L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN) - a randomized multicentre trial
- Matthias Kraft†1,
- Kathleen Kraft†1,
- Simone Gärtner1,
- Julia Mayerle1,
- Peter Simon1,
- Eckhard Weber1,
- Kerstin Schütte2,
- Jens Stieler3,
- Heide Koula-Jenik4,
- Peter Holzhauer4,
- Uwe Gröber5,
- Georg Engel6,
- Cornelia Müller7,
- You-Shan Feng9,
- Ali Aghdassi1,
- Claudia Nitsche1,
- Peter Malfertheiner2,
- Maciej Patrzyk8,
- Thomas Kohlmann9 and
- Markus M Lerch1Email author
© Kraft et al.; licensee BioMed Central Ltd. 2012
Received: 16 February 2012
Accepted: 6 July 2012
Published: 23 July 2012
Cachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia.
We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g) or placebo for 12 weeks. At entry patients reported a mean weight loss of 12 ± 2,5 (SEM) kg. During treatment body-mass-index increased by 3,4 ± 1,4% under L-Carnitine and decreased (−1,5 ± 1,4%) in controls (p < 0,05). Moreover, nutritional status (body cell mass, body fat) and quality-of-life parameters improved under L-Carnitine. There was a trend towards an increased overall survival in the L-Carnitine group (median 519 ± 50 d versus 399 ± 43 d, not significant) and towards a reduced hospital-stay (36 ± 4d versus 41 ± 9d,n.s.).
While these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinically relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine.
KeywordsPancreatic adenocarcinoma L-Carnitine Quality of life Survival Cancer cachexia Fatique syndrome
Adenocarcinoma of the pancreas is highly resistant to chemo- or radiotherapy , has a 5-year survival rate of only 4% and ranks as fourth leading cause of cancer death [2–4]. One reason contributing to this high mortality is cancer cachexia, defined as an unintended weight loss of more than 10% in 6 months, which is present in more than 80% of pancreatic cancer patients . Cancer cachexia is also a predictor for reduced quality of life, increased mortality, and poor response to therapy [6–10]. A deficiency of L-Carnitine has been proposed to be an underlying cause of cancer cachexia  and tumor associated fatigue [12–14]. Although L-Carnitine can be generated via endogenous conversion from lysine and methionine, 75% of the required levels are provided from food sources. In vitro studies in human tumor cell lines have shown a positive effect of L-Carnitine regarding the inhibition of apoptosis and DNA-damage . On the other hand, L-Carnitine is well known for its potential to modulate the inflammatory response mechanisms, which is known to play the predominant role in the generation of cancer cachexia, especially in pancreatic tumor patients . We therefore conducted a multicentre trial to investigate the role of oral L-Carnitine supplementation on cancer cachexia in pancreatic cancer (CARPAN).
Data are presented as means ± SEM and 95% confidence intervals where appropriate. Statistical analysis for intention-to-treat and per-protocol analysis was done by Student’s t test and Pearson's chi-square test for parametric and Mann–Whitney-U-Test for non-parametric analysis. Quality of life data were analyzed using ANOVA. Results were considered significant when p was <0,05.
Characteristics of the study population (n = 72) at baseline visit of the study (mean ± SEM)
L-Carnitine (n = 38)
Placebo (n = 34)
64.4 ± 1.67
64.4 ± 1.65
Karnofsky performance status
76.8 ± 1.87
80.0 ± 2.16
normal BMI (kg/m²)
28.0 ± 1.01
30.1 ± 0.84
baseline visit BMI (kg/m²)
24.7 ± 0.65
24.9 ± 0.89
Phase angle (°)
4.4 ± 0.16
4.4 ± 0.17
meanweight loss (kg)*
11.4 ± 1.28
12.3 ± 1.56
ECM/BCM index **
1.5 ± 0.11
1.4 ± 0
Cell percentage (%)
41.8 ± 1.22
42.70 ± 1.21
chemotherapy (n) 35 (92%) 30 (88%)
L-Carnitine level (μmol/l)
25.3 ± 2.29
24. 8 ± 2.11
33.8 ± 1.09
33.7 ± 1.20
31.3 ± 6.55
45.5 ± 10.39
8.3 ± 0.83
6.9 ± 0.46
CA 19–9 (U/ml)
14,095 ± 32,572
18,345 ± 35,950
Cancer cachexia and malnutrition are associated with an increased risk of surgical complications and higher toxicity levels of chemotherapy. Quality of life and overall survival of colon cancer patients can improve under early nutritional intervention . L-Carnitine is critical for energy generation by mitochondrial ß-oxidation and was found depleted under chemotherapy [24–26]. Its oral supplementation can normalize nutritional L-Carnitine deficiency [27, 28] and reduce chemotherapy related side effects [29, 30]. We therefore tested whether oral L-Carnitine supplementation has a clinical benefit in patients with advanced pancreatic cancer and found that L-Carnitine can reduce malnutrition, increase bodyweight and improve body composition.
When we planned and designed the study no persuasive data for clinical endpoints existed and we had to base the initial power calculations on inflammatory markers in humans under L-Carnitine treatment. While this study must be regarded as preliminary because inflammatory markers were found to be an unsuitable primary endpoint in our setting, the CARPAN trial provides the basis for a robust sample size calculation: a conclusive study of L-Carnitine benefits ought to enrol 148 patients in each arm to show a survival benefit with 90% power, and would need 157 patients in each arm to demonstrate an improvement in tumor fatigue. The presently available data show a benefit of L-Carnitine supplementation on body weight, body composition and some aspects of quality-of-life, even though it was underpowered to determine the statistical significance of other secondary endpoints. While the loss of significant changes in BCM at week 12 and a rapid increase in body fat between week 6 and 12 was an unexpected finding it might be explained by the underlying progressive tumor disease leading to changes in body composition, irrespective of gain of weight and due to reduced physical activity and progressive sarcopenia. Both are common findings in pancreatic tumors. In this context it is important to note, that the direct influence of L-Carnitine on tumor growth has not been measured in this study and is beyond the scope of this work. Future studies are needed to address this question as only recently L-Carnitine has been reported to modify apoptosis and DNA-damage in tumor cell lines of the brain via CPT-1 C .
The CARPAN trial could suggest that the clinical benefit of an inexpensive and very well tolerated oral L-Carnitine supplementation may reach the clinical benefit level previously shown for palliative Gemcitabine chemotherapy  in pancreatic cancer patients.
Bioelectrical impedance analysis
Brief fatigue inventory
Body mass index
Body cell mass
Extra cellular mass
Standard error of the mean
Tumor nekrose faktor α.
This study was supported by the Alfried-Krupp-von-Bohlen-und-Hahlbach-Foundation (Graduate Schools Tumour Biology and Free Radical Biology), the Deutsche Krebshilfe/ Dr. Mildred-Scheel-Stiftung (109102), the Deutsche Forschungsgemeinschaft (DFGgRK840-E3/E4, MA 4115/1-2/3, NI 1297/1-1), the Federal Ministry of Education and Research (BMBFgANI-MED 03152061A and BMBF 0314107) and the European Union (EU-FP-7: EPC-TM and EU-FP7-REGPOT-2010-1). KK and SG both received a Gerhard-Domagk-Stipendium of Greifswald University Medicine made possible through unrestricted educational grants from Medinal GmbH, Greven, Germany, Fresenius Kabi Germany GmbH Bad Homburg, Germany and Nutricia GmbH, Erlangen, Germany. L-Carnitine bulk compound was kindly provided by Lonza Ltd., Basel, Switzerland.
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