Search Results (388)

The activation mechanism of the reproductive axis in Kazakh ewes during the non-breeding season was explored by supplementation with glycerol complex (7% glycerol + tyrosine + vitamin B9). The experiment divided 50 ewes into five groups (n = 10). After 90 days of intervention, it was found that significant changes in serum DL-carnitine, N-methyl-lysine and other differential metabolites were observed in the GLY-Tyr-B9 group (p < 0.05, “p < 0.05” means significant difference, “p < 0.01” means “highly significant difference”). The bile acid metabolic pathway was specifically activated (p < 0.01). The group had a 50% estrus rate, ovaries contained 3–5 immature follicles, and HE staining showed intact granulosa cell structure. Serum E2/P4 fluctuated cyclically (p < 0.01), FSH/LH pulse frequency increased (p < 0.01), peak Glu/INS appeared on day 60 (p < 0.05), and LEP was negatively correlated with body fat percentage (p < 0.01). Molecular mechanisms revealed: upregulation of hypothalamic kiss-1/GPR54 expression (p < 0.01) drove GnRH pulses; ovarian CYP11A1/LHR/VEGF synergistically promoted follicular development (p < 0.05); the HSL of subcutaneous fat was significantly increased (p < 0.05), suggesting involvement of lipolytic supply. Glycerol activates the reproductive axis through a dual pathway—L-carnitine-mediated elevation of mitochondrial β-oxidation efficacy synergizes with kisspeptin/GPR54 signalling enhancement to re-establish HPO axis rhythms. This study reveals the central role of metabolic reprogramming in regulating seasonal reproduction in ruminants. Full article

Fibromyalgia is a complex disorder characterized by chronic widespread pain and a variety of related symptoms. Growing evidence suggests that the central and peripheral nervous systems are involved, with small fiber neuropathy playing a key role in its development. We retrospectively reviewed the medical records of 100 patients diagnosed with primary fibromyalgia. Those showing symptoms indicative of small fiber dysfunction who were treated with L-Acetyl Carnitine (LAC) and Palmitoylethanolamide (PEA) alongside standard care (SOC) were compared to matched controls who received only SOC. To ensure comparable groups, propensity score matching was used. Changes in Fibromyalgia Impact Questionnaire Revised (FIQR) scores over 12 weeks were analyzed using non-parametric tests due to the data’s non-normal distribution. After matching, 86 patients (43 in each group) were included. The group receiving LAC and PEA as add-on therapy experienced a significant median reduction in FIQR scores (−19.0 points, p < 0.001), while the SOC-only group showed no significant change. Comparisons between groups confirmed that the improvement was significantly greater in the LAC+PEA group (p < 0.001). These results suggest that adding LAC and PEA to standard care may provide meaningful symptom relief for fibromyalgia patients with suspected small fiber involvement. This supports the hypothesis that peripheral nervous system dysfunction contributes to the disease burden in this subgroup. However, further prospective controlled studies are needed to confirm these promising findings. Full article

L-carnitine and Mildronate are substances that can significantly rearrange the energy metabolism of cells. This can potentially cause changes in the bacterial composition of the gut microbiome and affect testis functionality and male sexual health. Mice of the C57Bl/6 line were used. Sexual behavior was assessed using physiological tests, and gene expression patterns were assessed by qPCR. High-throughput sequencing of mouse fecal microbiota was performed. We showed that long-term administration of Mildronate has no significant effect on the intestinal microbiome, and there was a compensatory increase in the expression of genes involved in fatty acid and leptin metabolism. No impairment of sexual motivation in male mice was observed. Prolonged L-carnitine supplementation caused a decrease in alpha diversity of bacteria and a decrease in some groups of microorganisms that are components of a healthy gut microflora. A correlation was observed between the level of bacteria from Firmicutes phylum, indicators of sexual motivation of mice, and the dynamics of body weight gain. Our results may indicate that metabolic modulators can have a significant impact on the structure of the bacterial community of the gut microbiome, which may influence male sexual health through the gut–semen axis. Full article

Osteoarthritis (OA) is a progressive joint disease that is commonly managed with palliative drugs, many of which are associated with undesirable side effects. This study investigated the therapeutic potential of a novel supplementation with guarana, selenium, and L-carnitine (GSC) in a rat model of chemically induced OA. Forty male Wistar rats (8–9 weeks old) received intra-articular sodium monoiodoacetate (Mia) to induce OA, and were subsequently treated with GSC. Inflammatory and oxidative stress parameters were analyzed at the end of the experiment. GSC supplementation enhanced endogenous antioxidant defenses, suggesting systemic antioxidant activity. However, no histological improvement was observed. In silico analyses indicated that Mia-induced OA may involve a complex molecular environment that GSC, at the tested dose, failed to modulate at the site of injury. Despite the limited local effects, these findings support the systemic benefits of GSC and highlight the potential of natural compound-based strategies in OA management. Given the adverse effects of conventional pharmacotherapy, the development of alternative, naturally derived treatments remains a promising avenue for future research. Full article

Background/Objectives: Carnitine deficiency is common in hemodialysis patients and may contribute to anemia, inflammation, dyslipidemia, and muscle symptoms. This review explores the potential benefits of L-carnitine supplementation in this population. Methods: A thorough literature search of the PubMed database was conducted to identify clinical trials and studies assessing the effects of L-carnitine supplementation on adult hemodialysis patients. Key outcomes included the effects on inflammation, lipid profile, anemia, glycemic control, and muscle function. Results: Evidence suggests that L-carnitine may reduce inflammatory markers and improve lipid profiles by lowering triglycerides and increasing high-density lipoprotein (HDL). Several studies reported reduced erythropoietin need and improved hemoglobin levels. However, some studies did not find benefits of carnitine supplementation on the mentioned parameters. Results for muscle cramps, glycemic control, and cardiac function remain inconsistent. Conclusions: L-carnitine supplementation shows potential benefits in the management of hemodialysis complications. However, further well-designed trials are needed to confirm efficacy and optimize treatment protocols. Full article

Carnitine (CA) is a chiral amino acid and mostly comes from meat and dairy products. CA cannot be found in fruits, vegetables, or other plants, so vegetarians are deficient in CA. CA exists in the form of D-carnitine (D-CA) and L-carnitine (L-CA); only L-carnitine has biological activity. L-CA promotes the oxidation of fatty acids and then causes the effect of weight loss. In this study, the fluorescence probe was established by using graphene oxide-modified cadmium telluride (CdTe) QDs (GO-CdTe QDs) for the chiral recognition of carnitine enantiomers. GO-CdTe QDs present fluorescence. D-CA enhances the fluorescence spectral signal of the GO-CdTe QDs system, while L-CA weakens its spectral signal. Based on this phenomenon, we determined D-carnitine and L-carnitine. Full article

Background/Objectives: This study aimed to evaluate the effects of four weeks of combined Acetyl-l-Carnitine and alpha-lipoic acid (ALA) supplementation on anaerobic and aerobic performance and fatigue resistance in trained cyclists, hypothesizing improvements in maximal aerobic power (MAP), Wingate test performance, and reduced lactate accumulation. Methods: In a double-blind, randomized trial, 41 male trained cyclists (age: 36 ± 12 years; MAP: 4.35 ± 0.60 W·kg⁻¹) were assigned to a supplement group (SUP, n = 19; 1200 mg/day Acetyl-l-Carnitine, 300 mg/day ALA, 1.1 mg Vitamin B1, 2.5 µg Vitamin B12) or placebo group (PLA, n = 22) for four weeks. Performance was assessed pre- and post-intervention via counter-movement jumps (CMJs), Wingate tests (WG₁, WG₂), and a graded exercise test (GXT). Blood lactate ([La⁻]) was measured post-Wingate. A three-way mixed ANOVA analyzed Wingate performance (session, order, and group), and a two-way ANOVA assessed MAP and fatigue effects. Results: MAP increased by 3.4% (314 ± 32 W to 324 ± 37 W; p = 0.005) with no group interaction (p = 0.457). Wingate peak power showed main effects for order (p < 0.001) and session (p = 0.011) but no group interaction (p = 0.676). SUP reduced [La⁻] by 1.5 mmol·L⁻¹ post-WG₂ in POST (p = 0.049). No significant group differences were found for CMJ or fatigue metrics. Conclusions: Four weeks of Acetyl-l-Carnitine and ALA supplementation did not enhance aerobic or anaerobic performance in trained cyclists, despite reducing blood lactate after high-intensity exercise, suggesting no ergogenic benefits. Full article

Objectives: To explore the metabolic changes in zebrafish larvae after infection with Mycobacterium marinum, this study adopted a widely targeted metabolomic approach to analyze the changes in the overall metabolic profiles of zebrafish larvae infected for 5 days. Methods: Data were collected by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Mass spectrometry data were processed using Analyst 1.6.3 and MultiQuant 3.0.3 software, and multivariate statistical analysis was carried out. The KEGG database, HMDB database, and CHEBI database were used to screen and identify differential metabolites, and metabolic pathway enrichment analysis was performed through KEGG pathways. Results: A total of 329 metabolites were detected, among which 61 differential metabolites were screened. Specifically, 41 metabolites, such as kynurenine, isoallolithocholic acid, 2′-deoxyguanosine, indole-3-carboxaldehyde, and L-lactic acid, were downregulated, while 20 metabolites, such as L-palmitoylcarnitine, myristoyl-L-carnitine, dodecanoylcarnitine, 2-isopropyl-malic acid, and 2-methylsuccinic acid, were upregulated. KEGG metabolic pathway enrichment analysis indicated that these differential metabolites were mainly involved in metabolic pathways such as pyrimidine metabolism, nucleotide metabolism, the pentose phosphate pathway, and purine metabolism. Conclusions: This study demonstrated that significant changes occurred in multiple metabolites and metabolic pathways in zebrafish larvae after infection with M. marinum. The research results have improved the understanding of zebrafish as a model organism in the field of Mycobacterium research and laid a solid foundation for subsequent metabolomic-related research using zebrafish. Full article

Objective: The present study investigated the relationship between protein and amino acid supplementation and various associated aspects among recreational gym goers at 2 gymnasiums in Oradea (Romania). Methods: A total of 165 gym goers (110 men and 55 women, most of them 18–30 years old) with high educational levels were included in the present study, which was conducted as face-to-face interviews. Results: Participants were divided into 4 groups: protein supplement users (PSUs, 42/165), creatine supplement users (CSUs, 38/165), L-carnitine supplement users (LcSUs, 37/165), and protein + creatine + L-carnitine supplement users (PCLcSUs, 48/165). Most consumers were young (18–30 years) and preferred the triple combination. Females consumed PS and CS (38.2% and 34.5%, respectively), while the most-used NSs by males were PCLcS (36.4%) and LcS (27.3%). Obese gym goers opted for LcS consumption (r = 0.999, p < 0.05). Creatine and L-carnitine were consumed for force training (65.79 and 62.16%), while PCLcS and PS were used in cardio + force and force training in equal measures (42.86 and 47.92%, respectively). Most PSUs were gym goers for 7–12 months and more than 1 year (r = 0.999 and r = 0.952, respectively, p < 0.05), while PCLcSUs had a training frequency of at least 5 times a week (r = 0.968, p < 0.05). Muscle mass growth was the primary training focus for all NS users (57.89%), followed by muscular tonus (40.54%, p < 0.05). Almost 30% of one-only NS users reported various side effects, whereas all PCLcSUs claimed side effects (p < 0.05). Conclusions: Age and gender were key factors in diet type, training type, frequency, duration, scope, NS type, and dose intake. The frequency of side effects substantially depended on the kind of NS and the dose consumed. The present study’s results highlight the need for health professionals’ advice and monitoring in personalized diets and protein and amino acid supplementation in recreational gym goers. Full article

Carnitine is essential for the mitochondrial transport of long-chain fatty acids and thus plays a pivotal role in energy metabolism, particularly in metabolically active organs, such as skeletal and cardiac muscle. In patients with dialysis, carnitine homeostasis is disrupted because of the reduced synthesis, impaired renal reabsorption, and carnitine loss during extracorporeal procedures. Carnitine deficiency is linked to a wide range of clinical manifestations, including muscle weakness, treatment-resistant anemia, intradialytic hypotension, mental disorder, and cardiovascular disease. This review provides a comprehensive overview of the physiological function of carnitine, elucidates the underlying mechanisms of carnitine deficiency in patients with dialysis, and explores the clinical consequences. Furthermore, the efficacy and limitations of L-carnitine supplementation in clinical practice are discussed based on the current literature. A better understanding of the pathophysiological and clinical relevance of carnitine deficiency may help facilitate personalized therapeutic strategies for patients with kidney diseases. Full article

Background: Newborns are referred primary carnitine deficiency (PCD) when a low free carnitine (C0) concentration (<10 μmol/L) is detected, leading to high false-positive referrals. To improve the follow-up protocol for PCD, various acylcarnitines and the summations were comprehensively evaluated in the present study. Methods: A retrospective study was performed using samples due to low C0 concentration. Data were available for 72 patients with genetically confirmed PCD, whereafter C0 with the selected sum of (butyrylcarnitine (C4) + isovalerylcarnitine (C5)) was validated in an additional cohort study including about 80,000 samples. Results: In the discovery study, C4, acetylcarnitine (C2) and C5 exhibited significant discriminant power in distinguishing PCDs from NoPCDs. The area under the ROC curve (AUC) was 99.792% (C4), 98.715% (C2) and 98.620% (C5). The excellent performances in sensitivity, specificity, negative predictive value, positive predictive value (PPV) and accuracy indexes suggested that C4, C2 and C5 would be ideal auxiliary indicators in improving the diagnostic performance of C0 for PCD. Multivariate ROC curve-based exploratory analysis showed that C5, C4 and C2 were the most top-ranked features in differentiating PCDs from NoPCDs. AUC for C4 + C5 was the highest with a cutoff required for 100% sensitivity at 0.181 μmol/L. In the validation cohort, adding C4 + C5 in the NBS program could elevate PPV from 0.75% to 1.54%. Conclusions: Our work revealed that C4 + C5 summation should be used as the auxiliary quantization indicator to reduce false-positive results for PCD. Full article

Ethylmalonic encephalopathy (EE) is a serious metabolic disorder that usually appears in early childhood development and the effects are seen primarily in the brain, gastrointestinal tract, and peripheral vessels. EE is caused by pathogenic variants in the gene that encodes the ETHE1 protein, and its main features are high levels of acidic compounds in body fluids and decreased activity of the mitochondrial complex IV, which limits energy production in tissues that require a large supply of energy. ETHE1 is a mitochondrial sulfur dioxygenase that plays the role of hydrogen sulfide (H₂S) detoxification, and, when altered, it leads to the accumulation of this gaseous molecule due to its deficient elimination. In this article, we characterised the pathophysiology of ETHE1 deficiency in cellular models, fibroblasts, and induced neurons, derived from a patient with a homozygous pathogenic variant in ETHE1. Furthermore, we evaluated the effect of the activation of the mitochondrial unfolded protein response (mtUPR) on the mutant phenotype. Our results suggest that mutant fibroblasts have alterations in ETHE1 protein expression levels, associated with elevated levels of H₂S and protein persulfidation, mitochondrial dysfunction, iron/lipofuscin accumulation, and oxidative stress. We also identified a cocktail of compounds consisting of pterostilbene, nicotinamide, riboflavin, thiamine, biotin, lipoic acid, and L-carnitine that improved the cellular and metabolic alterations. The positive effect of the cocktail was dependent on sirtuin 3 activation (SIRT3) and was also confirmed in induced neurons obtained by direct reprogramming. In conclusion, personalised precision medicine in EE using patient-derived cellular models can be an interesting approach for the screening and evaluation of potential therapies. In addition, the activation of the SIRT3 axe of mtUPR is a promising therapeutic strategy for rescuing ETHE1 pathogenic variants. Full article

Objective: Most recreational gym-goers independently consume nutritional supplements (NSs) without physician advice and a personalized diet. The present study examines the preference for nutritional supplements (NSs) based on protein and amino acids of 218 recreational gym-goers (males and females aged 18–60). It also investigates the NS’s impact on resistance training (RT) performance. Methods: All participants (n = 218) were regular members of two gym centers in Oradea. Baseline data and information about daily diet and supplement preferences were obtained through face-to-face interviews. At the same time, RT performance was assessed by measuring 1RM in six exercises three times (W0, W4, and W8). Results: Our findings reveal that 24.3% of participants did not consume NSs, while the majority (75.6%, p < 0.05) used them to improve their physical condition; men were more likely to consume NSs than women (83.3% vs. 63.9%, p < 0.05). Gym-goers were grouped based on their NS consumption: L-carnitine, creatine, whey protein (WP), and triple combination; the non-supplemented group was the control. The combination substantially correlated with a balanced diet, 3001–3500 and >3500 calories/day; creatine was appreciably associated with 2001–2500 calories/day; L-carnitine was associated with 151–200 g protein/day, while control was considerably linked with a vegetarian diet and <1000 calorie/day (r > 0.900, p < 0.05). The results showed that almost all participants exhibited progressive muscle strength improvements. As an overview, 1RM substantially varied with NS consumed, body weight status, and gender (p < 0.0001), except for the pull-up count, which varied with NS and gender (p < 0.0001). Additionally, 1RM significantly varied with age (deadlift and pull-ups), daily protein consumption (back squats, biceps, and triceps), daily calories (back squats), and diet type (biceps, triceps, and pull-up exercises), p < 0.05. On the other hand, most NSs associated with RT exercises led to a general increase in body weight. Only L-carnitine decreased it. Conclusions: Resistance training records of recreational athletes are significantly influenced by age, gender, body weight status, NS type, and daily diet features (p < 0.05). Our findings highlight the essential role of professional guidance in nutritional supplementation associated with a suitable diet for optimal RT performance of recreational athletes. Full article

Physiological oxidative stress plays a pivotal role in supporting proper growth and development. While moderate oxidative stress is essential for activating key metabolic pathways and maintaining normal cellular signaling, excessive production of reactive oxygen species (ROSs) can overwhelm the immature antioxidant systems of newborns, potentially leading to cellular damage and impaired physiological function. This vulnerability is particularly pronounced in the central nervous system, where limited detoxification capacity exacerbates the risk of oxidative damage, following hypoxic–ischemic events. Antioxidants agents—such as melatonin, erythropoietin, allopurinol, N-acetylcisteine, selenium, iminobiotin, taurine, and acetyl-L-carnitine—have demonstrated significant neuroprotective effects in preclinical experimental studies, reducing markers of oxidative injury and improving neurological outcomes. These neuroprotective agents have also been evaluated in clinical trials, demonstrating antioxidant effects. A major issue lies in the complexity of neurological damage, which is not associated with a single pathological pathway. Additionally, the inability of these agents to reach effective concentrations within the central nervous system, along with inconsistencies across clinical trials in terms of dosage and administration methods, hinders the ability to obtain robust results. Future efforts should therefore focus on the development of delivery systems capable of crossing the blood–brain barrier and on establishing standardized clinical trial protocols and study designs. This educational review aims to provide a comprehensive overview of emerging protective strategies, including antioxidant bioactive agents and nutritional interventions. It also explores the underlying mechanisms of oxidative stress and its impact on neonatal brain injury. Full article

Background/Objectives: Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite considered as a risk metabolite for various non-communicable diseases. This study aims to identify differences in the gut microbiota composition and concentrations of TMAO and related metabolites in subjects with and without metabolic syndrome (MetS). Methods: Plasma samples were collected following an overnight fast on two occasions from subjects with (n = 12) and without (n = 21) MetS. Feces samples were collected on the day before the first blood sampling. The gut microbiota was profiled using 16S rRNA full-gene amplification sequencing. TMAO and related methylamines were quantified using UPLC-MSMS. The fasted plasma glucose, plasma lipid profile, and HbA1c were determined, and blood pressure, circumference, height, and weight were measured. Results: A divergent gut microbiota composition was observed in feces samples from both groups. In contrast to subjects without MetS, subjects with MetS had a reduced microbial diversity, with lower Blautia glucerasea and higher Ruminococcus torques—a pattern associated with (increased) inflammation. Trimethylamine (TMA)-producing bacteria were low in abundance across both groups. While plasma TMAO and related methylamines displayed no significant differences between both groups, L-carnitine was elevated (p = 0.0191) in subjects with MetS. A strong positive correlation was detected between TMAO and TMA (r = 0.439, p = 0.003), with a tendency to correlate with carnitine (r = 0.212, p = 0.087). Conclusions: Subjects with MetS were characterized by gut microbiota favoring inflammation-associated species but not TMA producers. This suggests that TMAO may not play a role in MetS subjects without overt comorbidities, e.g., CVD or T2D. The influence of the gut microbiota on early MetS is likely mediated through inflammatory mechanisms driven by specific bacterial shifts rather than TMAO production. Full article