Life Extension Magazine April 2014
Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure.
BACKGROUND: B-type natriuretic peptide is released from the cardiac ventricles in response to increased wall tension. METHODS: We conducted a prospective study of 1,586 patients who came to the emergency department with acute dyspnea and whose B-type natriuretic peptide was measured with a bedside assay. The clinical diagnosis of congestive heart failure was adjudicated by two independent cardiologists, who were blinded to the results of the B-type natriuretic peptide assay. RESULTS: The final diagnosis was dyspnea due to congestive heart failure in 744 patients (47%), dyspnea due to noncardiac causes in 72 patients with a history of left ventricular dysfunction (5%), and no finding of congestive heart failure in 770 patients (49%). B-type natriuretic peptide levels by themselves were more accurate than any historical or physical findings or laboratory values in identifying congestive heart failure as the cause of dyspnea. The diagnostic accuracy of B-type natriuretic peptide at a cutoff of 100 pg per milliliter was 83.4%. The negative predictive value of B-type natriuretic peptide at levels of less than 50 pg per milliliter was 96%. In multiple logistic-regression analysis, measurements of B-type natriuretic peptide added significant independent predictive power to other clinical variables in models predicting which patients had congestive heart failure. CONCLUSIONS: Used in conjunction with other clinical information, rapid measurement of B-type natriuretic peptide is useful in establishing or excluding the diagnosis of congestive heart failure in patients with acute dyspnea.
N Engl J Med. 2002 Jul 18;347(3):161-7
Metabolic cardiology: the missing link in cardiovascular disease.
The importance of supporting energy production in heart cells and the preservation of the mitochondria in these cells will be the focus of a new frontier in cardiovascular prevention, treatment, and management. Many physicians are not trained to look at heart disease in terms of cellular biochemistry; therefore, the challenge in any metabolic cardiology discussion is in taking the conversation from the “bench to the bedside.” An understanding of the vital role that adenosine triphosphate (ATP) plays in the heart is critical for any physician or clinician considering therapeutic options that support ATP production and turnover in jeopardized cardiac muscle cells. Metabolic therapies that help cardiomyocytes meet their absolute need for ATP fulfill a major clinical challenge of preserving pulsatile cardiac function while maintaining cell and tissue viability. D-ribose, L-carnitine, and coenzyme Q10 work in synergy to help the ischemic or hypoxic heart preserve its energy charge. This article introduces how ATP, diastolic heart function, and metabolic support help maintain cardiac energy by preserving ATP substrates. Part 2 will investigate an in-depth biochemical discussion of congestive heart failure with physiologic, pathophysiologic, and treatment considerations.
Altern Ther Health Med. 2009 Mar-Apr;15(2):48-50
Endothelial aging associated with oxidative stress can be modulated by a healthy mediterranean diet.
Aging is a condition which favors the development of atherosclerosis, which has been associated with a breakdown in repair processes that occurs in response to cell damage. The dysregulation of the biological systems associated with aging are produced partly through damage which accumulates over time. One major source of this injury is oxidative stress, which can impair biological structures and the mechanisms by which they are repaired. These mechanisms are based on the pathogenesis of endothelial dysfunction, which in turn is associated with cardiovascular disease, carcinogenesis and aging. The dependent dysfunction of aging has been correlated with a reduction in the number and/or functional activity of endothelial progenitor cells, which could hinder the repair and regeneration of the endothelium. In addition, aging, inflammation and oxidative stress are endogenous factors that cause telomere shortening, which is dependent on oxidative cell damage. Moreover, telomere length correlates with lifestyle and the consumption of a healthy diet. Thus, diseases associated with aging and age may be caused by the long-term effects of oxidative damage, which are modified by genetic and environmental factors. Considering that diet is a very important source of antioxidants, in this review we will analyze the relationship between oxidative stress, aging, and the mechanisms which may be involved in a higher survival rate and a lower incidence of the diseases associated with aging in populations which follow a healthy diet.
Int J Mol Sci. 2013 Apr 24;14(5):8869-89
Relationship between plasma coenzyme Q10, asymmetric dimethylarginine and arterial stiffness in patients with phenotypic or genotypic familial hypercholesterolemia on long-term statin therapy.
OBJECTIVE: We investigated whether statin-treated heterozygous familial hypercholesterolemic (FH) patients have lower plasma coenzyme Q(10) (CoQ(10)) levels than low-density lipoprotein receptor (LDLR) mutation negative FH patients on equivalent statin doses, and whether lower CoQ(10) concentrations are associated with increased arterial stiffness. METHODS: Thirty LDLR mutation negative patients with clinical FH and 30 mutation positive FH patients matched for gender, statin duration and dose, and a further 30 controls were studied. Plasma CoQ(10) and asymmetric dimethylarginine (ADMA) levels were measured by HPLC and the augmentation index by pulse wave analysis. RESULTS: Plasma CoQ(10) levels, and the ratios of CoQ(10) to total cholesterol and LDL-cholesterol were similar in treated FH patients with identified LDLR mutations to mutation negative patients on equivalent doses of statin therapy (p>0.05). CoQ(10) and lipid levels were also comparable to controls not using any lipid modifying treatment. Arterial stiffness was higher in mutation negative patients (p=0.04) and there was a trend for an increase in mutation positive patients (p=0.09). ADMA was higher in the mutation positive group (p<0.01). The augmentation index corrected for age, blood pressure, and heart rate, was negatively correlated with plasma CoQ(10) within FH patients (p<0.05). CONCLUSION: Long-term, high-dose statin therapy does not lead to subnormal CoQ(10) concentrations in patients with phenotypic or genotypic FH. Arterial stiffness is elevated in FH patients compared to untreated controls, and low CoQ(10) levels are associated with increased arterial stiffness. CoQ(10) supplementation trials are warranted in FH patients.
Atherosclerosis. 2011 Sep;218(1):188-93
Effects of coenzyme Q10 supplementation on activities of selected antioxidative enzymes and lipid peroxidation in hypertensive patients treated with indapamide. A pilot study.
INTRODUCTION: An increase in oxidative stress is strongly documented in hypertensive patients. In blood vessels, oxidative stress increases the production of superoxide anion (O(2) (•-)) that reacts with nitric oxide (NO) and impairs the ability of endothelium to relax. Many reports indicate a beneficial effect of coenzyme Q10 (CoQ) in hypertension. Coenzyme Q10 therapy may lower O(2) (•-) and thus decrease the complications associated with hypertension. The aim of our study was to evaluate the effects of CoQ supplementation on antioxidative enzyme activities and lipid peroxidation in elderly hypertensive patients. MATERIAL AND METHODS: We determined the activities of superoxide dismutase (SOD-1) and glutathione peroxidase (GSH-Px) and the concentration of malondialdehyde (MDA) in erythrocytes of 27 elderly (mean age 72.5 ±6.1 year) hypertensive patients treated with indapamide at baseline and after 12 weeks of CoQ supplementation (60 mg twice a day) in comparison with 30 healthy elderly volunteers (mean age 76.8 ±8.5 year). RESULTS: Decrease of SOD-1 (p < 0.001) and insignificant reduction of GSH-Px activities and increase of MDA (p < 0.001) level were observed in hypertensive patients in comparison to healthy volunteers before supplementation. Coenzyme Q10 administration resulted in a significant increase only in SOD-1 activity (p < 0.001). CONCLUSIONS: The present study indicates that CoQ improves the most important component of the antioxidant defence system - SOD-1, which is responsible for O(2) (•-) scavenging. Coenzyme Q10 may be used as an additional therapeutic agent for prophylaxis and treatment of hypertension in elderly patients.
Arch Med Sci. 2010 Aug 30;6(4):513-8
The role of oral coenzyme Q10 in patients undergoing coronary artery bypass graft surgery.
OBJECTIVE: Cardiopulmonary bypass (CPB) is known to induce oxidative stress. Because total antioxidant level is reduced during CPB, the supplementation of an antioxidant might help in attenuating the oxidative stress response. The authors sought to evaluate the efficacy of oral coenzyme Q10, in attenuating the oxidative stress to CPB and altering the clinical outcome in patients undergoing coronary artery bypass graft (CABG) surgery. DESIGN: A prospective, randomized, single-center clinical study. SETTING: A cardiothoracic center of a tertiary hospital. PARTICIPANTS: Thirty patients scheduled for elective CABG surgery. INTERVENTIONS: The study group (n = 15) received oral coenzyme Q10, 150 to 180 mg/d, for 7 to 10 days preoperatively, whereas the control group (n = 15) did not receive any antioxidant or placebo. The anesthesia technique was standardized in both groups. Blood samples for total antioxidant level, blood glucose level, and clinical outcome parameters up to 24 hours postoperatively were compared. MEASUREMENTS AND MAIN RESULTS: There was no difference in the antioxidant level between the 2 groups at any point of time. However, in the study group, 24 hours after aortic clamp release, it was significantly higher than baseline (p < 0.05). The blood glucose was significantly lower in the study group at aortic clamp removal and 4 hours after clamp removal as compared with the control group (p = 0.01). The study group had significantly fewer reperfusion arrhythmias, lower total inotropic requirement, mediastinal drainage, blood product requirement, and shorter hospital stays compared with the control group. CONCLUSION: Oral coenzyme Q10 therapy for 7 to 10 days preoperatively could improve clinical outcome in patients undergoing CABG surgery. A larger study group is recommended for confirmation.
J Cardiothorac Vasc Anesth. 2008 Dec;22(6):832-9
Augmented efficacy of tamoxifen in rat breast tumorigenesis when gavaged along with riboflavin, niacin, and CoQ10: effects on lipid peroxidation and antioxidants in mitochondria.
Reactive oxygen species (ROS) play a major role in causing mitochondrial changes linked to cancer and metastasis. Uptake of antioxidants by tissue to reduce the ROS production could be instrumental in controlling cancer. Tamoxifen (TAM), a nonsteroidal anti-estrogen drug most used in the chemotherapy and chemoprevention of breast cancer. Riboflavin, niacin and coenzyme Q10 (CoQ10) are proved to be potent antioxidants and protective agents against many diseases including cancer. The objective of this research is to determine the therapeutic efficacy of combinatorial therapy on mammary carcinoma bearing rats in terms of the mitochondrial lipid peroxidation and antioxidant status especially MnSOD. Female albino rats of Sprague-Dawley strain were selected for the investigation. Mammary carcinoma was induced with 7,12-dimethyl benz(a)anthracene (DMBA: 25 mg), and the treatment was started by the oral administration of TAM (10 mg/kg body weight/day) along with riboflavin (45 mg/kg body weight/day), niacin (100 mg/kg body weight/day) and CoQ10 (40 mg/kg body weight/day) for 28 days. The levels of lipid peroxides, activities of enzymic and non-enzymic antioxidants were measured in the mitochondria isolated from the mammary gland and liver of control and experimental rats. Rats treated with DMBA showed an increase in mitochondrial lipid peroxidation (mammary gland 52.3%; liver 25.1%) accompanied by high malondialdehyde levels along with lowered activities of mitochondrial enzymic antioxidants [superoxide dismutase (mammary gland 19.9%; liver 24.8%), catalase (mammary gland 50%; liver 19.7%), glutathione peroxidase (mammary gland 47.8%; liver 31.1%)] and non-enzymic antioxidants [reduced glutathione (mammary gland 14.3%; liver 13.3%), Vitamin C (mammary gland 6.49%; liver 21.4%) and E (mammary gland 20.3%; liver 22.2%)]. Administration of combinatorial therapy restored lipid peroxide level and the activities of enzymic and non-enzymic antioxidants to near normalcy. In addition, antitumour activity was also found to be enhanced which is evident from the increased expression of tumour suppressor gene MnSOD thereby preventing cancer cell proliferation. These results suggested that TAM treatment is the most effective during co-administration of riboflavin, niacin and CoQ10 in terms of mitochondrial antioxidant and antitumour activity.
Chem Biol Interact. 2005 Feb 28;152(1):49-58
Suppression of azoxymethane-induced colonic premalignant lesion formation by coenzyme Q10 in rats.
Reactive oxygen species cause damage to proteins, lipids and DNA. Coenzyme Q10 (CoQ10) is a compound with mitochondrial bioenergetic functions. The reduced form of CoQ10 shows antioxidant activity. In the present study, effects of CoQ10 on development of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and mucin-depleted foci (MDF) in F344 male rats were investigated. To induce ACF and MDF, 6-week old rats were given two weekly subcutaneous injections of AOM (15 mg/kg body weight) and also received a control diet or experimental diets containing CoQ10 (200 or 500 ppm) for 4 weeks, starting one day before the first dose of AOM. At 10 weeks of age, all animals were sacrificed and their colons were evaluated for numbers and sizes of ACF and MDF. Administration of 200 and 500 ppm CoQ10 resulted in reduction of ACF numbers, to 77% and 68% of the carcinogen control value, respectively. The percentages of ACF consisting of more than 4 crypts in these groups were also significantly lower than in the controls. Treatment with 500 ppm CoQ10 furthermore decreased the number of sialomucin-producing ACF and MDF per colon to 42% and 38% of the carcinogen control value without CoQ10, respectively. These results suggest that CoQ10 may be an effective chemopreventive agent against colon carcinogenesis.
Asian Pac J Cancer Prev. 2006 Oct-Dec;7(4):599-603
Coenzyme Q10 attenuated DMH-induced precancerous lesions in SD rats.
Coenzyme Q10 (CoQ10) is known to be a compound with mitochondrial bioenergetic functions and antioxidant activity. In this study, we evaluated the effect of CoQ10 on the formation of aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH), DMH-induced leukocytic DNA damage and gene expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by real-time PCR in colonic mucosa of male SD rats. The animals were divided into three groups and fed a casein-based high-fat and low fiber diet (100 g lard+20 g cellulose/kg diet) with or without CoQ10 (0.4 mg in soybean oil/kg BW/d, i.p.). One week after beginning the diets, the rats were subjected to 6 wk of treatment with DMH (30 mg/kg/wk, s.c.) and CoQ10 treatments continued over the entirety of the experimental period (59 d). Administration of CoQ10 resulted in reduction of ACF numbers, to 20% of the carcinogen control value. CoQ10 supplementation induced an antigenotoxic effect on DMH-induced DNA damage in the blood cells. Colonic mucosa of DMH-injected rats had significantly greater COX-2 and iNOS gene expression than those of control rats, while treatment with CoQ10 induced an inhibitory effect on over-expression of COX-2 and iNOS in colon tumors. Our results provide evidence that CoQ10 has a protective effect on the process of colon carcinogenesis, suppressing the development of preneoplastic lesions, possibly by modulating COX-2 and iNOS gene expression in colonic mucosa and DNA damage in leukocytes, suggesting that CoQ10 has chemotherapeutic activity.
J Nutr Sci Vitaminol (Tokyo). 2010;56(2):139-44
Coenzyme Q10 to Treat Neurological Disorders: Basic Mechanisms, Clinical Outcomes, and Future Research Direction.
Coenzyme Q10 (CoQ10) plays a pivotal role in mitochondrial respiratory chain which is the cell power supply. CoQ10 serves as a physiological electron (e-) shuttle from complexes I and II to complex III, as well as a potent antioxidant. Neurons are characterized by high rates of metabolic activity and need to respond promptly to activity-dependent fluctuations in bioenergetic demand. Consequently, it is not surprising that mitochondrial alterations can promote neuronal dysfunction and degeneration. In several neurological disorders, dysfunction of the respiratory chain leads to reduced ATP levels and increased generation of reactive oxygen species. CoQ10 supplementation has been widely used to treat aging, stroke, neuromuscular diseases, Parkinson’s disease, Alzheimer’s disease, progressive supranuclear palsy, autosomal recessive cerebellar ataxias, amyotrophic lateral sclerosis and Huntington’s disease. Here we discuss a large number of preclinical and clinical trials for CoQ10. The mechanisms underlying the disease-modifying effects of CoQ10 are the principle subject of the current integrative review. The rational applications as a therapeutic agent in neurological disorders are discussed.
CNS Neurol Disord Drug Targets. 2013 Apr 4
Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer’s disease.
Increased oxidative stress is implicated in the pathogenesis of Alzheimer’s disease (AD). A large body of evidence suggests that mitochondrial dysfunction and increased reactive oxygen species occur prior to amyloid-b (Ab) deposition. Coenzyme Q10 (CoQ10), a component of the mitochondrial electron transport chain, is well characterized as a neuroprotective antioxidant in animal models and human trials of Huntington’s disease and Parkinson’s disease, and reduces plaque burden in AbPP/PS1 mice. We now show that CoQ10 reduces oxidative stress and amyloid pathology and improves behavioral performance in the Tg19959 mouse model of AD. CoQ10 treatment decreased brain levels of protein carbonyls, a marker of oxidative stress. CoQ10 treatment resulted in decreased plaque area and number in hippocampus and in overlying cortex immunostained with an Ab42-specific antibody. Brain Ab42 levels were also decreased by CoQ10 supplementation. Levels of amyloid-b protein precursor (AbPP) b-carboxyterminal fragments were decreased. Importantly, CoQ10-treated mice showed improved cognitive performance during Morris water maze testing. Our results show decreased pathology and improved behavior in transgenic AD mice treated with the naturally occurring antioxidant compound CoQ10. CoQ10 is well tolerated in humans and may be promising for therapeutic trials in AD.
J Alzheimers Dis. 2011;27(1):211-23