Effects of acute and 14-day coenzyme Q10 supplementation on exercise performance in both trained and untrained individuals

Background

To determine whether acute (single dose) and/or chronic (14-days) supplementation of CoQ10 will improve anaerobic and/or aerobic exercise performance by increasing plasma and muscle CoQ10 concentrations within trained and untrained individuals.

Methods

Twenty-two aerobically trained and nineteen untrained male and female subjects (26.1 ± 7.6 yrs, 172 ± 8.7 cm, 73.5 ± 17 kg, and 21.2 ± 7.0%) were randomized to ingest in a double-blind manner either 100 mg of a dextrose placebo (CON) or a fast-melt CoQ10 supplement (CoQ10) twice a day for 14-days. On the first day of supplementation, subjects donated fasting blood samples and a muscle biopsy. Subjects were then given 200 mg of the placebo or the CoQ10 supplement. Sixty minutes following supplement ingestion, subjects completed an isokinetic knee extension endurance test, a 30-second wingate anaerobic capacity test, and a maximal cardiopulmonary graded exercise test interspersed with 30-minutes of recovery. Additional blood samples were taken immediately following each exercise test and a second muscle biopsy sample was taken following the final exercise test. Subjects consumed twice daily (morning and night), 100 mg of either supplement for a period of 14-days, and then returned to the lab to complete the same battery of tests. Data was analyzed using repeated measures ANOVA with an alpha of 0.05.

Results

Plasma CoQ10 levels were significantly increased following 2 weeks of CoQ10 supplementation (p < 0.001); while a trend for higher muscle CoQ10 levels was observed after acute CoQ10 ingestion (p = 0.098). A trend for lower serum superoxide dismutase (SOD) was observed following acute supplementation with CoQ10 (p = 0.06), whereas serum malondialdehyde (MDA) tended to be significantly higher (p < 0.05). Following acute ingestion of CoQ10, plasma CoQ10 levels were significantly correlated to muscle CoQ10 levels; maximal oxygen consumption; and treadmill time to exhaustion. A trend for increased time to exhaustion was observed following 2 weeks of CoQ10 supplementation (p = 0.06).

Conclusion

Acute supplementation with CoQ10 resulted in higher muscle CoQ10 concentration, lower serum SOD oxidative stress, and higher MDA levels during and following exercise. Chronic CoQ10 supplementation increased plasma CoQ10 concentrations and tended to increase time to exhaustion. Results indicate that acute and chronic supplementation of CoQ10 may affect acute and/or chronic responses to various types of exercise.     

Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.     

Combination of the Elevated Stearic Acid Trait with Other Fatty Acid Traits in Soybean

Stearic acid is one of five major fatty acids found in soybean oil. It is a fully saturated lipid and is known for neutral or positive effects on LDL cholesterol when consumed by humans. Unfortunately, stearic acid only accounts for about 4% of the total seed oil produced in commodity soybean. Previous work has shown that stearic acid can reach levels as high as 28% of the total oil fraction when the SACPD-C gene, encoding the delta-9-stearoyl-acyl carrier protein desaturase responsible for most of the stearic acid variation in soybean seed, is ablated in combination with other loci. In order to increase stearic acid content and create soybeans with improved utility based on fatty acid composition, we combined mutations in SACPD-C with other mutations in the fatty acid biosynthetic pathway. Soybean plants carrying mutant alleles of both SACPD-C and FAD2-1A produce seed with stearic acid levels from 14% to 21%, and with elevated levels of oleic acid. Soybeans carrying mutations in both SACPD-C and FAD3A or FAD3C have both statistically significantly elevated levels of stearic acid (from 15–21%) and statistically reduced linolenic acid levels. Neither mutant combination appears to affect other agronomic properties such as plant morphology or seed protein levels making this a potentially viable trait.     

Epigenetic Regulation of Endothelial Dysfunction and Inflammation in Pulmonary Arterial Hypertension

Once perceived as a disorder treated by vasodilation, pulmonary artery hypertension (PAH) has emerged as a pulmonary vascular disease with severe endothelial cell dysfunction. In the absence of a cure, many studies seek to understand the detailed mechanisms of EC regulation to potentially create more therapeutic options for PAH. Endothelial dysfunction is characterized by complex phenotypic changes including unchecked proliferation, apoptosis-resistance, enhanced inflammatory signaling and metabolic reprogramming. Recent studies have highlighted the role of epigenetic modifications leading to pro-inflammatory response pathways, endothelial dysfunction, and the progression of PAH. This review summarizes the existing literature on epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs, which can lead to aberrant endothelial function. Our goal is to develop a conceptual framework for immune dysregulation and epigenetic changes in endothelial cells in the context of PAH. These studies as well as others may lead to advances in therapeutics to treat this devastating disease.     

Polyphenol Supplementation Reverses Age-Related Changes in Microglial Signaling Cascades

Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphenols offer one such means of rectifying age-related decline. Our group used mass spectrometry (MS) analysis to explicate the complex nature of these aging microglial pathways. In our first experiment, we compared primary microglia isolated from young and aged rats and identified 197 significantly differentially expressed proteins between these groups. Then, we performed bioinformatic analysis to explore differences in canonical signaling cascades related to microglial homeostasis and function with age. In a second experiment, we investigated changes to these pathways in aged animals after 30-day dietary supplementation with NT-020, which is a blend of polyphenols. We identified 144 differentially expressed proteins between the NT-020 group and the control diet group via MS analysis. Bioinformatic analysis predicted an NT-020 driven reversal in the upregulation of age-related canonical pathways that control inflammation, cellular metabolism, and proteostasis. Our results highlight salient aspects of microglial aging at the level of protein interactions and demonstrate a potential role of polyphenols as therapeutics for age-associated dysfunction.     

QSAR studies of the pyrethroid insecticides. Part 3. A putative pharmacophore derived using methodology based on molecular dynamics and hierarchical cluster analysis

Previous studies of the conformational behaviour of a group of synthetic pyrethroid insecticides have been extended to a more structurally diverse set. This includes compounds with different backbones and differing stereochemistry, with both Types I and II biological activity. These compounds also encompass a large range of biological activities. A parameterisation of the CHARMM force field for these compounds has been performed and the extra parameters are reported. Conformational sampling, using molecular dynamics (MD), has been performed for each of the 41 active structures. The accessible conformations of each have been characterised by the values of the common torsion angles using hierarchichal cluster analysis (HCA). A further CA, based on the centroids derived from the conformational sampling, identified a conformation common to at least 39 of the 41 structures. The critical torsion angles of this conformation lie at the centre of the molecule about the ester linkage and are defining an extended conformation, which differs from the minimum energy conformation of deltamethrin used previously. This may represent a putative pharmacophore for kill. The methods used here improve significantly on those used previously. The CHARMM force field was parameterised for the compounds and an improved method of conformational sampling, based on centroid clustering, has also been used.     

Search for Superconductivity in Lithium

We report on the results of a search for superconductivity in Li. We find no evidence for the predicted transition to superconductivity at any temperature down to 5 mK in magnetic fields down to 0.4 T. However, an unexpected Curie–Weiss temperature dependence in the magnetic susceptibility is observed. We discuss the possibility that this signal arises from the Li itself, the possibility that it arises from Kondo behavior, and the implications of the effect for the predicted T_c of Li.     

Determinant spreading associated with demyelination in a nonhuman primate model of multiple sclerosis

Definition of the immune process that causes demyelination in multiple sclerosis is essential to determine the feasibility of Ag-directed immunotherapy. Using the nonhuman primate, Callithrix jacchus jacchus (common marmoset), we show that immunization with myelin basic protein and proteolipid protein determinants results in clinical disease with significant demyelination. Demyelination was associated with spreading to myelin oligodendrocyte glycoprotein (MOG) determinants that generated anti-MOG serum Abs and Ig deposition in central nervous system white matter lesions. These data associate intermolecular "determinant spreading" with clinical autoimmune disease in primates and raise important issues for the pathogenesis and treatment of multiple sclerosis.     

"Milk makes me sick but my body needs it": conflict and contradiction in the establishment of authoritative knowledge

This article takes lactose intolerance as a topic for exploring clashes of power, authority, and knowledge in clinical interactions and interpretations of laywomen. In clinics providing maternal and child care, staff and clients jointly produced authoritative knowledge, most often a version of biomedicine. The Euroamerican staff tended to give advice that was biologically appropriate for them but not for many of their patients, a process reflecting what we refer to as biocentrism. Resulting information given to pregnant and lactating women and diagnoses of children's growth patterns were inappropriate in some cases, with potentially serious legal and health implications. Clinic staff often unwittingly ignored the efforts of their clients to begin a discussion of discrepancies between their bodily knowledge and clinic advice. Some women created their own syntheses, which supported the ascendancy of biomedical knowledge but were not in the interests of their own health.