Background: Mitochondria are both the cellular powerhouse and the major source of reactive oxygen species. Coenzyme Q(10) plays a key role in mitochondrial energy production and is recognized as a powerful antioxidant. For these reasons it can be argued that higher mitochondrial ubiquinone levels may enhance the energy state and protect from oxidative stress. Despite the large number of clinical studies on the effect of CoQ(10) supplementation, there are very few experimental data about the mitochondrial ubiquinone content and the cellular bioenergetic state after supplementation. Controversial clinical and in vitro results are mainly due to the high hydrophobicity of this compound, which reduces its bioavailability.

Principal Findings: We measured the cellular and mitochondrial ubiquinone content in two cell lines (T67 and H9c2) after supplementation with a hydrophilic CoQ(10) formulation (Qter®) and native CoQ(10). Our results show that the water soluble formulation is more efficient in increasing ubiquinone levels. We have evaluated the bioenergetics effect of ubiquinone treatment, demonstrating that intracellular CoQ(10) content after Qter supplementation positively correlates with an improved mitochondrial functionality (increased oxygen consumption rate, transmembrane potential, ATP synthesis) and resistance to oxidative stress.

Conclusions: The improved cellular energy metabolism related to increased CoQ(10) content represents a strong rationale for the clinical use of coenzyme Q(10) and highlights the biological effects of Qter®, that make it the eligible CoQ(10) formulation for the ubiquinone supplementation.

Background: Exhausting exercise induces muscle damage associated with high production of free radicals and pro-inflammatory mediators.

Aim: The objective of this study was to determine for the first time and simultaneously whether oral coenzyme Q(10) (CoQ(10)) supplementation can prevent over-expression of inflammatory mediators and oxidative stress associated with strenuous exercise.

Methods: The participants were classified in two groups: CoQ(10) group (CG) and placebo group (PG). The physical test consisted in a constant run (50 km) that combined several degrees of high effort (mountain run and ultra-endurance), in permanent climbing.

Results: Exercise was associated with an increase in TNF-α, IL-6, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and isoprostane levels, revealing the degree of inflammation and oxidative stress induced. Oral supplementation of CoQ(10) during exercise was efficient reducing oxidative stress (decreased membrane hydroperoxides, 8-OHdG and isoprostanes generation, increased catalase, and total antioxidant status), which would lead to the maintenance of the cell integrity. Data obtained also indicate that CoQ(10) prevents over-expression of TNF-α after exercise, together with an increase in sTNF-RII that limits the pro-inflammatory actions of TNF. Moreover, CoQ(10) supplementation reduced creatinine production.

Conclusions: CoQ(10) supplementation before strenuous exercise decreases the oxidative stress and modulates the inflammatory signaling, reducing the subsequent muscle damage.

Studies about Coenzyme Q (CoQ ) supplementation on strenuous exercise are scarce, especially those related with oxidative stress associated with physical activity and virtually nonexistent with the reduced form, Ubiquinol. The objective of this study was to determine, for the first time, whether a short-term supplementation with Ubiquinol can prevent oxidative stress associated to strenuous exercise. The participants (n = 100 healthy and well trained, but not on an elite level) were classified in two groups: Ubiquinol (experimental group), and placebo group (control). The protocol consisted of conducting two identical strenuous exercise tests with a rest period between tests of 24 h. Blood and urine samples were collected from the participants before supplementation (basal value) (T1), after supplementation (2 weeks) (T2), after first physical exercise test (T3), after 24 h of rest (T4), and after second physical exercise test (T5).The increase observed in the lactate, isoprostanes, DNA damage, and hydroperoxide levels reveals the severity of the oxidative damage induced by the exercise. There was a reduction in the isoprostanes, 8-OHdG, oxidized LDL, and hydroperoxydes in the supplemented Ubiquinol group, an increase in total antioxidant status, fat soluble antioxidant (both plasma and membrane), and CAT activity. Also, NO in the Ubiquinol-supplemented group was maintained within a narrow range. Oxidative stress induced by strenuous exercise is accumulative and increases transiently in subsequent sessions of physical activity. A short-term supplementation (2 weeks) with Ubiquinol (200 mg/day) before strenuous exercise, decreases oxidative stress and increases plasma NO, fact that could improve endothelial function, energetic substrate supply, and muscle recovery after strenuous exercise. © 2016 BioFactors, 42(6):612-622, 2016.

This study reports the effects of Q10, coenzyme Q10 or ubiquinone, a component of the electron transport chain in mitochondria, on nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), inhibitors of kappa B (IκB), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and hemeoxygenase 1 (HO-1) in rats after chronic exercise training for 6 weeks. 8-week old male Wistar rats were assigned randomly to one of four treatments planned in a 2 x 2 factorial arrangement of two condition (sedentary vs. exercise training), and two coenzyme Q10 levels (0 and 300 mg/kg per day for 6 weeks). The expression levels of the target proteins were determined in the heart, liver and muscle, and biochemical parameters including creatinine, urea, glucose and lipid profile were investigated in plasma. When compared with sedentary group, significant decreases in heart, liver and muscle NFκB levels by 45%, 26% and 44% were observed in Q10 supplemented rats after exercise training, respectively, while the inhibitory protein IκB increased by 179%, 111% and 127% in heart, liver and muscle tissues. Q10 supplementation caused an increase in Nrf2 (167%, 165% and 90%) and HO-1 (107%, 156% and 114%) after exercise training in heart, liver and muscle tissues (p < 0.05). No significant change was observed in any of the parameters associated with protein, carbohydrate and lipid metabolism, except that exercise caused a decrease in plasma triglyceride, which was further decreased by Q10. In conclusion, these results suggest that Q10 modulates the expression of NFκB, IκB, Nrf2 and HO-1 in exercise training, indicating an anti-inflammatory effect of Q10 and emphasizes its role in antioxidant defense. Key pointsCoenzyme Q10 is a component of the electron transport chain in mitochondria which is linked to the generation of energy in the cell.Coenzyme Q10 may inhibit the peroxidation of lipids, thus acting as an antioxidant and protects tissue against oxidative injury.Using of coenzyme Q10 can significantly elevate IκB, Nrf2 and HO-1 and reduce NFκB during exercise training.

Statins are cholesterol-lowering drugs widely used in the prevention of cardiovascular diseases; however, they are associated with various types of myopathies. Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and thus decrease biosynthesis of low-density lipoprotein cholesterol and may also reduce ubiquinones, essential coenzymes of a mitochondrial electron transport chain, which contain isoprenoid residues, synthesized through an HMG-CoA reductase-dependent pathway. Therefore, we hypothesized that statin treatment might influence physical performance through muscular mitochondrial dysfunction due to ubiquinone deficiency. The effect of two statins, atorvastatin and pravastatin, on ubiquinone content, mitochondrial function, and physical performance was examined by using statin-treated mice. Changes in energy metabolism in association with statin treatment were studied by using cultured myocytes. We found that atorvastatin-treated mice developed muscular mitochondrial dysfunction due to ubiquinone deficiency and a decrease in exercise endurance without affecting muscle mass and strength. Meanwhile, pravastatin at ten times higher dose of atorvastatin had no such effects. In cultured myocytes, atorvastatin-related decrease in mitochondrial activity led to a decrease in oxygen utilization and an increase in lactate production. Conversely, coenzyme Q(10) treatment in atorvastatin-treated mice reversed atorvastatin-related mitochondrial dysfunction and a decrease in oxygen utilization, and thus improved exercise endurance. Atorvastatin decreased exercise endurance in mice through mitochondrial dysfunction due to ubiquinone deficiency. Ubiquinone supplementation with coenzyme Q(10) could reverse atorvastatin-related mitochondrial dysfunction and decrease in exercise tolerance.

Background: Exercise increases skeletal muscle reactive oxygen species (ROS) production, which may contribute to the onset of muscular fatigue and impair athletic performance. Mitochondria-targeted antioxidants such as MitoQ, which contains a ubiquinone moiety and is targeted to mitochondria through the addition of a lipophilic triphenylphosphonium cation, are becoming popular amongst active individuals as they are designed to accumulate within mitochondria and may provide targeted protection against exercise-induced oxidative stress. However, the effect of MitoQ supplementation on cycling performance is currently unknown. Here, we investigate whether MitoQ supplementation can improve cycling performance measured as time to complete an 8 km time trial.

Method: In a randomized, double-blind, placebo-controlled crossover study, 19 middle-aged (age: 44 ± 4 years) recreationally trained (

Vo: 58.5 ± 6.2 ml·kg·min, distance cycled per week during 6 months prior to study enrollment: 158.3 ± 58.4 km) male cyclists completed 45 min cycling at 70% VO followed by an 8 km time trial after 28 days of supplementation with MitoQ (20 mg·day) and a placebo. Free F-isoprostanes were measured in plasma samples collected at rest, after 45 min cycling at 70% VO and after completion of the time trial. Respiratory gases and measures of rating of perceived exertion (RPE) were also collected.

Results: Mean completion time for the time trial was 1.3% faster with MitoQ (12.91 ± 0.94 min) compared to placebo (13.09 ± 0.95 min, p = 0.04, 95% CI [0.05, 2.64], d = 0.2). There was no difference in RPE during the time trial between conditions (p = 0.82) despite there being a 4.4% increase in average power output during the time trial following MitoQ supplementation compared to placebo (placebo; 270 ± 51 W, MitoQ; 280 ± 53 W, p = 0.04, 95% CI [0.49, 8.22], d = 0.2). Plasma F-isoprostanes were lower on completion of the time trial following MitoQ supplementation (35.89 ± 13.6 pg·ml) compared to placebo (44.7 ± 16.9 pg·ml p = 0.03).

Conclusion: These data suggest that MitoQ supplementation may be an effective nutritional strategy to attenuate exercise-induced increases in oxidative damage to lipids and improve cycling performance.

Ubiquinol (QH), a reduced form of coenzyme Q10, is a lipid antioxidant that is hydro-soluble and is commonly formulated in commercial supplements. Ubiquinol has been increasingly reported to exert antioxidant functions, in addition to its role in the cell energy-producing system of mitochondria and adenosine triphosphate (ATP) production. The aim of this study was to assess the potential beneficial effects of QH on anti-fatigue and ergogenic functions following physiological challenge. Forty 8-week-old male Institute of Cancer Research (ICR) mice were divided into four groups ( = 10 for each group): Group 1 (vehicle control or oil only); Group 2 (1X QH dose or 102.5 mg/kg); Group 3 (2X QH dose or 205 mg/kg); Group 4 (6X QH dose or 615 mg/kg). Anti-fatigue activity and exercise performance were studied using the forelimb grip strength experiment and exhaustive weight-loaded swimming time, and levels of serum lactate, ammonia, glucose, BUN (blood urea nitrogen), creatine kinase (CK), and free fatty acids (FFA) after an acute exercise challenge. The forelimb grip strength and exhaustive weight-loaded swimming time of the QH-6X group were significantly higher than those of the other groups. QH supplementation dose-dependently reduced serum lactate, ammonia, and CK levels and increased the FFA concentration after acute exercise. In addition, QH increased the liver and muscle glycogen content, an important energy source during exercise. Therefore, the results suggest that QH formulation is a safe dietary supplement for amelioration of fatigue and for promoting exercise performance.

The aim of this study was to investigate the effects of a combination of nutrients on physical performance, oxidative stress and mitochondrial biogenesis in rats subjected to exhaustive exercise. Rats were divided into sedentary control (SC), exhaustive exercise (EC) and exhaustive exercise with nutrient supplementation (EN). The nutrients include (mg/kg/day): R-α-lipoic acid 50, acetyl-L-carnitine 100, biotin 0.1, nicotinamide 15, riboflavin 6, pyridoxine 6, creatine 50, CoQ10 5, resveratrol 5 and taurine 100. Examination of running distances over the 4-week period revealed that EN rats ran significantly longer throughout the entire duration of the exhaustive exercise period compared with the EC rats. Nutrient supplementation significantly inhibited the increase in activities of alanine transaminase, lactate dehydrogenase and creatine kinase, reversed increases in malondialdehyde, inhibited decreases in glutathione S-transferase and total antioxidant capacity in plasma, and suppressed the elevation of reactive oxygen species and apoptosis in splenic lymphocytes. Nutrient supplementation increased the protein expression of mitochondrial complexes I, II and III, mtDNA number and transcription factors involved in mitochondrial biogenesis and fusion in skeletal muscle. These findings suggest that mitochondrial nutrient supplementation can reduce exhaustive exercise-induced oxidative damage and mitochondrial dysfunction, thus leading to enhancement of physical performance and of fatigue recovery.

Oxidative damage is related to aging and a wide range of human disorders. Mitochondria are in large part responsible for free radical production and they are also main targets of the attack of these toxic molecules. The resulting deleterious effects of the damage to mitochondria can be prevented by antioxidants. Melatonin is an endogenously-produced indoleamine that modulates numerous functions, including mitochondria-related functions; this result from its capacity to penetrate all morphophysiological barriers and to enter all subcellular compartments due to its amphiphilic nature. Furthermore, this indoleamine and its metabolites are powerful antioxidants and scavengers of free radicals, protecting cellular membranes, the electron transport chain and mitochondrial DNA from oxidative damage. These properties may make melatonin a potent protector against a variety of free radical-related diseases. By comparison, other conventional antioxidants have less efficacy due to their limited access to the mitochondria. In recent years, research has focused on the advancement of mitochondria-targeted antioxidants, such as MitoQ (composed by the lipophilic triphenylphosphonium cation conjugated to the endogenous antioxidant coenzyme Q10) and MitoE (composed by the triphenylphosphonium cation attached to the antioxidant α-tocopherol). Mitochondria-targeted antioxidants accumulate in several hundred-fold greater concentrations within mitochondria and protect these critical organelles from oxidative damage. Melatonin also seems to be a mitochondria-targeted antioxidant and has similar protective actions as the synthetic antioxidants. Further work is required to determine the therapeutic properties of these antioxidants in ameliorating diseases related to mitochondrial dysfunction.

Statins are cholesterol-lowering drugs widely used in the prevention of cardiovascular diseases; however, they are associated with various types of myopathies. Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and thus decrease biosynthesis of low-density lipoprotein cholesterol and may also reduce ubiquinones, essential coenzymes of a mitochondrial electron transport chain, which contain isoprenoid residues, synthesized through an HMG-CoA reductase-dependent pathway. Therefore, we hypothesized that statin treatment might influence physical performance through muscular mitochondrial dysfunction due to ubiquinone deficiency. The effect of two statins, atorvastatin and pravastatin, on ubiquinone content, mitochondrial function, and physical performance was examined by using statin-treated mice. Changes in energy metabolism in association with statin treatment were studied by using cultured myocytes. We found that atorvastatin-treated mice developed muscular mitochondrial dysfunction due to ubiquinone deficiency and a decrease in exercise endurance without affecting muscle mass and strength. Meanwhile, pravastatin at ten times higher dose of atorvastatin had no such effects. In cultured myocytes, atorvastatin-related decrease in mitochondrial activity led to a decrease in oxygen utilization and an increase in lactate production. Conversely, coenzyme Q(10) treatment in atorvastatin-treated mice reversed atorvastatin-related mitochondrial dysfunction and a decrease in oxygen utilization, and thus improved exercise endurance. Atorvastatin decreased exercise endurance in mice through mitochondrial dysfunction due to ubiquinone deficiency. Ubiquinone supplementation with coenzyme Q(10) could reverse atorvastatin-related mitochondrial dysfunction and decrease in exercise tolerance.

Background: Exercise increases skeletal muscle reactive oxygen species (ROS) production, which may contribute to the onset of muscular fatigue and impair athletic performance. Mitochondria-targeted antioxidants such as MitoQ, which contains a ubiquinone moiety and is targeted to mitochondria through the addition of a lipophilic triphenylphosphonium cation, are becoming popular amongst active individuals as they are designed to accumulate within mitochondria and may provide targeted protection against exercise-induced oxidative stress. However, the effect of MitoQ supplementation on cycling performance is currently unknown. Here, we investigate whether MitoQ supplementation can improve cycling performance measured as time to complete an 8 km time trial.

Method: In a randomized, double-blind, placebo-controlled crossover study, 19 middle-aged (age: 44 ± 4 years) recreationally trained (

Vo: 58.5 ± 6.2 ml·kg·min, distance cycled per week during 6 months prior to study enrollment: 158.3 ± 58.4 km) male cyclists completed 45 min cycling at 70% VO followed by an 8 km time trial after 28 days of supplementation with MitoQ (20 mg·day) and a placebo. Free F-isoprostanes were measured in plasma samples collected at rest, after 45 min cycling at 70% VO and after completion of the time trial. Respiratory gases and measures of rating of perceived exertion (RPE) were also collected.

Results: Mean completion time for the time trial was 1.3% faster with MitoQ (12.91 ± 0.94 min) compared to placebo (13.09 ± 0.95 min, p = 0.04, 95% CI [0.05, 2.64], d = 0.2). There was no difference in RPE during the time trial between conditions (p = 0.82) despite there being a 4.4% increase in average power output during the time trial following MitoQ supplementation compared to placebo (placebo; 270 ± 51 W, MitoQ; 280 ± 53 W, p = 0.04, 95% CI [0.49, 8.22], d = 0.2). Plasma F-isoprostanes were lower on completion of the time trial following MitoQ supplementation (35.89 ± 13.6 pg·ml) compared to placebo (44.7 ± 16.9 pg·ml p = 0.03).

Conclusion: These data suggest that MitoQ supplementation may be an effective nutritional strategy to attenuate exercise-induced increases in oxidative damage to lipids and improve cycling performance.

Introduction: Mitochondrial dysfunction causes myocardial disease. This study investigated the effects of MitoQ alone and in combination with moderate-intensity endurance training (EX) on cardiac function and content and mRNA expression of several proteins involved in mitochondrial quality control in isoproterenol (ISO)-induced heart injuries

Methods: Seven groups of CTL, ISO, ISO-EX, ISO-MitoQ-125, ISO-MitoQ-250, ISO-EX+MitoQ-125, and ISO-EX+MitoQ-250 were assigned. Rats were trained on a treadmill, and the MitoQ groups received MitoQ in drinking water for 8 weeks, starting one week after the induction of heart injury. Arterial pressure and cardiac function indices, mRNA expression, protein content, oxidant and antioxidant markers, fibrosis, and histopathological changes were assessed by physiograph, Real-Time PCR, immunofluorescence, calorimetry, Masson's trichrome, and H&E staining, respectively.

Results: The impacts of MitoQ-125, EX+MitoQ-125, and EX+MitoQ-250 on arterial pressure and left ventricular systolic pressure were higher than MitoQ-250 or EX alone. ± dp/dt max were higher in ISO-EX+MitoQ-125 and ISO-EX+MitoQ-250 than ISO-MitoQ-125 and ISO-MitoQ-250 groups, respectively. Histopathological scores and fibrosis decreased in ISO-EX, ISO-MitoQ-125, ISO-EX+MitoQ-125, and ISO-EX+MitoQ-250 groups. The restoration of MFN2, PINK-1, and FIS-1 changes was higher in ISO-EX+MitoQ-125 and ISO-EX+MitoQ-250 than ISO-EX, ISO-MitoQ-125 and ISO-MitoQ-250 groups. The expression of MFN2 and PINK-1 was lower in ISO-MitoQ-125 and ISO-EX+MitoQ-125 than ISO and CTL groups. The expression of FIS-1 in ISO-EX and ISO-EX+MitoQ-250 increased compared to CTL and ISO groups. MDA decreased in ISO-MitoQ-125 and ISO-EX+MitoQ-125 groups.

Conclusion: Exercise and MitoQ combination have additive effects on cardiac function by modulating cardiac mitochondria quality. This study provided a possible therapy to treat heart injuries.

Patients with CHF, NYHA class IV, often fail to achieve adequate plasma CoQ10 levels on supplemental ubiquinone at dosages up to 900 mg/day. These patients often have plasma total CoQ10 levels of less than 2.5 microg/ml and have limited clinical improvement. It is postulated that the intestinal edema in these critically ill patients may impair CoQ10 absorption. We identified seven patients with advanced CHF (mean EF 22%) with sub-therapeutic plasma CoQ10 levels with mean level of 1.6 microg/ml on an average dose of 450 mg of ubiquinone daily (150-600 mg/day). All seven of these patients were changed to an average of 580 mg/day of ubiquinol (450-900 mg/day) with follow-up plasma CoQ10 levels, clinical status, and EF measurements by echocardiography. Mean plasma CoQ10 levels increased from 1.6 microg/ml (0.9-2.0 microg/ml) up to 6.5 microg/ml (2.6-9.3 microg/ml). Mean EF improved from 22% (10-35%) up to 39% (10-60%) and clinical improvement has been remarkable with NYHA class improving from a mean of IV to a mean of II (I to III). Ubiquinol has dramatically improved absorption in patients with severe heart failure and the improvement in plasma CoQ10 levels is correlated with both clinical improvement and improvement in measurement of left ventricular function.

Alpha-lipoic acid (ALA) has long been the focus of interest due to its promising effects on cardiometabolic risk factors. The aim of this systematic review was to summarize findings from existing human intervention studies evaluating the effect of ALA on vascular function. We performed a systematic search in the PubMed, SCOPUS, and Web of science electronic databases from inception until 1 July 2020. A total of 1106 records were identified from the database search, of which 12 were eligible: nine addressed chronic effects and three measured acute effects of ALA on vascular function. Of 11 trials that evaluated endothelial function by methods such as flow-mediated dilation (n = 7), reactive hyperemia (n = 2) and ACh-induced endothelium-dependent vasodilation (n = 2), 10 reported a significant improvement in endothelial function. In contrast, none of six trials examining the response of endothelium-independent vasodilation reported the favorable impact. The effect of ALA on arterial stiffness measures has been poorly studied. ALA appears to improve endothelial function through increasing the bioavailability of endothelium-derived nitric oxide as well as decreasing oxidative stress and inflammation. In conclusion, these results suggest improvement of endothelial function, but not endothelium-independent vasodilation as a potential mechanism by which ALA attenuates cardiovascular diseases.

α-Lipoic acid (ALA) is a vitamin-like substance that is an indispensable supporting factor for a large number of enzymes. Due to its optical activity, ALA has optical isomers RALA and SALA. The major role of RALA is in energy metabolism. However, RALA cannot be used as a pharmaceutical or nutraceutical because it is sensitive to heat and acid conditions. Previous studies have shown that RALA complexed with γ-cyclodextrin (CD) has a higher antioxidant capacity than that of free RALA. The antioxidant enzyme system protects against intense exercise-induced oxidative damage and is related to the physical status of athletes. The aim of this study was to examine the effect of CD/RALA complex supplementation on antioxidant activity and performance during high-intensity exercise. Twenty-four male C3H/HeSlc mice were divided into four groups ( = 6): swimming+distilled water administration (C), swimming+CD/RALA supplementation (CD/RALA), swimming+RALA suplementation (RALA), and swimming+CD supplementation (CD). Blood ammonia elevation due to exercise stress was repressed by CD/RALA supplementation. The oxidative stress in the kidney increased after exercise and was reduced by CD/RALA supplementation. Our findings suggest that CD/RALA supplementation may be useful for improving the exercise performance in athletes.

Acylcarnitine metabolites have gained attention as biomarkers of nutrient stress, but their physiological relevance and metabolic purpose remain poorly understood. Short-chain carnitine conjugates, including acetylcarnitine, derive from their corresponding acyl-CoA precursors via the action of carnitine acetyltransferase (CrAT), a bidirectional mitochondrial matrix enzyme. We show here that contractile activity reverses acetylcarnitine flux in muscle, from net production and efflux at rest to net uptake and consumption during exercise. Disruption of this switch in mice with muscle-specific CrAT deficiency resulted in acetyl-CoA deficit, perturbed energy charge, and diminished exercise tolerance, whereas acetylcarnitine supplementation produced opposite outcomes in a CrAT-dependent manner. Likewise, in exercise-trained compared to untrained humans, post-exercise phosphocreatine recovery rates were positively associated with CrAT activity and coincided with dramatic shifts in muscle acetylcarnitine dynamics. These findings show acetylcarnitine serves as a critical acetyl buffer for working muscles and provide insight into potential therapeutic strategies for combatting exercise intolerance.

Several experimental studies have shown that levocarnitine reduces myocardial injury after ischemia and reperfusion by counteracting the toxic effect of high levels of free fatty acids, which occur in ischemia, and by improving carbohydrate metabolism. In addition to increasing the rate of fatty acid transport into mitochondria, levocarnitine reduces the intramitochondrial ratio of acetyl-CoA to free CoA, thus stimulating the activity of pyruvate dehydrogenase and increasing the oxidation of pyruvate. Supplementation of the myocardium with levocarnitine results in an increased tissue carnitine content, a prevention of the loss of high-energy phosphate stores, ischemic injury, and improved heart recovery on reperfusion. Clinically, levocarnitine has been shown to have anti-ischemic properties. In small short-term studies, levocarnitine acts as an antianginal agent that reduces ST segment depression and left ventricular end-diastolic pressure. These short-term studies also show that levocarnitine releases the lactate of coronary artery disease patients subjected to either exercise testing or atrial pacing. These cardioprotective effects have been confirmed during aortocoronary bypass grafting and acute myocardial infarction. In a randomized multicenter trial performed on 472 patients, levocarnitine treatment (9 g/day by intravenous infusion for 5 initial days and 6 g/day orally for the next 12 months), when initiated early after acute myocardial infarction, attenuated left ventricular dilatation and prevented ventricular remodeling. In treated patients, there was a trend towards a reduction in the combined incidence of death and CHF after discharge. Levocarnitine could improve ischemia and reperfusion by (1) preventing the accumulation of long-chain acyl-CoA, which facilitates the production of free radicals by damaged mitochondria; (2) improving repair mechanisms for oxidative-induced damage to membrane phospholipids; (3) inhibiting malignancy arrhythmias because of accumulation within the myocardium of long-chain acyl-CoA; and (4) reducing the ischemia-induced apoptosis and the consequent remodeling of the left ventricle. Propionyl-L-carnitine is a carnitine derivative that has a high affinity for muscular carnitine transferase, and it increases cellular carnitine content, thereby allowing free fatty acid transport into the mitochondria. Moreover, propionyl-L-carnitine stimulates a better efficiency of the Krebs cycle during hypoxia by providing it with a very easily usable substrate, propionate, which is rapidly transformed into succinate without energy consumption (anaplerotic pathway). Alone, propionate cannot be administered to patients in view of its toxicity. The results of phase-2 studies in chronic heart failure patients showed that long-term oral treatment with propionyl-L-carnitine improves maximum exercise duration and maximum oxygen consumption over placebo and indicated a specific propionyl-L-carnitine effect on peripheral muscle metabolism. A multicenter trial on 537 patients showed that propionyl-L-carnitine improves exercise capacity in patients with heart failure, but preserved cardiac function.

The benefits of physical exercise on health are diminished when it is non-planned, strenuous, or vigorous, which causes an increase in oxygen consumption and production of free radicals, particularly serious at the muscular level. Ubiquinol could help achieve an antioxidant, anti-inflammatory, and ergogenic effect. The aim of this study is to evaluate whether a supplementation of ubiquinol during a short period could have a positive effect on muscle aggression, physical performance, and fatigue perception in non-elite athletes after high intensity circuit weight training. One hundred healthy and well-trained men, (firemen of the Fire Department of Granada) were enrolled in a placebo-controlled, double-blinded, and randomized study, and separated into two groups: the placebo group (PG, = 50); and the ubiquinol group (UG, = 50), supplemented with an oral dose. Before and after the intervention, data related to the number of repetitions, muscle strength, and perceived exertion, as well as blood samples were collected. An increase was observed in the UG regarding average load and repetitions, revealing an improvement in muscle performance. Ubiquinol supplementation also reduced muscle damage markers, showing a protective effect on muscle fibers. Therefore, this study provides evidence that ubiquinol supplementation improves muscle performance and prevents muscle damage after strenuous exercise in a population of well-trained individuals who are not elite athletes.

Ubiquinol (QH), a reduced form of coenzyme Q10, is a lipid antioxidant that is hydro-soluble and is commonly formulated in commercial supplements. Ubiquinol has been increasingly reported to exert antioxidant functions, in addition to its role in the cell energy-producing system of mitochondria and adenosine triphosphate (ATP) production. The aim of this study was to assess the potential beneficial effects of QH on anti-fatigue and ergogenic functions following physiological challenge. Forty 8-week-old male Institute of Cancer Research (ICR) mice were divided into four groups ( = 10 for each group): Group 1 (vehicle control or oil only); Group 2 (1X QH dose or 102.5 mg/kg); Group 3 (2X QH dose or 205 mg/kg); Group 4 (6X QH dose or 615 mg/kg). Anti-fatigue activity and exercise performance were studied using the forelimb grip strength experiment and exhaustive weight-loaded swimming time, and levels of serum lactate, ammonia, glucose, BUN (blood urea nitrogen), creatine kinase (CK), and free fatty acids (FFA) after an acute exercise challenge. The forelimb grip strength and exhaustive weight-loaded swimming time of the QH-6X group were significantly higher than those of the other groups. QH supplementation dose-dependently reduced serum lactate, ammonia, and CK levels and increased the FFA concentration after acute exercise. In addition, QH increased the liver and muscle glycogen content, an important energy source during exercise. Therefore, the results suggest that QH formulation is a safe dietary supplement for amelioration of fatigue and for promoting exercise performance.

Background: To investigate the effect of Ubiquinol supplementation on physical performance measured as maximum power output in young and healthy elite trained athletes.

Methods: In this double-blind, placebo-controlled study, 100 young German well trained athletes (53 male, 47 female, age 19.9 ± 2.3 years) received either 300 mg Ubiquinol or placebo for 6 weeks. Athletes had to perform a maximum power output test and the performance in W/kg of bodyweight was measured at the 4 mmol lactate threshold on a cycling ergometer before the supplementation treatment (T1), after 3 weeks (T2) and after 6 weeks (T3) of treatment. In these 6 weeks all athletes trained individually in preparation for the Olympic Games in London 2012. The maximum power output was measured in Watt/kilogram body weight (W/kg bw).

Results: Both groups, placebo and Ubiquinol, significantly increased their physical performance measured as maximum power output over the treatment period from T1 to T3. The placebo group increased from 3.64 ± 0.49 W/kg bw to 3.94 ± 0.47 W/kg bw which is an increase of +0.30 ± 0.18 W/kg bw or +8.5% (±5.7). The Ubiquinol group increased performance levels from 3.70 W/kg bw (±0.56) to 4.08 W/kg bw (±0.48) from time point T1 to T3 which is an increase of +0.38 ± 0.22 W/kg bw or +11.0% (±8.2). The absolute difference in the enhancement of the physical performance between the placebo and the Ubiquinol group of +0.08 W/kg bodyweight was significant (p < 0.03).

Conclusions: This study demonstrates that daily supplementation of 300 mg Ubiquinol for 6 weeks significantly enhanced physical performance measured as maximum power output by +0.08 W/kg bw (+2.5%) versus placebo in young healthy trained German Olympic athletes. While adherence to a training regimen itself resulted in an improvement in peak power output, as observed by improvement in placebo, the effect of Ubiquinol supplementation significantly enhanced peak power production in comparison to placebo.

Statins are cholesterol-lowering drugs widely used in the prevention of cardiovascular diseases; however, they are associated with various types of myopathies. Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and thus decrease biosynthesis of low-density lipoprotein cholesterol and may also reduce ubiquinones, essential coenzymes of a mitochondrial electron transport chain, which contain isoprenoid residues, synthesized through an HMG-CoA reductase-dependent pathway. Therefore, we hypothesized that statin treatment might influence physical performance through muscular mitochondrial dysfunction due to ubiquinone deficiency. The effect of two statins, atorvastatin and pravastatin, on ubiquinone content, mitochondrial function, and physical performance was examined by using statin-treated mice. Changes in energy metabolism in association with statin treatment were studied by using cultured myocytes. We found that atorvastatin-treated mice developed muscular mitochondrial dysfunction due to ubiquinone deficiency and a decrease in exercise endurance without affecting muscle mass and strength. Meanwhile, pravastatin at ten times higher dose of atorvastatin had no such effects. In cultured myocytes, atorvastatin-related decrease in mitochondrial activity led to a decrease in oxygen utilization and an increase in lactate production. Conversely, coenzyme Q(10) treatment in atorvastatin-treated mice reversed atorvastatin-related mitochondrial dysfunction and a decrease in oxygen utilization, and thus improved exercise endurance. Atorvastatin decreased exercise endurance in mice through mitochondrial dysfunction due to ubiquinone deficiency. Ubiquinone supplementation with coenzyme Q(10) could reverse atorvastatin-related mitochondrial dysfunction and decrease in exercise tolerance.

Background: To investigate the effect of Ubiquinol supplementation on physical performance measured as maximum power output in young and healthy elite trained athletes.

Methods: In this double-blind, placebo-controlled study, 100 young German well trained athletes (53 male, 47 female, age 19.9 ± 2.3 years) received either 300 mg Ubiquinol or placebo for 6 weeks. Athletes had to perform a maximum power output test and the performance in W/kg of bodyweight was measured at the 4 mmol lactate threshold on a cycling ergometer before the supplementation treatment (T1), after 3 weeks (T2) and after 6 weeks (T3) of treatment. In these 6 weeks all athletes trained individually in preparation for the Olympic Games in London 2012. The maximum power output was measured in Watt/kilogram body weight (W/kg bw).

Results: Both groups, placebo and Ubiquinol, significantly increased their physical performance measured as maximum power output over the treatment period from T1 to T3. The placebo group increased from 3.64 ± 0.49 W/kg bw to 3.94 ± 0.47 W/kg bw which is an increase of +0.30 ± 0.18 W/kg bw or +8.5% (±5.7). The Ubiquinol group increased performance levels from 3.70 W/kg bw (±0.56) to 4.08 W/kg bw (±0.48) from time point T1 to T3 which is an increase of +0.38 ± 0.22 W/kg bw or +11.0% (±8.2). The absolute difference in the enhancement of the physical performance between the placebo and the Ubiquinol group of +0.08 W/kg bodyweight was significant (p < 0.03).

Conclusions: This study demonstrates that daily supplementation of 300 mg Ubiquinol for 6 weeks significantly enhanced physical performance measured as maximum power output by +0.08 W/kg bw (+2.5%) versus placebo in young healthy trained German Olympic athletes. While adherence to a training regimen itself resulted in an improvement in peak power output, as observed by improvement in placebo, the effect of Ubiquinol supplementation significantly enhanced peak power production in comparison to placebo.

The benefits of physical exercise on health are diminished when it is non-planned, strenuous, or vigorous, which causes an increase in oxygen consumption and production of free radicals, particularly serious at the muscular level. Ubiquinol could help achieve an antioxidant, anti-inflammatory, and ergogenic effect. The aim of this study is to evaluate whether a supplementation of ubiquinol during a short period could have a positive effect on muscle aggression, physical performance, and fatigue perception in non-elite athletes after high intensity circuit weight training. One hundred healthy and well-trained men, (firemen of the Fire Department of Granada) were enrolled in a placebo-controlled, double-blinded, and randomized study, and separated into two groups: the placebo group (PG, = 50); and the ubiquinol group (UG, = 50), supplemented with an oral dose. Before and after the intervention, data related to the number of repetitions, muscle strength, and perceived exertion, as well as blood samples were collected. An increase was observed in the UG regarding average load and repetitions, revealing an improvement in muscle performance. Ubiquinol supplementation also reduced muscle damage markers, showing a protective effect on muscle fibers. Therefore, this study provides evidence that ubiquinol supplementation improves muscle performance and prevents muscle damage after strenuous exercise in a population of well-trained individuals who are not elite athletes.

Studies about Coenzyme Q (CoQ ) supplementation on strenuous exercise are scarce, especially those related with oxidative stress associated with physical activity and virtually nonexistent with the reduced form, Ubiquinol. The objective of this study was to determine, for the first time, whether a short-term supplementation with Ubiquinol can prevent oxidative stress associated to strenuous exercise. The participants (n = 100 healthy and well trained, but not on an elite level) were classified in two groups: Ubiquinol (experimental group), and placebo group (control). The protocol consisted of conducting two identical strenuous exercise tests with a rest period between tests of 24 h. Blood and urine samples were collected from the participants before supplementation (basal value) (T1), after supplementation (2 weeks) (T2), after first physical exercise test (T3), after 24 h of rest (T4), and after second physical exercise test (T5).The increase observed in the lactate, isoprostanes, DNA damage, and hydroperoxide levels reveals the severity of the oxidative damage induced by the exercise. There was a reduction in the isoprostanes, 8-OHdG, oxidized LDL, and hydroperoxydes in the supplemented Ubiquinol group, an increase in total antioxidant status, fat soluble antioxidant (both plasma and membrane), and CAT activity. Also, NO in the Ubiquinol-supplemented group was maintained within a narrow range. Oxidative stress induced by strenuous exercise is accumulative and increases transiently in subsequent sessions of physical activity. A short-term supplementation (2 weeks) with Ubiquinol (200 mg/day) before strenuous exercise, decreases oxidative stress and increases plasma NO, fact that could improve endothelial function, energetic substrate supply, and muscle recovery after strenuous exercise. © 2016 BioFactors, 42(6):612-622, 2016.