|عنوان فارسی مقاله:||سنتز پروتئین ماهیچه در بیماران مبتلا به سرطان می تواند با مواد غذایی پزشکی خاص فرموله شده تحریک شود|
|عنوان انگلیسی مقاله:||Muscle protein synthesis in cancer patients can be stimulated with a specially formulated medical food|
|رشته های مرتبط:||پزشکی، زیست شناسی، ایمنی شناسی پزشکی، خون و آنکولوژی، علوم سلولی و مولکولی، میکروبیولوژی و علوم تغذیه|
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|نشریه||الزویر – Elsevier|
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Objective: Maintenance of muscle mass is crucial to improving outcome and quality of life in cancer patients. Stimulating muscle protein synthesis is the metabolic basis for maintaining muscle mass, but in cancer patients normal dietary intake has minimal effects on muscle protein synthesis. Adding leucine to high protein supplements stimulates muscle protein synthesis in healthy older subjects. The objective was to determine if a specially formulated medical food, high in leucine and protein, stimulates muscle protein synthesis acutely in individuals with cancer to a greater extent than a conventional medical food. Design: A randomized, controlled, double-blind, parallel-group design was used in 25 patients with radiographic evidence of cancer. Patients were studied before their cancer treatment was started or 4 weeks after their treatment was completed or halted. The fractional rate of muscle protein synthesis (FSR) was measured using the tracer incorporation technique with L-[ring-13C6]-phenylalanine. The experimental group (n ¼ 13) received a medical food containing 40 g protein, based on casein and whey protein and enriched with 10% free leucine and other specific components, while the control group (n ¼ 12) was given a conventionally used medical food based on casein protein alone (24 g). Blood and muscle samples were collected in the basal state and 5h hours after ingestion of the medical foods. Results: The cancer patients were in an inflammatory state, as reflected by high levels of C-reactive protein (CRP), IL-1b and TNF-a, but were not insulin resistant (HOMA). After ingestion of the experimental medical food, plasma leucine increased to about 400 mM as compared to the peak value of 200 mM, after the control medical food (p < 0.001). Ingestion of the experimental medical food increased muscle protein FSR from 0.073 (SD: 0.023) to 0.097 (SD: 0.033) %/h (p ¼ 0.0269). In contrast, ingestion of the control medical food did not increase muscle FSR; 0.073 (SD: 0.022) and 0.065 (SD: 0.028) %/h. Conclusions: In cancer patients, conventional nutritional supplementation is ineffective in stimulating muscle protein synthesis. This anabolic resistance can be overcome with a specially formulated nutritional supplement.
Cancer is often associated with a constellation of responses which together lead to cachexia. The term cachexia has most recently been defined and refers to “.a complex metabolic syndrome characterized by loss of muscle.”. 1 A crucial characteristic is that the muscle wasting is more rapid in cachexia than would be expected to occur due to decreased food intake alone, although anorexia is often one of several responses leading to cachexia. In addition to loss of appetite, metabolic changes occur in cancer patients that may amplify the loss of muscle. These metabolic responses may result from inflammation, insulin resistance, hypogonadism, or other causes.2 Cachexia and resulting muscle loss have been linked to poor outcomes in a variety of cancers,2 and therefore it can be hypothesized that a nutritional approach could help to minimize the effects of cachexia. There have not been extensive studies of protein metabolism in cancer patients. Whole body protein turnover appears to be elevated in post-absorptive cancer patients compared to normal individuals without cancer.3e5 The response is not simply due to weight loss.6 Despite the accelerated whole body protein turnover in patients prior to significant weight loss, the rate of muscle protein synthesis has been reported to be reduced in patients with established cachexia.7 Muscle protein is generally diminished in cancer patients, with deleterious effects on clinical outcome.1,8 Increasing muscle mass is important as recurrence of cancer in treated patients is directly related to the extent of muscle loss.
2. Are cancer patients resistant to stimulating protein synthesis?
In the presence of systemic inflammation, it appears to be extremely difficult to achieve whole body protein anabolism in cancer patients.9 It therefore seems that although food intake should be increased in cachectic cancer patients, gains in lean body mass are difficult to achieve unless specific metabolic abnormalities, like inflammation, are targeted.9 In cancer animal models, we observed a reduced postoperative increase of protein degradation, suggesting disturbed amino acid response capabilities in cancer.10e15 The metabolic basis for maintenance of lean body mass is that following a meal the stimulation of protein synthesis exceeds protein breakdown sufficiently to balance the net loss of protein in the post-absorptive or fasted state. Significant loss of lean body mass will occur if the protein synthetic response to anabolic stimuli such as amino acids is suppressed over a period of time. We therefore anticipate that the normal anabolic action of amino acids or protein on muscle protein synthesis is suppressed in cancer patients.