In this study, the efficacy of L-carnitine supplementation as a treatment for fatigue in patients with cancer was evaluated. It was a double-blind, placebo-controlled trial. Patients with invasive malignancies and fatigue were randomly assigned to either 2g per day of L-carnitine oral supplementation or matching placebo. The primary end point was the change in average daily fatigue from baseline to week 4 using the Brief Fatigue Inventory (BFI). The results showed that three hundred and seventy-six patients were randomly assigned to treatment with L-carnitine supplementation or placebo. L-carnitine supplementation resulted in signficant carninite plasma level increase by week 4. The primary outcome, fatigue, measured using the BFI, improved in both arms compared with baseline. There were no statistically significant differences between arms. Secondary outcomes, including fatigue measured by the Functional Assessment of Chronic Illness Therapy-Fatigue instrument, depression, and pain, did not show significant differences between arms. A separate analysis of patients who were carnitine-deficient at baseline did not show statistically significant improvement in fatigue or other outcomes after L-carnitine supplementation. The authors conclude that four weeks of 2g per day of L-carnitine did not improve fatigue in patients with invasive malignancies and good performance status. J Clin Oncol. 2012. PMID: 22987089.