Leucine Supplementation in Cancer Cachexia: Mechanisms and a Review of the Pre-Clinical Literature

Abstract

Cancer cachexia (CC) is a complex syndrome of bodily wasting and progressive functional decline. Unlike starvation, cachexia cannot be reversed by increased energy intake alone. Nonetheless, targeted nutritional support is a necessary component in multimodal syndrome management. Due to the highly catabolic nature of cancer cachexia, amino acid supplementation has been proposed. Interestingly, leucine has been found to increase protein synthesis and decrease protein degradation via mTORC1 pathway activation. Multiple pre-clinical studies have explored the impact of leucine supplementation in cachectic tumor-bearing hosts. Here, we provide an overview of leucine’s proposed modes of action to preserve lean mass in cachexia and review the current pre-clinical literature related to leucine supplementation during CC. Current research indicates that a leucine-rich diet may attenuate CC symptomology; however, these works are difficult to compare due to methodological differences. There is need for further pre-clinical work exploring leucine’s potential ability to modulate protein turnover and immune response during CC, as well as the impact of additive leucine on tumor growth.

Amino Acids in Cancer and Cachexia: An Integrated View

“…Positive effects of Leu supplementation were observed in animals fed with a high fat diet, with attenuation of mitochondrial dysfunction, fat mass, and hyperglycemia [ 105 ]. A few studies performed in animal models of cancer cachexia have shown that a diet rich in Leu was able to stimulate, in a dose-dependent manner, protein synthesis in skeletal muscle, resulting in reduced loss of lean body mass and muscle wasting [ 111 ]. These data were supported by improvements in muscle strength, physical performance, and inflammatory status [ 111 ].…”

“…A few studies performed in animal models of cancer cachexia have shown that a diet rich in Leu was able to stimulate, in a dose-dependent manner, protein synthesis in skeletal muscle, resulting in reduced loss of lean body mass and muscle wasting [ 111 ]. These data were supported by improvements in muscle strength, physical performance, and inflammatory status [ 111 ]. Simultaneously, skeletal muscle mitochondrial biogenesis was ameliorated after Leu supplementation in tumor-bearing rats, together with the increased expression of markers related to oxidative phosphorylation and energy production [ 111 ].…”

“…Simultaneously, skeletal muscle mitochondrial biogenesis was ameliorated after Leu supplementation in tumor-bearing rats, together with the increased expression of markers related to oxidative phosphorylation and energy production [ 111 ]. Unfortunately, recent evidence suggested an increase of tumor growth rate with a Leu-rich diet, promoting cancer development and for these reasons limiting the clinical potential [ 111 ].…”

GCs-beta and B-arrestins Regulate Nrf2 via NR4As Productive Pathway Mediated by B-adrenergic for Anti-inflammation and Adopting Myocardial and Immune Functions

“…That , Ras/Erk Signaling (which activated by S6K function) are Essential for Activating Protein Synthesis by Gq Protein-Coupled Receptor [123].…”

Evaluation of Geriatric Sarcopenia and Nutrition in the Case of Cachexia before Exitus: An Observational Study for Health Professionals

“…The identification of the first signs of cachexia through non-invasive, simple methods can bring advantages in the management of this disease, with the possibility of intervening in the underlying disease. If cachexia is in the advanced phase, none of the diet-therapeutic interventions seem to reach the desired goal [ 28 , 29 , 30 ]. This study aims to clarify the correlation between BIA-measured parameters, clinical parameters, and other nutrition-related assessments.…”