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L-Carnitine - Metabolic Functions and Meaning in Humans Life
Abstract
L-Carnitine is an endogenous molecule involved in fatty acid metabolism, biosynthesized within the human body using amino acids: L-lysine and L-methionine, as substrates. L-Carnitine can also be found in many foods, but red meats, such as beef and lamb, are the best choices for adding carnitine into the diet. Good carnitine sources also include fish, poultry and milk. Essentially, L-carnitine transports the chains of fatty acids into the mitochondrial matrix, thus allowing the cells to break down fat and get energy from the stored fat reserves. Recent studies have started to shed light on the beneficial effects of L-carnitine when used in various clinical therapies. Because L-carnitine and its esters help reduce oxidative stress, they have been proposed as a treatment for many conditions, i.e. heart failure, angina and weight loss. For other conditions, such as fatigue or improving exercise performance, L-carnitine appears safe but does not seem to have a significant effect. The presented review of the literature suggests that continued studies are required before L-carnitine administration could be recommended as a routine procedure in the noted disorders. Further research is warranted in order to evaluate the biochemical, pharmacological, and physiological determinants of the response to carnitine supplementation, as well as to determine the potential benefits of carnitine supplements in selected categories of individuals who do not have fatty acid oxidation defects.
... Accordingly, expanding evidence has suggested weight reducing and lipid-lowering effects of L-carnitine [19][20][21][22], a vitamin-like nutraceutical, increasingly consumed due to its purported beneficial therapeutic efficacy, particularly contributing in cardiometabolic risk factors amendment [23][24][25], which has been attributed to its pivotal role in lipid and glucose metabolism [24,26], mediated through participating in fatty acids beta-oxidation [27,28], enhancing energy expenditure [24], activating adipocyte lipolysis [29,30], stimulating the glycolytic pathway [24], ameliorating inflammation [31][32][33], and reducing food intake [30,34]. ...
... Accordingly, expanding evidence has suggested weight reducing and lipid-lowering effects of L-carnitine [19][20][21][22], a vitamin-like nutraceutical, increasingly consumed due to its purported beneficial therapeutic efficacy, particularly contributing in cardiometabolic risk factors amendment [23][24][25], which has been attributed to its pivotal role in lipid and glucose metabolism [24,26], mediated through participating in fatty acids beta-oxidation [27,28], enhancing energy expenditure [24], activating adipocyte lipolysis [29,30], stimulating the glycolytic pathway [24], ameliorating inflammation [31][32][33], and reducing food intake [30,34]. ...
... Accordingly, expanding evidence has suggested weight reducing and lipid-lowering effects of L-carnitine [19][20][21][22], a vitamin-like nutraceutical, increasingly consumed due to its purported beneficial therapeutic efficacy, particularly contributing in cardiometabolic risk factors amendment [23][24][25], which has been attributed to its pivotal role in lipid and glucose metabolism [24,26], mediated through participating in fatty acids beta-oxidation [27,28], enhancing energy expenditure [24], activating adipocyte lipolysis [29,30], stimulating the glycolytic pathway [24], ameliorating inflammation [31][32][33], and reducing food intake [30,34]. ...
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 approach to ameliorate cardiometabolic risk factors in healthy individuals with obesity. Further longer period studies are required to confirm these findings. (Iranian Registry of Clinical Trials (IRCT; https://irct.behdasht.gov.ir/trial/28048).
... L-carnitine is known for its role in supporting muscle function. It may reduce muscle damage and soreness following intense exercise, potentially aiding in faster recovery(Pekala et al., 2011). ...
... It also spares the use of amino acids as energy sources during exercise, making them potentially available for new protein synthesis, and decreases the accumulation of lactate. However, research findings on the effectiveness of supplemental carnitine on athletic performance are mixed(Pekala et al., 2011). ...
Background: Despite extensive research, the effects of L-carnitine supplementation on obesity treatment remain unclear and inconsistent. L-carnitine is known for transporting fatty acids into mitochondria for oxidation and is marketed as a weight loss supplement. This study aims to investigate the efficacy of L-carnitine supplementation during concurrent training on body composition and functional capacities in obese men.
Methodology: Thirty sedentary, obese males (age = 37.2 ± 1.5 years, body mass index = 33.8 ± 2.5 kg/m²) participated in this study. Participants were randomly assigned to three groups: Experimental group 1 (EXG 1): concurrent training with L-carnitine supplementation, Experimental group 2 (EXG 2): L-carnitine supplementation without training, and a Control group: no training or L-carnitine supplementation. Both experimental groups received 35 mg of L-carnitine per kg of body weight. Concurrent training was conducted for 8 weeks, with three sessions per week, at an intensity ranging from 60% to 75% of maximal heart rate reserve and one-repetition maximum. Various functional and body composition metrics were collected at three time points: pre-test, mid-test, and post-test.
Results: Significant improvements were observed in the EXG 1 group after 4 and 8 weeks in several variables: systolic blood pressure, maximal oxygen consumption, weight, body mass index, and one-repetition maximum. Additional improvements were noted after 8 weeks in diastolic blood pressure, resting heart rate, percentage of body fat, and fat-free mass. No significant changes were observed in the EXG 2 and Control groups.
Conclusion: L-carnitine supplementation combined with concurrent training is an effective approach for improving body composition and enhancing functional capacities in obese men. It is recommended that overweight men incorporate concurrent training into their regimen while taking L-carnitine.
... Additionally, L-carnitine participates in the oxidation of fatty acids in peroxisomes, maintaining the CoA/acyl-CoA ratio in the cell, and the utilization of ketone bodies. L-carnitine deficiency can lead to metabolic disorders affecting muscle and heart function and manifest as myopathy or heart disease [46]. Animal products, especially meat, are a very valuable source of L-carnitine in the human diet, and its content depends on the type of product, animal species, and the processing used. ...
The aim of this study was to assess the impact of tomato pomace (TP) on the content of volatile compounds and L-carnitine and the sensory characteristics of raw fermented sausages produced with reduced nitrite. The produced sausages were divided into three experimental groups: control sample, sample with 1.5% addition of freeze-dried tomato pomace, and sample with 2.5% addition of TP. The results showed that the addition of tomato pomace significantly affected the quality of raw fermented sausages. Lower L-carnitine content was observed in samples with TP. The main groups of volatile compounds identified in fermented sausages were alcohols, aldehydes, hydrocarbons, and ketones. The addition of TP influenced the smell and taste of the sausages, which were characterized by a more intense tomato taste and smell and more intense red color compared to the control sample. Despite the influence of TP addition on some sensory features, the products were characterized by a high score of overall quality of over 7 c.u. on a 10-point scale, similar to the control sausage.
... Acyl-CoA undergoes β-oxidation to generate acetyl-CoA, NADH, and FADH, which are substrates for the Krebs cycle and electron transport chain, thereby promoting ATP production [142]. It is synthesized in the body from lysine and methionine but can also be obtained from dietary sources or supplements [143]. LC reduces oxidative stress by preventing the accumulation of fatty acid intermediates, which can impair mitochondrial function through its metabolic role in fatty acid oxidation [144,145]. ...
Background Soccer is linked to an acute inflammatory response and the release of reactive oxygen species (ROS). Antioxidant supplements have shown promising effects in reducing muscle damage and oxidative stress and enhancing the recovery process after eccentric exercise. This critical review highlights the influence of antioxidant supplements on performance and recovery following soccer-related activity, training, or competition. Methods: English-language publications from the main databases that examine how antioxidant-based nutrition and supplements affect the recovery process before, during, and after soccer practice or competition were used. Results: Coenzyme Q10 (CoQ10), astaxanthin (Asx), red orange juice (ROJS), L-carnitine (LC), N-acetyl cysteine (NAC), beetroot (BET), turmeric root, and tangeretin reduce muscle damage (creatine kinase, myoglobin, cortisol, lactate dehudrogenase, muscle soreness). Tangeretin, docosahexaenoic acid (DHA), turmeric root, and aronia melanocarpa restrict inflammation (leukocytes, prostalagdin E2, C-reactive protein, IL-6 and 10). Q10, DHA, Asx, tangeretin, lippia citriodora, quercetin, allopurinol, turmeric root, ROJS, aronia melanocarpa, vitamins C-E, green tea (GTE), and sour tea (STE) reduce oxidative stress (malondialdehude, glutathione, total antioxidant capacity, superoxide dismutases, protein carbonyls, ascorbate, glutathione peroxidase, and paraoxonase 1). BET and NAC reinforce performance (endurance, jump, speed, strength). Conclusions: Further research is needed to determine the main mechanism and the acute and long-term impacts of antioxidant supplements in soccer.
Metabolomics, unlike traditional methods for analysing the nutritional content of fruits and vegetables, enables the detection of low-molecular-weight metabolites (<1 kDa), including carnitine and its derivatives, acylcarnitines. These compounds are integral to energy metabolism, facilitating mitochondrial transport of long-chain fatty acids, cytosolic export of short-chain fatty acids, stabilisation of the mitochondrial coenzyme A to acetyl-CoA ratio, preservation of membrane integrity, and reduction of lactate production. While carnitine profiles in various fruits and vegetables have been extensively studied, data on its presence in pomegranates remains limited. This study aims to elucidate the carnitine composition in five pomegranate cultivars using LC-MS/MS analysis. Results indicate significantly higher concentrations of free carnitine and acetylcarnitine in the Suruç variety, alongside other notable acylcarnitines, including propionylcarnitine, hydroxyisovalerylcarnitine, adipoylcarnitine, and oleylcarnitine. These findings position pomegranate as a promising dietary component with potential health benefits attributed to its carnitine content.
Aim/Hypothesis
Recently, we reported that increasing free carnitine availability resulted in elevated skeletal muscle acetylcarnitine concentrations and restored metabolic flexibility in individuals who have impaired glucose tolerance. Metabolic flexibility is defined as the capacity to switch from predominantly fat oxidation while fasted to carbohydrate oxidation while insulin stimulated. Here we investigated if carnitine supplementation enhances the capacity of skeletal muscle to form acetylcarnitine and thereby improves insulin sensitivity and glucose homeostasis in patients with type 2 diabetes (T2DM).
Methods
Thirty‐two patients followed a 12‐week L‐carnitine treatment (2970 mg/day, orally). Insulin sensitivity was assessed by a two‐step hyperinsulinemic‐euglycemic clamp. In vivo skeletal muscle acetylcarnitine concentrations at rest and post‐exercise (30 min, 70% W max ) and intrahepatic lipid content (IHL) were determined by proton magnetic resonance spectroscopy ( ¹ H‐MRS). All measurements were performed before and after 12 weeks of carnitine supplementation.
Results
Compliance with the carnitine supplementation was good (as indicated by increased plasma‐free carnitine levels ( p < 0.01) and pill count (97.1 ± 0.7%)). Insulin‐induced suppression of endogenous glucose production (31.9 ± 2.9 vs. 39.9 ± 3.2%, p = 0.020) and peripheral insulin sensitivity (Δ rate of glucose disappearance (ΔR d ): 10.53 ± 1.85 vs. 13.83 ± 2.02 μmol/kg/min, p = 0.005) improved after supplementation. Resting (1.18 ± 0.13 vs. 1.54 ± 0.17 mmol/kgww, p = 0.008) and post‐exercise (3.70 ± 0.22 vs. 4.53 ± 0.30 mmol/kgww, p < 0.001) skeletal muscle acetylcarnitine concentrations were both elevated after carnitine supplementation. Plasma glucose ( p = 0.083) and IHL ( p = 0.098) tended to be reduced after carnitine supplementation.
Conclusion
Carnitine supplementation improved insulin sensitivity and tended to lower IHL and fasting plasma glucose levels in patients with type 2 diabetes. Furthermore, carnitine supplementation increased acetylcarnitine concentration in muscle, which may underlie the beneficial effect on insulin sensitivity.
In Ukraine, conditions arising during the perinatal period accounted for 57.9% of infant mortality under 1 year of age in 2021, compared to 55.6% in 2017. Hypoxic-ischemic encephalopathy (HIE) remains a leading cause of neurological complications and disability, particularly in low-income countries, where its incidence reaches 10-20 cases per 1,000 newborns. Despite advances in medical care, the risk of irreversible brain damage from HIE remains high. The processes associated with HIE are marked by oxidative stress and disrupted ionic homeostasis, leading to neuroapoptosis and necrosis of brain cells. Objective: to investigate metabolic changes in newborns with HIE by assessing nitric oxide, malondialdehyde, sialic acids, eNOS gene variants, and the impact of L-carnitine on metabolite concentrations. Materials and Methods. The study included 30 neonates. The main group consisted of 16 children with HIE, monitored in an outpatient follow-up clinic and receiving levocarnitine. The comparison group included 14 randomly selected relatively healthy neonates without HIE. Levels of nitrites, nitrates, malondialdehyde, and sialic acids in urine were assessed during the early neonatal period and at 6-9 months of age in children with HIE. In the comparison group, metabolite levels were measured at 6-9 months of age. Results. The study revealed increased nitrite (1.71 vs. 2.7; p=0.003) and nitrate (3.72 vs. 5.42; p=0.010) levels in newborns with HIE, indicating activation of nitric oxide metabolism. Malondialdehyde levels decreased following L-carnitine treatment, suggesting reduced oxidative stress. Genetic analysis showed a higher frequency of the 894GT genotype in the eNOS gene among newborns with reduced sialic acid concentrations (0.2 vs. 0.59; p=0.008). Conclusion. L-carnitine shows potential neuroprotective effects in the treatment of HIE by stabilizing mitochondrial function and reducing oxidative stress. Further studies are needed to optimize therapeutic strategies.
Evidence indicates phenotypic and biological overlap between psychiatric and neurodegenerative disorders. Further identification of underlying mutual and unique biological mechanisms may yield novel multi-disorder and disorder-specific therapeutic targets. The metabolome represents an important domain for target identification as metabolites play critical roles in modulating a diverse range of biological processes. Here, we used Mendelian randomisation (MR) to test the causal effects of ~1000 plasma metabolites and ~300 metabolite ratios on anxiety, bipolar disorder, depression, schizophrenia, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease and multiple sclerosis. In total, 85 causal effects involving 77 unique metabolites passed FDR correction and robust sensitivity analyses (IVW-MR OR range: 0.73-1.48 p FDR ≤ 0.05). No evidence of reverse causality was identified. Multivariate analyses implicated sphingolipid metabolism in psychiatric disorder risk and carnitine derivatives in risk for amyotrophic lateral sclerosis and multiple sclerosis. However, polygenic risk scores for prioritised metabolites showed limited prediction in the UK Biobank. Downstream colocalisation in regions containing influential variants identified greater than suggestive evidence (PP.H 4 ≥ 0.6) for a shared causal variant for 29 metabolite/psychiatric disorder trait-pairs on chromosome 11 at the FADS gene cluster. Most of these metabolites were lipids containing linoleic or arachidonic acid. Additional colocalisation was identified between the ratio of histidine-to-glutamine, glutamine, Alzheimer's disease and SPRYD4 gene expression on chromosome 12. Although no single metabolite had a causal effect on a psychiatric and a neurodegenerative disease, results suggest a broad effect of lipids across brain disorders. Metabolites identified here may help inform future targeted interventions.
Defective sperm function is the most common cause of infertility, and until recently, was difficult to evaluate and treat. Mammalian spermatozoa membranes are rich in poly unsaturated fatty acids and are sensitive to oxygen induced damage mediated by lipid peroxidation. Hence, free radicals and reactive oxygen species [ROS] are associated with oxidative stress and are likely to play a number of significant and diverse roles in reproduction. The excessive generation of reactive oxygen species by abnormal spermatozoa and by contaminating leukocytes [leukocytospermia] has been identified as one of the few defined etiologies for male infertility. Moreover, environmental factors, such as pesticides, exogenous estrogens, and heavy metals may negatively impact spermatogenesis since male sperm counts were declined. In addition, aging is also likely to further induce oxidative stress. Limited endogenous mechanisms exist to reverse these damages. In a normal situation, the seminal plasma contains antioxidant mechanisms which are likely to quench these ROS and protect against any likely damage to spermatozoa. However, during genitourinary infection/inflammation these antioxidant mechanisms may downplay and create a situation called oxidative stress. Assessment of such oxidative stress status [OSS] may help in the medical treatment of male infertility by suitable antioxidants. The cellular damage in the semen is a result of an improper balance between ROS generation and scavenging activities. Therefore, numerous antioxidants such as vitamin C, vitamin E, glutathione, and coenzyme Q10, have proven beneficial effects in treating male infertility. A multi-faceted therapeutic approach to improve male fertility involves identifying harmful environmental and occupational risk factors, while correcting underlying nutritional imbalances to encourage optimal sperm production and function.
The affect of L-carnitine (Carnitene) on myocardial metabolism was evaluated by subjecting 18 patients with coronary artery disease to two rapid coronary sinus pacings separated by a 45-seconds recovery interval. Eleven patients received L-carnitine (40 mg/kg dissolved in 50 ml of saline solution) before the second pacing study (treated group), while the remaining seven received an equivalent volume of saline solution (untreated group). At rest, L-carnitine significantly (P < 0.001) reduced arterial free fatty acid (FFA) concentration, but not the myocardial A-V difference for FFA, while it did not produce significant effects on lactate arterial concentrations or on the myocardial A-V difference. In addition, at rest, L-carnitine had no effect on heart rate, pressure rate product, left ventricular systolic or diastolic pressures. During the two pacing periods the untreated group had almost identical metabolic and haemodynamic changes with marked lactate production in the coronary sinus and a significantly increased left ventricular end-diastolic pressure (LVEDP), P < 0.01. During the second pacing period in the treated group after L-carnitina administration, lactate production was converted to extraction, FFA percentage extraction was increased (P < 0.05) and the pacing-induced increase in LVEDP was reduced (P < 0.001). Pacing time to angina and pressure rate product, however, were not significantly changed. These results suggest that L-carnitine is able to modify FFA metabolism at rest and to prevent lactate production and LVEDP increase after atrial pacing without major haemodynamic effects.
Time for primary review 28 days.
The regulation of mammalian myocardial carbohydrate metabolism is complex in that it is linked to arterial substrate and hormone levels, coronary flow, inotropic state and the nutritional status of the tissue. Optimal cardiac function under normal and pathological conditions is dependent upon glycolysis and pyruvate oxidation. The purpose of this review is to examine the regulation of myocardial carbohydrate metabolism under physiological conditions, and during myocardial ischaemia and reperfusion. The therapeutic potential of a variety of pharmacological interventions affecting myocardial carbohydrate metabolism will then be discussed.
The tricarboxylic acid cycle (TCA cycle) provides reducing equivalents for mitochondrial oxidative phosphorylation, resulting in the condensation of ADP and inorganic phosphate to regenerate ATP, and is fueled by acetyl-CoA formed primarily from oxidation of pyruvate and fatty acids (Fig. 1). Cardiomyocytes oxidise fatty acids derived from both the plasma and the breakdown of intracellular triacylglycerol stores, while pyruvate is derived from either lactate dehydrogenase or glycolysis. The rates of these metabolic pathways are tightly coupled to the rate of contractile work, and conversely, contractile work is coupled to the supply of oxygen and the rate of oxidative phosphorylation (Fig. 1). Early studies in animals [1] and human [2, 3] showed that after an overnight fast the heart extracts free fatty acids (FFA), lactate and glucose from the blood, and that if one assumes complete oxidation of extracted substrates, fatty acids are the major oxidative fuel for the heart (60–100% of the oxygen consumption), with a lesser contribution from lactate and glucose (0–20% from each) [2, 3]. Subsequent studies by others using a variety of experimental approaches have confirmed these early results (see [4–7] for reviews).
Fig. 1
Schematic depiction of myocardial substrate metabolism. Abbreviations: G 6-P, glucose 6-phosphate; TCA, tricarboxylic acid; GT, GLUT 1 and GLUT 4 glucose …
Objectives: To assess the longitudinal effects of acetyl-L-carnitine (ALC) on patients diagnosed with Alzheimer's disease. Design: Longitudinal, double-blind, parallel-group, placebocontrolled. Setting: Twenty-four outpatient sites across the United States. Participants: A total of 334 subjects diagnosed with probable Alzheimer's disease by NINCDS-ADRDA criteria. These data were originally reported by Thal and colleagues (1996). Measurements: Cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) given every 3 months for 1 year. Results: The average rate of change was estimated using the trilinear approach, which allows for periods of both change and stability. Both the ALC group and the placebo group exhibited the same mean rate of change on the ADAS (0.68 points/month). However, a multiple regression analysis revealed a statistically significant Age × Drug interaction characterized by younger subjects benefiting more from ALC treatment than older subjects. Further analyses suggested that the optimal, though not statistically significant, cutpoint for ALC benefit was 61 years of age. Conclusions: ALC slows the progression of Alzheimer's disease in younger subjects, and the use of the trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials.
The ability of the rat liver to synthesize camitine from γ-butyrobetaine increases from low values in the fetus to adult values on the 8th day after birth. The rate of synthesis of camitine is greater when determined in the high-speed supernatant than in the low-speed supernatant of the liver. No synthesis could be shown to occur in neonatal rat kidney or neonatal brown adipose tissue.
We have previously described apparent active transport of carnitine into rat intestinal mucosa with intracellular accumulation against a concentration gradient in a process dependent upon the presence of sodium ions, oxygen, and energy. In the work described here, we sought to define the interaction between carnitine and the brush border membrane, which we presumed contained the transport mechanism. Using isolated rat jejunal brush border microvillous membrane vesicles, we found evidence of passive diffusion alone. We found no evidence of carrier-mediated transport—in particular no saturation over a concentration range, inhibition by structural analogs, transstimulation phenomenon, and no influence of sodium ions, potential difference or proton gradients. We conclude that a carnitine transporter does not exist in the brush border membrane of enterocytes and that other cellular mechanisms are responsible for the apparent active transport observed.
The review begins with brief introductory remarks about the significance of carnitine. This is followed by a historical section on its discovery and function, ending with a listing of carnitine-dependent enzymes. Carnitine acetyltransferase then becomes the entire focus of the review. The ubiquity of the protein in tissues and organelles is emphasized in an initial section. A discussion of its enzymology follows, beginning with physical properties and kinetics and ending with substrate and inhibitor specificities. The review concludes with a discussion of proposed molecular mechanisms.