An Integrated Low-Volume Nutritional Countermeasure to Maintain Muscle Mass and Function During Space Exploration

Mechanical unloading, an inherent characteristic of spaceflight, results in a loss of muscle mass and muscle strength. These losses threaten the integrity of space missions and crew health upon return to Earth's gravity. Nutrition-based countermeasures represent one of the few viable intervention strategies available during long-duration spaceflight. We added leucine (0.06 g / kg lean mass / meal-1; LEU) to the regular meals served 3 • d-1 to middle-aged adults (45-60 y, representative of long-duration crew members) during 14 d of horizontal bed rest (BR) and 7 d of rehabilitation. Changes in muscle mass were assessed by dual-energy X-ray absorptiometry (DEXA); strength was evaluated with standard isokinetic dynamometry. Stable isotope tracer methodology was used to quantify muscle protein synthesis pre-BR, post-BR, and post-rehabilitation. Ongoing analysis of muscle samples for measures of protein metabolism and cell signaling continues to be batched. All subjects have tolerated the supplement (leucine or placebo) well, with no complaints. Primary findings were: 1) leucine attenuated the loss of whole body lean mass during the first 7 d of BR compared to control subjects (LEU: -0.6±0.2 kg vs. CON: -1.1±0.2 kg, p<0.05) and reduced or prevented decrements in knee extensor strength (LEU: -8±3% vs. CON: -15±3%, p<0.05), ankle extensor strength (LEU: -13±5% vs. CON: -20±5%, p<0.05), and knee extensor endurance (LEU: -2±4% vs. CON: -14±3%, p<0.05) during 14 d BR; 2) LEU maintained both post-absorptive and post-prandial MPS during BR; in contrast, BR decreased post-absorptive MPS (pre-BR: 0.061% / h-1 vs. post-BR: 0.043% / h-1, p<0.05); 3) insulin area under the curve during an oral glucose tolerance test was unchanged in LEU after BR (21±8%) but elevated in CON (52±23%, p<0.05) and whole body insulin sensitivity in LEU was significantly increased above pre-BR values after 7 d rehabilitation (17±10% vs. CON: -9±9%, p<0.05).

Our long-term goal is to identify, prevent, and remedy defects in the metabolic pathway that contribute to the loss of muscle mass and function during exposure to microgravity. Protein catabolism and muscle loss occurs in many circumstances. The regulatory mechanisms controlling protein turnover are particularly sensitive to a reduction in the neuromuscular stimulus that occurs during physical inactivity or exposure to microgravity and it is clear that muscle loss is greatly exaggerated with increasing age. Demographic data indicate that the average age of shuttle crew members has increased from 40.7 yrs in 1995 to 46.7 yrs in 2007 with an increasing number of astronauts over 50 yrs of age. We contend that the loss of muscle mass and function during spaceflight is facilitated by an age-associated, progressive impairment in the ability to mount an anabolic response to standard mixed nutrient meals. Protein supplementation is routinely employed to combat inactivity and age-related muscle loss. However, aggressive supplementation regimens are often impractical or ineffective due to issues including increased satiety, poor palatability, cost, and compliance. Enriching daily meals with a low-volume leucine supplement reduced some of the deleterious effects of inactivity on skeletal muscle. This supplement has the potential to also benefit individuals whose ability to perform physical activity is compromised (e.g., hospitalized patients, frail elders).

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