S Shinde, N Patil, A Tendolkar
S Shinde, N Patil, A Tendolkar. Coenzyme Q10: A Review of Essential Functions. The Internet Journal of Nutrition and Wellness. 2004 Volume 1 Number 2.
This article represents a review of Coenzyme Q10 (CoQ10),a compound found naturally in the energy-producing center of the cell known as the mitochondria.
Coenzyme Q10 (CoQ10) is a compound found naturally in the energy-producing center of the cell known as the mitochondria. It was first isolated from the mitochondria of bovine hearts in 1957 at the University of Wisconsin.(1) Identification of the chemical structure and synthesis was completed by 1958.(2) Research conducted in the 1960s and 1970s demonstrated that CoQ10 acts as an antioxidant and plays a central role in mitochondrial oxidative phosphorylation. CoQ10 is involved in the making of an important molecule known as ATP. ATP serves as the cell's major energy source and drives a number of biological processes including muscle contraction and the production of protein. CoQ10 also works as an antioxidant.(1)
Antioxidants are substances that scavenge free radicals, damaging compounds in the body that alter cell membranes, tamper with DNA, and even cause cell death. Free radicals occur naturally in the body, but environmental toxins (including ultraviolet light, radiation, cigarette smoking, and air pollution) can also increase the number of these damaging particles. Free radicals are believed to contribute to the aging process as well as the development of a number of health problems including heart disease and cancer. Antioxidants such as CoQ10 can neutralize free radicals and may reduce or even help prevent some of the damage they cause.(3)
CoQ10 (2,3-dimethoxy-5-methylbenzoquinone) is chemically classified as a fat-soluble quinone ring attached to 10 isoprene side units, structurally similar to vitamin K.
Mechanism of Action
Electron Transport Chain to Produce ATP: CoQ10, found in the inner mitochondrial membrane, is the cofactor for at least three mitochondrial enzymes (complexes I, II and III) that play a vital role in oxidative phosphorylation. It functions as the only non-protein component of the electron transport chain (ETC) in addition to not being attached to a protein itself. This unique characteristic enables CoQ10 to move and transfer electrons between flavoproteins and cytochromes. Each pair of electrons processed by the ETC must first interact with CoQ10, which is considered the central rate-limiting constituent of the mitochondrial respiratory chain. Therefore, CoQ10 plays an essential role in adenosine triphosphate (ATP), or biological energy, production. (5,6,7,8)
Coenzyme Q Deficiency
Normal blood and tissue levels of CoQ10 have been well established by numerous investigators around the world. Significantly decreased levels of CoQ10 have been noted in a wide variety of diseases in both animal and human studies. Insufficient dietary CoQ10, impairment in CoQ10 biosynthesis, excessive utilization of CoQ10 by the body, or any combination of the three, may cause CoQ10 deficiency. Decreased dietary intake is presumed in chronic malnutrition and cachexia.(20)
The relative contribution of CoQ10 biosynthesis versus dietary CoQ10 is under investigation. Karl Folkers takes the position that the dominant source of CoQ10 in man is biosynthesis. This complex, 17-step process, requiring at least seven vitamins (vitamin B2 - riboflavin, vitamin B3 - niacinamide, vitamin B6, folic acid, vitamin B12, vitamin C, and pantothenic acid) and several trace elements, is, by its nature, highly vulnerable. Karl Folkers argues that suboptimal nutrient intake in man is almost universal and that there is subsequent secondary impairment in CoQ10 biosynthesis. This would mean that average or “normal” levels of CoQ10 are really suboptimal and the very low levels observed in advanced disease states represent only the tip of a deficiency “ice berg”.
HMG-CoA reductase inhibitors used to treat elevated blood cholesterol levels by blocking cholesterol biosynthesis also block CoQ10 biosynthesis.(21) The resulting lowering of blood CoQ10 level is due to the partially shared biosynthetic pathway of CoQ10 and cholesterol. In patients with heart failure this is more than a laboratory observation. It has a significant harmful effect, which can be negated by oral CoQ10 supplementation.(22)
Increased body consumption of CoQ10 is the presumed cause of low blood CoQ10 levels seen in excessive exertion, hypermetabolism, and acute shock states. It is likely that all three mechanisms (insufficient dietary CoQ10, impaired CoQ10 biosynthesis, and excessive utilization of CoQ10) are operable to varying degrees in most cases of observed CoQ10 deficiency.
What are the principal uses of CoQ?
CoQ10 supplementation is used primarily in the treatment of cardiovascular diseases such as elevated cholesterol levels, high blood pressure, congestive heart failure, cardiomyopathy, mitral valve prolapse, coronary artery bypass surgery, and angina. Considerable scientific studies have validated these uses.(10,11,12) CoQ10 has also been shown to be helpful in diabetes; periodontal disease; immune deficiency; cancer; as a weight-loss aid; and muscular dystrophy. Since the response of CoQ10 can take time, a noticeable improvement might not occur until 8 or more weeks after therapy is begun.
Several clinical trials and case series have provided evidence, supporting the use of CoQ10 in the prevention and treatment of various disorders related to oxidative stress.
Heart Disease ()
Researchers believe that the beneficial effect of CoQ10 in the prevention and treatment of heart disease is due to its ability to improve energy production in cells, inhibit blood clot formation, and act as an antioxidant. One important study, for example, found that people who received daily CoQ10 supplements within 3 days of a heart attack were significantly less likely to experience subsequent heart attacks and chest pain. In addition, these same patients were less likely to die of heart disease than those who did not receive the supplements.
Congestive Heart Failure (CHF)()
Levels of CoQ10 are low in people with CHF, a debilitating disease that occurs when the heart is not able to pump blood effectively. This can cause blood to pool in parts of the body such as the lungs and legs. Information from many research studies suggests that CoQ10 supplements help reduce swelling in the legs, enhance breathing by reducing fluid in the lungs, and increase exercise capacity in people with CHF. Not all studies agree, however. As a result, some experts conclude that CoQ10 supplements do not contribute any benefit to the usual conventional treatment for CHF. More conclusive research will help resolve the debate.
High Blood Pressure ()
Several studies involving small numbers of people suggest that CoQ10 may lower blood pressure. However, it may take 4 to 12 weeks before any beneficial effect is observed. More research with greater numbers of people is needed to assess the value of CoQ10 in the treatment of high blood pressure.
High Cholesterol ()
Levels of CoQ10 tend to be lower in people with high cholesterol compared to healthy individuals of the same age. In addition, certain cholesterol-lowering drugs called statins (such as atorvastatin, cerivastatin, lovastatin, pravastatin, simvastatin) appear to deplete natural levels of CoQ10 in the body. Taking CoQ10 supplements can correct the deficiency caused by statin medications without affecting the medication's positive effects on cholesterol levels.
CoQ10 supplements may improve heart health and blood sugar and help manage high cholesterol and high blood pressure in individuals with diabetes. (High blood pressure, high cholesterol, and heart disease are all common problems associated with diabetes). Despite some concern that CoQ10 may cause a sudden and dramatic drop in blood sugar (called hypoglycemia), two recent studies of people with diabetes given CoQ10 two times per day showed no hypoglycemic response. The safest bet if you have diabetes is to talk to your doctor or registered dietitian about the possible use of CoQ10.
Heart Surgery ()
Research indicates that introducing CoQ10 prior to heart surgery, including bypass surgery and heart transplantation, can reduce damage caused by free radicals, strengthen heart function, and lower the incidence of irregular heart beat (arrhythmias) during the recovery phase.
Breast Cancer ()
Studies of women with breast cancer suggest that CoQ10 supplements (in addition to conventional treatment and a nutritional regimen including other antioxidants and essential fatty acids) may shrink tumors, reduce pain associated with the condition, and cause partial remission in some individuals. It is important to recognize that the beneficial effects these women experienced cannot be attributed to CoQ10 alone. Additional antioxidants used in these studies include vitamins C, E, and selenium.
Preliminary studies also suggest that CoQ10 may:
Improve immune function in individuals with immune deficiencies (such as AIDS) and chronic infections (such as yeast and other viral infections)
Increase sperm motility leading to enhanced fertility
Be used as part of the treatment for Alzheimer's disease
Reduce damage from stroke
Boost athletic performance
Enhance physical activity in people with fatigue syndromes
Improve exercise tolerance in individuals with muscular dystrophy
Overview Clinical uses
Formulations and Dosage
Exogenous supplies of CoQ10 are found in foods such as fish and fish oils, organ meats and germ of whole grains. However, in some cases dietary intake may be inadequate to meet the body's needs. The average diet is estimated to provide approximately 10 mg/day of CoQ10. Commercially available CoQ10 is produced by the fermentation of beets and sugar cane, using special strains of yeast. Dosage forms currently available include powder-filled capsules, powder-based tablets, softgel capsules, fully solubilized softgel capsules, chewable wafers, intravenous solution, and intra-oral spray. Assessment of the bioavailability of various dosage formulations demonstrated that the fully solubilized softgel capsule (Q-gel) achieved the highest serum CoQ10 concentration.(39)
Doses of 30–60 mg/day (approximately 1 mg/kg of body weight) are generally recommended to prevent CoQ10 deficiency and to maintain normal serum concentrations of 0.7–1.0 µg/mL. However, therapeutic doses of 100–200 mg/day are advocated for the treatment of chronic heart disease. These higher doses may achieve serum concentrations of 2.0–3.0 µg/mL, reported by some investigators to have a positive impact on cardiovascular health. Doses used in the treatment of breast cancer range from 90–390 mg/day
Documented adverse effects associated with the use of CoQ10 in humans have been minor and include epigastric discomfort (0.39%), appetite suppression (0.23%), nausea (0.16%) and diarrhea (0.12%).(4) These complaints are dose-related and minimized with dose reduction and/or dose division. Higher than usual doses exceeding 300 mg/day have been associated with elevated serum LDH and SGOT levels, however no hepatic toxicity has been observed. Late night administration has also been reported to cause insomnia.(40)
Coenzyme Q10 is a fat-soluble compound primarily synthesized by the body and also consumed in the diet.
Coenzyme Q10 is required for mitochondrial ATP synthesis and functions as an antioxidant in cell membranes and lipoproteins.
Endogenous synthesis and dietary intake appear to provide sufficient coenzyme Q10 to prevent deficiency in healthy people.
Oral supplementation of coenzyme Q10 increases plasma, lipoprotein, and blood vessel levels, but it is unclear whether tissue coenzyme Q10 levels are increased, especially in healthy individuals.
Coenzyme Q10 supplementation has resulted in clinical and metabolic improvement in some patients with hereditary mitochondrial disorders.
Although coenzyme Q10 supplementation may be a useful adjunct to conventional medical therapy for congestive heart failure, additional research is needed.
Roles for coenzyme Q10 supplementation in other cardiovascular diseases, neurodegenerative diseases, cancer, and diabetes require further research.
Coenzyme Q10 supplementation does not appear to improve athletic performance.
Although coenzyme Q10 supplements are relatively safe, they may decrease the anticoagulant efficacy of warfarin (Coumadin).
Presently, it is unclear whether individuals taking cholesterol-lowering medications, known as HMG-CoA reductase inhibitors (statins), would benefit from coenzyme Q10
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