Coenzyme Q10 (CoQ10), also known as Ubiquinone (UQ), or Ubidecarenone, sometime written as Q for short, is a vitamin like substance, can be found in a wide variety of food and synthesised in all cells. It was first isolated in 1957 by Frederick L. Crane, and the precise chemical structure determined by Karl Folkers in 1958.

Q synthesised from amino acid tyrosine (head group) and acetyl-CoA (tail group), requiring several vitamins and trace minerals.

Q serves as electron carriers between the NADH dehydrogenase complex and the b-c1 complex of respiratory chain. Other aspects of Q function include its involvement in extramitochondrial electron transfer, CoQ also play a role in improvement in membrane fluidity. With Vitamin C, and or Vitamin E, Q serves as an antioxidant.

Old age, chronic infection and other chronic conditions such as congestive heart failure require Q supplementation in order to have normal level in their tissue, hoping to restore proper Q functions.

Depend on the disease being treated, therapeutic dose ranging from 30-60 mg twice daily to 50-100 mg two to three times daily, while maintenance dose 30-90 mg per day.

Medication used for hypercholesterolemia acting on the enzyme HMG-CoA reductase will effect tissue level of Q. Although HMG-CoA reductase inhibitors are safe and effective within certain dose range, continued vigilance of possible adverse consequences from Q lowering seems necessary especially for long term therapy.

Many works have been done in clinical application of Q especially in the field of cardiology. Over the past 50 years, research in other fields of medicine including immunology, oncology, pulmonology, dermatology are growing steadily with promising results.

Q supplement to conventional treatment of congestive heart failure reported to improve exercise capacity and quality of life.

In conclusion, it is the belief that Q should be administered to any patient with congestive heart failure in addition to conventional therapeutic drugs.


Coenzyme Q (CoQ), Ubiquinone (UQ) or also called Ubidecarenone is a vitamin-like substance, insoluble in water, can be found in a wide variety of foods and synthesised in nearly all cells.

Although it was identified as early as 1957 by Frederick Crane of Wisconsin (other thought it was first discovered by Moore et al in 1940), not so many medical graduates aware of its medical significance, and even fewer medical doctors who have experience in prescribing it.

This paper is intended to increase medical professional awareness of the basic knowledge and its clinical application, especially for congestive heart failure (CHF).

The history of Co Q10

Like many other discoveries of medical sciences, the discovery of Co Q10 was actually quite accidental. It was identified by postdoctoral students while performing experiments on beef heart mitochondria as a frothy substance that consistently rose to the top of their test tubes. Crane FL isolated it as yellow crystalline substances in 1957. A year later Karl Folkers at Merck, Sharp & Dohme determined the precise chemical structure. Yamamura Y (1960) is the first to use Coenzyme Q10 related compound in congestive heart failure. Around mid year of 1970 Japanese perfect industrial technology of fermentation to produce pure Co Q10 in significant quantities. Peter Mitchell receives Nobel Prize for Co Q10 and energy transfer. In the early of 1990, an explosion of use of CoQ10 in health food of American industry (Anonymous 2).

The Structure of Coenzyme Q10

Coenzyme Q (CoQ), ubiquinone (UQ), a lipophilic substituted benzoquinone (head group), is present in all animal and plant cells. It is endogenously synthesised in tissues and involved in a variety of cellular processes (Mahler HR1971). Professor Karl Folkers and co-workers determined the structure of CoQ in the year of 1958, at Merck, Inc. (Langsjoen PH) as shown in figure 1:

n (isoprenoid tail) in the formula varies from 6 in certain micro-organisms – in which case the compound is referred to as CoQ6 or UQ30 – to 10 in the mitochondria of most mammals – when its designation is CoQ10 or UQ50 (Mahler HR 1971)

CoQ10 or Q for short is found mainly in the inner mitochondrial membrane (50%) and is present in relatively high concentrations in the heart, liver, kidney, and pancreas of humans. It is also found in the extra mitochondria, e.g. in the cytosol, lysosome, Golgi apparatus, and in very close association with plasma membrane. In the circulating system, 60 % of Q is carried in the LDL (Langsjoen PH).

Coenzyme Q10 synthesis.

The name ubiquinone signifies its ubiquitous (wide spread) distribution in the human body. The comprehensive step in biosynthesis of Q is still to be clarified. The detail pathways of synthesis Q cannot be found in many standard textbooks of Biochemistry. The quinone (head group) of Q can be synthesised from amino acid tyrosine, in a multistage process requiring at least eight vitamins and several trace elements (Langsjoen PH). In the living organism, synthesis of isoprenoid tail of Q up to isoprene (isopentenylpyrophosphate) has a similar pathway as cholesterol, terpenoids, vitamin K, and carotenoid synthesis (Buehler LK.). Like cholesterol synthesis, HMG-CoA reductase plays role in controlling the synthesis. From the data and references available is not possible to construct the Q synthesis pathway comprehensively. The question intriguing is, when and how exactly the tail part joint or synthesise to make it one molecule with the head part of Q.  The probable pathway of Q synthesis is (figure 2 and 3):

T Jonassen and CF Clarke (2000), propose the biosynthetic pathway of Q, the step after head and tail “has been joint together” (figure 5). The COQ3 gene product, O-methyltransferase catalysis two O-methylation step. The first O-methylation step it convert 3,4-dihydroxy-5-polyprenyl-benzoic acid (compound 1) to 3-methoxy-4-hydroxy-5-polyprenylbenzoic acid (compound 2). The second step converts 2-polyprenyl-3-methyl-5-hydroxy-6-mehoxy-1,4-benzoquinol (compound 3) to ubiquinol-n (compound 4).

Electrochemical reaction of Coenzyme Q10

Coenzyme Q10 is the simplest of the electron carriers, is not a protein bound prosthetic group, dissolved in the lipid bilayer, able to picks up or donates either one or two electrons, and it picks up a proton from the medium along with each electron that it carries. When it donates its electrons to the next carrier in the chain, these protons are released (Alberts B et. al. 1983, Lehninger AL 1977, Mahler HR 1971)   (figure 4 and 5).

Coenzyme Q10 serves as carriers between the NADH dehydrogenase complex and the b-c1 complex of respiratory chain. Coenzyme Q10 with cytochrome c make two components that carry electrons between three mayor enzyme complexes of the respiratory chain diffuses rapidly in the plane of the membrane. Collisions between these mobile carriers and the enzyme complexes can account for the observed rates of electron transfer (each complex donates and receives an electron about once every 5 to 20 milliseconds) (Albert B et al 1983).

The plasma membrane coenzyme Q reductase (PMQR), which catalysis reduction of endogenous Q using either NADH or NADPH as hydrogen donors, primarily responsible for Q reduction in plasma membrane under normal (non-oxidative stress-associated) conditions (Arroyo An et al 2000).

With Vitamin C, and or Vitamin E, Q serves as an antioxidant (figure 6). Vitamin E is the major chain-breaking anti oxidant in membrane cells. The membrane associated redox couples; ubiquinol/ubiquinone can lower the steady state of concentrations of Vitamin E radicals (Packer L 1992).

Coenzyme Q10 has a characteristic light-absorbtic band at 270 to 290 nm, which disappears when it is reduced to its quinol (QH2) form; this spectral change is used to measure oxidation and reduction of Q/QH2.

Function of Coenzyme Q10 in human.

Since its discovery, there has been a slow but steady accumulation of world-wide clinical experience with Q. The fundamental importance of its clinical application is the bioenergetic effect (the production of ATP), particularly as related to cells with high metabolic demands such as cardiac myocytes. The second function of Q is an involvement in antioxidant. It is the only known naturally occurring lipid soluble antioxidant for which the body has enzyme systems capable of regenerating the active reduced ubiquinol form. Coenzyme Q10 is known to be closely linked to vitamin E, which serves to regenerate the reduced (active) a-tocopherol form of Vitamin E. Other function including its involvement in extramitochondrial electron transfer, e.g. plasma membrane oxidoreductase activity, involvement in cytosolic glycolysis, and potential activity in both Golgi apparatus and lysosome. Coenzyme Q10 also plays a role in improvement in membrane fluidity, as evidenced by a decrease in blood viscosity with Q supplementation  (Anonymous 1, 3).

Dietary sources and its medical supply

Coenzyme Q10, a naturally occurring substance found in many foods, is sold in pure form in capsules in most health-food stores in the United State (sold in the counter, without prescription). In pure form, Q has melting point around 48o C, its general formulae C59H90O4 with molecular weight equal to 863.4 (Martindale Pharmacopoeia, 1996) can be found in many countries in the world e.g. in Japan, Canada, United Kingdom and United State. It is also known as ubidecarenone. The formulated name is 2 Deca (3 methylbut-2-enylene)-5,6-dimethoxy-3 methyl-p-benzoquinon.

The nutritional sources of Q are heart, red meat, spinach, fish, broccoli, and nuts.

To day many Japanese companies produce large amount of Q using microorganisms in a fermentation process. In Japan, over ten million people use Q as a prescription medicine, usually for treatment or prevention of heart disease (Anonymous 2).

At the present time, in Indonesia not so many people know about Q, only two big major pharmaceutical companies introduce the product of Q.

Why do deficiencies of Coenzyme Q10 occur?

As mention earlier, the synthesis of Q is a complex process that takes place in all cells. The very concentrated Q in the body is in the liver, heart, kidney and pancreas. In human, most of the Q found in the body is synthesised from the raw material supplied by the daily food intake.   Deficiency of Q can be the result of many factors involves. It may cause by deficiency of food intake such as vitamins, or minerals, or failure of absorption. It can also be the result of disturbances or inhibition of its synthesis such as in old age or consuming of some particular drugs. Other factor, if requirement exceeded its production for example in chronic heavy athletes, suffering of serious chronic infectious disease, cancer and many other chronic conditions may also cause deficiency of Q (Anonymous 1, 2, 3; Langsjoen PH).

Dosage, side effects and Coenzyme Q10 toxicity

Depend on the disease being treated, therapeutic dose ranging from 30-60 mg twice daily to 50-100 mg two to three times daily, while maintenance dose 30-90 mg per day.

Occasional reports of nausea, anorexia, or skin eruptions have been reported with supplementation of Q, however there is no toxicity have been reported or suspected as being associated with Q (Anonymous 2).

Statins and Coenzyme Q10

One of the cholesterol reducing agent is lovastatin. It reduces cholesterol by inhibiting the enzyme HMG-CoA reductase. In 1990 Willis et al. Studied 40 rats and demonstrated significant tissue Q deficiency of heart and liver in the lovastatin treated rats, which easily be prevented by co-administration of Q.  Later in the same year, Folkers et al. and Langsjoen et al. demonstrated a decline of Q blood levels. It also demonstrated a significant clinical decompensation with a reduction in ejection fraction in 5 heart failure patients after the addition of lovastatin to their standard medical therapy plus 100 mg per day of Q. A doubling of their Q doses from 100 to 200 mg/day reversed this decompensation. Pravastatin or simvastatin reduced blood level of Q up to 40% (Ghirlanda et al 1992). Bargossi et al. (1994) showed that reduction of plasma Q by simvastatin could be prevented by simultaneous administration of Q. In 1997 Mortensen et al observed similar reduction in serum Q levels in a placebo controlled double blind trial. The authors concluded hat “although HMG-CoA reductase inhibitors are safe and effective within a limited time horizon, continued vigilance of possible adverse consequences from Q lowering seems important during long term therapy”. In the same year Palomaki et al. documented a decrease in the resistance of LDL cholesterol to oxidative stress after 6 weeks of lovastatin therapy, which is believed to be related to a decrease in the number of molecules of Q per each LDL cholesterol particle (Langjoen PH).

Effect of other drugs on Q function in the body.

Kishi T et al (1977) showed that propanolol inhibit Q-enzymes, and clinically can be identified as an adverse reaction on the heart, for example it depresses myocardial function.

Tricyclic antidepressants are antagonistic to Q (Glassman AH, Roose SP 1994). Research in anti depressant drugs, including amitriptyline, particularly when given in high doses, has been reported to produce arrhythmia, sinus tachycardia, and prolongation of the conduction time. Myocardial infarction and stoke have also been reported with Tricyclic antidepressant drugs (Pinto J et al 1982, Scahill L et al 1994).

Warfarin exerts its therapeutic effect by interfering with vitamin K metabolism. Q, also known as Ubidecarenone, has a chemical structure similar to various forms of vitamin K. In contrary to effects of a drug on Q function in the body, administration of Q on the patient with Warfarin will reduces the later drug responsiveness. When the individual stopped taking the Q their previous responsiveness to Warfarin resumed (Spiget O 1994).

Medical uses.

Over the past 50 years, research in Q mostly in the field of cardiology. Experience by Japanese scientist, Yuichi Yamamura (late 1960’s) involving application of Q in treating congestive heart failure with a good result; simulate further research in this field. Later Q has been used in other Cardiac conditions e.g., ischemic heart disease, hypertension, diastolic dysfunction of left ventricle, arrhythmia and reperfusion injury or it relates to coronary artery bypass graft surgery with favourable results (Anonymous 1, 3, Rauchova H and Lenaz G 2001).

Coenzyme Q appears involves in immune response. Unfortunately most of the research in immune effects of Q stopped around 1981 (James JS.1987).

Research in other medical application of Q is still in progress, including it usage in cancer therapy, male infertility, gastric ulcer, obesity, allergy and many others (Anonymous-1, 2, 3).

Recently, topical application of Q has been shown to prevent many of the detrimental effect of photo ageing  (Hoppe U 1999).

The used of Q in congestive heart failure.

Heart muscles require energy (in form of ATP) for either contraction during systolic pressure or for relaxation during diastolic pressure. During heart muscle relaxation require more ATP than when muscle contract.

Heart failure may be considered to be the condition in which cardiac function is abnormal. Heart failure is failing to pump blood at a rate correspondent with the requirements of the metabolising tissues and/or can do so only from an abnormally elevated ventricular diastolic volume. The causes of heart failure, including the underlying cause (congenital, acquired) and precipitating cause (thyrotoxicosis, hypertension, arrhythmia, myocardial infarction and many others) of heart failure. One or more of clinical manifestation of heart failure including dyspnea, orthopnea, nocturnal dyspnea, reduced exercise capacity, cerebral symptoms may be the cause of patients to consult their doctors.

When heart failure occurs in the presence of acute or chronic ischemic it can be attributed to reduced myocardial energy supplies. Calcium ion (Ca++) has been proposed as a key role in the development of heart failure. Decrease in its availability on the contractile site of myofilamints will impaired cardiac performance (Braunwald E 1994).

Folkers et al suggested the use of Q for the treatment of heart failure in 1970, on the basis of a reduction in the myocardial concentration of Q for patients with chronic heart failure. However he was not the first who used Q for heart failure of patients, since Yamamura of Japan in the mid-1960, became the first in the world to use coenzyme Q7 (Anonymous 2).

They are many possibilities as how Q works in congestive failure. How ever the basic mechanism probably are, supporting the supply of ATP, as free radical scavenger via semiquinone species, stabilisation of muscle cell membranes, and limiting platelet activity (Lampertico M, Comis S 1993).

Langsjoen PH & Langsjoen AM (Accessed July 2001) reviewed the use of Q in heart failure involving 1366 patients in 15 randomised controlled trial found only one study with 25 patients of dilated cardiomyopathy has no positive result, whereas the others had significant improvement.

The results obtained by different groups clearly indicate that administration of Q at a daily dose of 50-100 mg increases contractile activity rapidly (within 4 weeks). In one study involving 2,664 patients, after three months treatment of Q, symptoms decrease as follows:

Oedema 79%, pulmonary oedema 78%, liver enlargement 49%, venous congestion 72%, shortness of breath 53% and heart palpitation 75% (Anonymous 2).

Morisco C et al (1993) conducted a long-term multi-centre randomised controlled trial, in which a total of 641 patients with chronic congestive heart failure were enrolled. The result showed that the percentage incidence of acute pulmonary oedema was significantly smaller in the Q group than in the placebo group (p <0.001). While the incidence of arrhythmias was significantly higher in the placebo group (p <0.05), the occurrence of cardiac asthma was lower in the Q treated patients (p <0.001). When the result is projected, for every 1,000 cases of heart failure treated with Q for one year, hospitalisations would be reduced by 20 %.

In conclusion, it is the belief that Q should be administered to any patient with congestive heart failure in addition to conventional therapeutic drugs (Langsjoen PH, Langsjoen AM.). This is true when the response to the latter is not as good as expected or a faster clinical improvement is a major issued.

To see the figures double click :

Fig 1 thr Fig 6


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