Coenzyme Q10 (CoQ10) Research

Biomed Pharmacother 2002;56 Suppl 2:257s-265s

Singh RB, Kartik C, Otsuka K, Pella D, Pella J.

Autonomic functions, such as increased sympathetic and parasympathetic activity and the brain's suprachiasmatic nucleus, higher nervous centres, depression, hostility and aggression appear to be important determinants of heart rate variability (HRV), which is, itself, an important risk factor of myocardial infarction, arrhythmias, sudden death, heart failure and atherosclerosis. The circadian rhythm of these complications with an increased occurrence in the second quarter of the day may be due to autonomic dysfunction as well as to the presence of excitatory brain and heart tissues. While increased sympathetic activity is associated with increased levels of cortisol, catecholamines, serotonin, renin, aldosterone, angiotensin and free radicals; increased parasympathetic activity may be associated with greater levels of acetylecholine, dopamine, nitric oxide, endorphins, coenzyme Q10, antioxidants and other protective factors. Recent studies indicate that hyperglycemia, diabetes, hyperlipidemia, ambient pollution, insulin resistance and mental stress can increase the risk of low HRV. These risk factors, which are known to favour cardiovascular disease, seem to act by decreasing HRV. There is evidence that regular fasting may modulate HRV and other risk factors of heart attack. While exercise is known to decrease HRV, exercise training may not have any adverse effect on HRV. In a recent study among 202 patients with acute myocardial infarction (AMI), the incidence of onset of chest pain was highest in the second quarter of the day (41.0%), mainly between 4.0-8.0 AM, followed by the fourth quarter, usually after large meals (28.2%). Emotion was the second most common trigger (43.5%). Cold weather was a predisposing factor in 29.2% and hot temperature (> 40 degrees celsius) was common in 24.7% of the patients. Dietary n-3 fatty acids and coenzyme Q10 have been found to prevent the increased circadian occurrence of cardiac events in our randomized controlled trials, possibly by increasing HRV. We have also found that n-3 fatty acids plus CoQ can decrease TNF-alpha and IL-6 in AMI which are pro-inflammatory agents. There is evidence that dietary n-3 fatty acids canenhance hippocampal acetylecholine levels, which may be protective. Similarly, the stimulation of the vagus nerve may inhibit TNF synthesis in the liver and acetylecholine, the principal vagal neurotransmitter, significantly attenuates the release of pro-inflammatory cytokines TNF-alpha, interleukin 1,6 and 18, but not the anti-inflammatory cytokine IL-10 in experiments. Therefore, any agent which can enhance brain acetylecholine levels, may be used as a therapeutic agent in protecting the suprachiasmatic nucleus, higher nervous centres, vagal activity and sympathetic nerve activity which are known to regulate the body clock and HRV and the risk of SCD and heart attack.

PMID: 12653178 [PubMed - in process]

Mega-dose vitamins and minerals in the treatment of non-metastatic breast cancer: an historical cohort study.

Breast Cancer Res Treat 2002 Nov;76(2):137-43

Lesperance ML, Olivotto IA, Forde N, Zhao Y, Speers C, Foster H, Tsao M, MacPherson N, Hoffer A.

Department of Mathematics and Statistics, University of Victoria, Victoria, British Columbia, Canada. mlespera@uvic.ca

BACKGROUND: Alternative therapies such as mega-dose vitamins and minerals are commonly used by women with breast cancer, but their effect on recurrence and survival have rarely been evaluated. METHODS: Survival and recurrence outcomes for 90 women with unilateral non-metastatic breast cancer diagnosed between 1989 and 1998, and who had been prescribed mega-doses of beta-carotene, vitamin C, niacin, selenium, coenzyme Q10, and zinc in addition to standard therapies were compared with matched controls. The 90 treated patients were prescribed combinations from three to six of the vitamins and minerals listed above. The controls were matched (2:1) to the vitamin/mineral patients for age at diagnosis, presence of axillary lymph node metastasis, tumor stage, grade, estrogen receptor status, year of diagnosis, and prescription of systemic therapy. All subjects were patients of the British Columbia Cancer Agency, Vancouver Island Centre. FINDINGS: Median follow-up of surviving patients was 68 months (minimum 20 months, 133 months maximum). The vitamin/mineral patients and controls were well matched. Two endpoints were considered. Breast cancer-specific survival (p = 0.19) and disease-free survival (p = 0.08) times for the vitamin/mineral treated group were shorter, after adjusting for diagnostic variables using a Cox proportional hazards model. The hazard ratios for the vitamin/mineral treated group versus the control group were estimated at 1.75 (95% CI = 0.83-2.69) for disease-specific survival and 1.55 (95% CI = 0.94-2.54) for disease-free survival. Overall survival was similar for the two groups (log-rank test, p = 0.36). INTERPRETATION: Breast cancer-specific survival and disease-free survival times were not improved for the vitamin/mineral treated group over those for the controls.

PMID: 12452451 [PubMed - in process]

Nutritional and exercise-based therapies in the treatment of mitochondrial disease.

Curr Opin Clin Nutr Metab Care 2002 Nov;5(6):619-29

Mahoney DJ, Parise G, Tarnopolsky MA.

Departments of Medical Sciences, Kinesiology, and Medicine (Division of Neurology), McMaster University, Hamilton, Ontario, Canada.

PURPOSE OF REVIEW This review will critically summarize the nutritional and exercise-based interventions that have been used to treat mitochondrial disease, with a focus on the biochemical or molecular rationale for their use as well as recent advances in the field.RECENT FINDINGS Many nutritional-based treatment strategies have been used in an attempt to target energy impairment and its sequelae. Recently, coenzyme Q10, idebenone and triacylglycerol have been shown to bypass defective respiratory enzymes or scavenge free radicals, whereas creatine monohydrate has provided an alternative energy source. Thiamine has been used to decrease lactate levels and increase flux through aerobic metabolism, and riboflavin has been used as a precursor to complexes I and II. Several therapies employing various antioxidants in combination with other supplements have been effective at targeting several of the final common pathways of mitochondrial disease. Miscellaneous supplements, such as L-arginine and uridine, have also had recent success. However, although positive responses have been reported with these agents, many reports have shown no benefit, and there is widespread disparity in the literature. An alternative approach to treatment is exercise training. Both resistance and endurance exercise training have had positive outcomes in patients with mitochondrial disease, although several questions remain to be answered.SUMMARY There is no currently recognized treatment for mitochondrial disease. Future clinical trials are needed, as well as research into the potential for in-vitro screening of various compounds within affected cells from patients. Until this time, an accurate diagnosis will facilitate treatment on a case-by-case basis.

PMID: 12394637 [PubMed - in process]

Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline.

Arch Neurol 2002 Oct;59(10):1541-50

Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M; Parkinson Study Group.

Department of Neurosciences, Mail Code 0662, University of California-San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0662, USA. cshults@ucsd.edu

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. Coenzyme Q10 appears to slow the progressive deterioration of function in PD, but these results need to be confirmed in a larger study.

PMID: 12374491 [PubMed - indexed for MEDLINE]

Testicular toxicity effects of magnetic field exposure and prophylactic role of coenzyme Q10 and L-carnitine in mice.

Pharmacol Res 2002 Oct;46(4):363-70

Ramadan LA, Abd-Allah AR, Aly HA, Saad-el-Din AA.

Drug Radiation Research Department, NCRRT, Atomic Energy Authority, P.O. Box 29, Nasr City, Cairo, Egypt. laila_ramadan@hotmail.com

The protective effect of L-carnitine or coenzyme Q10 (CoQ10) against high magnetic field (20 mT) induced testicular toxicity in mice were evaluated. Animals were injected with L-carnitine (200 mg kg(-1), i.p.) or CoQ10 (200 mg kg(-1), p.o.) 1h before exposure to fractionated doses (30 min per day, three times per week for 2 weeks) or acute dose (3h) of magnetic field. Total sperm count, motility, daily sperm production, and testicular LDH-X activity as well as histopathological examination were investigated. Exposure of mice to fractionated doses of magnetic field caused a significant decrease in sperm count, motility, daily sperm production, and LDH-X activity, which was more pronounced than that of acute dose. Moreover, a marked testicular histopathological changes were observed after exposure to fractionated doses of magnetic field. Pretreatment of mice with L-carnitine or CoQ10 1h before exposure to magnetic field caused a significant recovery of mice testes damage induced by high magnetic field (20 mT).

PMID: 12361700 [PubMed - in process]

Can antioxidant diet supplementation protect against age-related mitochondrial damage?

Ann N Y Acad Sci 2002 Apr;959:508-16

Miquel J.

Department of Biotechnology, University of Alicante, E-03080 Alicante, Spain.

Harman's free radical theory of aging and our electron-microscopic finding of an age-related mitochondrial degeneration in the somatic tissues of the insect Drosophila melanogaster as well as in the fixed postmitotic Leydig and Sertoli cells of the mouse testis led us to propose a mitochondrial theory of aging, according to which metazoan senescence may be linked to oxygen stress-injury to the genome and membranes of the mitochondria of somatic differentiated cells. These concepts attract a great deal of attention, since, according to recent work, the mitochondrial damage caused by reactive oxygen species (ROS) and concomitant decline in ATP synthesis seem to play a key role not only in aging, but also in the fundamental cellular process of apoptosis. Although diet supplementation with antioxidants has not been able to increase consistently the species-characteristic maximum life span, it results in significant extension of the mean life span of laboratory animals. Moreover, diets containing high levels of antioxidants such as vitamins C and E seem able to reduce the risk of suffering age-related immune dysfunctions and arteriosclerosis. Presently, the focus of age-related antioxidant research is on compounds, such as deprenyl, coenzyme Q10, alpha-lipoic acid, and the glutathione-precursors thioproline and N-acetylcysteine, which may be able to neutralize the ROS at their sites of production in the mitochondria. Diet supplementation with these antioxidants may protect the mitochondria against respiration-linked oxygen stress, with preservation of the genomic and structural integrity of these energy-producing organelles and concomitant increase in functional life span.

PMID: 11976223 [PubMed - indexed for MEDLINE]

Coenzyme Q(10) improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus.

Diabetologia 2002 Mar;45(3):420-6

Watts GF, Playford DA, Croft KD, Ward NC, Mori TA, Burke V.

Department of Medicine, University of Western Australia, Royal Perth Hospital, Perth, Australia. gfwatts@cyllene.uwa.edu.au

AIM/HYPOTHESIS: We assessed whether dietary supplementation with coenzyme Q(10) improves endothelial function of the brachial artery in patients with Type II (non-insulin-dependent) diabetes mellitus and dyslipidaemia. METHODS: A total of 40 patients with Type II diabetes and dyslipidaemia were randomized to receive 200 mg of coenzyme Q(10) or placebo orally for 12 weeks. Endothelium-dependent and independent function of the brachial artery was measured as flow-mediated dilatation and glyceryl-trinitrate-mediated dilatation, respectively. A computerized system was used to quantitate vessel diameter changes before and after intervention. Arterial function was compared with 18 non-diabetic subjects. Oxidative stress was assessed by measuring plasma F(2)-isoprostane concentrations, and plasma antioxidant status by oxygen radical absorbance capacity. RESULTS: The diabetic patients had impaired flow-mediated dilation [3.8 % (SEM 0.5) vs 6.4 % (SEM 1.0), p = 0.016], but preserved glyceryl-trinitrate-mediated dilation, of the brachial artery compared with non-diabetic subjects. Flow-mediated dilation of the brachial artery increased by 1.6 % (SEM 0.3) with coenzyme Q(10) and decreased by -0.4 % (SEM 0.5) with placebo (p = 0.005); there were no group differences in the changes in pre-stimulatory arterial diameter, post-ischaemic hyperaemia or glyceryl-trinitrate-mediated dilation response. Coenzyme Q(10) treatment resulted in a threefold increase in plasma coenzyme Q(10) (p < 0.001) but did not alter plasma F(2)-isoprostanes, oxygen radical absorbance capacity, lipid concentrations, glycaemic control or blood pressure. CONCLUSION/INTERPRETATION: Coenzyme Q(10) supplementation improves endothelial function of conduit arteries of the peripheral circulation in dyslipidaemic patients with Type II diabetes. The mechanism could involve increased endothelial release and/or activity of nitric oxide due to improvement in vascular oxidative stress, an effect that might not be reflected by changes in plasma F(2)-isoprostane concentrations.

PMID: 11914748 [PubMed - indexed for MEDLINE]

Coenzymes Q9 and Q10, vitamin E and peroxidation in rat synaptic and non-synaptic occipital cerebral cortex mitochondria during ageing.

Biol Chem 2001 Jun;382(6):925-31

Battino M, Bompadre S, Leone L, Villa RF, Gorini A.

Institute of Biochemistry, Medical School, University of Ancona, Italy.

Great attention has been devoted both to ageing phenomena at the mitochondrial level and to the antioxidant status of membrane structures. These kinds of investigations are difficult to perform in the brain because of its heterogeneity. It is known that synaptic heavy mitochondria (HM) may represent an aged mitochondrial population characterized by a partial impairment of their typical mitochondrial function. We arranged a novel system requiring no extraction procedure, very limited handling of the samples and their direct injection into the HPLC apparatus, to carry out, for the first time, a systematic and concomitant determination of vitamin E, Coenzyme Q9 (CoQ9) and Coenzyme Q10 (CoQ10) contents in rat brain mitochondria. The trends found for CoQ9 and CoQ10 levels in synaptic and non-synaptic occipital cerebral cortex mitochondria during rat ageing are consistent with previous data. Hydroperoxides (HP) differed with age and it was confirmed that in the HM fraction the summation of contributions results in an oxidatively jeopardized subpopulation. We found that vitamin E seems to increase with age, at least in non-synaptic free (FM) and synaptic light (LM) mitochondria, while it was inclined to remain substantially constant in HM.

PMID: 11501757 [PubMed - indexed for MEDLINE]

Ubiquinone (coenzyme q10) and mitochondria in oxidative stress of parkinson's disease.

Biol Signals Recept 2001 May-Aug;10(3-4):224-53

Ebadi M, Govitrapong P, Sharma S, Muralikrishnan D, Shavali S, Pellett L, Schafer R, Albano C, Eken J.

Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, N.Dak. 58203-2817, USA. mebadi@medicine.nodak.edu

Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease affecting approximately1% of the population older than 50 years. There is a worldwide increase in disease prevalence due to the increasing age of human populations. A definitive neuropathological diagnosis of Parkinson's disease requires loss of dopaminergic neurons in the substantia nigra and related brain stem nuclei, and the presence of Lewy bodies in remaining nerve cells. The contribution of genetic factors to the pathogenesis of Parkinson's disease is increasingly being recognized. A point mutation which is sufficient to cause a rare autosomal dominant form of the disorder has been recently identified in the alpha-synuclein gene on chromosome 4 in the much more common sporadic, or 'idiopathic' form of Parkinson's disease, and a defect of complex I of the mitochondrial respiratory chain was confirmed at the biochemical level. Disease specificity of this defect has been demonstrated for the parkinsonian substantia nigra. These findings and the observation that the neurotoxin 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP), which causes a Parkinson-like syndrome in humans, acts via inhibition of complex I have triggered research interest in the mitochondrial genetics of Parkinson's disease. Oxidative phosphorylation consists of five protein-lipid enzyme complexes located in the mitochondrial inner membrane that contain flavins (FMN, FAD), quinoid compounds (coenzyme Q10, CoQ10) and transition metal compounds (iron-sulfur clusters, hemes, protein-bound copper). These enzymes are designated complex I (NADH:ubiquinone oxidoreductase, EC 1.6. 5.3), complex II (succinate:ubiquinone oxidoreductase, EC 1.3.5.1), complex III (ubiquinol:ferrocytochrome c oxidoreductase, EC 1.10.2.2), complex IV (ferrocytochrome c:oxygen oxidoreductase or cytochrome c oxidase, EC 1.9.3.1), and complex V (ATP synthase, EC 3.6.1.34). A defect in mitochondrial oxidative phosphorylation, in terms of a reduction in the activity of NADH CoQ reductase (complex I) has been reported in the striatum of patients with Parkinson's disease. The reduction in the activity of complex I is found in the substantia nigra, but not in other areas of the brain, such as globus pallidus or cerebral cortex. Therefore, the specificity of mitochondrial impairment may play a role in the degeneration of nigrostriatal dopaminergic neurons. This view is supported by the fact that MPTP generating 1-methyl-4-phenylpyridine (MPP(+)) destroys dopaminergic neurons in the substantia nigra. Although the serum levels of CoQ10 is normal in patients with Parkinson's disease, CoQ10 is able to attenuate the MPTP-induced loss of striatal dopaminergic neurons.

PMID: 11351130 [PubMed - indexed for MEDLINE]

Dietary cosupplementation with vitamin E and coenzyme Q(10) inhibits atherosclerosis in apolipoprotein E gene knockout mice.

Arterioscler Thromb Vasc Biol 2001 Apr;21(4):585-93

Thomas SR, Leichtweis SB, Pettersson K, Croft KD, Mori TA, Brown AJ, Stocker R.

Biochemistry Group, The Heart Research Institute, Camperdown, NSW, Australia.

Intimal oxidation of LDL is considered an important early event in atherogenesis, and certain antioxidants are antiatherogenic. Dietary coenrichment with vitamin E (VitE) plus ubiquinone-10 (CoQ(10), which is reduced during intestinal uptake to the antioxidant ubiquinol-10, CoQ(10)H(2)) protects, whereas enrichment with VitE alone can increase oxidizability of LDL lipid against ex vivo oxidation. In the present study, we tested whether VitE plus CoQ(10) cosupplementation is more antiatherogenic than either antioxidant alone, by use of apolipoprotein E-deficient (apoE-/-) mice fed a high-fat diet without (control) or with 0.2% (wt/wt) VitE, 0.5% CoQ(10), or 0.2% VitE plus 0.5% CoQ(10) (VitE+CoQ(10)) for 24 weeks. None of the supplements affected plasma cholesterol concentrations, whereas in the VitE and CoQ(10) groups, plasma level of the respective supplement increased. Compared with control, plasma from CoQ(10) or VitE+CoQ(10) but not VitE-supplemented animals was more resistant to ex vivo lipid peroxidation induced by peroxyl radicals. VitE supplementation increased VitE levels in aorta, heart, brain, and skeletal muscle, whereas CoQ(10) supplementation increased CoQ(10) only in plasma and aorta and lowered tissue VITE: All treatments significantly lowered aortic cholesterol compared with control, but only VitE+CoQ(10) supplementation significantly decreased tissue lipid hydroperoxides when expressed per parent lipid. In contrast, none of the treatments affected aortic ratios of 7-ketocholesterol to cholesterol. Compared with controls, VitE+CoQ(10) supplementation decreased atherosclerosis at the aortic root and arch and descending thoracic aorta to an extent that increased with increasing distance from the aortic root. CoQ(10) significantly inhibited atherosclerosis at aortic root and arch, whereas VitE decreased disease at aortic root only. Thus, in apoE-/- mice, VitE+CoQ(10) supplements are more antiatherogenic than CoQ(10) or VitE supplements alone and disease inhibition is associated with a decrease in aortic lipid hydroperoxides but not 7-ketocholesterol.

PMID: 11304477 [PubMed - indexed for MEDLINE]

Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension.

South Med J 2001 Nov;94(11):1112-7

Burke BE, Neuenschwander R, Olson RD.

Research Service, Department of Veterans Affairs Medical Center, Boise, Idaho 83702, USA.

BACKGROUND: Increasing numbers of the adult population are using alternative or complementary health resources in the treatment of chronic medical conditions. Systemic hypertension affects more than 50 million adults and is one of the most common risk factors for cardiovascular morbidity and mortality. This study evaluates the antihypertensive effectiveness of oral coenzyme Q10 (CoQ), an over-the-counter nutritional supplement, in a cohort of 46 men and 37 women with isolated systolic hypertension. METHODS: We conducted a 12-week randomized, double-blind, placebo-controlled trial with twice daily administration of 60 mg of oral CoQ and determination of plasma CoQ levels before and after the 12 weeks of treatment. RESULTS: The mean reduction in systolic blood pressure of the CoQ-treated group was 17.8 +/- 7.3 mm Hg (mean +/- SEM). None of the patients exhibited orthostatic blood pressure changes. CONCLUSIONS: Our results suggest CoQ may be safely offered to hypertensive patients as an alternative treatment option.

PMID: 11780680 [PubMed - indexed for MEDLINE]

Role of coenzyme Q10 in chronic heart failure, angina, and hypertension.

Pharmacotherapy 2001 Jul;21(7):797-806

Tran MT, Mitchell TM, Kennedy DT, Giles JT.

School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.

PURPOSE: Coenzyme Q10 (CoQ10) has a pathophysiologic role in many disease states. The purpose of this review is to provide recommendations regarding the safety, efficacy, and dosing of CoQ10 in the management of chronic heart failure (CHF), angina, and hypertension. DATA SOURCES: Literature pertaining to the safety and efficacy of CoQ10 specifically in cardiovascular indications was reviewed. We used relevant clinical trials, articles, reviews, and letters that were selected from a literature search of the MEDLINE database (1974-2000), Micromedex Healthcare Series, and the Natural Medicines Comprehensive Database. FINDINGS: Coenzyme Q10 administered orally has favorable actions in the described cardiovascular conditions and appears to be safe and well tolerated in the adult population. Issues concerning optimum target dosages, potential interactions, monitoring parameters, and the role of CoQ10 as a monotherapeutic agent need to be investigated further. Favorable effects of CoQ10 on ejection fraction, exercise tolerance, cardiac output, and stroke volume are demonstrated in the literature; thus, the use of CoQ10 as adjuvant therapy in patients with CHF may be supported. CONCLUSIONS: Coenzyme Q10 therapy in angina and hypertension cannot be substantiated until additional clinical trials demonstrate consistent beneficial effects. However, CoQ10 may be recommended as adjuvant therapy in selected patients with CHE At this time, CoQ10 should not be recommended as monotherapy or first-line therapy in any disease state.

PMID: 11444576 [PubMed - indexed for MEDLINE]

Genetic variation and nutrition in relation to coronary artery disease.

J Assoc Physicians India 1999 Dec;47(12):1185-90

Singh RB, Niaz MA.

Heart Research Laboratory, Medical Hospital and Research Centre, Civil Lines, Moradabad-10, UP 244 001.

There is evidence that coronary artery disease (CAD), hypertension, diabetes mellitus (DM) and hyperlipidemia develop due to interaction of genetic and environmental factors during transition from poverty to affluence. Rapid transition in diet and lifestyle factors may influence heritability of the variant phenotypes that are dependent on the nutrient environment for their expression. We are beginning to recognize the interaction of specific nutrients with the genetic code possessed by all nucleated cells. In the next millennium, the physician may be able to make nutrient intake recommendations not on physical characteristics but on the basis of the individual's phenotypic expression for health while suppressing his phenotypic expression for disease. We have demonstrated an increased susceptibility to CAD, diabetes, central obesity, hyperinsulinemia and lipoprotein(a) excess in Indians in younger age groups indicating a genetic predisposition to these problems due to interaction of gene and environment. Lipoprotein(a) is a genetic risk factor for CAD, diabetes and stroke and it is higher in South Indians than North Indians. Antioxidant vitamins, coenzyme Q10 and n-3 fatty acids may have a beneficial influence whereas linoleic acid, saturated fat and sugars may have adverse effects on phenotypic expression. There is significant evidence that genes are involved in determining enzymes, receptors, cofactors, structural components involved in regulation of blood pressure, the metabolism of lipids, lipoproteins and inflammatory and coagulation factors that are involved in determining an individual's risk. Majority of these genes are polymorphic. While some genes respond to nutritional modulation, others may not indicate any response.

PMID: 11225222 [PubMed - indexed for MEDLINE]

Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease.

J Hum Hypertens 1999 Mar;13(3):203-8

Singh RB, Niaz MA, Rastogi SS, Shukla PK, Thakur AS.

NKP Salve Institute of Medical Science, Nagpur, India.

In a randomised, double-blind trial among patients receiving antihypertensive medication, the effects of the oral treatment with coenzyme Q10 (60 mg twice daily) were compared for 8 weeks in 30 (coenzyme Q10: group A) and 29 (B vitamin complex: group B) patients known to have essential hypertension and presenting with coronary artery disease (CAD). After 8 weeks of follow-up, the following indices were reduced in the coenzyme Q10 group: systolic and diastolic blood pressure, fasting and 2-h plasma insulin, glucose, triglycerides, lipid peroxides, malondialdehyde and diene conjugates. The following indices were increased: HDL-cholesterol, vitamins A, C, E and beta-carotene (all changes P<0.05). The only changes in the group taking the B vitamin complex were increases in vitamin C and beta-carotene (P<0.05). These findings indicate that treatment with coenzyme Q10 decreases blood pressure possibly by decreasing oxidative stress and insulin response in patients with known hypertension receiving conventional antihypertensive drugs.

PMID: 10204818 [PubMed - indexed for MEDLINE]

Coenzyme Q in cardiovascular disease.

J Assoc Physicians India 1998 Mar;46(3):299-306

Singh RB, Niaz MA, Rastogi V, Rastogi SS.

Heart Research Laboratory, Medical Hospital and Research Centre, Moradabad, India.

Coenzyme Q10 or ubiquinone normally present in many plant and animal cells is an antioxidant. Coenzyme Q10 deficiency has been observed in patients with congestive heart failure, angina pectoris, coronary artery disease, cardiomyopathy, hypertension, mitral valve prolapse and after coronary revascularization. Coenzyme Q10 is involved in the synthesis of ATP and hence is useful in preventing cellular damage during ischaemia-reperfusion injury. The clinical benefits are mainly due to its ability to improve energy production, antioxidant activity, and membrane stabilizing properties. Several studies showed that coenzyme Q could be useful in patients with congestive heart failure, angina pectoris, cardiomyopathy, coronary artery disease and in the preservation of myocardium. Coenzyme Q10 is normally present in the low density lipoprotein cholesterol fraction and inhibits its oxidation. It can also regenerate vitamin E. Coenzyme Q10 is known for producing minor gastrointestinal discomfort and elevation in SGOT and LDH when used.

PMID: 11273351 [PubMed - indexed for MEDLINE]

Influence of coenzyme Q-10 on the hypotensive effects of enalapril and nitrendipine in spontaneously hypertensive rats.

Pol J Pharmacol 1994 Sep-Oct;46(5):457-61

Danysz A, Oledzka K, Bukowska-Kiliszek M.

Department of Pharmacology, Pharmaceutical Research Institute Rydygiera, Warszawa, Poland.

Administration of coenzyme Q-10 (10 mg/kg) once a day for 4 weeks decreased the arterial blood pressure in SHR's. Enalapril and nitrendipine administered in a single dose caused significant decrease of blood pressure. Application of enalapril and nitrendipine to rats chronically pretreated with coenzyme Q-10 revealed, that the maximal hypotensive effect was not greater, but it lasted much (ca. 2-times) longer. Independently of mechanism of this interaction it may be suggested that the chronic administration of coenzyme Q-10 would create the possibility of significant decrease of the frequency of some antihypertensive drug administration.

PMID: 7894534 [PubMed - indexed for MEDLINE]

Treatment of essential hypertension with coenzyme Q10.

Mol Aspects Med 1994;15 Suppl:S265-72

Langsjoen P, Langsjoen P, Willis R, Folkers K.

Institute for Biomedical Research, University of Texas at Austin 78712, USA.

A total of 109 patients with symptomatic essential hypertension presenting to a private cardiology practice were observed after the addition of CoQ10 (average dose, 225 mg/day by mouth) to their existing antihypertensive drug regimen. In 80 per cent of patients, the diagnosis of essential hypertension was established for a year or more prior to starting CoQ10 (average 9.2 years). Only one patient was dropped from analysis due to noncompliance. The dosage of CoQ10 was not fixed and was adjusted according to clinical response and blood CoQ10 levels. Our aim was to attain blood levels greater than 2.0 micrograms/ml (average 3.02 micrograms/ml on CoQ10). Patients were followed closely with frequent clinic visits to record blood pressure and clinical status and make necessary adjustments in drug therapy. Echocardiograms were obtained at baseline in 88% of patients and both at baseline and during treatment in 39% of patients. A definite and gradual improvement in functional status was observed with the concomitant need to gradually decrease antihypertensive drug therapy within the first one to six months. Thereafter, clinical status and cardiovascular drug requirements stabilized with a significantly improved systolic and diastolic blood pressure. Overall New York Heart Association (NYHA) functional class improved from a mean of 2.40 to 1.36 (P < 0.001) and 51% of patients came completely off of between one and three antihypertensive drugs at an average of 4.4 months after starting CoQ10. Only 3% of patients required the addition of one antihypertensive drug. In the 9.4% of patients with echocardiograms both before and during treatment, we observed a highly significant improvement in left ventricular wall thickness and diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 7752851 [PubMed - indexed for MEDLINE]

Coenzyme Q10 in essential hypertension.

Mol Aspects Med 1994;15 Suppl:s257-63

Digiesi V, Cantini F, Oradei A, Bisi G, Guarino GC, Brocchi A, Bellandi F, Mancini M, Littarru GP.

Third institute of Clinical Medicine and Medical Therapy, University of Florence Medical School, Italy.

This study was undertaken to clarify the mechanism of the antihypertensive effect of coenzyme Q10 (CoQ10). Twenty-six patients with essential arterial hypertension were treated with oral CoQ10, 50 mg twice daily for 10 weeks. Plasma CoQ10, serum total and high-density lipoprotein (HDL) cholesterol, and blood pressure were determined in all patients before and at the end of the 10-week period. At the end of the treatment, systolic blood pressure (SBP) decreased from 164.5 +/- 3.1 to 146.7 +/- 4.1 mmHg and diastolic blood pressure (DBP) decreased from 98.1 +/- 1.7 to 86.1 +/- 1.3 mmHg (P < 0.001). Plasma CoQ10 values increased from 0.64 +/- 0.1 microgram/ml to 1.61 +/- 0.3 micrograms/ml (P < 0.02). Serum total cholesterol decreased from 222.9 +/- 13 mg/dl to 213.3 +/- 12 mg/dl (P < 0.005) and serum HDL cholesterol increased from 41.1 +/- 1.5 mg/dl to 43.1 +/- 1.5 mg/dl (P < 0.01). In a first group of 10 patients serum sodium and potassium, plasma clinostatic and orthostatic renin activity, urinary aldosterone, 24-hour sodium and potassium were determined before and at the end of the 10-week period. In five of these patients peripheral resistances were evaluated with radionuclide angiocardiography. Total peripheral resistances were 2,283 +/- 88 dyne.s.cm-5 before treatment and 1,627 +/- 158 dyn.s.cm-5 after treatment (P < 0.02). Plasma renin activity, serum and urinary sodium and potassium, and urinary aldosterone did not change. In a second group of 11 patients, plasma endothelin, electrocardiogram, two-dimensional echocardiogram and 24-hour automatic blood pressure monitoring were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 7752838 [PubMed - indexed for MEDLINE]

Usefulness of coenzyme Q10 in clinical cardiology: a long-term study.

Mol Aspects Med 1994;15 Suppl:s165-75

Langsjoen H, Langsjoen P, Langsjoen P, Willis R, Folkers K.

University of Texas Medical Branch, Galveston 77551, USA.

Over an eight year period (1985-1993), we treated 424 patients with various forms of cardiovascular disease by adding coenzyme Q10 (CoQ10) to their medical regimens. Doses of CoQ10 ranged from 75 to 600 mg/day by mouth (average 242 mg). Treatment was primarily guided by the patient's clinical response. In many instances, CoQ10 levels were employed with the aim of producing a whole blood level greater than or equal to 2.10 micrograms/ml (average 2.92 micrograms/ml, n = 297). Patients were followed for an average of 17.8 months, with a total accumulation of 632 patient years. Eleven patients were omitted from this study: 10 due to non-compliance and one who experienced nausea. Eighteen deaths occurred during the study period with 10 attributable to cardiac causes. Patients were divided into six diagnostic categories: ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM), primary diastolic dysfunction (PDD), hypertension (HTN), mitral valve prolapse (MVP) and valvular heart disease (VHD). For the entire group and for each diagnostic category, we evaluated clinical response according to the New York Heart Association (NYHA) functional scale, and found significant improvement. Of 424 patients, 58 per cent improved by one NYHA class, 28% by two classes and 1.2% by three classes. A statistically significant improvement in myocardial function was documented using the following echocardiographic parameters: left ventricular wall thickness, mitral valve inflow slope and fractional shortening. Before treatment with CoQ10, most patients were taking from one to five cardiac medications. During this study, overall medication requirements dropped considerably: 43% stopped between one and three drugs. Only 6% of the patients required the addition of one drug. No apparent side effects from CoQ10 treatment were noted other than a single case of transient nausea. In conclusion, CoQ10 is a safe and effective adjunctive treatment for a broad range of cardiovascular diseases, producing gratifying clinical responses while easing the medical and financial burden of multidrug therapy.

PMID: 7752828 [PubMed - indexed for MEDLINE]

Isolated diastolic dysfunction of the myocardium and its response to CoQ10 treatment.

Clin Investig 1993;71(8 Suppl):S140-4

Langsjoen PH, Langsjoen PH, Folkers K.

Symptoms of fatigue and activity impairment, atypical precordial pain, and cardiac arrhythmia frequently precede by years the development of congestive heart failure. Of 115 patients with these symptoms, 60 were diagnosed as having hypertensive cardiovascular disease, 27 mitral valve prolapse syndrome, and 28 chronic fatigue syndrome. These symptoms are common with diastolic dysfunction, and diastolic function is energy dependent. All patients had blood pressure, clinical status, coenzyme Q10 (CoQ10) blood levels and echocardiographic measurement of diastolic function, systolic function, and myocardial thickness recorded before and after CoQ10 replacement. At control, 63 patients were functional class III and 54 class II; all showed diastolic dysfunction; the mean CoQ10 blood level was 0.855 micrograms/ml; 65%, 15%, and 7% showed significant myocardial hypertrophy, and 87%, 30%, and 11% had elevated blood pressure readings in hypertensive disease, mitral valve prolapse and chronic fatigue syndrome respectively. Except for higher blood pressure levels and more myocardial thickening in the hypertensive patients, there was little difference between the three groups. CoQ10 administration resulted in improvement in all; reduction in high blood pressure in 80%, and improvement in diastolic function in all patients with follow-up echocardiograms to date; a reduction in myocardial thickness in 53% of hypertensives and 36% of the combined prolapse and fatigue syndrome groups; and a reduced fractional shortening in those high at control and an increase in those initially low.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 8241699 [PubMed - indexed for MEDLINE]

Effect of coenzyme Q10 on structural alterations in the renal membrane of stroke-prone spontaneously hypertensive rats.

Biochem Med Metab Biol 1991 Apr;45(2):216-26

Okamoto H, Kawaguchi H, Togashi H, Minami M, Saito H, Yasuda H.

Department of Cardiovascular, Hokkaido University, Japan.

To test the hypothesis that structural abnormalities exist in the kidney membrane of spontaneously hypertensive rats, we examined the effect of long-term administration of coenzyme Q10 on membrane lipid alterations in the kidney of stroke-prone spontaneously hypertensive rats (SHRSP). As compared with normotensive Wistar-Kyoto rats, renal membrane phospholipids, especially phosphatidylcholine and phosphatidylethanolamine, decreased and renal phospholipase A2 activity was enhanced with age in untreated SHRSP. Treatment with coenzyme Q10 attenuated the elevation of blood pressure, the membranous phospholipid degradation, and the enhanced phospholipase A2 activity. These results suggest that one factor contributing to the progress of hypertension is a structural membrane abnormality that alters the physical and functional properties of the cell membrane, and coenzyme Q10 might protect the renal membrane from damage due to hypertension in SHRSP.

PMID: 1883628 [PubMed - indexed for MEDLINE]

Co-enzyme Q10: a new drug for cardiovascular disease.

J Clin Pharmacol 1990 Jul;30(7):596-608

Greenberg S, Frishman WH.

Department of Medicine, Mt. Sinai Hospital and Medical Center, New York, New York.

Co-enzyme Q10 (ubiquinone) is a naturally occurring substance which has properties potentially beneficial for preventing cellular damage during myocardial ischemia and reperfusion. It plays a role in oxidative phosphorylation and has membrane stabilizing activity. The substance has been used in oral form to treat various cardiovascular disorders including angina pectoris, hypertension, and congestive heart failure. Its clinical importance is now being established in clinical trails worldwide.

PMID: 2202752 [PubMed - indexed for MEDLINE]

Coenzyme Q10: a new drug for myocardial ischemia?

Med Clin North Am 1988 Jan;72(1):243-58

Greenberg SM, Frishman WH.

Department of Medicine, Mt. Sinai Hospital and Medical School, New York, New York.

A biochemical rationale for using CoQ in treating certain cardiovascular diseases has been established. CoQ subserves an endogenous function as an essential cofactor in several metabolic pathways, particularly oxidative respiration. As an exogenous source in supraphysiologic doses, CoQ may have pharmacologic effects that are beneficial to tissues rendered ischemic and then reperfused. Its mechanism of action appears to be that of a free radical scavenger and/or direct membrane stabilizer. Initial clinical studies performed abroad and in the United States indicate that CoQ may be effective in treating certain patients with ischemic heart disease, congestive heart failure, toxin-induced cardiotoxicity, and possibly hypertension. The most intriguing property of CoQ is its potential to protect and preserve ischemic myocardium during surgery. Currently, CoQ is still considered an experimental agent and only further studies will determine whether it will be useful therapy for human cardiovascular disease states.

PMID: 3276986 [PubMed - indexed for MEDLINE]

Clinical study of cardiac arrhythmias using a 24-hour continuous electrocardiographic recorder (5th report)--antiarrhythmic action of coenzyme Q10 in diabetics.

Tohoku J Exp Med 1983 Dec;141 Suppl:453-63

Fujioka T, Sakamoto Y, Mimura G.

An investigation was undertaken to evaluate the antiarrhythmic effect of CoQ10 on VPBs using the Holter ECG, in 27 patients with no clinical findings of organic cardiopathies. As a result, the effect of CoQ10 on VPBs was considered beneficial in 6 (22%) of 27 cases, consisting of 1 patient with hypertension and 5 patients with DM. Even in the remaining 2 patients with DM, the frequency of VPBs was reduced by 50% or more during treatment with CoQ10. The mean reduction of VPBs frequency in the 5 responders plus these 2 patients with DM was 85.7%. These findings suggest that CoQ10 exhibits an effective antiarrhythmic action not merely on organic heart disease but also on VPBs supervening on DM.

PMID: 6680522 [PubMed - indexed for MEDLINE]

Bioenergetics in clinical medicine. XVI. Reduction of hypertension in patients by therapy with coenzyme Q10.

Res Commun Chem Pathol Pharmacol 1981 Jan;31(1):129-40

Folkers K, Drzewoski J, Richardson PC, Ellis J, Shizukuishi S, Baker L.

Six untreated hypertensive patients and ten on therapy, but having elevated blood pressures, were treated with coenzyme Q10(CoQ10); 14/16 patients showed reductions (p less than 0.05-less than 0.001) in systolic pressures; 11/16 showed reductions (p less than 0.05-less than 0.001) in diastolic pressure; 9/10 showed reductions of elevated pressures to a normal range. By impedance cardiography and electrocardiography, there were no changes in cardiac outputs, stroke volumes and Heather Indices except for a few patients with changes of doubtful biological significance. 3/16 patients had exceptionally low basal specific activities of the succinate dehydrogenase-coenzyme Q10 reductase in blood which increased to a normal range on treatment. A greater deficiency of CoQ10 in the vascular system than in blood is likely. We consider that (1) the mechanism of reduction of elevated blood pressures by CoQ10 is based upon normalization or autoregulation of peripheral resistance rather than cardiac regulation, and (2) that the therapeutic activity of CoQ10 is not pharmacodynamic, but results from a translational increase in levels of CoQ10-enzymes in vascular tissue during ca. 4-12 weeks.

PMID: 7255868 [PubMed - indexed for MEDLINE]

Brain-heart connection and the risk of heart attack.

Antioxidative efficacy of parallel and combined supplementation with coenzyme Q10 and d-alpha-tocopherol in mildly hypercholesterolemic subjects: a randomized placebo-controlled clinical study.

Free Radic Res 2000 Sep;33(3):329-40

Kaikkonen J, Nyyssonen K, Tomasi A, Iannone A, Tuomainen TP, Porkkala-Sarataho E, Salonen JT.

Research Institute of Public Health, University of Kuopio, Finland.

It has been claimed that coenzyme Q10 (Q10) would be an effective plasma antioxidant since it can regenerate plasma vitamin E. To test separate effects and interaction between Q10 and vitamin E in the change of plasma concentrations and in the antioxidative efficiency, we carried out a double-masked, double-blind clinical trial in 40 subjects with mild hypercholesterolemia undergoing statin treatment. Subjects were randomly allocated to parallel groups to receive either Q10 (200 mg daily), d-alpha-tocopherol (700 mg daily), both antioxidants or placebo for 3 months. In addition we investigated the pharmacokinetics of Q10 in a separate one-week substudy. In the group that received both antioxidants, the increase in plasma Q10 concentration was attenuated. Only vitamin E supplementation increased significantly the oxidation resistance of isolated LDL. Simultaneous Q10 supplementation did not increase this antioxidative effect of vitamin E. Q10 supplementation increased and vitamin E decreased significantly the proportion of ubiquinol of total Q10, an indication of plasma redox status in vivo. The supplementations used did not affect the redox status of plasma ascorbic acid. In conclusion, only vitamin E has antioxidative efficiency at high radical flux ex vivo. Attenuation of the proportion of plasma ubiquinol of total Q10 in the vitamin E group may represent in vivo evidence of the Q10-based regeneration of the tocopheryl radicals. In addition, Q10 might attenuate plasma lipid peroxidation in vivo, since there was an increased proportion of plasma ubiquinol of total Q10.

PMID: 10993487 [PubMed - indexed for MEDLINE]

The effect of coenzyme Q10 in patients with congestive heart failure.

Ann Intern Med 2000 Apr 18;132(8):636-40

Khatta M, Alexander BS, Krichten CM, Fisher ML, Freudenberger R, Robinson SW, Gottlieb SS.

University of Maryland School of Medicine and Veterans Affairs Medical Center, Baltimore 21201, USA.

BACKGROUND: Coenzyme Q10 is commonly used to treat congestive heart failure on the basis of data from several unblinded, subjective studies. Few randomized, blinded, controlled studies have evaluated objective measures of cardiac performance. OBJECTIVE: To determine the effect of coenzyme Q10 on peak oxygen consumption, exercise duration, and ejection fraction. DESIGN: Randomized, double-blind, controlled trial. SETTING: University and Veterans Affairs hospitals. PATIENTS: 55 patients who had congestive heart failure with New York Heart Association class III and IV symptoms, ejection fraction less than 40%, and peak oxygen consumption less than 17.0 mL/kg per minute (or <50% of predicted) during standard therapy were randomly assigned. Forty-six patients completed the study. INTERVENTION: Coenzyme Q10, 200 mg/d, or placebo. MEASUREMENTS: Left ventricular ejection fraction (measured by radionuclide ventriculography) and peak oxygen consumption and exercise duration (measured by a graded exercise evaluation using the Naughton protocol) with continuous metabolic monitoring. RESULTS: Although the mean (+/-SD) serum concentration of coenzyme Q10 increased from 0.95+/-0.62 microg/mL to 2.2+/-1.2 microg/mL in patients who received active treatment, ejection fraction, peak oxygen consumption, and exercise duration remained unchanged in both the coenzyme Q10 and placebo groups. CONCLUSION: Coenzyme Q10 does not affect ejection fraction, peak oxygen consumption, or exercise duration in patients with congestive heart failure receiving standard medical therapy.

PMID: 10766682 [PubMed - indexed for MEDLINE]

Coenzyme Q versus hypertension: does CoQ decrease endothelial superoxide generation?

Med Hypotheses 1999 Oct;53(4):300-4

McCarty MF.

Nutrition 21, San Diego, CA 92109, USA.

Reports from several research groups--including two small double-blind clinical studies--indicate that supplemental coenzyme Q10 (CoQ) is moderately effective as a treatment for hypertension, in humans and in animals. Its efficacy is associated with a decrease in total peripheral resistance, and appears to reflect a direct impact of CoQ on the vascular wall. A reasonable interpretation of these findings is that CoQ is acting as an antagonist of vascular superoxide--either scavenging it, or suppressing its synthesis. By improving the efficiency of shuttle mechanisms that transfer high-energy electrons from the cytoplasm to the mitochondrial respiratory chain, CoQ may decrease cytoplasmic NADH levels and thereby diminish the reductive power that drives superoxide synthesis in endothelium and vascular smooth muscle. If CoQ therapy does indeed lower vascular superoxide levels, it can be expected to decrease the atherothrombotic risk associated with hypertension, and may have broader utility in the management of disorders characterized by endotheliopathy.

PMID: 10608264 [PubMed - indexed for MEDLINE]

Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio.

Br J Clin Pharmacol 1996 Sep;42(3):333-7

De Pinieux G, Chariot P, Ammi-Said M, Louarn F, Lejonc JL, Astier A, Jacotot B, Gherardi R.

Groupe de Recherche en Pathologie Neuromusculaire (ER 269), Faculte de Medecine de Creteil, Hopital Henri Mondor, France.

1. Statins inhibit synthesis of mevalonate, a precursor of ubiquinone that is a central compound of the mitochondrial respiratory chain. The main adverse effect of statins is a toxic myopathy possibly related to mitochondrial dysfunction. 2. This study was designed to evaluate the effect of lipid-lowering drugs on ubiquinone (coenzyme Q10) serum level and on mitochondrial function assessed by blood lactate/pyruvate ratio. 3. Eighty hypercholesterolaemic patients (40 treated by statins, 20 treated by fibrates, and 20 untreated patients, all 80 having total cholesterol levels > 6.0 mmol l-1) and 20 healthy controls were included. Ubiquinone serum level and blood lactate/pyruvate ratio used as a test for mitochondrial dysfunction were evaluated in all subjects. 4. Lactate/pyruvate ratios were significantly higher in patients treated by statins than in untreated hypercholesterolaemic patients or in healthy controls (P < 0.05 and P < 0.001). The difference was not significant between fibratetreated patients and untreated patients. 5. Ubiquinone serum levels were lower in statin-treated patients (0.75 mg l-1 +/- 0.04) than in untreated hypercholesterolaemic patients (0.95 mg l-1 +/- 0.09; P < 0.05). 6. We conclude that statin therapy can be associated with high blood lactate/ pyruvate ratio suggestive of mitochondrial dysfunction. It is uncertain to what extent low serum levels of ubiquinone could explain the mitochondrial dysfunction.

PMID: 8877024 [PubMed - indexed for MEDLINE]

Coenzyme Q10 in health and disease.

Eur J Clin Nutr 1999 Oct;53(10):764-70

Overvad K, Diamant B, Holm L, Holmer G, Mortensen SA, Stender S.

The Danish Nutrition Council, Soborg, Denmark.

The literature concerning the importance of coenzyme Q10 in health and disease has been reviewed. Usual dietary intake together with normal in vivo synthesis seems to fulfil the demands for Q10 in healthy individuals. The importance of Q10 supplementation for general health has not been investigated in controlled experiments. The literature allows no firm conclusions about the significance of Q10 in physical activity. In different cardiovascular diseases, including cardiomyopathy, relatively low levels of Q10 in myocardial tissue have been reported. Positive clinical and haemodynamic effects of oral Q10 supplementation have been observed in double-blind trials, especially in chronic heart failure. These effects should be further examined. No important adverse effects have been reported from experiments using daily supplements of up to 200 mg Q10 for 6-12 months and 100 mg daily for up to 6 y.

PMID: 10556981 [PubMed - indexed for MEDLINE]

Bioavailability of four oral coenzyme Q10 formulations in healthy volunteers.

Mol Aspects Med 1994;15 Suppl:s273-80

Weis M, Mortensen SA, Rassing MR, Moller-Sonnergaard J, Poulsen G, Rasmussen SN.

Royal Danish School of Pharmacy, Department of Pharmaceutics, Denmark.

The bioavailability of four different Coenzyme Q10 (CoQ) formulations was compared in ten healthy volunteers in a four-way randomised cross-over trial. The included formulations were: A hard gelatin capsule containing 100 mg of CoQ and 400 mg of Emcompress. Three soft gelatin capsules containing: 100 mg of CoQ with 400 mg of soy bean oil (Bioquinon); 100 mg of CoQ with 20 mg of polysorbate 80, 100 mg of lecithin and 280 mg of soy bean oil; and 100 mg of CoQ with 20 mg of polysorbate 80 and 380 mg of soy bean oil, respectively. The result suggests that the soya bean oil suspension of CoQ (Bioquinon has the highest bioavailability. A difference in basic AUC and AUC after p.o. administration of CoQ was observed with respect to sex. A characteristic two peak-pattern was observed at the concentration-time profile.

PMID: 7752839 [PubMed - indexed for MEDLINE]

Relative bioavailability and antioxidant potential of two coenzyme q10 preparations.

Ann Nutr Metab 2003;47(1):16-21

Kurowska EM, Dresser G, Deutsch L, Bassoo E, Freeman DJ.

KGK Synergize, Inc., London Health Sciences Centre, London, Ont., Canada.

Coenzyme Q10 (CoQ10) is synthesized by the human body and found in certain foods. Daily supplementation of CoQ10 could protect against heart disease but the bioavailability of CoQ10 supplements depends on the formulation taken. We compared the bioavailability and antioxidant properties of two commercial CoQ10 formulations, a commercial grade CoQ10 powder (commercial grade CoQ) and a new BT-CoQ10 BIO-TRANSFORMED((R)) (BT-CoQ10) obtained by fermentation of a soy-based, CoQ10-rich media with baker's yeast. Eleven healthy individuals participated in a randomized two-way crossover trial, with a 3-week washout period. Capsules containing 300 mg of either BT-CoQ10 or commercial grade CoQ10 were given daily for 1 week and multiple blood samples were taken for CoQ10, glutathione and glutathione peroxidase (GPx) determination. In 3 subjects, baseline plasma CoQ10 levels were lower prior to BT than prior to commercial grade CoQ treatment. In the remaining participants, ingestion of BT vs. commercial grade CoQ significantly increased maximum plasma CoQ10 concentration (+126%, p = 0.04) and tended to increase CoQ10 area under the curve from 0 to 24 h (+160%, p = 0.07). One week of treatment with each formulation increased plasma CoQ10 but did not alter plasma glutathione or GPx activity. The enhanced bioavailability of the BT product might be due to its predominantly reduced, hydrophilic membrane-complex form. Copyright 2003 S. Karger AG, Basel

PMID: 12624483 [PubMed - in process]