Abstract
            Introduction: Cancer-related fatigue (CRF) is a common and debilitating symptom that significantly impacts  patients’ quality of life and daily functioning. L-carnitine, a naturally occurring amino acid derivative  involved in energy metabolism, has been suggested as a potential therapeutic agent to alleviate fatigue.  
  Objectives: This study aimed to assess the effectiveness of L-carnitine supplementation in fatigue management  among cancer patients.  
  Patients and Methods: This randomized, double-blind clinical trial conducted at Imam Hossein hospital  enrolled 90 cancer patients receiving platinum-based chemotherapy between September 2024 and June  2025. Participants were randomly assigned to receive either L-carnitine or a placebo, with 45 patients  in each group. Eligible patients were over 18 years, experiencing fatigue, and provided informed written  consent. Demographic and clinical data were collected by a trained researcher who was blinded to the  group allocation. Fatigue levels were assessed using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) questionnaire at baseline, and at four and eight weeks. The primary outcome was the  comparison of FACIT-F scores both between and within the L-carnitine and control groups throughout the  study.  
  Results: The study results showed that although the fatigue scores were similar between the L-carnitine and  control groups at baseline, the L-carnitine group experienced a significantly greater improvement in fatigue  over time. By the fourth week, participants receiving L-carnitine exhibited significantly higher improvements  in fatigue scores compared to the control group, and this advantage was even more pronounced by the  eighth week. Additionally, the L-carnitine group continued to show a meaningful increase in fatigue score  improvements between the fourth and eighth weeks, while the control group’s scores remained relatively  stable during that period.  
  Conclusion: L-carnitine appears to be a safe and promising adjunctive therapy for managing CRF in patients  receiving platinum-based chemotherapy. Incorporation of L-carnitine supplementation into supportive care  protocols may improve patient outcomes and quality of life.  
  Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trials with code  (identifier: IRCT20241112063688N1; https://irct.behdasht.gov.ir/trial/80160), and ethical code from  Shahid Beheshti University of Medical Sciences (IR.SBMU.MSP.REC.1403.289; https://ethics.research.ac.ir/EthicsProposalView.php?id=492026).