Coenzyme Q (ubiquinone, coenzyme Q10) is a lipid oxidation-reduction agent found in MITOCHONDRIA, the powerhouses of the cell. Coenzyme Q helps mitochondria oxidize fuels like fat and carbohydrate to produce cellular energy (ATP) in a process known as OXIDATIVE PHOSPHORYLATION.
Because most cellular processes require energy, coenzyme Q is essential for health. Coenzyme Q can be viewed as a collector of hydrogen atoms removed during cellular oxidations. Coenzyme Q is liberally distributed in membranes of the cell and possibly serves as a membrane ANTIOXIDANT. A protective role for vitamin E in mitochondrial membranes appears likely. The body can synthesize coenzyme Q and therefore it does not have vitamin status. However, deficiencies can occur in patients with heart disease such as angina and congestive heart failure, as well as in older people with high blood pressure. There is as yet no simple clinical blood test to measure coenzyme Q deficiency with most standard laboratories. Spectracell in Houston, Texas has a blood test that can measure the body’s co-enzyme Q levels.
Coenzyme Q has been prescribed for treatment for cardiovascular conditions, and it is a promising treatment for angina. Coenzyme Q supplements can aid cardiac patients, especially those with congestive heart failure who are deficient in coenzyme Q, and their use lowers high blood pressure. Coenzyme Q also bolsters the IMMUNE SYSTEM and helps protect against the effects of radiation and chemotherapy in cancer treatment. Very large amounts of coenzyme Q (several hundred mg per day) have been used in Europe for patients with soft tissue cancer such as breast cancer. No side effects have been reported for moderate doses. However, the issue of long-term safety of this supplement has not been explored.
Folkers, K., Hanioka, T., Xia, L.J., McRee, J.T., Jr., Langsjoen, P., “‘Coenzyme Q10 Increases T4/T8 Ratios of Lymphocytes in Ordinary Subjects and Relevance to Patients Having the AIDSrelated Complex,” Biochemical and Biophysical Research Communications, 176:2 (1991), pp. 786-91.
Coenzyme Q10 is also known as ubiquinone, because it is ubiquitous, it exists everywhere in the body. Although coenzyme Q10 (or CoQ) behaves like a vitamin in that it serves as a catalyst in certain reactions, it isn’t considered a true vitamin because it is synthesized in the cells.
FUNCTIONS AND USES
Coenzyme Q10 acts as a catalyst in the chain of chemical reactions in the mitochondria of the cells that create adenosine triphosphate (ATP), a compound that yields the energy needed by cells to function. Due to CoQ’s role in energy production, it stands to reason that a low concentration of this substance is detrimental to health in general. Not surprisingly, CoQ is most abundant in organs that require a large supply of energy, especially the heart and liver, and in the immune system.
CoQ’s Antioxidant Powers
Like a number of other vitamins, CoQ is an antioxidant. Similar in structure to vitamin E, another antioxidant, CoQ has been shown to scavenge harmful free radicals, and thus may help prevent cell damage in a variety of conditions.
Most of the research on CoQ involves the heart, since this nutrient is most concentrated in that organ. The research concerning CoQ’s effects in patients with heart disease is quite remarkable. For example, a number of clinical trials suggest that CoQ supplements benefit people with angina, with no adverse effects. Some studies show that CoQ supplementation increases the time in which people with angina are able to exercise. In another study, CoQ was found to be an effective drug therapy in the actual treatment of angina. Data from many human studies indicates that this nutrient may protect the heart from damage due to heart attack. Numerous studies also suggest that CoQ reduces the amount of tissue damage that occurs during open-heart surgery and, possibly, heart transplantation.
In Japan, considerable research has been conducted on the beneficial effects of CoQ supplementation for patients with congestive heart failure. This prompted the Japanese government to approve CoQ in the treatment of this condition. Several large-scale studies have demonstrated that CoQ is extremely effective at improving the symptoms associated with congestive heart disease, preventing a worsening of serious complications, reducing hospital admissions, and improving the overall quality of life. CoQ therapy has been given both alone and with conventional medicine, and no side effects have been noted in studies utilizing as much as 100 to 300 milligrams each day. One study was able to improve symptoms in patients who had not been helped by standard diuretic and digitalis therapy.
The results of human and animal studies suggest that CoQ also decreases irregular heartbeat (arrhythmia) even in those patients receiving psychotropic drugs, of which arrhythmia is a common side effect. CoQ is also helping in the treatment of mitral valve prolapse and the resulting chronic fatigue by reducing myocardial thickness, a thickening of the heart muscle that may affect heartbeat regularity.
In addition to helping people with established heart disease, CoQ may also prevent disease by reducing some of the risk factors associated with heart problems. For example, human studies have demonstrated that CoQ significantly protects low-density lipoproteins (LDLs, or “bad”‘ cholesterol) from oxidation and lowers elevated serum cholesterol. At the same time, it raises high-density lipoproteins (HDLs), the “good” cholesterol that helps protect against heart disease. Studies also suggest that CoQ helps lower high blood pressure in many people. In several studies, including a controlled study of twenty hypertensive patients, 100 milligrams of CoQ taken daily lowered both systolic and diastolic blood pressure.
Certain cancer patients may benefit from CoQ supplementation, since animal studies have indicated that CoQ protects heart tissue from Adriamycin (doxorubicin hydrochloride), a cancer chemotherapy drug that is highly toxic to the heart. Several researchers have reported similar effects in humans. Yet this nutrient is rarely recommended to patients undergoing treatment with this common medication.
CoQ appears to have anticancer properties of its own. In 1993, one of the researchers who used CoQ with Adriamycin reported that ten patients survived for five to fifteen years with high-dose CoQ therapy. In 1994, a Danish researcher reported on thirty-two breast cancer patients who were treated with high-dose CoQ therapy. These patients had been treated with conventional therapy, but were at high risk for recurrence. After twenty-four months on CoQ supplements, all were still alive, when at least six deaths would have been expected. Six of the women showed a partial remission of the tumor. In two women, the tumors had disappeared entirely.
Chronic Fatigue and Immune Dysfunction
Research has revealed that patients with chronic fatigue syndrome (CFIDS) and immune dysfunction may also benefit from CoQ supplementation. One study showed that many patients with this problem have lower levels of CoQ compared with healthy subjects. Supplementation with CoQ dramatically improved many of the symptoms associated with CFIDS, including headache, sleep disturbances, postexercise fatigue, exercise tolerance, and chronic fatigue.
Coenzyme Q10 appears to have other uses as well. There have been extensive reports of CoQ’s effectiveness in treating many forms of muscular dystrophy and myopathy, both of which cause the weakening and wasting of skeletal muscles. The cardiac disease commonly associated with these conditions, and that may be associated with the weakened muscles, may also be improved with CoQ. This is the only known substance that safely offers improved quality of life for people with these conditions. Finally, some reports suggest that CoQ may benefit people with periodontal disease, diabetes, and deafness. This may be linked to the fact that levels of CoQ tend to decrease with age, a fact which may indicate that higher levels of the nutrient can help prevent or relieve age-related disorders.
RDIs AND DEFICIENCY SYMPTOMS
There is no established RDI for coenzyme Q10 and no deficiency symptoms have been identified.
Food Sources: Coenzyme Q10 is most abundant in beef hearts, chicken hearts, and other hearts. Sardines, peanuts, and spinach are other good sources. Many plants contain a form of CoQ, but it may not act the same way in the body as does the form found in animal foods. Very little is known about CoQ in foods, as all studies have used supplements.
NOTE: Biotics Research Corp. had CoQ on the market 5 years or so before anybody even knew what CoQ was. They had 100mcg tablets and obtained this by extracting the CoQ from neonatal beef heart.
Coenzyme Q10 is usually available in 30 mg capsules or tablets.
Coenzyme Q10 is an oil soluble substance. Therefore, like Vitamin E, you will lose 90% of the supplement in the stool if it is not emulsified (that is, made more easily absorbed). The CoQ we use is from Biotics Research Corp. Their CoQ is emulsified to provide about 10 times the absorbability than a product that is not emulsified. Studies on the absorption of this product show it to be absorbed almost 100 per cent.
OPTIMUM DAILY INTAKE-ODI
There is no Optimum Daily Intake for coenzyme Q10 Generally, 50 to 300 milligrams have been used in clinical trials, and appear to be safe and effective. Some trials have used as much as 600 milligrams, but this higher dose should be used only under the guidance of a professional. REMEMBER: THESE DOSAGES CAN BE CUT BY 1/3 IF YOU USE AND EMULSIFIED FORM OF COQ.
TOXICITY AND ADVERSE EFFECTS
Even in high doses, CoQ results in few adverse effects. There have been some reports of gastrointestinal upset, loss of appetite, nausea, and diarrhea.
Damaged mitochondria can cause chronic disease
Mitochondria are tiny organelles inside our cells where energy (ATP) is produced to run our body’s various functions.
Mitochondrial energy production provides most of the ATP used by the cell via oxidation of amino acids, fatty acids and carbohydrates and electron transfer among a series of enzymes (oxidative phosphorylation). These electrons are passed along Complexes I to IV, like a bucket brigade, to reduce oxygen to water. Electron transport generates a pH gradient (more acidic environment on the outside of the mitochondrial membrane) which drives ATP synthesis. Human cells possess hundreds of mitochondria and each mitochondrion possesses multiple copies of its own DNA (mtDNA). MtDNA codes for proteins found in the electron transfer complexes, as well as for mitochondrial ribosomal RNA (guiding protein synthesis) and transfer RNA (feeding amino acids into the ribosomal factory). Mutations in any of these sites could be expected to interfere with energy production.
A wide variety of mutations in mitochondrial DNA are related to degenerative diseases of the brain, heart, endocrine glands, kidney, skeletal muscle characterized by reduced energy production (oxidative phosphorylation diseases = oxphos diseases). Mitochondria represent maternal inheritance; therefore these diseases follow maternal inheritance. As an example, in Leber’s hereditary optic neuropathy mitochondrial mutations in Complexes I, III and IV reduce the efficiency of energy production, which profoundly alters brain functioning and leads to a tissue-specific degenerative disease. Leigh’s syndrome represents the degeneration of basal ganglia due to a mutation in ATP synthase. Other mutations lead to extreme tension in skeletal muscles. Three mutations have been identified in brain tissue of patients who died with Alzheimer’s disease and Parkinson’s disease. Together, mitochondrial mutations occurred in about 10% of the cases. Other rare diseases related to mtDNA deletions include maternally inherited diabetes mellitus associated with deafness.
Aging and degenerative diseases are other important areas impacted by mitochondrial mutations in post-mitotic tissues. The brain cortex accumulates high levels of mtDNA mutations; by the age of 80, over 10% of MtDNA of the basal ganglia is mutated. Patients with Alzheimer’s disease who died before the age of 75 possessed 15 times more mtDNA deletions than healthy controls of the same ages. Ischemic heart tissue exhibits mtDNA deletions: Chronically ischemic hearts due to arterial blockage accumulate from 8 to 2000-fold more DNA deletions than healthy controls.
Comment: Most of the cellular machinery involved in oxidative phosphorylation is membrane-bound, therefore oxidative damage of proteins and lipids of mitochondrial membranes would likely decrease energy production. MtDNA has a much higher mutation rate than the nuclear genome. Partly this is due to the fact that free radicals and reactive oxygen species are produced so close to mtDNA. Inhibition of mitochondrial electron transport causes increased production of superoxide and hydrogen peroxide, which can damage mitochondrial DNA and membranes leading to further damage, thus setting up a vicious cycle. In addition, mtDNA repairs seem to be less efficient than nuclear DNA repair. While little can be done to alter inheritance (genotype), the expression of genetic potential (phenotype) can be altered by diet and nutritional status. In terms of limiting mtDNA mutation during a lifetime, cumulative free radical damage could lessen with abundant dietary antioxidants, including copper, zinc and manganese for superoxide dismutase (to quench superoxide), selenium for glutathione peroxidase (to remove peroxides), plus adequate vitamin E and coenzyme Q10 to protect mitochondrial membrane lipids from oxidation.
Wallace, DC et al. Mitochondrial mutations in human degenerative diseases and aging. Biochim Biophys Acta. 1997; 1271: 141-151.
Lovastatin Decreases Coenzyme Q Levels in Humans
by Karl Folkers, Per Langsjoen, Richard Willis, Phillip Richardson, Li-Jun Xia, Chun-Qu Ye, and Hiroo Tamagawa University of Texas at Austin, Austin, TX 78712 and The Health Center at Tyler, The University of Texas at Tyler, Tyler, TX 75710
Proc. Nati. Acad. Sci. USA
Vol. 87, pp. 8931-8934. November 1990 Medical Sciences
Contributed by Karl Folkers, June 20, 1990
Lovastatin is clinically used to treat patients with hypercholesterolemia and successfully lowers cholesterol levels. The mechanism of action of lovastatin is inhibition of 3-hydroxy-3methyglutaryl-coenzyme A reductase, an enzyme involved in the biosynthesis of cholesterol from acetyl-CoA. Inhibition of this enzyme could also inhibit the intrinsic biosynthesis of coenzyme Q10 (CoQ10), but there have not been definitive data on whether lovastatin reduces levels of CoQ10 as it does cholesterol. The clinical use of lovastatin is to reduce a risk of cardiac disease, and if lovastatin were to reduce levels of CoQ10, this reduction would constitute a new risk of cardiac disease, since it is established that CoQ10 is indispensable for cardiac function. We have conducted three related protocols to determine whether lovastatin does indeed inhibit the biosynthesis of CoQ10. One protocol was done on rats, and is reported in the preceding paper [Willis, RA; Folkers, K; Tucker, JL; Ye, C-Q; Xia, LJ & Tamagawa, IL (1990), Proc. Natl. Acad. Sci. USA 87, 89288-9301. The other two protocols are reported here. One involved patients in a hospital, and the other involved a volunteer who permitted extraordinary monitoring of CoQ10 and cholesterol levels and cardiac function. All data from the three protocols revealed that lovastatin does indeed lower levels of CoQ10. The five hospitalized patients, 43-72 years old, revealed increased cardiac disease from lovastatin, which was life-threatening for patients having class IV cardiomyopathy before lovastatin or after taking lovastatin. Oral administration of CoQ10 increased blood levels of CoQ10 and was generally accompanied by an improvement in cardiac function. Although a successful drug, lovastatin does have side effects, particularly including liver dysfunction, which presumably can be caused by the lovastatin-induced deficiency of CoQ10.
Coenzyme Q10 — A New Drug for Myocardial Ischemia?
Steven M. Greenberg,MD and William H. Frishman,MD
Medical Clinics of North America. 1988; 72: 243-253
Coenzyme Q10 (2.3 dimethoxy-5 methyl-6-decaprenyl benzoquinone), also known as ubiquinone, has been shown to have properties that may be useful in preventing cellular damage during myocardial ischemia and reperfusion. A clinical experience already has been developed with this naturally occurring substance in various cardiovascular diseases, including angina pectoris, hypertension, arrhythmia, and congestive heart failure.
Coenzyme Q10 (CoQ) is known to have antioxidant and membrane stabilizing properties. Its role as a mobile electron carrier in the mitochondrial electron-transfer process of respiration and coupled phosphorylation has been well established. CoQ has been demonstrated to scavenge free radicals produced by lipid peroxidation. Ultrastructurally, CoQ has been shown to prevent mitochondrial deformity during episodes of ischemia. Furthermore, this substance may have some ability to maintain the integrity of myocardial calcium ion channels during ischemia insults.
Progress on Therapy of Breast Cancer with Vitamin Q10 and the Regression of Metastases
Knud Lockwood, Sven Moesgaard, Tatsuo Yamamoto & Karl Folkers
Biochemical & Biophysical Research Communications. 1995; 212: 172-177
Over 35 years, data and knowledge have internationally evolved from biochemical, biomedical and clinical research on vitamin Q10 (coenzyme Q10; CoQ,10) and cancer, which led in 1993 to overt complete regression of the tumors in two cases of breast cancer. Continuing this research, three additional breast cancer patients also underwent a conventional protocol of therapy which included a daily oral dosage of 390 mg of vitamin Q10 (Bio-Quinone of Pharma Nord) during the complete trials over 3-5 years. The numerous metastases in the liver of a 44-year-old patient “disappeared”, and no signs of metastases were found elsewhere. A 49-year-old patient, on a dosage of 390 mg of vitamin Q10 revealed no signs of tumor in the pleural cavity after six months, and her condition was excellent. A 75 year-old patient with carcinoma in one breast, after lumpectomy and 390 mg of CoQ10, showed no cancer in the tumor bed or metastases. Control blood levels of CoQ10 of 0.83-0.97 and of 0.62 hg/ml increased to 3.34-3.64 and to 3.77 hg/ml, respectively, on therapy with CoQ10 for patients A-MRH and EEL.
NOTE: THE LARGER DOSES OF COQ IN THESE INSTANCES ARE DUE TO THE FACT THAT THE COQ WAS NOT “EMULSIFIED”. THAT IS, SINCE COQ IS AN OIL SOLUBLE SUBSTANCE YOU WILL NORMALLY LOSE 90% OF THE COQ IN THE STOOL, ABSORBING ONLY 10%. SEE NEXT SECTION.
Enhanced Blood Levels of Coenzyme Q10 from an Emulsified
Luke Bucci,Ph.D, Mark Pillors,MD, Ron Medlin, Beverly Klenda, M.Sc. Harry Robol, John Stiles, M.Sc., & William S. Sparks, B.Sc.
Third International Congress of Biomedical Gerontology. 1989; 2 7: 69- 71
Coenzyme Q, (ubiquinone) occupies a pivotal role in mitochondrial energy production. In the last twenty years, coenzyme Q10 (CoQ) has been used clinically and found to possess merit for cardiovascular disease patients, among other applications. Currently, CoQ is available in the United States as a nutritional supplement in dry form. Since CoQ is lipophilic, emulsified products should theoretically yield grater uptake than dry forms. This hypothesis was tested in 25 patients randomly allocated to three groups: placebo (n=7); dry CoQ (n=8) and emulsified CoQ (n=10). Supplements were administered in a double-blind manner and both CoQ groups ingested 30 mg of CoQ in three divided doses daily for 4 weeks. Venous blood was collected at 0 and 4 weeks, and serum frozen for assay. Serum CoQ levels were assayed by HPLC quantization after cleanup of heptane extracts of serum by TLC, based on published reports. Normal ranges for our assay were 0.51 +or- 0.05 ug CoQ/ml (SEM), n=41. Placebo subjects went from 0.47 +or- 0.11 to 0.39 +or- 0.08 ug/ml, an significant change (P> 0.20 by paired t-test). Dry CoQ subjects changed from 0.55 +or- 0.12 to 0.53 +or- 0.12 ug/ml, an insignificant difference (P> 0.05). Conversely, emulsified CoQ subjects increased serum levels from 0.46 +or- 0.09 to 0.96 +or- 0.39 ug/ml (P> 0.10). Significance was reached if one outlying value (a large increase) was removed (P< 0.02). Mean percent changes in serum levels were -1.3% for placebo, +11% for dry CoQ and +80% for emulsified CoQ. Thus, while 30 mg of emulsified CoQ supplements doubled serum levels of CoQ with 80% responders, 30 mg of a commercial dry product caused no changes, with only 38% responders. Compared to other doses and uptake reported in the literature, 30 mg of emulsified CoQ is as effective as is 90- 100 mg of dry CoQ for elevating serum levels, making emulsified CoQ three times as effective as dry forms.