L-carnitine supplementation improves fatigue, mood and sleep in cancer patients with fatigue and carnitine deficiency

Abstract

8588 Background: Carnitine is a natural aminoacid derivative that plays a crucial role in cellular energy metabolism. To determine the dose and tolerability we conducted a phase II study with increasing doses of L-carnitine supplementation. In a preliminary analysis, we reported that L-carnitine could improve fatigue, mood and sleep. (Cruciani et al., 2004). Analysis of the full dataset has confirmed and extended these findings. Methods: Patients had active cancer, fatigue and a Karnofsky ≥50. Carnitine deficiency was defined as free carnitine <35 μm]/L for males and <25 for females (normal range 35–67 and 25–55 respectively), or a ratio of acyl/free carnitine >0.4. We utilized a standard maximum tolerated dose (MTD) design, with 3 patients assigned to each successive dose group, starting at 250 mg/day and increasing in each group by 500 mg/day to a maximum dose target of 3000 mg/day. Fatigue (measured by the BFI), depressed mood (CES-D), quality of sleep (ESS), and performance status (Karnofsky), as well as carnitine serum levels were assessed at baseline and after one week of L-carnitine supplementation. Results: Seven groups of three patients each received L-carnitine supplementation for a week with 250, 750, 1,250, 1,750, 2,250, 2,750 or 3,000 mg/day. Of the 27 patients accrued 21 completed the study. Of these, 17 (mean (SD) age = 63.0 (18), females=8) showed an increase in serum L-carnitine levels. The median (min, max) total carnitine increased from 31 (21, 68) to 51 (29, 111) (p < 0.001) and the free carnitine increased from 25.0 (17, 48) to 39 (25, 82) (p < 0.001). The median (min, max) BFI score at baseline was 63 (36, 81) versus 39 (8, 82) after one week (p<0.001). There was also a significant dose response for BFI (r = -0.61, p = 0.01). Median (min, max) CES-D at baseline was 31. (4, 48) and 18.0 (0, 40) after one-week (p = 0.001). Median (min, max) ESS at baseline was 13.7 (2, 22) and 10.3 (1, 18) after one week (p=0.003). Median Karnofsky score did not change (pre and post = 70). Side effects were not observed in any of the groups. Conclusions: This study suggests that L-carnitine is safe up to 3,000 mg/day. Supplementation was associated with improvements in fatigue and depression scores. Fatigue improved in a dose dependent manner. [Table: see text]