L-Carnitine Supplementation in Patients with Advanced Cancer and Carnitine Deficiency: A Double-Blind, Placebo-Controlled Study

Carnitine deficiency is prevalent in populations with chronic illness, including cancer: In a recent open-label study, L-carnitine supplementation was well tolerated and appeared to improve fatigue and other outcomes in cancer patients. To further evaluate this finding, adult patients with advanced cancer, carnitine deficiency (free carnitine more than 35 mu mol/L for males or less than 25 mu mol/L for females, or acyl/free carnitine ratio of more than 0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score of 50 or more, were randomly assigned to receive either L-carnitine (0.5 g/day for two days, followed by 1 g/day for two days, and then 2 g/day for 10 days) or placebo. This double-blind phase was followed by (in open-label phase, during which all patients received L-carnitine supplementation. for two weeks. Outcomes included the fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Linear Analog Scale Assessments (LASA), the Mini-Mental State Exam (MMSE), and the KPS. Twenty-nine patients (12 placebo, 17 L-carnitine) were included in the intent-to-treat (ITT) analysis. Front. baseline to the end of the double-blind phase, serum total and free L-carnitine increased from. 32.9 +/- 3.8 to 56.6 +/- 20.5 (P = 0.004), and from 22.9 +/- 19.4 to 45.3 +/- 17.2 (P = 0.004), respectively, in the L-carnitine-treated group, and from 28.2 +/- 10.2 to 36.2 +/- 8.7 (P = ns), and from, 22.6 +/- 7.9 to 28.7 +/- 8.6 (P = ns) in the placebo group, respectively. The planned ITT analysis revealed no significant improvement in any of the study's endpoints, and these negative findings were not, different when data from two patients who did not adhere to the protocol were eliminated. However, an exploratory covariate analysis that excluded these two protocol violators and included outcome data from, both the double-blind and open-label phases demonstrated significantly improved fatigue on the FACT-An fatigue subscale (P < 0.03), and significantly improved FACT-An functional well-being subscale (P < 0.03), and KPS (P < 0.003), in the group that started with L-carnitine during the double-blind phase. These data do not support the conclusion that L-carnitine in the doses tested reverses cancer-related fatigue in carnitine-deficient patients. However, L-carnitine supplementation does increase L-carnitine serum levels, and the positive findings in an exploratory analysis justify a larger study to determine if this strategy could be of benefit for a subpopulation of cancer patients. J Pain Symptom Manage 2009;37:622-631. (C) 2009 U.S. Cancer Pain, Relief Committee. Published by Elsevier Inc. All rights reserved.