The effects of l-carnitine supplementation on inflammatory factors, oxidative stress, and clinical outcomes in patients with sepsis admitted to the intensive care unit (ICU): study protocol for a double blind, randomized, placebo-controlled clinical trial

Abstract

Background Sepsis is a common cause for admission to the intensive care unit (ICU), and its incidence has been increasing. It is associated with a significant increase in serum inflammatory biomarkers such as C-reactive protein (CRP) and cytokines such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF). Sepsis is also associated with pathophysiological changes that include fluid accumulation in the lungs, eventually leading to acute respiratory distress syndrome (ARDS), tissue edema, hypotension, and acute kidney injury (AKI). Conventional therapies include antibiotics, but these may have important adverse effects, so novel therapeutic approaches are required. In animal studies, l-carnitine improves antioxidant status, and in some clinical trials, it has been shown to reduce inflammation. It has also been shown to improve respiratory distress and help maintain coenzyme A homeostasis, metabolic flexibility, promoting the normal function of the tricarboxylic acid (TCA) cycle, and oxidation of fatty acids by peroxisomes. We aim to determine the effects of very high doses of l-carnitine on inflammatory factors, oxidative stress, and clinical outcomes of patients with sepsis in ICU. Method and design In this double-blind, randomized controlled clinical trial, we will use block randomization of 60 patients with sepsis, aged between 20 and 65 years from Al-Zahra Hospital, Isfahan, Iran. The intervention group (n = 30) will receive three capsules of l-carnitine (each capsule contains 1000 mg l-carnitine; totally 3000 mg/day) for 7 days, and a control group (n = 30) will receive a placebo with the same dose and for the same duration in addition to usual care. At baseline, scores for clinical and nutritional status (Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), and NUTRIC Score) will be assessed. At beginning and end point of the study, inflammatory markers (CRP, erythrocyte sedimentation rate (ESR)), oxidative stress status (total oxidative stress (TOS), total antioxidant capacity (TAC)), and clinical variables will be evaluated also. The mortality rate will be assessed within 28 days of the beginning of the intervention. Discussion Because of the anti-inflammatory and antioxidant properties of l-carnitine, it is possible that using a high dose of 3000 mg daily of this nutritional supplement may reduce inflammation and oxidative stress and improve subsequent mortality of critically ill patients with sepsis. Trial registration Iranian Registry of Clinical Trials IRCT20201129049534N1. Registered on 2 May 2021.

The beneficial effects of l‐carnitine and infliximab in methotrexate‐induced hepatotoxicity: Emphasis on Notch1/Hes‐1 signaling

“…The anti-inflammatory effects of LC have been proved in both animal models and in human trials. [54][55][56] As expected, INF reduced the inflammatory effects by reducing the levels of TNF-α along with IL-6 and IL-1β. INF was shown to reduce TNF-α and IL-1β in lung and liver tissues subjected to CCL4.…”

L-Carnitine and Chronic Kidney Disease: A Comprehensive Review on Nutrition and Health Perspectives

“…It has also been associated with the etiology of minimal change disorder (MCD) and a potential function for B- and T-cell mediated immunity. Urinary CD80/creatinine values were highest in MCD compared to other glomerular diseases and were increased in DN with proteinuria >2 compared to controls [ 73 ]. However, several comorbidities of the kidney can be associated with other factors, such as kidney stones or urolithiasis, etc.…”

The effect of l-carnitine supplementation on mortality and clinical outcomes in ventilator-dependent critically ill patients with obesity and COVID-19: Protocol for a randomized double-blind placebo-controlled trial

“…According to previous studies, l -carnitine supplementation greater than 2 gr/day might have a greater beneficial effect. Finally, we decided to select 3 gr as the appropriate intervention with low adverse effects [ 19 , 20 ]. The l -carnitine capsule and identical placebo will be labeled by the clinical pharmacist with a unique code that will be produced by the www.sealedenvelope.com website and prescribed to the patients using a double-blind procedure.…”