l-Carnitine is a naturally occurring substance required in mammalian energy metabolism that functions by facilitating long-chain fatty acid entry into cellular mitochondria, thereby delivering substrate for oxidation and subsequent energy production. It has been purposed that l-carnitine may improve and preserve cognitive performance, and may lead to better cognitive aging through the life span, and several controlled human clinical trials with l-carnitine support the hypothesis that this substance has the ability to improve cognitive function. We further hypothesized that, since l-carnitine is an important co-factor of mammalian mitochondrial energy metabolism, acute administration of l-carnitine to human tissue culture cells should result in detectable increases in mitochondrial function. Cultures of SH-SY-5Y human neuroblastoma and 1321N1 human astrocytoma cells grown in 96-well cell culture plates were acutely administered l-carnitine hydrochloride, and then, mitochondrial function was assayed using the colorimetric 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt cell assay kit in a VERSAmax tunable microplate reader. Significant increases in mitochondrial function were observed when human neuroblastoma or human astrocytoma cells were exposed to 100 nM (20 μg l-carnitine hydrochloride/L) to 100 μM (20 mg l-carnitine hydrochloride/L) concentrations of l-carnitine hydrochloride in comparison to unexposed cells, whereas no significant positive effects were observed at lower or higher concentrations of l-carnitine hydrochloride. The results of the present study provide insights for how l-carnitine therapy may significantly improve human neuronal function, but we recommend that future studies further explore different derivatives of l-carnitine compounds in different in vitro cell-based systems using different markers of mitochondrial function.
Carnitine Cell vitality Mitochondria Neuron
This is a preview of subscription content, log in to check access.
This study was funded by the non-profit CoMeD, Inc., and by the non-profit Institute of Chronic Illnesses, Inc.
Conflict of interest
Geier DA, Kern JK, Davis G et al (2011) A prospective double-blind, randomized clinical trial of levocarntine to treat autism spectrum disorders. Med Sci Monit 17(6):PI15–PI23PubMedCrossRefGoogle Scholar
Owen L, Sunram-Lea SI (2011) Metabolic agents that enhance ATP can improve cognitive functioning: a review of the evidence for glucose, oxygen, pyruvate, creatine, and l-carnitine. Nutrients 3(8):735–755PubMedCrossRefGoogle Scholar
Malaguarnera M, Cammalleri L, Gargante MP et al (2007) l-carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. Am J Clin Nutr 86(6):1738–1744PubMedGoogle Scholar
Battistin L, Pizzolato G, Dam M et al (1989) Single-photon emission computed tomography studies with 99 m Tc-hexamethylpropyleneamine oxime in dementia: effects of acute administration of l-acetylcarnitine. Eur Neurol 29(5):261–265PubMedCrossRefGoogle Scholar
Geier DA, King PG, Geier MR (2009) Mitochondrial dysfunction, impaired oxidative-reduction activity, degeneration, and death in human neuronal and fetal cells induced by low-level exposure to Thimerosal and other metal compounds. Toxicol Environ Chem 91(4):735–749CrossRefGoogle Scholar
Nalecz KA, Nalecz MJ (1996) Carnitine-a known compound, a novel function in neural cells. Acta Neurobiol Exp 56(2):597–609Google Scholar
Nalecz KA, Miecz D, Berezowski V et al (2004) Carnitine: transport and physiological functions in the brain. Mol Aspects Med 25(5–6):551–567PubMedGoogle Scholar
Tulodziecka K, Czeredys M, Nalecz KA (2013) Palmitoylcarnitine affects localization of rowth associated proterin GAP-43 in plasma membrane subdomains and its interaction with Gα(0) in neuroblastoma NB-2a cells. Neurochem Res 38(3):519–529PubMedCrossRefGoogle Scholar
Yu J, Ye J, Han Y et al (2011) Protective effect of l-carnitine against H(2)O(2)-induced neurotoxicity in neuroblastoma (SH-SY5Y) cells. Neurol Res 33(7):708–716PubMedCrossRefGoogle Scholar
Adams JB, Audhya T, McDonough-Means S (2011) Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity. Nutr Metab 8(1):34CrossRefGoogle Scholar
Evangeliou A, Vlassopoulos D (2003) Carnitine metabolism and deficit-when supplementation is necessary? Curr Pharm Biotechnol 4(3):211–219PubMedCrossRefGoogle Scholar
Roehm NW, Rodgers GH, Hatfield SM et al (1991) An improved colorimetric assay for cell proliferation and viability utilizing the tetrazolium salt XTT. J Immunol Methods 142(2):257–265PubMedCrossRefGoogle Scholar
Berridge MV, Herst PM, Tan AS (2005) Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev 11:127–152PubMedCrossRefGoogle Scholar
Marshall NJ, Goodwin CJ, Holt SJ (1995) A critical assessment of the use of microculture tetrazolium assays to measure cell growth and function. Growth Regul 5(2):69–84PubMedGoogle Scholar