![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
* Human Adaptation and Countermeasures Office, NASA Lyndon B. Johnson Space Center, Houston, TX 77058;
Epidemiology and Public Health Nutrition, University of California-Berkeley, Berkeley, CA 94720; and
** Enterprise Advisory Services, Inc., Houston, TX 77058
2To whom correspondence should be addressed. E-mail: scott.m.smith{at}nasa.gov.
 |
ABSTRACT |
|---|
 TOP ABSTRACT SUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
KEY WORDS: • space flight • nutritional status • humans • bone resorption • weightlessness
In a vigorous human space exploration program, with mission durations far exceeding any Space Shuttle or International Space Station (ISS)3 mission duration to date, maintenance of crew member health will be of critical importance. Proper nutrition will be essential to this effort. In order to provide nutritional recommendations to crew members for long-duration space travel, we need to better understand how nutritional status and general physiology are affected by the microgravity environment. Dietary intake during space flight has often been inadequate (1–3), and this can greatly compromise nutritional status. Although some information is available about nutritional status during and after flight (1,4–7), the small sample sizes and incomplete data sets preclude a complete understanding of the role of nutrition in maintaining health in human space crews.
Data from both short- and long-duration space flights provide evidence that energy intake is typically 30–40% below the WHO recommendation, but energy expenditure is typically unchanged or even increased (1–3,8,9). This imbalance may explain some of the negative changes in overall nutritional status during flight. However, blood concentrations of some nutrients, such as vitamin D, continue to be low even when astronauts receive supplements during flight (4). Data from individual Skylab missions show that crew members on the longest mission (Skylab 4, 84 d), but not the shorter missions (28 and 59 d), had decreased serum 25-hydroxycholecalciferol [25(OH)-D3] at landing despite daily vitamin D supplementation (4). Similarly, in 2 separate studies, we reported that crew members on the Russian space station Mir had serum 25(OH)-D3 concentrations that were 32–36% less during and after long-duration (3- to 4-mo) missions than before the missions (1,5,10). Ground-based studies of subjects living in closed-chamber facilities for extended periods also support these data (1).
The space environment itself results in physiologic changes that can alter nutritional status. For example, changes in iron metabolism are closely associated with hematological alterations during space flight (1,11,12). Similarly, increased levels of radiation and oxidative stress during flight likely contribute to decreased antioxidant status during or after space flight.
In this study, we sought to better understand the nutritional status changes that occur during long-duration space flight. A secondary goal of this study was to determine whether changes in nutrient intake during flight were related to changes in nutritional status recorded after flight. The results presented here are data from astronauts who flew on 4- to 6-mo missions aboard the ISS. These data represent the first report of nutritional status from this space platform and the most complete nutritional assessment of space crews to date.
|
SUBJECTS AND METHODS |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Following the loss of the Space Shuttle Columbia and subsequent grounding of the U.S. Space Shuttle program, crew members from 3 of the ISS Expeditions (n = 4) landed in Russia instead of the United States. Thus, their postflight biological samples were collected in Star City, Russia. Postflight samples for the 5 expeditions (n = 7) that landed in the United States were collected at the Kennedy Space Center in Florida. Regardless of collection site, all samples were analyzed at the Johnson Space Center. The protocol for this study was approved by the Johnson Space Center Committee for the Protection of Human Subjects.
Food system. The ISS food system provides a menu with a cycle of 6 to 10 d. About half of the food items are supplied by the United States and the other half are supplied by Russia (13). Foods are packaged in single-serving containers and are thermostabilized, dehydrated, irradiated, intermediate moisture, or natural form (13). Before each mission, crew members participate in food-tasting sessions, and dietitians plan menus that will use crew choices and best fulfill the defined nutritional requirements for space flight (14). These requirements have been derived from space flight research, extrapolated from speculation about the effects of space flight on nutrient needs, or applied directly from ground-based dietary reference intakes for micronutrients and WHO recommendations (15). A key concern for space flight, and limitation of the food system, is vitamin D. Accordingly, vitamin D supplements (10 µg/d) were provided for the crew members. Some crew members consumed multivitamin supplements at their own discretion and/or in consultation with their flight surgeon.
FFQ. During flight, crew members were asked to record their dietary intake once per wk using an FFQ designed for use with the space flight food system. This FFQ has been validated in a ground-based model of long-duration space flight (1). Given the closed food system (with repetitive menu cycle), known portion sizes, and precise nutrient content for each food item in the system, the FFQ designed for space flight is much more reliable than a standard food questionnaire.
The FFQ is designed to obtain a near-real-time estimate of intakes of energy, protein, water, sodium, calcium, and iron, as well as to collect information about supplement use and any crew comments (16). The questionnaire input is transmitted to the ground, and results are calculated and reported to the flight surgeon within 24 to 48 h.
A unique FFQ was developed for each expedition to the International Space Station and was based on the specific menu for the crew on board and potential foods on board from earlier crews. Nutrient analyses by the NASA Johnson Space Center Water and Food Analytical Laboratory were used to categorize foods in the FFQ to optimize data from the nutrients of interest.
An additional ground-based validation of each FFQ was completed by comparing the nutrient analysis of the menu (using proximate analysis data) with results obtained by entering the menu items into the FFQ. This was done at 2 levels, 100% (assumed complete menu consumption) or 66% (inadequate consumption).
Body mass and body composition determinations. Body mass was determined before, during, and after each flight; body composition (bone mineral content, bone mineral density, lean body mass, fat mass) was determined before and after each flight. Body mass and body composition before and after flight were determined by dual-energy X-ray absorptiometry (DEXA) with a fan beam densitometer (Hologic QDR 4500W, Hologic). Whole-body scans for body composition assessment were performed about 180 and 45 d before launch (designated L-180 and L-45) and 5 d after landing (designated Return + 5 d, or R + 5).
Body mass during flight was determined using a body mass-measuring device. The body mass-measuring device exerts a known force on the body, and body acceleration is measured. According to Newton’s second law, body mass can be calculated from the force and acceleration. Body weight was also determined, using a standard clinical scale, before (L-180 and L-45) and after (landing day, R + 0) each flight.
Biological sample collection and processing. Preflight blood and initial urine samples were collected at about L-180 and L-45 for all crew members. For crew members landing in the United States, postflight samples were collected on R + 0 within 2 to 4 h of landing. For crew members on the expeditions that landed in Russia, postflight urine collection began on R + 1 or R + 2, and blood samples were collected 9 to 16 h after landing. Preflight blood samples were collected after an 8-h fast, but fasting did not always occur before collection of postflight blood samples. Crew members on the 5 Shuttle landings in the United States generally fasted 4 to 6 h before the R + 0 blood collection.
Blood samples were collected into appropriate tubes and processed to yield whole blood, plasma, or serum, depending on the specific analyte to be measured. A total of about 23.7 mL of blood was collected from each subject for all tests described herein.
During flight, blood samples were collected by finger stick for real-time analysis of blood pH and ionized calcium.
Pre- and postflight urine samples were collected over 48 h in individual bottles and stored in coolers until they were processed. Twenty-four-hour urine pools were created, pH was measured, and aliquots were prepared and frozen at –80°C for subsequent analysis.
Biochemical analyses. Regardless of sample collection site, analyses were performed at the Johnson Space Center by trained personnel. Most analyses were performed by standard commercial techniques, and all have been previously described in detail (1,17).
Statistical analysis. Statistical analyses were designed to test the hypothesis that nutritional status was different postflight compared to preflight. We accounted for the difference in landing site in a subset of crew members, because the timing of sample collections in those crew members is a potential confounding factor. We also controlled for duplicate preflight sessions in crew members. Details of the approach used are described herein. Because all sample analyses were performed at the Johnson Space Center, any effect of landing site is not related to sample analysis, but likely to the time of sample collection (i.e., number of hours from touchdown) that varied between the 2 sites.
Statistical analyses were performed with the data in their original form or on a transformed (reciprocal, square, or natural logarithm) scale to achieve normality and homogeneity of variability as determined by the Kolmogorov-Smirnov normality test. Data for some variables [RBC folate, body mass, 8-hydroxy-2'-deoxyguanosine (8OHdG), and serum selenium] could not be normalized; in these cases, the nonnormalized data were analyzed.
Student’s t test was used to analyze for differences between the 2 preflight collection times (L-180 and L-45). If no differences were noted (as occurred in all but 1 case), preflight mean values were determined and compared with postflight (R + 0 through R + 2) data using a two-way repeated measures ANOVA, with time and landing site (United States and Russia) as repeated factors. The dependent variables were the analytes measured. Post hoc Bonferroni tests were performed to assess specific differences between times or landing sites. For the case where L-180 and L-45 values were significantly different, L-45 (instead of the preflight mean) was compared with the postflight data using two-way repeated measures ANOVA. These cases are noted in the Results.
In instances where significant outliers existed (as determined by Grubbs’ test), the data were analyzed with and without the outlier and both results were reported. For some analyses in which correlations were assessed, the data were analyzed by simple linear regression and a Pearson correlation coefficient (r) was calculated. Statistical analyses were performed using SigmaStat software 3.01a (SPSS), and P < 0.05 was the level of significance. Data are expressed as means ± SD.
|
RESULTS |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
One way to validate the FFQ was to calculate the results obtained from entering the planned menu contents for each Expedition into the FFQ (at 100 or 66% of menu content, for high and low reference points) and compare the FFQ result to the exact nutrient data from proximate analysis of the same menu foods. The FFQ estimated the intake of energy within 97 ± 5% of proximate analysis at 100% intake and 97 ± 7% at 66% intake. Similar results were found for other nutrients (data not shown).
Food intake. The mean energy intake based on the FFQ for the entire in-flight period (n = 11) was 2284 ± 627 kcal (9563 ± 2625 kJ), which is equivalent to 80 ± 21% of the WHO recommendation (Fig. 1A). Total protein intake during flight was 102 ± 29 g, sodium intake was 4556 ± 1492 mg, calcium intake was 1068 ± 384 mg, and iron intake was 23 ± 12 mg. During flight, subjects reported consuming 5.7 ± 4.0 vitamin D supplements per week (each supplement contained 10 µg cholecalciferol, and this number accounts for the vitamin D from any multivitamin consumed). Subjects consumed a mean of 3.5 ± 2.9 multivitamin supplements per week.
|
|
|
Oxidative stress. The urinary concentration of 8OHdG was elevated about 32% after landing (P < 0.05), indicating that increased DNA damage was present after space flight (Table 2). RBC superoxide dismutase was less after landing, indicating a decreased antioxidant capacity during flight. Although postflight total antioxidant capacity (TAC) was not different from preflight TAC, on landing day 6 of the 11 crew members had TAC values below the low end of the normal clinical range (1.285 mmol/L) (individual data not shown). Malondialdehyde concentration was not changed after landing.
|
Serum concentrations of retinyl palmitate were significantly greater after landing than before launch (Table 2). Serum 
-tocopherol concentration was 46% less after long-duration space flight than before flight (P < 0.05), but 
-tocopherol was unchanged. Phylloquinone was 42% less after flight than before flight (P < 0.01 for normalized data). Of the water-soluble vitamins assessed, RBC folate concentrations were about 20% less (P < 0.01) after landing. Qualitative RBC transketolase data (with one exception preflight) were within the normal range (<15% activation) (18).
Bone markers. The vitamin D status indicator 25(OH)-D3 was 25% less after landing than before flight (P < 0.01), with concentrations ranging from 17 to 92 nmol/L (Table 3). The concentration of 1,25-dihydroxycholecalciferol, the active form of vitamin D, was not different after landing, although the serum concentration at landing for crew members with Russian landings tended to be greater than that of crew members with U.S. landings (P = 0.053). Unlike previous space flight findings, urinary calcium at landing did not differ (P = 0.50) from that before launch, but the blood concentration of ionized calcium was lower (P = 0.06) after landing than before launch. Eight of the 11 crew members had blood ionized calcium concentrations at or below the lower limit of the normal clinical range (1.19 mmol/L) (individual data not shown). All markers of bone resorption that were measured were significantly greater after landing than before launch (Table 3). The excretion of deoxypyridinoline was 75% greater (P < 0.01), excretion of N-telopeptide was about 40% greater (P < 0.001), and excretion of pyridinium crosslinks was 60% greater (P < 0.05) after landing than before launch. The timing of sample collection after flight may affect indicators of bone formation, because bone-specific alkaline phosphatase was greater for astronauts with Russian landings than for those with U.S. landings (P < 0.05) (Table 3). For osteocalcin, values from Russian landings were less after flight than before flight, and values from U.S. landings were greater after flight than before flight. Before launch, 25(OH)-D3 was inversely correlated with parathyroid hormone (PTH) (r = –0.72, P < 0.05), but this relation was not evident after landing.
|
|
|
DISCUSSION |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Vitamin D status was altered after long-duration space flight (about 4 to 6 mo). Despite the reported use of vitamin D supplements by some of the astronauts (5.7 ± 4.0 supplements/wk), the serum concentration of 25(OH)-D3 for the ISS crew members in this study was about 25% less after landing than before launch. Reported supplement use was not related to 25(OH)-D3 status (regression data not shown).
The normal range for serum 25(OH)-D3 is about 23 to 117 nmol/L, but the lower limit can vary from 20 to 37.5 nmol/L depending on the geographic location where the blood samples were collected (19). The cutoff point to define a vitamin D deficiency is a source of some controversy because past recommendations have been based solely on preventing rickets or osteomalacia and not on chronic deficiency diseases (20). It is now evident that vitamin D status is an important determinant for long-latency diseases as well and that marginal deficiencies should be considered as well as frank deficiencies (21–24). Several studies suggest that an optimal serum 25(OH)-D3 level is around 80 nmol/L (23,25,26), which would mean that 80–90% of the subjects had suboptimal vitamin D status before and after their flights. Not only was vitamin D status decreased after long-duration space flight, but also vitamin D metabolism or function may have been altered. Serum 25(OH)-D3 concentration is inversely proportional to serum PTH (20,27), and this relation was evident among crew members before flight but not after flight. The difference between the preflight and postflight relation of PTH and 25(OH)-D3 suggests that the body’s normal response to changes in vitamin D status was altered.
Altered vitamin D status after landing was accompanied by evidence of increased bone resorption. After landing, urinary markers of bone resorption were 40–75% greater than before launch; this supports previous findings (5,7,10,28,29).
No previous evidence exists for increased bone formation during flight, but increases have been noted after landing (5,10). Likewise, bone formation is unchanged during bed rest (a ground-based model of weightlessness) (30–33), but evidence suggests that bone formation increases after reambulation (34,35). The differences in timing of the sample collections at the Russian and U.S. landing sites may explain the significant effect of landing site on bone marker data.
Urinary magnesium and phosphorus concentrations were about 45% less after landing than before launch. Results of previous space flight studies are consistent with a significant decrease in urinary magnesium (4,36), possibly owing to a decrease in magnesium intake. Decreased urinary magnesium could be a point of concern for long-duration flights because of the role of magnesium in inhibiting calcium oxalate renal stones (37,38).
The role of vitamin K in space flight must be further evaluated because this study and others suggest that the serum concentration of vitamin K is less during space flight than before flight, and a decreased vitamin K status has negative implications for bone health (39). Vitamin K is involved in the formation of -carboxyglutamic acid (GLA) in proteins, such as osteocalcin and matrix GLA protein. Although the urinary excretion of GLA did not change significantly in this study, serum phylloquinone was 42% less (P < 0.05) after landing than before launch. Other studies demonstrate that vitamin K supplementation during space flight significantly elevates urinary GLA excretion and decreases the excretion rate of undercarboxylated osteocalcin, suggesting that vitamin K status is compromised during space flight (40,41).
Folate and vitamin E are also affected by space flight. The results of the present study provide no evidence that vitamin B-6, riboflavin, ß-carotene, or retinol was altered by exposure to microgravity. RBC folate decreased about 20% (P < 0.01). Before launch, the RBC folate of most subjects was at or near the upper limit of the normal range. After landing, the RBC folate of many subjects approached the lower limit of the normal range, and it is not known whether this decrease in folate status would level off or continue to decrease with missions of even longer duration. Food processing techniques do not reduce the availability of folate in the space flight diet (42). Thus inadequate food intake rather than limited folate availability during flight is likely a key factor contributing to the decrease in folate status. The number of multivitamins consumed per week was positively correlated (r = 0.62, P < 0.05) with RBC folate levels (data not shown), which suggests that the decreased folate status during flight is likely related to decreased folate intake. -Tocopherol but not -tocopherol was significantly decreased after landing. This may have been caused by decreased overall food intake or radiation/oxidative stress. The unchanged -tocopherol may relate to supplement use during flight.
Several oxidative stressors in the space flight environment have the potential to induce oxidative damage to biological systems. Two such stressors are radiation hazards and periods of exposure to hyperoxia. The decreased superoxide dismutase (SOD) after landing suggests that antioxidant capacity decreases during flight. Although there was no evidence that lipid peroxidation occurred, serum 8OHdG was greater after landing than before launch, suggesting that the amount of DNA damage was greater after flight. The magnitude of the increase in 8OHdG is similar to the effects of both active cigarette smoking and passive exposure to environmental cigarette smoke (43,44).
The findings reported here for hematologic variables and iron indices support previous preliminary data obtained from 2 subjects before and after long-duration space flight (1). The significant postflight decreases in hemoglobin, hematocrit, and MCV are consistent with previously reported RBC mass reduction (11,12). Along with findings after landing of significantly increased amounts of ferritin and decreased amounts of transferrin and slightly greater amounts of ferritin iron, these data suggest that iron metabolism is altered and that storage pools of iron may be shifted as a result of exposure to microgravity (45). Because ferritin concentration increased and serum iron concentration decreased, the possibility that these changes were caused by an acute inflammatory response cannot be ruled out (46). However, the finding that other acute-phase proteins (such as ceruloplasmin) did not change suggests that several mechanisms may be involved.
The data reported here provide evidence that nutritional status is altered during and after long-duration space flight. Four decades of human space flight have shown that many physiological systems are affected by space travel, and this has many implications for nutrition. Nutrients can be casualties of these effects, and in some cases they may be used as countermeasures to these effects. Moreover, additional efforts are required to better understand the role of nutrition in bone health and changes in body composition. Maintaining and monitoring nutritional status are important for ensuring crew health during space flight and will be critical as we begin to embark on longer duration exploration missions in the future.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
3 Abbreviations used: 25(OH)D3, 25-hydroxycholecalciferol; 3-MH, 3-methylhistidine; 8OHdG, 8-hydroxy-2'-deoxyguanosine; DEXA, dual-energy X-ray absorptiometry; GLA, -carboxyglutamic acid; GSH, glutathione; ISS, International Space Station; LBM, lean body mass; MCV, mean corpuscular volume; PTH, parathyroid hormone; SOD, superoxide dismutase; TAC, total antioxidant capacity.
Manuscript received 25 October 2004. Initial review completed 29 November 2004. Revision accepted 18 December 2004.
|
LITERATURE CITED |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
1. Smith, S. M., Davis-Street, J. E., Rice, B. L., Nillen, J. L., Gillman, P. L. & Block, G. (2001) Nutritional status assessment in semiclosed environments: ground-based and space flight studies in humans. J. Nutr. 131:2053-2061.
2. Leach, C., Alfrey, C., Suki, W., Leonard, J., Rambaut, P., Inners, L., Smith, S., Lane, H. & Krauhs, J. (1996) Regulation of body fluid compartments during short-term spaceflight. J. Appl. Physiol. 81:105-116.
3. Smith, S. M. & Lane, H. W. (1999) Gravity and space flight: effects on nutritional status. Curr. Opin. Clin. Nutr. Metab. Care 2:335-338.[Medline]
4. Leach, C. & Rambaut, P. (1977) Biochemical responses of the Skylab crewmen: an overview. Johnston, R. Dietlein, L. eds. Biomedical results from Skylab (NASA SP-377) 1977:204-216 National Aeronautics and Space Administration Washington, DC. .
5. Smith, S. M., Wastney, M. E., Morukov, B. V., Larina, I. M., Nyquist, L. E., Abrams, S. A., Taran, E. N., Shih, C. Y., Nillen, J. L., Davis-Street, J. E., Rice, B. L. & Lane, H. W. (1999) Calcium metabolism before, during, and after a 3-mo spaceflight: kinetic and biochemical changes. Am. J. Physiol. 277(1 Pt 2):R1-R10.
6. Rambaut, P. C., Smith, M. C., Jr & Wheeler, H. O. (1975) Nutritional studies. Johnston, R. S. Dietlein, L. F. Berry, C. A. eds. Biomedical Results of Apollo (NASA SP-368) 1975:277-302 National Aeronautics and Space Administration Washington, DC. .
7. Heer, M. (2002) Nutritional interventions related to bone turnover in European space missions and simulation models. Nutrition 18:853-856.[Medline]
8. Stein, T. P., Leskiw, M. J., Schluter, M. D., Hoyt, R. W., Lane, H. W., Gretebeck, R. E. & LeBlanc, A. D. (1999) Energy expenditure and balance during spaceflight on the space shuttle. Am. J. Physiol. 276:R1739-R1748.
9. Lane, H. W., Gretebeck, R. J., Schoeller, D. A., Davis-Street, J., Socki, R. A. & Gibson, E. K. (1997) Comparison of ground-based and space flight energy expenditure and water turnover in middle-aged healthy male US astronauts. Am. J. Clin. Nutr. 65:4-12.
10. Smith, S. M., Wastney, M. E., O’Brien, K. O., Morukov, B. V., Larina, I. M., Abrams, S. A., Davis-Street, J. E., Oganov, V. & Shackelford, L. C. (2005) Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the Mir space station. J. Bone Miner. Res. 20:208-218.[Medline]
11. Udden, M. M., Driscoll, T. B., Pickett, M. H., Leach-Huntoon, C. S. & Alfrey, C. P. (1995) Decreased production of red blood cells in human subjects exposed to microgravity. J. Lab. Clin. Med. 125:442-449.[Medline]
12. Alfrey, C. P., Udden, M. M., Leach-Huntoon, C., Driscoll, T. & Pickett, M. H. (1996) Control of red blood cell mass in spaceflight. J. Appl. Physiol. 81:98-104.
13. Perchonok, M. & Bourland, C. (2002) NASA food systems: past, present, and future. Nutrition 18:913-920.[Medline]
14. Lane, H. W. & Smith, S. M. (1999) Nutrition in space. Shils, M. E. Olson, J. A. Shike, M. Ross, A. C. eds. Modern Nutrition in Health and Disease 9th ed. 1999:783-788 Lippincott Williams & Wilkins Baltimore, MD. .
15. World Health Organization (1985) Energy and Protein Requirements. Report of a Joint FAO/WHO/UNU Expert Consultation 1985 WHO Geneva, Switzerland.
16. Soller, B. R., Cabrera, M., Smith, S. M. & Sutton, J. P. (2002) Smart medical systems with application to nutrition and fitness in space. Nutrition 18:930-936.[Medline]
17. Smith, S. M., Davis-Street, J. E., Fesperman, J. V., Smith, M. D., Rice, B. L. & Zwart, S. R. (2004) Nutritional assessment during a 14-d saturation dive: the NASA Extreme Environment Mission Operations V Project. J. Nutr. 134:1765-1771.
18. National Research Council (1998) Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 1998 The National Academy Press Washington, DC.
19. Institute of Medicine (1997) Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride 1997 National Academies Press Washington, DC.
20. National Research Council (2000) Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride 2000 The National Academy Press Washington, DC.
21. Grant, W. B. (2002) An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Cancer 94:272-281.[Medline]
22. Ahonen, M. H., Tenkanen, L., Teppo, L., Hakama, M. & Tuohimaa, P. (2000) Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 11:847-852.[Medline]
23. Trivedi, D. P., Doll, R. & Khaw, K. T. (2003) Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. Br. Med. J. 326:469.
24. Heaney, R. P. (2003) Long-latency deficiency disease: insights from calcium and vitamin D. Am. J. Clin. Nutr. 78:912-919.
25. Heaney, R. P., Dowell, M. S., Hale, C. A. & Bendich, A. (2003) Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J. Am. Coll. Nutr. 22:142-146.
26. Thomas, M. K., Lloyd-Jones, D. M., Thadhani, R. I., Shaw, A. C., Deraska, D. J., Kitch, B. T., Vamvakas, E. C., Dick, I. M., Prince, R. L. & Finkelstein, J. S. (1998) Hypovitaminosis D in medical inpatients. N. Engl. J. Med. 338:777-783.
27. Krall, E. A., Sahyoun, N., Tannenbaum, S., Dallal, G. E. & Dawson-Hughes, B. (1989) Effect of vitamin D intake on seasonal variations in parathyroid hormone secretion in postmenopausal women. N. Engl. J. Med. 321:1777-1783.[Abstract]
28. Smith, S. M., Nillen, J. L., Leblanc, A., Lipton, A., Demers, L. M., Lane, H. W. & Leach, C. S. (1998) Collagen cross-link excretion during space flight and bed rest. J. Clin. Endocrinol. Metab. 83:3584-3591.
29. Caillot-Augusseau, A., Lafage-Proust, M.-H., Soler, C., Pernod, J., Dubois, F. & Alexandre, C. (1998) Bone formation and resorption biological markers in cosmonauts during and after a 180-day space flight (Euromir 95). Clin. Chem. 44:578-585.
30. Shackelford, L. C., LeBlanc, A. D., Driscoll, T. B., Evans, H. J., Rianon, N. J., Smith, S. M., Spector, E., Feeback, D. L. & Lai, D. (2004) Resistance exercise as a countermeasure to disuse-induced bone loss. J. Appl. Physiol. 97:119-129.
31. LeBlanc, A. D., Driscol, T. B., Shackelford, L. C., Evans, H. J., Rianon, N. J., Smith, S. M., Feeback, D. L. & Lai, D. (2002) Alendronate as an effective countermeasure to disuse induced bone loss. J. Musculoskel. Neuron. Interact. 2:335-343.
32. Smith, S. M., Davis-Street, J. E., Fesperman, J. V., Calkins, D. S., Bawa, M., Macias, B. R., Meyer, R. S. & Hargens, A. R. (2003) 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. 18:2223-2230.[Medline]
33. Zerwekh, J. E., Ruml, L. A., Gottschalk, F. & Pak, C. Y. (1998) 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. 13:1594-1601.[Medline]
34. LeBlanc, A., Schneider, V., Spector, E., Evans, H., Rowe, R., Lane, H., Demers, L. & Lipton, A. (1995) Calcium absorption, endogenous excretion, and endocrine changes during and after long-term bed rest. Bone 16(4 suppl):301S-304S.[Medline]
35. Fiore, C. E., Pennisi, P., Ciffo, F., Scebba, C., Amico, A. & Di Fazzio, S. (1999) Immobilization-dependent bone collagen breakdown appears to increase with time: evidence for a lack of new bone equilibrium in response to reduced load during prolonged bed rest. Horm. Metab. Res. 31:31-36.[Medline]
36. Leach, C. S. (1992) Biochemical and hematologic changes after short-term space flight. Microgravit. Q. 2:69-75.
37. Su, C. J., Shevock, P. N., Khan, S. R. & Hackett, R. L. (1991) Effect of magnesium on calcium oxalate urolithiasis. J. Urol. 145:1092-1095.[Medline]
38. Grases, F., Conte, A., Genestar, C. & Costa-Bauza, A. (1992) Inhibitors of calcium oxalate crystallization and urolithiasis. Urol. Int. 48:409-414.[Medline]
39. Sato, Y., Tsuru, T., Oizumi, K. & Kaji, M. (1999) Vitamin K deficiency and osteopenia in disuse-affected limbs of vitamin D-deficient elderly stroke patients. Am. J. Phys. Med. Rehabil. 78:317-322.[Medline]
40. Caillot-Augusseau, A., Vico, L., Heer, M., Voroviev, D., Souberbielle, J.-C., Zitterman, A., Alexandre, C. & Lafage-Proust, M.-H. (2000) Space flight is associated with rapid decreases of undercarboxylated osteocalcin and increases of markers of bone resorption without changes in their circadian variation: observations in two cosmonauts. Clin. Chem. 46:1136-1143.
41. Vermeer, C., Wolf, J., Craciun, A. M. & Knapen, M. H. (1998) Bone markers during a 6-month space flight: effects of vitamin K supplementation. J. Gravit. Physiol. 5:65-69.[Medline]
42. Lane, H. W., Nillen, J. L. & Kloeris, V. L. (1995) Folic acid content in thermostabilized and freeze-dried space shuttle foods. J. Food Sci. 60:538-540.[Medline]
43. Kiyosawa, H., Suko, M., Okudaira, H., Murata, K., Miyamoto, T., Chung, M. H., Kasai, H. & Nishimura, S. (1990) Cigarette smoking induces formation of 8-hydroxydeoxyguanosine, one of the oxidative DNA damages in human peripheral leukocytes. Free Radic. Res. Commun. 11:23-27.[Medline]
44. Howard, D. J., Ota, R. B., Briggs, L. A., Hampton, M. & Pritsos, C. A. (1998) Environmental tobacco smoke in the workplace induces oxidative stress in employees, including increased production of 8-hydroxy-2'-deoxyguanosine. Cancer Epidemiol. Biomarkers Prev. 7:141-146.[Abstract]
45. Smith, S. M. (2002) Red blood cell and iron metabolism during space flight. Nutrition 18:864-866.[Medline]
46. Herbert, V., Jayatilleke, E., Shaw, S., Rosman, A. S., Giardina, P., Grady, R. W., Bowman, B. & Gunter, E. W. (1997) Serum ferritin iron, a new test, measures human body iron stores unconfounded by inflammation. Stem Cells 15:291-296.[Medline]
This article has been cited by other articles:
|
|
 |
|
  A. Chopard, M. Lecunff, R. Danger, G. Lamirault, A. Bihouee, R. Teusan, B. J. Jasmin, J. F. Marini, and J. J. Leger Large-scale mRNA analysis of female skeletal muscles during 60 days of bed rest with and without exercise or dietary protein supplementation as countermeasures Physiol Genomics, August 7, 2009; 38(3): 291 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Smith, S. R. Zwart, M. A. Heer, N. Baecker, H. J. Evans, A. H. Feiveson, L. C. Shackelford, and A. D. LeBlanc Effects of artificial gravity during bed rest on bone metabolism in humans J Appl Physiol, July 1, 2009; 107(1): 47 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Zwart, G. E. Crawford, P. L. Gillman, G. Kala, A. S. Rodgers, A. Rogers, A. M. Inniss, B. L. Rice, K. Ericson, S. Coburn, et al. Effects of 21 days of bed rest, with or without artificial gravity, on nutritional status of humans J Appl Physiol, July 1, 2009; 107(1): 54 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C De Luca, I Deeva, S Mariani, G Maiani, A Stancato, and L Korkina Monitoring antioxidant defenses and free radical production in space-flight, aviation and railway engine operators, for the prevention and treatment of oxidative stress, immunological impairment, and pre-mature cell aging Toxicology and Industrial Health, May 1, 2009; 25(4-5): 259 - 267. [Abstract] [PDF]
|
|
|
|
|
|
S. Trappe, D. Costill, P. Gallagher, A. Creer, J. R. Peters, H. Evans, D. A. Riley, and R. H. Fitts Exercise in space: human skeletal muscle after 6 months aboard the International Space Station J Appl Physiol, April 1, 2009; 106(4): 1159 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M Smith, K. K Gardner, J. Locke, and S. R Zwart Vitamin D supplementation during Antarctic winter Am. J. Clinical Nutrition, April 1, 2009; 89(4): 1092 - 1098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Zwart, G. Kala, and S. M. Smith Body Iron Stores and Oxidative Damage in Humans Increased during and after a 10- to 12-Day Undersea Dive J. Nutr., January 1, 2009; 139(1): 90 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Smith, S. A. Mathews Oliver, S. R. Zwart, G. Kala, P. A. Kelly, J. S. Goodwin, and C. B. Dyer Nutritional Status Is Altered in the Self-Neglecting Elderly J. Nutr., October 1, 2006; 136(10): 2534 - 2541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Minerva BMJ, March 12, 2005; 330(7491): 608 - 608. [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
