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 micromol/L for males or less than 25 micromol/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 1g/day for two days, and then 2g/day for 10 days) or placebo. This double-blind phase was followed by an 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. From 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.