Serum Carnitine Levels Research Articles

Effects of Atezolizumab plus Bevacizumab on Skeletal Muscle Volume and Cardiac Function in Patients with Hepatocellular Carcinoma

Introduction: Pharmacological treatment of unresectable hepatocellular carcinoma (uHCC) includes sorafenib and lenvatinib, a tyrosine kinase inhibitor, which are linked to low serum levels of carnitine and reduced skeletal muscle volume. Nowadays, atezolizumab plus bevacizumab (Atezo/Bev) combination therapy is recommended as the first-line treatment for patients with uHCC. However, the association with decreased muscle mass or cardiac function is unknown. Therefore, this study aimed to evaluate the effects of Atezo/Bev on skeletal muscle volume and cardiac function in patients with uHCC. Methods: This retrospective study included 55 adult Japanese patients with chronic liver diseases and uHCC treated with Atezo/Bev. Patients were divided into three groups according to age: middle, preold, and old. Serum levels of carnitine and cardiac function were measured before and after 3 weeks of treatment. The psoas muscle index (PMI) was measured before and after 6 weeks of treatment. Results: After treatment, the global longitudinal strain was significantly lower in the old group, whereas the PMI and ejection fraction were significantly lower in the preold and old groups. However, no significant difference in serum levels of total carnitine and those fractions with treatment in each group was found. Cardiac function decreased in the preold and old groups. Conclusion: When treating patients with uHCC by Atezo/Bev, caution should be taken in preold and old patients because they are vulnerable to decreased skeletal muscle mass and deterioration of cardiac function. Strength training and regular monitoring of cardiac function are encouraged in these groups.

Disturbed carnitine metabolism is independently correlated with sarcopenia and prognosis in patients on hemodialysis

Background & AimsSarcopenia is frequent in hemodialysis patients and associated with an increased likelihood of adverse outcomes. Early identification of the risk of sarcopenia and effective intervention are of great importance for dialysis patients. However, little research has been carried out on potential biomarkers of sarcopenia in hemodialysis patients. The aim of this study was to investigate whether serum carnitine or acylcarnitine levels are biomarkers of sarcopenia in hemodialysis patients, and whether these are prognostic factors for occurrence of complications. MethodsThis prospective clinical pilot study enrolled patients (n=259) who were treated in the Blood Purification Center from May 2021 to July 2022, all participants were followed-up for 1- year. Serum carnintine and acylcarnitine (AC) were measured using our previously reported targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The correlations between carnitine or acylcarnitine levels with sarcopenia and prognosis in patients were analysed. ResultsThe C0 (Free carnitine, FC) and total carnitine (TC) levels were significantly lower in the sarcopenia group than in the nonsarcopenia group (nonsarcopenia vs. sarcopenia: 20.97 (16.96, 25.83) vs. 17.77 (14.30, 22.78); p =0.002) and (nonsarcopenia vs. sarcopenia: 30.12 (24.76, 36.62) vs. 26.03 (21.30, 32.01); p = 0.003). Besides, significant difference between the groups were noted in low free carnitine (C0 < 20 μmol/L) patients (nonsarcopenia vs. sarcopenia: 72 (42.4%) vs. 56 (62.9%); p = 0.002) and high C2/ C0 ratio (> 0.4) patients (nonsarcopenia vs. sarcopenia: 36 (21.2%) vs. 30 (33.7%); p = 0.028). By multivariable analysis, the disturbed CM defined as C0 deficient and/or C2/C0 carnitine ratio abnormal rise was independently and significantly correlated with the prevalence of sarcopenia after adjusting for some confounding factors, such as age, gender and dialysis duration (P values for trend <0.05).Hemodialysis patients with sarcopenia [OR: 3.214 (1.307,7.904)] and disturbed CM [OR: 3.217 (1.112,9.305)] both had a 3-fold increased risk of falling and fracture after one year follow up. In addition, age and sarcopenia [OR: 2.883 (1.321, 6.289)] were independently and positively associated with incidence of Cardio- and cerebro-vascular events. ConclusionDisturbed carnitine metabolism is independently correlated with sarcopenia and prognosis in patients with hemodialysis. Serum carnitine level and C0/C2 ratio has the potential to be a simple, objective, and quick test for sarcopenia assessment whether such an intervention should be carried out for dialysis patients.

Low serum carnitine level is associated with increased urinary carnitine excretion in late pregnancy.

Carnitine is essential for fatty acid metabolism. Free carnitine (FCA) is excreted in the urine in the glomerulus, but is partly reabsorbed by a carnitine transporter. The mechanism underlying the decrease in serum carnitine level during pregnancy is unclear. To investigate whether low carnitine level is associated with increased renal excretion in pregnant women. We recruited 43 healthy pregnant and 25 non-pregnant women. Total carnitine (TCA) and FCA levels were measured using the enzymatic cycling method, and the acylcarnitine (ACA) level was calculated. Fractional excretion (FE) was calculated as carnitine clearance divided by creatinine clearance. The mean TCA, FCA, and ACA levels were lower at 12weeks of gestation in pregnant than non-pregnant women (P < .001); the levels decreased further at 36weeks, reaching 39%, 36%, and 52% of those in non-pregnant women, respectively (P < .001). The FEs were 3-4-fold higher in pregnant women than non-pregnant women. Pregnant women had a lower serum FCA/TCA ratio than non-pregnant women (0.788±0.098 vs 0.830±0.074, respectively; P < .05), whereas the urine FCA/TCA ratio was similar between the groups. Low carnitine level is associated with increased renal excretion during late pregnancy.

Carnitine functions as an enhancer of NRF2 to inhibit osteoclastogenesis via regulating macrophage polarization in osteoporosis

Osteoporosis, which manifests as reduced bone mass and deteriorated bone quality, is common in the elderly population. It is characterized by persistent elevation of macrophage-associated inflammation and active osteoclast bone resorption. Currently, the roles of intracellular metabolism in regulating these processes remain unclear. In this study, we initially performed bioinformatics analysis and observed a significant increase in the proportion of M1 macrophages in bone marrow with aging. Further metabolomics analysis demonstrated a notable reduction in the expression of carnitine metabolites in aged macrophages, while carnitine was not detected in osteoclasts. During the differentiation process, osteoclasts took up carnitine synthesized by macrophages to regulate their own activity. Mechanistically, carnitine enhanced the function of Nrf2 by inhibiting the Keap1-Nrf2 interaction, reducing the proteasome-dependent ubiquitination and degradation of Nrf2. In silico molecular ligand docking analysis of the interaction between carnitine and Keap1 showed that carnitine binds to Keap1 to stabilize Nrf2 and enhance its function. In this study, we found that the decrease in carnitine levels in aging macrophages causes overactivation of osteoclasts, ultimately leading to osteoporosis. A decrease in serum carnitine levels in patients with osteoporosis was found to have good diagnostic and predictive value. Moreover, supplementation with carnitine was shown to be effective in the treatment of osteoporosis.

L-Carnitine pretreatment ameliorates heat stress-induced acute kidney injury by restoring mitochondrial function of tubular cells.

A major complication of heat-related illness is the development of acute kidney injury (AKI) and damage to kidney tubular cells. Because kidney tubular cells use fatty acids as a major energy source, impaired fatty acid oxidation (FAO) may be associated with kidney injury due to heat stress. Carnitine is essential in the transportation of fatty acid into mitochondria for FAO. To date, there has been little attention given to the role of carnitine in heat-related illness and AKI. To evaluate the relationship between carnitine inadequacy and heat-related illness severity or AKI, we examined serum carnitine levels in patients with heat-related illness. We also used heat-stressed mice to investigate the effect of l-carnitine pretreatment on various kidney functions such as mitochondrial activity, proinflammatory changes in kidney macrophages, and histological damage. We observed an elevation in serum acylcarnitine levels, indicating carnitine insufficiency in patients with severe heat-related illness and/or AKI. l-Carnitine pretreatment ameliorated ATP production in murine tubular cell mitochondria and prevented a change in the kidney macrophage population dynamics observed in AKI: a decrease in tissue-resident macrophages, influx of bone marrow-derived macrophages, and change toward proinflammatory M1 polarization. In conclusion, carnitine insufficiency may be closely associated with severe heat-related illness and related AKI. Enhancement of the FAO pathway by l-carnitine pretreatment may prevent heat stress-induced AKI by restoring mitochondrial function.NEW & NOTEWORTHY Enhancing fatty acid oxidation (FAO) after acute kidney injury (AKI) improves renal outcomes. This report shows that carnitine insufficiency, which could inhibit FAO, correlates to severe heat-related illness and AKI in a clinical study. We also demonstrate that administering l-carnitine to mice improves mitochondrial respiratory function and prevents deleterious changes in renal macrophage, resulting in improved renal outcomes of heat-induced AKI. l-Carnitine may be an effective preventive treatment for severe heat-related illness and related AKI.

Serum Trimethylamine N-Oxide, Choline, Betaine, and Carnitine levels among Coronary Artery Disease patients

Background and aimRecent studies have linked Trimethylamine N-oxide (TMAO) to cardiovascular diseases; our study aimed to analyze the association between coronary artery disease (CAD) and TMAO. MethodsPubMed, Scopus, Embase, and Web of Science were searched using terms; such as “CAD” and “TMAO”. Only observational controlled studies were included. RevMan software version 5.4 was used for the analysis. ResultsA significant association was found between the CAD group and increased serum TMAO levels compared with the control group (MD = 1.16, 95% CI = 0.54 to 1.78, p-value =0.0003). This association remained significant among acute coronary syndrome (ACS) patients (MD=0.98, 95% CI =0.73 to 1.23, p-value <0.00001) and was also detected among young and old CAD patients (MD = 0.35, 95% CI = 0.06 to 0.64, p-value = 0.02 and MD = 1.36, 95% CI = 0.71 to 2.01, p-value <0.0001, respectively). On further analysis of intestinal metabolites, we detected an insignificant association between choline, betaine, carnitine, and CAD. According to our sensitivity analysis, TMAO is an acceptable discriminatory marker for CAD (0.721, SE was 0.0816, 95% CI 0.561 to 0.881). ConclusionTMAO is an acceptable discriminatory marker for CAD, with significantly higher levels among these patients regardless of their age. Other metabolites didn't show such an association. The role of serum level TMAO in the early diagnosis of CAD should be further explored.

Assessment of Serum Carnitine level in Children with Iron Deficiency Anemia

Assessment of Serum Carnitine level in Children with Iron Deficiency Anemia

Type 2–resistant starch and Lactiplantibacillus plantarum NCIMB 8826 result in additive and interactive effects in diet-induced obese mice

Little is known about how combining a probiotic with prebiotic dietary fiber affects the ability of either biotic to improve health. We hypothesized that prebiotic, high-amylose maize type 2–resistant starch (RS) together with probiotic Lactiplantibacillus plantarum NCIMB8826 (LP) as a complementary synbiotic results in additive effects on the gut microbiota in diet-induced obese mice and other body sites. Diet-induced obese C57BL/6J male mice were fed a high-fat diet adjusted to contain RS (20% by weight), LP (109 cells every 48 hours), or both (RS+LP) for 6 weeks. As found for mice fed RS, cecal bacterial alpha diversity was significantly reduced in mice given RS+LP compared with those fed LP and high-fat controls. Similarly, both RS+LP and RS also conferred lower quantities of cecal butyrate and serum histidine and higher ileal TLR2 transcript levels and adipose tissue interleukin-6 protein. As found for mice fed LP, RS+LP–fed mice had higher colonic tissue TH17 cytokines, reduced epididymal fat immune and oxidative stress responses, reduced serum carnitine levels, and increased transcript quantities of hepatic carnitine palmitoyl transferase 1α. Notably, compared with RS and LP consumed separately, there were also synergistic increases in colonic glucose and hepatic amino acids as well antagonistic effects of LP on RS-mediated increases in serum adiponectin and urinary toxin levels. Our findings show that it is not possible to fully predict outcomes of synbiotic applications based on findings of the probiotic or the prebiotic tested separately; therefore, studies should be conducted to test new synbiotic formulations.

Effects of Lenvatinib on Skeletal Muscle Volume and Cardiac Function in Patients with Hepatocellular Carcinoma

Introduction: Previously, we reported that the tyrosine kinase inhibitor (TKI) sorafenib decreases serum levels of carnitine and reduces skeletal muscle volume. Moreover, others reported that TKIs might lead to cardiomyopathy or heart failure. Therefore, this study aimed to evaluate the effects of lenvatinib (LEN) on skeletal muscle volume and cardiac function in patients with hepatocellular carcinoma (HCC). Methods: This retrospective study included 58 adult Japanese patients with chronic liver diseases and HCC treated with LEN. Blood samples were collected before and after 4 weeks of treatment, and serum carnitine fraction and myostatin levels were measured. Before and after 4–6 weeks of treatment, the skeletal muscle index (SMI) was evaluated from computed tomography images and cardiac function was assessed by ultrasound cardiography. Results: After treatment, SMI, serum levels of total carnitine, and global longitudinal strain were significantly lower, but serum levels of myostatin were significantly higher. Left ventricular ejection fraction showed no significant change. Conclusion: In patients with HCC, LEN decreases serum levels of carnitine, skeletal muscle volume, and worsens cardiac function.

The association of serum carnitine levels with severity of fatigue in patients with multiple sclerosis: A pilot study.

Background: Fatigue is a common complaint of patients with multiple sclerosis (MS), adversely affecting their quality of life. There is a lot of evidence showing that carnitine deficiency is linked to fatigue development and severity in some conditions. This study aimed to evaluate the association between free L-carnitine serum levels and the severity of fatigue in patients with MS. Methods: This case-control study included 30 patients with relapsing-remitting MS (RRMS) in two age-matched equal-number groups according to the presence or absence of fatigue. Fatigue was scored using the valid questionnaire of Fatigue Severity Scale (FSS) and serum level of free L-carnitine was measured simultaneously. Finally, the association between serum level of free L-carnitine and fatigue severity was evaluated in patients with MS. Results: The mean value of FSS in patients with fatigue was 48.80 ± 8.55, which was nearly two-fold higher than the group without fatigue. We found a significant correlation between the serum level of free L-carnitine and FSS and showed that the patients with fatigue had a significantly lower serum level of free L-carnitine compared to patients without fatigue (P < 0.001). Conclusion: Present study demonstrated that patients with lower serum levels of free L-carnitine were more likely to experience fatigue. We recommend that a higher dietary intake of carnitine might be a useful complementary treatment for MS-related fatigue.

Normalization of lipid oxidation defects arising from hypoxia early posthepatectomy prevents liver failure in mouse.

Surgical liver failure (SLF) develops when a marginal amount of hepatic mass is left after surgery, such as following excessive resection. SLF is the commonest cause of death due to liver surgery; however, its etiology remains obscure. Using mouse models of standard hepatectomy (sHx) (68%, resulting in full regeneration) or extended hepatectomy (eHx) (86%/91%, causing SLF), we explored the causes of early SLF related to portal hyperafflux. Assessing the levels of HIF2A with or without oxygenating agent inositol trispyrophosphate (ITPP) indicated hypoxia early after eHx. Subsequently, lipid oxidation (PPARA/PGC1α) was downregulated and associated with persisting steatosis. Mild oxidation with low-dose ITPP reduced the levels of HIF2A, restored downstream PPARA/PGC1α expression along with lipid oxidation activities (LOAs), and normalized steatosis and other metabolic or regenerative SLF deficiencies. Promotion of LOA with L-carnitine likewise normalized the SLF phenotype, and both ITPP and L-carnitine markedly raised survival in lethal SLF. In patients who underwent hepatectomy, pronounced increases in serum carnitine levels (reflecting LOA) were associated with better recovery. Lipid oxidation thus provides a link between the hyperafflux of O2-poor portal blood, the metabolic/regenerative deficits, and the increased mortality typifying SLF. Stimulation of lipid oxidation-the prime regenerative energy source-particularly through L-carnitine may offer a safe and feasible way to reduce SLF risks in the clinic.

Carnitine Intake and Serum Levels Associate Positively with Postnatal Growth and Brain Size at Term in Very Preterm Infants.

Carnitine has an essential role in energy metabolism with possible neuroprotective effects. Very preterm (VPT, &lt;32 gestation weeks) infants may be predisposed to carnitine deficiency during hospitalization. We studied the associations of carnitine intake and serum carnitine levels with growth and brain size at term equivalent age (TEA) in VPT infants. This prospective cohort study included 35 VTP infants admitted to Kuopio University Hospital, Finland. Daily nutrient intakes were registered at postnatal weeks (W) 1 and 5, and serum carnitine levels were determined at W1, W5, and TEA. The primary outcomes were weight, length, and head circumference Z-score change from birth to TEA, as well as brain size at TEA in magnetic resonance imaging. Carnitine intake at W1 and W5, obtained from enteral milk, correlated positively with serum carnitine levels. Both carnitine intake and serum levels at W1, W5, and TEA showed a positive correlation with weight, length, and head circumference Z-score change and with brain size at TEA. In linear models, independent positive associations of carnitine intake and serum carnitine levels with length and head circumference Z-score change and brain size at TEA were seen. In VPT infants, sufficient carnitine intake during hospitalization is necessary since it is associated with better postnatal growth and larger brain size at term age.

A Review of the Multi-Systemic Complications of a Ketogenic Diet in Children and Infants with Epilepsy.

Ketogenic diets (KDs) are highly effective in the treatment of epilepsy. However, numerous complications have been reported. During the initiation phase of the diet, common side effects include vomiting, hypoglycemia, metabolic acidosis and refusal of the diet. While on the diet, the side effects involve the following systems: gastrointestinal, hepatic, cardiovascular, renal, dermatological, hematologic and bone. Many of the common side effects can be tackled easily with careful monitoring including blood counts, liver enzymes, renal function tests, urinalysis, vitamin levels, mineral levels, lipid profiles, and serum carnitine levels. Some rare and serious side effects reported in the literature include pancreatitis, protein-losing enteropathy, prolonged QT interval, cardiomyopathy and changes in the basal ganglia. These serious complications may need more advanced work-up and immediate cessation of the diet. With appropriate monitoring and close follow-up to minimize adverse effects, KDs can be effective for patients with intractable epilepsy.

Evaluation of the relationship between serum carnitine levels and intradialytic complications in children with kidney failure.

Carnitine plays a crucial role in the metabolism of fatty acids as well as energy production. Previous research has suggested a significant decrease in carnitine levels in patients with kidney failure and those undergoing hemodialysis. Therefore, we designed this study to assess the prevalence and characteristics of carnitine deficiency and its association with hemodialysis complications in the pediatric population. This research was a pilot study of 29 children undergoing hemodialysis. Before hemodialysis, a 5-mL blood sample was drawn from each patient through a peripheral vein to measure serum-free carnitine levels, complete blood count with differential, blood urea nitrogen (BUN), creatinine, and electrolytes. Each patient was observed for intradialytic complications, including muscle cramps and hypotension, during 12 sessions of hemodialysis. We included 26 participants with a mean age of 14.23years undergoing hemodialysis. Carnitine deficiency was revealed in 54.8% of our participants. Also, there was no significant correlation between carnitine deficiency and age, gender, and BUN levels (P = 0.698, P = 0.43, and P > 0.05, respectively). Intradialytic complications, including episodes of hypotension and muscle cramps, were more frequent in patients with carnitine deficiency (P = 0.02, P = 0.01, respectively). Other reasons for muscle cramps, such as fluid overload, nutritional status, dialysis regimen, and other important lab results (phosphorus, magnesium, etc.), were ruled out. In conclusion, we found a higher prevalence of carnitine deficiency in pediatric hemodialysis patients. Carnitine deficiency was significantly associated with increased intradialytic symptoms, including muscle spasms and hypotension. Our results could support a potential role of carnitine supplementation in pediatric patients with kidney failure for controlling intradialytic complications, but this requires further investigation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Serum carnitine as a biomarker of sarcopenia and nutritional status in preoperative gastrointestinal cancer patients.

BackgroundSarcopenia is an important factor in the postoperative outcome of gastrointestinal cancer patients. However, little research has been carried out on potential biomarkers of sarcopenia. Carnitine is an amino acid derivative that is stored in skeletal muscle and is essential for muscle energy metabolism. The primary purpose of this study was to investigate whether serum carnitine level is a biomarker of sarcopenia in preoperative patients with gastrointestinal cancer. The secondary purposes were (i) to examine the associations between carnitine, nutritional status, and albumin level, and (ii) to determine whether carnitine is a prognostic factor for postoperative complications.MethodsOne hundred fourteen patients scheduled to undergo gastroenterological surgery between August 2016 and January 2017 were enrolled. Their mean age was 68.4 ± 10.5, and 64.9% were male. Serum carnitine fractions [total carnitine (TC), free l‐carnitine (FC), and acylcarnitine (AC)] were measured prior to surgery. The correlation between carnitine level and a variety of clinical features was analysed, including skeletal muscle index (SMI), sarcopenia, prognostic nutritional index (PNI), and postoperative complications.ResultsTumour locations included the oesophagus (n = 17), stomach (n = 16), pancreas (n = 20), bile duct (n = 9), liver [n = 33; primary liver cancer (n = 18), liver metastasis (n = 15)], and colorectal region (n = 19). TC and FC levels varied significantly by tumour location. TC and FC showed significant positive correlations with SMI [TC (r = 0.295, P = 0.0014), FC (r = 0.286, P = 0.0020)] and PNI [TC (P = 0.0178, r = 0.222), FC (P = 0.0067, r = 0.2526)]. These levels were significantly lower in the sarcopenia group (TC, P = 0.0124; FC, P = 0.0243). In addition, TC and FC showed significant positive correlations with ALB level [TC (P = 0.038 r = 0.19), FC (P = 0.016 r = 0.23)]. When patients were divided into high ALB (≥3.5 g/dL, 96 patients) and low ALB (<3.5 g/dL, 18 patients) groups, these correlations were no longer significant, but in the low ALB group there was a tendency towards a negative relationship between ALB level and both TC and FC. No significant relationship was found between postoperative complications and carnitine level.ConclusionsThis study suggests that carnitine level is a biomarker of sarcopenia and nutritional status. However, it did not find an association between carnitine level and postoperative complications.

Change in Anemia by Carnitine Supplementation in Patients Undergoing Peritoneal Dialysis: A Retrospective Observational Study.

Background: Carnitine supplementation improves various dialysis-related symptoms including erythropoietin-resistant anemia in patients who are undergoing hemodialysis. However, the utility of carnitine supplementation in patients who are undergoing peritoneal dialysis (PD) is not fully understood.Methods: Thirteen patients undergoing PD [mean age: 54.2 ± 14.8 years, males: 9/13 (69%)] administered oral carnitine supplementation (mean dose: 9.1 ± 3.3 mg/kg/day) for 4–6 months were retrospectively investigated. Changes in serum carnitine levels and other clinical variables including the erythropoietin resistance index (ERI) were analyzed after carnitine supplementation.Results: Carnitine supplementation increased serum total carnitine (48.5 ± 10.2 vs. 130.1 ± 37.2 μmol/L, P < 0.01), free carnitine (31.1 ± 8.3 vs. 83.1 ± 24.6 μmol/L, P < 0.01), and acyl carnitine (17.4 ± 2.8 vs. 46.9 ± 13.8, P < 0.01) levels. The acyl carnitine/free carnitine ratio was not affected (0.6 ± 0.1 vs. 0.6 ± 0.1, P = 0.75). Although the mean ERI was not affected by carnitine supplementation [13.7 ± 4.7 vs. 11.6 ± 3.4 IU/kg/(g/dL)/week, P = 0.28], the ERI change rate was significantly decreased (1.00 ± 0.00 vs. 0.87 ± 0.11, P < 0.01).Conclusion: Carnitine supplementation may improve erythropoietin resistance in patients who are undergoing PD.

Serum Carnitine Levels in Preterm Infants with Respiratory Distress Syndrome

Background: Respiratory distress syndrome [RDS] is among the most common diseases in preterm infants. Numerous causes of RDS have been recently diagnosed and researchers have identified the presence of low serum carnitine in preterm infants with RDS.The aim of this study: to evaluate serum carnitine levels in preterm infants with RDS.Patients and methods: Eighty preterm infants were divided into two groups; group 1 consisted of 50 preterm with RDS in the first 6h of life constituted Group [A] as they were preterm infants with RDS with normal serum carnitine levels while Group [B] represented infants with carnitine deficiency. Control group 2 consisted of 30 preterm infants without RDS in the first 6 h of life. All cases and their mothers included in the study were subjected to a thorough history taking, thorough clinical examination and measurement of serum carnitine.Results: The cases groups had significantly lower serum L-carnitine than the controls group [25.56 ± 11.14 vs. 34.53 ± 2.54], and carnitine deficiency in RDS cases [32%]. Concerning weight, cases with carnitine deficiency had higher weight than cases with normal carnitine and control. With regard to clinical manifestations, there was a statistically significant difference between the cases subgroups in Down score indicting severe RDS in cases with carnitine deficiency. There was a statistically significant difference among cases subgroups regarding radiological findings. The cases with carnitine deficiency had worse X-ray, more need for surfactant therapy and MV than the cases with normal carnitine.Conclusion: Preterm neonates with RDS were demonstrated to be associated with a significant reduction in carnitine level compared to RDS- free preterm ones.

Primary Carnitine Deficiency and Autism Spectrum Disorder is there a Relationship?

Carnitine plays essential role in energy metabolism .Systemic primary carnitine deficiency 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. The decrease carnitine results in impaired fatty acid oxidation. Primary carnitine deficiency presents a hypoketotic, hypoglycemia and hepatic encephalopathy. Recently, primary carnitine deficiency has been associated with neurodevelopmental disorders including autism spectrum disorders. A seven year-old schoolgirl with intellectual deficit, autistic features and primary carnitine deficiency has been reported. A significant decrease in carnitine levels has been shown in patients with autism and this has been related to the existence of a mitochondrial disease and more severe autism. The early identification of patients with low levels of carnitine or primary carnitine deficiency, with the different methods of measuring free carnitine, including tandem mass spectrometry could help to identify these patients early and achieve an early treatment and better neurological prognosis, because autism spectrum disorders may be preventable in this subgroup. We hope that this paper is useful to neurologists and pediatricians, and may give them more reason to suspect a diagnosis of PCD and autism.

Exogenous L-carnitine ameliorates burn-induced cellular and mitochondrial injury of hepatocytes by restoring CPT1 activity

BackgroundImpaired hepatic fatty acid metabolism and persistent mitochondrial dysfunction are phenomena commonly associated with liver failure. Decreased serum levels of L-carnitine, a amino acid derivative involved in fatty-acid and energy metabolism, have been reported in severe burn patients. The current study aimed to evaluate the effects of L-carnitine supplementation on mitochondrial damage and other hepatocyte injuries following severe burns and the related mechanisms.MethodsSerum carnitine and other indicators of hepatocytic injury, including AST, ALT, LDH, TG, and OCT, were analyzed in severe burn patients and healthy controls. A burn model was established on the back skin of rats; thereafter, carnitine was administered, and serum levels of the above indicators were evaluated along with Oil Red O and TUNEL staining, transmission electron microscopy, and assessment of mitochondrial membrane potential and carnitine palmitoyltransferase 1 (CPT1) activity and expression levels in the liver. HepG2 cells pretreated with the CPT1 inhibitor etomoxir were treated with or without carnitine for 24 h. Next, the above indicators were examined, and apoptotic cells were analyzed via flow cytometry. High-throughput sequencing of rat liver tissues identified several differentially expressed genes (Fabp4, Acacb, Acsm5, and Pnpla3) were confirmed using RT-qPCR.ResultsSubstantially decreased serum levels of carnitine and increased levels of AST, ALT, LDH, and OCT were detected in severe burn patients and the burn model rats. Accumulation of TG, evident mitochondrial shrinkage, altered mitochondrial membrane potential, decreased ketogenesis, and reduced CPT1 activity were detected in the liver tissue of the burned rats. Carnitine administration recovered CPT1 activity and improved all indicators related to cellular and fatty acid metabolism and mitochondrial injury. Inhibition of CPT1 activity with etomoxir induced hepatocyte injuries similar to those in burn patients and burned rats; carnitine supplementation restored CPT1 activity and ameliorated these injuries. The expression levels of the differentially expressed genes Fabp4, Acacb, Acsm5, and Pnpla3 in the liver tissue from burned rats and etomoxir-treated hepatocytes were also restored by treatment with exogenous carnitine.ConclusionExogenous carnitine exerts protective effects against severe burn-induced cellular, fatty-acid metabolism, and mitochondrial dysfunction of hepatocytes by restoring CPT1 activity.

Factors associated with blood carnitine levels in adult epilepsy patients with chronic valproic acid therapy

AimsValproic acid (VPA) is a widely used antiepileptic drug for the treatment of epilepsy, seizures, and bipolar and psychiatric disorders. A deficiency of carnitine, a compound involved in energy production, is associated with chronic VPA use. However, the clinical factors affecting blood carnitine levels and their pathophysiology remain unclear. Hence, we aimed to identify the factors that correlated with serum carnitine levels in epilepsy patients receiving chronic VPA therapy. MethodsThis observational study included 138 epilepsy patients receiving chronic VPA therapy. Serum total and free carnitine levels, routine blood tests and drug concentrations were assessed. The correlation between carnitine levels and other factors were calculated using Spearman's rank correlation coefficients, and a principal component analysis (PCA) and a multiple linear regression analysis were performed. ResultsOverall, serum free carnitine levels showed significant negative correlations with epilepsy duration, VPA treatment duration, daily VPA dose, and blood VPA concentration. A significant positive correlation was observed with erythrocyte count, hemoglobin levels, and creatinine levels. Of the 138 patients, 21 (15.2 %) with serum free carnitine levels of <20 μmol/L had significantly longer disease duration, a higher daily VPA dose, and lower blood clobazam concentrations. In the 48 VPA monotherapy patients, serum free carnitine levels showed a significant negative correlation with disease duration and duration of VPA therapy. Furthermore, in the 2.1 % patients receiving VPA monotherapy, serum free carnitine levels were <20 μmol/L. PCA resulted in seven factor solution (eigenvalue >1; 71.67 % explained variance). Component 1 clearly revealed the maximal loading for serum free carnitine level (.792) and the most negative loading for disease duration of epilepsy (−.595). A linear regression analysis revealed that the duration of epilepsy, serum creatinine level, and daily dose of VPA were significant (p < .01) factors that affected serum free carnitine levels. ConclusionsThe effects of combination therapy with VPA and other anti-epileptic drug(s) on carnitine levels are higher than that of VPA monotherapy. Additionally, epilepsy duration may affect serum free carnitine level.