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BACKGROUND: The nutritional intake of formula‐fed newborns is often limited to a single source, so it must be supplemented with essential nutrients for the growth and proper development of infants. Taurine, l‐carnitine, and choline are considered conditionally essential nutrients especially in newborns and infants. RESULTS: In this work, a simple routine hydrophilic interaction liquid chromatography‐electrospray ionization‐tandem mass spectrometry (HILIC‐ESI‐MS/MS) method was developed and validated for the simultaneous determination of these semi‐essential nutrients in infant and adult/pediatric milk formulas. The extraction recoveries were between 90% and 114%. Precision of the method offered relative standard deviation below 5% and 7% for intra‐day and inter‐day precision, respectively. The proposed method was successfully applied to quantification of taurine, l‐carnitine, and choline in milk formula. The contents found were in good agreement with those provided on the product label for almost all samples. CONCLUSION: In view of these results, it can be concluded that the developed method can be a useful approach for the simultaneous determination of taurine, l‐carnitine and choline in powdered milk samples, so it can be useful in the routine quality control of this kind of samples. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: L-carnitine is essential in lipid metabolism and reportedly has preventive effects for arrhythmia. Our objective was to examine the incidence of postoperative atrial fibrillation (POAF) and changes in serum biomarker levels following perioperative L-carnitine administration in patients with lung cancer. Methods: Thirteen patients undergoing a lobectomy with preoperative serum brain natriuretic peptide levels >24 pg/mL were perioperatively administered L-carnitine for 5 days (3 g/3×). Accurate 95% confidence intervals (CI) for POAF incidence were calculated. Serum biomarkers for POAF in lung cancer and target proteins for L-carnitine were evaluated by using open-source data from proteomic analysis. Results: The incidence of POAF was 38.5% (95% CI 13.9%–68.4%). Fatty acid-binding protein 4 (FABP4) was selected as a candidate biomarker from 1472, 63, and 26 proteins related to lung cancer, L-carnitine, and AF, respectively. A positive correlation was observed between the predicted POAF incidence rate and preoperative FABP4 levels (Pearson's r = 0.5183). The mean change in serum FABP4 after L-carnitine administration for 5 days was −2.9 ng/mL (95% CI −4.9 to −0.89 ng/mL). Conclusions: The incidence of POAF after a lobectomy was 38.5% after the perioperative administration of L-carnitine for patients at a high risk of POAF. The serum FABP4 level demonstrates potential as a candidate biomarker for POAF prediction. [ABSTRACT FROM AUTHOR]

Background: Migraine is a severe neurological disorder that is recognized as one of the most common debilitating diseases worldwide. Although the exact cause of migraine is not known, research suggests that inflammation, oxidative stress, mitochondrial dysfunction, and insufficient nutrients may contribute to its development. Studies indicate that nutrition-based approaches are safer and more cost-effective strategies for managing migraine symptoms compared to medication. In this regard, the impact of nutrition, as a complementary medicine, is largely attributed to that of certain nutrients on inflammation and mitochondrial function. It is hypothesized that alpha-linolenic acid and L-carnitine, which possess anti-inflammatory and antioxidant properties, may be synergically beneficial for migraine patients. Therefore, this study will be conducted to assess the efficacy of alpha-linolenic acid and L-carnitine co-supplementation in patients with migraine. Methods: This is a parallel, randomized, triple-blind, placebo-controlled clinical trial, in which 80 women aged 20 to 50 years with migraine will be assigned to receive either intervention group (n = 40) receiving both 1000 mg/day flaxseed oil and 500 mg/day L-carnitine simultaneously for 12 weeks, or control group (n = 40) receiving both 1000 mg/day paraffin oil and 500 mg/day maltodextrin as the placebos for the same duration. The primary outcomes include changes in clinical symptoms of migraine, including frequency, severity, and duration of attacks, serum levels of C–reactive protein (CRP), total antioxidant capacity (TAC), nitric oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD). Secondary outcomes include mental health, sleep quality, and quality of life (QOL). Discussion: In this study, we aim to investigate the potential benefits of combining alpha-linolenic acid and L-carnitine as a treatment option for migraine sufferers. Migraine, characterized by recurrent severe headaches, affects a significant portion of the population and can significantly impact an individual's quality of life. By studying alternative therapies such as alpha-linolenic acid and L-carnitine, researchers hope to expand the range of treatment options available and potentially provide relief to migraine sufferers. Trial registration: Iranian Registry of Clinical Trials (www.irct.ir) (ID: IRCT20121216011763N57). Registration date: 29 March 2023. Trial status: The protocol is version 1.0 dated December 30, 2023. Recruitment began on July 10, 2023, and is expected to be completed by January 22, 2024. [ABSTRACT FROM AUTHOR]

Objectives: The evidence suggests that l-carnitine may reduce mortality in critically ill patients with sepsis. However, the conclusions of different studies are inconsistent. A meta-analysis was conducted to evaluate the effect of l-carnitine compliance on mortality in patients with sepsis. Methods: A search of the PubMed, Embase, and Cochrane Library databases was conducted on 1 June 2024. The risk ratio (RR) was pooled with a 95% confidence interval (CI) for dichotomous data. The publications were subjected to a review in accordance with the guidelines set forth in the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This study has been registered with INPLASY (number INPLASY202460086). Results: A total of 356 patients were included in four randomized controlled trials. The results indicated that L-carnitine supplementation was not associated with 28-day mortality in sepsis patients (RR: 0.65; 95% CI 0.33–1.28; I2 = 70%; P = 0.21). And there was no significant effect on 12-month mortality (RR: 0.72; 95% CI 0.47–1.11; I2 = 0%; P = 0.14) compared to placebo. Conclusions: The use of l-carnitine was not found to be significantly correlated with 28-day or 12-month mortality in patients with sepsis. [ABSTRACT FROM AUTHOR]

Background: Various fumigant products containing aluminium phosphide, known as rice pills, are widely used to kill insects in many parts of Iran, including the northern provinces. Poisoning with zinc phosphide as a rat poison also has the same side effects as aluminium phosphide. This poisoning has no specific antidote, and the treatment is auxiliary, and one of the effective auxiliary treatments is L-carnitine. This review study aimed to determine the prevalence of aluminium phosphide poisoning and treatment with intravenous L-carnitine. Materials and Methods: This study was a narrative review conducted in 2023. Search keywords aluminium phosphide, zinc phosphide, intravenous L-carnitine, and poisoning in Persian and English languages in databases including Magiran, PubMed, Wiley, Science Direct, web of Sciences, SID, Scopus, and Google Scholar were done from 1970 to 2022. Relevant articles were identified, and the most important and valuable points were presented after review. Results: According to the findings of most studies, aluminium phosphide pills had the most adverse effects as toxic substances. Conclusion: Due to the prevalence of its consumption among young people with low education levels, there was a need for physicians to treat these patients as quickly as possible accurately. It is also necessary to raise awareness about its potentially dangerous side effects and to monitor closely the distribution of this poisonous pill in its distribution centers. Moreover, the quick start of supportive treatment with antioxidants and L-carnitine can help in this poisoning that does not have a specific antidote. Very effective and useful. [ABSTRACT FROM AUTHOR]

Malonyl-CoA decarboxylase (MLYCD) deficiency, also known as malonic aciduria (MAD), is a rare autosomal recessive inherited metabolic defect. In this study, we aimed to investigate the clinical and molecular features of five patients with MAD in order to increase clinicians' awareness of the disease. Sanger sequencing was used to detect and genetically analyze the MLYCD variations in the preexisting patients and their parents. Five patients with MAD (5 months to 9.6 years old; two males and three females) rarely exhibited metabolic decompensation episodes or seizures. All patients exhibited varying degrees of developmental delay and hypotonia. Our study expands the spectrum of variants of the MLYCD gene. MLYCD gene variations were detected in all five patients, and five new variants were identified: c.60delG (p.Arg21Glyfs*52), c.928C > T (p.Arg310*), c.1293G > T (p.Trp431Cys), c.721T > C (p.Ser241Pro), and Exons 4–5 deletion. Additionally, there is no correlation between various genotypes and phenotypes. A high-medium-chain triglyceride and low-long-chain triglyceride diet supplemented with L-carnitine was effective in most patients and may improve cardiomyopathy and muscle weakness. Newborn screening may aid in the early diagnosis, treatment, and prognosis of this rare disorder. [ABSTRACT FROM AUTHOR]

Background Despite extensive research, the effects of L-carnitine supplementation in treating obesity are still unclear and equivocal. L-carnitine transports fatty acids into mitochondria for oxidation and is marketed as a weight loss supplement. The purpose of the present research is to investigate the efficacy of L-carnitine during concurrent training on the functional capacities and body composition in obese men. Methods Thirty nonactive, obese males (age = 37.2 ± 1.5 years; body mass index = 33.8 ± 2.5 kg/m 2) participated in this research. The participants were randomly divided into three groups: experimental group 1 (EXP1)—concurrent training with L-carnitine supplementation; experimental group 2 (EXP2)—L-carnitine supplementation without training; and control group—without training or L-carnitine supplementation. Concurrent training was performed for 8 weeks, three sessions per week, with a training intensity ranging from 60 to 75% of the maximum heart rate reserve and one-repetition maximum. Both experimental groups were supplemented with 35 mg L-carnitine supplement per kilogram body weight. Various functional and body composition variables were collected at three time points (pre-test, mid-test, and post-test). Results A number of variables were significantly improved in EXP1 after 4 and 8 weeks (systolic blood pressure, maximal oxygen consumption, weight, body mass index, and one-repetition maximum) and only after 8-weeks (diastolic blood pressure, resting heart rate, percentage of body fat, and fat-free mass). No significant changes were observed for EXP2 and the control group. Conclusion L-carnitine supplementation, in conjunction with concurrent training, emerges as a highly effective approach for enhancing body composition and boosting functional capacities in obese adult men. Therefore, it is recommended that overweight male individuals integrate concurrent training into their regimen while taking L-carnitine. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the effectiveness of oral L-carnitine administration in patients after treatment failure to lay the groundwork for targeted in vivo use. Methods and materials: A total of 515 In Vitro Fertilization (IVF) patients undergoing subsequent cycles were included after applying exclusion criteria. They were divided into a control group of 362 patients and a study group of 153 patients who received oral L-carnitine until oocyte retrieval.140 patients were matched according to maternal age, infertility duration, body mass index (BMI), day three top-quality embryos rate, by propensity score matching (PSM). The study investigated the relationship between L-carnitine treatment and in vivo oocyte maturation, normal fertilization, and subsequent embryo development. Results: Following PSM, initial differences in BMI and Day3 top-quality embryo rate between groups were nullified, we created two comparable cohorts with highly similar characteristics. In the subsequent cycles, the study group showed significant improvements in in vivo oocyte maturation rate at retrieval (p=0.002), normal in vitro fertilization rate (p=0.003), blastocyst formation rate (p=0.003), and usable blastocyst rate compared to controls. Although there was no significant difference in the top-quality embryo rate on Day 3, the study group showed a 10% increase in the upper quartile (55.35% vs. 66.67%). The cumulative clinical pregnancy and live birth rates showed a significant improvement (59.82% vs. 68.42%, p=0.004, 47.41% vs. 59.80%, p=0.002). Furthermore, self-control analysis revealed substantial enhancements (p<0.001) in all outcome measures following L-carnitine administration, resulting in the birth of 74 healthy neonates without congenital anomalies. Conclusion: We theorized that daily oral intake of L-carnitine before oocyte retrieval could boost oocyte quality and embryonic development, thus improving IVF outcomes. Ongoing investigations hold the potential to offer valuable insights into the applications and mechanisms underlying the therapeutic effectiveness of L-carnitine. [ABSTRACT FROM AUTHOR]

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Radiotherapy (RAD) is a common cancer treatment method, but it can have unintended lung side effects. L-carnitine (LCAR) is an amino acid with antioxidant and anti-inflammatory properties. This study aims to demonstrate the effects of LCAR against radiation-induced acute lung injury and to elucidate its possible protective molecular mechanisms. A total of 32 Wistar albino rats were separated into four groups: control, RAD (10 Gy once on 1st day), RAD + LCAR (intraperitoneally, 200 mg/kg/d, for 10 days), and LCAR. At the end of the experiment, the rats were euthanized, and the lung tissues were collected for histopathological, immunohistochemical, biochemical, and genetic analysis. Emphysema, pronounced hyperemia, increased total oxidant status, and increased caspase-3 and TNF-α immunostainings were all seen in the lung tissues of the RAD group. LCAR treatment reduced these negative effects. In addition, AMPK and SIRT1 gene expressions increased in the RAD + LCAR group compared to the RAD group, while TGF-1ß gene expression decreased. While RAD caused major damage to the lungs of rats, LCAR application reduced this damage through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. Specifically, LCAR reduced fibrosis while attenuating RAD-induced inflammation and oxidative stress via the AMPK/SIRT1/TGF-1ß pathway. Therefore, LCAR can be considered a supplement to reduce complications associated with RAD. [ABSTRACT FROM AUTHOR]

The reproductive performance of Egyptian buffalo might be determined by genetic variants, but it is also affected by environmental factors. The possible action of L-carnitine (LC) on the maturation of Egyptian buffalo oocytes has not been determined yet. This study aims to estimate the effects of supplementing LC on the in-vitro fertilization (IVF) of Egyptian buffaloes. We evaluated blastocyst and apoptosis rates in order to substantiate the potential development of cumulus oocytes-complexes (COC) and determine the effect of LC in reducing the occurrence of apoptosis under in vitro maturation (IVM) conditions for buffalo blastocysts. The tissue culture media included a control culture medium and other three LC supplemented media (2, 3 or, 4 mM LC). All LC treatments had higher COCs percentages at the metaphase II (MII) compared to the control group. The 2 Mmol LC treatment had the highest percentage of oocytes maturation rate at metaphase (47%) compared to the control group (33.3%). The same treatment had a higher percentage of cleaved embryos (75.4% vs 64.9%) and blastocyst rates (43,4% vs. 31,5%, respectively). Furthermore, the same 2 Mmol LC treatment had a lower apoptotic rate of blastocyst compared to the control group (35,8% vs 58,3%). In conclusion, LC could increase the maturation and blastocyst rates of oocytes and reduce apoptosis in Egyptian buffalo embryos. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that gut bacteria‐derived trimethylamine N‐oxide (TMAO) elevates the risk of cardiovascular disease, and dietary fiber holds the potential to attenuate TMAO formation. However, the effectiveness of dietary fiber, such as inulin, in inhibiting TMAO formation remains controversial. Therefore, this study investigated the effect of inulin supplementation on TMAO formation in mice with high TMAO levels induced by a high‐fat diet (HFD) combined with choline and L‐carnitine. Results showed that HFD treatment significantly elevated blood TMAO concentrations and increased the abundances of TMAO formation‐associated gut bacteria, as well as the abundances of functional genes responsible for TMA formation. While the supplementation of choline and L‐carnitine greatly enhanced blood trimethylamine (TMA) and TMAO levels, inulin supplementation did not significantly affect TMAO levels and had limited impact on TMA‐associated gut bacteria, except for Desulfitobacterium hafniense. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Review the effectiveness and dosing of L‐carnitine for valproic‐acid induced toxicity.A literature review of the pharmacokinetics and clinical use of L‐carnitine was performed.Valproic acid is a fatty acid used for numerous therapeutic indications ranging from epilepsy to bipolar disorder. The metabolism of valproic acid produces both therapeutic and toxic metabolites. Whilst it has a good safety profile, adverse effects of valproic acid in chronic use include hepatotoxicity ranging from transient elevation of liver enzymes to fulminant liver failure and hyperammonaemia with resultant encephalopathy. L‐carnitine is an essential cofactor for mitochondrial fatty acid metabolism, which is an important source of energy in cardiac and skeletal muscle. Physiological concentrations of L‐carnitine are maintained in man by exogenous dietary intake and endogenous synthesis. Following exogenous oral administration of L‐carnitine, the bioavailability ranges from 14% to 18%. After bolus intravenous administration of L‐carnitine in doses ranging from 20 to 100 mg/kg, the volume of distribution is 0.2–0.3 L/kg, and the fraction excreted unchanged in urine is 0.73–0.95, suggesting that renal clearance of L‐carnitine is dose dependent due to saturable renal reabsorption at supraphysiological concentrations.There is evidence supporting the use of L‐carnitine in treating hyperammonaemia and hepatotoxicity following chronic therapeutic use and after acute overdose of valproic acid, but the optimal dose and route of administration is unknown. Based on the pharmacokinetics of L‐carnitine, we advocate the administration of L‐carnitine for valproic‐acid induced hyperammonaemia or hepatotoxicity as an intravenous loading dose of 5 mg/kg followed by a continuous intravenous infusion instead of the oral or intravenous boluses that are currently advocated. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of oral roxadustat plus L-carnitine for dialysis-induced anemia in patients with chronic renal failure (CRF). Methods: This was a retrospective analysis of 46 patients conducted on 100 CRF cases with dialysisinduced anemia treated at Xinjiang Armed Police Crops Hospital from March 2020 to March 2023. The participants were randomly distributed into study (n = 54) and control groups (n = 46). The control group received oral roxadustat (100 mg for patients weighing 45 - 60 kg, and 120 mg for patients = 60 kg, thrice per week), while the study group was administered roxadustat in combination with L-carnitine (2 g injected using the dialysis machine before the end of each session). Anemia indices, and iron metabolism indices in the two groups were assessed before treatment and 3 months after treatment. Adverse effects were compared between groups. Results: The study group showed significantly higher red blood cell count, haemoglobin level as well as haematocrit after treatment compared to control group (p > 0.05). Also, total iron binding capacity, and serum iron and ferritin levels were significantly higher in the study group than in the control group (p < 0.05). Conclusion: Roxadustat combined with L-carnitine significantly reduces anemia and improves iron metabolism without increasing adverse reactions. However, there is a need for additional studies to assess the therapeutic potential of this combined regimen. [ABSTRACT FROM AUTHOR]

The addition of antioxidants to cryopreservation media reportedly improves sperm post‐thaw quality and reproductive performance after artificial insemination. Therefore, the objectives of this study were to evaluate if the addition of L‐carnitine and pyruvate to freezing media, or their addition to samples after thawing, improves the post‐thaw quality of equine spermatozoa. Thus, in Experiment 1, stallion semen samples were cryopreserved in: (1) EDTA–glucose–based extender with 20% egg yolk and 5% dimethylformamide (EDTA control); (2) skim milk–based extender with 20% egg yolk and 5% dimethylformamide (milk control); (3) Extender 1 supplemented with 50 mM L‐carnitine and 10 mM pyruvate (EDTA‐carnitine‐pyruvate); and (4) Extender 2 supplemented with 50 mM L‐carnitine and 10 mM pyruvate (milk‐carnitine‐pyruvate). In Experiment 2, 50 mM L‐carnitine and 10 mM pyruvate were added post‐thaw to samples cryopreserved with extenders 1 and 2 (EDTA control and milk control). Sperm kinematic parameters, DNA fragmentation, membrane lipid peroxidation, acrosome status and viability were evaluated after thawing. No significant differences (p > 0.05) were observed for most of the kinematic parameters, DNA fragmentation, membrane lipid peroxidation, acrosome status and viability of spermatozoa, between the samples frozen in the presence or absence of L‐carnitine and pyruvate, nor between the samples after the post‐thaw addition of these components. A higher (p < 0.05) mean velocity and higher (p < 0.05) amplitude of lateral head displacement were observed in the samples frozen in the milk‐based extender with the addition of L‐carnitine and pyruvate after thawing. The addition of 50 mM L‐carnitine and 10 mM pyruvate, either to the freezing extenders or after thawing, was not deleterious for sperm; however, it did not improve equine sperm motility, viability, acrosome and DNA integrity, nor decrease membrane lipid peroxidation after thawing. [ABSTRACT FROM AUTHOR]

This observational cohort study investigated the potential of a novel sperm-washing medium (SWM) enriched with serotonin (5-HT), L-carnitine (L-C), and coenzyme Q10 (CoQ10) to enhance sperm motility and reduce DNA damage. It compared this innovative medium (5-HT/L-C/CoQ10 SWM) with two widely used commercial media (SWM 1 and SWM 2). Ninety-eight volunteers from an infertility clinic provided semen samples, which were divided into three aliquots for analysis in different SWMs: group 1, SWM was composed of hydroxyethyl piperazineethanesulfonic acid (HEPES), sodium bicarbonate, human serum albumin (HSA), taurine, and gentamicin sulfate (SWM 1); group 2, SWM was composed of HEPES, sodium bicarbonate, and HSA (SWM 2); and group 3, SWM was composed of HEPES-buffered human tubal fluid supplemented with 5-HT, L-C, and CoQ10 (5-HT/L-C/CoQ10 SWM). Sperm motility was categorized as progressive, nonprogressive, or immotile. Apoptosis, reactive oxygen species (ROS) production, and DNA fragmentation were also assessed. There were no significant differences in total or progressive sperm motility among the groups. Spermatozoa in group 3 exhibited reduced apoptosis, necrosis, and ROS levels and increased viability. No significant differences were observed in the DNA fragmentation index among groups. The 5-HT/L-C/CoQ10 SWM reduced sperm oxidative stress and apoptosis compared with those of the two commercially available SWMs, suggesting that 5-HT/L-C/CoQ10 SWM could be useful for enhancing in vitro fertilization success rates.

Abstract Background Migraine is a severe neurological disorder that is recognized as one of the most common debilitating diseases worldwide. Although the exact cause of migraine is not known, research suggests that inflammation, oxidative stress, mitochondrial dysfunction, and insufficient nutrients may contribute to its development. Studies indicate that nutrition-based approaches are safer and more cost-effective strategies for managing migraine symptoms compared to medication. In this regard, the impact of nutrition, as a complementary medicine, is largely attributed to that of certain nutrients on inflammation and mitochondrial function. It is hypothesized that alpha-linolenic acid and L-carnitine, which possess anti-inflammatory and antioxidant properties, may be synergically beneficial for migraine patients. Therefore, this study will be conducted to assess the efficacy of alpha-linolenic acid and L-carnitine co-supplementation in patients with migraine. Methods This is a parallel, randomized, triple-blind, placebo-controlled clinical trial, in which 80 women aged 20 to 50 years with migraine will be assigned to receive either intervention group (n = 40) receiving both 1000 mg/day flaxseed oil and 500 mg/day L-carnitine simultaneously for 12 weeks, or control group (n = 40) receiving both 1000 mg/day paraffin oil and 500 mg/day maltodextrin as the placebos for the same duration. The primary outcomes include changes in clinical symptoms of migraine, including frequency, severity, and duration of attacks, serum levels of C–reactive protein (CRP), total antioxidant capacity (TAC), nitric oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD). Secondary outcomes include mental health, sleep quality, and quality of life (QOL). Discussion In this study, we aim to investigate the potential benefits of combining alpha-linolenic acid and L-carnitine as a treatment option for migraine sufferers. Migraine, characterized by recurrent severe headaches, affects a significant portion of the population and can significantly impact an individual's quality of life. By studying alternative therapies such as alpha-linolenic acid and L-carnitine, researchers hope to expand the range of treatment options available and potentially provide relief to migraine sufferers. Trial registration Iranian Registry of Clinical Trials ( www.irct.ir ) (ID: IRCT20121216011763N57). Registration date: 29 March 2023. Trial status The protocol is version 1.0 dated December 30, 2023. Recruitment began on July 10, 2023, and is expected to be completed by January 22, 2024.

Abstract Objectives The evidence suggests that l-carnitine may reduce mortality in critically ill patients with sepsis. However, the conclusions of different studies are inconsistent. A meta-analysis was conducted to evaluate the effect of l-carnitine compliance on mortality in patients with sepsis. Methods A search of the PubMed, Embase, and Cochrane Library databases was conducted on 1 June 2024. The risk ratio (RR) was pooled with a 95% confidence interval (CI) for dichotomous data. The publications were subjected to a review in accordance with the guidelines set forth in the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This study has been registered with INPLASY (number INPLASY202460086). Results A total of 356 patients were included in four randomized controlled trials. The results indicated that L-carnitine supplementation was not associated with 28-day mortality in sepsis patients (RR: 0.65; 95% CI 0.33–1.28; I 2 = 70%; P = 0.21). And there was no significant effect on 12-month mortality (RR: 0.72; 95% CI 0.47–1.11; I 2 = 0%; P = 0.14) compared to placebo. Conclusions The use of l-carnitine was not found to be significantly correlated with 28-day or 12-month mortality in patients with sepsis.

Abstract Background Cancer cachexia‐induced skeletal muscle fibrosis (SMF) impairs muscle regeneration, alters the muscle structure and function, reduces the efficacy of anticancer drugs, diminishes the patient's quality of life and shortens overall survival. RUNX family transcription factor 2 (Runx2), a transcription factor, and collagen type I alpha 1 chain (COL1A1), the principal constituent of SMF, have been linked previously, with Runx2 shown to directly modulate COL1A1 mRNA levels. l‐Carnitine, a marker of cancer cachexia, can alleviate fibrosis in liver and kidney models; however, its role in cancer cachexia‐associated fibrosis and the involvement of Runx2 in the process remain unexplored. Methods Female C57 mice (48 weeks old) were inoculated subcutaneously with MC38 cells to establish a cancer cachexia model. A 5 mg/kg dose of l‐carnitine or an equivalent volume of water was administered for 14 days via oral gavage, followed by assessments of muscle function (grip strength) and fibrosis. To elucidate the interplay between the deltex E3 ubiquitin ligase 3L(DTX3L)/Runx2/COL1A1 axis and fibrosis in transforming growth factor beta 1‐stimulated NIH/3T3 cells, a suite of molecular techniques, including quantitative real‐time PCR, western blot analysis, co‐immunoprecipitation, molecular docking, immunofluorescence and Duolink assays, were used. The relevance of the DTX3L/Runx2/COL1A1 axis in the gastrocnemius was also explored in the in vivo model. Results l‐Carnitine supplementation reduced cancer cachexia‐induced declines in grip strength (>88.2%, P 57.9%, P

Abstract Background Generally, it is not well known that Lowe’s syndrome may coexist with hyperammonemia and hipocarnitynemia. The importance of hyperammonemia in the diagnosis of kidney diseases is not completely understood. Case presentation We present the history of a 13-year-old boy, admitted to the hospital due to proteinuria. In the past, the boy was diagnosed with binocular cataracts in infancy. Then he went through neurological diagnostic tests which diagnosed muscular hypotonia and psychomotor retardation but no inherited errors of metabolism were found. Proteinuria has been observed since the age of 2. Ultrasound imaging at the age of 5 showed the presence of a shading deposit in the kidney. At the age of 13, the boy was referred to the Pediatric Nephrology Ward. The laboratory tests revealed: a reduction of glomerular filtration rate, metabolic acidosis, proteinuria, hypercalciuria, increased activity of AST (SGOT), CK, LDH, hyperammonemia, and decreased concentration of total carnitine in blood serum. Based on the clinical presentation, Lowe’s syndrome was diagnosed. The genetic testing revealed an OCRL gene hemizygous mutation. Conclusion Lowe’s syndrome is an example of a disease in which clinical symptoms—although occurring early and in high intensity—may not raise the suspicion of tubulopathy for a long time if they are not analyzed in a complex manner. There is a necessity to educate healthcare practitioners from other fields about the extrarenal symptoms of genetically determined tubulopathies. l-carnitine deficiency may be a symptom of proximal tubulopathy, including Lowe’s syndrome. l-carnitine deficiency leads to disturbances in the efficiency of the urea cycle, which results in hyperammonemia. Hyperammonemia is not only a symptom of inborn errors of metabolism and liver failure, but it may also lead to the diagnosis of tubulopathy. Since carnitine supplementation could have the desired beneficial effect on the patient’s general condition, it is postulated to conduct further studies on larger groups of patients with Lowe’s syndrome.

Objective: Decreased bone density and strength increase the risk of fracture and thus the rates of morbidity and mortality. L-carnitine (LC) is a supplement commonly used by individuals who participate in sports, especially to increase muscle mass. The aim of this study was to investigate the effect of LC on bone strength. Materials and Methods: In our main study 10 male Wistar rats per group, a tendon injury model was applied by clamping the left Achilles tendons of rats except the control group. LC (100 mg/kg/day) was administered intraperitoneally every day for 5 weeks in the pre-LC group and for 4 weeks in the post-LC group. LC was not given to the control group. Apart from to our main study, remaining right os femurs of rats were extracted at the end of the experiment to test bone strength to reduce the number of animals used in scientific research. 3-D bending test was performed on the extracted bones using a Zwick Roell Z0.5 mechanical testing machine. Results: There were no significant differences among the groups in the parameters and measurements used to evaluate bone strength (p>0.05). Conclusion: LC supplementation had no beneficial or detrimental effects on bone strength in healthy subjects.

Obesity is a condition where the body is overweight due to fat accumulation, each exceeding 20-25% of body weight for men and women. L-carnitine is a nutrient that plays a role in transporting fat to the mitochondria to be burned and converted into energy for the body. Sufficient L-carnitine allows the body to burn fat at optimal levels. This research aims to determine the side effects of fed L-carnitine supplements against liver histology. This study used a completely randomized design (CRD) with four groups comprising six albino rats. The treatments were fed orally by distilled water 1 ml/day (Control), P1 fed by L-carnitine supplement dose 100 mg/kg body weight orally 1ml/day, P2 fed by L-carnitine supplement dose 150 mg/kg body weight orally 1ml/day, P3 fed by L-carnitine supplement dose 200 mg/kg body weight orally 1ml/day. Treatments were given to albino rats every day for 90 days. Variables observed measured were lipid degeneration, central vein dilation, and pyknotic nuclei. Data were analyzed with the statistical program (SPSS 22.0 for Windows) with One Way ANOVA. The results showed that feeding L-carnitine supplements in high doses for long periods can damage the liver cells of male rats. The microscopic liver damage statistical analysis showed significant differences (P

Objective: To assess the effects of L-carnitine on the outcomes of patients with moderate to severe coronavirus disease 2019 (COVID-19) in intensive care unit (ICU). Methods: This double-blind clinical trial was carried out in 2022-2023. 64 Patients with COVID-19 were selected from Amiralmomenin and Khansari hospitals in Arak, Iran. They were randomly assigned to the control and the L-carnitine treatment group via block randomization. Venous blood gases, disease severity, and levels of D-dimer, lactate dehydrogenase, ferritin, and C-reactive protein were daily assessed during the seven days of the intervention, and the length of ICU stay, the need for endotracheal intubation, and mortality rate were documented. Results: There were significant differences in length of ICU stay, the need for endotracheal intubation, and levels of D-dimer, lactate dehydrogenase, ferritin, APACHE II score, and C-reactive protein between the two groups (P0.05). Conclusions: L-carnitine can improve outcomes of patients with COVID-19. Therefore, it can be used as an adjuvant therapy for these patients. Trial registration: Iranian Registry of Clinical Trials identifier IRCT20141209020258N165.

Abstract Aims L-carnitine plays a role related to cardiometabolic factors, but its effectiveness and safety in CVD are still unknown. We aim to assess the effect of L-carnitine supplementation on CVD risk factors. Methods A systematic literature search was conducted in PubMed, Web of Science, and Scopus until October 2022. The main outcomes were lipid profiles, anthropometric parameters, insulin resistance, serum glucose levels, leptin, blood pressure, and inflammatory markers. The pooled weighted mean difference (WMD) was calculated using a random-effects model. Results We included the 21 RCTs (n = 2900) with 21 effect sizes in this study. L-carnitine supplementation had a significant effect on TG (WMD = − 13.50 mg/dl, p = 0.039), LDL (WMD = − 12.66 mg/dl, p

Abstract Colistin is a polymyxin antibiotic currently experiencing renewed clinical interest due to its efficacy in the treatment of multidrug resistant (MDR) bacterial infections. The frequent onset of acute dose-dependent kidney injury, with the potential of leading to long-term renal damage, has limited its use and hampered adequate dosing regimens, increasing the risk of suboptimal plasma concentrations during treatment. The mechanism of colistin-induced renal toxicity has been postulated to stem from mitochondrial damage, yet there is no direct evidence of colistin acting as a mitochondrial toxin. The aim of this study was to evaluate whether colistin can directly induce mitochondrial toxicity and, if so, uncover the underlying molecular mechanism. We found that colistin leads to a rapid permeability transition of mitochondria isolated from mouse kidney that was fully prevented by co-incubation of the mitochondria with desensitizers of the mitochondrial transition pore cyclosporin A or L-carnitine. The protective effect of L-carnitine was confirmed in experiments in primary cultured mouse tubular cells. Consistently, the relative risk of colistin-induced kidney damage, calculated based on histological analysis as well as by the early marker of tubular kidney injury, Kim-1, was halved under co-administration with L-carnitine in vivo. Notably, L-carnitine neither affected the pharmacokinetics of colistin nor its antimicrobial activity against relevant bacterial strains. In conclusion, colistin targets the mitochondria and induces permeability transition thereof. L-carnitine prevents colistin-induced permeability transition in vitro. Moreover, L-carnitine co-administration confers partial nephroprotection in mice treated with colistin, without interfering with its pharmacokinetics and antibacterial activity.

Abstract Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by DanioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify l-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathways, improving muscle endurance and swim speed in LMNA(R453W) fish. Transcriptomic profiling reveals upstream regulators and affected genes contributing to motor dysfunction, cardiac anomalies, and ion flux dysregulation in LMNA mutant transgenic fish. These findings faithfully mimic clinical manifestations of muscular laminopathies, including dysmorphism, early mortality, decreased fiber size, and muscle dysfunction in zebrafish. Furthermore, our drug screening results suggest l-carnitine and creatine treatments as potential rescuers of muscle endurance in LMNA(L35P) and LMNA(R453W) zebrafish models. Our study offers valuable insights into the future development of potential treatments for LMNA-related muscular laminopathy.

Introduction: Peritoneal ultrafiltration (PUF) has been proposed as an additional therapeutic option for refractory congestive heart failure (RCHF) patients. Despite promising observational studies and/or case report results, limited clinical trial data exist, and so far, PUF solutions remain only indicated for chronic kidney diseases. In this article, we described a multicenter, randomized, controlled, unblinded, adaptive design clinical trial, about to start, investigating the effects of PolyCore™, an innovative PUF solution, in the treatment of RCHF patients. Methods: The Peritoneal Ultrafiltration in Cardiorenal Syndrome (PURE) study is a phase II, multicenter, randomized, controlled, unblinded, adaptive design clinical trial that aims to evaluate the safety and efficacy of PUF, using PolyCore™ as the investigational solution, in the treatment of RCHF patients who present with prominent right ventricular failure due to afterload mismatch, functional tricuspid regurgitation and enlarged cava vein consequent to intravascular fluid overload. Approximately 84 patients will be randomized 1:1 either to continue with their prescribed guideline-directed medical therapy or to add the PUF treatment on top of it. The primary objective is to evaluate if PUF treatment has an impact on the composite endpoint of the patient’s mortality or worsening of the patient’s condition such as hospitalization for cardiovascular causes, increasing the initial daily dose of loop diuretic or worsening of renal function. Statistical analysis for the primary endpoint will be standard survival analysis to estimate the failure rate at month 7 for each group via Kaplan-Meier curves. Sensitivity analysis and various secondary analyses, including a multiple events analysis, will be conducted to evaluate the robustness of the primary endpoint results. Safety will be evaluated for up to 12 months. Conclusion: The PURE study was designed to evaluate the safety and efficacy of peritoneal ultrafiltration with PolyCore™ on top of guideline-directed medical therapy in patients with RCHF, assuming a combined clinical endpoint of mortality or worsening patients’ condition. If successful, the treatment should allow for an improvement of the RCHF symptoms, decreasing hospitalization rate of patients. [ABSTRACT FROM AUTHOR]

Background: Generally, it is not well known that Lowe's syndrome may coexist with hyperammonemia and hipocarnitynemia. The importance of hyperammonemia in the diagnosis of kidney diseases is not completely understood. Case presentation: We present the history of a 13-year-old boy, admitted to the hospital due to proteinuria. In the past, the boy was diagnosed with binocular cataracts in infancy. Then he went through neurological diagnostic tests which diagnosed muscular hypotonia and psychomotor retardation but no inherited errors of metabolism were found. Proteinuria has been observed since the age of 2. Ultrasound imaging at the age of 5 showed the presence of a shading deposit in the kidney. At the age of 13, the boy was referred to the Pediatric Nephrology Ward. The laboratory tests revealed: a reduction of glomerular filtration rate, metabolic acidosis, proteinuria, hypercalciuria, increased activity of AST (SGOT), CK, LDH, hyperammonemia, and decreased concentration of total carnitine in blood serum. Based on the clinical presentation, Lowe's syndrome was diagnosed. The genetic testing revealed an OCRL gene hemizygous mutation. Conclusion: Lowe's syndrome is an example of a disease in which clinical symptoms—although occurring early and in high intensity—may not raise the suspicion of tubulopathy for a long time if they are not analyzed in a complex manner. There is a necessity to educate healthcare practitioners from other fields about the extrarenal symptoms of genetically determined tubulopathies. l-carnitine deficiency may be a symptom of proximal tubulopathy, including Lowe's syndrome. l-carnitine deficiency leads to disturbances in the efficiency of the urea cycle, which results in hyperammonemia. Hyperammonemia is not only a symptom of inborn errors of metabolism and liver failure, but it may also lead to the diagnosis of tubulopathy. Since carnitine supplementation could have the desired beneficial effect on the patient's general condition, it is postulated to conduct further studies on larger groups of patients with Lowe's syndrome. [ABSTRACT FROM AUTHOR]

Dietary L-carnitine (LC) and nucleotides (NT) are additives used independently in fish feeds. However, whether they work antagonistically or synergistically in fish nutrition is currently unknown. We explored the interactive effect between dietary LC and NT on growth performance, feed utilization, antioxidant capacity, and hepatic lipid metabolism in juvenile largemouth bass (Micropterus salmoides) juvenile fed a high dietary lipid level of 160 g/kg. Four experimental diets including basal diet (BD; no additives), 0.2 g/kg LC and 0 NT g/kg (LCNT0), 0.2 g/kg LC and 5 g/kg NT (LCNT5), and 0.2 g/kg LC and 10 g/kg NT (LCNT10) were formulated. These diets were administered twice daily to 30 fish weighing 10.3 ± 0.2 g in triplicate tanks for 9 weeks. We found that fish reared on diet LCNT10 increased significantly final body weight and weight gain than those reared on BD and LCNT0 diet (P ˂ 0.05). Feeding LCNT5 diet increased significantly feed intake than LCNT0 diet (P < 0.05). Fish fed with LCNT0 and LCNT10 diets lowered significantly FCR compared to BD and LCNT5 diet (P ˂ 0.05). Retention efficiency of nitrogen, phosphorus, and energy increased significantly in fish fed with LCNT10 diet than on BD and LCNT0 diet (P ˂ 0.05). The LCNT0, LCNT5, and LCNT10 diets reduced serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and malondialdehyde content of largemouth bass than BD (P < 0.05). Furthermore, LCNT5 and LCNT10 diets increased liver GSH-Px and CAT activities in fish compared to BD (P < 0.05). The BD upregulated the mRNA expression of carnitine palmitoyltransferase-1 and peroxisome proliferators-activated receptor α genes than LCNT0, LCNT5, and LCNT10 diets (P < 0.05). Taken together, dietary LC and NT supplementation synergistically promote growth rate, feed utilization efficiency, and antioxidant capacity in juvenile largemouth bass. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess L-carnitine's effects on adult male rats' lung damage brought on by amiodarone, which is a potent antiarrhythmic with limited clinical efficacy due to potentially life-threatening amiodarone-induced lung damage. Because of the resemblance among the structural abnormalities in rats' lungs that follows amiodarone medication and pulmonary toxicity in human beings, this animal model may be an appropriate example for this disease entity. Amiodarone produced pulmonary toxicity in twenty-four healthy male albino rats (150–180 g) over a period of 6 weeks. Four groups of six rats each were established: control, sham, amiodarone, and L-carnitine plus amiodarone. Histological, ultrastructural, oxidative stress, and inflammatory markers were determined during a 6-week exposure experiment. Amiodarone-induced lung damage in rats may be brought on due to oxidative stress producing significant pulmonary cytotoxicity, as evidenced by the disruption of the mitochondrial structure, severe fibrosis, and inflammatory response of the lung tissue. Lungs already exposed to such harmful effects may be partially protected by the antioxidant L-carnitine. Biochemical markers of lung damage brought on by amiodarone include lung tissue levels of the enzyme's catalase, superoxide dismutase, and reduced glutathione. The levels of lipid peroxides in lung tissue measured as malondialdehyde increased significantly upon exposure to amiodarone. In addition, the levels of tumor necrosis factor alpha were significantly elevated in response to amiodarone. The effect of L-carnitine on amiodarone-induced pulmonary toxicity was studied in rats. It is interesting to note that the intake of L-carnitine in rats treated with amiodarone partially restored the biochemical and histopathological alterations brought on by amiodarone to their original levels. Tumor necrosis factor alpha levels were significantly reduced upon L-carnitine exposure. These results suggest that L-carnitine can be used to treat amiodarone-induced pulmonary dysfunction. [ABSTRACT FROM AUTHOR]

Stress-oxidative-induced sexual dysfunction has been widely reported to be associated with drug use disorders, particularly buprenorphine (Bu). This study aimed to evaluate the protective effect of L-carnitine (LC) in ameliorating stress-induced oxidative sexual dysfunction in a rat model of Bu addiction. Forty-eight adult male Wistar rats were randomly divided into three equal groups (n = 16) including the control (received tap water), Bu, and Bu + LC groups. On days 28 and 56 (as short and long time use of Bu, respectively) from the start of the study, eight rats from each group were randomly selected. Blood samples were collected for sex hormonal assays, including free testosterone (FT), total testosterone (TT), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) using ELISA. To analyze the sperm parameters, testicular anti-oxidant capacity, histological, immunohistochemical, and molecular analysis, the rats were sacrificed after collecting blood samples. The long-term Bu group exhibited the lowest sperm parameter index, mRNA and protein expression levels of BCL2, antioxidant activity, as well as the highest mRNA expression levels of caspase-3 and BAX, protein expression of BAX, and histological and hormonal changes. The LC + Bu group showed the higher and lower sperm parameter index, mRNA and protein expression level of BCL2, and antioxidant activity than those of the Bu and control groups, respectively. In addition, LC + Bu showed the lowest and highest mRNA expression levels of caspase-3 and BAX, protein expression of BAX, and histological and hormonal changes than those of the Bu and control groups, respectively. The administration of LC showed promising results in alleviating Bu-induced testicular degeneration by increasing testicular antioxidant capacity and inhibiting the apoptosis pathway. [ABSTRACT FROM AUTHOR]

Objective: Decreased bone density and strength increase the risk of fracture and thus the rates of morbidity and mortality. L-carnitine (LC) is a supplement commonly used by individuals who participate in sports, especially to increase muscle mass. The aim of this study was to investigate the effect of LC on bone strength. Materials and Methods: In our main study 10 male Wistar rats per group, a tendon injury model was applied by clamping the left Achilles tendons of rats except the control group. LC (100 mg/kg/day) was administered intraperitoneally every day for 5 weeks in the pre-LC group and for 4 weeks in the post-LC group. LC was not given to the control group. Apart from to our main study, remaining right os femurs of rats were extracted at the end of the experiment to test bone strength to reduce the number of animals used in scientific research. 3-D bending test was performed on the extracted bones using a Zwick Roell Z0.5 mechanical testing machine. Results: There were no significant differences among the groups in the parameters and measurements used to evaluate bone strength (p>0.05). Conclusion: LC supplementation had no beneficial or detrimental effects on bone strength in healthy subjects. [ABSTRACT FROM AUTHOR]

Cholinesterase inhibitors (ChEIs) insecticide poisoning is a serious global health concern that results in hundreds of thousands of fatalities each year. Although inhibition of the cholinesterase enzyme is the main mechanism of ChEI poisoning, oxidative stress is considered the mechanism underlying the related complications. The study aimed to assess the oxidative status of the patients with ChEI insecticide poisoning and the role of L-carnitine as adjuvant therapy in their management. Human studies on the efficacy and safety of L-carnitine in treating insecticide poisoning are limited despite its growing research interest as a safe antioxidant. This prospective study was conducted on eighty patients with acute ChEIs insecticide poisoning admitted to Alexandria Poison Center, Alexandria Main University Hospital, Egypt. Patients were allocated into two equal groups randomly. The L-carnitine (LC) group received the conventional treatment (atropine & toxogonin) and LC and the standard treatment (ST) group received the standard treatment only. Outcome measures were fatality rate, the total administered dose of atropine & toxogonin, length of hospital stay, and the requirement for ICU admission or mechanical ventilation. The study results revealed that malondialdehyde (MDA) significantly decreased in the LC group. Cholinesterase enzyme levels increased significantly after treatment in the LC group than in the ST group. The LC group needed lower dosages of atropine and toxogonin than the ST group. Also, the LC group showed no need for ICU admission or mechanical ventilation. The study concluded that LC can be considered a promising adjuvant antioxidant treatment in acute ChEIs pesticide poisoning. [ABSTRACT FROM AUTHOR]

Maca (Lepidium meyenii Walp) is renowned for its phytochemicals, including amino acids, saponins, and macamides, confer nutritional and medicinal benefits. This study analyzed the bioactive constituents of maca via solid-state fermentation with Rhizopus oligosporus for 0–15 days. After fermentation, the l-carnitine content reached 157.3 μg/g. A 93% increase in macamide B was recorded after 7-day fermentation. Total flavonoid and saponin contents increased by 88.2% and 110.3%, respectively. The fermentation process significantly enhanced the physicochemical attributes of maca; in particular, its water retention and cholesterol-binding capacities increased by 1.73- and 4.30-fold, respectively, compared with the non-fermented maca. Moreover, fermented maca exhibited stronger antioxidant and α-glucosidase-inhibiting effects than non-fermented maca. Finally, the neuroprotective effect of maca on HT-22 cells increased by 23% after 5-day fermentation. These findings demonstrate the potential of fermented maca as a novel ingredient for foods, beverages, and pharmaceuticals. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the associations of choline, betaine, dimethylglycine (DMG), L-carnitine, and Trimethylamine-N-oxide (TMAO) with the risk of Gestational diabetes mellitus (GDM) as well as the markers of glucose homeostasis. Methods: We performed a case-control study including 200 diagnosed GDM cases and 200 controls matched by maternal age (±2 years) and gestational age (±2 weeks). Concentrations of serum metabolites were measured by the high-performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS). Results: Compared to the control group, GDM group had significantly lower serum betaine concentration and betaine/choline ratio, and higher DMG concentration. Furthermore, decreased betaine concentration and betaine/choline ratio, increased DMG concentration showed significant association with the risk of GDM. In addition, serum betaine concentrations were negatively associated with blood glucose levels at 1-h post-glucose load (OGTT-1h), and both betaine and L-carnitine concentrations were positively associated with 1,5-anhydroglucitol levels. Betaine/choline ratio was negatively associated with OGTT-1h and blood glucose levels at 2-h post-glucose load (OGTT-2h) and serum choline concentrations were negatively associated with fasting blood glucose and positively associated with OGTT-2h. Conclusion: Decreased serum betaine concentrations and betaine/choline ratio, and elevated DMG concentrations could be significant risk factors for GDM. Furthermore, betaine may be associated with blood glucose regulation and short-term glycemic fluctuations. [ABSTRACT FROM AUTHOR]

Streptococcus mutans is a major pathogenic habitant of oral caries. Owing to its physiological and biochemical features, it prevails in the form of plaque biofilm together with another important mutans streptococci species, Streptococcus sobrinus. Both species are considered as initiators of cavity lesions, and biofilm is essential to the dental caries process. Compared with the planktonic populations, the biofilm form has higher resistance to environmental conditions and antibiotics. Dental plaques also secure the long-term survival of microorganisms and protection from any stress conditions. To address the need for new antibiofilm agents, we have focused on L-carnitine-fumarate, a fumarate-conjugated quaternary ammonium compound. Using the macro-broth susceptibility testing method, we established its MIC value as 6.0 mg/mL. The MBC value, determined from the broth dilution minimum inhibitory concentration test by sub-culturing it to BHI agar plates, was established as 7.0 mg/mL. Antibiofilm efficacy was tested in 96-well plates coated with saliva using BHI broth supplemented with 1% sucrose as a standard approach. The obtained results allowed us to assess the MIBC as 7.5 mg/mL and the MBBC value as 10.0 mg/mL. The latter concentration also caused approximately 20% eradication of pre-existing biofilm. EPS-rich matrix, forming the core of the biofilm and enabling a confined acidic microenvironment, was also examined and confirmed the effectiveness of 10.0 mg/mL L-carnitine-fumarate concentration in inhibiting EPS formation. Furthermore, the anti-adherent and anti-aciduric impacts of L-carnitine-fumarate were investigated and revealed significant inhibitory effects at sub-MIC concentrations. The influence of L-carnitine-fumarate on the phosphotransferase system was investigated as well. Our results provide a new insight into the antibacterial potential of L-carnitine-fumarate as a valuable compound to be considered for alternative or adjunct anti-caries and antibiofilm preventive approaches. [ABSTRACT FROM AUTHOR]

Aims: L-carnitine plays a role related to cardiometabolic factors, but its effectiveness and safety in CVD are still unknown. We aim to assess the effect of L-carnitine supplementation on CVD risk factors. Methods: A systematic literature search was conducted in PubMed, Web of Science, and Scopus until October 2022. The main outcomes were lipid profiles, anthropometric parameters, insulin resistance, serum glucose levels, leptin, blood pressure, and inflammatory markers. The pooled weighted mean difference (WMD) was calculated using a random-effects model. Results: We included the 21 RCTs (n = 2900) with 21 effect sizes in this study. L-carnitine supplementation had a significant effect on TG (WMD = − 13.50 mg/dl, p = 0.039), LDL (WMD = − 12.66 mg/dl, p < 0.001), FBG (WMD = − 6.24 mg/dl, p = 0.001), HbA1c (WMD = -0.37%, p = 0.013) HOMA-IR (WMD = -0.72, p = 0.038 (, CRP (WMD = − 0.07 mg/dl, P = 0.037), TNF-α (WMD = − 1.39 pg/ml, p = 0.033), weight (WMD = − 1.58 kg, p = 0.001 (, BMI (WMD = − 0.28 kg/m2, p = 0.017(, BFP (WMD = − 1.83, p < 0.001) and leptin (WMD = − 2.21 ng/ml, p = 0.003 (in intervention, compared to the placebo group, in the pooled analysis. Conclusions: This meta-analysis demonstrated that administration of L-carnitine in diabetic and glucose intolerance patients can significantly reduce TG, LDL-C, FBG, HbA1c, HOMA-IR, CRP, TNF-α, weight, BMI, BFP, and leptin levels. PROSPERO registration code: CRD42022366992. [ABSTRACT FROM AUTHOR]

Colistin is a polymyxin antibiotic currently experiencing renewed clinical interest due to its efficacy in the treatment of multidrug resistant (MDR) bacterial infections. The frequent onset of acute dose-dependent kidney injury, with the potential of leading to long-term renal damage, has limited its use and hampered adequate dosing regimens, increasing the risk of suboptimal plasma concentrations during treatment. The mechanism of colistin-induced renal toxicity has been postulated to stem from mitochondrial damage, yet there is no direct evidence of colistin acting as a mitochondrial toxin. The aim of this study was to evaluate whether colistin can directly induce mitochondrial toxicity and, if so, uncover the underlying molecular mechanism. We found that colistin leads to a rapid permeability transition of mitochondria isolated from mouse kidney that was fully prevented by co-incubation of the mitochondria with desensitizers of the mitochondrial transition pore cyclosporin A or L-carnitine. The protective effect of L-carnitine was confirmed in experiments in primary cultured mouse tubular cells. Consistently, the relative risk of colistin-induced kidney damage, calculated based on histological analysis as well as by the early marker of tubular kidney injury, Kim-1, was halved under co-administration with L-carnitine in vivo. Notably, L-carnitine neither affected the pharmacokinetics of colistin nor its antimicrobial activity against relevant bacterial strains. In conclusion, colistin targets the mitochondria and induces permeability transition thereof. L-carnitine prevents colistin-induced permeability transition in vitro. Moreover, L-carnitine co-administration confers partial nephroprotection in mice treated with colistin, without interfering with its pharmacokinetics and antibacterial activity. [ABSTRACT FROM AUTHOR]

Background: Melatonin and L-carnitine are free radical scavengers with antiapoptotic and antioxidant properties that improve oocyte development. Objective: This study aimed to find the possible effect of combining 2 antioxidant agents of melatonin and L-carnitine on oocyte morphology, maturation, apoptosis, and expression of bone morphogenetic protein 15 (BMP-15) and growth differentiation factor 9 (GDF-9) genes in a mice model. Materials and Methods: To overstimulation, 60 female NMRI mice were injected intraperitoneally using mare serum gonadotropin. On day 2 post-injection, 70 cumulus-oocyte complexes were collected from each mouse. The collected oocytes randomly were then divided into 4 groups including, the control, melatonin, L-carnitine, and melatonin + L-carnitine groups. The morphology and maturation rate of the oocytes was evaluated using a light microscope. Apoptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and the expression of BMP-15 and growth and differentiation factor GDF-9 genes was also evaluated by real-time polymerase chain reaction. Results: Oocyte diameter significantly was increased in combination treatment of L-carnitine and melatonin compared to other groups (p < 0.05). L-carnitine group showed the highest mean percentage of oocyte cytoplasmic pattern. Results of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling indicated that the lowest apoptosis rate belonged to the melatonin + L-carnitine group. Moreover, the combination groups showed the highest number of oocytes and maturation rate. The BMP-15 and GDF-9 genes were significantly upregulated in all treatment groups compared to the control group. Conclusion: Our results suggested a combination of melatonin + L-carnitine administration as a more effective choice for in vitro promotion of oocyte maturation. [ABSTRACT FROM AUTHOR]

In this experiment, brewer's yeast was used to replace part of the fish meal in the feed to formulate a high-fat and low-protein feed for Taiwan loach. The effects of brewer's yeast on the growth performance, muscle quality, hepatopancreas and pancreas carnitine content, intestinal flora, immunity, and antioxidant ability of Taiwan loach were preliminarily investigated. In experiment 1, 600 Taiwan loaches were randomly divided into 4 groups, and 1% (group A), 4% (group B), 8% (group C), and 12% (group D) of brewer's yeast was substituted for an equal amount of fishmeal in the basal diets. The loaches in each group were fed for 60 d. In experiment 2, 60 Taiwan loaches were selected and randomly divided into a control group (Group E) and a test group (Group F). The loaches were fed the basal diet and the high-fat and low-protein diet supplemented with 8% fishmeal, replaced by brewer's yeast. The experiment lasted for 60 days, and the growth performance, hepatopancreas carnitine content, muscle quality, intestinal flora, plasma antioxidant, and immune capacity indices of loaches in each group were determined. The results were as follows: the weight gain rate and specific growth rate were significantly higher in group C than those in groups A, B, and D (P < 0.05); the intestinal length ratio, muscle hardness, hepatopancreatic carnitine content, plasma superoxide dismutase activity, catalase activity, total antioxidant capacity, and lysozyme activity were significantly greater in group F than those in group E (P < 0.05); the Lactobacillus and Bifidobacterium counts in Group F were considerably higher than those in Group E (P < 0.05), and the Salmonella counts in Group F was significantly lower than that in Group E (P < 0.05); the survival rate, weight gain rate, bait coefficient, muscle crude protein, crude fat, viscosity, elasticity, cohesion, chewability, and restorative capacity were not significantly different between Group F and Group E (P > 0.05). The above results showed that adding 8% brewer's yeast to feed Taiwan loach instead of fish meal could enhance its hepatopancreatic carnitine synthesis, optimize the intestinal flora, improve the body's immune and antioxidant ability, and have a certain promotional effect on the intestinal development and muscle quality improvement. [ABSTRACT FROM AUTHOR]

L-carnitine (LC) through diet is highly beneficial for critical patients. Studies have found that acetyl-L-carnitine (ALC) can reduce cerebral edema and neurological complications in TBI patients. It significantly improves their neurobehavioral and neurocognitive functions. ALC has also been shown to have a neuroprotective effect in cases of global and focal cerebral ischemia. Moreover, it is an effective agent in reducing nephrotoxicity by suppressing downstream mitochondrial fragmentation. LC can reduce the severity of renal ischemia-reperfusion injury, renal cast formation, tubular necrosis, iron accumulation in the tubular epithelium, CK activity, urea levels, Cr levels, and MDA levels and restore the function of enzymes such as SOD, catalase, and GPx. LC can also be administered to patients with hyperammonemia (HA), as it can suppress ammonia levels. It is important to note, however, that LC levels are dysregulated in various conditions such as aging, cirrhosis, cardiomyopathy, malnutrition, sepsis, endocrine disorders, diabetes, trauma, starvation, obesity, and medication interactions. There is limited research on the effects of LC supplementation in critical illnesses such as TBI, AKI, and HA. This scarcity of studies highlights the need for further research in this area. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) represents a prevalent ocular surface disease. The development of effective nutritional management strategies for DED is crucial due to its association with various factors such as inflammation, oxidative stress, deficiencies in polyunsaturated fatty acids (PUFAs), imbalanced PUFA ratios, and vitamin insufficiencies. Extensive research has explored the impact of oral nutritional supplements, varying in composition and dosage, on the symptoms of DED. The main components of these supplements include fish oils (Omega-3 fatty acids), vitamins, trace elements, and phytochemical extracts. Beyond these well-known nutrients, it is necessary to explore whether novel nutrients might contribute to more effective DED management. This review provides a comprehensive update on the therapeutic potential of nutrients and presents new perspectives for combination supplements in DED treatment. [ABSTRACT FROM AUTHOR]

Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by DanioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify l-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathways, improving muscle endurance and swim speed in LMNA(R453W) fish. Transcriptomic profiling reveals upstream regulators and affected genes contributing to motor dysfunction, cardiac anomalies, and ion flux dysregulation in LMNA mutant transgenic fish. These findings faithfully mimic clinical manifestations of muscular laminopathies, including dysmorphism, early mortality, decreased fiber size, and muscle dysfunction in zebrafish. Furthermore, our drug screening results suggest l-carnitine and creatine treatments as potential rescuers of muscle endurance in LMNA(L35P) and LMNA(R453W) zebrafish models. Our study offers valuable insights into the future development of potential treatments for LMNA-related muscular laminopathy. [ABSTRACT FROM AUTHOR]

Myocardial injury in open-heart surgery is related to several factors including ischemia–reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. The aim of this study was to study the effect of L-carnitine on myocardial injury in children undergoing open-heart surgery. This clinical trial was performed on 60 children with congenital heart disease (CHD) who underwent open-heart surgery. They were randomized into two groups: L-carnitine group who received L-carnitine 50 mg\kg\day once daily for 1 month before cardiac surgery and control group who received placebo for 1 month before cardiac surgery. Left ventricular cardiac function was assessed by conventional echocardiography to measure left ventricular ejection fraction (LVEF) and two-dimensional speckle tracking echocardiography (2D-STE) to determine left ventricular global longitudinal strain (2D-LV GLS). Blood samples were obtained pre-operatively at baseline before the administration of L-carnitine or placebo and 12 h post-operatively to measure the level of malondialdehyde (MDA), superoxide dismutase (SOD), fas, caspase-3, creatinine kinase-MB (CK-MB), and troponin I. L-carnitine group had significantly lower post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I), but they had significantly higher SOD post-operative level compared to the control group. In addition, post-operative LVEF and 2D-LVGLS were significantly lower in the control group compared to L-carnitine group. Conclusion: L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery. Trial registration: The clinical trial was registered at www.pactr.org with registration number PACTR202010570607420 at 29/10/2020 before recruiting the patients. What is Known: • Myocardial injury in open-heart surgery is related to several factors including ischemia–reperfusion injury, generation of reactive oxygen species, increased production of inflammatory mediators, and enhancement of apoptosis of cardiomyocytes. • L-carnitine was reported to have myocardial protective effects in rheumatic valvular surgery and coronary artery bypass graft (CABG) in adults; however, there is no evidence on its effectiveness in children undergoing open-heart surgery. What is New: • L-carnitine significantly lowered the post-operative level of oxidative stress marker (MDA), apoptosis markers (fas and caspase-3), and myocardial injury markers (CK-MB and troponin I) in the treatment group. • L-carnitine can reduce myocardial injury, improve post-operative left ventricular cardiac function, and may provide myocardium protection in children with CHD who underwent open-heart surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic kidney disease (CKD) is common in old dogs and cats. Patients with CKD have impaired renal structures and decreased renal function. Because renal degeneration is generally irreversible, treatment of CKD is focused mainly on conserving the remaining renal function. In this study, we retrospectively evaluated the effects of oligo-fucoidan, fucoxanthin, and L-carnitine in canine CKD patients. The supplements were supplied for 6 months and showed a reno-protective effect, consistent with previous animal model studies. Based on our results, the combination of oligo-fucoidan, fucoxanthin, and L-carnitine has the potential to delay the progression of canine CKD and be used as an adjuvant therapy. Chronic kidney disease (CKD) commonly occurs in old dogs and cats. Oligo-fucoidan, fucoxanthin, and L-carnitine (OFL) compounds have a variety of reno-protective properties, including anti-inflammatory, anti-oxidative, and anti-fibrotic effects. Because their effects have not been investigated in naturally occurring canine CKD, we examined their reno-protective activities in dog patients with CKD. A total of 50 patients (OFL, n = 28; control, n = 22) were included in the analysis. A significant difference was identified in serum blood urea nitrogen and creatinine concentrations between the control and OFL groups at 6 months. No significant difference in electrolytes was found between the groups. A significant difference was identified in serum creatinine concentration between the control and OFL groups in azotemic (CKD IRIS stage 2–4) at 6 months. The OFL compounds showed a reno-protective effect, consistent with previous animal studies. The OFL combination can potentially delay the progression of canine CKD and be used as an adjuvant therapy. [ABSTRACT FROM AUTHOR]

Introduction: The torsion of the testis is a surgical emergent situation which is common; however there are no effective measures to avoid damage of the testis after untwisting this torsion. L-carnitine (LC) is an essential micronutrient with strong anti-apoptotic, anti-inflammatory and antioxidant potencies that can reverse oxidative stress induced testicular damage. Aim of the Work: To evaluate the potential protective role of LC against the testicular damage induced by ischemia-reperfusion (IR) injury in rabbits. Materials and Methods: 50 adult male rabbits weighing 1300-1600 g were divided into 5 groups (10 rabbits per group). Acute IR testicular injury was induced in rabbits by twisting the left spermatic cord 720º for 2 h. Group 1: Control group and divided into two subgroups (subgroup A negative control and subgroup B positive control); Group 2: Sham-operated; Group 3: Ischemia group; Group 4: IR group (testicular IR was induced without LC); Group 5: IR+LC testicular IR was induced and LC was given by intra-peritoneal injection at a dose of 500 mg/kg immediately after torsion. At the experimental end, tissue samples of left testes were collected from all rabbits of the five groups and evaluated biochemically and histologically. Results: Ischemia-reperfusion resulted in disturbance of the oxidant/antioxidant status markers, loss of normal architecture of spermatogenic cells, apparent increase in the number of caspase-3 positive spermatogenic cells as well as abnormal fragmented chromatin material in addition to lack of halos around the sperm nuclei. However, the intra-peritoneal administration of LC immediately after torsion significantly improved these changes caused by IR on the testes. Conclusion: Administration of LC reduced the testicular damage induced by the ischemia-reperfusion. [ABSTRACT FROM AUTHOR]

Synthetic organic insecticides such as pyrethroids, organophosphates, neonicotinoids, and others have the potential to disrupt ecosystems and are often toxic to humans. Thiamethoxam (TMX), a neonicotinoid insecticide , is a widely used insecticide with neurotoxic potential. l-Carnitine (LC) is regarded as the "gatekeeper" in charge of allowing long-chain fatty acids into cell mitochondria. LC is an endogenous chemical that is renowned for its prospective biological activity in addition to its role in energy metabolism. This study investigated the protective effects of LC against TMX-induced neurotoxicity in male Wistar rats. For 28 days, animals were divided into four groups and treated daily with either LC (300 mg/kg), TMX (100 mg/kg), or both at the aforementioned doses. Our results revealed marked serum lipid profile and electrolyte changes, declines in brain antioxidants and neurotransmitters (acetylcholine, dopamine, and serotonin levels) with elevations in thiobarbituric acid reactive substances and proinflammatory cytokine levels, as well as acetylcholinesterase and monoamine oxidase brain activity in TMX-treated rats. TMX also increased the expression of caspase-3 and glial fibrillary acidic protein. In contrast, pretreatment with LC attenuated TMX-induced brain injury by suppressing oxidative stress and proinflammatory cytokines and modulating neurotransmitter levels. It also ameliorated the expression of apoptotic and astrogliosis markers. It could be concluded that LC has antioxidant, anti-inflammatory, anti-astrogliosis, and anti-apoptotic potential against TMX neurotoxicity. [ABSTRACT FROM AUTHOR]

Migraine is associated with inflammation and oxidative imbalance. This randomized controlled trial examined the effects of alpha-linolenic acid (ALA) and L-carnitine co-supplementation on inflammatory status and oxidative stress in 80 women with migraine. Serum markers were measured before and after the intervention. Compared to placebo, ALA and L-carnitine co-supplementation significantly reduced nitric oxide (−6.10; 95 % CI (−9.08, −3.12) vs. 1.77; 95 % CI (−3.21, 6.76) nmol/mL, P = 0.038), malondialdehyde (−5.47; 95 % CI (−6.33, −4.62) vs. −0.15; 95 % CI (−0.50, −0.20) nmol/mL, P = 0.011), and C-reactive protein (−0.44; 95 % CI (−0.47, −0.41) vs. −0.02; 95 % CI (−0.05, 0.007) mg/L, P = 0.007) levels. It also increased total antioxidant capacity (185.60; 95 % CI (159.69, 211.50) vs. 5.22; 95 % CI (−29.21, 39.66) nmol/mL, P = 0.045) and superoxide dismutase activity (301.42; 95 % CI (230.63, 372.21) vs. 15.20; 95 % CI (−8.15, 38.55) U/mL, P = 0.009), suggesting potential benefits for migraine management.

Background: Fertility rates are declining globally, and male infertility is increasingly recognized as a significant challenge. This study aims to present the latest findings on the effectiveness and safety of combining traditional Chinese medicine (TCM) with L-carnitine (LC) for treating male infertility. Methods: We searched 8 databases. Randomized controlled trials of TCM combined with LC therapy versus LC alone in the treatment of male infertility. The outcome included: pregnancy rate, sperm motility, concentration, volume, viability and liquefaction time. Subgroup analyses were also performed according to type of TCM, type of dosage form, and different TCM treatments, and the source of the high heterogeneity was explored. The study is registered on PROSPERO (CRD42023421497). Results: 1129 subjects from 12 of the 1833 eligible studies fulfilled the criteria. Compared with LC treatment alone, the combination of TCM and LC significantly improved pregnancy rate [RR = 1.65, 95 % CI (1.37–2.00)], grade (a+b) sperm motility [SMD = 1.56, 95 % CI (1.12, 2.01)], grade (a) sperm motility [SMD = 1.04, 95 % CI (0.69, 1.38)], sperm concentration [SMD = 1.39, 95 % CI (0.91, 1.86)], and sperm viability [SMD = 1.72, 95 % CI (0.83, 2.60)]. Subgroup analyses indicated that Compound Xuanju Capsule and Yougui Capsule demonstrated better efficacy. And the decoction and not-decoction each had their own advantages. Conclusions: The combination of TCM with LC can have a dual effect: increasing pregnancy rates and sperm quality. Therefore, this combination is a recommended therapeutic strategy and a more appropriate type of TCM can be selected according to the patient's own characteristics.