Does Dietary Provision of Guanidinoacetic Acid Induce Global DNA Hypomethylation in Healthy Men and Women?

Background/Aims: Guanidinoacetic acid (GAA) is an experimental dietary additive and has been reported to induce methyl depletion when provided by the diet. However, no study evaluated whether supplemental GAA affects DNA methylation, a critical epigenetic process for genome regulation. Methods: In this open-label, repeated-measure interventional trial, we evaluated the impact of 12 weeks of GAA supplementation on global DNA methylation in 14 healthy participants (8 women and 6 men, age 22.2 +/- 2.3 years, body mass index 24.8 +/- 5.7). Results: Dietary provision of GAA had no effect on global DNA methylation, with 5-methylcytosine (m5C) nonsignificantly increased by 13.4% at postadministration when averaged across participants (95% confidence interval -5.5 to 32.3; p = 0.26). Notable DNA hypomethylation (corresponding to a 5% drop in m5C) was found in 3 of 14 participants at follow-up. Conclusion: Global DNA methylation seems to be unaltered by dietary provision of 3 g of GAA per day for 12 weeks in healthy men and women

Ionic liquids as potentially new antifungal agents against Alternaria species

The fungal genus Alternaria Nees 1816 includes the most prevalent pathogenic species that can cause crop diseases such as blight, black spot, and dark leaf spot. In accordance with the aim of developing modern sustainable approaches in agriculture for the replacement of synthetic and toxic substances with environmentally friendly alternatives, the objective of this study was to examine thein vitro antifungal activities of 18 newly synthesized ionic liquids (ILs) against three Alternaria strains: A. padwickii, A. dauci and A. linicola. The antifungal activities of the ILs were estimated via a microdilution method to establish minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) values. The results confirmed that 17 of the 18 ILs showed strain specificity, including good antifungal activity toward Alternaria strains, with MIC and MFC values in the range of 0.04 to 0.43 mol dm(-3). The strongest antifungal effects toward all analyzed Alternaria strains were displayed by the compounds with long alkyl chains: [omim][Cl] (MIC/MFC: 0.042 mol dm(-3)), [dmim][Cl] (MIC/MFC: 0.043 mol dm(-3)), [ddmim][Cl] (MIC/MFC: 0.053 mol dm(-3)), [ddTSC][Br] (MIC/MFC: 0.053 mol dm(-3)), and [Allyl-mim][Cl] (MIC/MFC: 0.054 mol dm(-3)). The introduction of oxygen as a hydroxyl group resulted in less-pronounced toxicity towards Alternaria compared to the introduction of an ether group, while the contribution of the hydroxyl group was shown to be a more determining factor than the prolongation of the side-chain, resulting in overall fungicidal activity decrease. Our results indicate the possibility that the most effective ILs ([Allyl-mim][Cl], [omim][Cl], [dmim][Cl], [ddmim][Cl], [bTSC][Br], [hTSC][Br], [oTSC][Br], [dTSC][Br], and [ddTSC][Br]) could be applied to the control of plant diseases caused by Alternaria species, based on their potential as an environmentally friendly crop protection approach. Since salts based on TSC cations are significantly cheaper to synthesize, stable under mild conditions, and environmentally friendly after degradation, thiosemicarbazidium-based ILs can be a suitable replacement for commercially available imidazolium ILs

Searching for a better formulation to enhance muscle bioenergetics: A randomized controlled trial of creatine nitrate plus creatinine vs. creatine nitrate vs. creatine monohydrate in healthy men

A novel creatine blend (creatine nitrate mixed with creatinine, CN‐CRN) has been anecdotally suggested to be superior to traditional creatine formulations for bioavailability and performance. However, does CN‐CRN supremely affects creatine levels in the blood and skeletal muscle of healthy humans remain currently unknown. This randomized, controlled, double‐blind, crossover trial evaluated the acute effects of single‐dose CN‐CRN on serum creatine levels, and 5‐days intervention with CN‐CRN on skeletal muscle creatine and safety biomarkers in healthy men. Ten healthy young men (23.6 ± 2.9 years) were allocated to receive either CN‐CRN (3 grams of creatine nitrate mixed with 3 grams of creatinine), pure creatine nitrate (3 grams, CN), or regular creatine monohydrate (3 grams, CRM) by oral administration. We found that CN‐CRN resulted in a more powerful rise in serum creatine levels comparing to either CN or CRM after a single‐dose intervention, as evaluated with the area under the concentration–time curve calculation (701.1 ± 62.1 (µmol/L) × min versus 622.7 ± 62.9 (µmol/L) × min versus 466.3 ± 47.9 (µmol/L) × min; p < .001). The peak serum creatine levels at 60‐min sampling interval were significantly higher in CN‐CRN group (183.7 ± 15.5 µmol/L), as compared to CN group (163.8 ± 12.9 µmol/L) and CRM group (118.6 ± 12.9 µmol/L) (p < .001). This was accompanied by a significantly superior increase in muscle creatine levels after CN‐CRN administration at 5‐days follow‐up, as compared to CN and CRM, respectively (9.6% versus 8.0% versus 2.1%; p = .01). While 2 out of 10 participants were found to be nonresponsive to CN intervention (20.0%) (e.g., no amplification in muscle creatine levels found at 5‐days follow‐up), and 3 participants out of 10 were nonresponsive in CRM trial (30%), no nonresponders were found after CN‐CRN administration, with individual upswing in total muscle creatine varied in this group from 2.0% (lowest increment) to 16.8% (highest increment). Supplemental CN‐CRN significantly decreased estimated glomerular filtration rate (eGFR) at 5‐days follow‐up, as compared to other interventions (p = .004), with the average reduction was 14.8 ± 7.7% (95% confidence interval; from 9.3 to 20.3). Nevertheless, no single participant experienced a clinically relevant reduction in eGFR (< 60 ml/min/1.73 m2) throughout the course of the trial. Liver enzymes remained in reference ranges throughout the study, with no participant experienced high liver blood tests (e.g., AST > 40 units per L or ALT >56 units per L). Besides, no participant reported any major side effects during the trial, while the odors of CN‐CRN and CN formulations were considered somewhat unpleasant in 8 out of 10 participants (80.0%). Our results suggest that CN‐CRN is a preferred and relatively safe alternative to traditional creatine formulations for improved creatine bioavailability in the blood and skeletal muscle after single‐dose and 5‐days interventions

Searching for a better formulation to enhance muscle bioenergetics: A randomized controlled trial of creatine nitrate plus creatinine vs.

A novel creatine blend (creatine nitrate mixed with creatinine, CN‐CRN) has been anecdotally suggested to be superior to traditional creatine formulations for bioavailability and performance. However, does CN‐CRN supremely affects creatine levels in the blood and skeletal muscle of healthy humans remain currently unknown. This randomized, controlled, double‐blind, crossover trial evaluated the acute effects of single‐dose CN‐CRN on serum creatine levels, and 5‐days intervention with CN‐CRN on skeletal muscle creatine and safety biomarkers in healthy men. Ten healthy young men (23.6 ± 2.9 years) were allocated to receive either CN‐CRN (3 grams of creatine nitrate mixed with 3 grams of creatinine), pure creatine nitrate (3 grams, CN), or regular creatine monohydrate (3 grams, CRM) by oral administration. We found that CN‐CRN resulted in a more powerful rise in serum creatine levels comparing to either CN or CRM after a single‐dose intervention, as evaluated with the area under the concentration–time curve calculation (701.1 ± 62.1 (µmol/L) × min versus 622.7 ± 62.9 (µmol/L) × min versus 466.3 ± 47.9 (µmol/L) × min; p < .001). The peak serum creatine levels at 60‐min sampling interval were significantly higher in CN‐CRN group (183.7 ± 15.5 µmol/L), as compared to CN group (163.8 ± 12.9 µmol/L) and CRM group (118.6 ± 12.9 µmol/L) (p < .001). This was accompanied by a significantly superior increase in muscle creatine levels after CN‐CRN administration at 5‐days follow‐up, as compared to CN and CRM, respectively (9.6% versus 8.0% versus 2.1%; p = .01). While 2 out of 10 participants were found to be nonresponsive to CN intervention (20.0%) (e.g., no amplification in muscle creatine levels found at 5‐days follow‐up), and 3 participants out of 10 were nonresponsive in CRM trial (30%), no nonresponders were found after CN‐CRN administration, with individual upswing in total muscle creatine varied in this group from 2.0% (lowest increment) to 16.8% (highest increment). Supplemental CN‐CRN significantly decreased estimated glomerular filtration rate (eGFR) at 5‐days follow‐up, as compared to other interventions (p = .004), with the average reduction was 14.8 ± 7.7% (95% confidence interval; from 9.3 to 20.3). Nevertheless, no single participant experienced a clinically relevant reduction in eGFR (< 60 ml/min/1.73 m2) throughout the course of the trial. Liver enzymes remained in reference ranges throughout the study, with no participant experienced high liver blood tests (e.g., AST > 40 units per L or ALT >56 units per L). Besides, no participant reported any major side effects during the trial, while the odors of CN‐CRN and CN formulations were considered somewhat unpleasant in 8 out of 10 participants (80.0%). Our results suggest that CN‐CRN is a preferred and relatively safe alternative to traditional creatine formulations for improved creatine bioavailability in the blood and skeletal muscle after single‐dose and 5‐days interventions

Guanidinoacetic Acid and Creatine are Associated with Cardiometabolic Risk Factors in Healthy Men and Women: A Cross-Sectional Study

Guanidinoacetic acid (GAA) conversion to creatine is thought to be involved in cardiometabolic disturbances through its role in biological methylation and insulin secretion. We evaluated the association of serum GAA and creatine with cardiometabolic risk factors in a cohort of 151 apparently healthy adults (82 women and 69 men) aged 18–63 years. Serum levels of GAA and creatine were measured with liquid chromatography-tandem mass spectrometry. A multiple linear regression model adjusted for age and sex was employed to examine the relationship of serum GAA and creatine with cardiometabolic risk factors. Higher GAA levels were associated with an unfavorable cardiometabolic risk profile (higher insulin, higher total homocysteine, and higher body fat percentage), while having elevated serum creatine levels (≥31.1 µmol/L) was associated with being overweight (body mass index ≥ 25.0 kg/m). The results from our study suggest a possible role of the GAA–creatine axis in the pathogenesis of cardiovascular and metabolic diseases

A single session of exhaustive exercise markedly decreases circulating levels of guanidinoacetic acid in healthy men and women

We evaluated the effects of exercise on circulating concentrations of guanidinoacetic acid (GAA) and creatine in 23 healthy volunteers subjected to running to exhaustion and free-weight bench-press to volitional failure. Blood was taken before and following each exercise session. Running induced a significant decrease in serum GAA by 20.1% (PThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Physicochemical and structural properties of lidocaine-based ionic liquids with anti-inflammatory anions

This journal is © The Royal Society of Chemistry. The purpose of this paper was to examine the density, viscosity and electrical conductivity at different temperatures, as well as the thermal stability and structural properties of previously reported ionic liquids based on active pharmaceutical ingredients. Lidocaine-based ionic liquids, with ibuprofen and salicylate as counterion, were prepared first. Their structures were confirmed by infrared, mass and 1H and 13C nuclear magnetic resonance spectroscopy. The Newtonian behaviour of lidocaine ibuprofenate was confirmed from viscosity measurement results, while it was impossible to determine for lidocaine salicylate. The interactions and structures of the studied ionic liquids were analyzed based on the measured density values, viscosity, electrical conductivity, and calculated values of thermal expansion coefficients and activation energy of viscous flow. From a theoretical aspect, DFT and MD calculations were performed. The obtained descriptors and radial distribution, as well as structural functions, were used to understand the structural organization of the synthesized ionic liquids

Short-term fasting affects biomarkers of creatine metabolism in healthy men and women

We studied the effects of 24-h fasting on serum levels of guanidinoacetic acid (GAA), creatine, and creatinine in 24 non-vegetarian healthy adults. Blood was taken before and following an intervention, with levels corrected for fasting-induced changes in plasma volume. Food abstention induced a significant decrease in serum GAA by 39.5% (p < 0.001), while creatinine levels increased by 14.7% (p < 0.01); the concentration of creatine remains unchanged. The reduction in GAA during fasting may indicate an increased demand for creatine production for this energy-demanding condition and/or potential kidney dysfunction which requires further exploration

Correlation between lipophilicity of newly synthesized ionic liquids and selected: Fusarium genus growth rate

© 2019 The Royal Society of Chemistry. The purpose of the present study was to examine the effectiveness of 23 different synthesized ionic liquids (ILs) on Fusarium culmorum and Fusarium oxysporum growth rate. The strategy of IL synthesis was a structural modification of ionic liquids through changing the polarity of imidazolium and pycolinium cations and replacing halide anions with well known antifungal anions (cinnamate, caffeate and mandelate). The findings clearly suggest that the type of alkyl chain on the cation is the most determining factor for IL toxicity. In order to examine how IL structure affects their toxicity towards Fusarium genus, lipophilic descriptor AlogP is calculated from density functional theory and correlated with Fusarium growth rate. All these results demonstrate the high level of the interdependency of lipophilicity and toxicity for investigated ILs towards the Fusarium genus. The data collected in this research suggest that the inhibitory influence of ILs is more pronounced in the case of F. oxysporum