L-carnitine Not Effective for Cancer Fatigue

Jill Stein
Published: Thursday, Nov 08, 2012
Dr. Ricardo A. Cruciani

Ricardo A. Cruciani, MD

L-carnitine does not reduce fatigue in patients with cancer, according to data from the largest clinical study to date examining the effect of the popular supplement in patients with invasive malignancy and fatigue. The results come from a phase III trial showing that patients receiving a daily regimen of L-carnitine did not experience improved fatigue versus placebo on the widely validated Brief Fatigue Inventory (BFI).

Ricardo A. Cruciani, MD, vice-chairman and chief of the Pain Division at Beth Israel Medical Center in New York City, and associates randomized 376 patients with an invasive malignant disorder and moderate-to-severe fatigue 1:1 to either 1 g of oral L-carnitine twice daily or placebo over a 4-week period. Study participants were drawn from 24 sites associated with ECOG. The primary endpoint in the trial was the difference between arms in change in BFI from baseline to week 4.

The data showed that BFI-measured fatigue improved in both study groups compared with baseline (L-carnitine: -0.96; 95% CI, -1.32 to -0.60; placebo: -1.11; 95% CI, -1.44 to -0.78), with no statistically significant differences between groups (P = .57).

There were no significant differences between treatment groups on secondary endpoints, including fatigue measured by the Functional Assessment of Chronic Illness Therapy– Fatigue scale.

When analyzed separately, patients who were carnitine-deficient at baseline had no statistically significant improvement in fatigue or other outcomes after L-carnitine supplementation.

Cruciani et al cautioned that their study has “important limitations.” For example, 25% to 30% of patients did not complete evaluations, and it was not known whether those individuals had an improvement in fatigue or actually worsened. The investigators were quick to emphasize, however, that the proportion of missing follow-up evaluations is typical of that seen in prior studies that have symptoms as primary outcomes.

Table. Effect of L-Carnitine Supplementation on Fatigue From Baseline to Week 4

Subgroup L-Carnitine Placebo
n Mean* n Mean
Overall 145 -0.96 138 -1.11
Fatigue level
Mild fatigue† 43 -0.29 45 -0.72
Severe fatigue 101 -1.26 93 -1.30
Carnitine-deficient at baseline
Yes 46 -1.03 38 -1.33
No 96 -0.95 94 -1.06

*Mean = change in average daily fatigue from baseline to week 4 using the Brief Fatigue Inventory.
†Defined as score <7 for "Fatigue worst" item on Brief Fatigue Inventory.

Other issues noted by the researchers that could weaken their results include the fact that the dose and duration of L-carnitine supplementation and patient population included in the study differ from those of some other investigations that have reported favorable results, and depression and pain commonly occur in patients with advanced cancer and “could confound the fatigue analysis.”

Adults and children with chronic diseases are at increased risk of carnitine deficiency because of decreased intake and increased utilization or elimination, the authors noted. Open-label studies in adults had previously suggested that L-carnitine supplementation might reduce fatigue in patients with cancer who are carnitine-deficient due to chemotherapy, and that the supplement might also also improve sleep and depressed mood.


Cruciani RA, Zhang JJ, Manola J, et al. L-carnitine supplementation for the management of fatigue in patients with cancer: an Eastern Cooperative Oncology Group phase III, randomized, double-blind, placebo-controlled trial [published online ahead of print September 17, 2012]. J Clin Oncol. doi: 10.1200/JCO.2011.40.2180.



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