L-carnitine and cancer cachexia. I. L-carnitine distribution and metabolic disorders in cancer cachexia

Abstract

Abstract. Cancer cachexia (CC), a progressive loss of body mass, is associated with decreased energy production. Abnormally low levels of L-carnitine (LC) in skeletal muscle means that mitochondrial β-oxidation of long-chain fatty acids (LCFA) does not occur efficiently in patients with CC. We assessed the influence of CC on LC distribution and the effects of parenteral lipid emulsions on plasma LC levels and urinary excretion. Fifty patients with CC were randomly assigned to total parenteral nutrition (TPN) with long-chain triglycerides (LCTs), or LCTs plus medium-chain triglycerides (MCTs) as 50/50. Patients were further separated into those with body-mass index (BMI) ≤19 kg/m 2 and BMI >19 kg/m 2 . Plasma concentrations of total LC (TC) and free LC (FC) and their urinary excretion were measured, along with skeletal muscle LC levels. On average, plasma FC and TC were higher than reference values in all patients. Patients with BMI ≤19 kg/m 2 had lower plasma FC and TC than those with BMI >19 kg/m 2 . Skeletal muscle FC in the BMI ≤19 kg/m 2 group was lower than reference value, but within the normal range in others. LC and FC urinary excretion was higher than reference values. Plasma LC and its urinary excretion were higher in patients administered pure LCTs relative to those given MCTs/LCTs. A decrease in skeletal muscle LC in cancer patients with CC (BMI ≤19 kg/m 2 ) correlates with an increase in its plasma levels and increased renal excretion. A diet of MCTs/LCTs reduces LC release from muscle to plasma and urine more effectively than LCTs.

L-carnitine and cancer cachexia. II. Effects of lipid emulsion used in total parenteral nutrition on parameters of hemostasis and inflammatory state in L-carnitine deficiency in myocytes

“…In part I of this study (14), a deficiency in LC was found in the skeletal muscles of patients with CC. Muscle degradation is considered to be the main cause, along with dietary restrictions and a decrease in endogenous LC synthesis.…”

“…In Part I of this study (14), we showed that patients with CC have significant shortages of LC in their skeletal muscles. Thus, LC deficiency is likely to be an additional factor that affects hemostasis and the immune system regardless of the type of fat emulsion used.…”

Medium-chain triglycerides/long-chain triglycerides versus long-chain triglycerides in treatment of cancer patients with major body mass loss. Survival in patients with refractory cachexia

“…Long-chain fatty acids (LCFA) require L-carnitine as a transporter into the mitochondrial matrix, while the MCT do not. The L-carnitine concentration in the skeletal muscles and serum is reduced below reference values in CC patients due to the rate of skeletal muscle degradation (secondary to reduced dietary intake of L-carnitine) and loss in urine [ 21 ]. The serum L-carnitine deficiency is replenished from muscle storage after some delay [ 22 ].…”

Effects of acute oral feeding on protein metabolism and muscle protein synthesis in individuals with cancer

“…In skeletal muscle and heart muscles, carnitine regulates the mitochondrial ratio of free coenzyme A to acyl-coenzyme A, which is required for fatty acid oxidation. People with cancer, especially those underweight or with cachexia, are at risk of and often present with carnitine deficiency (47).…”

“…People with cancer often have a decreased caloric intake and increased metabolic requirements, and numerous antineoplastic drugs can interfere with the absorption and synthesis of carnitine (47). This has led to preliminary studies on L-carnitine supplementation in people with cancer cachexia.…”