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

In the etiopathogenesis of certain muscle diseases, metabolic defects play an important role, which are often caused genetically. The results of the histopathologi-cal and biochemical studies indicate a number of structural and functional abnorma-lities in the muscle cells, particularly in the mitochondria They are characterized by an abnormal size, shape and location chaotic crests, accumulation of lipids and glyco-gen, as well as crystal inclusions.

Also disrupted the work of the mitochondrial respiratory chain, which is manifested in violation of energy production and consumption. As a result, develop clinical symptoms of metabolic myopathies, whose treatment is often not very successful. Because certain expectations associated with the possibility of correction of metabolic abnormalities that underlie these disease using exogenous coenzyme Q10.

Noted, for example, that in mice with genetically determined muscular dystrophy ubiquinone improves physical abilities and prolongs life. Similar results were obtained in humans, patients polimiopatiey and muscle wasting. There was a significant increase in exercise tolerance and normalization of biochemical abnormalities, primarily reducing phosphokinase in the blood plasma.

In a randomized, double-blind study Folkers and co-workers for 3 months gave 12 patients with muscular dystrophy 100 mg of CoQ10. An increase in left ventricular ejection, and improved overall health in 4 of 8 people. In terms of subjective manifestations observed increase in exercise tolerance, reduce pain in the legs, better control of the lower limbs and decrease fatigue.

In 1998, Jude and co-workers examined the effects of coenzyme Q10 supplements on the health of patients with chronic fatigue syndrome, which interferes with the production of energy in the mitochondria, resulting in a greatly reduced ability to perform physical work and maximum execution time.

First of all, it is noted that for these patients characteristically low content of CoQ10 in the blood and muscle. Acceptance of ubiquinone in doses of 100 and 300 mg clearly increases its levels in the blood and tissues of these patients and increased exercise tolerance, and the effect was stronger expressed at a higher dose. However, after the cessation of therapy (after 60 and 90 days) the condition of patients returned to the initial level.

Treatment of periodontitis, due to the complex etiology, is a difficult task. The main factor responsible for periodontal inflammation is bacterial plaque. Penetration of bacteria in periodontal tissues may also inhibit local immunity.

It is known that any regenerative processes, including periodontal tissues require efficient power generation that is heavily dependent on the respective amount of ubiquinone. Studies of the effect of coenzyme Q10 on periodontal disease were started about 20 years ago in several centers in the USA (in particular, Wilkinson et al.), Japan (Sizukuisi et al.), and more recently in the Nordic countries (Nylander and Nordlund, Moe).

Results obtained for today suggest that exogenous CoQ10, except for participation in the production of high-energy phosphates, has positive impact on the local immune protection of gum tissues, altered by inflammation. It is also assumed an impact on the bacterial flora of the oral cavity by changing its composition and enzyme activity.

Numerous studies have shown a reduction in the level of ubiquinone in biopsies taken from the gum at 60-96% of patients with periodontal disease, and in 86% of cases also low levels of this substance in leukocytes. These results clearly show that parodontopathy often associated with lack of CoQ10.

It was noted that particularly beneficial effect on some of the symptoms of periodontal disease has a simultaneous oral intake of coenzyme Q10 and its local application (in periodontal pockets). As a result of this therapy reduces bleeding and swelling of the gums, teeth reel, depth and number of pockets, as well as the amount of purulent discharge. Clinical improvement correlates with increased activity of CoQ10-dependent enzymes in samples from the gums, and with the increase in the blood content of ubiquinone.

Effect of CoQ10 on the changes in the periodontium may be enhanced by taking it in combination with vitamin B6. Mc Rea with employees using this therapy received a clear improvement in periodontal indexes and reducing the number of bacteria. They also found a definite link between the improvement in patients and immune activity in terms of value of production of IgG, and the ratio of T4/T8.

Proliferation and differentiation of cells, as well as antibody production are bio-energetic processes. Deficiency of coenzyme Q10 in the human body can therefore disrupt its ability to maintain an adequate level of these processes. This assumption is supported by the observations that indicate an increase in the content of immunoglobulin G in the serum of patients treated with CoQ10 in cardiovascular disease, diabetes or cancer. Regular studies showed an increase in not only the content of the immunoglobulin G, but also the number of T4 lymphocytes and increasing T4 to T8 ratio.

Evidence of the positive impact of coenzyme Q10 on the immune system is also a fact that this substance has an effect on the course of infection and certain tumors. When giving ubiquinone to mice with granulocytopenia infected by Pseudomonas aeruginosa, their survival is significantly increased. All infected mice that were not given CoQ10, died 2 days later, while when giving CoQ10 over 50% of the mice survived.

Scaglione and colleagues showed that patients treated with coenzyme Q10 at a dose of 180 mg daily for 3 months, antibody titer after vaccination against hepatitis B was significantly higher than in placebo group. These observations were confirmed by Barbieri with employees. At the same time, CoQ10 does not affect the number of inflammatory mediators such as thromboxane B2, leukotriene B4, prostaglandin E2, interleukin-6 and tumor necrosis factor.

Particular interesting are studies on the effect of ubiquinone in the development of some cancers. Weber and his colleagues found a very dramatic reduction of CoQ10 level in the blood of children with cancer of the hematopoietic system (to 50%), and traditional chemotherapy resulted in a further reduction of this level. The authors believe that the low levels of ubiquinone may be the result of increased oxidative stress and accelerated metabolism in tumor tissue.

This question has been the subject of clinical studies conducted by Marie with employees. They have paid attention to the fact that patients with cancer of the colon, lung and breast cancer are significantly reduced coenzyme Q10 levels in the blood, which can be prevented by supplementation of coenzyme 300 mg per day. Using this method, they were able to improve the overall antioxidant activity determined by testing the blood of patients.

Other authors note that coenzyme Q10 can inhibit the production of certain cytokines, accompanied by the development of tumors.

In the study of Lockwood with staff who gave CoQ10 along with other antioxidants to 32 women suffering from breast cancer, 6 women have reached remission (which was also confirmed by fluoroscopy). The remaining 26 patients, it was also noted improvement in clinical status, which permitted to significantly reduce the dose of analgesics (morphine).

These issues were the subject of speech of Hodges at the first conference of the International Association of coenzyme Q10, who has put a dramatic question: "Can coenzyme Q10 play a role in the treatment of cancer? ". According to him, there is every reason for the use of coenzyme Q10 in the treatment of cancer, not only for to fill the gaps, but also to obtain a certain therapeutic effect. Hodges substantiates the need for a substantial increase applied doses of CoQ10 and its combination with other antioxidants (such as Vitamin E and selenium), and also unsaturated fatty acids.

An interesting area in researches of therapeutic usefulness of coenzyme Q10 is diabetes, especially type 2. It has long been known that patients with diabetes have a clear shortage of ubiquinone in the blood. Some authors see a certain role of deficiency of the substance in the pathogenesis of diabetes.

Factor of mitochondrial respiratory chain activity is a key component of the signal transmission mechanism through which the increase in blood glucose levels increases secretion of insulin by beta cells of the pancreas. It seems that a particularly important role in this respect is playing by a normal function of the mitochondrial glycerol-3-phosphorane dehydrogenase.

It seems that in patients with diabetes, action of this enzyme becomes less pronounced. Low levels of CoQ10 in the body in diabetes can further inhibit its function and thereby exacerbate the degree of disorder of metabolism.

Japanese researchers in several studies showed improved activity of the pancreatic beta cells and the control of metabolism in patients with Type 2 diabetes who received CoQ10 supplements. It is possible that this reaction was due to an increase in enzyme activity in mitochondria of beta cells.

C. Liu and co-workers reported an improvement in the function of pancreas beta cells after taking of coenzyme Q10 in patients with mitochondrial encephalopathy, lactic acidosis, a set of symptoms similar to stroke and diabetes.

It turned out that the majority of obese people have a deficiency of coenzyme Q10. Researchers compared two groups of obese patients: one with diet alone, while in other patients received an additional 100 mg of ubiquinone per day. Weight loss in the second group was three times higher. This primarily applies to patients with obesity who have been diagnosed with CoQ10 deficiency.

In some cases, a tendency to obesity is associated with impaired energy producti-on. This defect can be partially genetically determined. People with a high incidence of obesity in the family have 50% reduced postprandial thermogenesis, that indicating the inborn error of energy expenditure.

Neutralization of harmful substances received from the environment and drugs is largely due to oxidation processes - or rather, in the course of oxidative phosphory-lation, which requires CoQ10. The most impressive results in terms of reducing the toxic effects of drugs via ubiquinone are presented in chapter "Interaction of coenzyme Q10 with drugs".

Interesting results were obtained also by A. Dlugosz, which assesses the impact of harmful factors on workers of paint industries. It was found that intake of coenzyme Q10 reduces some of the toxic effects from the exposure of organic solvents. Those of workers who received CoQ10 at dose of 30 or 60 mg daily for four weeks have showed a statistically significant reduction in the amount of lipid peroxidation products.

It was noted that the prophylactic intake of coenzyme Q10 in mice reduces the risk of developing cancer, provoked by dibenzopyrene, and prolongs their lifespan. At the same time, beneficial effect of CoQ10 increased with increasing dose.

As has been mentioned, CoQ10 is an essential link in the electron transport chain and an important antioxidant that plays a major role in mitochondrial energy production, as well as in cell membranes. Violation of these processes plays an important role in the onset of neurodegenerative disorders. There is evidence of the connection between these disorders and Alzheimer's disease, Huntington's disease (chorea), Parkinson's disease and multiple sclerosis.

For many years attempts have been made to use of coenzyme Q10 in the treatment of these diseases. Obtained data encouraging the use of ubiquinone in complex therapy as a supplement to proven therapeutic regimens, but it still needs an objective documentation.

Several theories explain the aging process through an overall decline in the body's bio-energy as a result of the predominance of oxidative processes (oxidative stress), and loss of the ability of cells and tissues to regeneration.

Experimental proof of the effectiveness of coenzyme Q10 in slowing the aging are studies of Bliznyakov who published in 1980 the results of long-term testing of action of coenzyme Q10 in mice. It was found that mice that received ubiquinone lived much longer than mice in the control group. The average life span of mice in the control group was 20 months, and mice that received CoQ10 - 31,2 months, i.e., 56% more.

The authors report that mice treated with CoQ10, despite the passage of time, remained active, and their appearance was much better compared to the control animals. Bliznyakov's studies suggest that receiving of CoQ10 by mice, to make up for its loss due to aging, significantly prolongs their life. It is hard to believe that this can only refer to the mice.

CoQ10 interaction with other drugs has not been fully investigated. Most of the available data relates to the interaction of ubiquinone and antibiotics of anthracycline group (antineoplastic agents), especially doxorubicin. The mechanism of interaction between these two substances at the level of the heart muscle is difficult and reduces to:

1. Oppositely directed impact on the activity of enzymes of the respiratory chain.
2. Protection of membrane lipids and other cellular structures against free radicals produced by a biotransformation process of doxorubicin.
3. Probability of competition, due to the presence of quinone groups in both compounds, for one and the same receptor in cardiac muscle cells.

It should be emphasized that coenzyme Q10, reducing doxorubicin cardiotoxicity, does not weaken its anticancer action. Doxorubicin destroys cells by blocking the synthesis of DNA and RNA, as well as violations of the processes of repair of damaged DNA. This effect also is not suppressed by coenzyme Q10. CoQ10 protects myocardial cells from the damaging effects of free radicals produced during the metabolism of anthracyclines.

The results obtained by a group of Japanese researchers have shown that diazoxide and methyldopa inhibit the activity of succinate dehydrogenase, and pro-pranolol, metoprolol, hydralazine, clonidine and hydrochlorothiazide reduce the activity of NADH-oxidase. Also, some psychotropic, antidepressive and oral antidiabe-tic drugs counteract the enzymes of the respiratory chain. Theoretically, all these drugs can block the action of coenzyme Q10.

The inclusion of CoQ10 in the standard therapy in hypertension or heart failure allows to improve hemodynamics (reduced blood pressure, increased cardiac output) and the general condition of patients. Danish with co-workers have shown that CoQ10 extends antihypertensive effect of enalapril and nitrendipine. This observation confirms previous suggestions of other authors about the possibility of reducing the dosage of antihypertensive drugs in hypertensive patients receiving at the same time exogenous CoQ10.

Hamada and co-workers found that coenzyme Q10 eliminates the negative inotropic effect of propranolol in studies in healthy volunteers. Experiments in isolated rat hearts showed that simultaneous addition of L-carnitine and CoQ10 to perfusion fluid has a much stronger effect on cardiac output and the concentration of ATP than either of these substances alone. Synergistic effect of carnitine and coenzyme Q10 appears on several levels:

• Carnitine increases the utilization of long chain fatty acids, allowing their transport into the mitochondria where they undergo to beta-oxidation. This process is an important source of energy for cells. At deficiency of carnitine, fatty acids undergo esterification instead oxidation and accumulate in the cytoplasm in the form of triglycerides. Coenzyme Q10 stimulates this process due to the re-oxidation of reduced coenzymes (NADH and FADH2) in the respiratory chain.
• Carnitine reduces VLDL and chylomicrons content, speeding up their metabolism. At the same time it increases the HDL. Exogenous CoQ10 inhibits cholesterol biosynthesis by blocking the synthesis of mevalonic acid - a precursor as CoQ10, and cholesterol.
• Interaction between these substances is especially evident in situations where tissues needs in energy suddenly increases (during physical effort), or in certain pathological conditions. Deficiency of carnitine and coenzyme Q10 may limit the ability to meet this need.
• Carnitine and coenzyme Q10 both protect cell membranes from harmful factors. The first of these compounds provide protection against long-chain fatty acids (acting as a detergent). The second acts as a powerful antioxidant, and protecting the reduced sulfhydryl groups, stabilizes the cell membrane.
• It was found that carnitine and CoQ10 together act much more strongly than each of them alone, on the energy resources and use of adenine nucleotides in the tissues of the heart muscle of rats subjected to hypoxia, reperfusion or chemical inhibition of the respiratory chain. It was also noted that CoQ10 and carnitine together exhibit more powerful protective effect on the heart exposed to doxorubicin than any of these compounds individually.

Recently, it has provided important information about the interaction of statins with CoQ10. Statins are used to treat hypercholesterolemia, and their performance is evaluated very highly. Their mechanism of action is based on the inhibition of 3-hydroxy-3-methylglutaryl-CoA acetyl. It turned out, however, that when blocking this enzyme, biosynthesis of coenzyme Q10 is inhibited simultaneously. The result may be a violation of the functions of many organs, including the heart, muscles and liver.

According to E. Bliznyakov, some of the side effects of statins, such as muscle pain, myopathy, rhabdomyolysis, peripheral neuropathy, gastrointestinal problems, liver damage, the occurrence or accelerated development of cataracts and cancer, may be directly or indirectly related to the deficiency of coenzyme Q10 arising in the course of this therapy. It is assumed that the combined use of these drugs and exogenous CoQ10 may reduce the risk of such complications.

Loop with colleagues evaluated the effects of alcohol and lovastatin, which were given together and separately, on the concentration of antioxidants (alpha-tocopherol, retinoids and CoQ10), as well as the products of lipid peroxidation in the liver and rat plasma. One more group of animals received coenzyme Q10 together with the tested drugs. It has been found that the alcohol reduced content of coenzyme in the liver of rats by an average of 40%. Adding of CoQ10 eliminates this effect of alcohol or lovastatin. However, with simultaneous application of alcohol and lovastatin, protective effect of CoQ10 has already not manifested.

Watts with colleagues found that patients who received simvastatin have lower content CoQ10 and lower relation CoQ10/cholesterol than the control group. The observations of these authors confirm the conclusion about the need to receive coenzyme Q10 people taking statins.

In 1994 there was a report that reported the possibility of reducing the anti-coagulative effect of warfarin at its reception in conjunction with coenzyme Q10.

All currently available observation and clinical studies have shown that exogenous CoQ10 is practically nontoxic, both in terms of acute toxicity well as chronic. This is not surprising considering that this substance is produced naturally in the human body.

Overvad with employees, bringing in 1999 results of modern research on the role of coenzyme Q10 in healthcare branch and in the treatment of various diseases, noted that there was not any serious side effects in people taking this substance at doses up to 200 mg for 6 to 12 months or 100 mg over six years. In people taking coenzyme Q10 sporadically, sometimes there were nausea, loss of appetite, diarrhea, skin redness and slight increase of lactate dehydrogenase and serum transaminases in the blood.

This article is for informational purposes only; It does not replace a visit to a doctor or professional advice.

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