Nutritional factors are among the postulated causes of fatigue, a highly prevalent symptom in the cancer population, with serious impact on patients' quality of life. Deficiency of the micronutrient carnitine may play a role by reducing energy production through fatty acid oxidation. We present preliminary data of an open-label, dose-finding study to determine safety and maximally tolerated dose (MTD) of 1 week of L-carnitine supplementation in cancer patients with fatigue and carnitine deficiency. Patients who met inclusion/exclusion criteria underwent carnitine level determination. Eighty-three percent of these patients (15/18) had carnitine deficiency. Preliminary data analysis of 13 patients showed that total carnitine increased from 30.0 +/- 6.9 to 41.0 +/- 12.1 (mean +/- SD) after 1 week of supplementation (P = 0.01), and free carnitine increased from 24.3 +/- 6.1 to 33.8 +/- 9.8 (P = 0.004). Outcome measures were fatigue (BFI score), depression (CES-D), sleep disruption (ESS), and performance status (Karnofsky). Median (min, max) BFI score at baseline was 73 (46, 82) versus 50 (3, 82) after 1-week supplementation (P = 0.009). CES-D score at baseline was 29 (16, 42) and 22 (8, 32) after 1 week (P = 0.028). ESS at baseline was 46.5 (0, 69) and 30.4 (0, 72) after 1 week (P = 0.015). Karnofsky score did not change significantly (P = 0.38). We are currently conducting a randomized, double-blind, placebo-controlled study to rigorously assess the role of L-carnitine for the treatment of fatigue and depression in cancer patients.