Effects of high-protein intake on bone turnover in long-term bed rest in women

Bed rest (BR) causes bone loss, even in otherwise healthy subjects. Several studies suggest that ambulatory subjects may benefit from high-protein intake to stimulate protein synthesis and to maintain muscle mass. However, increasing protein intake above the recommended daily intake without adequate calcium and potassium intake may increase bone resorption. We hypothesized that a regimen of high-protein intake (HiPROT), applied in an isocaloric manner during BR, with calcium and potassium intake meeting recommended values, would prevent any effect of BR on bone turnover. After a 20-day ambulatory adaptation to a controlled environment, 16 women participated in a 60-day, 6\ub0 head-down-tilt (HDT) BR and were assigned randomly to 1 of 2 groups. Control (CON) subjects (n = 8) received 1 g/(kg body mass\ub7day)-1 dietary protein. HiPROT subjects (n = 8) received 1.45 g protein/(kg body mass\ub7day)-1 plus an additional 0.72 g branched-chain amino acids per day during BR. All subjects received an individually tailored diet (before HDTBR: 1888 \ub1 98 kcal/day; during HDTBR: 1604 \ub1 125 kcal/day; after HDTBR: 1900 \ub1 262 kcal/day), with the CON group's diet being higher in fat and carbohydrate intake. High-protein intake exacerbated the BR-induced increase in bone resorption marker C-telopeptide (>30%) (p < 0.001) by the end of BR. Bone formation markers were unaffected by BR and high-protein intake. We conclude that high-protein intake in BR might increase bone loss. Further long-duration studies are mandatory to show how the positive effect of protein on muscle mass can be maintained without the risk of reducing bone mineral density

Calcium Isotopes in Human Urine as a Diagnostic Tool for Bone Loss: Additional Evidence for Time Delays in Bone Response to Experimental Bed Rest

The calcium (Ca) isotopic composition in urine during bed rest has been demonstrated to be systematically light, indicating a negative bone mineral balance (i.e., bone loss). Here we present new Ca isotope data on urine during the “nutritional countermeasures” (NUC) bed rest study. We analyzed the Ca isotopic composition of 24 h pooled urine samples from seven healthy male subjects during baseline data collection (BDC), head-down-tilt bed rest and recovery. Additionally, we analyzed urine from two follow-up examinations after the regeneration phase. We observed a change in Ca isotopic composition during the bed rest phase, indicative of bone loss with a time delay of 10 to 21 days. We also observe that the Ca isotopic composition of urine is strongly dependent on the individual Ca metabolism and varies between subjects. We relate this individuality in Ca metabolism to differences in the amounts of Ca being recycled in the kidneys. Previous studies have shown that the more Ca is reabsorbed in the kidneys the more enriched the urine becomes in heavy isotopes of calcium. The Ca isotopic composition of urine is thus modified by more than one process and cannot be used in a straightforward manner to monitor net bone mineral balance. To overcome this problem, we propose a new baseline approach for using Ca isotopes, which effectively cancels out the effects of individual renal Ca reabsorption. This allows us to detect bone loss in patients without ambiguity by combining measurements of the Ca isotopic composition of urine and daily Ca excretion rate and comparing these to data collected on healthy individuals with a normal steady-state bone balance

On the combined effects of normobaric hypoxia and bed rest upon bone and mineral metabolism: Results from the PlanHab study

AbstractBone losses are common as a consequence of unloading and also in patients with chronic obstructive pulmonary disease (COPD). Although hypoxia has been implicated as an important factor to drive bone loss, its interaction with unloading remains unresolved. The objective therefore was to assess whether human bone loss caused by unloading could be aggravated by chronic hypoxia.In a cross-over designed study, 14 healthy young men underwent 21-day interventions of bed rest in normoxia (NBR), bed rest in hypoxia (HBR), and hypoxic ambulatory confinement (HAmb). Hypoxic conditions were equivalent to 4000m altitude. Bone metabolism (NTX, P1NP, sclerostin, DKK1) and phospho-calcic homeostasis (calcium and phosphate serum levels and urinary excretion, PTH) were assessed from regular blood samples and 24-hour urine collections, and tibia and femur bone mineral content was assessed by peripheral quantitative computed tomography (pQCT).Urinary NTX excretion increased (P<0.001) to a similar extent in NBR and HBR (P=0.69) and P1NP serum levels decreased (P=0.0035) with likewise no difference between NBR and HBR (P=0.88). Serum total calcium was increased during bed rest by 0.059 (day D05, SE 0.05mM) to 0.091mM (day D21, P<0.001), with no additional effect by hypoxia during bed rest (P=0.199). HAmb led, at least temporally, to increased total serum calcium, to reduced serum phosphate, and to reduced phosphate and calcium excretion.In conclusion, hypoxia did not aggravate bed rest-induced bone resorption, but led to changes in phospho-calcic homeostasis likely caused by hyperventilation. Whether hyperventilation could have mitigated the effects of hypoxia in this study remains to be established

Effects of short-term hypercaloric nutrition on orthostatic tolerance in healthy individuals: a randomized controlled crossover study

Reduced-caloric intake lowers blood pressure through sympathetic inhibition, and worsens orthostatic tolerance within days. Conversely, hypercaloric nutrition augments sympathetic activity and blood pressure. Because dietary interventions could be applied in patients with syncope, we tested the hypothesis that short-term hypercaloric dieting improves orthostatic tolerance. In a randomized crossover trial, 20 healthy individuals (7 women, 26.7 ± 8 years, 22.6 ± 2 kg/m²) followed a 4-day hypercaloric (25% increase of energy intake by fat) or normocaloric nutritional plan, with a washout period of at least 23 days between interventions. We then performed head-up tilt table testing with incremental lower body negative pressure while recording beat-by-beat blood pressure and heart rate. The primary endpoint was orthostatic tolerance defined as time to presyncope. Time to presyncope during combined head-up tilt and lower body negative pressure did not differ between hypercaloric and normocaloric dieting (median 23.19 versus 23.04 min, ratio of median 1.01, 95% CI of ratio 0.5-1.9). Heart rate, blood pressure, heart rate variability, and blood pressure variability in the supine position and during orthostatic testing did not differ between interventions. We conclude that 4 days of moderate hypercaloric nutrition does not significantly improve orthostatic tolerance in healthy individuals. Nevertheless, given the important interaction between energy balance and cardiovascular autonomic control in the brain, caloric intake deserves more attention as a potential contributor and treatment target for orthostatic intolerance

The impact of microgravity and gravitational countermeasures on the gut microbiome of humans enrolled in the AGBRESA study

The Artificial Gravity Bed Rest Study – AGBRESA – was the first joint study conducted by DLR, ESA and NASA to simulate the effects of microgravity on healthy subjects. Moreover, the study included the use of artificial gravity protocols in a short-arm human centrifuge as a measure to counteract the negative effects of weightlessness. The health of the gut translates into the overall wellbeing since the disruption of the gut symbiotic networks – dysbiosis – could be due to either diet, antibiotic ingestion, sleep disturbance, physical activity or psychological stresses. In recent times, the gut microbiome has changed from being a complementary addition to our digestive tract to a potentially life-changing role by directly being the source of stimuli which revealed to impact neurochemistry, behavior and overall physiological status. Combined, microbial fluctuations could alter the intestinal microbiota composition and bacterial metabolite production, or more severely, in the disruption of host intestinal barrier integrity and the immune system activity, triggering intestinal inflammation syndromes and making the gut a very relevant organ to be studied in the context of spaceflight. Thus, 12 subjects, 8 males, were subjected to bed rest at negative 6-degree inclination for a period of 60 days with a preceding baseline of 15 days and posterior recovery period of 14 days. In other to characterize the gut microenvironment of healthy humans in simulated microgravity, fecal samples were collected during the baseline stage (once), during the head-down tilt treatment (at days 10, 30, and 50) and during the recovery period (once), and the samples were then processed for 16S rRNA sequencing and taxonomic analysis of the gut microenvironment. The characterization of the prokaryote flora was conducted 1) throughout time in contrast to the baseline reference and 2) in the context of the gravitational countermeasure vs the bed-rest-only control. The analysis revealed the detection of commensal microorganisms described to positively impact the gut such as Bifidobacterium spp., Lactobacillus spp., Akkermansia spp. and Enterococus spp.. Interestingly, we were able to detect pathogens like Campylobacter hominis which has been linked to severe bowel diseases ulcerative colitis and Crohn's disease. Also, opportunistic microorganisms such as Fusobacterium spp., Prevotella spp., Pseudomonas spp., Staphylococcus and Streptococcus spp., could potentially indicate an imbalance of the microbial networks and be a good an indicator of dysbiosis. Additionally, we set aside samples to undergo proteomic and metabolite analysis to improve the characterization of the gut microenvironment under microgravity simulation and the extent of the gravitational countermeasure recovery on bowel condition. Overall, the microgravity simulation performed on the AGBRESA study did not impact dramatically the fitness of the participants. Nonetheless, the analysis of the gut provides important insights on the triggers that occur during the adaptation of human physiology to long term exposure to spaceflight conditions and whether these relate to the described complications associated with gut disease

Markers of bone metabolism during 14 days of bed rest in young and older men

OBJECTIVE: We aimed at comparing markers of bone metabolism during unloading in young and older men, and to assess countermeasure effectiveness. METHODS: 16 older (60\ub12 years) and 8 younger men (23\ub13 years) underwent bed rest (BR) for 14 days. A subgroup of the Older performed cognitive training during BR and supplemented protein and potassium bicarbonate afterwards. Biochemical markers of bone and calcium/phosphate metabolism were assessed. RESULTS: At baseline urinary NTX and CTX were greater in younger than in older subjects (P0.17). P1NP was greater in young than in older subjects (P<0.001) and decreased during BR in the Young (P<0.001). Sclerostin increased during BR across groups (P=0.016). No systematic effects of the countermeasure were observed. CONCLUSION: In men, older age did not affect control of bone metabolism, but bone turnover was reduced. During BR formation markers were reduced only in younger men whereas resorption markers increased to a comparable extent. Thus, we assume that older men are not at an elevated, and possibly even at a reduced risk to lose bone when immobilize

Analysis of bacterial profiles of AGBRESA participants – a study concerning terrestrial astronauts under simulated microgravity

Introduction: Long-term space missions are accompanied by harmful environmental conditions like microgravity. Due to the reduced gravity, astronauts adapt to their environment resulting in tissue fluidic shifts. Since the knowledge about microbiome data in space is sparse and conduction of experiments at the ISS is complex, suitable analogs are needed. Therefore, the first cooperative bed-rest study called Artificial Gravity Bed-Rest study with ESA (AGBRESA), by NASA, ESA and DLR offered optimal features to investigate possible correlations between microbial shifts and physiological microgravity by using -6° head-downtilt (HDT). The aim of this survey was to identify changes within the standardized conditions, such as diet and wrongly distributed tissue fluids to reveal causal connections among health state and microbial communities

Mission d'étude technique et économique sur la production fruitière en Colombie

\u3cp\u3eRisk for premature osteoporosis is a major health concern in astronauts and cosmonauts; the reversibility of the bone lost at the weight-bearing bone sites is not established, although it is suspected to take longer than the mission length. The bone three-dimensional structure and strength that could be uniquely affected by weightlessness is currently unknown. Our objective is to evaluate bone mass, microarchitecture, and strength of weight-bearing and non-weight-bearing bone in 13 cosmonauts before and for 12 months after a 4-month to 6-month sojourn in the International Space Station (ISS). Standard and advanced evaluations of trabecular and cortical parameters were performed using high-resolution peripheral quantitative computed tomography. In particular, cortical analyses involved determination of the largest common volume of each successive individual scan to improve the precision of cortical porosity and density measurements. Bone resorption and formation serum markers, and markers reflecting osteocyte activity or periosteal metabolism (sclerostin, periostin) were evaluated. At the tibia, in addition to decreased bone mineral densities at cortical and trabecular compartments, a 4% decrease in cortical thickness and a 15% increase in cortical porosity were observed at landing. Cortical size and density subsequently recovered and serum periostin changes were associated with cortical recovery during the year after landing. However, tibial cortical porosity or trabecular bone failed to recover, resulting in compromised strength. The radius, preserved at landing, unexpectedly developed postflight fragility, from 3 months post-landing onward, particularly in its cortical structure. Remodeling markers, uncoupled in favor of bone resorption at landing, returned to preflight values within 6 months, then declined farther to lower than preflight values. Our findings highlight the need for specific protective measures not only during, but also after spaceflight, because of continuing uncertainties regarding skeletal recovery long after landing.\u3c/p\u3

The impact of bed rest on human skeletal muscle metabolism

Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest

Bone loss in microgravity

That bone is lost in space is now commonly known, but this recognition was quite a surprise when human spaceflight began. What is less well known, but no less true, is that the loss concentrates on the leg bones. Is it caused by fluid shifts, simple mechanics or space food? Loss of density in the leg bones can amount to a reduction of one-quarter within 6 months of spaceflight (Vico et al. 2000), a magnitude and rate that seem to outweigh the bone losses of 5–10% experienced by women after menopause. A substantial risk of fracture would thus arise for longterm missions were they done without adequate countermeasures. So, how could we try to prevent that kind of bone loss, or, as the physiologist would say, what is the cause of it