Spaceflight Metabolism and Nutritional Support

  • Scott M. SmithEmail author
  • Helen W. Lane
  • Sara R. Zwart


Nutrition plays a multifaceted role during space flight. Although its most obvious function is maintaining general health through the consumption of required nutrients, the most important specific functions of proper nutrition are maintaining endocrine and immune system function, skeletal and muscle integrity, and hydration status of spaceflight crews. In addition, interpersonal interactions during mealtimes build team morale and enhance productivity. Providing high-quality, palatable foods is imperative for ensuring adequate nutritional intake, and careful assessment is required to monitor the success or failure of the food system and to ensure crew health. We believe that acknowledging the full role of nutrition will be of paramount importance to the success of extended-duration space missions.


Spaceflight metabolism and nutrition Nutrition in space flights Metabolism in space flights Astronauts and nutrition Astronaut metabolism Space food systems Physiologic effects of space flight Food in space flight 


  1. 1.
    Smith SM, Zwart SR, Kloeris V, Heer M. Nutritional biochemistry of space flight. New York: Nova Science Publishers; 2009.Google Scholar
  2. 2.
    Smith SM, Zwart SR. Nutritional biochemistry of spaceflight. Adv Clin Chem. 2008;46:87–130.PubMedGoogle Scholar
  3. 3.
    Leach CS, Alfrey CP, Suki WN, Leonard JI, Rambaut PC, Inners LD, et al. Regulation of body fluid compartments during short-term spaceflight. J Appl Physiol. 1996;81(1):105–16.PubMedGoogle Scholar
  4. 4.
    Lane HW, Gretebeck RJ, Schoeller DA, Davis-Street J, Socki RA, Gibson EK. Comparison of ground-based and space flight energy expenditure and water turnover in middle-aged healthy male US astronauts. Am J Clin Nutr. 1997;65(1):4–12.PubMedGoogle Scholar
  5. 5.
    Altman PL, Talbot JM. Nutrition and metabolism in spaceflight. J Nutr. 1987;117:421–7.PubMedGoogle Scholar
  6. 6.
    Stein TP, Schluter MD. Excretion of amino acids by humans during space flight. Acta Astronaut. 1998;42(1–8):205–14.PubMedGoogle Scholar
  7. 7.
    Johnson PC, Leach CS, Rambaut PC. Estimates of fluid and energy balances of Apollo 17. Aerosp Med. 1973;44:1227–30.PubMedGoogle Scholar
  8. 8.
    Rambaut PC, Leach CS, Johnson PC. Calcium and phosphorus change of the Apollo 17 crew members. Nutr Metab. 1975;18(2):62–9.PubMedGoogle Scholar
  9. 9.
    Rambaut PC, Smith MC Jr, Wheeler HO. Nutritional studies. In: Johnston RS, Dietlein LF, Berry CA, editors. Biomedical results of Apollo (NASA SP-368). Washington: National Aeronautics and Space Administration; 1975. p. 277–302.Google Scholar
  10. 10.
    Stein TP, Leskiw MJ, Schluter MD, Hoyt RW, Lane HW, Gretebeck RE, et al. Energy expenditure and balance during spaceflight on the space shuttle. Am J Physiol Regul Integr Comp Physiol. 1999;276:R1739–48.Google Scholar
  11. 11.
    Rambaut PC, Leach CS, Whedon GD. A study of metabolic balance in crewmembers of Skylab IV. Acta Astronaut. 1979;6(10):1313–22.PubMedGoogle Scholar
  12. 12.
    Leach CS. Biochemistry and endocrinology results. In: Nicogossian AE, editor. The Apollo-Soyuz Test Project medical report (NASA SP-411). Washington: National Aeronautics and Space Administration; 1977. p. 87–100.Google Scholar
  13. 13.
    Leach CS, Rambaut PC. Biochemical responses of the Skylab crewmen: an overview. In: Johnston RS, Dietlein LF, editors. Biomedical results from Skylab (NASA SP-377). Washington: National Aeronautics and Space Administration; 1977. p. 204–16.Google Scholar
  14. 14.
    Smith SM, Heer MA, Shackelford L, Sibonga JD, Ploutz-Snyder L, Zwart SR. Benefits for bone from resistance exercise and nutrition in long-duration spaceflight: evidence from biochemistry and densitometry. J Bone Miner Res. 2012;27:1896–906.PubMedGoogle Scholar
  15. 15.
    Klicka MV. Development of space foods. J Am Diet Assoc. 1964;44:358–61.PubMedGoogle Scholar
  16. 16.
    Klicka MV, Hollender HA, Lachance PA. Foods for astronauts. J Am Diet Assoc. 1967;51(3):238–45.PubMedGoogle Scholar
  17. 17.
    LaChance PA, Berry CA. Luncheon in space. Nutr Today. 1967;2:2–11.Google Scholar
  18. 18.
    Heidelbaugh ND, Smith MC Jr, Rambaut PC, Lutwak L, Huber CS, Stadler CR, et al. Clinical nutrition applications of space food technology. J Am Diet Assoc. 1973;62(4):383–9.PubMedGoogle Scholar
  19. 19.
    Bourland C, Kloeris V, Rice B, Vodovotz Y. Food systems for space and planetary flights. In: Lane HW, Schoeller DA, editors. Nutrition in spaceflight and weightlessness models. Boca Raton: CRC Press; 2000. p. 19–40.Google Scholar
  20. 20.
    Bourland CT. Advances in food systems for space flight. Life Support Biosph Sci. 1998;5:71–7.PubMedGoogle Scholar
  21. 21.
    Gretebeck RJ, Siconolfi SF, Rice B, Lane HW. Physical performance is maintained in women consuming only foods used on the U.S. Space Shuttle. Aviat Space Environ Med. 1994;65(11):1036–40.PubMedGoogle Scholar
  22. 22.
    World Health Organization. Energy and protein requirements. Report of a joint FAO/WHO/UNU expert consultation. Geneva: World Health Organization; 1985.Google Scholar
  23. 23.
    National Aeronautics and Space Administration Johnson Space Center. Nutritional requirements for International Space Station (ISS) missions up to 360 days. Report No.: JSC-28038. Houston: National Aeronautics and Space Administration Lyndon B. Johnson Space Center; 1996.Google Scholar
  24. 24.
    National Aeronautics and Space Administration Johnson Space Center. Nutrition requirements, standards, and operating bands for exploration missions. Report No.: JSC-63555. Houston: Lyndon B. Johnson Space Center; 2005. 144p.Google Scholar
  25. 25.
    Institute of Medicine. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (macronutrients). Washington: National Academies Press; 2002. 1045p.Google Scholar
  26. 26.
    Smith MC, Berry CA. Dinner on the moon. Nutr Today. 1969;4:37–42.Google Scholar
  27. 27.
    Watt DG, Money KE, Bondar RL, Thirsk RB, Garneau M, Scully-Power P. Canadian medical experiments on Shuttle flight 41-G. Can Aeronaut Space J. 1985;31(3):215–26.PubMedGoogle Scholar
  28. 28.
    Heidelbaugh ND. Taste and aroma testing. Skylab 4 Preliminary Biomedical Report (JSC-08818). Houston: NASA Johnson Space Center; 1975.Google Scholar
  29. 29.
    Budylina SM, Khvatova VA, Volozhin AI. Effect of orthostatic and antiorthostatic hypokinesia on taste sensitivity in men. Kosm Biol Aviakosm Med. 1976;10:27–30.Google Scholar
  30. 30.
    Kurliandskii V, Khvatova VA, Budylina SM. Functional mobility of taste receptors of the tongue under conditions of prolonged hypodynamia. Stomatologiia (Mosk). 1974;53(6):13–5.Google Scholar
  31. 31.
    Vickers ZM, Rice BL, Rose MS, Lane HW. Simulated microgravity [bed rest] has little influence on taste, odor or trigeminal sensitivity. J Sens Stud. 2001;16(1):23–32.PubMedGoogle Scholar
  32. 32.
    Agureev AN, Kalandarov S, Segal DE. Optimization of cosmonauts’ nutrition during the period of acute adaptation and at the closing stage of the mission. Aviakosm Ekolog Med. 1997;31(6):47–51.PubMedGoogle Scholar
  33. 33.
    Rambaut P, Leach C, Leonard J. Observations in energy balance in man during spaceflight. Am J Physiol. 1977;233:R208–12.PubMedGoogle Scholar
  34. 34.
    Michel EL, Rummel JA, Sawin CF, Buderer MC, Lem JD. Results of Skylab medical experiment M-171 – metabolic activity. In: Johnston RS, Dietlein LF, editors. Biomedical results from Skylab (NASA SP-377). Washington: National Aeronautics and Space Administration; 1977. p. 372–87.Google Scholar
  35. 35.
    Lane HW, LeBlanc AD, Putcha L, Whitson PA. Nutrition and human physiological adaptations to space flight. Am J Clin Nutr. 1993;58:583–8.PubMedGoogle Scholar
  36. 36.
    Smirnov KV, Ugolev AM. Digestion and absorption In: Leach Huntoon CL, Antipov VV, Grigoriev AI, editors. Space biology and medicine. III, Book 1, Humans in spaceflight. Reston: American Institute for Aeronautics and Astronautics; 1996. p. 211–30.Google Scholar
  37. 37.
    Stein TP, Leskiw MJ, Schluter MD, Donaldson MR, Larina I. Protein kinetics during and after long-duration spaceflight on MIR. Am J Physiol Endocrinol Metab. 1999;276:E1014–21.Google Scholar
  38. 38.
    Stein TP, Leskiw MJ. Oxidant damage during and after spaceflight. Am J Physiol Endocrinol Metab. 2000;278(3):E375–82.PubMedGoogle Scholar
  39. 39.
    Curtas S, Chapman G, Meguid MM. Evaluation of nutritional status. Nurs Clin North Am. 1989;24:301–13.PubMedGoogle Scholar
  40. 40.
    Anderson SA. Core indicators of nutritional state for difficult to sample populations (Life sciences research office report). J Nutr. 1990;120(Suppl 11):1559–600.Google Scholar
  41. 41.
    Huntoon CL, Whitson PA, Sams CF. Hematologic and immunologic functions. In: Nicogossian AE, Huntoon CL, Pool SL, editors. Space physiology and medicine. 3rd ed. Philadelphia: Lea & Febiger; 1994. p. 351–62.Google Scholar
  42. 42.
    Schmitt DA, Schaffer L. Confinement and immune function. Adv Space Biol Med. 1993;3:229–35.PubMedGoogle Scholar
  43. 43.
    Leonard JI, Leach CS, Rambaut PC. Quantitation of tissue loss during prolonged space flight. Am J Clin Nutr. 1983;38:667–79.PubMedGoogle Scholar
  44. 44.
    Jowsey J. Bone at the cellular level: the effects of inactivity. In: Murray RH, McCally M, editors. Hypogravic and hypodynamic environments NASA Special Pub SP-269. Washington: National Aeronautics and Space Administration; 1971. p. 111–9.Google Scholar
  45. 45.
    Leach CS, Altchuler SI, Cintron-Trevino NM. The endocrine and metabolic responses to space flight. Med Sci Sports Exerc. 1983;15:432–40.PubMedGoogle Scholar
  46. 46.
    Smith SM, Wastney ME, Morukov BV, Larina IM, Nyquist LE, Abrams SA, et al. Calcium metabolism before, during, and after a 3-mo spaceflight: kinetic and biochemical changes. Am J Physiol. 1999;277(1 Pt 2):R1–10.PubMedGoogle Scholar
  47. 47.
    Schoeller DA, Ravussin E, Schutz Y, Acheson KJ, Baertschi P, Jequier E. Energy expenditure by doubly labeled water: validation in humans and proposed calculation. Am J Physiol Regul Integr Comp Physiol. 1986;250(5 Pt 2):R823–30.Google Scholar
  48. 48.
    Gretebeck RJ, Schoeller DA, Gibson EK, Lane HW. Energy expenditure during antiorthostatic bed rest (simulated microgravity). J Appl Physiol. 1995;78(6):2207–11.PubMedGoogle Scholar
  49. 49.
    Lovejoy JC, Smith SR, Zachwieja JJ, Bray GA, Windhauser MM, Wickersham PJ, et al. Low-dose T(3) improves the bed rest model of simulated weightlessness in men and women. Am J Physiol Endocrinol Metab. 1999;277(2 Pt 1):E370–9.Google Scholar
  50. 50.
    Cree MG, Paddon-Jones D, Newcomer BR, Ronsen O, Aarsland A, Wolfe RR, et al. Twenty-eight-day bed rest with hypercortisolemia induces peripheral insulin resistance and increases intramuscular triglycerides. Metabolism. 2010;59(5):703–10.PubMedGoogle Scholar
  51. 51.
    Fitts RH, Romatowski JG, Peters JR, Paddon-Jones D, Wolfe RR, Ferrando AA. The deleterious effects of bed rest on human skeletal muscle fibers are exacerbated by hypercortisolemia and ameliorated by dietary supplementation. Am J Physiol Cell Physiol. 2007;293(1):C313–20.PubMedGoogle Scholar
  52. 52.
    Waligora JM, Horrigan DJ. Metabolism and heat dissipation during Apollo EVA periods. In: Johnston RS, Dietlein LF, Berry CA, editors. Biomedical results of Apollo (NASA SP-368). Washington: National Aeronautics and Space Administration; 1975. p. 115–28.Google Scholar
  53. 53.
    Berry CA, Catterson AD. Pre-Gemini medical predictions versus Gemini flight results. In: Excerpts from Gemini summary conference, Manned Spacecraft Center, Houston, TX, 1–2 Feb 1967. Houston: Manned Spacecraft Center, National Aeronautics and Space Administration; 1967. p. 197–218.Google Scholar
  54. 54.
    Gauer OH, Henry JP. Circulatory basis of fluid volume control. Physiol Rev. 1963;43:423–81.PubMedGoogle Scholar
  55. 55.
    Smith SM, Krauhs JM, Leach CS. Regulation of body fluid volume and electrolyte concentrations in spaceflight. Adv Space Biol Med. 1997;6:123–65.PubMedGoogle Scholar
  56. 56.
    Huntoon CL, Cintrón NM, Whitson PA. Endocrine and biochemical functions. In: Nicogossian AE, Huntoon CL, Pool SL, editors. Space physiology and medicine. 3rd ed. Philadelphia: Lea & Febiger; 1994. p. 334–50.Google Scholar
  57. 57.
    Leach Huntoon CS, Grigoriev AI, Natochin YV. Fluid and electrolyte regulation in spaceflight. San Diego: Univelt, Inc.; 1998. 219p.Google Scholar
  58. 58.
    Nicogossian AE, Sawin CF, Huntoon CL. Overall physiologic response to space flight. In: Nicogossian AE, Huntoon CL, Pool SL, editors. Space physiology and medicine. 3rd ed. Philadelphia: Lea & Febiger; 1994. p. 213–27.Google Scholar
  59. 59.
    Johnson P, Driscoll T, LeBlanc A. Blood volume changes. In: Johnston R, Dietlein L, editors. Biomedical results from Skylab (NASA SP-377). Washington: National Aeronautics and Space Administration; 1977. p. 235–41.Google Scholar
  60. 60.
    Bungo MW, Johnson PC Jr. Cardiovascular examinations and observations of deconditioning during the space shuttle orbital flight test program. Aviat Space Environ Med. 1983;54:1001–4.PubMedGoogle Scholar
  61. 61.
    Hyatt KH, West DA. Reversal of bedrest-induced orthostatic intolerance by lower body negative pressure and saline. Aviat Space Environ Med. 1977;48(2):120–4.PubMedGoogle Scholar
  62. 62.
    Vernikos J, Convertino VA. Advantages and disadvantages of fludrocortisone or saline load in preventing post-spaceflight orthostatic hypotension. Acta Astronaut. 1994;33:259–66.PubMedGoogle Scholar
  63. 63.
    Leach CS, Inners LD, Charles JB. Changes in total body water during space flight. In: Bungo MW, Bagian TM, Bowman MA, Levitan BM, editors. Results of the life sciences DSOs conducted aboard the Space Shuttle, vol. 1981–1986. Houston: Space Biomedical Research Institute, Johnson Space Center; 1987. p. 49–53.Google Scholar
  64. 64.
    Thornton WE, Ord J. Physiological mass measurements in Skylab. In: Johnston RS, Dietlein LF, editors. Biomedical results from Skylab (NASA SP-377). Washington: National Aeronautics and Space Administration; 1977. p. 175–82.Google Scholar
  65. 65.
    Drummer C, Heer M, Dressendörfer RA, Strasburger CJ, Gerzer R. Reduced natriuresis during weightlessness. Clin Investig. 1993;71:678–86.PubMedGoogle Scholar
  66. 66.
    Gerzer R, Drummer C, Heer M. Antinatriuretic kidney response to weightlessness. Acta Astronaut. 1994;33:97–100.PubMedGoogle Scholar
  67. 67.
    Gerzer R, Heer M, Drummer C. Body fluid metabolism at actual and simulated microgravity. Med Sci Sports Exerc. 1996;28(10 Suppl):S32–5.PubMedGoogle Scholar
  68. 68.
    Balakhovskiy I, Natochin Y. Metabolism under the extreme conditions of spaceflight and during its simulation. Moscow: Nauka Press; 1973. 212p.Google Scholar
  69. 69.
    Vernikos J. Metabolic and endocrine changes. In: Sandler H, Vernikos J, editors. Inactivity: physiological effects. Orlando: Academic Press, Inc.; 1986. p. 99–121.Google Scholar
  70. 70.
    Drummer C, Gerzer R, Baisch F, Heer M. Body fluid regulation in micro-gravity differs from that on Earth: an overview. Pflugers Arch. 2000;441(2–3 Suppl):R66–72.PubMedGoogle Scholar
  71. 71.
    Drummer C, Norsk P, Heer M. Water and sodium balance in space. Am J Kidney Dis. 2001;38(3):684–90.PubMedGoogle Scholar
  72. 72.
    Norsk P, Christensen NJ, Bie P, Gabrielsen A, Heer M, Drummer C. Unexpected renal responses in space. Lancet. 2000;356(9241):1577–8.PubMedGoogle Scholar
  73. 73.
    Greenleaf JE. Mechanisms for negative water balance during weightlessness: immersion or bed rest? Physiologist. 1985;28(6 Suppl):S38–9.PubMedGoogle Scholar
  74. 74.
    Leach CS, Johnson PC. Influence of spaceflight on erythrokinetics in man. Science. 1984;225(4658):216–8.PubMedGoogle Scholar
  75. 75.
    Alfrey CP, Udden MM, Leach-Huntoon C, Driscoll T, Pickett MH. Control of red blood cell mass in spaceflight. J Appl Physiol. 1996;81:98–104.PubMedGoogle Scholar
  76. 76.
    Udden MM, Driscoll TB, Pickett MH, Leach-Huntoon CS, Alfrey CP. Decreased production of red blood cells in human subjects exposed to microgravity. J Lab Clin Med. 1995;125:442–9.PubMedGoogle Scholar
  77. 77.
    Johnson PC. In: Dunn CDR, editor. Current concepts in erythropoiesis The erythropoietic effects of weightlessness. New York: John Wiley & Sons Ltd.; 1983. p. 279–300.Google Scholar
  78. 78.
    Fischer CL, Johnson PC, Berry CA. Red blood cell mass and plasma volume changes in manned space flight. JAMA. 1967;200:579–83.PubMedGoogle Scholar
  79. 79.
    Mengel CE. Red cell metabolism studies on Skylab. In: Johnston RS, Dietlein LF, editors. Biomedical results from Skylab (NASA SP-377). Washington: National Aeronautics and Space Administration; 1977. p. 242–8.Google Scholar
  80. 80.
    Smith SM, Davis-Street JE, Fontenot TB, Lane HW. Assessment of a portable clinical blood analyzer during space flight. Clin Chem. 1997;43(6 Pt 1):1056–65.PubMedGoogle Scholar
  81. 81.
    Alfrey CP, Udden MM, Huntoon CL, Driscoll T. Destruction of newly released red blood cells in space flight. Med Sci Sports Exerc. 1996;28(10 Suppl):S42–4.PubMedGoogle Scholar
  82. 82.
    Kimzey S, Fischer C, Johnson P, Ritzmann S, Mengel C. Hematology and immunology studies. In: Johnston R, Dietlein L, Berry C, editors. Biomedical results of Apollo (NASA SP-368). Washington: National Aeronautics and Space Administration; 1975. p. 197–226.Google Scholar
  83. 83.
    Kimzey SL. Hematology and immunology studies. In: Johnston RS, Dietlein LF, editors. Biomedical results from Skylab (NASA SP-377). Washington: National Aeronautics and Space Administration; 1977. p. 249–82.Google Scholar
  84. 84.
    Risso A, Ciana A, Achilli C, Antonutto G, Minetti G. Neocytolysis: none, one or many? A reappraisal and future perspectives. Front Physiol. 2014;5:54.PubMedPubMedCentralGoogle Scholar
  85. 85.
    De Santo NG, Cirillo M, Kirsch KA, Correale G, Drummer C, Frassl W, et al. Anemia and erythropoietin in space flights. Semin Nephrol. 2005;25(6):379–87.PubMedGoogle Scholar
  86. 86.
    Rice L, Ruiz W, Driscoll T, Whitley CE, Tapia R, Hachey DL, et al. Neocytolysis on descent from altitude: a newly recognized mechanism for the control of red cell mass. Ann Intern Med. 2001;134(8):652–6.PubMedGoogle Scholar
  87. 87.
    Leach CS, Rambaut PC. Biochemical observations of long duration manned orbital spaceflight. J Am Med Womens Assoc. 1975;30(4):153–72.Google Scholar
  88. 88.
    Smith SM. Red blood cell and iron metabolism during space flight. Nutrition. 2002;18(10):864–6.PubMedGoogle Scholar
  89. 89.
    Smith SM, Davis-Street JE, Rice BL, Nillen JL, Gillman PL, Block G. Nutritional status assessment in semiclosed environments: ground-based and space flight studies in humans. J Nutr. 2001;131(7):2053–61.PubMedGoogle Scholar
  90. 90.
    Smith SM, Zwart SR, Block G, Rice BL, Davis-Street JE. The nutritional status of astronauts is altered after long-term space flight aboard the International Space Station. J Nutr. 2005;135(3):437–43.PubMedGoogle Scholar
  91. 91.
    Zwart SR, Morgan JL, Smith SM. Iron status and its relations with oxidative damage and bone loss during long-duration space flight on the International Space Station. Am J Clin Nutr. 2013;98:217–23.PubMedGoogle Scholar
  92. 92.
    Zwart SR, Jessup JM, Ji J, Smith SM. Saturation diving alters folate status and biomarkers of DNA damage and repair. PLoS One. 2012;7(2):e31058.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Zwart SR, Kala G, Smith SM. Body iron stores and oxidative damage in humans increased during and after a 10- to 12-day undersea dive. J Nutr. 2009;139(1):90–5.PubMedGoogle Scholar
  94. 94.
    Smith SM, Davis-Street JE, Fesperman JV, Smith MD, Rice BL, Zwart SR. Nutritional assessment during a 14-d saturation dive: the NASA Extreme Environment Mission Operations V Project. J Nutr. 2004;134:1765–71.PubMedGoogle Scholar
  95. 95.
    Johnson PC, Driscoll TB, Fischer CL. Blood volume changes in divers of Tektite I. Aerosp Med. 1971;42:423–6.PubMedGoogle Scholar
  96. 96.
    Dunn CDR, Lange RD, Kimzey SL, Johnson PC, Leach CS. Serum erythropoietin titers during prolonged bedrest; relevance to the “anaemia” of space flight. Eur J Appl Physiol. 1984;52:178–82.Google Scholar
  97. 97.
    National Aeronautics and Space Administration Johnson Space Center. Nutritional requirements for Extended Duration Orbiter missions (30–90 d) and Space Station Freedom (30–120 d). Report No.: JSC-32283. Houston: National Aeronautics and Space Administration Lyndon B. Johnson Space Center; 1993.Google Scholar
  98. 98.
    National Aeronautics and Space Administration Johnson Space Center. Nutritional status assessment for extended-duration space flight. Report No.: JSC-28566, Revision 1. Houston: Lyndon B. Johnson Space Center; 1999.Google Scholar
  99. 99.
    Institute of Medicine. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington: National Academy Press; 2001. 773p.Google Scholar
  100. 100.
    LeBlanc A, Rowe R, Schneider V, Evans H, Hedrick T. Regional muscle loss after short duration spaceflight. Aviat Space Environ Med. 1995;66:1151–4.PubMedGoogle Scholar
  101. 101.
    Day MK, Allen DL, Mohajerani L, Greenisen MC, Roy RR, Edgerton VR. Adaptations of human skeletal muscle fibers to spaceflight. J Gravit Physiol. 1995;2(1):P47–50.PubMedGoogle Scholar
  102. 102.
    Whedon GD, Lutwak L, Rambaut PC, Whittle MW, Smith MC, Reid J, et al. Mineral and nitrogen metabolic studies, experiment M071. In: Johnston RS, Dietlein LF, editors. Biomedical results from Skylab (NASA SP-377). Washington: National Aeronautics and Space Administration; 1977. p. 164–74.Google Scholar
  103. 103.
    Thornton WE, Rummel JA. Muscle deconditioning and its prevention in space flight. In: Johnston RS, Dietlein LF, editors. Biomedical results from Skylab (NASA SP-377). Washington: National Aeronautics and Space Administration; 1977. p. 191–7.Google Scholar
  104. 104.
    Ferrando AA, Lane HW, Stuart CA, Davis-Street J, Wolfe RR. Prolonged bed rest decreases skeletal muscle and whole body protein synthesis. Am J Physiol Endocrinol Metab. 1996;270(4 Pt 1):E627–E33.Google Scholar
  105. 105.
    Coburn SP, Thampy KG, Lane HW, Conn PS, Ziegler PJ, Costill DL, et al. Pyridoxic acid excretion during low vitamin B-6 intake, total fasting, and bed rest. Am J Clin Nutr. 1995;62(5):979–83.PubMedGoogle Scholar
  106. 106.
    Stein TP, Leskiw MJ, Schluter MD. Effect of spaceflight on human protein metabolism. Am J Physiol Endocrinol Metab. 1993;264:E824–8.Google Scholar
  107. 107.
    Stein TP, Leskiw MJ, Schluter MD. Diet and nitrogen metabolism during spaceflight on the shuttle. J Appl Physiol (1985). 1996;81(1):82–97.Google Scholar
  108. 108.
    Stein TP, Schluter MD, Moldawer LL. Endocrine relationships during human spaceflight. Am J Physiol Endocrinol Metab. 1999;276(1 Pt 1):E155–62.Google Scholar
  109. 109.
    Ushakov AS, Vlasova TF. Free amino acids in human blood plasma during space flights. Aviat Space Environ Med. 1976;47(10):1061–4.PubMedGoogle Scholar
  110. 110.
    Stein TP, Schluter MD. Plasma amino acids during human spaceflight. Aviat Space Environ Med. 1999;70(3 Pt 1):250–5.PubMedGoogle Scholar
  111. 111.
    Leach CS, Rambaut PC, Di Ferrante N. Amino aciduria in weightlessness. Acta Astronaut. 1979;6:1323–33.PubMedGoogle Scholar
  112. 112.
    LeBlanc A, Lin C, Shackelford L, Sinitsyn V, Evans H, Belichenko O, et al. Muscle volume, MRI relaxation times (T2), and body composition after spaceflight. J Appl Physiol. 2000;89(6):2158–64.PubMedGoogle Scholar
  113. 113.
    Ferrando AA, Williams BD, Stuart CA, Lane HW, Wolfe RR. Oral branched-chain amino acids decrease whole-body proteolysis. JPEN J Parenter Enteral Nutr. 1995;19(1):47–54.PubMedGoogle Scholar
  114. 114.
    Stuart CA, Shangraw RE, Peters EJ, Wolfe RR. Effect of dietary protein on bed-rest-related changes in whole-body-protein synthesis. Am J Clin Nutr. 1990;52(3):509–14.PubMedGoogle Scholar
  115. 115.
    Ferrando AA, Paddon-Jones D, Hays NP, Kortebein P, Ronsen O, Williams RH, et al. EAA supplementation to increase nitrogen intake improves muscle function during bed rest in the elderly. Clin Nutr. 2010;29(1):18–23.PubMedGoogle Scholar
  116. 116.
    Paddon-Jones D, Sheffield-Moore M, Urban RJ, Sanford AP, Aarsland A, Wolfe RR, et al. Essential amino acid and carbohydrate supplementation ameliorates muscle protein loss in humans during 28 days bedrest. J Clin Endocrinol Metab. 2004;89(9):4351–8.PubMedGoogle Scholar
  117. 117.
    Brooks NE, Cadena SM, Vannier E, Cloutier G, Carambula S, Myburgh KH, et al. Effects of resistance exercise combined with essential amino acid supplementation and energy deficit on markers of skeletal muscle atrophy and regeneration during bed rest and active recovery. Muscle Nerve. 2010;42(6):927–35.PubMedPubMedCentralGoogle Scholar
  118. 118.
    Zwart SR, Davis-Street JE, Paddon-Jones D, Ferrando AA, Wolfe RR, Smith SM. Amino acid supplementation alters bone metabolism during simulated weightlessness. J Appl Physiol. 2005;99(1):134–40.PubMedGoogle Scholar
  119. 119.
    Stein TP, Blanc S. Does protein supplementation prevent muscle disuse atrophy and loss of strength? Crit Rev Food Sci Nutr. 2011;51(9):828–34.PubMedGoogle Scholar
  120. 120.
    Zachwieja JJ, Smith SR, Lovejoy JC, Rood JC, Windhauser MM, Bray GA. Testosterone administration preserves protein balance but not muscle strength during 28 days of bed rest. J Clin Endocrinol Metab. 1999;84(1):207–12.Google Scholar
  121. 121.
    Smith SM, Heer M, Wang Z, Huntoon CL, Zwart SR. Long-duration space flight and bed rest effects on testosterone and other steroids. J Clin Endocrinol Metab. 2012;97(1):270–8.Google Scholar
  122. 122.
    Strollo F. Hormonal changes in humans during spaceflight. Adv Space Biol Med. 1999;7:99–129.PubMedGoogle Scholar
  123. 123.
    Ferrando AA, Tipton KD, Bamman MM, Wolfe RR. Resistance exercise maintains skeletal muscle protein synthesis during bed rest. J Appl Physiol (1985). 1997;82(3):807–10.Google Scholar
  124. 124.
    Shackelford LC, LeBlanc AD, Driscoll TB, Evans HJ, Rianon NJ, Smith SM, et al. Resistance exercise as a countermeasure to disuse-induced bone loss. J Appl Physiol. 2004;97(1):119–29.PubMedGoogle Scholar
  125. 125.
    Smith SM, Zwart SR, Heer M, Hudson EK, Shackelford L, Morgan JL. Men and women in space: bone loss and kidney stone risk after long-duration spaceflight. J Bone Miner Res. 2014;29(7):1639–45.PubMedGoogle Scholar
  126. 126.
    LeBlanc AD, Spector ER, Evans HJ, Sibonga JD. Skeletal responses to space flight and the bed rest analog: a review. J Musculoskelet Neuronal Interact. 2007;7(1):33–47.PubMedGoogle Scholar
  127. 127.
    Sibonga JD, Cavanagh PR, Lang TF, LeBlanc AD, Schneider VS, Shackelford LC, et al. Adaptation of the skeletal system during long-duration spaceflight. Clin Rev Bone Miner Metab. 2008;5(4):249–61.Google Scholar
  128. 128.
    Heer M, Kamps N, Biener C, Korr C, Boerger A, Zittermann A, et al. Calcium metabolism in microgravity. Eur J Med Res. 1999;4:357–60.PubMedGoogle Scholar
  129. 129.
    Morey-Holton E, Whalen R, Arnaud S, Van Der Meulen M. The skeleton and its adaptation to gravity. In: Fregly M, Blatteis C, editors. Environmental physiology. Handbook of physiology, vol. 1. New York: Oxford University Press; 1996. p. 691–719.Google Scholar
  130. 130.
    Arnaud SB, Schneider VS, Morey-Holton E. In: Sandler H, Vernikos J, editors. Inactivity: physiological effects Effects of inactivity on bone and calcium metabolism. Orlando: Academic Press, Inc.; 1986. p. 49–76.Google Scholar
  131. 131.
    Schneider VS, McDonald J. Skeletal calcium homeostasis and countermeasures to prevent disuse osteoporosis. Calcif Tissue Int. 1984;36(Suppl 1):S151–44.PubMedGoogle Scholar
  132. 132.
    Rambaut PC, Johnston RS. Prolonged weightlessness and calcium loss in man. Acta Astronaut. 1979;6:1113–22.PubMedGoogle Scholar
  133. 133.
    LeBlanc A, Schneider V, Shackelford L, West S, Oganov V, Bakulin A, et al. Bone mineral and lean tissue loss after long duration space flight. J Musculoskelet Neuronal Interact. 2000;1(2):157–60.PubMedGoogle Scholar
  134. 134.
    Oganov VS, Rakhmanov AS, Novikov VE, Zatsepin ST, Rodionova SS, Cann C. The state of human bone tissue during space flight. Acta Astronaut. 1991;23:129–33.PubMedGoogle Scholar
  135. 135.
    Oganov VS, Grigoriev AI, Voronin LI, Rakhmanov AS, Bakulin AV, Schneider VS, et al. Bone mineral density in cosmonauts after flights lasting 4.5–6 months on the Mir orbital station. Aviakosm Ekolog Med. 1992;26(5–6):20–4.PubMedGoogle Scholar
  136. 136.
    Smith MC Jr, Rambaut PC, Vogel JM, Whittle MW. Bone mineral measurement—experiment M078. In: Johnston RS, Dietlein LF, editors. Biomedical results from Skylab (NASA SP-377). Washington: National Aeronautics and Space Administration; 1977. p. 183–90.Google Scholar
  137. 137.
    Stupakov GP, Kazeykin VS, Kozlovskiy AP, Korolev VV. Evaluation of changes in human axial skeletal bone structures during long-term spaceflights. Kosm Biol Aviakosm Med. 1984;18(2):33–7.PubMedGoogle Scholar
  138. 138.
    Rambaut PC, Goode AW. Skeletal changes during space flight. Lancet. 1985;2(8463):1050–2.PubMedGoogle Scholar
  139. 139.
    Whedon G, Lutwak L, Rambaut P, Whittle M, Leach C, Reid J, et al. Effect of weightlessness on mineral metabolism; metabolic studies on Skylab orbital flights. Calcif Tissue Res. 1976;21(Suppl):423–30.PubMedGoogle Scholar
  140. 140.
    Whedon GD. Disuse osteoporosis: physiological aspects. Calcif Tissue Int. 1984;36:S146–50.PubMedGoogle Scholar
  141. 141.
    Whitson PA, Pietrzyk RA, Pak CY. Renal stone risk assessment during Space Shuttle flights. J Urol. 1997;158(6):2305–10.PubMedGoogle Scholar
  142. 142.
    Whitson P, Pietrzyk R, Pak C, Cintron N. Alterations in renal stone risk factors after space flight. J Urol. 1993;150:803–7.PubMedGoogle Scholar
  143. 143.
    Whitson P, Pietrzyk R, Sams C. Space flight and the risk of renal stones. J Gravit Physiol. 1999;6(1):P87–8.PubMedGoogle Scholar
  144. 144.
    Whitson PA, Pietrzyk RA, Morukov BV, Sams CF. The risk of renal stone formation during and after long duration space flight. Nephron. 2001;89:264–70.PubMedGoogle Scholar
  145. 145.
    Whitson PA, Pietrzyk RA, Sams CF. Urine volume and its effects on renal stone risk in astronauts. Aviat Space Environ Med. 2001;72(4):368–72.PubMedGoogle Scholar
  146. 146.
    Vico L, Collet P, Guignandon A, Lafage-Proust MH, Thomas T, Rehaillia M, et al. Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts. Lancet. 2000;355(9215):1607–11.PubMedGoogle Scholar
  147. 147.
    LeBlanc AD, Schneider VS, Evans HJ, Engelbretson DA, Krebs JM. Bone mineral loss and recovery after 17 weeks of bed rest. J Bone Miner Res. 1990;5:843–50.PubMedGoogle Scholar
  148. 148.
    Tilton FE, Degioanni JJC, Schneider VS. Long-term follow-up of Skylab bone demineralization. Aviat Space Environ Med. 1980;51:1209–13.PubMedGoogle Scholar
  149. 149.
    Smith SM, Nillen JL, LeBlanc A, Lipton A, Demers LM, Lane HW, et al. Collagen cross-link excretion during space flight and bed rest. J Clin Endocrinol Metab. 1998;83(10):3584–91.PubMedGoogle Scholar
  150. 150.
    Grigoriev AI, Oganov VS, Bakulin AV, Poliakov VV, Voronin LI, Morgun VV, et al. Clinical and physiological evaluation of bone changes among astronauts after long-term space flights. Aviakosm Ekolog Med. 1998;32:21–5.PubMedGoogle Scholar
  151. 151.
    Smith SM, Wastney ME, O’Brien KO, Morukov BV, Larina IM, Abrams SA, et al. Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the Mir space station. J Bone Miner Res. 2005;20(2):208–18.PubMedGoogle Scholar
  152. 152.
    Sibonga JD, Evans HJ, Sung HG, Spector ER, Lang TF, Oganov VS, et al. Recovery of spaceflight-induced bone loss: bone mineral density after long-duration missions as fitted with an exponential function. Bone. 2007;41(6):973–8.PubMedGoogle Scholar
  153. 153.
    Collet P, Uebelhart D, Vico L, Moro L, Hartmann D, Roth M, et al. Effects of 1- and 6-month spaceflight on bone mass and biochemistry in two humans. Bone. 1997;20(6):547–51.PubMedGoogle Scholar
  154. 154.
    Caillot-Augusseau A, Lafage-Proust MH, Soler C, Pernod J, Dubois F, Alexandre C. Bone formation and resorption biological markers in cosmonauts during and after a 180-day space flight (Euromir 95). Clin Chem. 1998;44(3):578–85.PubMedGoogle Scholar
  155. 155.
    Pavy-Le Traon A, Heer M, Narici MV, Rittweger J, Vernikos J. From space to Earth: advances in human physiology from 20 years of bed rest studies (1986–2006). Eur J Appl Physiol. 2007;101(2):143–94.PubMedGoogle Scholar
  156. 156.
    Smith SM, Zwart SR, Heer MA, Baecker N, Evans HJ, Feiveson AH, et al. Effects of artificial gravity during bed rest on bone metabolism in humans. J Appl Physiol. 2009;107(1):47–53.PubMedPubMedCentralGoogle Scholar
  157. 157.
    Zerwekh JE, Ruml LA, Gottschalk F, Pak CY. The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects. J Bone Miner Res. 1998;13(10):1594–601.PubMedGoogle Scholar
  158. 158.
    LeBlanc A, Schneider V, Spector E, Evans H, Rowe R, Lane H, et al. Calcium absorption, endogenous excretion, and endocrine changes during and after long-term bed rest. Bone. 1995;16(4 Suppl):301S–4S.PubMedGoogle Scholar
  159. 159.
    Arnaud SB, Sherrard DJ, Maloney N, Whalen RT, Fung P. Effects of 1-week head-down tilt bed rest on bone formation and the calcium endocrine system. Aviat Space Environ Med. 1992;63(1):14–20.PubMedGoogle Scholar
  160. 160.
    LeBlanc A, Schneider V, Krebs J, Evans H, Jhingran S, Johnson P. Spinal bone mineral after 5 weeks of bed rest. Calcif Tissue Int. 1987;41:259–61.PubMedGoogle Scholar
  161. 161.
    Deitrick JE, Whedon GD, Shorr E. Effects of immobilization upon various metabolic and physiologic functions of normal men. Am J Med. 1948;4:3–36.PubMedGoogle Scholar
  162. 162.
    Hwang TIS, Hill K, Schneider V, Pak CYC. Effect of prolonged bedrest on the propensity for renal stone formation. J Clin Endocrinol Metab. 1988;66:109–12.PubMedGoogle Scholar
  163. 163.
    Donaldson CL, Hulley SB, Vogel JM, Hattner RS, Bayers JH, McMillan DE. Effect of prolonged bed rest on bone mineral. Metabolism. 1970;19(12):1071–84.PubMedGoogle Scholar
  164. 164.
    Zwart SR, Hargens AR, Lee SM, Macias BR, Watenpaugh DE, Tse K, et al. Lower body negative pressure treadmill exercise as a countermeasure for bed rest-induced bone loss in female identical twins. Bone. 2007;40(2):529–37.PubMedGoogle Scholar
  165. 165.
    Monga M, Macias B, Groppo E, Kostelec M, Hargens A. Renal stone risk in a simulated microgravity environment: impact of treadmill exercise with lower body negative pressure. J Urol. 2006;176(1):127–31.PubMedGoogle Scholar
  166. 166.
    Zerwekh JE. Nutrition and renal stone disease in space. Nutrition. 2002;18(10):857–63.PubMedGoogle Scholar
  167. 167.
    Zerwekh JE, Odvina CV, Wuermser LA, Pak CY. Reduction of renal stone risk by potassium-magnesium citrate during 5 weeks of bed rest. J Urol. 2007;177(6):2179–84.PubMedGoogle Scholar
  168. 168.
    Smith SM, Davis-Street JE, Fesperman JV, Calkins DS, Bawa M, Macias BR, et al. Evaluation of treadmill exercise in a lower body negative pressure chamber as a countermeasure for weightlessness-induced bone loss: a bed rest study with identical twins. J Bone Miner Res. 2003;18:2223–30.PubMedGoogle Scholar
  169. 169.
    Smith SM, Zwart SR, Heer M, Lee SMC, Baecker N, Meuche S, et al. WISE-2005: Supine treadmill exercise within lower body negative pressure and flywheel resistive exercise as a countermeasure to bed rest-induced bone loss in women during 60-day simulated microgravity. Bone. 2008;42(3):572–81.PubMedGoogle Scholar
  170. 170.
    Arnaud SB, Wolinsky I, Fung P, Vernikos J. Dietary salt and urinary calcium excretion in a human bed rest spaceflight model. Aviat Space Environ Med. 2000;71:1115–9.PubMedGoogle Scholar
  171. 171.
    Baecker N, Frings-Meuthen P, Heer M, Mester J, Liphardt AM. Effects of vibration training on bone metabolism: results from a short-term bed rest study. Eur J Appl Physiol. 2012;112(5):1741–50.PubMedGoogle Scholar
  172. 172.
    Vico L, Chappard D, Alexandre C, Palle S, Minaire P, Riffat G, et al. Effects of a 120 day period of bed-rest on bone mass and bone cell activities in man: attempts at countermeasure. Bone Miner. 1987;2:383–94.PubMedGoogle Scholar
  173. 173.
    Lueken SA, Arnaud SB, Taylor AK, Baylink DJ. Changes in markers of bone formation and resorption in a bed rest model of weightlessness. J Bone Miner Res. 1993;8(12):1433–8.PubMedGoogle Scholar
  174. 174.
    Smith SM, Heer M. Calcium and bone metabolism during space flight. Nutrition. 2002;18:849–52.PubMedGoogle Scholar
  175. 175.
    Morgan JL, Skulan JL, Gordon GW, Romaniello SJ, Smith SM, Anbar AD. Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes. Proc Natl Acad Sci U S A. 2012;109(25):9989–94.PubMedPubMedCentralGoogle Scholar
  176. 176.
    Smith SM, McCoy T, Gazda D, Morgan JL, Heer M, Zwart SR. Space flight calcium: implications for astronaut health, spacecraft operations, and Earth. Nutrients. 2012;4(12):2047–68.PubMedPubMedCentralGoogle Scholar
  177. 177.
    Elias AN, Gwinup G. Immobilization osteoporosis in paraplegia. J Am Paraplegia Soc. 1992;15:163–70.PubMedGoogle Scholar
  178. 178.
    Stewart AF, Akler M, Byers CM, Segre GV, Broadus AE. Calcium homeostasis in immobilization: an example of resorptive hypercalciuria. N Engl J Med. 1982;306:1136–40.PubMedGoogle Scholar
  179. 179.
    Meythaler JM, Tuel SM, Cross LL. Successful treatment of immobilization hypercalcemia using calcitonin and etidronate. Arch Phys Med Rehabil. 1993;74:316–9.PubMedGoogle Scholar
  180. 180.
    Klein L, van der Noort S, DeJak JJ. Sequential studies of urinary hydroxyproline and serum alkaline phosphatase in acute paraplegia. Med Serv J Can. 1966;22(7):524–33.PubMedGoogle Scholar
  181. 181.
    Naftchi NE, Viau AT, Sell GH, Lowman EW. Mineral metabolism in spinal cord injury. Arch Phys Med Rehabil. 1980;61:139–42.PubMedGoogle Scholar
  182. 182.
    Minaire P, Meunier P, Edouard C, Bernard J, Courpron P, Bourret J. Quantitative histological data on disuse osteoporosis: comparison with biological data. Calcif Tissue Int. 1974;17:57–73.Google Scholar
  183. 183.
    Smith BJ, King JB, Lucas EA, Akhter MP, Arjmandi BH, Stoecker BJ. Skeletal unloading and dietary copper depletion are detrimental to bone quality of mature rats. J Nutr. 2002;132(2):190–6.PubMedGoogle Scholar
  184. 184.
    Smith BJ, Lucas EA, Turner RT, Evans GL, Lerner MR, Brackett DJ, et al. Vitamin E provides protection for bone in mature hindlimb unloaded male rats. Calcif Tissue Int. 2005;76(4):272–9.PubMedGoogle Scholar
  185. 185.
    Smith SM, Dillon EL, DeKerlegand DE, Davis-Street JE. Variability of collagen crosslinks: impact of sample collection period. Calcif Tissue Int. 2004;74(4):336–41.PubMedGoogle Scholar
  186. 186.
    LeBlanc AD, Driscol TB, Shackelford LC, Evans HJ, Rianon NJ, Smith SM, et al. Alendronate as an effective countermeasure to disuse induced bone loss. J Musculoskelet Neuronal Interact. 2002;2(4):335–43.PubMedGoogle Scholar
  187. 187.
    Skulan J, Bullen T, Anbar AD, Puzas JE, Shackelford L, LeBlanc A, et al. Natural calcium isotopic composition of urine as a marker of bone mineral balance. Clin Chem. 2007;53(6):1155–8.PubMedGoogle Scholar
  188. 188.
    Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington: National Academies Press; 2011. 482p.Google Scholar
  189. 189.
    Morey-Holton ER, Schnoes HK, DeLuca HF, Phelps ME, Klein RF, Nissenson RH, et al. Vitamin D metabolites and bioactive parathyroid hormone levels during Spacelab 2. Aviat Space Environ Med. 1988;59:1038–41.PubMedGoogle Scholar
  190. 190.
    Heer M, Frings-Meuthen P, Titze J, Boschmann M, Frisch S, Baecker N, et al. Increasing sodium intake from a previous low or high intake affects water, electrolyte and acid-base differently. Br J Nutr. 2009;101(9):1286–94.PubMedGoogle Scholar
  191. 191.
    Frings-Meuthen P, Buehlmeier J, Baecker N, Stehle P, Fimmers R, May F, et al. High sodium chloride intake exacerbates immobilization-induced bone resorption and protein losses. J Appl Physiol. 2011;111(2):537–42.PubMedGoogle Scholar
  192. 192.
    Frings-Meuthen P, Baecker N, Heer M. Low-grade metabolic acidosis may be the cause of sodium chloride-induced exaggerated bone resorption. J Bone Miner Res. 2008;23(4):517–24.PubMedGoogle Scholar
  193. 193.
    Drummer C, Hesse C, Baisch F, Norsk P, Elmann-Larsen B, Gerzer R, et al. Water and sodium balances and their relation to body mass changes in microgravity. Eur J Clin Invest. 2000;30(12):1066–75.PubMedGoogle Scholar
  194. 194.
    Heer M, Baisch F, Kropp J, Gerzer R, Drummer C. High dietary sodium chloride consumption may not induce body fluid retention in humans. Am J Physiol Renal Physiol. 2000;278(4):F585–95.PubMedGoogle Scholar
  195. 195.
    Domrongkitchaiporn S, Pongskul C, Sirikulchayanonta V, Stitchantrakul W, Leeprasert V, Ongphiphadhanakul B, et al. Bone histology and bone mineral density after correction of acidosis in distal renal tubular acidosis. Kidney Int. 2002;62(6):2160–6.PubMedGoogle Scholar
  196. 196.
    Cunningham J, Fraher LJ, Clemens TL, Revell PA, Papapoulos SE. Chronic acidosis with metabolic bone disease. Effect of alkali on bone morphology and vitamin D metabolism. Am J Med. 1982;73(2):199–204.PubMedGoogle Scholar
  197. 197.
    Breslau NA, Brinkley L, Hill KD, Pak CY. Relationship of animal protein-rich diet to kidney stone formation and calcium metabolism. J Clin Endocrinol Metab. 1988;66(1):140–6.PubMedGoogle Scholar
  198. 198.
    Hahn TJ, Halstead LR, DeVivo DC. Disordered mineral metabolism produced by ketogenic diet therapy. Calcif Tissue Int. 1979;28(1):17–22.PubMedGoogle Scholar
  199. 199.
    Kurtz I, Maher T, Hulter HN, Schambelan M, Sebastian A. Effect of diet on plasma acid-base composition in normal humans. Kidney Int. 1983;24(5):670–80.PubMedGoogle Scholar
  200. 200.
    Relman AS, Lennon EJ, Lemann J Jr. Endogenous production of fixed acid and the measurement of the net balance of acid in normal subjects. J Clin Invest. 1961;40:1621–30.PubMedPubMedCentralGoogle Scholar
  201. 201.
    Remer T, Manz F. Estimation of the renal net acid excretion by adults consuming diets containing variable amounts of protein. Am J Clin Nutr. 1994;59(6):1356–61.PubMedGoogle Scholar
  202. 202.
    Remer T, Manz F. Potential renal acid load of foods and its influence on urine pH. J Am Diet Assoc. 1995;95(7):791–7.PubMedGoogle Scholar
  203. 203.
    Michaud DS, Troiano RP, Subar AF, Runswick S, Bingham S, Kipnis V, et al. Comparison of estimated renal net acid excretion from dietary intake and body size with urine pH. J Am Diet Assoc. 2003;103(8):1001–7; discussion 7.PubMedGoogle Scholar
  204. 204.
    Lemann J Jr, Relman AS. The relation of sulfur metabolism to acid-base balance and electrolyte excretion: the effects of DL-methionine in normal man. J Clin Invest. 1959;38:2215–23.PubMedPubMedCentralGoogle Scholar
  205. 205.
    Frassetto LA, Todd KM, Morris RC Jr, Sebastian A. Estimation of net endogenous noncarbonic acid production in humans from diet potassium and protein contents. Am J Clin Nutr. 1998;68(3):576–83.PubMedGoogle Scholar
  206. 206.
    Zwart SR, Pierson D, Mehta S, Gonda S, Smith SM. Capacity of omega-3 fatty acids or eicosapentaenoic acid to counteract weightlessness-induced bone loss by inhibiting NF-kappaB activation: from cells to bed rest to astronauts. J Bone Miner Res. 2010;25(5):1049–57.PubMedGoogle Scholar
  207. 207.
    Terano T. Effect of omega 3 polyunsaturated fatty acid ingestion on bone metabolism and osteoporosis. World Rev Nutr Diet. 2001;88:141–7.PubMedGoogle Scholar
  208. 208.
    Fernandes G, Bhattacharya A, Rahman M, Zaman K, Banu J. Effects of n-3 fatty acids on autoimmunity and osteoporosis. Front Biosci. 2008;13:4015–20.PubMedGoogle Scholar
  209. 209.
    Griel AE, Kris-Etherton PM, Hilpert KF, Zhao G, West SG, Corwin RL. An increase in dietary n-3 fatty acids decreases a marker of bone resorption in humans. Nutr J. 2007;6:2–10.PubMedPubMedCentralGoogle Scholar
  210. 210.
    Hogstrom M, Nordstrom P, Nordstrom A. n-3 Fatty acids are positively associated with peak bone mineral density and bone accrual in healthy men: the NO2 Study. Am J Clin Nutr. 2007;85(3):803–7.PubMedGoogle Scholar
  211. 211.
    Sun D, Krishnan A, Zaman K, Lawrence R, Bhattacharya A, Fernandes G. Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice. J Bone Miner Res. 2003;18(7):1206–16.PubMedGoogle Scholar
  212. 212.
    Zhao Y, Joshi-Barve S, Barve S, Chen LH. Eicosapentaenoic acid prevents LPS-induced TNF-alpha expression by preventing NF-kappaB activation. J Am Coll Nutr. 2004;23(1):71–8.PubMedGoogle Scholar
  213. 213.
    Whitehouse AS, Tisdale MJ. Increased expression of the ubiquitin-proteasome pathway in murine myotubes by proteolysis-inducing factor (PIF) is associated with activation of the transcription factor NF-kappaB. Br J Cancer. 2003;89(6):1116–22.PubMedPubMedCentralGoogle Scholar
  214. 214.
    Whitehouse AS, Khal J, Tisdale MJ. Induction of protein catabolism in myotubes by 15(S)-hydroxyeicosatetraenoic acid through increased expression of the ubiquitin-proteasome pathway. Br J Cancer. 2003;89(4):737–45.PubMedPubMedCentralGoogle Scholar
  215. 215.
    Novak TE, Babcock TA, Jho DH, Helton WS, Espat NJ. NF-kappa B inhibition by omega -3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription. Am J Physiol Lung Cell Mol Physiol. 2003;284(1):L84–9.PubMedGoogle Scholar
  216. 216.
    Kang JX, Weylandt KH. Modulation of inflammatory cytokines by omega-3 fatty acids. Subcell Biochem. 2008;49:133–43.PubMedGoogle Scholar
  217. 217.
    Jimi E, Aoki K, Saito H, D’Acquisto F, May MJ, Nakamura I, et al. Selective inhibition of NF-kappaB blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo. Nat Med. 2004;10(6):617–24.PubMedGoogle Scholar
  218. 218.
    Lin RW, Chen CH, Wang YH, Ho ML, Hung SH, Chen IS, et al. (−)-Epigallocatechin gallate inhibition of osteoclastic differentiation via NF-kappaB. Biochem Biophys Res Commun. 2009;379(4):1033–7.PubMedGoogle Scholar
  219. 219.
    Albertazzi P, Coupland K. Polyunsaturated fatty acids. Is there a role in postmenopausal osteoporosis prevention? Maturitas. 2002;42(1):13–22.PubMedGoogle Scholar
  220. 220.
    Watkins BA, Lippman HE, Le Bouteiller L, Li Y, Seifert MF. Bioactive fatty acids: role in bone biology and bone cell function. Prog Lipid Res. 2001;40(1–2):125–48.PubMedGoogle Scholar
  221. 221.
    Raisz LG, Fall PM. Biphasic effects of prostaglandin E2 on bone formation in cultured fetal rat calvariae: interaction with cortisol. Endocrinology. 1990;126(3):1654–9.PubMedGoogle Scholar
  222. 222.
    Vanek C, Connor WE. Do n-3 fatty acids prevent osteoporosis? Am J Clin Nutr. 2007;85(3):647–8.PubMedGoogle Scholar
  223. 223.
    Heaney RP, Carey R, Harkness L. Roles of vitamin D, n-3 polyunsaturated fatty acid, and soy isoflavones in bone health. J Am Diet Assoc. 2005;105(11):1700–2.PubMedGoogle Scholar
  224. 224.
    Buck AC, Davies RL, Harrison T. The protective role of eicosapentaenoic acid [EPA] in the pathogenesis of nephrolithiasis. J Urol. 1991;146(1):188–94.PubMedGoogle Scholar
  225. 225.
    Yasui T, Suzuki S, Itoh Y, Tozawa K, Tokudome S, Kohri K. Eicosapentaenoic acid has a preventive effect on the recurrence of nephrolithiasis. Urol Int. 2008;81(2):135–8.PubMedGoogle Scholar
  226. 226.
    Tulloch I, Smellie WS, Buck AC. Evening primrose oil reduces urinary calcium excretion in both normal and hypercalciuric rats. Urol Res. 1994;22(4):227–30.PubMedGoogle Scholar
  227. 227.
    Lenin M, Thiagarajan A, Nagaraj M, Varalakshmi P. Attenuation of oxalate-induced nephrotoxicity by eicosapentaenoate-lipoate (EPA-LA) derivative in experimental rat model. Prostaglandins Leukot Essent Fatty Acids. 2001;65(5–6):265–70.PubMedGoogle Scholar
  228. 228.
    Vermeer C, Wolf J, Knapen MH. Microgravity-induced changes of bone markers: effects of vitamin K-supplementation. Bone. 1997;20(4 Suppl):16S.Google Scholar
  229. 229.
    Zwart SR, Booth SL, Peterson JW, Wang Z, Smith SM. Vitamin K status in spaceflight and ground-based models of spaceflight. J Bone Miner Res. 2011;26(5):948–54.PubMedGoogle Scholar
  230. 230.
    Mader TH, Gibson CR, Pass AF, Kramer LA, Lee AG, Fogarty J, et al. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology. 2011;118(10):2058–69.PubMedPubMedCentralGoogle Scholar
  231. 231.
    Zwart SR, Gibson CR, Mader TH, Ericson K, Ploutz-Snyder R, Heer M, et al. Vision changes after spaceflight are related to alterations in folate- and vitamin B-12-dependent one-carbon metabolism. J Nutr. 2012;142(3):427–31.PubMedPubMedCentralGoogle Scholar
  232. 232.
    Zwart SR, Gibson CR, Smith SM. Spaceflight ophthalmic changes, diet, and vitamin metabolism. In: Preedy VR, editor. Handbook of diet, nutrition and the eye. Waltham: Academic Press; 2014. p. 393–9.Google Scholar
  233. 233.
    National Research Council. Committee on Life Sciences, Food and Nutrition Board, Subcommittee on the Tenth Edition of the RDAs. Recommended dietary allowances. 10th ed. Washington: National Academy Press; 1989. 249p.Google Scholar
  234. 234.
    National Aeronautics and Space Administration Johnson Space Center. Nutritional requirements for Space Station Freedom crews. Houston: NASA Conference Publication #3146; 1991.Google Scholar
  235. 235.
    Smith SM, Lane HW. Nutritional biochemistry of space flight. Life Support Biosph Sci. 1999;6(1):5–8.PubMedGoogle Scholar
  236. 236.
    Cooper M, Douglas G, Perchonok M. Developing the NASA food system for long-duration missions. J Food Sci. 2011;76(2):R40–8.PubMedGoogle Scholar
  237. 237.
    Perchonok MH, Cooper MR, Catauro PM. Mission to Mars: food production and processing for the final frontier. Annu Rev Food Sci Technol. 2012;3:311–30.PubMedGoogle Scholar
  238. 238.
    Smith SM, Feeback DL. In: Kost GJ, editor. Principles and practice of point-of-care testing Point-of-care testing in space and at high altitude. Baltimore: Lippincott Williams & Wilkins; 2002. p. 413–4.Google Scholar
  239. 239.
    Heer M, Boerger A, Kamps N, Mika C, Korr C, Drummer C. Nutrient supply during recent European missions. Pflugers Arch. 2000;441(2–3 Suppl):R8–14.PubMedGoogle Scholar
  240. 240.
    Soller BR, Cabrera M, Smith SM, Sutton JP. Smart medical systems with application to nutrition and fitness in space. Nutrition. 2002;18(10):930–6.PubMedGoogle Scholar
  241. 241.
    Pietrzyk RA, Feiveson AH, Whitson PA. Mathematical model to estimate risk of calcium-containing renal stones. Miner Electrolyte Metab. 1999;25(3):199–203.PubMedGoogle Scholar
  242. 242.
    Pietrzyk RA, Jones JA, Sams CF, Whitson PA. Renal stone formation among astronauts. Aviat Space Environ Med. 2007;78(4 Suppl):A9–13.PubMedGoogle Scholar
  243. 243.
    Garnero P, Shih WJ, Gineyts E, Karpf DB, Delmas PD. Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate treatment. J Clin Endocrinol Metab. 1994;79(6):1693–700.PubMedGoogle Scholar
  244. 244.
    Zeitlin C, Hassler DM, Cucinotta FA, Ehresmann B, Wimmer-Schweingruber RF, Brinza DE, et al. Measurements of energetic particle radiation in transit to Mars on the Mars Science Laboratory. Science. 2013;340(6136):1080–4.PubMedPubMedCentralGoogle Scholar
  245. 245.
    Chylack LT Jr, Peterson LE, Feiveson AH, Wear ML, Manuel FK, Tung WH, et al. NASA study of cataract in astronauts (NASCA). Report 1: cross-sectional study of the relationship of exposure to space radiation and risk of lens opacity. Radiat Res. 2009;172(1):10–20.PubMedPubMedCentralGoogle Scholar
  246. 246.
    Cucinotta FA, Manuel FK, Jones J, Iszard G, Murrey J, Djojonegro B, et al. Space radiation and cataracts in astronauts. Radiat Res. 2001;156(5 Pt 1):460–6.PubMedPubMedCentralGoogle Scholar
  247. 247.
    Hall EJ. Radiobiology for the radiologist. Hagerstown: Harper & Row, Publishers; 1973.Google Scholar
  248. 248.
    Rock CL, Jacob RA, Bowen PE. Update on the biological characteristics of the antioxidant micronutrients: vitamin C, vitamin E, and the carotenoids. J Am Diet Assoc. 1996;96:693–702.PubMedGoogle Scholar
  249. 249.
    Brewster MA. Vitamins. In: Kaplan LA, Pesce AJ, editors. Clinical chemistry: theory, analysis, and correlation. St. Louis: Mosby-Year Books, Inc.; 1996. p. 760–92.Google Scholar
  250. 250.
    Thomas JA. Oxidative stress, oxidant defense, and dietary constituents. In: Shils ME, Olson JA, Shike M, Ross AC, editors. Modern nutrition in health and disease. 9th ed. Baltimore: Williams & Wilkins; 1999. p. 751–60.Google Scholar
  251. 251.
    Singh RB, Ghosh S, Niaz MA, Singh R, Beegum R, Chibo H, et al. Dietary intake, plasma levels of antioxidant vitamins, and oxidative stress in relation to coronary artery disease in elderly subjects. Am J Cardiol. 1995;76(17):1233–8.PubMedGoogle Scholar
  252. 252.
    Halliwell B. Antioxidants. In: Ziegler EE, Filer Jr LJ, editors. Present knowledge in nutrition. 7th ed. Washington: International Life Sciences Institute; 1996. p. 596–603.Google Scholar
  253. 253.
    Heer M, Zittermann A, Hoetzel D. Role of nutrition during long-term spaceflight. Acta Astronaut. 1995;35(4–5):297–311.PubMedGoogle Scholar
  254. 254.
    Lane HW, Nillen JL, Kloeris VL. Folic acid content in thermostabilized and freeze-dried space shuttle foods. J Food Sci. 1995;60:538–40.PubMedGoogle Scholar
  255. 255.
    Beard JL. Iron. In: Bowman BA, Russell RM, editors. Present knowledge in nutrition. I. 9th ed. Washington: International Life Sciences Institute; 2006. p. 430–44.Google Scholar
  256. 256.
    Beard JL, Borel MJ, Derr J. Impaired thermoregulation and thyroid function in iron-deficiency anemia. Am J Clin Nutr. 1990;52(5):813–9.PubMedGoogle Scholar
  257. 257.
    Fairbanks VF. Iron in medicine and nutrition. In: Shils ME, Olson JA, Shike M, Ross AC, editors. Modern nutrition in health and disease. 9th ed. Baltimore: Lippincott Williams & Wilkins; 1999. p. 193–221.Google Scholar
  258. 258.
    Fontecave M, Pierre JL. Iron: metabolism, toxicity and therapy. Biochimie. 1993;75:767–73.PubMedGoogle Scholar
  259. 259.
    Fontecave M, Jaouen M, Mansuy D, Costa D, Zalma R, Pezerat H. Microsomal lipid peroxidation and oxy-radicals formation are induced by insoluble iron-containing minerals. Biochem Biophys Res Commun. 1990;173(3):912–8.PubMedGoogle Scholar
  260. 260.
    Miller DM, Buettner GR, Aust SD. Transition metals as catalysts of ‘autooxidation’ reactions. Free Radic Biol Med. 1990;8:95–108.PubMedGoogle Scholar
  261. 261.
    Bottiger LE, Carlson LA. Risk factors for ischaemic vascular death in men in Stockholm Prospective Study. Atherosclerosis. 1980;36:389–408.Google Scholar
  262. 262.
    Lauffer RB. Iron stores and the international variation in mortality from coronary artery disease. Lancet. 1991;2:1288–9.Google Scholar
  263. 263.
    Sullivan JL. The iron paradigm of ischemic heart disease. Am Heart J. 1989;117:1177–88.PubMedGoogle Scholar
  264. 264.
    Sullivan JL. Stored iron and ischemic heart disease: empirical support for a new paradigm (Editorial Comment). Circulation. 1992;86:1036–7.PubMedGoogle Scholar
  265. 265.
    Salonen JT, Nyyssonen K, Korpela H, Tuomilehto J, Seppanen R, Salonen R. High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. Circulation. 1992;86(3):803–11.PubMedGoogle Scholar
  266. 266.
    Sempos CT, Looker AC, Gillum RF, Makuc DM. Body iron stores and the risk of coronary heart disease. N Engl J Med. 1994;330(16):1119–24.PubMedGoogle Scholar
  267. 267.
    Ascherio A, Willett WC. Are body iron stores related to the risk of coronary heart disease? (Editorial). N Engl J Med. 1994;330:1152–4.PubMedGoogle Scholar
  268. 268.
    Knekt P, Reunanen A, Takkunen H, Aromaa A, Heliovaara M, Hakulinen T. Body iron stores and risk of cancer. Int J Cancer. 1994;56(3):379–82.PubMedGoogle Scholar
  269. 269.
    Salonen JT, Korpela H, Nyyssonen K, Porkkala E, Tuomainen TP, Belcher JD, et al. Lowering of body iron stores by blood letting and oxidation resistance of serum lipoproteins: a randomized cross-over trial in male smokers. J Intern Med. 1995;237(2):161–8.PubMedGoogle Scholar
  270. 270.
    Rajaram S, Weaver CM, Lyle RM, Sedlock DA, Martin B, Templin TJ, et al. Effects of long-term moderate exercise on iron status in young women. Med Sci Sports Exerc. 1995;27(8):1105–10.PubMedGoogle Scholar
  271. 271.
    Weaver CM, Rajaram S. Exercise and iron status. J Nutr. 1992;122(3 Suppl):782–7.PubMedGoogle Scholar
  272. 272.
    Moore RJ, Friedl KE, Tulley RT, Askew EW. Maintenance of iron status in healthy men during an extended period of stress and physical activity. Am J Clin Nutr. 1993;58(6):923–7.PubMedGoogle Scholar
  273. 273.
    Vidnes A, Opstad PK. Serum ferritin in young men during prolonged heavy physical exercise. Scand J Haematol. 1981;27(3):165–70.PubMedGoogle Scholar
  274. 274.
    Singh A, Smoak BL, Patterson KY, LeMay LG, Veillon C, Deuster PA. Biochemical indices of selected trace minerals in men: effect of stress. Am J Clin Nutr. 1991;53(1):126–31.PubMedGoogle Scholar
  275. 275.
    Lindemann R, Ekanger R, Opstad PK, Nummestad M, Ljosland R. Hematological changes in normal men during prolonged severe exercise. Am Correct Ther J. 1978;32(4):107–11.PubMedGoogle Scholar
  276. 276.
    McMonigal K, Sauer RL, Smith SM, Pattinson T, Gillman PL, Davis-Street JE, et al. Physiological effects of iodinated water on thyroid function. In: Lane HW, Sauer RL, Feeback DL, editors. Isolation: NASA experiments in closed-environment living. San Diego: Univelt, Inc.; 2002. p. 369–95.Google Scholar
  277. 277.
    McMonigal KA, Braverman LE, Dunn JT, Stanbury JB, Wear ML, Hamm PB, et al. Thyroid function changes related to use of iodinated water in the U.S. Space Program. Aviat Space Environ Med. 2000;71(11):1120–5.PubMedGoogle Scholar
  278. 278.
    Smith SM, Zwart SR, McMonigal KA, Huntoon CL. Thyroid status of Space Shuttle crewmembers: effects of iodine removal. Aviat Space Environ Med. 2011;82(1):49–51.PubMedGoogle Scholar
  279. 279.
    Zwart SR, Kloeris VL, Perchonok MH, Braby L, Smith SM. Assessment of nutrient stability in foods from the space food system after long-duration spaceflight on the ISS. J Food Sci. 2009;74(7):H209–17.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Scott M. Smith
    • 1
    Email author
  • Helen W. Lane
    • 2
  • Sara R. Zwart
    • 3
  1. 1.Biomedical Research and Environmental Sciences DivisionNASA Johnson Space CenterHoustonUSA
  2. 2.NASA Johnson Space CenterHoustonUSA
  3. 3.Preventive Medicine and Community Health DivisionUniversity of Texas Medical Branch at GalvestonGalvestonUSA

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