Nutritional Interventions in Cancer Cachexia: Evidence and Perspectives From Experimental Models

Abstract

Cancer cachexia is a complex metabolic syndrome characterized by involuntary skeletal muscle loss and is associated with poor clinical outcome, decreased survival and negatively influences cancer therapy. No curative treatments are available for cancer cachexia, but nutritional intervention is recommended as a cornerstone of multimodal therapy. Optimal nutritional care is pivotal in the treatment of cancer cachexia, and the effects of nutrients may extend beyond provision of adequate energy uptake, targeting different mechanisms or metabolic pathways that are affected or deregulated by cachexia. The evidence to support this notion derived from nutritional intervention studies in experimental models of cancer cachexia is systematically discussed in this review. Moreover, experimental variables and readout parameters to determine skeletal muscle wasting and cachexia are methodologically evaluated to allow critical comparison of similar studies. Single- and multinutrient intervention studies including qualitative modulation of dietary protein, dietary fat, and supplementation with specific nutrients, such as carnitine and creatine, were reviewed for their efficacy to counteract muscle mass loss and its underlying mechanisms in experimental cancer cachexia. Numerous studies showed favorable effects on impaired protein turnover and related metabolic abnormalities of nutritional supplementation in parallel with a beneficial impact on cancer-induced muscle wasting. The combination of high quality nutrients in a multitargeted, multinutrient approach appears specifically promising, preferentially as a multimodal intervention, although more studies investigating the optimal quantity and combination of nutrients are needed. During the review process, a wide variation in timing, duration, dosing, and route of supplementation, as well as a wide variation in animal models were observed. Better standardization in dietary design, and the development of experimental models that better recapitulate the etiology of human cachexia, will further facilitate successful translation of experimentally-based multinutrient, multimodal interventions into clinical practice.

The Utility of Body Composition Assessment in Nutrition and Clinical Practice: An Overview of Current Methodology

“…The routine assessment of body composition has also shown clinical significance for the treatment of cancer, specifically as it pertains to cachexia and lymphedema. Cancer cachexia falls under the umbrella of sarcopenia, where it is defined as a multifactorial syndrome that causes extreme weight loss and muscle wasting, with or without the loss of fat [ 31 , 32 ]. Cachexia can occur in up to 80% of patients with advanced stage cancer and has been associated with nearly 20% of cancer-related deaths [ 33 ].…”

Creatine in T Cell Antitumor Immunity and Cancer Immunotherapy

“…The safety of long-term creatine supplementation in both healthy individuals and patients has been well documented, which provides a clear and expedient path forward for utilizing creatine supplementation to treat cancer [ 13 , 64 , 96 , 97 , 98 , 99 ]. Additionally, creatine supplementation can augment muscle and enhance strength, which may also benefit cancer patients suffering from cachexia at their late stages [ 63 , 64 , 100 , 101 ]. Both oral and intravenous administration routes can be effective in animal tumor models [ 44 ].…”

“…These results suggest that creatine supplementation can function as an adjunctive therapeutic intervention with other anticancer agents. Moreover, given the beneficial effects of creatine on muscle mass and physical function, emerging evidence has suggested that creatine supplementation may also have therapeutic potential for attenuating cancer-related weight loss and maintaining muscle function for cancer patients [ 63 , 64 ]. However, application in various cancer contexts has just began and further studies are needed to fully understand the impact of creatine supplementation on clinical outcomes in the cancer patient population at a risk of muscle wasting.…”

Novel Nutrition-Based Nomograms to Assess the Outcomes of Lung Cancer Patients Treated With Anlotinib or Apatinib

“…These factors may explain the relatively strong correlation between muscle loss and mortality. Although cancer cachexia cannot be treated with nutritional therapy alone, optimal nutritional care is recommended as a cornerstone of multimodal therapy (39). Getting enough dietary protein is a prerequisite for the maintenance or gain of skeletal muscle mass (40), whereas, the muscle wasting associated with cancer is troublesome and cannot be completely reversed with enhanced nutritional support (1).…”