COQ10 What Does It Do?

Coenzyme Q10 (COQ10) is a fat-soluble quinone widely present in the mitochondria of cells of living organisms, and it is one of the intermediate links in the respiratory chain and an important hydrogen transporter, as well as a natural antioxidant, free radical scavenger, and a nutrient that can improve cellular metabolism [1]. It is a nutrient that improves cellular metabolism [ 1 ]. When the body is deficient in this nutrient, related diseases may occur, and correcting the deficiency will prevent, regulate, and assist in the treatment of the related diseases.

Because COQ10 has the functions of improving cellular energy metabolism, scavenging free radicals, maintaining biofilm stability and permeability, and improving the functions of the body's antioxidant system and immune system, it has been widely used in medicines, health care products, health food and beauty care products, especially in the cardio-cerebral vascular system, the immune system, and degenerative diseases of aging with a certain degree of significance for the conditioning, prevention and treatment [2, 3].

1. COQ10 Changes in structure and chemical name expression

 COQ10 Molecular Formula C5 9 H9 0 O4, molecular weight 863.36, yellow or orange crystalline powder. Its structure is similar to vitamin K. The original chemical name was 2,3-dimethoxy 5-methyl 6-decyloisopentenyl-1,4-benzoquinone. Since 2000, the chemical name of COQ10 has been differently expressed as follows.

The chemical name and structure of COQ10 introduced in the 1986 edition of The Miracle Nutrient Coenzyme Q10[4] in the United States of America are shown as 2,3-dimethoxy-5-methyl 6-decylisopentenyl-1,4-benzoquinone.

Fig. 1 One of the chemical structure diagrams of COQ10

The chemical name and structure of COQ10 in the Pharmacopoeia of the People's Republic of China, 2005 edition, is 2-[(3,7,11,15,19,23,27,31,35,39)-decamethyl-2,6,10,14,18,22,26,30,34,38-tetradecadecenyl]-5,6-dimethoxy 3-methylp-benzoquinone.

The chemical name and structure of CQO 10   in the 2010 edition of the Pharmacopoeia of the People's Republic of China has been updated to read: 2-[(all-E)3,7,11,15,19,23,27,31,35,39 -decamethyl-2,6,10,14,18,22,26,30,34,38 -tetradecadienyl]-5,6-dimethoxy-3-methyl-P-COQ benzoquinone.

Figure 3 COQ10 Chemical Structure Diagram III

The quinone nucleus of COQ10 is the functional center, the fatty long side chain can be localized to the inner mitochondrial membrane, and dimethoxy and methyl groups are associated with enzyme specificity.

2. Extraction and Synthesis of COQ10 [5].

COQ10 extraction and synthesis are mainly biological extraction, chemical synthesis and microbial fermentation.

2. 1 Bio-extraction Method   

COQ10 has been produced traditionally since 50 years ago and is extracted from animal organs such as pig, cow and sheep heart and liver.  The pure product obtained has an all-trans structure and is essentially free of chemical residues.  However, the limited source of raw materials, low content and high cost of the organs have greatly restricted the industrialized production, which is seldom used nowadays except for the great scientific research value.

2.2 Chemical Synthesis   

The synthesis of the parent nucleus, the lengthening of the side chain, and the condensation of the parent nucleus and the side chain are the three key processes to be solved. Side chain synthesis is divided into two major categories: semi-chemical synthesis based on cannabinol extracted from tobacco and full chemical synthesis without cannabinol as a raw material.

2.2.1 Semi-chemical Syntheses   

In the early 1980s, Japan realized the extraction process of synthesizing COQ10 from tobacco by extracting cannabinol, using CO Q0 (methyl dimethoxybenzoquinone), which was obtained by bromination, etherification and oxidation of p-methylbenzoquinone, as the parent raw material and cannabinol as the side chain raw material.  The condensation of cannabinol with CO Q0 gives COQ10, which is an isoprene dimer with an all-trans configuration. COQ10 is then condensed with CO Q0 to obtain COQ10. 80% of COQ10 production plants in the world use this method. China is a large tobacco producing country, with certain advantages in raw materials, there are still differences on whether to use CO Q0 or CO Q1 as the mother nucleus raw material, and there are still many difficulties in the production process, resulting in the high production cost of COQ10, and we can only maintain the status quo by selling the crude products of cannabinol.

2.2.2 Fully Synthetic Method   

The mother nucleus synthesis can be the same as the semi-synthesis method, and instead of relying on the natural raw material, geraniol (monoterpene monomer derivatives), which is cheap and easy to obtain, is used to construct the side chain of COQ10. However, it requires multiple couplings, a long route, low overall yield, difficulty in synthesizing linear unsaturated side chains, and harsh synthesis conditions, making industrial production more difficult at present.

2.2.3 Fermentation   

Microbial fermentation is a promising method for COQ10 production in recent years and has become a hot research topic. As microbial cells are easy to grow in large-scale culture, the side chain of the cultured cells is in all-trans configuration, which is easy to be absorbed by the organism, with high bioavailability and good clinical efficacy.  Moreover, there is almost no harmful chemical residue in the product, which is safer than the chemical synthesis method. However, there are still some problems that need to be solved in terms of improving fermentation efficiency, purification, high-precision separation equipment and technology, and cost reduction. At present, only Nissin and Kyowa Fermentation Co., Ltd. have used this method for industrial production.

3. COQ10 and Energy

Energy is the basis of life, and cells depend on energy metabolism to perform their functions. Cells obtain energy through biological oxidation, and energy is produced by nutrients in the mitochondria of cells.  Energy is produced from nutrients in the mitochondria of the cell. Nutrients are produced and transformed into energy by electron transport systems such as COQ10.  

COQ10 binds to the inner membrane of mitochondria and is an important member of the electron transport system, acting as a linker and intermediate link. Thanks to the participation of COQ10, the conversion from nutrient to energy substance ATP can be completed, and energy can be released and utilized. Energy cannot be generated only by nutrients without the participation of COQ10, let alone transformed, stored and utilized, and COQ10 is an energy promoter and activator, which is known as the biological driving force [6], and one of the main components of "energy synergist", which is also known as anti-fatigue substance [7].

4. COQ10 Deficiency and the Significance of Conducting Clinical COQ10 Assays

Numerous studies have shown that COQ10 is required by the human body, and its deficiency can lead to related diseases and even death in severe cases. The amount of COQ10 in human plasma has a normal value of about 0.8 μg per milliliter or (783.3 ± 86.3) mg-L-1 [4]. Because the amount of COQ10 in the body decreases with aging, the health level declines and many diseases may occur.  Therefore, it is important to measure the amount of COQ10 in human plasma. Studies have shown that the amount of COQ10 in various tissues and organs is different, and each has a different normal value, especially the energy-related organs and systems are more sensitive.

For example, pancreatic COQ10 levels decline by up to 83% with aging, and plasma COQ10 levels decline by up to 65% due to diabetes. The cardiovascular system, which is closely related to COQ10, and the myocardium and brain, which are closely related to COQ10, have similar conditions.  Therefore, COQ10 has been called "an indicator of the state of human health". In Japan, a large number of tests have been conducted, and a large amount of data from autopsies and biopsies show that the amount of COQ10 in the plasma and related tissues of patients with cardiovascular and cerebrovascular diseases, radiotherapy, AIDS, hepatitis, cancer, and the elderly and infirm is lower than that of normal people [8].

Therefore, determining the normal value of COQ10 in clinical tests and monitoring the amount of COQ10 in the human body are of great significance to the maintenance of human health and the diagnosis, treatment and prevention of diseases. The author of this paper has already put forward this point of view ten years ago. Nowadays, Europe, America, Japan and other developed countries have begun to measure the content of COQ10 in the human body as a biochemical test index.

The methods for the determination of COQ10 content are very mature, and there are many reports: photometric method, chromatographic method, voltammetric method, chemiluminescence method, fluorescence method, electron nuclear magnetic resonance method, and so on, among which the most commonly used method is liquid chromatography［7］.

5. Causes of COQ10 Deficiency in Humans [ 1 ]

It has been reported that genetic defects can cause a 90% decrease in COQ10 in epidermal fibroblasts compared to normal [9]. In addition, the synthesis of many vitamins and microelements in the body requires a 17-step reaction to synthesize. The body mainly takes in food and uses food as the raw material for synthesis.  There are other reasons for the insufficiency of COQ10 in the human body.

Poor dietary habits such as imbalanced diets, partial diets, vegetarian diets, and weight loss have resulted in insufficient intake and insufficient raw materials for the synthesis of COQ10 in the human body. Cardiovascular, cerebrovascular, cancer and other related diseases, and the body's ability to ingest and synthesize COQ10 decreases with age (after 30-40 years old) [9].

Certain drugs, such as the radiotherapy drugs cyclophosphamide and adriamycin, statin lipid-lowering drugs, and chlorpromazine, disrupt the enzyme HMG-COA, which synthesizes COQ10, or inhibit the activity of the related enzyme, resulting in impaired synthesis of COQ10 [ 10 ].

People with poor cardiac function, low antioxidant and immune function, and abnormalities in blood lipids, blood glucose, and blood pressure have low levels of COQ10 in their subhealthy state.

Heavy physical and mental laborers with excessive energy consumption require more energy substances and COQ10, an energy-boosting nutrient. The amount of nutrients (including COQ10) taken by some athletes in the United States is about 2 to 5 times that of ordinary people. COQ10 is one of the essential ingredients in many kinds of health food for athletes. In addition, today's high-speed, fast-paced work and life style makes people nervous, pressure increases, coupled with air and environmental pollution, especially food pollution, etc. have increased the body's demand for COQ10.

6 . Consequences of COQ10 Deficiency in Humans

The total amount of COQ10 in the human body is only 500 ~ 1,500 mg, and the amount of COQ10 in different organs and tissues of the body varies and has a normal value, which gradually decreases with internal and external changes.  Clinical symptoms may not be obvious when there is a mild deficiency of COQ10 in the tissues, but when the level of COQ10 falls below 25% of the normal level, obvious symptoms of disease will appear.

COQ10 can be used to successfully prevent and assist in the treatment of related diseases. Since the discovery of COQ10 53 years ago, hundreds of pharmacological and clinical studies have clearly demonstrated the importance of this nutrient in the prevention and treatment of related diseases and the maintenance of human health.

7. Dosage of COQ10

COQ10 is a nutrient that can be found in a variety of capacities, including pharmaceuticals, nutraceuticals, and foods. However, the amount of COQ10 used to replenish nutrients, regulate body functions and prevent certain diseases varies greatly.  Generally, the therapeutic dosage is higher than the healthcare dosage. Some people think that the low dosage in China is due to the low average body weight of Chinese people, but if the dosage is less than half of that in Europe and the United States, then it is not in line with the norm.  For example, the 2000 edition of the Chinese Pharmacopoeia provides only three small sizes of 5, 10, and 15 mg of oral COQ10 for therapeutic use, and one bottle is equivalent to only 1 to 2 pills in foreign countries.

The general dosage of COQ10 for Chinese people is about 30 mg per day, while softgels containing 300 mg of COQ10 per capsule are common in foreign health supplements.  Recently, the consumption of COQ10 in health products has been raised to 50 mg per day, which is a big step forward from the previous level, but the amount is still small. It is inevitable that a small dose will not achieve therapeutic effects, which is one of the reasons why it is called a "placebo".

In his recommendation for a complete and balanced cellular nutritional supplement regimen, Dr. Schrader, M.D., suggests that the basic health dosage of COQ10 is 20-30 mg per day, while for specific diseases, COQ10 is one of the preferred optimizers, i.e., an additional 100-300 mg of COQ10 per day should be added to the nutritional supplements [11]. Higher doses are needed for various diseases.  In Europe and the United States, COQ10 has been formally used as a nutritional supplement since 1985, and now the amount of COQ10 used is 100-300 mg.

In The Coenzyme Q10 Phenomenon [12], the recommended dose for patients with cardiovascular disease, periodontal disease, and HMG-CoA reductase inhibitors is 90 ~ 120 mg; for angina pectoris, arrhythmia, hypertension, and gingival disease, the recommended dose is 120 ~ 400 mg; for congestive heart failure and dilated cardiomyopathy, the recommended dose is 240 ~ 450 mg. The recommended dose for congestive heart failure, dilated cardiomyopathy, etc. is 240-450 mg. For severe immune disorders, such as cancer, even higher doses are needed.

The evaluation of the dose-effect relationship of COQ10 is currently one of the topics of interest in the study of COQ10.

8 .Clinical Applications of COQ10

Since COQ10 is a nutrient that improves energy metabolism in human cells, its antioxidant properties make it a free radical scavenger. COQ10 can be considered as a preventive, therapeutic, and adjunctive treatment for all diseases associated with impaired energy metabolism, free radical damage, and dysfunction of the immune and antioxidant systems.  This is one of the reasons why COQ10 can be used in many diseases.

8. 1 Applications in the Cardiovascular System   

The most sensitive to energy is the cardiovascular system, and COQ10 was firstly applied in cardiology and cerebral medicine, which is called cardio-cerebral nutritional supplement, metabolic cardiotonic agent, cardiomyocyte energizer [13], a drug that nourishes the myocardium and improves the metabolism of the myocardium [14], and it is an important cofactor in the treatment of energy metabolism disorders.

8.1.1 Treatment of Congestive Heart Failure   

COQ10 has antioxidant and membrane stabilizing effects, and can improve myocardial energy metabolism and correct the symptoms of heart failure such as reduced myocardial contractility. Studies have shown that the levels of COQ10 in the myocardium and blood of patients with heart failure are obviously low, and supplementation of COQ10 can significantly improve the cardiac function of animals with experimental heart failure and patients with heart failure [15].

In congestive heart failure, the energy metabolism of cardiomyocyte mitochondria is impaired, ATP is insufficient, and myocardial COQ10 content is often reduced at autopsy. COQ10 can improve myocardial energy metabolism, improve myocardial mechanical force, and produce positive inotropic effect, and the combination of COQ10 and digitalis can reduce the toxicity and increase the effect, so that the cardiac output will increase. The effective rate of COQ10 in 435 cases of congestive heart failure was 41.4%, and the efficacy of COQ10 is also better in patients with significantly lower cardiac output, such as heart failure caused by chronic cardiac valvular disease and coronary artery disease, as well as senile heart failure［13］. Long-term treatment with COQ10 is a major advance in the control of heart failure. The etiology of heart failure may be due to COQ10 deficiency [8, 16].

8.1.2 Myocardial Protection Against Cardiomyopathy  

COQ10 and conventional therapies for cardiomyopathy can significantly improve patient survival [8, 17]. COQ10 protects against structural and functional abnormalities caused by myocardial ischemia and reperfusion, maintains oxidative phosphorylation and cellular ATP production, and prevents cytosolic and mitochondrial calcium overload, which improves cardiac function in the elderly.

Langsjoen [8] reported that 137 patients with cardiomyopathy characterized by low mean ejection fraction and congestive heart failure were compared with 182 patients. In the former, COQ10 was added to conventional drug therapy (cardiotonic, diuretic, and vasodilator) at 100 mg per day; in the latter, COQ10 was not added, and at 36 months, the survival rate was 75% with COQ10 compared with 25% without, which was a significant difference. COQ10 can improve myocardial energy metabolism disorder, protect the structural integrity of myocardial cells and mitochondria, prevent myocardial damage caused by viruses and their toxins, and improve the symptoms of arrhythmia caused by myocarditis.

8.1.3 Prevention of Coronary Heart Disease and Angina Pectoris and Improvement of Their Symptoms

A large number of statistics show that oxygen free radicals increase during the onset or termination of angina pectoris. A large amount of oxygen free radicals often leads to necrosis of cardiomyocytes, proliferation of fibrous tissue and scar formation, and disorders of intra- and extracellular structure and metabolism. COQ10 is an antioxidant and free radical scavenger in human body, which can improve myocardial metabolism, improve the symptoms such as chest pressure and palpitation, reduce the number of angina attacks, and the rate of improvement of ECG under exercise load is higher than that of ECG in quiet time, and it is more effective for patients with low left heart function.

In 72 patients with coronary artery disease, the average efficiency was 62%, and the effects of conventional antianginal drugs (nitrates, beta-blockers and calcium antagonists) on heart rate and blood pressure did not occur [1].

8.1.4 Antiarrhythmics    

COQ10 improves myocardial energy metabolism, relatively raises the threshold of ventricular arrhythmia, and relieves part of the arrhythmia. It is effective for atrial premature beats, paroxysmal ventricular fibrillation, and ectopic rhythms caused by rheumatic myocarditis, viral myocarditis, coronary heart disease, and other diseases [18].

8.1. 5 Adjunctive Therapy for Primary Hypertension with Low COQ10   

Many patients with primary hypertension have low COQ10, and supplementation of COQ10 can help lower blood pressure. COQ10 can reduce the peroxidation state of blood vessels, reduce superoxide in endothelial cells and vascular smooth muscle cells, protect and reduce the damage of vascular endothelial cells, improve the abnormality of cytoplasmic NADH level, and maintain vascular tone of the active substances, NO and PGI2, to diastole peripheral vasculature and reduce the peripheral resistance, and thus play a role in lowering the blood pressure [9]. This is related to the fact that COQ10 can lower aldosterone and reduce sodium and water retention [19].

8.1.6 Mitigation of Damage Caused by Ischemic Myocardial Reperfusion

COQ10 can alleviate the damage caused by ischemic myocardial reperfusion by its anti-free radical and membrane stabilizing effects. Ischemic myocardial reperfusion generates a large number of cytotoxic substances, such as oxygen radicals, hydroxyl radicals and hydrogen peroxide radicals, which inactivate and denature the membrane proteins, overload the intracellular calcium due to calcium inward flow, and impede the synthesis of ATP and CP, which finally lead to the damage and necrosis of the cells. COQ10 can protect the structural integrity of mitochondria, preventing mitochondrial lysis and destruction of cardiac fibers, and preventing the depletion of substances necessary for ATP resynthesis. COQ10 is clinically valuable in the treatment of ischemic and infarctive cardiovascular diseases [1].

8.2 Adjustment of Cellular Immune Function to Minimize Adverse Effects of Radiotherapy Drugs

Toxicity of certain drugs to the myocardium The long-term use of COQ10 in cancer patients can alleviate some of the adverse effects caused by radiotherapy and chemotherapy.  COQ10 antagonizes the toxicity of the anticancer drugs Adriamycin and Cyclophosphamide on the myocardium. COQ10 can reduce the elevation of urea nitrogen and creatinine caused by Adriamycin to the normal level; COQ10 can alleviate the reduction of ATP content of cardiomyocytes caused by Adriamycin, increase the function of the heart and prevent the occurrence of heart failure. Since adriamycin destroys the enzyme system of cardiomyocytes and causes insufficient synthesis of COQ10, supplementation with COQ10 protects the enzyme system of cardiomyocytes, scavenges free radicals produced by adriamycin, and reduces the damage of cardiomyocytes caused by free radicals and lipid peroxides［1］. In clinical practice, anticancer drugs are often used in combination with COQ10 [1, 19].

8.3 Antagonizing Statin Toxicity

Improvement of therapeutic effects in patients with hyperlipidemia Lipid-lowering statins reduce HMG-CoA reductase activity by inhibiting the

Mevalonate production, which is required for the synthesis of COQ10 in the body, decreases, leading to a decrease in COQ10.

Combined application of COQ10 can prevent the statin-induced reduction of COQ10, reduce the production of low-density lipid oxides, reverse the side effects caused by statins, and have no effect on the cholesterol-lowering effect of statins.  In conclusion, it is clear from the results of the current clinical study that the combination of statins with COQ10 will not reduce or even enhance the lipid-lowering effect of statins, and can reverse the myocardial injury caused by statins alone [10].

8.4 Promote Insulin Synthesis and Secretion to Improve Complications of Diabetes Mellitus

The pancreas is an organ rich in COQ10. Insulin synthesis requires energy, and COQ10 provides energy for the synthesis of insulin by pancreatic islet β-cells. Insufficient COQ10 in the mitochondria of the pancreatic β-cells may cause a decrease in insulin synthesis and secretion, and supplementation of appropriate amounts of COQ10 can promote insulin synthesis and secretion.

The initial form of insulin is insulinogen, which is synthesized by the granular endoplasmic reticulum of pancreatic β-cells, assumes a granular form in the Golgi apparatus, and is converted to insulin when it is released from the cell. Much of the energy required for this synthesis, transport, and release is supplied by an energy-producing mechanism within the mitochondria involving COQ10.

In patients with diabetes mellitus, the amount of COQ10 in the serum is significantly lower; the amount of COQ10 in the pancreas is significantly lower with aging. Supplementation of COQ10 can promote the synthesis and secretion of insulin, promote the utilization and conversion of sugar, effectively regulate blood glucose and improve the complications of diabetes [9].

8.5 Skin Care, Anti-Aging    

With the aging of human body and the influence of the environment, the content of COQ10 decreases, and the skin's ability to resist free radical damage and antioxidant gradually decreases, resulting in the aging of the skin. COQ10 can improve the body's ability to resist free radical damage and improve the skin's nutritional status.  Thus, it can make the skin moisturized, reduce wrinkles, lighten age spots, maintain skin elasticity and luster, and play a certain role in slowing down skin aging［20］.

9. Combination of COQ10 and VE

Since COQ10 and VE are both antioxidants, they are stabilizers for each other; they are both fat-soluble, and their good compatibility is more conducive to certain preparation processes and product stability. Therefore, they are often used to formulate softgel dosage forms.

9.1 Characterization of the Effects of COQ10 and VE  

COQ10 and VE both have antioxidant properties and are compatible antioxidant partners in the body. In the process of scavenging free radicals, due to the difference in redox potentials, VE bears the brunt of the scavenging process and binds with the free radicals first, generating tocopherol free radicals, which lose antioxidant capability. "This is known as vitamin Bio. This is known as the "regeneration" of the vitamin, which means that it enhances the antioxidant function and has a long-lasting effect. This means that VE is protected in the presence of COQ10 [21]. The combination of the two is reasonable.

The combination of COQ10 and VE in clinical practice is mainly due to their antioxidant properties, which strengthen the anti-free radical damage and anti-atherosclerotic effects, and jointly maintain the functions of cardiovascular and immune systems.

9.2 Common Conditions Requiring Both COQ10 and VE Supplementation   

COQ10 and VE are important for the recovery of many diseases. According to the 2002 edition of Dalton Chen's "Nutritional and Health Foods", there are 35 diseases that require supplementation of COQ10 and 62 diseases that require supplementation of VE in foreign health food formulas. Among them, 25 diseases require supplementation of both COQ10 and VE.

10. Summary

COQ10 is associated with energy metabolism, antioxidant, free radical damage, membrane stabilization, and immune function, and is closely related to many physiological functions and disease development in the human body.

COQ10 deficiency can lead to related diseases, which can also lead to COQ10 deficiency in the blood and related tissues.  Supplementation of these deficiencies may be useful in the prevention, management, and adjunctive treatment of related diseases. Measurement of COQ10 in whole blood and related organs is clinically important.

COQ10 exists in cellular mitochondria and is embedded in the inner membrane of mitochondria, exogenous COQ10 can work only when it enters into intracellular mitochondria, COQ10 deficiency in human body is a slow process, and correcting the deficiency of COQ10 also needs a process, so the slow onset of COQ10 is inevitable. Therefore, in addition to improving the bioavailability of COQ10, the speed of COQ10 entering the cell and entering the mitochondria from the cell should also be considered in order to improve the speed of onset of action.

The low domestic dose of COQ10 is one of the reasons why the efficacy of COQ10 is not obvious, and the use of COQ10 is to add COQ10 to the conventional treatment, which should also be done for difficult diseases. This kind of treatment is called metabolic therapy, which is the supplementation and improvement of the original treatment, and it is not a replacement therapy [22], so COQ10 cannot be used alone for metabolic therapy of a certain disease.

COQ10 has few adverse effects, but although COQ10 is derived from and used in the body, reports that COQ10 produced by various methods inevitably carries impurities that are not favorable to health, causes gastrointestinal irritation, and may cause coagulation, etc., should be noted, and further research on this topic is needed.

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