What Is It COQ10?

COQ10, as one of the important elements indispensable to human life, is widely found in various tissues and cells of mammals. It was discovered in 1957, and its chemical structure was identified by Dr. Karuforukas of the University of Texas in 1958, for which it was awarded the Priestly Medal, the highest honor of the American Chemical Society [1-2]. In 1958, Dr. Karuforukas of the University of Texas recognized its chemical structure and received the Priestly Medal, the highest honor of the American Chemical Society [1-2]. At the same time, he proposed that coenzyme Q10 plays an important role in cardiac function, and he took coenzyme Q10 in real life until his death at the age of 91, as an active professor he was always energetically engaged in scientific research activities.

COQ10 is a strong antioxidant, one of the most important coenzymes in the human body, and plays an important role in electron transport in the respiratory chain of the mitochondria and the production of adenosine triphosphate (ATP). It has been widely used in the fields of cardiovascular, neuromuscular, tumor immunity and diabetes, and there have been a large number of research reports on it. Coenzyme Q10 has been widely used in nutritional and healthcare products and food additives in the United States, Europe, Japan and other countries more than 20 years ago. In recent years, China has paid more attention to the study of coenzyme Q10, especially in cardiovascular diseases, and has made a lot of progress in recent years. In this paper, we present a comprehensive and systematic review of the progress of coenzyme Q10 in cardiovascular diseases in recent years [2-4].

1. Physical And Chemical Properties of Coenzyme Q10

Coenzyme Q10 is the only endogenous lipid with redox function in mammalian body, its structure is similar to vitamin K, vitamin E and plastoquinone, also known as ubiquinone, decenoquinone, ubiquinone, etc., and its chemical formula is: 2,3-dimethoxy-5-methyl-6-(+)isopentadienylbenzoquinone. Different ubiquinone molecules have different numbers of side chain isoprenoid units. In humans and mammals, the number of side chain isoprenoid units on the six positions of the mother nucleus is different, and in humans and mammals, the polyisoprenoid on the six positions of the mother nucleus is polymerized at a degree of 10 and is named Coenzyme Q10. The molecular weight of Coenzyme Q10 is 863.36, and it is not water soluble because of its fat solubility. Coenzyme Q10 has a molecular weight of 863.36 and is insoluble in water and methanol due to its lipid solubility. It is soluble in chloroform, benzene, carbon tetrachloride, acetone and ether, and slightly soluble in ethanol, etc. Coenzyme Q10 is susceptible to light exposure. Coenzyme Q10 is easily decomposed by light, but less affected by temperature and humidity. The content of coenzyme Q10 was determined by high performance liquid chromatography (HPLC).

CoQ10 is present in various organs and subcellular tissues, and its content in the inner membrane of mitochondria is much higher than that of other components of the respiratory chain. Because of its lipid solubility, CoQ10 has a high degree of mobility in the inner membrane, and it is particularly suitable for carrying electrons and protons in the oxidative respiratory chain of mitochondria, it can promote the production of ATP and improve the energy starvation of the cells by transferring electrons to the polymerase complex II and III; CoQ10 protects human tissues and cells by delivering hydrogen to free radicals, thus eliminating oxygen radicals and preventing oxidation of proteins, lipids and deoxyribonucleic acid (DNA).

The parent enzyme of Coenzyme Q10 is synthesized in the body from tyrosine, while its isoprenoid side chain is synthesized from acetyl coenzyme A via the mevalonate pathway. Therefore, β-blockers, which act by blocking the mevalonate pathway, and statins, which act by lowering cholesterol, affect the synthesis of coenzyme Q10 in the body, resulting in a decrease in the level of coenzyme Q10 in the human body.

2. Distribution, Absorption and Metabolism of Coenzyme Q10 in the Human Body

Coenzyme Q10 is widely distributed in the human body, and it exists in various organs, tissues, subcellular fractions, and plasma. However, its content varies greatly, with a high mass concentration in tissues and organs such as liver, heart, kidney and pancreas, and the total content of Coenzyme Q10 in the human body ranges from 500 to 1500 mg. The distribution of Coenzyme Q10 in cells is as follows: 25% to 30% in the nucleus, 40% to 50% in the mitochondrion, 15% to 20% in the microsomes, and 5% to 10% in the cytoplasm. In humans, the ability to synthesize coenzyme Q10 reaches its peak at the age of 20, and is maintained until the age of about 50, after which it declines yearly. The decrease in the mass concentration of coenzyme Q10 is particularly obvious in the highly energy-intensive heart, with a decrease of more than 50% in the myocardium of a 77-year-old compared with that of a 20-year-old [2-4].

Coenzyme Q10 is mainly synthesized by the body and supplemented with dietary supplements. Coenzyme Q10 is found in relatively high levels in foods such as sardines, swordfish, animal offal (heart, liver, kidney), blackfish, mackerel, beef, pork, chicken thighs, soybean oil, and peanuts. Consumption of about 1 catty of sardines, 2 catty of beef or 3 catty of peanuts can provide about 30mg of Coenzyme Q10 each.

To maintain normal plasma concentrations, the human body needs to supplement about 30-60 mg of coenzyme Q10 per day. However, the daily intake of coenzyme Q10 in a normal diet is about 2-5 mg, which is far from meeting the needs of the body in pathological conditions. Exogenous coenzyme Q10 is slowly absorbed from the small intestine into the lymphatics, blood and tissues; studies have shown that the absorption and bioavailability of fat-soluble coenzyme Q10 is low and varies widely among individuals, and that age, sex, lipoprotein status, diet, dosage form, or other factors may affect bioavailability.1 In the Wistar strain of male rats and rabbits, a single oral dose of 0.6 mg/kg of coenzyme Q10 was administered for 1 h and 2 h, respectively, and the results showed that coenzyme Q10 was not available in the diet. In Wistar strain male rats and rabbits, 0.6 mg/kg of coenzyme Q10 was given orally at one time, and the highest blood mass concentration was reached after 1 h and 2 h, respectively, and the mass concentration of the drug in the heart, liver, kidney and other tissues increased at 4 h. The drug was mainly excreted via the liver and gallbladder from the intestinal tract (85%~91%), and a very small amount of it was excreted in the urine [4-5].

The plasma concentration of coenzyme Q10 is commonly used to assess the status of coenzyme Q10 in the human body, and the plasma mass concentration of coenzyme Q10 in normal subjects has been reported to be 0.40-1.91 μmol/l (0.34-1.65 μg/ml) in different studies. The synthesis of coenzyme Q10 in the human body requires the participation of at least seven vitamins, including vitamin B2, nicotinic acid, vitamin B6, folate, vitamin B12, vitamin C, pantothenic acid, and several trace minerals. The synthesis of Coenzyme Q10 requires at least seven vitamins, including vitamin B2, niacin, vitamin B6, folic acid, vitamin B12, vitamin C, pantothenic acid, and some micronutrients, and it is a complex process that involves 17 steps of biosynthesis and 12 proteins, and it is susceptible to a variety of factors, such as genes, age, nutrition, and drugs [2,4,6].

The endogenous level of coenzyme Q10 is regulated by physiological factors and is related to the oxidative activity of the body. The parent nucleus of coenzyme Q10, benzoquinone, is synthesized in vivo using tyrosine as the raw material, whereas the isoprenoid side chain is synthesized from acetyl-coenzyme A through the mevalonate pathway; therefore, the use of antihypertensive drugs, such as β-blockers and cholesterol-lowering drugs such as statins, which function by blocking the mevalonate pathway, also affects ubiquinone synthesis and thus the synthesis of ubiquinone, which affects the body [2,4,6]. The use of β-blockers, which block the mevalonate pathway, and statins, which lower cholesterol, can also affect the synthesis of ubiquinone in the body, which in turn affects the synthesis of coenzyme Q10 [4,5,7].

Primary Coenzyme Q10 Deficiency is a hereditary genetic abnormality that leads to impaired synthesis of coenzyme Q10 in humans and is associated with a range of fatal multi-system disorders, including cardio, cerebral, renal, neuromuscular, and other clinical manifestations. Ultra-high-dose supplementation of coenzyme Q10 (5-50 mg/kg/day) may be effective in halting the progression of the disease and may even reverse the neuromuscular, cardiac, and renal pathology that has already occurred, without serious adverse effects. Early genetic diagnosis during the asymptomatic period is the key to effective treatment [8].

3. What Is Coenzyme Q10 Used For?

3.1 Mechanism of Action Against Cardiovascular Disease

Coenzyme Q10 is an obligatory component of the mitochondrial respiratory chain in all cells, a key cofactor in mitochondrial oxidative phosphorylation, and a key component in the production of adenosine triphosphate (ATP). The quinone structure of the molecular composition of coenzyme Q10, as described earlier, gives it a key role in the transfer of protons and electrons in the mitochondrial oxidative respiratory chain, a role that is necessary for the health of all organs and tissues throughout the body, particularly in energy-intensive organs and tissues.

It has been shown that coenzyme Q10 is a coenzyme for at least three mitochondrial enzymes (NADH-coenzyme Q reductase, cytochrome complex bc1, and succinate dehydrogenase), and that it transfers electrons in mitochondrial electron transfer from complex 1 (NADH-coenzyme Q reductase) to complex 3 (cytochrome complex bc1) and from complex 2 (succinate dehydrogenase) to complex 3 [2, 3, 4]. 3,4], by relying on this series of electron transfer, thus completing the energy production and conversion, so coenzyme Q10 is an element of cellular energy production and activator of respiratory metabolism in organisms, and the appropriate amount of coenzyme Q10 is necessary for cellular respiration and the production of ATP.

Bioenergy starvation is a new theory in the field of heart failure. In chronic cardiac insufficiency, ventricular remodeling occurs and myocardial energy consumption increases, which directly leads to energy depletion; on the other hand, myocardial hypertrophy gradually occurs due to myocardial mechanical pulling effect, which further aggravates myocardial energy consumption, and then leads to myocardial apoptosis and necrosis, which adds to myocardial remodeling, and a vicious circle is formed repeatedly; thus it can be seen that energy starvation in cardiac cells is a key factor in the development of heart failure. Thus, it is clear that energy starvation of cardiomyocytes plays a key role in the pathogenesis of heart failure. Coenzyme Q10 plays a key role in myocardial biological function, which is the rate-limiting enzyme for ATP production in mitochondria and a key component of the electron transport chain [9], and can effectively alleviate myocardial energy starvation.

Coenzyme Q10 is abundant in the myocardium, and many studies have shown that the reduction or depletion of myocardial coenzyme Q10 is an important mechanism for the development of clinical congestive heart failure, and some studies have even shown that the content of coenzyme Q10 in the myocardium is closely related to the degree and symptoms of heart failure, so some people call coenzyme Q10 a promoter and activator of energy metabolism in cardiac myocytes [10].

Coenzyme Q10 is a potent antioxidant. In mitochondria, coenzyme Q10 eliminates oxygen free radicals and inhibits the damage of free radicals to biological membranes by delivering hydrogen to free radicals. Meanwhile, in lysosomes, Golgi apparatus and plasma membrane, coenzyme Q10 plays an antioxidant role by directly reacting with free radicals and promoting the reduction and regeneration of oxidized vitamin E and vitamin C, thus effectively preventing the damage of membrane phospholipid peroxidation and oxidative damage of mitochondrial DNA and membrane proteins caused by free radicals. In the circulation, coenzyme Q10 can stabilize low-density lipoprotein (LDL) particles and prevent lipid peroxidation damage, thus exerting beneficial cardiovascular effects [11].

Oxidative stress has been found to have a significant effect on cardiac function. When levels of Reactive Oxygen Species (ROS) are elevated, they react with numerous proteins, DNA, cell membranes, and other biomolecules, resulting in significant cellular damage.1 The renin-angiotensin-aldosterone system plays an important role in the development of cardiac structural and functional abnormalities. The renin-angiotensin-aldosterone system plays an important role in the development of structural and functional abnormalities in the myocardium, and increased production of ROS and angiotensin II induces c-jun N-terminal kinase (JNK) and mitogen activation. Increased production of ROS and angiotensin II induces c-jun N-terminal kinase (JNK) and mitogen activated protein kinases p38 (MAPKp38) signal-regulated kinase-1. In addition, increased oxidative stress products and cytokines directly stimulate cardiomyocyte growth and hypertrophy. Myocardial hyperfibrosis and depression of myocardial compliance are important factors in the progression of heart failure, and severe oxidative stress can lead to perivascular and tissue fibrosis, cardiomyocyte hypertrophy, and consequent diastolic dysfunction [4,12].

Reduced coenzyme Q10 prevents the formation of lipid peroxyl radicals by influencing the initiation of lipid peroxidation. The efficient sequential regeneration of lipids initiates and participates in the process of lipid peroxidation, which explains why coenzyme Q10 acts as a potent antioxidant against free radicals in biological membranes [13].

Apoptosis induced by oxidative stress is an important factor in the development of heart failure, especially in the advanced stages of heart failure. With increased oxidative stress, neuroendocrine and inflammatory responses are activated, leading to the initiation of a programmed cell death in cardiac myocytes. 7 genes regulated by coenzyme Q10 are known to be involved in apoptosis [14].

Recently, it has been shown that coenzyme Q10 can affect the expression of hundreds of genes and exert multiple biological effects through the induction of gene transcription and anti-inflammatory effects through nuclear factor-κB1-dependent gene expression; therefore, it can be an effective gene regulator [15].

Chronic heart failure is associated with chronic inflammation, and it has been found that patients with chronic heart failure have increased levels of circulating cytokines, soluble receptors, and soluble adhesion molecules. Long-term activation of the inflammatory response promotes the development of heart failure by activating cytokines and chemokines secreted by different cell types, leading to myocardial fibrosis and changes in the structural shape of the left ventricle. Recent studies have confirmed the anti-inflammatory effects of coenzyme Q10, the mechanism of which may be related to the down-regulation of nitric oxide (NO) levels [16].

3.2 Coenzyme Q10 and High Blood Pressure

Oxidative stress plays an important role in all aspects of hypertension, and the different causes will lead to a common result of excessive ROS production, which can induce and exacerbate hypertension. In addition to excessive ROS production, reduced antioxidant capacity is also an important contributor to oxidative stress in hypertensive patients. It has been shown that the lower the level of coenzyme Q10 in the elderly, the higher the prevalence of hypertension. Coenzyme Q10 reduces mitochondrial superoxide production by increasing the efficiency of electron transfer from complexes I and II. CoQ10 also acts as an antioxidant by scavenging free radicals and reducing lipid peroxidation at the plasma membrane level.

Nitric oxide (NO) plays an important role in the development of hypertension and its complications, and ROS reduces the effects of NO by oxidatively modifying LDL (oxidized low-density lipoprotein) and reacting directly with NO to form peroxynitrite. Coenzyme Q10 inhibits oxidized LDL-mediated down-regulation of endothelial nitric oxide synthase and up-regulation of inducible nitric oxide synthase. Coenzyme Q10 reduces peripheral resistance by preserving NO. In some forms of hypertension, there is an increase in the production of superoxide radicals, which reduces NO activity, and coenzyme Q10, through its antioxidant action, prevents the inactivation of NO by free radicals [17].

Prostaglandin (PG) is a potent vasodilator, and coenzyme Q10 promotes the production of PGI2 and increases the sensitivity of arterial smooth muscle to PGI2.1 Clinical trials have shown that some patients with elevated blood pressure may benefit from adjunctive therapy with coenzyme Q10.

Clinical trials have shown that some patients with elevated blood pressure may benefit from adjunctive therapy with coenzyme Q10 and that some patients with essential hypertension may discontinue one or more antihypertensive medications when taking coenzyme Q10. Burke et al. [18] found that 12 weeks of treatment with coenzyme Q10 lowered systolic blood pressure in patients with hypertension in a randomized, double-blind, placebo-controlled trial. A non-evidence-based review [19] concluded that coenzyme Q10 reduced systolic blood pressure up to 17 mm Hg (1 mm Hg = 0.133 3 kPa) and diastolic blood pressure up to 10 mm Hg in patients with hypertension without significant adverse effects, and the supplement was considered safe and well tolerated.

A recent double-blind randomized controlled study showed that treatment with coenzyme Q10 did not significantly affect blood pressure in obese subjects [20]. Notably, coenzyme Q10 had no direct vasodilatory or hypotensive effects in healthy animals or humans. This suggests that the antihypertensive effect of coenzyme Q10 is specific to hypertensive patients with enhanced oxidative stress. a 2016 meta-analysis did not demonstrate an exact antihypertensive effect of coenzyme Q10 [21].

3.3 Coenzyme Q10 and Diabetes

Diabetes mellitus is one of the major risk factors for cardiovascular disease, and coenzyme Q10 has been reported to be very beneficial in diabetes mellitus [22]. Diabetes mellitus is a chronic metabolic disorder, which is a syndrome of glucose, protein and lipid metabolism disorders caused by the lack of insulin or the increase of insulin-antagonistic hormones or the failure of insulin to play its normal physiological role in the target cells, and many studies have shown that oxidative stress plays an important role in the process of diabetes mellitus.  treatment of diabetes [23].

It was found that the plasma concentration of coenzyme Q10 was reduced in patients with type 2 diabetes mellitus, and the decreased level of coenzyme Q10 weakened the body's ability to resist oxidative stress, impaired mitochondrial function in high energy-consuming tissues, leading to β-cell failure, and may be related to subclinical diabetic cardiomyopathy. Coenzyme Q10 supplementation may reduce oxidative stress, thereby increasing the body's antioxidant capacity, slowing beta cell function, lowering glycosylated hemoglobin (HbA1c), and improving vascular endothelial function.

In a 12-week, double-blind, placebo-controlled trial of 74 diabetic patients, a group taking 100 mg of CoQ10 twice a day significantly improved glycemic control compared to a placebo control group. A similar effect was seen in an 8-week double-blind, placebo-controlled trial of 59 men with diabetes. In addition, clinical studies have demonstrated that 12 weeks of treatment with coenzyme Q10 in diabetic patients improves clinical prognosis and diabetic polyneuropathy, raising the possibility of coenzyme Q10 as a future treatment for peripheral neuropathy in type 2 diabetes mellitus [24]. These results suggest that early and long-term administration of the antioxidant coenzyme Q10 in diabetic patients may be a promising treatment for type 2 diabetic neuropathy.

3.4 Coenzyme Q10 And Anti-fatigue

Patients with cardiovascular diseases often suffer from a series of chronic fatigue syndromes, such as generalized exhaustion, weakness of limbs, memory loss, poor concentration, and a decline in the quality of life due to heart failure or the use of medications such as β-blockers and statins. Chronic fatigue syndrome is a complex disease characterized by severe and disabling fatigue. The etiology and pathophysiological mechanisms of chronic fatigue syndrome are still unclear; there is no known cause, no established diagnostic test, and no universally effective treatment.

However, some studies have suggested that oxidative stress is a contributing factor, and experiments have found that chronic fatigue syndrome is accompanied by inflammation, varying degrees of oxidative stress, and low levels of antioxidants. Although it remains to be seen whether oxidative damage is a cause or a consequence of the disease, some studies have suggested that supplementation of coenzyme Q10 in this population may improve the symptoms and quality of life, and be successful in the prevention and treatment of chronic fatigue syndrome.

Chronic fatigue syndrome can be successfully prevented and treated by supplementation with Coenzyme Q10 in this population. Experiments have shown that adequate levels of coenzyme Q10 in the body are necessary for proper muscle function. Biochemical analyses of myocyte extracts have shown that when coenzyme Q10 concentrations fall below 20% of normal, the functional activity of cellular mitochondrial complexes I+II and I+III is severely reduced, and several studies have clearly shown that supplementation with 100-150 mg of coenzyme Q10 per day can significantly improve the condition of patients suffering from muscular dystrophy.

In an 8-week randomized, controlled, double-blind trial, 80 patients with chronic fatigue syndrome were enrolled and divided into two groups of coenzyme Q10-supplemented and placebo patients who played two matches per day and were assessed for fatigue, pain, and sleep at baseline, and then re-assessed by self-reported questionnaires at weeks 4 and 8, respectively. The results showed that patients in the coenzyme Q10 supplemented group felt less fatigue at follow-up compared to the placebo group (p=0.03) [25].

In the past few years, the clinical research and application of coenzyme Q10 have made great progress, and a large number of studies have shown that coenzyme Q10 is extremely important in the prevention and treatment of heart failure and the vascular protection of atherosclerosis, and that it has demonstrated amazing effects in both symptomatic improvement and anti-aging. The clinical application of coenzyme Q10 has also made great progress, and there are many vivid cases of clinical benefit in the middle-aged and elderly population, both in anti-aging health care and in the prevention and treatment of cardiovascular disease. However, there is still a serious lack of understanding of coenzyme Q10 among clinicians, and we are looking forward to more and better clinical studies on coenzyme Q10, as well as more evidence of the clinical benefits of coenzyme Q10 in clinical practice.

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