Effects of oral meal feeding on whole body protein breakdown and protein synthesis in cachectic pancreatic cancer patients

Background: Pancreatic cancer is often accompanied by cachexia, a syndrome of severe weight loss and muscle wasting. A suboptimal response to nutritional support may further aggravate cachexia, yet the influence of nutrition on protein kinetics in cachectic patients is poorly understood. Methods: Eight cachectic pancreatic cancer patients and seven control patients received a primed continuous intravenous infusion of l‐[ring‐2H5]phenylalanine and l‐[3,3‐2H2]tyrosine for 8 h and ingested sips of water with l‐[1‐13C]phenylalanine every 30 min. After 4 h, oral feeding was started. Whole body protein breakdown, protein synthesis, and net protein balance were calculated. Results are given as median with interquartile range. Results: Baseline protein breakdown and protein synthesis were higher in cachectic patients compared with the controls (breakdown: 67.1 (48.1–79.6) vs. 45.8 (42.6–46.3) µmol/kg lean body mass/h, P = 0.049; and synthesis: 63.0 (44.3–75.6) vs. 41.8 (37.6–42.5) µmol/kg lean body mass/h, P = 0.021). During feeding, protein breakdown decreased significantly to 45.5 (26.9–51.1) µmol/kg lean body mass/h (P = 0.012) in the cachexia group and to 33.7 (17.4–37.1) µmol/kg lean body mass/h (P = 0.018) in the control group. Protein synthesis was not affected by feeding in cachectic patients: 58.4 (46.5–76.1) µmol/kg lean body mass/h, but was stimulated in controls: 47.9 (41.8–56.7) µmol/kg lean body mass/h (P = 0.018). Both groups showed a comparable positive net protein balance during feeding: cachexia: 19.7 (13.1–23.7) and control: 16.3 (13.6–25.4) µmol/kg lean body mass/h (P = 0.908). Conclusion: Cachectic pancreatic cancer patients have a higher basal protein turnover. Both cachectic patients and controls show a comparable protein anabolism during feeding, albeit through a different pattern of protein kinetics. In cachectic patients, this is primarily related to reduced protein breakdown, whereas in controls, both protein breakdown and protein synthesis alterations are involved

Measuring muscle protein synthesis in humans and the influence of nutritional state

In 1982 and 2011, Clinical Science published papers that used infusion of stable isotope-labeled amino acids to assess skeletal muscle protein synthesis in the fasted and fed state and before and after a period of increased intake of omega-3 fatty acids, respectively; both of these papers have been highly cited. An overview of the study designs, key findings and novel features, and a consideration of the lasting impact of these two papers is presented.The earlier paper introduced stable isotope tracer approaches in humans that showed consuming a meal will increase whole body oxidation, synthesis, and breakdown of protein, but that protein synthesis is greater than breakdown resulting in net accumulation of protein. The paper also demonstrated that consuming a meal promotes net protein synthesis in skeletal muscle.The later paper introduced the concept that omega-3 polyunsaturated fatty acids are able to improve anabolism by reporting that 8 weeks consumption of high-dose omega-3 fatty acids by healthy young and middle-aged adults increased skeletal muscle protein synthesis during a hyperaminoacidemic–hyperinsulinemic clamp compared with what was seen during the clamp at study entry. Omega-3 fatty acids also increased the phosphorylation of important signaling proteins in muscle, including mammalian target of rapamycin, p70s6k, and Akt, during the clamp.These two papers remain relevant because they offer experimental approaches to study human (patho)physiology in different contexts, they present novel insights into the impact of nutritional state (feeding) and specific nutrients (omega-3 fatty acids) on muscle protein synthesis, and they suggest ways to explore the potential of interventions to help prevent and reverse the age-, disease-, and disuse-associated decline in muscle mass.<br/

Hydrolyzed casein and whey protein meals comparably stimulate net whole-body protein synthesis in COPD patients with nutritional depletion without an additional effect of leucine co-ingestion

Photograph of a scene at Fort Cobb Lake State Park

The effect of acute tryptophan depletion on the BOLD response during performance monitoring and response inhibition in healthy male volunteers

Rationale: Serotonin (5-HT) was implicated in both clinical and experimental studies in flexible, goal-directed behavior. However, the way in which 5-HT manipulations affect brain activation patterns underlying different subprocesses of cognitive flexibility remains largely unknown. Objectives: The aim of this study was to investigate the effect of a transient lowering of 5-HT on brain activation during performance monitoring and response inhibition. Materials and methods: We used acute tryptophan depletion (ATD), a well-known method to reduce central 5-HT, to investigate the effect of a transient lowering of 5-HT on the blood-oxygen-level dependent (BOLD) response in an event-related functional MRI study. Thirteen healthy male volunteers performed a modified Go/NoGo task in a counterbalanced, placebo-controlled, within-subject design. Results: ATD significantly lowered plasma tryptophan but did not affect mood and cognitive performance. ATD decreased the BOLD response in the dorsomedial prefrontal cortex (BA 8) during performance monitoring. ATD did not affect the BOLD response during response inhibition. Conclusions: This study provides more evidence for the suggested role of 5-HT in performance monitoring. Because ATD studies have revealed inconsistent effects of ATD on performance and on brain activation, it was suggested that gender and personality traits are important variables to take into account for future research

The underappreciated role of low muscle mass in the management of malnutrition

Preserving muscle is not only crucial for maintaining proper physical movement, but also for its many metabolic and homeostatic roles. Lowmusclemass has been shown to adversely affect health outcomes in a variety of disease states (eg, chronic obstructive pulmonary disease, cancer, cardiovascular disease) and leads to an increased risk for readmission andmortality in hospitalized patients. Lowmusclemass is now included in themost recent diagnostic criteria for malnutrition. Currentmanagement strategies for malnutrition may not prioritize the maintenance and restoration of muscle mass. This likely reflects the challenge of identifying and measuring this body composition compartment in clinical practice and the lack of awareness by health care professionals of the importance that muscle plays in patient health outcomes. As such, we provide a reviewof current approaches andmake recommendations formanaging lowmusclemass and preventing muscle loss in clinical practice. Recommendations to assist the clinician in the optimalmanagement of patients at risk of lowmusclemass include the following: (1) placemuscle mass at the core of nutritional assessment andmanagement strategies; (2) identify and assess lowmuscle mass; (3) develop amanagement pathway for patients at risk of lowmusclemass; (4) optimize nutrition to focus on muscle mass gain versus weight gain alone; and (5) promote exercise and/or rehabilitation therapy to help maintain and build muscle mass. The need to raise awareness of the importance of screening andmanaging ‘at risk’ patients so it becomes routine is imperative for change to occur. Health systems need to drive clinicians to treat patients with this focused approach, and the economic benefit