The role of acetyl-L-carnitine (LAC) in the treatment of mental disorders

Authors

DOI:

https://doi.org/10.2478/cpp-2019-0017

Keywords:

cetyl-L-carnitine, depression, mental disorders

Abstract

Introduction: Currently, there are no fully reliable biomarkers to identify individuals suffering from depression, and conventional antidepressant treatment has its limitations. The potential influence of acetyl-L-carnitine (LAC) on the treatment  of mental disorders, including depressive disorders, was noted already in the 1980s.

Goal and method: The literature on the role of LAC in the treatment of mental disorders, in particular depressive disorders, was reviewed using the Google Scholar and Pub Med databases. Two lines of research were considered:
1. the role of LAC in the therapy of various mental disorders and
2. the role of LAC in the treatment of depression and dysthymia.

Conclusions: Because LAC is safe to use and has a very good tolerance profile, authors have explored its role in the treatment of many neurological and psychiatric diseases. There are studies showing that LAC supplementation has a positive effect on ADHD treatment outcomes in boys diagnosed with fragile X syndrome and plays a role in the treatment of dementia. Research has also been conducted on the impact of LAC on the treatment of depressive and dysthymic disorders. Positive outcomes of such therapy have been reported. An important correlation has been observed between LAC concentrations and the severity and onset of depressive symptoms. For instance, reduced levels of LAC have been found in people with treatment-refractory depression. It has also been proposed that LAC could decrease vulnerability to depression.

References

1. Kessler RC, Bromet EJ. The epidemiology of depression across cultures. Annu Rev Public Health. 2013;34:119-38

2. Friedrich MJ. Depression Is the Leading Cause of Disability Around the World. JAMA. 2017 Apr 18;317(15):1517

3. Rush AJ, Warden D, Wisniewski SR, Fava M, Trivedi MH, Gaynes BN, Nierenberg AA. STAR*D: revising conventional wisdom. CNS Drugs. 2009 Aug;23(8):627-47

4. Tempesta E, Casella L, Pirrongelli C, Janiri L, Calvani M, AnconaL. L-acetylcarnitine in depressed elderly subjects. A cross-over study vs placebo. Drugs Exp Clin Res. 1987;13(7):417-23.

5. Farrell S, Vogel J, Bieber LL. Entry of acetyl-L-carnitine into biosynthetic pathways. Biochim Biophys Acta. 1986 Mar 21;876(1):175-7.

6. Brunner S, Kramar K, Denhardt DT, Hofbauer R. Cloning and characterization of murine carnitine acetyltransferase: evidence for a requirement during cell cycle progression.Biochem J. 1997 Mar 1;322 (Pt 2):403-10.

7. Wu D, Govindasamy L, Lian W, Gu Y, Kukar T, Agbandje-McKenna M, McKenna R. Structure of human carnitine acetyltransferase. Molecular basis for fatty acyl transfer. J Biol Chem. 2003 Apr 11;278(15):13159-65. Epub 2003 Jan 31.

8. Santina Chiechio, Pier Luigi Canonico, and Mariagrazia Grilli. l-Acetylcarnitine: A Mechanistically Distinctive and Potentially Rapid-Acting Antidepressant Drug. Int J Mol Sci. 2018 Jan; 19(1): 11

9. Bruna Cuccurazzu, Valeria Bortolotto, Maria Maddalena Valente, Federica Ubezio, Aleardo Koverech, Pier Luigi Canonico, and Mariagrazia Grilli. Upregulation of mGlu2 Receptors via NF-κB p65 Acetylation Is Involved in the Proneurogenic and Antidepressant Effects of Acetyl-l-Carnitine. Neuropsychopharmacology. 2013 Oct; 38(11): 2220-2230

10. Ferrari F, Gorini A, Villa RF. Functional proteomics of synaptic plasma membrane ATP-ases of rat hippocampus: effect of l-acetylcarnitine and relationships with Dementia and Depression pathophysiology. Eur J Pharmacol. 2015 Jun 5;756:67-74

11. Rueda JR, Guillén V, Ballesteros J, Tejada MI, Solà I.10. L-acetylcarnitine for treating fragile X syndrome. Cochrane Database Syst Rev. 2015 May 19;(5):CD010012

12. Torrioli MG, Vernacotola S, Peruzzi L, Tabolacci E, Mila M, Militerni R, Musumeci S, Ramos FJ, Frontera M, Sorge G, Marzullo E, Romeo G, Vallee L, Veneselli E, Cocchi E, Garbarino E, Moscato U, Chiurazzi P, D'Iddio S, Calvani M, Neri G. A doubleblind, parallel, multicenter comparison of L-acetylcarnitine with placebo on the attention deficit hyperactivity disorder in fragile X syndrome boys. Am J Med Genet A. 2008 Apr 1;146A(7):803-12

13. Salvioli G, Neri M. L-acetylcarnitine treatment of mental decline in the elderly. Drugs Exp Clin Res. 1994;20(4):169-76

14. Bersani G, Meco G, Denaro A, Liberati D, Colletti C, Nicolai R, Bersani FS, Koverech A. L-Acetylcarnitine in dysthymic disorder in elderly patients: a double-blind, multicenter, controlled randomized study vs. fluoxetine. Eur Neuropsychopharmacol. 2013 Oct;23(10):1219-25

15. Bella R, Biondi R, Raffaele R, Pennisi G. Effect of acetyl-Lcarnitine on geriatric patients suffering from dysthymic disorders. Int J Clin Pharmacol Res. 1990;10(6):355-60

16. Bigford GE, Del Rossi G. Supplemental substances derived from foods as adjunctive therapeutic agents for treatment of neurodegenerative diseases and disorders. Adv Nutr. 2014 Jul 14;5(4):394-403

17. Bruno A, Pandolfo G, Crucitti M, Lorusso S, Zoccali RA, Muscatello MR. Acetyl-L-Carnitine Augmentation of Clozapine in Partial-Responder Schizophrenia: A 12-Week, Open-Label Uncontrolled Preliminary Study. Clin Neuropharmacol. 2016 Nov/Dec;39(6):277-280

18. Nemeroff CB. Paradise Lost: The Neurobiological and Clinical Consequences of Child Abuse and Neglect. Neuron. 2016 Mar 2;89(5):892-909

19. Nasca C, Bigio B, Lee FS, Young SP, Kautz MM, Albright A, Beasley J, Millington DS, Mathé AA, Kocsis JH, Murrough JW, McEwen BS, Rasgon. Acetyl-l-carnitine deficiency in patients with major depressive disorder. Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):8627-8632

20. Veronese N, Stubbs B, Solmi M, Ajnakina O, Carvalho AF, Maggi S. Acetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis. Psychosom Med. 2018 Feb/Mar;80(2):154-159

21. Nasca C, Xenos D, Barone Y, Caruso A, Scaccianoce S, Matrisciano F, Battaglia G, Mathé AA, Pittaluga A, Lionetto L, Simmaco M, Nicoletti F. L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4804-9

22. Fell MJ, et al. N-(4-((2-(trifluoromethyl)-3-hydroxy-4-(isobutyryl) phenoxy)methyl)benzyl)-1-methyl-1H-imidazole-4-carboxamide (THIIC), a novel metabotropic glutamate 2 potentiator with potential anxiolytic/antidepressant properties: In vivo profiling suggests a link between behavioral and central nervous system neurochemical changes. J Pharmacol Exp Ther. 2011;336:165–177

23. Robert M. Post. Myriad of implications of acetyl-l-carnitine deficits in depression. PNAS August 21, 2018 115 (34) 8475-8477

24. Wang SM, Han C, Lee SJ, Patkar AA, Masand PS, Pae CU. A review of current evidence for acetyl-l-carnitine in the treatment of depression. J Psychiatr Res. 2014 Jun;53:30-7

25. Martinotti G, Andreoli S, Reina D, Di Nicola M, Ortolani I, Tedeschi D, Fanella F, Pozzi G, Iannoni E, D'Iddio S, Prof LJ. Acetyl-l-Carnitine in the treatment of anhedonia, melancholic and negative symptoms in alcohol dependent subjects. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jun 1;35(4):953-8

26. Bigio B, Mathé AA, Sousa VC, Zelli D, Svenningsson P, McEwen BS, Nasca C. Epigenetics and energetics in ventral hippocampus mediate rapid antidepressant action: Implications for treatment resistance. Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7906-1

Downloads

Published

2020-01-15