L-Carnitine

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation, largely mediated by pro-inflammatory cytokines. Considering the established involvement of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and transforming growth factor-beta1 (TGF-β1) in RA, this research aimed to assess efficacy and safety of L-carnitine as an adjunct therapy targeting these pathways. Forty-six patients with active RA were randomly divided into two equal groups. Group1 (control group) received disease-modifying antirheumatic drugs (DMARDs), including methotrexate, leflunomide, and hydroxychloroquine. Group2 (L-carnitine group) received, DMARDs plus L-carnitine 500 mg twice daily for 12 weeks. A clinical evaluation was conducted, which included tender joint count (TJC), swollen joint count (SJC), pain intensity quantified via the visual analogue scale (VAS), and morning stiffness duration. Additionally, the Disease Activity Score in 28 joints (DAS28) and functional capability as measured by a modified health assessment questionnaire (MHAQ) were assessed. Laboratory evaluation included C-reactive protein (CRP), STAT3, and TGF-β1 measurement. All evaluations were executed both at baseline and following a 12-week treatment period. After 12 weeks, the L-carnitine group showed significant improvement in morning stiffness, VAS, TJC, CRP, DAS28, and MHAQ compared to baseline. While no significant within-group changes were observed in STAT3, TGF-β1 in the L-carnitine group, STAT3 levels increased significantly in the control group compared to baseline. In conclusion, L-carnitine in combination with DMARDs may enhance clinical outcomes in RA by mitigating systemic inflammation. Nevertheless, its impact on STAT3 and TGF-β1 remains unclear and warrants further research.

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

Trazodone (TRZ) is an antidepressant drug which widely used to treat insomnia, but it has a cardiotoxic effect which considered one of the TRZ limitations. The aim of this study was to investigate the protective role of L-carnitine in rats against TRZ-induced cardiotoxicity, as well as to look into the molecular mechanisms underlying its cardioprotective effects via autophagy-mediated cell death and oxidative stress. Male albino rats were randomized into four experimental groups (n = 8): normal control, TRZ group (TRZ, 20 mg/kg/day), L-carnitine group (LC, 200 mg/kg/day), and Co-treated group (L-carnitine and TRZ). All treatments were administered via oral gavage for 4 weeks. Cardiac enzymes (AST & CK-MB) and serum cardiac troponin T(cTnI) were assessed. Oxidative stress biomarkers in heart tissue (malondialdehyde; MDA, total thiol, and catalase activity) were measured. Autophagy related-genes (ATG-5 and Beclin-1), P62, and TNF-α were quantified. AST and CK-MB and cTnI significantly (p < 0.001) were increased with enhanced autophagy as well as severe histopathological changes which were manifested as scattered chronic inflammatory cells with focal fragmentation of myocardial fibers and loss of nuclei in TRZ-treated group. However, daily administration of L-carnitine (200 mg/kg) for 28 days completely reversed TRZ-induced the increased cardiac enzymes, autophagy, and myocardial inflammatory processes to the normal values. TRZ administration might have the potential to cause cardiotoxic effects that can be treated with L-carnitine administration.

Valproic acid (VPA), a widely prescribed short-chain fatty acid for managing epilepsy, psychiatric conditions, and migraines, offers significant therapeutic benefits despite its concerning toxicity profile. This study extends our previously developed Quantitative Systems Pharmacology (QSP) model by incorporating age, sex, and formulation-related covariates to characterize VPA-induced toxicity across diverse populations. We developed virtual populations representing four demographic groups: toddlers (0-2 years), children (2-14 years), women (14-40 years), and men (14-40 years). Age-appropriate dosing regimens were simulated: 35 mg/kg/day for toddlers, 25 mg/kg/day for children, and 15 mg/kg/day for adults. The model successfully predicted overall incidences of hyperammonemia (29%), hyperlipidemia (54%), and hepatotoxicity (2%), aligning with previously reported clinical data. Notably, our model revealed distinct age-dependent toxicity patterns, with significantly lower incidences in toddlers compared to similar profiles observed in children and adult women. Formulation comparison demonstrated that extended-release formulations showed consistent directional trends toward lower adverse effect incidences compared to delayed-release formulations across all endpoints. The model also quantitatively assessed L-carnitine supplementation (CS) benefits, suggesting that administering L-carnitine at twice the VPA dose (in mg) effectively prevents hyperammonemia and maintains physiological fatty acid levels. This work advances our understanding of VPA-induced toxicity mechanisms across populations and provides evidence-based recommendations for optimizing formulation selection and CS in both pediatric and adult patients receiving VPA therapy.

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

OBJECTIVE: Long-term efficacy data for L-carnitine in managing blood ammonia concentration (BAC) and preventing hepatic encephalopathy recurrence remain limited. This multicenter study examined the long-term effects of L-carnitine on BAC, hepatic encephalopathy-related events, and clinical outcomes in patients with liver cirrhosis. METHODS: Of 444 patients who received L-carnitine between April 2012 and March 2021, we enrolled 242 patients with hyperammonemia or hepatic encephalopathy (median Child-Pugh score 9) in this retrospective study across four institutions. RESULTS: Median BAC decreased from baseline 123 μg/dl to 95.5, 88, 83, 96, and 86 μg/dl at 12, 24, 48, 96, and 192 weeks, respectively (all P  < 0.05). BAC normalization occurred at a median of 100 days overall, but significantly faster at 63 days with initial doses more than 1500 mg/day versus 4.7 months with less than or equal to 1500 mg/day ( P  = 0.0034). Among 113 patients followed for 2 years pre- and posttreatment, hepatic encephalopathy-related hospitalizations decreased dramatically from 183 to 62 ( P  < 0.001). Cumulative hepatic encephalopathy-related event incidence at 6, 12, and 24 months was 15.5, 18.1, and 23.7%, respectively. Model for End-Stage Liver Disease scores improved significantly at 1 year ( P  = 0.0059). Multivariate analysis identified ascites, albumin-bilirubin score, and HCC as independent prognostic factors for survival. Only 2.1% of patients experienced mild, transient gastrointestinal adverse events (all grade 1). CONCLUSION: Long-term L-carnitine administration effectively reduces BAC and hepatic encephalopathy-related hospitalizations with excellent safety. Higher initial doses (>1500 mg/day) achieve more rapid BAC normalization and should be considered for patients with significant hyperammonemia.