Aviation, Space, and Environmental Medicine x Vol. 80, No. 5, Section II x May 2009
Z WART SR, O LIVER SAM, F ESPERMAN JV, K ALA G, K RAUHS J, E RICSON
K, S MITH SM. Nutritional status assessment before, during, and after
long-duration head-down bed rest. Aviat Space Environ Med 2009;
80(5,Suppl.):A 15 – 22 .
Introduction: Bed rest is a valuable ground-based model for many of
the physiological changes that are associated with spacefl ight. Nutri-
tional changes during and after 60 or 90 d of head-down bed rest were
evaluated. Methods: A total of 13 subjects (8 men, 5 women; ages 26 –
54 yr) participated in either 60 or 90 d of bed rest. Blood and urine were
collected twice before bed rest and about once per month during bed
rest. Samples were stored frozen and batch analyzed. Data were ana-
lyzed using repeated-measures analysis of variance. Results: During bed
rest, markers of bone resorption (such as N-telopeptide excretion, P ,
0.001) increased and serum concentration of parathyroid hormone de-
creased ( P , 0.001). Also, oxidative damage markers such as superoxide
dismutase increased ( P , 0.05), and after 90 d of bed rest, total antioxi-
dant capacity decreased ( P , 0.05). During bed rest, iron status indices
showed patterns of increased iron stores with a decreased concentration
of transferrin receptors ( P , 0.01). Discussion: These changes are similar
to some of those observed during spacefl ight, and further document the
utility of bed rest as a model of spacefl ight.
Keywords: spacefl ight , nutrition , weightlessness , bone resorption , para-
thyroid hormone , oxidative stress , antioxidants , iron , transferrin .
loss, inadequate dietary intake, decreased nutrient stores,
increased oxidative damage due to factors such as ra-
diation exposure and increased iron stores, and altered
nutrient metabolism ( 41 ). Designing and testing counter-
measures to mitigate these negative physiological effects
of spacefl ight require a solid understanding of changes in
nutrient status during spacefl ight, because macro- and
micronutrients are essential for every cell and function in
the body. Data from 11 International Space Station (ISS)
astronauts suggest that their nutritional status is compro-
mised after long-duration spacefl ight ( 40 ). Some of the
most striking changes are decrements in vitamin D, folate,
vitamin K, and vitamin E status, and increases in markers
of bone resorption and oxidative damage. Changes in uri-
nary excretion of phosphorus and magnesium were also
evident after 4 to 6 mo of spacefl ight ( 40 ).
That vitamin D status is decreased after long-duration
spacefl ight is clearly indicated by results of studies from
Skylab, Mir, and ISS missions ( 17,33,39,40 ). Even for
crewmembers who used supplements, 25-hydroxyvitamin
D status decreased ( 17,40 ). The low levels of vitamin D in
the space food supply and the absence of ultraviolet
OME OF THE CLINICAL concerns for long-duration
spacefl ight (longer than 30 d) are bone and muscle
light during spacefl ight likely contribute to this phe-
nomenon. Altered vitamin D status is accompanied by
evidence of increased bone resorption during and after
spacefl ight ( 31,33,40 ). During spacefl ight, the excretion
rates of urinary markers of bone resorption are typically
100 – 150% of their prefl ight values ( 3,5,31,33,39 ). Loss of
bone mineral is increased by skeletal unloading during
weightlessness ( 10,21,33,36,39,41 ).
Evidence exists that during and after spacefl ight, along
with changes in nutrient status, the metabolism of cer-
tain nutrients is altered ( 41 ), and iron is one of these nu-
trients. The data suggest that as a result of microgravity,
storage pools of iron are shifted so that less iron is in red
blood cells and more is stored in ferritin, and less iron is
transported (less transferrin) ( 35,40 ). Serum ferritin con-
centration is signifi cantly increased, the amount of ferri-
tin iron is slightly greater than before launch, and the
amount of transferrin is decreased. Red blood cell mass
also decreases ( 1,6,14,43 ). After landing, a delay in re-
placing red blood cells often leads to decreased hemoglo-
bin, hematocrit, and mean corpuscular volume ( 34,40 ).
Like other physiological effects of weightlessness,
changes in nutrient status and metabolism can be stud-
ied in the bed rest analog of weightlessness. The qualita-
tive effects of bed rest on bone and calcium homeostasis
are similar to the effects of spacefl ight, but the quantita-
tive effects are generally less than (about half) those of
spacefl ight ( 41 ). As reviewed by Meck and colleagues
( 23 ) and others ( 25 ), bed rest is a good model for space-
fl ight, but lack of standard procedures has limited the
ability to draw conclusions across studies. This report is
one of a series of reports on the Flight Analogs Project,
which is designed to lay the groundwork for a standard
bed rest protocol. Standard procedures were developed
From the Nutritional Biochemistry Laboratory, Human Adaptation
and Countermeasures Division, NASA Johnson Space Center, Houston,
TX; Enterprise Advisory Services, Inc., Houston, TX; Wyle, Houston,
TX; Indiana University-Purdue University, Fort Wayne, IN; and
Universities Space Research Association, Houston, TX.
Address reprint requests to: Scott M. Smith, Ph.D., NASA Johnson
Space Center, Mail Code SK, 2101 NASA Parkway, Houston, TX 77058;
Reprint & Copyright © by the Aerospace Medical Association,
Nutritional Status Assessment Before, During, and
After Long-Duration Head-Down Bed Rest
Sara R. Zwart , Susan A. Mathews Oliver ,
J. Vernell Fesperman , Geeta Kala , Jane Krauhs ,
Karen Ericson , and Scott M. Smith
A22 Aviation, Space, and Environmental Medicine x Vol. 80, No. 5, Section II x May 2009
NUTRITIONAL STATUS IN BED REST — ZWART ET AL
SL, eds. Space physiology and medicine, 3rd ed. Philadelphia,
PA: Lea & Febiger; 1994:213-27.
25. 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 : 143 – 94 .
26. Pawlak W , Kedziora J , Zolynski K , Kedziora-Kornatowska K,
Blaszczyk J, Witkowski P. Free radicals generation by
granulocytes from men during bed rest . J Gravit Physiol
1998; 5 :P 131 – 2 .
27. Pawlak W , Kedziora J , Zolynski K , Kedziora-Kornatowska K,
Blaszczyk J, Witkowski P, Zieleniewski J. Effect of long term
bed rest in men on enzymatic antioxidative defence and lipid
peroxidation in erythrocytes . J Gravit Physiol 1998; 5 :P 163 – 4 .
28. Smith SM , Oliver SM , Zwart S , Kala G, Kelly PA, Goodwin JS,
Dryer CB. Nutritional status in self-neglecting elderly . J Nutr
2006 ; 136 : 2534 – 41 .
29. Smith SM , Davis-Street J , Rice BL , Lane HW. Nutrition in space .
Nutr Today 1997; 32 : 6 – 12 .
30. Smith SM , Davis-Street JE , Fontenot TB , Lane HW. Assessment
of a portable clinical blood analyzer during space fl ight . Clin
Chem 1997; 43 : 1056 – 65 .
31. Smith SM , Nillen JL , LeBlanc A , Lipton A, Demers LM, Lane HW,
Leach CS. Collagen cross-link excretion during space fl ight and
bed rest . J Clin Endocrinol Metab 1998; 83 : 3584 – 91 .
32. Smith SM , Lane HW . Nutritional biochemistry of space fl ight . Life
Support Biosph Sci 1999 ; 6 : 5 – 8 .
33. Smith SM , Wastney ME , Morukov BV , Larina IM, Nyquist LE,
Abrams SA, et al. Calcium metabolism before, during, and
after a 3-mo spacefl ight: kinetic and biochemical changes . Am
J Physiol 1999; 277 ( 1, Pt 2 ): R1 – 10 .
34. Smith SM , Davis-Street JE , Rice BL , Nillen JL, Gillman PL, Block
G. Nutritional status assessment in semiclosed environments:
ground-based and space fl ight studies in humans . J Nutr
2001; 131 : 2053 – 61 .
35. Smith SM . Red blood cell and iron metabolism during space fl ight .
Nutrition 2002 ; 18 : 864 – 6 .
36. Smith SM , Heer M . Calcium and bone metabolism during space
fl ight . Nutrition 2002 ; 18 : 849 – 52 .
37. 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 .
38. 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 .
39. 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 fl ight on the
Mir space station . J Bone Miner Res 2005; 20 : 208 – 18 .
40. Smith SM , Zwart SR , Block G , Rice BL, Davis-Street JE. The
nutritional status of astronauts is altered after long-term space
fl ight aboard the International Space Station. J Nutr 2005 ;
135 : 437 – 43 .
41. Smith SM, Zwart SR. Nutritional biochemistry of spacefl ight.
[Review.] Adv Clin Chem 2008; 46:87-130.
42. Su CJ , Shevock PN , Khan SR , Hackett RL. Effect of magnesium on
calcium oxalate urolithiasis . J Urol 1991; 145 : 1092 – 5 .
43. 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 .
44. 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 : 1594 – 601 .
45. Zezerov AE , Ivanova SM , Morukov BV , Ushakov AS. [Lipid
peroxidation in the human blood during a 120-day period
of anti-orthostatic hypokinesia] . Kosm Biol Aviakosm Med
1989; 23 : 28 – 33 .