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BACKGROUND The inflammatory cytokine progranulin has been proposed to play a role in obesity and its associated comorbidities such as insulin resistance. OBJECTIVE In a longitudinal study, we analyzed the links between progranulin, parameters of fat mass, insulin resistance, and metabolic syndrome (MetS) in obese children. METHODS We measured the following parameters in 88 obese children at baseline, at the end of a 1-year lifestyle intervention and 1-year later (=2 years after baseline): progranulin, bioactive leptin, body mass index-SD score (BMI-SDS), waist circumference, body fat based on skinfold measurements and bioimpedance analyses, lipids, transaminases, insulin resistance index homeostasis model assessment (HOMA), and blood pressure. As a control, we determined progranulin in 23 normal-weight children. RESULTS The progranulin concentrations did not differ significantly (P = .795) between obese and normal-weight children. Progranulin concentrations decreased significantly during and after the lifestyle intervention in children with and without decrease of BMI-SDS. There was no relationship between progranulin concentrations and pubertal stage or gender. Progranulin was not significantly associated with insulin resistance HOMA, parameters of the MetS or transaminases both in cross-sectional and longitudinal multiple linear regression analyses adjusted to multiple confounders. Progranulin was significantly, negatively related to age (b-coefficient -1.24 ± .97, P = .012, r2 = .07). CONCLUSIONS Our data do not support the hypothesis that progranulin is an important link between obesity, insulin resistance, and MetS in childhood.

Objective This study analyzed the relationships between bioactive leptin, conventionally measured leptin, and parameters of fat mass and distribution in obese children before and after weight reduction. Methods We determined bioactive leptin (bioLep), conventional measured leptin (conLep), weight, height, body fat based on skinfold measurements and bioimpedance analyses, waist circumference (wc), and pubertal stage in 88 obese children participating in a lifestyle intervention at baseline and one year later. Results We identified no child with homozygous or heterozygous status for bioinactive leptin mutations. The baseline associations between bioLep and BMI (r = 0.53), BMI-SDS (r = 0.48), body fat (bioimpedance: r = 0.61, skinfold thickness: r = 0.49), wc (r = 0.42), and waist to height ratio (whr) (r = 0.39) were stronger than the associations between conLep and BMI (r = 0.50), BMI-SDS (r = 0.44), body fat (bioimpedance: r = 0.57, skinfold thickness: r = 0.41), wc (r = 0.41), and whr (r = 0.37). The changes of bioLep were stronger related to changes of BMI-SDS (r = 0.54), body fat (bioimpedance r = 0.59, skinfold thickness: r = 0.37), wc (r = 0.22), and whr (r = 0.21) than the associations between changes of conLep and changes of BMI-SDS (r = 0.48), body fat (bioimpedance: r = 0.56, skinfold thickness: r = 0.43), wc (r = 0.20), and whr (r = 0.20). The same findings were observed in multiple linear regression analyses adjusted to multiple confounders. In contrast to changes of conLep (r = 0.22), the changes of bioLep during intervention were not related to weight regain after the end of intervention. BioLep concentrations did not differ between prepubertal girls and boys, but were higher in pubertal girls compared to pubertal boys (p = 0.031). Conclusions Bioactive leptin was stronger related to fat mass and distribution compared to conventionally measured leptin.

Chemerin has been suggested as a potential link between obesity and associated comorbidities in humans. Therefore, we studied the relationships between chemerin, parameters of fat mass, and Metabolic Syndrome (MetS) in obese children before and after weight reduction. We determined chemerin, bioactive leptin (bioLep), BMI-SDS, waist circumference (WC), body fat based on skinfold measurements and bioimpedance analyses, lipids, transaminases, insulin resistance index HOMA, and blood pressure in 88 obese children participating in a lifestyle intervention at baseline and 1 year later. Furthermore, we determined chemerin concentrations in 23 normal-weight children. Obese children demonstrated significantly (p

Coenzyme Q10 (CoQ10) is synthesized in almost all human tissues and presumably involved in age-related alterations and diseases. Here, we examined the impact of aging and sex on the serum CoQ10 status in 860 European adults ranging in age from 18 to 82 years. We identified an inverse U-shaped relationship between CoQ10 concentration and age. Women showed lower cholesterol-adjusted CoQ10 levels than men, irrespective of age. As observed in both sexes, the decrease in CoQ10 concentration in older subjects was accompanied by a shift in the redox status in favour of the oxidized form. A strong positive correlation was found for total CoQ10 and cholesterol concentrations (Spearman’s, p≤1E-74). We found strong negative correlations between total (Spearman’s, p≤1E-07) and between cholesterol-adjusted CoQ10 concentration (Spearman’s, p≤1E-14) and the proportion of the oxidized form of CoQ10. These correlations were not dependent on age and sex and were attenuated by supplementation with 150 mg/day reduced CoQ10 for 14 days. Overall, our results are useful to define risk groups with critical CoQ10 status in humans. In particular, older subjects were characterized by impaired CoQ10 status due to their lowered serum CoQ10 concentration and concomitant decrease of CoQ10 redox capacity.

Introduction Coenzyme Q10 (CoQ10) is a lipophilic endogenously synthesised antioxidant that is present in nearly all human tissues and plays an important role in mitochondrial energy production. It has been postulated that smoking has a consumptive effect on CoQ10. Material and methods To further define the relation between smoking and the serum CoQ10 status, 276 healthy volunteers aged 19 to 62 years were grouped into non-smokers (n = 113; 77 male, 36 female) and smokers (n = 163; 102 male, 61 female). Serum lipid profile was analysed by standard clinical chemistry. Coenzyme Q10 concentration and redox status were analysed by high-pressure liquid chromatography with electrochemical detection. Results Male smokers showed higher serum CoQ10 levels than female smokers. This sex-related difference was accounted for when CoQ10 was related to low-density lipoprotein (LDL) cholesterol as the main carrier of CoQ10 in the circulation. Neither LDL-adjusted CoQ10 concentration nor redox status significantly differed when smokers and non-smokers were compared. Regarding the smoking history, the number of cigarettes consumed per day did not significantly affect the CoQ10 status. Interestingly, with increasing time of smoking habit we observed increasing levels of LDL-adjusted serum CoQ10 concentration (Spearman's p < 0.002) and of the reduced form of CoQ10 (Spearman's p < 0.0001). Conclusions As an adaptive response to oxidative stress in long-term smokers an increased demand for antioxidant capacity may be covered by increasing levels of LDL-adjusted CoQ10 serum concentrations and by a concomitantly increased availability of the reduced, active form of CoQ10, possibly by induction of enzymes that are involved in converting CoQ10ox to CoQ10red.

Coenzyme Q10 (CoQ10) exists in a reduced (ubiquinol) and an oxidized (ubiquinone) form in all human tissues and functions, amongst others, in the respiratory chain, redox-cycles, and gene expression. As the status of CoQ10 is an important risk factor for several diseases, here we determined the CoQ10 status (ubiquinol, ubiquinone) in a large Caucasian study population (n = 1,911). The study population covers a wide age range (age: 18–83 years, 43.4% men), has information available on more than 10 measured clinical phenotypes, more than 30 diseases (presence vs. absence), about 30 biomarkers, and comprehensive genetic information including whole-genome SNP typing (>891,000 SNPs). The major aim of this long-term resource in CoQ10 research is the comprehensive analysis of the CoQ10 status with respect to integrated health parameters (i.e., fat metabolism, inflammation), disease-related biomarkers (i.e., liver enzymes, marker for heart failure), common diseases (i.e., neuropathy, myocardial infarction), and genetic risk in humans. Based on disease status, biomarkers, and genetic variants, our cohort is also useful to perform Mendelian randomisation approaches. In conclusion, the present study population is a promising resource to gain deeper insight into CoQ10 status in human health and disease. © 2015 BioFactors, 41(4):211–221, 2015

Coenzyme Q10 (CoQ10) is synthesized in most human tissues, with high concentration in the skeletal muscle. CoQ10 functions in the mitochondrial respiratory chain and serves as a potent liphophilic antioxidant in membranes. CoQ10 deficiency impairs mitochondrial ATP synthesis and increases oxidative stress. It has been suggested that plasma CoQ10 status is not a robust proxy for the diagnosis of CoQ10 deficiency. We determined the concentration and redox-status of CoQ10 in plasma and muscle tissue from 140 healthy children (0.8–15.3 y) by high-performance liquid chromatography (HPLC) with electrochemical detection. There was no correlation between CoQ10 concentration or redox status between plasma and muscle tissue. Lipid-related CoQ10 plasma concentrations showed a negative correlation with age (Spearman’s, P ≤ 0.02), but there was no significant age-related correlation for muscle concentration. In muscle tissue, we found a distinct shift in the redox status in favor of the oxidized proportion with increasing age (Spearman’s, P ≤ 0.00001). Reference values for muscle CoQ10 concentration (40.5 ± 12.2 pmol/mg wet tissue) and CoQ10 redox status (46.8 ± 6.8% oxidized within total) were established for healthy children. The age-related redox shift in muscle tissue suggests changes in antioxidative defense during childhood. The reference values established here provide a necessary prerequisite for diagnosing early CoQ10 deficiency.

Dietary restriction (DR) is a robust intervention that extends both health span and life span in many organisms. Ubiquinol and ubiquinone represent the reduced and oxidized forms of coenzyme Q (CoQ). CoQ plays a central role in energy metabolism and functions in several cellular processes including gene expression. Here we used the model organism Caenorhabditis elegans to determine level and redox state of CoQ and expression of genes in response to DR. We found that DR down-regulates the steady-state expression levels of several evolutionary conserved genes (i.e. coq-1) that encode key enzymes of the mevalonate and CoQ-synthesizing pathways. In line with this, DR decreases the levels of total CoQ and ubiquinol. This CoQ-reducing effect of DR is obvious in adult worms but not in L4 larvae and is also evident in the eat-2 mutant, a genetic model of DR. In conclusion, we propose that DR reduces the level of CoQ and ubiquinol via gene expression in the model organism C. elegans.

Ubiquinone and ubiquinol represent the oxidized and reduced forms of Coenzyme Q10 (CoQ10). CoQ10 is present in membranes of almost all human tissues and organs, with highest concentration in the heart. In patients with heart failure, serum levels of the N-terminal pro-brain natriuretic peptide (NT-proBNP) are an indicator of disease severity. Here, we investigated the relationship between serum levels of CoQ10 and NT-proBNP in healthy volunteers of an elderly study population (mean age 52 years, n = 871). We found a negative association between serum levels of ubiquinol and NT-proBNP (P

Coenzyme Q (CoQ) is necessary for mitochondrial energy production and modulates the expression of genes that are important for inflammatory processes, growth and detoxification reactions. A cellular surveillance-activated detoxification and defenses (cSADDs) pathway has been recently identified in C. elegans. The down-regulation of the components of the cSADDs pathway initiates an aversion behavior of the nematode. Here we hypothesized that CoQ regulates genes of the cSADDs pathway. To verify this we generated CoQ-deficient worms ("CoQ-free") and performed whole-genome expression profiling. We found about 30% (120 genes) of the cSADDs pathway genes were differentially regulated under CoQ-deficient condition. Remarkably, 83% of these genes were down-regulated. The majority of the CoQ-sensitive cSADDs pathway genes encode for proteins involved in larval development (enrichment score (ES) = 38.0, p = 5.0E(-37)), aminoacyl-tRNA biosynthesis, proteasome function (ES 8.2, p = 5.9E(-31)) and mitochondria function (ES 3.4, p = 1.7E(-5)). 67% (80 genes) of these genes are categorized as lethal. Thus it is shown for the first time that CoQ regulates a substantial number of essential genes that function in the evolutionary conserved cellular surveillance-activated detoxification and defenses pathway in C. elegans.

Coenzyme Q (CoQ, ubiquinone) is an essential component of the respiratory chain, a cofactor of pyrimidine biosynthesis and acts as an antioxidant in extra mitochondrial membranes. More recently CoQ has been identified as a modulator of apoptosis, inflammation and gene expression. CoQ deficient Caenorhabditis elegans clk-1 mutants show several phenotypes including a delayed postembryonic growth. Using wild type and two clk-1 mutants, here we established an experimental set-up to study the consequences of endogenous CoQ deficiency or exogenous CoQ supply on gene expression and growth. We found that a deficiency of endogenous CoQ synthesis down-regulates a cluster of genes that are important for growth (i.e., RNA polymerase II, eukaryotic initiation factor) and up-regulates oxidation reactions (i.e., cytochrome P450, superoxide dismutase) and protein interactions (i.e., F-Box proteins). Exogenous CoQ supply partially restores the expression of these genes as well as the growth retardation of CoQ deficient clk-1 mutants. On the other hand exogenous CoQ supply does not alter the expression of a further sub-set of genes. These genes are involved in metabolism (i.e., succinate dehydrogenase complex), cell signalling or synthesis of lectins. Thus, our work provides a comprehensive overview of genes which can be modulated in their expression by endogenous or exogenous CoQ. As growth retardation in CoQ deficiency is linked to the gene expression profile we suggest that CoQ promotes growth via gene expression.

Coenzyme Q derivatives (CoQ) are lipid soluble antioxidants that are synthesized endogenously in almost all species and function as an obligatory cofactor of the respiratory chain. There is evidence that CoQ status is altered by age in several species. Here we determined level and redox-state of CoQ in different age groups of pigs, mice and Caenorhabditis elegans. Since these species are very different with respect to lifespan, reproduction and physiology, our approach could provide some general tendencies of CoQ status in ageing organisms. We found that CoQ level decreases with age in pigs and mice, whereas CoQ content increases in older worms. As observed in all three species, ubiquinone, the oxidized form of CoQ, increases with age. Additionally, we were able to show that supplementation of ubiquinol-10, the reduced form of human CoQ(10), slightly increases lifespan of post-reproductive worms. In conclusion, the percentage of the oxidized form of CoQ increases with age indicating higher oxidative stress or rather a decreased anti-oxidative capacity of aged animals. (C) 2014 BioFactors

The antioxidant status of coenzyme Q10 (CoQ10) was investigated in plasma, erythrocytes, and platelets of juvenile patients with anorexia nervosa. Blood for analysis of the CoQ10 status was taken from 16 juvenile patients suffering from anorexia nervosa (restricting form) at the time point of admission to the hospital and at discharge after about 12 weeks. Plasma and blood cells isolated by a density gradient were stored at -84 °C until analysis. CoQ10 concentration and redox status were measured by high pressure liquid chromatography with electrochemical detection and internal standardization. The improvement of physical health during the hospital refeeding process was followed up by the body mass index (BMI). The antioxidant status of plasma CoQ10 in juvenile patients suffering from anorexia nervosa indicated no abnormalities in comparison to healthy controls. However, the decreased concentration of CoQ10 observed in platelets at the time point of hospital admission may represent mitochondrial CoQ10 depletion. This initial deficit improved during the hospital refeeding process. The platelet CoQ10 concentration showed a positive correlation to the BMI of the patients.

Mitochondrial complex I appears to be dysfunctional in progressive supranuclear palsy (PSP). Coenzyme Q(10) (CoQ(10)) is a physiological cofactor of complex I. Therefore, we evaluated the short-term effects of CoQ(10) in PSP. We performed a double-blind, randomized, placebo-controlled, phase II trial, including 21 clinically probable PSP patients (stage < or = III) to receive a liquid nanodispersion of CoQ(10) (5 mg/kg/day) or matching placebo. Over a 6-week period, we determined the change in CoQ(10) serum concentration, cerebral energy metabolites (by (31)P- and (1)H-magnetic resonance spectroscopy), motor and neuropsychological dysfunction (PSP rating scale, UPDRS III, Hoehn and Yahr stage, Frontal Assessment Battery, Mini Mental Status Examination, Montgomery Asberg Depression Scale). CoQ(10) was safe and well tolerated. In patients receiving CoQ(10) compared to placebo, the concentration of low-energy phosphates (adenosine-diphosphate, unphosphorylated creatine) decreased. Consequently, the ratio of high-energy phosphates to low-energy phosphates (adenosine-triphosphate to adenosine-diphosphate, phospho-creatine to unphosphorylated creatine) increased. These changes were significant in the occipital lobe and showed a consistent trend in the basal ganglia. Clinically, the PSP rating scale and the Frontal Assessment Battery improved slightly, but significantly, upon CoQ(10) treatment compared to placebo. Since CoQ(10) appears to improve cerebral energy metabolism in PSP, long-term treatment might have a disease-modifying, neuroprotective effect.

Introduction: SLOS is caused by a defect of cholesterol synthesis. HMG-CoA reductase inhibitors have been shown to improve biochemical parameters in this condition, but they have also been associated with CoQ 10 deficiency in patients with hypercholesterolemia. The aim of this study was to analyse plasma and intracellular CoQ 10 levels in SLOS patients and to determine the influence of HMG-CoA reductase inhibitors. Methods: Plasma concentrations of CoQ 10 and vitamin E were measured in 14 patients, intracellular CoQ 10 levels were determined in platelets of 10 patients with SLOS and compared to controls. Results: Plasma CoQ 10 and vitamin E levels were significantly lower in SLOS patients. This difference equalised after adjustment to cholesterol concentrations. Treatment with simvastatin did not influence CoQ 10 levels and redox status. Platelet CoQ 10 concentrations were similar between patients and controls but there were striking differences in the CoQ 10 redox status with a decrease of oxidised CoQ 10 . Conclusion: Decreased concentrations of plasma CoQ 10 and vitamin E in SLOS patients are due to a diminished carrier capacity. The higher percentage of reduced CoQ 10 in platelets points to an up-regulation of mitochondrial protection mechanisms. Further studies are needed to evaluate a possible benefit of CoQ 10 supplementation in SLOS patients.

Coenzyme Q10 (CoQ10) is used by the body as an endogenous antioxidant. This property combined with its essential function in mitochondrial energy production suggests that it may have therapeutic potential in cancer treatment. As part of the body's antioxidant defence against free radical production, CoQ10 concentrations may change during anti-cancer chemotherapy. Our study measured CoQ10 concentration in the plasma of 27 children with acute lymphoblastic leukaemia (ALL) at the time of diagnosis, during induction (protocol ALL-BFM 2000), and post induction treatment. The starting values were compared to the CoQ10 concentrations in 92 healthy children. The total CoQ10 concentration and its redox status were measured by HPLC using electrochemical detection and internal standardisation. While the CoQ10 concentration in the plasma of children with ALL was within a normal range at the time of diagnosis (0.99 +/- 0.41 pmol/microl), a drastic increase was observed during induction treatment (2.19 +/- 1.01 pmol/mul on day 33). This increase was accompanied by shift in the redox status in favour of the reduced form of CoQ10. The increase in CoQ10 concentration during induction treatment may be attributed to the activation of a natural antioxidative defence mechanism, endocrine influence on CoQ10 synthesis from steroid treatment, or a shift in CoQ10 from the damaged cells to the plasma after cell lysis.

Objective To determine the short-term effects of coenzyme Q10 (CoQ10) on the antioxidative status and tinnitus expression in patients with chronic tinnitus aurium. Study design A 16-week prospective nonrandomized clinical trial (n = 20). Tinnitus and Short Form-36 Questionnaires (TQ/SF-36) were evaluated together with the plasma concentrations of CoQ10, malondialdehyde, and the total antioxidant status. Results The mean plasma CoQ10 concentration rose under external CoQ10 supply and remained elevated after medication stopped without overall effects on the tinnitus score. However, in a subgroup of 7 patients with low initial plasma CoQ10 concentration and significant increase in the plasma CoQ10 level, a clear decrease in the TQ score was observed. Conclusion In patients with a low plasma CoQ10 concentration, CoQ10 supply may decrease the tinnitus expression. Significance This is the first study to examine the effect of CoQ10 in chronic tinnitus aurium.

Coenzyme Q10 (CoQ10) concentration in blood cells was analyzed by HPLC and compared to plasma concentration before, during, and after CoQ10 (3 mg/kg/day) supplementation to human probands. Lymphocyte DNA 8-hydroxydeoxy-guanosine (8-OHdG), a marker of oxidative stress, was analyzed by Comet assay. Subjects supplemented with CoQ10 showed a distinct response in plasma concentrations after 14 and 28 days. Plasma levels returned to baseline values 12 weeks after treatment stopped. The plasma concentration increase did not affect erythrocyte levels. However, after CoQ10 supplementation, the platelet level increased; after supplementation stopped, the platelet level showed a delayed decrease. A positive correlation was shown between the plasma CoQ10 level and platelet and white blood cell CoQ10 levels. During CoQ10 supplementation, delayed formation of 8-OHdG in lymphocyte DNA was observed; this effect was long-lasting and could be observed even 12 weeks after supplementation stopped. Intracellular enrichment may support anti-oxidative defense mechanisms.

Studies in humans and cell culture as well as bioinformatics suggested that Coenzyme Q(10) (CoQ10) functions as an anti-inflammatory molecule. Here we studied the influence of CoQ10 (Kaneka Q10) on secretion of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) by using the human and murine monocytic cell lines THP-1 and RAW264.7 expressing human apolipoprotein E3 (apoE3) or pro-inflammatory apoE4. Incubation of cells with physiological (0.1-10 microM) and supra-physiological (10 to100 microM) concentrations of CoQ10 led to an intracellular accumulation of its reduced form without any cytotoxic effects. Stimulation of cell models with lipopolysaccharide (LPS) resulted in a substantially release of TNF-alpha. When THP-1 cells were pre-incubated with 10 microM CoQ10, the LPS-induced TNF-alpha release was significantly decreased to 72 +/- 32%. This effect is similar to those obtained by 10 microM N-Acetyl-Cysteine, a well known reference antioxidant. In RAW264.7-apoE3 and -apoE4 cells, significant reductions of LPS-induced TNF-alpha secretion to 73.3 +/- 2.8% and 74.7 +/- 8.9% were found with 2.5 microM and 75 microM CoQ10, respectively. In conclusion, CoQ10 has moderate anti-inflammatory effects in two monocytic cell lines which could be mediated by its antioxidant activity.

In the present study the relationship between the CoQ10 redox state (% oxidized form of CoQ10 ) and the serum level of c-reactive protein (CRP) was investigated in a large Caucasian study population (n = 1319). In order to evaluate independently the influence of the variables that predict the outcome of CRP, an analysis of covariance (ANCOVA) was performed with CRP as the dependent variable. Gender was taken as an independent factor and CoQ10 redox and BMI as independent covariates. Results were substantiated with findings from a human intervention study (n = 53), receiving 150 mg/day ubiquinol for 14 days. Spearman's correlation revealed a significant (P 0.001) association between the CoQ10 redox state and CRP concentrations in the whole study population. Thus, higher CRP concentrations were found in subjects having more oxidized CoQ10 . Similar results were evident for further inflammatory markers (interleukin-6, number of leucocytes). The ANCOVA revealed a significant (P 0.001) prediction of CRP concentrations by CoQ10 redox state, after controlling for the effect of BMI and separately for gender. In the intervention study it was further found that the oral intake of ubiquinol increased its proportion significantly (P 0.001), with the highest increase in those persons having a low basal serum ubiquinol content (92.3%). Here it was discovered that the ubiquinol status significantly correlated to the concentration of the inflammation marker monocyte chemotactic protein 1. It is concluded that CoQ10 redox state predicts the concentration of CRP. Persons at risk with lower ubiquinol status, higher BMI, and low grade inflammation may benefit from ubiquinol supplementation. © 2016 BioFactors, 42(3):268-276, 2016.

Coenzyme Q (CoQ) is necessary for mitochondrial energy production and modulates the expression of genes that are important for inflammatory processes, growth and detoxification reactions. A cellular surveillance-activated detoxification and defenses (cSADDs) pathway has been recently identified in C. elegans. The down-regulation of the components of the cSADDs pathway initiates an aversion behavior of the nematode. Here we hypothesized that CoQ regulates genes of the cSADDs pathway. To verify this we generated CoQ-deficient worms ("CoQ-free") and performed whole-genome expression profiling. We found about 30% (120 genes) of the cSADDs pathway genes were differentially regulated under CoQ-deficient condition. Remarkably, 83% of these genes were down-regulated. The majority of the CoQ-sensitive cSADDs pathway genes encode for proteins involved in larval development (enrichment score (ES) = 38.0, p = 5.0E(-37)), aminoacyl-tRNA biosynthesis, proteasome function (ES 8.2, p = 5.9E(-31)) and mitochondria function (ES 3.4, p = 1.7E(-5)). 67% (80 genes) of these genes are categorized as lethal. Thus it is shown for the first time that CoQ regulates a substantial number of essential genes that function in the evolutionary conserved cellular surveillance-activated detoxification and defenses pathway in C. elegans.

Background : Coenzyme Q10 (CoQ10) originates from food intake as well as from endogenous synthesis. While plasma concentrations may be influenced by dietary uptake, little is known whether concentrations in plasma reflect or influence intracellular concentrations. Methods : For clinical routine investigation of intracellular CoQ10 contents, blood erythrocytes and platelets were isolated by Ficoll separating solution and CoQ10 analysed using HPLC. The intracellular concentrations were compared to environmental plasma concentrations of 50 clinically healthy infants and additionally after exogenous pharmaceutical supplementation of CoQ10 (3 mg/kg/day) to 12 adult probands for 14 days. Results : In healthy children, no correlation between plasma concentration and content in blood cells was found. A negative correlation exists between the year of life of the infants and CoQ10 concentrations in plasma correlated to cholesterol content. Probands supplemented with CoQ10 showed a distinct response in plasma concentrations after 14 days. While excessive environmental supplementation was without influence on erythrocyte concentrations, a positive correlation exists between plasma content and concentrations in platelets as mitochondria containing cell lines. Conclusions : Under physiologically normal conditions, blood cells or organs may regulate their CoQ10 content independently from environmental supply. Effects may be expected in situations of deficiency or excessive supply. Erythrocyte concentration of CoQ10 keeps independent from environmental supply. Thus incorporation into outer cell membranes may be limited. However, an excessive environmental supply may influence inner compartments like mitochondrial membranes.

Respiratory instability as well as tissue damage by free radicals (oxidative stress) have been hypothesized to play a role in cases of sudden and unexpected infant death in the first year of life. The ratio of the oxidized/reduced form of redox compounds in the circulation could be used as a marker of oxidative stress. Therefore, the sleep apnoea rate and redox status of coenzyme Q10 (CoQ10) (percentage of the oxidized form in total CoQ10) were measured in a population of clinically healthy infants in their first year of life in order to study whether a physiological parameter of respiratory instability is related to a biochemical parameter of oxidative stress. Between May and December 1999, 323 infants in the first year of life were referred to a paediatric sleep laboratory. Sleep apnoea rate, periodic breathing and parameters of oxygenation (SaO2 and TcPO2) were calculated based on polysomnographic recordings. The CoQ10 redox status was calculated based on high-pressure liquid chromatographic (HPLC) analysis. Statistical analysis showed an age-dependent decrease in apnoea rate (r=−0.38) and CoQ10 redox status (r=−0.40). An increased CoQ10 redox status (median: 16.6%; range: 7.3–29.7%) was found in infants with high apnoea rates above the 90th percentile of a reference group in comparison with infants with apnoea rates below the 90th percentile of a reference group (median: 10.4%; range: 5.1–20.4%; P=0.031). These findings may indicate that high apnoea rates are accompanied by increased formation of free radicals in clinically healthy infants in the first year of life.

Ubiquinone and ubiquinol represent the oxidized and reduced forms of Coenzyme Q10 (CoQ10). CoQ10 is present in membranes of almost all human tissues and organs, with highest concentration in the heart. In patients with heart failure, serum levels of the N-terminal pro-brain natriuretic peptide (NT-proBNP) are an indicator of disease severity. Here, we investigated the relationship between serum levels of CoQ10 and NT-proBNP in healthy volunteers of an elderly study population (mean age 52 years, n = 871). We found a negative association between serum levels of ubiquinol and NT-proBNP (P 0.001). Accordingly, the CoQ10 redox state (% oxidized form of CoQ10) is positively associated with serum NT-proBNP level (P 0.001). Compared to patients who survived a myocardial infarction (n = 21), healthy subjects have lower NT-proBNP level (500.39 ± 631.28 pg/ml vs. 76.90 ± 120.27 pg/ml, P 0.001), higher ubiquinol serum level (0.43 ± 0.19 µmol/L vs. 0.71 ± 0.32 µmol/L; P 0.001), and a lower CoQ10 redox state (27.6 ± 13.8% vs. 17.6 ± 10.1%; P 0.001). Interestingly, ubiquinol supplementation (150 mg/day; 14 day; n = 53) slightly reduces the expression of CLCN6, a gene related to NT-proBNP level. In summary, higher serum levels of ubiquinol are associated with lower serum NT-proBNP levels in healthy elderly subjects. However, to what extent a high serum level of ubiquinol is a protective factor for heart failure remains to be elucidated in prospective studies.

Coenzyme Q derivatives (CoQ) are lipid soluble antioxidants that are synthesized endogenously in almost all species and function as an obligatory cofactor of the respiratory chain. There is evidence that CoQ status is altered by age in several species. Here we determined level and redox-state of CoQ in different age groups of pigs, mice and Caenorhabditis elegans. Since these species are very different with respect to lifespan, reproduction and physiology, our approach could provide some general tendencies of CoQ status in ageing organisms. We found that CoQ level decreases with age in pigs and mice, whereas CoQ content increases in older worms. As observed in all three species, ubiquinone, the oxidized form of CoQ, increases with age. Additionally, we were able to show that supplementation of ubiquinol-10, the reduced form of human CoQ10 , slightly increases lifespan of post-reproductive worms. In conclusion, the percentage of the oxidized form of CoQ increases with age indicating higher oxidative stress or rather a decreased anti-oxidative capacity of aged animals.

Coenzyme Q10 (CoQ10) is a lipophilic redox molecule that is present in membranes of almost all cells in human tissues. CoQ10 is, amongst other functions, essential for the respiratory transport chain and is a modulator of inflammatory processes and gene expression. Rare monogenetic CoQ10 deficiencies show noticeable symptoms in tissues (e.g. kidney) and cell types (e.g. neurons) with a high energy demand. To identify common genetic variants influencing serum CoQ10 levels, we performed a fixed effects meta-analysis in two independent cross-sectional Northern German cohorts comprising 1300 individuals in total. We identified two genome-wide significant susceptibility loci. The best associated single nucleotide polymorphism (SNP) was rs9952641 (P value = 1.31 × 10 -8, β = 0.063, CI0.95 [0.041, 0.085]) within the COLEC12 gene on chromosome 18. The SNP rs933585 within the NRXN-1 gene on chromosome 2 also showed genome wide significance (P value = 3.64 × 10 -8, β = -0.034, CI0.95 [-0.046, -0.022]). Both genes have been previously linked to neuronal diseases like Alzheimer's disease, autism and schizophrenia. Among our 'top-10' associated variants, four additional loci with known neuronal connections showed suggestive associations with CoQ10 levels. In summary, this study demonstrates that serum CoQ10 levels are associated with common genetic loci that are linked to neuronal diseases.

Swine tissues were used as surrogates for human tissues with coenzyme Q10 (CoQ10) as the primary endogenous quinoid to establish a reliable method for the analysis of total CoQ10 concentration and redox status using the reduced and oxidized forms of CoQ9 as internal standards. Specimens of frozen swine tissues were disrupted by bead milling using 2-propanol as the homogenization medium supplemented with the internal standards. After hexane extraction, CoQ10 was analyzed via high-performance liquid chromatography with electrochemical detection. The method is linear (12-60 mg fresh muscle tissue/sample), sensitive (~200 pmol CoQ10/sample), and reproducible (coefficients of variation of 6.0 and 3.2% for total CoQ10 and 2.4 and 3.2% for the redox status of within-day and day-to-day precision, respectively), with analytic recoveries for ubiquinone-10, ubihydroquinone-10, and total Q10 of 91, 104, and 94%, respectively. The concentration and redox status were stable for at least 3 months at -84°C. The total CoQ10 concentrations (pmol/mg fresh tissue) in swine tissues were as follows: lung (17.4±1.42), skeletal muscle (26.7±2.57), brain (40.7±4.02), liver (62.1±31.0), kidney (111.7±37.08), and heart muscle (149.1±36.78). Significant tissue-specific variations were also found for the redox status (% oxidation of total): swine liver (~28), lung (~36), kidney (~37), heart muscle (~57), skeletal muscle (~61), and brain (~67).

Background Coenzyme Q10 (CoQ10) is essential for mitochondrial energy production and serves as an antioxidants in extra mitochondrial membranes. The genetics of primary CoQ10 deficiency has been described in several studies, whereas the influence of common genetic variants on CoQ10 status is largely unknown. Here we tested for non-synonymous single-nucleotidepolymorphisms (SNP) in genes involved in the biosynthesis (CoQ3G272S , CoQ6M406V, CoQ7M103T), reduction (NQO1P187S, NQO2L47F) and metabolism (apoE3/4) of CoQ10 and their association with CoQ10 status. For this purpose, CoQ10 serum levels of 54 healthy male volunteers were determined before (T0) and after a 14 days supplementation (T14) with 150 mg/d of the reduced form of CoQ10. Findings At T0, the CoQ10 level of heterozygous NQO1P187S carriers were significantly lower than homozygous S/S carriers (0.93 ± 0.25 μM versus 1.34 ± 0.42 μM, p = 0.044). For this polymorphism a structure homology-based method (PolyPhen) revealed a possibly damaging effect on NQO1 protein activity. Furthermore, CoQ10 plasma levels were significantly increased in apoE4/E4 genotype after supplementation in comparison to apoE2/E3 genotype (5.93 ± 0.151 μM versus 4.38 ± 0.792 μM, p = 0.034). Likewise heterozygous CoQ3G272S carriers had higher CoQ10 plasma levels at T14 compared to G/G carriers but this difference did not reach significance (5.30 ± 0.96 μM versus 4.42 ± 1.67 μM, p = 0.082). Conclusions In conclusion, our pilot study provides evidence that NQO1P187S and apoE polymorphisms influence CoQ10 status in humans.

Studies in vitro and in mice indicate a role for Coenzyme Q(10) (CoQ(10) ) in gene expression. To determine this function in relationship to physiological readouts, a 2-week supplementation study with the reduced form of CoQ(10) (ubiquinol, Q(10) H(2) , 150 mg/d) was performed in 53 healthy males. Mean CoQ(10) plasma levels increased 4.8-fold after supplementation. Transcriptomic and bioinformatic approaches identified a gene-gene interaction network in CD14-positive monocytes, which functions in inflammation, cell differentiation, and peroxisome proliferator-activated receptor-signaling. These Q(10) H(2) -induced gene expression signatures were also described previously in liver tissues of SAMP1 mice. Biochemical and NMR-based analyses showed a reduction of low density lipoprotein (LDL) cholesterol plasma levels after Q(10) H(2) supplementation. This effect was especially pronounced in atherogenic small dense LDL particles (19-21 nm, 1.045 g/L). In agreement with gene expression signatures, Q(10) H(2) reduces the number of erythrocytes but increases the concentration of reticulocytes. In conclusion, Q(10) H(2) induces characteristic gene expression patterns, which are translated into reduced LDL cholesterol levels and altered parameters of erythropoiesis in humans.

Our present view of the function(s) of the pineal gland has been derived primarily from a comparative approach using several small rodent species which show pronounced seasonal reproductive cycles. Although it had been known for several decades that these seasonal reproductive cycles are controlled by the photoperiod, the idea of a functional link between the pineal gland and mammalian photoperiodism in general, developed slowly. Today it is well established that the pineal gland and one of its compounds, namely melatonin, convey the photoperiodic message. The gonadotropic effect(s) of the pineal gland and of melatonin certainly are of major importance for an adequate adaptation of the animals to a seasonally changing environment. However, photoperiod not only has a strong impact on the reproductive system, but also on many other organs and physiological functions. All functions which appear to be controlled by the photoperiod can be influenced by modifying the output signal of the pineal gland, i.e. melatonin. The major importance of the pineal organ in small mammals seems to be the precise temporal and sequential coordination of all of these functions, in order to meet the varying energetic demands of the different seasons.

BACKGROUND: Diabetes and obesity are metabolic disorders induced by an excessive dietary intake of fat, usually related to inflammation and oxidative stress. AIMS: The aim of the study is to investigate the effect of the antioxidant coenzyme Q10 (CoQ10) on hepatic metabolic and inflammatory disorders associated with diet-induced obesity and glucose intolerance. METHODS: C57bl6/j mice were fed for 8 weeks, either a control diet (CT) or a high fat diet plus 21% fructose in the drinking water (HFF). CoQ10 supplementation was performed in this later condition (HFFQ). RESULTS: HFF mice exhibit increased energy consumption, fat mass development, fasting glycemia and insulinemia and impaired glucose tolerance. HFF treatment promoted the expression of genes involved in reactive oxygen species production (NADPH oxidase), inflammation (CRP, STAMP-2) and metabolism (CPT1alpha) in the liver. CoQ10 supplementation decreased the global hepatic mRNA expression of inflammatory and metabolic stresses markers without changing obesity and tissue lipid peroxides compared to HFF mice. HFF diets paradoxically decreased TBARS (reflecting lipid peroxides) levels in liver, muscle and adipose tissue versus CT group, an effect related to vitamin E content of the diet. CONCLUSION: In conclusion, HFF model promotes glucose intolerance and obesity by a mechanism independent on the level of tissue peroxides. CoQ10 tends to decrease hepatic stress gene expression, independently of any modulation of lipid peroxidation, which is classically considered as its most relevant effect.

Clinical studies demonstrated the efficacy of Coenzyme Q(10) (CoQ(10)) as an adjuvant therapeutic in cardiovascular diseases, mitochondrial myopathies and neurodegenerative diseases. More recently, expression profiling revealed that Coenzyme Q(10) (COQ(10)) influences the expression of several hundred genes. To unravel the functional connections of these genes, we performed a text mining approach using the Genomatix BiblioSphere. We identified signalling pathways of G-protein coupled receptors, JAK/STAT, and Integrin which contain a number of CoQ(10) sensitive genes. Further analysis suggested that IL5, thrombin, vitronectin, vitronectin receptor, and C-reactive protein are regulated by CoQ(10) via the transcription factor NF kappa B1. To test this hypothesis, we studied the effect of CoQ(10) on the NF kappa B1-dependent pro-inflammatory cytokine TNF-alpha. As a model, we utilized the murine macrophage cell lines RAW264.7 transfected with human apolipoprotein E3 (apoE3, control) or pro-inflammatory apoE4. In the presence of 2.5 mu M or 75 mu M CoQ(10) the LPS-induced TNF-alpha response was significantly reduced to 73.3 +/- 1 2.8% and 74.7 +/- 8.9% in apoE3 or apoE4 cells, respectively. Therefore, the in silico analysis as well as the cell culture experiments suggested that CoQ(10) exerts anti-inflammatory properties via NF kappa B1-dependent gene expression.

Hyperglycaemia has been reported to cause increased production of oxygen free radicals. Oxidative stress may contribute to the pathogenesis of diabetic complications. Coenzyme Q(10) (CoQ(10)) is known for its key role in mitochondrial bioenergetics and is considered as a potent antioxidant and free radical scavenger. This study was conducted to evaluate plasma and blood cell concentrations of CoQ(10) in accordance to its redox capacity in children with diabetes mellitus type 1. CoQ(10) plasma and blood cell concentrations and redox status were measured using high-performance liquid chromatography with electrochemical detection in 43 children with diabetes mellitus type 1 and compared with 39 healthy children. In addition, the diabetic patients were subdivided according to their haemoglobin A1c (HbA1c) values into two groups, that is, those with good control (8%) and those with poor control (8%), and the CoQ(10) status was compared between the two groups. Children with type 1 diabetes showed increased plasma levels of CoQ(10) in comparison to healthy children. While CoQ(10) erythrocyte and platelet concentrations did not differ, in the diabetes group, the platelet redox status differed with a significantly increased part of reduced CoQ(10). This difference in concentration and redox status in comparison to healthy controls may be attributed to the subgroup of patients with poor control, as the subdivision of diabetic patients according to their HbA1c values shows. In diabetic children, especially in those with poor control, an increase in plasma concentration and intracellular redox capacity of the antioxidant CoQ(10) may contribute to the body's self-protection during a state of enhanced oxidative stress.

Mitochondrial complex I appears to be dysfunctional in progressive supranuclear palsy (PSP). Coenzyme Q(10) (CoQ(10)) is a physiological cofactor of complex I. Therefore, we evaluated the short-term effects of CoQ(10) in PSP. We performed a double-blind, randomized, placebo-controlled, phase II trial, including 21 clinically probable PSP patients (stageor = III) to receive a liquid nanodispersion of CoQ(10) (5 mg/kg/day) or matching placebo. Over a 6-week period, we determined the change in CoQ(10) serum concentration, cerebral energy metabolites (by (31)P- and (1)H-magnetic resonance spectroscopy), motor and neuropsychological dysfunction (PSP rating scale, UPDRS III, Hoehn and Yahr stage, Frontal Assessment Battery, Mini Mental Status Examination, Montgomery Asberg Depression Scale). CoQ(10) was safe and well tolerated. In patients receiving CoQ(10) compared to placebo, the concentration of low-energy phosphates (adenosine-diphosphate, unphosphorylated creatine) decreased. Consequently, the ratio of high-energy phosphates to low-energy phosphates (adenosine-triphosphate to adenosine-diphosphate, phospho-creatine to unphosphorylated creatine) increased. These changes were significant in the occipital lobe and showed a consistent trend in the basal ganglia. Clinically, the PSP rating scale and the Frontal Assessment Battery improved slightly, but significantly, upon CoQ(10) treatment compared to placebo. Since CoQ(10) appears to improve cerebral energy metabolism in PSP, long-term treatment might have a disease-modifying, neuroprotective effect.

Major hallmarks in the pathophysiology of Parkinson disease are cellular energy depletion and oxidative stress leading to cellular dysfunction and death. Coenzyme Q(10) (CoQ(10)) is an electron acceptor bridging mitochondrial complexes I and II/III and a potent antioxidant that consistently partially recovers the function of dopaminergic neurons.To determine whether nanoparticular CoQ(10) is safe and displays symptomatic effects in patients with midstage Parkinson disease without motor fluctuations.Multicenter, randomized, double-blind, placebo-controlled, stratified, parallel-group, single-dose trial.Academic and nonacademic movement disorder clinics.One hundred thirty-one patients with Parkinson disease without motor fluctuations and a stable antiparkinsonian treatment. Intervention Random assignment to placebo or nanoparticular CoQ(10) (100 mg 3 times a day) for a treatment period of 3 months. Stratification criterion was levodopa treatment.The subjects underwent evaluation with the Unified Parkinson's Disease Rating Scale (UPDRS) at each visit on a monthly basis. The primary outcome variable was the change of the sum score of the UPDRS parts II and III between the baseline and 3-month visits.One hundred thirty-one subjects were randomized according to the protocol. The mean changes of the sum UPDRS parts II/III score were -3.69 for the placebo group and -3.33 for the CoQ(10) group (P = .82). Statistical analysis according to the stratification did not result in significant changes of the primary outcome variable. No secondary outcome measure showed a significant change between the placebo group and the CoQ(10) group. The frequency and quality of adverse events were similar in both treatment groups.Nanoparticular CoQ(10) at a dosage of 300 mg/d is safe and well tolerated and leads to plasma levels similar to 1200 mg/d of standard formulations. Add-on CoQ(10) does not display symptomatic effects in midstage Parkinson disease.

Coenzyme Q10 (CoQ10) is used by the body as an endogenous antioxidant and performs essential functions in mitochondrial energy production. The value of CoQ10 as a biomarker for oxidative stress will be severely restricted if there are huge individual daily variations in its concentration. For analysis of diurnal changes in CoQ10 plasma and blood cell concentrations, blood was collected from nine healthy adults (at two- or three-hour intervals for plasma, and three times a day for blood cells). CoQ10 was analysed by HPLC using electrochemical detection and internal standardisation. Daytime variations in CoQ10 concentration in plasma are maintained within narrow limits and show no statistically significant difference (Kruskal-Wallis). However, a drop at night-time (0300 h) is accompanied by a drop in total cholesterol concentration. Remarkable inter-individual differences in blood cell (erythrocytes, platelets, white blood cells) content of CoQ10 occur with only slight intra-individual daily variations. A correlation (Spearman) is found for cholesterol and CoQ10 content in circulation which may be explained by the carrier capacity of blood for this highly lipophilic substance. Moreover, a diurnal change in hepatic HMG-CoA reductase activity may suggest a common diurnal regulation of synthesis of both CoQ10 and cholesterol.

In contrast to other lipophilic antioxidants Coenzyme Q10 originates from food intake as well as from endogenous synthesis. The CoQ10 concentration and lipid content of maternal milk and maternal plasma was investigated during early lactation. Breast milk was obtained from 23 women: A: colostrums (24-48 hours postpartum), B: transitional milk (day 7 pp), C: mature milk (day 14 pp). At the same time capillary blood specimens were collected. Milk and plasma were stored at -84 degrees C until CoQ10 was analysed after hexane extraction by HPLC. The lipid content was determined by PAP-analysis of cholesterol. The plasma content of CoQ10 was the highest soon after delivery (A: 1.29, B:1.20, C:1.07 pmol/microl; Wilcoxon p < 0.05 A vs. C and B vs. C). This tendency was still evident after lipid-adjustment (A:209, B:180, C:175 micromol CoQ10/mol cholesterol; Wilcoxon p < 0.01 A vs. B and C). The level of CoQ10 in milk showed a gradual decline during early lactation (A:0.80, B:0.57, C:0.44 pmol/microl; Wilcoxon p < 0.02 A vs. B and C). After lipid-adjustment this tendency became even more evident (A: 137, B:86, C:67 micromol CoQ10/mol cholesterol; Wilcoxon p < 0.002 A vs. B and C, p < 0.05 B vs. C). The content of CoQ10 in plasma and milk showed a correlation with early milk (Spearman p < 0.005) but not with mature milk. Although lipid content is low the colostrums is a rich source for the lipophilic antioxidant CoQ10.

Introduction: Increased attention has been paid to the role of lipophilic antioxidants in childhood nutrition and diseases during recent years. The lipophilic antioxidant coenzyme Q10 (CoQ10) is known as an effective inhibitor of oxidative damage. In contrast to other lipophilic antioxidants like α-tocopherol the plasma concentrations of CoQ10 in childhood are poorly researched. The aim of this study was to determine plasma level and redox status (oxidized form in total CoQ10 in %) of CoQ10 in clinically healthy infants, preschoolers and school-aged children. Methods: Plasma level and redox status of CoQ10 were measured by HPLC in 199 clinically healthy children, three groups of infants [1st-4th month (n = 35), 5th-8th month (n = 25), 9th-12th month (n = 25) ], preschoolers (n = 60) and school-aged children (n = 54). The CoQ10 plasma levels were related to plasma cholesterol concentrations. The median and the 5th and 95th percentile were calculated. Results: Plasma levels and redox status of CoQ10 in infants were significantly higher than in preschoolers and school-aged children. The CoQ10 redox status in the 1st-4th month was significantly increased when compared to the remaining subgroups of infants. In elder children the CoQ10 redox status stabilized. Conclusion: This is the first study concerning age-related values of plasma level and redox status of CoQ10 in apparently healthy children. Decreased CoQ10 values could be involved in various pathological conditions affecting childhood. Therefore, the application of age-adjusted reference values may provide more specific criteria to define threshold values for CoQ10 deficiency in plasma.

Objectives: In hyperthyroidism, increased oxygen consumption and free radical production in the stimulated respiratory chain leads to oxidative stress. Apart from its antioxidative function, coenzyme Q10 (CoQ10) is involved in electron transport in the respiratory chain. The aim of this study was to determine whether there is a correlation between an increased respiratory chain activity and the state of CoQ10 in children with hyperthyroidism. Methods: The CoQ10 plasma concentration was measured by high-performance liquid chromatography in 12 children with hyperthyroidism before and after treatment. Results: In the hyperthyroid state, the plasma level of CoQ10 was significantly decreased in comparison with the level in the euthyroid state. The correction of the hyperthyroid state resulted in a normalization of the CoQ10 level. Conclusion: Plasma CoQ10 deficiency appears to be related to the stimulated respiratory chain activity in children with hyperthyroidism.

Background: The membrane-associated antioxidant coenzyme Q10 (CoQ10) or ubiquinone-10 is frequently measured in serum or plasma. However, little is known about the total contents or redox status of CoQ10 in blood cells. Methods: We have developed a method for determination of CoQ10 in erythrocytes. Total CoQ10 in erythrocytes was compared to the amounts of ubiquinone-10 and ubihydroquinone-10 in plasma using high-pressure liquid chromatography (HPLC) with electrochemical detection and internal standardisation (ubiquinone-9, ubihydroquinone-9). Results: Investigations in 10 healthy probands showed that oral intake of CoQ10 (3 mg/kg/day) led to a short-term (after 5 h, 1.57±0.55 pmol/μl plasma) and long-term (after 14 days, 4.00±1.88 pmol/μl plasma, p

A HPLC-method was developed for the simultaneous detection of the lipophilic antioxidants ubiquinol-10, ubiquinone-10, alpha-tocopherol, and gamma-tocopherol in plasma macrosamples (100 microl) as well as microsamples (10 microl) using electrochemical detection with internal standardization (gamma-tocotrienol, ubiquinol-9, ubiquinone-9). The use of a mobile phase containing ammonium formate instead of lithium perchlorate as conductivity salt and the use of a PEEK column instead of a steel column improved the reproducibility of the method. The components were separated on a RP C18 column. The detection limits for all components were between 1 and 28 fmol. The within-day precision varied between 3 and 13% for all measured substances. The analytical recovery was between 93 and 109%. The plasma levels from 10 healthy donors were determined in microsamples and macrosamples taken by micropuncture or venous puncture, respectively. A good correlation of the antioxidant levels for both methods strengthened the reliability and the transferability of the results. The present method can be used to assess the role of these antioxidants in diseases associated with oxidative damage in childhood.

The reduced form of Coenzyme Q10 (CoQ10), ubiquinol (Q10H2), serves as a potent antioxidant in mitochondria and lipid membranes. There is evidence that Q10H2 protects against oxidative events in lipids, proteins and DNA. Serum gamma-glutamyltransferase (GGT) activity is associated with cardiovascular diseases. In a physiological range, activity of GGT is a potential early and sensitive marker of inflammation and oxidative stress. In this study, we first examined the relationship between CoQ10 status and serum GGT activity in 416 healthy participants between 19 and 62 years of age in a cross-sectional study (cohort I). In the second step, 53 healthy males (21–48 years of age; cohort II) underwent a 14-day Q10H2 supplementation (150 mg/d) to evaluate the effect of Q10H2 supplementation on serum GGT activity and GGT1 gene expression. There was a strong positive association between CoQ10 status and serum GGT activity in cohort I. However, a gender-specific examination revealed differences between male and female volunteers regarding the association between CoQ10 status and serum GGT activity. Q10H2 supplementation (cohort II) caused a significant decrease in serum GGT activity from T0 to T14 (p