactions with other medications.

It should be emphasized that, in some models of hypertension, the antihypertensive effect of CoQ10 continued for some time after drug discontinuation.

COENZYME Q10 AND MUSCLE DISEASES

In the etiopathogenesis of certain muscle diseases a metabolic defect, often, plays an important role genetically conditioned. Results of histopathological examinations and biochemicals indicate a number structural and functional disorders of cells muscles, and they are especially relevant mitochondria – they are characterized by an incorrect size, shape, chaotic comb arrangement, accumulation of lipids and glucogen and crystalline inclusions. Does not work also a normal mitochondrial chain respiratory disease, which manifests itself as a disorder energy generation and consumption. As a result, they develop symptoms of metabolic myopathy develop clinically, whose treatment is often not very effective. This is why some hope is posed by the possibility of correction metabolic disorders underlying these diseases by exogenous CoQ10.

For example, it has been observed that the administration of ubiquinone genetically conditioned mice muscular dystrophy improves their physical performance and extends life. Similar results were obtained in people suffering from polymyopathies and muscular numbness. Physical efficiency has improved significantly and normalization of biochemical disturbances, i.e. primarily reducing the level of kinase plasma creatine phosphate [4].

In a randomized, double-blind Folkers trial et al. administered to 12 patients for 3 months with muscular dystrophy 100 mg CoQ10. Observed increasing the ejection fraction left ventricle, as well as improving overall well-being in 4 out of 8 patients. In terms of subjective symptoms, increased tolerance was achieved effort, pain alleviation On the legs, better control of the functions of the lower limbs and less martyrdom [5].

In 1998, Judy et al. assessed the impact of supplementation CoQ10 on the well-being of people with the syndrome chronic fatigue, during which disturbed the production of energy in the mitochondria remains – as a result, your ability to exercise is significantly reduced effort and the maximum duration of its execution. First of all, it was noticed that in patients for this reason, the concentration of Ingestion of CoQ10 in the blood and muscles. Administration these people ubiquinone in doses of 100 and 300 mg per day markedly increased its level of e blood and tissues and increased their ability to overcoming physical effort; the effect was evident bigger after a higher dose. However after treatment discontinuation (after 60 and 90 days), the condition of patients reverted to the state before treatment.

COENZYME Q10 AND PARODONTOSIS

Treatment of periodontal diseases due to its complex nature the etiology presents serious difficulties. Primary the factor responsible for the inflammation the periodontium has a plaque. Bacterial infiltration to peridontal tissues, it can also be disabling local activity of the immune system [3].

It is known that all repair processes, including peridental tissues, require efficient energy production, to a large extent depending on the appropriate amount of ubiquinone. Works over the influence of CoQ10 on periodontal disease started about 20 years ago in numerous centers The United States [among others Wilkinson et al.], Japan [Shizukuishi et al.], and more recently in the Scandinavian countries [Nylander and Nordlund, Moe]. The data collected so far suggests that exogenous CoQ10, out of proportion in the process of producing high-energy of phosphorus compounds, has a beneficial effect on the local level the immune defense of the inflamed gum. Moreover, an influence on the bacterial flora in the mouth through the lesion its composition and enzymatic activity [4].

Reduced levels have been found in numerous studies ubiquinone in gum biopsies in 60-96% of patients with periodontal diseases, and in 86% of cases low concentrations of this substance in leukocytes [5]. This discovery clearly shows That periodontopathy is often associated with a deficiency CoQ10.

It was noted that a particularly beneficial effect on some of the symptoms of periodontitis are simultaneous administration of CoQ10 generally and locally (into pockets perineal). As a result of such therapy gingival bleeding and swelling and mobility decreased teeth, depth and number of pockets approx. and the volume of purulent discharge. Improvement the clinical condition correlated with an increase in enzyme activity dependent on CoQ10 in collected samples gums and increased ubiquinone levels in the blood [3].

The influence of CoQ10 on periodontal changes is possible strengthen it by taking it together with vitamin B6. Mc Ree et al., Using this method of therapy, showed a marked improvement in the assessment of the indicator gingivitis and reducing the number of bacteria. Moreover, they found a specific correlation between the improvement condition and the activity of the system in the assessment of IgG production and the T4 / T8 ratio [9].

COENZYME Q10 AND PROCESSES RESISTANT

Cell proliferation and differentiation, and production antibodies are bioenergetic processes. CoQ10 deficiency in the human body can therefore, it interferes with the body’s ability to maintain these processes at the appropriate level. Assumption this is confirmed by observations pointing to increase in serum immunoglobulin G concentration patients taking CoQ10 for illnesses cardiovascular system, diabetes or cancer. In the next research not only found an increase immunoglobulin G levels, but also numbers T4 lymphocytes and an increase in the ratio of T4 lymphocytes to T8 [3].

Evidence of the beneficial effects of CoQ10 on the immune system is also affected by the assessment this substance on the course of infections and some neoplastic diseases. Administering ubiquinone to mice with granulocytopenia, infected with pus stick blue, significantly increases survival animal. Infected, unprotected mice coenzyme, all died after 2 days, while when more than 50% of mice were administered CoQ10 it survived [4]. Sciaglione et al. Showed that in people receiving CoQ10 at a dose of 180 mg titer antibodies per day for 3 months after vaccination against viral hepatitis type B was significantly higher than in the group receiving a placebo. This observation was confirmed by Barbieri et al. CoQ10 no on the other hand, it influences the concentration of inflammation mediators, such as: thromboxane B2, leukotriene B4, prostaglandin E2, interleukin 6 and necrosis factor tumors.

The research on the influence of ubiquinone on the course of some. Weber et al. downright dramatic lowering the level of CoQ10 in the blood of children with cancer the hematopoietic system (up to 50%), and the activation of conventional chemotherapy caused a further decline in this level. Authors postulate that low ubiquinone values ​ may be the result of increased oxidative stress and accelerated metabolism in neoplastic tissue. This issue became the subject of research clinical trials, Mari et al. They noticed that in the sick with colon, lung and mammary carcinoma occurs to a significant reduction in the level of CoQ10 in the blood that can be counteracted by giving this substance a treatment at a dose of 300 mg per day. Also obtained thus an increase in total endurance antioxidant, determined in the blood of patients [4]. Other authors have noted that CoQ10 may inhibit the production of some cancer associated cytokines [3].

In the studies by Lockwood et al., In which CoQ10 has been administered in conjunction with other antioxidants 32 women with breast cancer, 6 were obtained remissions (confirmed, inter alia, by tests X-rays). In the remaining 26 patients, clinical improvement was also noticed, which made it possible a significant reduction in the doses of painkillers (morphine).

He focuses his speech on these problems Hodgess at The First Conference of the International Coenzyme Q10 Association, putting the dramatic the question: “Does CoQ10 play a role in the treatment of cancer?” In his opinion, there is a full justification for the use of CoQ10 in cancer patients – not only to make up for shortages, but also to achieve specific results therapeutic. Hodgess suggests necessity a significant increase in the doses administered CoQ10 together with other oxidants (such as vitamin E, selenium) and unsaturated acids fatty foods [4].

COENZYME Q10 AND DIABETES

An interesting field of research on the usefulness CoQ10 in treatment turns out to be diabetes, especially type 2 It has been known for many years that patients with diabetes have a pronounced ubiquinone deficiency in blood. Some authors see a role deficiency of this compound in the etiopathogenesis of diabetes. A stimulus enhancing the activity of the mitochondrial body the respiratory chain is critical component of the signal transduction mechanism, through which has elevated blood glucose levels increases insulin secretion by beta cells pancreas. It seems that a particularly important role plays a proper mitochondrial function in this respect glycerol-3-phosphate dehydrogenase. It is assumed that in diabetics, expression this enzyme is reduced. Low CoQ10 ingestion in the body of diabetic patients may impair his function even more, thus aggravating the degree of metabolic disturbances.

Japanese researchers have shown in several cases improving pancreatic beta cell function and control metabolic rate in patients with type 2 diabetes, those receiving CoQ10 supplementation. You can’t exclude that this reaction was the result of improvementactivity of mitochondrial enzymes in cells beta. Liou C. et al. Observed an improvement pancreatic beta cell function after application CoQ10 in a patient with mitochondrial encephalopathy, lactic acidosis syndrome of episodes similar to stroke and diabetes [3].

COENZYME Q10 AND OBESITY

It turned out that in the majority of obese people, CoQ10 deficiency is severe. Patients with obese Ia treated with diet alone with patients who have been using it diet and took an additional 100 mg of ubiquinone daily. Weight loss in the second the group was three times larger. It concerned mainly all obese people diagnosed with CoQ10 deficiency [4].

A tendency to obesity in some cases it is associated with disturbed energy production. Yeah the abnormality may be partially genetic conditioned. People with family obesity in an interview have a 50% reduced post-meal thermogenesis, suggesting the presence of a congenital defect in energy expenditure [5].

COENZYME Q10 AND DETOXIFICATION PROCESSES

Detoxification of harmful environmental substances and drugs very much through the process oxidation, and more precisely – in the course of phosphorylation for which CoQ10 is required. The most spectacular reduction results the toxicity of drugs by ubiquinone was obtained with adriamycin (read: “CoQ10 drug interactions”).

The evaluative research by A. D∏ugosz is also interesting exposure of paint and varnish factory workers to harmful factors in the workplace. It has been found that administration of CoQ10 reduces certain toxic effects of organic solvents on the employees among them. In people receiving CoQ10 at a dose of 30 or 60 mg per day for four weeks has been found statistically significant reduction in production lipid peroxidation [11].

It has been observed that prophylactic administration CoQ10 reduces the risk of developing cancer in mice induced by dibenzopyrene and elongation regret the survival of these animals. Beneficial impact CoQ10 on the above-mentioned parameters was increasing along with the applied dose.

COENZYME Q10 AND NEURODEGENERATIVE DISEASES

As has been mentioned many times, CoQ10 is an essential component of the electron transport chain and an important acting antioxidant a major role in both mitochondria and membranes phones. Disturbances in these processes they play an important role in various neurodegenerative processes. There is evidence of a involvement of these disturbances in Alzheimer’s disease, Huntington’s disease (chorea), Parkinson’s disease and sclerosis scattered. Trials have been carried out for many years supporting the treatment of these diseases with the help of CoQ10. The data collected so far is an incentive to apply ubiquinone in combination therapy as a supplement proven therapeutic regimens, but still require objective documentation [4].

COENZYME Q10 AND AGING

Some describe the aging process as a universal bioenergy deficiency – resulting from the predominance of oxidative processes (oxidative stress) and the inability to regain the re-energization of cells, tissues and the entire body.

Experimental evidence of the effectiveness of CoQ10 in delaying the aging process is provided by the results of the studies by Blizniakov, who in 1980 published the results of long-term use of CoQ10 in mice. It turned out that mice receiving ubiquinone lived much longer than mice in the control group. The mean life of the control mice was 20 months, and the CoQ10-treated mice 31.2 months – a 56% increase in life expectancy.

The authors of the study found that the mice given CoQ10, despite the passage of time, were normally active and their external appearance was clearly better than that of the control animals. Thus, the results of Blizniakov’s research show that administering CoQ10 to mice and replenishing its deficiency during the aging process can significantly extend life. It cannot be ruled out that this may only apply to mice [4].

COENZYME Q10 INTERACTIONS

The interactions of CoQ10 with other drugs are not fully understood. Most of the data concern the interaction of ubiquinone with anthracycline antibiotics, especially doxorubicin. The mechanism of interaction of these two substances at the level of the heart muscle is complex and boils down to:

1. opposing effects on the activity of enzymes in the respiratory chain
2. protection of membrane lipids and other cell structures against the influence of free radicals produced in the biotransformation of doxorubicin
3. the probability of competing due to the presence of the quinone group in both compounds for the same receptor in the heart muscle.

It should be emphasized that CoQ10, by reducing the cardiotoxicity of doxorubicin, does not weaken its antitumor effect. Doxorubicin destroys cells by blocking DNA and RNA synthesis and by damaging DNA repair processes. And this action is inhibited by CoQ10. This compound protects the heart muscle cell against the destructive action of free radicals generated in the anthracycline biotransformation process.

Mitomycin C, cyclophosphamide and 5-fluorouracil have an inhibitory, although weaker influence on the enzymes of the respiratory chain [3].

The results of studies by a group of Japanese researchers indicate that diazoxide and methyldopa inhibit the activity of succinate dehydrogenesis, while propranolol, metoprolol, hydralazine, clonidine and hydrochlorothiazide reduce the activity of NADH-oxidase. Some psychotropic drugs, antidepressants, and oral antidiabetics also reduce the activity of respiratory chain enzymes. Theoretically, all of these drugs can block the action of CoQ10.

The addition of CoQ10 to the standard therapy of arterial hypertension or circulatory failure improved hemodynamic parameters (lowering blood pressure, increasing cardiac output) and overall health. Danysz et al. [4] showed that CoQ10 prolonged the antihypertensive effect of enalapril and nitrendipine. This observation is confirmed by the earlier suggestions of other authors about the possibility of reducing the doses of antihypertensive drugs in people with hypertension, simultaneously receiving exogenous CoQ10.

Hamada et al. Observed that CoQ10 abrogated the negative inotropic effects of propranolol in a study in healthy volunteers.

In an experiment on isolated rat hearts, it was shown that the simultaneous administration of L-carnitine and CoQ10 to the perfusion fluid had a much stronger effect on cardiac output and ATP concentration than either of these substances alone.

The synergism of the action of carnitine and CoQ10 takes place on several planes [3]:

• Carnitine increases the consumption of long-chain fatty acids by enabling their transport to the interior of the mitochondria, where they undergo beta-oxidation. This process is an important source of energy for the cell. In the case of a carnitine deficiency, fatty acids are esterified instead of oxidized
  and are accumulated in the cytoplasm in the form of triglycerides. CoQ10 stimulates this process by reoxidating reduced coenzymes (NADH and FADH2) in the respiratory chain.
• Carnitine lowers the concentration of VLDL and chylomicrons, accelerating their metabolism. At the same time it increases HDL concentration. Exogenous CoQ10 inhibits cholesterol biosynthesis by reverse blocking the synthesis of mevalonate acid, a precursor to both CoQ10 and cholesterol.
• The interaction between these compounds is especially pronounced in the event of a sudden increase in the energy requirements of tissues (effort) or in certain pathological conditions. Carnitine and CoQ10 deficiency limits the ability to meet these needs.
• Both carnitine and CoQ10 protect the cell membranes from harmful factors. The first of these compounds protects the membranes against the effects of long-chain fatty acids (they act as detergents). The second one acts as a strong antioxidant and protects the reduced sulfhydryl groups and stabilizes the cell membranes.
• CoQ10 and carnitine have been observed to have a much greater effect than either drug alone on the energy resources and the adenine nucleotide pool in sections of the heart muscle of rats undergoing hypoxia, reperfusion or chemical respiratory depression. It has also been noted that the combined administration of CoQ10 with carnitine has a stronger protective effect on the heart treated with doxorubicin than the use of either of these substances alone.

Recently, the interaction of statins with CoQ10 has been highlighted. Statins are used in the treatment of hypercholesterolaemia and their effectiveness is assessed very highly. The mechanism of action is based on the inhibition of 3-hydroxy-3-methylglutaryl-acetyl-CoA reductase. It turned out, however, that blocking this enzyme also decreased CoQ10 biosynthesis. As a consequence, many organs may be disturbed, incl. heart, muscles and livers [3].

According to E. Bliznakov, some side effects during statin therapy, e.g. myalgia, myopathy, rhabdomyolysis, peripheral neuropathy, gastrointestinal complaints, liver damage, initiation or acceleration of cataract and cancer development, could be an indirect or immediate result of CoQ10 this treatment. It has been suggested that the combined use of these drugs and exogenous CoQ10 may reduce the risk of these complications.
[12].

Loop et al. Assessed the effect of alcohol and lovastatin administered separately or together on the concentration of antioxidants (alpha-tocopherol, retinoids and CoQ10) and lipid peroxidation products in the liver and plasma of rats. Another group of animals received CoQ10 concurrently with test compounds. It was found that alcohol lowered the coenzyme content in the rat liver by an average of 40%. CoQ10 canceled out the adverse effects of alcohol or lovastatin on this phenomenon. However, it was not effective in the case of concomitant use of alcohol and lovastatin.

Watts et al. Observed that patients treated with simvastatin had a lower CoQ10 concentration and lower CoQ10 / cholesterol ratio than controls. The observations of these authors support the hypothesis about the need for CoQ10 use in statin users.

In 1994, a report was published indicating a possible reduction of the anticoagulant effect of warfarin by CoQ10 [3].

ADVERSE EFFECTS AND TOXICITY OF CoQ10

Observations and clinical trials to date indicate that the exogenous CoQ10 is practically non-toxic, both in terms of acute and chronic toxicity. This is not surprising given the fact that this compound occurs naturally in the human body.
Overvad et al., Summarizing in 1999 the current knowledge about the role of CoQ10 in health and various diseases, concluded that no serious side effects were observed in people taking the substance up to 200 mg for 6 to 12 months or 100 mg in 6 years. Nausea, loss of appetite, diarrhea, skin redness and a slight increase in serum lactate dehydrogenase and transaminases have been reported sporadically in people taking CoQ10 preparations [3].

SUMMARY

The results of many preclinical and clinical studies presented above indicate the safety and therapeutic efficacy of coenzyme Q10 in some disease states. These data seem to support the hypothesis that disturbances in energy production and release are at the root of many diseases. Correction of disturbed bioenergetic processes by administering exogenous coenzyme Q10 may reduce the patient’s ailments, alleviate the course or even completely eliminate the disease. It should be emphasized, however, that the therapeutic effect is usually obtained after a longer period of using this compound (weeks, months) and, above all, in people with endogenous ubiquinone deficiency.

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