We propose that enriching daily meals with a low-volume leucine supplement will reduce the deleterious effects of microgravity on skeletal muscle and facilitate recovery during rehabilitation. We employed our established 14 day bed rest protocol to model the skeletal muscle unloading that occurs during microgravity. We also examined recovery of muscle mass and functional capacity during a 7 day rehabilitation period. We studied 2 groups: CON (Bedrest/Recovery + Placebo), LEU (Bedrest/Recovery + Leucine). We assessed: a) markers of translation initiation, b) muscle protein synthesis, c) muscle mass and body composition, and d) strength and aerobic capacity.

We tested the following hypotheses: 1. Bedrest will blunt the anabolic response to a mixed nutrient meal, facilitating a loss of muscle mass and functional capacity that is only partially restored during rehabilitation. 2. Enriching daily meals with leucine will promote protein synthesis and maintain the anabolic response to mixed nutrient meal ingestion. This will preserve lean muscle mass and function during bedrest and facilitate the recovery of functional and metabolic capacity during rehabilitation. This project builds on our recent series of bed rest studies and seeks to provide a refined and practical countermeasure that is supported by comprehensive mechanistic evidence.

Primary findings were: 1) leucine attenuated the loss of whole body lean mass during the first 7 d of bed rest 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 bed rest; 2) LEU maintained both post-absorptive and post-prandial MPS during bed rest; in contrast, bed rest decreased post-absorptive MPS (pre-bed rest: 0.061% • h-1 vs. post-bed rest: 0.043% • h-1, p<0.05); 3) insulin area under the curve during an oral glucose tolerance test was unchanged in LEU after bed rest (21±8%) but elevated in CON (52±23%, p<0.05) and whole body insulin sensitivity in LEU was significantly increased above pre-bed rest values after 7 d rehabilitation (17±10% vs. CON: -9±9%, p<0.05). Leucine is an inexpensive, low volume supplement that can be easily incorporated into the daily meals of middle-aged adults to maintain muscle protein synthesis and protect muscle mass, strength, and insulin sensitivity during periods of physical inactivity characteristic of hospitalized acute illness and spaceflight.

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).

We propose that enriching daily meals with a low-volume leucine supplement will reduce the deleterious effects of microgravity on skeletal muscle and facilitate recovery during rehabilitation. We will employ our established 14 day bed rest protocol to model the skeletal muscle unloading that occurs during microgravity. We will also examine recovery of muscle mass and functional capacity during a 7 day rehabilitation period. We will study 2 groups: CON (Bedrest/Recovery + Placebo; n=15), LEU (Bedrest/Recovery + Leucine; n=15). We will assess a) markers of translation initiation, b) muscle protein synthesis, c) muscle mass and body composition and d) strength and aerobic capacity.

We will test the following hypotheses: 1. Bedrest will blunt the anabolic response to a mixed nutrient meal, facilitating a loss of muscle mass and functional capacity that is only partially restored during rehabilitation. 2. Enriching daily meals with leucine will promote protein synthesis and maintain the anabolic response to mixed nutrient meal ingestion. This will preserve lean muscle mass and function during bedrest and facilitate the recovery of functional and metabolic capacity during rehabilitation.

This project builds on our recent series of bed rest studies and seeks to provide a refined and practical countermeasure that is supported by comprehensive mechanistic evidence. Research plans for 2012-2013 include completion of subject recruitment and data analysis. We anticipate the successful completion of the project by mid-2013.

Preliminary results indicate that the nutritional intervention has been successful in attenuating the loss of both muscle mass and muscle strength during bed rest. Subjects given the alanine placebo (CON) lost 3-times more total lean body mass than subjects receiving leucine supplementation during bed rest (CON: -3021 ± 400 g vs. LEU: -966 ± 264 g; p=0.001). Following rehabilitation, lean mass deficits persisted in CON while LEU returned to near pre-bed rest values (CON: -1746 ± 303 g; LEU: -140 ± 367 g). The loss of isometric knee extensor peak torque was also three times greater in CON (-20.3 ± 6.8%) vs. LEU (-7.0 ± 2.5%; p=0.07). Changes in knee extensor total work during a 20 repetition isokinetic endurance test at 180 • s-1 followed a similar pattern (CON: -18.0 ± 7.4% vs. LEU: -5.3 ± 2.8%; p=0.08). These preliminary data indicate that, in the absence of exercise countermeasures, low-volume leucine supplementation may partially attenuate losses in muscle mass and strength during bed rest and facilitate recovery upon resumption of activity in middle-aged adults.

We will employ our established 14 day bed rest protocol to model the skeletal muscle unloading that occurs during microgravity. We will also examine recovery of muscle mass and functional capacity during a 7 day rehabilitation period. We will study 2 groups: CON (Bedrest/Recovery + Placebo; n=15), LEU (Bedrest/Recovery + Leucine; n=15). We will assess a) markers of translation initiation, b) muscle protein synthesis, c) muscle mass and body composition and d) strength and aerobic capacity.

We will test the following hypotheses:

1. Bedrest will blunt the anabolic response to a mixed nutrient meal, facilitating a loss of muscle mass and functional capacity that is only partially restored during rehabilitation.

2. Enriching daily meals with leucine will promote protein synthesis and maintain the anabolic response to mixed nutrient meal ingestion. This will preserve lean muscle mass and function during bedrest and facilitate the recovery of functional and metabolic capacity during rehabilitation.

This project builds on our recent series of bed rest studies and seeks to provide a refined and practical countermeasure that is supported by comprehensive mechanistic evidence. Research plans for 2011-2012 include continued subject recruitment and data analysis.

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.

We propose that enriching daily meals with a low-volume leucine supplement will reduce the deleterious effects of microgravity on skeletal muscle and facilitate recovery during rehabilitation. This supplement has the potential to also benefit individuals whose ability to perform physical activity is compromised (e.g., hospitalized patients, frail elders).

BACKGROUND

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. Previous work has demonstrated that an essential amino acid supplement rich in leucine maintains leg lean mass in young adults during bed rest inactivity. Fourteen days of leucine supplementation has also been shown to increase basal and post-prandial muscle protein synthesis in healthy, ambulatory older adults.

METHODS

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 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.

RESULTS

Preliminary data indicate that during BR, LEU lost 1172 ± 525 g of whole body lean mass compared to 2704 ± 347 g for control (CON). After 1 wk of rehabilitation, LEU regained nearly all lean mass (-108 ± 765 g) while CON remained below pre-BR values (-1448 ± 78 g). After BR, isometric knee extensor strength was decreased 17.4% in CON and only 2.9% in LEU and was partially restored during rehabilitation. Early results also indicate that muscle protein synthesis in response to feeding was preserved in the LEU group.

CONCLUSION

These preliminary data indicate that, in the absence of exercise countermeasures, low-volume leucine supplementation may partially attenuate losses in muscle mass and strength during bed rest and facilitate recovery upon resumption of activity in middle-aged adults.

We will employ our established 14 day bed rest protocol to model the skeletal muscle unloading that occurs during microgravity. We will also examine recovery of muscle mass and functional capacity during a 7 day rehabilitation period. We will study 2 groups: CON (Bedrest/Recovery + Placebo; n=15), LEU (Bedrest/Recovery + Leucine; n=15). We will assess a) markers of translation initiation, b) muscle protein synthesis, c) muscle mass and body composition and d) strength and aerobic capacity.

We will test the following hypotheses:

1. Bedrest will blunt the anabolic response to a mixed nutrient meal, facilitating a loss of muscle mass and functional capacity that is only partially restored during rehabilitation.

2. Enriching daily meals with leucine will promote protein synthesis and maintain the anabolic response to mixed nutrient meal ingestion. This will preserve lean muscle mass and function during bedrest and facilitate the recovery of functional and metabolic capacity during rehabilitation.

This project builds on our recent series of bed rest studies and seeks to provide a refined and practical countermeasure that is supported by comprehensive mechanistic evidence.

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.

We propose that enriching daily meals with a low-volume leucine supplement will reduce the deleterious effects of microgravity on skeletal muscle and facilitate recovery during rehabilitation. This supplement has the potential to also benefit individuals whose ability to perform physical activity is compromised (e.g., hospitalized patients, frail elders).

The study remains blinded and blood and muscle samples are being batched and will be analyzed in groups of 3-4 to avoid wasteful laboratory supply costs. Subjects are tolerating bed rest and the study procedures very well. We have had no complaints or adverse events.

Demographic data indicate that the average age of shuttle crew members has increased from 40.7 years in 1995 to 46.7 years in 2007, with an increasing number of astronauts over 50 years of age. Dr. Douglas Paddon-Jones and colleagues 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.

The project seeks to determine if enriching daily meals with a low-volume leucine supplement will reduce the deleterious effects of microgravity on skeletal muscle and facilitate recovery during rehabilitation. The study will use an established 14-day bed-rest protocol to model the skeletal muscle unloading that occurs during microgravity. It will also examine recovery of muscle mass and functional capacity during a seven-day rehabilitation period.

The researchers will study two groups: CON (Bed Rest/Recovery + Placebo; n=15) and LEU (Bed Rest/Recovery + Leucine; n=15). The study will assess the following: markers of translation initiation, muscle protein synthesis, muscle mass and body composition, and strength and aerobic capacity.

Hypotheses

1) Bed rest will blunt the anabolic response to a mixed-nutrient meal, facilitating a loss of muscle mass and functional capacity that is only partially restored during rehabilitation.

2) Enriching daily meals with leucine will promote protein synthesis and maintain the anabolic response to mixed-nutrient meal ingestion. This will preserve lean muscle mass and function during bed rest and facilitate the recovery of functional and metabolic capacity during rehabilitation.

This project builds on our recent series of bed-rest studies and seeks to provide a refined and practical countermeasure that is supported by comprehensive mechanistic evidence.