Martina Heer

Benefits for bone from resistance exercise and nutrition in long-duration spaceflight: Evidence from biochemistry and densitometry

Exercise has shown little success in mitigating bone loss from long‐duration spaceflight. The first crews of the International Space Station (ISS) used the “interim resistive exercise device” (iRED), which allowed loads of up to 297 lbf (or 1337 N) but provided little protection of bone or no greater protection than aerobic exercise. In 2008, the Advanced Resistive Exercise Device (ARED), which allowed absolute loads of up to 600 lbf (1675 N), was launched to the ISS. We report dietary intake, bone densitometry, and biochemical markers in 13 crewmembers on ISS missions from 2006 to 2009. Of these 13, 8 had access to the iRED and 5 had access to the ARED. In both groups, bone‐specific alkaline phosphatase tended to increase during flight toward the end of the mission (p = 0.06) and increased 30 days after landing (p < 0.001). Most markers of bone resorption were also increased in both groups during flight and 30 days after landing (p < 0.05). Bone densitometry revealed significant interactions (time and exercise device) for pelvis bone mineral density (BMD) and bone mineral content (p < 0.01), hip femoral neck BMD (p < 0.05), trochanter BMD (p < 0.05), and total hip BMD (p < 0.05). These variables were unchanged from preflight only for ARED crewmembers, who also returned from flight with higher percent lean mass and lower percent fat mass. Body mass was unchanged after flight in both groups. All crewmembers had nominal vitamin D status (75 ± 17 nmol/L) before and during flight. These data document that resistance exercise, coupled with adequate energy intake (shown by maintenance of body mass determined by dual‐energy X‐ray absorptiometry [DXA]) and vitamin D, can maintain bone in most regions during 4‐ to 6‐month missions in microgravity. This is the first evidence that improving nutrition and resistance exercise during spaceflight can attenuate the expected BMD deficits previously observed after prolonged missions.

Short‐term bed rest impairs amino acid‐induced protein anabolism in humans

Diminished muscular activity is associated with alterations of protein metabolism. The aim of this study was to evaluate the effect of short‐term muscle inactivity on regulation of whole‐body protein deposition during amino acid infusion to simulate an experimental postprandial state. We studied nine healthy young volunteers at the end of 14 day periods of strict bed rest and of controlled ambulation using a cross‐over design. Subjects received a weight‐maintaining diet containing 1 g protein kg−1 day−1. l[1‐13C]leucine was used as a marker of whole‐body protein kinetics in the postabsorptive state and during a 3 h infusion of an amino acid mixture (0.13 g amino acid (kg lean body mass)−1 h−1). In the postabsorptive state, bed rest decreased (P < 0.05) the rate of leucine disposal (Rd) to protein synthesis and tended to decrease leucine rate of appearance (Ra) from proteolysis, whereas the rate of leucine oxidation did not change significantly. Amino acid infusion increased leucine Rd to protein synthesis and oxidation and decreased leucine Ra from proteolysis in both the bed rest and ambulatory conditions. Changes from basal in leucine Rd to protein synthesis were lower (P < 0.05) during bed rest than those in the ambulatory period, whereas changes in leucine Ra from proteolysis and oxidation were not significantly different. During amino acid infusion, net leucine deposition into body protein was 8 ± 3% lower during bed rest than during the ambulatory phase. In conclusion, short‐term bed rest leads to reduced stimulation of whole‐body protein synthesis by amino acid administration. Results of this study were, in part, presented at the meeting, Experimental Biology, 2004, Washington DC.

Calorie Restriction Modulates Inactivity-Induced Changes in the Inflammatory Markers C-Reactive Protein and Pentraxin-3

CONTEXT Energy balance and physical activity potentially influence systemic inflammation. OBJECTIVE Our objective was to test the hypothesis that moderate energy restriction may prevent activation of inactivity-induced inflammatory response. DESIGN Participants were studied four times at the end of 14-d periods of experimental bed rest or controlled ambulation, after receiving eucaloric or hypocaloric diets. SETTING The study was conducted at the clinical research center of the German Space Agency. SUBJECTS Nine healthy young volunteers participated. INTERVENTIONS Energy intake was calibrated to physical activity and decreased by about 20% in hypocaloric conditions. MAIN OUTCOME MEASURES Changes in body fat by dual-energy x-ray absorptiometry as well as plasma inflammatory markers and cytokine mRNA levels in blood cells were measured. RESULTS Fat mass did not change significantly in eucaloric conditions and decreased in hypocaloric periods (-1.0 +/- 0.3 and -1.0 +/- 0.3 kg in ambulatory and bed rest, respectively). Bed rest in eucaloric conditions increased plasma C-reactive protein (CRP) (+143 +/- 53%) and both the ratios between plasma IL-6 and IL-10 (4+/-1 times) and white blood cell IL-6 and IL-10 mRNAs (5 +/- 1 times). Energy restriction prevented bed-rest-mediated increases in CRP and the IL-6 to IL-10 ratio. Bed rest increased (P = 0.03) long pentraxin-3 (PTX3) plasma concentration, without significant activity-by-diet interaction. In all conditions (n = 36), CRP and PTX3 were inversely correlated (r = -0.61; P < 0.001). Changes in fat mass, leptin, and IL-6 directly correlated with CRP and inversely correlated with PTX3. IL-10 inversely correlated with CRP and directly correlated with PTX3 (r = 0.52; P < 0.01). CONCLUSIONS Calorie restriction prevents the inflammatory response induced by 14 d of bed rest. We suggest an inverse regulation of CRP and PTX3 in response to changes in energy balance.

Effects of whey protein supplements on metabolism: evidence from human intervention studies

Purpose of reviewEpidemiological studies indicate that the consumption of milk and dairy products is inversely associated with a lower risk of metabolic disorders and cardiovascular diseases. In particular, whey protein seems to induce these effects because of bioactive compounds such as lactoferrin, immunoglobulins, glutamine and lactalbumin. In addition, it is an excellent source of branch chained amino acids. This review summarizes recent findings on the effects of whey protein on metabolic disorders and the musculoskeletal system. Recent findingsWe identified 25 recently published intervention trials examining chronic and/or acute effects of whey protein supplementation on lipid and glucose metabolism, blood pressure, vascular function and on the musculoskeletal system. Whey protein appears to have a blood glucose and/or insulin lowering effect partly mediated by incretins. In addition, whey protein may increase muscle protein synthesis. In contrast there are no clear-cut effects shown on blood lipids and lipoproteins, blood pressure and vascular function. For bone metabolism the data are scarce. SummaryIn summary, whey protein may affect glucose metabolism and muscle protein synthesis. However, the evidence for a clinical efficacy is not strong enough to make final recommendations with respect to a specific dose and the duration of supplementation.

High serum leptin levels subsequent to weight gain predict renewed weight loss in patients with anorexia nervosa

It has repeatedly been shown that high serum leptin levels at target weight ensue from therapeutically induced weight gain in patients with anorexia nervosa (AN). It was hypothesized that elevated leptin levels may be an important factor underlying the difficulties of maintaining the target-weight in AN patients after re-feeding. The aim of this study was to examine if serum leptin levels at discharge from inpatient treatment predict renewed weight loss within 2 months after discharge and upon a 1 yr follow-up. Univariate variance analysis (ANOVA) revealed that 60% (cor. R2=0.60, P=0.002) of the variance in the BMI standard deviation score (BMI-SDS) 2 months after discharge was explained by the model consisting of the independent variables lg10 leptin levels at discharge (P=0.019) and at admission (P=0.069) and BMI-SDS at admission (P=0.002) and delta BMI between admission and discharge (P=0.047). Similarly, 60% (cor. R2=0.60, P=0.005) of the variance in BMI-SDS 1 yr after discharge was explained by lg10 leptin levels at discharge (P=0.046) and at admission (P=0.052) and BMI-SDS at admission (P=0.008) and 2 months after discharge (P=0.007) and delta BMI between admission and discharge (P=0.933). Patients with a poor outcome after 1 yr (n=9, ANCOVA, group: descriptive P=0.041), but not recovered patients (n=9, P=0.649), had lg10 leptin levels at discharge higher than those of controls when adjusted for BMI and % body fat at discharge. In conclusion, high serum leptin levels at discharge from inpatient treatment may indicate a risk for renewed weight loss and an unfavorable 1 yr outcome in AN.

Calcium and bone metabolism during space flight

Weightlessness induces bone loss. Understanding the nature of this loss and developing means to counteract it are significant challenges to potential human exploration missions. This article reviews the existing information from studies of bone and calcium metabolism conducted during space flight. It also highlights areas where nutrition may play a specific role in this bone loss, and where countermeasures may be developed to mitigate that loss.

WISE-2005: Supine treadmill exercise within lower body negative pressure and flywheel resistive exercise as a countermeasure to bed rest-induced bone loss in women during 60-day simulated microgravity☆

Bone loss associated with disuse during bed rest (BR), an analog of space flight, can be attenuated by exercise. In previous studies, the efficacy of either aerobic or resistive exercise countermeasures has been examined separately. We hypothesized that a regimen of combined resistive and aerobic exercise during BR would prevent bone resorption and promote bone formation. After a 20-day ambulatory adaptation to controlled confinement and diet, 16 women participated in a 60-day, 6 degrees head-down-tilt BR and were assigned randomly to one of the two groups. Control subjects (CON, n=8) performed no countermeasure. Exercise subjects (EX, n=8) participated in an exercise program during BR, alternating between supine treadmill exercise within lower body negative pressure (3-4 d wk(-1)) and flywheel resistive exercise (2-3 d wk(-1)). By the last week of BR, excretion of helical peptide (CON, 79%+/-44 increase; EX, 64%+/-50, mean+/-SD) and N-terminal cross-linking telopeptide (CON, 51%+/-34; EX, 43%+/-56), markers of bone resorption, were greater than they were before BR in both groups (P<0.05). However, serum concentrations of the bone formation marker procollagen type I N propeptide were greater in EX than CON throughout and after bed rest (P<0.05), while concentrations of the bone formation marker bone alkaline phosphatase tended to be greater in EX than CON. Dual-energy X-ray absorptiometry results indicated that the exercise treatment significantly (P<0.05) attenuated loss of hip and leg bone mineral density in EX compared to CON. The combination of resistive and aerobic exercise did not prevent bone resorption but did promote bone formation, and helped mitigate the net bone loss associated with simulated microgravity.

Effects of artificial gravity during bed rest on bone metabolism in humans

We report results from a study designed to explore the utility of artificial gravity (AG) as a countermeasure to bone loss induced by microgravity simulation. After baseline testing, 15 male subjects underwent 21 days of 6 degrees head-down bed rest to simulate the deconditioning associated with spaceflight. Eight of the subjects underwent 1 h of centrifugation (AG; 1 G(z) at the heart, 2.5 G(z) at the feet) each day for 21 days, whereas seven of the subjects served as untreated controls (Con). Blood and urine were collected before, during, and after bed rest for bone marker determinations. Bone mineral density (BMD) and bone mineral content (BMC) were determined by dual-energy X-ray absorptiometry and peripheral quantitative computerized tomography before and after bed rest. Urinary excretion of bone resorption markers increased during bed rest, but the AG and Con groups did not differ significantly. The same was true for serum C-telopeptide. During bed rest, bone alkaline phosphatase (ALP) and total ALP tended to be lower in the AG group (P = 0.08, P = 0.09). Neither BMC nor BMD changed significantly from the pre-bed rest period in AG or Con groups, and the two groups were not significantly different. However, when AG and Con data were combined, there was a significant (P < 0.05) effect of time for whole body total BMC and total hip and trochanter BMD. These data failed to demonstrate efficacy of this AG prescription to prevent the changes in bone metabolism observed during 3 wk of bed rest.

Vision Changes after Spaceflight Are Related to Alterations in Folate– and Vitamin B-12–Dependent One-Carbon Metabolism

Approximately 20% (7 of 38) of astronauts on International Space Station (ISS) missions have developed measurable ophthalmic changes after flight. This study was conducted to determine if the folate- and vitamin B-12-dependent 1-carbon metabolic pathway is altered in these individuals. Since 2006, we have conducted experiments on the ISS to evaluate nutritional status and related biochemical indices of astronauts before, during, and after flight. Data were modeled to evaluate differences between individuals with ophthalmic changes (n = 5) and those without them (n = 15), all of whom were on ISS missions of 48-215 d. We also determined whether mean preflight serum concentrations of the 1-carbon metabolites and changes in measured cycloplegic refraction after flight were associated. Serum homocysteine (Hcy), cystathionine, 2-methylcitric acid (2MCA), and methylmalonic acid concentrations were 25-45% higher (P < 0.001) in astronauts with ophthalmic changes than in those without them. These differences existed before, during, and after flight. Preflight serum concentrations of Hcy and cystathionine, and mean in-flight serum folate, were correlated with change (postflight relative to preflight) values in refraction (P < 0.05), and preflight serum concentrations of 2MCA tended to be associated (P = 0.06) with ophthalmic changes. The biochemical differences observed in crewmembers with vision issues strongly suggest that their folate- and vitamin B-12-dependent 1-carbon transfer metabolism was affected before and during flight. The consistent differences in markers of 1-carbon metabolism between those who did and those who did not develop changes in vision suggest that polymorphisms in enzymes of this pathway may interact with microgravity to cause these pathophysiologic changes.

The effect of therapeutically induced weight gain on plasma leptin levels in patients with anorexia nervosa

Previously it was shown that hyperleptinemia ensues from the therapeutically induced weight gain in patients with anorexia nervosa (AN). However, not all studies have been able to confirm this finding. To further investigate leptin secretion during weight gain in AN and potential functional implications serum leptin levels, body mass index (BMI),% body fat, fT3, fT4 and TSH of 18 adolescent AN patients (BMI at admission: 14.4+/-1.2) were examined four times during 11 weeks of re-feeding and compared to 18 weight stable controls. Additionally, serum leptin levels, BMI and % body fat were determined in patients reaching target weight after 11-20 weeks (mean 14.3+/-3) of inpatient re-feeding. At admission patients showed lower lg10 leptin levels (P=0.000) and BMI (P=0.000) than controls. At target weight patients still had significantly lower BMI (P=0.000) and% body fat (P=0.000) than controls but lg10 leptin levels of patients were higher than those of controls when adjusted for BMI and% body fat (ANCOVA, group P=0.038). In patients, correlation coefficients between lg10 leptin levels and BMI increments increased during the 11 weeks of re-feeding. BMI,% body fat and fT3 levels were not significantly correlated to lg10 leptin levels in week 11, however, 53% of the variance of leptin levels (corrected R(2)=0.53, P=0.001) was explained by BMI increments between weeks 7 and 11 (P=0.001) and lg10 leptin level at admission (P=0.002). In conclusion, we confirmed weight gain induced hyperleptinemia in AN. Further research is required to assess if this phenomenon contributes to renewed weight loss.