Nutraceuticals and Exercise against Muscle Wasting during Cancer Cachexia

Abstract

Cancer cachexia (CC) is a debilitating multifactorial syndrome, involving progressive deterioration and functional impairment of skeletal muscles. It affects about 80% of patients with advanced cancer and causes premature death. No causal therapy is available against CC. In the last few decades, our understanding of the mechanisms contributing to muscle wasting during cancer has markedly increased. Both inflammation and oxidative stress (OS) alter anabolic and catabolic signaling pathways mostly culminating with muscle depletion. Several preclinical studies have emphasized the beneficial roles of several classes of nutraceuticals and modes of physical exercise, but their efficacy in CC patients remains scant. The route of nutraceutical administration is critical to increase its bioavailability and achieve the desired anti-cachexia effects. Accumulating evidence suggests that a single therapy may not be enough, and a bimodal intervention (nutraceuticals plus exercise) may be a more effective treatment for CC. This review focuses on the current state of the field on the role of inflammation and OS in the pathogenesis of muscle atrophy during CC, and how nutraceuticals and physical activity may act synergistically to limit muscle wasting and dysfunction.

Targeting the Activin Receptor Signaling to Counteract the Multi-Systemic Complications of Cancer and Its Treatments

“…Hence, future studies are warranted to conclusively elucidate whether larger muscles at diagnosis may play an active role in improving cancer prognosis. Further, to the extent of validating exercise as a potentially powerful therapeutic strategy in cachexia, animal models that enable exercise interventions (e.g., resistance training [226,227]) should be developed [228,229] and tested in cancer [230] together with appropriate nutrition/nutraceutical strategies [231] to elucidate whether promoting better muscle mass and/or function also ultimately affects survival in cancer.…”

Chemotherapy-Induced Myopathy: The Dark Side of the Cachexia Sphere

“…Several investigations into therapeutic strategies to mitigate the debilitating effects of cancer cachexia are underway with multiple candidates showing promise. These include exercise and multi-target pharmaceutical/nutraceutical adjuvant interventions [ 127 , 128 ] ( Figure 4 ). Herein, we summarise the current knowledge and provide insights surrounding these candidate strategies to better inform future investigations.…”

Metabolic Remodeling in Skeletal Muscle Atrophy as a Therapeutic Target

“…Among the polyphenols, epigallocatechin-3-gallate (EGCG), curcumin, resveratrol, and quercetin have been reported to reduce the catabolic pathways in cachectic muscle, by inhibiting the UPS pathway, whilst inducing IGF-1 anabolic signaling [ 197 ]. Moreover, resveratrol and quercetin are known inducers of SIRT1, thereby promoting mitochondrial biogenesis, preserving muscle oxidative capacity and increasing exercise tolerance [ 198 , 199 , 200 ], in addition to exerting anti-inflammatory, antioxidant, and anticarcinogenic effects through several mechanisms [ 201 ].…”