L-carnitine supplementation in cancer patients with fatigue and carnitine deficiency

Abstract

8025 Background: Fatigue is highly prevalent in the cancer population and nutritional factors are among the postulated causes. Deficiency of the micronutrient L-carnitine could play a role by reducing energy production through fatty acid oxidation. We are presenting preliminary data of an open-label, dose-finding study to determine safety of one week L-carnitine supplementation in cancer patients with fatigue and carnitine deficiency. Methods: Patients with cancer, fatigue and carnitine deficiency, >18 years, Karnofsky score >50, and at least one week after completion of chemotherapy, were accrued. Carnitine deficiency= free carnitine <35 mmols/L for males and <25 for females or a ratio of acyl-carnitine (total -free)/free>0.4. A standard up-down dose finding design was utilized to determine the MTD of L-carnitine given by mouth. The beginning dose was 250 mg/day; doses were increased by 500 mg up to 3000 mg/day. Three patients were enrolled at each dose level. Fatigue (BFI), depressed mood (CES-D), quality of sleep (ESS), and performance status (Karnofsky Performance Status), were assessed at baseline and after one week of L-carnitine supplementation. Results: 18 patients that fulfilled predictors for carnitine deficiency (decreased caloric intake and muscle mass) were accrued to date. 14 (age range=34–67, females=6) were deficient (78%). Three dose levels of 3 patients completed 250, 750, and 1250 mg/day. There were no adverse effects. Preliminary analysis showed mean (SD) total carnitine increment from 27.7 (7.6) to 38.1 (9) after one week of supplementation (p=0.02); free carnitine increased from 23.0 (6.2) to 30.9 (6.8) (p=0.01). Mean (SD) BFI score was 71.1 (11.0) and 43.7 (27.9) after one week (p=0.018). Median (min, max) CES-D and ESS were 31.3 (16,48), 17.5 (0, 24) and 22.0 (6, 40)(p=0.01) and 8 (0,15)(p=0.027)after one week respectively. Median Karnofsky did not change significantly (p=0.32). Conclusions: The prevalence of carnitine deficiency in this study population was (78%). This study suggests that L-carnitine supplementation is safe up to 1250 mg /day and this dose may improve fatigue, mood, sleep in cancer patients with carnitine deficiency. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ligand Pharmaceuticals Sigma Thau; UCB Pharma; Ligand; Pfizer; Perdue