scholarly journals New Insights into the Metabolism of the Flavanones Eriocitrin and Hesperidin: A Comparative Human Pharmacokinetic Study

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 435
Author(s):  
María Ángeles Ávila-Gálvez ◽  
Juan Antonio Giménez-Bastida ◽  
Antonio González-Sarrías ◽  
Juan Carlos Espín
Keyword(s):  
Phase Ii ◽  
Pharmacokinetic Study ◽  
Cardiometabolic Risk ◽  
Individual Variability ◽  
Plasma Metabolites ◽  
Human Metabolism ◽  
Metabolic Markers ◽  
Regular Consumption ◽  
Human Pharmacokinetic ◽  
Health Related

The intake of hesperidin-rich sources, mostly found in orange juice, can decrease cardiometabolic risk, potentially linked to the gut microbial phase-II hesperetin derivatives. However, the low hesperidin solubility hampers its bioavailability and microbial metabolism, yielding a high inter-individual variability (high vs. low-producers) that prevents consistent health-related evidence. Contrarily, the human metabolism of (lemon) eriocitrin is hardly known. We hypothesize that the higher solubility of (lemon) eriocitrin vs. (orange) hesperidin might yield more bioavailable metabolites than hesperidin. A randomized-crossover human pharmacokinetic study (n = 16) compared the bioavailability and metabolism of flavanones from lemon and orange extracts and postprandial changes in oxidative, inflammatory, and metabolic markers after a high-fat-high-sugars meal. A total of 17 phase-II flavanone-derived metabolites were identified. No significant biomarker changes were observed. Plasma and urinary concentrations of all metabolites, including hesperetin metabolites, were higher after lemon extract intake. Total plasma metabolites showed significantly mean lower Tmax (6.0 ± 0.4 vs. 8.0 ± 0.5 h) and higher Cmax and AUC values after lemon extract intake. We provide new insights on hesperetin-eriodictyol interconversion and naringenin formation from hesperidin in humans. Our results suggest that regular consumption of a soluble and eco-friendly eriocitrin-rich lemon extract could provide a circulating concentration metabolites threshold to exert health benefits, even in the so-called low-producers.

scholarly journals Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers

2021 ◽  
Vol 12 ◽  
Author(s):  
Anne Michelli Reis Silveira ◽  
Gustavo Henrique Bueno Duarte ◽  
Anna Maria Alves de Piloto Fernandes ◽  
Pedro Henrique Dias Garcia ◽  
Nelson Rogerio Vieira ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Individual Variability ◽  
Lipid Lowering ◽  
Plasma Metabolites ◽  
Pharmacokinetic Parameters ◽  
Metabolic Markers ◽  
Coronary Artery Disease Prevention ◽  
Artery Disease ◽  
Endogenous Metabolites

Rosuvastatin is a well-known lipid-lowering agent generally used for hypercholesterolemia treatment and coronary artery disease prevention. There is a substantial inter-individual variability in the absorption of statins usually caused by genetic polymorphisms leading to a variation in the corresponding pharmacokinetic parameters, which may affect drug therapy safety and efficacy. Therefore, the investigation of metabolic markers associated with rosuvastatin inter-individual variability is exceedingly relevant for drug therapy optimization and minimizing side effects. This work describes the application of pharmacometabolomic strategies using liquid chromatography coupled to mass spectrometry to investigate endogenous plasma metabolites capable of predicting pharmacokinetic parameters in predose samples. First, a targeted method for the determination of plasma concentration levels of rosuvastatin was validated and applied to obtain the pharmacokinetic parameters from 40 enrolled individuals; then, predose samples were analyzed using a metabolomic approach to search for associations between endogenous metabolites and the corresponding pharmacokinetic parameters. Data processing using machine learning revealed some candidates including sterols and bile acids, carboxylated metabolites, and lipids, suggesting the approach herein described as promising for personalized drug therapy.

scholarly journals Effects of Extreme Weight Loss on Cardiometabolic Health in Children With Metabolic Syndrome: A Metabolomic Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingxin Liu ◽  
Lin Zhu ◽  
Jing Liao ◽  
Xiaoguang Liu
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Weight Loss ◽  
Body Composition ◽  
Organic Acids ◽  
Cardiometabolic Risk ◽  
The Body ◽  
Cardiometabolic Risk Factors ◽  
Plasma Metabolites ◽  
Cardiometabolic Health

Objectives: To evaluate the effect of extreme weight loss programs on circulating metabolites and their relationship with cardiometabolic health in children with metabolic syndrome.Methods: This study was a quasi-experimental design with a pretest and post-test. Thirty children with metabolic syndrome and aged 10–17years were recruited to an extreme weight loss program (i.e., exercise combined with diet control). The primary outcomes included plasma metabolites, body composition, and cardiometabolic risk factors. A total of 324 metabolites were quantitatively detected by an ultra-performance liquid chromatography coupled to tandem mass spectrometry system, and the variable importance in the projection (VIP) value of each metabolite was calculated by the orthogonal projection to latent structures discriminant analysis. The fold change (FC) and p value of each metabolite were used to screen differential metabolites with the following values: VIP>1, p value<0.05, and |log2FC|>0.25. Pathway enrichment and correlation analyses between metabolites and cardiometabolic risk factors were also performed.Result: A large effect size was observed, presenting a weight loss of −8.9kg (Cohen’s d=1.00, p<0.001), body mass index reduction of −3.3kg/m2 (Cohen’s d=1.47, p<0.001), and body fat percent reduction of −4.1 (%) (Cohen’s d=1.22, p<0.001) after the intervention. Similar improvements were found in total cholesterol (Cohen’s d=2.65, p<0.001), triglycerides (Cohen’s d=2.59, p<0.001), low-density lipoprotein cholesterol (Cohen’s d=2.81, p<0.001), glucose metabolism, and blood pressure. A total of 59 metabolites were changed after the intervention (e.g., aminoacyl-tRNA biosynthesis, glycine, serine, and threonine metabolism; nitrogen metabolism, tricarboxylic acid cycle, and phenylalanine, tyrosine, and tryptophan biosynthesis). The changes in metabolites (e.g., amino acids, fatty acids, organic acids, and carnitine) were related to lipid metabolism improvement (p<0.05). Organic acids and carnitines were associated with changes in the body composition (p<0.05).Conclusion: Exercise combined with dietary control improved the body composition and cardiometabolic health in children with metabolic syndrome, and these changes may be related to plasma metabolites.

scholarly journals Champ4life Study Protocol: A One-Year Randomized Controlled Trial of a Lifestyle Intervention for Inactive Former Elite Athletes with Overweight/Obesity

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 286
Author(s):  
Analiza M. Silva ◽  
Catarina L. Nunes ◽  
Catarina N. Matias ◽  
Filipe Jesus ◽  
Rúben Francisco ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Physical Activity ◽  
Lifestyle Intervention ◽  
Elite Athletes ◽  
Resting Energy Expenditure ◽  
Overweight And Obesity ◽  
Metabolic Markers ◽  
Health Related ◽  
Former Elite Athletes

Preventive and educational programs directed to former elite athletes in the areas of healthy living are required. This is particularly relevant as obesity and health-related problems are observed in retired athletes, especially in those whose current levels of physical activity are below the recommendations. During their sports career, elite athletes are supported by a multidisciplinary team; upon retirement, no support is provided for the transition to a different lifestyle. So far, no program has been implemented to promote sustained healthy lifestyle behaviors in the post-career transition and evidence is lacking for such an intervention. Firstly, we aim to determine if Champ4life, a 1-year lifestyle intervention targeting inactive former athletes with overweight and obesity, is effective for reducing total and abdominal fat. Secondly, our purpose is to assess the effectiveness of the intervention on the levels of physical activity and sedentary behavior, resting energy expenditure, cardio-metabolic markers, physical fitness, energy balance components, eating self-regulation markers, and quality of life over 12 months. Champ4life is an evidence- and theory-based program using a randomized control trial design (intervention vs. control group) that will be conducted on 94 inactive former elite athletes with overweight and obesity. The first four months of the Champ4Life program include a nutritional appointment and 12 weekly, 90-min sessions. Classroom sessions seek to provide participants with key information and a toolbox of behavior change techniques to initiate and sustain long-term lifestyle changes. Participants will undergo baseline, 4-month, and 12-month measurements of body composition (primary outcomes), resting energy expenditure, physical fitness, metabolic markers, energy balance related-markers, and quality of life (secondary outcome). This trial will provide evidence on the effectiveness of the Champ4life program, a pioneer lifestyle intervention for retired athletes, offering tools for sustained changes in physical activity, sedentary behavior and diet, aiming to improve body composition and overall health-related markers.

scholarly journals PPARGC1A rs8192678 and NRF1 rs6949152 Polymorphisms Are Associated with Muscle Fiber Composition in Women

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1012
Author(s):  
Thomas Yvert ◽  
Eri Miyamoto-Mikami ◽  
Takuro Tobina ◽  
Keisuke Shiose ◽  
Ryo Kakigi ◽  
...  
Keyword(s):  
Muscle Fiber ◽  
Vastus Lateralis ◽  
Endurance Performance ◽  
Individual Variability ◽  
Lower Proportion ◽  
Vastus Lateralis Muscle ◽  
Mhc I ◽  
Fiber Composition ◽  
Individual Variations ◽  
Health Related

PPARGC1A rs8192678 G/A (Gly482Ser) and NRF1 rs6949152 A/G polymorphisms have been associated with endurance athlete status, endurance performance phenotypes, and certain health-related markers of different pathologies such as metabolic syndrome, diabetes, and dyslipidemia. We hypothesized that they could be considered interesting candidates for explaining inter-individual variations in muscle fiber composition in humans. We aimed to examine possible associations of these polymorphisms with myosin heavy-chain (MHC) isoforms as markers of muscle fiber compositions in vastus lateralis muscle in a population of 214 healthy Japanese subjects, aged between 19 and 79 years. No significant associations were found in men for any measured variables. In contrast, in women, the PPARGC1A rs8192678 A/A genotype was significantly associated with a higher proportion of MHC-I (p = 0.042) and with a lower proportion of MHC-IIx (p = 0.033), and the NRF1 rs6949152 AA genotype was significantly associated with a higher proportion of MHC-I (p = 0.008) and with a lower proportion of MHC IIx (p = 0.035). In women, the genotype scores of the modes presenting the most significant results for PPARGC1A rs8192678 G/A (Gly482Ser) and NRF1 rs6949152 A/G polymorphisms were significantly associated with MHC-I (p = 0.0007) and MHC IIx (p = 0.0016). That is, women with combined PPARGC1A A/A and NRF1 A/A genotypes presented the highest proportion of MHC-I and the lowest proportion of MHC-IIx, in contrast to women with combined PPARGC1A GG+GA and NRF1 AG+GG genotypes, who presented the lowest proportion of MHC-I and the highest proportion of MHC-IIx. Our results suggest possible associations between these polymorphisms (both individually and in combination) and the inter-individual variability observed in muscle fiber composition in women, but not in men.

Determination of lacosamide in human plasma by LC–MS/MS and its application to a human pharmacokinetic study

2020 ◽  
Vol 3 (6) ◽  
pp. 216-224
Author(s):  
Siva Sankara Rao Yadlapalli ◽  
Naresh Kumar Katari ◽  
Surendra Babu Manabolu Surya
Keyword(s):  
Human Plasma ◽  
Pharmacokinetic Study ◽  
Human Pharmacokinetic

scholarly journals Effects of physical activity and sedentary behaviour on cardiometabolic risk factors and cognitive function in children: protocol for a cohort study

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e030322 ◽  
Author(s):  
Yajie Lv ◽  
Li Cai ◽  
Zhaohuan Gui ◽  
Xia Zeng ◽  
Minyi Tan ◽  
...  
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Cohort Study ◽  
Cognitive Function ◽  
Sedentary Behaviour ◽  
Phase Ii ◽  
Cardiometabolic Risk ◽  
Cardiometabolic Risk Factors ◽  
Related Potentials

IntroductionAlthough studies showed that physical activity (PA) and sedentary behaviour (SB) were associated with cardiometabolic risk factors and cognitive function, both independent and combined associations among them are inconsistent. Cardiometabolic risk factors are also associated with cognitive function, but research of children is limited. Additionally, the brain level mechanisms have not been fully established. The proposed study aims to explore the associations and mechanisms of PA and SB on cognitive function and cardiometabolic risk factors in children.Methods and analysisThis is a school-based prospective cohort study. A total of 8324 participants of this study are primary school students aged 7–12 years old who are followed up every 2 years from January 2017 to December 2026. We used a stratified cluster random sampling to select five primary schools in Guangzhou, China. There are three phases at baseline. At phase I, we collect PA, SB and cognitive function by questionnaires and also conduct anthropometric and biochemical measurements in all participants. At phase II, PA, SB and cognitive function are measured respectively by accelerometers and cognitive tasks among participants randomly selected from four subgroups with different SB and PA levels. At phase III, event-related potentials are recorded using electroencephalogram during a cognitive task among participants randomly selected from phase II. We plan to follow-up all participants until they graduate from high school. The process applied at baseline and follow-up are approximately identical.Ethics and disseminationProcedures described in this manuscript have been approved by the Ethical Review Committee for Biomedical Research, School of Public Health, Sun Yat-sen University (L2016-010). All parents or guardians of participants signed the informed consent form voluntarily before participating in the study. The findings of the study will be published in peer-reviewed journals.Trial registration numberNCT03582709

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