l‐carnitine and cancer cachexia: Clinical and experimental aspects

Abstract

Cancer cachexia is a multifaceted syndrome characterized, among many symptoms, by extensive muscle wasting. Chronic systemic inflammation, partly triggered and sustained by cytokines, as well as increased oxidative stress contributes to the pathogenesis of this complex metabolic disorder. l-carnitine plays a central role in the metabolism of fatty acids and shows important antioxidant and anti-inflammatory properties. Systemic carnitine depletion has been described in several diseases, and it is characterized by fatigue, muscle weakness, and decreased tolerance to metabolic stress. In cachectic cancer patients, low serum carnitine levels have been reported, and this change has been suggested to play an important contributory role in the development of cachexia. Based on these data, carnitine supplementation has been tested in preliminary studies concerning human cachexia, resulting in improved fatigue and quality of life. We present here a review of clinical and experimental evidence regarding the use of carnitine supplementation in the management of cancer cachexia.

L‐Carnitine Suppresses Loss of Skeletal Muscle Mass in Patients With Liver Cirrhosis

“…Thus, carnitine had antioxidant effects that might protect against skeletal muscle loss. In patients with cancer cachexia, in which chronic systemic inflammation and increased oxidative stress are major pathogeneses and skeletal muscle loss is a major feature, carnitine supplementation is effective for symptoms of cachexia through anti‐inflammatory and oxidant effects . In this study, the inflammatory parameters, such as the neutrophil–lymphocyte ratio and C reactive protein, in patients with L‐carnitine supplementation without a reduction in ammonia tended to decrease compared to controls without reduced ammonia (http://onlinelibrary.wiley.com/doi/10.1002/hep4.1207/full).…”

Identification of anticancer drugs for hepatocellular carcinoma through personalized genome‐scale metabolic modeling

“…l ‐Carnitine has powerful antioxidant and anti‐inflammatory properties and has a decisive role in the metabolism of FAs and energy by regulating the free CoA and acyl‐CoA ratio in the mitochondria (Silverio et al , ). l ‐Carnitine is involved in the transport of activated long‐chain FAs from the cytosol to the mitochondria where these mobilized FAs can be degraded through β‐oxidation.…”

Changes in liver gluconeogenesis during the development of Walker‐256 tumour in rats

“…Inhibition of gluconeogenesis from pyruvate probably did not involve a reduction in its hepatic uptake, as there was inhibition of gluconeogenesis from alanine in the WK5 group, in a condition of higher availability of pyruvate within the hepatocytes (Table 1). Inhibition of gluconeogenesis from pyruvate may have involved, among other factors, inhibition of gluconeogenic enzymes, which catalyse reactions after the pyruvate step (Figure 7), and pro-inflammatory cytokines such as TNFa and interleukins IL1b and IL10 produced by the tumour and the tissues of the tumour-bearing host (Fearon et al 1991;Moldawer et al 1992;Yanagawa et al 1995;Noguchi et al 1996;Matthys & Billiau 1997;Metzger et al 1997;Mantovani et al 2000;Yerkovich et al 2004;Caton et al 2009;Carson & Baltgalvis 2010;Silvério et al 2011). However, the unchanged gluconeogenesis from glycerol in the WK5, WK8 and WK12 groups (Table 1) excludes the possibility of inhibition of fructose 1,6-biphosphatase and glucose 6-phosphatase, enzymes that catalyse reactions after the entry of glycerol in the gluconeogenic pathway (Figure 7).…”