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1.
Plasma free carnitine in severe trauma: Influence of the association with traumatic brain injury.
Vardon Bounes, F, Faure, G, Rouget, A, Conil, JM, Georges, B, Geeraerts, T, Fourcade, O, Minville, V, Delmas, C
Injury. 2018;(3):538-542
Abstract
BACKGROUND Metabolic response to severe trauma requires early nutritional resuscitation. Carnitine is essential for lipolysis, the energy source during this hypercatabolic phase. However l-carnitine is not present in nutritional replacement solutions. Furthermore, free carnitine depletion, defined as carnitine plasma level under 36μmol/L, was not adequately reported in adult patients with severe trauma. The aim of this study was to assess plasma free carnitine levels and factors of variation in severe trauma. METHOD Our observational study concerned 38 trauma patients including 18 with traumatic brain injury (TBI). On the third day after trauma, plasma free carnitine concentration was determined (by enzymatic method) while patients received artificial nutrition. RESULTS Low plasmatic free carnitine concentration was evidenced in 95% of the patients with a median value of 18μmol/L (11-47). Univariate analysis showed that mean arterial pressure, serum urea, CKD-EPI and patients with TBI were significantly associated with plasma free carnitine concentration less than 18μmol/L. Lower plasma free carnitine concentration was observed in the group of patients with TBI with 17.72μmol/L (11-36) versus 21.5μmol/L (11-47) for others patients (p=0.031). Logistic regression analysis showed that severe trauma with TBI and CKD-EPI above 94mL/min/1.73m2 appeared to be independent predictor of lower free carnitine plasmatic concentration (Goodness of fit=0.87 and AUC=0.89). CONCLUSION Our observations support hypotheses that plasma free carnitine concentration is lowered in severe injured patients especially for TBI patients and patients with estimated GFR above 94mL/min/1.73m2.
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2.
The effect of L-carnitine supplementation on serum leptin concentrations: a systematic review and meta-analysis of randomized controlled trials.
Nazary-Vannani, A, Ghaedi, E, Mousavi, SM, Teymouri, A, Rahmani, J, Varkaneh, HK
Endocrine. 2018;(3):386-394
Abstract
PURPOSE The actual effects of L-carnitine administration on leptin serum level is inconsistent. In order to assess the efficacy of L-carnitine supplementation on serum leptin we conducted a meta-analysis of randomized controlled trials (RCTs). METHODS Seven studies with 325 cases and 330 controls were included. The pooled weighted mean difference (WMD) was calculated by random-effects model. The heterogeneity across studies was evaluated by using Cochrane's Q and I2 tests. In addition, we carried out the metaninf command to test the effect of each individual study on the overall result. RESULTS L-carnitine supplementation seemed to have no significant effect on serum leptin concentrations (WMD: -0.565 ng/mL; 95% CI: -2.417 to 1.287, p = 0.550). However, between-study heterogeneity was higher across all studies (I2 = 84.3%, p < 0.0001). Subgroup analysis to find the sources of heterogeneity showed that L-carnitine dosage (g) ( < 2 g: I2 = 00.0%, p = 0.408), and study population (diabetes: I2 = 46.7%, p = 0.153, and non-diabetes: I2 = 15.1%, p = 0.317) were the potential sources of heterogeneity. Besides, a more significant reduction in serum leptin concentration was observed with a daily dose of ≥ 2 mg L-carnitine (WMD: -2.742 ng/mL; 95% CI: -3.039 to -2.444, p < 0.001), in diabetic patients (WMD: -2.946 ng/mL; 95% CI: -3.254 to -2.638, p < 0.001), and with intervention duration <12 weeks (WMD: -2.772 ng/mL; 95% CI: -3.073 to -2.471, p < 0.001). CONCLUSION L-carnitine consumption does not reduce serum leptin significantly. However, a significant effect on leptin was observed in diabetic patients and patients who received doses more than 3 mg per day in the course of <12 weeks.
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3.
Does skeletal muscle carnitine availability influence fuel selection during exercise?
Stephens, FB
The Proceedings of the Nutrition Society. 2018;(1):11-19
Abstract
Fat and carbohydrate are the major fuel sources utilised for oxidative, mitochondrial ATP resynthesis during human skeletal muscle contraction. The relative contribution of these two substrates to ATP resynthesis and total energy expenditure during exercise can vary substantially, and is predominantly determined by fuel availability and exercise intensity and duration. For example, the increased ATP demand that occurs with an increase in exercise intensity is met by increases in both fat and carbohydrate oxidation up to an intensity of approximately 60-70 % of maximal oxygen consumption. When exercise intensity increases beyond this workload, skeletal muscle carbohydrate utilisation is accelerated, which results in a reduction and inhibition of the relative and absolute contribution of fat oxidation to total energy expenditure. However, the precise mechanisms regulating muscle fuel selection and underpinning the decline in fat oxidation remain unclear. This brief review will primarily address the theory that a carbohydrate flux-mediated reduction in the availability of muscle carnitine to the mitochondrial enzyme carnitine palmitoyltransferase 1, a rate-limiting step in mitochondrial fat translocation, is a key mechanism for the decline in fat oxidation during high-intensity exercise. This is discussed in relation to recent work in this area investigating fuel metabolism at various exercise intensities and taking advantage of the discovery that skeletal muscle carnitine content can be nutritionally increased in vivo in human subjects.
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4.
Decompensated Chronic Heart Failure Reduces Plasma L-carnitine.
Moreira da Silva Guimarães, S, de Souza Cruz, WM, de Souza Weigert, G, Scalco, FB, Colafranceschi, AS, Ribeiro, MG, Boaventura, GT
Archives of medical research. 2018;(4):278-281
Abstract
The heart has an intense aerobic metabolism and is among the most metabolically active organs in the body. Its tissue stores fatty acid, the main energetic substrate, and requires high concentrations of plasma L-carnitine. This nutrient is essential in the transport of fatty acids to the mitochondria to generate energy and maintain the proper concentration of coenzyme A free. In decompensated chronic heart failure metabolic changes, associated with inflammation, alter the metabolism of L-carnitine and compromise cardiac energy metabolism. The aim of this study was to evaluate plasma L-carnitine in chronic heart failure patients during cardiac decompensation. A cross-sectional study was conducted with 109 volunteers with chronic heart failure. Participants were stratified in the compensated (HF compensated) and decompensated (decompensated HF) groups. Plasma L-carnitine was evaluated by the spectrophotometric enzymatic method. Low plasma L-carnitine was found in the decompensated HF group (p = 0.0001). In this group it was also observed that 29.1% of the participants presented plasma L-carnitine below the reference range (<20 mmol). Reduced plasma L-carnitine in patients with decompensated chronic systolic heart failure was founded. These findings suggest that plasma L-carnitine assessment may be helpful in clinical practice for the treatment of patients with cardiac decompensation.
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5.
A review of micronutrients in sepsis: the role of thiamine, l-carnitine, vitamin C, selenium and vitamin D.
Belsky, JB, Wira, CR, Jacob, V, Sather, JE, Lee, PJ
Nutrition research reviews. 2018;(2):281-290
Abstract
Sepsis is defined as the dysregulated host response to an infection resulting in life-threatening organ dysfunction. The metabolic demand from inefficiencies in anaerobic metabolism, mitochondrial and cellular dysfunction, increased cellular turnover, and free-radical damage result in the increased focus of micronutrients in sepsis as they play a pivotal role in these processes. In the present review, we will evaluate the potential role of micronutrients in sepsis, specifically, thiamine, l-carnitine, vitamin C, Se and vitamin D. Each micronutrient will be reviewed in a similar fashion, discussing its major role in normal physiology, suspected role in sepsis, use as a biomarker, discussion of the major basic science and human studies, and conclusion statement. Based on the current available data, we conclude that thiamine may be considered in all septic patients at risk for thiamine deficiency and l-carnitine and vitamin C to those in septic shock. Clinical trials are currently underway which may provide greater insight into the role of micronutrients in sepsis and validate standard utilisation.
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6.
Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial.
Mercadal, L, Tezenas du Montcel, S, Chonchol, MB, Debure, A, Depreneuf, H, Servais, A, Bassilios, N, Assogba, U, Allouache, M, Prié, D
American journal of nephrology. 2018;(5):349-356
Abstract
BACKGROUND The use of L-carnitine has been proposed in haemodialysis (HD) when deficiency is present to improve anaemia resistant to erythropoietin stimulating agent, intradialytic hypotension or cardiac failure. We tested the effects of L-carnitine supplementation on parameters of chronic kidney disease-mineral bone disorder. METHODS CARNIDIAL was a randomized, double-blinded trial having included 92 incident HD subjects for a 1-year period to receive L-carnitine versus placebo. Determinant factors of C-terminal fibroblast growth factor 23 (cFGF23) and intact FGF23 were studied including Klotho level. The L-carnitine effect on mineral metabolism was analyzed between groups by mixed linear models for repeated measurements. RESULTS Klotho was below the lower limit of quantification (LLOQ) in 55% of the 163 samples. In multivariate analysis, cFGF23 was positively correlated with calcium and phosphate and was higher in subjects having Klotho > LLOQ. No correlation existed between Klotho and phosphate and phosphate was even higher in subjects having Klotho > LLOQ (p < 0.001). Both forms of FGF23 were not related to iron markers nor to IV iron dose. No L-carnitine effect was detected on parathyroid hormone (PTH) or FGF23 during the study period where PTH slightly decreased over time, whereas FGF23 increased. But calcium and phosphate increased more in the L-carnitine group. CONCLUSION L-carnitine supplementation increased calcium and phosphate plasma concentrations with no detected downregulation effect on PTH and FGF23. (Clinical Trial 00322322, May 5, 2006).
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7.
Levocarnitine and vitamin B complex for the treatment of pegaspargase-induced hepatotoxicity: A case report and review of the literature.
Blackman, A, Boutin, A, Shimanovsky, A, Baker, WJ, Forcello, N
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2018;(5):393-397
Abstract
Asparaginase is a chemotherapeutic agent that is commonly used in combination with other medications for the treatment of acute lymphoblastic leukemia. An adverse effect of asparaginase includes hepatotoxicity, which can lead to severe liver failure and death. Several reports have documented successful treatment of asparaginase-induced hepatotoxicity using levocarnitine (l-carnitine) and vitamin B complex. Herein, we report a patient with acute lymphoblastic leukemia that experienced acute liver injury following pegaspargase administration. Our patient was successfully treated with l-carnitine and vitamin B complex for 8 days and achieved recovery of hepatic function. Furthermore, we review the current literature and provide a recommendation on a regimen that can be used as an option for the treatment of asparaginase-induced hepatic injury.
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8.
Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: a randomised trial.
Blancquaert, L, Baguet, A, Bex, T, Volkaert, A, Everaert, I, Delanghe, J, Petrovic, M, Vervaet, C, De Henauw, S, Constantin-Teodosiu, D, et al
The British journal of nutrition. 2018;(7):759-770
Abstract
Balanced vegetarian diets are popular, although they are nearly absent in creatine and carnosine and contain considerably less carnitine than non-vegetarian diets. Few longitudinal intervention studies investigating the effect of a vegetarian diet on the availability of these compounds currently exist. We aimed to investigate the effect of transiently switching omnivores onto a vegetarian diet for 6 months on muscle and plasma creatine, carnitine and carnosine homeostasis. In a 6-month intervention, forty omnivorous women were ascribed to three groups: continued omnivorous diet (control, n 10), vegetarian diet without supplementation (Veg+Pla, n 15) and vegetarian diet combined with daily β-alanine (0·8-0·4 g/d) and creatine supplementation (1 g creatine monohydrate/d) (Veg+Suppl, n 15). Before (0 months; 0M), after 3 months (3M) and 6 months (6M), a fasted venous blood sample and 24-h urine was collected, and muscle carnosine content was determined by proton magnetic resonance spectroscopy (1H-MRS). Muscle biopsies were obtained at 0M and 3M. Plasma creatine and muscle total creatine content declined from 0M to 3M in Veg+Pla (P=0·013 and P=0·009, respectively), whereas plasma creatine increased from 0M in Veg+Suppl (P=0·004). None of the carnitine-related compounds in plasma or muscle showed a significant time×group interaction effect. 1H-MRS-determined muscle carnosine content was unchanged over 6M in control and Veg+Pla, but increased in Veg+Suppl in soleus (P<0·001) and gastrocnemius (P=0·001) muscle. To conclude, the body creatine pool declined over a 3-month vegetarian diet in omnivorous women, which was ameliorated when accompanied by low-dose dietary creatine supplementation. Carnitine and carnosine homeostasis was unaffected by a 3- or 6-month vegetarian diet, respectively.
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9.
Inborn Errors of Metabolism with Myopathy: Defects of Fatty Acid Oxidation and the Carnitine Shuttle System.
El-Gharbawy, A, Vockley, J
Pediatric clinics of North America. 2018;(2):317-335
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Abstract
Fatty acid oxidation disorders (FAODs) and carnitine shuttling defects are inborn errors of energy metabolism with associated mortality and morbidity due to cardiomyopathy, exercise intolerance, rhabdomyolysis, and liver disease with physiologic stress. Hypoglycemia is characteristically hypoketotic. Lactic acidemia and hyperammonemia may occur during decompensation. Recurrent rhabdomyolysis is debilitating. Expanded newborn screening can detect most of these disorders, allowing early, presymptomatic treatment. Treatment includes avoiding fasting and sustained extraneous exercise and providing high-calorie hydration during illness to prevent lipolysis, and medium-chain triglyceride oil supplementation in long-chain FAODs. Carnitine supplementation may be helpful. However, conventional treatment does not prevent all symptoms.
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[Myocardial protective effect of L-carnitine in children with hand, foot and mouth disease caused by Coxsackie A16 virus].
Cui, YJ, Song, CL, Chen, F, Li, P, Cheng, YB
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics. 2017;(8):908-912
Abstract
OBJECTIVE To investigate the myocardial protective effect of L-carnitine in children with hand, foot and mouth disease (HFMD) caused by Coxsackie A16 virus and possible mechanisms. METHODS A total of 60 HFMD children with abnormal myocardial enzyme after Coxsackie A16 virus infection were enrolled and randomly divided into L-carnitine group and fructose-1,6-diphosphate group (fructose group), with 30 children in each group. The two groups were given L-carnitine or fructose diphosphate in addition to antiviral and heat clearance treatment. Another 30 healthy children who underwent physical examination were enrolled as control group. The changes in myocardial zymogram, malondialdehyde (MDA), superoxide dismutase (SOD), and apoptosis factors sFas and sFasL after treatment were compared between groups. RESULTS There was no significant difference in treatment response between the L-carnitine group and the fructose group (P>0.05). One child in the fructose group progressed to critical HFMD, which was not observed in the L-carnitine group. Before treatment, the L-carnitine group and the fructose group had significantly higher indices of myocardial zymogram and levels of MDA, sFas, and sFasL and a significantly lower level of SOD than the control group (P<0.05), while there were no significant differences in these indices between the L-carnitine group and the fructose group (P>0.05). After treatment, the L-carnitine group and the fructose group had significant reductions in the indices of myocardial zymogram and levels of MDA, sFas, and sFasL and a significant increase in the level of SOD (P<0.05); the fructose group had a significantly higher level of creatine kinase (CK) than the control group and the L-carnitine group, and there were no significant differences in other myocardial enzyme indices, MDA, sFas, and sFasL between the L-carnitine group and the fructose group, as well as between the L-carnitine and fructose groups and the control group (P>0.05). SOD level was negatively correlated with aspartate aminotransferase, lactate dehydrogenase (LDH), CK, and creatine kinase-MB (CK-MB) (r=-0.437, -0.364, -0.397, and -0.519 respectively; P<0.05), and MDA level was positively correlated with LDH and CK-MB (r=0.382 and 0.411 respectively; P<0.05). CONCLUSIONS L-carnitine exerts a good myocardial protective effect in children with HFMD caused by Coxsackie A16 virus, possibly by clearing oxygen radicals and inhibiting cardiomyocyte apoptosis.