, Volume 9, Issue 4, pp 828–838 | Cite as

Carnitine and acylcarnitine profiles in dried blood spots of patients with acute myocardial infarction

  • Haseeb Ahmad Khan
  • Abdullah Saleh Alhomida
  • Halima Al Madani
  • Samia Hasan Sobki
Original Article


Earlier studies have suggested an important role of carnitine pathway in cardiovascular pathology. However, the redistribution of carnitine and acylcarnitine pools, as a result of altered carnitine metabolism, is not clearly known in patients with acute myocardial infarction (AMI). We compared the carnitine and acylcarnitine profiles of 65 AMI patients, including 26 ST-elevated myocardial infarction (STEMI) and 39 non-ST-elevated myocardial infarction (NSTEMI), 28 patients with chest pain and 154 normal controls. The levels of carnitine and acylcarnitines in the blood spots were determined using LC-MS/MS. Total and free carnitine levels were significantly higher in all the patient groups in the following order: STEMI > NSTEMI > chest pain. The levels of short- and medium-chain acylcarnitines were significantly higher in patient groups. Among the long-chain acylcarnitines, C14:2 and C16:1 levels were significantly increased in STEMI and NSTEMI. The ratio of free carnitine to short-chain or medium-chain acylcarnitines was significantly decreased in STEMI, NSTEMI and chest pain patients however a significant increase was observed in the ratio of carnitine to long-chain acylcarnitines in all the patient groups as compared to normal controls. In conclusion, alterations in carnitine and acylcarnitine levels in the blood of AMI patients indicate the possibility of impaired carnitine homeostasis in ischemic myocardium. The clinical implications of these findings for the risk screening or diagnosis and prognosis of AMI require additional follow-up studies on large number of patients. We also suggest that a dual-marker strategy using carnitine (longer plasma half-life) in combination with troponin (shorter plasma half-life) could be a more promising biomarker strategy in risk stratification of patients.


Acute myocardial infarction Carnitine Acylcarnitines Biomarker 

Supplementary material

11306_2013_505_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 16 kb)


  1. Aarsetoey, H., Aarsetoey, R., Lindner, T., Staines, H., Harris, W. S., & Nilsen, D. W. (2011). Low levels of the omega-3 index are associated with sudden cardiac arrest and remain stable in survivors in the subacute phase. Lipids, 46, 151–161.CrossRefPubMedGoogle Scholar
  2. Adams, S. H., Hoppel, C. L., Lok, K. H., Zhao, L., Wong, S. W., Minkler, P. E., et al. (2009). Plasma acylcarnitine profiles suggest incomplete long-chain fatty acid beta-oxidation and altered tricarboxylic acid cycle activity in type 2 diabetic African-American women. Journal of Nutrition, 139, 1073–1081.CrossRefPubMedGoogle Scholar
  3. Alpert, J. S., Thygesen, K., Antman, E., & Bassand, J. P. (2000). Myocardial infarction redefined: A consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Journal of the American College of Cardiology, 36, 959–969.CrossRefPubMedGoogle Scholar
  4. Aoyagi, T., Sugiura, S., Eto, Y., et al. (1997). Inhibition of carnitine synthesis protects against left ventricular dysfunction in rats with myocardial ischemia. Journal of Cardiovascular Pharmacology, 30, 468–474.CrossRefPubMedGoogle Scholar
  5. Barns, R. J., Bowling, F. G., Brown, G., Clague, A. E., & Thompson, A. (1991). Carnitine in dried blood spots: A method suitable for neonatal screening. Clinica Chimica Acta, 197, 27–33.CrossRefGoogle Scholar
  6. Bartels, G. L., Remme, W. J., Pillay, M., Schönfeld, D. H., & Kruijssen, D. A. (1994). Effects of l-propionylcarnitine on ischemia-induced myocardial dysfunction in men with angina pectoris. American Journal of Cardiology, 74, 125–130.CrossRefPubMedGoogle Scholar
  7. Berthiaume, J. M., Young, M. E., Chen, X., McElfresh, T. A., Yu, X., & Chandler, M. P. (2012). Normalizing the metabolic phenotype after myocardial infarction: Impact of subchronic high fat feeding. Journal of Molecular and Cellular Cardiology, 53, 125–133.CrossRefPubMedGoogle Scholar
  8. Bieber, L. L. (1988). Carnitine. Annual Review of Biochemistry, 57, 261–283.CrossRefPubMedGoogle Scholar
  9. Bohmer, T., Eiklid, K., & Jonsen, J. (1977). Carnitine uptake into human heart cells in culture. Biochimica et Biophysica Acta, 465, 627–633.CrossRefPubMedGoogle Scholar
  10. Breitling, L. P., Rothenbacher, D., Grandi, N. C., März, W., & Brenner, H. (2011). Prognostic usefulness of free fatty acids in patients with stable coronary heart disease. American Journal of Cardiology, 108, 508–513.CrossRefPubMedGoogle Scholar
  11. Bressler, R., Gay, R., Copeland, J. G., Bahl, J. J., Bedotto, J., & Goldman, S. (1989). Chronic inhibition of fatty acid oxidation: New model of diastolic dysfunction. Life Sciences, 44, 1897–1906.CrossRefPubMedGoogle Scholar
  12. Buja, L. M. (1991). Lipid abnormalities in myocardial cell injury. Trends in Cardiovascular Medicine, 1, 40–45.CrossRefPubMedGoogle Scholar
  13. Cao, Y., Wang, Y. X., Liu, C. J., Wang, L. X., Han, Z. W., & Wang, C. B. (2009). Comparison of pharmacokinetics of l-carnitine, acetyl-l-carnitine and propionyl-l-carnitine after single oral administration of l-carnitine in healthy volunteers. Clinical and Investigative Medicine, 32, E13–E19.PubMedGoogle Scholar
  14. Chiu, K. M., Schmidt, M. J., Havighurst, T. C., Shug, A. L., Daynes, R. A., Keller, E. T., et al. (1999). Correlation of serum l-carnitine and dehydro-epiandrosterone sulphate levels with age and sex in healthy adults. Age and Ageing, 28, 211–216.CrossRefPubMedGoogle Scholar
  15. Covino, M., Simeoni, B., Montalto, M., et al. (2012). Reduced performance of Troponin T for acute coronary syndromes diagnosis in the elderly and very elderly patients: a retrospective study of 2688 patients. European Review for Medical and Pharmacological Sciences, 16(Suppl 1), 8–15.PubMedGoogle Scholar
  16. Davini, P., Bigalli, A., Lamanna, F., & Boem, A. (1992). Controlled study on l-carnitine therapeutic efficacy in post-infarction. Drugs Under Experimental and Clinical Research, 18, 355–365.PubMedGoogle Scholar
  17. DiDonato, S., Garavaglia, B., Rimoldi, M., & Carrara, F. (1992). Clinical and biomedical phenotypes of carnitine deficiencies. In R. Ferrari, S. Dimauro, & G. Sherwood (Eds.), l -carnitine and its role on medicine (pp. 81–98). London: Academic Press.Google Scholar
  18. Ford, D. A., Han, X., Horner, C. C., & Gross, R. W. (1996). Accumulation of unsaturated acylcarnitine molecular species during acute myocardial ischemia: Metabolic compartmentalization of products of fatty acyl chain elongation in the acylcarnitine pool. Biochemistry, 35, 7903–7909.CrossRefPubMedGoogle Scholar
  19. Galan, P., Kesse-Guyot, E., Czernichow, S., Briancon, S., Blacher, J., Hercberg, S., et al. (2010). Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. BMJ, 341, c6273.CrossRefPubMedGoogle Scholar
  20. Haltern, G., Peiniger, S., Bufe, A., Reiss, G., Gülker, H., & Scheffold, T. (2010). Comparison of usefulness of heart-type fatty acid binding protein versus cardiac troponin T for diagnosis of acute myocardial infarction. American Journal of Cardiology, 105, 1–9.CrossRefPubMedGoogle Scholar
  21. Hendrickson, S. C., St Louis, J. D., Lowe, J. E., & Abdel-aleem, S. (1997). Free fatty acid metabolism during myocardial ischemia and reperfusion. Molecular and Cellular Biochemistry, 166, 85–94.CrossRefPubMedGoogle Scholar
  22. Hernandiz Martínez, A., Pallares Carratala, V., Cosín Aguilar, J., et al. (1997). Effects of l-carnitine on the regional function of the stunned myocardium caused by ischemia of short duration. Revista Espanola de Cardiologia, 50, 650–657.CrossRefPubMedGoogle Scholar
  23. Hoppel, C. (2003). The role of carnitine in normal and altered fatty acid metabolism. American Journal of Kidney Diseases, 41, S4–S12.CrossRefPubMedGoogle Scholar
  24. Ino, T., Sherwood, W. G., Benson, L. N., Wilson, G. J., Freedom, R. M., & Rowe, R. D. (1988). Cardiac manifestations in disorders of fat and carnitine metabolism in infancy. Journal of the American College of Cardiology, 11, 1301–1308.CrossRefPubMedGoogle Scholar
  25. Kanna, M., Nonogi, H., Sumida, H., et al. (2001). Usefulness of serum troponin T levels on day three or four in predicting survival after acute myocardial infarction. American Journal of Cardiology, 87, 294–297.CrossRefPubMedGoogle Scholar
  26. Kar, S., & Webel, R. (2012). Fish oil supplementation and coronary artery disease: does it help? Molecular Medicine, 109, 142–145.Google Scholar
  27. Katus, H. A., Remppis, A., Looser, S., Hallermeier, K., Scheffold, T., & Kubler, W. (1989). Enzyme linked immune assay of cardiac troponin T for the detection of acute myocardial infarction in patients. Journal of Molecular and Cellular Cardiology, 21, 1349–1353.CrossRefPubMedGoogle Scholar
  28. Katus, H. A., Remppis, A., Scheffold, T., Diederich, K. W., & Kuebler, W. (1991). Intracellular compartmentation of cardiac troponin T and its release kinetics in patients with reperfused and nonreperfused myocardial infarction. American Journal of Cardiology, 67, 1360–1367.CrossRefPubMedGoogle Scholar
  29. Kim, Y. J., Jeong, D. W., Lee, J. G., et al. (2012). Omega-3 index and smoking in patients with acute ST-elevation myocardial infarction taking statins: A case-control study in Korea. Lipids in Health and Disease, 11, 43.CrossRefPubMedGoogle Scholar
  30. Kromhout, D., Geleijnse, J. M., de Goede, J., et al. (2011). n-3 Fatty acids, ventricular arrhythmia-related events, and fatal myocardial infarction in postmyocardial infarction patients with diabetes. Diabetes Care, 34, 2515–2520.CrossRefPubMedGoogle Scholar
  31. Levitan, E. B., Wolk, A., & Mittleman, M. A. (2010). Fatty fish, marine omega-3 fatty acids and incidence of heart failure. European Journal of Clinical Nutrition, 64, 587–594.CrossRefPubMedGoogle Scholar
  32. Li, K., Sun, Q. B., Liu, X. Z., & Shi, Y. H. (2009). Correlation of serum carnitine levels with age and sex among Chinese adults in Nanjing. Zhonghua Nan Ke Xue, 15, 337–340.PubMedGoogle Scholar
  33. Liepinsh, E., Vilskersts, R., Loca, D., Kirjanova, O., Pugovichs, O., Kalvinsh, I., et al. (2006). Mildronate, an inhibitor of carnitine biosynthesis, induces an increase in gamma-butyrobetaine contents and cardioprotection in isolated rat heart infarction. Journal of Cardiovascular Pharmacology, 48, 314–319.CrossRefPubMedGoogle Scholar
  34. Lyck Hansen, M., Saaby, L., Nybo, M., Rasmussen, L. M., Thygesen, K., Mickley, H., et al. (2012). Discordant diagnoses of acute myocardial infarction due to the different use of assays and cut-off points of cardiac troponins. Cardiology, 122, 225–229.CrossRefPubMedGoogle Scholar
  35. Marquis, N. R., & Fritz, I. B. (1964). Enzymological determination of free carnitine concentrations in rat tissues. Journal of Lipid Research, 5, 184–187.PubMedGoogle Scholar
  36. Masson, S., Anand, I., Favero, C., et al. (2012). Serial measurement of cardiac troponin T using a highly sensitive assay in patients with chronic heart failure: Data from 2 large randomized clinical trials. Circulation, 125, 280–288.CrossRefPubMedGoogle Scholar
  37. Millington, D. S., Kodo, N., Norwood, D. L., & Roe, C. R. (1990). Tandem mass spectrometry: A new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism. Journal of Inherited Metabolic Disease, 13, 321–324.CrossRefPubMedGoogle Scholar
  38. Moe, K. T., & Wong, P. (2010). Current trends in diagnostic biomarkers of acute coronary syndrome. Annals of the Academy of Medicine Singapore, 39, 210–215.Google Scholar
  39. Moselhy, S. S., & Demerdash, S. H. (2009). Serum free l-carnitine in association with myoglobin as a diagnostic marker of acute myocardial infarction. Clinical Biochemistry, 42, 78–82.CrossRefPubMedGoogle Scholar
  40. Narin, F., Narin, N., Andaç, H., Ergin, A., Coşkun, A., Ustdal, M., et al. (1997). Carnitine levels in patients with chronic rheumatic heart disease. Clinical Biochemistry, 30, 643–645.CrossRefPubMedGoogle Scholar
  41. Olivieri, F., Galeazzi, R., Giavarina, D., et al. (2012). Aged-related increase of high sensitive Troponin T and its implication in acute myocardial infarction diagnosis of elderly patients. Mechanisms of Ageing and Development, 133, 300–305.CrossRefPubMedGoogle Scholar
  42. Paulson, D. J., Schmidt, M. J., Traxler, J. S., Ramacci, M. T., & Shug, A. L. (1984). Improvement of myocardial function in diabetic rats after treatment with l-carnitine. Metabolism, 33, 358–363.CrossRefPubMedGoogle Scholar
  43. Pauly, D. F., & Pepine, C. J. (2003). The role of carnitine in myocardial dysfunction. American Journal of Kidney Diseases, 41, S35–S43.CrossRefPubMedGoogle Scholar
  44. Ramsden, C. E., Hibbeln, J. R., Majchrzak, S. F., & Davis, J. M. (2010). n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: A meta-analysis of randomised controlled trials. British Journal of Nutrition, 104, 1586–1600.CrossRefPubMedGoogle Scholar
  45. Regitz, V., & Fleck, E. (1992). Role of carnitine in heart failure. In R. Ferrari, S. Dimauro, & G. Sherwood (Eds.), l -carnitine and its role on medicine (pp. 295–323). London: Academic Press.Google Scholar
  46. Regitz, V. R., Shug, A. L., & Fleck, E. (1990). Defective myocardial carnitine metabolism in congestive heart failure secondary to dilated cardiomyopathy and coronary, hypertensive, and valvular diseases. American Journal of Cardiology, 65, 755–760.CrossRefPubMedGoogle Scholar
  47. Regitz, V., Shug, A. L., Schüler, S., Yankah, C., Hetzer, R., & Fleck, E. (1988). Heart failure in dilated cardiomyopathy and coronary heart disease. The contribution of biochemical parameters to assessing the prognosis. Deutsche Medizinische Wochenschrift, 113, 781–786.CrossRefPubMedGoogle Scholar
  48. Rizzon, P., Biasco, G., Di Biase, M., et al. (1989). High doses of l-carnitine in acute myocardial infarction: Metabolic and antiarrhythmic effects. European Heart Journal, 10, 502–508.PubMedGoogle Scholar
  49. Roe, C. R., Millington, D. S., Maltby, D. A., Bohan, T. P., & Hoppel, C. L. (1984). l-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia. Journal of Clinical Investigation, 73, 1785–1788.CrossRefPubMedGoogle Scholar
  50. Roe, C. R., Millington, D. S., Maltby, D. A., Bohan, T. P., Kahler, S. G., & Chalmers, R. A. (1985). Diagnostic and therapeutic implications of medium-chain acylcarnitines in the medium-chain acyl-coA dehydrogenase deficiency. Pediatric Research, 19, 459–466.CrossRefPubMedGoogle Scholar
  51. Roger, V. L. (2007). Epidemiology of myocardial infarction. Medical Clinics of North America, 91, 537–552.CrossRefPubMedGoogle Scholar
  52. Rondeau, I., Picard, S., Bah, T. M., Roy, L., Godbout, R., & Rousseau, G. (2011). Effects of different dietary ω-6/3 polyunsaturated fatty acids ratios on infarct size and the limbic system after myocardial infarction. Canadian Journal of Physiology and Pharmacology, 89, 169–176.CrossRefPubMedGoogle Scholar
  53. Samuel, S., Peskin, B., Arondekar, B., Alperin, P., Johnson, S., Blumenfeld, I., et al. (2011). Estimating health and economic benefits from using prescription omega-3 fatty acids in patients with severe hypertriglyceridemia. American Journal of Cardiology, 108, 691–697.CrossRefPubMedGoogle Scholar
  54. Sartorelli, L., Ciman, M., Rizzoli, V., & Siliprandi, N. (1982). On the transport mechanisms of carnitine and its derivative in rat heart slices. Italian Journal of Biochemistry, 31, 261–268.PubMedGoogle Scholar
  55. Schmidt-Sommerfeld, E., Werner, D., & Penn, D. (1988). Carnitine plasma concentrations in 353 metabolically healthy children. European Journal of Pediatrics, 147, 356–360.CrossRefPubMedGoogle Scholar
  56. Shah, S. H., Sun, J. L., Stevens, R. D., et al. (2012). Baseline metabolomic profiles predict cardiovascular events in patients at risk for coronary artery disease. American Heart Journal, 163(844–850), e1.PubMedGoogle Scholar
  57. Siliprandi, N., Di Lisa, F., Pivetta, A., Miotto, G., & Siliprandi, D. (1987). Transport and function of l-carnitine and l-propionylcarnitine: Relevance to some cardiomyopathies and cardiac ischemia. Zeitschrift fur Kardiologie, 76, 34–40.PubMedGoogle Scholar
  58. Singh, R. B., Niaz, M. A., Agarwal, P., Beegum, R., Rastogi, S. S., & Sachan, D. S. (1996). A randomised, double-blind, placebo-controlled trial of l-carnitine in suspected acute myocardial infarction. Postgraduate Medical Journal, 72, 45–50.CrossRefPubMedGoogle Scholar
  59. Sirolli, V., Rossi, C., Di Castelnuovo, A., et al. (2012). Toward personalized hemodialysis by low molecular weight amino-containing compounds: future perspective of patient metabolic fingerprint. Blood Transfusion, 10(Suppl 2), s78–s88.PubMedGoogle Scholar
  60. Solfrizzi, V., Capurso, C., Colacicco, A. M., et al. (2006). Efficacy and tolerability of combined treatment with l-carnitine and simvastatin in lowering lipoprotein(a) serum levels in patients with type 2 diabetes mellitus. Atherosclerosis, 188, 455–461.CrossRefPubMedGoogle Scholar
  61. Takiyama, N., & Matsumoto, K. (1998). Age-and sex-related differences of serum carnitine in a Japanese population. Journal of the American College of Nutrition, 17, 71–74.CrossRefPubMedGoogle Scholar
  62. Tarantini, G., Scrutinio, D., Bruzzi, P., Boni, L., Rizzon, P., & Iliceto, S. (2006). Metabolic treatment with l-carnitine in acute anterior ST segment elevation myocardial infarction. A randomized controlled trial. Cardiology, 106, 215–223.CrossRefPubMedGoogle Scholar
  63. Tegalaers, F. P. W., Pickkers, M. M. G., & Seelen, P. J. (1989). Effect of deproteinization and reagent buffer on the enzymatic assay of l-carnitine in serum. Journal of Clinical Chemistry and Clinical Biochemistry, 27, 967–972.Google Scholar
  64. Tripp, M. E., & Shug, A. L. (1984). Plasma carnitine concentrations in cardiomyopathy patients. Biochemical Medicine, 32, 199–206.CrossRefPubMedGoogle Scholar
  65. Vernez, L., Dickenmann, M., Steiger, J., Wenk, M., & Krähenbühl, S. (2006). Effect of l-carnitine on the kinetics of carnitine, acylcarnitines and butyrobetaine in long-term haemodialysis. Nephrology Dialysis Transplantation, 21, 450–458.CrossRefGoogle Scholar
  66. Whitmer, J. T. (1987). l-carnitine treatment improves cardiac performance and restores high-energy phosphate pools in cardiomyopathic Syrian hamster. Circulation Research, 61, 396–408.CrossRefPubMedGoogle Scholar
  67. Wu, J. H., Lemaitre, R. N., Imamura, F., King, I. B., Song, X., Spiegelman, D., et al. (2011). Fatty acids in the de novo lipogenesis pathway and risk of coronary heart disease: The Cardiovascular Health Study. American Journal of Clinical Nutrition, 94, 431–438.CrossRefPubMedGoogle Scholar
  68. Xue, Y. Z., Wang, L. X., Liu, H. Z., Qi, X. W., Wang, X. H., & Ren, H. Z. (2007). l-carnitine as an adjunct therapy to percutaneous coronary intervention for non-ST elevation myocardial infarction. Cardiovascular Drugs and Therapy, 21, 445–448.CrossRefPubMedGoogle Scholar
  69. Yamada, K. A., McHowat, J., Yan, G. X., Donahue, K., Peirick, J., Kléber, A. G., et al. (1994). Cellular uncoupling induced by accumulation of long-chain acylcarnitine during ischemia. Circulation Research, 74, 83–95.CrossRefPubMedGoogle Scholar
  70. Yoon, H. R., Hong, Y. M., Boriack, R. L., & Bennett, M. J. (2003). Effect of l-carnitine supplementation on cardiac carnitine palmitoyltransferase activities and plasma carnitine concentrations in adriamycin-treated rats. Pediatric Research, 53, 788–792.CrossRefPubMedGoogle Scholar
  71. Zeghichi-Hamri, S., de Lorgeril, M., Salen, P., Chibane, M., de Leiris, J., Boucher, F., et al. (2010). Protective effect of dietary n-3 polyunsaturated fatty acids on myocardial resistance to ischemia-reperfusion injury in rats. Nutrition Research, 30, 849–857.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Haseeb Ahmad Khan
    • 1
  • Abdullah Saleh Alhomida
    • 1
  • Halima Al Madani
    • 2
  • Samia Hasan Sobki
    • 2
  1. 1.Department of BiochemistryCollege of Science, King Saud UniversityRiyadhSaudi Arabia
  2. 2.Division of Clinical Biochemistry, Department of PathologyPrince Sultan Military Medical CityRiyadhSaudi Arabia

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