Author: Journal of Pain and Symptom Management
Date: 5 December 2006
INTRODUCTION:Fatigue is extremely prevalent in the cancer population, particularly among those with advanced illness.The underlying causes for fatigue are multifactorial and include the disease itself, antineoplastic therapies, and diverse comorbidities such as anemia, poor nutrition, deconditioning,mood disorders, centrally acting drugs, and varied endocrine and metabolicabnormalities.Micronutrient deficiencies may be amongthe nutritional and metabolic disorders that influence the development of fatigue.Carnitine,a micronutrient involved in the productionof energy at the cellular level, is commonly deficient in chronically ill patients and has been considered a candidate molecule potentially responsible for some cases of cancer-related fatigue. Winter et al. reported that 53% of patients with chronic illness had carnitine deficiency,8 a finding confirmed in a surveyof cancer patients age matched to normal controls.Esteban-Cruciani et al. identified carnitine deficiency in a high proportion of pediatric patients with chronic illness, including acquired immune deficiency syndrome and cancer.Carnitine deficiency may predispose tochronic fatigue by impairing utilization oflong chain fatty acids in energy metabolism.Long chain fatty acids are the preferred source of energy by muscle and cardiac cells because they have a high yield of adenosine triphosphate(ATP), their consumption does not compromise other cellular functions, and they can be stored in large quantities.Carnitine is required to translocate long chainfatty acid substrate into the cell, where it is metabolized to release energy.Patient with cancer are at risk for carnitine deficiency due to decreased oral intake and increased renal losses. Concerns that L-carnitinesupplementation could accelerate cancer progression or interfere with some chemotherapies have not been confirmed in preclinica lstudies.The hypothesis that L-carnitine treatment could improve cancer-related fatigueor lead to other positive outcomes deserves further evaluation. The first step inthis process is to assess safety and tolerability of clinically relevant doses of L-carnitine while better defining a dose range associated with symptom effects for future controlled trials.These aims were pursued through a Phase I/II open-label trial in a population with advanced cancer. A preliminary analysis of some of these data was reported previously.
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