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1.
The effect of L-carnitine supplementation on insulin resistance, sex hormone-binding globulin and lipid profile in overweight/obese women with polycystic ovary syndrome: a randomized clinical trial.
Sangouni, AA, Pakravanfar, F, Ghadiri-Anari, A, Nadjarzadeh, A, Fallahzadeh, H, Hosseinzadeh, M
European journal of nutrition. 2022;(3):1199-1207
Abstract
PURPOSE Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women. Insulin resistance and dyslipidemia are linked to PCOS. L-Carnitine supplementation as a management strategy for women with PCOS has been proposed. The effect of L-carnitine supplementation on insulin resistance, sex hormone-binding globulin (SHBG) and lipid profile in overweight/obese women with PCOS was investigated. METHODS This randomized, double-blind, controlled clinical trial, was conducted on 62overweight/obese women with PCOS. Participants were randomly assigned into two groups to receive 1000 mg/day L-carnitine or placebo (1000 mg starch) for 12 weeks. RESULTS L-Carnitine supplementation compared to the placebo showed a significant improvement in insulin [- 0.7 (- 7.3 to 4.0) vs. 0.7 (- 3.0 to 5.2); P = 0.001], homeostatic model assessment for insulin resistance [- 0.4 (- 1.7 to 1.1) vs. 0.0 (- 0.7 to 1.3); P = 0.002], quantitative insulin sensitivity check index (+ 0.01 ± 0.02 vs. - 0.01 ± 0.01; P = 0.02) and a non-significant change toward improvement in SHBG (+ 11.5 ± 40.2 vs. - 3.2 ± 40.2; P = 0.2). However, there was no significant differences between the two groups in serum levels of fasting plasma glucose, total cholesterol, triglyceride, low density lipoprotein-cholesterol and high density lipoprotein cholesterol (P > 0.05). CONCLUSION 12-week L-carnitine supplementation in overweight or obese women with PCOS ameliorate insulin resistance, but has no effect on SHBG and lipid profile. Studies with higher dosages and duration of L-carnitine intake are required. The trial was registered on 30 December 2019 at Iranian Registry of Clinical Trials IRCT20191016045131N1. TRIAL REGISTRATION Registered on 30th December 2019 at Iranian Registry of Clinical Trials (IRCT20191016045131N1).
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2.
Possible Neuroprotective Effects of l-Carnitine on White-Matter Microstructural Damage and Cognitive Decline in Hemodialysis Patients.
Ueno, Y, Saito, A, Nakata, J, Kamagata, K, Taniguchi, D, Motoi, Y, Io, H, Andica, C, Shindo, A, Shiina, K, et al
Nutrients. 2021;(4)
Abstract
Although l-carnitine alleviated white-matter lesions in an experimental study, the treatment effects of l-carnitine on white-matter microstructural damage and cognitive decline in hemodialysis patients are unknown. Using novel diffusion magnetic resonance imaging (dMRI) techniques, white-matter microstructural changes together with cognitive decline in hemodialysis patients and the effects of l-carnitine on such disorders were investigated. Fourteen hemodialysis patients underwent dMRI and laboratory and neuropsychological tests, which were compared across seven patients each in two groups according to duration of l-carnitine treatment: (1) no or short-term l-carnitine treatment (NSTLC), and (2) long-term l-carnitine treatment (LTLC). Ten age- and sex-matched controls were enrolled. Compared to controls, microstructural disorders of white matter were widely detected on dMRI of patients. An autopsy study of one patient in the NSTLC group showed rarefaction of myelinated fibers in white matter. With LTLC, microstructural damage on dMRI was alleviated along with lower levels of high-sensitivity C-reactive protein and substantial increases in carnitine levels. The LTLC group showed better achievement on trail making test A, which was correlated with amelioration of disorders in some white-matter tracts. Novel dMRI tractography detected abnormalities of white-matter tracts after hemodialysis. Long-term treatment with l-carnitine might alleviate white-matter microstructural damage and cognitive impairment in hemodialysis patients.
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3.
The Effect of L-Carnitine on Mortality Rate in Septic Patients: A Systematic Review and Meta-Analysis on Randomized Clinical Trials.
Abdollahi, H, Abdolahi, M, Sedighiyan, M, Jafarieh, A
Endocrine, metabolic & immune disorders drug targets. 2021;(4):673-681
Abstract
BACKGROUND Recent clinical trial studies have reported that L-carnitine supplementation can reduce the mortality rate in patients with sepsis, but there are no definitive results in this context. The current systematic review and meta-analysis aimed to evaluate the effect of L-carnitine supplementation on 28-day and one-year mortality in septic patients. METHODS A systematic search conducted on Pubmed, Scopus and Cochrane Library databases up to June 2019 without any language restriction. The publications were reviewed based on the Cochrane handbook and preferred reporting items for systematic reviews and meta-analyses (PRISMA). To compare the effects of L-carnitine with placebo, Risk Ratio (RR) with 95% confidence intervals (CI) were pooled according to the random effects model. RESULTS Across five enrolled clinical trials, we found that L-carnitine supplementation reduce one-year mortality in septic patients with SOFA> 12 (RR: 0.68; 95% CI: 0.49 to 0.96; P= 0.03) but had no significant effect on reducing 28-day mortality ((RR: 0.93; 95% CI: 0.68 to 1.28; P= 0.65) compared to placebo. Finally, we observed that based on current trials, L-carnitine supplementation may not have clinically a significant effect on mortality rate. CONCLUSION L-carnitine patients with higher SOFA score can reduce the mortality rate. However, the number of trials, study duration and using a dosage of L-carnitine are limited in this context and further large prospective trials are required to clarify the effect of L-carnitine on mortality rate in septic patients.
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4.
Effect of L-carnitine supplementation on renal anemia in patients on hemodialysis: a meta-analysis.
Zhu, Y, Xue, C, Ou, J, Xie, Z, Deng, J
International urology and nephrology. 2021;(10):2149-2158
Abstract
BACKGROUND L-carnitine is an amino acid derivative that is thought to be helpful for treating renal anemia in hemodialysis patients. However, the mechanism remains to be fully elucidated. METHODS A literature search was performed on PubMed, Embase, and Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) and conduct a meta-analysis for investigating the effect of L-carnitine in the treatment of renal anemia in participants receiving hemodialysis. RESULTS A total of 18 eligible trials with 1090 participants were included in this study. L-carnitine can significantly increase plasma free L-carnitine levels (mean difference [MD]: 140.53, 95% confidence interval [CI] 102.22-178.85; P < 0.00001), decrease the erythropoietin responsiveness index (ERI; MD: -2.72, 95% CI -3.20 to -2.24; P < 0.00001) and the required erythropoiesis-stimulating agent (ESA) doses (MD: -1.70, 95% CI -2.04 to -1.36; P < 0.00001). However, the use of L-carnitine was not associated with a higher hemoglobin level (MD: 0.18, 95% CI -0.20 to 0.55; P = 0.35) and hematocrit level (MD: 1.07, 95% CI -0.73 to 2.87; P = 0.24). In subgroup analyses, the effects of L-carnitine supplementation on renal anemia in patients on hemodialysis were independent of the treatment duration and intervention routes. CONCLUSION The present meta-analysis indicated that L-carnitine therapy significantly increased plasma L-carnitine concentrations, improved the response to ESA, decreased the required ESA doses in patients receiving hemodialysis, and maintained hemoglobin and hematocrit levels. L-carnitine supplementation should be supported in hemodialysis patients. However, the relationship between L-carnitine treatment and long-term outcomes is still unclear. Further high-quality RCTs are needed to verify our findings.
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5.
L-Carnitine Tartrate Supplementation for 5 Weeks Improves Exercise Recovery in Men and Women: A Randomized, Double-Blind, Placebo-Controlled Trial.
Stefan, M, Sharp, M, Gheith, R, Lowery, R, Ottinger, C, Wilson, J, Durkee, S, Bellamine, A
Nutrients. 2021;(10)
Abstract
UNLABELLED L-carnitine tartrate has been shown to improve relatively short-term recovery among athletes. However, there is a lack of research on the longer-term effects in the general population. OBJECTIVE The primary objectives of this randomized double-blind, placebo-controlled trial were to evaluate the effects of daily L-carnitine tartrate supplementation for 5 weeks on recovery and fatigue. METHOD In this study, eighty participants, 21- to 65-years-old, were recruited. Participants were split into two groups of forty participants each, a placebo, and a L-carnitine Tartrate group. Seventy-three participants completed a maintenance exercise training program that culminated in a high-volume exercise challenge. RESULTS Compared to placebo, L-carnitine tartrate supplementation was able to improve perceived recovery and soreness (p = 0.021), and lower serum creatine kinase (p = 0.016). In addition, L-carnitine tartrate supplementation was able to blunt declines in strength and power compared to placebo following an exercise challenge. Two sub-analyses indicated that these results were independent of gender and age. Interestingly, serum superoxide dismutase levels increased significantly among those supplementing with L-carnitine tartrate. CONCLUSIONS These findings agree with previous observations among healthy adult subjects and demonstrate that L-carnitine tartrate supplementation beyond 35 days is beneficial for improving recovery and reducing fatigue following exercise across gender and age.
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6.
Evaluation of Plasma Free Amino Acid and Carnitine Levels in Patients with Cesarean Scar Pregnancy.
Tammo, O, Uyanikoglu, H, Koyuncu, İ
Combinatorial chemistry & high throughput screening. 2021;(9):1436-1445
Abstract
AIM AND OBJECTIVE This study aimed to explore the plasma free amino acid (FAA) and carnitine levels in pregnant women with cesarean scar pregnancy (CSP), and to compare them with those of healthy pregnant women. MATERIALS AND METHODS This prospective and randomized controlled study was conducted in patients admitted to Harran University Medical Faculty Hospital Obstetrics Clinic between January 2018 and January 2019. A total of 60 patients were included in the study, and the patients were divided into two groups: the CSP group (n = 30) and the healthy pregnant group as the control group (n = 30). The blood samples were taken from the participants between 7 - 12 weeks of gestation. Twenty-seven carnitines and their esters and 14 FAAs were analysed by liquid chromatography - mass spectrometry (LC-MS/MS). RESULTS The mean plasma concentrations of some carnitines, including C2, C5, C5-OH, C5-DC, C6, C8-1, C12, C14, C14-1, C14-2, C16, C16-1, C18, and C18-1 were significantly higher in the CSP group than in the control group. However, other carnitines, including C0, C3, C4, C4-DC, C5- 1, C6-DC, C8, C8-DC, C10, C10-1, C18-1-OH, and C18-2, were similar in both groups. The plasma levels of some FAAs, including Methyl Glutaryl, Leu, Met, Phe, Arg, Orn, and Glu values, were significantly higher in the CSP group than in the control group. However, there was no statistical significance in other FAA levels, including Val, Asa, Tyr, Asp, Ala, Cit, and Gly between the two groups. Additionally, Pearson's correlation analysis showed that there were significantly positive correlations between many FAA and carnitine values. CONCLUSION Since several plasma carnitines and FAA levels were higher in the CSP group than in the control group, we think that scar pregnancy increases the metabolic need for myometrial invasion. Also, we think that these results may be useful in clinical practice for CSP diagnosis.
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7.
Efficacy and Safety of the Combination of Superoxide Dismutase, Alpha Lipoic Acid, Vitamin B12, and Carnitine for 12 Months in Patients with Diabetic Neuropathy.
Didangelos, T, Karlafti, E, Kotzakioulafi, E, Kontoninas, Z, Margaritidis, C, Giannoulaki, P, Kantartzis, K
Nutrients. 2020;(11)
Abstract
AIM: To investigate the efficacy of Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine, and Vitamin B12 (B12) in one tablet in Diabetic Neuropathy (DN). PATIENTS-METHODS In this prospective, double-blind, placebo-controlled study, 85 patients with Diabetes Mellitus Type 2 (DMT2) were randomly assigned, either to receive the combination of four elements (active group, n = 43), or placebo (n = 42) for 12 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured the vibration perception threshold (BIO), and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Pain (PS) and quality of life (QL) questionnaires were administered. RESULTS At follow-up, BIO, MNSIQ, QL, PAIN, and SNCV, SNAP, and B12 levels had significantly improved inactive group (p <0.001, p <0.001, p <0.001, p <0.001, p = 0.027, p = 0.031, and p <0.001 respectively), whereas the inplacebo group MCR (mean circular resultant) and PAIN deteriorated (p <0.001, p <0.001). The changes in MNSIQ, QL, SNCV, BIO, and PAIN differed significantly between groups (p <0.001, p <0.001, p = 0.031, p <0.001, and p <0.001 respectively). CONCLUSIONS The combination of the four elements in one tablet for 12 months in patients with DMT2 improved all indices of peripheral neuropathy, including SNAP and SNCV, pain, and Quality of Life perception, except CARTs and MNSIE.
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8.
Beneficial effects of l-carnitine supplementation for weight management in overweight and obese adults: An updated systematic review and dose-response meta-analysis of randomized controlled trials.
Askarpour, M, Hadi, A, Miraghajani, M, Symonds, ME, Sheikhi, A, Ghaedi, E
Pharmacological research. 2020;:104554
Abstract
Despite preclinical studies demonstrating the efficacy of l-carnitine supplementation for weight management, findings in clinical setting are contradictory. Electronic bibliographical databases were systematically searched up to February 2019 with no limitation in language, including Scopus, PubMed, ISI Web of Science and Cochrane Library. Clinical trials registry platform were also searched. All randomized controlled trials (RCTs) which reported an effect of l-carnitine supplementation on obesity-related indices were included. Weighted mean difference (WMD) was estimated using a random-effect model (DerSimonian-Laird method). Eventually 43 eligible RCTs were included for quantitative analysis. Meta-analysis results revealed that l-carnitine supplementation significantly decreased weight (WMD: -1.129 kg, 95 % CI: -1.590, -0.669; I2: 63.4), body mass index (BMI) (WMD: -0.359 kg/m2, 95 % CI: -0.552, -0.167; I2: 85.2) and fat mass (WMD: -1.158 kg, 95 % CI: -1.763, -0.554, I2: 15.5). However, l-carnitine supplementation did not change body fat percentage (WMD: -0.874 %, 95 % CI: -1.890, 0.142, I2: 98.2) or waist circumference (WMD: -0.883 mg/dl, 95 % CI: -1.770, 0.004, I2: 74.8). l-Carnitine supplementation changed weight (r = -0.98) and BMI (r = -0.67) in a non-linear fashion based on carnitine dosage and BMI according to trial duration (r = -0.04). Interestingly subgroup analysis revealed that l-carnitine showed anti-obesity effects only in overweight and obese subjects; l-carnitine decreased weight, and BMI alone when combined with other lifestyle modifications. Anthropometric indexes were not changed following l-carnitine supplementation among patients' undergoing hemodialysis. Our study revealed that l-carnitine supplementation might have a positive effects in achieving an improved body weight and BMI especially in overweight and obese subjects.
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9.
A Pilot Study on the Effects of l-Carnitine and Trimethylamine-N-Oxide on Platelet Mitochondrial DNA Methylation and CVD Biomarkers in Aged Women.
Bordoni, L, Sawicka, AK, Szarmach, A, Winklewski, PJ, Olek, RA, Gabbianelli, R
International journal of molecular sciences. 2020;(3)
Abstract
l-carnitine supplementation has been used for cardiovascular health protection for a long time. Recently, trimethylamine-N-oxide (TMAO), which is an end product of l-carnitine metabolism via the activity of microbiota, has been identified as a cardiovascular disease (CVD) biomarker. The aim of this study was to assess the effect of 6 months of l-carnitine supplementation in a group of aged women engaged in a regular physical training. Platelet mitochondrial DNA methylation, an emerging and innovative biomarker, lipid profile and TMAO levels have been measured. TMAO increased after l-carnitine supplementation (before 344.3 ± 129.8 ng/mL vs. after 2216.8 ± 1869.0 ng/mL; n = 9; paired t-test, p = 0.02). No significant effects on TMAO were exerted by training alone (n = 9) or by l-leucine supplementation (n = 12). TMAO levels after 6 months of l-carnitine supplementation were associated with higher low-density lipoprotein-cholesterol (LDL-c) (Spearman Rho = 0.518, p = 0.003) and total cholesterol (TC) (Spearman Rho = 0.407, p = 0.026) levels. l-carnitine supplementation increased D-loop methylation in platelets (+6.63%; paired t-test, p = 0.005). D-loop methylation was not directly correlated to the TMAO augmentation observed in the supplemented group, but its increase inversely correlated with TC (Pearson coefficient = -0.529, p = 0.029) and LDL-c (Pearson coefficient = -0.439, p = 0.048). This evidence supports the hypothesis that the correlation between l-carnitine, TMAO and atherosclerosis might be more complex than already postulated, and the alteration of mitochondrial DNA (mtDNA) methylation in platelets could be involved in the pathogenesis of this multifactorial disease.
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10.
Influence of Besifovir Dipivoxil Maleate Combined with L-Carnitine on Hepatic Steatosis in Patients with Chronic Hepatitis B.
Jung, YW, Kim, M, Kim, BK, Park, JY, Kim, DY, Ahn, SH, Han, KH, Kim, SU
Journal of Korean medical science. 2020;(17):e104
Abstract
BACKGROUND Besifovir dipivoxil maleate (BSV) with L-carnitine is the first-line antiviral agent for chronic hepatitis B (CHB) infection. We investigated whether BSV combined with L-carnitine improves hepatic steatosis (HS). METHODS Treatment-naïve patients with CHB who were initiated on antiviral therapy (AVT) were enrolled. The magnitude of HS was assessed using hepatic steatosis index (HSI), and HS improvement was defined as a ≥ 10% reduction in the HSI score from the baseline. RESULTS The mean age of the study patients was 56 years with a male predominance (n = 178, 64.7%). The mean body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count were 23.5 kg/m², 49.6 IU/L, 49.0 IU/L, and 191.3 × 10⁹/L, respectively. The mean HSI and fibrosis (FIB)-4 index were 32.6 and 0.5, respectively. After 6 months of AVT, platelet count (mean, 191.3→167.0 × 10⁹/L), fasting glucose (mean, 113.1→105.9 mg/dL), AST (mean, 49.6→28.0 IU/L), ALT (mean, 49.0→33.9 IU/L), and total cholesterol (mean, 170.0→162.1 mg/dL) levels significantly decreased (all P < 0.05). In the BSV group, AST (mean, 95.2→30.2 IU/L) and ALT (mean, 81.1→31.1 IU/L) levels significantly reduced (all P < 0.05), whereas HSI and FIB-4 index were maintained (all P > 0.05). In the univariate analysis, age, BMI, diabetes, cirrhosis, fasting glucose level, and ALT were significantly associated with HS improvement (all P < 0.05). CONCLUSION BSV with L-carnitine did not show any improvement of HS in patients with CHB. Further prospective randomized controlled studies are needed to validate the potential beneficial effects of BSV with L-carnitine in CHB infection.