l-Carnitine and heart disease.
Wang Zhong-Yu,Liu Ying-Yi,Liu Guo-Hui,Lu Hai-Bin,Mao Cui-Ying
Life sciences
Cardiovascular disease (CVD) is a key cause of deaths worldwide, comprising 15-17% of healthcare expenditure in developed countries. Current records estimate an annual global average of 30 million cardiac dysfunction cases, with a predicted escalation by two-three folds for the next 20-30years. Although β-blockers and angiotensin-converting-enzymes are commonly prescribed to control CVD risk, hepatotoxicity and hematological changes are frequent adverse events associated with these drugs. Search for alternatives identified endogenous cofactor l-carnitine, which is capable of promoting mitochondrial β-oxidation towards a balanced cardiac energy metabolism. l-Carnitine facilitates transport of long-chain fatty acids into the mitochondrial matrix, triggering cardioprotective effects through reduced oxidative stress, inflammation and necrosis of cardiac myocytes. Additionally, l-carnitine regulates calcium influx, endothelial integrity, intracellular enzyme release and membrane phospholipid content for sustained cellular homeostasis. Carnitine depletion, characterized by reduced expression of "organic cation transporter-2" gene, is a metabolic and autosomal recessive disorder that also frequently associates with CVD. Hence, exogenous carnitine administration through dietary and intravenous routes serves as a suitable protective strategy against ventricular dysfunction, ischemia-reperfusion injury, cardiac arrhythmia and toxic myocardial injury that prominently mark CVD. Additionally, carnitine reduces hypertension, hyperlipidemia, diabetic ketoacidosis, hyperglycemia, insulin-dependent diabetes mellitus, insulin resistance, obesity, etc. that enhance cardiovascular pathology. These favorable effects of l-carnitine have been evident in infants, juvenile, young, adult and aged patients of sudden and chronic heart failure as well. This review describes the mechanism of action, metabolism and pharmacokinetics of l-carnitine. It specifically emphasizes upon the beneficial role of l-carnitine in cardiomyopathy.
10.1016/j.lfs.2017.12.015
Relationship of Acylcarnitines to Myocardial Ischemic Remodeling and Clinical Manifestations in Chronic Heart Failure.
Journal of cardiovascular development and disease
BACKGROUND:Progressive myocardial remodeling (MR) in chronic heart failure (CHF) leads to aggravation of systolic dysfunction (SD) and clinical manifestations. Identification of metabolomic markers of these processes may help in the search for new therapeutic approaches aimed at achieving reversibility of MR and improving prognosis in patients with CHF. METHODS:To determine the relationship between plasma acylcarnitine (ACs) levels, MR parameters and clinical characteristics, in patients with CHF of ischemic etiology (n = 79) and patients with coronary heart disease CHD (n = 19) targeted analysis of 30 ACs was performed by flow injection analysis mass spectrometry. RESULTS:Significant differences between cohorts were found for the levels of 11 ACs. Significant positive correlations (r > 0.3) between the medium- and long-chain ACs (MCACs and LCACs) and symptoms (CHF NYHA functional class (FC); r = 0.31-0.39; < 0.05); negative correlation (r = -0.31-0.34; < 0.05) between C5-OH and FC was revealed. Positive correlations of MCACs and LCACs (r = 0.31-0.48; < 0.05) with the left atrium size and volume, the right atrium volume, right ventricle, and the inferior vena cava sizes, as well as the pulmonary artery systolic pressure level were shown. A negative correlation between C18:1 and left ventricular ejection fraction (r = -0.31; < 0.05) was found. However, a decrease in levels compared to referent values of ACs with medium and long chain lengths was 50% of the CHF-CHD cohort. Carnitine deficiency was found in 6% and acylcarnitine deficiency in 3% of all patients with chronic heart disease. CONCLUSIONS:ACs may be used in assessing the severity of the clinical manifestations and MR. ACs are an important locus to study in terms of altered metabolic pathways in patients with CHF of ischemic etiology and SD. Further larger prospective trials are warranted and needed to determine the potential benefits to treat patients with CV diseases with aberrate AC levels.
10.3390/jcdd10100438
L-Carnitine Reduces Myocardial Oxidative Stress and Alleviates Myocardial Ischemia-Reperfusion Injury by Activating Nuclear Transcription-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) Signaling Pathway.
Zhao Tana,Chen Shangjun,Wang Bingxin,Cai Dongliang
Medical science monitor : international medical journal of experimental and clinical research
BACKGROUND Myocardial ischemia-reperfusion injury (IRI) is an important injury mechanism of myocardial infarction. The purpose of this study was to explore the effects of L-carnitine (LC) on myocardial IRI and its mechanism. MATERIAL AND METHODS The IRI model was made by ligating the left anterior descending coronary artery. Then, we injected LC intraperitoneally into the rats of the experimental group to assess the effect of LC on IRI rats by use of serum markers, Western blot, and qRT-PCR. H9c2 cells were cultured and then treated with hypoxia-reoxygenation. The effect of LC on oxidative stress, apoptosis, and nuclear transcription-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway of H9c2 cells were detected by Western blot, RT-PCR, and flow cytometry. RESULTS LC significantly reduced malondialdehyde (MDA), creatine kinase (CK), and lactate dehydrogenase (LDH) levels in rat myocardial tissue and increased superoxide dismutase (SOD) expression. LC also increased the expression of SOD1/2 and Bcl-2 in rat myocardial tissue and H9c2 cells and decreased the expression of caspase3/8 and Bax. In addition, LC increased the expression of Nrf2/HO-1 signaling pathway-related molecules in H9c2 cells and increased the activity of the Nrf2/HO-1 signaling pathway. Moreover, inhibition of the Nrf2/HO-1 signaling pathway attenuated the protective effect of LC on H9c2 cells. CONCLUSIONS LC can activate the Nrf2/HO-1 signaling pathway and reduce oxidative stress and apoptosis in cardiomyocytes, thereby reducing myocardial IRI.
10.12659/MSM.923251
The effects of L-carnitine supplementation on indicators of inflammation and oxidative stress: a systematic review and meta-analysis of randomized controlled trials.
Fathizadeh Hadis,Milajerdi Alireza,Reiner Željko,Amirani Elaheh,Asemi Zatollah,Mansournia Mohammad Ali,Hallajzadeh Jamal
Journal of diabetes and metabolic disorders
Objective:Several trials investigated the efficacy of L-carnitine administration on markers of inflammation and indicators of oxidative stress; however, their findings are controversial. The aim of this study was to conduct a comprehensive meta-analysis and a critical review, which would analyze all randomized controlled trials (RCTs) in order to determine the effects of L-carnitine supplementation on inflammatory markers and oxidative stress. Methods:An electronic search was performed using Scopus, Cochrane Library, PubMed, Google scholar and Web of Science databases on publications from 1990 up to May 2020. Human RCTs conducted in healthy subjects or participants with certain disorders which investigating the efficacy of L-carnitine supplementation compared to control (placebo, usual treatment or no intervention) on inflammation and oxidative markers were included. Data were pooled applying a random-effects model and as the overall effect size, weighted mean difference (WMD) was presented. Between heterogeneity among studies was computed using Cochran's Q test and I-square (I). Quality of studies assessed using the Jadad scale. Dose-response analysis was measured using meta-regression. The funnel plot, as well as the Egger's regression test was applied to determine the publication bias. Results:44 trials (reported 49 effect sizes for different outcomes of interest) met the inclusion criteria for this meta-analysis. According to the findings, L-carnitine supplementation resulted in a significant reduction in C-reactive protein (CRP) (WMD: -0.10; 95% CI: -0.14, -0.06), interleukin 6 (IL-6) (WMD: -1.87; 95% CI: -2.80, -0.95), tumor necrosis factor-α (TNF-α) levels (WMD: -1.43; 95% CI: -2.03, -0.84), and malondialdehyde (MDA) (WMD: -0.47; 95% CI: -0.76, -0.18) levels, while there was a significant increase in superoxide dismutase (SOD) (WMD: 2.14; 95% CI: 1.02, 3.25). However, no significant effects of L-carnitine on glutathione peroxidase (GPx) (WMD: 0.02; 95% CI: -0.01, 0.05) and total antioxidant capacity (TAC) (WMD: 0.14; 95% CI: -0.05, 0.33) were found. Conclusions:L-carnitine supplementation was associated with lowering of CRP, IL-6, TNF-α, and MDA, and increasing SOD levels, but did not affect other inflammatory and oxidative stress biomarkers.
10.1007/s40200-020-00627-9
The effect of L-carnitine on inflammatory mediators: a systematic review and meta-analysis of randomized clinical trials.
Haghighatdoost F,Jabbari M,Hariri Mitra
European journal of clinical pharmacology
AIM AND BACKGROUND:Reducing inflammation by nutritional supplements may help to reduce the risk of many chronic diseases. Our aim in this meta-analysis was to determine the effect of L-carnitine on inflammatory mediators including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). METHODS:Our systematic search to find relevant randomized clinical trials (RCTs) was performed up to October 2018 using ISI Web of Science, Google Scholar, PubMed/Medline, and SCOPUS. In this meta-analysis, the weighted mean differences (WMD) with standard errors (SE) were used to pool the data. WMD was calculated by subtracting change-from-baseline mean values in the control group from change-from-baseline mean values in the intervention group in each study. To identify heterogeneity among studies, the I statistic was employed. The protocol was registered with PROSPERO (No. CRD42019116695). RESULTS:Thirteen articles were included in our systematic review and meta-analysis. The results of the meta-analysis indicated that L-carnitine supplementation was significantly associated with lower levels of CRP in comparison to controls (WMD = -1.23 mg/L; 95% CI: -1.73, -0.72 mg/dL; P < 0.0001). Also, a slight but statistically significant decrease was observed in IL-6 and TNF-α levels (WMD = -0.85 pg/dL; 95% CI: -1.38, -0.32 pg/dL; P = 0.002 and WMD = -0.37 pg/dL; 95% CI: -0.68, -0.06 pg/dL; P = 0.018, respectively). CONCLUSION:Our results indicate that L-carnitine reduced inflammatory mediators, especially in studies with a duration of more than 12 weeks. Further studies with different doses and intervention durations and separately in men and women are necessary.
10.1007/s00228-019-02666-5
Efficacy and Safety of L-Carnitine Treatment for Chronic Heart Failure: A Meta-Analysis of Randomized Controlled Trials.
Song Xiaolong,Qu Huiyan,Yang Zongguo,Rong Jingfeng,Cai Wan,Zhou Hua
BioMed research international
. Whether additional benefit can be achieved with the use of L-carnitine (L-C) in patients with chronic heart failure (CHF) remains controversial. We therefore performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of L-C treatment in CHF patients. . Pubmed, Ovid Embase, Web of Science, and Cochrane Library databases, Chinese National Knowledge Infrastructure (CNKI) database, Wanfang database, Chinese Biomedical (CBM) database, and Chinese Science and Technology Periodicals database (VIP) until September 30, 2016, were identified. Studies that met the inclusion criteria were systematically evaluated by two reviewers independently. . 17 RCTs with 1625 CHF patients were included in this analysis. L-C treatment in CHF was associated with considerable improvement in overall efficacy (OR = 3.47, < 0.01), left ventricular ejection fraction (LVEF) (WMD: 4.14%, = 0.01), strike volume (SV) (WMD: 8.21 ml, = 0.01), cardiac output (CO) (WMD: 0.88 L/min, < 0.01), and E/A (WMD: 0.23, < 0.01). Moreover, treatment with L-C also resulted in significant decrease in serum levels of BNP (WMD: -124.60 pg/ml, = 0.01), serum levels of NT-proBNP (WMD: -510.36 pg/ml, < 0.01), LVESD (WMD: -4.06 mm, < 0.01), LVEDD (WMD: -4.79 mm, < 0.01), and LVESV (WMD: -20.16 ml, 95% CI: -35.65 to -4.67, < 0.01). However, there were no significant differences in all-cause mortality, 6-minute walk, and adverse events between L-C and control groups. . L-C treatment is effective for CHF patients in improving clinical symptoms and cardiac functions, decreasing serum levels of BNP and NT-proBNP. And it has a good tolerance.
10.1155/2017/6274854
Efficacy of L-Carnitine for Dilated Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.
BioMed research international
BACKGROUND:L-carnitine mediates the utilization of fatty acids and glucose in the myocardium. The potential of L-carnitine in managing dilated cardiomyopathy (DCM) in patients has been extensively reported, with additional benefits. OBJECTIVE:This meta-analysis purposed to explore the clinical efficacy of L-carnitine therapy on DCM patients. METHODS:We searched publications up to May 2020 from several databases including PubMed, Embase, Cochrane Library, Chinese Biomedical (CBM) database, Chinese Science and Technology Periodicals database (VIP), Chinese National Knowledge Infrastructure (CNKI) database, and Wanfang database. Subsequently, publications that met the inclusion criteria were systematically evaluated by two independent reviewers. RESULTS:A total of 23 RCTs conducted in China with 1455 DCM patients were included in this study. In the meta-analysis, L-carnitine therapy was associated with a considerable improvement in the overall efficacy (RR = 1.28, 95% CI (1.21-1.36), < 0.0001), left ventricular ejection fraction (LVEF) (MD = 6.16%, 95% CI (4.50, 7.83), < 0.0001), and cardiac output (CO) (MD = 0.88 L/min, 95% CI (0.51, 1.25), < 0.0001) as compared to the control group. Moreover, L-carnitine therapy significantly decreased left ventricular end-diastolic dimension (LVEDD) (MD = -2.53, 95% CI (-3.95, -1.12), = 0.0005), brain natriuretic peptide (BNP) (SMD = -1.71 ng/L, 95% CI (-3.02, -0.40), = 0.01), and the transforming growth factor-beta (TGF-1) (MD = -56.78 ng/L, 95% CI (-66.02, -47.53), < 0.0001). CONCLUSIONS:L-carnitine potentially enhanced the therapeutic efficiency in DCM patients. Following weaknesses in the evidence due to low methodological quality and high clinical heterogeneity in the included studies, well-designed trials are recommended.
10.1155/2021/9491615
Analyzing Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis: Potential Role of L-carnitine.
Modanloo Mona,Shokrzadeh Mohammad
Iranian journal of kidney diseases
Mitochondrial dysfunction, apoptosis and oxidative stress, are the interrelated events underlining the pathology of numerous diseases including cardiovascular, neurologic, and metabolic disorders. Due to playing a critical role in glucose and fatty acids' metabolism, L-carnitine probably has the potential to adjust these unfavorable events. The present review has evolved based on existing literature that investigated the mechanisms of L-carnitine and its derivatives based mitochondrial dysfunction, oxidative stress, and apoptosis related modulation. The released studies have been searched with the databases including Google Scholar, Scopus, and PubMed out of which overall 76 full-length articles have been chosen and recruited in this review. L-carnitine exerts protective effects against these cellular events in several manners including the maintenance of mitochondrial functions and decreasing the production of reactive oxygen species at different points. In clinical setting, these effects could be applied to treat a variety of associated diseases.
The effect of l-carnitine supplementation on lipid profile and glycaemic control in adults with cardiovascular risk factors: A systematic review and meta-analysis of randomized controlled clinical trials.
Asadi Maryam,Rahimlou Mehran,Shishehbor Farideh,Mansoori Anahita
Clinical nutrition (Edinburgh, Scotland)
BACKGROUND & AIMS:Several randomized clinical trials (RCTs) have investigated the effect of l-carnitine supplementation on lipid profile and glycaemic control in adults with cardiovascular risk factors; however, the results were conflicting. Therefore, a meta-analysis was performed to assess the effect of l-carnitine on lipid profile and glycaemic control in adults with cardiovascular risk factors. METHODS:We searched PubMed, Scopus, Cochrane Databases, Google Scholar, ProQuest, Web of Science and Embase for randomized, placebo-controlled human trials that investigated the effect of l-carnitine supplementation on lipid profile and glycaemic control up to April 2017. From the eligible trials, 24 articles were selected for the meta-analysis. The meta-analysis was performed in a random-effects model. Heterogeneity was determined by I statistics and Cochrane Q test. RESULTS:The result showed significant effect of l-carnitine on TC (WMD: -13.73 [95% CI: -22.28, -5.17] mg/dL; P < 0.001), LDL-C (WMD = - 7.70 [95% CI: - 11.80, -3.61]mg/dL; p < 0.001), HDL-C (WMD = 0.82 [95% CI: 0.44, 1.21] mg/dL; P > 0.001), Lp(a) (WMD = - 7.13 [95% CI: -9.82,- 4.43]mg/dL; P < 0.001), FPG (WMD = -6.25 [95% CI: -10.35, -2.16] mg/dL; P < 0.001), HbA1C (WMD (%) = - 0.35 [95% CI: -0.65,- 0.05]; p = 0.02) and HOMA-IR (WMD (%) = - 0.94 [95% CI: -1.89, -0.00]; P = 0.05). No effect of l-carnitine was detected in TG, Apo A-I and Apo B 100 on pooled effect size. Additionally, sensitivity analysis showed l-carnitine supplementation could improve glycaemic control, particularly along with hypocaloric diet. CONCLUSION:This meta-analysis showed that l-carnitine supplementation could improve lipid profile levels, particularly in doses more than 1500 mg/day. More RCTs with large sample sizes, focusing on gut microbiome profiles and dietary patterns are needed to better understand the effect of l-carnitine on patients with cardiovascular risk factors.
10.1016/j.clnu.2019.01.020
L-Carnitine improves mechanical responses of cardiomyocytes and restores Ca homeostasis during aging.
Histochemistry and cell biology
L-Carnitine (β-hydroxy-γ-trimethylaminobutyric acid, LC) is a crucial molecule for the mitochondrial oxidation of fatty acids. It facilitates the transport of long-chain fatty acids into the mitochondrial matrix. The reduction in LC levels during the aging process has been linked to numerous cardiovascular disorders, including contractility dysfunction, and disrupted intracellular Ca homeostasis. The aim of this study was to examine the effects of long-term (7 months) LC administration on cardiomyocyte contraction and intracellular Ca transients ([Ca]) in aging rats. Male albino Wistar rats were randomly assigned to either the control or LC-treated groups. LC (50 mg/kg body weight/day) was dissolved in distilled water and orally administered for a period of 7 months. The control group received distilled water alone. Subsequently, ventricular single cardiomyocytes were isolated, and the contractility and Ca transients were recorded in aging (18 months) rats. This study demonstrates, for the first time, a novel inotropic effect of long-term LC treatment on rat ventricular cardiomyocyte contraction. LC increased cardiomyocyte cell shortening and resting sarcomere length. Furthermore, LC supplementation led to a reduction in resting [Ca] level and an increase in the amplitude of [Ca] transients, indicative of enhanced contraction. Consistent with these results, decay time of Ca transients also decreased significantly in the LC-treated group. The long-term administration of LC may help restore the Ca homeostasis altered during aging and could be used as a cardioprotective medication in cases where myocyte contractility is diminished.
10.1007/s00418-023-02215-3
The effects of L-carnitine supplementation on cardiovascular risk factors in participants with impaired glucose tolerance and diabetes: a systematic review and dose-response meta-analysis.
Diabetology & metabolic syndrome
AIMS:L-carnitine plays a role related to cardiometabolic factors, but its effectiveness and safety in CVD are still unknown. We aim to assess the effect of L-carnitine supplementation on CVD risk factors. METHODS:A systematic literature search was conducted in PubMed, Web of Science, and Scopus until October 2022. The main outcomes were lipid profiles, anthropometric parameters, insulin resistance, serum glucose levels, leptin, blood pressure, and inflammatory markers. The pooled weighted mean difference (WMD) was calculated using a random-effects model. RESULTS:We included the 21 RCTs (n = 2900) with 21 effect sizes in this study. L-carnitine supplementation had a significant effect on TG (WMD = - 13.50 mg/dl, p = 0.039), LDL (WMD = - 12.66 mg/dl, p < 0.001), FBG (WMD = - 6.24 mg/dl, p = 0.001), HbA1c (WMD = -0.37%, p = 0.013) HOMA-IR (WMD = -0.72, p = 0.038 (, CRP (WMD = - 0.07 mg/dl, P = 0.037), TNF-α (WMD = - 1.39 pg/ml, p = 0.033), weight (WMD = - 1.58 kg, p = 0.001 (, BMI (WMD = - 0.28 kg/m, p = 0.017(, BFP (WMD = - 1.83, p < 0.001) and leptin (WMD = - 2.21 ng/ml, p = 0.003 (in intervention, compared to the placebo group, in the pooled analysis. CONCLUSIONS:This meta-analysis demonstrated that administration of L-carnitine in diabetic and glucose intolerance patients can significantly reduce TG, LDL-C, FBG, HbA1c, HOMA-IR, CRP, TNF-α, weight, BMI, BFP, and leptin levels. PROSPERO registration code: CRD42022366992.
10.1186/s13098-024-01415-8
Effect of L-Carnitine Supplementation on Reverse Remodeling in Patients with Ischemic Heart Disease Undergoing Coronary Artery Bypass Grafting: A Randomized, Placebo-Controlled Trial.
da Silva Guimarães Sheila,de Souza Cruz Wanise,da Silva Licinio,Maciel Gabrielle,Huguenin Ana Beatriz,de Carvalho Monicque,Costa Bárbara,da Silva Geisiane,da Costa Carlos,D'Ippolito João Alvaro,Colafranceschi Alexandre,Scalco Fernanda,Boaventura Gilson
Annals of nutrition & metabolism
During cardiac failure, cardiomyocytes have difficulty in using the substrates to produce energy. L-carnitine is a necessary nutrient for the transport of fatty acids that are required for generating energy. Coronary artery graft surgery reduces the plasma levels of L-carnitine and increases the oxidative stress. This study demonstrates the effect of L-carnitine supplementation on the reverse remodeling of patients undergoing coronary artery bypass graft. Patients with ischemic heart failure who underwent coronary graft surgery were randomized to group A - supplemented with L-carnitine or group B controls. Left ventricular ejection fraction, left ventricular systolic and diastolic diameters were assessed preoperatively, 60 and 180 days after surgery. Our study included 28 patients (26 [93.0%] males) with a mean age ± SD of 58.1 ± 10.5 years. The parameters for the evaluation of reverse remodeling did not improve after 60 and 180 days of coronary artery bypass grafting in comparison between groups (p > 0.05). Evaluation within the L-carnitine group showed a 37.1% increase in left ventricle ejection fraction (p = 0.002) and 14.3% (p = 0.006) and 3.3% (p > 0.05) reduction in systolic and diastolic diameters, respectively. L-carnitine supplementation at a dose of 50 mg/kg combined with artery bypass surgery did not demonstrate any additional benefit in reverse remodeling. However, evaluation within the L-carnitine group may indicate a clinical benefit of L-carnitine supplementation.
10.1159/000465531