NASA Human Research Program Research Articles

Men and women in space: bone loss and kidney stone risk after long‐duration space flight (257.3)

Bone loss on Earth is more prevalent in women than men, leading to the assumption that women may be at greater risk from bone loss during flight. Until recently, the number of women having flown long‐duration missions was too small to allow any type of statistical analysis. We report here data from 42 astronauts on long‐duration missions to the International Space Station, 33 men and 9 women. Bone mineral density (dual‐energy X‐ray absorptiometry), bone biochemistry (from blood and urine samples), and renal stone risk factors were evaluated before and after flight. Data were analyzed in two groups, based on available resistance exercise equipment. The response of bone mineral density to flight was the same for men and women, and the typical decrease in bone mineral density (whole body and/or regional) after flight was not observed for either sex for those using an Advanced Resistive Exercise Device. Bone biochemistry, specifically markers of formation and resorption, generally responded similarly in male and female astronauts. The response of urinary supersaturation risk to space flight was not significantly different between men and women, although risks were typically increased after flight in both groups and risks were generally greater in men than in women before and after flight. Overall, the bone and renal stone responses of men and women to space flight were not different.Grant Funding Source: Funded by the NASA Human Research Program.

Quality factors for space radiation: A new approach

NASA has derived new models for radiological risk assessment based on epidemiological data and radiation biology including differences in Relative Biological Effectiveness for leukemia and solid tumors. Comprehensive approaches were used to develop new risk cross sections and the extension of these into recommendations for risk assessment during space missions. The methodology relies on published data generated and the extensive research initiative managed by the NASA Human Research Program (HRP) and reviewed by the National Academy of Sciences. This resulted in recommendations for revised specifications of quality factors, QNASA(Z,β) in terms of track structure concepts that extend beyond LET alone. The new paradigm for quality factors placed demands on radiation monitoring procedures that are not satisfied by existing dosimetry systems or particle spectrometers that are practical for space exploration where mass, volume, band width and power consumption are highly constrained. We have proposed a new definition of quality factors that relaxes the requirements for identifying charge, Z, and velocity, β, of the incident radiation while still preserving the functional form of the inherent risk functions. The departure from the exact description of QNASA(Z,β) is that the revised values are new functions of LET for solid cancers and leukemia. We present the motivation and process for developing the revised quality factors. We describe results of extensive simulations using GCR distributions in free space as well as the resulting spectra of primary and secondary particles behind aluminum shields and penetration through water. In all cases the revised dose averaged quality factors agreed with those based on the values obtained using QNASA(Z,β). This provides confidence that emerging technologies for space radiation dosimetry can provide real time measurements of dose and dose equivalent while satisfying constraints on size, mass, power and bandwidth. The revised quality factors are sufficiently generalized to be applicable to radiation protection practices beyond space exploration.

Space habitation and microbiology: status and roadmap of space agencies.

The ubiquitous nature of microbiology is reflected in the diversity of microbiological research and operational efforts at NASA. For example, the impact of microorganisms on other planets and the protection of Earth from the potential of microbial life elsewhere is the responsibility of the Office of Planetary Protection (http://planetaryprotection.nasa.gov/ about). While the Office of Planetary Protection does not include forward or back contamination to or from a low Earth orbit, research platforms, such as the ISS, are being used to better understand the survival of microorganisms and corresponding contamination control in the extreme conditions of space (2, 4, 10). Another example is the NASA Center for Astrobiology, which focuses on the origin, evolution, distribution, and future of life in the universe (https:// astrobiology.nasa.gov/). The large focus on microbiology is within its human exploration operations. NASA has historically set microbiological requirements, including stringent monitoring regimes, to mitigate risks to the health and performance of astronauts. Microorganisms can have both positive and negative impacts on many aspects of human spaceflight, including the risk and prevention of infectious diseases, performance of Environmental Control and Life Support Systems (ECLSS), spaceflight foods, and vehicle design and integrity. Even though a great amount of information has been obtained, several key questions regarding the impact of microorganisms on human spaceflight still remain. Research into the uncertainties of risks that may affect crew health are the responsibility of the NASA Human Research Program (http://www.nasa.gov/exploration/human research/). The research that addresses our fundamental understanding of space life science and its translation for benefits to the general public on Earth is the responsibility of NASA Space Biology.

The Effects of High Dietary Iron and Radiation Exposure on Markers of Oxidative Stress and Immune Status of Rats

During space flight astronauts are exposed to increased iron stores and radiation. These can independently cause oxidative damage leading to negative health effects including heart disease, cataracts, and cancer. We investigated the combined effects of high dietary iron (650 mg iron/kg diet vs. 45 mg iron/kg diet for controls) and radiation exposure (0.375 Gy of Cs‐137 every other day for 16 days, a total of 3 Gy) on markers of oxidative stress and immune system variables in Sprague‐Dawley rats (n=8/group). Oxidative stress was affected by both treatments, evidenced by increased liver glutathione peroxidase (P < 0.01) and serum catalase (P < 0.01). Effects of iron intake and radiation on the white blood cell count interacted significantly (P < 0.05), with iron increasing the cell count only in the non‐irradiated group. The T‐cell CD4:CD8 ratio was decreased by radiation (P < 0.0001). When various leukocyte subsets from treated rats were stimulated with mitogens, their cytokine production profiles were altered. Serum iron concentration was negatively correlated with monocyte production of cytokines after LPS stimulation. Both dietary iron and radiation, alone and interactively, contributed to increased oxidative stress and resulted in overall immune system alterations, which could contribute negatively to astronaut health during space flight.Grant Funding Source: Funded by the NASA Human Research Program.

Potential Anesthesia Protocols for Space Exploration Missions

In spaceflight beyond low Earth's orbit, medical conditions requiring surgery are of a high level of concern because of their potential impact on crew health and mission success. Whereas surgical techniques have been thoroughly studied in spaceflight analogues, the research focusing on anesthesia is limited. To provide safe anesthesia during an exploration mission will be a highly challenging task. The research objective is thus to describe specific anesthesia procedures enabling treatment of pre-identified surgical conditions. Among the medical conditions considered by the NASA Human Research Program Exploration Medical Capability element, those potentially necessitating anesthesia techniques have been identified. The most appropriate procedure for each condition is thoroughly discussed. The substantial cost of training time necessary to implement regional anesthesia is pointed out. Within general anesthetics, ketamine combines the unique advantages of preservation of cardiovascular stability, the protective airway reflexes, and spontaneous ventilation. Ketamine side effects have for decades tempered enthusiasm for its use, but recent developments in mitigation means broadened its indications. The extensive experience gathered in remote environments, with minimal equipment and occasionally by insufficiently trained care providers, confirms its high degree of safety. Two ketamine-based anesthesia protocols are described with their corresponding indications. They have been designed taking into account the physiological changes occurring in microgravity and the specific constraints of exploration missions. This investigation could not only improve surgical care during long-duration spaceflights, but may find a number of terrestrial applications in isolated or austere environments.

Predicting Head Injury Risk During International Space Station Increments

NASA's Human Research Program is using a probabilistic risk assessment approach to identify acute and chronic medical risks to manned spaceflight. The objective of this project was to estimate the likelihood of a neurological head injury to a crewmember severe enough to require medical assessment, treatment, or evacuation during a typical International Space Station (ISS) increment. A 2 degree-of-freedom analytical model of the human head was created to allow for analysis of the impact response. The output of the model is acceleration of the head, which was used to determine the probability that the simulated impact resulted in a head injury with an Abbreviated Injury Scale (AIS) score of 3 or greater. These data were then integrated into a probabilistic risk assessment, which outputs a likelihood of injury with a representative measure of the uncertainty. A Monte Carlo simulation was performed to vary input parameters over their defined distributions. The mean probability of a moderate neurological injury (AIS 3 or greater) occurring due to a head impact by a crewmember translating through the ISS is 1.16 x 10(-4) per 6-mo mission increment (2.32 x 10(-4) per year). Our head injury prediction model has shown that there is a low, yet not insignificant, probability of neurological head injury of AIS score 3 or greater. The results from this simulation will be input into the parent Integrated Medical Model, which incorporates the risks of over 80 different medical events in order to inform mission planning scenarios.

Human health and performance considerations for near earth asteroids (NEA)

Humans are considered as a system in the design of any deep space exploration mission. The addition of many potential near asteroid (NEA) destinations to the existing multiple mission architecture for Lunar and Mars missions increases the complexity of human health and performance issues that are anticipated for exploration of space. We suggest that risks to human health and performance be analyzed in terms of the 4 major parameters related to multiple mission architecture: destination, duration, distance and vehicle design. Geological properties of the NEA will influence design of exploration tasks related to sample handling and containment, and extravehicular activity (EVA) capabilities including suit ports and tools. A robotic precursor mission that collects basic information on NEA surface properties would reduce uncertainty about these aspects of the mission as well as aid in mission architecture and exploration task design. Key mission parameters are strongly impacted by duration and distance. The most critical of these is deep-space radiation exposure without even the temporary shielding of a nearby large planetary body. The current space radiation permissible exposure limits (PEL) limits mission duration to 3–10 months depending on age, gender and stage of the solar cycle. Duration also impacts mission architectures including countermeasures for bone, muscle, and cardiovascular atrophy during continuous weightlessness; and behavioral and psychological issues resulting from isolation and confinement. Distance affects communications and limits abort and return options for a NEA mission. These factors are anticipated to have important effects on crew function and autonomous operations, as well as influence medical capability, supplies and training requirements of the crew. The design of a habitat volume that can maintain the physical and psychological health of the crew and support mission operations with limited intervention from earth will require an integrated research and development effort between NASA's Human Research Program (HRP), engineering and human factors groups. Packaging food to extend shelf life and waste management will be important components of vehicle subsystem design.

High dietary iron and radiation exposure increase biomarkers of oxidative stress in blood and liver of rats

Radiation exposure and increased iron (Fe) status independently cause oxidative damage that can result in protein, lipid, and DNA oxidation. During space flight astronauts are exposed to both increased radiation and increased Fe stores. Increased body Fe results from a decrease in red blood cell mass and the typically high Fe content of the food system. In this study we investigated the combined effects of radiation exposure (0.375 Gy of Cs‐137 every other day for 16 days; a total of 3 Gy) and high dietary Fe (650 mg Fe/kg diet vs. 45 mg Fe/kg for controls) in Sprague‐Dawley rats (n=8/group). Liver and serum Fe were significantly increased in the high dietary Fe groups. Likewise, radiation exposure increased serum ferritin and Fe concentrations. These data indicate that total body Fe stores increase with both radiation exposure and excess dietary Fe. Hematocrit decreased in the group exposed to radiation, providing a possible mechanism for the shift in Fe indices after radiation exposure. Markers of oxidative stress were also affected by both radiation and high dietary Fe, evidenced by increased liver glutathione peroxidase (GPX) and serum catalase as well as decreased serum GPX. Our results reveal preliminary indications of the synergistic effects of protracted (fractionated) radiation exposure and increased dietary Fe, warranting further study.Grant Funding Source: This research was funded by the NASA Human Research Program. Dr. Morgan's efforts and travel are supported through an appointment to the NASA Postdoctoral Program at the Johnson Space Center, administered by Oak Ridge Associated Universities through a contract with NASA

High dietary iron and 137Cs radiation exposure induce oxidative stress and reduce bone mass

Astronauts are exposed to increased iron (Fe) stores and risk radiation exposure during spaceflight. We hypothesized that a high Fe diet and radiation exposure would independently increase markers of oxidative stress and result in loss of bone mass. Male rats (3‐mo‐old, n=32) were randomized to receive an adequate (45 mg Fe/kg) or high (650 mg Fe/kg) Fe diet for 4 wks and either 3 Gy (8 fractions, 0.375 Gy each) of 137Cs radiation (γ RAD) or sham exposure starting on d 14. Ex vivo pQCT quantified volumetric bone mineral density (vBMD); bone mechanical strength (ultimate load, UL) was assessed by 3‐pt bending (midshaft tibia) and compression of the femoral neck. Serum Fe and catalase increased only with the combined treatment, whereas serum glutathione peroxidase decreased in all groups. γRAD and high Fe diet lowered proximal tibial (PT) cancellous vBMD (by −15% and − 12%, respectively); high Fe diet produced a small decrease in femoral neck (FN) total vBMD (−4%, p=0.07). Cortical vBMD at midshaft tibia was lower after high Fe diet, but not after γRAD. Higher serum Fe levels at 4 wks were associated with lower PT cancellous vBMD (r = −0.61); higher serum catalase was associated with lower vBMD at the 3 different bone sites (r = − 0.52). No significant differences in UL at mid‐shaft tibia or FN were detected. Oxidative stress is increased by fractionated γRAD and iron overload and is associated with a negative impact on bone mass.Grant Funding Source : NASA Human Research Program and NSBRI via NASA NCC9‐588

Using natural stable calcium isotopes to rapidly assess changes in bone mineral balance using a bed rest model to induce bone loss

Spaceflight and metabolic bone diseases disrupt normal bone mineral balance (BMB) resulting in bone loss. Bed rest, by stimulating bone loss, provides the opportunity to evaluate new methods to monitor BMB in healthy individuals suffering bone loss. Natural variations in the Ca isotope ratio occur because bone formation depletes soft tissue of light Ca isotopes preferentially, while bone resorption releases that isotopically light Ca back into soft tissue (Skulan & DePaolo, 1999). Using a bed rest model, we demonstrate that the Ca isotope ratio of urine shifts in a direction consistent with bone loss after just 7 days of bed rest, long before measurable changes in bone mineral density (BMD) occur. The Ca isotope variations are consistent with changes observed in urinary N‐teleopeptide, a bone resorption marker. Bone specific alkaline phosphatase, a bone formation marker, is unchanged. The established relationship between Ca isotopes and BMB can be used to quantitatively translate changes in the Ca isotope ratio to changes in BMD using a mathematical model. This model predicts that subjects lost 0.25 ± 0.07% (± SD) of their bone mass from day 7 to 30 of bed rest, consistent with bone loss rates from 90 day bed rest studies as measured by DXA scans. The rapid signal observed using Ca isotopes and the potential to quantitatively assess bone loss makes this technique particularly well suited for the study of bone metabolism.Grant Funding Source: NASA Human Research Program. Dr. Morgan is supported through an appointment to the NASA Postdoctoral Program at JSC, administered by ORAU.

Urinary acid excretion can predict changes in bone metabolism during space flight

Mitigating space flight‐induced bone loss is critical for space exploration, and a dietary countermeasure would be ideal. We present here preliminary data from a study in which we examined the role of dietary intake patterns in bone mineral loss of astronauts during space flight. Crew members (n=5) were asked to consume a prescribed diet with either a low (0.3–0.6 g/mEq) or high (1.0–1.3 g/mEq) ratio of animal protein to potassium (APro:K) before and during space flight for 4‐d periods. Diets were controlled for energy, total protein, calcium, and sodium. On the last day of each of the 4‐d controlled diet sessions, 24‐h urine samples were collected. Dietary potential renal acid load was used to predict 24‐ h urinary acid excretion, which was correlated with urinary n‐telopeptide (NTX, Pearson R = 0.99 and 0.80 for the high and low APro:K sessions, respectively, p<0.001). The amount of protein, when expressed as the percentage of total energy (but not as total grams) was also correlated with urinary NTX (R = 0.66, p<0.01). These results, from healthy individuals in a unique environment, will be important for better understanding diet and bone interrelationships during space flight as well as on Earth. The study was funded by the NASA Human Research Program.

Human Factors Research for Space Exploration: Measurement, Modeling, and Mitigation

As part of NASA's Human Research Program, the Space Human Factors Engineering Project serves as the bridge between Human Factors research and Human Spaceflight applications. Our goal is to be responsive to the operational community while addressing issues at a sufficient level of abstraction to ensure that our tools and solutions generalize beyond the point design. In this panel, representatives from four of our research domains will discuss the challenges they face in solving current problems while also enabling future capabilities.

Intake of fish and omega‐3 (n‐3) fatty acids: effect on bone during actual and simulated weightlessness

Space flight has many negative effects on human physiology, including bone and muscle loss. These are some of the systems on which intakes of fish and n‐3 fatty acids have positive effects. These effects are likely to occur through inhibition of inflammatory cytokines (such as TNFα) and thus inhibition of downstream NF‐κB activation. We documented this effect in a 3D cell culture model, where NF‐κB activation in osteoclasts was inhibited by eicosapentaenoic acid, an n‐3 fatty acid. We have extended these studies and report here (a) NF‐κB expression in peripheral blood mononuclear cells of Space Shuttle crews on 2‐wk missions, (b) the effects of n‐3 fatty acid intake after 60 d of bed rest (a weightlessness analog), and (c) the effects of fish intake in astronauts after 4 to 6 mo on the International Space Station. After Shuttle flights of ~2 wk, NF‐κB p65 expression at landing was increased (P <0.001). After 60 d of bed rest, higher intake of n‐3 fatty acids was associated with less N‐telopeptide excretion (Pearson r = −0.62, P < 0.05). Higher consumption of fish during flight was associated with higher bone mineral density (Pearson r = −0.46, P < 0.05). Together with our earlier findings, these data provide mechanistic cellular and preliminary human evidence of the potential for n‐3 fatty acids to counteract bone loss associated with spaceflight. This study was supported by the NASA Human Research Program.

NASA Human Research Program Summaries: Modeling Bone Recovery After Long-Duration Spaceflight and Monitoring Changes in Bone Strength

NASA Human Research Program Summaries: Modeling Bone Recovery After Long-Duration Spaceflight and Monitoring Changes in Bone Strength

Efficacy of vitamin D supplementation in an Antarctic ground analog of space flight

Vitamin D is critical for persons with limited exposure to ultraviolet (UV) light, including space travelers. Recent studies indicate that optimal serum 25‐hydroxyvitamin D (25‐OH vit D) should be ≥ 80 nM. This study was designed to define the dose of vitamin D needed to maintain 25‐OH vit D at > 80 nM in persons with limited UV‐B exposure. It was conducted during winter in Antarctica at McMurdo Station, when UV‐B radiation levels are essentially zero. The 66 subjects recruited for this blinded study were randomly divided into 3 groups for vitamin D supplementation: 2000 IU/d (n = 18), 1000 IU/d (n = 18), and 400 IU/d (n = 19). Some subjects (n = 7) did not take supplements or took ones of their own choosing. Blood samples were collected about every 2 mo during the winter. About 5 mo after supplementation started, analysis of samples from subjects (n=9, 5, 11, and 3 for the 2000 IU/d, 1000 IU/d, 400 IU/d, and no pill groups) who completed 4 blood draws showed that 25‐OH vit D increased 63% in the 2000 IU/d group (to 82 ± 28 nM), 61% in the 1000 IU/d group (to 85 ± 36 nM), and 51% in the 400 IU/d group (to 64 ± 13 nM). It decreased 13% (to 35 ± 16 nM) in the group not taking supplements. These data will enable us to provide space crews with evidence‐based recommendations for vitamin D supplementation. The findings also have implications for other persons with limited UV light exposure, including polar workers and the elderly. This study was supported by the NASA Human Research Program.

Oxidative Damage during a 10‐ to 12‐d Saturation Dive

The NASA Extreme Environment Mission Operations (NEEMO) underwater habitat is a useful spaceflight analog. The increased air pressure in the habitat exposes crew members to higher oxygen pressures, which increase their risk for oxidative damage to DNA, proteins, and lipids. DNA oxidation occurs at an increased level, similar to that observed in smokers and astronauts returning from space. Astronauts in space and NEEMO crew members also have changes in iron metabolism. Newly formed red blood cells are destroyed and body iron stores are elevated. Excess iron can act as an oxidant and cause tissue damage. In this study we investigated aspects of oxidative damage and tested whether toxic forms of iron were present when iron stores increased during NEEMO missions. Subjects (n = 12) participated in 10‐ to 12‐d saturation dives, and blood and 24‐h urine samples were collected twice before, twice during, and twice after the dive. During the dive, ferritin was significantly (P < 0.001) higher, transferrin tended to be lower (P = 0.053), and transferrin receptors were lower (P < 0.001). Total homocysteine was significantly (P < 0.001) elevated and superoxide dismutase activity was decreased (P < 0.05). Labile plasma iron was measurable during the dive but not before or after it. These data indicate that the NEEMO environment increases iron stores, which may cause oxidative damage. This study was supported by the NASA Human Research Program.