Search

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.

Rotifer are important food resources in aquaculture hatcheries, and several studies have shown that L-carnitine (LC) can promote the growth performance of rotifers. The aim of this study was to investigate the nature of beneficial effects of LC on rotifer Brachionus rotundiformis. The feeding behavior of rotifers were evaluated at different LC concentrations (0, 1, 10 and 100 mg L−1). Meanwhile, the effects of LC on growth performance, free LC content, amino acid and fatty acid composition of rotifers were analyzed. The results indicated that LC (10 and 100 mg L−1) treatments significantly improved the filtration and ingestion rates of rotifers fed microalgae or baker’s yeast, In addition, LC (10 and 100 mg L−1) not only significantly accumulated in rotifers, but also significantly improved the rotifer growth performance. After 48 h of LC treatment, the rotifer population density significantly increased. Concerning the biochemical composition of rotifers, 100 mg L−1 LC can increase the carbohydrates content, decrease the protein and lipid content in the rotifers. And the LC treatment could significantly decrease the total SFA content of rotifers, while significantly increase the total HUFA content of rotifers. Moreover, the levels of LC supplementation were positively correlated with the contents of Thr, Gly, Ala, Leu, Tyr, Phe, Lys, His, Arg and Pro in rotifers. Overall, adding LC could not only accumulate in rotifers, but also promote the growth performance of rotifers by improving their feeding behavior and their nutritional value.

An 11-month-old girl with severe acidosis, lethargy and vomiting, was diagnosed with holocarboxylase synthetase deficiency. She received biotin and was stable until age 8 years when vomiting, severe acidosis, hypoglycemia, and hyperammonemia developed. Management with intravenous glucose aiming to stimulate anabolism led to hyperglycemic ketoacidosis. Insulin therapy rapidly corrected biochemical parameters, and clinical status improved. We propose that secondary Krebs cycle disturbances affecting pancreatic beta cells impaired glucose-stimulated insulin secretion, resulting in insulinopenia.

ABSTRACT: The current study was conducted to examine the effect of l-carnitine (LC) supplementation on telomere length and mitochondrial DNA copy number (mtDNAcn) per cell in mid-lactation cows challenged by lipopolysaccharide (LPS) in blood and liver. The mRNA abundance of 31 genes related to inflammation, oxidative stress, and the corresponding stress response mechanisms, the mitochondrial quality control and the protein import system, as well as the phosphatidylinositol 3-kinase/protein kinase B pathway, were assessed using microfluidics integrated fluidic circuit chips (96.96 dynamic arrays). In addition to comparing the responses in cows with or without LC, our objectives were to characterize the oxidative and inflammatory status by assessing the circulating concentration of lactoferrin (Lf), haptoglobin (Hp), fibrinogen, derivates of reactive oxygen metabolites (dROM), and arylesterase activity (AEA), and to extend the measurement of Lf and Hp to milk. Pluriparous Holstein cows were assigned to either a control group (CON, n = 26) or an LC-supplemented group (CAR; 25 g LC/cow per day; d 42 ante partum to d 126 postpartum (PP), n = 27). On d 111 PP, each cow was injected intravenously with LPS (Escherichia coli O111:B4, 0.5 µg/kg). The mRNA abundance was examined in liver biopsies of d −11 and +1 relative to LPS administration. Plasma and milk samples were frequently collected before and after the challenge. After LPS administration, circulating plasma fibrinogen and serum dROM concentrations increased, whereas AEA decreased. Moreover, serum P4 initially increased by 3 h after LPS administration and declined thereafter irrespective of grouping. The Lf concentrations increased in both groups after LPS administration, with the CAR group showing greater concentrations in serum and milk than the CON group. After LPS administration, telomere length in blood increased, whereas mtDNAcn per cell decreased; however, both remained unaffected in liver. For mitochondrial protein import genes, the hepatic mRNA abundance of the translocase of the mitochondrial inner membrane (TIM)-17B was increased in CAR cows. Moreover, TIM23 increased in both groups after LPS administration. Regarding the mRNA abundance of genes related to stress response mechanisms, 7 out of 14 genes showed group × time interactions, indicating a (local) protective effect due to the dietary LC supplementation against oxidative stress in mid-lactating dairy cows. For mtDNAcn and telomere length, the effects of the LPS-induced inflammation were more pronounced than the dietary supplementation of LC. Dietary LC supplementation affected the response to LPS primarily by altering mitochondrial dynamics. Regarding mRNA abundance of genes related to the mitochondrial protein import system, the inner mitochondrial membrane translocase (TIM complex) seemed to be more sensitive to dietary LC than the outer mitochondrial membrane translocase (TOM complex).

Breast cancer stem cells (BCSCs) are a small subpopulation of breast cancer cells, capable of metastasis, recurrence, and drug resistance in breast cancer patients. Therefore, targeting BCSCs appears to be a promising strategy for the treatment and prevention of breast cancer metastasis. Mounting evidence supports the fact that carnitine, a potent antioxidant, modulates various mechanisms by enhancing cellular respiration, inducing apoptosis, and reducing proliferation and inflammatory responses in tumor cells. The objective of this study was to investigate the impact of L-carnitine (LC) on the rate of proliferation and induction of apoptosis in CD44+ CSCs. To achieve this, the CD44+ cells were enriched using the Magnetic-activated cell sorting (MACS) isolation method, followed by treatment with LC at various concentrations. Flow cytometry analysis was used to determine cell apoptosis and proliferation, and western blotting was performed to detect the expression levels of proteins. Treatment with LC resulted in a significant decrease in the levels of p-JAK2, p-STAT3, Leptin receptor, and components of the leptin pathway. Moreover, CD44+ CSCs-treated cells with LC exhibited a reduction in the proliferation rate, accompanied by an increase in the percentage of apoptotic cells. Hence, it was concluded that LC could potentially influence the proliferation and apoptosis of CD44+ CSC by modulating the expression levels of specific protein.

The aim of this study was to evaluate the effect of l-carnitine (L-CAR) treatment on isoprenaline (ISO) administered kidney and heart impairment in male Long Evans rats. Four groups of rats were engaged in this study such as control, ISO, control + L-CAR, and ISO + L-CAR, where n = 6 in each group. The rats were also provided with chow food and water ad libitum. At the end of the study, all rats were sacrificed, and blood and tissue samples were collected for bio-chemical analysis. Oxidative stress parameters and antioxidant enzyme activities were determined in plasma and tissues. Antioxidant and inflammatory genes expression were analyzed in the kidney cortex, and histopathological studies of kidney tissues were performed. This study showed that creatinine and uric acid in plasma were significantly increased in ISO-administered rats. l-carnitine treatment lowered the uric acid and creatinine level. ISO-administered rats showed increased lipid peroxidation and declined levels of antioxidant enzymes activities in kidneys and heart. l-carnitine treatment restored antioxidant enzymes activities and protect against oxidative stress in kidney and heart. This effect is correlated with the restoration of Nrf-2-HO-1 genes expression followed by increased SOD and catalase genes expression in the kidney. l-carnitine treatment also prevented the TNF-α, IL-6, and NF-кB expression in kidneys of ISO administered rats. Histopathology staining showed that l-carnitine treatment prevented kidney damage and collagen deposition in ISO administered rats. The result of this study exhibited that l-carnitine treatment reduced oxidative stress and increased antioxidant enzyme activities by enhancing antioxidant genes expression in ISO administered rats.

Background: Coronavirus disease 2019 (COVID-19) still remains a pandemic accounting for at least 15% of intensive care unit (ICU) admissions. Recently, it has been observed that l-carnitine levels, which play an important role in fatty acid metabolism, have an inverse association with the severity of COVID-19 and its complications, hence a potential role for supplementing with this nutraceutical has been suggested. The current protocol describes a trial aiming to an evaluation of the effect of l-carnitine intervention on mortality and clinical outcomes in ICU-admitted patients with COVID-19. Methods: This parallel-group, randomized, placebo-controlled, and double-blind clinical trial involves 50 participants and will be performed at the ICU of Artesh (AJA) Hospital, Mashhad, IRAN. Eligible participants will be randomized into two groups: 1) the intervention group will receive 1000 mg l-carnitine capsules 3 times a day, and 2) the placebo group will receive 1000 mg placebo capsules 3 times a day. Assessments will be performed at baseline, 7 and 28 days after study initiation. The primary outcome includes changes in serum levels of C-reactive protein (CRP). Secondary outcomes include the length of stay in the ICU, ICU mortality, hospital mortality, 28-day mortality, duration of mechanical ventilation (MV), and the neutrophil-lymphocyte ratio (NLR). Conclusion: Based on previous evidence, l-carnitine may reduce inflammation and oxidation stress and improve respiratory function. However, the effects of l-carnitine on ventilator-dependent COVID-19 critically ill patients have not been assessed yet, justifying the necessity to conduct a clinical study in this field. c

Introduction: L-carnitine possibly impacts insulin sensitivity and glucose metabolism. However, its therapeutic role in diabetes is poorly understood. Methods: A systematic review and meta-analysis were conducted using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception through June 30, 2021. Included studies evaluated the use of L-carnitine in diabetes on fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), weight, or body mass index (BMI). Weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated using the DerSimonian and Laird random-effects model. Results: Seventeen studies involving 1622 patients were included. Reductions in FBG (WMD = -0.46 mmol/L, 95% CI = -0.68 to -0.23 mmol/L), HbA1c (WMD = -0.5%, 95% CI = -0.8 to -0.1%), TC (WMD = -0.29 mmol/L, 95% CI = -0.42 to -0.16 mmol/L), and LDL-C (WMD = -0.23 mmol/L, 95% CI = -0.39 to -0.07 mmol/L) were significant. Effects on HDL-C, TG, weight, or BMI were insignificant. Doses between 1001 to 2000 mg showed greatest benefit (p

ABSTRACT: The purpose of this study was to investigate the production performance, antioxidant parameters, egg yolk cholesterol content, and expression of genes related to cholesterol metabolism in laying hens fed L-carnitine (LC) and L-carnitine-loaded solid lipid nanoparticles (LC-SLNs). A total of 350 Hy-Line (w-36) laying hens at 50 wk of age (1520.0 ± 0.7 g) were randomly assigned to 35 units (5 replicates and 50 hens in each treatment) with seven dietary treatments as a completely randomized design. The dietary treatments were corn-soybean meal-based diets, including 1) Control (basal diet); 2) Basal diet +50 mg/kg LC (50LC); 3) Basal diet +100 mg/kg LC (100LC); 4) Basal diet +150 mg/kg LC (150LC); 5) Basal diet +50 mg/kg LC-SLNs (50LC-SLNs); 6) Basal diet +100 mg/kg LC-SLNs (100LC-SLNs) and 7) Basal diet +150 mg/kg LC-SLNs (150LC-SLNs). Results showed that the 50LC-SLNs had the least feed conversion ratio (FCR) in all groups (P < 0.05). The dietary supplementation of 100LC-SLNs decreased (P < 0.01) the egg yolk cholesterol concentration from 14.71 to 11.76 mg/g yolk (25%). The 50LC-SLNs group produced the most total antioxidant capacity with a difference of 58.44% compared to the control group (P < 0.01). The greatest amount of total superoxide dismutase was found for 50LC-SLNs (P < 0.05), while the glutathione peroxidase was not affected by the experimental treatments (P > 0.05). Serum malondialdehyde levels were reduced by 50.52% in laying hens fed 50LC-SLNs compared to the control group (P < 0.05). The transcript level of 3-hydroxy-3-methylglutaryl coenzyme A reductase was significantly decreased (P < 0.01) in the LC and LC-SLNs groups. The expression of cholesterol 7α-hydroxylase was significantly increased (P < 0.01) in the plain LC (∼83%) and LC-SLNs (∼91%) groups. The inclusion of LC-SLNs in the diet increased (P < 0.05) the villus height and decreased villus width in all three parts of the small intestine. Dietary inclusion of LC was found to reduce egg yolk and serum cholesterol content by improving the production performance and antioxidant status. The LC-SLNs groups were more affected than the plain LC groups, which may be attributed to the increased bioavailability of LC.

Background: 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., Methods: Sanger sequencing was used to detect and genetically analyze the MLYCD variations in the preexisting patients and their parents., Results: 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., Conclusion: 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

ABSTRACT: In this study, different levels of Omega-3 fatty acids and L-carnitine (LC) were used in diets for laying hens. The effects of these supplements were examined on productive performance, antioxidant properties, cholesterol content, and yolk fatty acid profiles in the laying hens. A population of 120 Lohmann LSL-Lite laying hens (34-wk-old) were used in 2 × 3 factorial arrangements with 2 diets (control = 0.031 and 0.48% omega-3 fatty acids) and 3 levels of L-carnitine (0, 100, 200 mg/kg of diet) in a completely randomized design with 6 treatments. While having 5 replicates and 4 birds per replicate, the total period of the experiment lasted for 10 wk. The eggs were weighed daily, parallel to measurements of egg production, daily feed intake, feed conversion ratio, and egg mass. When the hens reached 44 wk of age, the measurements were aimed at fatty acid profiles, malondialdehyde (MDA), and cholesterol concentration in egg yolk. Feeding the hens on diets enriched by omega-3 fatty acids led to higher levels of egg production than those fed on control diets, but their daily feed intake was generally lower (P < 0.05). Egg weight decreased in birds that were fed on diets enriched with omega-3 fatty acids without L-carnitine, or with diets which contained 100 mg/kg L-carnitine, compared to control diets which contained 0 mg/kg L-carnitine (P < 0.05). Egg mass increased in birds that were fed on diets enriched with omega-3 fatty acids and which contained 200 mg/kg L-carnitine, compared to the control diet with 0 or 100 mg/kg L-carnitine (P < 0.05). The analysis of fatty acid profiles showed that L-carnitine and omega-3 fatty acids caused a significant increase in the percentage of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), C18: 1 (n-9), arachidonic acid (ARA) C20: 4 (n-6), and Σ n-3 in the eggs of birds (P < 0.05). Based on the results, adding L-carnitine (200 mg/kg) to diets that were already enriched with omega-3 fatty acids increased the level of production and led to a longer maintenance of fatty acids in the eggs. Also, oxidative stability was enhanced in the yolk of eggs.

The current study aimed to discover more effective drugs to treat osteoporosis (OP) with fewer side effects. OP was induced in 24 rats using dexamethasone (DEX) 7 mg/kg intramuscular once weekly for four weeks, with six rats as a negative control. The osteoporotic rats were divided into one untreated group (positive control) and three treated groups (n = 6) that received L-carnitine (L-Car) (100 mg/kg/d), simvastatin (SIMV) (10 mg/kg/d), and L-Car + SIMV in the same previous doses, all treatments were orally for four weeks. At the end of the experiment, serum calcium (Ca), phosphorous (P), alkaline phosphatase (ALP), osteoprotegerin (OPG), total antioxidant (TAO), creatine kinase (CK), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were measured. The femur was histopathologically examined. Serum Ca, OPG, and TAO levels increased significantly, while P and ALP levels decreased in the L-Car and SIMV treated groups compared to the DEX-treated group. Moreover, there was a significant decrease in CK, ALT, and AST levels in the L-Car and L-Car + SIMV treated groups compared to the DEX treated group. Conclusions: L-Car and SIMV have antiosteoporotic effects, as well as a synergistic effect. Moreover, L-Car ameliorates SIMV-induced myotoxicity and hepatoxicity.

In recent years, the dramatically high lipid level has been used in fish feeds, resulting in low survival rates of fish and huge economic losses. Based on these issues, a six-week feeding experiment was conducted to investigate whether diet supplements with L-carnitine can be used to relieve detrimental impacts on growth performance, hepatic lipid accumulation, antioxidant, anti-inflammatory and non-specific immune status, as well as intestinal morphology of Trachinotus ovatus, fed on a high-fat diet. Three isonitrogenous diets were formulated to either include or exclude high-fat and L-carnitine (lipid positive (LP): 130 g kg−1 lipid, lipid negative (LN): 210 g kg−1 lipid, lipid negative with L-carnitine (LNC): 210 g kg−1 lipid with 0.6 g kg−1 L-carnitine). Results indicated that the growth performance and mid-intestine villi length of T. ovatus in the LN group were significantly lower than that of the LP group (p 0.05) and significantly higher levels in the LNC group (p 0.05). In conclusion, L-carnitine can relieve the detrimental impact on growth performance of T. ovatus exposed to a high-fat diet treatment by reducing hepatic lipid accumulation and improving intestinal morphology, anti-inflammatory and non-specific immune status, but could not mitigate oxidative pressure.

This study was to compare study on the effects of supplemental L-carnitine on fatty acids composition, energy status and related genes expression in Cyprinus carpio var. Jian and Rhynchocypris lagowskii. Different concentrations of L-carnitine were added to the basal diets of two species of fish, in which Cyprinus carpio were supplemented with 0, 50 (LC), 200 (AC) and 800 (HC) mg/kg, and Rhynchocypris lagowskii were supplemented at 0, 200 (LC), 400 (AC) and 800 (HC) mg/kg, respectively, for 8 weeks. Results showed that in liver of AC group on C. carpio, the changes of HUFA and ∑DHA+EPA showed a significant downward trend, while the changes of PUFA, EFA and ∑n3 + n6 showed an upward trend. The above trend in liver of the AC group on R. lagowskii was opposite to C. carpio. With the exception of HUFA, the changes of fatty acids of AC group in muscles of the two fish were completely different. The content of ATP and AMP in liver and muscle in AC and HC groups of two fish species showed a decreasing trend, while the change trend of ADP content was opposite. AMP/ATP ratio in liver and muscle showed a trend of first increasing and then decreasing in the treatment groups of two fish species. The relative gene expression levels of AMPKα1, AMPKα2, ACC2 and CPT-I of liver and muscle in treatment groups of C. carpio showed a decreasing trend, while these values showed an opposite trend in liver of R. lagowskii. Consequently, the different fish species may be the main reason that affects the regulation of fatty acid metabolism by exogenous L-carnitine. In addition, AMPK, acting as an energy receptor is a key effector in regulation of fatty acids metabolism by L-carnitine. Further study of AMPK function in fatty acids metabolism of fish is thus warranted.

This study investigated the effect of solid-state fermentation of wild turmeric (Curcuma aromatica) with Rhizopus oligosporus, a common fungus found in fermented soy tempeh, on phytochemical and biological properties. Ultra-performance liquid chromatography–tandem mass spectrometry showed that fermented wild turmeric has higher concentrations of curcumin, demethoxycurcumin, bisdemethoxycurcumin, phenolic compounds and total flavonoid-curcuminoid after fermentation for 1-, 3-, and 5-day relative to non-fermented turmeric. The l-carnitine content reached 242 µg g−1 extract after fermentation for 7-day. Wild turmeric had 1.47- and 2.25-fold increases in ORAC and FRAP, respectively, after 3-day fermentation. The inhibitory effects of fermented wild turmeric on lipid accumulation from 3T3-L1 cells, nitric oxide production from lipopolysaccharide-stimulated RAW264.7 murine macrophages, and melanin formation by B16F10 mouse melanoma cells with α-MSH increased 1.08-, 1.44-, and 1.52-fold, respectively, after 3-day fermentation. Based on these results, fermented wild turmeric product can be used as a functional ingredient in the cosmeceutical and nutraceutical industries.

l-carnitine (LC) transports fatty acids to the mitochondria for energy production, reducing lipid availability for peroxidation through β-oxidation. This research examines the effect of LC supplementation to two skimmed milk-based extenders on the cryosurvival of chilled (5°C) and frozen-thawed Peruvian Paso horse spermatozoa .An initial experiment determined the optimal LC concentration (0, 1, 5, 10, 25, and 50 mM) when added to INRA-96® and UHT (skimmed milk + 6% egg yolk) extenders, using nine ejaculates from three stallions chilled for up to 96 h. Subsequently, the effect of 25 mM LC supplementation (the optimal concentration) on chilling (INRA-96) and freezing (INRA-Freeze®) extenders was evaluated using eight pooled samples from sixteen ejaculates (2 ejaculates/pool) from four stallions. Results indicated that all LC concentrations produced significantly higher values (P<0.05) for kinematic variables (total [TM] and progressive motilities, curvilinear [VCL] and straight-line [VSL] velocity, and beat-cross frequency [BCF]), and the integrity of plasma/acrosome membranes (IPIA) compared to non-supplemented chilled sperm samples for up to 96 h with both extenders. Moreover, the use of 25 mM LC was more efficient (P<0.05) in preserving the post-chilled values of velocity, BCF, and IPIA for the long term than lower LC concentrations (1-10 mM). Post-thaw values of total motility, the amplitude of lateral head displacement (ALH), and IPIA were significantly improved (P<0.05) when INRA-Freeze extender was supplemented with 25 mM LC. In conclusion, supplementation of l-carnitine to skimmed milk-based extenders enhanced kinematic variables and protected the membrane integrity in chilled and frozen-thawed Peruvian Paso horse spermatozoa., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest to declare., (Copyright © 2024 Society for Cryobiology. Published by Elsevier Inc. All rights reserved.)

Brief introduction: Myocardial infarction (MI) is a common manifestation of certain cardiac diseases where oxidative stress and fibrosis aggravate the condition markedly. Main objective of the study: Investigation of L-carnitine’s cardioprotective roles and mechanism of action in a rat model of MI. Methods: To develop a MI animal model, Isoproterenol (ISO) was administered in male Long Evans rats where animals were divided into five groups (six rats/group). The oxidative stress and antioxidant enzyme activities were determined by different biochemical tests. The real-time PCR was performed to determine the expression of TNF-α and Il-1β. Histopathological observations by hematoxylin-eosin and Masson trichrome were made to observe the tissue damage and fibrosis in heart and kidney. Significant findings from the study: The ISO-treated rats showed increased levels of troponin I and lipid peroxidation and lower antioxidant enzyme activity in heart and kidney tissues. The levels of TNF-α and IL-1β were also increased in ISO-rats. Co-administration of L-carnitine with ISO reversed all these parameters. The elevated levels of uric acid and creatinine kinase and ALP, AST and ALT activities in ISO-rats were also significantly reduced by L-carnitine administration. L-carnitine markedly decreased the infiltration of inflammatory cells and improved the tissue architecture in heart and kidney. Control animals did not show any appreciable response upon L-carnitine administration. Relevant contribution to knowledge: These results suggest that L-carnitine plays a defensive role against cardiac and renal damage in ISO-treated MI rat model via suppressing oxidative stress and increasing antioxidant enzyme functions through inhibition of TNF-α and IL-1β.

Obesity is increasing rapidly across the globe. It is widely accepted that natural products with a long safety background may modulate obesity. The current work aimed to investigate the effect of Nigella sativa, atorvastatin, or L-Carnitine on high-fat diet-induced obesity in white male albino rats. A regular basal diet was fed to 7 rats, and a high-fat diet (HFD) was fed to 24 rats throughout the study for 12 weeks. The HFD group was split equally into four subgroups, each containing six rats. The first group fed on HFD with no medication, the second group received HFD+ Nigella sativa, the third group received HFD+ atorvastatin, and the fourth group received HFD+L-carnitine. At the beginning of the seventh week (the start of the treatment regimen), Nigella sativa, atorvastatin, or L-Carnitine were administered for six weeks. Glucose, body weight, serum atherogenic index (AI), ALT, and AST activities were analyzed. The pathological alterations in the hepatic tissues were examined microscopically and scored. The results revealed that the HFD diet significantly increased the final body weight, serum AI, and serum levels of liver enzymes. Treatment with L-carnitine or Nigella sativa significantly normalized the lipid profile and decreased the final body weight, serum AI, and Serum ALT. Histopathological examination of the liver of HFD received rats showed features of steatosis, which were mitigated by the administration of Nigella sativa or L-Carnitine, while atorvastatin had no significant effect on the improvement of hepatic lesions. Collectively, study findings showed that Nigella sativa or L-Carnitine has mitigated effects on metabolic and histopathological changes in the liver tissues of rats fed with HFD.

Rotifer Brachionus rotundiformis is the first live food for larval fish that can generally be plagued by ammonia (AC) in intensive culture systems. Ammonia accumulates enough to cause rotifer death. L-carnitine (LC) as a supplement of a vitamin-like nutrient can ameliorate rotifer growth performance and reproduction. The present study investigated the effects of LC on growth performance, antioxidant enzymatic activity, bacterial numbers and eradication of AC toxicity in rotifer. During a 7-day culture experiment added different concentration LC, Acute toxicity tests of AC and a batch culture experiment treated with LC and AC were performed. The results indicated that suitable LC concentration (1−100 mgL−1) treatment promoted significantly the rotifer population growth, while the AC was opposite and the AC median lethal concentration (LC50)-24 h was 12.24 mg L-1. Batch culture results showed that, under AC stress, LC significantly increased the rotifer population density and egg rate, and reduced rotifer malondialdehyde (MDA) level, increased rotifer Superoxide dismutase (SOD), Catalase (CAT), glutathione peroxidase (GPx) and total antioxidant capacity (T-AOC) activities. For the bacterial numbers, all treatments presented an increasing trend during the culture period, and there was a significant correlation with the rotifer population density especially in the group LC + AC. Overall, our results indicate that the rotifer growth can be inhibited by the AC, and under AC stress, LC can also improve the population growth, anti-stress ability of rotifer and the bacterial numbers in the medium. The amelioration of rotifer-growth may be linked to the anti-stress ability and the bacterial numbers.

The activation of the Nrf2/HO-1 signaling pathway regulates cellular antioxidant stress and exerts anti-inflammatory and cytoprotective effects against acute lung injury (ALI). The present study aimed to evaluate the therapeutic role of L-carnitine (LC) against potassium dichromate (PD) - induced acute lung injury in adult male albino rats via modulation of Nrf2/HO-1 signaling pathway. For this purpose, forty rats were randomly allocated into 5 groups (8 rats each). The normal group received intranasal (i.n.) saline, while the ALI group received intranasal instillation of PD as a single dose of 2 mg/kg. The 3d – 5th groups received PD then after 24 h administered L-carnitine (25, 50 and 100 mg/kg; orally) for 3 consecutive days. The therapeutic effect of L-carnitine was evaluated by assessment of serum levels of glutathione (GSH) and malondialdehyde (MDA) along with measurement of lung contents of transforming growth factor β1 (TGFβ1), protein kinase B (AKT), Nuclear factor erythroid-2 related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 enzyme (NQO1) and glutathione cysteine ligase modifier subunit (GCLM) expression. Post-treatment with L-carnitine effectively increased the levels of GSH and AKT, elevated Nrf2 and its target genes and decreased the levels of MDA and TGFβ1 in comparison with PD control rats. Additionally, L-carnitine effectively reduced the number of goblet cell, inhibited the mucus formation in bronchioles and interstitial inflammatory infiltrate as well as alleviated the destruction of alveolar walls, and the congestion of blood vessels in lung tissue induced by PD. Our findings showed that L-carnitine may be a promising therapeutic agent against PD-induced acute lung injury.

The aim of current study was to investigate the effect of dietary L-Carnitine (LC) in immature roosters on reproductive hormones, lipid profile and testicular histology at the time of maturity. Eighteen 12-wk-old breeder roosters (Ross 308) of similar weights were randomly allocated into 3 dietary treatments (LC-0: basic diet, LC-250: basic diet + 250 mg LC/kg of diet, LC-500: basic diet + 500 mg of LC/kg of diet) in 6 replicates. The feeding program and photoperiod regimen were performed based on ROSS 308 management handbook. Dietary LC supplementation markedly improved testicle weight and testicle index (p < 0.05). Comb height was also affected by LC supplementation (p < 0.05). The testicle weight and index, comb height, and shank lengths improved linearly with increasing levels of dietary LC (p < 0.05). The LC-250 and LC-500 diets significantly improved the number of sertoli cells (NSC), height epithelium seminiferous tubules (HEST), seminiferous tubules diameter (STD), spermiogenesis index (SI) and tubular differentiation index (TDI) of rooster's testis tissue (p < 0.05). The number of seminiferous tubules (NST) was affected by of the amount of LC (p < 0.05). The roosters on the LC-250 mg/kg diet had longer HEST compared to roosters that received the LC-500 mg/kg diet (p < 0.05). Testicular histology parameters increased in a linear and quadratic manner in response to increasing levels of LC (p < 0.05). Dietary LC significantly increased (p < 0.05) plasma concentrations of testosterone, GnRH, LH, FSH and High-Density Lipoprotein (HDL), but reduced the plasma concentration of Low-Density Lipoprotein (LDL). However, no significant differences were observed between LC-250 and LC-500 groups in these parameters. Plasma testosterone, GnRH, LH, LDL and HDL were affected in a linear and quadratic manner in response to increasing levels of LC (p < 0.05). Similarly, FSH increased linearly with increasing dietary LC (p < 0.05). Thus, adding up to 250 mg of LC per kg of diet of the rooster chicken can improve reproductive hormones, blood lipids and testicular histology parameters at the time of maturity.

Branched-chain amino acids (BCAA) reverse malnutrition and l-carnitine leads to the reduction of hyperammonemia and muscle cramps in cirrhotic patients. BCAA and l-carnitine are involved in glucose and fatty acid metabolism, however their mechanistic activity in cirrhotic liver is not fully understood. We aim to define the molecular mechanism(s) and combined effects of BCAA and l-carnitine using a cirrhotic rat model. Rats were administered carbon tetrachloride for 10 weeks to induce cirrhosis. During the last 6 weeks of administration, cirrhotic rats received BCAA, l-carnitine or a combination of BCAA and l-carnitine daily via gavage. We found that BCAA and l-carnitine treatments significantly improved hepatocellular function associated with reduced triglyceride level, lipid deposition and adipophilin expression, in cirrhotic liver. Lipidomic analysis revealed dynamic changes in hepatic lipid composition by BCAA and l-carnitine administrations. BCAA and l-carnitine globally increased molecular species of phosphatidylcholine. Liver triacylglycerol and phosphatidylcholine hydroperoxides were significantly decreased by BCAA and l-carnitine. Furthermore, serum and liver ATP levels were significantly increased in all treatments, which were attributed to the elevation of mature cardiolipins and mitochondrial component gene expressions. Finally, BCAA and l-carnitine dramatically reduced hepatocellular death. In conclusion, BCAA and l-carnitine treatments attenuate hepatocellular damage through the reduction of lipid peroxides and the overall maintenance of mitochondrial integrity within the cirrhotic liver. These effectiveness of BCAA and l-carnitine support the therapeutic strategies in human chronic liver diseases.

Background: Severe acute malnutrition (SAM) is a major public health concern among low- and middle-income countries, where the majority of the children encountering this acute form of malnutrition suffer from environmental enteric dysfunction (EED). However, evidence regarding the effects of L-carnitine supplementation on the rate of weight gain and EED biomarkers in malnourished children is limited., Objectives: We aimed to investigate the role of L-carnitine supplementation on the rate of weight gain, duration of hospital stays, and EED biomarkers among children with SAM., Methods: A prospective, double-blind, placebo-controlled, randomized clinical trial was conducted at the Nutritional Rehabilitation Unit (NRU) of Dhaka Hospital, International Centre for Diarrheal Disease Research, Bangladesh. Children with SAM aged 9-24 mo were randomly assigned to receive commercial L-carnitine syrup (100 mg/kg/d) or placebo for 15 d in addition to standard of care. A total of 98 children with Weight-for-Length-z-score (WLZ) < -3 Standard deviation were enrolled between October 2021 and March 2023. Analyses were conducted on an intention-to-treat basis., Results: The primary outcome variable, "rate of weight gain," was comparable between L-carnitine and placebo groups (2.09 ± 2.23 compared with 2.07 ± 2.70; P = 0.973), which was consistent even after adjusting for potential covariates (age, sex, Weight-for-Age z-score, asset index, and WASH practices) through linear regression [ß: 0.37; 95% confidence interval (CI): -0.63,1.37; P = 0.465]. The average hospital stay was ∼4 d. The results of adjusted median regression showed that following intervention, there was no significant difference in the EED biomarkers among the treatment arms; Myeloperoxidase (ng/mL) [ß: -1342.29; 95% CI: -2817.35, 132.77; P = 0.074], Neopterin (nmol/L) [ß: -153.33; 95% CI: -556.58, 249.91; P = 0.452], alpha-1-antitrypsin (mg/mL) [ß: 0.05; 95% CI: -0.15, 0.25; P = 0.627]. Initial L-carnitine (μmol/L) levels (median, interquartile range) for L-carnitine compared with placebo were 54.84 (36.0, 112.9) and 59.74 (45.7, 96.0), whereas levels after intervention were 102.05 (60.9, 182.1) and 105.02 (73.1, 203.7)., Conclusions: Although our study findings suggest that L-carnitine bears no additional effect on SAM, we recommend clinical trials with a longer duration of supplementation, possibly with other combinations of interventions, to investigate further into this topic of interest. This trial was registered at clinicaltrials.gov as NCT05083637., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Mitochondrial trifunctional protein (TFP) deficiency is a rare inherited metabolic disorder caused by defects in fatty acid β-oxidation (FAO) of long-chain fatty acids, leading to impaired energy production. Fasting avoidance, fatty acid-restricted diets, and supplementation with medium-chain triglycerides are recommended as a treatment, but there are no pharmaceutical treatments available with strong evidence of efficacy. Bezafibrate, which enhances the transcription of FAO enzymes, is a promising therapeutic option for FAO disorders (FAODs). The effectiveness of bezafibrate for FAODs has been reported in some clinical trials, but few clinical studies have investigated its in vivo efficacy toward TFP deficiency.Herein, we describe two Japanese patients with TFP deficiency. Patient 1 presented with recurrent myalgia since the age of 5 years. Laboratory findings showed increased serum levels of long-chain fatty acids and reduced expression of TFPα and TFPβ in his skin fibroblasts. Based on these findings, he was diagnosed with the myopathic type of TFP deficiency. Patient 2 suddenly exhibited cardiopulmonary arrest one day after birth. Elevated levels of creatine kinase and long-chain acylcarnitines were observed. Genetic analysis identified compound heterozygous variants in HADHB (c.1175C>T/c.1364T>G). He was diagnosed with the lethal type of TFP deficiency. Although both patients were treated with dietary therapy and l-carnitine supplementation, they experienced frequent myopathic attacks associated with respiratory infections and exercise. After the initiation of bezafibrate, their myopathic manifestations were markedly reduced, leading to an improvement in quality of life without any side effects.Our clinical findings indicate that bezafibrate combined with other treatments such as dietary therapy may be effective in improving myopathic manifestations in TFP deficiency.

High nutritive microalgae is a key factor that affecting the live feeds nutritional value and subsequently fish fry quality. We evaluated the effect of l-carnitine supplementation level on the population growth, photosynthetic pigment biosynthesis, and antioxidant capability of the pigment-protein complexes in the marine Chlorella sp. Five different l-carnitine levels (0, 5, 50, 100, and 200 mg L−1) were supplemented in the microalgae media for 10 days. The results demonstrated that l-carnitine increased the population density and specific growth rate in LC 5 (P < 0.05). While the β-carotene and iron contents were elevated in LC 5 and LC 50 (P < 0.05). Apart from, chlorophyll a, chlorophyll b, and magnesium contents were higher in the LC 5 (P < 0.05). While LC 5 had higher metal chelation in pigment-protein complexes (P < 0.05). Meanwhile, psy and chld gene expressions were up-regulated in the LC 5 and LC 50 (P < 0.05). Taken together, LC 5 and LC 50 could improve the population growth, pigment synthesis, antioxidant capacity and up-regulate the relative expression levels of photosynthetic pigment synthesis genes in marine Chlorella sp. Therefore, l-carnitine has comprehensive effects on algae production.

L-carnitine is a functional aquafeed additive for enhancing lipid catabolism by elevating mitochondrial fatty acid β-oxidation and modulating energy metabolism to provide a “protein sparing effect”. However, results on the effects of dietary l-carnitine on nutrient metabolism in fish are still conflicting. We explored comprehensively the effects of dietary l-carnitine on energy metabolism in Nile tilapia. We fed Nile tilapia for eight weeks with diets supplemented with l-carnitine or not. We conducted metabolic tracking tests by intraperitoneally injecting individual fish with 14C-labeled palmitic acid (PA), glucose (Glu) and an amino acid mixture (AAs). After the feeding trial, insignificant growth-promoting effect of l-carnitine was obtained in treated fish. However, l-carnitine significantly reduced the lipid content in whole body and muscle accompanied by increasing the free carnitine concentration and fatty acid β-oxidation efficiency. Moreover, l-carnitine elevated concentrations of serum glucose, pyruvate and lactate, and increased glycogen and protein deposition in muscle. These results suggest that ingested glucose and protein prefer to be reserved in carnitine-fed fish with sufficient fatty acids oxidation for energy. Nevertheless, after a 14C-labeled single nutrient injection, carnitine-fed fish showed a higher oxidation rate of [1-14C]-PA, d-[1-14C]-Glu and l-[14C (U)]-AAs. Our study indicates that, the effects of l-carnitine on nutrient metabolism are correlated with the abundance of individual macronutrients such that an inadequate lipid supply would cause dietary l-carnitine supplementation to elevate higher breakdown of glucose and protein for energy generation. The present study provides new insights on the regulation mechanism of l-carnitine on nutrient metabolism in fish.

KAATSU training at greatly reduced intensities has been proven to result in substantial increases in both muscle hypertrophy and strength. Nevertheless, this revolutionary training method (combined with the restriction of venous blood flow from the working muscle) may cause underlying hypoxia and neurotransmitter dysfunction, which are linked to neuromuscular fatigue. Hence, an exploration of KAATSU training-induced hypoxic and neurodegenerative events is of utmost importance before promoting this training mode, although KAATSU has been shown to result in numerous positive training adaptations. Furthermore, based on substantial evidence, L-carnitine supplementation exerts neuroprotective effects by attenuating hypoxic stress and neurotransmitter dysfunction. However, studies directly examining the effects of KAATSU exercise on both hypoxia and neurotransmitter dysfunction, which would aggravate the detrimental effects of neuromuscular fatigue, are lacking. In addition, an expansion of the applications of L-carnitine to a smaller-molecule field for treating KAATSU training-evoked neuromuscular fatigue requires further clarification. Therefore, this review aims to present the current evidence for the effectiveness of exogenous L-carnitine at reducing the amount of hypoxic damage and its neuroprotective effects mediated by increasing cerebral acetylcholine levels. Simply, L-carnitine administration may be an important contributor to the mechanisms curtailing KAATSU training-induced neuromuscular fatigue.

L-Carnitine (L-C) is a conditionally essential nutrient required for β-oxidation and cell energy production whose unbalanced metabolism is associated with a variety of diseases. L-C increased cell proliferation, differentiation and mineralization of human osteoblast in culture. The present study evaluated the effect of L-C on intracellular calcium signaling, an important modulator of cell proliferation and differentiation in human osteoblasts by means of Fura-2 fluorescence coupled to video imaging technique. 5 mM L-C promoted a calcium influx from the extracellular milieu by depolarizing L-type calcium channels. Moreover, L-C depleted the calcium stores of the mitochondria and of the endoplasmic reticulum through phospholipase C activation. The inhibition of the calcium sensing receptor with 10 µM NPS-2143 prevented the L-C dependent cytosolic calcium increase suggesting that this calcium mobilization is mediated by Calcium Sensing Receptor activation. These results unravel that L-C might be part of a complex nutritional environment which tunes osteoblast activity.

A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative (2'-deoxy-2', 2'-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine, JDR) in rat plasma was developed and validated. The conventional plasma sample preparation method of nucleoside analogues is solid-phase extraction (SPE) which is time-consuming and cost-expensive. In this study, gradient elution with small particles size solid phase was applied to effectively separate gemcitabine and JDR, and protein precipitation pretreatment was adopted to remove plasma protein and extract the analytes with high recovery(>81%). Method validation was performed as per the FDA guidelines, and the standard curves were found to be linear in the range of 5–4000 ng/ml for JDR and 4–4000 ng/ml for gemcitabine, respectively. The lower limit of quantitation (LLOQ) of gemcitabine and JDR was 4 and 5 ng/ml, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limits. Finally, the developed method was successfully applied to investigate the pharmacokinetic studies of JDR and gemcitabine after oral administration to rats.

Isovaleric acidemia (IVA) is an organic acid disease caused by a deficiency of isovaleryl-CoA dehydrogenase. Deficiency of this enzyme leads to accumulation of organic acids, such as isovalerylcarnitine and isovalerylglycine. The proposed IVA treatments include leucine restriction and l-carnitine and/or glycine supplementation, which convert isovaleric acid into non-toxic isovalerylcarnitine and isovalerylglycine, respectively. We examined the therapeutic response using the leucine load test and performed a 10-year follow-up in the patient. Methods: We evaluated the patient with IVA beginning at 5 years of age, when he presented with a mild to intermediate metabolic phenotype. Ammonia, free carnitine, isovalerylcarnitine, and isovalerylglycine were analyzed in the urine and blood after a meal consisting of 1600 mg leucine with glycine alone (250 mg/kg/day), l-carnitine alone (100 mg/kg/day), or both glycine and l-carnitine for four days each. Results: (Leucine load test) Three hours after the meal, serum ammonia levels increased most dramatically with glycine treatment alone, then with both in combination, and least with l-carnitine alone. Urinary isovalerylglycine levels increased 2-fold more with glycine supplementation than those following supplementation with both agents or with l-carnitine alone. Treatment with both agents resulted in a gradual increase in urinary acylcarnitine levels during the 6-h period following the leucine load, reaching concentrations comparable to those observed with l-carnitine alone. (Clinical course) After initiation of both glycine (200 mg/kg/day) and l-carnitine (100 mg/kg/day) supplementation at 5 years of age, doses were gradually reduced to 111.7 mg/kg/day and 55.8 mg/kg/day, respectively, at 15 years of age. His mind and body had developed without any sequelae. Discussion: We concluded that l-carnitine conjugated isovaleric acid earlier than glycine. Additionally, during the 10-year follow-up period, the patient displayed no clinical deterioration.

This study investigated the time course of lipid accumulation during IVM and assessed the role of lipid modulators added during IVM on lipid content, nuclear maturation, oxidative stress, mitochondrial activity, gene expression, and cryosurvival of cat oocytes. First, the lipid content of immature COCs was compared to those subjected to different IVM duration times (24, 28, and 32 h). Then, the lipid content was investigated after the use of different lipid modulators [conjugated linoleic acid (CLA), forskolin (FSK), l-carnitine (LC)]. Subsequently, both the CONTROL group and MIX 18 (CLA+FSK+LC) were compared regarding nuclear maturation, mitochondrial activity, reactive oxygen 19 species (ROS), and glutathione (GSH) levels, to the expression of SDHA, GDF9, BMP15, ZAR-1, 20 PRDX1, SIRT1, and SIRT3 genes (normalized by ACTB and YWHAZ genes); and to vitrification and 21 post-warming viability assessment. When not using any lipid modulator, an increase (P < 0.05) in lipid content could be observed after 28 h of IVM. The MIX group showed the greatest (P < 0.05) reduction in oocyte lipid content after 28 h of IVM. No difference (P > 0.05) was observed in the MII rate in the CONTROL (45%) and MIX (41%) groups and in mitochondrial activity ((1.00 ± 0.35 A U vs 1.19 ± 0.14 A U). Although ROS and GSH levels were higher (P < 0.05) in MIX than in CONTROL, the redox balance (ROS/GSH) was greater (P < 0.05) in the latter (C:1.00 ± 0.20 b vs M:0.26 ± 0.06 a A.U). The GDF9, HSP70, PRDX1, and SIRT1 transcripts were downregulated (P < 0.05) in MIX-oocytes, compared to the CONTROL. After vitrification, MIX (74%) presented a higher (P < 0.05) viability compared to control (53%). In conclusion, MIX can reduce the total lipid content and improve viability after cryopreservation, however, it seems to affect the oocyte metabolism in a way that still needs to be better understood in the cat biological model., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: We aimed to determine the effect of L-carnitine and spongostan on cartilage healing in an experimental animal model with a full-thickness cartilage defect., Methods: In the study 32 Sprague-Dawley rats were divided into four groups in equal numbers. A cartilage defect with a diameter of 1 mm and a depth of 3 mm was created in the femoral intercondylar region of rats in groups A, B, and C. Group A received no treatment in the defective area. Group B received treatment with spongostan. Group C received treatment with spongostan soaked in L-carnitine. Group D served as the healthy control group. The rats were euthanized 6 weeks after the treatment. Histological evaluation of the condyles was done with the modified Mankin scoring., Results: In the histopathological imaging of the cartilage structure, it was observed that in group A, there was complete disorganization and cellular structure was completely absent up to the subchondral bone. In group B, moderate structural improvement, partially intact appearance in border integrity and mostly diffuse hypercellularity were observed. In group C, a near-normal healing, a completely intact appearance in boundary integrities and normal or hypercellularity in cellular structure were observed. The total score of the modified Mankin decreases numerically from A to D. There was no statistically significant difference observed between the A-B (p = 0.176), C-D (p = 0.145), and C-B (p = 0.580) groups, while significant differences were detected between the A-C (p = 0.004), B-D (p = 0.007), and A-D (p = 0.000) groups., Conclusion: It has been known that mitochondrial activity is reduced in the osteoarthritis, and as a result, decrease in cellular activity occurs with ATP synthesis. For this reason, we found that L-carnitine, which we expect to stimulate cell proliferation by stimulating ATP synthesis, makes a positive contribution to cartilage healing, as expected. It has been found that combining spongostan with L-carnitine for the treatment of cartilage healing, instead of applying spongostan alone, provides near-normal healing., Competing Interests: Declaration of Competing Interest The authors of this article have no competing interests to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Vascular dysfunction is thought to play a major role in the development of diabetic cardiovascular disease. The roles of endothelial dysfunction, oxidative stress, and dyslipidemia will be considered. Melatonin as well as L-carnitine were shown to possess strong antioxidant properties. Diabetes induced with high fat diet (for 8 weeks) and multipl low doses intraperitoneal injection of STZ (twice, 30 mg/kg/d i.p). The diabetic animals were randomly assigned to one of the experimental groups as follows: Control group (C), high fat diet (HFD), STZ-induced diabetic group (HFD+STZ) , HFD+STZ diabetic group received melatonin (10 mg/kg/d i.p), HFD+STZ diabetic group received L-carnitine (0.6 g/kg/d i.p), and HFD+STZ diabetic group received glibenclamide (5 mg/kg/d, oral). The serum fasting blood glucose, insulin, total cholesterol, HDL- cholesterol, LDL-cholesterol, triglyceride and malondialdehyde (MDA) levels were tested. Acetylcholine induced endothelium-dependent relaxation and sodium nitroprusside induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. Also, glutathione peroxidase (GPx), superoxide dismutase (SOD) and nitric oxide (NO) levels activities were determined in rat liver. According to our results melatonin and L-carnitine treatment decreased fasting blood glucose, total cholesterol, and LDL levels. MDA levels significantly decreased with the melatonin treatment whereas SOD levels were not significantly changed between the groups. The results suggest that especially melatonin restores the vascular responses and endothelial dysfunction in diabetes.

Trimethylamine N-oxide (TMAO) was recently discovered as a novel and independent risk factor for promoting atherosclerosis while it has been found to be generated from dietary carnitine through metabolism of gut microbiota for decades. Antibiotics were found to successfully inhibit the pathway of gut microbiota-dependent TMAO formation, as well as prevention of atherosclerosis. However, the side effects and resistance potential of antibiotics limit their potential application. Allicin is a well-established antimicrobial phytochemical naturally found in fresh blended garlic and easily acquired from diet. Here we demonstrated that the plasma TMAO levels in C57BL/6 mice fed with dietary carnitine were 4–22 times greater than that in the control chow diet group during carnitine challenge test. Interestingly, the differences of plasma TMAO level were not seen when comparing mice in carnitine plus allicin diet group with the control chow diet group. The results of this study suggest that dietary allicin may be capable of protecting the host from producing TMAO when carnitine is consumed through its impact on gut microbiota. Allicin and dietary fresh garlic containing allicin may be used as functional foods for the prevention of atherosclerosis.

The cardiovascular and liver protection of carnitine (CNT) in a high-fat diet was investigated. Male C57BL/6 mice were divided randomly into four groups: 1) CON: Control, 2) HFD: high-fat diet, 3) CNTL: HFD + 500 mg CNT/kg BW, and 4) CNTH: HFD + 1500 mg CNT/kg BW. After a 25-week experimental period, CNT supplementation reduced (p

Phenylketonuria (PKU) is the most common inherited metabolic disorders caused by severe deficiency or absence of phenylalanine hydroxylase activity that converts phenylalanine (Phe) to tyrosine. PKU patients were treated with a Phe restricted diet supplemented with a special formula containing l-carnitine (L-car), well-known antioxidant compound. The lack of treatment can cause neurological and cognitive impairment, as severe mental retardation, neuronal cell loss and synaptic density reduction. Although Phe has been widely demonstrated to be involved in PKU neurotoxicity, the mechanisms responsible for the CNS injury are still not fully known. In this work, we evaluated markers of neurodegeneration, namely BDNF (brain-derived neurotrophic factor), PAI-1 total (Plasminogen activator inhibitor-1 total), Cathepsin D, PDGF AB/BB (platelet-derived growth factor), and NCAM (neuronal adhesion molecule) in plasma of PKU patients at early and late diagnosis and under treatment. We found decreased Phe levels and increased L-car concentrations in PKU patients treated with L-car compared to the other groups, indicating that the proposed treatment was effective. Furthermore, we found increased BDNF levels in the patients under treatment compared to patients at early diagnosis, and a positive correlation between BDNF and L-car and a negative correlation between BDNF and Phe. Our results may indicate that in PKU patients treated with L-car there is an attempt to adjust neuronal plasticity and recover the damage suffered, reflecting a compensatory response to brain injury., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Obesity is a major global health issue, resulting in significant costs and increased mortality rates. Finding effective treatments for obesity is therefore essential. This study investigated the combined effects of L-Carnitine (LC) and Conjugated Linoleic Acid (CLA) on weight loss and adipose tissue microRNA levels., Subjects /methods: Forty male Wistar rats weighing 150-200 g and about 8 weeks old were fed either a normal fat diet (NFD) or a high-fat diet (HFD) for 8 weeks. Afterwards, the HFD group was randomly divided into four subgroups: control, LC (200 mg kg -1 ), CLA (500 mg kg -1 ), and both (n = 8 in each group). The study lasted for an additional 4 weeks. The animals' weights were recorded regularly, and after 12 weeks, miRNAs were extracted from epididymal adipose tissue and analysed using real-time PCR. The miRNA expression levels of miR-27a and miR-143 were compared between groups using Kolmogorov-Smirnov and one-way ANOVA tests in SPSS software., Results: At the end of the first 8 weeks, the HFD group weighed significantly more than the NFD group. LC significantly decreased weight gain (4.2%) compared to the control group, whereas CLA alone (3.5%) or in combination with LC (3.1%) did not significantly slow weight gain. Real-time PCR results showed that the HFD group had higher miR-143 levels and lower miR-27a levels compared to the NFD group. LC and CLA increased miR-27a expression after 4 weeks, but their combination decreased miR-27a expression. CLA alone reduced miR-143 expression, whereas LC had almost no effect. Their combination also reduced miR-143 expression., Conclusion: CLA and LC, which are considered weight loss supplements, can potentially regulate metabolism and cellular pathways. However, their combination did not show a synergistic effect on weight loss, possibly due to the reduction in miR-27a expression. Further studies are needed to evaluate the effects of combined fat burners on obesity treatment., Competing Interests: Declaration of Competing Interest None of the authors have any conflict of interest, financial or otherwise., (Published by Elsevier Ltd.)

Early feed restriction of lambs promotes a permanent mitochondrial dysfunction that impairs β-oxidation of fatty acids along the whole life. Therefore, dietary l-carnitine might help to improve the mitochondrial function of these lambs, thus modifying lipid metabolism and meat quality traits. In order to test this hypothesis an experiment was carried out with 22 Merino lambs that were subjected to an early feed restriction during the suckling period. Once weaned, the lambs were allocated to a control group (CTRL, n = 11) being fed ad libitum a complete pelleted diet during the fattening phase, whereas the second group (CARN, n = 11) received the same diet formulated with 3 g/kg of l-carnitine. Carcass characteristics were not affected (P > 0.05) by treatment. However, lambs fed l-carnitine showed higher amounts of intramuscular fat (26.5 vs. 33.6 g/kg fresh matter; P = 0.047) with a lower ratio between polyunsaturated and saturated fatty acids (0.425 vs 0.333; P = 0.023) and a higher atherogenic (0.507 vs 0.597; P < 0.001) and thrombogenic index (1.23 vs 1.42; P < 0.001). An increase in lightness (P < 0.05) and a tendency to improved oxidative stability in cooked meat (P = 0.066) were also observed in the CARN group. Consequently, dietary l-carnitine supplied during the fattening period of early feed restricted lambs modifies meat quality traits thus increasing lightness, oxidative stability and intramuscular fat content, but worsening the fatty acid profile., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hyperammonemia, a major pathophysiological factor in hepatic encephalopathy, impairs long-term potentiation (LTP) of synaptic transmission, a cellular model of learning and memory, in the hippocampus. We have now studied the protective action of taurine on this paradigm by analyzing LTP characteristics in mouse hippocampal slices treated with ammonium chloride (1 mM) in the presence of taurine (1 mM), an ubiquitous osmolyte, antioxidant, and neuromodulator, as well as other substances with such properties. Ammonia-treated slices displayed a significant impairment of LTP maintenance. Taurine and the mitochondrial enhancer l-carnitine, but not the antioxidants (ascorbate, carnosine, and the novel compound GVS-111) or the osmolyte betaine prevented this impairment. The protective effect of taurine was preserved under the blockade of inhibitory GABAA and glycine receptors. It is suggested that taurine may rescue the mechanisms of hippocampal synaptic plasticity by improving mitochondrial function under hyperammonemic conditions.

Because hyperammonemia is thought to contribute to the pathogenesis of hepatic encephalopathy, we examined the effects of ammonia on ATP levels, neuronal morphology, and synaptic function in rat hippocampal slices. Although ammonia did not alter ATP levels supported by 10 mM glucose, ammonia significantly depressed ATP levels in the presence of 3.3 mM glucose or 10 mM pyruvate, suggesting effects on respiratory energy metabolism. Ammonia also impaired synaptic function and neuronal integrity sustained by pyruvate. In 10 mM glucose, ammonia inhibited the induction and maintenance of long-term potentiation (LTP) in a concentration-dependent fashion. These inhibitory effects of ammonia were overcome by l-carnitine. DL-APV, an antagonist of NMDA receptors, also diminished the effects of ammonia on ATP levels and LTP induction, indicating that ammonia impairs neuronal function via altered metabolism and untimely NMDA receptor activation. These results suggest that l-carnitine and NMDA receptor antagonists have the potential to preserve neuronal function during hyperammonemia.

The purpose of this study was to investigate the production performance, antioxidant parameters, egg yolk cholesterol content, and expression of genes related to cholesterol metabolism in laying hens fed L-carnitine (LC) and L-carnitine-loaded solid lipid nanoparticles (LC-SLNs). A total of 350 Hy-Line (w-36) laying hens at 50 wk of age (1520.0 ± 0.7 g) were randomly assigned to 35 units (5 replicates and 50 hens in each treatment) with seven dietary treatments as a completely randomized design. The dietary treatments were corn-soybean meal-based diets, including 1) Control (basal diet); 2) Basal diet +50 mg/kg LC (50LC); 3) Basal diet +100 mg/kg LC (100LC); 4) Basal diet +150 mg/kg LC (150LC); 5) Basal diet +50 mg/kg LC-SLNs (50LC-SLNs); 6) Basal diet +100 mg/kg LC-SLNs (100LC-SLNs) and 7) Basal diet +150 mg/kg LC-SLNs (150LC-SLNs). Results showed that the 50LC-SLNs had the least feed conversion ratio (FCR) in all groups (P < 0.05). The dietary supplementation of 100LC-SLNs decreased (P < 0.01) the egg yolk cholesterol concentration from 14.71 to 11.76 mg/g yolk (25%). The 50LC-SLNs group produced the most total antioxidant capacity with a difference of 58.44% compared to the control group (P < 0.01). The greatest amount of total superoxide dismutase was found for 50LC-SLNs (P < 0.05), while the glutathione peroxidase was not affected by the experimental treatments (P > 0.05). Serum malondialdehyde levels were reduced by 50.52% in laying hens fed 50LC-SLNs compared to the control group (P < 0.05). The transcript level of 3-hydroxy-3-methylglutaryl coenzyme A reductase was significantly decreased (P < 0.01) in the LC and LC-SLNs groups. The expression of cholesterol 7α-hydroxylase was significantly increased (P < 0.01) in the plain LC (∼83%) and LC-SLNs (∼91%) groups. The inclusion of LC-SLNs in the diet increased (P < 0.05) the villus height and decreased villus width in all three parts of the small intestine. Dietary inclusion of LC was found to reduce egg yolk and serum cholesterol content by improving the production performance and antioxidant status. The LC-SLNs groups were more affected than the plain LC groups, which may be attributed to the increased bioavailability of LC., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: l-Carnitine was suggested to prevent the progression of atherosclerosis, myocardial and neurologic injury, and exhibited cardioprotective effects. However, epidemiological data on circulating l-carnitine and risks of cardiovascular events in the setting of stroke is rare. We aimed to explore the relationships between plasma l-carnitine and cardiovascular events and stroke recurrence after ischemic stroke in a nested case-control study., Methods and Results: A total of 323 cardiovascular events (including 264 recurrent strokes) and 323 matched controls (free of recurrent cardiovascular events) were included. Study outcomes included cardiovascular events and recurrent stroke after ischemic stroke. Plasma l-carnitine concentrations were measured by ultra-high-performance LC-MS/MS. Conditional logistic regression models were used to estimate odds ratios (ORs) of stroke outcomes. Plasma l-carnitine was inversely associated with cardiovascular events (OR = 0.69, 95% CI: 0.57-0.84 per SD) and recurrent stroke (OR = 0.72, 95% CI: 0.58-0.88 per SD) after adjusting for established risk confounders. Compared with the lowest tertile of l-carnitine, adjusted ORs of cardiovascular events and recurrent stroke for participants in the highest tertiles were 0.35 (95% CI: 0.21-0.57) and 0.36 (95% CI: 0.21-0.62), respectively. In addition, l-carnitine provided incremental predictive ability beyond established risk factors, shown by increase in C statistics, net reclassification improvement and integrated discrimination improvement., Conclusions: Higher l-carnitine levels were associated with lower risks of cardiovascular events and recurrent stroke after ischemic stroke. Our findings provided evidence supporting plasma l-carnitine as a potential prognostic marker in risk discrimination and stratification in patients with ischemic stroke., Trial Registration: Clinicaltrials.gov as NCT01840072. URL: https://www., Clinicaltrials: gov., Competing Interests: Declaration of competing interest The authors declare no financial interests or potential conflicts of interest., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

In this study, different levels of Omega-3 fatty acids and L-carnitine (LC) were used in diets for laying hens. The effects of these supplements were examined on productive performance, antioxidant properties, cholesterol content, and yolk fatty acid profiles in the laying hens. A population of 120 Lohmann LSL-Lite laying hens (34-wk-old) were used in 2 × 3 factorial arrangements with 2 diets (control = 0.031 and 0.48% omega-3 fatty acids) and 3 levels of L-carnitine (0, 100, 200 mg/kg of diet) in a completely randomized design with 6 treatments. While having 5 replicates and 4 birds per replicate, the total period of the experiment lasted for 10 wk. The eggs were weighed daily, parallel to measurements of egg production, daily feed intake, feed conversion ratio, and egg mass. When the hens reached 44 wk of age, the measurements were aimed at fatty acid profiles, malondialdehyde (MDA), and cholesterol concentration in egg yolk. Feeding the hens on diets enriched by omega-3 fatty acids led to higher levels of egg production than those fed on control diets, but their daily feed intake was generally lower (P < 0.05). Egg weight decreased in birds that were fed on diets enriched with omega-3 fatty acids without L-carnitine, or with diets which contained 100 mg/kg L-carnitine, compared to control diets which contained 0 mg/kg L-carnitine (P < 0.05). Egg mass increased in birds that were fed on diets enriched with omega-3 fatty acids and which contained 200 mg/kg L-carnitine, compared to the control diet with 0 or 100 mg/kg L-carnitine (P < 0.05). The analysis of fatty acid profiles showed that L-carnitine and omega-3 fatty acids caused a significant increase in the percentage of eicosapentaenoic acid (EPA), docosahexaenoic  acid (DHA), C18: 1 (n-9), arachidonic acid (ARA) C20: 4 (n-6), and Σ n-3 in the eggs of birds (P < 0.05). Based on the results, adding L-carnitine (200 mg/kg) to diets that were already enriched with omega-3 fatty acids increased the level of production and led to a longer maintenance of fatty acids in the eggs. Also, oxidative stability was enhanced in the yolk of eggs., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Valproic acid (VPA) is a common antiepileptic drug that is also used routinely for various psychiatric disorders. VPA toxicity typically manifests as central nervous system depression, while hyperammonemic encephalopathy and hepatotoxicity are potentially life-threatening complications., Case Report: We describe the case of a 56-year-old man who presented to the emergency department after an intentional VPA overdose, was found to have hyperammonemia, and was treated with L-carnitine exclusively. He was subsequently admitted to the hospital for monitoring and serial laboratory testing. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although VPA toxicity has conventionally been managed by gastric decontamination, L-carnitine, and, in severe and refractory cases, extracorporeal removal, recent literature supports the use of carbapenem antibiotics, particularly meropenem. Thus, we report the details of current treatment modalities for VPA toxicity by reviewing current literature., (Copyright © 2022 Elsevier Inc. All rights reserved.)