Effects of L-carnitine on treatment outcomes of COVID-19 patients hospitalized in intensive care units: A double-blind randomized clinical trial

Abstract

Objective: To assess the effects of L-carnitine on the outcomes of patients with moderate to severe coronavirus disease 2019 (COVID-19) in intensive care unit (ICU). Methods: This double-blind clinical trial was carried out in 2022-2023. 64 Patients with COVID-19 were selected from Amiralmomenin and Khansari hospitals in Arak, Iran. They were randomly assigned to the control and the L-carnitine treatment group via block randomization. Venous blood gases, disease severity, and levels of D-dimer, lactate dehydrogenase, ferritin, and C-reactive protein were daily assessed during the seven days of the intervention, and the length of ICU stay, the need for endotracheal intubation, and mortality rate were documented. Results: There were significant differences in length of ICU stay, the need for endotracheal intubation, and levels of D-dimer, lactate dehydrogenase, ferritin, APACHE II score, and C-reactive protein between the two groups (P<0.05). However, the groups did not significantly differ in mortality rate and venous blood gas indexes (P>0.05). Conclusions: L-carnitine can improve outcomes of patients with COVID-19. Therefore, it can be used as an adjuvant therapy for these patients. Trial registration: Iranian Registry of Clinical Trials identifier IRCT20141209020258N165.

Keywords

L-carnitine / COVID-19 / ICU / Critically ill / Mortality / Clinical outcome

References

[1] Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID—19) outbreak — An update on the status. Mil Med Res 2020; 7(1): 11.

[2] Yousefzadeh M, Asgarian A, Ahangari R, Yazdi Z, Savari M, Mirzaie M, et al. Maternal death due to severe and critical COVID—19 in Qom, Iran: A case series. J Acute Dis 2022; 11(6): 243-246.

[3] Häder A, Köse—Vogel N, Schulz L, Mlynska L, Hornung F, Hagel S, et al. Respiratory infections in the aging lung: Implications for diagnosis, therapy, and prevention. Aging Dis 2023; 14(4): 1091-1104.

[4] Patankar A, Modi P, Uppe A, Tuppekar B, Chandrakar S, Nair G, et al. COVID—19 and management of severe acute respiratory infection (SARI): A questionnaire—based study among indian healthcare professionals. Curr Health Sci J 2020; 46(2): 156-166.

[5] Sadeghi Dousari A, Taati Moghadam M, Satarzadeh N. COVID—19 (Coronavirus disease 2019): A new coronavirus disease. Infect Drug Resist 2020; 13: 2819-2828.

[6] Mehri A, Sotoodeh Ghorbani S, Farhadi—Babadi K, Rahimi E, Barati Z, Taherpour N, et al. Risk factors associated with severity and death from COVID—19 in Iran: A systematic review and meta—analysis study. J Intensive Care Med 2023; 38(9): 825-837.

[7] Thomas P, Baldwin C, Bissett B, Boden I, Gosselink R, Granger CL, et al. Physiotherapy management for COVID—19 in the acute hospital setting: Clinical practice recommendations. J Physiother 2020; 66(2): 73-82.

[8] Armstrong RA, Kane AD, Cook TM. Outcomes from intensive care in patients with COVID—19: A systematic review and meta—analysis of observational studies. Anaesthesia 2020; 75(10): 1340-1349.

[9] Lavrentieva A, Kaimakamis E, Voutsas V, Bitzani M. An observational study on factors associated with ICU mortality in Covid—19 patients and critical review of the literature. Sci Rep 2023; 13(1): 7804.

[10] Borujerdi R, Adeli SH, Mohammadbeigi A, Aliasl F, Asghari A, Hormati A, et al. Effects of Iranian polyherbal syrup (Zufa syrup) on oxygen saturation and clinical symptoms in suspected patients with COVID—19: A triple—blinded, randomized, placebo—controlled trial. Med Gas Res 2022; 12(2): 44-50.

[11] Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, evaluation, and treatment of coronavirus (COVID—19). StatPearls Publishing LLC: StatPearls Publishing; 2024.

[12] Li JL, Wang QY, Luan HY, Kang ZC, Wang CB. Effects of L—carnitine against oxidative stress in human hepatocytes: Involvement of peroxisome proliferator—activated receptor alpha. J Biomed Sci 2012; 19(1): 32.

[13] Kononov SU, Meyer J, Frahm J, Kersten S, Kluess J, Bühler S, et al. Dietary L—carnitine affects leukocyte count and function in dairy cows around parturition. Front Immunol 2022; 13: 784046.

[14] Sharma S, Aramburo A, Rafikov R, Sun X, Kumar S, Oishi PE, et al. L—carnitine preserves endothelial function in a lamb model of increased pulmonary blood flow. Pediatr Res 2013; 74(1): 39-47.

[15] Talebi SS, Ghasemi M, Etminani—Esfahani M, Mohammadi Y, Haddadi R. Effects of L—carnitine supplementation in patients with mild—to—moderate COVID—19 disease: A pilot study. Pharmacol Rep 2022; 74(6): 1296-1305.

[16] Organization WH. Living guidance for clinical management of COVID—19: Living guidance, 23 November 2021. World Health Organization; 2021.

[17] Rahmanzade R, Rahmanzadeh R, Hashemian SM, Tabarsi P. Iran's approach to COVID—19: Evolving treatment protocols and ongoing clinical trials. Front Public Health 2020; 8: 551889.

[18] Hantoushzadeh S, Shamshirsaz AA, Aleyasin A, Seferovic MD, Aski SK, Arian SE, et al. Maternal death due to COVID—19. Am J Obstet Gynecol 2020; 223(1): 109.e1-109.e16.

[19] Badaro R, Barbosa JD, de Araujo Neto CA, Machado BA, Soares MB, de Senna V, et al. A randomized clinical trial to evaluate the efficacy of L—carnitine L—tartrate to modulate the effects of SARS—CoV—2 infection. Front Nutr 2023; 10: 1134162.

[20] Liu W, Tao ZW, Wang L, Yuan ML, Liu K, Zhou L, et al. Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. Chin Med J 2020; 133(9): 1032-1038.

[21] Mardani R, Ahmadi Vasmehjani A, Zali F, Gholami A, Mousavi Nasab SD, Kaghazian H, et al. Laboratory parameters in detection of COVID—19 patients with positive RT—PCR: A diagnostic accuracy study. Arch Acad Emerg Med 2020; 8(1): e43.

[22] Duranay M, Akay H, Yilmaz FM, Senes M, Tekeli N, Yücel D. Effects of L—carnitine infusions on inflammatory and nutritional markers in haemodialysis patients. Nephrol Dial Transplant 2006; 21(11): 3211-3214.

[23] Fathizadeh H, Milajerdi A, Reiner Ž, Amirani E, Asemi Z, Mansournia MA, et al. The effects of L—carnitine supplementation on indicators of inflammation and oxidative stress: A systematic review and meta—analysis of randomized controlled trials. J Diab Metab Disord 2020; 19(2): 1879-1894.

[24] Pagano G, Manfredi C, Pallardó FV, Lyakhovich A, Tiano L, Trifuoggi M. Potential roles of mitochondrial cofactors in the adjuvant mitigation of proinflammatory acute infections, as in the case of sepsis and COVID—19 pneumonia. Inflamm Res 2021; 70(2): 159-170.

[25] Mollica G, Senesi P, Codella R, Vacante F, Montesano A, Luzi L, et al. L—carnitine supplementation attenuates NAFLD progression and cardiac dysfunction in a mouse model fed with methionine and choline—deficient diet. Dig Liver Dis 2020; 52(3): 314-323.

[26] Sahebnasagh A, Avan R, Monajati M, Hashemi J, Habtemariam S, Negintaji S, et al. L—carnitine: Searching for new therapeutic strategy for sepsis management. Curr Med Chem 2022; 29(18): 3300-3323.

[27] Yarizadh H, Shab—Bidar S, Zamani B, Vanani AN, Baharlooi H, Djafarian K. The effect of L—carnitine supplementation on exercise—induced muscle damage: A systematic review and meta—analysis of randomized clinical trials. J Am Coll Nutrit 2020; 39(5): 457-468.

[28] Li C, Ou R, Wei Q, Shang H. Carnitine and COVID—19 susceptibility and severity: A Mendelian randomization study. Front Nutrit 2021; 8: 780205.

[29] Alhasaniah AH. L—carnitine: Nutrition, pathology, and health benefits. Saudi J Biol Sci 2023; 30(2): 103555.

[30] Durazzo A, Lucarini M, Nazhand A, Souto SB, Silva AM, Severino P, et al. The nutraceutical value of carnitine and its use in dietary supplements. Molecules 2020; 25(9): 2127.

[31] Blanca AJ, Ruiz—Armenta MV, Zambrano S, Salsoso R, Miguel—Carrasco JL, Fortuño A, et al. Leptin induces oxidative stress through activation of NADPH oxidase in renal tubular cells: Antioxidant effect of L—carnitine. J Cell Biochem 2016; 117(10): 2281-2288.

[32] 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. JPEN J Parenteral Enteral Nutrit 2014; 38(6): 736-743.

[33] Ozturk MA, Kardas Z, Kardas F, Gunes T, Kurtoglu S. Effects of L—carnitine supplementation on respiratory distress syndrome development and prognosis in premature infants: A single blind randomized controlled trial. Exp Ther Med 2016; 11(3): 1123-1127.

[34] Sahebkar A. Effect of L—carnitine supplementation on circulating C—reactive protein levels: A systematic review and meta—analysis. J Med Biochem 2015; 34(2): 151-159.

[35] Sharma S, Aramburo A, Rafikov R, Sun XT, Kumar S, Oishi PE, et al. L—carnitine preserves endothelial function in a lamb model of increased pulmonary blood flow. Pediatr Res 2013; 74(1): 39-47.