L-Carnitine Effects on Clinical Status and Mortality Rate in Septic Patients: A Systematic Literature Review

Document Type : Review Article


1 Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Department of Anesthesiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

4 Clinical Research Development Unit, Mashhad University of Medical Sciences, Mashhad, Iran.


Introduction: Sepsis is one of the major causes of high morbidity and mortality in intensive care units (ICU) and severe sepsis leads to some metabolic disorder. The previous studies indicate that l-carnitine deficiency in septic patients and causing mitochondria dysfunction and worsening metabolic disorder. Reducing mortality in sepsis by nutritional supplements may help mitigate the risk of clinical outcomes in sepsis patients. Methods: Our systematic search to find relevant studies was performed up to March 2020, using ISI Web of Science, Google Scholar, EMBASE, PubMed/MEDLINE and SCOPUS databases. In this systematic review, the aim was to assess whether l-carnitine or levocarnitine may reduce the risk of mortality in patients with sepsis. Result: 10 articles were included in our systematic review. The results of the review showed that plasma carnitine levels were significantly associated with the Sequential Organ Failure Assessment score (SOFA) (p <0.001). On the other hand, other studies showed carnitine supplementation had no significant effect on SOFA score change in a short time, while carnitine deficiency was associated with significantly increased SOFA score in critically ill patients.  L-carnitine supplementation indicated a significant decline in 28 days’ mortality as well. Conclusion: Evidencefrom limited data suggested that carnitine may helps to reduce mortality risk in sepsis patients, but further studies are required with different doses and durations.


  1.  Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med, 2013. 41(5): p. 1167-74.
  2.  Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS. The third international consensus definitions for sepsis and septic shock (Sepsis-3). Jama. 2016;315(8):801-10.
  3. Annane D, Sébille V, Charpentier C, Bollaert PE, François B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troché G, Chaumet-Riffaut P. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. Jama. 2002;288(7):862-71.
  4. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive care medicine. 2017;43(3):304-77.
  5. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher Jr CJ. Efficacy and safety of recombinant human activated protein C for severe sepsis. New England journal of medicine. 2001;344(10):699-709.
  6. Mikkelsen ME, Miltiades AN, Gaieski DF, Goyal M, Fuchs BD, Shah CV, Bellamy SL, Christie JD. Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Critical care medicine. 2009 May 1;37(5):1670-7.
  7. Englert JA, Rogers AJ. Metabolism, metabolomics, and nutritional support of patients with sepsis. Clinics in chest medicine. 2016 Jun 1;37(2):321-31.
  8. Hogan P, Plourde R, Fortier M, Brindamour D, Lagrenade-Verdant C, Demers-Marcil S, Dupuis S. Refractory Hyperlactatemia After a Septic Shock in a Patient With Carnitine Deficiency: A Case Report. Journal of pharmacy practice. 2020 Feb;33(1):113-6.
  9. Calvani M, Reda E, Arrigoni-Martelli E. Regulation by carnitine of myocardial fatty acid and carbohydrate metabolism under normal and pathological conditions. Basic research in cardiology. 2000;95(2):75-83.
  10. Puskarich MA, Shapiro NI, Massey MJ, Kline JA, Jones AE. Lactate clearance in septic shock is not a surrogate for improved microcirculatory flow. Academic Emergency Medicine. 2016;23(6):690-3.
  11. Takeyama NA, Takagi DA, Matsuo NO, Kitazawa YA, Tanaka TA. Altered hepatic fatty acid metabolism in endotoxicosis: effect of L-carnitine on survival. American Journal of Physiology-Endocrinology and Metabolism. 1989;256(1):E31-8.
  12. Pekala J, Patkowska-Sokola B, Bodkowski R, Jamroz D, Nowakowski P, Lochynski S, Librowski T. L-carnitine-metabolic functions and meaning in humans life. Current drug metabolism. 2011 Sep 1;12(7):667-78.
  13. Jones AE, Puskarich MA, Shapiro NI, Guirgis FW, Runyon M, Adams JY, Sherwin R, Arnold R, Roberts BW, Kurz MC, Wang HE. Effect of levocarnitine vs placebo as an adjunctive treatment for septic shock: the Rapid Administration of Carnitine in Sepsis (RACE) randomized clinical trial. JAMA network open. 2018;1(8):e186076.
  14. Gasparetto A, Corbucci GG, De RB, Antonelli M, Bagiella E, D'Iddio S, Trevisani C. Influence of acetyl-L-carnitine infusion on haemodynamic parameters and survival of circulatory-shock patients. International journal of clinical pharmacology research. 1991;11(2):83-92.
  15. Puskarich MA, Kline JA, Krabill V, Claremont H, Jones AE. Preliminary safety and efficacy of L‐carnitine infusion for the treatment of vasopressor‐dependent septic shock: a randomized control trial. Journal of Parenteral and Enteral Nutrition. 2014 Aug;38(6):736-43.
  16. Puskarich MA, Evans CR, Karnovsky A, Das AK, Jones AE, Stringer KA. Septic Shock Non-Survivors Have Persistently Elevated Acylcarnitines Following Carnitine Supplementation. Shock (Augusta, Ga.). 2018;49(4):412-419.
  17. Evans CR, Karnovsky A, Puskarich MA, Michailidis G, Jones AE, Stringer KA. Untargeted metabolomics differentiates L-carnitine treated Septic shock 1-year survivors and nonsurvivors. J Proteome Res. 2019;18(5):2004-11.
  18. Gibault JP, Frey A, Guiraud M, Schirardin H, Bouletreau P, Bach AC. Effects of L‐carnitine infusion on intralipid clearance and utilization. Study carried out in septic patients of an intensive care unit. Journal of Parenteral and Enteral Nutrition. 1988 Jan;12(1):29-34.
  19. Nanni G, Pittiruti M, Giovannini I, Boldrini G, Ronconi P, Castagneto M. Plasma carnitine levels and urinary carnitine excretion during sepsis. J Parenter Enteral Nutr. 1985 Jul;9(4):483-90.
  20. Chung KP, Chen GY, Chuang TY, Huang YT, Chang HT, Chen YF, Liu WL, Chen YJ, Hsu CL, Huang MT, Kuo CH. Increased plasma acetylcarnitine in sepsis is associated with multiple organ dysfunction and mortality: a multicenter cohort study. Crit Care Med. 2019;47(2):210-8.
  21. Dalia M, El-Sayed HM, El-Hawy MA, Abou El-Naga NT. L-carnitine serum level in healthy and septic neonates. 2018.
  22. Ferrario M, Cambiaghi A, Brunelli L, Giordano S, Caironi P, Guatteri L, Raimondi F, Gattinoni L, Latini R, Masson S, Ristagno G. Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach. Sci Rep, 2016;6:20391
  23. Weiss SL, Haymond S, Ranaivo HR, Wang D, De Jesus VR, Chace DH, Wainwright MS. Evaluation of asymmetric dimethylarginine, arginine, and carnitine metabolism in pediatric sepsis. Pediatr Crit Care Med, 2012;13(4):e210-8.
  24. Hogan P, Plourde R, Fortier M, Brindamour D, Lagrenade-Verdant C, Demers-Marcil S, Dupuis S. Refractory Hyperlactatemia After a Septic Shock in a Patient With Carnitine Deficiency: A Case Report. Journal of pharmacy practice. 2020;33(1):113-6.
  25. Maitra U, Chang S, Singh N, Li L. Molecular mechanism underlying the suppression of lipid oxidation during endotoxemia. Molecular immunology. 2009;47(2-3):420-5.
  26. Feingold KR, Wang Y, Moser A, Shigenaga JK, Grunfeld C. LPS decreases fatty acid oxidation and nuclear hormone receptors in the kidney. Journal of lipid research. 2008;49(10):2179-87.
  27. Andrejko KM, Deutschman CS. Altered hepatic gene expression in fecal peritonitis: Changes in transcription of gluconeogenic, β-oxidative, and ureagenic genes. Shock. 1997;7(3):164-9.
  28.  Kang HM, Ahn SH, Choi P, Ko YA, Han SH, Chinga F, Park AS, Tao J, Sharma K, Pullman J, Bottinger EP. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nature medicine. 2015 Jan;21(1):37-46.