High coenzyme Q10 plasma levels improve stress and damage markers in professional soccer players during competition.

Ubiquinol, the reduced form of Coenzyme Q10 (CoQ10), is a key factor in bioenergetics and antioxidant protection. During competition, professional soccer players suffer from considerable physical stress causing high risk of muscle damage. For athletes, supplementation with several antioxidants, including CoQ10, is widely recommended to avoid oxidative stress and muscle damage. We performed an observational study of plasma parameters associated with CoQ10 levels in professional soccer players of the Spanish First League team Athletic Club de Bilbao over two consecutive seasons (n = 24-25) in order determine their relationship with damage, stress and performance during competition. We analyzed three different moments of the competition: preterm, initial phase and mid phase. Metabolites and factors related with stress (testosterone/cortisol) and muscle damage (creatine kinase) were determined. Physical activity during matches was analyzed over the 2015/16 season in those players participating in complete matches. In the mid phase of competition, CoQ10 levels were higher in 2015/16 (906.8 ± 307.9 vs. 584.3 ± 196.3 pmol/mL, p = 0.0006) High levels of CoQ10 in the hardest phase of competition were associated with a reduction in the levels of the muscle-damage marker creatine kinase (Pearsons' correlation coefficient (r) = - 0.460, p = 0.00168) and a trend for the stress marker cortisol (r = -0.252, p = 0.150). Plasma ubiquinol was also associated with better kidney function (r = -0.287, p = 0.0443 for uric acid). Furthermore, high CoQ10 levels were associated with higher muscle performance during matches. Our results suggest that high levels of plasma CoQ10 can prevent muscle damage, improve kidney function and are associated with higher performance in professional soccer players during competition.

Age-dependent impact of two exercise training regimens on genomic and metabolic remodeling in skeletal muscle and liver of male mice.

Skeletal muscle adapts to different exercise training modalities with age; however, the impact of both variables at the systemic and tissue levels is not fully understood. Here, adult and old C57BL/6 male mice were assigned to one of three groups: sedentary, daily high-intensity intermittent training (HIIT), or moderate intensity continuous training (MICT) for 4 weeks, compatible with the older group's exercise capacity. Improvements in body composition, fasting blood glucose, and muscle strength were mostly observed in the MICT old group, while effects of HIIT training in adult and old animals was less clear. Skeletal muscle exhibited structural and functional adaptations to exercise training, as revealed by electron microscopy, OXPHOS assays, respirometry, and muscle protein biomarkers. Transcriptomics analysis of gastrocnemius muscle combined with liver and serum metabolomics unveiled an age-dependent metabolic remodeling in response to exercise training. These results support a tailored exercise prescription approach aimed at improving health and ameliorating age-associated loss of muscle strength and function in the elderly.

Resveratrol Regulates the Expression of Genes Involved in CoQ Synthesis in Liver in Mice Fed with High Fat Diet.

Resveratrol (RSV) is a bioactive natural molecule that induces antioxidant activity and increases protection against oxidative damage. RSV could be used to mitigate damages associated to metabolic diseases and aging. Particularly, RSV regulates different aspects of mitochondrial metabolism. However, no information is available about the effects of RSV on Coenzyme Q (CoQ), a central component in the mitochondrial electron transport chain. Here, we report for the first time that RSV modulates COQ genes and parameters associated to metabolic syndrome in mice. Mice fed with high fat diet (HFD) presented a higher weight gain, triglycerides (TGs) and cholesterol levels while RSV reverted TGs to control level but not weight or cholesterol. HFD induced a decrease of COQs gene mRNA level, whereas RSV reversed this decrease in most of the COQs genes. However, RSV did not show effect on CoQ9, CoQ10 and total CoQ levels, neither in CoQ-dependent antioxidant enzymes. HFD influenced mitochondrial dynamics and mitophagy markers. RSV modulated the levels of PINK1 and PARKIN and their ratio, indicating modulation of mitophagy. In summary, we report that RSV influences some of the metabolic adaptations of HFD affecting mitochondrial physiology while also regulates COQs gene expression levels in a process that can be associated with mitochondrial dynamics and turnover.

Design of High-Throughput Screening of Natural Extracts to Identify Molecules Bypassing Primary Coenzyme Q Deficiency in Saccharomyces cerevisiae.

Coenzyme Q10 (CoQ10) deficiency syndrome is a rare disease included in the family of mitochondrial diseases, which is a heterogeneous group of genetic disorders characterized by defective energy production. CoQ10 biosynthesis in humans requires at least 11 gene products acting in a multiprotein complex within mitochondria. The high-throughput screening (HTS) method based on the stabilization of the CoQ biosynthesis complex (Q-synthome) produced by the COQ8 gene overexpression is proven here to be a successful method for identifying new molecules from natural extracts that are able to bypass the CoQ6 deficiency in yeast mutant cells. The main features of the new approach are the combination of two yeast targets defective in genes with different functions on CoQ6 biosynthesis to secure the versatility of the molecule identified, the use of glycerol as a nonfermentable carbon source providing a wide growth window, and the stringent conditions required to mark an extract as positive. The application of this pilot approach to a representative subset of 1200 samples of the Library of Natural Products of Fundación MEDINA resulted in the finding of nine positive extracts. The fractionation of three of the nine extracts allowed the identification of five molecules; two of them are present in molecule databases of natural extracts and three are nondescribed molecules. The use of this screening method opens the possibility of discovering molecules with CoQ10-bypassing action useful as therapeutic agents to fight against mitochondrial diseases in human patients.

Comparative Bioavailability of Different Coenzyme Q10 Formulations in Healthy Elderly Individuals.

Coenzyme Q10 (CoQ10) plays a central role in mitochondrial oxidative phosphorylation. Several studies have shown the beneficial effects of dietary CoQ10 supplementation, particularly in relation to cardiovascular health. CoQ10 biosynthesis decreases in the elderly, and consequently, the beneficial effects of dietary supplementation in this population are of greater significance. However, most pharmacokinetic studies have been conducted on younger populations. The aim of this study was to investigate the single-dose bioavailability of different formulations of CoQ10 in a healthy geriatric population. A randomized, three-period, crossover bioavailability study was conducted on 21 healthy older adults (aged 65-74). The treatment was a single dose with a one-week washout period. Three different formulations containing the equivalent of 100 mg of CoQ10 were used: Q10Vital® water-soluble CoQ10 syrup (the investigational product-IP); ubiquinol capsules (the comparative product-CP); and ubiquinone capsules (the standard product-SP). Ubiquinone/ubiquinol was followed in the plasma for 48 h. An analysis of the ratio of the area under the baseline-corrected concentration curve (ΔAUC48) for total CoQ10 and a comparison to SP yielded the following: The bioavailability of CoQ10 in the IP was 2.4-fold higher (95% CI: 1.3-4.5; p = 0.002), while the bioavailability of ubiquinol (CP) was not significantly increased (1.7-fold; 95% CI: 0.9-3.1, p = 0.129). No differences in the redox status of the absorbed coenzyme Q10 were observed between formulations, showing that CoQ10 appeared in the blood mostly as ubiquinol, even if consumed as ubiquinone.

Bioavailability of coenzyme Q10 supplements depends on carrier lipids and solubilization.

OBJECTIVES: Bioavailability of supplements with coenzyme Q10 (CoQ10) in humans seems to depend on the excipients of formulations and on physiological characteristics of the individuals. The aim of this study was to determine which factors presented in CoQ10 supplements affect the different response to CoQ10 in humans. METHODS: We tested seven different supplement formulations containing 100 mg of CoQ10 in 14 young, healthy individuals. Bioavailability was measured as area under the curve of plasma CoQ10 levels over 48 h after ingestion of a single dose. Measurements were repeated in the same group of 14 volunteers in a double-blind crossover design with a minimum of 4 wk washout between intakes. RESULTS: Bioavailability of the formulations showed large differences that were statistically significant. The two best absorbable formulations were soft-gel capsules containing ubiquinone (oxidized CoQ10) or ubiquinol (reduced CoQ10). The matrix used to dissolve CoQ10 and the proportion and addition of preservatives such as vitamin C affected the bioavailability of CoQ10. Although control measurements documented that all formulations contained 100 mg of either CoQ10 or ubiquinol, some of the participants showed high and others lower capacity to reach high increase of CoQ10 in blood, indicating the participation of individual unknown physiological factors. CONCLUSION: This study highlights the importance of individually adapted selection of best formulations to reach the highest bioavailability of CoQ10 in humans.