Co-enzyme Q10 - fundamentally important for cellular energetics
What is Co-enzyme Q10?
Coenzyme Q10 is an essential component of the mitochondrial electron transport process of respiration and coupled oxidative phosphorylation. It is therefore of fundamental importance to the intracellular energy producing systems.
It has many useful applications in cellular energetics, including enhanced physical performance, oxygen utilisation and endurance with reduced fatigue during and after exercise. Other areas of proven effectiveness of Coenzyme Q10 include the cardiovascular system, the immune system and wound healing.
Coenzyme Q10 Clinical Applications...
- Cardiovascular disease
- Angina pectoris
- Congestive heart failure
- Cardiotoxicity from psychotropic drugs
- Cerebrovascular function (stroke)
- Gastric ulcer
- Physical performance
- Periodontal disease (gingivitis)
- Immune insufficiency (infections)
- Breast cancer
- Muscular dystrophy
- Mitochondrial energy defects
- Athletic performance
- Pre - surgery
- Chronic fatigue
- Free radical stress
Coenzyme Q10 Technical Information...
Coenzyme Q10, also known as Ubiquinone, is a naturally occurring molecule, similar in structure to vitamin E. It is a co-factor in the electron transport chain, the biochemical pathway in cellular respiration from which ATP (adenosine triphosphate) and metabolic energy are derived. Since most cellular functions are dependent on availability of energy, Co Q is essential for the health of all human tissues and organs.
Deficiencies of CO Q10 have been reported in a wide range of conditions, including cardiovascular disease, hypertension and periodontal disease.
In addition, animal studies have shown that the decline in Coenzyme Q10 levels that occurs with age may be partly responsible for age related deterioration of the immune system.
The studies examining Co-enzyme Q10 as a therapeutic agent indicate that it may protect tissues from damage that results from reduced blood flow. Coenzyme Q10 is an effective lipid soluble antioxidant and free radical scavenger. In performing this function, Co-enzyme Q10 is capable of stabilising cell membranes, calcium influx through membrane calcium channels and preventing depletion of metabolites necessary for the synthesis of ATP.
Oral Coenzyme Q10 seems to have a low clearance rate from the plasma and therefore has a relatively long plasma half-life of 33.9 hours. The metabolic fate of Co-enzyme Q10 has not been fully characterised. Following absorption from the gastrointestinal tract, Co-enzyme Q10 is taken up by the chylomicrons. The major portion of an exogenous dose of Co Q10 is deposited in the liver and packaged into VLD lipoprotein. Following this step, Co Q10 appears to be concentrated into certain specific sites that include adrenal, spleen, lung, kidney and myocardial tissues.
Coenzyme Q10 Stability...
Studies conducted at the University of California, Berkley, Department of Physiology/Anatomy, by Dr A Almada indicated that a large variation in potency exists between different manufacturers and their label stated potency.
Coenzyme Q10 is very unstable and is susceptible to oxidation, thermal decomposition and photodegradation. Preparations which expose Co Q to air during formulation (powdered preparations incorporated into tablets and two piece gelatin capsules) had the lowest potency of samples assayed. Lack of additional antioxidants, such as alpha tocopherol and SOD (superoxide dismutase), increases susceptibility to oxidation during processing and would require excessive amounts of Co Q10 in the preparation in order to maintain label potency over time.
Co-enzyme Q10 can be stabilised by using a hydrophobic dispersion process where, under nitrogen, it is suspended in oleic acid in order to prevent oxidation and provide optimal activity and nutrient bioavailability.
Kanamori compared the bioavailability of the stabilised oil form of Co Q10 in a soft gel capsule to that of unstabilised powdered or tableted forms. After four days of supplementation, the increase in plasma Co Q10 levels of the soft gel capsule was twice that of the tableted or powdered form.
Studies have shown that hydrophobically stabilised Coenzyme Q10 displays the highest percentage yields (96%) of the label claim. The hermetically sealed opaque gelatin capsule creates a protective microenvironment within the capsule which minimises oxidation and photodegradation.
Coenzyme Q10 in Clinical Medicine...
Degenerative lesions of the myocardium impair pump function and can be found in most types of cardiovascular disease, including hypertensive, atherosclerotic and vascular heart disease, as well as primary cardiomyopathy.
These lesions presumably result from repeated insults, such as ischaemic events, inflammation, stress induced catecholamine release and other toxic factors. These insults all cause lipid peroxidation of cellular membranes, defects in mitochondrial function and structure (with resultant impairment of cellular energy production), membrane permeability changes and uncoordinated influxes of ions, alterations in protein synthesis and at least a state of functional metabolic impairment.
Co Q10's activity as a free radical scavenger and membrane stabilising agent helps prevent lipid peroxidation of cellular membranes and preserves mitochondrial structural components and function.
The therapeutic use of Co-enzyme Q10 in cardiovascular disease has been well documented in both animal and human trials. In animals, Co Q10 reduced infarct size resulting from acute coronary occlusion and protected the myocardium against experimentally induced cardiomyopathy and myocarditis. In humans, myocardial biopsies in patients with various cardiac diseases showed a Coenzyme Q10 deficiency in 50-75% of cases.
In 1985, Kamikawa and co-workers reported on the results of a double-blind, randomised crossover study comparing oral Co Q10 (150 mg/day for four weeks) with placebo in patients with chronic stable angina. Compared to placebo, Co-enzyme Q10 reduced the frequency of anginal episodes by 53%.
There was also a significant increase in treadmill exercise tolerance (time to onset of chest pain and time to development of ST segment depression) during Coenzyme Q10 treatment.
Congestive Heart Failure
Approximately 31 clinical trials from Japan have described the favourable effects of intravenous or oral Co-enzyme Q10 in patients with congestive heart failure (CHF) of various aetiologies.
As a result of these experiments, in 1997, the Japanese government granted approval to market Coenzyme Q10 for CHF treatment. In one study, 20 patients with CHF due to either ischaemic or hypertensive heart disease were treated with coq10 30 mg/day for 1 - 2 months. Fifty-five percent of the patients reported subjective improvement, 50% a decrease in the New York Heart Association classification and 30% showed a "remarkable" decrease in chest congestion as seen on chest x-ray.
It appears that Coenzyme Q10 is most beneficial to those patients with the greatest tissue deficiency of endogenous Co-enzyme Q10.
Subjective improvements in CHF were confirmed with increased cardiac output, stroke volume, cardiac index and ejection fraction. This positive ionotropic effect of Co Q10 is not as potent as that of digitalis and might be used in combination with digitalis (in severe CHF) to reduce the dosage of digitalis and the risk of digitalis toxicity.
In addition, Coenzyme Q10 prevents the negative ionotropic (improvement of cardiac contractility) of beta-blocker therapy without affecting the beneficial effect on myocardial oxygen consumption.
A deficiency of Coenzyme Q10 has been found in the blood of myocardial tissue of patients with severe cardiomyopathy.
In one double-blind trial, daily administration of 100 mg of Coenzyme Q10 for 17 weeks increased the cardiac ejection fraction significantly, reduced shortness of breath and increased muscle strength. These improvements lasted as long as the patients were continuously treated. Of 80 patients treated, 89% improved while on Co-enzyme q10.
Yamagami and co-workers identified deficiencies in Coq10 enzyme activity in the leucocytes of 45 patients with known chronic hypertension.
Treatment with Coenzyme Q10 (60 mg/day for 8 weeks) produced a significant decrease in blood pressure in the group as a whole and 54% of the patients had a mean systolic blood pressure fall of greater than 10%.
Whether Co-enzyme Q10 deficiency is a cause or effect of hypertension, correction of this deficiency may improve blood pressure control in selected patients.
Susceptibility to gastric ulcers is a function not only of the amount of acid secreted, but also of the resistance of the gastric mucosa to damage. The process of healing and tissue repair and the production of the protective gastric mucus are highly energy dependent and therefore require the presence of adequate amounts Co-enzyme Q10.
The hypoxic state of gastric tissue, due to cell type changes and reduced vascular supply in advancing age, may explain why gastric ulcers frequently become intractable in elderly patients or in individuals with chronic heart or lung disease.
Coenzyme Q10 administration to mice with gastric ulcers (kept under mild hypoxic conditions (17% oxygen)) prevented the adverse effect of hypoxia on gastric ulcer healing.
Nine morbidly obese subjects (5 with low Coenzyme Q10 levels) were given 100 mg/day of Coq10, along with a 650 Kcal/day diet. After 8-9 weeks the mean weight loss in the Co-enzyme Q10 deficient group was 13.5 kg, compared with 5.8 kg in those with initially normal levels of Coenzyme Q10. This study suggests that treatment with this coenzyme may accelerate weight loss resulting from a low calorie diet.
Six healthy sedentary men (mean age of 21.5 years) performed a bicycle ergometer test before and after taking CoQ10 (60 mg/day) for 4-8 weeks. Coenzyme Q10 improved certain performance parameters, including work capacity at submaximal heart rate, maximal workload, maximal oxygen consumption and oxygen transport.
Co-enzyme Q10 deficiency has been reported in gingival tissue in patients with periodontal disease. The frequency of Co-enzyme Q10 deficiency in several studies ranged from 60%-90%.
Periodontitis may itself lead to localised Coenzyme Q10 deficiency, however, 86% of patients also have a low level of leukocyte CoQ10, indicating the presence of a systemic imbalance.
Oral treatment with Coenzyme Q10 (50 mg/day) has been seen to reverse the deficiency in gingival tissue with a healing of lesions in three weeks, compared to the usual 6 months in controls.
Double-blind studies with Co-enzyme Q10 on patients with both acute or chronic cerebral apoplexy showed a significant improvement in mental disturbances, lower extremity performance and overall symptom picture.
Clinical studies conducted with oral Co-enzyme Q10 at dosage levels of 30-45 mg/day showed that Co Q10 had a beneficial effect on subjective symptoms or nervous signs in patients with cephalotrauma, sequela and cerebrovascular performances.
The prevailing opinion suggests that Coenzyme Q10 may have a potential role in protecting myocardium that is rendered ischaemic and is subsequently reperfused.
From a clinical standpoint, it would appear that Coenzyme Q10 might have a role as an ischaemic modifier in several cardiac conditions, including unstable angina, acute myocardial infarction, or following clot lysis by mechanical or fibrinolytic means. Coq10's ischaemic modifying capacities may also be helpful during surgical procedures such as cardiac valve replacement, coronary artery bypass grafting and possibly heart transplantation.
Cardiotoxicity from Psychotropic Drugs
Cardiac side effects frequently occur from the use of certain psychotropic drugs, including phenothiazines and tricyclic antidepressants. The cardiotoxicity of these drugs is caused by inhibition of Coenzyme Q10 dependent enzymes resulting in impaired respiration in myocardial cells.
In two clinical studies, CoQ10 supplementation ameliorated electrocardiographic changes in patients on psychotropic drugs.
In an early study, coenzyme Q7 (120 mg/day) was given to 39 stable diabetics for periods ranging from 2-18 weeks. This treatment reduced fasting blood sugar by at least 20% in 14 of the 39 patients (36%) and by at least 30% in 12 of the 39 patients (31%), a total of 67%. Ketone bodies fell by at least 30% in 13 of 22 patients (59%). In some cases, termination of Co Q7 treatment resulted in an increase in blood sugar and blood ketone bodies.
This study was pioneered in 1966 before Coenzyme Q10 was commercially available. Since Co Q7 and Co-enzyme Q10 are considered to be interchangeable in the body, similar results might be expected from Coenzyme Q10. This was confirmed by Shimura in 1981. Fifteen diabetes sufferers were administered 60 mg/day of Coenzyme Q10 with results showing a promotion in insulin synthesis and secretion as well as peripheral glucose utilisation.
Tissues and cells involved with immune function are highly energy dependent and therefore require an adequate supply of Coenzyme Q10 for optimal function.
Several studies have documented an immune enhancing effect of Co-enzyme Q10. Co Q7 (converted to Co-enzyme Q10) prolongs the survival of mice experimentally infected with Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae or Candida albicans. Two of 10 mice treated with Coq10 injections survived a 5-10 fold lethal dose of E. coli, which killed all 10 control animals.
In human studies, patients with cardiovascular disease, diabetes or cancer were treated for long periods with Co-enzyme Q10 (60 mg/day). Significant increases in the level of immunoglobulin G (IgG) were found in the serum of these patients after 27-98 days of Co-q10 treatment. This increase in serum IgG within the normal range could, according to the authors, represent a correction of immunodeficiency or an increase in immunocompetence.
Recent studies using high dose Coenzyme Q10 in patients with high-risk breast cancer have demonstrated some promising results. Thirty-two patients were treated with 90 mg of Coenzyme Q10, antioxidants and fatty acids. Six of these high-risk patients showed partial tumour regression. In one of these 6 cases, the dosage of Co-enzyme Q10 was increased to 390 mg and after one month the tumour was no longer palpable. Within another month, mammography confirmed absence of the tumour. Encouraged by this result, another patient was put on 300 mg per day and within 3 months there was no residual tumour.
In a double-blind study, 100 mg of Coenzyme Q10 was given daily for three months to 12 patients with progressive muscular dystrophy.
Co-enzyme Q10 treatment resulted in significant improvement in cardiac output and stroke volume, as well as increased physical wellbeing in 4 of 8 patients. Subjective improvements included increased exercise tolerance, reduced leg pain, better control of leg function and less fatigue. The enhancement of cardiac function and physical wellbeing constitutes an important advance in the management of muscle diseases for which no other effective therapy exists.
Ishigami et. al. examined the number of sperm and their motility in patients with infertility, after treatment with Co-enzyme Q10 and reported that this substance might be useful for the treatment of male infertility.
Shitara et. al. started 154 patients with paroxysmal deafness on Co-enzyme Q10 in a dose of 30 mg/day and found that after four weeks the patients responded to Coenzyme Q10, whether it was used alone or in conjunction with steroids.
Tamaoki et al. treated Bell's paralysis (facial paralysis) with Coenzyme Q10 in a dose of 30 mg/day for 10-30 days and found that the rate of healing was 85.3% compared to the control group with 63.3%.
Immune function tends to decline with advancing age. Elderly mice were found to have thymus atrophy, marked Coenzyme Q10 deficiency in thymus tissue and pronounced suppression of the immune response. This immune suppression was partially reversed by the treatment with Co-enzyme Q10. Thus, Coenzyme Q10 supplementation may benefit age-related immunosuppression.