Thomas Menke

Short-term effects of coenzyme Q10 in progressive supranuclear palsy: A randomized, placebo-controlled trial

Mitochondrial complex I appears to be dysfunctional in progressive supranuclear palsy (PSP). Coenzyme Q10 (CoQ10) is a physiological cofactor of complex I. Therefore, we evaluated the short‐term effects of CoQ10 in PSP. We performed a double‐blind, randomized, placebo‐controlled, phase II trial, including 21 clinically probable PSP patients (stage ≤ III) to receive a liquid nanodispersion of CoQ10 (5 mg/kg/day) or matching placebo. Over a 6‐week period, we determined the change in CoQ10 serum concentration, cerebral energy metabolites (by 31P‐ and 1H‐magnetic resonance spectroscopy), motor and neuropsychological dysfunction (PSP rating scale, UPDRS III, Hoehn and Yahr stage, Frontal Assessment Battery, Mini Mental Status Examination, Montgomery Åsberg Depression Scale). CoQ10 was safe and well tolerated. In patients receiving CoQ10 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 CoQ10 treatment compared to placebo. Since CoQ10 appears to improve cerebral energy metabolism in PSP, long‐term treatment might have a disease‐modifying, neuroprotective effect.

Coenzyme Q10 supplementation lowers hepatic oxidative stress and inflammation associated with diet-induced obesity in mice.

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 glycaemia and insulinemia and impaired glucose tolerance. HFF treatment promoted the expression of genes involved in reactive oxygen species production (NADPH oxidase), inflammation (CRP, STAMP2) 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.

Effects of Ubiquinol-10 on MicroRNA-146a Expression In Vitro and In Vivo

MicroRNAs (miRs) are involved in key biological processes via suppression of gene expression at posttranscriptional levels. According to their superior functions, subtle modulation of miR expression by certain compounds or nutrients is desirable under particular conditions. Bacterial lipopolysaccharide (LPS) induces a reactive oxygen species-/NF-κB-dependent pathway which increases the expression of the anti-inflammatory miR-146a. We hypothesized that this induction could be modulated by the antioxidant ubiquinol-10. Preincubation of human monocytic THP-1 cells with ubiquinol-10 reduced the LPS-induced expression level of miR-146a to 78.9 ± 13.22%. In liver samples of mice injected with LPS, supplementation with ubiquinol-10 leads to a reduction of LPS-induced miR-146a expression to 78.12 ± 21.25%. From these consistent in vitro and in vivo data, we conclude that ubiquinol-10 may fine-tune the inflammatory response via moderate reduction of miR-146a expression.

Coenzyme Q10 in plasma and erythrocytes: comparison of antioxidant levels in healthy probands after oral supplementation and in patients suffering from sickle cell anemia

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/microl plasma) and long-term (after 14 days, 4.00+/-1.88 pmol/microl plasma, p<0.05 vs. -1 h, 1.11+/-0.24 pmol/microl plasma) increase in plasma concentrations while decreasing the redox status of CoQ10 (after 14 days, 5.37+/-1.31% in plasma, p<0.05 vs. -1 h, 6.74+/-0.86% in plasma). However, in these healthy probands, CoQ10 content in red blood cells remained unchanged despite excessive supplementation. In addition, plasma and erythrocyte concentrations of CoQ10 were measured in five patients suffering from sickle cell anemia, a genetic anemia characterised by an overall accelerated production of reactive oxygen species. While these patients showed normal or decreased plasma levels of CoQ10 with a shifting of the redox state in favour of the oxidised part (10.8-27.2% in plasma), the erythrocyte concentrations of CoQ10 were dramatically elevated (280-1,093 pmol/10(9) ERY vs. 22.20+/-6.17 pmol/10(9) ERY). CONCLUSIONS We conclude that normal red blood cells may regulate their CoQ10 content independently from environmental supplementation, but dramatic changes may be expected under pathological conditions.

Ubiquinol-induced gene expression signatures are translated into altered parameters of erythropoiesis and reduced low density lipoprotein cholesterol levels in humans

Studies in vitro and in mice indicate a role for Coenzyme Q10 (CoQ10) in gene expression. To determine this function in relationship to physiological readouts, a 2‐week supplementation study with the reduced form of CoQ10 (ubiquinol, Q10H2, 150 mg/d) was performed in 53 healthy males. Mean CoQ10 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 Q10H2‐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 Q10H2 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, Q10H2 reduces the number of erythrocytes but increases the concentration of reticulocytes. In conclusion, Q10H2 induces characteristic gene expression patterns, which are translated into reduced LDL cholesterol levels and altered parameters of erythropoiesis in humans.

Antioxidant level and redox status of coenzyme Q10 in the plasma and blood cells of children with diabetes mellitus type 1

Abstract:  Hyperglycaemia has been reported to cause increased production of oxygen free radicals. Oxidative stress may contribute to the pathogenesis of diabetic complications. Coenzyme Q10 (CoQ10) 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 CoQ10 in accordance to its redox capacity in children with diabetes mellitus type 1. CoQ10 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 CoQ10 status was compared between the two groups. Children with type 1 diabetes showed increased plasma levels of CoQ10 in comparison to healthy children. While CoQ10 erythrocyte and platelet concentrations did not differ, in the diabetes group, the platelet redox status differed with a significantly increased part of reduced CoQ10. 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 CoQ10 may contribute to the body’s self‐protection during a state of enhanced oxidative stress.

Plasma Levels of Coenzyme Q10 in Children with Hyperthyroidism

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.

A comparative study into alterations of coenzyme Q redox status in ageing pigs, mice, and worms

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.

Determination of coenzyme Q10 tissue status via high-performance liquid chromatography with electrochemical detection in swine tissues (Sus scrofa domestica).

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).

Relationships between polysomnographic variables, parameters of glucose metabolism, and serum androgens in obese adolescents with polycystic ovarian syndrome.

The aim of this study was to compare polysomnographic variables of obese adolescents with polycystic ovarian syndrome (PCOS) to those of healthy controls and to analyse whether polysomnographic variables correlate to parameters of body weight/body composition, to serum androgens and to parameters of glucose metabolism. Thirty‐one obese adolescents with PCOS (15.0 years ± 1.0, body mass index 32.7 kg per m2 ± 6.2) and 19 healthy obese adolescents without PCOS (15.2 years ± 1.1, body mass index 32.4 kg per m2 ± 4.0) underwent polysomnography to compare apnoea index, hypopnoea index, apnoea–hypopnoea index, the absolute number of obstructive apnoeas, percentage sleep Stages 1, 2, 3 and 4 of non‐rapid eye movement (NREM) sleep, percentage of REM sleep, TIB, total sleep time (TST), sleep‐onset latency, total wake time (TWT), wakefulness after sleep onset (WASO) and sleep efficiency. Furthermore, we correlated polysomnographic variables to parameters of body weight/body composition, to serum androgens and to parameters of glucose metabolism. We found no differences between the two groups concerning the respiratory indices, percentage sleep Stages 2, 3 and 4 of NREM sleep, TIB and sleep‐onset latency. The girls with PCOS differed significantly from the controls regarding TST, WASO, TWT, sleep efficiency, percentage Stage 1 of NREM sleep and percentage of REM sleep. We found a weak significant correlation between insulin resistance and apnoea index and between insulin resistance and apnoea–hypopnoea index. Concerning the respiratory variables, adolescents with PCOS do not seem to differ from healthy controls; however, there seem to be differences concerning sleep architecture.