What is CoQ10?Heart Energy Engine and More.

article content dotArticle Content:

Actions and Pharmacology for CoQ10(Co Q 10).

Coenzyme Q10 CAS 303-98-0 photo picture image Actions:Supplemental CoQ10 may have cardioprotective, cytoprotective and neuroprotective activities:

 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.

 Since the actions of supplemental CoQ10 have yet to be clarified, the mechanism of these actions is a matter of speculation. However, much is known about the biochemistry of CoQ10. CoQ10 is an essential cofactor in the mitochondrial electron transport chain, where it accepts electrons from complex I and II, an activity that is vital for the production of ATP.

 CoQ10 has antioxidant activity in mitochondria and cellular membranes, protecting against peroxidation of lipid membranes. It also inhibits the oxidation of LDL-cholesterol. LDL-cholesterol oxidation is believed to play a significant role in the pathogenesis of atherosclerosis.

 CoQ10 is biosynthesized in the body and shares a common synthetic pathway with cholesterol. CoQ10 levels decrease with aging in humans. Why this occurs is not known but may be due to decreased synthesis and/or increased lipid peroxidation which occurs with aging.

 Membrane Stabilization and Fluidity:

 The membrane stabilizing property of CoQ10 has been postulated to involve the phospholipid-protein interaction that increases prostaglandin (especially prostacyclin) metabolism. It is thought that CoQ10 stabilizes myocardial calcium-dependent ion channels and prevents the depletion of metabolites essential for ATP synthesis. CoQ10 also decreases blood viscosity, and improves blood flow to cardiac muscle in patients with ischemic heart disease.

 Pharmacokinetics and Clinical uses Overview:

 CoQ10 is absorbed from the small intestine into the lymphatics; from there it enters the blood. Absorption of CoQ10 is poor. Well over 60% of an oral dose is excreted in the feces. Furthermore, absorption of CoQ10 is highly variable and depends not only on food intake but also on the amount of lipids present in the food. Absorption is lower on an empty stomach and greater when taken with food of high lipid content. In the blood, CoQ10 is partitioned into the various lipoprotein particles, including VLDL, LDL and HDL.

 It takes about three weeks of daily dosing with CoQ10 to reach maximal serum concentrations, which then plateau with continuous daily dosing. CoQ10 is distributed to the various tissues of the body and is able to enter the brain. The main elimination of CoQ10 occurs via bile.

 Congestive Heart Failure (CHF):

 Several open and controlled studies have examined the efficacy of CoQ10 as adjunctive therapy for treating CHF. The presence of increasing symptoms associated with CHF has been correlated to the severity of CoQ10 deficiency. In one study, the mean myocardial tissue level (dry weight) of CoQ10 from endomyocardial biopsies obtained during catheterization in control subjects, New York Heart Association (NYHA) Class I with normal hemodynamic findings and normal biopsy morphology, were compared to that of NYHA Functional Class III or IV patients; these levels were reported as 0.42 and 0.28, respectively. The authors concluded that CoQ10 myocardial tissue levels in CHF patients are on average 33% lower than in control patients. The degree of CoQ10 deficiency correlated with the severity of symptoms and presence of dilated cardiomyopathy in NYHA Class III and IV patients. Study by Jameson et al. analyzed serum CoQ10, alpha-tocopherol, and free cholesterol levels in 94 consecutive hospitalized patients over 50 years of age. Patients exhibiting a significantly lower serum free cholesterol-related CoQ10 value (CoQ10 levels expressed per milligram of free cholesterol) had an increased risk of CHF, severe myalgia, concomitant use of cytostatic and lipid-lowering drug therapy, and/or death within a six-month follow-up.

 Myocardial infarction and cardiac surgery:

 The heart muscle may become oxygen-deprived (ischemic) as the result of myocardial infarction (MI) or during cardiac surgery. Increased generation of ROS when the heart muscle's oxygen supply is restored (reperfusion) is thought to be an important contributor to myocardial damage occurring during ischemia-reperfusion. Pretreatment of animals with coenzyme Q10 has been found to decrease myocardial damage due to ischemia-reperfusion. Another potential source of ischemia-reperfusion injury is aortic clamping during some types of cardiac surgery, such as coronary artery bypass graft (CABG) surgery. Three out of 4 placebo-controlled trials found that coenzyme Q10 pretreatment (60-300 mg/d 7-14 days prior to surgery) provided some benefit in short-term outcome measures after CABG surgery. In the placebo-controlled trial that did not find preoperative coenzyme Q10 supplementation to be of benefit, patients were treated with 600 mg of coenzyme Q10 twelve hours prior to surgery, suggesting that preoperative coenzyme Q10 treatment may need to commence at least one week prior to CABG surgery in order to realize any benefit. Although the results are promising, these trials have included relatively few people and have only examined outcomes shortly after CABG surgery.

 Hypertension:

 The results of several small, uncontrolled studies in humans suggest that coenzyme Q10 supplementation could be beneficial in the treatment of hypertension. More recently, two short-term placebo-controlled trials found that coenzyme Q10 supplementation resulted in moderate blood pressure decreases in hypertensive individuals. The addition of 120 mg/d of coenzyme Q10 to conventional medical therapy for 8 weeks in patients with hypertension and coronary artery disease decreased systolic blood pressure by an average of 12 mm Hg and diastolic blood pressure by an average of 6 mm Hg compared to a placebo containing B-complex vitamins. In patients with isolated systolic hypertension, supplementation with 120 mg/d of coenzyme Q10 and 300 IU/day of vitamin E for 12 weeks resulted in an average decrease of 17 mm Hg in systolic blood pressure compared with 300 IU/day of vitamin E alone. Further research is needed to determine whether coenzyme Q10 supplementation can provide significant long-term benefit in the treatment of hypertension.

 Diabetes mellitus:

 Diabetes mellitus is a condition of increased oxidative stress and impaired energy metabolism. Plasma levels of reduced coenzyme Q10 (CoQH2) have been found to be lower in diabetic patients than healthy controls when normalized to plasma cholesterol levels. However, supplementation with 100 mg/d of coenzyme Q10 for 3 months neither improved glycemic (blood glucose) control nor decreased insulin requirements in Type 1 (insulin-dependent) diabetics compared to placebo. Similarly, 200 mg/d of coenzyme Q10 supplementation for 6 months did not improve glycemic control or serum lipid profiles in Type 2 (non-insulin dependent) diabetics. Since coenzyme Q10 supplementation did not interfere with glycemic control in either study, the authors of both studies concluded that coenzyme Q10 supplements could be used safely in diabetic patients as adjunct therapy for cardiovascular diseases.

 Cancer:

 Numerous studies have noted the incidence of CoQ10 deficiency in a variety of cancers including breast, lung, prostate, pancreatic and colon cancer. In an open-label study of 32 breast cancer patients with metastases to axillary lymph nodes, 90 mg/day of CoQ10 plus high-dose antioxidant therapy with vitamin C, vitamin E, beta carotene, selenium, and omega-3 and omega-6 fatty acids were given in addition to conventional surgery and chemotherapy. During the 18-month study period, none of the patients showed signs of further metastases and six of the 32 patients had partial tumor regression.

 Immune Modulation:

 Studies have demonstrated that the degree of CoQ10 deficiency is correlated with the severity of immune compromised diseases. Patients with acquired immune deficiency syndrome (AIDS) showed statistically significant lower CoQ10 serum concentrations than AIDS-related complex (ARC) patients, who in turn had lower levels than healthy subjects. 31 A clinical case series of eight adult patients treated with 60 mg/day of CoQ10 reported significant increases in serum IgG levels over 1 to 4 months.
 Coenzyme Q10 CAS 303-98-0 photo picture image

 Neurodegenerative Diseases:

 Parkinson's disease:Parkinson's disease is a degenerative neurological disorder characterized by tremors, muscular rigidity, and slow movements. It is estimated to affect approximately 1% of Americans over the age of 65. Although the causes of Parkinson's disease are not all known, decreased activity of complex I of the mitochondrial electron transport chain and increased oxidative stress in a part of the brain called the substantia nigra are thought to play a role. Coenzyme Q10 is the electron acceptor for complex I as well as an antioxidant, and decreased ratios of reduced to oxidized coenzyme Q10 have been found in platelets of individuals with Parkinson's disease. A 16-month randomized placebo-controlled trial evaluated the safety and efficacy of 300, 600, or 1200 mg/d of coenzyme Q10 in 80 people with early Parkinson's disease. Coenzyme Q10 supplementation was well tolerated at all doses and associated with slower deterioration of function in Parkinson's disease patients compared to placebo. However, the difference was statistically significant only in the group taking 1200 mg/d. Although these preliminary findings are promising, they need to be confirmed in larger clinical trials before recommending the use of coenzyme Q10 in early Parkinson's disease.

 Huntington's disease:Huntington's disease is an inherited neurodegenerative disorder characterized by selective degeneration of nerve cells known as striatal spiny neurons. Symptoms, such as movement disorders and impaired cognitive function, typically develop in the fourth decade of life and progressively deteriorate over time. Animal models indicate that impaired mitochondrial function and glutamate-mediated neurotoxicity may play roles in the pathology of Huntington's disease. Coenzyme Q10 supplementation has been found to decrease brain lesion size in animal models of Huntington's disease and to decrease brain lactate levels in Huntington's disease patients. However, feeding transgenic mice that express the Huntington's disease protein a combination of coenzyme Q10 and remacemide resulted in only transiently improved motor performance and did not prolong survival.Remacemide is an antagonist of the neuronal receptor that is activated by glutamate. A 30-month randomized placebo-controlled trial of coenzyme Q10 (600 mg/d), remacemide, or both in 347 patients with early Huntington's disease found that neither coenzyme Q10 nor remacemide significantly altered the decline in total functional capacity, although coenzyme Q10 supplementation (with or without remacemide) resulted in a nonsignificant 13% decrease in the decline.Currently, there is insufficient evidence to support a recommendation for coenzyme Q10 supplementation in early Huntington's disease.

Last PageNext Page

Reference:

citations1.What is CoQ10?Heart Energy Engine and More.

last edit date:13th,May.2009.