Serum Total Carnitine Research Articles

Brody myopathy associated with novel compound heterozygous ATP2A1 mutations (P6-8.015)

<h3>Objective:</h3> To describe a case of presumed Brody myopathy associated with novel compound heterozygous ATP2A1 mutations. <h3>Background:</h3> Brody myopathy is a rare autosomal recessive skeletal muscle disease characterized by exertional muscle cramps, weakness, and/or rhabdomyolysis associated with clinical myotonia. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 19-year-old man with normal development and motor milestones presented to neuromuscular clinic after two episodes of exercise-induced muscle weakness and rhabdomyolysis in the past 6-months. Peak creatinine phosphokinase (CPK) was &gt;63,000 units/L and he quickly returned to baseline after each episode with intravenous fluids and supportive care. Remaining initial testing including serum total carnitine and acylcarnitine levels, and urine organic acid levels, were normal. He provided additional history of progressive difficulty relaxing leg and handgrip muscles after exertion since childhood, and multiple episodes of asymptomatic dark-colored urine provoked by strenuous exercise over the past two years. Physical examination showed bilateral grip and percussion myotonia with otherwise normal muscle bulk, strength, and remaining neurologic examination. Electromyography was normal. Genetic testing including myotonic dystrophy types 1 and 2, Pompe disease, and non-dystrophic myotonic disorders was notable for compound heterozygous ATP2A1 gene c.2032C&gt;T (p.Arg678Cys) and c.2176G&gt;A (p.Val726Met) variants of uncertain significance. Separate pathogenic mutations in this gene cause Brody myopathy, a non-dystrophic myotonic disorder characterized by exertional rhabdomyolysis. The patient is presumed to have Brody myopathy due to novel compound heterozygous ATP2A1 mutations. <h3>Conclusions:</h3> Brody myopathy should be considered in individuals presenting with muscle cramps, clinical myotonia, and exertional rhabdomyolysis. Clinical features and electromyographic findings are milder than myotonic dystrophies, Pompe disease, and typical non-dystrophic myotonic disorders. Genetic testing including ATP2A1 gene sequencing aids diagnosis. Management is supportive, although individuals should be aware of a 5% association with malignant hyperthermia-like episodes after exposure to volatile anesthetics. <b>Disclosure:</b> Dr. Walia has nothing to disclose. Dr. Su has nothing to disclose.

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.

Clinical Effects of L-Carnitine Supplementation on Physical Performance in Healthy Subjects, the Key to Success in Rehabilitation: A Systematic Review and Meta-Analysis from the Rehabilitation Point of View.

L-carnitine supplementation improves body strength, sports endurance and exercise capacity, as well as delaying the onset of fatigue. The aim of this study was to identify the correct dosage of supplementation to obtain improvements in physical performance and evaluate the changes related to L-carnitine supplementation in specific metabolic parameters, such as serum lactate, VO2, serum total and free carnitine at rest and after physical activities, in healthy subjects. The search was conducted on PubMed, EMBASE, Cochrane Library, Scopus and Web of Science and identified 6404 articles with the keywords: “carnitine” AND “exercises” OR “rehabilitation” OR “physical functional performance” OR “physical activity” OR “sports” OR “health” OR “healthy”. A total of 30 publications met the inclusion criteria and were included in the systematic review. The meta-analysis did not show any significant differences in serum lactate values at rest and after exercise in healthy subjects who took L-carnitine supplementation (p > 0.05). On the contrary, L-carnitine administration significantly changed maximal oxygen consumption (VO2) at rest (p < 0.005), serum free and total carnitine at rest and after exercise (p < 0.001). The dosage of supplementation that obtained a significant change in serum total carnitine was 2 g/dL for 4 weeks at rest, 1 g/dL for 3 weeks after exercise, and in serum free carnitine was 2 g/dL for 3 weeks and 2 g/dL for 4 weeks at rest. Based on our study, serum total and free carnitine at rest and after exercise, and VO2 at rest could be used to clinically follow individuals during physical activity and rehabilitation programs. Moreover, the supplementation should have a correct dosage to have maximum effect. Other robust trials are needed to find the best dosage to obtain positive results in metabolic parameters and in physical performance.

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.

Correlation between serum carnitine level and Soluble Receptors for Advance Glycation End Products(sRAGE) in Clomiphene Citrate Resistant- PCOS Women

The most frequently diagnosed condition in women at the age of reproduction is the polycystic ovarian syndrome (PCOS).it could be related to a complex endocrine condition, due to its heterogeneity and uncertainty about its etiology, as the clinical highlights of PCOS incorporate those related to reproductive signs such as decreased frequency of ovulation, irregular menstrual cycles, decreased fertility. Carnitine plays a substantial role in weight loss, glucose tolerance, insulin function and fatty acid metabolism. Thus carnitine plays a crucial role in controlling obesity, insulin resistance, oxidative stress that are associated with PCOS .While, AGEs are a diverse group of reactive molecules that are formed endogenously by non-enzymatic reactions of carbonyl group of carbohydrates with free amino groups of proteins, nucleic acids or lipids. The soluble form of receptors of AGE (sRAGE) could play an important role in management obesity, insulin resistance, hyperandrogenism, oxidative stress which could be related to PCOS. This study was aimed to investigate serum levels of carnitine &amp; soluble receptors for advanced glycation end products (sRAGE) in clomiphene resistant PCOS .Besides assessing the correlation between serum levels of carnitine ,as well as, soluble receptors of AGE with hormonal ( LH, FSH&amp; Testosterone) and metabolic ( serum glucose , serum insulin &amp; HOMA-IR) markers in these patients .&#x0D; The study included thirty women with clomiphene resistant PCOS and thirty apparently healthy women, as a control .In order to measure serum total carnitine and serum soluble receptor of advance glycation end product (sRAGE in PCOS and control groups.&#x0D; The results of our study have shown a decreased serum levels of total carnitine in PCOS group in comparison with control group (48.05 and 59.73 nmol/ml, respectively), but there was no significant elevation in serum levels of sRAGE in patients group as compared with control group .In addition to a significant correlation between serum total carnitine and serum sRAGE levels (r=0.45, P-value=0.03). &#x0D; In conclusion serum total carnitine level was low in Clomiphene resistant-PCOS patients in comparison with control group. Although, sRAGE levels in clomiphene resistant- PCOS patients were not significantly different from the age and BMI-matching controls, but a significant correlation between serum total carnitine and sRAGE was detected.&#x0D; Key words: Poly cystic ovarian syndrome, soluble receptor of advance glycation end products (sRAGE) , SerumTotal Carnitine

Astımlı çocuklarda leptin, adiponektin ve karnitin düzeylerinin akciğer fonksiyonları, astım şiddeti ve BMI ile ilişkisinin değerlendirilmesi

Purpose: The aim of this study is to evaluate the relationship between serum levels of leptin, adiponectin and carnitine with lung function, disease severity and BMI (Body Mass Index) in children with asthma. Materials and methods: 97 Pediatric patients with not in acute attack period bronchial asthma and 40 healthy control subjects were included in the study. Pulmonary function tests done to all asthma patients with a spirometer. Children with asthma were divided into 3 groups according to GINA criteria, mild intermittent, mild persistent, and moderate persistent, with using symptoms and spirometric parameters according to the severity of airway obstruction. Leptin, total carnitine and adiponectin analyzes were performed from venous blood by ELISA method. Results: Patient group serum leptin values were found to be significantly higher than the control group serum leptin values (p = 0.001). Patient group serum total carnitine values were found to be significantly lower than the control group (p = 0.001). Moderate persistent group adiponectin and total carnitine values were found to be significantly lower than mild intermittent group (p <0.05). A weak negative correlation was found between leptin and total carnitine, eosinophil, BMI values. A weak negative correlation was found between total carnitine and eosinophil, BMI values. A moderate negative correlation was found between age and leptin, adiponectin, total carnitine values. Conclusions: It suggested that leptin levels increased, adiponectin and total carnitine levels decreased in children with asthma and at the same time the decrease in adiponectin and total carnitine levels may be associated with disease severity.

MON-065 Prevention of 6-Mercaptopurine-Induced Hypoglycemia by Levocarnitine Replacement

Background: Symptomatic hypoglycemia has been reported in children less than 6 years of age receiving 6-Mercaptopurine for acute lymphoblastic anemia (ALL); however, the mechanism of 6-Mercaptopurine-induced hypoglycemia has been unclear. Objective: The objective was to investigate the metabolism in a 3-year-old patient with hypoglycemia induced by 6-Mercaptopurine during maintenance therapy for ALL. Methods: We reviewed test results including serum total and free carnitine levels at time of hypoglycemia in a 3-year-old child with ALL who had repeatedly low plasma glucose as a side effect of 6-Mercaptopurine. Hypoglycemia defined as plasma glucose <50 mg/dL was detected using a glucose meter and each time verified in the clinical laboratory. After Levocarnitine was added to 6-Mercaptopurine therapy, the glycemic control was assessed using a glucose meter, the clinical laboratory, and a continuous glucose monitor; serum total and free carnitine levels were repeated when hypoglycemia resolved. Results: Our patient presented with fatigue, tremors and plasma glucose 39 mg/dL to 47 mg/dL, corrected with a sugary beverage. He had plasma ACTH 38 pg/mL, serum cortisol 10 mcg/dL, total carnitine 24 nmol/mL (expected 35 - 84), free carnitine 18 nmol/mL (expected 24 - 63), plasma free fatty acids 1.62 mmol/L (expected >1.5), beta-hydroxybutyrate of 0.2 mmol/L to 0.7 mmol/L (expected >2.0), and urine ketone bodies negative when plasma glucose was between 33 mg/dL and 39 mg/dL. Plasma insulin was undetectable at time of hypoglycemia, and serum glucose increased by less than 30 points in response to Glucagon IV. Serum IGF-1 as measure of growth hormone effect and thyroid function were normal. Hypoglycemia continued to daily recur especially during the night despite bedtime snacks high in complex carbohydrates and was prevented only by Levocarnitine 25 mg/kg/dose every 12 hours PO that raised serum total and free carnitine levels. The patient remained hypoglycemia-free one month after Levocarnitine was added to 6-Mercaptopurine therapy, in particular, he had average glucose 114 mg/dL with standard deviation 30 mg/dL, glucose 70 mg/dL to 140 mg/dL 93% of the time, and glucose <55 mg/dL 0% of the time. Conclusions: Our patient had symptomatic hypoketotic hypoglycemia related to moderately reduced serum total and free carnitine, corrected with Levocarnitine replacement. Increase in plasma free fatty acids without expected increase in plasma and urine ketone bodies may be sign of impaired synthesis of carnitine, which is required for transport of fatty acids into the mitochondria to produce ketone bodies. Measuring serum total and free carnitine in hypoglycemia induced by 6-Mercaptopurine is helpful in identifying children, who may benefit from Levocarnitine replacement.

Liver-Oriented Acute Metabolic Effects of A Low Dose of L-Carnitine under Fat-Mobilizing Conditions: Pilot Human Clinical Trial.

The acute metabolic effect of low dosages of L-carnitine under fat-mobilizing conditions was investigated. Healthy subjects (Study 1: n=5; Study 2: n=6) were asked to fast overnight. Then, 30 min of aerobic exercise on a cycle ergometer was performed after supplementation, followed by a 3.5-h sedentary recovery phase. The following ingestion patterns were used: Study 1 (i) noningestion, (ii) 750 mg of L-carnitine (LC), and (iii) 750 mg of LC+50 g of carbohydrate (CHO); Study 2 (iv) noningestion, (v) 500 mg of LC, (vi) 30 mg of CoQ10, and (vii) 500 mg of LC+30 mg of CoQ10. The energy expenditure (EE) and nonprotein respiratory quotient (npRQ) were measured during the pre-exercise, postexercise, and recovery periods. Serum free carnitine, acetylcarnitine, total carnitine (Study 1 and 2), and ketone bodies (Study 2) were measured. The 750 mg LC treatment significantly facilitated fat oxidation during the recovery phases (p<0.05) without elevating EE. The higher fat oxidation associated with LC was completely suppressed by CHO. CoQ10 affected neither npRQ nor EE. npRQ was significantly correlated with the serum total ketone bodies (R=-0.68, p<0.001) and acetylcarnitine (R=-0.61--0.70, p<0.001). The highest correlation was found between acetylcarnitine and total ketone bodies immediately after exercise (R=0.85, p<0.001). In conclusion, LC enhanced liver fat utilization and ketogenesis in an acute manner without stimulating EE under fat-mobilizing conditions.

Effects of the Menstrual Cycle on Serum Carnitine and Endurance Performance of Women.

This study aimed to investigate the effect of the menstrual cycle on serum carnitine and the endurance performance of healthy women. Fifteen eumenorrheic women underwent cycle ergometer exercise at 60% maximal oxygen uptake (V̇ O2max) for 45 min, followed by exercise at an intensity that was increased to 80% V̇ O 2max until exhaustion, during two menstrual cycle phases, including the early follicular phase (FP) and the midluteal phase (LP). The blood levels of estradiol, progesterone, total carnitine, free carnitine, and acylcarnitine were assessed. Compared with the FP, the LP had significantly lower serum total carnitine (p<0.05) and free carnitine (p<0.01). Moreover, the group with decreased endurance performance in the LP than in the FP showed a significantly higher change in serum free carnitine compared with the group that showed improved endurance performance in the LP than in the FP (p<0.05). The results of this study suggested that the changes in serum free carnitine during the menstrual cycle might influence endurance performance.

Effect of L-Carnitine on Amino Acid Metabolism in Elderly Patients Undergoing Regular Hemodialysis

Introduction: Among patients regularly undergoing hemodialysis, hypocarnitinaemia often develops as a consequence of inadequate dietary intake, reduced synthesis in the body, and considerable losses during hemodialysis. Objectives: To evaluate the effects of L-carnitine supplementation on patients with end-stage kidney disease (ESKD) who underwent hemodialysis. Methods: Thirty-one patients with ESKD, comprising 18 men and 13 women, with a median age of 72 (range 58–89) years, who underwent regular hemodialysis received treatment with L-carnitine for 1 year. The total and free carnitine, acylcarnitine, and amino acids (AA) levels before and after L-carnitine treatment were analyzed, and the blood biochemistry results and clinical profiles of the subjects were compared before and after treatment. Results: The median (interquartile range [IQR]) serum total and free carnitine and acylcarnitine levels significantly increased from 34.5 (28.2–44.3), 20.9 (15.8–27.6), and 14.1 (11.2–17.6) µmol/L, respectively to 407.4 (371.6–493.5), 270.2 (228.3–316.0), and 155.0 (136.1–168.5) µmol/L, respectively, after treatment (all p < 0.001). The median (IQR) blood valine, tyrosine, phenylalanine, and citrulline levels increased from 0.94 (0.80–1.09), 0.45 (0.39–0.55), 0.61 (0.56–0.79), and 1.04 (0.79–1.26) mg/dL, respectively to 1.24 (1.13–1.54), 0.76 (0.62–0.85), 0.90 (0.70–1.04), and 1.22 (0.92–1.39) mg/dL, respectively, following L-carnitine treatment (p < 0.001, p < 0.001, p = 0.002, and p = 0.030, respectively); however, the median (IQR) blood arginine level decreased from 0.20 (0.13–0.24) to 0.09 (0.06–0.14) mg/dL after treatment (p < 0.001). The median (IQR) percentage fractional shortening (41.5 vs. 41.9%; p = 0.012) and left ventricular ejection fraction (65.2 vs. 67.3%; p = 0.036) increased significantly following treatment. Conclusions: L-Carnitine increased the blood acylcarnitine levels, enhanced fatty acid metabolism, and affected AAs metabolism; this may be beneficial for energy production within the cardiac and skeletal muscles.

Relationship of Serum Carnitine Level with Falls and Gait Disturbance in the Elderly.

Gait disturbance and falls are serious events that can impair activities of daily living (ADL) in the elderly. On the other hand, carnitine plays essential roles in energy production, and carnitine deficiency leads to low activity levels. We examined whether a lower serum carnitine concentration was correlated with falls and gait disturbances in the elderly. We performed a cross-sectional study. One hundred and ninety-eight elderly patients (male, 83; female, 115; 81 ± 6 years old) were enrolled in this study. Physical performance (hand grip strength, leg strength, walking speed, one-leg standing time, and tandem gait steps) and frailty status (The Edmonton Frail Scale: EFS) were evaluated. The serum total, free, and acylated carnitine levels were measured using an enzyme cycling method. We then investigated the associations between the serum carnitine level, history of falls, and the results of these physical examinations. Of the 198 subjects, 56 (28%) had a history of falls within the past one year. The patients with a history of falls had lower serum total carnitine and free carnitine levels than those without a history of falls. Regarding the physical performance results, the patients with a history of falls had higher EFS scores, a weaker hand grip strength, a slower walking speed, a shorter one-leg standing time, and a smaller number of tandem gait steps than those without a history of falls. A logistic regression analysis showed that the low serum total carnitine concentration was identified as an independent factor associated with a history of falls, a slow walking speed after adjustments for age, sex and modified EFS. A low serum carnitine level is associated with a history of falls and gait disturbances in elderly people.

L-Carnitine improves gastrointestinal disorders and altered the intestinal microbiota in hemodialysis patients.

Patients receiving hemodialysis also manifest gastrointestinal symptoms, such as constipation, caused by restriction of water intake and the loss of body water balance. Because dietary carnitine deficiency is considered to cause smooth muscle dysmotility of the gastrointestinal tract similarly to that in skeletal muscles, carnitine deficiency in hemodialysis patients may be one cause of gastrointestinal discomfort and dysfunctions. We performed a multicenter nonrandomized single-arm prospective clinical trial. Fifteen Japanese patients receiving hemodialysis were administered L-carnitine tablets (900 mg) for 3 months, and clinical and biochemical analyses were performed before and after treatment. The serum total carnitine level was increased significantly by supplementation with L-carnitine for 3 months (from 40.9 ± 2.6 μmol/l to 172.3 ± 19.0 μmol/l, p<0.05). The myasthenia score was decreased significantly by the supplementation (from 1.3 ± 0.3 to 0.8 ± 0.2, p<0.05). The frequency of passing stool tended to increase with the treatment for 3 months (from 4.2 ± 0.5 times/week to 4.8 ± 0.5 times/week). A phyla-level analysis of the microbiota showed that the composition of the individual microbiota was not different between before and after supplementation. A genus-level analysis, however, revealed that the relative abundance of genus Clostridium subcluster 4 was significantly decreased by the supplementation (from 7.7 ± 1.9% to 4.7 ± 1.3%, p<0.05). Oral supplementation of L-carnitine to the patients receiving hemodialysis improved not only their muscle discomfort but also their gastrointestinal disorders and microbiota, although its effect on the prognosis of hemodialysis patients should be further investigated.

Carnitine dynamics and their effects on hyperammonemia in cirrhotic Japanese patients

Supplementation with levocarnitine preparations has been reported to improve hepatic encephalopathy, but no detailed investigations have addressed the dynamics of carnitine or its supplementation indication in cirrhosis patients. We studied carnitine dynamics in cirrhotic patients by measuring serum and liver tissue carnitine levels and tested the effects of levocarnitine supplementation on concurrent hyperammonemia. In a pilot cohort of seven patients with liver cirrhosis and five patients without cirrhosis, the serum and liver carnitine concentrations were measured. Then the serum carnitine fractions were analyzed in 70 liver cirrhosis patients. Among them, a levocarnitine preparation (1800mg/day) was supplemented orally for 3months in 27 patients with refractory hyperammonemia, and the effects were evaluated. A significant correlation was observed between serum and liver tissue carnitine concentrations (r = 0.69, P <0.05). The serum total carnitine concentration was 68.4 ± 4.7μmol/L, the free carnitine concentration was 53.2 ± 2.6μmol/L, and the acylcarnitine concentration was 13.2 ± 1.1μmol/L in 70 cirrhotic patients (reference values are 45-91, 36-74, 6-23μmol/L, respectively). There was no correlation between blood ammonia and serum carnitine concentrations. The serum carnitine concentration rose with levocarnitine supplementation, reaching steady state after 1month and, in parallel, refractory hyperammonemia was significantly improved. The cut-off level for a 20% decrease in blood ammonia was identified as 62.0μmol/L total carnitine concentration by receiver-operating characteristic curve analysis, with an area under the curve of 0.69. Serum carnitine concentrations were within standard levels in the majority of liver cirrhosis patients. In patients with concurrent hyperammonemia, the levocarnitine supplementation reduced blood ammonia levels.

L-carnitine prevents metabolic steatohepatitis in obese diabetic KK-Ay mice.

Pharmacological treatment for metabolic syndrome-related non-alcoholic steatohepatitis has not been established. We investigated the effect of L-carnitine, an essential substance for β-oxidation, on metabolic steatohepatitis in mice. Male KK-Ay mice were fed a high-fat diet (HFD) for 8weeks, with supplementation of L-carnitine (1.25mg/mL) in drinking water for the latter 4weeks. Serum total carnitine levels were decreased following HFD feeding, whereas the levels were reversed almost completely by L-carnitine supplementation. In mice given L-carnitine, exacerbation of hepatic steatosis and hepatocyte apoptosis was markedly prevented even though HFD feeding was continued. Body weight gain, as well as hyperlipidemia, hyperglycemia, and hyperinsulinemia, following HFD feeding were also significantly prevented in mice given L-carnitine. High-fat diet feeding elevated hepatic expression levels of carnitine palmitoyltransferase 1A mRNA; however, production of β-hydroxybutyrate in the liver was not affected by HFD alone. In contrast, L-carnitine treatment significantly increased hepatic β-hydroxybutyrate contents in HFD-fed mice. L-carnitine also blunted HFD induction in sterol regulatory element binding protein-1c mRNA in the liver. Furthermore, L-carnitine inhibited HFD-induced serine phosphorylation of insulin receptor substrate-1 in the liver. L-carnitine decreased hepatic free fatty acid content in 1week, with morphological improvement of swollen mitochondria in hepatocytes, and increases in hepatic adenosine 5'-triphosphate content. L-carnitine ameliorates steatohepatitis in KK-Ay mice fed an HFD, most likely through facilitating mitochondrial β-oxidation, normalizing insulin signals, and inhibiting de novo lipogenesis in the liver. It is therefore postulated that supplementation of L-carnitine is a promising approach for prevention and treatment of metabolic syndrome-related non-alcoholic steatohepatitis.

Carnitine Deficiency: A Causative Clue or a Sequel in Carboplatin Myelosuppression

We have previously demonstrated that carnitine deficiency aggravated paracetamol-induced hepatopathy and carboplatin-induced nephropathy. As a continuum, we have addressed in the current study as to whether carboplatin-induced myelosuppression would be exacerbated by carnitine deficiency. Challenging male Wistar rats with a single dose of carboplatin (35 mg/kg, IP) induced bone marrow suppression manifested as anemia, leucopenia, thrombocytopenia as well as increased frequencies of the micronucleated bone marrow cells; MPCE and MNCE with notable reduction in the P/N ratio. The platinum drug also elevated serum TNF-a and reduced serum free and total carnitine levels. Besides, ATP levels in red and T cells were lowered. Likewise, the mitochondrial membrane potential in T lymphocytes was reduced following the use of the potentiometric dye; JC-1, and this was well correlated with cellular ATP production. Carnitine deficiency exacerbated carboplatin myelotoxicity as it exaggerated all biochemical, hematological and cytogenetic parameters. To address as to whether carnitine deficiency was a causative clue or merely a sequel of carboplatin myelotoxicity, L-carnitine was supplemented ahead of carboplatin challenege. Herein, L-carnitine mitigated all the biochemical, hematological and cytogenetic effects possibly via modulating the release of TNF-a, cellular ATP production and restoring the mitochondrial membrane potential. Irrespective of the mechanisms involved, the current results may afford the potential role for carnitine supplementation as add-on nutraceutical in carboplatin-based chemotherapy.

Carnitine deficiency presenting with a decreased mental state in a patient with amyotrophic lateral sclerosis receiving long-term tube feeding: a case report

IntroductionL-carnitine is an important metabolic mediator involved in fatty acid transport. It is obtained from the diet, particularly from animal products, such as red meat. Previous reports have revealed that long-term tube feeding with a commercial product containing no or low levels of carnitine can lead to an altered mental state caused by hyperammonemia.Case presentationA 72-year-old Japanese man had a 12-year history of amyotrophic lateral sclerosis. He was bedridden and had required mechanical ventilation and enteral tube feeding for 10 years at home. His main enteral solution was a commercial product that contained low carnitine levels, and he sometimes received coffee and homemade products such as miso soup. Our patient’s ability to communicate gradually deteriorated over a period of one year. His serum total carnitine level was abnormally low, at 26.7μmol/L (normal range, 45 to 91μmol/L), but his ammonium level was normal. His mental state improved dramatically after starting L-carnitine supplementation (600mg twice daily).ConclusionThis case highlights the importance of avoiding carnitine deficiency in patients with amyotrophic lateral sclerosis undergoing long-term tube feeding. These patients experience progressive muscle atrophy that might cause impaired carnitine storage and might manifest as communication difficulties. Carnitine deficiency can be misdiagnosed as a progression of systemic muscle atrophy. Clinicians should be aware of this disorder and should consider periodically measuring carnitine levels, regardless of the patient’s serum ammonium levels.

Effects of fermented barley on lipid and carnitine profiles in C57BL/6J mice

The aim of the present study was to investigate the effects of fermented barley supplementation on blood lipid profiles, carnitine concentrations, and hepatic mRNA levels of enzymes involved in fatty acid metabolism. Thirty-two C57BL/6J male mice were divided into 4 groups; normal diet control group (ND), high fat diet control group (HD), high fat diet plus barley supplemented group (BR), and high fat diet plus fermented barley supplemented group (BR-F). BR-F supplementations decreased total cholesterol (TC) and LDL-cholesterol in serum, triglyceride (TG) in liver. Serum total carnitine (TCNE) concentrations were significantly higher in the BR-F group than HD group. BR-F supplementations significantly increased hepatic lipolysis regulating gene expression such as carnitine palmitoyltransferase-I (CPT-I), peroxisome proliferator-activated receptor-α (PPARα), whereas significantly decreased lipogenic enzyme expression such as acetyl CoA carboxylase (ACC). These results suggest that the fermented barley has anti-obesity properties.

Evaluation of Serum Total Carnitine Values in Persons with Severe Motor and Intellectual Disabilities with Enteral (Tube) Feeding

Evaluation of Serum Total Carnitine Values in Persons with Severe Motor and Intellectual Disabilities with Enteral (Tube) Feeding

L-Carnitine Improves the Asthma Control in Children with Moderate Persistent Asthma

The objective. was to investigate L-Carnitine level and the effects of its supplementation in children with moderate persistent Asthma. Methods. Free and total serum carnitine levels were measured in 50 children having moderate persistent asthma and 50 healthy control children. The patients group was randomly divided into two subgroups. Subgroup A was supplemented with L-carnitine for 6 months while subgroup B was used as a placebo controls. Both subgroups were assessed by pulmonary function tests (PFT) and childhood-asthma control test (C-ACT) before and 6 months after carnitine supplementation. Results. Total and free carnitine levels were significantly lower in patient group than in control group. PFT and C-ACT showed significant improvements in asthmatic children supplemented with L-carnitine than in those who were not supplemented. Conclusion. L-carnitine levels were initially lower in moderate persistent asthmatic children as compared to healthy control children. Asthmatic children who received L-carnitine supplementation showed statistically significant improvement of C-ACT and PFT.

Severe muscle cramps after intravenous administration of amiodarone - a novel, potentially dose-dependent adverse effect

Amiodarone is a widely available anti-arrhythmic agent used to treat both ventricular and refractory supra-ventricular tachyarrhythmias. The most widely recognized adverse effects of amiodarone include those affecting the eyes, lungs, liver, heart, skin and thyroid. Amiodarone also causes a spectrum of neuromuscular adverse effects, but these usually develop after long-term administration. This report describes a case of acute onset severe muscle cramps in a young man, which developed after initiation of intravenous amiodarone therapy. A 32-year-old Caucasian man was admitted to the cardiac electrophysiology service for ongoing management of recurrent intra-atrial tachycardia. He had a history of congenital heart disease, and had several cardiac electrophysiology studies which showed re-entrant intra-atrial tachycardia, which had recurred in spite of treatment with various anti-arrhythmic agents, multiple electrical cardioversions, radiofrequency catheter ablation and a Cox maze IV procedure. His medication regimen included digoxin, sotalol, furosemide, lisinopril and coumadin. Laboratory tests on admission revealed normal serum electrolytes, hepatic and renal function, normal thyroid-stimulating hormone concentration and an international normalized ratio (INR) of 2.9. After being aggressively diuresed with intravenous furosemide, he received two 250 mg doses of intravenous amiodarone and was then started on a continuous infusion of 900 mg over the next 24 h. About 12 h after initiation of intravenous amiodarone, the patient started complaining of episodic, severe muscle cramps affecting his neck, back, thighs and calves. He described these episodes as involuntary, sustained, painful contractions of the muscles, about 6–8 episodes every hour, each lasting up to 2 min in duration, and not associated with tremors or paresthesiae. A detailed neurological examination revealed no cranial nerve deficits, no focal motor or sensory deficits, normal gait and co-ordination, symmetric deep tendon reflexes and no muscle fasciculations. The only relevant positive finding on physical examination was mild tenderness over the affected muscle groups in his calves. Repeat laboratory tests showed a normal serum chemistry profile (including ionized and total calcium, magnesium and phosphorus concentrations), normal serum creatinine and creatine phosphokinase (CK), normal free T4 concentrations and a normal urinalysis without myoglobinuria. No relevant drug–drug interactions were identified to explain his muscle cramps. He was started on low dose cyclobenzaprine (2.5 mg three times a day) with partial improvement in his symptoms, and amiodarone was continued orally at a dose of 400 mg three times a day. The following day, he underwent direct current cardioversion with 50 joules, and his cardiac rhythm converted to a normal sinus rhythm alternating with an atrial-paced rhythm. His muscle cramps continued unabated, and follow-up neurological examination and laboratory tests remained normal, except for mild elevation of total serum CK (348 units per litre). The oral maintenance dose of amiodarone was reduced to 200 mg once daily, and over the next 12 h or so, the patient's cramps completely resolved. A battery of screening tests for an inherited metabolic myopathy, including serum ketones, lactate, pyruvate, lactate dehydrogenase, uric acid, free and total serum carnitine concentrations, a quantitative serum acylcarnitine profile and serum free fatty acid profile, were within normal limits. Using the Naranjo probability scale for adverse drug effects [1], this case of acute onset severe muscle cramps scored 7 points. This score places this adverse event in the ‘probable’ category for causal association with amiodarone treatment. The patient was continued on the lower maintenance dose of oral amiodarone, and has not had recurrence of muscle cramps after 6 weeks' follow-up. This case has been reported to the United States Food and Drug Administration (FDA) through its Safety Information and Adverse Event Reporting (MedWatch) Program [2]. The prevalence of amiodarone-induced neurotoxicity ranges from 27.5% to 74% [3–5]. The most commonly reported neurologic adverse effects of amiodarone include tremors, ataxia and peripheral neuropathy, but cases of encephalopathy, parkinsonism, optic neuropathy and myopathy have also been reported. Most reports of amiodarone-induced neurotoxicity are in patients on long-term oral maintenance therapy. However, in the literature there are no reports of acute neurotoxicity or myopathy after the use of intravenous amiodarone. A recent consensus guideline recommends monitoring for neurologic adverse effects such as weakness, paresthesiae, tremors and gait abnormalities during follow-up of patients on long-term amiodarone therapy [6]. However, many widely used adverse event monitoring guidelines [7, 8] do not include specific recommendations for monitoring neurologic symptoms. Clinicians need to be cognizant of the known neurotoxic effects of amiodarone therapy. A baseline neurologic examination should be performed in all patients being started on amiodarone therapy, and published recommendations for pharmacovigilance of amiodarone induced adverse effects should include baseline assessment and monitoring for neurologic adverse effects. In conclusion, this is a case of acute, severe muscle cramps associated with the use of intravenous amiodarone in a young man with congenital heart disease, which resolved spontaneously after conversion to oral amiodarone and dose reduction.