Article

Efficacy of L-carnitine administration on fatigue, nutritional status, oxidative stress, and related quality of life in 12 advanced cancer patients undergoing anticancer therapy

Department of Medical Oncology, University of Cagliari, Monserrato, Italy.
Nutrition (Impact Factor: 3.05). 03/2006; 22(2):136-45. DOI: 10.1016/j.nut.2005.06.003
Source: PubMed

ABSTRACT Fatigue is a multidimensional symptom that is described in terms of perceived energy, mental capacity, and psychological status: it can impair daily functioning and lead to negative effects on quality of life. It is one of the most common side effects of chemotherapy and radiotherapy. In recent studies, l-carnitine (LC) supplementation has been demonstrated to be able to improve fatigue symptoms in patients with cancer.
In the present study we tested the efficacy and safety of LC supplementation in a population of patients who had advanced cancer and developed fatigue, high blood levels of reactive oxygen species, or both. As outcome measures we evaluated fatigue and quality of life in relation to oxidative stress, nutritional status, and laboratory variables, mainly levels of reactive oxygen species, glutathione peroxidase, and proinflammatory cytokines. From March to July 2004, 12 patients who had advanced tumors (50% at stage IV) at different sites were enrolled (male-to-female ratio 2:10, mean age 60 y, range 42-73). Patients were only slightly anemic (hemoglobin 10.9 g/dL) and hemoglobin levels did not change after treatment. LC was administered orally at 6 g/d for 4 wk. All patients underwent antineoplastic treatment during LC supplementation.
Fatigue, as measured by the Multidimensional Fatigue Symptom Inventory-Short Form, decreased significantly, particularly for the General and Physical scales, and for quality of life in each subscale of quality of life in relation to oxidative stress. Nutritional variables (lean body mass and appetite) increased significantly after LC supplementation. Levels of reactive oxygen species decreased and glutathione peroxidase increased but not significantly. Proinflammatory cytokines did not change significantly.
Improvement of symptoms with respect to fatigue and quality of life in relation to oxidative stress may be explained mainly by an increase in lean body mass, which may be considered the most important nutritional or functional parameter in assessing the cachectic state of patients. In this view, fatigue with related symptoms can well be considered an important constituent of cancer-related anorexia cachexia syndrome.

Download full-text

Full-text

Available from: Giovanni Mantovani, Aug 13, 2015
0 Followers
 · 
137 Views
  • Source
    • "Rationale for treatment plan The agents included in our combined treatment approach have been selected on the basis of our previously published studies carried out in patients with cancer cachexia [11] [12] with the following rationale. L-Carnitine plays a pivotal role in modulating cell energy metabolism [13]. The cyclooxygenase-2 inhibitor celecoxib is able to inhibit the inflammatory process and has an effect on weight loss [14]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Myelofibrosis (MF) is characterized by shortened survival and a greatly compromised quality of life. Weight loss and cachexia seem to be the most important factors influencing survival in myelofibrosis patients. We aimed to assess the efficacy of an integrated supportive therapy in improving cachexia and MF-related symptoms. Methods We report a case of a single MF patient who presented weight loss and cachexia associated with severe anemia, fatigue, fever and bone pain. The circulating levels of inflammatory, oxidative stress parameters, hepcidin and erythropoietin were evaluated and were above normal ranges. The patient was treated with a multitargeted approach specifically developed for cachexia including oral L-carnitine, celecoxib, curcumin, lactoferrin and subcutaneous recombinant human erythropoietin (EPO)-α. Results Surprisingly, after 1 year, the protocol obtained in addition to improving cachexia features, the remission of all MF symptoms, associated with a reduction of inflammatory, oxidative stress parameters, hepcidin and EPO. Conclusions Since our protocol was targeted to inflammation and the metabolic state, its effectiveness may emphasize the role of inflammation in the pathogenesis of MF symptoms and gives a hint for the study of new integrated therapeutic strategies.
    Nutrition 08/2014; 31(1). DOI:10.1016/j.nut.2014.07.016 · 3.05 Impact Factor
  • Source
    • "In cancer patients with cachexia, low-serum carnitine levels have been often reported (Vinci et al. 2005; Malaguarnera et al. 2006), and this change has been suggested to play an important contributory role in the development of cachexia (Vinci et al. 2005). In addition, many studies demonstrate that L-carnitine supplementation yields clinical benefits to cancer patients (Cruciani et al. 2004; Gramignano et al. 2006; Laviano et al. 2006; Hoang et al. 2007; Mantovani et al. 2008). It was our aim to examine the effect of L-carnitine supplementation upon the disrupted lipid pathways in the liver of tumour-bearing rats. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cancer cachexia causes metabolic alterations with a marked effect on hepatic lipid metabolism. L-Carnitine modulates lipid metabolism and its supplementation has been proposed as a therapeutic strategy in many diseases. In the present study, the effects of L-carnitine supplementation on gene expression and on liver lipid metabolism-related proteins was investigated in cachectic tumour-bearing rats. Wistar rats were assigned to receive 1 g/kg of L-carnitine or saline. After 14 days, supplemented and control animals were assigned to a control (N), control supplemented with L-carnitine (CN), tumour-bearing Walker 256 carcinosarcoma (TB) and tumour-bearing supplemented with L-carnitine (CTB) group. The mRNA expression of carnitine palmitoyltransferase I and II (CPT I and II), microsomal triglyceride transfer protein (MTP), liver fatty acid-binding protein (L-FABP), fatty acid translocase (FAT/CD36), peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and organic cation transporter 2 (OCTN2) was assessed, and the maximal activity of CPT I and II in the liver measured, along with plasma and liver triacylglycerol content. The gene expression of MTP, and CPT I catalytic activity were reduced in TB, who also showed increased liver (150%) and plasma (3.3-fold) triacylglycerol content. L-Carnitine supplementation was able to restore these parameters back to control values (p<0.05). These data show that L-carnitine preserves hepatic lipid metabolism in tumour-bearing animals, suggesting its supplementation to be of potential interest in cachexia.
    Amino Acids 04/2011; 42(5):1783-92. DOI:10.1007/s00726-011-0898-y · 3.65 Impact Factor
  • Source
    • "A recent report shows that patients treated with carnitine display reduced fatigue and increased appetite and lean body mass with respect to nontreated patients. In addition, ROS levels decreased and GPX increased [132]. These data suggest that reduction of oxidative stress in cancer patients is associated with improved muscle mass and function. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Changes in the skeletal muscle protein mass frequently occur in both physiological and pathological states. Muscle hypotrophy, in particular, is commonly observed during aging and is characteristic of several pathological conditions such as neurological diseases, cancer, diabetes, and sepsis. The skeletal muscle protein content depends on the relative rates of synthesis and degradation, which must be coordinately regulated to maintain the equilibrium. Pathological muscle depletion is characterized by a negative nitrogen balance, which results from disruption of this equilibrium due to reduced synthesis, increased breakdown, or both. The current view, mainly based on experimental data, considers hypercatabolism as the major cause of muscle protein depletion. Several signaling pathways that probably contribute to muscle atrophy have been identified, and there is increasing evidence that oxidative stress, due to reactive oxygen species production overwhelming the intracellular antioxidant systems, plays a role in causing muscle depletion both during aging and in chronic pathological states. In particular, oxidative stress has been proposed to enhance protein breakdown, directly or by interacting with other factors. This review focuses on the possibility of using antioxidant treatments to target molecular pathways involved in the pathogenesis of skeletal muscle wasting.
    Free Radical Biology and Medicine 10/2009; 47(7-47):906-916. DOI:10.1016/j.freeradbiomed.2009.07.002 · 5.71 Impact Factor
Show more