Serum Carnitine Research Articles

Effects of l-carnitine supplementation on cardiovascular and bone turnover markers in patients with pemphigus vulgaris under corticosteroids treatment: A randomized, double-blind, controlled trial.

Pemphigus vulgaris (PV) is a severe, bullous, autoimmune disease of the skin and mucous membranes. Corticosteroids are usually the main core treatment for controlling PV, which could lead to several side effects such as insulin resistance, osteoporosis, and cardiovascular disorders. The aim of this study is to evaluate the protective effects of l-carnitine (LC) supplementation in PV patients under corticosteroid treatment. In this randomized, double-blind, placebo-controlled clinical trial, 48 patients with PV were divided randomly into two groups to receive 2 g LC (n = 24) or a placebo (n = 24) for 8 weeks, respectively. Serum levels of osteopontin (OPN), bone morphogenic protein 4 (BMP4), cystatin C, systolic and diastolic blood pressure, 25 hydroxyvitamin D3, and LC were evaluated at the beginning and at the end of the study. LC supplementation demonstrated a significant increase in serum carnitine (p < .001). In addition, at the end of the trial, LC supplementation significantly decreased serum BMP4 (p = .003), OPN (p = .03), and cystatin C (p = .001) levels. There was no significant effect on blood pressure in comparison with the placebo. During study, no harmful side effects were reported by patients. These findings indicate that LC supplementation significantly leads to favorable changes in OPN, BMP4, and cystatin C in PV patients under corticosteroid therapy. However, further investigations are required to confirm these results.

A simple and precise method for measurement of serum free carnitine and acylcarnitines by isotope dilution HILIC-ESI-MS/MS

Recent studies have found that carnitine and acylcarnitines (AcyCNs) are potential biomarkers for many metabolic diseases, including inherited disorders, diabetes and coronary atherosclerotic artery disease (CAD). Here we presented and validated a method for measurement of free carnitine and twelve AcyCNs in human serum by using electrospray ionization tandem mass spectrometry (ESI-MS/MS). Serum samples were mixed with isotopic labeled internal standards and extracted with isopropanol. Carnitine and AcyCNs were separated within 5min by isocratic elution on a hydrophilic interaction liquid chromatographic column (HILIC) and detected with electrospray ionization (ESI) in positive ion mode with multiple reaction monitor (MRM) mode. This method was linear in response with correlation coefficients higher than 0.999. Analytical recoveries were 89.4%–105.4% with an average of 98.7%. The intra-run and total imprecisions were 0.9–4.7% and 1.5–14.1%, respectively. Stability tests showed that all the compounds were stable in serum for at least 6 month at −80 °C, but unstable when stored at room temperature (RM) and 4 °C.Serum carnitine and AcyCNs concentrations of 472 apparently healthy subjects were analyzed. Significant associations between the metabolites and traditional CAD risk factors were observed. The established HILIC–ESI-MS/MS method was simple, precise, and sensitive and may be used as an efficient tool in CAD risk assessment and research.

ASIC3-dependent metabolomics profiling of serum and urine in a mouse model of fibromyalgia

Fibromyalgia (FM) is characterized by chronic widespread pain. The pathogenesis of FM remains unclear. No specific biomarkers are available. Animal models of FM may provide an opportunity to explore potential biomarkers in a relative homogenous disease condition. Here, we probed the metabolomics profiles of serum and urine in a mouse model of FM induced by intermittent cold stress (ICS). We focused on the role of acid-sensing ion channel 3 (ASIC3) in the metabolomics profiling because ICS treatment induced chronic widespread muscle pain lasting for 1 month in wild-type (Asic3+/+) but not Asic3-knockout (Asic3−/−) mice. Serum and urine samples were collected from both genotypes at different ICS stages, including before ICS (basal level) and post-ICS at days 10 (middle phase, P10) and 40 (recovery phase, P40). Control naïve mice and ICS-induced FM mice differed in 1H-NMR- and LC-MS-based metabolomics profiling. On pathway analysis, the leading regulated pathways in Asic3+/+ mice were taurine and hypotaurine, cysteine and methionine, glycerophospholipid, and ascorbate and aldarate metabolisms, and the major pathways in Asic3−/− mice involved amino acid-related metabolism. Finally, we developed an algorithm for the impactful metabolites in the FM model including cis-aconitate, kynurenate, taurine, pyroglutamic acid, pyrrolidonecarboxylic acid, and 4-methoxyphenylacetic acid in urine as well as carnitine, deoxycholic acid, lysoPC(16:0), lysoPC(20:3), oleoyl-L-carnitine, and trimethylamine N-oxide in serum. Asic3−/− mice were impaired in only muscle allodynia development but not other pain symptoms in the ICS model, so the ASIC3-dependent metabolomics changes could be useful for developing diagnostic biomarkers specific to chronic widespread muscle pain, the core symptom of FM. Further pharmacological validations are needed to validate these metabolomics changes as potential biomarkers for FM diagnosis and/or treatment responses.

First Case Report of Primary Carnitine Deficiency Manifested as Intellectual Disability and Autism Spectrum Disorder

Systemic primary carnitine deficiency (PCD) is a genetic disorder caused by decreased or absent organic cation transporter type 2 (OCTN2) carnitine transporter activity, resulting in low serum carnitine levels and decreased carnitine accumulation inside cells. In early life, PCD is usually diagnosed as a metabolic decompensation, presenting as hypoketotic hypoglycemia, Reye syndrome, or sudden infant death; in childhood, PCD presents with skeletal or cardiac myopathy. However, the clinical presentation of PCD characterized by autism spectrum disorder (ASD) with intellectual disability (ID) has seldom been reported in the literature. In this report, we describe the clinical features of a seven-year-old girl diagnosed with PCD who presented atypical features of the disease, including a developmental delay involving language skills, concentration, and attention span, as well as autistic features and brain alterations apparent in magnetic resonance imaging. We aim to highlight the difficulties related to the diagnostic and therapeutic approaches used to diagnose such patients. The case reported here presented typical signs of PCD, including frequent episodes of hypoglycemia, generalized muscle weakness, decreased muscle mass, and physical growth deficits. A molecular genetic study confirmed the definitive diagnosis of the disease (c.1345T>G (p.Y449D)) in gene SLC22A5, located in exon 8. PCD can be accompanied by less common clinical signs, which may delay its diagnosis because the resulting global clinical picture can closely resemble other metabolic disorders. In this case, the patient was prescribed a carnitine-enriched diet, as well as oral carnitine at a dose of 100 mg/kg/day. PCD has a better prognosis if it is diagnosed and treated early; however, a high level of clinical suspicion is required for its timely and accurate diagnosis.

Metabolic disorder of amino acids, fatty acids and purines reflects the decreases in oocyte quality and potential in sows

Oocyte quality is closely related to female fertility. Nevertheless, core nutritional metabolites influencing oocyte quality are unclear. Herein, comprehensive metabolomics analysis of follicular fluid, serum, and urine from low reproductive performance (LRP) and normal reproductive performance (NRP) sows was conducted. Twenty-seven, fourteen and sixteen metabolites (involved in metabolism of amino acids, fatty acids, purine and pyrimidine) were altered in follicular fluid, serum and urine, respectively, in LRP compared with NRP sows, and could decrease oocyte quality and developmental potential, ultimately leading to low fertility. Deoxyinosine, guanidine acetate, thymidine, 5,6-epoxy-eicosatrienoic acid, carnosine, docosahexaenoic acid and carbamoyl phosphate in follicular fluid, cysteine, carnitine, serotonin, hypoxanthine, valine and arginine in serum, as well as carnitine, phenyl glycine, N-acetyl glutamine, propionyl carnitine and choline in urine could be selected as diagnostic markers to indicate oocyte quality. Consistent with metabolomics data, we confirmed changes in concentrations of fatty acids and amino acids in follicular fluid. Targeting purine metabolism, elevating levels of deoxyinosine in in-vitro maturation medium of porcine oocyte significantly promoted the blastocyst rate. Collectively, this study provided new information of potential targets for predicting oocyte quality and developmental potential, and may help with strategies for early diagnosis or therapeutic/dietary intervention in improving reproductive outcomes.

Serum carnitine levels of children with epilepsy: Related factors including valproate

ObjectiveThis study measured the serum carnitine levels in patients with epilepsy and determined the factors contributing to low carnitine levels. MethodsWe measured the serum carnitine levels in 94 consecutive patients with epilepsy, including the free carnitine (FC) and acylcarnitine fractions, using an enzyme cycling method. We defined a low FC as a serum FC level < 36 μmol/L. Age, body mass index (BMI), standard deviation score of BMI (BMI-SDS), use of valproate, cognitive disorder, and feeding problems differed between patients with low and normal FC. In patients taking valproate, the associations of the serum FC level with the platelet count and serum ammonia and amylase levels were analyzed. ResultsUnivariate analysis showed that a low BMI and BMI-SDS, the use of valproate, and cognitive disorder were more frequent in patients with a low FC. Logistic regression analysis revealed that a low BMI-SDS and cognitive disorders were independently associated with a low FC. Among the patients taking valproate, a low BMI-SDS and age were associated with a low FC. The serum FC and ammonia levels were inversely correlated, whereas no correlation was observed between the serum FC level and platelet count or serum amylase level. ConclusionA low BMI and cognitive disorders were related to a low FC in patients with epilepsy and the serum carnitine levels should be monitored in these patients.

Study of serum and seminal carnitine levels in Egyptian men with chronic hepatitis C

Objective The aim of the study was to evaluate the serum and seminal carnitine levels in Egyptian men with chronic hepatitis C virus (HCV) infection. Background In 2015, HCV still affects a substantial proportion of the Egyptian population, in the 1–59 year age, 5.3 million persons are positive for HCV antibodies. Numerous studies have investigated the benefits of carnitine supplementation on improving the complications of viral hepatitis, like steatosis and hepatic encephalopathy. Patients and methods A cross-sectional study was conducted on 35 patients with HCV attending the hepatitis outpatient clinic, in Shebin El-Kom Teaching Hospital, Egypt. Moreover, 20 healthy individuals were also included as a control group. They were all subjected to history taking and serum and semen carnitine level examination. Results Results revealed an insignificant difference between patients with HCV and healthy individuals concerning age, residence, and serum urea level. However, a significant difference was found between the groups regarding serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, creatinine level, prothrombin activity (%), and serum and semen carnitine levels. Moreover, a nonsignificant positive correlation (r = 0.331, P = 0.052) was founded between serum and semen carnitine levels in patients with HCV; in addition, a nonsignificant negative correlation (r = −0.364, P = 0.301) was found between serum and semen carnitine levels in the control group. Conclusion Results concluded that patients with HCV had significantly higher serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, urea, and creatinine level. However, they had significantly lower prothrombin activity and serum and semen carnitine levels compared with the healthy group. Moreover, an insignificant correlation was detected between serum and semen carnitine levels for patients with HCV. So, many studies on various world population with this trend are warranted.

Carnitine deficiency in epileptic children treated with a diversity of anti-epileptic regimens

BackgroundCarnitine deficiency is relatively common in epileptic patients. The risk factors reported include the combination of valproic acid with other antiepileptic drugs (AEDs), young age, multiple neurologic disabilities, non-ambulatory status, and being underweight.ObjectivesTo study the level of carnitine deficiency and its associated risk factors among a group of children with idiopathic epilepsy treated with different AEDs.Patients and methodsFifty children with idiopathic epilepsy and 40 age-matched controls were enrolled. For all, serum carnitine level was measured by enzyme-linked immune sorbent assay (ELISA).ResultsThe mean carnitine level was lower in cases compared to controls (p = 0.04). Patients receiving monotherapy treatment had a high percentage of carnitine deficiency compared to controls (p = 0.04). Patients receiving valproate with other AEDs had a lower level of carnitine compared to controls (p = 0.03). The age of the patients, the duration of treatment, and the doses of different AEDs were not risk factors for carnitine deficiency.ConclusionsCarnitine deficiency is common in our population, and the use of valproate with other AEDs is considered the most important risk factor for it in epileptic children.

Determinants of the urinary and serum metabolome in children from six European populations

BackgroundEnvironment and diet in early life can affect development and health throughout the life course. Metabolic phenotyping of urine and serum represents a complementary systems-wide approach to elucidate environment–health interactions. However, large-scale metabolome studies in children combining analyses of these biological fluids are lacking. Here, we sought to characterise the major determinants of the child metabolome and to define metabolite associations with age, sex, BMI and dietary habits in European children, by exploiting a unique biobank established as part of the Human Early-Life Exposome project (http://www.projecthelix.eu).MethodsMetabolic phenotypes of matched urine and serum samples from 1192 children (aged 6–11) recruited from birth cohorts in six European countries were measured using high-throughput 1H nuclear magnetic resonance (NMR) spectroscopy and a targeted LC-MS/MS metabolomic assay (Biocrates AbsoluteIDQ p180 kit).ResultsWe identified both urinary and serum creatinine to be positively associated with age. Metabolic associations to BMI z-score included a novel association with urinary 4-deoxyerythronic acid in addition to valine, serum carnitine, short-chain acylcarnitines (C3, C5), glutamate, BCAAs, lysophosphatidylcholines (lysoPC a C14:0, lysoPC a C16:1, lysoPC a C18:1, lysoPC a C18:2) and sphingolipids (SM C16:0, SM C16:1, SM C18:1). Dietary-metabolite associations included urinary creatine and serum phosphatidylcholines (4) with meat intake, serum phosphatidylcholines (12) with fish, urinary hippurate with vegetables, and urinary proline betaine and hippurate with fruit intake. Population-specific variance (age, sex, BMI, ethnicity, dietary and country of origin) was better captured in the serum than in the urine profile; these factors explained a median of 9.0% variance amongst serum metabolites versus a median of 5.1% amongst urinary metabolites. Metabolic pathway correlations were identified, and concentrations of corresponding metabolites were significantly correlated (r > 0.18) between urine and serum.ConclusionsWe have established a pan-European reference metabolome for urine and serum of healthy children and gathered critical resources not previously available for future investigations into the influence of the metabolome on child health. The six European cohort populations studied share common metabolic associations with age, sex, BMI z-score and main dietary habits. Furthermore, we have identified a novel metabolic association between threonine catabolism and BMI of children.

Acylcarnitine profiles in serum and muscle of dairy cows receiving conjugated linoleic acids or a control fat supplement during early lactation

Acylcarnitines (ACC) are formed when fatty acid (FA)-coenzyme A enters the mitochondria for β-oxidation and the tricarboxylic acid cycle through the carnitine shuttle. Concentrations of ACC may vary depending on the metabolic conditions, but can accumulate when rates of β-oxidation exceed those of tricarboxylic acid. This study aimed to characterize muscle and blood serum acylcarnitine profiles, to determine the mRNA abundance of muscle carnitine acyltransferases, and to test whether dietary supplementation (from d 1 in milk) with conjugated linoleic acids (CLA; 100 g/d; each 12% of trans-10,cis-12 and cis-9,trans-11 CLA; n = 11) altered these compared with control fat-supplemented cows (CTR; n = 10). Blood samples and biopsies from the semitendinosus musclewere collected on d -21, 1, 21, and 70 relative to parturition. Serum and muscle ACC profiles were quantified using a targeted metabolomics approach. The CLA supplement did not affect the variables examined. The serum concentration of free carnitine decreased with the onset of lactation. The concentrations of acetylcarnitine, hydroxybutyrylcarnitine, and the sum of short-chain ACC in serum were greater from d -21 to 21 than thereafter. The serum concentrations of long-chain ACC tetradecenoylcarnitine (C14:1) and octadecenoylcarnitine (C18:1) concentrations were greater on d 1 and 21 compared with d -21. Muscle carnitine remained unchanged, whereas short- and medium-chain ACC, including propenoylcarnitine (C3:1), hydroxybutyrylcarnitine, hydroxyhexanoylcarnitine, hexenoylcarnitine (C6:1), and pimelylcarnitine were increased on d 21 compared with d -21 and decreased thereafter. In muscle, the concentrations of long-chain ACC (from C14 to C18) were elevated on d 1. The mRNA abundance of carnitine palmitoyltransferase 1, muscle isoform (CPT1B) increased 2.8-fold from d -21 to 1, followed by a decline to nearly prepartum values by d 70, whereas that of CPT2 did not change over time. The majority of serum and muscle short- and long-chain ACC were positively correlated with the FA concentrations in serum, whereas serum carnitine and C5 were negatively correlated with FA. Time-related changes in the serum and muscle ACC profiles were demonstrated that were not affected by the CLA supplement at the dosage used in the present study. The elevated concentrations of long-chain ACC species in muscle and of serum acetylcarnitine around parturition point to incomplete FA oxidation were likely due to insufficient metabolic adaptation in response to the load of FA around parturition.

Nonhuman Primates with Acute Radiation Syndrome: Results from a Global Serum Metabolomics Study after 7.2 Gy Total-Body Irradiation.

Threats of nuclear terrorism coupled with potential unintentional ionizing radiation exposures have necessitated the need for large-scale response efforts of such events, including high-throughput biodosimetry for medical triage. Global metabolomics utilizing mass spectrometry (MS) platforms has proven an ideal tool for generating large compound databases with relative quantification and structural information in a short amount of time. Determining metabolite panels for biodosimetry requires experimentation to evaluate the many factors associated with compound concentrations in biofluids after radiation exposures, including temporal changes, pre-existing conditions, dietary intake, partial- vs. total-body irradiation (TBI), among others. Here, we utilize a nonhuman primate (NHP) model and identify metabolites perturbed in serum after 7.2 Gy TBI without supportive care [LD70/60, hematologic (hematopoietic) acute radiation syndrome (HARS) level H3] at 24, 36, 48 and 96 h compared to preirradiation samples with an ultra-performance liquid chromatography quadrupole time-of-flight (UPLC-QTOF) MS platform. Additionally, we document changes in cytokine levels. Temporal changes observed in serum carnitine, acylcarnitines, amino acids, lipids, deaminated purines and increases in pro-inflammatory cytokines indicate clear metabolic dysfunction after radiation exposure. Multivariate data analysis shows distinct separation from preirradiation groups and receiver operator characteristic curve analysis indicates high specificity and sensitivity based on area under the curve at all time points after 7.2 Gy irradiation. Finally, a comparison to a 6.5 Gy (LD50/60, HARS level H2) cohort after 24 h postirradiation revealed distinctly increased separations from the 7.2 Gy cohort based on multivariate data models and higher compound fold changes. These results highlight the utility of MS platforms to differentiate time and absorbed dose after a potential radiation exposure that may aid in assigning specific medical interventions and contribute as additional biodosimetry tools.

Response to Letter to the Editor: “Serum Carnitine Metabolites and Incident Type 2 Diabetes Mellitus in Patients With Suspected Stable Angina Pectoris”

Response to Letter to the Editor: “Serum Carnitine Metabolites and Incident Type 2 Diabetes Mellitus in Patients With Suspected Stable Angina Pectoris”

Renal dysfunction is rare in Fukuyama congenital muscular dystrophy

BackgroundThe leading cause of death in patients with Fukuyama congenital muscular dystrophy (FCMD) is congestive heart failure or respiratory dysfunction, which is same as that in Duchenne muscular dystrophy (DMD). Recent studies reported that renal dysfunction is a common complication and an increasing cause of death in advanced DMD. It can be attributable to circulatory instability or inappropriate use of drugs for treating cardiac dysfunction. MethodsWe retrospectively evaluated renal function in 38 genetically diagnosed patients with FCMD (range, 1.3–32.9 years; mean age, 13.7 ± 6.9 years) using cystatin C. We examined possible relationships of cystatin C with blood natriuretic peptide and creatinine levels along with cardiac echocardiography findings. ResultsTwenty-five patients were treated for cardiac dysfunction. Elevated cystatin C level was detected only in two, who also showed proteinuria, glycosuria, hematuria, and extremely high β2-microglobulin levels on urine tests, and were thus diagnosed with renal tubular cell damage. Because both patients were treated for intractable epilepsy with various antiepileptic drugs, including valproic acid (VPA), and had low serum carnitine levels, renal tubular cell damage was considered as an adverse effect of VPA. Unlike patients with DMD, no patient with FCMD had renal dysfunction. Such a rare occurrence of renal dysfunction can be attributable to mild cardiac dysfunction, short disease duration, and careful and early fluid management. ConclusionRenal dysfunction is rare in patients with FCMD; however, renal tubular cell damage should be ascertained, particularly in those undergoing VPA treatment for epilepsy.

Impact of L-Carnitine on Bisphenol A-Induced Kidney Damage in Rats

The present study aimed to explore the protective effects of L-carnitine on the oxidative stress induced by Bisphenol A (BPA) in rat kidneys. Forty male adult rats were allocated into four groups (10 rats each); placebo, BPA (50 mg/kg bwt per os), L-carnitine (500 mg/kg bwt i.p), and the BPA/L-carnitine-treated group. After 70 days, blood and kidneys were collected for measurement of renal function, oxidative/antioxidative status, histopathological analyses, and gene expression of nrf2. BPA significantly increased serum urea and carnitine levels suggesting renal damage evidenced by hydropic degenerative changes and hydronephrosis. The level of malondialdehyde (MDA) in kidney was elevated along with decline in renal total antioxidant capacity (TAC) and reduced glutathione (GSH) concentrations following challenged with BPA. Notably, the expression of nrf2 mRNA transcript in kidney tissues was down-regulated after BPA-induced toxicity. L-carnitine treatment ameliorates the damaged effects of BPA on kidneys as indicated by low levels of serum urea and carnitine, and renal MDA. Further, L-carnitine enhances the antioxidants (TAC, and GSH), with up-regulation of nrf2 expression in kidney tissues. Our results suggest the renoprotective activity of L-carnitine in BPA-induced kidney injuries through induction of antioxidant system and modulation of oxidative stress

Repeated Combined Chemotherapy with Cisplatin Lowers Carnitine Levels in Gastric Cancer Patients

Background/Aims: Carnitine plays an important role in the metabolism of fatty acids. It has also been reported that the administration of anticancer drugs may lead to reductions in serum carnitine levels due to decreased activity of organic cation transporter novel 2, which plays a role in the reabsorption of carnitine in the tubules of the kidney. We therefore studied the change in carnitine levels when chemotherapy was administered repeatedly to patients with gastric cancer. Methods: Ten patients with upper gastrointestinal cancer were enrolled in this study between December 2014 and August 2015. All patients were administered chemotherapy consisting of TS-1 and cisplatin every 3 weeks: 3 received it as adjuvant therapy post resection, the remaining 7 received it as treatment for unresectable tumors. Before the start of each chemotherapy cycle, serum was collected. Results: The mean total carnitine level was 54.5 ± 13.7 μmol/L prior to commencing chemotherapy; it was 46.7 ± 13.5 and 41.4 ± 14.8 μmol/L at the second and third cycles respectively. The total carnitine level was decreased in a statistically significant manner (p = 0.0039). The serum level of total protein and cholinesterase was also decreased significantly (p = 0.0218 and p = 0.0418). Conclusion: Carnitine levels decreased during repeated chemotherapy in patients with gastric cancer, and they are associated with the nutritional status.

Development and validation of an ultrahigh performance liquid chromatography-high resolution tandem mass spectrometry quantification method for hypoglycin A and methylene cyclopropyl acetic acid carnitine in horse serum in cases of atypical myopathy.

Atypical myopathy (AM) is a fatal disease in horses presumably caused by hypoglycine A (HGA) from ingested maple seeds and its active metabolite methylene cyclopropyl acetic acid (MCPA). The aim of this study was the development and validation of a rapid and simple assay for HGA and MCPA-carnitine in horse serum and its application to authentic samples. Identification and quantification were carried out by ultra high performance liquid chromatography-high resolution tandem mass spectrometry (UHPLC-HRMS/MS) with full-scan/data-dependent MS/MS. Chromatographic separation was performed by isocratic elution on a hydrophilic interaction liquid chromatography (HILIC) column (100 x 2.1mm, 1.7μm). Serum samples (250μL) were worked up by protein precipitation. The method was validated according to international guidelines with respect to selectivity, linearity, accuracy, precision, matrix effects, and recovery. The calibration range was from 100 to 2000ng/mL for HGA and from 10 to 1000ng/mL for MCPA-carnitine. HGA and MCPA-carnitine showed acceptable accuracy and precision (bias -3.0% to 1.1%; RSD 9.2% to 12.4%). The limit of quantification (LOQ) was defined as the lowest calibrator and well below the lowest published serum concentrations in affected horses. Matrix effects ranged from -79% to +20% (RSD 4.2% to 14.4%), recoveries from 17.9% to 21.1% (RSD 2.3% to 10.8 %) for low and high quality control samples, respectively. Applicability was tested in 10 authentic AM cases. In all specimens, relevant amounts of HGA and MCPA-carnitine were found (570-2000ng/mL; ~8.5-150ng/mL, respectively). The developed assay allows reliable identification and quantification of HGA and MCPA-carnitine in horse serum and will be helpful to further study the association between HGA/MCPA and AM.

Decreased level of serum carnitine might lead to arteriosclerosis progression via the accumulation of advanced glycation end products in maintenance hemodialysis patients

BackgroundCarnitine is reported to improve insulin resistance and reduce oxidative stress. Hyperglycemia and increased oxidative stress are well known to promote the production of advanced glycation end products (AGEs) that can lead to arteriosclerosis in patients with maintenance hemodialysis (HD). In the present study, we aimed to determine whether decreased level of serum carnitine accelerated arteriosclerosis and to clarify the relationships between carnitine, AGEs, and arteriosclerosis in HD patients.MethodsWe recruited 116 patients (65 men and 51 women, 62 ± 13 years) undergoing HD three times a week. We measured pre-HD serum free carnitine prior to the first weekly session. AGE level was quantitatively evaluated by measuring skin autofluorescence (SAF) with AGE reader. Arteriosclerosis was evaluated by measuring carotid intima-media thickness (cIMT). Relationships between free carnitine, SAF, and cIMT were analyzed, and significant limiting factors for arteriosclerosis were identified using univariate and multivariate regression analyses.ResultsFree carnitine ranged from 14.9 to 53.3 μmol/L (mean, 28.6 ± 8.1 μmol/L). Free carnitine was negatively correlated with SAF (r = − 0.223, P = 0.017) and cIMT (r = − 0.252, P = 0.006). SAF was positively correlated with cIMT (r = 0.263, P = 0.005). Free carnitine was identified as a significant independent limiting factor for cIMT (β = -0.194, P = 0.037).ConclusionsDecreased level of serum carnitine might lead to the progression of arteriosclerosis via the AGE accumulation in HD patients.

Effects of L-carnitine supplementation on biomarkers of oxidative stress, antioxidant capacity and lipid profile, in patients with pemphigus vulgaris: a randomized, double-blind, placebo-controlled trial.

Pemphigus vulgaris (PV), as an autoimmune disease including mucosa and the skin, is associated with several complications and comorbidities. The present study planned to determine the effect of L-carnitine (LC) supplementation on biomarkers of oxidative stress (OS), antioxidant capacity and lipid profile in PV patients.Subjects/MethodsFifty two control and patients with PV, participated in the current randomized, double-blind, placebo-controlled clinical trial. The patients were allocated randomly to receive 2 g per day LC tartrate subdivided into two equal doses of 1 g before breakfast and dinner (n=26) or placebo (n=26) for 8 weeks. Anthropometric, lipid profile and OS values were determined at baseline and end of intervention period. LC intake significantly reduced serum levels of triglycerides, total-, LDL- cholesterol and oxidative stress index (OSI; P<0.05). In addition, supplementation with LC resulted to a meaningful increase in levels of total antioxidant capacity (TAC) (P=0.05) and serum carnitine (P<0.001). LC intake revealed non-significant change in serum total oxidant capacity (P=0.15) and HDL- cholesterol (P=0.06) in comparison to the placebo. LC consumption may have favorable results on TAC, OSI and lipid profiles in patients with PV. The results were in line with the idea that LC supplementation can be associated with positive effects on metabolic status and OS of patients with PV.European Journal of Clinical Nutrition advance online publication, 23 August 2017; doi:10.1038/ejcn.2017.131.

Risk factors for sodium valproate-induced renal tubular dysfunction.

To explore the risk factors for the development of sodium valproate (VPA)-induced renal tubular dysfunction for early diagnosis and treatment. The subjects were selected from patients who were diagnosed with epilepsy and administered VPA. Blood and spot urine samples were collected and measured the concentration of VPA, the level of serum phosphorus, serum uric acid, serum free carnitine, serum cystatin-c, and urine β2-microglobulin (BMG). Patients with urine BMG/creatinine levels above 219.2 were treated as renal proximal tubular dysfunction (RTD), with all others treated as non-RTD. Eighty-seven patients, 4-48years, 53 men and 34 women, were studied. RTD group is 17 patients and non-RTD group is 70 patients. Univariate analyses revealed that the RTD patients were more likely to be bedridden, receiving enteral tube feeding, taking more anticonvulsants, and demonstrating significantly lower serum levels of free carnitine, uric acid, and phosphorus. Among them, bedridden, free serum carnitine, and phosphorus levels were associated with the development of RTD by multivariate analysis. Bedridden patients receiving VPA are susceptible to hypocarnitinemia, which can cause RTD and may lead to FS. Therefore, urinary BMG should be measured regularly in all patients receiving VPA to assess renal tubular function. An additional measurement of serum free carnitine level should be considered in patients who developed RTD. Supplementation of carnitine for those patients to prevent such complication deserves for further study.

Carnitine and Adiponectin Levels in Breast Cancer after Radiotherapy.

In this study, serum carnitine (CRNT) and adiponectin (APN) levels and the correlation of these parameters in patients with breast cancer before and after treatment with radiotherapy (RT) were determined.Materials and methodsSerum adiponectin and carnitine levels were assessed in 58 patients with breast carcinoma and 30 control subjects. Serum carnitine and APN levels were determined using a specific enzyme-linked immunosorbent assay.ResultsWhile serum carnitine level was significantly lower in the patients with breast cancer after RT compared with the control group and before treatment (p=0.002 and p=0.019, respectively), serum APN level was significantly higher than in the control group and before treatment ( p=0.003 and p=0.027, respectively). Carnitine level showed a negative correlation with APN level in the patients after RT (r= -0.626, p= 0.001). There was no correlation between carnitine and APN levels in subjects of control group and before treatment. Also, neither carnitine nor APN levels demonstrated correlation other parameters.ConclusionsResults suggest that increased serum adiponectin and decreased carnitine levels in breast cancer after RT than control group. Carnitine level showed a negative correlation with APN level in the patient with breast cancer after RT. While carnitine, HDL-C and total cholesterol levels are decreased, trygliceride and LDL-C levels are increased in patients than control group. In addition, serum APN concentration was inversely correlated with serum carnitine levels. Furthermore, increased serum APN level in breast cancer after RT might be associated with hypocarnitinemia.