L-카르니틴 (체중)

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.

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: 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.

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.

OBJECTIVE: To explore the comparative effectiveness of nutritional supplements in improving glycolipid metabolism and endocrine function in patients with polycystic ovary syndrome (PCOS). METHOD: Randomized controlled clinical trials on the effects of nutritional supplements in PCOS patients were searched in PubMed, Embase, Cochrane Library, and Web of Science from their establishments to March 15, 2023. Then, literature screening, data extraction, and network meta-analysis were performed. This study was registered at PROSPERO (registration number CRD 42023441257). RESULT: Forty-one articles involving 2,362 patients were included in this study. The network meta-analysis showed that carnitine, inositol, and probiotics reduced body weight and body mass index (BMI) compared to placebo, and carnitine outperformed the other supplements (SUCRAs: 96.04%, 97.73%, respectively). Omega-3 lowered fasting blood glucose (FBG) (SUCRAs: 93.53%), and chromium reduced fasting insulin (FINS) (SUCRAs: 72.90%); both were superior to placebo in improving insulin resistance index (HOMA-IR), and chromium was more effective than Omega-3 (SUCRAs: 79.99%). Selenium was potent in raising the quantitative insulin sensitivity index (QUICKI) (SUCRAs: 87.92%). Coenzyme Q10 was the most effective in reducing triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels (SUCRAs: 87.71%, 98.78%, and 98.70%, respectively). Chromium and probiotics decreased TG levels, while chromium and vitamin D decreased TC levels. No significant differences were observed in high-density lipoprotein cholesterol (HDL-C), total testosterone (TT), sex-hormone binding globulin (SHBG), and C-reactive protein (CRP) between nutritional supplements and placebo. CONCLUSION: Carnitine was relatively effective in reducing body mass, while chromium, Omega-3, and selenium were beneficial for improving glucose metabolism. Meanwhile, coenzyme Q10 was more efficacious for improving lipid metabolism. However, publication bias may exist, and more high-quality clinical randomized controlled trials are needed. © 2023 Hu et al.

L-carnitine supplementation may be beneficial in improving inflammatory conditions and reducing the level of inflammatory cytokines. Therefore, according to the finding of randomized controlled trials (RCTs), the systematic review and meta-analysis aimed to investigate the effect of L-carnitine supplementation on inflammation in adults. To obtain acceptable articles up to October 2022, a thorough search was conducted in databases including PubMed, ISI Web of Science, the Cochrane Library, and Scopus. A random-effects model was used to estimate the weighted mean difference (WMD). We included the 48 RCTs (n = 3255) with 51 effect sizes in this study. L-carnitine supplementation had a significant effect on C-reactive protein (CRP) (p < 0.001), interleukin-6 (IL-6) (p = 0.001), tumor necrosis factor-α (TNF-α) (p = 0.002), malondialdehyde (MDA) (p = 0.001), total antioxidant capacity (TAC) (p = 0.029), alanine transaminase (ALT) (p < 0.001), and aspartate transaminase (AST) (p < 0.001) in intervention, compared to the placebo group. Subgroup analyses showed that L-carnitine supplementation had a lowering effect on CRP and TNF-α in trial duration ≥ 12 weeks in type 2 diabetes and BMI ≥ 25 kg/m2. L-carnitine supplementation reduced ALT levels in overweight and normal BMI subjects at any trial dose and trial duration ≥ 12 weeks and reduced AST levels in overweight subjects and trial dose ≥ 2 g/day. This meta-analysis revealed that L-carnitine supplementation effectively reduces the inflammatory state by increasing the level of TAC and decreasing the levels of CRP, IL-6, TNF-α and MDA in the serum. © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. Several clinical trials have investigated the influence of carnitine on metabolic variables in PCOS, but have yielded conflicting results. This study aimed to summarize the clinical evidence of the effects of carnitine on weight management, glycemic and serum lipids controls in women with PCOS by conducting a meta-analysis of randomized control trials (RCTs). PubMed, Embase, Web of Sciences, Scopus, and the CENTRAL database were searched from inception to March 2021 for eligible articles. Study selection and assessment of quality were conducted independently by two investigators. Effect sizes for each outcome were reported with the weighted mean differences (WMDs) and 95% confidence intervals (CIs). The statistical heterogeneity of the included clinical trials was tested using the I2 statistic. Six studies with 672 PCOS participants were included for meta-analysis. Our results revealed that carnitine supplements significantly decreased total cholesterol, low-density lipoprotein-cholesterol, triglycerides, body weight, body mass index, hip circumference, and waist circumference (All p < .05). In addition, carnitine intervention also improved the levels of high-density lipoprotein cholesterol. However, no significant changes were seen in glucose homeostasis parameters. These results were stable after sensitivity analysis, and no significant publication biases were detected. Based on current evidence, carnitine supplementation in women with PCOS had beneficial effects on weight loss and lipid profiles. Further large-scale, well-designed RCTs are required to confirm these results.

Liver fat accumulation is an important pathophysiological feature of non-alcoholic fatty liver disease that may be modulated by dietary supplements (DS). A systematic search of the literature was conducted for randomized controlled trials (RCTs) pertaining to the effect of a DS on liver fat as assessed using quantitative tomographic imaging in human adults. Where feasible, data were pooled, and meta-analyses conducted using random-effect model. Quality assessment was done according the Cochrane Collaboration's tool for assessing risk of bias. Twenty RCTs, involving 1171 overweight and obese adults, of which 36% were females, with or without comorbidities, were included. Only RCTs assessing omega-3 fatty acids (n = 4) and resveratrol (n = 4) qualified for meta-analysis. Results did neither favor omega-3 (effect size -1.17; weighted mean difference (WMD) (95% confidence interval (CI)) -3.62, 1.28; p < 0.001) nor resveratrol supplementation (0.18; 95% CI -1.08, 1.43; p = 0.27). The findings of the qualitatively summarized RCTs suggested that catechins (n = 1), Lactobacillus reuteri (n = 1), and carnitine (n = 1) may reduce liver fat. All other DS did not show any influence. The current evidence is scarce, of limited quality and does not support DS use to reduce liver fat. Further well-designed trials are warranted.

BACKGROUND: Multiple sclerosis (MS) is a common demyelinating disease of the central nervous system. Although the exact pathogenesis remains unknown, the leading theory is that it results from immune system dysregulation. Approved disease-modifying therapy appears to modulate the immune system to improve MS-related outcomes. There is substantial interest in the ability of dietary interventions to influence MS-related outcomes. This is an update of the Cochrane Review 'Dietary interventions for multiple sclerosis' (Farinotti 2003; Farinotti 2007; Farinotti 2012). OBJECTIVES: To assess the effects of dietary interventions (including dietary plans with recommendations for specific whole foods, macronutrients, and natural health products) compared to placebo or another intervention on health outcomes (including MS-related outcomes and serious adverse events) in people with MS. SEARCH METHODS: On 30 May 2019, we searched CENTRAL, MEDLINE, Embase, and Web of Science. We also searched ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (ICTRP), and Networked Digital Library of Theses and Dissertations (NDLTD). We checked reference lists in identified trials and requested information from trial authors to identify any additional published or unpublished data. SELECTION CRITERIA: We included any randomized controlled trial (RCT) or controlled clinical trial (CCT) examining the effect of a dietary intervention versus placebo or another intervention among participants with MS on MS-related outcomes, including relapses, disability progression, and magnetic resonance imaging (MRI) measures. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Planned primary outcomes were number of participants experiencing relapse and change in disability progression, according to a validated disability scale at the last reported follow-up. Secondary outcomes included MRI activity, safety, and patient-reported outcomes. We entered and analysed data in Review Manager 5. MAIN RESULTS: We found 41 full-text articles examining 30 trials following full-text review. Participants were adults with MS, defined by est

BACKGROUND AND AIM: Clinical evidence which investigated the effects of l-carnitine, a vitamin-like substance, on weight loss had led to inconsistent results. This study therefore aimed to examine the effect of l-carnitine supplementation on body weight and composition by including the maximum number of randomized controlled trials (RCTs) and to conduct a dose-response analysis, for the first time. METHODS AND RESULTS: Online databases were searched up to January 2019. In total, 37 RCTs (with 2292 participants) were eligible. Meta-analysis showed that l-carnitine supplementation significantly decreased body weight [Weighted mean difference (WMD) = -1.21 kg, 95% confidence interval (CI): -1.73, -0.68; P < 0.001], body mass index (BMI) (WMD = -0.24 kg/m2, 95% CI: -0.37, -0.10; P = 0.001), and fat mass (WMD = -2.08 kg, 95% CI: -3.44, -0.72; P = 0.003). No significant effect was seen for waist circumference (WC) and body fat percent. The meta-analysis of high-quality RCTs only confirmed the effect on body weight. A non-linear dose-response association was seen between l-carnitine supplementation and body weight reduction (P < 0.001) suggesting that ingestion of 2000 mg l-carnitine per day provides the maximum effect in adults. This association was not seen for BMI, WC and body fat percent. CONCLUSIONS: l-carnitine supplementation provides a modest reducing effect on body weight, BMI and fat mass, especially among adults with overweight/obesity.

OBJECTIVE: Weight loss in older men with obesity and hypogonadism accelerates musculoskeletal decline, yet the underlying metabolic mechanisms remain unclear. Testosterone replacement therapy (TRT), when added to lifestyle therapy (LT), mitigates this decline, but its metabolic basis has not been defined. We examined skeletal muscle metabolomic adaptations to LT with or without TRT, focusing on glycolysis, the pentose phosphate pathway (PPP), the tricarboxylic acid (TCA) cycle, and carnitine metabolism to identify dominant pathways of metabolic adaptation. DESIGN: Randomized, double-blind, placebo-controlled trial (LITROS). METHODS: Eighty-three men aged 65 years or older with obesity (BMI ≥30 kg/m2), hypogonadism (testosterone <10.4 nmol/L), and frailty (Physical Performance Test score ≤31) were randomized to 26 weeks of LT plus TRT (LT+TRT) or LT plus placebo (LT+Pbo). A metabolomic substudy was performed in 44 participants, who underwent serial biopsies of the vastus lateralis for targeted LC-MS/MS analysis of intermediates in glycolysis, PPP, TCA cycle, and carnitine metabolism. RESULTS: Among the pathways examined, only glycolysis showed a consistent and significant response to LT+TRT versus LT+Pbo (between-group p = 0.005). This response was characterized by increases in preparatory (G6P/F6P, FBP) and payoff (3PG, 2PG, PEP) intermediates, along with higher lactate concentrations, whereas pyruvate remained stable. The PPP showed limited changes, and neither the TCA cycle nor carnitine metabolites exhibited consistent patterns. In LT+TRT, the glycolysis factor score was positively correlated with VO2peak (r=0.47, p = 0.04) and inversely correlated with triglycerides (r=-0.52, P = 0.01) and the metabolic syndrome score (r=-0.48, p = 0.02). No significant correlations were observed in LT+Pbo. CONCLUSIONS: TRT during LT selectively enhances skeletal muscle glycolysis, identifying glycolic activation as the dominant metabolic adaptation in this mechanistic study. By increasing glycolytic flux under calorie restriction, TRT may produce efficient ATP generation while conserving amino acids, supporting muscle and bone preservation and improving aerobic and cardiome

BACKGROUND: Treatment related toxicities for management of cancer lead to significant deterioration in the quality of life, increased morbidity, hospital admissions, and increased treatment interruptions. We carried out this study, to reduce treatment related toxicities without compromising treatment efficacy. OBJECTIVES: Evaluate L-carnitine in reducing toxicities in HNSCC patients undergoing concurrent chemoradiation. METHODOLOGY: Study conducted in the Department of Radiotherapy tertiary care center in Northern India from August 2018 to 2020. All patients were randomized into the study arm and control arm; the study arm received oral L-carnitine 500 mg thrice daily, with symptomatic treatment for chemoradiotherapy-induced toxicity. The control arm received only symptomatic treatment for chemoradiation-induced toxicities. Toxicity assessment was done biweekly during treatment using RTOG (Radiation Therapy Oncology Group) criteria for toxicity assessment. Nutritional assessment was done by comparing hemoglobin, albumin, and weight loss during treatment. Fatigue was assessed using the Brief Fatigue Inventory (BFI) and the quality of life was assessed using the EORTC-QLQ-C30 questionnaire. Response evaluation for the primary tumor and neck nodes was done using RECIST 1.1. RESULTS: Significant decrease in severity and delay in onset of dermatitis, mucositis, laryngeal reactions, and dysphagia were observed; however, no such benefit was seen in xerostomia. Treatment response was comparable in both arms. Mean post-treatment BFI in the test arm versus control arm was 37.22 and 52.24 (p-value 0.042), respectively. 28.75% of patients in the control arm and none in the study arm had albumin levels < 3.4 g/dL. Median weight loss in the test arm was 5.2% and in the control arm was 7.4%. Hospital admission was significantly less in the test arm. CONCLUSION: L-carnitine can be given to HNSCC patients receiving concurrent chemoradiation to lessen treatment related toxicity, but larger, multicentric randomized trials required to substantiate this conclusion. © 2025 Wiley Periodicals LLC.

AIM: We aimed to assess the effects of acarbose and vildagliptin on levels of plasma trimethylamine N-oxide (TMAO) and its metabolic precursor in overweight and obese patients with type 2 diabetes mellitus and ascertain the correlation between TMAO and characteristics of diabetes. METHODS: This study employed a randomized, controlled, open interventional design and recruited 100 participants who were overweight/obese and newly diagnosed with type 2 diabetes at Pinggu Hospital, Beijing Friendship Hospital, Capital Medical University, between December 2016 and December 2017. Using the sealed envelope method, participants were randomly allocated (1:1) to either the acarbose group (n = 50) or the vildagliptin group (n = 50). Participants received 6 months of treatment with oral glucose-lowering medications, acarbose, or vildagliptin. Anthropometric measurements, including height, weight, waist and hip circumferences, and blood pressure, were recorded at baseline and 3 and 6 months after the intervention. Blood samples were obtained to assess blood glucose, insulin, gut hormones, TMAO, and metabolic precursors. Data analysis focused on intragroup and intergroup variations. RESULTS: Baseline characteristics, including weight, BMI, waist and hip circumferences, blood glucose, and gut hormone levels, were comparable between the acarbose and vildagliptin groups (all p>0.05). Intragroup analysis indicated a significant decrease in TMAO levels at 6 months compared with baseline (adjusted p<0.05). L-carnitine and γ-butyrobetaine levels significantly increased at 6 months (all adjusted p<0.05), whereas betaine and choline levels remained non-significant throughout the intervention. Intergroup analysis revealed significantly lower TMAO levels in the acarbose group at 6 months (p<0.05), without significant intergroup differences in L-carnitine, γ-butyrobetaine, choline, or betaine levels (all p>0.05). In the acarbose group, positive correlations were observed between changes in TMAO and BMI, waist circumference, postprandial glucose, fasting insulin, fasting C-peptide, and HOMA-IR from baseline to 6 months (p<0.05). CONCLUSIONS: Both acarbose and vildagliptin treatments signif

Obesity, a chronic disease with pandemic proportions, is recognized as a major risk factor for cardiometabolic disorders due to its association with atherogenic dyslipidemia, a common characteristic attributed to visceral adiposity in patients with obesity. Atherogenic and visceral-obesity indices have been conceded as surrogate cardiovascular diseases (CVD) indicators surpassing the conventional markers due to stronger predictive power for obesity-induced cardiometabolic risk and CVD mortality rate. Nutraceuticals have been suggested as emerging approaches to counteract obesity-associated cardiometabolic disorders. Considering the evidence addressing the ameliorating effects of either L-carnitine or biotics on metabolic indices, also the reports addressing higher efficacy of concomitant supplementation versus single-therapies, this clinical trial was conducted to assess the effects of L-carnitine + multi-species/multi-strain synbiotic combined supplementation compared to L-carnitine mono-therapy on atherogenic-indices, body composition, visceral obesity, and appetite sensations in 46 metabolically healthy women with obesity, randomly assigned to co-supplementation (L-carnitine-tartrate (2 × 500 mg/dl) + synbiotic (one capsule/day)) or mono-therapy (L-carnitine-tartrate (2 × 500 mg/dl) + maltodextrin (one capsule/day)) groups for 8 weeks. L-carnitine + synbiotic co-supplementation led to a significantly greater reduction in atherogenic-indices including atherogenic-index-of-plasma (AIP), Castelli's-risk-index-I (CRI-I), Castelli's-risk-index-II (CRI-II), atherogenic-coefficient (AC), lipoprotein-combine index (LCI), systolic blood pressure (SBP), fat-mass (FM) weight/percent, visceral-adiposity index (VAI), waste-to-height ratio (WHtR), body-adiposity index (BAI), and appetite sensation scores compared to L-carnitine mono-therapy. L-carnitine + synbiotic combined supplementation was more efficient in improving atherogenic-indices as cardiovascular risk markers, body composition, visceral obesity, and appetite sensations in metabolically healthy women with obesity. Therefore, simultaneous supplementation of L-carnitine + synbiotic might be considered a promising

DESCRIPTION OF THE WORK: Leptin is a reliable predictive and surrogate marker of the efficacy of multitargeted treatment of cancer cachexia. PURPOSE: To the best of our knowledge, no study has assessed the predictive role of biomarkers in establishing the effectiveness of anti-cachectic treatment, which remains a complex issue. Herein, we aimed to find a marker that can detect early response to anti-cachectic treatment. PATIENTS AND METHODS: From January 2012 to December 2022, all consecutive eligible advanced cancer patients with cachexia were prospectively enrolled in an exploratory and validation cohort according to eligibility criteria. All patients received a combined anti-cachectic treatment consisting of megestrol acetate plus celecoxib plus l-carnitine plus antioxidants that showed efficacy in a previous phase III randomized study. Primary endpoints were an increase in lean body mass (LBM), a decrease in resting energy expenditure (REE), a decrease in fatigue, and improvement in global quality of life. RESULTS: A total of 553 consecutive patients were recruited. Twenty patients dropped out, equally distributed over the exploratory (11 patients) and validation (9 patients) cohorts, for early death due to disease progression. Then, 533 patients were deemed assessable. Leptin level changes inversely correlated with circulating levels of inflammatory mediators and reflected the improvement of body composition, energy metabolism, functional performance, and quality of life. At multivariate regression analysis, at week 8, leptin change was an independent predictor of LBM, skeletal muscle index (SMI), grip strength increase, and REE; at week 16, leptin change was an independent predictor of the same parameters and improvement in Eastern Cooperative Oncology Group performance status. The ability of leptin to predict changes in LBM, SMI, REE, and grip strength was superior to that of other inflammatory markers when comparing the receiver operating curves. Moreover, increasing delta leptin values were associated with significantly better outcomes in LBM, SMI, REE, grip strength, and fatigue. CONCLUSIONS: Leptin is a reliable predictive marker for multitargeted ant

BACKGROUND: Severe acute malnutrition (SAM) is a major public health concern among low- and middle-income countries, where the majority of the children encountering this acute form of malnutrition suffer from environmental enteric dysfunction (EED). However, evidence regarding the effects of L-carnitine supplementation on the rate of weight gain and EED biomarkers in malnourished children is limited. OBJECTIVES: We aimed to investigate the role of L-carnitine supplementation on the rate of weight gain, duration of hospital stays, and EED biomarkers among children with SAM. METHODS: A prospective, double-blind, placebo-controlled, randomized clinical trial was conducted at the Nutritional Rehabilitation Unit (NRU) of Dhaka Hospital, International Centre for Diarrheal Disease Research, Bangladesh. Children with SAM aged 9-24 mo were randomly assigned to receive commercial L-carnitine syrup (100 mg/kg/d) or placebo for 15 d in addition to standard of care. A total of 98 children with Weight-for-Length-z-score (WLZ) < -3 Standard deviation were enrolled between October 2021 and March 2023. Analyses were conducted on an intention-to-treat basis. RESULTS: The primary outcome variable, "rate of weight gain," was comparable between L-carnitine and placebo groups (2.09 ± 2.23 compared with 2.07 ± 2.70; P = 0.973), which was consistent even after adjusting for potential covariates (age, sex, Weight-for-Age z-score, asset index, and WASH practices) through linear regression [ß: 0.37; 95% confidence interval (CI): -0.63,1.37; P = 0.465]. The average hospital stay was ∼4 d. The results of adjusted median regression showed that following intervention, there was no significant difference in the EED biomarkers among the treatment arms; Myeloperoxidase (ng/mL) [ß: -1342.29; 95% CI: -2817.35, 132.77; P = 0.074], Neopterin (nmol/L) [ß: -153.33; 95% CI: -556.58, 249.91; P = 0.452], alpha-1-antitrypsin (mg/mL) [ß: 0.05; 95% CI: -0.15, 0.25; P = 0.627]. Initial L-carnitine (μmol/L) levels (median, interquartile range) for L-carnitine compared with placebo were 54.84 (36.0, 112.9) and 59.74 (45.7, 96.0), whereas levels after intervention were 102.05 (60.9, 182.1) and 105.02 (73.1, 203

Oxidative stress is one of the main mechanisms responsible for male infertility. Various conditions such as varicocele, obesity, advanced age, and lifestyle can lead to an increase in reactive oxygen species, causing an oxidative imbalance in the reproductive environment. Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizing the egg. Excessive reactive oxygen species can affect sperm metabolism, leading to immobility, impaired acrosome reaction, and cell death, thereby impairing reproductive success. This double-blind randomized study evaluated the effect of supplementation with L-carnitine, acetyl-L-carnitine, vitamins, and other nutrients on semen quality in 104 infertile patients with or without varicocele, while also investigating the impact of factors such as obesity and advanced age on treatment. Sperm concentration significantly increased in the supplemented group compared to the placebo group ( P = 0.0186). Total sperm count also significantly increased in the supplemented group ( P = 0.0117), as did sperm motility ( P = 0.0120). The treatment had a positive effect on patients up to 35 years of age in terms of sperm concentration ( P = 0.0352), while a body mass index (BMI) above 25 kg m -2 had a negative effect on sperm concentration ( P = 0.0110). Results were not showing a net benefit in stratifying patients in accordance with their BMI since sperm quality increase was not affected by this parameter. In conclusion, antioxidant supplementation may be beneficial for infertile patients and has a more positive effect on younger patients with a normal weight.

OBJECTIVE: To investigate the effect of L-carnitine supplementation during the controlled ovarian stimulation (COS) cycle with antagonist protocol in patients with polycystic ovary syndrome (PCOS) diagnosis undergoing IVF/ICSI treatment. METHODS AND MATERIALS: This was a double-blind clinical trial study including 110 patients with PCOS attended to Royan Institute between March 2020 and February 2023. At the beginning of the COS cycle, the eligible patients were allocated into two groups randomly according to the coding list of the drugs prepared by the statistical consultant. In the experimental group, patients received 3 tablets daily (L-carnitine 1000 mg) from the second day of menstruation of the previous cycle until the puncture day in the cases of freeze-all embryos (6 weeks) or until the day of the pregnancy test (8 weeks) in fresh embryo transfer cycle. In the control group, patients received 3 placebo tablets for the same period of time. Weight assessment and fasting blood sugar and insulin tests, as well as serum lipid profile were also measured at the baseline and ovum pick-up day. The results of the COS cycle as well as the implantation and pregnancy rates were compared between groups. RESULTS: Finally, 45 cases in L-carnitine group versus 47 cases in the placebo group were completed study per protocol. Data analysis showed that the two groups were homogeneous in terms of demographic characteristics and baseline laboratory tests and severity of PCOS. There is no statistically significant difference in terms of the oocyte recovery ratio and oocyte maturity rate, and the number and quality of embryos, as well as the rates of the fertilization, chemical and clinical pregnancy between groups. However, the means of weight (P < 0.001) and serum levels of fasting blood sugar (P = 0.021), fasting insulin (P = 0.004), triglyceride (P < 0.001) and cholesterol (P < 0.001), LDL (P < 0.001) have significantly decreased in women after consuming L-carnitine supplementation. CONCLUSION: The oral intake of L-carnitine during COS in PCOS women for 6 weeks had no effect on COS and pregnancy outcomes. However, taking this supplement for 6 weeks has been associated with

BACKGROUND: Obesity, a multifactorial disorder with pandemic dimensions, is conceded a major culprit of morbidity and mortality worldwide, necessitating efficient therapeutic strategies. Nutraceuticals and functional foods are considered promising adjuvant/complementary approaches for weight management in individuals with obesity who have low adherence to conventional treatments. Current literature supports the weight-reducing efficacy of pro/pre/synbiotics or L-carnitine; however, the superiority of the nutraceutical joint supplementation approach over common single therapies to counter obesity and accompanying comorbidities is well documented. This study was designed to assess the effects of L-carnitine single therapy compared with L-carnitine and multistrain/multispecies synbiotic co-supplementation on anthropometric and cardiometabolic indicators in women with obesity. METHODS: The current placebo-controlled double-blind randomized clinical trial was performed on 46 women with obesity, randomly allocated to either concomitant supplementation [L-carnitine tartrate (2 × 500 mg/day) + multistrain/multispecies synbiotic (1 capsule/day)] or monotherapy [L-carnitine tartrate (2 × 500 mg/day) + maltodextrin (1 capsule/day)] groups for 8 weeks. Participants in both groups received healthy eating dietary advice. RESULTS: Anthropometric, lipid, and glycemic indices significantly improved in both intervention groups; however, L-carnitine + synbiotic co-administration elicited a greater reduction in the anthropometric measures including body mass index (BMI), body weight, and neck, waist, and hip circumferences (p < 0.001, <0.001, <0.001, = 0.012, and =0.030, respectively) after adjusting for probable confounders. Moreover, L-carnitine + synbiotic joint supplementation resulted in a greater reduction in fasting blood sugar (FBS), insulin (though marginal), and homeostatic model assessment of insulin resistance (HOMA-IR) and more increment in quantitative insulin sensitivity check index (QUICKI; p = 0.014, 0.051, 0.024, and 0.019, respectively) compared with the L-carnitine + placebo monosupplementation. No significant intergroup changes were found for the lipid profile

STUDY OBJECTIVE: Levocarnitine (L-carnitine) has shown promise as a metabolic-therapeutic for septic shock, where mortality approaches 40%. However, high-dose (≥ 6 grams) intravenous supplementation results in a broad range of serum concentrations. We sought to describe the population pharmacokinetics (PK) of high-dose L-carnitine, test various estimates of kidney function, and assess the correlation of PK parameters with pre-treatment metabolites in describing drug response for patients with septic shock. DESIGN: Population PK analysis was done with baseline normalized concentrations using nonlinear mixed effect models in the modeling platform Monolix. Various estimates of kidney function, patient demographics, dose received, and organ dysfunction were tested as population covariates. DATA SOURCE: We leveraged serum samples and metabolomics data from a phase II trial of L-carnitine in vasopressor-dependent septic shock. Serum was collected at baseline (T0); end-of-infusion (T12); and 24, 48, and 72 h after treatment initiation. PATIENTS AND INTERVENTION: Patients were adaptively randomized to receive intravenous L-carnitine (6 grams, 12 grams, or 18 grams) or placebo. MEASUREMENTS AND MAIN RESULTS: The final dataset included 542 serum samples from 130 patients randomized to L-carnitine. A two-compartment model with linear elimination and a fixed volume of distribution (17.1 liters) best described the data and served as a base structural model. Kidney function estimates as a covariate on the elimination rate constant (k) reliably improved model fit. Estimated glomerular filtration rate (eGFR), based on the 2021 Chronic Kidney Disease Epidemiology collaboration (CKD-EPI) equation with creatinine and cystatin C, outperformed creatinine clearance (Cockcroft-Gault) and older CKD-EPI equations that use an adjustment for self-identified race. CONCLUSIONS: High-dose L-carnitine supplementation is well-described by a two-compartment population PK model in patients with septic shock. Kidney function estimates that leverage cystatin C provided superior model fit. Future investigations into high-dose L-carnitine supplementation should consider baseline metabolic status and

Metabolic dysfunction-associated fatty liver disease (MAFLD) and diabesity (diabetes related to obesity) are interrelated since glucose and lipid alterations play a vital role in the development of both disorders. Due to their multi-variant metabolic features, more than one drug or natural product may be required to achieve proper therapeutic effects. This study aimed to evaluate the effectiveness of a formulation containing co-micronized palmitoylethanolamide and rutin (PEA-Rut) associated with hydroxytyrosol (HT), namely NORM3, against hepatic damage and metabolic alterations in high-fat diet (HFD)-induced diabesity in mice. NORM3 decreased the body weight and fat mass of obese mice. The formulation improved HFD-altered insulin sensitivity and hepatic glucose production and metabolism, as shown by glucose, insulin, pyruvate tolerance tests, Western blot, and real-time PCR. In the liver, NORM3 limited macro- and micro-vacuolar steatosis, as revealed by morphological analysis, and reduced the associated hepatic inflammation. NORM3 counteracted lipid dysfunctions of HFD animals, activating AMPK, a key cellular energy sensor, and normalizing the expression of carnitine palmitoyl-transferase (CPT)1, a rate-limiting enzyme of fatty acid β-oxidation, and other genes involved in lipid homeostasis. Relevantly, the hepatic antioxidant activity of NORM3 was proved (reduced ROS and increased detoxifying factors and enzymes). Finally, in vitro synergistic protective effects of the components (PEA-Rut and HT) on H2O2-induced oxidative challenge in HepG2 were determined (ROS production, inflammation, and antioxidant defense). Our results show the beneficial effect of NORM3 and its potential as an innovative phytotherapeutic combination in limiting hepatic damage progression and counteracting glucose and lipid dysmetabolism associated with diabesity. © 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.

Short-chain fatty acid (SCFA) acetate, a byproduct of dietary fiber metabolism by gut bacteria, has multiple immunomodulatory functions. The anti-inflammatory role of acetate is well documented; however, its effect on monocyte chemoattractant protein-1 (MCP-1) production is unknown. Similarly, the comparative effect of SCFA on MCP-1 expression in monocytes and macrophages remains unclear. We investigated whether acetate modulates TNFα-mediated MCP-1/CCL2 production in monocytes/macrophages and, if so, by which mechanism(s). Monocytic cells were exposed to acetate with/without TNFα for 24 h, and MCP-1 expression was measured. Monocytes treated with acetate in combination with TNFα resulted in significantly greater MCP-1 production compared to TNFα treatment alone, indicating a synergistic effect. On the contrary, treatment with acetate in combination with TNFα suppressed MCP-1 production in macrophages. The synergistic upregulation of MCP-1 was mediated through the activation of long-chain fatty acyl-CoA synthetase 1 (ACSL1). However, the inhibition of other bioactive lipid enzymes [carnitine palmitoyltransferase I (CPT I) or serine palmitoyltransferase (SPT)] did not affect this synergy. Moreover, MCP-1 expression was significantly reduced by the inhibition of p38 MAPK, ERK1/2, and NF-κB signaling. The inhibition of ACSL1 attenuated the acetate/TNFα-mediated phosphorylation of p38 MAPK, ERK1/2, and NF-κB. Increased NF-κB/AP-1 activity, resulting from acetate/TNFα co-stimulation, was decreased by ACSL1 inhibition. In conclusion, this study demonstrates the proinflammatory effects of acetate on TNF-α-mediated MCP-1 production via the ACSL1/MAPK/NF-κB axis in monocytic cells, while a paradoxical effect was observed in THP-1-derived macrophages.

PURPOSE: To investigate the mechanistic effects of combined exposure to caffeine and catechins on lipid metabolism in mice. METHODS: Seventy mice were randomly assigned to seven groups and fed diets containing varying doses of caffeine and catechins for 24 weeks. Body weight gain, intraperitoneal adipose tissue (IPAT) weight, serum biochemical parameters, and enzymatic activities, mRNA and protein expression levels of lipid metabolism-related enzymes in the liver and IPAT were analyzed. RESULTS: Following administration of caffeine and catechins, body weight gain, IPAT weight, serum and liver concentrations of total cholesterol and triglyceride were markedly reduced. Lipase activities, including that of AMP-activated protein kinase (AMPK), acyl-CoA oxidase, carnitine acyltransferase, adipose triglyceride lipase, and hormone-sensitive lipase, were significantly upregulated; however, fatty acid synthase (FAS) activity in the liver was suppressed. Combined exposure to caffeine and catechins significantly upregulated mRNA and protein expression levels of lipases while downregulating FAS mRNA expression and protein expression of peroxisome proliferator-activated receptor γ2. CONCLUSIONS: The combination of caffeine and catechins regulated the enzymatic activities, mRNA, and protein expression levels of lipid metabolism-related enzymes, resulting in suppression of body weight gain and IPAT weight in mice, potentially through activation of the AMPK signaling pathway. This study indicates that chronic intake of both caffeine and catechins can synergistically contribute to prevention of obesity and lifestyle-related diseases.

The etiology of cardiovascular disease (CVD) is impacted by multiple modifiable and non-modifiable risk factors including dietary choices, genetic predisposition, and environmental exposures. However, mechanisms linking diet, exposure to pollutants, and CVD risk are largely unclear. Recent studies identified a strong link between plasma levels of nutrient-derived Trimethylamine N-oxide (TMAO) and coronary artery disease. Dietary precursors of TMAO include carnitine and phosphatidylcholine, which are abundant in animal-derived foods. Dioxin-like pollutants can upregulate a critical enzyme responsible for TMAO formation, hepatic flavin containing monooxygenase 3 (FMO3), but a link between dioxin-like PCBs, upregulation of FMO3, and increased TMAO has not been reported. Here, we show that mice exposed acutely to dioxin-like PCBs exhibit increased hepatic FMO3 mRNA, protein, as well as an increase in circulating levels of TMAO following oral administration of its metabolic precursors. C57BL/6 mice were exposed to 5μmol PCB 126/kg mouse weight (1.63mg/kg). At 48h post-PCB exposure, mice were subsequently given a single gavage of phosphatidylcholine dissolved in corn oil. Exposure to 5 μmole/kg PCB 126 resulted in greater than 100-fold increase in FMO3 mRNA expression, robust induction of FMO3 protein, and a 5-fold increase in TMAO levels compared with vehicle treated mice. We made similar observations in mice exposed to PCB 77 (49.6mg/kg twice); stable isotope tracer studies revealed increased formation of plasma TMAO from an orally administered precursor trimethylamine (TMA). Taken together, these observations suggest a novel diet-toxicant interaction that results in increased production of a circulating biomarker of cardiovascular disease risk.

Our study wants to evaluate the effects of one year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight, glycemic and lipid control, and insulin resistance state in type 2 diabetic patients. Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) > 8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA(1c), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, high sensitivity-C reactive protein (Hs-CRP). We observed a faster, and better decrease of body weight, HbA(1c), FPG, PPG, LDL-C, HOMA-IR with orlistat plus L-carnitine compared to orlistat. A faster improvement of TC, Tg, FPI, resistin, RBP-4, visfatin, and Hs-CRP was reached with orlistat plus L-carnitine compared to orlistat. We can safely conclude that the association of orlistat plus L-carnitine was better than orlistat in improving body weight, glycemic and lipid profile, insulin resistance, and inflammatory parameters and no significant adverse events were recorded.

BACKGROUND: Uncertainty exists regarding the treatment of patients with nonalcoholic fatty liver disease (NAFLD) who are unable to lose weight and/or change lifestyle. The present study assesses the effectiveness and safety of pharmacological and dietary supplement interventions for NAFLD. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched for randomized controlled trials (RCTs) both in adults and in children. RESULTS: Fifteen (2 pediatric patients and 13 adults) RCTs met the inclusion criteria. A significant effect on normalization of alanine transaminase was found in patients treated with metformin compared with vitamin E, and in those treated with high-dose (3 g) carnitine vs diet. In contrast, there was no difference in patients treated with pioglitazone combined with vitamin E versus vitamin E alone, ursodeoxycholic acid (UDCA) combined with vitamin E or alone versus placebo, or UDCA versus combination of vitamin E and vitamin C, and in patients treated with vitamin E, probucol, N-acetylcysteine, low doses of carnitine, or Yo Jyo Shi Ko compared with placebo. Aspartate aminotransferase normalization was significantly higher in those treated with UDCA combined with vitamin E versus UDCA alone or placebo, and in those treated with metformin. Small number of subjects, high drop-out rates, and numerous interventions in 1 study limit the value of many studies. Only 7 RCTs analyzed biopsy specimens, but most of them have significant methodological limitations. Pioglitazone had reduced liver necrosis and inflammation in 1 large study. CONCLUSIONS: Limited data do not allow one to draw firm conclusions on the efficacy of various treatments for NAFLD.

This study tested the hypothesis that the determinants of mild liver injury are prerequisites for more severe idiosyncratic hepatotoxicity. This study verified whether the possible risk factors for rare idiosyncratic valproic acid (VPA)-induced hepatotoxicity, VPA clearance and/or serum carnitine concentrations are common to those for a mild elevation in transaminases in VPA-treated patients. VPA clearance was calculated in 172 Japanese patients with epilepsy, using a non-linear mixed-effects regression program. Carnitine concentrations were determined in a subset of 60 patients. The relationships between VPA clearance, carnitine concentration and levels of transaminases and ammonia were evaluated by Pearson's correlation coefficients. The final model of VPA apparent clearance (CL/F) was as follows: CL/F (L h(-1) = 0.012 x (BW/40)(0.34) x dose(0.55) x 0.90(gender) x 1.32(PHT) x 1.11(CBZ) x 1.12(PB), where BW = total body weight (kg); gender = 1 if female, 0 if male; PHT/CBZ/PB = 1 if phenytoin, carbamazepine, or phenobarbital, respectively, is coadministrated, otherwise 0. Either a higher VPA clearance or acyl/free carnitine ratio and a lower total and/or free carnitine concentration, but not VPA concentration, were associated with the mild elevation in transaminases or ammonia. These results support the initial hypothesis, while also helping to clarify the mechanism of severe idiosyncratic hepatotoxicity with VPA.

High fructose feeding (60 g/100 g diet) in rodents induces alterations in both glucose and lipid metabolism. The present study was aimed to evaluate whether intraperitoneal carnitine (CA), a transporter of fatty acyl-CoA into the mitochondria, could attenuate derangements in carbohydrate metabolizing enzymes and glucose overproduction in high fructose-diet fed rats. Male Wistar rats of body weight 150-160 g were divided into 4 groups of 6 rats each. Groups 1 and 4 animals received control diet while the groups 2 and 3 rats received high fructose-diet. Groups 3 and 4 animals were treated with CA (300 mg/Kg body weight/day, i.p.) for 30 days. At the end of the experimental period, levels of carnitine, glucose, insulin, lactate, pyruvate, glycerol, triglycerides and free fatty acids in plasma were determined. The activities of carbohydrate metabolizing enzymes and glycogen content in liver and muscle were assayed. Hepatocytes isolated from liver were studied for the gluconeogenic activity in the presence of substrates such as pyruvate, lactate, glycerol, fructose and alanine. Fructose-diet fed animals showed alterations in glucose metabolizing enzymes, increased circulating levels of gluconeogenic substrates and depletion of glycogen in liver and muscle. There was increased glucose output from hepatocytes of animals fed fructose-diet alone with all the gluconeogenic substrates. The abnormalities associated with fructose feeding such as increased gluconeogenesis, reduced glycogen content and other parameters were brought back to near normal levels by CA. Hepatocytes from these animals showed significant inhibition of glucose production from pyruvate (74.3%), lactate (65.4%), glycerol (69.6%), fructose (56.2%) and alanine (63.6%) as compared to CA untreated fructose-fed animals. The benefits observed could be attributed to the effect of CA on fatty acyl-CoA transport.

Soy products are mainly composed of proteins, phytochemicals such as isoflavones, soy lipids, and carbohydrates. It is unclear whether an individual component alone or a combined effect of multiple bioactive compounds contributes to the beneficial properties of soy. We investigated the effect of dietary genistein (the principal soy isoflavone) alone and combined with L-carnitine to evaluate possible synergistic effects on the intentionally induced prediabetic state characterized by insulin resistance and obesity in C57Bl/6J mice fed a high-fat diet (HD). In the HD-alone group, abdominal and back fat relative to total body weight were significantly higher compared with other groups including those fed normal diet (ND). Among the HD groups, final weight gains of the HD plus genistein (HD+G) and HD plus genistein plus L-carnitine (HD+G+C) groups were lower compared with that of the control (HD-alone). Especially in liver, the results showed that genistein with carnitine transcriptionally up-regulated expressions of acyl-coenzyme A synthetase (ACS) and carnitine palmitoyltransferase-I (CPT-I) by approximately 50% and 40%, respectively, compared with genistein alone. However, the up-regulation of CPT-I did not directly reflect the enzyme activity of CPT-I. On the other hand, the effects of genistein and genistein with carnitine on the expressions of ACS and CPT-I in muscle were not significant. Our study suggests that genistein with carnitine exerts anti-obesity effects, probably by modulating peroxisome proliferator-activated receptor-associated genes. However, further work is needed to elucidate the possible mechanisms by which genistein and carnitine intervene.

The study aimed to evaluate the effect of L-carnitine on hepatic cytochrome P450-dependent monooxygenases exposed to methanol. Male Spraque-Dawley rats were given methanol (1/4 LD50 and 1/2 LD50) together with L-carnitine (1g/kg body weight). The parameters of microsome electron transport chains I and II and the levels of CYP2E1, CYP2B1/2 and CYP1A2 were measured 8, 12, 24, 48, 72 and 96 h after exposure. L-carnitine did not affect cytochrome P450 but it significantly increased at 72 and 96 h NADPH-cytochrome P450 reductase. It stimulated cytochrome b5 at 48 and 96 h and NADH-cytochrome b5 reductase activity at 12, 72 and 96 h. Methanol, especially the lower dose, inhibited cytochrome P450 after 48 h, but the higher methanol dose inhibited NADH-cytochrome b5 reductase activity in this time. L-carnitine, combined with the lower dose of methanol, stimulated NADPH-cytochrome P450 reductase after 48 h and cytochrome b5 and NADH-cytochrome b5 reductase over the whole period of observation. L-carnitine stimulated CYP2B1/2 but not CYP2E1 and CYP1A2. Methanol stimulated CYP2E1 at 24 h, but CYP1A2 at 96 h in the studied doses. CYP2B1/2 was induced by the lower dose of methanol at 24 h but by the higher one at 96 h. When given together, L-carnitine and methanol (1/2 LD50) significantly stimulated CYP2E1 up to 170% at 24 h and 145% at 96 h. Metabolism-based herb-drug interaction of Corydalis Bungeanae Herba with berberine in vitro and in vivo in rats. Mao X(1), Zhao H(1), Wang Q(1), Li H(1), Yang L(1), Hu Z(1), Zhang F(1), Guo X(1), Peng Y(1), Zheng J(1)(2). Author information: (1)Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, P. R. China. (2)State Key Laboratory of Functions and Applications of Medicinal Plants, Key Laboratory of Pharmaceutics of Guizhou Province and Guizhou Medical University, Guiyang, Guizhou, P. R. China. Corynoline (CRL) and berberine (BER) are the major bioactive components found in traditional Chinese medicines Corydalis Bungeanae Herba (Corydalis bungeanae) and Coptidis Rhizoma, respectively. The two herbs serve as anti-inflammatory agents and are generally applied to many prescriptions. The aims of the stud