Skip to main content

Prolonged Oral L-carnitine Substitution Increases Bicycle Ergometer Performance in Patients with Severe, Ischemically Induced Cardiac Insufficiency

Cardiovascular Drugs and Therapy volume 13, pages 537–546 (1999)Cite this article

Abstract

Summary. Acute and chronic L-carnitine application exerts protective effects in a number of cardiac diseases. These favourable effects are attributed to improvements of the energy metabolism and have been found both in animal experiments and in man. In order to investigate the effect of long-time oral L-carnitine substitution on physical performance, 41 patients suffering from class NYHA II or III cardiac insufficiency were recruited for a clinical study. Following the double-blind, randomized, placebo-controlled design of the study, 20 patients were given 3 × 1g L-carnitine daily for 120 days whereas the control group (21 patients) received placebo. Bicycle ergometer tests were used to determine maximum performance, systolic and diastolic blood pressure, heart rate, and ST changes. Four series of tests were carried out: on day 0 (before the first substrate application), on the 60th and the 120th day (during L-carnitine or placebo application), and on the 180th day (60 days after the end of substitution). A significant improvement in performance (significantly higher maximum performance during bicycle ergometry) could be found within the carnitine group on the 60th and 120th day of L-carnitine application; and haemodynamical parameters showed a tendency to improve, too. These effects, which were attributed to L-carnitine, could be detected even 60 days after the end of substitution. No corresponding changes were found in the placebo group.

The findings presented in this paper support suggestions of other authors that L-carnitine in combination with the usual medication (digitalis, β-blockers, calcium antagonists, nitrates) improves performance and effort tolerance in patients with cardiac insufficiency. Moreover, the findings suggest a favourable long-term effect, which lasts beyond the actual L-carnitine application, on the performance of patients with advanced cardiac insufficiency.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Bremer J. Carnitine—Metabolism and functions. Phys Revs 1983;63:1420–1480.

    Google Scholar 

  2. Bieber LL. Carnitine. Ann Rev Biochem 1988;57:261–283.

    Google Scholar 

  3. Ramsay RR, Tubbs PK. The mechanism of fatty acid uptake by heart mitochondria: An acylcarnitine-carnitine exchange. FEBS Lett 1975;54:21–25.

    Google Scholar 

  4. Bremer J, Hokland B. Role of carnitine-dependent metabolic pathways in heart disease without primary ischemia. Z Kardiol 1987;76(Suppl 5):9–13.

    Google Scholar 

  5. Liedtke AJ. Alteration of carbohydrate and lipid metabolism in the acutely ischemic heart. Prog Cardiovasc Dis 1981;25:321–330.

    Google Scholar 

  6. Opie LH. Carbohydrates and Lipids. In: L Opie, The Heart: Physiology, Metabolism, Pharmacology and Therapy. London: Grune & Stratton Inc., 1986: 118–135.

    Google Scholar 

  7. Feuvray D, Leblond Y. Metabolism of long chain fatty acids in the normal and in the pathological heart: Effects of ischemia. Diabetes Metab 1984;10:316–323.

    Google Scholar 

  8. Schoonderwoerd R, Broekhoven-Schokker S, Hülsmann WC, Stam HCG. Enhanced lipolysis of mycardial triglyceroles during low-flow ischemia and anoxia in the isolated rat heart. Bas Res Cardiol 1989;84:165–173.

    Google Scholar 

  9. Van der Vusse GJ, Glatz JFC, Stam HCG, Reneman RS. Fatty acid homeostasis in the normoxic and ischemic heart. Phys Rev 1992;72:881–940.

    Google Scholar 

  10. Shug AL, Subramanian R. Modulation of adenine nucleotide translocase activity during myocardial ischemia. Z Kardiol 1987;76(Suppl 5):26–33

    Google Scholar 

  11. Bieber LL, Emaus R, Valkner K, Farrell S. Possible functions of short-chain and medium-chain carnitine acyltransferases. Fed Proc 1982;41:2858–2862.

    Google Scholar 

  12. Spagnoli LG, Corsi M, Villaschi S, Palmieri G, Maccari F. Myocardial carnitine deficiency in acute myocardial infarction. Lancet 1982;1:1419–1420.

    Google Scholar 

  13. Suzuki Y, Masumura Y, Kobayashi A, Yamazaki N, Harada Y, Osawa M. Myocardial carnitine deficiency in chronic heart failure. Lancet 1982;1:116

    Google Scholar 

  14. Paulson DJ, Shug AL. Tissue specific depletion of L-carnitine in rat heart and skeletal muscle by D-carnitine. Life Sci 1981;28:2931–2938.

    Google Scholar 

  15. Löster H, Punzel M. Effects of L-carnitine on mechanical recovery of isolated rat hearts in relation to the perfusion with glucose and palmitate. Mol Cell Biochem 1998;185:65–75.

    Google Scholar 

  16. Broderick TL, Quinney HA, Lopaschuk GD. Carnitine stimulation of glucose oxidation in fatty acid perfused isolated working rat heart. J Biol Chem 1992;267:3758–3763.

    Google Scholar 

  17. Engel AG, Angelini C. Carnitine deficiency of human muscle with associated lipid storage myopathy: A new syndrome. Science 1973;179:899–902.

    Google Scholar 

  18. Borchard U. L-Carnitin—ein neuer therapeutischer Ansatz bei Kardiomyopathie und ischämischen Herzerkrankungen. Z prakt Kardioangiologie 1987;(Sonderheft II):3–5.

  19. Opie LH. Role of carnitine in fatty acid metabolism of normal and ischemic myocardium. Am Heart J 1979;97:375–388.

    Google Scholar 

  20. Bartels GL, Remme WJ, Pillay M, et al. Acute improvement of cardiac function with intravenous L-propionylcarnitine in humans. J Cardiovasc Pharmacol 1992;20:157–164.

    Google Scholar 

  21. Kamikawa T, Suzuki Y, Kobayashi A, et al. Effects of L-carnitine on exercise tolerance in patients with stable angina pectoris. Jpn Heart J 1984;25:587–597.

    Google Scholar 

  22. Lagioia R, Scutinio D, Mangini SG, et al. Propionyl-L-carnitine: A new compound in the metabolic approach to the treatment of effort angina. Int J Cardiol 1992;34:167–172.

    Google Scholar 

  23. Liedtke AJ, De Maison L, Nellis SH. Effects of L-propionylcarnitine on mechanical recovery during reflow in intact hearts. Am J Physiol 1988;255:H169–H176.

    Google Scholar 

  24. Schiavoni G, Pennestri F, Mongiardo R, Mazzari M, Manzoli U. Cardiodynamic effects of L-carnitine in ischemic cardiopathy. Drugs Exptl Clin Res 1983;11:171–185.

    Google Scholar 

  25. Yang XP, Samaja M, English E, et al. Hemodynamic and metabolic activities of propionyl-L-carnitine in rats with pressure-overload cardiac hypertrophy. J Cardiovasc Pharmacol 1992;20:88–98.

    Google Scholar 

  26. Cacciatore L, Cerio R, Ciarimboli M, et al. The therapeuthic effect of L-carnitine in patients with exercise-induced stable angina: a controlled study. Drugs Exptl Clin Res 1991;17:225–235.

    Google Scholar 

  27. 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;23:569–572.

    Google Scholar 

  28. Canale C, Terrachini V, Biagini A, et al. Bicycle ergometer and echocardiographic study in healthy subjects and patients with angina pectoris after administration of L-carnitine: Semiautomatic computerized analysis of M-mode tracings. Int J Clin Pharmacol Ther Toxicol 1988;26:221–224.

    Google Scholar 

  29. Cherchi A, Lai C, Onnis E, et al. Propionyl carnitine in stable effort angina. Cardiovasc Drugs Ther 1990;4:481–486.

    Google Scholar 

  30. Gasparetto A, Corbucci GG, De Blasi AA, et al. Influence of acetyl-L-carnitine infusion on haemodynamic parameters and survival of circulatory-shock patients. Int J Clin Pharmacol Res 1991;11:83–92.

    Google Scholar 

  31. Ghidini O, Azzurro M, Vita G, Sartori G. Evaluation of the therapeutic efficacy of L-carnitine in congestive heart failure. Int J Clin Pharmacol Ther Toxicol 1988;26:217–220.

    Google Scholar 

  32. Giordano MP, Corsi M, Roncarolo P et al. Effect of L-carnitine on systolic time intervals in coronary artery disease. Curr Ther Res 1983;33:305–311.

    Google Scholar 

  33. Fazekas T, Csati S, Selmeczi A, Udvary E, Szekeres L. Effects of L-carnitine in acute myocardial ischemia. Acta Physiol Hung 1986;67:199–205.

    Google Scholar 

  34. Biagini A, Opie LH, Rovai D, Mazzei MG, Carpeggiani C, Maseri A. Intravenous dl-carnitine fails to increase the double-product during atrial pacing in patients with effort angina. A double-blind randomized study. G Ital Cardiol 1983;13:291–294.

    Google Scholar 

  35. Bartels GL, Remme WJ, Pillay M, Schönfeld DHW, Kruijssen, DACM. Effects of L-propionylcarnitine on ischemia induced myocardial dysfunction in men with angina pectoris. Am J Cardiol 1994;74:125–130.

    Google Scholar 

  36. Ferrari R, Di Lisa F, De Jong JW, et al. Prolonged propionyl-L-carnitine pre-treatment of rabbit: biochemical, hemodynamic and electrophysiological effects on myocardium. J Mol Cell Cardiol 1992;24:219–232.

    Google Scholar 

  37. Ferrari F, Cucchini F, Visioli O. The metabolic effects of L-carnitine in angina pectoris. Int J Cardiol 1984;5:213–216.

    Google Scholar 

  38. Ferrari R, Visioli O. Effects of L-carnitine in coronary artery disease patients. In: Ferrari R, DiMauro S, Sherwood G, eds. L-Carnitine and Its Role in Medicine: From Function to Therapy. New York: Academic Press, 1992:265–282.

    Google Scholar 

  39. Brevetti G, Perna S. Metabolic and clinical effects of L-carnitine in peripheral vascular disease. In: Ferrari R, Di-Mauro S, Sherwood G, eds. L-Carnitine and Its Role in Medicine: From Function to Therapy. New York: Academic Press, 1992:359–378

    Google Scholar 

  40. Cherchi A, Fonzo R, Lai C, Mercuro G, Corsi M. Influence of carnitine on the effort tolerance test in angina pectoris. Boll Soc Ital Cardiol 1978;23:71–89.

    Google Scholar 

  41. Thomsen JH, Shug AL, Yap VU, Patel AK, Karras TJ, DeFelice SL. Improved pacing tolerance of the ischemic human myocardium after administration of carnitine. Am J Cardiol 1979;43:300–305.

    Google Scholar 

  42. Kosolcharoen P, Nappi J, Peduzzi P, et al. Improved exercise tolerance after administration of carnitine. Curr Ther Res 1981;30:753–764.

    Google Scholar 

  43. Hülsmann WC, Dubelaar N. Carnitine in metabolism of paced cardiac and skeletal muscles: prevention of acidosis and improvement of vascular flow. In: Ferrari R, DiMauro S, Sherwood G, eds. L-Carnitine and Its Role in Medicine: From Function to Therapy. New York: Academic Press, 1992:345–358

    Google Scholar 

  44. Regitz V, Fleck E. Role of carnitine in heart failure. In: Ferrari R, DiMauro S, Sherwood G, eds. L-Carnitine and Its Role in Medicine: From Function to Therapy. New York: Academic Press, 1992:295–323

    Google Scholar 

  45. Kobayashi A, Fujisawa S. Effect of L-carnitine on mitochondrial acyl CoA esters in the ischemic dog heart. J Mol Cell Cardiol 1994;26:499–508.

    Google Scholar 

Download references

Author information

Affiliations

  1. Institute of Clinical Chemistry and Pathobiochemistry, University of Leipzig, Germany

    Heinz Löster & Konstant Miehe

  2. Medical Clinic I, University of Leipzig, Germany

    Michael Punzel, Olaf Stiller, Hans Pankau & Joachim Schauer

Authors
  1. Heinz Löster
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Konstant Miehe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Punzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Olaf Stiller
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hans Pankau
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joachim Schauer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Löster, H., Miehe, K., Punzel, M. et al. Prolonged Oral L-carnitine Substitution Increases Bicycle Ergometer Performance in Patients with Severe, Ischemically Induced Cardiac Insufficiency. Cardiovasc Drugs Ther 13, 537–546 (1999). https://doi.org/10.1023/A:1007883822625

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007883822625

  • L-carnitine
  • chronic ischemic cardiac disease
  • bicycle ergometry
  • long term treatment