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All sourcesNASA NTRSDOE OSTI
NASA NTRS2014

Fibroblast Growth Factor-23 in Bed Rest and Spaceflight

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. Presented with an imbalanced dietary phosphorus to calcium ratio, increased secretion of FGF23 will inhibit renal phosphorus reabsorption, resulting in increased excretion and reduced circulating phosphorus. Increased intake and excretion of phosphorus is associated with increased kidney stone risk in both the terrestrial and microgravity environments. Highly processed foods and carbonated beverages are associated with higher phosphorus content. Ideally, the dietary calcium to phosphorus ratio should be at minimum 1:1. Nutritional requirements for spaceflight suggest that this ratio not be less than 0.67 (3), while the International Space Station (ISS) menu provides 1020 mg Ca and 1856 mg P, for a ratio of 0.55 (3). Subjects in NASA's bed rest studies, by design, have consumed intake ratios much closer to 1.0 (4). FGF23 also has an inhibitory influence on PTH secretion and 1(alpha)-hydroxylase, both of which are required for activating vitamin D with the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Decreased 1,25-dihydroxyvitamin D will result in decreased intestinal phosphorus absorption, and increased urinary phosphorus excretion (via decreased renal reabsorption). Should a decrease in 1,25- dihydroxyvitamin D be necessary to reduce intestinal phosphorus absorption, calcium absorption will also proportionally be reduced, potentially leading to skeletal demineralization. Demineralization of bone can increase kidney stone risk, a medical issue that could prove detrimental to mission success. Given the interrelationships described above, we sought to determine circulating FGF23 concentrations in spaceflight and ground analog studies to better understand the potential effects of dietary phosphorus on bone and calcium metabolism. We analyzed serum from ISS astronauts participating in studies of bone biochemistry, including the Nutrition SMO and Pro K experiments, and we also evaluated FGF23 during extended-duration bed rest. Serum intact FGF23 levels were determined using an ELISA kit from Kainos laboratories in Japan. While initial evaluation of the data showed no changes over time during flight or bed rest, evaluation continues of FGF23 data in light of dietary factors, PTH, vitamin D status, and other biochemical and endocrine factors.

Bokhari, R.↗
NASA NTRS1999

Nutritional Aspects of Crewmembers' Cardiovascular Health Indicated by Dietary Lipids

This summer's project examined the relationships between dietary and physiological factors on serum lipoproteins using data from past United States astronauts. Nutritional assessment was required to determine whether a relationship existed between dietary intake and risk of cardiovascular disease (CVD) in crewmembers. Risk for CVD was assessed by the measurement of preflight, inflight, and postflight serum lipoproteins. The purpose of this project was to evaluate the dietary practices of past crewmembers before and during flight, and to examine their relationship with blood indicators of lipid status. Because of mortality and morbidity associated with CVD, such assessments are critical for the maintenance of astronaut health before, during, and after space flight. It was anticipated that the results from this project would assess the effects space flight and diet have on cardiovascular health, thus, defining the adequacy of the current dietary recommendations during space travel. It was hypothesized that the mean preflight serum lipoproteins compared to mean postflight serum lipoproteins would not be statistically different and that the current inflight diet is adequate in nutrient content, having little or no effect on lipoprotein levels.

Thurston, Marcelle A.↗
NASA NTRS2012

Effects of High Dietary HEME Iron and Radiation on Cardiovascular Function

The radiation related health risks to astronauts is of particular concern to NASA. Data support that exposure to radiation is associated with a number of disorders including a heightened risk for cardiovascular diseases. Independent of radiation, altered nutrient status (e.g. high dietary iron) also increases ones risk for cardiovascular disease. However, it is unknown whether exposure to radiation in combination with high dietary iron further increases ones cardiovascular risk. The intent of our proposal is to generate compulsory data examining the combined effect of radiation exposure and iron overload on sensitivity to radiation injury to address HRP risks: 1) Risk Factor of Inadequate Nutrition; 2) Risk of Cardiac Rhythm Problems; and 3) Risk of Degenerative Tissue or other Health Effects from Space Radiation. Towards our goal we propose two distinct pilot studies using the following specific aims: Vascular Aim 1: To determine the short-term consequences of the independent and combined effects of exposure to gamma radiation and elevated body iron stores on measures of endothelial function and cell viability and integrity. We hypothesize that animals that have high body iron stores and are exposed to gamma radiation will show a greater reduction in endothelial dependent nitric oxid production and larger pathological changes in endothelial integrity than animals that have only 1 of those treatments (either high iron stores or exposure to gamma radiation). Vascular Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with endothelial cell function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with endothelial cell function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment. Cardiac Aim 1: To determine the short-term consequences of the independent and combined effects of gamma radiation and elevated body iron stores on measures of cardiac structure. We hypothesize that modifications to cardiac structure and function will be greater in rats with high body iron stores and exposed to gamma radiation than in rats that have only 1 of those treatments. Cardiac Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with cardiac structure and function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with cardiac contractile function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment.

Westby, Christian M.↗
NASA NTRS1990

Cyanobacteria in CELSS: Growth strategies for nutritional variation and nitrogen cycling

Cyanobacteria (blue-green algae) are versatile organisms which are capable of adjusting their cellular levels of carbohydrate, protein, and lipid in response to changes in the environment. Under stress conditions there is an imbalance between nitrogen metabolism and carbohydrate/lipid synthesis. The lesion in nitrogen assimilation is at the level of transport: the stress condition diverts energy from the active accumulation of nitrate to the extrusion of salt, and probably inhibits a cold-labile ATP'ace in the case of cold shock. Both situations affect the bioenergetic status of the cell such that the nitrogenous precursors for protein synthesis are depleted. Dispite the inhibition of protein synthesis and growth, photosynthetic reductant generation is relatively unaffected. The high O2 reductant would normally lead to photo-oxidative damage of cellular components; however, the organism copes by channeling the 'excess' reductant into carbon storage products. The increase in glycogen (28 to 35 percent dry weight increase) and the elongation of lipid fatty acid side chains (2 to 5 percent dry weight increase) at the expense of protein synthesis (25 to 34 percent dry weight decrease) results in carbohydrate, lipid and protein ratios that are closer to those required in the human diet. In addition, the selection of nitrogen fixing mutants which excrete ammonium ions present an opportunity to tailor these micro-organisms to meet the specific need for a sub-system to reverse potential loss of fixed nitrogen material.

Fry, I. V.↗
NASA NTRS2006

Effects of gamma-Radiation on Select Lipids and Antioxidants

Radiation encountered on an extended duration space mission (estimates of 3 Sieverts for a mission to Mars) poses a threat not only to human health, but also to the quality, nutritional value, and palatability of the food system. Free radicals generated by radiation interaction with foods may initiate many unwanted reactions including: 1) autoxidation in lipids that alters flavor, odor, and concentrations of essential fatty acids, and 2) depletion of antioxidants food products and dietary supplements. Studies have shown that antioxidants may provide long term health protection from oxidative stress caused by radiation exposure; therefore, consumption of antioxidants will be important. Stability of essential fatty acids is also important for astronauts long-term health status. The objectives of this study were to characterize the effects of low dose gamma-radiation on lipids and antioxidants by monitoring oxidation and reducing power, respectively, in model systems. Select oils and antioxidants were exposed to levels of gamma-radiation ranging from 0 to 1000 Gy (1 Gy = 1 Sv) using a Gammacell 220 and stored at ambient or elevated temperatures (65 C) for up to 3 months prior to analysis. A Fricke dosimeter was used to verify differences between the radiation doses administered. Primary and secondary products of lipid oxidation in soybean and peanut oils were monitored using conjugated diene and 2-thiobarbituric acid (TBARs) assays. Changes in fatty acid composition and formation and vitamin E levels were also measured. The reducing power of antioxidant compounds, including vitamins C and E and beta-carotene, was determined using the ferric reducing antioxidant power (FRAP) assay. Significant differences (alpha =0.05) were present between all radiation doses tested using the Fricke dosimeter. Increasing radiation doses above 3 Sv resulted in significantly (alpha =0.05) elevated levels of oxidation and free fatty acids in soybean and peanut oils. Decreases in concentrations of essential fatty acids upon increasing radiation doses were also observed. Increasing radiation doses caused significant (alpha =0.05) decreases in reducing power and hence the effectiveness of vitamins C and E as well as beta-carotene. This work establishes a need for quantifying the effects of space relevant radiation doses in the development of a food system for an extended duration mission and for identifying threshold radiation levels that will impact the useful shelf-life of the variety of foods that will be sent. Eventual rancidity of lipids and the loss of antioxidant bioprotective effects are major concerns for the acceptability and nutritional profile of a food system.

Gandolph, Jacob↗
NASA NTRS2015

Physiological Health Challenges for Human Missions to Mars

During the next decades, manned space missions are expected to be aiming at the Lagrange points, near Earth asteroids, and Mars flyby and/or landing. The question is therefore: Are we ready to go? To answer this with a yes, we are currently using the International Space Station to develop an integrated human physiological countermeasure suite. The integrated countermeasure suite will most likely encounter: 1) Exercise devices for aerobic, dynamic and resistive exercise training; 2) sensory‐motor computer training programs and anti‐motion sickness medication for preparing EVAs and G‐transitions; 3) lower limb bracelets for preventing and/or treating the VIIP (vision impairment and intracranial pressure) syndrome; 4) nutritional components for maintenance of bone, muscle, the cardiovascular system and preventing oxidative stress and damage and immune deficiencies (e. g. omega‐3 fatty acids, PRO/K, anti‐oxidants and less salt and iron); 5) bisphosphonates for preventing bone degradation.; 6) lower body compression garment and oral salt and fluid loading for landing on a planetary surface to combat orthostatic intolerance; 7) laboratory analysis equipment for individualized monitoring of biomarkers in blood, urine and saliva for estimation of health status in; 8) advanced ultrasound techniques for monitoring bone and cardiovascular health; and 9) computer modeling programs for individual health status assessments of efficiency and subsequent adjustments of countermeasures. In particular for future missions into deep space, we are concerned with the synergistic effects of weightlessness, radiation, operational constraints and other spaceflight environmental factors. Therefore, increased collaboration between physiological, behavioral, radiation and space vehicle design disciplines are strongly warranted. Another venue we are exploring in NASA's Human Research Program is the usefulness of artificial gravity for mitigating the health risks of long duration weightlessness.

Norsk, Peter↗
NASA NTRS1991

Regulatory physiology discipline science plan

The focus of the Regulatory Physiology discipline of the Space Physiology and Countermeasures Program is twofold. First, to determine and study how microgravity and associated factors of space flight affect the regulatory mechanisms by which humans adapt and achieve homeostasis and thereby regulate their ability to respond to internal and external signals; and, second, to study selected physiological systems that have been demonstrated to be influenced by gravity. The Regulatory Physiology discipline, as defined here, is composed of seven subdisciplines: (1) Circadian Rhythms, (2) Endocrinology, (3) Fluid and Electrolyte Regulation, (4) Hematology, (5) Immunology, (6) Metabolism and Nutrition, and (7) Temperature Regulation. The purpose of this Discipline Science Plan is to provide a conceptual strategy for NASA's Life Sciences Division research and development activities in the area of regulatory physiology. It covers the research areas critical to NASA's programmatic requirements for the Extended-Duration Orbiter, Space Station Freedom, and exploration mission science activities. These science activities include ground-based and flight; basic, applied, and operational; and animal and human research and development. This document summarizes the current status of the program, outlines available knowledge, establishes goals and objectives, identifies science priorities, and defines critical questions in regulatory physiology. It contains a general plan that will be used by both NASA Headquarters Program Offices and the field centers to review and plan basic, applied, and operational intramural and extramural research and development activities in this area.

Source record↗
NASA NTRS1996

Further Characterization of CELSS Wastes: A Review of Solid Wastes Present to Support Potential Secondary Biomass Production

Controlled ecological life support systems (CELSS) may one day play an essential role in extraterrestrial colonies. Key to the success of any CELSS will be the system's ability to approach a self-supporting status through recovery and reuse of basic resources. Primary CELSS solid wastes with potential to support secondary biomass production will be inedible plant biomass and metabolic human wastes. Solid waste production is summarized and reported as 765 g N per day per person, including 300 g C and 37 g N per day per person. One Resource Recovery configuration using the bioprocessing of solid wastes into a Tilapia feed stream is examined. Based on estimated conversion efficiencies, 12 g of protein per day per person is produced as a nutrition supplement. The unique tissue composition of crops produced at the Kennedy Space Center CELSS Program highlights the need to evaluate Resource Recovery components with data generated in the CELSS environment.

Muller, Matthew S.↗
NASA NTRS2007

Assessment of Immune Status, Latent Viral Reactivation and Stress during Long Duration Bed Rest as an Analog for Spaceflight

As logistical access for in-flight space research becomes more limited, the use of ground based spaceflight analogs for life science studies will increase. These studies are particularly important as NASA progresses towards the Lunar and eventually Mars missions outlined in the 2005 Vision for Space Exploration. Countermeasures must be developed to mitigate the clinical risks associated with exploration class space missions. In an effort to coordinate studies across multiple disciplines, NASA has selected 90-day bed rest as the analog of choice, and initiated the Flight Analogs Project to implement research studies with or without the evaluation of countermeasures. Although bed rest is not the analog of choice to evaluate spaceflight-associated immune dysfunction, a standard Immune Assessment was developed for subjects participating in the 90-day bed best studies. The Immune Assessment consists of: leukocyte subset distribution, T cell functional responses, intracellular cytokine production profiles, latent viral reactivation, virus specific T cell levels, virus specific T cell function, stress hormone levels and a behavioral assessment using stress questionnaires. The purpose of the assessment during the initial studies (without countermeasure) is to establish control data against which future studies (with countermeasure) will be evaluated. It is believed that some of the countermeasures planned to be evaluated in future studies, such as exercise, pharmacologic intervention or nutritional supplementation, have the ability to impact immune function. Therefore immunity will likely be monitored during those studies. The data generated during the first three control studies showed that the subjects in general did not display altered peripheral leukocyte subsets, constitutive immune activation, significant latent viral reactivation (EBV, VZV) or altered T cell function. Interestingly, for some subjects the level of constitutively activated T cells (CD8+/CD69+) and virus-specific T cells (CMV and EBV) both decreased during the studies. This likely reflects the isolation of the subjects (from an immunological perspective) and absence of everyday subclinical challenges to the immune system. Cortisol levels (plasma and saliva) did not vary significantly during the studies. This probably reflects a lack of physiological stress during the study and the stress of readaptation to the 1xG environment at R+1. These data demonstrate the absence of significant immune alteration during 90-day bed rest, and establish control data against which future studies (including countermeasures) may be compared.

Crucian, Brian E.↗
NASA NTRS1990

Nitrogen nutrition and temporal effects of enhanced carbon dioxide on soybean growth

Plants grown on porous media at elevated CO2 levels generally have low concentrations of tissue N and often appear to require increased levels of external N to maximize growth response. This study determines if soybean [Glycine max (L.) Merr. Ransom'] grown hydroponically at elevated CO2 requires increases in external NO3- concentrations beyond levels that are optimal at ambient CO2 to maintain tissue N concentrations and maximize the growth response. This study also investigates temporal influences of elevated CO2 on growth responses by soybean. Plants were grown vegetatively for 34 d in hydroponic culture at atmospheric CO2 concentrations of 400, 650, and 900 microliters L-1 and during the final 18 d at NO3- concentrations of 0.5, 1.0, 5.0 and 10.0 mM in the culture solution. At 650 and 900 microliters L-1 CO2, plants had maximum increases of 31 and 45% in dry weight during the experimental period. Plant growth at 900 microliters L-1 CO2 was stimulated earlier than at 650 microliters L-1. During the final 18 d of the experiment, the relative growth rates (RGR) of plants grown at elevated CO2 declined. Elevated CO2 caused increases in total N and total NO3(-)-N content and leaf area but not leaf number. Enhancing CO2 levels also caused a decrease in root:shoot ratios. Stomatal resistance increased by 2.1- and 2.8-fold for plants at the 650 and 900 microliters L-1 CO2, respectively. Nitrate level in the culture solutions had no effect on growth or on C:N ratios of tissues, nor did increases in CO2 levels cause a decrease in N concentration of plant tissues. Hence, increases in NO3- concentration of the hydroponic solution were not necessary to maintain the N status of the plants or to maximize the growth response to elevated CO2.

NASA Program CELSS↗
NASA NTRS2014

Bone Metabolism on ISS Missions

Spaceflight-induced bone loss is associated with increased bone resorption (1, 2), and either unchanged or decreased rates of bone formation. Resistive exercise had been proposed as a countermeasure, and data from bed rest supported this concept (3). An interim resistive exercise device (iRED) was flown for early ISS crews. Unfortunately, the iRED provided no greater bone protection than on missions where only aerobic and muscular endurance exercises were available (4, 5). In 2008, the Advanced Resistive Exercise Device (ARED), a more robust device with much greater resistance capability, (6, 7) was launched to the ISS. Astronauts who had access to ARED, coupled with adequate energy intake and vitamin D status, returned from ISS missions with bone mineral densities virtually unchanged from preflight (7). Bone biochemical markers showed that while the resistive exercise and adequate energy consumption did not mitigate the increased bone resorption, bone formation was increased (7, 8). The typical drop in circulating parathyroid hormone did not occur in ARED crewmembers. In 2014, an updated look at the densitometry data was published. This study confirmed the initial findings with a much larger set of data. In 42 astronauts (33 male, 9 female), the bone mineral density response to flight was the same for men and women (9), and those with access to the ARED did not have the typical decrease in bone mineral density that was observed in early ISS crewmembers with access to the iRED (Figure 1) (7). Biochemical markers of bone formation and resorption responded similarly in men and women. These data are encouraging, and represent the first in-flight evidence in the history of human space flight that diet and exercise can maintain bone mineral density on long-duration missions. However, the maintenance of bone mineral density through bone remodeling, that is, increases in both resorption and formation, may yield a bone with strength characteristics different from those that existed before space flight. Studies to assess bone strength after flight are underway at NASA, to better understand the results of bone remodeling. Studies are also underway to evaluate optimized exercise protocols and nutritional countermeasures. Regardless, there is clear evidence of progress being made to protect bone during spaceflight.

Smith, S. M.↗
NASA NTRS2015

Human System Risk Management for Space Flight

This brief abstract reviews the development of the current day approach to human system risk management for space flight and the development of the critical components of this process over the past few years. The human system risk management process now provides a comprehensive assessment of each human system risk by design reference mission (DRM) and is evaluated not only for mission success but also for long‐term health impacts for the astronauts. The discipline of bioastronautics is the study of the biological and medical effects of space flight on humans. In 1997, the Space Life Sciences Directorate (SLSD) initiated the Bioastronautics Roadmap (Roadmap) as the "Critical Path Roadmap", and in 1998 participation in the roadmap was expanded to include the National Space Biomedical Research Institute (NSBRI) and the external community. A total of 55 risks and 250 questions were identified and prioritized and in 2000, the Roadmap was base-lined and put under configuration control. The Roadmap took into account several major advisory committee reviews including the Institute of Medicine (IOM) "Safe Passage: Astronaut care for Exploration Missions", 2001. Subsequently, three collaborating organizations at NASA HQ (Chief Health and Medical Officer, Office of Space Flight and Office of Biological & Physical Research), published the Bioastronautics Strategy in 2003, that identified the human as a "critical subsystem of space flight" and noted that "tolerance limits and safe operating bands must be established" to enable human space flight. These offices also requested a review by the IOM of the Roadmap and that review was published in October 2005 as "A Risk Reduction Strategy for Human Exploration of Space: A Review of NASA's Bioastronautics Roadmap", that noted several strengths and weaknesses of the Roadmap and made several recommendations. In parallel with the development of the Roadmap, the Office of the Chief Health and Medical Officer (OCHMO) began a process in 2004 of evaluating the tolerance limits and safe operating bands called for in the Bioastronautics Strategy. Over the next several years, the concept of the "operating bands" were turned into Space Flight Human System Standards (SFHSS), developed by the technical resources of the SLSD at the NASA Johnson Space Center (JSC). These standards were developed and reviewed at the SLSD and then presented to the OCHMO for acceptance. The first set of standards was published in 2007 as the NASA‐STD‐3001, Volume 1, Crew Health that elaborated standards for several physiological areas such as cardiovascular, musculoskeletal, radiation exposure and nutrition. Volume 2, Human Factors, Habitability and Human Health was published in 2011, along with development guidance in the Human Integration Design Handbook (HIDH). Taken together, the SFHSS Volumes 1 and 2, and the HIDH replaced the NASA‐STD‐3000 with new standards and revisions of the older document. Three other changes were also taking place that facilitated the development of the human system risk management approach. In 2005, the life sciences research and development portfolio underwent a comprehensive review through the Exploration Systems Architecture Study (ESAS) that resulted in the reformulation of the Bioastronautics Program into Human Research Program (HRP) that was focused on appropriate mitigation results for high priority human health risks. The baseline HRP budget was established in August 2005. In addition, the OCHMO formulated the Health and Medical Technical Authority (HMTA) in 2006 that established the position of the Chief Medical Officer (CMO) at the NASA JSC along with other key technical disciplines, and the OCHMO became the responsible office for the SFHSS as noted above. The final change was the establishment in 2008 of the Human System Risk Board (HSRB), chaired by the CMO with representation from the HRP, SLSD management and technical experts. The HSRB then began to review all human system risks, established a comprehensive risk management and configuration management plan and data sharing policy. These major developments of standards, the HRP, the HMTA and a forum for review of human system risks (HSRB) facilitated the integration of human research, medical operations, systems engineering and many other disciplines in the comprehensive review of human system risks. The HSRB began a comprehensive review of all potential inflight medical conditions and events and over the course of several reviews consolidated the number of human system risks to 30 where the greatest emphasis is placed for investing program dollars for risk mitigation. The HSRB considers all available evidence from human research, medical operations and occupational surveillance in assessing the risks for appropriate mitigation and future work. All applicable DRMs (low earth orbit 6 and 12 months, deep space sortie for 30 days and 1 year, a one year lunar mission, and a planetary mission for 3 years) are considered as human system risks are modified by the hazards associated with space flight such as microgravity, exposure to radiation, distance from the earth, isolation and a closed environment. Each risk has a summary assessment representing the state of knowledge/evidence base for that risk, the available risk mitigations, traceability to the SFHSS and program requirements, and future work required. These data then can drive coordinated budgets across the HRP, the International Space Station, Crew Health and Safety and Advanced Exploration System budgets. These risk assessments were completed for 6 DRMs in December of 2014 and serve as the baseline for which subsequent research and technology development and crew health care portfolios can be assessed. The HSRB will review each risk at least annually and especially when new information is available that must be considered for effective risk mitigation. The current status of each risk can be reported to program management for operations, budget reviews and general oversight of the human system risk management program.

Davis, Jeffrey↗