Muscle protein synthesis in cancer patients can be stimulated with a specially formulated medical food

Abstract

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-(13)C(6)]-phenylalanine. The experimental group (n = 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 = 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-1 β and TNF-α, but were not insulin resistant (HOMA). After ingestion of the experimental medical food, plasma leucine increased to about 400 μM as compared to the peak value of 200 μM, 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 = 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.

Fig. 1

Study design. Stable isotope infusion was a primed-continuous L-[ring-¹³C₆]phenylalanine infusion.

Fig. 2

Plasma leucine, isoleucine, valine and phenylalanine levels after intake of the medical foods. A significant groups effect was observed with respect to leucine (P < 0.001), but not for isoleucine, valine or phenylalanine (P > 0.35 for all).

Fig. 3

Enrichment of L-[ring-¹³C₆]phenylalanine in plasma (top panel) and muscle (middle panel) samples. The whole body rate of appearance of phenylalanine in the bottom panel.

Fig. 4

Muscle protein fractional synthetic rate (FSR) in cancer patients in the post-absorptive state and after intake of a medical food, calculated from the intracellular MPE of Phenylalanine M+6. The postabsorbative FSR means of the groups were not found to be significantly different (P = 0.43); however, mean FSR of the experimental group (N = 12) was found to be significantly greater than that of the control group (N = 12) (ANCOVA P = 0.023).

Fig. 5

Plasma glucose and insulin levels after intake of the medical food in the experimental and control groups. There was no significant group-by-time interaction for glucose and insulin levels (P > 0.10). There was significant group effect for glucose (p = 0.044), but not for insulin (P = 0.553). For both glucose and insulin, a signicant time effect was observed (P < 0.001).