Abstract
Cachexia is a significant clinical problem associated with very poor quality of life, reduced treatment tolerance and outcomes, and a high mortality rate. Mechanistically, any sizeable loss of skeletal muscle mass must be underpinned by a structural imbalance between muscle protein synthesis and breakdown rates. Recent data indicate that the loss of muscle mass with aging is, at least partly, attributed to a blunted muscle protein synthetic response to protein feeding. Whether such anabolic resistance is also evident in conditions where cachexia is present remains to be addressed. Only few data are available on muscle protein synthesis and breakdown rates in vivo in cachectic cancer patients. When calculating the theoretical changes in basal or postprandial fractional muscle protein synthesis and breakdown rates that would be required to lose 5% of body weight within a six-month period, we can define the changes that would need to occur to explain the muscle mass loss observed in cachectic patients. If changes in both post-absorptive and postprandial muscle protein synthesis and breakdown rates contribute to the loss of muscle mass, it would take alterations as small as 1%–2% to induce a more than 5% decline in body weight. Therefore, when trying to define impairments in basal and/or postprandial muscle protein synthesis or breakdown rates using contemporary stable isotope methodology in cancer cachexia, we need to select large homogenous groups of cancer patients (>40 patients) to allow us to measure physiological and clinically relevant differences in muscle protein synthesis and/or breakdown rates. Insight into impairments in basal or postprandial muscle protein synthesis and breakdown rates in cancer cachexia is needed to design more targeted nutritional, pharmaceutical and/or physical activity interventions to preserve skeletal muscle mass and, as such, to reduce the risk of complications, improve quality of life, and lower mortality rates during the various stages of the disease.
Highlights
The rapid weight loss that accompanies cancer is known as cancer cachexia
To evaluate whether changes in post-absorptive muscle protein synthesis and/or breakdown rates contribute to the muscle wasting observed in cachectic cancer patients, relatively large cohorts of as much as
Directions synthesis4.and breakdown rates contribute to the muscle wasting observed in cachectic cancer patients
Summary
The rapid weight loss that accompanies cancer is known as cancer cachexia. Cachexia is associated with impaired physical function [1], reduced tolerance to anticancer therapy [2], and increased mortality [3]. 20 kg/m2 and ongoing weight loss of more than 2%, or show an appendicular skeletal muscle index consistent with sarcopenia and any degree of weight loss >2% are generally classified as suffering from cachexia This consensus definition [10] reflects the complex interplay between reduced food intake and metabolic impairments and identifies the loss of skeletal muscle mass as being key in the development of functional and metabolic impairments in patients. This supports the concept that skeletal muscle mass can be regarded as both a marker for the syndrome as well as an important therapeutic target. Only few data are available on the impact of tumor burden and the stage of the disease and its treatment on basal or postprandial muscle protein synthesis and breakdown rates in vivo in cachectic cancer patients [13,14,15,16]
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