L-Carnitine

Women with overweight or obesity face heightened risks of insulin resistance, metabolic syndrome, and type 2 diabetes. L-carnitine, a key mediator of mitochondrial fatty acid transport, has been proposed to improve glycemic regulation, yet evidence in this subgroup remains unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of carnitine supplementation versus placebo on glycemic markers in overweight or obese women. Major databases were searched through October 2025. Weighted mean differences (WMDs) with 95 % confidence intervals (CIs) were calculated using random-effects models. Predefined subgroup analyses explored dose and intervention duration effects. A total of eight studies comprising nine randomized controlled trial (RCT) arms were included. Carnitine supplementation significantly reduced fasting blood sugar (FBS; WMD -2.93 mg/dL, 95 % CI -5.20 to -0.65), fasting insulin (WMD -3.54 μU/mL, 95 % CI -7.00 to -0.07), and HOMA-IR (WMD -0.69, 95 % CI -1.26 to -0.13), but had no significant effect on QUICKI. Subgroup analyses indicated stronger effects at higher doses (≥2000 mg/day) and longer durations (≥12 weeks). Sensitivity analyses confirmed the robustness of findings, with no evidence of publication bias. Carnitine supplementation yields modest but clinically meaningful improvements in fasting glucose, insulin levels, and insulin resistance among overweight and obese women, particularly with higher dosages and longer interventions. These results highlight carnitine's potential as an adjunctive nutritional strategy.

OBJECTIVE: To compare the effects of nutritional supplements on lung function and exercise tolerance in chronic obstructive pulmonary disease (COPD). METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science for randomized controlled trials (RCTs) on nutritional supplements in COPD patients, with the search ending December 31, 2023. Two authors independently screened studies, extracted data, and assessed quality using the Cochrane risk of bias tool. Data were analyzed using RevMan 5.4 and R 4.2.3. RESULTS: Forty-eight studies with 2481 COPD patients were included. Network meta-analysis showed six supplements significantly improved the 6-minute walk distance (6MWD) (all p<0.05), with the top three being: Coenzyme Q10+ Creatine [MD=63, 95% CI (36, 90)], L-carnitine [MD=53, 95% CI (24, 82)], and anabolic steroids [MD=44, 95% CI (7.1, 82)]. Four supplements improved FEV1%(all p<0.05): nanocurcumin [MD=13, 95% CI (7.7, 18)], Vitamin D [MD=7.5, 95% CI (5.1, 9.9)], probiotics [MD=7.1, 95% CI (5.2, 9.1)] and BSO [MD=4.9, 95% CI (1.6, 8.3)]. In pairwise comparisons, nanocurcumin outperformed BSO and Probiotics. Nanocurcumin [MD=12, 95% CI (4.6, 19), p<0.05] improved FEV1/FVC, and nitrate [MD=26, 95% CI (9.7, 42), p<0.05] was effective for the Incremental Shuttle Walk Test (ISWT). Traditional Chinese Medicine (TCM) products [MD=-1.3, 95% CI (-1.9, -0.67)], melatonin (MLT) [MD=-0.9, 95% CI (-1.6, -0.21)] and Calcitriol [MD=-0.66, 95% CI (-0.93, -0.39)] improved the modified Medical Research Council(mMRC) dyspnea score (all p<0.05), with comparable efficacy among them. CONCLUSION: Nutritional supplements improve lung function and exercise endurance in COPD. Coenzyme Q10+Creatine is most effective for endurance, while Nanocurcumin has the greatest impact on lung function. © 2025 Zeng et al.

AIMS: Obesity, one of the most frequent health risks, represents a global public health problem. The potential impact of L-carnitine, a vital nutrient for energy metabolism, on weight loss is worth considering. However, given the inconclusive results from recent meta-analyses on L-carnitine, we conducted an umbrella meta-analysis of placebo-controlled and controlled trials to evaluate the effect of L-carnitine on anthropometric indices. METHODS: Data synthesis: A comprehensive search approach using the relevant keywords was performed in PubMed, Web of Science, Scopus databases, and Google Scholar up to March 2023. Meta-analyses published in English that provided quantitative statistical analyses regarding the effects of L-carnitine on body weight, waist circumference (WC), and body mass index (BMI) were included. A random-effects model and subgroup analysis were performed based on the L-carnitine dosage and study population. RESULTS: A total of 16,352 participants were included. Intervention durations ranged from 8 to 30 weeks, with L-carnitine dosages ranging between 150 and 4000 mg/day. The pooled results of the eight included meta-analyses indicated that L-carnitine supplementation can significantly decrease weight (effect size (ES) = -1.11; 95% confidence intervals (CIs): -1.90, -0.33, p = 0.005; I2 = 90.6%, p < 0.001), BMI (ES = -0.33; 95% CI: -0.61, -0.04, p = 0.026; I2 = 89.8%, p < 0.001), and WC (ES = -1.34; 95% CI: -1.83, -0.85, p < 0.001; I2 = 00.0%, p = 0.442). CONCLUSION: The findings of this umbrella meta-analysis support that supplementation of L-carnitine supplementation can successfully manage weight, BMI, and WC reduction. Therefore, L-carnitine might help treat obesity. PROSPERO Registration Number: CRD42022307951. © 2025 The Author(s). Published by IMR Press.

PURPOSE: Heart failure is a significant complication among patients undergoing hemodialysis, often associated with left ventricular hypertrophy and dysfunction. L-carnitine, crucial for fatty acid metabolism, has shown promise in improving cardiac function. This systematic review and meta-analysis aim to evaluate the safety and efficacy of L-carnitine supplementation in improving cardiac function in hemodialysis patients. METHODOLOGY: A comprehensive search of PubMed, Cochrane, and EMBASE was conducted up to October 3, 2024, to identify relevant studies. The trials assessing the effects of L-carnitine on echocardiographic parameters such as left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), and diastolic function were included. A random-effects model was applied to pool data, and heterogeneity was assessed using the I2 statistic. RESULTS: A total of 23 studies were included in the systematic review, with 7 studies involving 426 participants being meta-analyzed. L-carnitine supplementation significantly improved LVEF (MD = 1.64, 95% CI 0.10-3.17, p = 0.04), with low heterogeneity (I2 = 37%). However, no significant changes were observed for LVMI (MD = -3.19, p = 0.60) or diastolic markers (E/A ratio MD = -0.13, p = 0.47; E/e ratio MD = -0.35, p = 0.67). CONCLUSION: L-carnitine supplementation significantly improves cardiac function, particularly systolic function (LVEF) in hemodialysis patients. However, its effects on LVMI and markers of diastolic function are inconclusive. Future large-scale trials are warranted to further elucidate its role in cardiac function among this population. © 2025. The Author(s), under exclusive licence to Springer Nature B.V.

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

BACKGROUND: Although nutraceutical-based treatments are often offered for erectile dysfunction (ED), their efficacy remains doubtful, and the choice of one substance over the other is challenged by the dearth of head-to-head comparative studies. AIM: We aimed to compare the efficacy of available nutraceutical interventions, alone or in combination with phosphodiesterase type 5 inhibitors (PDE5i), in improving erectile function in men with ED through a network meta-analysis (NMA), which incorporates direct and indirect evidence into one model thus generating a hierarchy of effectiveness. METHODS: PubMed, Scopus, Web of Sciences, and Cochrane Library databases were searched for randomized placebo-controlled trials (RCTs) assessing the effect of any nutraceutical regimen in improving erectile function when compared to each other, placebo, and/or PDE5i in men with ED. Data were included in a random-effects NMA, where efficacy of treatments was ranked by surface under the cumulative ranking curve (SUCRA). Two NMAs were also conducted separately for organic and non-organic ED. Reciprocal comparisons between all treatments were analyzed by league tables. OUTCOMES: The main outcome was the standardized mean difference in the score of the International Index of Erectile Function (IIEF)-5 or IIEF-6. RESULTS: Fifteen RCTs provided information on 1000 men with ED. In the overall NMA, compared to placebo, the combination propionyl L-carnitine (PLC) + acetyl L-carnitine (ALC) + Sildenafil was associated with the highest SUCRA (97%) in improving erectile function score, followed by L-Arginine + Tadalafil (84%), Sildenafil (79%), Tadalafil (72%), and L-Arginine (52%). No other treatment regimen showed efficacy with statistical significance. In patients with organic ED, the efficacy of Sildenafil and Tadalafil was significantly improved by PLC + ALC and L-Arginine, respectively. On the contrary, in non-organic ED, nutraceuticals did not improve the therapeutic performance of daily Tadalafil. CLINICAL IMPLICATIONS: This NMA contributes valuable insights into the potential of nutraceutical interventions for ED. STRENGTHS AND LIMITATIONS: We employed strict inclusion criteria relat

PURPOSE: L-carnitine supplementation has been recommended to improve cardiometabolic health markers in diabetic patients. Our purpose was to assess the dose-dependent effects of l-carnitine supplementation on cardiometabolic risk factors in patients with type 2 diabetes. METHODS: PubMed/Medline, Scopus, and Web of Science were searched until May 2022 for randomized controlled trials that examined the impact of l-carnitine supplementation on cardiometabolic risk factors in adults with type 2 diabetes. The mean difference (MD) and its 95% confidence interval (CI) were estimated utilizing a random-effects model. Nonlinear dose-response associations were modeled with restricted cubic splines. The certainty of evidence was rated using the GRADE approach. FINDINGS: Twenty-one randomized trials with 2041 patients with type 2 diabetes were included. We found that every 1 g/d supplementation with l-carnitine significantly reduced body mass index (MD: -0.37 kg/m2, 95% CI: -0.59, -0.15; I2 =93%, n=13, GRADE=low), HbA1c (MD: -0.16%, 95% CI: -0.32, -0.01; I2 = 94%, n = 18, GRADE = moderate), and low-density lipoprotein cholesterol (MD: -0.11 mmol/L, 95% CI: -0.16, -0.05; I2 = 91%, n = 11, GRADE = high). There were also reductions in serum triglycerides (MD: 0.07 mmol/L), total cholesterol (MD: -0.13 mmol/L), and fasting plasma glucose (MD: -0.17 mmol/L). A U-shaped effect was demonstrated for body mass index, with the largest reduction at 2 g/d. A linear reduction was seen for serum triglycerides, total cholesterol, and fasting plasma glucose up to l-carnitine supplementation of 4 g/d. IMPLICATIONS: L-carnitine supplementation resulted in a small reduction in serum lipids and plasma glucose in patients with type 2 diabetes. However, due to high statistical heterogeneity, the results should be interpreted very cautiously.

SCOPE: Comprehensive assessment of l-carnitine's safety and effectiveness in reducing inflammatory markers in osteoarthritis (OA) patients. METHODS AND RESULTS: Journal articles on l-carnitine for OA are gathered using computer searches of PubMed, Embase, the Cochrane Library, and Web of Science. The kind of literature that is found is restricted to clinical randomized controlled trials (RCTs). The Cochrane Handbook risk of bias assessment tool RevMan 5.4 software is used to conduct a meta-analysis. The systematic assessment comprises eight trials totaling 619 patients; the included studies' quality is mediocre. The study's findings demonstrate that OA patients' Western Ontario and McMaster University (WOMAC) function improves and that treatment efficacy outperforms that of the control group (mean difference [MD] = -7.75, 95% CI [-14.63, -0.86]; Z = 2.21; p = 0.03), WOMAC total (MD = -10.24, 95% CI [-18.97, -1.51]; Z = 2.30; p = 0.02), and visual analogue scale (VAS) pain (MD = -14.01, 95% CI [-16.16, -11.85]; Z = 12.74; p < 0.00001). The studies that are methodically reviewed also discover heterogeneity, which may have resulted from the created pooled data and requires more analysis. CONCLUSION: In patients with OA, l-carnitine effectively decreases clinical signs and symptoms, inflammatory markers, pain, and stiffness indicators, and significantly improves WOMAC and VAS scores. © 2024 Wiley‐VCH GmbH.

BACKGROUND: Pressure ulcers are localized injuries to the skin or the underlying tissue, or both, and are common in older and immobile people, people with diabetes, vascular disease, or malnutrition, as well as those who require intensive or palliative care. People with pressure ulcers often suffer from severe pain and exhibit social avoidance behaviours. The prevention and treatment of pressure ulcers involves strategies to optimize hydration, circulation, and nutrition. Adequate nutrient intake can reduce the risk factor of malnutrition and promote wound healing in existing pressure ulcers. However, it is unclear which nutrients help prevent and treat pressure ulcers. This is an update of an earlier Cochrane Review. OBJECTIVES: To evaluate the benefits and harms of nutritional interventions (special diets, supplements) for preventing and treating pressure ulcers in people with or without existing pressure ulcers compared to standard diet or other nutritional interventions. SEARCH METHODS: We used extensive Cochrane search methods. The latest search was in May 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in people with or without existing pressure ulcers, that compared nutritional interventions aimed at preventing or treating pressure ulcers with standard diet or other types of nutritional interventions. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcome for prevention studies was the proportion of participants who developed new (incident) pressure ulcers. For treatment studies, our primary outcomes were time to complete pressure ulcer healing, number of people with healed pressure ulcers, size and depth of pressure ulcers, and rate of pressure ulcer healing. Secondary outcomes were side effects, costs, health-related quality of life and acceptability. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We included 33 RCTs with 7920 participants. Data for meta-analysis were available from 6993 participants. Pressure ulcer prevention Eleven studies (with 12 arms) compared six types of nutritional interventions for the prevention of pressure ulcers. Compared to standard diet,

PURPOSE: Hypertension stands as a prominent risk factor for cardiovascular disease, making it of utmost importance to address. Studies have shown that L-carnitine supplementation may lower blood pressure (BP) parameters in different populations. Therefore, we have conducted a systematic review and dose-response meta-analysis of published Randomized Controlled Trials (RCTs), including the most recent articles on the effect of L-carnitine supplementation on BP. METHODS: PubMed, ISI Web of Science, Cochrane databases, and Scopus were used to collect RCT studies published up to October 2022 without limitations in language. Inclusion criteria were adult participants and recipients of L-carnitine in oral supplemental forms. The funnel plot test, Begg's test, and Egger's test were used to examine publication bias. FINDINGS: After the search strategy, 22 RCTs (n = 1412) with 24 effect sizes fulfilled the criteria. It was found L-Carnitine supplementation did not have a significant effect on systolic blood pressure (SBP) (mm Hg) (weighted mean difference [WMD] = -1.22 mm Hg, 95% CI: -3.79, 1.35; P = 0.352; I2 = 85.0%, P < 0.001), and diastolic blood pressure (mm Hg) (WMD = -0.50 mm Hg, 95% CI: -1.49, 0.48; P = 0.318; I2 = 43.4%, P = 0.021) in the pooled analysis. Subgroup analyses have shown that L-carnitine supplementation had no lowering effect on SBP in any subgroup. However, there was a significant reduction in diastolic blood pressure in participants with a baseline body mass index >30 kg/m2 (WMD = -1.59 mm Hg; 95% CI: -3.11, -0.06; P = 0.041; I2 = 41.3%, P = 0.164). There was a significant nonlinear relationship between the duration of L-carnitine intervention and changes in SBP (coefficients = -6.83, P = 0.045). IMPLICATIONS: L-carnitine supplementation in adults did not significantly affect BP. But anyway, more studies should be done in this field on different individuals.

BACKGROUND/OBJECTIVES: Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite from L-carnitine and choline (abundant in meat and eggs), is linked to CVD and T2D. This study investigated whether TMAO responses to animal-based foods differ between individuals with and without metabolic syndrome (MetS), in relation to their gut microbiota composition. SUBJECTS/METHODS: In a randomized crossover trial, 12 MetS (≥3 criteria according to the Adult Treatment Panel III: elevated waist circumference, fasting glucose, triglycerides, and blood pressure or reduced HDL cholesterol) and 21 non-MetS subjects consumed two test meals (3 hard-boiled eggs or 170 g meat balls) after overnight fasting, with ≥1-week washout. Blood was collected at baseline and 0.5, 1, 2, 4, and 6 h postprandially; urine was collected over 6 h. Fecal samples (collected pre-first day of intervention) underwent 16S rRNA sequencing. Plasma and urinary TMAO, TMA, choline, and carnitine were quantified using UPLC-MS/MS. RESULTS: MetS subjects exhibited a non-significant trend towards higher incremental AUCs for plasma TMA, TMAO, choline, and carnitine after consuming both foods, with a 30-50% higher urinary TMAO excretion (but similar for TMA) versus non-MetS subjects. This exploratory analysis also indicated that MetS subjects had reduced gut microbial diversity, featuring decreased Blautia glucerasea (butyrate producer) and increased Ruminococcus torques (pro-inflammatory), a profile associated with inflammation but not TMA production. CONCLUSION: No significant increase in plasma methylamines after choline and carnitine challenge was observed in subjects with MetS compared with non-MetS. In MetS subjects (without CVD and T2D), gut microbiota composition was characterized by increased pro-inflammatory bacteria rather than TMAO-generating bacteria. The lack of statistical significance with regard to plasma TMAO response could be due to an insufficient sample size rather than the absence of an effect. Nevertheless, the observed elevation might still be clinically relevant, supported by concurrent differences in microbiota composition. These preliminary findings warrant validation in larger coho

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. © 2025. The Author(s).

Polycystic ovary syndrome is a complex heterogenous reproductive endocrine disorder affecting mainly reproductive age women worldwide. The syndrome primarily is associated with hyperandrogenism, hyperinsulinemia, menstrual irregularity, infertility, hormonal dysregulation and obesity. Here, we examined the effects of Acetyl-L-Carnitine, L-Arginine, CoQ10, (Carnitine + Arginine + CoQ10) and Metformin, alone and in combination, on PCOS management. The trial included 63 females diagnosed with PCOS. The participants were treated with either Carnitine + Arginine + CoQ10 alone (nutraceutical group) or in combination with metformin (combination group) for six months. The outcome measures included demographic, anthropometric, clinical, endocrine, metabolic, quality of Life and stress response of the participants. Over 24 weeks, both treatment regimens improved metabolic, hormonal, and psychological outcomes in women with PCOS. Repeated-measures ANCOVA showed significant group × time interactions for BMI (p < .001, η2 = .220), waist circumference (p < .001, η2 = .314), and hip circumference (p < .001, η2 = .428), favoring the combination group. Hormonal responses varied: DHEAS (p = .045, η2 = .082), FAI (p < .001, η2 = .223), testosterone (p = .004, η2 = .113), and prolactin (p = .032, η2 = .072) declined more in the combination group, whereas LH decreased more in the nutraceutical group (p < .001, η2 = .231). Quality of life improved significantly in both arms, with greater gains in the combination group (p = .037, η2 = .071). Oxidative stress (MDA) also declined significantly in both groups (p = .003), with larger numerical reductions in the combination arm (- 22% vs - 6%), though between-group differences were not significant (p = .329). Both nutraceutical and combination therapies led to significant improvements in metabolic, hormonal, and psychological outcomes in women with PCOS over 24 weeks. Repeated-measures ANCOVA confirmed greater reductions in BMI, waist and hip circumference, DHEAS, FAI, testosterone, and prolactin, as well as superior quality-of-life gains with combination therapy. Nutraceutical therapy exerted stronger effects on LH suppression, while oxid

STUDY QUESTION: Does the addition of three antioxidants to culture media during gamete collection, insemination, and embryo culture increase the clinical pregnancy rate from fresh blastocyst transfers? SUMMARY ANSWER: The clinical pregnancy rate from fresh blastocyst transfers was not increased by the addition of antioxidants to IVF and embryo culture media. WHAT IS KNOWN ALREADY: Addition of antioxidants to media is beneficial in mouse IVF, embryo culture, and cryopreservation. Prospective clinical trials of sibling human oocytes found an improvement in embryo quality and increased pregnancy rates from frozen blastocyst transfers in older patients. STUDY DESIGN, SIZE, DURATION: Single-centre, prospective randomized controlled trial, superiority study comparing media with or without the addition of antioxidants from January 2019 to November 2021. A total of 1482 patients were randomized before egg collection. Patients and their doctors were blinded to the treatment group. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients undergoing IVF/ICSI cycles and intending to undergo a fresh transfer of a single blastocyst were recruited. Exclusion criteria were previous participation in the study, use of cryopreserved oocytes/embryos, artificial oocyte activation, freeze-all cycle, or extraction of sperm from testicular biopsy. Seven hundred thirty-nine patients were randomized to control media and 743 patients to media containing the 'A3' antioxidant combination of acetyl-L-carnitine, α-lipoic acid, and N-acetyl-L-cysteine (treatment group). MAIN RESULTS AND THE ROLE OF CHANCE: The clinical pregnancy rate per randomized patient per cycle from fresh embryo transfer was not different between the control and antioxidant media (26.1% vs 22.9%; P > 0.05; RR 0.88 (95% CI 0.73-1.05)). In the Per Protocol population, which excludes patients with protocol violations or without a fresh transfer due to freeze-all or no embryo available, there was also no difference in between the control and antioxidant media in clinical pregnancy rate (36.7% vs 33.2%; P > 0.05; RR 0.90 (95% CI 0.76-1.07)) and live birth rate (32.4% vs 29.5%, P > 0.05). In the Intention-to-Treat population, antioxi

OBJECTIVE: To observe the effectiveness and safety of Huotujiji prescription for patients with asthenospermia of spleen-kidney yang-deficiency. METHODS: Patients with spleen-kidney-yang deficiency type of asthenospermia were divided into two groups by randomized control method. The patients in the control group were treated with L-carnitine oral solution alone. And the patients in experimental group were treated with Huotujiji prescription. Semen volume, sperm concentration, PR, TCM symptom score and spouse pregnancy were compared between the two groups before and after treatment. RESULTS: A total of 115 patients were included in the study, with 55 in the experimental group and 60 in the control group. In the experimental group, the sperm concentration before and after treatment were (160.71±53.7)×106/mL, (187.19±41.89)×106/mL, and PR were (20.37±9.42)%, (26.7±6.92)%, respectively. PR+NP were (32.06±8.49)% and (34.89±7.25)%. After the treatment, the sperm motility of both groups significantly improved compared to pre-treatment levels (P<0.05). And the experimental group's sperm concentration also showed a significant increase after the treatment (P<0.05). The pregnancy rate of spouses in the control group was 11.67%, which was 29.09% in the experimental group. The pregnancy rate of the spouses in the two groups showed a statistically significant difference (P<0.05). After 12weeks of treatment, the Traditional Chinese Medicine (TCM) symptom scores in the control group did not decrease significantly compared to those before treatment (P> 0.05). In contrast, the TCM symptom scores in the experimental group decreased significantly after treatment (P<0.05). Moreover, compared with the control group, the TCM symptom scores of the experimental group decreased significantly after treatment (P<0.05). CONCLUSION: Huotujiji prescription can safely and effectively improve the sperm quality and vitality of patients with spleen-kidney-yang deficiency type of asthenospermia, improve the symptoms of patients, and increase the pregnancy rate of their spouses, which is worthy of clinical promotion.

BACKGROUND & AIMS: Sarcopenia, characterized by loss of skeletal muscle mass and strength, is a common complication of advanced liver disease and worsens post-transplant outcomes. While L-carnitine may improve muscle mass and function, its impact on sarcopenic liver transplant candidates remains unclear. We aimed to evaluate the impact of L-carnitine supplementation on clinical outcomes and mortality in sarcopenic patients following liver transplantation. METHODS: This randomized, controlled study included 53 HCV-related cirrhotic patients awaiting liver transplantation, divided into three groups: sarcopenia with L-carnitine (n = 18), sarcopenia without L-carnitine (n = 18), and non-sarcopenia (n = 17). Clinical, anthropometric, muscle mass, and biochemical parameters (secondary outcomes) were evaluated before and 6 months after transplantation, along with post-transplant mortality (primary outcome). RESULTS: Sarcopenic patients receiving L-carnitine showed significant post-transplant improvements in ascites, lower limb edema, anthropometric measures (TSF, MAC, handgrip), and biochemical markers (INR, albumin, bilirubin, platelets). Compared to patients without L-carnitine, the supplemented group achieved greater gains in muscle mass index (1 vs. 0 cm2/m2; P = 0.014), TSF (4 vs. -4 mm; P = 0.049), BMI (2 vs. -2 kg/m2; P = 0.026), and reductions in bilirubin (-15.2 vs. 20.5 mmol/L; P = 0.001). Mortality was significantly lower in the L-carnitine group (16.7 % vs. 55.6 %; P = 0.003), with survival rates comparable to non-sarcopenic patients. CONCLUSION: L-carnitine supplementation in sarcopenic liver transplant candidates significantly improved post-transplant outcomes, muscle mass, and survival with mortality rates comparable to non-sarcopenic patients. These findings suggest a potential role of L-carnitine in optimizing pre-transplant care and enhancing post-transplant outcomes in this high-risk population.

BACKGROUND: L-carnitine supplementation is thought to enhance exercise performance, particularly in moderate and high-intensity activities, but evidence supporting this is mixed. This study aimed to assess whether acute L-carnitine tartrate supplementation could improve CrossFit® performance, specifically during the "Cindy" workout, a high-intensity exercise protocol. METHODS: In a randomized, double-blind, placebo-controlled crossover design, 20 trained male recreational CrossFit® athletes completed the "Cindy" workout within a 20 min period after ingesting either 3 g of L-carnitine tartrate or a placebo 90 min before exercise. Performance was measured by total repetitions completed. Secondary outcomes included ratings of perceived exertion (RPE), gastrointestinal issues, and blood pressure (BP) measurements. RESULTS: The results showed that L-carnitine supplementation did not significantly affect the number of repetitions performed (202.4 ± 69.9 vs. 204.5 ± 78.8, p = 0.810) compared to the placebo. There were also no significant differences in RPE (6.3 ± 1.5 vs. 6.9 ± 1.4, p = 0.180) or BP changes between groups. However, 10% of participants reported difficulty sleeping after L-carnitine supplementation. CONCLUSIONS: The findings suggest that 3 g of L-carnitine tartrate does not enhance CrossFit® performance in recreational athletes. Further research is needed to clarify its potential benefits, especially with larger samples and consideration of factors like sex and carbohydrate co-ingestion.

Background: The therapeutic response in Graves' Disease (GD) remains largely unpredictable. Patients often experience persistent symptoms that are poorly correlated with thyroid hormone levels, an undefined treatment duration, and the need for long-term or definitive therapies. Based on the nuclear antagonistic properties of L-carnitine (LCT) on thyroid hormone action and the immunomodulatory role of selenium (Se), we aimed to assess the impact of adding a combined LCT and Se supplement to standard methimazole (MMI) therapy on the biochemical profile and quality of life (QoL) of patients with overt GD. Methods: This multicenter prospective randomized trial enrolled 60 consecutive patients with newly diagnosed overt GD. Participants were randomized to receive either standard treatment with MMI alone (Control Group) or MMI plus the combined LCT/Se supplement (Intervention Group). TSH, fT3, fT4, and TSH-receptor antibodies (TRAb) levels were evaluated every two months for up to 24 months or until spontaneous remission or definitive therapy. At each visit, patients completed a symptom questionnaire addressing the frequency of typical thyrotoxic symptoms. Results: No significant differences were observed between groups in the trend or time-to-normalization of TSH, fT3, and fT4 levels. However, the Intervention Group reached TRAb negativity significantly earlier (HR = 2.35 (1.14-4.81), p = 0.016), with a synergistic interaction with MMI therapy. MMI requirements were consistently lower in the Intervention Group, both in average dosage (p = 0.013) and cumulative dose (p = 0.020). The rate of spontaneous remission was significantly higher (OR = 11.22 (3.35-46.11), p < 0.001). Overall symptom burden did not differ significantly between groups; however, the supplement exerted an independent effect in reducing the severity of tremor, irritability, mood lability, heat intolerance, and exertional dyspnea. Conclusions: Our findings suggest the clinical benefits of adding combined LCT and Se supplementation to MMI in the treatment of overt GD, including shorter disease duration, lower cumulative MMI exposure and earlier TRAb normality, that could positively influence TRAb-rela

OBJECTIVE: To evaluate the clinical efficacy and safety of Wuziyuye Decoction in the treatment of type-II diabetes mellitus (DM) with qi-yin deficiency complicated by asthenospermia. METHODS: We selected 100 cases of type-II DM with qi-yin deficiency complicated by asthenospermia treated in the First Hospital Affiliated to Ningbo University from January 2023 to March 2024, and randomly assigned them to receive Wuziyuye Decoction (the trial group, n = 50) and oral L-carnitine solution (the control group, n = 50) in addition to Western medicine to reduce fasting blood glucose to normal in both groups. After 12 weeks of medication, we followed up the patients for 24 weeks, obtained their semen parameters, traditional Chinese medicine (TCM) syndrome scores and levels of reproductive hormones, and the clinical pregnancy outcomes of their partners, followed by comparison of the data collected between the two groups before and after treatment. RESULTS: After 12 weeks of treatment, the trial group showed significant improvement over the baseline in the percentage of progressive motility (PR%) (［35.5±6.1］% vs ［18.0±4.2］%, P<0.05), sperm concentration (［54.0±33.4］ vs ［40.0±36.1］ × 10⁶/ml, P<0.05), and TCM syndrome score (4.5±2.3 vs 18.5±5.2, P<0.05), but no statistically significant difference in the semen volume (［2.85±0.36］ vs ［2.84±0.59］ ml, P>0.05), while the controls exhibited markedly improved percentage of PR% (［29.5±6.2］% vs ［18.5±4.5］%, P<0.05) and sperm concentration (［45.0±34.1］ vs ［42.0±38.3］ × 10⁶/ml, P<0.05), but no statistically significant difference in the semen volume (［3.04±0.89］ vs ［2.90±0.78］ ml, P>0.05) and TCM syndrome score (17.2±4.5 vs 17.8±4.8, P>0.05). The patients treated with Wuziyuye Decoction achieved even more significant improvement than the controls in the percentage of PR%, sperm concentration and TCM syndrome score (P<0.05), but there were no statistically significant differences in the reproductive hormone levels and clinical pregnancy outcomes between the two groups of patients after treatment (P>0.05). And no severe adverse reactions were observed in either group. CONCLUSION: Wuziyuye Decoction is safe and effective for the treatment

OBJECTIVE: To observe the clinical efficacy and action mechanism of Jujing Decoction (JJD) in the treatment of asthenoteratozoospermia (ATZ) by comparing JJD with combined administration of the antioxidant stress drug and sperm energy metabolism agent. METHODS: According to the inclusion criteria, we enrolled 67 male patients with ATZ in this randomized controlled clinical study and treated them by oral administration of JJD (the JJD group, n = 34) or natural vitamin E combined with L-carnitine solution (the positive control group, n = 33), both for 12 weeks. We collected the semen parameters, sperm DNA fragmentation index (DFI), sperm mitochondrial membrane potential (MMP), seminal plasma reactive oxygen species (ROS) and superoxide dismutase (SOD) levels from the patients, observed the ultrastructure of sperm mitochondria under the transmission electron microscope (TEM) before and after treatment, and analyzed the clinical efficacy and action mechanism of JJD by comparing the data obtained between the two groups. RESULTS: Treatment and follow-up were completed in 60 of the cases, 30 in the JJD and 30 in the positive control group. The total rate of clinical effectiveness was significantly higher in the JJD than in the positive control group (76.8% vs 43.3%, P< 0.05). Compared with the baseline, the percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS), DFI and MMP were significantly improved (P< 0.05), the level of seminal plasma ROS decreased (P> 0.05), and that of SOD remarkably increased (P< 0.05) after treatment with JJD; PMS, MNS, DFI and MMP were also improved (P> 0.05), seminal plasma ROS decreased (P> 0.05) and SOD increased (P< 0.05) in the positive controls after medication. In comparison with the positive controls, the patients treated with JJD showed even more significant improvement in PMS (［29.37 ± 14.56］% vs ［42.68 ± 15.86］%, P< 0.05), MNS (［1.84 ± 1.32］% vs ［3.66 ± 1.72%］%, P< 0.05), DFI (［32.66 ± 5.23］% vs ［16.61 ± 4.20］%, P< 0.05) and MMP (［46.47 ± 9.48］% vs ［61.79 ± 8.61］%, P< 0.05), ROS (［7.08 ± 0.51］ vs ［5.06 ± 0.52］ μmol/L, P> 0.05), and SOD (［100.65 ± 10.59］ vs ［139.05 ± 14.71］ U/ml, P< 0.05). TEM reveale

Transporters of the SLC22 family, such as organic cation transporter 1 (OCT1), possess very broad substrate specificity. It is unclear to what extent the inhibitory potencies of OCT1 depend on the substrate used. Here, we describe a multisubstrate drug cocktail that allows for the simultaneous testing of drug-drug interactions using 8 different victim drugs: fenoterol, salbutamol, sumatriptan, zolmitriptan, ipratropium, trospium, methylnaltrexone, and metformin. There were no significant differences in Michaelis constant (KM) and vmax of the OCT1-mediated uptake of the substrates alone or in the cocktail. Depending on the victim drug analyzed, we observed 6.7-fold differences in the inhibitory potency of fenoterol (IC50 of 0.75 μM for metformin and 5.1 μM for sumatriptan). Similarly, the inhibitory potency of verapamil varied 6.7-fold (IC50 of 1.3 μM for zolmitriptan and 8.7 μM for ipratropium). Two groups of inhibitors showed strong correlations in their victim-dependent inhibitory potencies. Group 1 comprised verapamil, quinidine, fenoterol, and ipratropium, and group 2 comprised metformin, sumatriptan, and trimethoprim. By comparing OCT1 paralogs and orthologs, the broadest substrate spectra were observed for OCT1 and multidrug and toxin extrusion 1, followed by OCT2, multidrug and toxin extrusion 2-K, and OCT3. In contrast, organic cation transporters novel 1 and organic cation transporters novel 2 exhibited very narrow substrate specificity, transporting only L-carnitine and L-ergothioneine, respectively. In conclusion, OCT1 demonstrates substantial differences in inhibitory potencies, depending on the victim drug used. We developed a cocktail approach that enables rapid screening for such differences, facilitating the identification of drug-drug interactions at the early stages of drug development. This approach can be extended to other transporters with broad substrate specificity. SIGNIFICANCE STATEMENT: Polyspecific transporters have a broad substrate-binding cavity with no defined single binding position. Consequently, inhibitors may exhibit different inhibitory potencies depending on the victim drug used for testing. Here, we demonstrate this for orga

As part of a narrative review of various publications describing the clinical use of urine- and plasma-based drug transporter biomarkers, it was determined that the utilization of coproporphyrin I, a hepatic organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 biomarker, has been reported for 28 different drug-drug interaction (DDI) perpetrator drugs. Similarly, biomarkers for liver organic cation transporter 1 (isobutyryl-l-carnitine, N = 7 inhibitors), renal organic cation transporter 2 and multidrug and toxin extrusion proteins (N1-methylnicotinamide, N = 13 inhibitors), renal organic anion transporter (OAT) 1 and 3 (pyridoxic acid, N = 7 inhibitors), and breast cancer resistance protein (riboflavin, N = 3 inhibitors) have also been described. Increased use of biomarkers has also been accompanied by modeling efforts to enable DDI predictions and development of multiplexed methods to facilitate their bioanalysis. Overall, there is consensus that exploratory biomarkers such as coproporphyrin I can be integrated into decision trees encompassing in vitro transporter inhibition data, DDI risk assessments, and follow-up Phase 1 studies. Therefore, sponsors can leverage biomarkers to evaluate dose-dependent inhibition of selected transporters, use them jointly with drug probes to deconvolute DDI mechanisms, and integrate in vitro data packages to establish calibrated (biomarker informed) DDI risk assessment cutoffs. Although transporter biomarker science has progressed, reflected by its inclusion in the recently issued International Council for Harmonisation DDI guidance document (M12), some biomarkers still require further validation. There is also a need for biomarkers that can differentiate specific transporters (e.g., OATP1B3 vs OATP1B1 and OAT1 vs OAT3). © 2025, The American College of Clinical Pharmacology.

Severe valproic acid (VPA) overdose is characterized by coma (sometimes with cerebral oedema), respiratory depression, hypotension and metabolic abnormalities. Traditional management of VPA poisoning has been limited to gastrointestinal decontamination, L-carnitine supplementation and, in severe cases, haemodialysis. Recently, interest has developed in the use of carbapenem antibiotics as an adjunctive therapy in patients with severe VPA poisoning. Carbapenems inhibit acylpeptide hydrolase, the enzyme responsible for reconstituting VPA from VPA-glucuronide, and transiently promote distribution of VPA into erythrocytes. In patients receiving VPA therapeutically, carbapenems lower VPA concentrations abruptly, dramatically, and for a sustained period. This article discusses the possibility of exploiting this pharmacokinetic drug-drug interaction in patients with or at risk of severe VPA poisoning. © 2025 British Pharmacological Society.

A novel multi-functional micelle delivery system was developed for enhancing the oral absorption of paclitaxel (PTX). The delivery carriers were constructed by modifying chitosan-stearic acid (CS-SA) micelles with L-carnitine (LC) and co-encapsulating quercetin (Que), and the PTX-loaded micelles were prepared by film-sonication dispersing technique. The as-prepared micelles showed homogeneous spherical shapes with a small particle size of 148.3 ± 1.7 nm, high drug loading of 7.05% and low critical micelle concentration (CMC) of 16.89 µg/ml. Compared to the in-house PTX formulation similar to the commercial injection Taxol™, the target PTX-loaded micelles had obvious sustained-release effects and exhibited an oral relative bioavailability of 168.08%. The cellular uptake studies of Caco-2 cells confirmed the micellar modification of LC and the co-loading of Que played important roles in promoting the absorption of drug loaded in micelles. The CYP3A4 enzyme test demonstrated the micelles had an inhibitory effect on the metabolic enzyme due to the presence of Que. These findings confirmed the potential of the multi-functional chitosan polymeric micelles based on synergistic effect as an effective oral delivery system. © 2024. Controlled Release Society.

Abrocitinib is an oral Janus kinase 1 (JAK1) inhibitor currently approved in the United Kingdom for the treatment of moderate-to-severe atopic dermatitis (AD). As patients with AD may use medications to manage comorbidities, abrocitinib could be used concomitantly with hepatic and/or renal transporter substrates. Therefore, we assessed the potential effect of abrocitinib on probe drugs and endogenous biomarker substrates for the drug transporters of interest. In vitro studies indicated that, among the transporters tested, abrocitinib has the potential to inhibit the activities of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporter 3 (OAT3), organic cation transporter 1 (OCT1), and multidrug and toxin extrusion protein 1 and 2K (MATE1/2K). Therefore, subsequent phase I, two-way crossover, open-label studies in healthy participants were performed to assess the impact of abrocitinib on the pharmacokinetics of the transporter probe substrates dabigatran etexilate (P-gp), rosuvastatin (BCRP and OAT3), and metformin (OCT2 and MATE1/2K), as well as endogenous biomarkers for MATE1/2K (N1 -methylnicotinamide (NMN)) and OCT1 (isobutyryl-L -carnitine (IBC)). Co-administration with abrocitinib was shown to increase the plasma exposure of dabigatran by ~ 50%. In comparison, the plasma exposure and renal clearance of rosuvastatin and metformin were not altered with abrocitinib co-administration. Similarly, abrocitinib did not affect the exposure of NMN or IBC. An increase in dabigatran exposure suggests that abrocitinib inhibits P-gp activity. By contrast, a lack of impact on plasma exposure and/or renal clearance of rosuvastatin, metformin, NMN, or IBC suggests that BCRP, OAT3, OCT1, and MATE1/2K activity are unaffected by abrocitinib. © 2022 Pfizer Inc. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

There is a growing interest in using endogenous compounds as drug transporter biomarkers to facilitate drug-drug interaction (DDI) risk assessment in early phase I clinical trials. Compared to other drug transporters, however, no valid biomarker for hepatic organic cation transporter (OCT) 1 has been described to date. The present work represents the first report of an endogenous compound, isobutyryl-l-carnitine (IBC), as a potential clinical OCT1 biomarker for DDI assessment. A hydrophilic interaction chromatography (HILIC)-mass spectrometry/high resolution mass spectrometry (MS/HRMS) assay with a simple sample preparation method was developed. The assay is capable of simultaneously quantifying multiple endogenous compounds, including IBC, thiamine, N1-methylnicotinamide (1-NMN), creatinine, carnitine, and metformin, which is a probe for OCT1 and OCT2 and MATE1 and MATE2K (multidrug and toxin extrusion proteins) in clinical studies. The HRMS assay was fit-for-purpose validated in human plasma and demonstrated good linearity, accuracy, and precision for all analytes. It was further applied to two phase I clinical trials to evaluate potential biomarkers for OCT1 and additional cation transporters (renal OCT2, MATE1, and MATE2K). The clinical data demonstrated that plasma IBC changes correlated well with in vitro data and supported its use as a liver OCT1 biomarker. The described HILIC-MS/HRMS assay can be used as a "biomarker cocktail" to simultaneously assess clinical DDI risk for the inhibition of OCT1/2 and MATEs in clinical studies with new drug candidates.

PURPOSE: The aim of the present study was to evaluate the effect of acetyl-l-carnitine (ALC) and N-acetyl cysteine (NAC) on ionizing radiation (IR)-induced cytotoxicity and change in DNA damage-related genes in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. METHODS: HEI-OC1 cells were irradiated with 5 Gy radiation and treated by eight combinations of NAC and/or ALC: control, NAC, ALC, IR, NAC + IR, ALC + NAC, ALC + IR, and ALC + NAC + IR. Cell viability, apoptotic cell death, and DNA damage were measured at the 72nd hour. Eighty-four IR-induced DNA-damage-related genes were determined by RT-PCR gene array and >10-fold changes were considered significant. RESULTS: IR decreased cell viability by about 50% at 72 hours of incubation. In particular, the ALC and/or NAC combination before IR protected the HEI-OC1 cells (p < .05). Single and combination treatment prior to IR led to lower apoptotic cell death (p < .05). There was a significant lower DNA damage in ALC + NAC + IR group compared to IR group (p < .05). Expressions of Brca2, Xpc, Mlh3, Rad51, Xrcc2, Hus1, Rad9a, Cdkn1a, Gadd45a which are the DNA-repair genes were found to be significantly higher in NAC + ALC + IR group than those in individual treatment of ALC or NAC. CONCLUSIONS: ALC and/or NAC treatment prior to IR led to higher cell viability and lower apoptotic cell damage compared to the IR group. The results of the study show that the ALC + NAC combination treatment inhibits DNA damage and induces DNA-repair genes to repair radiation damage, and this combination treatment is more effective against radiation-induced DNA damage than NAC or ALC therapy individually.

Cyclosporine A (CsA) is an immunosuppressive drug commonly used in organ transplant patients to prevent allograft rejections. Ketamine is a pediatric anesthetic that noncompetitively inhibits the calcium-permeable N-methyl-d-aspartic acid receptors. Adverse drug-drug interaction effects between ketamine and CsA have been reported in mammals and humans. However, the mechanism of such drug-drug interaction is unclear. We have previously reported adverse effects of combination drugs, such as verapamil/ketamine and shown the mechanism through intervention by other drugs in zebrafish embryos. Here, we show that ketamine and CsA in combination produce developmental toxicity even leading to lethality in zebrafish larvae when exposure began at 24 h post-fertilization (hpf), whereas CsA did not cause any toxicity on its own. We also demonstrate that acetyl l-carnitine (ALCAR) completely reversed the adverse effects. Both ketamine and CsA are CYP3A4 substrates. Although ketamine and CsA independently altered the expression of the hepatic marker CYP3A65, a zebrafish ortholog of human CYP3A4, both drugs together induced further increase in CYP3A65 expression. In the presence of ALCAR, however, CYP3A65 expression was normalized. ALCAR has been shown to prevent ketamine toxicity in mammal and zebrafish. In conclusion, CsA exacerbated ketamine toxicity and ALCAR reversed the effects. These results, providing evidence for the first time on the reversal of the adverse effects of CsA/ketamine interaction by ALCAR, would prove useful in addressing potential occurrences of such toxicities in humans. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Administration of Aacetylsalicylic acid in children with viral infections (influence B, chickenpox) can be related with development of Reye syndrome - severe encephalopathy and liver insufficiency with mortality in 50% of cases. During Reye syndrome most important is deficiency of carnitine and hepatocyte damage. Decreased amount of carnitine impairs the energy function of mitochondria and gluconeogenesis as well as production of urea. As a result develops toxic encephalopathy and liver insufficiency. The goal of the research was assessment of efficacy of L-Carnitine, Corvitin and their combination on functional state of liver in experimental model of Reye Syndrome in rats. The study was performed on mature white male Wistar rates with body mass 150-180g. 50 rats were randomly divided into 5 groups (10 rats in each group). The model of Reye syndrome was induced in accordance with A.Vengersky's method. Intraperitoneal administration of 4-pentenoic acid was performed once daily during seven days, the used dosage was 20mg/kg. The treatment of toxic hepatitis was carried with intraperitoneal administration of L-Carnitine 300mg/kg, Corvitine 100mg/kg and concurrent administration of these drugs. Monotherapy with Corvitin and L-Carnitin successfully improved liver function and equally decreased indicators of hepatocyte's cytolyses and increased levels of glucose and urea. The markers of cholestasis was slightly more improved during use of L-Carnitine. Simultaneous use of both drugs was effective in rats with Reye syndrome, indicators of liver damage normalized and herewith, no mortality outcome was observed. The most pronounced hepatoprotective effect of concurrent administration of L-Carnitine and Corvitin may be due to synergic action of these drugs and such regime can be recommended for correction of liver function during Reye syndrome.

The long-term administration of valproic acid (VPA) may decrease the plasma concentrations of l-carnitine in epileptic patients. l-Carnitine is essential for the β-oxidation of fatty acids. The aim of this study is to determine whether endogenous l-carnitine affects the pharmacokinetics of VPA in l-carnitine-deficient (CD) rats. An l-carnitine deficiency was induced in rats using sodium pivalate. The pharmacokinetics of VPA were examined following its intravenous or oral administration to rats. The plasma and urine concentrations of VPA and its metabolites were determined using gas chromatography-mass spectrometry methods. Plasma VPA concentrations were slightly higher in CD rats than in control rats, whereas no significant differences were observed in the area under the curve or mean residence times of VPA between the 2 groups. After i.v. administration, the slope of the elimination phase (k) was significantly higher in CD rats than in control rats (p < 0.01). Some of the β-oxidation metabolites of VPA in plasma and urine decreased, while the glucuronide metabolites of VPA in urine increased complementarily in CD rats. Based on these results, it was concluded that hypocarnitinemia could affect the pharmacokinetics of VPA.