Mass Spectrometric Analysis of L-carnitine and its Esters: Potential Biomarkers of Disturbances in Carnitine Homeostasis

Author(s): Judit Bene*, Andras Szabo, Katalin Komlósi, Bela Melegh

Journal Name: Current Molecular Medicine

Volume 20 , Issue 5 , 2020

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Abstract:

Purpose: After a golden age of classic carnitine research three decades ago, the spread of mass spectrometry opened new perspectives and a much better understanding of the carnitine system is available nowadays. In the classic period, several human and animal studies were focused on various distinct physiological functions of this molecule and these revealed different aspects of carnitine homeostasis in normal and pathological conditions. Initially, the laboratory analyses were based on the classic or radioenzymatic assays, enabling only the determination of free and total carnitine levels and calculation of total carnitine esters’ amount without any information on the composition of the acyl groups. The introduction of mass spectrometry allowed the measurement of free carnitine along with the specific and sensitive determination of different carnitine esters. Beyond basic research, mass spectrometry study of carnitine esters was introduced into the newborn screening program because of being capable to detect more than 30 metabolic disorders simultaneously. Furthermore, mass spectrometry measurements were performed to investigate different disease states affecting carnitine homeostasis, such as diabetes, chronic renal failure, celiac disease, cardiovascular diseases, autism spectrum disorder or inflammatory bowel diseases.

Results: This article will review the recent advances in the field of carnitine research with respect to mass spectrometric analyses of acyl-carnitines in normal and various pathological states.

Conclusion: The growing number of publications using mass spectrometry as a tool to investigate normal physiological conditions or reveal potential biomarkers of primary and secondary carnitine deficiencies shows that this tool brought a new perspective to carnitine research.

Keywords: L-carnitine, acylcarnitines, mass spectrometry, carnitine homeostasis, cardiovascular diseases, diabetes, autism spectrum disorder, chronic renal failure.

[1]
Gulewitsch W, Krimberg R. Zur kenntnis der extraktivstoffe der muskeln. II. Mitteilung. Über das carnitin. Hoppe Seylers Z Physiol Chem 1905; 45: 326-30.
[http://dx.doi.org/10.1515/bchm2.1905.45.3-4.326]
[2]
Tomita M, Sendju Y. Über die oxyaminoverbindungen, welche diebiuretreaktion zeigen. III. Spaltung der g-amino-b-oxy-buttersäure in die optisch-aktiven komponenten. Hoppe Seylers Z Physiol Chem 1927; 169: 263-77.
[http://dx.doi.org/10.1515/bchm2.1927.169.4-6.263]
[3]
Fritz I. The effect of muscle extracts on the oxidation of palmitic acid by liver slices and homogenates. Acta Physiol Scand 1955; 34(4): 367-85.
[http://dx.doi.org/10.1111/j.1748-1716.1955.tb01256.x] [PMID: 13282744]
[4]
Bremer J. Carnitine-metabolism and functions. Physiol Rev 1983; 63(4): 1420-80.
[http://dx.doi.org/10.1152/physrev.1983.63.4.1420] [PMID: 6361812]
[5]
Hoppel C. The role of carnitine in normal and altered fatty acid metabolism. Am J Kidney Dis 2003; 41(4)(Suppl. 4): S4-S12.
[http://dx.doi.org/10.1016/S0272-6386(03)00112-4] [PMID: 12751049]
[6]
Brass EP, Hoppel CL. Carnitine metabolism in the fasting rat. J Biol Chem 1978; 253(8): 2688-93.
[PMID: 632294]
[7]
Millington DS, Kodo N, Norwood DL, Roe CR. Tandem mass spectrometry: a new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism. J Inherit Metab Dis 1990; 13(3): 321-4.
[http://dx.doi.org/10.1007/BF01799385] [PMID: 2122093]
[8]
Bieber LL. Carnitine. Annu Rev Biochem 1988; 57: 261-83.
[http://dx.doi.org/10.1146/annurev.bi.57.070188.001401 ] [PMID: 3052273]
[9]
McGarry JD. The mitochondrial carnitine palmitoyltransferase system: its broadening role in fuel homoeostasis and new insights into its molecular features. Biochem Soc Trans 1995; 23(2): 321-4.
[http://dx.doi.org/10.1042/bst0230321] [PMID: 7672352]
[10]
Adeva-Andany MM, Calvo-Castro I, Fernández-Fernández C, Donapetry-García C, Pedre-Piñeiro AM. Significance of l-carnitine for human health. IUBMB Life 2017; 69(8): 578-94.
[http://dx.doi.org/10.1002/iub.1646] [PMID: 28653367]
[11]
Evangeliou A, Vlassopoulos D. Carnitine metabolism and deficit--when supplementation is necessary? Curr Pharm Biotechnol 2003; 4(3): 211-9.
[http://dx.doi.org/10.2174/1389201033489829] [PMID: 12769764]
[12]
Duran M, Loof NE, Ketting D, Dorland L. Secondary carnitine deficiency. J Clin Chem Clin Biochem 1990; 28(5): 359-63.
[PMID: 2199597]
[13]
Reda E, D’Iddio S, Nicolai R, Benatti P, Calvani M. The carnitine system and body composition. Acta Diabetol 2003; 40(Suppl. 1): S106-13.
[http://dx.doi.org/10.1007/s00592-003-0040-z] [PMID: 14618447]
[14]
Reuter SE, Evans AM. Carnitine and acylcarnitines: pharmacokinetic, pharmacological and clinical aspects. Clin Pharmacokinet 2012; 51(9): 553-72.
[http://dx.doi.org/10.1007/BF03261931] [PMID: 22804748]
[15]
Calvani M, Benatti P, Mancinelli A, et al. Carnitine replacement in end-stage renal disease and hemodialysis. Ann N Y Acad Sci 2004; 1033: 52-66.
[http://dx.doi.org/10.1196/annals.1320.005] [PMID: 15591003]
[16]
Meyburg J, Schulze A, Kohlmueller D, Linderkamp O, Mayatepek E. Postnatal changes in neonatal acylcarnitine profile. Pediatr Res 2001; 49(1): 125-9.
[http://dx.doi.org/10.1203/00006450-200101000-00024] [PMID: 11134502]
[17]
Sayed-Ahmed MM. Role of carnitine in cancer chemotherapy-induced multiple organ toxicity. Saudi pharmaceutical journal: SPJ : the official publication of the Saudi Pharmaceutical Society 2010; 18(4): 195-206.
[http://dx.doi.org/10.1016/j.jsps.2010.07.008]
[18]
Ramos-Roman MA, Sweetman L, Valdez MJ, Parks EJ. Postprandial changes in plasma acylcarnitine concentrations as markers of fatty acid flux in overweight and obesity. Metabolism 2012; 61(2): 202-12.
[http://dx.doi.org/10.1016/j.metabol.2011.06.008] [PMID: 21820684]
[19]
Rebouche CJ. Carnitine function and requirements during the life cycle. FASEB J 1992; 6(15): 3379-86.
[http://dx.doi.org/10.1096/fasebj.6.15.1464372] [PMID: 1464372]
[20]
Almannai M, Alfadhel M, El-Hattab AW. Carnitine Inborn Errors of Metabolism. Molecules 2019; 24(18) E3251
[http://dx.doi.org/10.3390/molecules24183251] [PMID: 31500110]
[21]
Stanley CA. New genetic defects in mitochondrial fatty acid oxidation and carnitine deficiency. Adv Pediatr 1987; 34: 59-88.
[PMID: 3318304]
[22]
Nezu J, Tamai I, Oku A, et al. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet 1999; 21(1): 91-4.
[http://dx.doi.org/10.1038/5030] [PMID: 9916797]
[23]
El-Hattab AW, Scaglia F. Disorders of carnitine biosynthesis and transport. Mol Genet Metab 2015; 116(3): 107-12.
[http://dx.doi.org/10.1016/j.ymgme.2015.09.004] [PMID: 26385306]
[24]
Melegh B, Bene J, Mogyorósy G, et al. Phenotypic manifestations of the OCTN2 V295X mutation: sudden infant death and carnitine-responsive cardiomyopathy in Roma families. Am J Med Genet A 2004; 131(2): 121-6.
[http://dx.doi.org/10.1002/ajmg.a.30207] [PMID: 15487009]
[25]
Frigeni M, Balakrishnan B, Yin X, et al. Functional and molecular studies in primary carnitine deficiency. Hum Mutat 2017; 38(12): 1684-99.
[http://dx.doi.org/10.1002/humu.23315] [PMID: 28841266]
[26]
Wang Y, Ye J, Ganapathy V, Longo N. Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency. Proc Natl Acad Sci USA 1999; 96(5): 2356-60.
[http://dx.doi.org/10.1073/pnas.96.5.2356] [PMID: 10051646]
[27]
Lahrouchi N, Lodder EM, Mansouri M, et al. Exome sequencing identifies primary carnitine deficiency in a family with cardiomyopathy and sudden death. Eur J Hum Genet 2017; 25(6): 783-7.
[http://dx.doi.org/10.1038/ejhg.2017.22] [PMID: 28295041]
[28]
Mutlu-Albayrak H, Bene J, Oflaz MB, Tanyalçın T, Çaksen H, Melegh B. Identification of SLC22A5 gene mutation in a family with carnitine uptake defect. Case Rep Genet 2015; 2015 259627
[http://dx.doi.org/10.1155/2015/259627] [PMID: 26075114]
[29]
Sun Y, Wang YY, Jiang T. Clinical features and genotyping of patients with primary carnitine deficiency identified by newborn screening. J Pediatr Endocrinol Metab 2017; 30(8): 879-83.
[http://dx.doi.org/10.1515/jpem-2017-0002] [PMID: 28753539]
[30]
Rasmussen J, Hougaard DM, Sandhu N, et al. Primary carnitine deficiency: Is foetal development affected and can newborn screening be improved? JIMD Rep 2017; 36: 35-40.
[http://dx.doi.org/10.1007/8904_2016_30] [PMID: 28105570]
[31]
Schimmenti LA, Crombez EA, Schwahn BC, et al. Expanded newborn screening identifies maternal primary carnitine deficiency. Mol Genet Metab 2007; 90(4): 441-5.
[http://dx.doi.org/10.1016/j.ymgme.2006.10.003] [PMID: 17126586]
[32]
El-Hattab AW, Li FY, Shen J, Powell BR, Bawle EV, Adams DJ, et al. Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects. Genetics in medicine : official journal of the American College of Medical Genetics 2010; 12(1): 19-24.
[http://dx.doi.org/10.1097/GIM.0b013e3181c5e6f7]
[33]
Pons R, De Vivo DC. Primary and secondary carnitine deficiency syndromes. J Child Neurol 1995; 10(Suppl. 2): S8-S24.
[http://dx.doi.org/10.1177/0883073895010002S03] [PMID: 8576570]
[34]
Tanphaichitr V, Leelahagul P. Carnitine metabolism and human carnitine deficiency. Nutrition 1993; 9(3): 246-54.
[PMID: 8353366]
[35]
Melegh B, Kerner J, Bieber LL. Pivampicillin-promoted excretion of pivaloylcarnitine in humans. Biochem Pharmacol 1987; 36(20): 3405-9.
[http://dx.doi.org/10.1016/0006-2952(87)90318-2] [PMID: 3675603]
[36]
Melegh B, Kerner J, Jaszai V, Bieber LL. Differential excretion of xenobiotic acyl-esters of carnitine due to administration of pivampicillin and valproate. Biochem Med Metab Biol 1990; 43(1): 30-8.
[http://dx.doi.org/10.1016/0885-4505(90)90005-L] [PMID: 2106908]
[37]
Jones LL, McDonald DA, Borum PR. Acylcarnitines: role in brain. Prog Lipid Res 2010; 49(1): 61-75.
[http://dx.doi.org/10.1016/j.plipres.2009.08.004] [PMID: 19720082]
[38]
Sunny NE, Satapati S, Fu X, et al. Progressive adaptation of hepatic ketogenesis in mice fed a high-fat diet. Am J Physiol Endocrinol Metab 2010; 298(6): E1226-35.
[http://dx.doi.org/10.1152/ajpendo.00033.2010] [PMID: 20233938]
[39]
Meyburg J, Schulze A, Kohlmueller D, et al. Acylcarnitine profiles of preterm infants over the first four weeks of life. Pediatr Res 2002; 52(5): 720-3.
[http://dx.doi.org/10.1203/00006450-200211000-00018] [PMID: 12409519]
[40]
Melegh B, Kerner J, Sándor A, Vincellér M, Kispál G. Effects of oral L-carnitine supplementation in low-birth-weight premature infants maintained on human milk. Biol Neonate 1987; 51(4): 185-93.
[http://dx.doi.org/10.1159/000242650] [PMID: 3580423]
[41]
Melegh B. Carnitine supplementation in the premature. Biol Neonate 1990; 58(Suppl. 1): 93-106.
[http://dx.doi.org/10.1159/000243304] [PMID: 2265223]
[42]
Bene J, Komlósi K, Melegh BI, Decsi T, Koletzko B, Sauerwald U. Differences in circulating carnitine status of preterm infants fed fortified human milk or preterm infant formula. J Pediatr Gastroenterol Nutr 2013; 57(5): 673-6.
[http://dx.doi.org/10.1097/MPG.0b013e31829fad06] [PMID: 23783025]
[43]
Talián GC, Komlósi K, Decsi T, Koletzko B, Melegh B. Determination of carnitine ester patterns during the second half of pregnancy, at delivery, and in neonatal cord blood by tandem mass spectrometry: complex and dynamic involvement of carnitine in the intermediary metabolism. Pediatr Res 2007; 62(1): 88-92.
[http://dx.doi.org/10.1203/PDR.0b013e3180676cca] [PMID: 17515842]
[44]
Knottnerus SJG, Bleeker JC, Wüst RCI, et al. Disorders of mitochondrial long-chain fatty acid oxidation and the carnitine shuttle. Rev Endocr Metab Disord 2018; 19(1): 93-106.
[http://dx.doi.org/10.1007/s11154-018-9448-1] [PMID: 29926323]
[45]
Lindner M, Hoffmann GF, Matern D. Newborn screening for disorders of fatty-acid oxidation: experience and recommendations from an expert meeting. J Inherit Metab Dis 2010; 33(5): 521-6.
[http://dx.doi.org/10.1007/s10545-010-9076-8] [PMID: 20373143]
[46]
Lehotay DC, Hall P, Lepage J, Eichhorst JC, Etter ML, Greenberg CR. LC-MS/MS progress in newborn screening. Clin Biochem 2011; 44(1): 21-31.
[http://dx.doi.org/10.1016/j.clinbiochem.2010.08.007] [PMID: 20709048]
[47]
Briand G, Lemaire-Ewing S, Parente F, Garnotel R. [Mass spectrometry and inherited metabolic diseases diagnosis]. Ann Biol Clin (Paris) 2015; 73(1): 93-106.
[http://dx.doi.org/10.1684/abc.2014.1022] [PMID: 25582726]
[48]
Minkler PE, Stoll MS, Ingalls ST, Kerner J, Hoppel CL. Quantitative acylcarnitine determination by UHPLC-MS/MS--Going beyond tandem MS acylcarnitine “profiles”. Mol Genet Metab 2015; 116(4): 231-41.
[http://dx.doi.org/10.1016/j.ymgme.2015.10.002] [PMID: 26458767]
[49]
Yoon HR. Screening newborns for metabolic disorders based on targeted metabolomics using tandem mass spectrometry. Ann Pediatr Endocrinol Metab 2015; 20(3): 119-24.
[http://dx.doi.org/10.6065/apem.2015.20.3.119] [PMID: 26512346]
[50]
Van Hove JL, Kahler SG, Feezor MD, et al. Acylcarnitines in plasma and blood spots of patients with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase defiency. J Inherit Metab Dis 2000; 23(6): 571-82.
[http://dx.doi.org/10.1023/A:1005673828469] [PMID: 11032332]
[51]
Vilskersts R, Kuka J, Liepinsh E, et al. Methyl-γ-butyrobetaine decreases levels of acylcarnitines and attenuates the development of atherosclerosis. Vascul Pharmacol 2015; 72: 101-7.
[http://dx.doi.org/10.1016/j.vph.2015.05.005] [PMID: 25989106]
[52]
Anderson SG, Dunn WB, Banerjee M, et al. Evidence that multiple defects in lipid regulation occur before hyperglycemia during the prodrome of type-2 diabetes. PLoS One 2014; 9(9) e103217
[http://dx.doi.org/10.1371/journal.pone.0103217] [PMID: 25184286]
[53]
Spiekerkoetter U, Lindner M, Santer R, et al. Treatment recommendations in long-chain fatty acid oxidation defects: consensus from a workshop. J Inherit Metab Dis 2009; 32(4): 498-505.
[http://dx.doi.org/10.1007/s10545-009-1126-8] [PMID: 19452263]
[54]
Nasser M, Javaheri H, Fedorowicz Z, Noorani Z. Carnitine supplementation for inborn errors of metabolism. Cochrane Database Syst Rev 2012; 2(2) CD006659
[http://dx.doi.org/10.1002/14651858.CD006659.pub3] [PMID: 22336821]
[55]
Capristo E, Addolorato G, Mingrone G, et al. Changes in body composition, substrate oxidation, and resting metabolic rate in adult celiac disease patients after a 1-y gluten-free diet treatment. Am J Clin Nutr 2000; 72(1): 76-81.
[http://dx.doi.org/10.1093/ajcn/72.1.76] [PMID: 10871564]
[56]
Vuoristo M, Kesäniemi YA, Gylling H, Miettinen TA. Metabolism of cholesterol and apolipoprotein B in celiac disease. Metabolism 1993; 42(11): 1386-91.
[http://dx.doi.org/10.1016/0026-0495(93)90187-S] [PMID: 8231831]
[57]
Rosenthal E, Hoffman R, Aviram M, Benderly A, Erde P, Brook JG. Serum lipoprotein profile in children with celiac disease. J Pediatr Gastroenterol Nutr 1990; 11(1): 58-62.
[http://dx.doi.org/10.1097/00005176-199007000-00012] [PMID: 2388134]
[58]
Green PH, Jabri B. Coeliac disease. Lancet 2003; 362(9381): 383-91.
[http://dx.doi.org/10.1016/S0140-6736(03)14027-5] [PMID: 12907013]
[59]
Lerner A, Gruener N, Iancu TC. Serum carnitine concentrations in coeliac disease. Gut 1993; 34(7): 933-5.
[http://dx.doi.org/10.1136/gut.34.7.933] [PMID: 8344581]
[60]
Yüce A, Demir H, Temizel IN, Koçak N. Serum carnitine and selenium levels in children with celiac disease. Indian J Gastroenterol 2004; 23(3): 87-8.
[PMID: 15250563]
[61]
Curione M, Danese C, Viola F, et al. Carnitine deficiency in patients with coeliac disease and idiopathic dilated cardiomyopathy. Nutr Metab Cardiovasc Dis 2005; 15(4): 279-83.
[http://dx.doi.org/10.1016/j.numecd.2005.01.002] [PMID: 16054552]
[62]
Uslu N, Demir H, Karagöz T, Saltik-Temizel IN. Dilated cardiomyopathy in celiac disease: role of carnitine deficiency. Acta Gastroenterol Belg 2010; 73(4): 530-1.
[PMID: 21299168]
[63]
Karakoç E, Erdem S, Sökmensüer C, Kansu T. Encephalopathy due to carnitine deficiency in an adult patient with gluten enteropathy. Clin Neurol Neurosurg 2006; 108(8): 794-7.
[http://dx.doi.org/10.1016/j.clineuro.2005.10.012] [PMID: 16325996]
[64]
Ciacci C, Peluso G, Iannoni E, et al. L-Carnitine in the treatment of fatigue in adult celiac disease patients: a pilot study. Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2007; 39(10): 922-8.
[65]
Bene J, Komlósi K, Gasztonyi B, Juhász M, Tulassay Z, Melegh B. Plasma carnitine ester profile in adult celiac disease patients maintained on long-term gluten free diet. World J Gastroenterol 2005; 11(42): 6671-5.
[http://dx.doi.org/10.3748/wjg.v11.i42.6671] [PMID: 16425363]
[66]
Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002; 347(6): 417-29.
[http://dx.doi.org/10.1056/NEJMra020831] [PMID: 12167685]
[67]
Petkau JM, Eksteen B. Selective biologics for ulcerative colitis and Crohn’s disease - clinical utility of vedolizumab. Biologics 2016; 10: 33-52.
[PMID: 27022240]
[68]
Roediger WE. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet 1980; 2(8197): 712-5.
[http://dx.doi.org/10.1016/S0140-6736(80)91934-0] [PMID: 6106826]
[69]
Gasbarrini G, Mingrone G, Giancaterini A, et al. Effects of propionyl-L-carnitine topical irrigation in distal ulcerative colitis: a preliminary report. Hepatogastroenterology 2003; 50(53): 1385-9.
[PMID: 14571743]
[70]
Roediger WE, Heyworth M, Willoughby P, Piris J, Moore A, Truelove SC. Luminal ions and short chain fatty acids as markers of functional activity of the mucosa in ulcerative colitis. J Clin Pathol 1982; 35(3): 323-6.
[http://dx.doi.org/10.1136/jcp.35.3.323] [PMID: 7068924]
[71]
Scheppach W, Sommer H, Kirchner T, et al. Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology 1992; 103(1): 51-6.
[http://dx.doi.org/10.1016/0016-5085(92)91094-K] [PMID: 1612357]
[72]
Rashed MS. Clinical applications of tandem mass spectrometry: ten years of diagnosis and screening for inherited metabolic diseases. J Chromatogr B Biomed Sci Appl 2001; 758(1): 27-48.
[http://dx.doi.org/10.1016/S0378-4347(01)00100-1] [PMID: 11482732]
[73]
Bene J, Komlósi K, Havasi V, et al. Changes of plasma fasting carnitine ester profile in patients with ulcerative colitis. World J Gastroenterol 2006; 12(1): 110-3.
[http://dx.doi.org/10.3748/wjg.v12.i1.110] [PMID: 16440427]
[74]
Siguel EN, Lerman RH. Prevalence of essential fatty acid deficiency in patients with chronic gastrointestinal disorders. Metabolism 1996; 45(1): 12-23.
[http://dx.doi.org/10.1016/S0026-0495(96)90194-8] [PMID: 8544768]
[75]
Kinsella JE, Lokesh B, Broughton S, Whelan J. Dietary polyunsaturated fatty acids and eicosanoids: potential effects on the modulation of inflammatory and immune cells: an overview. Nutrition 1990; 6(1): 24-44.
[PMID: 2135755]
[76]
Danese C, Cirene M, Colotto M, et al. Cardiac involvement in inflammatory bowel disease: role of acylcarnitine esters. Clin Ter 2011; 162(4): e105-9.
[PMID: 21912810]
[77]
Iwamoto J, Honda A, Miyamoto Y, et al. Serum carnitine as an independent biomarker of malnutrition in patients with impaired oral intake. J Clin Biochem Nutr 2014; 55(3): 221-7.
[http://dx.doi.org/10.3164/jcbn.14-77] [PMID: 25411530]
[78]
Peltekova VD, Wintle RF, Rubin LA, et al. Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet 2004; 36(5): 471-5.
[http://dx.doi.org/10.1038/ng1339] [PMID: 15107849]
[79]
Bene J, Komlósi K, Magyari L, et al. Plasma carnitine ester profiles in Crohn’s disease patients characterized for SLC22A4 C1672T and SLC22A5 G-207C genotypes. Br J Nutr 2007; 98(2): 345-50.
[http://dx.doi.org/10.1017/S0007114507705020] [PMID: 17391561]
[80]
Talián G, Lakner L, Bene J, et al. Plasma carnitine ester profiles in Crohn’s disease and ulcerative colitis patients with different IGR2230a_1 genotypes. Int J Immunogenet 2009; 36(6): 329-35.
[http://dx.doi.org/10.1111/j.1744-313X.2009.00834.x] [PMID: 19735486]
[81]
Demirkol M, Sewell AC, Böhles H. The variation of carnitine content in human blood cells during disease--a study in bacterial infection and inflammatory bowel disease. Eur J Pediatr 1994; 153(8): 565-8.
[http://dx.doi.org/10.1007/BF02190659] [PMID: 7957402]
[82]
Adlouni HA, Katrib K, Férard G. Changes in carnitine in polymorphonuclear leukocytes, mononuclear cells, and plasma from patients with inflammatory disorders. Clin Chem 1988; 34(1): 40-3.
[PMID: 3338182]
[83]
Schreiber S, Nikolaus S, Hampe J. Activation of nuclear factor kappa B inflammatory bowel disease. Gut 1998; 42(4): 477-84.
[http://dx.doi.org/10.1136/gut.42.4.477] [PMID: 9616307]
[84]
Segain JP, Raingeard de la Blétière D, Bourreille A, et al. Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn’s disease. Gut 2000; 47(3): 397-403.
[http://dx.doi.org/10.1136/gut.47.3.397] [PMID: 10940278]
[85]
Psychogios N, Hau DD, Peng J, et al. The human serum metabolome. PLoS One 2011; 6(2) e16957
[http://dx.doi.org/10.1371/journal.pone.0016957] [PMID: 21359215]
[86]
Demir Djekic R. Mehmed Novo, Michael Henein. Metabolomics in atherosclerosis. IJC Metab Endocr 2015; 8: 26-30.
[http://dx.doi.org/10.1016/j.ijcme.2014.11.004]
[87]
Rhee EP, Yang Q, Yu B, et al. An exome array study of the plasma metabolome. Nat Commun 2016; 7: 12360.
[http://dx.doi.org/10.1038/ncomms12360] [PMID: 27453504]
[88]
Zhong Z, Liu J, Zhang Q, et al. Targeted metabolomic analysis of plasma metabolites in patients with coronary heart disease in southern China. Medicine (Baltimore) 2019; 98(7) e14309
[http://dx.doi.org/10.1097/MD.0000000000014309] [PMID: 30762730]
[89]
Gillies PJ, Bell FP. Arterial and plasma carnitine levels in rabbits: influence of age and dietary cholesterol. Exp Mol Pathol 1976; 25(3): 402-11.
[http://dx.doi.org/10.1016/0014-4800(76)90048-4] [PMID: 1001407]
[90]
Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 2013; 19(5): 576-85.
[http://dx.doi.org/10.1038/nm.3145] [PMID: 23563705]
[91]
Rizza S, Copetti M, Rossi C, et al. Metabolomics signature improves the prediction of cardiovascular events in elderly subjects. Atherosclerosis 2014; 232(2): 260-4.
[http://dx.doi.org/10.1016/j.atherosclerosis.2013.10.029] [PMID: 24468136]
[92]
Shah SH, Bain JR, Muehlbauer MJ, et al. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ Cardiovasc Genet 2010; 3(2): 207-14.
[http://dx.doi.org/10.1161/CIRCGENETICS.109.852814] [PMID: 20173117]
[93]
Shah AA, Craig DM, Sebek JK, et al. Metabolic profiles predict adverse events after coronary artery bypass grafting. J Thorac Cardiovasc Surg 2012; 143(4): 873-8.
[http://dx.doi.org/10.1016/j.jtcvs.2011.09.070] [PMID: 22306227]
[94]
Vorkas PA, Shalhoub J, Isaac G, et al. Metabolic phenotyping of atherosclerotic plaques reveals latent associations between free cholesterol and ceramide metabolism in atherogenesis. J Proteome Res 2015; 14(3): 1389-99.
[http://dx.doi.org/10.1021/pr5009898] [PMID: 25565173]
[95]
Ahmad T, Kelly JP, McGarrah RW, et al. Prognostic implications of long-chain acylcarnitines in heart failure and reversibility with mechanical circulatory support. J Am Coll Cardiol 2016; 67(3): 291-9.
[http://dx.doi.org/10.1016/j.jacc.2015.10.079] [PMID: 26796394]
[96]
Gupte AA, Hamilton DJ, Cordero-Reyes AM, et al. Mechanical unloading promotes myocardial energy recovery in human heart failure. Circ Cardiovasc Genet 2014; 7(3): 266-76.
[http://dx.doi.org/10.1161/CIRCGENETICS.113.000404] [PMID: 24825877]
[97]
Tamamoğullari N, Siliğ Y, Içağasioğlu S, Atalay A. Carnitine deficiency in diabetes mellitus complications. J Diabetes Complications 1999; 13(5-6): 251-3.
[http://dx.doi.org/10.1016/S1056-8727(99)00052-5] [PMID: 10764998]
[98]
Bene J, Hadzsiev K, Melegh B. Role of carnitine and its derivatives in the development and management of type 2 diabetes. Nutr Diabetes 2018; 8(1): 8.
[http://dx.doi.org/10.1038/s41387-018-0017-1] [PMID: 29549241]
[99]
Winter SC, Simon M, Zorn EM, et al. Relative carnitine insufficiency in children with type I diabetes mellitus. Am J Dis Child 1989; 143(11): 1337-9.
[PMID: 2816861]
[100]
Mamoulakis D, Galanakis E, Dionyssopoulou E, Evangeliou A, Sbyrakis S. Carnitine deficiency in children and adolescents with type 1 diabetes. J Diabetes Complications 2004; 18(5): 271-4.
[http://dx.doi.org/10.1016/S1056-8727(03)00091-6] [PMID: 15337500]
[101]
Möder M, Kiessling A, Löster H, Brüggemann L. The pattern of urinary acylcarnitines determined by electrospray mass spectrometry: a new tool in the diagnosis of diabetes mellitus. Anal Bioanal Chem 2003; 375(2): 200-10.
[http://dx.doi.org/10.1007/s00216-002-1654-7] [PMID: 12560963]
[102]
Adams SH, Hoppel CL, Lok KH, et al. Plasma acylcarnitine profiles suggest incomplete long-chain fatty acid beta-oxidation and altered tricarboxylic acid cycle activity in type 2 diabetic African-American women. J Nutr 2009; 139(6): 1073-81.
[http://dx.doi.org/10.3945/jn.108.103754] [PMID: 19369366]
[103]
Mihalik SJ, Goodpaster BH, Kelley DE, et al. Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity. Obesity (Silver Spring) 2010; 18(9): 1695-700.
[http://dx.doi.org/10.1038/oby.2009.510] [PMID: 20111019]
[104]
Newgard CB, An J, Bain JR, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 2009; 9(4): 311-26.
[http://dx.doi.org/10.1016/j.cmet.2009.02.002] [PMID: 19356713]
[105]
Zhang X, Zhang C, Chen L, Han X, Ji L. Human serum acylcarnitine profiles in different glucose tolerance states. Diabetes Res Clin Pract 2014; 104(3): 376-82.
[http://dx.doi.org/10.1016/j.diabres.2014.04.013] [PMID: 24837145]
[106]
Bene J, Márton M, Mohás M, et al. Similarities in serum acylcarnitine patterns in type 1 and type 2 diabetes mellitus and in metabolic syndrome. Ann Nutr Metab 2013; 62(1): 80-5.
[http://dx.doi.org/10.1159/000345759] [PMID: 23296094]
[107]
Sun L, Liang L, Gao X, et al. Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study. Diabetes Care 2016; 39(9): 1563-70.
[http://dx.doi.org/10.2337/dc16-0232] [PMID: 27388475]
[108]
Guasch-Ferré M, Ruiz-Canela M, Li J, et al. Plasma acylcarnitines and risk of type 2 diabetes in a Mediterranean population at high cardiovascular risk. J Clin Endocrinol Metab 2019; 104(5): 1508-19.
[PMID: 30423132]
[109]
Schooneman MG, Vaz FM, Houten SM, Soeters MR. Acylcarnitines: reflecting or inflicting insulin resistance? Diabetes 2013; 62(1): 1-8.
[http://dx.doi.org/10.2337/db12-0466] [PMID: 23258903]
[110]
Bouchouirab FZ, Fortin M, Noll C, Dube J, Carpentier AC. Plasma palmitoyl-carnitine (AC16:0) is a marker of increased postprandial nonesterified incomplete fatty acid oxidation rate in adults with type 2 diabetes. Canadian journal of diabetes 2018; 42(4): 382-8. e1
[111]
Veenstra-Vanderweele J, Christian SL, Cook EH Jr. Autism as a paradigmatic complex genetic disorder. Annu Rev Genomics Hum Genet 2004; 5: 379-405.
[http://dx.doi.org/10.1146/annurev.genom.5.061903.180050] [PMID: 15485354]
[112]
Devlin B, Scherer SW. Genetic architecture in autism spectrum disorder. Curr Opin Genet Dev 2012; 22(3): 229-37.
[http://dx.doi.org/10.1016/j.gde.2012.03.002] [PMID: 22463983]
[113]
Rossignol DA, Frye RE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry 2012; 17(3): 290-314.
[http://dx.doi.org/10.1038/mp.2010.136] [PMID: 21263444]
[114]
Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun 2011; 25(1): 40-5.
[http://dx.doi.org/10.1016/j.bbi.2010.08.003] [PMID: 20705131]
[115]
Filipek PA, Juranek J, Nguyen MT, Cummings C, Gargus JJ. Relative carnitine deficiency in autism. J Autism Dev Disord 2004; 34(6): 615-23.
[http://dx.doi.org/10.1007/s10803-004-5283-1] [PMID: 15679182]
[116]
Cox KB, Hamm DA, Millington DS, et al. Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse. Hum Mol Genet 2001; 10(19): 2069-77.
[http://dx.doi.org/10.1093/hmg/10.19.2069] [PMID: 11590124]
[117]
Clark-Taylor T, Clark-Taylor BE. Is autism a disorder of fatty acid metabolism? Possible dysfunction of mitochondrial beta-oxidation by long chain acyl-CoA dehydrogenase. Med Hypotheses 2004; 62(6): 970-5.
[http://dx.doi.org/10.1016/j.mehy.2004.01.011] [PMID: 15142659]
[118]
Thomas RH, Foley KA, Mepham JR, Tichenoff LJ, Possmayer F, MacFabe DF. Altered brain phospholipid and acylcarnitine profiles in propionic acid infused rodents: further development of a potential model of autism spectrum disorders. J Neurochem 2010; 113(2): 515-29.
[http://dx.doi.org/10.1111/j.1471-4159.2010.06614.x] [PMID: 20405543]
[119]
Fallon J. Could one of the most widely prescribed antibiotics amoxicillin/clavulanate “augmentin” be a risk factor for autism? Med Hypotheses 2005; 64(2): 312-5.
[http://dx.doi.org/10.1016/j.mehy.2004.06.023] [PMID: 15607562]
[120]
Frye RE, Melnyk S, Macfabe DF. Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder. Transl Psychiatry 2013. 3e220
[121]
Lv QQ, You C, Zou XB, Deng HZ. Acyl-carnitine, C5DC, and C26 as potential biomarkers for diagnosis of autism spectrum disorder in children. Psychiatry Res 2018; 267: 277-80.
[http://dx.doi.org/10.1016/j.psychres.2018.06.027] [PMID: 29945069]
[122]
Bartel LL, Hussey JL, Shrago E. Perturbation of serum carnitine levels in human adults by chronic renal disease and dialysis therapy. Am J Clin Nutr 1981; 34(7): 1314-20.
[http://dx.doi.org/10.1093/ajcn/34.7.1314] [PMID: 7258121]
[123]
Rodriguez-Segade S. Alonso dlP, Paz JM, Novoa D, Arcocha V, Romero R, et al. Carnitine deficiency in haemodialysed patients. Clinica chimica acta; international journal of clinical chemistry 1986; 159(3): 249-56.
[124]
Golper TA, Wolfson M, Ahmad S, et al. Multicenter trial of L-carnitine in maintenance hemodialysis patients. I. Carnitine concentrations and lipid effects. Kidney Int 1990; 38(5): 904-11.
[http://dx.doi.org/10.1038/ki.1990.289] [PMID: 2266674]
[125]
Brass EP, Adler S, Sietsema KE, Hiatt WR, Orlando AM, Amato A. CHIEF Investigators. Intravenous L-carnitine increases plasma carnitine, reduces fatigue, and may preserve exercise capacity in hemodialysis patients. Am J Kidney Dis 2001; 37(5): 1018-28.
[http://dx.doi.org/10.1016/S0272-6386(05)80019-8] [PMID: 11325685]
[126]
Debska-Slizień , Kawecka A, Wojnarowski K, et al. Correlation between plasma carnitine, muscle carnitine and glycogen levels in maintenance hemodialysis patients. Int J Artif Organs 2000; 23(2): 90-6.
[http://dx.doi.org/10.1177/039139880002300205] [PMID: 10741803]
[127]
Steiber AL, Weatherspoon LJ, Spry L, Davis AT. Serum carnitine concentrations correlated to clinical outcome parameters in chronic hemodialysis patients. Clin Nutr 2004; 23(1): 27-34.
[http://dx.doi.org/10.1016/S0261-5614(03)00085-2] [PMID: 14757390]
[128]
Kamei Y, Kamei D, Tsuchiya K, Mineshima M, Nitta K. Association between 4-year all-cause mortality and carnitine profile in maintenance hemodialysis patients. PLoS One 2018; 13(8) e0201591
[http://dx.doi.org/10.1371/journal.pone.0201591] [PMID: 30133480]
[129]
Evans A. Dialysis-related carnitine disorder and levocarnitine pharmacology. Am J Kidney Dis 2003; 41(4)(Suppl. 4): S13-26.
[http://dx.doi.org/10.1016/S0272-6386(03)00113-6] [PMID: 12751050]
[130]
Reuter SE, Evans AM, Faull RJ, Chace DH, Fornasini G. Impact of haemodialysis on individual endogenous plasma acylcarnitine concentrations in end-stage renal disease. Ann Clin Biochem 2005; 42(Pt 5): 387-93.
[http://dx.doi.org/10.1258/0004563054889954] [PMID: 16168195]
[131]
Csiky B, Bene J, Wittmann I, Sulyok E, Melegh B. Effect of hemodialysis session on the dynamics of carnitine ester profile changes in L:-carnitine pretreated end-stage renal disease patients. Int Urol Nephrol 2013; 45: 847-55.
[PMID: 22684763]
[132]
Ahmad S. L-carnitine in dialysis patients. Semin Dial 2001; 14(3): 209-17.
[http://dx.doi.org/10.1046/j.1525-139X.2001.00055.x] [PMID: 11422928]
[133]
Zhang YM, Zhuo L, Hu J, et al. Clinical significance of different carnitine levels for improving the prognosis of patients undergoing hemodialysis. Ren Fail 2016; 38(10): 1654-8.
[http://dx.doi.org/10.1080/0886022X.2016.1229967] [PMID: 27758157]
[134]
Kaneko M, Fukasawa H, Ishibuchi K, Niwa H, Yasuda H, Furuya R. L-carnitine Improved the Cardiac Function via the Effect on Myocardial Fatty Acid Metabolism in a Hemodialysis Patient. Intern Med 2018; 57(24): 3593-6.
[http://dx.doi.org/10.2169/internalmedicine.1055-18] [PMID: 30146554]
[135]
Maruyama T, Maruyama N, Higuchi T, et al. Efficacy of L-carnitine supplementation for improving lean body mass and physical function in patients on hemodialysis: a randomized controlled trial. Eur J Clin Nutr 2019; 73(2): 293-301.
[http://dx.doi.org/10.1038/s41430-018-0348-y] [PMID: 30353121]
[136]
Bene J, Csiky B, Komlosi K, Sulyok E, Melegh B. Dynamic adaptive changes of the serum carnitine esters during and after L-carnitine supplementation in patients with maintenance haemodialysis. Scand J Clin Lab Invest 2011; 71(4): 280-6.
[http://dx.doi.org/10.3109/00365513.2011.560674] [PMID: 21366497]
[137]
Bene J, Csiky B, Wittmann I, Sulyok E, Melegh B. Dramatic decrease of carnitine esters after interruption of exogenous carnitine supply in hemodialysis patients. Ren Fail 2012; 34(5): 555-8.
[http://dx.doi.org/10.3109/0886022X.2012.664509] [PMID: 22417076]
[138]
Suzuki A, Sakai Y, Hashimoto K, Osawa H, Tsuruoka S. Kinetics of carnitine concentration after switching from oral administration to intravenous injection in hemodialysis patients. Ren Fail 2018; 40(1): 196-200.
[http://dx.doi.org/10.1080/0886022X.2018.1455587] [PMID: 29616582]
[139]
Van Blerkom J, Davis PW, Lee J. ATP content of human oocytes and developmental potential and outcome after in-vitro fertilization and embryo transfer. Hum Reprod 1995; 10(2): 415-24.
[http://dx.doi.org/10.1093/oxfordjournals.humrep.a135954] [PMID: 7769073]
[140]
Nagano M, Katagiri S, Takahashi Y. ATP content and maturational/developmental ability of bovine oocytes with various cytoplasmic morphologies. Zygote 2006; 14(4): 299-304.
[http://dx.doi.org/10.1017/S0967199406003807] [PMID: 17266788]
[141]
McKeegan PJ, Sturmey RG. The role of fatty acids in oocyte and early embryo development. Reprod Fertil Dev 2011; 24(1): 59-67.
[http://dx.doi.org/10.1071/RD11907] [PMID: 22394718]
[142]
Van Hoeck V, Sturmey RG, Bermejo-Alvarez P, et al. Elevated non-esterified fatty acid concentrations during bovine oocyte maturation compromise early embryo physiology. PLoS One 2011; 6(8) e23183
[http://dx.doi.org/10.1371/journal.pone.0023183] [PMID: 21858021]
[143]
Moawad AR, Tan SL, Xu B, Chen HY, Taketo T. L-carnitine supplementation during vitrification of mouse oocytes at the germinal vesicle stage improves preimplantation development following maturation and fertilization in vitro. Biol Reprod 2013; 88(4): 104.
[http://dx.doi.org/10.1095/biolreprod.112.107433] [PMID: 23446455]
[144]
Kitano Y, Hashimoto S, Matsumoto H, et al. Oral administration of l-carnitine improves the clinical outcome of fertility in patients with IVF treatment. Gynecological endocrinology: The official journal of the International Society of Gynecological Endocrinology 2018; 34(8): 684-8.
[http://dx.doi.org/10.1080/09513590.2018.1431769]
[145]
Baka S, Malamitsi-Puchner A. Novel follicular fluid factors influencing oocyte developmental potential in IVF: a review. Reprod Biomed Online 2006; 12(4): 500-6.
[http://dx.doi.org/10.1016/S1472-6483(10)62005-6] [PMID: 16740225]
[146]
Várnagy A, Bene J, Sulyok E, Kovács GL, Bódis J, Melegh B. Acylcarnitine esters profiling of serum and follicular fluid in patients undergoing in vitro fertilization. Reprod Biol Endocrinol 2013; 11: 67.
[http://dx.doi.org/10.1186/1477-7827-11-67] [PMID: 23866102]
[147]
Montjean D, Entezami F, Lichtblau I, Belloc S, Gurgan T, Menezo Y. Carnitine content in the follicular fluid and expression of the enzymes involved in beta oxidation in oocytes and cumulus cells. J Assist Reprod Genet 2012; 29(11): 1221-5.
[http://dx.doi.org/10.1007/s10815-012-9855-2] [PMID: 23054356]
[148]
Dunning KR, Robker RL. Promoting lipid utilization with l-carnitine to improve oocyte quality. Anim Reprod Sci 2012; 134(1-2): 69-75.
[http://dx.doi.org/10.1016/j.anireprosci.2012.08.013] [PMID: 22917873]
[149]
Gervais A, Battista MC, Carranza-Mamane B, Lavoie HB, Baillargeon JP. Follicular fluid concentrations of lipids and their metabolites are associated with intraovarian gonadotropin-stimulated androgen production in women undergoing in vitro fertilization. J Clin Endocrinol Metab 2015; 100(5): 1845-54.
[http://dx.doi.org/10.1210/jc.2014-3649] [PMID: 25695883]
[150]
Beydoun A, Sackellares JC, Shu V. Safety and efficacy of divalproex sodium monotherapy in partial epilepsy: a double-blind, concentration-response design clinical trial. Neurology 1997; 48(1): 182-8.
[http://dx.doi.org/10.1212/WNL.48.1.182] [PMID: 9008516]
[151]
Marson AG, Al-Kharusi AM, Alwaidh M, et al. SANAD Study group. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet 2007; 369(9566): 1016-26.
[http://dx.doi.org/10.1016/S0140-6736(07)60461-9] [PMID: 17382828]
[152]
Bond DJ, Lam RW, Yatham LN. Divalproex sodium versus placebo in the treatment of acute bipolar depression: a systematic review and meta-analysis. J Affect Disord 2010; 124(3): 228-34.
[http://dx.doi.org/10.1016/j.jad.2009.11.008] [PMID: 20044142]
[153]
D'Amico D. Pharmacological prophylaxis of chronic migraine: a review of double-blind placebo-controlled trials. Neurological sciences: official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2010; S23-8.
[http://dx.doi.org/10.1007/s10072-010-0268-7]
[154]
Melegh B, Pap M, Morava E, Molnar D, Dani M, Kurucz J. Carnitine-dependent changes of metabolic fuel consumption during long-term treatment with valproic acid. J Pediatr 1994; 125(2): 317-21.
[http://dx.doi.org/10.1016/S0022-3476(94)70218-7] [PMID: 8040784]
[155]
Okumura A, Kurahashi H, Iwayama H, Numoto S. Serum carnitine levels of children with epilepsy: Related factors including valproate. Brain Dev 2019; 41(6): 516-21.
[http://dx.doi.org/10.1016/j.braindev.2019.02.010] [PMID: 30827788]
[156]
Werner T, Treiss I, Kohlmueller D, et al. Effects of valproate on acylcarnitines in children with epilepsy using ESI-MS/MS. Epilepsia 2007; 48(1): 72-6.
[http://dx.doi.org/10.1111/j.1528-1167.2006.00833.x] [PMID: 17241210]
[157]
Silva MF, Selhorst J, Overmars H, et al. Characterization of plasma acylcarnitines in patients under valproate monotherapy using ESI-MS/MS. Clin Biochem 2001; 34(8): 635-8.
[http://dx.doi.org/10.1016/S0009-9120(01)00272-7] [PMID: 11849623]
[158]
Kossak BD, Schmidt-Sommerfeld E, Schoeller DA, Rinaldo P, Penn D, Tonsgard JH. Impaired fatty acid oxidation in children on valproic acid and the effect of L-carnitine. Neurology 1993; 43(11): 2362-8.
[http://dx.doi.org/10.1212/WNL.43.11.2362] [PMID: 8232957]
[159]
Hirose S, Mitsudome A, Yasumoto S, Ogawa A, Muta Y, Tomoda Y. Valproate therapy does not deplete carnitine levels in otherwise healthy children. Pediatrics 1998; 101(5) E9
[http://dx.doi.org/10.1542/peds.101.5.e9] [PMID: 9565442]
[160]
Nakajima Y, Ito T, Maeda Y, et al. Evaluation of valproate effects on acylcarnitine in epileptic children by LC-MS/MS. Brain Dev 2011; 33(10): 816-23.
[http://dx.doi.org/10.1016/j.braindev.2010.12.003] [PMID: 21196091]
[161]
Morand R, Todesco L, Donzelli M, Fischer-Barnicol D, Mullen PJ, Krähenbühl S. Effect of short- and long-term treatment with valproate on carnitine homeostasis in humans. Ther Drug Monit 2012; 34(4): 406-14.
[http://dx.doi.org/10.1097/FTD.0b013e3182608e2f] [PMID: 22743351]
[162]
Kulhas Celik I, Tasdemir HA, Ince H, Celik H, Sungur M. Evaluation ofserum free carnitine/acylcarnitine levels and left ventricular systolic functions in children with idiopathic epilepsy receiving valproic acid. Clin Neurol Neurosurg 2018; 170: 106-12.
[http://dx.doi.org/10.1016/j.clineuro.2018.05.005] [PMID: 29772401]
[163]
Nakajima Y, Ito T, Maeda Y, et al. Detection of pivaloylcarnitine in pediatric patients with hypocarnitinemia after long-term administration of pivalate-containing antibiotics. Tohoku J Exp Med 2010; 221(4): 309-13.
[http://dx.doi.org/10.1620/tjem.221.309] [PMID: 20651467]
[164]
Brass EP, Mayer MD, Mulford DJ, Stickler TK, Hoppel CL. Impact on carnitine homeostasis of short-term treatment with the pivalate prodrug cefditoren pivoxil. Clin Pharmacol Ther 2003; 73(4): 338-47.
[http://dx.doi.org/10.1016/S0009-9236(02)17636-3] [PMID: 12709724]


open access plus

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 5
Year: 2020
Published on: 28 April, 2020
Page: [336 - 354]
Pages: 19
DOI: 10.2174/1566524019666191113120828

Article Metrics

PDF: 36
HTML: 5
EPUB: 1
PRC: 1