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.

Background Critically ill patients must be monitored constantly in intensive care units (ICUs). Among many laboratory variables, nutritional status indicators are a key role in the prognosis of diseases. We investigated the effects of l-carnitine adjunctive therapy on monitoring variables in critical illness. Method A prospective, double-blind, randomized controlled trial was implemented in a medical ICU. Participants were 54 patients, aged > 18 years, with multiple conditions, randomly assigned to receive 3 g l-carnitine per day or placebo, along with enteral feeding, for 1 week. Primary outcomes included monitoring variables related to nutritional status. Result Of 54 patients randomly assigned, 51 completed the trial. Serum albumin (Alb) (P-value: 0.001), total protein (P-value: 0.003), and calcium (Ca) (0.044) significantly increased in the intervention vs. control group. Alanine transaminase (ALT) (0.022), lactate (<0.001), creatinine (Cr) (0.005), and international normalized ratio (INR) (0.049) decreased meaningfully in the intervention vs. control group. Conclusion l-Carnitine supplementation in critically ill patients can improve several parameters including INR, Cr, ALT, lactate, Ca, Alb, and total protein. Trial registration Iranian Registry of Clinical Trials IRCT 20151108024938N2. This trial was approved by the Research Ethics Committee of Mashhad University of Medical Sciences (registration code: IR.MUMS.fm.REC.1396.671) (available at https://en.irct.ir/trial/30748, May 2018).

Background Critically ill patients must be monitored constantly in intensive care units (ICU). Among many laboratory variables, nutritional status indicators are a key role in the prognosis of diseases. We investigated the effects of L-carnitine adjunctive therapy on monitoring variables in critical illness. Method A prospective, double-blind, randomized controlled trial was implemented in a medical ICU. Participants were 54 patients, aged > 18 years, with multiple conditions, randomly assigned to receive 3 gr L-carnitine per day or placebo, along with enteral feeding, for 1 week. Primary outcomes included monitoring variables related to nutritional status. Result Of 54 patients randomly assigned, 51 completed the trial. Serum albumin (Alb) (P value: 0.001), total protein (P value: 0.003), and calcium (Ca) (0.044) significantly increased in the intervention vs. control group. Alanine transaminase (ALT) (0.022), lactate (< 0.001), creatinine (Cr) (0.005), and international normalized ratio (INR) (0.049) decreased meaningfully in the intervention vs. control group. Conclusion L-carnitine supplementation in critically ill patients can improve several parameters including INR, Cr, ALT, Lactate, Ca, Alb, and total protein. Trial Registration: This trial was approved by the Research Ethics Committee of Mashhad University of Medical Sciences (registration code: IR.MUMS.fm.REC.1396.671) and was registered in the Iranian Registry of Clinical Trials (registration code: IRCT 20151108024938N2) (Available in https://en.irct.ir/trial/30748).

Context Cardiovascular disease is the leading cause of death worldwide. Low-calorie, low-fat therapeutic diets (TDs) developed by the US National Cholesterol Education Program, ie, the Step I and II diets and the therapeutic lifestyle changes diet, are approximately similar and are the initial therapeutic interventional approaches for lifestyle modification. Objective This systematic review with meta-analysis was undertaken to evaluate the effects of TDs diet on blood lipids, apolipoprotein A-1, apolipoprotein B, blood pressure, fasting blood glucose, and insulin. Data Sources A comprehensive search of the PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar databases until October 2022 was performed to identify clinical trials investigating the effects of TDs on the aforementioned parameters. Data Extraction One investigator screened the records and extracted data, and another reviewed the extracted data. Data Analysis A total of 910 records were retrieved. After records were screened for eligibility, 34 clinical trials met the inclusion criteria. The pooled analysis from the random-effects model revealed a significant reduction in total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-1, and apolipoprotein B in the TD intervention group vs the control group. The overall effects of TDs on fasting blood glucose, insulin, and blood pressure were not significant, but the results of subgroup analysis revealed a significant reduction in fasting blood glucose with the Step II diet and an intervention duration of more than 24 weeks. For blood pressure, the Step I diet and an intervention duration of more than 24 weeks resulted in significant reduction. There was no evidence of publication bias, but strong heterogeneity was observed. Conclusion Therapeutic diets have promising effects on lipid profile parameters, glycemic indexes, and blood pressure, which can promote cardiovascular health. Systematic Review Registration PROSPERO registration no. CRD42021259355.