Review Articles

Coenzyme Q10 (Ubiquinone) : Implications in Clinical Practice
Deepak Langade*, Pratibha Tarapure#, Abhay Jagtap**, Preeti Arora***,
Sanjeev Anand***

INTRODUCTION
Coenzyme Q10 (CoQ10) is a lipophilic compound naturally found throughout the
body. It is an endogenously synthesized provitamin that serves as a lipid soluble
electron carrier in the mitochondrial electron transport.1 The alternative names
ubidecarenone and ubiquinone, meaning ubiquitous quinone, allude to the presence of
CoQ10 in all cells.2 The cellular effects of CoQ10 may be important in patients with
cardiac diseases especially coronary artery disease and congestive cardiac failure. It has
been used as an adjunctive therapy for various cardiovascular conditions and in some
countries it is available as over-the-counter nutritional supplement.

Coenzyme-Q exists in several forms and can be found in microorganisms, plants and mammals
including humans. Co-enzymes q6, q7, q8 are found in yeast and bacteria whereas co enzyme
q9 is found in rats and mice. CoQ10 is prevalent in humans, with high endogenous
concentration found in the heart, liver, kidney and pancreas. Current CoQ10 supplements are
manufactured by the fermentation of beets and sugarcane.

USA in 1957.6 decaprenyl benzoquinones. (Fig. professor Yamamura of Japan became the first in the world to use coenzyme q7 a related Compound in the treatment of human diseases viz. 3.5 gm. sardines and mackerel. Dietary intake of CoQ10 is 2-5 mg per day. which is always inadequate to provide levels in the body required to be beneficial in pathological states. The biosynthesis of the compound is multifold. 2). In 1960.5 methyl . the benzoquinone ring structure from tyrosine. History CoQ10 was first isolated from beef heart mitochondria by Dr.1 In 1958. Chemistry Chemically CoQ10 is 2. poultry and broccoli. 3 dimethoxy .4 to 1. congestive heart failure. (HMG-COA) reductase reaction that is similar in cholesterol synthesis. Peter Mitchell received the Noble prize for his contribution to the understanding of biological energy transfer through the formulation of the chemiosmotic theory.It can be synthesized in the body therefore CoQ10 is not considered to be an essential nutrient. It is present in foods such as beef. 1). with the isoprenyl side chain deriving from mevolonate. and condensation of these structures through polyprenyl transferase enzyme activity. The total body content of CoQ10 is 0. Frederick Crane of University of Wisconsin. peanuts. which includes the vital proton motive role of CoQ10 in energy transfer systems. fish oils. professor Karl Folkers and coworkers determined the precise chemical tructure of CoQ10 as 2. meaning the ubiquitous quinone. dimethoxy-5 methyl-6 decaprenyl benzoquinones synthesized and were the first to produce it by fermentation. It is a naturally occurring fat-soluble quinone ubiquitous in eukaryotic cells. Professor Morton introduced the name ubiquinone. .3 Other sources of CoQ10 are soy oil. (Fig. In 1978.4 The primary regulation of CoQ10 biosynthesis is the 3 hydroxy-methyl glutaryl coenzyme a.. Synthesis CoQ10 is synthesized in almost all tissues in the body from the amino acid “Tyrosine”.

Other mechanisms of action may include stabilization of calcium dependent slow channels. enabling reversible reactions between these enzymes in the mitochondrial electron transport chain. and alteration of prostaglandin metabolism. It serves as an electron acceptor for one group of enzymes and as an electron donor to the next group of enzymes in the electron transport chain. Coenzyme-Q participates in the electron transport inside the mitochondria of the cell. and supplementation with CoQ10 may inhibit lipid oxidizability. CoQ10 directly regulates NADH and succinate dehyrogenase. CoQ10 as Energizer CoQ10 participates in the electron transport inside the mitochondria of the cell. Thus CoQ10 acts as an energizer where it improves the efficiency of the cells to utilize all available energy from its sources. It is a central rate-limiting constituent of the mitochondrial respiratory chain. CoQ10 is the important coenzyme responsible for taking up electrons and pushing H+ into the intermembrane space. It serves as an electron acceptor for one group of enzymes and as an electron donor to the next group of enzymes in the electron transport chain. is structurally similar to vitamin-K5.5 Physiological role of CoQ10 I. it is involved in the manufacture of ATP. ATP synthase is like a turbine where higher concentrations of H+ leads to more energy trapping and ATP formation and vice-versa.are gained or lost by CoQ10. It is an essential component in the synthesis of ATP and exhibits both anti-oxidants and membrane stabilizing property. inhibition of intracellular phospholipases. The [H]+ accumulated in the intermembrane space of mitochondria is driven back into the mitochondria matrix via ATP syntheses (complex-v) with formation of ATP. thus either H+ or e. thus either hydrogen ions or electrons are gained or lost by CoQ10. CoQ10 acts as a redox link between flavoproteins and cytochromes that are needed for oxidative phosphorylation and synthesis of ATP. Thus. Thus. It serves as an electron transport carrier during the processes of respiration and oxidative phosphorylation. whereas deficiency of which may lead to loss of energy generated during the metabolic processes in the form of heat. CoQ10 is an essential component in the ATP synthesis in the mitochondria and high concentrations of CoQ10 can increase the total utilization of energy released by the metabolic processes in the body. .Mechanism of Action CoQ10 is a lipid soluble benzoquinone with a 10-isoprenyl unit side chain. It helps transport electron from complex-i to complex-ii and from complex-ii to complex-iii. which generates most of the ATP within the cell. CoQ10 must be reduced to ubiquinol to wield its anti-oxidative function.

Free radicals have high propensity to damage cellular DNA leading to activation of carcinogenesis. ischaemia reperfusion injury. gets converted to reduced CoQ (Ubiquinol). Free radicals bring about modulation of inflammatory process by regulating prostaglandin synthesis. industrial pollutants. thus rendering free radicals into harmless compounds. They also lead to fatty acid peroxidation and damage to the cell architecture and function. It itself is a strong directly acting endogenous antioxidant. They also damage the various cellular metabolic processes and interfere with ion channels located on the cells. CoQ10 acts as an antioxidant by decreasing formation of free radicals. . sunlight and ionizing radiation can generate free radicals. These unpaired electrons can easily react with cell components to cause free radicals injury or oxidative damage. diabetes mellitus. which have one or more unpaired electrons. hypertension. It improves the transport of electrons (e-) and protons (H+) and thus prevents the formation of superoxide radicals that would otherwise form from the released O2. Suproxide anion (O2-). which indicates slow absorpiton from the GI tract possibly due to the high molecular weight and low water solubility of CoQ10.5 hours. Various drugs. Tmax is approximately 6. plasma membrane and the cytoplasm. Other possible roles of CoQ It may be involved in maintenance of cell membrane integrity of RBCs and maintains optimum blood viscosity. congestive heart failure. endoplasmic reticulum. dyslipidaemia and many other conditions. Reduced CoQ10 then gives up electrons and gets reactivated again for further activity. With high doses of dietary CoQ10. Antioxidant effects of CoQ10 It is well known that free radicals cause oxidative damage in various chronic disease states like atherosclerotic heart disease. pesticides.II.2 Uptake of dietary CoQ10 in the liver does not affect the synthesis of endogenous CoQ10. Free radicals are the substances. It acts as a substrate for free radicals and accepts the free electrons from free radicals. Hydroxyl radicals (OH-).peak plasma levels occur between 5 and 10 hours. tobacco smoke. It stabilizes the calcium channels and may promote apoptosis in malignant cells and may improve the immune status of patients. peroxisomes. Pharmacokinetics Absorption In animal studies CoQ10 has an oral bioavailability of 2-3%. III. chemicals. Following ingestion of 100 mg of CoQ10. CoQ10 is found to regenerate the oxidized Vitamin-E thus converting it into a strong antioxidant. whereas in the body they are being constantly formed in the lysosomes. The unutilized oxygen in the body can lead to the formation of free oxygen radicals viz. the blood concentration in both rats and humans can be increased about 2 to 4-fold.

The excretion of CoQ10 predominantly occurs via the biliary tract. administration of CoQ10 increases the energy synthesis in the mitochondria and significantly improves the cardiac function (contraction and relaxation). Thus. therapy with CoQ10 may be considered to be an efficacious aid in the traditional treatment of chronic congestive heart failure along with other agents used in CHF. cardiac bypass surgery. In humans. In patients of dyslipidaemia who are on statins.7 Following absorption from the GI tract.37 mg/ml. mitochondria function in the cardiac myocytes can be significantly impaired in deficiency of CoQ10. Patients with severe CHF. liver. kidney. Heart failure often is characterized by an energy depletion status that has been associated with low endogenous CoQ10 levels. there is an apparent deficiency of CoQ10 and concurrent CoQ10 administration in such patients significantly improves the cellular function and reduces the complications of dyslipidaemia. Role in pathological conditions Role in CHF Coenzyme Q10 supplementation as an adjunct to CHF standard therapy is reported to have positive outcomes. CoQ10 is also useful in patients with hypertension. Therefore.004 ± 0. i. and more energy is required for relaxation. and pancreas. cyanosis. pulmonary rales. CoQ10 also reduces the ischaemia-reperfusion injury seen in patients recovering from myocardial ischaemia. The major portion of an exogenous dose of CoQ10 is deposited in the liver and packaged into VLDL lipoprotein. cardiac transplantation.Distribution The mean plasma levels after a single 100 mg oral dose of CoQ10 in human subjects is 1. cardiac muscle fibres require calcium for contraction and relaxation. decreases end diastolic ventricular pressure and improves the ejection fraction in CHF. Since energy synthesis (ATP Synthesis) from fats requires a higher oxygen concentration. CoQ10 administration has shown to reduce the signs and symptoms of CHF like oedema. which decrease cholesterol synthesis by HMG-CoA reductase inhibition. These cells rely heavily on fat sources of energy and hence contain more mitochondria.e. CoQ10 is found in relatively high concentrations in the heart. Its antioxidant properties contribute to prevention of lipid peroxidation. Metabolism and Excretion It is assumed that metabolism and excretion of exogenous CoQ10 is analogous to endogenously produced CoQ10.5 As with other muscle types. which alleviates the oxidative stress inherent in CHF.6 The plasma half-life of CoQ10 in different tissues varies between 49-125 hours. cardiomyopathies and ischaemic heart disease. especially in patients with deficient levels of the provitamin. CoQ10 is taken up by chylomicrons. NYHA class III and IV tend to have . hepatomegaly and breathlessness on exertion. The possible usefulness of the CoQ10 in the treatment of CHF may be related to its ability to increase ATP synthesis and enhancement of myocardial contractility.

20.e.24-29 Male infertility Three important parameters in infertility are count.14. pulmonary rales.8-11 Two large multicenter. allowing tissue to reach higher levels of energy expenditure. placebo-controlled studies involving patients with stable angina pectoris. added to conventional therapy in patients with severe CHF (NYHA class III and IV). and palpitations. morphology and motility of sperm cells. or b-adrenergic blockers. Deficient activity of this enzyme can result in decreased levels of CoQ10. Role in hypertension These effect of CoQ10 to decrease blood pressure is attributed to the correction of endogenous pro-vitamin deficiency. patients with severe diseases may be more likely to attain a favourable clinical response to CoQ10 supplementation.23 Statistically significant decreases in systolic and diastolic blood pressure were observed with CoQ10 dosages ranging from 30-360 mg/day in patients with hypertension but these results are not consistent among the trials.lower levels of endogenous CoQ10 than that of patients with NYHA class-I CHF or healthy subjects.13 Role in angina The mechanism for improved exercise tolerance in patients with stable angina may be due to ischaemic myocardial protection by CoQ10. reduced exercise-induced ischaemic ST-segment depression. or reduction of free radicals formation create distinctions between the anti-anginal effects of CoQ10 and the effects of other agents such as nitrates.15-19 All of these studies determined that CoQ10 dosages of 60-600 mg/day significantly prolonged exercise duration.22 Having identified same deficiency in human subject with chronic hypertension.5 Possible activities of the coenzyme in the maintenance of oxidative phosphorylation. calcium channel blockers. oedema.20.12.21. dyspnoea.20. and delayed the onset of stable angina pectoris when compared with placebo. The ability of exogenous CoQ10 to protect the ischaemic myocardium and reduce or delay signs and symptoms of angina is suggested by six small randomized. The sperm count and morphology may be adversely affected due to damage by free radicals. Studies reported clinical benefits from short-term (1-4 wks) and long-term (3 months - 6 yrs) therapy with oral CoQ10 supplements.21 In a study of hypertensive rats. patients with NYHA class II and III and class III and IV CHF) who experienced clinical improvement in signs and symptoms such as cyanosis. enhancement of ATP synthesis.5. investigators conducted a pilot study in which they concluded that increased succinate dehydrogenase CoQ10 reductase activity and subsequent increased CoQ10 level lead to decreases in systolic and diastolic blood pressures. double-blind. The reduced sperm motility is the consequence of decrease in energy . 50-100 mg/day.4. The two studies examined a total of more than 4000 patients with varying severity of CHF (i. open-label studies evaluated the efficacy and safety of CoQ10 as adjuvant therapy in CHF.5 Thus. a deficiency in the activity of succinate de-hydrogenase CoQ10 reductase in leucocytes was found.

30 Just before ovulation.production ATP. which only allows sperms.3. Asymptomatic elevations in . CoQ10 prevents the sperm from free radical induced damage. After administration. and hence optimal mitochondrial ATP generation plays an important role in sperm motility. which are normal. The motility of sperm requires a high-energy expenditure. and good correlation has been demonstrated between these levels and sperm motility/count. CoQ10 increases the membrane integrity of sperm and increases defense mechanism of the sperm.31 Due to its lipophillic nature. CoQ10 encourages better sperm viability due to proving protection against the damaging effects of reactive oxygen species. and possess adequate motility. heartburn. epigastric pain.13% to 16.34%. diarrhoea. Whenever there is oligoasthenozoospermia. This is called ferning and. Since the complete process of spermatogenesis requires a long time CoQ10 should be administered at least for a period of 10 to 12 weeks Side-effects In therapeutic dosages. CoQ10 has been found to be useful in idiopathic asthenozoospermia. In this study subjects with history of primary infertility received 200 mg twice daily of CoQ10 for 6 months.081-1. which is loss or decrease of sperm motility in semen. the available sperm also have a high chance of being damaged by free radicals. to navigate successfully so as to reach the ovum for fertilization in the optimal 69 minutes of time. Testicular tissue and sperm viability are particularly vulnerable to peroxidation injury produced by free radicals and reactive oxygen species.066 mmol. The reasons why sperms are vulnerable to damaging effects of these are: wide surface of the sperm membranes. Motility of sperm cells also increased from 9. lack of protection in the female genital tract once the sperms are ejaculated. the quantity of water and mucus increases in the living cells of the cervix in female. At the end of study period CoQ10 levels in seminal plasma and phosphatidylcholine increased significantly. CoQ10 gets incorporated in the sperm mitochondria during the process of spermatogenesis. and appetite-suppression.5 Gastrointestinal effects of CoQ10 may be lessened with a dosage reduction or may subside with continued therapy. The CoQ10 concentration in serum is usually 0. CoQ10 has proved to be relatively devoid of major side effects. as a result of the latter channels is formed in mucus. The sperm motility is directly dictated by its ability to generate ATP. The water and salt interact with the glycoproteins present in mucus to form crystal. Because of its antioxidant and free radical scavenging activity. and also by enhancing sperm motility. The most common adverse effects are nausea. In Jan 2004 a study was conducted to evaluate role of CoQ10 in male infertility. However. Asthenospermia and ATP The main concentration of mitochondria in the sperm is in its midpiece. which in turn is dependent on CoQ10 production. Increased lipid peroxidation of sperm leads to its damage and thereby causing infertility. poor cytoplasmic defense mechanisms. the prevalence of these adverse effects was less than 1% in reported studies.

g. lovastatin) may result in the diminution of CoQ10 blood levels due to interruption of synthesis. cases of serious hepatotoxicity have not been reported. Use of HMG-CoA reductase inhibitors (statins i. or other dietary supplements are not known.43 The concomitant use of warfarin and CoQ10 should be avoided due to the risk of thrombotic complications. glyburide.. whereas reinstatement of therapy resulted in improvement.40 The oral antidiabetic agents (i. and stroke volume were demonstrated in CHF. and interactions between CoQ10 and food.6. phenformin. acetohexamide. herbs. These clinically significant .38-41 Other antilipidaemic agents such as cholestyramine of fibrate derivatives do not appear to affect CoQ10 concentrations. pravastatin. subsequent onset of fatigue and dyspnoea indicating clinical relapse occurred in 88% of 16 patients. cardiac output.42 CoQ10 is structurally related to vitamin-K and subsequently possesses procoagulant effects..35 Clinical relapse was noted on withdrawal of CoQ10. which in turn acts as a chemical energy carrier in the biosynthesis of insulin.35 Safety profile of CoQ10 during pregnancy and lactation has not been established. simvastatin. NADH and succinate dehydrogenase) resulting in reductions in serum CoQ10 levels. Several reports describe decreases in international normalized ratio (INR) after the addition of CoQ10 in patients previously stabilized with warfarin therapy.e.serum lactate dehydrogenase and hepatic enzymes were observed and may occur with oral dosages of CoQ10 in excess of 300 mg/day. Conclusions CoQ10 administered orally has favourable actions in various cardiovascular conditions and appears to be safe and well tolerated in the adult population.e.36 Drug interactions A drug interaction may occur between HMG-CoA reductase inhibitors and CoQ10 because the coenzyme is a byproduct of the cholesterol biosynthetic pathway. and tolazamide) may inhibit enzymes (e. A conservative approach to CoQ10 therapy is to support its use as adjuvant treatment for CHF. Its favourable effects on ejection fraction. reduced insulin requirements were observed in patients with diabetes who were taking CoQ10 because it exerts favourable effects on ATP. angina or hypertension.42 CoQ10 supplementation in patients with hepatic insufficiency or biliary obstruction may increase serum CoQ10 levels because this molecule is metabolized in liver and excreted primarily through the biliary tract. however. Also.36-37 In one withdrawal study. The potentially critical interaction can result as a diminished response to warfarin therapy. exercise tolerance. yet 75% improved and regained their clinical status with resumption of CoQ10.

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