Coenzyme Q10 Definition

Coenzyme Q10 (CoQ 10) or ubiquinone is essentially a vitamin or vitamin-like substance. Disagreements on nomenclature notwithstanding, vitamins are defined as organic compounds essential in minute amounts for normal body function acting as coenzymes or precursors to coenzymes. They are present naturally in foods and sometimes are also synthesized in the body. CoQ10 likewise is found in small amounts in a wide variety of foods and is synthesized in all tissues. The biosynthesis of CoQ10 from the amino acid tyrosine is a multistage process requiring at least eight vitamins and several trace elements. Coenzymes are cofactors upon which the comparatively large and complex enzymes absolutely depend for their function. Coenzyme Q10 is the coenzyme for at least three mitochondrial enzymes (complexes I, II and III) as well as enzymes in other parts of the cell. Mitochondrial enzymes of the oxidative phosphorylation pathway are essential for the production of the high-energy phosphate, adenosine triphosphate (ATP), upon which all cellular functions depend. The electron and proton transfer functions of the quinone ring are of fundamental importance to all life forms; ubiquinone in the mitochondria of animals, plastoquinone in the chloroplast of plants, and menaquinone in bacteria. The term "bioenergetics" has been used to describe the field of biochemistry looking specifically at cellular energy production. In the related field of free radical chemistry, CoQ10 has been studied in its reduced form as a potent antioxidant.

Structure

History

CoQ10 was first isolated from beef heart mitochondria by Dr. Frederick Crane of Wisconsin, U.S.A., in 1957 (2). The same year, Professor Morton of England defined a compound obtained from vitamin A deficient rat liver to be the same as CoQ10(3). Professor Morton introduced the name ubiquinone, meaning the ubiquitous quinone. In 1958, Professor Karl Folkers and coworkers at Merck, Inc., determined the precise chemical structure of CoQ10: 2,3 dimethoxy-5 methyl-6 decaprenyl benzoquinone 1), synthesized it, and were the first to produce it by fermentation. In the mid-1960's, Professor Yamamura of Japan became the first in the world to use coenzyme Q7 (a related compound) in the treatment of human disease: congestive heart failure. In 1966, Mellors and Tappel showed that reduced CoQ6 was an effective antioxidant In 1972 Gian Paolo Littarru of Italy along with Professor Karl Folkers documented a deficiency of CoQ10 in human heart disease By the mid-1970's, the Japanese perfected the industrial technology to produce pure CoQ10 in quantities sufficient for larger clinical trials. Peter Mitchell received the Nobel Prize in 1978 for his contribution to the understanding of biological energy transfer through the formulation of the chemiosmotic theory, which includes the vital protonmotive role of CoQ10 in energy transfer systems

In the early 1980's, there was a considerable acceleration in the number and size of clinical trials. These resulted in part from the availability of pure CoQ10 in large quantities from pharmaceutical companies in Japan and from the capacity to directly measure CoQ10 in blood and tissue by high performance liquid chromatography. Lars Ernster of Sweden, enlarged upon CoQ10's importance as an antioxidant and free radical scavenger Professor Karl Folkers went on to receive the Priestly Medal from the American Chemical Society in 1986 and the National Medal of Science from President Bush in 1990 for his work with CoQ10 and other vitamins.

COENZYME Q10 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. CoQ10 deficiency may be caused by insufficient dietary CoQ10, impairment in CoQ10 biosynthesis, excessive utilization of CoQ10 by the body, or any combination of the three. Decreased dietary intake is presumed in chronic malnutrition and cachexia.

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 biosynthesisThe 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

Increased body consumption of CoQ10 is the presumed cause of low blood CoQ10 levels seen in excessive exertion, hyper metabolism, 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.

Clinical Applications

§ High blood pressure (hypertension)
Preliminary research suggests that CoQ10 causes small decreases in blood pressure (systolic and possibly diastolic). Low blood levels of CoQ10 have been found in people with hypertension, although it is not clear if CoQ10 "deficiency" is a cause of high blood pressure. It is not known what dose is safe or effective. CoQ10 is less commonly used to treat hypertension than it is for other heart conditions such as congestive heart failure. Well-designed long-term research is needed to strengthen this recommendation.

Standardization

Standardization involves measuring the amount of certain chemicals in products to try to make different preparations similar to each other. It is not always known if the chemicals being measured are the "active" ingredients. CoQ10 products sold in stores have been found to contain variable amounts of claimed ingredients. Early studies used low doses, while more recent research suggests that higher doses may be safe and have greater effects.

Allergies
In theory, allergic reactions to supplements containing CoQ10 may occur.

Side Effects and Warnings

There are few serious reported side effects of CoQ10. Side effects are typically mild and brief, stopping without any treatment needed. Reactions may include nausea, vomiting, stomach upset, heartburn, diarrhea, loss of appetite, skin itching, rash, insomnia, headache, dizziness, irritability, increased light sensitivity of the eyes, fatigue, or flu-like symptoms.

CoQ10 may lower blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary.

Low blood platelet number was reported in one person taking CoQ10. However, other factors (viral infection, other medications) may have been responsible. Lowering of platelets may increase the risk of bruising or bleeding, although there are no known reports of bleeding from CoQ10. Caution is advised in people who have bleeding disorders or who are taking drugs that increase the risk of bleeding. Dosing adjustments may be necessary.

CoQ10 may decrease blood pressure, and caution is advised in patients with low blood pressure or taking blood pressure medications. Elevations of liver enzymes have been reported rarely, and caution is advised in people with liver disease or taking medications that may harm the liver. CoQ10 may lower blood levels of cholesterol or triglycerides. Thyroid hormone levels may be altered based on one study.

Organ damage due to lack of oxygen/blood flow during intense exercise has been reported in a study of patients with heart disease, although the specific role of CoQ10 is not clear. Vigorous exercise is often discouraged in people using CoQ10 supplements.