Serum Free Carnitine Levels Research Articles

Effect of parenteral L-carnitine in hospitalized patients with moderate to severe COVID-19: A randomized double-blind clinical trial

Introduction: Pro-inflammatory responses have an important role in developing coronavirus disease 2019 (COVID-19). L-carnitine (LC) has been known to possess anti-inflammatory, anticoagulant, and antiviral effects. So, we aimed to evaluate the efficacy of LC in hospitalized patients with moderate-to-severe COVID-19. Methods: This double-blind, placebo-controlled, randomized clinical trial was conducted on hospitalized patients with moderate to severe COVID-19. The patients were randomized (1:1) to receive LC (n = 50) at a dose of 20 mg/kg or matching placebo (n = 51) from normal saline once daily for 14 days or until hospitalization and standard care. The primary outcome was hospital mortality and disease severity according to the World Health Organization's clinical progression scale. We also assessed the free carnitine level at baseline and the end of the study. C-reactive protein (CRP), ferritin, D-dimer, lactate dehydrogenase (LDH), and improvement of respiratory conditions were chosen as secondary outcomes Results: From 104 patients who met the inclusion criteria, 101 individuals’ data were analyzed. The LC group showed a significant reduction in LDH levels (P = 0.003), although CRP, ferritin, and D-dimer levels did not significantly differ from the placebo group. Also, no significant difference was observed in disease severity, oxygenation status, hospital mortality, or hospital stay between the two groups. Additionally, there was no increase in serum-free carnitine levels in the LC group (P > 0.05 for all). Conclusion: The results of the current study did not support the superiority of LC over placebo in improving oxygenation, decreasing mortality, and hospital stay, as well as CRP, ferritin, and D-dimer in moderate to severe COVID-19 patients. Trial Registration: IRCT20170609034406N10; https://en.irct.ir/trial/60306.

Pathophysiological roles of the serum acylcarnitine level and acylcarnitine/free carnitine ratio in patients with cardiovascular diseases

IntroductionL-carnitine exerts protective effects, such as maintaining mitochondrial functions and decreasing reactive oxygen species, while acylcarnitine (AC) is linked to the development of heart failure and atherosclerosis. HypothesisSerum carnitines play important pathophysiological roles in cardiovascular diseases. MethodsPre-operative biochemical data were obtained from 117 patients (71 men, average age 69.9 years) who underwent surgery for cardiovascular diseases. Measurements included pre-operative biochemical data including estimated glomerular filtration rate (eGFR), physical functions, skeletal muscle mass index (SMI) measured by bioelectrical impedance analysis, anterior thigh muscle thickness (MTh) measured by ultrasound, and routine echocardiography. Carnitine components were measured with the enzyme cycling method. Muscle wasting was diagnosed based on the Asian Working Group for Sarcopenia criteria. ResultsPlasma brain natriuretic peptide (BNP) level was correlated with serum free carnitine (FC) and AC level, and the acylcarnitine/free carnitine ratio (AC/FC). AC/FC was elevated with stage of chronic kidney disease. In multivariate analysis, log (eGFR) and log (BNP) were extracted as independent factors to define log (serum AC) (eGFR: β = 0.258, p = 0.008; BNP: β = 0.273, p = 0.011), even if corrected for age, sex and body mass index. AC/FC was negatively correlated with hand-grip strength (r = -0.387, p = 0.006), SMI (r = -0.314, p = 0.012), and anterior thigh MTh (r = -0.340, p = 0.014) in men. ConclusionsA significant association between serum AC level and AC/FC, and chronic kidney disease and heart failure exists in patients with cardiovascular diseases who have undergone cardiovascular surgery. Skeletal muscle loss and muscle wasting are also linked to the elevation of serum AC level and AC/FC.

Carnitine supplementation increases serum concentrations of free carnitine and total acylcarnitine in preterm neonates: A retrospective cohort study.

Our goal was to determine the efficacy of the American Society for Parenteral and Enteral Nutrition's recommended carnitine dosage of 5 mg/kg/day in maintaining normal serum free carnitine and total acylcarnitine levels in preterm neonates receiving parenteral nutrition (PN). A retrospective cohort study was conducted on neonates born <30 weeks gestation and weighing <1250 g, comparing those who received carnitine supplementation to those without supplementation. Free carnitine and total acylcarnitine data were collected from routine newborn screens in the first days of life and on full enetral feeds. Univariate analysis was performed, and those factors that were significantly different between the two groups were adjusted for using mixed effects analysis. There were 108 supplemented and 45 unsupplemented neonates in the study. At baseline, free carnitine (19.8 ± 3.3 vs 18.9 ± 3.7 µmol/L, P = 0.53) and total acylcarnitine (26.6 ± 5.1 vs 22.5 ± 7.1 µmol/L, P = 0.11) were similar between the two groups. At full enteral feeds, compared with unsupplemented group, supplemented infants had significantly higher free carnitine (27.1 ± 16.4 vs 17.1 ± 8.5 µmol/L, P < 0.001) and total acylcarnitine (30.3 ± 11.5 vs 20.2 ± 10.1 µmol/L, P < 0.001). None of the supplemented neonates developed biochemical carnitine deficiency as compared with 18% in the unsupplemented group (P < 0.001). No difference was observed in time to reach full lipid provision, and there were no differences in the change in the triglyceride levels from baseline to the time on full PN lipid provision (P = 0.39). Preterm neonates routinely supplemented with parenteral carnitine at 5 mg/kg/day demonstrated higher free carnitine and total acylcarnitine levels at full feeds, with none developing biochemical carnitine deficiency.

Association of carnitine insufficiency with sarcopenia and dynapenia in patients with heart failure.

L-carnitine transports fatty acids into mitochondria and contributes to energy metabolism in skeletal muscles. However, the association between carnitine insufficiency and skeletal muscle weakness, namely sarcopenia and dynapenia, in patients with heart failure (HF) remains unclear. In total, 124 patients with HF were enrolled in this study. Carnitine insufficiency was indicated by a decrease in serum free carnitine (FC) levels of less than 36 μmol/L or an elevated serum acylcarnitine (AC) to free carnitine (FC) ratio (AC/FC ratio) of 0.27 or higher. Skeletal muscle weakness was defined as reduced handgrip strength and classified into two phenotypes: sarcopenia (low muscle strength with low skeletal muscle mass) and dynapenia (low muscle strength with normal skeletal muscle mass). Patients with carnitine insufficiency had a significantly higher prevalence of muscle weakness and a lower 6-min walk distance than those without carnitine insufficiency (P < 0.05). A machine learning model showed that older age (≥77 years) and, in patients aged 64-76 years, a higher AC/FC ratio (≥0.31) were associated with sarcopenia. However, there was only a week association between carnitine levels and dynapenia. The effect of carnitine insufficiency on skeletal muscle weakness was greater in patients with low skeletal muscle mass than in those with normal skeletal muscle mass (P < 0.05 for interaction). Carnitine insufficiency is more closely associated with sarcopenia than with dynapenia in patients with HF, suggesting carnitine insufficiency as a potential therapeutic target for sarcopenia in these patients. Geriatr Gerontol Int 2023; 23: 524-530.

Serum free carnitine levels in children with Kawasaki disease.

Carnitine plays an essential role in the transfer of long-chain fatty acids to the mitochondria for β-oxidation. No study has characterized carnitine in children with Kawasaki disease (KD). The objective of this study was to elucidate the characteristics of serum free carnitine (FC) in hospitalized pediatric patients with KD. We retrospectively analyzed 45 patients with KD in whom serum FC levels were measured. We investigated the clinical and laboratory parameters before intravenous immunoglobulin was administered, including serum FC levels, according to the response to intravenous immunoglobulin (IVIG). We also analyzed the relationship among serum FC, laboratory data, and clinical variables. IVIG was effective in 33 children (responders) and was ineffective in 12 children (non-responders). Serum FC levels were higher in non-responders than in responders: 35.3 μmol/L (range, 26.8-118.4 μmol/L) vs 31.4 μmol/L (range, 20.9-81.2 μmol/L), P <0.05. FC levels before IVIG in 80% of responders were below the normal range. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and FC were higher in non-responders than in responders. FC levels were correlated with AST (R2 = 0.364, P = 0.0015) and ALT (R2 = 0.423, P < 0.001) levels. Free carnitine levels were elevated in some patients with KD, especially in those who were refractory to IVIG. Additionally, FC levels in children with KD correlated with ASL and ALT levels.

Levocarnitine Supplementation Suppresses Lenvatinib-Related Sarcopenia in Hepatocellular Carcinoma Patients: Results of a Propensity Score Analysis.

This study investigated the inhibitory effect of levocarnitine supplementation on sarcopenia progression in hepatocellular carcinoma (HCC) patients treated with lenvatinib. We evaluated the skeletal muscle index (SMI). After propensity score matching for age, sex, modified albumin-bilirubin grade, baseline presence of sarcopenia, and branched-chain amino acid administration, we selected 17 patients who received levocarnitine supplementation after starting lenvatinib therapy and 17 propensity-score-matched patients who did not receive levocarnitine. Sarcopenia was present in 76% of the patients at baseline. Changes in baseline SMI at 6 and 12 weeks of treatment were significantly suppressed in the group with levocarnitine supplementation compared with those without (p = 0.009 and p = 0.018, respectively). While there were no significant differences in serum free carnitine levels in cases without levocarnitine supplementation between baseline and after 6 weeks of treatment (p = 0.193), free carnitine levels were significantly higher after 6 weeks of treatment compared with baseline in cases with levocarnitine supplementation (p < 0.001). Baseline SMI and changes in baseline SMI after 6 weeks of treatment were significantly correlated with free carnitine levels (r = 0.359, p = 0.037; and r = 0.345, p = 0.045, respectively). Levocarnitine supplementation can suppress sarcopenia progression during lenvatinib therapy.

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.

Possible correlation between increased serum free carnitine levels and increased skeletal muscle mass following HCV eradication by direct acting antivirals

We aimed to evaluate factors associated with changes in skeletal muscle mass in hepatitis C virus (HCV)-infected patients after treatment with direct-acting antivirals (DAAs). Consecutive HCV-infected patients after treatment with DAA were recruited into the study. Patients who achieved sustained virological response (SVR); and had complete clinical information, preserved serum samples at baseline and SVR48, and skeletal muscle mass evaluations based on the psoas muscle mass index (PMI) on computed tomography at baseline and ≥ 12 months were included. Altogether, 70.7% of patients (41/58) showed increased PMI after DAA therapy, and mean relative PMI was significantly higher after DAA therapy than at baseline. There were no significant associations between baseline clinical factors routinely examined in clinical practice and increased PMI. Among factors reported to be associated with skeletal muscle loss in patients with chronic liver disease, serum zinc levels and total and free carnitine levels increased significantly after DAA therapy and only changes in serum free carnitine levels were significantly associated with an increased PMI (r = 0305, P = 0.020). In conclusion, increased skeletal muscle mass after successful HCV eradication by DAAs was significantly associated with increased serum-free carnitine levels. l-carnitine supplementation may be beneficial in patients with low skeletal muscle mass after DAA.

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.

Effect of L-carnitine supplementation on lipid profile and apolipoproteins in children on hemodialysis: a randomized placebo-controlled clinical trial

Cardiovascular disease (CVD) is the leading cause of death in children with chronic kidney disease (CKD) and accounts for 40% of all deaths among pediatric patients with stage5 chronic kidney disease (CKD5). Dyslipidemia is common in children with CKD and is considered one of the major causes of CVD in these patients. As carnitine plays a key role in lipid metabolism and because plasma levels are reduced in hemodialysis patients, the aim of this study was to determine the effects of L-carnitine supplementation on serum lipid profiles, apolipoproteins, and free carnitine (FC) levels. A total of 30 children on hemodialysis (6-18 years) were enrolled and 24 completed the study. Twelve patients received 50 mg/kg/day L-carnitine, while the other 12 patients received placebo for 10 weeks. Serum FC, total cholesterol (TC), LDL-C, HDL-C, TG, Apolipoprotein B (ApoB), and Apolipoprotein A1 (ApoA1) were determined at the baseline and after the intervention. One-way repeated measures analysis was used to evaluate the effects of L-carnitine supplementation. Oral L-carnitine supplementation led to decreased ApoB levels and ApoB/ApoA1 ratio, but these changes were not significant compared to placebo. Meanwhile, L-carnitine supplementation significantly reduced serum LDL-C and TC and increased serum FC compared to placebo. No significant changes were observed in serum TG and HDL-C levels. Given the significant reduction in LDL-C and TC levels, L-carnitine supplementation had positive effects on improving hyperlipidemia in children receiving hemodialysis. For more decisive results, studies with longer duration of L-carnitine therapy on children receiving hemodialysis with significant dyslipidemia are recommended. We registered the present trial in the Iranian Registry of Clinical Trials website (available at: http://www.irct.ir , identifier: IRCT20170202032367N2).

Carnitine supplementation prevents carnitine deficiency caused by pivalate-conjugated antibiotics in patients with epilepsy prescribed valproate

We measured carnitine levels before and after pivalate-conjugated antibiotic (PCA) use in six patients with epilepsy who were prescribed valproate (VPA). Three of the patients were on carnitine supplementation when PCA use started. Serum FC levels were within the normal range (37.2–49.0 μmol/L) in all six patients before PCA use. After PCA use, the serum free carnitine (FC) levels remained within the normal range (48.0–68.2 μmol/L) in all three patients on carnitine supplementation, but were below the normal range (18.7–30.8 μmol/L) in the three patients not on carnitine supplementation. No remarkable changes in serum VPA levels, platelet count, amylase or ammonia level was evident in any patients in relation to PCA use. Carnitine deficiency due to PCA use was prevented by carnitine supplementation in patients with epilepsy who were taking VPA. Carnitine supplementation can support patients at risk of carnitine deficiency.

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.

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.

Prevalence of Carnitine Deficiency and Decreased Carnitine Levels in Patients on Peritoneal Dialysis.

Background: Carnitine deficiency is common in patients on dialysis. Serum free carnitine concentration is significantly lower in patients on hemodialysis (HD) than in healthy individuals. However, there are few reports on serum free carnitine concentration in patients on peritoneal dialysis (PD). Methods: We examined serum concentrations of total, free, and acylcarnitine and the acylcarnitine/free carnitine ratio in 34 PD and 34 age-, sex-, and dialysis duration-matched HD patients. We investigated the prevalence of carnitine deficiency and clinical factors associated with carnitine deficiency in the PD group. Results: Prevalence of carnitine deficiency was 8.8% in the PD group and 17.7% in the HD group (p = 0.283). High risk of carnitine deficiency was found in 73.5% of the PD group and 76.4% of the HD group (p = 0.604). Carnitine insufficiency was found in 82.3% of the PD group and 88.2% of HD group (p = 0.733). Multivariate analysis revealed that duration of dialysis and age were independent predictors of serum free carnitine level in the PD group. Conclusions: The prevalence of carnitine deficiency, high risk of carnitine deficiency, and carnitine insufficiency in PD patients was 8.8%, 73.5%, and 82.3%, respectively. These rates were comparable to those in patients on HD.

Kinetics of Serum Carnitine Fractions in Patients with Chronic Kidney Disease Not on Dialysis.

Carnitine plays a pivotal role in energy synthesis through β-oxidation in mitochondria. Serum and tissue levels of free carnitine are significantly decreased in dialysis patients, whereas acylcarnitine levels are increased. However, the precise kinetics and fate of carnitine fractions in chronic kidney disease (CKD) patients who are not on dialysis have not been clarified. This study aims to determine the kinetics of serum carnitine fractions in patients who were not on dialysis. Seventy-five CKD patients not on dialysis were recruited in this study. Serum and urinary carnitine fraction levels were measured to evaluate the kinetics and regulation of serum carnitine fractions. Carnitine fractions were measured by the enzymatic cycling method. Total and free serum carnitine levels did not change with progression of CKD, whereas acylcarnitine levels and the acyl/free carnitine ratio significantly increased. Serum acylcarnitine levels were inversely associated with estimated glomerular filtration rate (r2 = 0.239, p < 0.001), but free carnitine levels were not. Serum free carnitine levels were positively associated with urinary free carnitine excretion (r2 = 0.214, p < 0.001), but serum acylcarnitine levels were not. Multiple stepwise regression analysis revealed that urinary free carnitine excretion and blood urea nitrogen were independent determinants of serum free carnitine and acylcarnitine levels, respectively. The present study demonstrated that serum acylcarnitine levels increased with renal dysfunction independent of urinary excretion levels. Serum free carnitine was not affected by renal function in CKD patients who were not on dialysis.

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.

Carnitine deficiency is associated with decreased exercise activity in hemodialysis patients

Background and aimCarnitine deficiency is common and associated with muscle atrophy in hemodialysis (HD) patients. We investigated whether carnitine levels could be an independent predictor for exercise capacity in these patients.MethodA total of 37 patients (mean age, 55.9 ± 13.4 years) who underwent HD three times a week were enrolled in this study. Carnitine fraction levels were measured by the enzyme cycling method. Univariate and multiple stepwise regression analyses were performed to determine the correlation between free carnitine levels and the value of exercise capacity examined by the time-up-and-go test (TUG), knee extension strength, functional reach test (FRT), and 10-m walk test, and thigh and calf circumferences as markers of muscle mass.ResultsSerum free carnitine levels were significantly decreased in HD patients. Free carnitine levels were associated with TUG (inversely; r2 = 0.120, P = 0.035), knee extension strength (r2 = 0.129, P = 0.029), FRT (r2 = 0.246, P = 0.002), and the 10-m walk test (inversely; r2 = 0.149, P = 0.018). Multiple stepwise regression analysis revealed that free carnitine was an independent predictor for FRT (β = 0.369, P < 0.001). There was no correlation between free carnitine levels and thigh and calf circumferences.ConclusionLow serum free carnitine levels were associated with decreased exercise capacity in HD patients, suggesting that carnitine deficiency may be a promising therapeutic target for HD-associated muscle weakness in HD patients. This study was retrospectively registered.

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.

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.

Effects of L-carnitine supplementation on nutritional, immunological, and cardiac parameters in hemodialysis patients: a pilot study

L-carnitine is an essential compound that facilitates the transport of long-chain fatty acid across the inner mitochondrial membrane for β-oxidation. However, the effect of L-carnitine supplementation remains to be fully explored in patients with chronic kidney disease. We aimed in this study to determine the multidirectional effects of L-carnitine supplementation on clinical parameters in more detail. We orally administered L-carnitine to maintain serum-free carnitine levels within the normal range (30 to 70 μmol/L) for 6 months in 21 hemodialysis (HD) patients (age, 74 ± 11 years; time on HD, 60 ± 84 months). L-carnitine supplementation significantly increased serum transferrin from 155 ± 41 to 175 ± 48 mg/dL (p < 0.01) and retinol-binding protein from 8.9 ± 2.5 to 10.0 ± 3.4 mg/dL (p < 0.05). The triceps skinfold thickness was also significantly increased (p < 0.05), while the skeletal muscle mass in limbs and handgrip strength was not. L-carnitine enhanced natural killer (NK) cell activity at the E (effector cell)/T (target cell) ratio of 20:1 from 17.3 ± 14.1 to 20.8 ± 17.7 % (p < 0.01). In addition, L-carnitine improved left ventricular functional shortening (p < 0.01) with a significant decrease of brain natriuretic peptide (BNP) from 621.4 ± 666.8 to 412.0 ± 426.0 pg/mL (p < 0.05). These findings suggest that oral L-carnitine treatment improves immunological and cardiac markers in HD patients. In contrast, L-carnitine did not change the skeletal mass-related parameters during the 6-month follow-up.