L-carnitine Supplementation Research Articles

L-carnitine and Zinc supplementation impedes intestinal damage in methotrexate-treated adjuvant-induced arthritis rats: Reinstating enterocyte proliferation and trace elements

BackgroundMethotrexate (MTX), a folic acid analogue, is used as a first-line treatment for rheumatoid arthritis (RA) since it has more therapeutic mechanisms than any other drug. Being an undeniable drug for the treatment of arthritis, even low-dose MTX provokes intestinal toxicity as a primary adverse effect and does not revive an anti-inflammatory element. Thus, our study aims to elucidate the anti-arthritic and prophylactic activity of supplements L-carnitine (L) and zinc (Z) against MTX-mediated intestinal damage in arthritis rats. MethodsThe rats were assessed for arthritic parameters such as body weight, paw volume, x-ray scan, and serum trace elements level. To analyze the toxic effects of MTX in the rats, intestine pH, mucosal weight, digestive enzymes, myeloperoxidase, histopathological, and immunohistochemical analysis were performed. ResultsOur study demonstrated that the arthritic parameters have shown that MTX has an ameliorative effect on arthritic rats. Besides, our findings showed that low-dose MTX (2.5 mg/kg b.w.) given once a week for two weeks during arthritis treatment had toxic effects in the rat's intestine, as evidenced by changes in intestine pH and mucosal weight, decreased digestive enzymes, increased MPO, and degenerative changes in histopathological analysis. Concurrent therapy of LZ with MTX, on the other hand, restored the modifications in these parameters. ConclusionMTX in combination with LZ effectively manages arthritis than monotherapy and significantly prevents MTX-induced intestinal damage in arthritis rats. Thus, LZ could be used as an improved therapeutic and safety for MTX-instigated intestinal damage during arthritis treatments. Therefore, our combination of L-carnitine and zinc with MTX would be promising prophylactic activity for arthritis patients.

The Effect of L-carnitine supplement on seminal fluid parameters in males with infertility

Background: Male infertility is a significant problem affecting 7.5% of the male population. Approximately 60% of these cases are idiopathic and related to sperm dysfunctions such as oligo-astheno-teratozoospermia (OAT).Aim: The aim of this study was to verify the effect of L-carnitine on sperm parameters in patients who presented with infertility.Patients and Methods: The clinical trial study conducted on a total 142 men but 8 patients with varicocele were excluded. So this study was conducted on the remainder 134 patients presenting with infertility due to idiopathic oligo-astheno-zoospermia (mean age± SD: 30.6 ± 6.07), who didn't use L-carnitine previously. Sample divided into 2 groupd (70 patients treated with L carnitine and 64 with placebo). L-carnitine was prescribed orally at a daily dose of 2 gm/day for 3 months. Before onset of drug intake and after the ending of the L-carnitine treatment, semen analysis was performed. Results: Seminal fluid analysis has been done before treatment and then 3 months after treatment. The mean values of sperm count, total motility and normal morphology of astheno-spermic and oligo-astheno-teratospermic were found significantly at (p<0.05). There is a trend toward an improvement in seminal fluid parameters was noted when comparing baseline with 3 months points in both the placebo and the carnitine arm.The results of the present study clearly demonstrated that L-carnitine at a daily dose of 2 gm/day for a treatment period of 3 months can improve sperm concentration, sperm count, percentage of actively motile sperm, and progressive motile sperm count among men with idiopathic oligo- and/or astheno-zoospermia.Conclusion: The present study concluded that L-carnitine at a daily dose of 2 gm/day for a treatment period of 3 months had positive effect and can be treat infertility.

L-carnitine enhances developmental potential of bovine oocytes matured under high lipid concentrations in vitro

Maternal obesity elevates non-esterified fatty acids (NEFA) follicular concentrations. Bovine cumulus-oocyte complexes (COCs) matured in vitro under high NEFA have altered metabolism and reduced quality. Systemically, obesity promotes altered mitochondrial metabolism linked to L-carnitine insufficiency. We hypothesized that L-carnitine supplementation during IVM of bovine COCs in the presence of high NEFA would lessen the negative effects of exposure to excessive lipids on embryonic development and oxidative stress. COCs were collected from abattoir ovaries and matured in four groups: CON (control), LC (3 mM L-carnitine), HN (high NEFA: 200uM oleic, 150uM palmitic and 75uM stearic acid), and HNLC (HN and LC). Mature oocytes were assayed for aerobic and anaerobic metabolism utilizing oxygen and pH microsensors or fertilized in vitro (D0). Cleavage (D3) and blastocyst (D7, D8) rates were assessed. D3 embryos with ≥ 4 cells were stained for cytosolic and mitochondrial ROS. D8 blastocysts were assayed for gene transcript abundance of metabolic enzymes. Oocyte metabolism was not affected by IVM treatment. D3 formation of embryos with ≥ 4 cells were lower in LC or HN than CON or HNLC; blastocyst rates were greater for CON and lower for HN than LC and HNLC. D3 embryo mitochondrial and cytosolic ROS were reduced in HNLC when compared to other groups. IVM in HN altered blastocyst gene transcript abundance when compared to CON, but not LC or HNLC. In conclusion, supplementation with L-carnitine protects oocytes exposed to high NEFA during IVM and improves their developmental competence, suggesting that high lipid exposure may lead to L-carnitine insufficiency in bovine oocytes.

The Synergistic Effects of the Combination of L-Carnitine and Lycopene on the Lycopene Bioavailability and Duodenal Health of Roosters.

The objective of this study was to investigate the impact of Lycopene and L-Carnitine, individually or in combination, on various physiological and molecular factors related to intestinal health and absorption ability in Roosters, such as intestinal morphology, serum biochemical parameters, genes involved in Lycopene uptake, nutritional transport genes, and tight junction genes. The findings of the study revealed that the combination of L-Carnitine and Lycopene supplementation had been found to increase the serum concentration levels of TP and ALB. Interestingly, the relative mRNA expression of genes responsible for Lycopene uptakes, such as SR-BI and BCO2, was higher in the LC group compared to other groups. Additionally, the expression of specific nutritional transport genes in the duodenum was significantly affected by both CAR and LC supplementation groups. The tight junction gene OCLN showed a significant increase in expression in the combination group compared to using either Lycopene or L-Carnitine alone. This study concludes that using Lycopene and L-carnitine in combination in poultry feed can potentially improve intestinal morphology and serum biochemical parameters, increase Lycopene bioavailability, improve nutrients uptake, and enhance the integrity of duodenal tight junctions in Roosters.

L-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy.

Lenvatinib is an oral tyrosine kinase inhibitor that acts on multiple receptors involved in angiogenesis. Lenvatinib is a standard agent for the treatment of several types of advanced cancers; however, it frequently causes muscle-related adverse reactions. Our previous study revealed that lenvatinib treatment reduced carnitine content and the expression of carnitine-related and oxidative phosphorylation (OXPHOS) proteins in the skeletal muscle of rats. Therefore, this study aimed to evaluate the effects of L-carnitine on myotoxic and anti-angiogenic actions of lenvatinib. Co-administration of L-carnitine in rats treated with lenvatinib for 2weeks completely prevented the decrease in carnitine content and expression levels of carnitine-related and OXPHOS proteins, including carnitine/organic cation transporter 2, in the skeletal muscle. Moreover, L-carnitine counteracted lenvatinib-induced protein synthesis inhibition, mitochondrial dysfunction, and cell toxicity in C2C12 myocytes. In contrast, L-carnitine had no influence on either lenvatinib-induced inhibition of vascular endothelial growth factor receptor 2 phosphorylation in human umbilical vein endothelial cells or angiogenesis in endothelial tube formation and mouse aortic ring assays. These results suggest that L-carnitine supplementation could prevent lenvatinib-induced muscle toxicity without diminishing its antineoplastic activity, although further clinical studies are needed to validate these findings.

Effects of Combined L-Carnitine Supplementation and Moderate-Intensity Exercises on Oxidative Stress, Antioxidant, and Anti-Inflammatory Responses in Overweight and Obese Individuals: A Randomized Controlled Trial

INTRODUCTION: Obesity has been associated to persistent oxidative stress and inflammation that could lead to chronic diseases. MATERIALS AND METHODS: Sixty[1]eight overweight and obese participants aged 29.03 ± 6.02 years old were randomly assigned, with 17 participants per group, into sedentary control (C), L-carnitine supplement alone (S), exercise alone (E), and combined L-carnitine supplementation and exercise (SE) groups. The participants in S and SE groups took one tablet of 1000 mg of L-carnitine every day. The E and SE groups performed brisk walking exercise for 30 minutes at 50% HRmax followed by Tabata exercise for 10 to 20 minutes per session, 3 sessions per week. During pre- and post-tests, blood markers of participants were assessed to determine their reactive oxygen species (ROS), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and interleukin-6 (IL-6) levels. All the observed parameters were analysed using two-way mixed ANOVA for repeated measures to determine significant differences within and between the groups and comparisons of mean differences were performed using one way ANOVA. RESULTS: Results showed that there were significant decreases in ROS and MDA in the S, E, and SE groups at post-test after 12 weeks of intervention. The greatest reduction of these parameters were observed in SE group among all groups. At the post-test, both CAT and SOD levels increased in the S, E, and SE groups. Regarding IL-6, it was found to be increased in C and E groups. In contrast, there were significant decreases in S and SE groups following the intervention. CONCLUSION: Twelve weeks of L-carnitine supplementation and engagement in brisk walking and Tabata exercise had significant improvement on oxidative stress, antioxidant, and anti-inflammatory responses in overweight and obese individuals.

Randomised Clinical Trial of Combined L-Carnitine Supplement and Exercise on Biochemical Markers and Exercise Performance: A Systematic Review

Aim and design: L-carnitine supplementation combined with exercise may enhance metabolic responses and improve exercise performance. Thus, this systematic review article aims to identify the effects of the L-carnitine supplement on biochemical markers, and exercise performance when combined with exercise. Data Sources: The articles are screened and reviewed based on titles, abstracts and keywords. Only peer-reviewed studies written in the English language, dated January 2000 to March 2021, were considered in this review. Review Methods: The PRISMA method is used for this study. PubMed, EBSCOHost, SpringerLINK, and Scopus databases were used to systematically search. Results: From a search 731 articles, 12 articles were identified related to effect of L-carnitine intake with exercises on biochemical markers and exercise performance. Studies showed that L-carnitine supplementation can be consumed daily during aerobic or anaerobic exercises by different population including patients. Its combination could improve serum lipid profiles, antioxidant properties, markers of metabolic, oxidative stress, and inflammatory, and exercise performance. Conclusion and Impact: This review provides information regarding the beneficial effects of L-carnitine supplement with recommended dosages and exercise prescriptions on overall body health in human.

Dietary L-carnitine supplementation for heat stressed juvenile pearl gentian grouper(Epinephelusllanolatus (Epinephelus♂×Epinephelusfuscoguttatus♀): Effects on the antioxidant enzyme, survival, and gene expression

The effects of increasing dietary inclusion levels of L-carnitine at 0 (control group) 200, 400, 600, 1200, 1400, and 1600 mg/kg were evaluated in juvenile hybrid groupers exposed to heat shock stress. The feeding trial was conducted for eight weeks. After the feeding trial, hybrid groupers were subjected to a heat stress test for an hour at a temperature of 36 °C to determine the influence of the treatments on survival, biochemical parameters, and gene expression. The results of the current study showed that the survival rate of hybrid grouper was low in fish fed the control diet. A large number of survivors were observed in the treatment group with 400 mg/kg L-carnitine supplementation (LC 400), obtaining the highest survival rate. Heat stress decreased (P < 0.05) the activities of alkaline phosphatase and acid phosphatase in the control group but was increased in fish fed the LC 400 diet. Additionally, in the LC 400 treatment, malondialdehyde content decreased considerably (P < 0.05) compared to LC0. Hybrid grouper exposed to a high temperature of 36 °C for 1 h without L-carnitine (LC0, control group) supplementation showed the most increased Aspartate Aminotransferase activity (2.04 U L−1). Additionally, the LC 400 group reached the maximal value for the expressions of genes in the PPARs (peroxisome proliferator-activated receptors) signaling pathway, which showed a tendency of downregulation and, subsequently, up-regulation. The gene expression of FAS (fatty acid synthase) was discovered upstream and downstream (P < 0.05). The lowest mRNA level was found in the lowest L-carnitine supplementation treatment (200 mg/kg). A CPT-1 (carnitine palmitoyltransferase) that controls fatty acid oxidation showed upstream and downstream activity in response to increasing doses of L-carnitine supplementation. Our findings showed that dietary supplementation with L-carnitine 400 mg/kg reduced heat stress-related mortality and oxidative damage by enhancing the survival and oxidative enzymes of grouper, which provides a nutritional method of minimizing the consequences of heat exposure.

Liver Lipidomics Analysis Revealed the Novel Ameliorative Mechanisms of L-Carnitine on High-Fat Diet-Induced NAFLD Mice

The beneficial effects of L-carnitine on non-alcoholic fatty liver disease (NAFLD) were revealed in previous reports. However, the underlying mechanisms remain unclear. In this study, we established a high fat diet (HFD)-induced NAFLD mice model and systematically explored the effects and mechanisms of dietary L-carnitine supplementation (0.2% to 4%) on NAFLD. A lipidomics approach was conducted to identify specific lipid species involved in the ameliorative roles of L-carnitine in NAFLD. Compared with a normal control group, the body weight, liver weight, concentrations of TG in the liver and serum AST and ALT levels were dramatically increased by HFD feeding (p < 0.05), accompanied with obvious liver damage and the activation of the hepatic TLR4/NF-κB/NLRP3 inflammatory pathway. L-carnitine treatment significantly improved these phenomena and exhibited a clear dose-response relationship. The results of a liver lipidomics analysis showed that a total of 12 classes and 145 lipid species were identified in the livers. Serious disorders in lipid profiles were noticed in the livers of the HFD-fed mice, such as an increased relative abundance of TG and a decreased relative abundance of PC, PE, PI, LPC, LPE, Cer and SM (p < 0.05). The relative contents of PC and PI were significantly increased and that of DG were decreased after the 4% L-carnitine intervention (p < 0.05). Moreover, we identified 47 important differential lipid species that notably separated the experimental groups based on VIP ≥ 1 and p < 0.05. The results of a pathway analysis showed that L-carnitine inhibited the glycerolipid metabolism pathway and activated the pathways of alpha-linolenic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and Glycosylphosphatidylinositol (GPI)-anchor biosynthesis. This study provides novel insights into the mechanisms of L-carnitine in attenuating NAFLD.

Carnitine affects Octanoate Oxidation to Carbon Dioxide and Dicarboxylic Acids in Colostrum-Deprived Piglets: In Vivo Analysis of Mechanisms Involved Based on CoA- and Carnitine-Ester Profiles

Newborn, colostrum-deprived piglets (n = 21) were used to study the effects of L-carnitine supplementation on the in vivo oxidation of [1-14C]octanoate to CO2 and dicarboxylic acids. Pigs were fitted with arterial and bladder catheters and were infused with octanoate (supplying 35–100% of piglets' energy expenditure) and with or without valproate for a period of 24 h. After achieving steady-state octanoate oxidation, carnitine was coinfused [50 µmol/kg0.75 prime plus 20 µmol/(h·kg0.75)], and deviations in the octanoate oxidation rate, dicarboxylic acid excretion rate, and carnitine metabolism were monitored. At the end of the 24-h infusion, samples of liver and muscle were analyzed for carnitine- and CoA-esters by HPLC. Carnitine stimulated octanoate oxidation by 7% (P < 0.05) and decreased dicarboxylic acid excretion by 45% (P < 0.05). Carnitine supplementation increased (P < 0.05) concentrations of carnitine and acetyl carnitine in hepatic tissue (three- and 55-fold, respectively) and plasma (seven- and 11-fold); whereas, muscle-carnitine concentration doubled upon carnitine supplementation, but acetyl carnitine concentration remained unaltered. Urinary excretion of acetyl and free carnitine also increased with carnitine supplementation, but accounted for <10% of carnitine infused. Hepatic total CoA and CoA esters increased with carnitine supplementation, whereas muscle acetyl-CoA decreased. Valproate had only marginal effects on octanoate metabolism. These data confirm the hypothesis that carnitine affects the in vivo oxidation of octanoate in colostrum-deprived piglets and suggest that the effects may be mediated by aiding the export of excess acetyl groups from muscle or by enhancing uptake of octanoate into liver mitochondria.

Effects of Dietary Supplementation of L-Carnitine and Mannan-Oligosaccharides on Growth Performance, Selected Carcass Traits, Content of Basic and Mineral Components in Liver and Muscle Tissues, and Bone Quality in Turkeys.

The study aimed to determine the effect of L-carnitine and Bio-Mos administration on selected production performance, slaughter parameters, elemental and mineral content of liver, breast and thigh muscles, and physical, morphometric, strength and bone mineral composition parameters of turkeys. The experiment was conducted on 360 six-week-old Big-6 turkey females, randomly divided into three groups of 120 birds each (six replicates of 20 birds). The turkeys of the control group were fed standard feed without additives; group II was fed with drinking water, a preparation containing L-carnitine at a dose of 0.83 mL/L, while group III was provided mixed feed with 0.5% Bio-Mos. The addition of L-carnitine and Bio-Mos increased body weight at 16 weeks (p = 0.047) and reduced the proportion of fat in the breast muscle (p = 0.029) and liver (p = 0.027). It also modified the content of some minerals in breast muscle, thigh muscle, liver, and bone. Furthermore, the addition of L-carnitine and Bio-Mos increased bone mass and length and modified the value of selected morphometric and strength parameters. The results indicate a positive effect of the applied feed additives on selected rearing indices and carcass quality while improving the elasticity and fracture toughness of the femur. There is a need for further research to determine optimal doses of L-carnitine and Bio-Mos in poultry nutrition.

Analysis of clinical features, biochemical indices and genetic variants among children with Short/branched-chain acyl-CoA dehydrogenase deficiency detected by neonatal screening

To investigate the clinical manifestations, biochemical abnormalities and pathogenic variants among children with Short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency detected by neonatal screening. A total of 2 730 852 newborns were screened from January 2016 to December 2021 with liquid chromatography tandem mass spectrometry. Suspected SBCAD deficiency patients were diagnosed by urine organic acid analysis and high-throughput gene sequencing analysis. The clinical, biochemical and genetic changes of the confirmed cases were analyzed, in addition with guidance for diet and life management, L-carnitine supplement, and survey of growth and intellectual development. Twelve cases of SBCAD deficiency were diagnosed, which yielded a prevalence of 1/227 571. The lsovaleryl carnitine (C5) of primary screening blood samples was between 0.6 and 2.1 µmol/L, all exceeded the normal range. C5/acety1 carnitine (C2) was between 0.02 and 0.12, with 6 cases exceeding the normal range. C5/propionyl carnitine (C3) was between 0.1 and 1.16, with 5 cases exceeding the normal range. Free carnitine (C0) was between 18.89 and 58.12 µmol, with 1 case exceeding the normal range. Three neonates with abnormal screening results were recommended to have appropriate restriction for protein intake and two were given L-carnitine. During follow-up, their C5 has ranged from 0.22 to 2.32 µmol/L, C5/C2 has ranged from 0.01 to 0.31, C5/C3 has ranged from 0.14 to 1.7. C5 or C5/C2 and C5/C3 were transiently normal in all patients except for case 8 during the neonatal screening and follow-up. C0 was 17.42 ∼ 76.83 µmol/L Urine organic acid analysis was carried out in 9 of the 12 cases, and 2-methylbutyroglycine was elevated in 8 cases. Urine organic acid analysis was carried out in 9 cases, and 2-methylbutyrylglycine was increased in 8 cases. Genetic analysis was carried out for 11 children, and in total 6 ACADSB gene variants were identified, which included 4 missense variants (c.655G>A, c.923G>A, c.461G>A, c.1165A>G), 1 frameshift variant (c.746del) and 1 nonsense variant (c.275C>G). Among these, the C.461G>A variant was unreported previously. The most common variants were c.1165A>G (40.9%) and C.275C>G (22.7%). The patients were followed up for 18 days to 55 months. Only one patient had mental retardation, with the remainders having normal physical and mental development. SBCAD deficiency is a rare disease. The detection rate of newborn screening in this study was 1/227 571. Early intervention can be attained in most asymptomatic patients through neonatal screening. In this study, the common gene variants are c.1165A>G and c.275C>G.

L-Carnitine and Chronic Kidney Disease: A Comprehensive Review on Nutrition and Health Perspectives.

Progressive segmental glomerulosclerosis is acknowledged as a characteristic of Chronic Kidney Disease (CKD). It is a major health issue that exponentially reduces health and economy and also causes serious morbidity and mortality across the globe. This review is aimed at comprehending the health perspectives of L-Carnitine (LC) as an adjuvant regimen for alleviating CKD and its associated complications. The data were gathered from different online databases such as Science Direct, Google Scholar, ACS publication, PubMed, Springer, etc., using keywords such as CKD/Kidney disease, current epidemiology and its prevalence, LC supplementations, sources of LC, anti-oxidant and anti-inflammatory potential of LC and its supplementation for mimicking the CKD and its associated problem, etc. Various items of literature concerning CKD were gathered and screened by experts based on their inclusion and exclusion criteria. The findings suggest that, among the different comorbidities such as oxidative stress and inflammatory stress, erythropoietin-resistant anemia, intradialytic hypotension, muscle weakness, myalgia, etc., are considered as the most significant onset symptoms in CKD or hemodialysis patients. LC or creatine supplementation provides an effective adjuvant or therapeutic regimen that significantly reduces oxidative and inflammatory stress and erythropoietin-resistant anemia and evades comorbidities such as tiredness, impaired cognition, muscle weakness, myalgia, and muscle wasting. However, no significant changes were found in biochemical alteration such as creatinine, uric acid, urea, etc., after creatine supplementation in a patient with renal dysfunction. The expert-recommended dose of LC or creatine to a patient is approached for better outcomes of LC as a nutritional therapy regimen for CKD-associated complications. Hence, it can be suggested that LC provides an effective nutritional therapy to ameliorate impaired biochemicals and kidney function and to treat CKD and its associated complications.

Effects of Various Lipid Sources and L-Carnitine Supplementation on the Growth Performance, Body Composition, and Antioxidants Enzyme Ability of Dog Conch Larvae, Laevistrombus canarium

A feeding experiment was conducted to study the effects of dietary lipid sources and L-carnitine on the growth performance, body component, muscle fatty acid composition, and antioxidant enzyme ability of average weight of 0.28 g dog conch larvae, Laevistrombus canarium. Three sources of lipid: fish oil, soybean oil, and beef tallow were tested in combination with two levels (0 and 0.5%) of L-carnitine. The dog conch larvae fed diets containing fish oil with L-carnitine supplementation exhibited the highest weight gain. After air exposure challenge, the liver tissue of dog conch fed the diets containing soybean oil and beef tallow without supplemented L-carnitine had lower levels of superoxide dismutase (SOD, U min−1), phenoloxidase (PO, U min−1), and glutathione peroxidase (GPx, mU/mL) activity. The activity of SOD, PO, and GPx of dog conch larvae increased with increasing levels of dietary L-carnitine. In particular, dog conch larvae fed the diet containing fish oil supplemented with L-carnitine exhibited significantly ( P &lt; 0.05 ) enhanced antioxidant responses. The thiobarbituric acid reactive substances (TBARS) in the muscle tissue of dog conch larvae fed the diet containing fish oil without L-carnitine supplementation showed significantly ( P &lt; 0.05 ) higher activity. It was concluded that dietary administration of L-carnitine can enhance resistance against beta-oxidation, and the administration of fish oil in the diet was the best strategy to promote growth due to high nutritional availability.

Quantitative systems pharmacology Model to characterize valproic acid-induced hyperammonemia and the effect of L-carnitine supplementation

Valproic acid (VPA) is a short-chain fatty acid widely prescribed in the treatment of seizure disorders and epilepsy syndromes, although its therapeutic value may be undermined by its toxicity. VPA serious adverse effects are reported to have a significant and dose-dependent incidence, many associated with VPA-induced hyperammonemia. This effect has been linked with reduced levels of carnitine; an endogenous compound involved in fatty acid's mitochondrial β-oxidation by facilitation of its entrance via the carnitine shuttle. High exposure to VPA can lead to carnitine depletion causing a misbalance between the intra-mitochondrial β-oxidation and the microsomal ω-oxidation, a pathway that produces toxic metabolites such as 4-en-VPA which inhibits ammonia elimination. Moreover, a reduction in carnitine levels might be also related to VPA-induced obesity and lipids disorder. In turn, L-carnitine supplementation (CS) has been recommended and empirically used to reduce VPA's hepatotoxicity. The aim of this work was to develop a Quantitative Systems Pharmacology (QSP) model to characterize VPA-induced hyperammonemia and evaluate the benefits of CS in preventing hyperammonemia under both chronic treatment and after VPA overdosing. The QSP model included a VPA population pharmacokinetics model that allowed the prediction of total and unbound concentrations after single and multiple oral doses considering its saturable binding to plasma proteins. Predictions of time courses for 2-en-VPA, 4-en-DPA, VPA-glucuronide, carnitine, ammonia and urea levels, and for the relative change in fatty acids, Acetyl-CoA, and glutamate reflected the VPA induced changes and the efficacy of the treatment with L-carnitine. The QSP model was implemented to give a rational basis for the L-carnitine dose selection to optimize CS depending on VPA dosage regime and to assess the currently recommended L-carnitine rescue therapy after VPA overdosing. Results show that a L-carnitine dose equal to the double of the VPA dose using the same interdose interval would maintain the ammonia levels at baseline. The QSP model may be expanded in the future to describe other adverse events linked to VPA-induced changes in endogenous compounds.

Effect of Supplementation of Diets with L-Carnitine and Methionin on Broiler Chicken Productive Performance.

The poultry industry is one of the pillars of food security in the world, as it is relied upon to provide meat and eggs to meet the increasing food demands. Therefore, this study was designed to investigate the effect of L-carnitine and methionine supplementation to the standard diets of broiler chickens in productive performance of broiler (Ross 308). One Hundred- fifty broiler chicks unsexed (Ross 308) with an initial weight with 43 g, were obtained from Al-Habbaniya hatchery (commercial hatchery). All the animals were within an average weight of 40 g (one-day old chicks). The experimental groups were as follows: the animals in T1 group received basal diet without any addition, the animals in T1 group received basal diet supplemented with lead acetate 400 mg/kg feed , the animals in T3 group received diet supplemented with carnitine 300 mg + lead acetate 400 mg, the animals in T4 group received basal diet supplemented with methionine 100 mg + lead acetate 400 mg, the animals in T5 group received basal diet supplemented with methionine 100 mg + carnitine 300 mg + lead acetate 400 mg. Body weight gain and feed consumption were weekly recorded. Feed conversion ratio was also calculated. Results showed that Birds in (T5) fed diets with (carnitine + methionine) observed highest live body weights comparison with T3 (carnitine + lead acetate) and T4 (adding methionine+ lead acetate). Data of results showed no significant differences were recorded in body weight gain. Also, Results obtained increase with feed consumption for treatment T5, while birds in T1 and T4 recorded lowest means in feed consumed. However, birds in T4 and T5 observed best feed conversion ratio as compare with T1, T2 and T3. Therefore, it can conclude that addition carnitine and methionine enhanced broiler productive performance.

The effect of l-carnitine supplementation on mortality and clinical outcomes in ventilator-dependent critically ill patients with obesity and COVID-19: Protocol for a randomized double-blind placebo-controlled trial

BackgroundCoronavirus 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. MethodsThis 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). ConclusionBased 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

Twenty-Four Weeks of L-Carnitine Combined with Leucine Supplementation Does Not Increase the Muscle Carnitine Content in Healthy Active Subjects

Introduction: To increase the total carnitine (TC) content in muscles, L-carnitine (LC) should be co-ingested with carbohydrates to induce an insulin response. Leucine has an insulin secretagogue effect. Therefore, the primary aim of this study was to examine the effects of 24 weeks of LC and leucine supplementation on the skeletal muscle TC content, muscle mass, and strength in active college-aged subjects. The secondary aim was to determine the activation of the Akt/mTOR signaling pathway in skeletal muscles after supplementation. Methods: Over the 24 weeks, the participants were supplemented with either 1 g of LC-L-tartrate and 3 g of leucine per day (LC + L group; n = 7) or 4 g of leucine per day (L group; n = 7) as a placebo. Before and 24 weeks after the initiation of the study protocol, the free carnitine (FC) and TC content in plasma and muscle samples, as well as body composition and muscle strength, were measured. In addition, the phosphorylation of the Akt/mTOR pathway proteins in muscles was evaluated. Results: Plasma FC and TC content increased in LC + L group after 24 weeks of supplementation (p = 0.003 and 0.010, respectively). However, the skeletal muscle FC and TC contents were not affected by the supplementation protocol. No changes were noted in the body mass and composition; serum insulin-like growth factor-1 concentration; and phosphorylation of the signaling pathway proteins Akt, mTOR, and p70S6K. Conclusion: LC supplementation may have the potential to exert beneficial effects in muscle atrophy. Therefore, additional research is necessary to investigate the effect of various LC supplementation protocols.

Effects of high-dose L-carnitine supplementation on diaphragmatic function in patients with respiratory failure: A randomized clinical trial

ABSTRACT Objectives Evaluation of diaphragmatic function by bedside ultrasound provides information on the degree of disability and the response to treatment intervention in respiratory failure patients with associated respiratory muscle fatigue. This study aimed to assess the impact of high and low-dose L-carnitine supplementation on diaphragmatic muscle function. Methods This was a prospective, randomized, controlled clinical trial (trial registration number NCT05322447), for which approval was obtained from our institutional ethics committee (R80/2021). Participating patients were randomly assigned to two groups of 30 patients each. In the low-dose group, L-carnitine was administered at a dose of 6 g/day. The high-dose group received an intravenous infusion of 18 g/day of L-carnitine. On days 0, 3, and 7, diaphragmatic function was assessed by ultrasound, and serum levels of L-carnitine were measured. Results Both diaphragmatic excursion (DE) and diaphragmatic thickening fraction (DTf) measurements were positively correlated with serum L-carnitine levels (+r = 0.58 and +r = 0.61, respectively; p< 0.001). High-dose L-carnitine independently influenced the DE only, both in an unadjusted model (p = 0.04) and after adjustment for age and sex (p = 0.02). However, it had no significant effect on DTf, either before (p = 0.25) or after (p = 0.17) adjustment. Conclusion Serum levels of L-carnitine are positively correlated with the two measures of diaphragmatic function (DE and DTf). Moreover, high-dose L-carnitine supplementation had rapid and significant positive effects on DE. This improvement indirectly enhanced patient outcomes and resulted in shorter stays in the Intensive Care Unit and hospital.

HEPARIN AND HYPOTAURINE SUPPLEMENTATION IMPROVE THE FERTILIZATION RATE OF SHEEP OOCYTES MATURED IN MEDIA CONTAINING L-CARNITINE IN VITRO

This study to do examine the effectiveness of using heparin and hypotaurine to improve the in vitro fertilization rate. In first stage, oocytes were matured in the maturation medium supplemented with 0.3 mg/mL L-carnitine to improve nuclear maturation. In second stage, matured oocytes were fertilized with semen incubated in fertilization medium supplemented with 0.1 IU/mL heparin and 10 µM hypotaurine. The final concentration of sperm used was 5x106 spermatozoa/mL, and its interaction with oocytes was carried out for 12 hours in 5% CO2 incubator at 38.5° C. The results showed that percentage of oocytes that reached metaphase II was significantly higher (P0.05) in media supplemented with 0.3 mg/mL L-carnitine compared to control (88.2±4.9% vs 79.8±5.1%). Furthermore, fertilization rate was characterized by formation of 2 PN was significantly higher (P0.05) in media supplemented with heparin and hypotaurine than control (82.6±2.0% vs 73.3±2.4%). In conclusion, L-carnitine supplementation at dose of 0.3 mg/mL on maturation media was effective in increasing percentage of matured oocytes. The combination of 0.1 IU/mL heparin and 10 µM hypotaurine in fertilization medium was also successful in elevating the percentage of fertilized oocytes.