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Project Title:  An Integrated Low-Volume Nutritional Countermeasure to Maintain Muscle Mass and Function During Space Exploration Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/2009  
End Date: 06/30/2013  
Task Last Updated: 11/08/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Paddon-Jones, Douglas  Ph.D. / The University of Texas Medical Branch 
Address:  Deptartment of Nutrition and Metabolism 
301 University Blvd 
Galveston , TX 77555-1124 
Email: djpaddon@UTMB.EDU 
Phone: 409-772-3073  
Congressional District: 14 
Web:  
Organization Type: UNIVERSITY 
Organization Name: The University of Texas Medical Branch 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Urban, Randall  The University of Texas Medical Branch 
Protas, Elizabeth  The University of Texas Medical Branch 
Rasmussen, Blake  The University of Texas Medical Branch 
Sheffield-Moore, Melinda  The University of Texas Medical Branch 
Project Information: Grant/Contract No. NCC 9-58-MA02001 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Unique ID: 7524 
Solicitation / Funding Source: 2008 Crew Health NNJ08ZSA002N 
Grant/Contract No.: NCC 9-58-MA02001 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Aerobic:Risk of Reduced Physical Performance Capabilities Due to Reduced Aerobic Capacity
(2) Muscle:Risk of Impaired Performance Due to Reduced Muscle Mass, Strength and Endurance
Human Research Program Gaps: (1) M08:What is the minimum exercise regimen needed to maintain fitness levels for tasks? (Gap merged with M7, per IRP Rev F)
Task Description: 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. 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.

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.

Research Impact/Earth Benefits: 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).

Task Progress & Bibliography Information FY2013 
Task Progress: 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).

Bibliography Type: Description: (Last Updated: 09/28/2016) 

Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Casperson SL, Sheffield-Moore M, Hewlings SJ, Paddon-Jones D. "Leucine supplementation chronically improves muscle protein synthesis in older adults consuming the RDA for protein." Clinical Nutrition. 2012 Aug;31(4):512-9. Epub 2012 Feb 20. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640444/ ; PubMed PMID: 22357161 , Aug-2012
Articles in Peer-reviewed Journals Drummond MJ, Dickinson JM, Fry CS, Walker DK, Gundermann DM, Reidy PT, Timmerman KL, Markofski MM, Paddon-Jones D, Rasmussen BB, Volpi E. "Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults." Am J Physiol Endocrinol Metab. 2012 May 15;302(9):E1113-22. Epub 2012 Feb 14. http://dx.doi.org/10.1152/ajpendo.00603.2011 ; PubMed PMID: 22338078; PubMed Central PMCID: PMC3361979 , May-2012
Articles in Peer-reviewed Journals English KL, Mettler JA, Ellison JB, Mamerow MM, Arentson-Lantz E, Pattarini JM, Ploutz-Snyder R, Sheffield-Moore M, Paddon-Jones D. "Leucine partially protects muscle mass and function during bed rest in middle-aged adults." Am J Clin Nutr. 2016 Feb;103(2):465-73. Epub 2015 Dec 30. http://dx.doi.org/10.3945/ajcn.115.112359 ; PubMed PMID: 26718415; PubMed Central PMCID: PMC4733256 , Feb-2016
Articles in Peer-reviewed Journals Arentson-Lantz EJ, English KL, Paddon-Jones D, Fry CS. "Fourteen days of bed rest induces a decline in satellite cell content and robust atrophy of skeletal muscle fibers in middle-aged adults." J Appl Physiol (1985). 2016 Apr 15;120(8):965-75. Epub 2016 Jan 21. http://dx.doi.org/10.1152/japplphysiol.00799.2015 ; PubMed PMID: 26796754; PubMed Central PMCID: PMC4835912 , Apr-2016
Articles in Peer-reviewed Journals Arentson-Lantz EJ, Paddon-Jones D, Fry CS. "The intersection of disuse-induced muscle atrophy and satellite cell content: reply to Snijders, Nederveen, and Parise." J Appl Physiol (1985). 2016 Jun 15;120(12):1491. http://dx.doi.org/10.1152/japplphysiol.00167.2016 ; PubMed PMID: 27306845 , Jun-2016
Awards English K. "Charles F. Otis Endowed Award for Clinical Research, November 2011." Nov-2011
Awards English K. "Environmental and Exercise Physiology's (EEP) Space Biomedical Research Institute Predoctoral Gravitational Physiology Award (APS), April 2012." Apr-2012
Awards English K. "NASA/Texas Space Grant Consortium Graduate Fellowship, June 2012." Jun-2012
Project Title:  An Integrated Low-Volume Nutritional Countermeasure to Maintain Muscle Mass and Function During Space Exploration Reduce
Fiscal Year: FY 2012 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/2009  
End Date: 06/30/2013  
Task Last Updated: 08/08/2012 
Download report in PDF pdf
Principal Investigator/Affiliation:   Paddon-Jones, Douglas  Ph.D. / The University of Texas Medical Branch 
Address:  Deptartment of Nutrition and Metabolism 
301 University Blvd 
Galveston , TX 77555-1124 
Email: djpaddon@UTMB.EDU 
Phone: 409-772-3073  
Congressional District: 14 
Web:  
Organization Type: UNIVERSITY 
Organization Name: The University of Texas Medical Branch 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Urban, Randall  The University of Texas Medical Branch 
Protas, Elizabeth  The University of Texas Medical Branch 
Rasmussen, Blake  The University of Texas Medical Branch 
Sheffield-Moore, Melinda  The University of Texas Medical Branch 
Project Information: Grant/Contract No. NCC 9-58-MA02001 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Unique ID: 7524 
Solicitation / Funding Source: 2008 Crew Health NNJ08ZSA002N 
Grant/Contract No.: NCC 9-58-MA02001 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Aerobic:Risk of Reduced Physical Performance Capabilities Due to Reduced Aerobic Capacity
(2) Muscle:Risk of Impaired Performance Due to Reduced Muscle Mass, Strength and Endurance
Human Research Program Gaps: (1) M08:What is the minimum exercise regimen needed to maintain fitness levels for tasks? (Gap merged with M7, per IRP Rev F)
Task Description: 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. 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.

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.

Research Impact/Earth Benefits: 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. 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).

Task Progress & Bibliography Information FY2012 
Task Progress: 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 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.

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.

Bibliography Type: Description: (Last Updated: 09/28/2016) 

Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Casperson SL, Sheffield-Moore M, Hewlings SJ, Paddon-Jones D. "Leucine supplementation chronically improves muscle protein synthesis in older adults consuming the RDA for protein." Clin Nutr. [Epub 2012 Feb 20] PubMed PMID: 22357161 , Jun-2012
Awards English K. "Charles F. Otis Endowed Award for Clinical Research, July 2011." Jul-2011
Awards English K. "Texas Space Grant Consortium Fellow, September 2011." Sep-2011
Project Title:  An Integrated Low-Volume Nutritional Countermeasure to Maintain Muscle Mass and Function During Space Exploration Reduce
Fiscal Year: FY 2011 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/2009  
End Date: 06/30/2013  
Task Last Updated: 08/05/2011 
Download report in PDF pdf
Principal Investigator/Affiliation:   Paddon-Jones, Douglas  Ph.D. / The University of Texas Medical Branch 
Address:  Deptartment of Nutrition and Metabolism 
301 University Blvd 
Galveston , TX 77555-1124 
Email: djpaddon@UTMB.EDU 
Phone: 409-772-3073  
Congressional District: 14 
Web:  
Organization Type: UNIVERSITY 
Organization Name: The University of Texas Medical Branch 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Urban, Randall  The University of Texas Medical Branch 
Protas, Elizabeth  The University of Texas Medical Branch 
Rasmussen, Blake  The University of Texas Medical Branch 
Sheffield-Moore, Melinda  The University of Texas Medical Branch 
Project Information: Grant/Contract No. NCC 9-58-MA02001 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Unique ID: 7524 
Solicitation / Funding Source: 2008 Crew Health NNJ08ZSA002N 
Grant/Contract No.: NCC 9-58-MA02001 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Aerobic:Risk of Reduced Physical Performance Capabilities Due to Reduced Aerobic Capacity
(2) Muscle:Risk of Impaired Performance Due to Reduced Muscle Mass, Strength and Endurance
Human Research Program Gaps: (1) M08:What is the minimum exercise regimen needed to maintain fitness levels for tasks? (Gap merged with M7, per IRP Rev F)
Task Description: 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. 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. 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 2011-2012 include continued subject recruitment and data analysis.

Research Impact/Earth Benefits: 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.

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).

Task Progress & Bibliography Information FY2011 
Task Progress: Leucine Attenuates Bed Rest-Induced Muscle Loss and Enhances Recovery in Middle-Aged Adults: Preliminary Results

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.

Bibliography Type: Description: (Last Updated: 09/28/2016) 

Show Cumulative Bibliography Listing
 
 None in FY 2011
Project Title:  An Integrated Low-Volume Nutritional Countermeasure to Maintain Muscle Mass and Function During Space Exploration Reduce
Fiscal Year: FY 2010 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/2009  
End Date: 06/30/2013  
Task Last Updated: 08/06/2010 
Download report in PDF pdf
Principal Investigator/Affiliation:   Paddon-Jones, Douglas  Ph.D. / The University of Texas Medical Branch 
Address:  Deptartment of Nutrition and Metabolism 
301 University Blvd 
Galveston , TX 77555-1124 
Email: djpaddon@UTMB.EDU 
Phone: 409-772-3073  
Congressional District: 14 
Web:  
Organization Type: UNIVERSITY 
Organization Name: The University of Texas Medical Branch 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Urban, Randall  The University of Texas Medical Branch 
Grady, James  The University of Texas Medical Branch 
Protas, Elizabeth  The University of Texas Medical Branch 
Rasmussen, Blake  The University of Texas Medical Branch 
Sheffield-Moore, Melinda  The University of Texas Medical Branch 
Project Information: Grant/Contract No. NCC 9-58-MA02001 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Unique ID: 7524 
Solicitation / Funding Source: 2008 Crew Health NNJ08ZSA002N 
Grant/Contract No.: NCC 9-58-MA02001 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Aerobic:Risk of Reduced Physical Performance Capabilities Due to Reduced Aerobic Capacity
(2) Muscle:Risk of Impaired Performance Due to Reduced Muscle Mass, Strength and Endurance
Human Research Program Gaps: (1) M08:What is the minimum exercise regimen needed to maintain fitness levels for tasks? (Gap merged with M7, per IRP Rev F)
Task Description: 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. 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. 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 Impact/Earth Benefits: 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.

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).

Task Progress & Bibliography Information FY2010 
Task Progress: The study "An integrated low-volume nutritional countermeasure to maintain muscle mass and function during space exploration" is progressing well. Bed rest studies are complex and require substantial start up efforts; however, recruitment and analysis procedures have been established. We have hired two post-doctoral fellows and a research coordinator to assist with the project. Subject screening have enrollment efforts have been successful to date. Three subjects have successfully completed the study; approximately 5 others are in queue.

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.

Bibliography Type: Description: (Last Updated: 09/28/2016) 

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Articles in Peer-reviewed Journals English KL, Paddon-Jones D. "Protecting muscle mass and function in older adults during bed rest." Curr Opin Clin Nutr Metab Care. 2010 Jan;13(1):34-9. http://dx.doi.org/10.1097/MCO.0b013e328333aa66 ; PMID: 19898232 , Jan-2010
Awards Paddon-Jones D. "Health Professions Award for Scholarship Excellence, December 2009." Dec-2009
Project Title:  An Integrated Low-Volume Nutritional Countermeasure to Maintain Muscle Mass and Function During Space Exploration Reduce
Fiscal Year: FY 2009 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 07/01/2009  
End Date: 06/30/2013  
Task Last Updated: 07/13/2009 
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Principal Investigator/Affiliation:   Paddon-Jones, Douglas  Ph.D. / The University of Texas Medical Branch 
Address:  Deptartment of Nutrition and Metabolism 
301 University Blvd 
Galveston , TX 77555-1124 
Email: djpaddon@UTMB.EDU 
Phone: 409-772-3073  
Congressional District: 14 
Web:  
Organization Type: UNIVERSITY 
Organization Name: The University of Texas Medical Branch 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Grady, James  University of Texas Medical Branch 
Urban, Randall  University of Texas Medical Branch 
Sheffield-Moore, Melinda  University of Texas Medical Branch 
Protas, Elizabeth  University of Texas Medical Branch 
Rasmussen, Blake  University of Texas Medical Branch 
Project Information: Grant/Contract No. NCC 9-58-MA02001 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Unique ID: 7524 
Solicitation / Funding Source: 2008 Crew Health NNJ08ZSA002N 
Grant/Contract No.: NCC 9-58-MA02001 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Aerobic:Risk of Reduced Physical Performance Capabilities Due to Reduced Aerobic Capacity
(2) Muscle:Risk of Impaired Performance Due to Reduced Muscle Mass, Strength and Endurance
Human Research Program Gaps: (1) M08:What is the minimum exercise regimen needed to maintain fitness levels for tasks? (Gap merged with M7, per IRP Rev F)
Task Description: This project's 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.

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.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2009 
Task Progress: New project for FY2009.

Bibliography Type: Description: (Last Updated: 09/28/2016) 

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 None in FY 2009