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An open-label, single-center pilot study to test the effects of an amino acid mixture in older patients admitted to internal medicine wards.
Bellanti, F, Buglio, AL, Stasio, ED, Bello, GD, Tamborra, R, Dobrakowski, M, Kasperczyk, A, Kasperczyk, S, Vendemiale, G
Nutrition (Burbank, Los Angeles County, Calif.). 2020;:110588
Abstract
OBJECTIVE Older patients are frequently subjected to prolonged hospitalization and extended bed rest, with a negative effect on physical activity and caloric intake. This results in a consistent loss of muscle mass and function, which is associated with functional decline and high mortality. The aim of this study was to investigate the effect of 1 wk of oral amino acid (AA) supplementation in older patients subjected to low mobility during hospitalization. METHODS Hospitalized older patients (69-87) were included in the control group (n = 50) or were administered 25 g of AA mixture (n = 44) twice daily throughout 7 d of low mobility. We collected data related to length of stay as primary outcome measure. In-hospital mortality, 90-d postdischarge mortality, 90-d postdischarge rehospitalization, and falls also were considered. Moreover, variations of anthropometric measures, body composition and muscle architecture/strength, circulating interleukins, and oxidative stress markers between the beginning and the end of the supplementation period were analyzed as secondary outcomes. RESULTS Similar values were reported between the two groups regarding age (76.6 ± 6.8 versus 79 ± 7.2 y old), body weight (61.5 ± 14.3 versus 62.1 ± 16.1 kg), and body mass index (28.7 ± 4.15 versus 28.1 ± 3.62 kg/m2). Although no difference in terms of in-hospital, 90-d postdischarge, or overall mortality rate was observed between the two groups, a reduction in length of stay, 90-d postdischarge hospitalization, and falls was observed in the AA supplementation group rather than in controls. Furthermore, the AA mixture limited muscle architecture/strength impairment and circulating oxidative stress, which occurred during hospitalization-related bed rest. The latter data was associated with increased circulating levels of anti-inflammatory cytokines interleukin-4 and -10. CONCLUSIONS These results suggest that the AA mixture limits several alterations associated with low mobility in older hospitalized patients, such as length of stay, 90-d postdischarge hospitalization, and falls, preventing the loss of muscle function, as well as the increase of circulating interleukins and oxidative stress markers.
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Locomotion replacement exercise cannot counteract cartilage biomarker response to 5 days of immobilization in healthy adults.
Liphardt, AM, Mündermann, A, Heer, M, Achtzehn, S, Niehoff, A, Mester, J
Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 2020;(11):2373-2382
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Biomarkers of cartilage metabolism are sensitive to changes in the biological and mechanical environment and can indicate early changes in cartilage homeostasis. The purpose of this study was to determine if a daily locomotion replacement program can serve as a countermeasure for changes in cartilage biomarker serum concentration caused by immobilization. Ten healthy male subjects (mean ± 1 standard deviation; age: 29.4 ± 5.9 years; body mass: 77.7 ± 4.1 kg) participated in the crossover 5-day bed rest study with three interventions: control (CON), standing (STA), and locomotion replacement training (LRT). Serum samples were taken before, during, and after bed rest. Biomarker concentrations were measured using commercial enzyme-linked immunosorbent assays. Cartilage oligomeric matrix protein (COMP) levels after 24 hours of bed rest decreased independently of the intervention (-16.8% to -9.8%) and continued to decrease until 72 hours of bed rest (minimum, -23.2% to -20.6%). LRT and STA did not affect COMP during bed rests (P = .056) but there was a strong tendency for a slower decrease with LRT (-9.4%) and STA (-11.7%) compared with CON (-16.8%). MMP-3 levels decreased within the first 24 hours of bed rest (CON: -22.3%; STA: -14.7%; LRT: -17%) without intervention effect. Both COMP and MMP-3 levels recovered to baseline levels during the 6-day recovery period. MMP-1, MMP-9, and TNF-α levels were not affected by immobilization or intervention. COMP and MMP-3 are mechano-sensitive cartilage biomarkers affected by immobilization, and simple interventions such as standing upright or LRT during bed rest cannot prevent these changes. Clinical significance: simple locomotion interventions cannot prevent cartilage biomarker change during bed rest.
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The negative effect of unloading exceeds the bone-sparing effect of alkaline supplementation: a bed rest study.
Frings-Meuthen, P, Bernhardt, G, Buehlmeier, J, Baecker, N, May, F, Heer, M
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2019;(2):431-439
Abstract
UNLABELLED Potassium bicarbonate was administrated to an already alkaline diet in seven male subjects during a 21-day bed rest study and was able to decrease bed rest induced increased calcium excretion but failed to prevent bed rest-induced bone resorption. INTRODUCTION Supplementation with alkali salts appears to positively influence calcium and bone metabolism and, thus, could be a countermeasure for population groups with an increased risk for bone loss. However, the extent to which alkalization counteracts acid-induced bone resorption or whether it merely has a calcium and bone maintenance effect is still not completely understood. In the present study, we hypothesized that additional alkalization to an already alkaline diet can further counteract bed rest-induced bone loss. METHODS Seven healthy male subjects completed two parts of a crossover designed 21-day bed rest study: bed rest only (control) and bed rest supplemented with 90 mmol potassium bicarbonate (KHCO3) daily. RESULTS KHCO3supplementation during bed rest resulted in a more alkaline status compared to the control intervention, demonstrated by the increase in pH and buffer capacity level (pH p = 0.023, HCO3p = 0.02, ABE p = 0.03). Urinary calcium excretion was decreased during KHCO3 supplementation (control 6.05 ± 2.74 mmol/24 h; KHCO3 4.87 ± 2.21 mmol/24 h, p = 0.03); whereas, bone formation was not affected by additional alkalization (bAP p = 0.58; PINP p = 0.60). Bone resorption marker UCTX tended to be lower during alkaline supplementation (UCTX p = 0.16). CONCLUSIONS The more alkaline acid-base status, achieved by KHCO3 supplementation, reduced renal calcium excretion during bed rest, but was not able to prevent immobilization-induced bone resorption. However, advantages of alkaline salts on bone metabolism may occur under acidic metabolic conditions or with respect to the positive effect of reduced calcium excretion within a longer time frame. TRIAL REGISTRATION Trial number: NCT01509456.
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Improving Dietary Protein Quality Reduces the Negative Effects of Physical Inactivity on Body Composition and Muscle Function.
Arentson-Lantz, EJ, Galvan, E, Ellison, J, Wacher, A, Paddon-Jones, D
The journals of gerontology. Series A, Biological sciences and medical sciences. 2019;(10):1605-1611
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Abstract
BACKGROUND Brief periods of physical inactivity can compromise muscle health. Increasing dietary protein intake is potentially beneficial but complicated by difficulties reconciling anabolic potential with a realistic food volume and energy intake. We sought to determine whether increasing dietary protein quality could reduce the negative effects of physical inactivity. METHODS Twenty healthy, older men and women completed 7 days of bed rest followed by 5 days of rehabilitation. Volunteers consumed a mixed macronutrient diet (MIXED N = 10; 68 ± 2 years; 1,722 ± 29 kcal/day; 0.97 ± 0.01 g protein/kg/day) or an isoenergetic, whey-augmented, higher protein quality diet (WHEY: N = 10; 69 ± 1 years; 1,706 ± 23 kcal/day; 0.90 ± 0.01 g protein/kg/day). Outcomes included body composition, blood glucose, insulin, and a battery of physical function tests. RESULTS During bed rest, both groups experienced a 20% reduction in knee extension peak torque (p < .05). The WHEY diet partially protected leg lean mass (-1,035 vs. -680 ± 138 g, MIXED vs. WHEY; p = .08) and contributed to a greater loss of body fat (-90 vs. -233 ± 152 g, MIXED vs. WHEY; p < .05). Following rehabilitation, knee extension peak torque in the WHEY group fully recovered (-10.0 vs. 2.2 ± 4.1 Nm, MIXED vs. WHEY; p = .05). Blood glucose, insulin, aerobic capacity, and Short Physical Performance Battery (SPPB) changes were similar in both dietary conditions (p > .05). CONCLUSIONS Improving protein quality without increasing total energy intake has the potential to partially counter some of the negative effects of bed rest in older adults.
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Alkalinization with potassium bicarbonate improves glutathione status and protein kinetics in young volunteers during 21-day bed rest.
Biolo, G, Di Girolamo, FG, Heer, M, Sturma, M, Mazzucco, S, Agostini, F, Situlin, R, Vinci, P, Giordano, M, Buehlmeier, J, et al
Clinical nutrition (Edinburgh, Scotland). 2019;(2):652-659
Abstract
BACKGROUND & AIMS Physical inactivity is associated with lean body mass wasting, oxidative stress and pro-inflammatory changes of cell membrane lipids. Alkalinization may potentially counteract these alterations. We evaluated the effects of potassium bicarbonate supplementation on protein kinetics, glutathione status and pro- and anti-inflammatory polyunsaturated fatty acids (PUFA) in erythrocyte membranes in humans, during experimental bed rest. METHODS Healthy, young, male volunteers were investigated at the end of two 21-day bed rest periods, one with, and the other without, daily potassium bicarbonate supplementation (90 mmol × d-1), according to a cross-over design. Oxidative stress in erythrocytes was evaluated by determining the ratio between reduced (GSH) and oxidized glutathione (GSSG). Glutathione turnover and phenylalanine kinetics, a marker of whole body protein metabolism, were determined by stable isotope infusions. Erythrocyte membranes PUFA composition was analyzed by gas-chromatography. RESULTS At the end of the two study periods, urinary pH was 10 ± 3% greater in subjects receiving potassium bicarbonate supplementation (7.23 ± 0.15 vs. 6.68 ± 0.11, p < 0.001). Alkalinization increased total glutathione concentrations by 5 ± 2% (p < 0.05) and decreased its rate of clearance by 38 ± 13% (p < 0.05), without significantly changing GSH-to-GSSG ratio. After alkalinization, net protein balance in the postabsorptive state improved significantly by 17 ± 5% (p < 0.05) as well as the sum of n-3 PUFA and the n-3-to-n-6 PUFA ratio in erythrocyte membranes (p < 0.05). CONCLUSIONS Alkalinization during long-term inactivity is associated with improved glutathione status, anti-inflammatory lipid pattern in cell membranes and reduction in protein catabolism at whole body level. This study suggests that, in clinical conditions characterized by inactivity, oxidative stress and inflammation, alkalinization could be a useful adjuvant therapeutic strategy.
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The Effect of a Low Glycemic Index Pulse-Based Diet on Insulin Sensitivity, Insulin Resistance, Bone Resorption and Cardiovascular Risk Factors during Bed Rest.
Gao, R, Duff, W, Chizen, D, Zello, GA, Chilibeck, PD
Nutrients. 2019;(9)
Abstract
We determined the effects of a low glycemic-index pulse-based diet (i.e., containing lentils, chick peas, beans, and split peas) compared to a typical hospital diet on insulin sensitivity assessed by the Matsuda index from the insulin and glucose response to a two-hour oral glucose tolerance test, insulin resistance assessed by the homeostatic model assessment of insulin resistance (HOMA-IR), bone resorption assessed by 24 h excretion of urinary n-telopeptides(Ntx) and cardiovascular risk factors (blood lipids, blood pressure, arterial stiffness and heart rate variability) during bed rest. Using a randomized, counter-balanced cross-over design with one-month washout, six healthy individuals (30 ± 12 years) consumed the diets during four days of bed rest. The Matsuda index, HOMA-IR, urinary Ntx and cardiovascular risk factors were determined at baseline and after the last day of bed rest. Compared to the typical hospital diet, the pulse-based diet improved the Matsuda index (indicating increased insulin sensitivity; baseline to post-bed rest: 6.54 ± 1.94 to 6.39 ± 2.71 hospital diet vs. 7.14 ± 2.36 to 8.75 ± 3.13 pulse-based diet; p = 0.017), decreased HOMA-IR (1.38 ± 0.54 to 1.37 ± 0.50 hospital diet vs. 1.48 ± 0.54 to 0.88 ± 0.37 pulse-based diet; p = 0.022), and attenuated the increase in Ntx (+89 ± 75% hospital diet vs. +33 ± 20% pulse-based diet; p = 0.035). No differences for changes in cardiovascular risk factors were found between the two diet conditions, with the exception of decreased diastolic blood pressure during day three of bed rest in the pulse-based versus hospital diet (61 ± 9 vs. 66 ± 7 mmHg; p = 0.03). A pulse-based diet was superior to a hospital diet for maintaining insulin sensitivity, preventing insulin resistance, attenuating bone resorption and decreasing diastolic blood pressure during four days of bed rest.
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Metabolic Inflexibility Is an Early Marker of Bed-Rest-Induced Glucose Intolerance Even When Fat Mass Is Stable.
Rudwill, F, O'Gorman, D, Lefai, E, Chery, I, Zahariev, A, Normand, S, Pagano, AF, Chopard, A, Damiot, A, Laurens, C, et al
The Journal of clinical endocrinology and metabolism. 2018;(5):1910-1920
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CONTEXT The effects of energy-balanced bed rest on metabolic flexibility have not been thoroughly examined. OBJECTIVE We investigated the effects of 21 days of bed rest, with and without whey protein supplementation, on metabolic flexibility while maintaining energy balance. We hypothesized that protein supplementation mitigates metabolic inflexibility by preventing muscle atrophy. DESIGN AND SETTING Randomized crossover longitudinal study conducted at the German Aerospace Center, Cologne, Germany. PARTICIPANTS AND INTERVENTIONS Ten healthy men were randomly assigned to dietary countermeasure or isocaloric control diet during a 21-day bed rest. OUTCOME MEASURES Before and at the end of the bed rest, metabolic flexibility was assessed during a meal test. Secondary outcomes were glucose tolerance by oral glucose tolerance test, body composition by dual energy X-ray absorptiometry, ectopic fat storage by magnetic resonance imaging, and inflammation and oxidative stress markers. RESULTS Bed rest decreased the ability to switch from fat to carbohydrate oxidation when transitioning from fasted to fed states (i.e., metabolic inflexibility), antioxidant capacity, fat-free mass (FFM), and muscle insulin sensitivity along with greater fat deposition in muscle (P < 0.05 for all). Changes in fasting insulin and inflammation were not observed. However, glucose tolerance was reduced during acute overfeeding. Protein supplementation did not prevent FFM loss and metabolic alterations. CONCLUSIONS Physical inactivity triggers metabolic inflexibility, even when energy balance is maintained. Although reduced insulin sensitivity and increased fat deposition were observed at the muscle level, systemic glucose intolerance was detected only in response to a moderately high-fat meal. This finding supports the role of physical inactivity in metabolic inflexibility and suggests that metabolic inflexibility precedes systemic glucose intolerance.
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Effects of β-hydroxy-β-methylbutyrate on skeletal muscle mitochondrial content and dynamics, and lipids after 10 days of bed rest in older adults.
Standley, RA, Distefano, G, Pereira, SL, Tian, M, Kelly, OJ, Coen, PM, Deutz, NEP, Wolfe, RR, Goodpaster, BH
Journal of applied physiology (Bethesda, Md. : 1985). 2017;(5):1092-1100
Abstract
Loss of muscle mass during periods of disuse likely has negative health consequences for older adults. We have previously shown that β-hydroxy-β-methylbutyrate (HMB) supplementation during 10 days of strict bed rest (BR) attenuates the loss of lean mass in older adults. To elucidate potential molecular mechanisms of HMB effects on muscle during BR and resistance training rehabilitation (RT), we examined mediators of skeletal muscle mitochondrial dynamics, autophagy and atrophy, and intramyocellular lipids. Nineteen older adults (60-76 yr) completed 10 days BR followed by 8-wk RT rehabilitation. Subjects were randomized to either HMB (3 g/day HMB; n = 11) or control (CON; n = 8) groups. Skeletal muscle cross-sectional area (CSA) was determined by histology from percutaneous vastus lateralis biopsies. We measured protein markers of mitochondrial content [oxidative phosphorylation (OXPHOS)], fusion and fission (MFN2, OPA1, FIS1, and DRP1), autophagy (Beclin1, LC3B, and BNIP3), and atrophy [poly-ubiquinated proteins (poly-ub)] by Western blot. Fatty acid composition of several lipid classes in skeletal muscle was measured by infusion-MS analysis. Poly-ub proteins and OXPHOS complex I increased in both groups following BR (P < 0.05, main effect for time), and muscle triglyceride content tended to increase following BR in the HMB group (P = 0.055). RT rehabilitation increased OXPHOS complex II protein (P < 0.05), and total OXPHOS content tended (P = 0.0504) to be higher in HMB group. In addition, higher levels of DRP1 and MFN2 were maintained in the HMB group after RT (P < 0.05). BNIP3 and poly-ub proteins were significantly reduced following rehabilitation in both groups (P < 0.05). Collectively, these data suggest that HMB influences mitochondrial dynamics and lipid metabolism during disuse atrophy and rehabilitation.NEW & NOTEWORTHY Mitochondrial content and dynamics remained unchanged over 10 days of BR in older adults. HMB stimulated intramuscular lipid storage as triacylglycerol following 10 days of bed rest (BR) and maintained higher mitochondrial OXPHOS content and dynamics during the 8-wk resistance exercise rehabilitation program.
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Anabolic resistance assessed by oral stable isotope ingestion following bed rest in young and older adult volunteers: Relationships with changes in muscle mass.
Biolo, G, Pišot, R, Mazzucco, S, Di Girolamo, FG, Situlin, R, Lazzer, S, Grassi, B, Reggiani, C, Passaro, A, Rittweger, J, et al
Clinical nutrition (Edinburgh, Scotland). 2017;(5):1420-1426
Abstract
BACKGROUND & AIMS Aging and experimental bed rest are associated with muscle atrophy and resistance to post-prandial stimulation of protein synthesis or anabolic resistance (AR). We have used in young and older adult volunteers, during short-term bed rest, a quick and non-invasive method, based on a single oral bolus of the stable isotope L[ring-2H5]phenylalanine (D5Phe), to determine post-prandial AR, defined as ratio between irreversible hydroxylation and incorporation into body protein of ingested phenylalanine. METHODS We compared in older (O, 59 ± 1 y) and young (Y, 23 ± 1 y) healthy male volunteers the effects of two-week bed rest on post-prandial protein kinetics, assessed during absorption of a standard ready-to-use oral nutritional supplement, through stable-labeled isotope amino acid D5Phe, diluted in water, given as single oral load. The metabolic fate of D5Phe is either utilization for protein synthesis or irreversible hydroxylation to L[ring-2H4]tyrosine (D4Tyr). AR was defined as ratio between the areas under the curves of D4Tyr-to-D5Phe plasma concentrations over 6 h meal absorption. To determine the relationships between AR and muscle changes following bed rest, quadriceps muscle volume (QMV) was determined by magnetic resonance imaging (MRI). RESULTS At baseline, in pooled Y and O subjects, values of AR were inversely correlated with QMV (R = -0.75; p < 0.03). Following 2-weeks of inactivity, there were significant bed rest effects on AR (p < 0.01) and QMV (p < 0.03), as well as significant bed rest × group interaction for AR (p < 0.03; +9.2% in Y; +21.9% in O) and QMV (p < 0.05; -5.7% in Y; -%7.3 in O). In pooled subjects, the percentage delta changes in AR and QMV, induced by bed rest, were inversely correlated (R = -0.57; p < 0.05). CONCLUSION Bed rest-induced AR is much greater in the older than in younger adults. We have developed a new, simple, non-invasive method for the assessment of AR. The results indicate that this metabolic abnormality is a key mechanism for sarcopenia of aging and inactivity.
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The effect of alternate-day caloric restriction on the metabolic consequences of 8 days of bed rest in healthy lean men: a randomized trial.
Harder-Lauridsen, NM, Nielsen, ST, Mann, SP, Lyngbæk, MP, Benatti, FB, Langkilde, AR, Law, I, Wedell-Neergaard, AS, Thomsen, C, Møller, K, et al
Journal of applied physiology (Bethesda, Md. : 1985). 2017;(2):230-241
Abstract
UNLABELLED Physical activity and alternate-day fasting/caloric restriction may both ameliorate aspects of the metabolic syndrome, such as insulin resistance, visceral fat mass accumulation, and cognitive impairment by overlapping mechanisms. The purpose of this study was to test the hypothesis that alternate-day caloric restriction (ADCR) with overall energy balance would reduce insulin resistance and accumulation of visceral fat, in addition to improving cognitive functions, after 8 consecutive days in bed. Healthy, lean men (n = 20) were randomized to 1) 8 days of bed rest with three daily isoenergetic meals (control group, n = 10); and 2) 8 days of bed rest with 25% of total energy requirements every other day and 175% of total energy requirements every other day (ADCR group). Oral glucose tolerance testing, dual-energy X-ray absorptiometry (DXA) scans, magnetic resonance imaging of the abdomen and brain, V̇o2max, and tests for cognitive function were performed before and after bed rest. In addition, daily fasting blood samples and 24-h glucose profiles by continuous glucose monitoring system were assessed during the 8 days of bed rest period. Bed rest induced insulin resistance, visceral fat accumulation, and worsening of mood. No positive effects emerged from ADCR on these negative health outcomes. Compared with the control group, ADCR was associated with improved and steadier glycemic control on fasting days and higher glycemic fluctuation and indexes of insulin resistance on overeating days. In contrast to our hypothesis, the metabolic impairment induced by 8 days of bed rest was not counteracted by ADCR with overall energy balance. NEW & NOTEWORTHY Alternate-day caloric restriction without overall energy reduction does not ameliorate the metabolic impairment induced in lean men by 8 days of bed rest.