В обзоре представлены результаты целого ряда экспериментальных и клинических исследований, доказывающих перспективность применения L-карнитина в клинике внутренних болезней. Дополнительный прием L-карнитина за счет антиоксидантных и антигипоксантных свойств в дополнение к основной этиопатогенетической терапии назначается кардиологами, нефрологами, неврологами, геронтологами. Ранее проведенные нами экспериментальные исследования показали отсутствие влияния L-карнитина на активность системы Р450 CYP 3А4, что снижает вероятность возникновения межлекарственного взаимодействия на уровне метаболизма лекарственных препаратов, метаболизирующихся Р450 3А4. При использовании L-карнитина в составе комплексной фармакотерапии, препарат обладает повышенным профилем безопасности у коморбидных пациентов, принимающих L-карнитин.
The review presents the results of a number of experimental and clinical studies proving the prospects of using L-carnitine in the clinic of internal diseases. Due to the antioxidant and antihypoxant properties, the additional use of L-carnitine in addition to the main etiopathogenetic therapy is prescribed by cardiologists, nephrologists, neurologists, gerontologists. Experimental studies we conducted earlier showed no effect of L-carnitine on the activity of the P450 CYP 3A4 system, which reduces the likelihood of drug-drug interaction at the level of metabolism of drugs metabolized by P450 3A4. When using L-carnitine as part of complex pharmacotherapy, the drug has an increased safety profile in comorbid patients taking L-carnitine.
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16. Costell M, O'Connor JE, Grisolia S. Age-dependent decrease of carnitine content in muscle of mice and humans. Biochem Biophys Res Commun. 1989;161(3):1135-43.
17. Hagen TM, Ingersoll RT, Wehr CM, et al. Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proc Natl Acad Sci USA. 1998;95(16):9562-6.
18. Pesce V, Fracasso F, Cassano P, Lezza AM, Cantatore P, Gadaleta MN. Acetyl-L-carnitine supplementation to old rats partially reverts the age-related mitochondrial decay of soleus muscle by activating peroxisome proliferator-activated receptor gamma coactivator-1alpha-dependent mitochondrial biogenesis. Rejuvenation Res. 2010;13(2-3):148-51.
19. Gomez LA, Heath SH, Hagen TM. Acetyl-l-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the l-carnitine content in the rat heart. Mech Ageing Dev. 2012;133(2-3):99-106.
20. Hagen TM, Liu J, Lykkesfeldt J, et al. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci USA. 2002;99(4):1870-5.
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1. Kukes VG, Sychev DA. Personalized medicine: new possibilities to improve the safety of pharmacotherapy. Chem. 2010;(10):38-40 (In Russ.)
2. Makhova AA. Influence of therapeutic doses of vitamins B on the pharmacokinetics and pharmacodynamics of the NSAIDs: diss. ... Phd. M., 2010; 107 p. (In Russ.)
3. Rebouche CJ. Carnitine. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern Nutrition in Health and Disease. 10th ed. Philadelphia: Lippincott, Williams & Wilkins; 2006:537-544.
4. Rebouche CJ. Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann NY Acad Sci. 2004;1033:30-41.
5. De Grandis D, Minardi C. Acetyl-L-carnitine (levacecarnine) in the treatment of diabeic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. Drugs RD. 2002;3(4):223-31.
6. Gross CJ, Henderson LM, Savaiano DA. Uptake of L-carnitine, D-carnitine and acetyl-L-carnitine by isolated guinea-pig enterocytes. Biochim Biophys Acta. 1986;886(3):425-33.
7. Foster DW. The role of the carnitine system in human metabolism. Ann NY Acad Sci. 2004;1033:1-16.
8. Astashkin EI, Glezer MG. Effect of L-carnitine on oxydative stress at cardiovascular diseases. Cardiology and Cardiovascular Surgery. 2012;6(2):58-65 (In Russ.)
9. Lombard KA, Olson AL, Nelson SE, Rebouche CJ. Carnitine status of lactoovovegetarians and strict vegetarian adults and children. Am J Clin Nutr. 1989;50(2):301-6.
10. 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.
11. Stanley CA. Carnitine deficiency disorders in children. Ann NY Acad Sci. 2004;1033:42-51.
12. Seim H, Eichler K, Kleber H. L(-)-Carnitine and its precursor, gamma-butyrobetaine. In: Kramer K, Hoppe P, Packer L, eds. Nutraceuticals in Health and Disease Prevention. New York: Marcel Dekker, Inc; 2001:217-256.
13. Pons R, De Vivo DC. Primary and secondary carnitine deficiency syndromes. J Child Neurol. 1995;10(Suppl 2):8-24.
14. Calvani M, Benatti P, Mancinelli A, et al. Carnitine replacement in end-stage renal disease and hemodialysis. Ann NY Acad Sci. 2004;1033:52-66.
15. Food and Nutrition Board, Institute of Medicine. Vitamin C. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington D.C.: National Academy Press; 2000:95-185.
16. Costell M, O'Connor JE, Grisolia S. Age-dependent decrease of carnitine content in muscle of mice and humans. Biochem Biophys Res Commun. 1989;161(3):1135-43.
17. Hagen TM, Ingersoll RT, Wehr CM, et al. Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proc Natl Acad Sci USA. 1998;95(16):9562-6.
18. Pesce V, Fracasso F, Cassano P, Lezza AM, Cantatore P, Gadaleta MN. Acetyl-L-carnitine supplementation to old rats partially reverts the age-related mitochondrial decay of soleus muscle by activating peroxisome proliferator-activated receptor gamma coactivator-1alpha-dependent mitochondrial biogenesis. Rejuvenation Res. 2010;13(2-3):148-51.
19. Gomez LA, Heath SH, Hagen TM. Acetyl-l-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the l-carnitine content in the rat heart. Mech Ageing Dev. 2012;133(2-3):99-106.
20. Hagen TM, Liu J, Lykkesfeldt J, et al. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci USA. 2002;99(4):1870-5.
21. Liu J, Head E, Gharib AM, et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci USA. 2002;99(4):2356-61.
22. Davini P, Bigalli A, Lamanna F, Boem A. Controlled study on L-carnitine therapeutic efficacy in post-infarction. Drugs Exp Clin Res. 1992;18(8):355-65.
23. Xue YZ, Wang LX, Liu HZ, Qi XW, Wang XH, Ren HZ. L-carnitine as an adjunct therapy to percutaneous coronary intervention for non-ST elevation myocardial infarction. Cardiovasc Drugs Ther. 2007;21(6):445-8.
24. Iyer R, Gupta A, Khan A, Hiremath S, Lokhandwala Y. Does left ventricular function improve with L-carnitine after acute myocardial infarction? J Postgrad Med. 1999;45(2): 38-41.
25. Colonna P, Iliceto S. Myocardial infarction and left ventricular remodeling: results of the CEDIM trial. Carnitine Ecocardiografia Digitalizzata Infarto Miocardico. Am Heart J. 2000;139(2 Pt 3):124-30.
26. Iliceto S, Scrutinio D, Bruzzi P, et al. Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: the L-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) Trial. J Am Coll Cardiol. 1995;26(2):380-7.
27. Tarantini G, Scrutinio D, Bruzzi P, Boni L, Rizzon P, Iliceto S. Metabolic treatment with L-Carnitine in acute anterior ST segment elevation myocardial infarction. A randomized controlled trial. Cardiology. 2006;106(4):215-23.
28. Semigolovskiy NYu, Vertinskiy EK, Azanov BA, Ivanova EV. Positive inotropic properties of levocarnitine in low ejection syndrome among patients wiht acute myocardial infarction. Cardiology and Cardiovascular Surgery. 2013;(3):43-6 (In Russ.)
29. Gleser MG, Kiseleva AE, Astashkin EI. The effect of L-carnitine on the dispersion of the QT interval in patients with acute coronary syndrome. Cardiology. 2015;55(3):4-9 (In Russ.)
30. Glezer MG, Kiseleva AE, Astashkin EI. Effect of L-carnitine on CV and QTc in patients with acute coronary syndrome. The heart. 2015;14(2/82):78-84 (In Russ.)
31. Glezer MG, Kiseleva AE, Prokofieva EB, Astashkin EI. Effect of L-carnitine on echocardiographic parameters in patients with acute coronary syndrome. Heart Failure J. 2015;16(4):234-40 (In Russ.)
32. Асташкин Е.И., Глезер М.Г. Влияние L-карнитина на оксидативный стресс при сердечно-сосудистых заболеваниях. Медицинский Совет. 2016;10:94-100 [Astashkin EI, Glezer MG. The effect of L-carnitine on oxidative stress in cardiovascular diseases. Medical advice. 2016;10:94-100 (In Russ.)].
33. Astashkin EI, Glezer MG, Orekhova NS, Grachev SV, Kiseleva AE. Influence of L-carnitine on reactive oxygen species production by blood phagocytes in postinfarction cardiosclerosis patients. Cardiovascular therapy and prevention. 2016;15(5):28-32 (In Russ.)
34. Rizos I. Threeyear survival of patients with heart failure caused by dilated cardiomyopathy and L-carnitine administration. Am Heart J. 2000;139(2 Pt 3):120-3.
35. Xiaolong Song, Huiyan Qu, Zongguo Yang, Jingfeng Rong, Wan Cai and Hua Zhou. Efficacy and Safety of L-Carnitine Treatment for Chronic Heart Failure: A Meta-Analysis of Randomized Controlled Trials. BioMed Research International. 2017;(2017). Article ID 6274854, 11 p. doi:10.1155/2017/6274854
36. Cacciatore L, Cerio R, Ciarimboli M, et al. The therapeutic effect of L-carnitine in patients with exercise-induced stable angina: a controlled study. Drugs Exp Clin Res. 1991;17(4):225-35.
37. Cherchi A, Lai C, Angelino F, et al. Effects of L-carnitine on exercise tolerance in chronic stable angina: a multicenter, double-blind, randomized, placebo controlled crossover study. Int J Clin Pharmacol Ther Toxicol. 1985;23(10):569-72.
38. Iyer RN, Khan AA, Gupta A, Vajifdar BU, Lokhandwala YY. L-carnitine moderately improves the exercise tolerance in chronic stable angina. J Assoc Physicians India. 2000;48(11):1050-2.
39. DiNicolantonio JJ, Lavie CJ, Fares H, et al. L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis. Mayo Clin Proc. 2013;88(6):544-51.
40. Guarnieri G, Situlin R, Biolo G. Carnitine metabolism in uremia. Am J Kidney Dis. 2001;38(4 Suppl 1):63-7.
41. Hurot JM, Cucherat M, Haugh M, Fouque D. Effects of L-carnitine supplementation in maintenance hemodialysis patients: a systematic review. J Am Soc Nephrol. 2002;13(3):708-14.
42. Kazmi WH, Obrador GT, Sternberg M, et al. Carnitine therapy is associated with decreased hospital utilization among hemodialysis patients. Am J Nephrol. 2005;25(2):106-15.
43. Weinhandl ED, Rao M, Gilbertson DT, Collins AJ, Pereira BJ. Protective effect of intravenous levocarnitine on subsequent-month hospitalization among prevalent hemodialysis patients, 1998 to 2003. Am J Kidney Dis. 2007;50(5):803-12.
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Авторы
Ж.М. Сизова, Е.В. Ших, А.А. Махова
ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
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Zh.M. Sizova, E.V. Shikh, A.A. Makhova
I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia