Space nutrition: the key role of neurosensory, cardiovascular, gastrointestinal, nutrition in human space flight circadian rhythms, and musculoskeletal

Catalano Enrico1 physiology. Psychosocial aspects of nutrition are also important for more 1Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM), productive missions and crew morale. Via Giuseppe Giusti, 9, 50121 Firenze (FI), Research conducted to determine the impact Italy. e-mail: [email protected] of spaceflight on human physiology and subsequent nutritional requirements will also have direct and indirect applications in Earth- Corresponding author based nutrition research. Cumulative Catalano Enrico nutritional research over the past five decades Consorzio Interuniversitario Nazionale per la has resulted in the current nutritional Scienza e Tecnologia dei Materiali (INSTM), requirements for astronauts. Realization of the Via Giuseppe Giusti, 9, 50121 Firenze (FI), Italy. e-mail: [email protected] full role of nutrition during spaceflight is critical for the success of extended-duration

missions. Long-duration missions will require

quantitation of nutrient requirements for Abstract maintenance of health and protection against the effects of microgravity. From the basic impact of nutrient intake on health maintenance to the psychosocial benefits of mealtime, great advancements in Keywords: Space nutrition, space flight, nutritional sciences for support of human effects of microgravity, astronauts, space food space travel have occurred over the past 50 years. Nutrition in space has many areas of 1. Introduction impact, including provision of required nutrients and maintenance of endocrine, Nutrition has played a critical role throughout immune, and musculoskeletal systems. It is the history of exploration, and space affected by environmental conditions such as exploration is no exception. The purpose of radiation, temperature, and atmospheric this article is to review our current knowledge pressures, and these are reviewed. Nutrition of space flight nutrition and food science. with respect to space flight is closely Humans have adapted well to space flight, interconnected with other life sciences and over the past 50 years, we have research disciplines including the study of substantially increased our understanding of hematology, immunology, as well as the various physiologic changes that occur 1 during and after space flight [1]. Nutrition in Realization of the full role of nutrition during space has many aspects of impact, including spaceflight is critical for the success of provision of required nutrients and extended-duration missions. Research maintenance of endocrine, immune, and conducted to determine the impact of musculoskeletal systems. However, the spaceflight on human physiology and underlying mechanisms for many of these subsequent nutritional requirements will also alterations remain unclear. This article have direct and indirect applications in Earth- describes prior and ongoing nutritional based nutrition research. research undertaken with the goal of assuring Understanding the nutritional requirements of human health and survival during space flight. space travelers and the role of nutrition in Nutrition and food science research overlap human adaptation to microgravity are as with or are integral to many other aspects of critical to crew safety and mission success as space medicine and physiology including any of the mechanical systems of the psychological health, sleep and circadian spacecraft itself. There are many facets to rhythmicity, taste and odor sensitivities, nutrition and health on Earth. Space flight radiation exposure, body fluid shifts, and introduces further complications, and many wound healing and to changes in the gaps remain in our knowledge of the musculoskeletal, neurosensory, relationships between nutrition and health in gastrointestinal, hematologic, and space that need to be filled before we can immunologic systems. Nutrient intake play a safely embark on “exploration” missions, that fundamental role from health maintenance to is, missions beyond low Earth orbit. At the the psychosocial benefits of mealtime, the surface of these unknowns is the need to role of nutrition in space is evident. Recent understand and define basic nutrient advances in genomics and proteomics are just requirements during extended stays in beginning to be applied in space biomedical microgravity. Beyond this lies the need to research, and it is likely that findings from characterize the role of nutrition in the such studies will be applicable to applied adaptation of physiological systems to human nutritional science. microgravity, and/or the impact of these Long-duration missions will require the right changes on nutrition. Additionally, amount of nutrient requirements for environmental impacts (including radiation, maintenance of health and protection against and spacecraft and spacesuit atmospheres) can the effects of microgravity. Psychosocial alter nutritional status and nutritional aspects of nutrition will also be important for requirements of space flight. For surface more productive missions and crew morale. missions (on, for example, the moon and 2

Mars), partial gravity may complicate the amounts. Weightlessness impacts almost situation further. Finally, many potential every system in the body, including those of targets for nutritional countermeasures exist, the bones, muscles, heart and blood vessels, where modified dietary intake may help to and nerves. There are many facets to counteract or mitigate some of the negative maintaining eucaloric intake during space effects of space flight on the human body. flight, including energy requirements; The US space life sciences research physiological changes in taste and satiety; community has developed a set of critical scheduling issues of allotting time for meal questions and a road map to clearly preparation, consumption, and cleanup; food emphasize research efforts that ultimately will quality; and even food availability [4]. Little reduce to humans the risk associated with research has been done on differences in fuel space travel and habitation [2]. Relevant components (protein, carbohydrate, fat) research has been conducted in space and on during space flight, or on cofactors (eg, the ground using animal models and human vitamins) of energy utilization. We review ground-based analogs [3]. Throughout the these here, highlighting what has been done five-decade history of human space flight, and potential areas of future research. nutrition and food research have been an integral component of various missions. 2.1 Space food

Space food is a variety of food products, 2. Astronaut nutrition specially created and processed for Spacecraft, the space environment, and consumption by astronauts in outer space. The weightlessness itself all impact human food has specific requirements of providing physiology. Clean air, drinkable water, and balanced nutrition for individuals working in effective waste collection systems are space, while being easy and safe to store, required for maintaining a habitable prepare and consume in the machinery-filled environment. Adequate energy intake is low gravity environments of manned perhaps the single most important aspect of spacecraft [1]. In recent years, space food has astronaut nutrition [4]. This is not only been used by various nations engaging on because energy in and of itself is more space programs as a way to share and show important than other nutritional factors, but off their cultural identity and facilitate also because if enough food is consumed to intercultural communication. Although meet energy needs, then generally other astronauts consume a wide variety of foods nutrients will also be consumed in reasonable and beverages in space, the initial idea was to 3 supply astronauts with a formula diet that process called resorption) and formation of would supply all the needed vitamins and new bone tissue. Chemicals in the blood and nutrients [2]. With the long-duration missions urine can be measured to determine the aboard the International Space Station (ISS), relative amounts of bone resorption and it has become clear that more emphasis needs formation. During spaceflight, bone to be placed on improving human habitability. resorption increases significantly, and In fact, in the last years a new project: “The formation either remains unchanged or Vegetable Production System” (VEGGIE) decreases slightly [5]. The net effect of this was developed to provide a means to supply imbalance is a loss of bone mass. Bone loss, crews with a continuous source of fresh food especially in the legs, is increased during and a tool for relaxation and recreation. The spaceflight. This is most important on flights Veggie provides lighting and nutrient longer than thirty days, because the amount of delivery, but utilizes the cabin environment bone lost increases as the length of time in for temperature control and as a source of space increases. Weightlessness also increases carbon dioxide to promote growth [64]. excretion of calcium in the urine and the risk of forming kidney stones. Both of these The Vegetable Production System (Veggie) is conditions are related to bone loss [5]. a deployable plant growth unit capable of producing salad-type crops to provide the Calcium and bone metabolism remain key crew with a palatable, nutritious, and safe concerns for space travelers, and ground- source of fresh food and a tool to support based models of space flight have provided a relaxation and recreation. During 2015 red vast literature to complement the smaller set romaine lettuce was cultivated and consumed of reports from flight studies. Increased bone on board on ISS by the crew members [65]. resorption and largely unchanged bone Veggie will remain on the station formation result in the loss of calcium and permanently and could become a research bone mineral during space flight, which alters platform for other top-growing plant the endocrine regulation of calcium experiments. metabolism [6]. Physical, pharmacologic, and nutritional means have been used to

counteract these changes. In 2012, heavy 3. Bone and nutrition in space resistance exercise plus good nutritional and vitamin D status were demonstrated to reduce Bone is a living tissue, and is constantly being loss of bone mineral density on long-duration remodeled. This remodeling is achieved International Space Station missions [6]. through breakdown of existing bone tissue (a

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Uncertainty continues to exist, however, as to spacecraft are shielded to prevent this whether the bone is as strong after flight as it exposure. Because of this, all of the was before flight and whether nutritional and astronauts' vitamin D has to be provided by exercise prescriptions can be optimized their diet. However, it is very common for during space flight. Findings from these vitamin D levels to decrease during studies not only will help future space spaceflight [7]. explorers but also will broaden our Multiple risks are associated with bone loss understanding of the regulation of bone and during space flight. Almost immediately upon calcium homeostasis on Earth. entering weightlessness, bone resorption Whereas nutrition is critical for virtually all increases, and calcium (and other minerals) systems, the interaction of nutrition with bone are released into the blood and urine. This is perhaps more extensive and complex than increases kidney stone risk on short missions, most of its interactions with body systems. and on longer missions, chronic bone and Many nutrients are important for healthy calcium loss can increase risks to bone health bone, particularly calcium and vitamin D. both in the near term (eg, risk of fractures) When a food containing calcium is eaten, the and in the long term (eg, risk of osteoporosis- calcium is absorbed by the intestines and goes like bone degradation). into the bloodstream. Absorption of calcium Sodium intake is also a concern during from the intestines decreases during spaceflight, because space diets tend to have spaceflight. Even when astronauts take extra relatively high amounts of sodium. Increased calcium as a supplement, they still lose bone dietary sodium is associated with increased [7]. amounts of calcium in the urine and may relate to the increased risk of kidney stones. Bone is the body’s reservoir of calcium, The potential effect of these and other which provides structure and strength to bone, nutrients on the maintenance of bone health but also provides a ready resource to maintain during spaceflight highlights the importance blood calcium levels during periods with of optimal dietary intake. The changes in insufficient dietary provision of calcium. bone during spaceflight are very similar to Several nutrients are required for the those seen in certain situations on the ground synthesis of bone, including protein and [7]. There are similarities to osteoporosis, and vitamins D, K, and C. On Earth, the body can even paralysis. While osteoporosis has many produce vitamin D after the skin is exposed to causes, the end result seems to be similar to the sun's ultraviolet light. In space, astronauts spaceflight bone loss. Paralyzed individuals could receive too much ultraviolet light, so 5 have biochemical changes very similar to Typically, these losses are small (1 percent to those of astronauts. This is because in both 5 percent of body mass), but they can reach cases the bones are not being used for 10 percent to 15 percent of preflight body support. In fact, one of the ways spaceflight mass. Although a 1 percent body-weight loss bone loss is studied is to have people lie in can be explained by loss of body water, most bed for several weeks. Using this approach, of the observed loss of body weight is scientists attempt to understand the accounted for by loss of muscle and adipose mechanisms of bone loss and to test ways to (fat) tissue. Exposure to microgravity reduces counteract it. If they can find ways to muscle mass, volume, and performance, successfully counteract spaceflight bone loss, especially in the legs, on both short and long doctors may be able to use similar methods to flights [9-11]. treat people with osteoporosis or paralysis. It Weightlessness leads to loss of muscle mass is not clear whether bone mass lost in space is and muscle volume, weakening muscle fully replaced after returning to Earth. It is performance, especially in the legs. The loss also unclear whether the quality (or strength) is believed to be related to a metabolic stress of the replaced bone is the same as the bone associated with spaceflight. These findings that was there before a spaceflight. are similar to those found in patients with Preliminary data seem to show that some serious diseases or trauma, such as burn crew members do indeed regain their preflight patients. bone mass, but this process takes about two or three times as long as their flight. The ability The primary countermeasure against muscle to understand and counteract weightlessness- loss remains adequate energy intake, which induced bone loss remains a critical issue for will no doubt include protein, but protein astronaut health and safety. The International supplements are not required. Use of protein Space Station provides the opportunity for and amino acid supplementation has long monitoring the effects of space flight on bone been studied as a potential means to mitigate physiology to be documented, along with the muscle loss associated with space flight, but testing of countermeasures aimed at results have been inconclusive at best [12, counteracting bone loss [8]. 13]. It remains unclear whether nutritional

measures beyond the consumption of 4. Muscle loss in microgravity conditions adequate energy and protein would be beneficial in reducing muscle atrophy [14]. Loss of body weight (mass) is a consistent finding throughout the history of spaceflight. 6

Exercise routines have not succeeded in hormones may increase in the circulation as maintaining muscle mass or strength of part of the stress response to microgravity astronauts during spaceflight. Most of the conditions, including epinephrine and exercises performed have been aerobic (e.g., norepinephrine, adrenocorticotropin, cortisol. treadmill, stationary bicycle). Use of These hormones play a role in the elevation of resistance exercise, in which a weight (or plasma glucose and fatty acids, in increased another person) provides resistance to lipolytic activity in adipose tissue, in reducing exercise against, has been proposed to aid in lipogenesis and in raising glycogen content in the maintenance of both muscle and bone the liver [20]. These hormones have been during flight. Ground-based studies (not done measured during and after space flight: data in space) of resistance exercise show that it from previous space missions show increases may be helpful, not only for muscle but also in catabolic hormones (cortisol, glucagone) for bone [8]. Studies being conducted on the and a prolonged elevation of 3- International Space Station are testing the methylhistidine excretion, suggesting a effectiveness of this type of exercise for chronic metabolic stress response that may be astronauts. influenced not only by mission length but also by energy intake, exercise regimen and even Exercise is the most common first-pass gender [21]. Such changes may indeed be approach to maintaining muscle mass and involved in promoting muscle and bone loss, strength [15]. The exercise regimens tested as in impairing immune status, in the regulation countermeasures to date have generally not of body fluids and electrolytes that affects the succeeded in maintaining muscle mass or cardiovascular response to microgravity. strength (or bone mass) during space flight Catecholamines as well as renin-aldosterone [15-17]. Many types of exercise protocols are also involved in fluid balance, being part have been proposed to aid in the maintenance of sodium-retaining endocrine systems; of both muscle and bone during flight, but consistent observations in various missions these have yet to be fully tested on orbit [18, (Mir 97, Spacelab mission D-2, Euromir 94) 19]. revealed an elevated activity that may lead to sodium storage without an accompanying fluid retention [22]. This may be part of the 5. Endocrine system function related to the reason leading to an extravasation of fluid nutritional status in the space flight after an increase in vascular permeability. An The endocrine system appears to be sensitive enormous capacity for sodium in the extra- to the conditions of space flight. Several vascular space and a mechanism that allows

7 the dissociation between water and sodium differences in the immunomodulatory effects handling may contribute to fluid balance of candidate probiotic bacteria should be adaptation in weightlessness [23]. taken into consideration and the positive effect should be studied in weightlessness 6. Gastrointestinal function during space models. The use of prebiotics partly missions overcomes the limitations of probiotics. Astronauts experience gastrointestinal Prebiotics are growth substrates and not changes early in flight, gaseous stomach viable entities, specifically directed toward occurs due to the inability of gases to rise. potentially beneficial bacteria already Furthermore the effects of micro-gravity are growing in the colon [25]. presumed to alter the contact of the gastric contents with the gastrointestinal mucus. However, cephalic fluid shifts, in combination 7. Cardiovascular health and nutrition in with commonly observed dehydration, could space possibly affect gastrointestinal motility Cardiovascular issues are a key concern for through reduced splanchnic flow. The effect space travelers, but the role of nutrition in of chronic inactivity increases transit time and cardiovascular adaptation has not yet been potentially changes gastrointestinal microflora well characterized [26-28]. It is worth noting [24]. Gastrointestinal integrity and bacterial that multiple studies are being planned or are balance may be improved by probiotics and underway on ISS to shed light on this area in prebiotics that should be studied for a possible the near future. Omega-3 fatty acids have a inclusion in space foods. Probiotics, defined clear beneficial impact on cardiovascular as microbial food supplements that health on Earth, but such effects have not beneficially affect the host improving its been evaluated during space flight [29]. intestinal microbial balance, have been Nonetheless, the initial efforts being made to studied to change the composition of colonic increase fish and omega-3 fatty acid intake in microbiota by increasing bacterial groups astronauts for the benefit of other systems such as Bifidobacteria and Lactobacilli that (bone, muscle) will likely have positive are perceived as exerting health-promoting effects here as well [29]. properties. However, these changes may be transient, and the implantation of exogenous bacteria becomes limited. On the other hand, since astronauts do have an impaired immune function, as discussed in the next section,

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8. Iron metabolism during space flight have underlined its increase post-flight probably due to a combination of augmented Space flight-induced hematologic changes metabolic activity and loss of some host have been observed since the initial days of antioxidant defences in-flight [31, 32]. space exploration. Space flight anemia is a widely recognized phenomenon in astronauts. The effect is more pronounced after long- The implications of hematologic changes for duration space flight. The effects last for long-term space flight may have several weeks after landing. In humans there consequences on the health of astronauts [30]. is increased lipid peroxidation in erythrocyte Reduction in circulating red blood cells and membranes, reduction in some blood plasma volume results in a 10% to 15% antioxidants, and increased urinary excretion decrement in circulatory volume. This effect of markers for oxidative damage to lipids and appears to be a normal physiologic adaptation DNA, respectively: 8-iso-prostaglandin F2α to weightlessness and results from the and 8-oxo-7,8 dihydro-2 deoxyguanosine [31, removal of newly released blood cells from 33]. the circulation [30]. Iron availability Decreasing the imbalance between the increases, and (in the few subjects studied) production of endogenous oxidant defenses iron stores increase during long-duration and oxidant production by increasing the space flight. The consequences of these supply of dietary antioxidants may lessen the changes are not fully understood. severity of the postflight increase in oxidative stress. The antioxidant defence system can be implemented to counteract oxidative stress by 9. Oxidative stress and space flight supplementing vitamins in dietary intake of Space flight is associated with an increase in astronauts such as tocopherols and oxidative stress and to significantly high tocotrienols (vitamin E), ascorbate (vitamin radiation, even with considerable shielding on C), vitamin A and its precursors betacarotene the spacecraft. In the human body, solar and other carotenoids, trace elements and radiation or low wavelength electromagnetic minerals such as copper, manganese, zinc, radiation (such as gamma rays) from the earth selenium and iron [34]. Actual or space environment can split water to recommendations of vitamin C intake have generate reactive free radicals. These reactive been raised from 60 to 100 mg per day, free radicals can react in the body leading to during space flights [4, 35]. Dietary and oxidative damage to lipids, proteins and antioxidant defences appear to play a DNA. Recent data on the oxidant damage protective role in muscle cells by reducing

9 associated oxidative damage to lipids, nucleic intracranial pressure, optic disc edema, globe acids, and proteins [34]. However, iron flattening, optic nerve sheath thickening, supplementation in microgravity is not hyperopic shifts, choroidal folds, cotton wool recommended because the reduction in red spots and retinal changes [39]. The etiology cell mass and the consequent increase in iron of the refractive and structural ophthalmic stores could augment free radical generation. changes is currently not known and continues to be researched, but biochemical evidence Dietary intake and/or supplementation of indicates that the folate- and vitamin B12- particular nutrients showed also an important dependent 1-carbon transfer pathway may be prophylactic role against photo-oxidative involved. Nutrition is known to be an damage to cell membranes [36]. Nutritional important factor for ophthalmic health in countermeasures in space with antioxidant general. supplementation provide a great opportunity for research within space flight models, whereas the main concern is to counteract the 11. Immune changes in space flight potential for long-term oxidative damage in Optimal function of the immune system is humans under these conditions. impaired in the presence of malnutrition.

Without adequate nutrition, the immune 10. Ophthalmic changes in space flight system is clearly deprived of the components Microgravity is the dominant cause of many needed to generate an effective immune physiological changes during spaceflight and response [40, 41]. Nutrients act as is thought to contribute significantly to the antioxidants and as cofactors [42]. Exposure observed ophthalmic changes. Ophthalmic of animals and humans to space flight health among astronauts has gotten attention conditions has resulted in numerous in recent years because of a newly identified alterations in immunological parameters, for issue for some crewmembers. In addition to a instance, decreases in blast transformation of general increase in cataract risk, some lymphocytes, cytokine production, and crewmembers have experienced vision-related natural killer cell activity. After flight, changes after long-duration space flight [37, alterations in leukocyte subset distribution 38]. have also been reported for humans and animals [43]. Disruption of nutritional It has recently been recognized that vision balance and dietary intake of astronauts and changes are actually quite common in cosmonauts during space flight, which is astronauts and are associated with a constellation of findings including elevated 10 often accompanied by a stress response, might antioxidant vitamins, can have profound influence their immune response [44, 45]. effects on immune function [50-52]. Such a Findings of energy deficiency on long lack of nutrients also leads to deregulation of duration missions increase susceptibility to the balanced host response [53]. In fact, infections [46]. Studies on cosmonauts during several micronutrients such as vitamin A, space flight have shown that IgG levels were beta-carotene, folic acid, vitamin B12, unchanged, whereas IgA and IgM levels were vitamin C, riboflavin, iron, selenium, zinc sometimes increased [47]. A decreased have immunomodulating actions [54, 55]. cytotoxicity in cosmonauts after space flight Recent work demonstrates that some nutrients can be proposed, and this includes the such as arginine, glutamine, nucleotides and defective function of NK cells and the omega-3 fatty acids may affect immune reduced number of circulating effector cells function [56]. The dietetic intake of these [48]. Physical and psychological stress nutrients should be considered in order to associated with space flight resulted in recommend appropriate nutritional decreased virus-specific T-cell immunity and supplementation aimed at reducing immune reactivation of EBV [49]; almost certainly changes due to sub-optimal nutrition that may immunity changes in space are similar to eventually have negative consequences on those occurring during acute stress conditions. immune status and susceptibility to a variety Therefore, it is reasonable to consider stress- of pathogens. Detailed information on the related immunotherapy approaches in the effects of many micronutrients during space practice of space medicine mainly because flight are mandatory before specific concerns have been raised about the possible nutritional recommendations can be made, risks of post-flight infections. A decrease in especially with respect to their relationship the number of T-lymphocytes and impairment with immune system function. of their function is an important effect of Moreover, the latest data (from healthy weightlessness on the immune system. From a subjects and patients with inflammatory nutritional point of view, we have to consider diseases) show that probiotics can be used as that deficiency of zinc is associated with innovative tools to improve the intestine’s similar changes in T-lymphocytes. immunologic barrier and produce a gut- Suggestions that modifications to the diet may stabilizing effect. Many of the probiotic have a beneficial effect on health are not new. effects are mediated via immune regulation, It is well known from ground research that a in particular by control of the balance of lack of macronutrients or selected proinflammatory and antiinflammatory micronutrients, like zinc, selenium, and the cytokines [57]. Recent results demonstrate

11 that dietary consumption of specific learn regarding the impact of weightlessness probiotics can enhance natural immunity in on absorption, metabolism, and excretion of healthy elderly subjects [58]. This evidence nutrients, and this will ultimately determine suggests that the consumption of cultures of the nutrient requirements for extended- beneficial live microorganisms that act as duration space flight. Existing nutritional probiotics should be evaluated in target requirements for extended-duration space specific populations, including astronauts. flight have been formulated based on limited flight research, and extrapolation from ground-based research. In this regard,

NASA’s Nutritional Biochemistry Laboratory was charged with defining the nutritional 12. Discussion requirements for space flight. This is Adequate nutrition is critical for maintenance accomplished through both operational and of crew health during and after extended- research projects. A nutritional status duration space flight. Provision of a variety of assessment program is included operationally available foods [59] with positive sensory for all International Space Station astronauts. characteristics [60], and adequate time for This medical requirement includes preparation and consumption of meals biochemical and dietary assessments, and is enhances food intake by the crew members. completed before, during, and after the The observed changes in food intake, missions. This program will provide hypothalamic monoamines, and peripheral information about crew health and nutritional hormones suggest that besides microgravity, status, and will also provide assessments of continuous light exposure contributes to the countermeasure efficacy. observed anorexia, and its metabolic sequelae Although experience with long-term space including bone loss [61]. Poor or inadequate flight has provided considerable confidence in sleep may affect eating and drinking behavior, the ability of the human body to recover from thus, generating the potential for nutritional space flight and readapt to the Earth problems. environment, effects observed on the long Skylab, Mir, and NASA-Mir missions have The impact of weightlessness on human convinced flight physicians and scientists that physiology is profound, with effects on many countermeasures and monitoring are essential systems related to nutrition, including bone, to the success of long duration spaceflight. muscle, hematology, fluid and electrolyte Countermeasures are methods used to limit regulation. Additionally, we have much to the negative physical and psychological 12 effects of the space environment on humans. NASA has an exciting new vision of future Nutrition and foods are essential for spaceflight to favour the return of humans to maintenance of health and for enabling certain the moon in preparation for visits to Mars and countermeasures such as exercise. Critical possibly beyond. Moon missions are essential questions and a road map point to the to the exploration of more distant worlds. important areas of nutrition and food science Extended lunar stays build the experience and research needed in the future. These include expertise needed for the long-term space development and use of genomic and missions required to visit other planets. proteomic research and development and use Moreover NASA is working toward sending of other advanced technologies. There must astronauts to a near-Earth asteroid by 2025, be interactions between the various then on to the vicinity of the Red Planet by disciplines to determine the underlying the mid-2030s. Part of this preparation mechanisms and to apply them to nutritional involves studying the psychological and requirements to ensure a healthy and physiological effects of long-term spaceflight, productive crew. However, due to limitations which the agency investigated during 2015 on of spaceflight research opportunities, ground- one-year missions to the International Space based models are essential for understanding Station (The standard stay for astronauts nutrition-related physiologic changes and aboard the orbiting lab has been six months). their underlying mechanisms. Nutrition The biggest challenge to human exploration research efforts require a wide range of of deep-space destinations is related to high models and interdisciplinary approaches radiation levels beyond Earth orbit. With including contributions from physiology, current spacecraft technology, astronauts can biochemistry, psychology, food science and cruise through deep space for a maximum of technology, horticulture, and advanced one year or so before accumulating a medical technologies. dangerously high radiation dose, researchers say. As a result, many intriguing solar system 13. Conclusions targets remain off-limits to human exploration

After 55 years of human spaceflight from the at the moment. A one-year spaceflight cap first human Yuri Gagarin to journey into outer would still allow manned missions to some space and a great deal of space life sciences intriguing destinations, such as Mars. research, much has been learned about human For future long-term mission replacement of adaptation to microgravity exposure. gravity by centrifugation (“artificial gravity”) has been proposed as a multi-system

13 countermeasure [102, 103], but particularly From a nutrition perspective, critical for bone. Although some initial studies have questions remain regarding the nutrient been completed, the optimal artificial gravity requirements for extended‐duration missions prescription for bone, including dose, and the ability of nutrients to serve as duration, and frequency of centrifugation, countermeasures to mitigate some of the remains to be identified [82, 104], along with negative effects of spaceflight. Nutrition is an its potential impact on nutrition and related essential part of maintaining the endocrine systems [105, 106]. and immune system, skeletal and muscle integrity, and the hydration status of the space In fact, data gathered by NASA’s Curiosity crew, all of which are important for extended- rover suggest that astronauts could endure a duration missions and in those where six-month outbound flight, a 600-day stay on strenuous extravehicular activities are the Martian surface and the six-month journey required. In addition, the psychological home without accumulating a worryingly high aspects of individuals during space flights radiation dose. underline the role of the mealtime perceived Mars missions will require additional as a welcome break from job-related activities technological and biomedical advances. as well as a chance to socialize. Current scenarios, based on existing Initial studies are underway to better propulsion technology, are for missions of understand nutritional requirements in about 1-1.5 years, with 6 months of transit to microgravity, the stability of nutrients in Mars, 2-6 month stay on the Mars surface and foods stored in space, and oxidative damage another 6‐month voyage to return. On these and how to counteract it. Moreover the design flights, early return will not be possible, and of future space suits is currently underway, thus in situ medical capabilities are needed. and one of the considerations is expanding the Determining what diagnostic testing is ability to provide nutrition during required and developing technologies to allow extravehicular activity, either by making a such testing in microgravity or 1/3‐gravity nutritional beverage available in the suit or by will be challenging, to say the least. making it possible for an astronaut to easily It can be realistically predicted that nutritional exit the suit for a snack or lunch. balance and dietary adequacy will become From a food perspective, storage of foods for increasingly important on future long-term up to 5 years will be required (as much of the space flights especially regarding future food as possible will be sent ahead of the missions to the International Space Station crewed mission), and ensuring adequate and to Mars. nutrient content at the time of consumption 14 will be critical. For astronauts depending for months to years on a closed food system, any nutrient deficiency or excess could be Bibliography catastrophic.

Diet will be important for the efficacy of the countermeasures and prevention of 1. Nicogossian AE, Pool SL, Uri JJ. compounding problems. Further efforts will Historical perspectives. In: be implemented to ameliorate dietary Nicogossian AE, Huntoon CL, Pool adequacy and food safety in order to SL, eds. Space physiology and counteract deleterious physiological changes, medicine. Philadelphia: Lea & Febiger psychosocial repercussions and 1994; 3. microbiological hazards. Finally, all space 2. Vodovotz Y, Smith SM, Lane HW. food systems will be designed to meet not Food and nutrition in space: only individual nutritional requirements but application to human health. Nutrition also different food preferences and eating 2000; 16:534. habits, according to the different cultural 3. Gretebeck RJ, Greenleaf JE. Utility of background and country of origin of the crew ground-based simulations of members. weightlessness. In: Lane HW, Schoeller DA, eds. Nutrition in The question of in situ production of food spaceflight and weightlessness based on crops will be the solution and the models. Boca Raton: CRC Press, additional value to provide a set of nutrients 2000; 69. for crew members. Vitamins A, B12, C, D, E, 4. Smith SM, Zwart SR. Nutritional K, etc. as well as mineral salts could be used biochemistry of spaceflight. Adv Clin in future as countermeasures for the radiation Chem. 2008; 46:87-130. exposure of deep space during long‐duration 5. Weaver CM, LeBlanc A, Smith SM. space missions. Genetically modified foods Calcium and related nutrients in bone could also be the key to solve sudden metabolism. In: Lane HW, Schoeller nutritional problems during long-term DA, editors. Nutrition in spaceflight missions. Nutrition will be the key-factor for and weightlessness models. Boca the next phases of exploration beyond this Raton, FL: CRC Press. 2000; p. 179- planet, and space nutrition will ensure optimal 201. health and mission success. 6. Sibonga JD. Spaceflight-induced bone loss: is there an osteoporosis risk?

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Curr Osteoporos Rep. 2013; 11(2):92- deconditioning during bed rest in 8. women. J Appl Physiol. 2014. 7. Smith SM, Heer MA, Shackelford LC, 13. Brooks N, Cloutier GJ, Cadena SM, Sibonga JD, Ploutz-Snyder L, Zwart Layne JE, et al. Resistance training SR. Benefits for bone from resistance and timed essential amino acids exercise and nutrition in long-duration protect against the loss of muscle mass spaceflight: Evidence from and strength during 28 days of bed rest biochemistry and densitometry. J and energy deficit. J Appl Physiol. Bone Miner Res. 2012; 27(9):1896- 2008; 105(1):241-8. 906. 14. Trappe TA, Burd NA, Louis ES, Lee 8. Hackney KJ, Scott JM, Hanson AM, GA, et al. Influence of concurrent English KL, Downs ME, Ploutz- exercise or nutrition countermeasures Snyder LL. The Astronaut-Athlete: on thigh and calf muscle size and Optimizing Human Performance in function during 60 days of bed rest in Space. J Strength Cond Res. 2015; women. Acta Physiol (Oxf). 2007; 29(12):3531-45. 191(2):147-59. 9. Rambaut P, Leach C, Leonard J. 15. Baldwin KM. Future research Observations in energy balance in man directions in seeking countermeasures during spaceflight. Am J Physiol. to weightlessness. J Gravit Physiol. 1977; 233:R208-12. 1995; 2(1):P51-3. 10. Fitts RH, Riley DR, Widrick JJ. 16. Di Prampero PE, Narici MV. Muscles Invited review: microgravity and in microgravity: from fibres to human skeletal muscle. J Appl Physiol. 2000; motion. J Biomech. 2003; 36(3):403- 89(2):823-39. 12. 11. Gopalakrishnan R, Genc KO, Rice AJ, 17. Trappe S, Costill D, Gallagher P, Lee SM, et al. Muscle volume, Creer A, et al. Exercise in space: strength, endurance, and exercise human skeletal muscle after 6 months loads during 6-month missions in aboard the International Space Station. space. Aviat Space Environ Med. J Appl Physiol. 2009; 106(4):1159-68. 2010; 81(2):91-102. 18. Ferrando AA, Tipton KD, Bamman 12. Lee SM, Schneider SM, Feiveson AH, MM, Wolfe RR. Resistance exercise Macias BR, et al. WISE-2005: maintains skeletal muscle protein Countermeasures to prevent muscle synthesis during bed rest. J Appl Physiol (1985). 1997; 82(3):807-10.

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19. Hawkey A. The importance of physiology in microgravity. Acta exercising in space. Interdiscip Sci Cardiol. 2005; 60(2):129-51. Rev. 2003; 28(2):130-8. 27. Zhang LF. Region-specific vascular 20. Popova IA, Grigoriev AI. Metabolic remodeling and its prevention by effect of space flight. Adv Space Biol artificial gravity in weightless Med. 1994; 4:69-83. environment. Eur J Appl Physiol. 21. Stein TP, Wade CE. The 2013; 113(12):2873-95. catecholamine response to spaceflight: 28. Moore AD, Lee SMC, Stenger MB, role of diet and gender. Am J Physiol Platts SH. Cardiovascular exercise in Endocrinol Metab. 2001; the U.S. space program: past, present, 281(3):E500-506. and future. Acta Astronaut. 2010; 22. Drummer C, Hesse C, Baisch F, Norsk 66:974-88. P, Elmann-Larsen B, Gerzer R, Heer 29. Rizos EC, Ntzani EE, Bika E, M. Water and sodium balances and Kostapanos MS, et al. Association their relation to body mass changes in between omega-3 fatty acid microgravity Eur J Clin Invest. 2000; supplementation and risk of major 30(12): 1066-1075. cardiovascular disease events: a 23. Drummer C, Norsk P, Heer M. Water systematic review and meta-analysis. and sodium balance in space. Am J JAMA. 2012; 308(10):1024-33 Kidney Dis. 2001; 38(3):684-690. 30. Smith SM. Red blood cell and iron 24. Lane HW, Schoeller DA. Overview: metabolism during space flight. history of nutrition and spaceflight. In: Nutrition. 2002; 18(10):864-6. Lane HW, Schoeller DA (eds) 31. Stein TP, Leskiw MJ. Oxidant damage Nutrition in Spaceflight and during and after spaceflight. Am J Weightlessness Models. CRC Press Physiol Endocrinol Metab. 2000; LLC 1999; pp 1-18. 278(3):E375-382. 25. Gibson GR, Roberfroid MB. Dietary 32. Stein T. Space flight and oxidative modulation of the human colonic stress. Nutrition 2002; 18(10):867. microbiota: introducing the concept of 33. Smith SM, Davis-Street JE, Rice BL, prebiotics. J Nutr. 1995; 125:1401- Nillen JL, et al. Nutritional status 1412. assessment in semiclosed 26. Aubert AE, Beckers F, Verheyden B. environments: ground-based and space Cardiovascular function and basics of flight studies in humans. J Nutr. 2001; 131(7):2053-61.

17

34. Sacheck JM, Blumberg JB. Role of overview. J Nutr. 1992; 122(3 vitamin E and oxidative stress in Suppl):591-6. exercise. Nutrition 2001; 17(10):809- 41. Mizock BA. Immunonutrition and 814 critical illness: an update. Nutrition. 35. Donald B, McCormick Nutritional 2010; 26(7-8):701-7. recommendation for spaceflight. In: 42. Cunningham-Rundles S, McNeeley Lane HL, Schoeller DA (eds) DF, Moon A. Mechanisms of nutrient Nutrition in Spaceflight and modulation of the immune response. J Weightlessness Models. CRC Press Allergy Clin Immunol. 2005; LLC 1999; pp 253-259. 115(6):1119-28. 36. Bone RA, Landrum JT, Dixon Z, 43. Sonnenfeld G. Space flight, Chen Y, Llerena CM. Lutein and microgravity, stress, and immune zeaxanthin in the eyes, serum and diet responses. Adv Space Res. 1999; of human subjects. Exp Eye Res. 23(12):1945-1953. 2000; 71(3):239-245. 44. Sonnenfeld G. The immune system in 37. Chylack LT, Jr., Feiveson AH, space, including Earth-based benefits Peterson LE, Tung WH, et al. NASCA of space-based research. Curr Pharm Report 2: longitudinal study of Biotechnol. 2005 Aug;6(4):343-9. relationship of exposure to space 45. Sonnenfeld G, Shearer WT. Immune radiation and risk of lens opacity. function during space flight. Nutrition. Radiat Res. 2012; 178(1):25-32. 2002 Oct;18(10):899-903. 38. Cucinotta FA, Manuel FK, Jones J, 46. Chandra RK Nutrition and Iszard G, et al. Space radiation and immunology: from the clinic to the cataracts in astronauts. Radiat Res. cellular biology and back again. Proc 2001; 156(5 Pt 1):460-6. Nutr Soc. 1999; 58:681-683. 39. Mader TH, Gibson CR, Pass AF, 47. Konstantinova IV, Rykova MP, Kramer LA, et al. Optic disc edema, Lesnyak AT, Antropova EA. Immune globe flattening, choroidal folds, and changes during long-duration hyperopic shifts observed in missions. J Leukoc Biol. 1993; astronauts after long-duration space 54(3):189-201. flight. Ophthalmology. 2011; 48. Konstantinova IV, Rykova M, 118(10):2058-69. Meshkov D, Peres C, Husson D, 40. Beisel WR. History of nutritional Schmitt DA. Natural killer cells after immunology: introduction and

18

ALTAIR mission. Acta Astronaut. effects on immunity. Am J Clin Nutr. 1995; 36(8-12):713-718. 2001; 73(2 S):444S-450S. 49. Stowe RP, Pierson DL, Barrett AD. 58. Arunachalam K, Gill HS, Chandra Elevated stress hormone levels relate RK. Enhancement of natural immune to Epstein-Barr virus reactivation in function by dietary consumption of astronauts. Psychosom Med. 2001; Bifidobacterium lactis (HN019). Eur J 63(6):891-895. Clin Nutr. 2000; 54(3):263-267. 50. Chandra RK. Nutrient regulation of 59. Rolls BJ. Experimental analyses of the immune functions. Forum Nutr. 2003; effects of variety in a meal on human 56:147-8. feeding. Am J Clin Nutr. 1985; 51. Chandra RK. Nutrition and the 42(5S):932-939. immune system: an introduction. Am J 60. Nestle M,Wing R, Birch L, DiSogra Clin Nutr. 1997; 66(2):460S-3S. L, Drewnowski A, Middleton S, 52. Keith ME, Jeejeebhoy KN. Sigman-Grant M, Sobal J, Winston M, Immunonutrition. Baillieres Clin Economos C. Behavioural and social Endocrinol Metab. 1997; 11(4):709- influences on food choice. Nutr Rev. 38. 1998; 56(5 Pt 2):S50-64. 53. Wintergerst ES, Maggini S, Hornig 61. Varma M, Sato T, Zhang L, Meguid DH. Contribution of selected vitamins MM. Space flight related anorexia. and trace elements to immune Lancet. 2000; 356(9230):681. function. Ann Nutr Metab. 2007; 62. Levine DS, Greenleaf JE. 51(4):301-23. Immunosuppression during 54. Bhaskaram P Micronutrient spaceflight deconditioning. Aviat malnutrition, infection, and immunity: Space Environ Med. 1998; 69(2):172- an overview. Nutr Rev. 2002; 60(5 Pt 177. 2): S40-45. 63. Stein TP. Protein and muscle 55. Chandra RK Nutrition and the homeostasis: the role of nutrition. In: immune system: an introduction. Am J Lane HL, Schoeller DA (eds) Clin Nutr (1997) 66(2):460S-463S. Nutrition in Spaceflight and 56. Schneider H, Atkinson SW. Weightlessness Models. CRC Press Immunonutrition - fact or fad. J Nutr LLC 1999; pp 141-177. Health Aging. 2000; 4(2):120-123. 64. NASA - Veggie Plant Growth System 57. Isolauri E, Sutas Y, Kankaanpaa P, Activated on International Space Station - 05.16.14. Arvilommi H, Salminen S. Probiotics: http://www.nasa.gov/content/veggie- 19

plant-growth-system-activated-on- international-space-station/

65. NASA - Vegetable Production System (Veggie) - 07.20.16. http://www.nasa.gov/mission_pages/st ation/research/experiments/383.html

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