Exogenous CoQ10 supplementation prevents plasma ubiquinone reduction induced by HMG-CoA reductase inhibitors.

The biosynthetic pathway of the CoQ polyisoprenoid side chain, starting from acetyl-CoA and proceeding through mevalonate and isopentenylpyrophosphate, is the same as that of cholesterol. We performed this study to evaluate whether vastatins (hypocholesterolemic drugs that inhibit HMG-CoA reductase) modify blood levels of ubiquinone. Thirty-four unrelated outpatients with hypercholesterolemia (IIa phenotype) were treated with 20 mg of simvastatin for a 6-month period (group S) or with 20 mg of simvastatin plus 100 mg CoQ10 (group US). The following parameters were evaluated at time 0, 45, 90, 135 and 180 days: total plasma cholesterol (TC), HDL-cholesterol, LDL-cholesterol (LDL-C), triglycerides (TG), apo A1, apo B and CoQ10 in plasma and platelets. In the S group, there was a marked decrease in TC and LDL-C (from 290.3 mg/dl to 228.7 mg/dl for TC and from 228.7 mg/dl to 167.6 mg/dl for LDL-C) and in plasma CoQ10 levels from 1.08 mg/dl to 0.80 mg/dl. In contrast, in the US group we observed a significant increase of CoQ10 in plasma (from 1.20 to 1.48 mg/dl) while the hypocholesterolemic effect was similar to that observed in the S group. Platelet CoQ10 also decreased in the S group (from 104 to 90 ng/mg) and increased in the US group (from 95 to 145 ng/mg). This study demonstrates that simvastatin lowers both LDL-C and apo B plasma levels together with the plasma and platelet levels of CoQ10, and that CoQ10 therapy prevents both plasma and platelet CoQ10 decrease, without affecting the cholesterol lowering effect of simvastatin.

Can oxypurines plasma levels classify the type of physical exercise?

BACKGROUND: A laboratory-based model able to describe muscle energy status during physical exercise and changes in myofibrillar composition in response to training would be desirable. Lactate and ammonia concentrations are not sufficient for a comprehensive knowledge of these systems. All muscle fibres, irrespective of the type, show ATP depletion and IMP accumulation following exhausting muscular exercise with quantitative differences due to the different concentrations of deaminase. We studied the plasma concentration of metabolites of oxypurine cascade to test their reliability to classify different exercises. METHODS: We studied 52 athletes, measuring plasma metabolites at the beginning and at the end of their specific field exercise (cycle pursuers, 8 cases; soccer players, 19; marathon runners, 25). K3EDTA-blood samples were assayed for plasma hypoxanthine, xanthine, and inosine, using an HPLC technique, as well as ammonia and lactate by means of enzymatic methods. RESULTS AND CONCLUSIONS: Basal oxypurines levels were not different in relation to any specific physical exercise. Post-exercise oxypurines, namely hypoxanthine, were more precise predictors of muscle energy exhaustion than strain intensity or duration. Plasma levels of hypoxanthine may be elevated also in the presence of normal xanthine and uric acid concentrations, due to an exhaustion of the enzymatic pathway, to a reduced activity of xanthine-oxidase or finally to a substrate-dependent inhibition of the process.

Effect of ubidecarenone oral treatment on aerobic power in middle-aged trained subjects.

BACKGROUND: Coenzyme Q10 (CoQ10) plays an important role in oxidative mithocondrial phosphorylation and prevents lipid peroxidation in biological membranes. During sustained physical exercise, reactive oxygen species (ROS) production increase through several mechanism; one of them is the purine nucleotide cycle activation by shifting xanthine-dehydrogenase to xanthine-oxidase during AMP breakdown. The aim of this study was to evaluate the effect of CoQ10 treatment on aerobic power. EXPERIMENTAL DESIGN: according to a single blind study design, 28 health male cyclists were randomized into two groups (CoQ10 or placebo) and remained on treatments for eight weeks; there were 5 drop-outs and only 23 subjects were completely evaluated. Before and at the end of the eight weeks, cyclists underwent cardiopulmonary exercise testing. MEASURES: a software system performed the necessary calculations to obtain the following parameters: oxygen uptake, CO2 production, minute ventilation, oxygen ventilatory equivalent, carbon dioxide ventilatory equivalent, oxygen pulse. Finally oxygen peak and anaerobic threshold were determined. Moreover blood inosine, hypoxanthine, xanthine, lactate and CoQ10 levels were measured before and immediately after each test. RESULTS: The results of this study showed that at the end of the eight weeks there was no difference between the two groups concerning physiological and metabolic parameters, but muscular exhaustion was reached at higher workloads in the CoQ10 group. CONCLUSIONS: In our experience ubidecarenone oral treatment does not improve aerobic power. The little improvement of tolerance to higher workloads may be due to the antioxidant activity of CoQ10.

Reduced ubiquinone plasma levels in patients with liver cirrhosis and in chronic alcoholics.

Ubiquinone (CoQ10 coenzyme) is part of the respiratory chain in mitochondria, and acts as a scavenger in oxidative stress in cell membranes. Ubiquinone is mainly synthesized in the liver and partly derived from the diet; its plasma levels significantly correlate with tissue levels in experimental animals and in pathological states in man. By means of an original high-performance liquid chromatography technique, we measured ubiquinone plasma levels in 10 healthy subjects, in 27 patients with cirrhosis and in 22 chronic alcoholics with normal liver function. Ubiquinone levels were markedly reduced in cirrhosis (0.25 [SD 0.21] microgram/ml vs. 0.92 [0.38] in controls; P < 0.001), without any difference between alcohol- and non-alcohol-related disease. Also, in chronic alcoholics ubiquinone levels were nearly halved (0.49 [0.24]). In cirrhosis, ubiquinone plasma levels significantly correlated with cholesterol (P < 0.05), and with total bilirubin levels (P < 0.01). Our study highlights a remarkable deficiency in ubiquinone levels in patients with cirrhosis and in chronic alcoholics, to which both reduced hepatic synthesis and nutritional defects may contribute.

Improved high-performance liquid chromatographic method for the determination of coenzyme Q10 in plasma.

Coenzyme (Co) Q10 was dissociated from lipoproteins in plasma by treatment with methanol and extraction with n-hexane. Subsequent clean-up on silica gel and C18 solid-phase extraction cartridges with complete recovery (99 +/- 1.2%) produced a clean extract. High-performance liquid chromatographic (HPLC) separation was performed on a C18 reversed-phase column. Three simple, rapid procedures are presented: HPLC with final UV (275 nm) detection, a microanalysis utilizing a three-electrode electrochemical detector and a microanalysis with column-switching HPLC and electrochemical detection. The methods correlate very well with classical ethanol-n-hexane extraction with UV detection. The identity and purity of the Co Q10 peak were investigated and the resulting methods were concluded to be suitable for total plasma Co Q10 determination. The average level in healthy subjects was 0.80 +/- 0.20 mg/l; the minimum detectable Co Q10 plasma level was 0.05 and 0.005 mg/l for UV and electrochemical detection, respectively. The methods were applied to many samples and the plasma Co Q10 reference values for healthy subjects, athletes, hyperthyroid, hypothyroid and hypercholesterolaemic patients are given.

Exogenous CoQ10 preserves plasma ubiquinone levels in patients treated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

Ubiquinone is a carrier of the mitochondrial respiratory chain which regulates oxidative phosphorylation: it also acts as a membrane stabilizer preventing lipid peroxidation. In man the quinone ring originates from tyrosine, while the formation of the polyisoprenoid lateral chain starts from acetyl CoA and proceeds through mevalonate and isopentenylpyrophosphate; this biosynthetic pathway is the same as the cholesterol one. We therefore performed this study to evaluate whether statins (hypocholesterolemic drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase) modify blood levels of ubiquinone. Thirty unrelated outpatients with primary hypercholesterolemia (IIa phenotype) were treated with 20 mg of simvastatin for a 3-month period (group S) or with 20 mg of simvastatin plus 100 mg CoQ10 (group US). The following parameters were evaluated at time 0, and at 45 and 90 days: total plasma cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, Apo A1, Apo B and CoQ10 in plasma and in platelets. In the S group, there was a marked decrease in total cholesterol low-density lipoprotein-cholesterol and in plasma CoQ10 levels from 1.08 mg/dl to 0.80 mg/dl. In contrast, in the US group we observed a significant increase of plasma CoQ10 (from 1.20 to 1.48 mg/dl) while the hypocholesterolemic effect was similar to that observed in the S group. Platelet CoQ10 also decreased in the S group (from 104 to 90 ng/mg) and increased in the US group (from 95 to 145 ng/mg).(ABSTRACT TRUNCATED AT 250 WORDS)