Price range: 1-2 containers: $28.50 each.  3-5: $27.50.  6+:  $26.50

Co-Enzyme Q-10 is now considered an essential nutrient because of its possible role in treatments for a wide variety of conditions, including high blood pressure, congestive heart failure, heart disease, high cholesterol, breast cancer, gum disease, Alzheimer’s disease, and immune system deficiencies. (See Mayo Clinic below.)

CoQ-10 functions in the body in three ways: it increases energy production in cells, enhances the immune system, and acts as a powerful antioxidant.

Because the muscles in the heart require higher amounts of energy than other tissues, CoQ-10 is particularly important to the cardiovascular system, where it is found in higher concentrations than elsewhere in the body. 

Studies have shown that supplementation with CoQ10 can significantly improve recovery from a heart attack and even reduce the risk of death and stroke.  For this reason, CoQ10 is widely prescribed to patients in Germany and Japan, where the most research has been performed on CoQ10.


HOW CO-ENZYME Q-10 WORKS:

CoQ10 works by improving the ability of mitochondria to absorb ATP.  Mitochondria are the parts of cells which convert ATP to useable energy.  When there is a healthy concentration of CoQ10 in the body, all the systems benefit from a more efficient supply of energy.  CoQ10 can also inhibit blood clotting.  These abilities make CoQ10 a promising supplement in the maintenance of cardiovascular health.


CoQ10 is an Antioxidant...

Antioxidants scavenge free radicals, naturally occurring compounds which cause damage to cells and DNA.  Environmental conditions such as pollution, smoking, and radiation can increase the number of free radicals in the body, so it is especially important to add extra antioxidants to the diet.  Protecting cells in the central nervous system from free radicals can prevent or slow the development of dementias such as Parkinson’s disease and Alzheimer’s disease.  CoQ10 has been researched as a possible treatment for these conditions, and studies have been promising.

SEE BELOW FOR STUDIES


Dietary Intake of CoQ-10:

CoQ-10 can be produced naturally by the body, but because the biological process is so complex, it requires an adequate diet with sufficient levels of many important vitamins and minerals.  Furthermore, according the National Health and Nutrition Examination Survey (NHANES), a study conducted by the CDC, many Americans do not receive adequate amounts of these vitamins and minerals in their diet.  Old age and disease conditions can prevent the body from properly absorbing all the essential nutrients it needs, even from a well-balanced diet.  Supplementation with CoQ-10 can make up for this insufficiency, contributing to better overall health.

View Related Products

Return to Top of Page

USES FOR CO-ENZYME Q-10 ACCORDING TO THE MAYO CLINIC:

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.

Alzheimer's disease
Promising preliminary evidence from human research suggests that CoQ10 supplements may slow down, but not cure, dementia in people with Alzheimer's disease. Additional well-designed studies are needed to confirm this result before a firm recommendation can be made.

Angina (chest pain from clogged heart arteries)
Preliminary small human studies suggest that CoQ10 may reduce angina and improve exercise tolerance in people with clogged heart arteries. Better studies are needed before a firm recommendation can be made.

Anthracycline chemotherapy heart toxicity
Anthracycline chemotherapy drugs, such as doxorubicin (Adriamycin®), are commonly used to treat cancers such as breast cancer or lymphoma. Heart damage (cardio-myopathy) is a major concern with the use of anthracyclines, and CoQ10 has been suggested to protect the heart. However, studies in this area are small and not high quality and the effects of CoQ10 remain unclear.

Breast cancer
Several studies in women with breast cancer report reduced levels of CoQ10 in diseased breast tissue or blood. It has been suggested by some researchers that raising CoQ10 levels with supplements might be helpful. However, it is not clear if CoQ10 is beneficial in these patients, or if the low levels of CoQ10 may actually be a part of the body's natural response to cancer, helping to fight disease. Supplementation with CoQ10 has not been proven to reduce cancer, and has not been compared to other forms of treatment for breast cancer.

Cardiomyopathy (dilated, hypertrophic)
There is conflicting evidence from research on the use of CoQ10 in patients with dilated or hypertrophic cardiomyopathy. Different levels of disease severity have been studied (New York Heart Association heart failure classes I through IV). Some studies report improved heart function (ejection fraction, stroke volume, cardiac index, exercise tolerance), while others find no improvements. Most trials are small or not well designed. Better research is needed in this area before a recommendation can be made.

Exercise performance
The effects of CoQ10 on exercise performance have been tested in athletes, normal healthy individuals, and in people with chronic lung disease. Results are variable, with some research suggesting benefits, and other studies showing no effects. Most trials have not been well-designed. Better research is necessary before a firm conclusion can be drawn.

Friedreich's ataxia
Preliminary research reports promising evidence for the use of CQ10 in the treatment of Friedreich's ataxia. Further evidence is necessary before a firm conclusion can be drawn.

Gum disease (periodontitis)
Preliminary human studies suggest possible benefits of CoQ10 taken by mouth or placed on the skin or gums in the treatment of periodontitis. Improvements in bleeding, swelling, and pain are reported. However, available studies are small and not high quality. Better research is needed before a conclusion can be drawn.

Heart attack (acute myocardial infarction)
There is preliminary human study of CoQ10 given to patients within three days after a heart attack. Reductions in deaths, abnormal heart rhythms, and second heart attacks are reported, although better research is needed before a firm conclusion can be drawn.

Heart conditions (mitral valve prolapse in children)
There is early data to support the use of CoQ10 in children with mitral valve prolapse. Well-designed clinical trials are needed before a recommendation can be made.

Heart failure
The evidence for CoQ10 in the treatment of heart failure is controversial and remains unclear. Different levels of disease severity have been studied (New York Heart Association classes I through IV). Several studies have shown benefits of co-enzyme Q-10 in people who have been diagnosed with chronic heart failure (with or without cardiomyopathy), including in transplant recipients. Some studies report improved heart function (ejection fraction, stroke volume, cardiac index, exercise tolerance), while others find no improvements.

Most trials are small or not well designed. In some parts of Europe, Russia, and Japan, CoQ10 is considered a part of standard therapy for congestive heart failure patients. Better research is needed in this area studying effects on quality of life, hospitalization, and death rates before a recommendation can be made.

Heart protection during surgery
Several studies suggest that the function of the heart may be improved after major heart surgeries such as coronary artery bypass graft (CABG) or valve replacement when CoQ10 is given to patients before or during surgery. Better studies that measure effects on long-term heart function and survival are necessary before a recommendation can be made.

HIV/AIDS
There is limited evidence that natural levels of CoQ10 in the body may be reduced in people with HIV/AIDS. There is no reliable scientific research showing that CoQ10 supplements have any effect on this disease.

Increasing sperm count (idiopathic spermatozoa)
There is early evidence that supports the use of CoQ10 in the treatment of increasing sperm count and motility. Better studies are needed before a strong recommendation can be made.

Kidney failure
There is initial data from one small trial to support the use of CoQ10 in the treatment of kidney (renal) failure. More research is needed before a recommendation can be made.

Migraine
There is fair evidence to support the use of CoQ10 treatment in migraine prevention or treatment. However, more well-designed studies are needed to confirm these findings.

Mitochondrial diseases and Kearns-Sayre syndrome
COQ10 is often recommended for patients with mitochondrial diseases, including myopathies, encephalomyopathies, and Kearns-Sayre syndrome. Several early studies report improvements in metabolism and physical endurance in patients with these conditions after treatment with CoQ10, although most available research is not high quality or definitive. Better studies are needed before a strong recommendation can be made.

Muscular dystrophies
Preliminary studies in patients with muscular dystrophy taking COQ10 supplements describe improvements in exercise capacity, heart function, and overall quality of life. Additional research is needed in this area.

Parkinson's disease
There is promising human evidence for the use of CoQ10 in the treatment of Parkinson's disease. Better-designed trials are needed to confirm these results.

RETURN TO TOP


           
SAMPLES OF CITATIONS :


Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics.
Author:           Bhagavan,-H-N; Chopra,-R-K
Citation:         Free-Radic-Res. 2006 May; 40(5): 445-53
Abstract:        Available data on the absorption, metabolism and pharmacokinetics of coenzyme Q10 (CoQ10) are reviewed in this paper. CoQ10 has a fundamental role in cellular bioenergetics. CoQ10 is also an important antioxidant. Because of its hydrophobicity and large molecular weight, absorption of dietary CoQ10 is slow and limited. In the case of dietary supplements, solubilized CoQ10 formulations show enhanced bioavailability. The T(max) is around 6 h, with an elimination half-life of about 33 h. The reference intervals for plasma CoQ10 range from 0.40 to 1.91 micromol/l in healthy adults. With CoQ10 supplements there is reasonable correlation between increase in plasma CoQ10 and ingested dose up to a certain point. Animal data show that CoQ-10 in large doses is taken up by all tissues including heart and brain mitochondria. This has implications for therapeutic applications in human diseases, and there is evidence for its beneficial effect in cardiovascular and neurodegenerative diseases. CoQ10 has an excellent safety record.


Antioxidants, supplements, and Parkinson's disease.
Author:           Weber,-C-A; Ernst,-M-E
Citation:         Ann-Pharmacother. 2006 May; 40(5): 935-8
Abstract:        OBJECTIVE: To review the use of antioxidants and other supplements for the prevention and treatment of Parkinson's disease (PD). DATA SOURCES: Biomedical literature was accessed through MEDLINE (1996-June 2005); key search terms included Parkinson's disease, coenzyme Q10 (CoQ10), antioxidants, supplements, and glutathione. Pertinent references cited in those articles were also evaluated for inclusion in this review. DATA SYNTHESIS: Three main antioxidants or supplements have been studied for use in the prevention or treatment of PD: tocopherol, CoQ10, and glutathione. These agents have been studied because of their potential to alter the course of 2 common theories of PD pathogenesis: free radical generation and mitochondrial complex-1 deficiency. The literature search revealed 3 large clinical studies of tocopherol (2 observational, 1 prospective randomized), 4 trials of CoQ10, and 1 study of glutathione. With the exception of the large observational studies with tocopherol and one study of CoQ10 that enrolled 80 patients, each of the other studies retrieved included fewer than 30 patients and were conducted for 3 months or less. Antioxidant supplementation, in particular tocopherol, did not appear to alter the course of PD. However, in 2 of the studies of CoQ10 and in the study of glutathione, a small but statistically significant improvement in PD symptoms was observed. CONCLUSIONS: At present, antioxidants and supplements appear to have a limited role in the prevention or treatment of PD. Of those reviewed here, CoQ-10 appears to provide some minor treatment benefits. More study is necessary to determine whether CoQ10 has a significant role as primary or adjunctive therapy in PD.


Dietary supplements and weight control in a middle-age population.
Author:           Nachtigal,-M-C; Patterson,-R-E; Stratton,-K-L; Adams,-L-A; Shattuck,-A-L; White,-E
Citation:         J-Altern-Complement-Med. 2005 Oct; 11(5): 909-15
Abstract:        OBJECTIVES: Obesity is rapidly becoming a health problem of epidemic proportions, bringing with it a host of health concerns. This study investigates the association of long-term (10-year) use of 14 nutritional supplements, marketed as weight-control aids, with weight change over the past 10 years among individuals age 53 to 57 years. METHODS: Data are from the VITamins And Lifestyle (VITAL) cohort study of western Washington. Participants (n = 15,655) completed questionnaires about 10-year supplement use, diet, health habits, height, and present and former weights. The following supplements that are sometimes marketed for weight control or loss were examined: multivitamins; vitamins B6 and B12; chromium; coenzyme Q10, dehydroepiandrosterone, essential fatty acids (EFAs), fiber, garlic (Allium sativum), ginkgo (Ginkgo biloba), ginseng (Panax spp.), melatonin, soy, and St. John's wort (Hypericum perforatum). Linear regression was used to model 10-year change in weight from age 45 to ages 53-57, stratified by sex and body mass index (BMI, kg/m2) (normal, overweight, or obese) at age 45 years. Models were controlled for race/ethnicity, education, energy intake, physical activity, weight at age 45 years, and smoking. RESULTS: Among overweight or obese men and women, long-term use of multivitamins, vitamins B6 and B12, and chromium were significantly associated with lower levels of weight gain. For example, with chromium, weight gain in the past 10 years for obese men was 11.7 lb for no use, 6.1 lb for <150 microg/day (10-year average), and a weight loss of 3.1 lb for > or = 150 microg/day (p for trend, <0.05). Among obese women, weight gain was 14.1 lb, 7.9 lb, and 3.2 lb for the three groups respectively (p for trend, <0.01). CONCLUSIONS: These data suggest that long-term users of certain supplements experienced less weight gain than individuals who did not use the supplements. Further study is necessary before recommendations regarding these supplements can be made.


Coenzyme Q10 protects from aging-related oxidative stress and improves mitochondrial function in heart of rats fed a polyunsaturated fatty acid (PUFA)-rich diet.
Author:                       Ochoa,-J-J; Quiles,-J-L; Huertas,-J-R; Mataix,-J
Citation:         J-Gerontol-A-Biol-Sci-Med-Sci. 2005 Aug; 60(8): 970-5
Abstract:        Coenzyme Q(10) supplementation on age-related changes in oxidative stress and function of heart mitochondria in rats fed a polyunsaturated fatty acid (PUFA)-rich diet was investigated. Two groups of rats were fed for 24 months on a PUFA-rich diet, differing in supplementation or not with coenzyme Q(10). Animals were killed at 6, 12, or 24 months. Fatty-acid profile, hydroperoxides, alpha-tocopherol, coenzyme Q, catalase and glutathione peroxidase activities, and cytochromes a+a(3), b, c+c(1) and cytochrome c oxidase activity were measured. Coenzyme Q(10)-supplemented animals showed lower hydroperoxide levels; higher content and/or activity of alpha-tocopherol, coenzyme Q, and catalase; and a slightly lower decrease in mitochondrial function. According to that, previously reported positive effects of coenzyme Q supplementation on the life span of rats fed a PUFA-rich diet might be a consequence, at least in part, of a lower oxidative stress level and perhaps, to a minor extent, of a smaller decrease in mitochondrial function.


Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline.
Author:           Shults, C W : Oakes, D : Kieburtz, K : Beal, M F : Haas, R : Plumb, S : Juncos, J L : Nutt, J : Shoulson, I : Carter, J : Kompoliti, K : Perlmutter, J S : Reich, S : Stern, M : Watts, R L : Kurlan, R : Molho, E : Harrison, M : Lew, M
Citation:         Arch-Neurol. 2002 Oct; 59(10): 1541-50
Abstract:        BACKGROUND: Parkinson disease (PD) is a degenerative neurological disorder for which no treatment has been shown to slow the progression. OBJECTIVE: To determine whether a range of dosages of coenzyme Q10 is safe and well tolerated and could slow the functional decline in PD. DESIGN: Multicenter, randomized, parallel-group, placebo-controlled, double-blind, dosage-ranging trial. SETTING: Academic movement disorders clinics. PATIENTS: Eighty subjects with early PD who did not require treatment for their disability. INTERVENTIONS: Random assignment to placebo or coenzyme Q10 at dosages of 300, 600, or 1200 mg/d. MAIN OUTCOME MEASURE: The subjects underwent evaluation with the Unified Parkinson Disease Rating Scale (UPDRS) at the screening, baseline, and 1-, 4-, 8-, 12-, and 16-month visits. They were followed up for 16 months or until disability requiring treatment with levodopa had developed. The primary response variable was the change in the total score on the UPDRS from baseline to the last visit. RESULTS: The adjusted mean total UPDRS changes were +11.99 for the placebo group, +8.81 for the 300-mg/d group, +10.82 for the 600-mg/d group, and +6.69 for the 1200-mg/d group. The P value for the primary analysis, a test for a linear trend between the dosage and the mean change in the total UPDRS score, was.09, which met our prespecified criteria for a positive trend for the trial. A prespecified, secondary analysis was the comparison of each treatment group with the placebo group, and the difference between the 1200-mg/d and placebo groups was significant (P =.04). CONCLUSIONS: Coenzyme Q10 was safe and well tolerated at dosages of up to 1200 mg/d. Less disability developed in subjects assigned to coenzyme Q10 than in those assigned to placebo, and the benefit was greatest in subjects receiving the highest dosage. Co-enzyme Q-10 appears to slow the progressive deterioration of function in PD, but these results need to be confirmed in a larger study.


Vitamins, supplements, herbal medicines, and arrhythmias.
Author:           Chung,-M-K
Citation:         Cardiol-Rev. 2004 Mar-Apr; 12(2): 73-84
Abstract:        Nutritional and herbal supplements may have harmful or beneficial effects on arrhythmias. Potential supplements that may have antiarrhythmic activity include omega-3 polyunsaturated fatty acids (N-3 PUFA), coenzyme Q10, and carnitine. Clinical studies show that N-3 PUFA or fish oil supplementation appears to reduce mortality and sudden death. Coenzyme Q10, used in treatment of heart failure, and carnitine and its derivatives may have beneficial effects on arrhythmias, although clinical studies have been limited. Antioxidant supplements may be beneficial, but large studies with vitamin E have been disappointing in that it does not reduce mortality. Correction of electrolyte disturbances has been long advised and magnesium supplementation has been beneficial in the treatment of torsades de pointes and in some studies after cardiac surgery. However, routine electrolyte supplementation with empiric potassium or magnesium in non-deficient patients has not been convincingly beneficial. Several herbal supplements have also been promoted to have antiarrhythmic activity. However, clinical studies are lacking to support routine use of these herbal medications. In addition, some herbal supplements may cause serious proarrhythmia, and many supplements significantly interact with warfarin and digoxin.

RETURN TO TOP



SUMMARY BY PDRHEALTH:

There are many studies, spanning more than two decades, reporting positive results from the use of CoQ10 as adjunctive therapy in the treatment of congestive heart failure. CoQ10 has been an approved drug in Japan for use in congestive heart failure since 1974. It has also been approved for this use in some other countries. Several studies have demonstrated a strong correlation between severity of heart disease and severity of CoQ10 deficiency. Some have suggested that this deficiency is the primary cause of some variations of heart muscle dysfunction, while others believe it plays a secondary role in the etiology of heart failure.

Early studies of congestive heart failure focused on idiopathic dilated cardiomyopathy, testing CoQ10 against placebo using echocardiography to assess heart function.

Echocardiographic improvement seen in these studies was generally slow but sustained and was accompanied by diminished fatigue, chest pain, dyspnea and palpitations. Normal heart size and function were restored in some patients using only CoQ10; this occurred primarily in patients with recent onset of congestive heart failure.

Subsequently, nearly all of the several placebo-controlled studies investigating CoQ10's effects on heart muscle function have reported significant positive results. One multi-center Italian study included 2,664 patients with congestive heart failure. No notable adverse effects on drug interactions have been reported in these studies except for one report that noted a slight diminution in coumadin activity.

Many studies to date have examined CoQ10 as an addition to standard medical treatments. In several studies involving hypertension and other manifestations of cardiovascular disease, there was a significant reduction in the use of concomitant drug therapies when CoQ10 was added to the treatment regimen.

It is now known that the HMG-CoA reductase inhibitors, while very effective in lowering cholesterol levels, also significantly lower levels of CoQ10. This may be particularly hazardous for patients with heart failure, suggesting a possible indication for CoQ10 in many, if not all, individuals using these cholesterol-lowering drugs. There has been some suggestion that CoQ10, especially if it could be more readily absorbed, might be a cholesterol-lowering agent itself. There is, however, no evidence for this.

Significant CoQ10 deficiencies have been noted in diseased gingiva. CoQ10's efficacy in reducing gingival inflammation and periodontal pocket-depth has been demonstrated in placebo-controlled trials. Claims that CoQ10 might be an effective anti-cancer agent are based upon a few suggestive case histories that will require far more rigorous clinical investigation before these claims can be properly evaluated. Similarly, claims that CoQ10 might be useful in AIDS and some other immune dysfunctions are premature.

It is not unreasonable to hypothesize that CoQ10 might be helpful in muscular dystrophy—and there is some very preliminary animal and clinical data suggesting that it might be. Muscular dystrophy is usually associated with cardiac disease. Research is ongoing but to date is inconclusive.

There is also some evidence that CoQ10 might boost energy and speed recovery of exercise-related muscle exhaustion and damage. This work, too, needs more rigorous followup.

There is no evidence that CoQ10 can inhibit obesity.

RETURN TO TOP

INTRODUCTION TO COENZYME Q10

By PETER H. LANGSJOEN, M.D., F.A.C.C.

DEFINITION
Coenzyme Q-10 (CoQ10) 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 (Fig. 1) as a potent antioxidant. The bioenergetics and free radical chemistry of CoQ10 are reviewed in Gian Paolo Littarru's book, Energy and Defense, published in 1994(1).

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 (Fig. 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 (4,5). In 1972 Gian Paolo Littarru of Italy along with Professor Karl Folkers documented a deficiency of CoQ10 in human heart disease (6). 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 (7,8,9,10).

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 (11). 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(12).

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(13). 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(14).

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.

TREATMENT OF HEART DISEASE WITH COENZYME Q10
CoQ10 is known to be highly concentrated in heart muscle cells due to the high energy requirements of this cell type. For the past 14 years, the great bulk of clinical work with CoQ10 has focused on heart disease. Specifically, congestive heart failure (from a wide variety of causes) has been strongly correlated with significantly low blood and tissue levels of CoQ10 (15). The severity of heart failure correlates with the severity of CoQ10 deficiency (16). This CoQ10 deficiency may well be a primary etiologic factor in some types of heart muscle dysfunction while in others it may be a secondary phenomenon. Whether primary, secondary or both, this deficiency of CoQ10 appears to be a major treatable factor in the otherwise inexorable progression of heart failure.

Pioneering trials of CoQ10 in heart failure involved primarily patients with dilated weak heart muscle of unknown cause (idiopathic dilated cardiomyopathy). CoQ10 was added to standard treatments for heart failure such as fluid pills (diuretics), digitalis preparations (Lanoxin), and ACE inhibitors. Several trials involved the comparison between supplemental CoQ10 and placebo on heart function as measured by echocardiography. CoQ10 was given orally in divided doses as a dry tablet chewed with a fat containing food or an oil based gel cap swallowed at mealtime. Heart function, as indicated by the fraction of blood pumped out of the heart with each beat (the ejection fraction), showed a gradual and sustained improvement in tempo with a gradual and sustained improvement in patients' symptoms of fatigue, dyspnea, chest pain, and palpitations.

The degree of improvement was occasionally dramatic with some patients developing a normal heart size and function on CoQ10 alone. Most of these dramatic cases were patients who began CoQ10 shortly after the onset of congestive heart failure. Patients with more established disease frequently showed clear improvement but not a return to normal heart size and function.

Internationally, there have been at least nine placebo controlled studies on the treatment of heart disease with CoQ10:two in Japan,two in the United States, two in Italy, two in Germany, and one in Sweden (17,18,19,20,21,22,23,24,25). All nine of these studies have confirmed the effectiveness of CoQ10 as well as its remarkable safety. There have now been eight international symposia on the biomedical and clinical aspects of CoQ10 (from 1976 through 1993 (26,27,28,29,30,31,32,33)). These eight symposia comprised over 300 papers presented by approximately 200 different physicians and scientists from 18 different countries. The majority of these scientific papers were Japanese (34%), with American (26%), Italian (20%) and the remaining 20% from Sweden, Denmark, Germany, United Kingdom, Belgium, Australia, Austria, France, India, Korea, Netherlands, Poland, Switzerland, USSR, and Finland. The majority of the clinical studies concerned the treatment of heart disease and were remarkably consistent in their conclusions: that treatment with CoQ10 significantly improved heart muscle function while producing no adverse effects or drug interactions.
It should be mentioned that a slight decrease in the effectiveness of the blood thinner, coumadin, was noted in a case by a Norwegian clinician (34).

This possible drug - CoQ10 interaction has not been observed by other investigators even when using much higher doses of CoQ10 for up to seven years and involving 25 patients treated with coumadin concomitantly with CoQ10 (this is still, as of this date, unpublished data).

The efficacy and safety of CoQ10 in the treatment of congestive heart failure, whether related to primary cardiomyopathies or secondary forms of heart failure, appears to be well established (35,36,37,38,39, 40,41,42). The largest study to date is the Italian multicenter trial, by Baggio et al., involving 2664 patients with heart failure (43).

The most recent work in heart failure examined the effect of CoQ10 on diastolic dysfunction, one of the earliest identifiable signs of myocardial failure that is often found in mitral valve prolapse, hypertensive heart disease and certain fatigue syndromes (44,45). Diastolic dysfunction might be considered the common denominator and a basic cause of symptoms in these three diagnostic groups of disease. Diastole is the filling phase of the cardiac cycle. Diastolic function has a larger cellular energy requirement than the systolic contraction and, therefore, the process of diastolic relaxation is more highly energy dependent and thus more highly dependent on CoQ10.

In simplier terms, it takes more energy to fill the heart than to empty it. Diastolic dysfunction is a stiffening' of the heart muscle which interferes with the heart's ability to function as an effective pump. It is seen early in the course of many common cardiac disorders and is demonstrable by echocardiography. This stiffening returns towards normal with supplemental CoQ10 in tempo with clinical improvement.

It is important to note that in all of the above clinical trials, CoQ10 was used in addition to traditional medical treatments, not to their exclusion. In one study by Langsjoen et al (46), of 109 patients with essential hypertension, 51% were able to stop between one and three antihypertensive drugs at an average of 4.4 months after starting CoQ10 treatment while the overall New York Heart Association (NYHA) functional class improved significantly from a mean of 2.40 to 1.36. Hypertension is reduced when diastolic function improves. In another study(39), there was a gradual and sustained decrease in dosage or discontinuation of concomitant cardiovascular drug therapy: Of 424 patients with cardiovascular disease, 43% were able to stop between one and three cardiovascular drugs with CoQ10 therapy. The authors conclude that the vitamin-like substance, CoQ10, "may be ushering in the new era of cellular/biochemical treatment of disease, complementing and extending the systems-oriented, macro and microscopic approach that has served us well to this point".

FREQUENTLY ASKED QUESTIONS
Over the past several years, there has been a steady increase in public interest and awareness of nutritional supplements and vitamins. Along with this accelerated interest has come an understandable explosion in the number and complexity of questions raised by patients about vitamins in general. By and large, these questions are quite difficult to answer. I personally am frequently asked the following questions:

1. What is CoQ-10?
It is a fat-soluble vitamin-like substance present in every cell of the body and serves as a coenzyme for several of the key enzymatic steps in the production of energy within the cell. It also functions as an antioxidant which is important in its clinical effects. It is naturally present in small amounts in a wide variety of foods but is particularly high in organ meats such as heart, liver and kidney, as well as beef, soy oil, sardines, mackerel, and peanuts. To put dietary CoQ10 intake into perspective, one pound of sardines, two pounds of beef, or two and one half pounds of peanuts, provide 30 mg of CoQ10. CoQ10 is also synthesized in all tissues and in healthy individuals normal levels are maintained both by CoQ10 intake and by the body's synthesis of CoQ10. It has no known toxicity or side effects.

2. Should I take CoQ-10?
This question can be asked in two ways. First, should a reasonably healthy person take CoQ10 to stay healthy or to become more robust? At present I do not believe anyone knows the answer to this question. Second, should a person with an illness such as congestive heart failure take CoQ10? As with any change in nutrition, diet, medication, or even activity, CoQ10 should be discussed with one's physician. As improvement in heart function occurs, a patient should have regular medical follow up with particular attention to concomitant drug therapy. The attached references will provide detailed information on the clinical use of CoQ10 and can be obtained from any good medical library.

3. What is the dosage of CoQ-10?
The dosage of CoQ10 used in clinical trials has evolved over the past 20 years. Initially, doses as small as 30 to 45 mg per day were associated with measurable clinical responses in patients with heart failure. More recent studies have used higher doses with improved clinical response, again in patients with heart failure. Most studies with CoQ10 involve the measurement of the level of CoQ10 in blood. CoQ10 shows a moderate variability in its absorption, with some patients attaining good blood levels of CoQ10 on 100 mg per day while others require two or three times this amount to attain the same blood level.

All CoQ10 available today in the United States is manufactured in Japan and is distributed by a number of companies who place the CoQ10 either in pressed tablets, powder-filled capsules, or oil-based gelcaps. CoQ10 is fat-soluble and absorption is significantly improved when it is chewed with a fat-containing food. Published data on the dosage of CoQ10 relates almost exclusively to the treatment of disease states. There is no information on the use of CoQ10 for prevention of illness. This is an extremely important question which, to date, does not have an answer.

4. If CoQ-10 is so effective in the treatment of heart failure, why is it not more generally used in this country?
The answer to this question is found in the fields of politics and marketing and not in the fields of science or medicine. The controversy surrounding CoQ10 likewise is political and economic as the previous 30 years of research on CoQ10 have been remarkably consistent and free of major controversy. Although it is not the first time that a fundamental and clinically important discovery has come about without the backing of a pharmaceutical company, it is the first such discovery to so radically alter how we as physicians must view disease.

While the pharmaceutical industry does a good job at physician and patient education on their new products, the distributors of CoQ10 are not as effective at this. This education is very costly and can only be done with the reasonable expectation of patent protected profit. CoQ10 is not patentable. The discovery of CoQ10 was based primarily on support from the National Heart Institute of NIH (National Institutes of Health) at the Institute for Enzyme Research, University of Wisconsin.

THE FUTURE OF COENZYME Q-10
In the past 50 years the driving force in medicine has been the development of drugs and procedures to modify the pathophysiology of illness. As viewed from the trenches of medical practice, the advances in drug therapy, although notable and clearly helpful, appear to have reached a plateau. Most of the "new" drugs over the past several years are primarily variants of old drugs. By comparison, the impressive advances made by basic scientists, biochemists, and molecular biologists, are only now beginning to be appreciated by the medical profession, and the enormous potential of these basic science advances has yet to be pursued.

Modern medicine seems to be based on an "attack strategy", a philosophy of treatment formed in response to the discovery of antibiotics and the development of surgical/anesthetic techniques.

Disease is viewed as something that can be attacked selectively - with antibiotics, chemotherapy, or surgery - assuming no harm to the host. Even chronic illnesses, such as diabetes and hypertension, yield simple numbers which can be furiously assaulted with medications. Amidst the miracles and drama of 20th century medicine we may have forgotten the importance of host support, as if time borrowed with medications and surgery were restorative in and of itself. Yet, in this age, a patient may be cured of leukemia through multiple courses of chemotherapy and bone marrow transplantation, only to die slowly of unrecognized thiamine (vitamin B1) deficiency(47).

Like the vitamins discovered in the early part of this century, CoQ10 is an essential element of food that can now be used medicinally to support the sick host in conditions where nutritional depletion and cellular dysfunction occur. Surely, the combination of disease attacking strategy and host supportive treatments would yield much better results in clinical medicine.

Since CoQ10 is essential to the optimal function of all celltypes,it is not surprising to find a seemingly diverse number of disease states which respond favorably to CoQ10 supplementation. All metabolically active tissues are highly sensitive to a deficiency ofCoQ10. CoQ10's function as a free radical scavenger only adds to the protean manifestations of CoQ10 deficiency. Preliminary observations in a wide variety of disease states have already been published (48,49,50,51,52,53,54,55,56,57,58).

One of the disease states which has received attention is cancer. Low levels of CoQ10 in the blood of some cancer patients have been noted (59), but overall, there is little data regarding cancer. The best work to date documents a significant reduction in the cardiac toxicity of the chemotherapy drug Adriamycin (52,53,54). The cardiac toxicity of Adriamycin and related drugs may well relate to free radical generation and this might explain the benefit of CoQ10 in its capacity as a free radical scavenger. The studies on Adriamycin cardiotoxicity were of short duration and did not specifically note any favorable or detrimental effect on the clinical course of the cancer itself. It is reasonable to assume that optimal nutrition (which would include optimal levels of CoQ10) is generally beneficial in any disease state, including cancer.

Another interesting topic is the relationship between the immune system and CoQ10. Immune function is extraordinarily complex and undoubtedly is influenced by numerous nutritional variables.

There are some encouraging preliminary data from the study of AIDS patients (50,51). End stage AIDS, like other overwhelming illnesses, has been associated with a significant deficiency in CoQ10. Regarding AIDS and cancer, it would be foolish to make premature statements about future utility of CoQ10, but it is even more foolish to ignore the importance of adequate CoQ10 levels in these disease states. Adequate CoQ10 supplementation (with close attention to plasma CoQ10 levels) is analogous to adequate hydration, and any treatment of critically ill patients should not ignore this easily measured and correctable deficiency.

The antioxidant or free radical quenching properties of CoQ10 serve to greatly reduce oxidative damage to tissues as well as significantly inhibit the oxidation of LDL cholesterol (much more efficiently than vitamin E) (60,61). This has great implications in the treatment of ischemia and reperfusion injury as well as the potential for slowing the development of atherosclerosis. In keeping with the free radical theory of aging, these antioxidant properties of CoQ10 have clear implications in the slowing of aging and age related degenerative diseases. There is epidemiologic evidence in humans that uniformly shows a gradual decline in CoQ10 levels after the age of twenty.


Until recently, attention has been focused on requirements for CoQ10 in energy conversion in the mitochondrial compartment of cells or on the antioxidant properties of CoQ10. New evidence shows that CoQ10 is present in other cell membranes. In the outer membrane it may contribute to the control of cell growth, especially in lymphocytes (the implications are far reaching (62,63,64,65)). The clinical experience with CoQ10 in heart failure is nothing short of dramatic, and it is reasonable to believe that the entire field of medicine should be re-evaluated in light of this growing knowledge. We have only scratched the surface of the biomedical and clinical applications of CoQ10 and the associated fields of bioenergetics and free radical chemistry.

ACKNOWLEDGEMENTS
Sincere appreciation is expressed to Hans Langsjoen of the University of Texas Medical Branch at Galveston, Karl Folkers and Richard Willis of the University of Texas at Austin, Frederick Crane of Purdue University in Indiana, Lars Ernster of the Stockholm University, Sweden, Gian Paolo Littarru, of the University of Ancona Medical School, Italy, and my wife Alena Langsjoen for their help in the completion of this manuscript.

Peter H. Langsjoen, M.D., F.A.C.C., P.A. 1120 Medical Dr.  Tyler, Tx 75701 Copyright 1994

RETURN TO TOP



REFERENCES:
1.   Gian Paolo Littarru (1994) Energy and Defense. Facts and perspectives on CoenzymeQ10 in biology and medicine. Casa Editrice Scientifica Internazionale, pp 1-91.
2.   Crane F.L., Hatefi Y., Lester R.I., Widmer C. (1957) Isolation of a quinone from beef heart mitochondria.   In:  Biochimica et Biophys. Acta, vol. 25, pp 220-221.
3.   Morton R.A., Wilson G.M., Lowe J.S., Leat W.M.F. (1957) Ubiquinone.  In:  Chemical Industry,  pp 1649.
4.   Mellors A., Tappel A.L. (1966) Quinones and quinols as inhibitors of lipid peroxidation.  Lipids, vol. 1, pp 282-284.
5.   Mellors A., Tappel A.L. (1966) The inhibition of mitochondrial peroxidation by ubiquinone and ubiquinol.  J.  Biol. Chem., vol. 241, pp 4353-4356.
6.   Littarru G.P., Ho L., Folkers K. (1972) Deficiency of Coenzyme Q10 in human heart disease.  Part I and II.  In:Internat. J. Vit. Nutr. Res., 42, n. 2, 291:42, n. 3:413.
7.   Mitchell P. (1976) Possible molecular mechanisms of the protonmotive function of cytochrome systems.  In:  J.  Theoret. Biol., vol. 62, pp 327-367.
8.   Mitchell P. (1991) The vital protonmotive role of coenzyme Q.  In:  Folkers K., Littarru G.P., Yamagami T. (eds)iomedical and Clinical Aspects of Coenzyme Q, vol. 6,Elsevier, Amsterdam, pp 3-10.
9.   Mitchell P. (1988) Respiratory chain systems in theory and  practice.  In:  Advances in Membrane Biochemistry andBioenergetics, Kim C.H., et al. (eds), Plenum Press, New   York, pp 25-52.
10.  Mitchell P. (1979) Kelin's respiratory chain concept and its chemiosmotic consequences. In: Journal Science, vol. 206, pp 1148-1159.
11.   Ernster L. (1977) Facts and ideas about the function of coenzyme Q10 in the Mitochondria.  In:  Folkers K., Yamamura Y. (eds)  Biomedical and Clinical Aspects of Coenzyme Q. Elsevier, Amsterdam, pp 15-8.
12.   Littarru G.P., Lippa S., Oradei A., Fiorni R.M., Mazzanti L. Metabolic and diagnostic implications of blood CoQ10 levels. In: Biomedical and Clinical Aspects of Coenzyme Q, vol. 6991) Folkers K., Yamagami T., and Littarru G. P. (eds)  Elsevier, Amsterdam, pp 167-178.
13.   Ghirlanda G., Oradei A., Manto A., Lippa S., Uccioli L.,Caputo S., Greco A.V., Littarru G.P. (1993) Evidence of Plasma CoQ10 - Lowering Effect by HMG-CoA ReductaseInhibitors: A double blind , placebo-controlled study.  Clin. Pharmocol., J. 33, 3, 226-229.
14.   Folkers K., Langsjoen Per H.,Willis R., Richardson P., Xia L.,Ye C., Tamagawa H. (1990) Lovastatin decreases   coenzyme Q levels in humans.  Proc. Natl. Acad Sci. Vol., pp.8931-8934.
15.   Folkers K., Vadhanavikit S., Mortensen S.A. (1985) Biochemical rationale and myocardial tissue data on the  effective therapy of cardiomyopathy with coenzyme Q10.  In:  Proc. Natl. Acad. Sci., U.S.A., vol. 82(3), pp 901-904.
16.   Mortensen S.A., Vadhanavikit S., Folkers K. (1984)  Deficiency of coenzyme Q10 in myocardial failure.  In:  Drugs Exptl. Clin. Res. X(7) 497-502.
17.   Hiasa Y., Ishida T., Maeda T., Iwanc K., Aihara T., and MoriH. (1984) Effects of coenzyme Q10 on exercise tolerance in patients with stable angina pectoris.  In:   Biomedical andClinical Aspects of Coenzyme Q, vol. 4 (1984) Folkers K.,Yamamura Y., (eds) Elsevier, Amsterdam, pp 291-301.
18.   Kamikawa T., Kobayashi A., Yamashita T., Hayashi H., and Yamazaki N. (1985) Effects of coenzyme Q10 on exercise   tolerance in chronic stable angina pectoris.  In:  Am. J. Cardiol.; 56:247-251.
19.   Langsjoen Per.H., Vadhanavikit S., Folkers K. (1985)  Response of patients in classes III and IV of cardiomyopathy to therapy in a blind and crossover trial with coenzyme Q10. In:  Proc. Natl.  Acad. of Sci., U.S.A., vol. 82, pp 4240-4244.
20.   Judy W.V., Hall J.H., Toth P.D., Folkers K. (1986) Double  blind-double crossover study of coenzyme Q10 in heart failure.  In:  Folkers K., Yamamura Y. (eds) Biomedical andclinical aspects of coenzyme Q, vol. 5.  Elsevier, Amsterdam, pp 315-323.
21.   Rossi E., Lombardo A., Testa M., Lippa S., Oradei A., Littarru G.P., Lucente M. Coppola E., Manzoli U.  Coenzyme Q10 in ischaemic cardiopathy. In:  Biomedical and ClinicalAspects of Coenzyme Q, vol. 6 (1991) Folkers K., Yamagami T., and Littarru G. P. (eds) Elsevier, Amsterdam, pp 321-326.
22.   Morisco C., Trimarco B., Condorelli M.  Effect of coenzyme  Q10 therapy in patients with congestive heart failure: A  long-term multicenter randomized study.  In:  Seventh International Symposium on Biomedical and Clinical Aspects   of Coenzyme Q  Folkers K., Mortensen S.A., Littarru G.P.,  Yamagami T., and Lenaz G. (eds) The Clinical Investigator,  (1993) 71:S  34-S 136.
23.   Schneeberger W., Muller-Steinwachs J., Anda L.P., Fuchs W., Zilliken F., Lyson K., Muratsu K., and Folkers K. A  clinical double blind and crossover trial with coenzyme Q10 on patients with cardiac disease.  In:  Biomedical and Clinical Aspects of Coenzyme Q, vol. 5 (1986) Folkers K.,Yamamura Y., (eds) Elsevier, Amsterdam, pp 325-333.
24.   Schardt F., Welzel D., Schiess W., and Toda K. Effect of coenzyme Q10 on ischaemia-induced ST-segment depression: A double blind, placebo-controlled crossover study.  In: Biomedical and Clinical Aspects of Coenzyme Q, vol. 6 (1991) Folkers K., Yamagami T., and Littarru G. P. (eds)  Elsevier, Amsterdam, pp 385-403.
25.   Swedberg K., Hoffman-Berg C., Rehnqvist N., Astrom H.  (1991) Coenzyme Q10 as an adjunctive in treatment ofcongestive heart failure.  In: 64th Scientific Sessions   American Heart Association, Abstract 774-6.
26.   Biomedical and Clinical Aspects of Coenzyme Q. (1977)  Folkers K., Yamamura Y. (eds) Elsevier, Amsterdam, pp 1-315.
27.   Biomedical and Clinical Aspects of Coenzyme Q, Vol. 2 (1980) Yamamura Y., Folkers K., and Ito Y. (eds) Elsevier, Amsterdam, pp 1-456.
28.   Biomedical and Clinical Aspects of Coenzyme Q, Vol. 3  (1981) Folkers K., Yamamura Y., (eds) Elsevier,   Amsterdam, pp 1-414.
29.   Biomedical and Clinical Aspects of Coenzyme Q , Vol. 41983) Folkers K., Yamamura Y., (eds) Elsevier,  Amsterdam, pp 1-432.
30.   Biomedical and Clinical Aspects of Coenzyme Q, Vol. 5(1986) Folkers K., Yamamura Y., (eds) Elsevier, Amsterdam, pp 1-410.
31.   Biomedical and Clinical Aspects of Coenzyme Q, Vol. 6 (1991) Folkers K., Yamagami T., and Littarru G. P. (eds)  Elsevier, Amsterdam, pp 1-555.
32.   Seventh International Symposium on Biomedical and Clinical Aspects of Coenzyme Q (1993) Folkers K., Mortensen S.A.,   Littarru G.P., Yamagami T., and Lenaz,G. (eds) The Clinical Investigator, Supplement to Vol.71 /  Issue 8, pp S51-S177.
33.   Eighth International Symposium on Biomedical and Clinical  Aspects of Coenzyme Q (1994) Littarru G.P., Battino M. , Folkers K. (Eds) The Molecular Aspects of Medicine, Vol.15 (Supplement), pp S1-S294.
34.   Spigset O. (1994) Reduced effect of warfarin caused by ubidecarenone.  Lancet  Nov 12 Vol. 344, pp. 8933.
35.   Mortensen S.A., Vadhanavikit S., Folkers K. (1984) Deficiency of coenzyme Q10 in myocardial failure. In: Drugs Exptl. Clin. Res., vol. X(7), pp 497-502.
36.   Mortensen S.A., Vadhanavikit S., Baandrup U., Folkers K.   (1985) Long term coenzyme Q10 therapy:  a major advance in the management of resistant myocardial failure. In: Drugs Exp. Clin. Res., vol.11(8), pp 581-593.
37.   Langsjoen P.H., Folkers K., Lyson K., Muratsu K., Lyson T., Langsjoen P. H.  Effective and safe therapy with coenzyme Q10 for cardiomyopathy.  In:  Klin. Wochenschr. (1988) 66:583-593.
38.   Langsjoen P. H., Langsjoen, P. H., Folkers, K. (1989) Long  term efficacy and safety of coenzyme Q10 therapy fori diopathic dilated cardiomyopathy.  In:  The American Journal of Cardiology, Vol. 65, pp 521 - 523.
39.   Mortensen S.A., Vadhanavikit S., Muratsu K., Folkers K.  (1990) Coenzyme Q10:  Clinical benefits with biochemical correlates suggesting a scientific breakthrough in the management of chronic heart failure.  In:  Int. J. Tissue  React., Vol. 12 (3), pp 155-162.
40.   Ursini T., Gambini C., Paciaroni E., and Littarru G.P. Coenzyme Q10 treatment of heart failure in the elderly: Preliminary results.  In: Biomedical and Clinical Aspects of  Coenzyme Q, vol. 6 (1991) Folkers K., Yamagami T., and Littarru G. P. (eds) Elsevier, Amsterdam, pp 473-480.
41.   Poggessi L., Galanti G., Comeglio M., Toncelli L., Vinci M.  (1991) Effect of coenzyme Q10 on left ventricular function in patients with dilative cardiomyopathy.  Curr. Ther. Res.49:878-886.
42.   Langsjoen H.A., Langsjoen P. H., Langsjoen P. H., Willis R., Folkers K. (1994) Usefulness of coenzyme Q10 in clinical cardiology, a long-term study.  In: Eighth International Symposium on Biomedical and Clinical Aspects of  Coenzyme Q, Littarru G.P., Battino M. , Folkers K. (Eds) The Molecular Aspects of Medicine, Vol. 15 (Supplement), pp S165-S175.
43.   Baggio E., Gandini R., Plancher A.C., Passeri M., Carmosino G.  Italian multicenter study on safety and efficacy of coenzyme Q10 adjunctive therapy in heart failure. In:  Eighth International Symposium on Biomedical and Clinical Aspects of Coenzyme Q (1994) Littarru G.P., Battino M. , Folkers K.Eds) The Molecular Aspects of Medicine, Vol. 15 (Supplement), pp S287-S294.
44.   Langsjoen Per H., Langsjoen Peter H., Folkers K.  Isolated  diastolic dysfunction of the myocardium and its response to  CoQ10 treatment. In:  Seventh International Symposium on Biomedical and Clinical Aspects of Coenzyme Q.  Folkers, K., Mortensen S.A., Littarru G.P., Yamagami T., and LenazG. (eds) The Clinical Investigator, (1993) 71:S 140-S 144.
45.   Oda T.  Recovery of the Frank-Starling mechanism by coenzyme Q10 in patients with load-induced contractilitydepression.  In:  Eighth International Symposium on Biomedical and Clinical Aspects of Coenzyme Q (1994)  Littarru G.P., Battino M., Folkers K. (Eds) The Molecular   Aspects of Medicine, Vol.15 (Supplement), pp S149-S154.
46.   Langsjoen P. H., Langsjoen P. H., Willis R., Folkers K. (1994) Treatment  of essential hypertension with coenzyme  Q10.  In:  Eighth International Symposium on Biomedical and  Clinical Aspects of Coenzyme Q (1994) Littarru G.P., Battino M. , Folkers K. (Eds) The Molecular Aspects of  Medicine, Vol. 15 (Supplement), pp S287-S294.
47.   Pihko H., Saarinen U., and Paetau A. (1989)  Wernicke  encephalopathy - a preventable cause of death: Report of 2 children with malignant disease.  Pediatric Neurology vol. 5no. 4, pp 237-242.
48.   Hansen I.L. (1976) Bioenergetics in clinical medicine.  Gingival leucocytic deficiencies of coenzyme Q10 in patients with periodontal disease.  In:  Research Communications in  Chemical Pathology and Pharmacology, vol. 14, no. 4, pp 729-738.
49.   Iwamoto Y., Watanabe T., Okamoto H., Ohata N., Folkers K.  Clinical effect of coenzyme Q10 on periodontal disease.  In: Folkers, K., Yamamura, Y., (eds)  Biomedical and ClinicalAspects of Coenzyme Q10, (1981) vol. 3, Elsevier, Amsterdam, pp 109-119.
50.   Folkers K., Langsjoen P. H.,  et al. (1988) Biochemical deficiencies of coenzyme Q10 in HIV-infection and the exploratory treatment.  Biochemical and Biophysical  Research Communications vol. 153, no. 2, pp 888-896.
51.   Langsjoen P. H., Langsjoen P. H., Folkers K., Richardson P. Treatment of patients with human immunodeficiency virus infection with coenzyme Q10.  In:  Folkers K., Littarru G.P., and Yamagami, T., (eds) Biomedical and Clinical Aspects of  Coenzyme Q, (1991) vol. 6, pp 409-415.
52.   Cortes E.P, Mohinder G., Patel M., Mundia A., and Folkers K.  Study of Administration of coenzyme Q10 to Adriamycin   treated cancer patients.  In:Biomedical and Clinical Aspects   of Coenzyme Q (1977).  Folkers K., Yamamura Y. (eds)Elsevier, Amsterdam, pp 267-273.
53.   Combs A.B., Faria D.T., Leslie S.W., and Bonner H.W. (1981) Effect of coenzyme Q10 on Adriamycin induced changes in myocardial calcium.  In: Biomedical and Clinical Aspects of Coenzyme Q, vol. 3  Folkers, K., Yamamura Y., (eds) Elsevier, Amsterdam, pp 137-144.
54.   Judy W.V. Hall J., H., Dugan W., Toth P.D., and Folkers K. Coenzyme Q10 reduction of Adriamycin toxicity.  In:Biomedical and Clinical Aspects of Coenzyme Q (1983),vol. 4  Folkers K., Yamamura Y., (eds) Elsevier, Amsterdam,  pp 231-241.
55.   Lockwood K., Moesgaard S., Yamamoto T., Folkers K. Progress on therapy of breast cancer with vitamin Q10 and  the regression of metastases. Biochem Biophys Res Commun 1995 Jul 6;212(1):172-7.
56.   Lockwood K., Moesgaard S., Hanioka T., Folkers K. Apparent partial remission of breast cancer in 'high risk' patients supplemented with nutritional antioxidants, essentialfatty acids and coenzyme Q10.  Mol Aspects Med 1994;15 Suppl:s231-40.
57.   Lockwood K., Moesgaard S., Folkers K.   Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10.  Biochem Biophys Res Commun  1994 Mar 30;199(3):1504-8.
58.   Folkers K., Brown R., Judy W.V., and Morita M. (1993) Survival of cancer patients on therapy with coenzyme Q10.  Biochem. Biophys. Res. Comm., Ms. No. G-8658.
59.   Mellstedt H., Osterborg A., Nylander M., Morita M., and Folkers K.  A deficiency of coenzyme Q10 (CoQ10) in conventional cancer therapy and blood levels of CoQ10 in cancer patients in Sweden.  In:  Eighth International Symposium on Biomedical and Clinical Aspects of Coenzyme Q (1994) The Molecular Aspects of Medicine, in print.
60.   Bowry V.W., Mohr D., Cleary J., Stocker R.  (1995) Prevention of tocopherol-mediated peroxidation in  ubiquinol-10-free human low density lipoprotein.  J Biol Chem 1995 Mar 17;270(11):5756-63.
61.   Ingold K.U., Bowry V.W., Stocker R., Walling C. (1993) Autoxidation of lipids and antioxidation by alpha-tocopherol and ubiquinol in homogeneous solution and in aqueous  dispersions of lipids: Unrecognized consequences of lipid particle size as exemplified by oxidation of human low density lipoprotein. Proc Natl Acad Sci U S A 1993 Jan 1;90(1):45-9.
62.   Sun I.L., Sun E.E., Crane F.L., Morre, V.J., Lindgren A., and Low H.  Requirement for coenzyme Q in plasma membrane electron transport.  In:  Proc. Nat. Acad. Sci. U SA  89, 1126-11130 (1992).
63.   Linnane A.W., Zhang C., Baumer A., Nagley P. (1992) Mitochondrial DNA mutation and the aging process: bioenergy and pharmacological intervention. Mutation  Research 275, pp. 195-208.
64.   Martinius R.D., Linnane A.W., Nagley P. (1993) Growth of human namalwa cells lacking oxidative phosphorylation can be sustained by redox compounds potassium ferricyanide or coenzyme Q10 putatively acting through the plasma membrane oxidase.  In:  Biochem. Mol. Biol. Internat. 31, 997-1005.
65.   Lawin A., Martinius R.D., McMullen G., Nagley P., Vaillant F., Wolvetang E. J., Linnane A.W.  The universality of bioenergetic disease: The role of mitochondrial DNA mutation and the putative inter-relationship between mitochondria and plasma membrane NADH oxidases.  In: Eighth International Symposium on Biomedical and Clinical Aspects of Coenzyme Q (1994) Littarru G.P., Battino M. , Folkers K. (Eds) The Molecular Aspects of Medicine, Vol. 15 (Supplement), pp S13-S27.

RETURN TO TOP OF PAGE

RETURN TO HOME PAGE