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A metabolic study of the effects of space flight on various chemical elements, particularly those with special relevance to the musculo-skeletal system, was carried out on the nine astronauts who participated in the three Skylab flights of 28, 59 and 84 days in 1973-1974. The study required of the cooperating crewmen constant dietary intake, continuous 24-hour urine collections and total fecal collections for 21-31 days before each flight, throughout each flight and for 17-18 days post-flight. Increases in urinary calcium and negative calcium balances during space flight were generally similar to those found in previous immobilization and bedrest studies. The persistence of these alterations in calcium metabolism throughout the flights suggested that calcium losses would continue in weightlessness for a very long time. Significant losses of nitrogen and phosphorus occurred, associated with observed reduction in muscle tissue. Both mineral and muscle losses occurred despite vigorous exercise regimens in flight. It was concluded that unless protective measures can be developed, capable musculo-skeletal function is likely to be impaired in space flights, ultimately to be conducted to Mars, of 11/2 to 3 years duration.

A metabolic balance study was conducted on the three crewmembers of the 84-day Skylab IV earth orbital mission. Dietary intake was controlled, monitored, and kept very nearly constant for a period commencing 21 days prior to flight, throughout flight, and for a period of 18 days postflight. Within the first 30 days of flight urine calcium rose to a level approx. 100% above preflight levels and remained elevated for the remainder of the flight. Fecal calcium excretion increased more slowly but continued to accelerate throughout the flight and did not return to baseline levels during the postflight period. Urinary nitrogen increased to 25-30% above preflight levels within one month following launch and thereafter gradually subsided toward control values. The overall losses of calcium averaged approx. 200 mg per day throughout the mission while nitrogen losses averaged 590 mg. Various other indices of musculoskeletal deterioration are discussed and correlated. The parallelism between the effects of weightlessness and bed rest is reviewed. It is noted, that no evidence is yet available as to the identity of the initial biological response to the absence of gravity.

An investigation was undertaken to determine the metabolic cost of life in space. Energy intake was determined throughout the 28-, 59- and 84-day flights for each of the nine Skylab astronauts. Metabolic excretions were quantitatively collected and analyzed for a variety of biochemical constituents. Body mass was determined each day and body volume was ascertained by stereophotogrammetric means immediately pre- and post-flight. A ground-based control period of at least 3 weeks preceded each flight, and one of at least 18 days followed each flight. Examination of the data reveals that all crew members lost mass in flight, and that this loss did not result in a net increase in density. Elevated urinary and blood nitrogen, a net negative calcium and nitrogen balance and a decrease in the radiographic density of certain bones support the conclusion that lean body mass decreased. That the loss was primarily proteinaceous in nature is evidenced by the comparatively small net change in total body water and by a decrease in total body potassium each measured by isotopic dilution techniques. These changes in body composition, despite a constant caloric intake in flight and on the ground, suggest that the body's demand for exogenous nutrient energy is not measurably changed by exposure to null gravity flight up to 84 days in duration.

The state of vitamin D nutrition depends on synthesis in the skin under the influence of sunlight as well as on dietary intake. In European countries that do not fortify milk with vitamin D, reduced sun exposure is the major factor leading to a fall in body stores of vitamin D with age and to a high frequency of hypovitaminosis D in the elderly sick. In the US, because vitamin D is added to milk and the use of vitamin D supplements is more common, the dietary intake of vitamin D is relatively more important than in Europe, and the total vitamin D intake and body stores of vitamin D are generally higher. Nevertheless, body stores of vitamin D probably fall with age in the US as they do in Europe, and it is likely that some sick elderly persons in the US, especially among those confined to institutions, become vitamin D deficient. For several reasons, the vitamin D requirement increases with age, and a total supply of 15 to 20 micrograms/day (600 to 800 IU) from all sources is recommended. Special attention should be paid to persons most likely to need supplementation, such as the housebound, persons with malabsorption, and persons with interruption of the enterohepatic circulation. Osteomalacia, the bone disease produced by severe vitamin D deficiency, is less common in the US than in Europe, but subclinical vitamin D deficiency may contribute to the pathogenesis of hip fractures, both through increased liability to fall and through PTH-mediated bone loss. The extent to which vitamin D deficiency contributes to hip fractures in the US is unknown, and is an important area for future research. Excess intake of vitamin D or of its metabolites may result in hypercalcemia and extra-osseous calcification, particularly in arterial walls and in the kidney, leading to chronic renal failure. The dose of vitamin D that causes significant hypercalcemia is highly variable between individuals but is rarely less than 1000 micrograms/day. Smaller doses can cause hypercalciuria and nephrolithiasis and possibly impaired renal function. Vitamin D administration may raise plasma cholesterol but there is no convincing evidence that the risk of myocardial infarction is increased. The recommended total supply for the elderly of 20 micrograms/day is most unlikely to be harmful, except in patients with sarcoidosis or renal calculi.

Prediction that the various stresses of flight, particularly weightlessness, would bring about significant derangements in the metabolism of the musculoskeletal system has been based on various observations of long-term immobilized or inactive bed rest. The only attempt at controlled measurement of metabolic changes in space prior to Skylab, a study during the 14-day Gemini VII flight, revealed rather modest losses of important elements. The three astronauts of Skylab II consumed a planned day-by-day, quite constant, dietary intake of major metabolic elements in mixed foods and beverages and provided virtually complete collections of excreta for 31 days preflight, during the 28 days inflight, and for 17 days postflight. Analyses showed that, in varying degree among the crewmen, urinary calcium increased gradually during flight in a pattern similar to that observed in bed-rest studies: the mean plateau peak of urinary calcium excretion in the latter part of flight was double preflight levels. Fecal calcium excretion did not change significantly, but calcium balance, owing to the urinary calcium rise, became either negative or less positive than in preflight measurement. Increased excretion and negative balance of nitrogen and phosphorus indicated appreciable loss of muscle tissue in all three crewmen. Significant losses also occurred inflight in potassium, sodium, and magnesium. Based on the similarity in pattern and degree between these observations and those in bed rest of the losses in calcium, phosphorus, and nitrogen, musculoskeletal integrity would not be threatened in space flights of up to at least 3 months. However, if similar changes occur, indicative of continuing losses of these elements, in the planned Skylab flights for considerably more than 28 days, concern for capable musculoskeletal function should be serious for flights of very many months' duration, and greater research attention will need to be given to development of protective counter-measures.

The average elderly person is in negative calcium balance and accordingly is losing bone mass. While factors such as decreased mechanical loading of the skeleton undoubtedly figure in this age-related loss, a growing body of evidence suggests that inadequate calcium intake may contribute to this loss. On any given day men and women in the US 65 yr or older ingest about 600 and 480 mg calcium, respectively. Calcium intake in the elderly is less than in the young, and reduced absorption efficiency further lowers effective intake. Additionally, other nutrients such as protein and fiber, taken in excess, effectively increase the calcium requirement. Estrogen withdrawal at menopause leads to a decrease in intestinal calcium absorption efficiency and in renal calcium conservation, both effects equivalent to an effective increase in calcium intake requirement. Thus it is not surprising that all studies of mean requirements for zero balance performed in elderly subjects have yielded values above the current RDA for the US. The available evidence thus suggests that the RDA for adults should surely not be lowered below its current level (800 mg), but that, instead, it ought to be raised. It is not possible to say with certainty to exactly what level, but available evidence is compatible with allowances of at least 1200 to 1500 mg/day. Further, the evidence indicates that the mean requirement ought to be thought of as a complex function of age, sex, absorption efficiency, intake of protein, fiber, and probably other nutrients, estrogen status, and mechanical loading. Extensive experience with calcium supplements indicates that daily intakes up to at least 2.5 g of elemental calcium are quite safe in all persons except for certain subsets of the population uncommon among the elderly (eg, those with sarcoidosis, active tuberculosis, or other absorptive hypercalciuric syndromes). At the same time it must be said that osteoporosis is a complex, multifactorial disorder, and that factors unrelated to calcium nutrition undoubtedly play important, even dominant roles in many--perhaps most--osteoporotics. The available evidence, taken together, does not indicate that raising calcium intake will abolish the problem of osteoporosis. It does indicate, however, that calcium nutrition is considerably more important in the genesis of osteoporosis than has been commonly thought for the past 35 yr. As our listing of "important issues" indicates, the full extent of that importance, in both pathogenesis and prophylaxis, remains to be elucidated.(ABSTRACT TRUNCATED AT 400 WORDS)

A metabolic study of the effects of space flight on various chemical elements, particularly those with special revelance to the musculoskeletal system, was carried out on the three astronauts of the SL-3 mission for 21 d preflight, during the 60 d flight phase, and for 17 d postflight. The study required of the cooperating crewmen quite constant dietary intake, continuous 24-hour urine collections and total fecal collections. Urinary calcium was significantly increased during flight in all three crewmen with man-to-man variation in pattern and amount; the degree of calcium loss was, in general, similar to that in the prior study of the 28-d Skylab flight (SL-2). The similarity to bedrest immobilization in the pattern of urinary calcium increases and of total calcium shifts suggested that calcium losses would continue for a very long time. Significant losses of nitrogen and phosphorus occurred that were associated with observed reduction in muscle tissue. Both mineral and muscle losses occurred despite vigorous exercise regimens during flight. It was concluded that these studies give warning that capable musculoskeletal function may be significantly impaired during prolonged space flights lasting 1.5 to 3 years unless protective measures are developed.

Many studies and observations have shown the bone-losing effects of physical inactivity of various forms. Contrariwise, less precise studies and observations have supported the reasonable premise that mechanical loading of the skeleton via physical activity shifts the balance of bone remodeling in favor of bone formation, and appears to do so at all ages. Some interesting starts have been made in research to discover the mechanisms of the action on bone of mechanical loading, but many pathways remain to be explored. Besides the mechanical forces, we need to know more about the interrelations of muscle function, probably mediated through muscle-tendon pull on periosteum, and more about other likely influences, notably changes in circulation to bones. The practical significance relative to calcium metabolism and aging of what has been learned thus far on the effects of activity, is that prolonged inactivity, either in a chair or in bed, is to be avoided, because of its deleterious effects, and that reasonably energetic gravitational exercise, such as walking or possibly jogging, promotes maintenance of bone health.

Prior to the Mercury program, extensive efforts were undertaken to find ways of minimizing the mass of in-flight food systems. Such efforts were directed to the use of dehydrated, energy-dense foodstuffs and to the possibilities of nutrient recyclization. As the space program became a reality, nutritional scientists were more concerned with the mechanics of food consumption in weightless flight and with the problems of structuring convention foods in a way that would facilitate their use in weightlessness. It soon became clear that there was no substantial impediment to normal gastrointestinal function in flight, and attention was shifted to more subtle metabolic phenomenons. It became apparent that slight changes occurred in skeletal density, muscle mass, and overall body composition. Recognition of these changes led to extensive ground-based simulation studies and carefully designed in-flight experiments. Data are presented on the requirements for metabolic energy in flight and on the losses that have been observed in the major elemental constituents of the body. It is concluded that convincing evidence is not yet avialable on the ability of man to adapt to long-term weightless flight. Although his nutritional requirements are qualitatively similar during flight, the sophisticated manipulation of nutrient profiles shows promise of counteracting some of the deteriorative processes that are known to occur.

Immobilization in plaster, bed rest, and the weightless state all result in calcium loss which if continued for a few months will result in detectable demineralization of the lower extremities. The upper extremities are "different" bones (presumably differently programmed genetically), for they have not been seen to develop X-ray-detectable demineralization except after several months of severe paralysis. The substantial losses of calcium in inactivity are accompanied by sizeable losses of nitrogen, reflective of muscle atrophy. Hence, we do not know how much of the bone loss in disuse is mediated by diminished direct physical forces on bone, how much by decreased muscle pull on periosteum, and how much perhaps by circulatory or other changes.

Eight healthy young men (ages 19–35), four older men (ages 38–42), three obese subjects (two women and one man, ages 20–34) were individually exposed on one or more occasions to 10 C (50 F) air in the Metabolic Chamber for periods of 2–4 hr. A minimal amount of clothing was worn: the males wore shorts and the females wore halters and shorts. Air movement was routinely less than 50 ft/min and relative humidity 50% or less. Body fatness among the subjects ranged from 13 to 45% of body weight. The metabolic response to cold determined from Vo2 and Vco2 was significantly and inversely related to per cent body fat according to the regression equation: kcal/(m2·hr) = 65.2 – 0.520 (% fat) ± 0.115. Total body insulation after 2 hr of exposure was significantly and directly related to per cent body fat and inversely related to the metabolic response. Despite these significant relationships, wide individual differences were observed in the metabolic response to cold between pairs of subjects of like age, previous history of cold exposure, and body fatness.

A physical model of calcium absorption was developed from analysis of data obtained on 23 subjects, including 13 patients having a variety of abnormalities of calcium metabolism. The model was tested and found consistent in all subjects studied. This technique provides a quantitative description of the rate of entry of oral dose of (47)Ca into the circulation as a function of time by analysis of serum or forearm radioactivity in response to intravenous and oral administration of (47)Ca. The kinetics of the absorption process as proposed by the model are characterized by an initial delay phase of 15-20 min, by a maximal rate of absorption at 40-60 min after ingestion, and by 95% completion of the absorption within 2(1/2) hr. Partial identification of the physiological counterparts of the model was possible by introduction of the isotope at various levels of the gut. Although the region of the duodenum was found to have the greatest rate of absorption per unit length in normal subjects, it was least responsive to stimulation by parathyroid hormone and suppression by calcium loading. Furthermore, the response of the gut to parathyroid hormone was delayed, whereas the suppression of absorption by intravenous or oral calcium loading was rapid and dramatic. The implications of these observations are discussed.