ALBERT

Description: High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P 〈 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P 〈 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P 〈 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P 〈 0.05). During bed rest, urinary pH decreased (P 〈 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

Description: Current human space travel consists primarily of long-duration missions onboard the International Space Station (ISS), but in the future may include exploration-class missions to nearby asteroids, Mars, or its moons. These missions will expose astronauts to increased risk of oxidative and inflammatory damage from a variety of sources, including radiation, psychological stress, reduced physical activity, diminished nutritional status, and hyperoxic exposure during extravehicular activity. Evidence exists that increased oxidative stress and inflammation can accelerate the development of atherosclerosis.

Description: In several studies we tested the concepts that diet can alter acid-base balance and that reducing the dietary acid load has a positive effect on maintenance of bone. In study 1, (n = 11, 60-90 d bed rest), the renal acid load of the diet was estimated from its chemical composition, and was positively correlated with urinary markers of bone resorption (P less than 0.05); that is, the greater the acid load, the greater the excretion of bone resorption markers. In study 2, in males (n = 8, 30 d bed rest), an estimate of the ratio of nonvolatile acid precursors to base precursors in the diet was positively correlated (P less than 0.05) with markers of bone resorption. In study 3, for 28 d subjects received either a placebo (n = 6) or an essential amino acid supplement (n = 7) that included methionine, a known acid precursor. During bed rest (28 d), urinary calcium was greater than baseline levels in the supplemented group but not the control group (P less than 0.05), and in the supplemented group, urinary pH decreased (P less than 0.05). In study 4, less bone resorption occurred in space crew members who received potassium citrate (n = 6) during spaceflight of 4-6 months than in crew members who received placebo or were not in the study (n = 8) (P less than 0.05). Reducing acid load has the potential to mitigate increased bone resorption during spaceflight, and may serve as a bone loss countermeasure.

Description: Ground-based analogs of spaceflight are an important means of studying physiological and nutritional changes associated with space travel, particularly since exploration missions are anticipated, and flight research opportunities are limited. A clinical nutritional assessment of the NASA Extreme Environment Mission Operation V (NEEMO) crew (4 M, 2 F) was conducted before, during, and after the 14-d saturation dive. Blood and urine samples were collected before (D-12 and D-1), during (MD 7 and MD 12), and after (R + 0 and R + 7) the dive. The foods were typical of the spaceflight food system. A number of physiological changes were reported both during the dive and post dive that are also commonly observed during spaceflight. Serum hemoglobin and hematocrit were decreased (P less than 0.05) post dive. Serum ferritin and ceruloplasmin significantly increased during the dive, while transferring receptors tended to go down during the dive and were significantly decreased by the last day (R + 0). Along with significant hematological changes, there was also evidence for increased oxidative damage and stress during the dive. 8-hydroxydeoxyguanosine was elevated (P less than 0.05) during the dive, while glutathione peroxidase and superoxide disrnutase activities were decreased (P less than 0.05) during the dive. Serum C-reactive protein (CRP) concentration also tended to increase during the dive, suggesting the presence of a stress-induced inflammatory response, Decreased leptin during the dive (P less than 0.05) may also be related to the increased stress. Similar to what is observed during spaceflight, subjects had decreased energy intake and weight loss during the dive. Together, these similarities to spaceflight provide a model to further define the physiological effects of spaceflight and investigate potential countermeasures.

Description: The prospect of a lunar outpost to conduct science and learn how to live and work off the Earth is exciting. The nutritional sciences will focus on the issues of over all health, with emphasis on skeletal muscle health and prevention of radiation damage. There is a great deal of research needed to determine the nutritional and food component potential for preventing the changes that occur in space flight. Further research is also needed on the interactions of systems and countermeasures, such as protein-amino acid needs for enhancement of muscle protein synthesis while not being detrimental for bone health. The interrelationship between radiation exposure, nutrition, and food components has just begun.

Description: Astronauts on long duration space flight missions to the moon or mars are exposed to radiation and have increase iron (Fe) stores, both of which can independently induce oxidative stress and may exacerbate bone mass loss and strength. We hypothesize a high Fe diet and a fractionated gamma radiation exposure would increase oxidative stress and lower bone mass. Three mo-old, SD rats (n=32) were randomized to receive an adequate Fe diet (45 mg Fe/kg diet) or a high Fe diet (650 mg Fe/kg diet) for 4 wks and either a cumulative 3 Gy dose (fractionated 8 x 0.375 Gy) of gamma radiation (Cs-137) or sham exposure starting on day 14. Elisa kit assessed serum catalase, clinical analyzer assessed serum Fe status and ex vivo pQCT scans measured bone parameters in the proximal/midshaft tibia and femoral neck. Mechanical strength was assessed by 3-pt bending and femoral neck test. There is a significant decrease in trabecular bone mineral density (BMD) from radiation (p less than 0.05) and a trend in diet (p=0.05) at the proximal tibia. There is a significant interaction in cortical BMD from the combined treatments at the midshaft tibia (p less than 0.05). There is a trending decrease in total BMD from diet (p=0.07) at the femoral neck. In addition, high serum Fe was correlated to low trabecular BMD (p less than 0.05) and high serum catalase was correlated to low BMD at all 3 bone sites (p less than 0.05). There was no difference in the max load of the tibia or femoral neck. Radiation and a high iron diet increases iron status and catalase in the serum and decreases BMD.

Description: Several classic twin studies show genetic effects on markers of bone health, including bone mineral density and parathyroid hormone (PTH). This study was performed to assess the relative contribution of genetics to biochemical markers of bone metabolism. Fifteen sets of identical twins (8 male, 7 female) were housed in a clinical research center where diet was controlled (15% protein, 55% carbohydrate, 30% fat) for 3 consecutive days. Each day, 24-h urine pools were collected and N-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and serum PTH were measured. The broad-sense heritability factor (H2) is an estimation of the portion of the total variance of a given phenotype that is attributable to genetic variance. H2 was estimated from the correlation coefficient of the phenotype data. H2 for NTX was 94% for males and 80% for females, DPD was 88% for males and 97% for females, urinary calcium excretion was 97% for males and 90% for females, and PTH was 92% for males and 79% for females. Since environmental variability was minimized for the 3 days of data collection, these heritability factors are likely overestimated. Nonetheless, the data support the concept that PTH is a predominantly heritable trait, and suggest that NTX, DPD, and calcium excretion are as well. These biochemical data support the previously documented heritability of bone health.

Description: Dietary potassium and protein intakes predict net endogenous acid production in humans. Intracellular buffers, including exchangeable bone mineral, play a crucial role in balancing chronic acid-base perturbations in the body; subsequently, chronic acid loads can potentially contribute to bone loss. Bone is lost during space flight, and a dietary countermeasure would be desirable for many reasons. We studied the ability of diet protein and potassium to predict levels of bone resorption markers in males and females. Identical twin pairs (8 M, 7 F) were assigned to 2 groups: bed rest (sedentary, SED) or bed rest with supine treadmill exercise in a lower body negative pressure chamber (EX). Diet was controlled for 3 d before and 30 d of bed rest (BR). Urinary Ca, N-telopeptide (NTX), and pyridinium crosslinks (PYD) were measured before and on days 5, 12, 19, and 26 of BR. Data were analyzed by Pearson correlation (P〈0.05). The ratio of dietary animal protein/potassium intake was not correlated with NTX before BR for males or females, but they were positively correlated in both groups of males during bed rest. Dietary animal protein/potassium and urine Ca were correlated before and during bed rest for the males, and only during bed rest for the females. Conversely, the ratio of dietary vegetable protein/potassium intake was negatively correlated with urinary calcium during bed rest for the females, but there was no relationship between vegetable protein/potassium intake and bone markers for the males. These data suggest that the ratio of animal protein/potassium intake may affect bone, particularly in bed rest subjects. These data show that the type of protein and gender may be additional factors that modulate the effect of diet on bone metabolism during bed rest. Altering this ratio may help prevent bone loss on Earth and during space flight.

Description: Many nutritional factors influence bone, from the basics of calcium and vitamin D, to factors which influence bone through acid/base balance, including protein, sodium, and more. Fibroblast growth factor 23 (FGF23) is a recently identified factor, secreted from osteocytes, which is involved in classic (albeit complex) feedback loops controlling phosphorus homeostasis through both vitamin D and parathyroid hormone (PTH) (1, 2). As osteocytes are gravity sensing cells, it is important to determine if there are changes in FGF23 during spaceflight. In extreme cases, such as chronic kidney disease, FGF23 levels are highly elevated. FGF23 imbalances, secondary to dietary influences, may contribute to skeletal demineralization and kidney stone risk during spaceflight.

Description: The Nutritional Status Assessment Supplemental Medical Objective was an experiment initiated to expand nominal pre- and postflight clinical nutrition testing, and to gain a better understanding of the time course of changes during flight. The primary activity of this effort was collecting blood and urine samples 5 times during flight for analysis after return to Earth. Samples were subjected to a battery of tests, including nutritional, physiological, general chemistry, and endocrinology indices. These data provide a comprehensive survey of how nutritional status and related systems are affected by 4-6 months of space flight. Analyzing the data will help us to define nutritional requirements for long-duration missions, and better understand human adaptation to microgravity. This expanded set of measurements will also aid in the identification of nutritional countermeasures to counteract, for example, the deleterious effects of microgravity on bone and muscle and the effects of space radiation.