Stefan M Pasiakos1, Claire E Berryman2, J Philip Karl3, Harris R Lieberman4, Jeb S Orr5, Lee M Margolis6, John A Caldwell7, Andrew J Young8, Monty A Montano9, William J Evans10, Oshin Vartanian11, Owen T Carmichael12, Kishore M Gadde13, Melissa Harris14, Jennifer C Rood15. 1. Military Nutrition Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA. Electronic address: stefan.m.pasiakos.civ@mail.mil. 2. Military Nutrition Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA; Oak Ridge Institute for Science and Education, Belcamp, MD, USA. Electronic address: claire.e.berryman.ctr@mail.mil. 3. Military Nutrition Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA. Electronic address: james.p.karl.civ@mail.mil. 4. Military Nutrition Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA. Electronic address: harris.r.lieberman.civ@mail.mil. 5. Military Nutrition Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA. Electronic address: jeb.s.orr.mil@mail.mil. 6. Military Nutrition Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA. Electronic address: lee.m.margolis.ctr@mail.mil. 7. Oak Ridge Institute for Science and Education, Belcamp, MD, USA. 8. Military Nutrition Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA; Oak Ridge Institute for Science and Education, Belcamp, MD, USA. Electronic address: andrew.j.young.ctr@mail.mil. 9. MyoSyntax Corporation, Worcester, MA, USA. Electronic address: mmontano@myosyntax.com. 10. University of California at Berkeley, Berkeley, CA, USA; Duke University, Durham, NC, USA. Electronic address: bill.evans@duke.edu. 11. Oak Ridge Institute for Science and Education, Belcamp, MD, USA; Defence Research and Development Canada, University of Toronto, Canada. Electronic address: oshin.vartanian@drdc-rddc.gc.ca. 12. Pennington Biomedical Research Center, Baton Rouge, LA, USA. Electronic address: owen.carmichael@pbrc.edu. 13. Pennington Biomedical Research Center, Baton Rouge, LA, USA. Electronic address: kishore.gadde@pbrc.edu. 14. Pennington Biomedical Research Center, Baton Rouge, LA, USA. Electronic address: melissa.harris@pbrc.edu. 15. Pennington Biomedical Research Center, Baton Rouge, LA, USA. Electronic address: jennifer.rood@pbrc.edu.
Abstract
BACKGROUND: The physiological consequences of severe energy deficit include hypogonadism and the loss of fat-free mass. Prolonged energy deficit also impacts physical performance, mood, attentiveness, and decision-making capabilities. This study will determine whether maintaining a eugonadal state during severe, sustained energy deficit attenuates physiological decrements and maintains mental performance. This study will also assess the effects of normalizing testosterone levels during severe energy deficit and recovery on gut health and appetite regulation. METHODS: Fifty physically active men will participate in a 3-phase, randomized, placebo-controlled study. After completing a 14-d, energy-adequate, diet acclimation phase (protein: 1.6g∙kg-1∙d-1; fat: 30% total energy intake), participants will be randomized to undergo a 28-d, 55% energy deficit phase with (DEF+TEST: 200mg testosterone enanthate per week) or without (DEF) exogenous testosterone. Diet and physical activity will be rigorously controlled. Recovery from the energy deficit (ad libitum diet, no testosterone) will be assessed until body mass has been recovered within ±2.5% of initial body mass. Body composition, stable isotope methodologies, proteomics, muscle biopsies, whole-room calorimetry, molecular biology, activity/sleep monitoring, personality and cognitive function assessments, functional MRI, and comprehensive biochemistries will be used to assess physiological and psychological responses to energy restriction and recovery feeding while volunteers are in an expected hypogonadal versus eugonadal state. DISCUSSION: The Optimizing Performance for Soldiers (OPS) study aims to determine whether preventing hypogonadism will mitigate declines in physical and mental function that typically occur during prolonged energy deficit, and the efficacy of testosterone replacement on recovery from severe underfeeding. TRIAL REGISTRATION: NCT02734238.
BACKGROUND: The physiological consequences of severe energy deficit include hypogonadism and the loss of fat-free mass. Prolonged energy deficit also impacts physical performance, mood, attentiveness, and decision-making capabilities. This study will determine whether maintaining a eugonadal state during severe, sustained energy deficit attenuates physiological decrements and maintains mental performance. This study will also assess the effects of normalizing testosterone levels during severe energy deficit and recovery on gut health and appetite regulation. METHODS: Fifty physically active men will participate in a 3-phase, randomized, placebo-controlled study. After completing a 14-d, energy-adequate, diet acclimation phase (protein: 1.6g∙kg-1∙d-1; fat: 30% total energy intake), participants will be randomized to undergo a 28-d, 55% energy deficit phase with (DEF+TEST: 200mg testosterone enanthate per week) or without (DEF) exogenous testosterone. Diet and physical activity will be rigorously controlled. Recovery from the energy deficit (ad libitum diet, no testosterone) will be assessed until body mass has been recovered within ±2.5% of initial body mass. Body composition, stable isotope methodologies, proteomics, muscle biopsies, whole-room calorimetry, molecular biology, activity/sleep monitoring, personality and cognitive function assessments, functional MRI, and comprehensive biochemistries will be used to assess physiological and psychological responses to energy restriction and recovery feeding while volunteers are in an expected hypogonadal versus eugonadal state. DISCUSSION: The Optimizing Performance for Soldiers (OPS) study aims to determine whether preventing hypogonadism will mitigate declines in physical and mental function that typically occur during prolonged energy deficit, and the efficacy of testosterone replacement on recovery from severe underfeeding. TRIAL REGISTRATION: NCT02734238.
Authors: Alyssa N Varanoske; Melissa N Harris; Callie Hebert; Emily E Howard; Neil M Johannsen; Steven B Heymsfield; Frank L Greenway; Lee M Margolis; Harris R Lieberman; Robbie A Beyl; David D Church; Arny A Ferrando; Stefan M Pasiakos; Jennifer C Rood Journal: J Appl Physiol (1985) Date: 2022-07-07
Authors: J Philip Karl; Claire E Berryman; Melissa N Harris; Harris R Lieberman; Kishore M Gadde; Jennifer C Rood; Stefan M Pasiakos Journal: J Endocr Soc Date: 2020-03-03
Authors: Stefan M Pasiakos; Claire E Berryman; J Philip Karl; Harris R Lieberman; Jeb S Orr; Lee M Margolis; John A Caldwell; Andrew J Young; Monty A Montano; William J Evans; Oshin Vartanian; Owen T Carmichael; Kishore M Gadde; Neil M Johannsen; Robbie A Beyl; Melissa N Harris; Jennifer C Rood Journal: EBioMedicine Date: 2019-07-27 Impact factor: 8.143
Authors: Emily E Howard; Lee M Margolis; Claire E Berryman; Harris R Lieberman; J Philip Karl; Andrew J Young; Monty A Montano; William J Evans; Nancy R Rodriguez; Neil M Johannsen; Kishore M Gadde; Melissa N Harris; Jennifer C Rood; Stefan M Pasiakos Journal: Am J Physiol Endocrinol Metab Date: 2020-08-10 Impact factor: 4.310
Authors: Alyssa N Varanoske; Melissa N Harris; Callie Hebert; Emily E Howard; Neil M Johannsen; Steven B Heymsfield; Frank L Greenway; Lee M Margolis; Harris R Lieberman; David D Church; Arny A Ferrando; Jennifer C Rood; Stefan M Pasiakos Journal: Contemp Clin Trials Commun Date: 2021-07-03