Effects of Resistive Vibration Exercise Combined with Whey Protein and KHCO3 on Bone Tturnover Markers in Head-down Tilt Bed Rest (MTBR-MNX Study)

High protein intake further increases bone resorption markers in head-down tilt bed rest (HDBR), most likely induced by low-grade metabolic acidosis. Adding an alkaline salt to a diet with high protein content prevents this additional rise of bone resorption markers in HDBR. In addition, high protein intake, specifically whey protein, increases muscle protein synthesis and improves glucose tolerance, which both are affected by HDBR. Resistive vibration exercise (RVE) training counteracts the inactivity-induced bone resorption during HDBR. To test the hypothesis that WP plus alkaline salt (KHCO3) together with RVE during HDBR will improve bone turnover markers, we conducted a randomized, three-campaign crossover design study with 12 healthy, moderately fit male subjects (age 34+/-8 y, body mass [BM] 70 +/- 8 kg). All study campaigns consisted of a 7-d ambulatory period, 21days of -6 deg. head-down tilt bed rest (HDBR), and a 6-d recovery period. Diet was standardized and identical across phases. In the control (CON) campaign, subjects received no supplement or RVE. In the intervention campaigns, subjects received either RVE alone or combined with WP and KHCO3 (NEX). WP was applied in 3 doses per day of 0.6 g WP/kg BM together with 6 doses of 15 mmol KHCO3 per day. Eleven subjects completed the RVE and CON campaign, 8 subjects completed all three campaigns. On day 21 of HDBR excretion of the bone resorption marker C-telopeptide (CTX) was 80+/-28% (p<0.001) higher than baseline, serum calcium concentrations increased by 12 +/- 29% (p<0.001) and serum osteocalcin concentrations decreased by 6+/-12% (p=0.001). Urinary CTX excretion was 11+/- 25% (p=0.02) lower on day 21 of HDBR in the RVE- and tended to decrease by 3+/- 22% (p=0.06) in the NEX campaign compared to CON. Urinary calcium excretion was higher on day 21 in HDBR in the RVE and NEX (24+/- 43% p=0.01; 25+/- 37% p=0.03) compared to the CON campaign. We conclude that combination of RVE with WP/KHCO3 was not superior to RVE alone in any of these results

Whey protein with potassium bicarbonate supplement attenuates the reduction in muscle oxidative capacity during 19 days bed rest.

The effectiveness of whey protein plus potassium bicarbonate enriched-diet (WP+KHCO3) to mitigate disuse-induced changes in muscle fibre oxidative capacity and capillarization was investigated in a 21-day crossover design bed rest study. Ten healthy men (31±6 years) once received WP+KHCO3 and once received a standardized isocaloric diet. Muscle biopsies were taken two days before and during the 19th day of bed rest (BR) from the soleus (SOL) and vastus lateralis (VL) muscle. Whole body aerobic power (VO2max), muscle fatigue and isometric strength of knee extensor and plantar flexor muscles were monitored. Muscle fiber types and capillaries were identified by immunohistochemistry. Fiber oxidative capacity was determined as the optical density (OD) at 660 nm of succinate dehydrogenase (SDH)-stained sections. The product of fiber cross-sectional area and SDH-OD (integrated SDH) indicated the maximal oxygen consumption of that fiber. The maximal oxygen consumption supported by a capillary was calculated as the integrated SDH in its supply area. BR reduced isometric strength of knee extensor muscles (P<0.05), and the fiber oxidative capacity (P<0.001) and VO2max (P=0.042), but had no significant impact on muscle capillarization or fatigue resistance of thigh muscles. The maximal oxygen consumption supported by a capillary was reduced by 24% in SOL and 16% in VL (P<0.001). WP+KHCO3 attenuated the disuse-induced reduction in fiber oxidative capacity in both muscles (P<0.01). In conclusion, following 19 days bed rest, the decrement in fiber oxidative capacity is proportionally larger than the loss of capillaries. WP+KHCO3 appears to attenuate disuse-induced reductions in fiber oxidative capacity

Einfluss einer hohen Natriumchlorid-Zufuhr und Kaliumbicarbonat-Ingestion auf Säure-Basen Status und Proteinstoffwechsel

Der charakteristische Muskelabbau der unteren Extremitäten in Immobilisation wird mit parallel beobachteten Proteinverlusten in Verbindung gebracht. Die selektive Atrophie wird auf eine Reduktion der mechanischen Belastung zurückgeführt, kann aber beispielsweise durch diätetische Einflussfaktoren verstärkt werden. So wird eine hohe Zufuhr von Natriumchlorid (NaCl) infolge azidogener Eigenschaften als unabhängiger Risikofaktor für Proteinverluste diskutiert. Ziel der Arbeit war es daher zum einen, die Auswirkungen einer hohen NaCl-Zufuhr auf den Säure-Basen-Status und Proteinstoffwechsel immobilisierter Versuchspersonen zu untersuchen. Da alkalische Mineralsalze bei metabolischer Azidose eine antikatabole Wirkung haben, sollte zum anderen der Einfluss einer oralen Gabe von Kaliumbicarbonat (KHCO3) auf NaCl-induzierte Veränderungen des Säure-Basen-Status und erwartete Proteinverluste untersucht werden. Die Fragestellungen wurden im Rahmen von zwei stationär im Stoffwechsellabor des Instituts für Luft- und Raumfahrtmedizin (Köln) durchgeführten Interventionsstudien (Salty Life 7 und 8) bearbeitet. Beide Studien bestanden aus je zwei Studienteilen, welche von acht männlichen Versuchspersonen im randomisierten crossover design absolviert wurden. Die Intervention der Salty Life 7-Studie war eine 14-tägige Bettruhe in 6º Kopftieflage (head-down-tilt bed rest, HDTBR,) während der die Diät durch eine hohe (7,0 mmol NaCl/kgKG/d) bzw. niedrige (0,7 mmol NaCl/kgKG/d) NaCl-Zufuhr gekennzeichnet war. In der Salty Life 8-Studie waren die Probanden in beiden zehntägigen Interventionsphasen „gehfähig“ (ambulatory, ambulant) und erhielten eine hohe NaCl-Zufuhr (7,3 mmol NaCl/kgKG/d). Diese wurde in einem Studienteil durch die Supplementation von 3 x 30 mmol KHCO3/d ergänzt. Den Interventionsphasen ging eine stationäre Adaptationsphase voraus. Während der gesamten Studiendauer erfolgte eine standardisierte Nährstoffzufuhr, die streng kontrolliert wurde. Zur Erfassung des systemischen Säure-Basen-Status wurden Blutgasanalysen durchgeführt, Parameter zur Differentialdiagnostik (Anionenlücke, Chloridkonzentration im Serum) erhoben und pH-Wert sowie Netto-Säureausscheidung im 24h-Urin bestimmt. Veränderungen des Gesamtkörper-Proteingehalts sind anhand der Stickstoffbilanz, berechnet aus Stickstoffaufnahme und -ausscheidung im 24h-Urin, erfasst worden. In der Salty Life 8-Studie wurden zusätzlich Messungen der postabsorptiven Gesamtkörper-Proteinkinetik anhand der Tracer Dilution-Methode durchgeführt. Die Konzentration des anabolen Stoffwechselhormons IGF-1 wurde im Serum, die Ausscheidung der Glucocorticoide (GCs) Cortisol und Cortison im 24h-Urin analysiert. Die hohe NaCl-Zufuhr hatte in Immobilisation im Vergleich zur niedrigen NaCl-Zufuhr eine hyperchlorämische, latente metabolische Azidose zur Folge. Immobilisationsbedingte renale Stickstoffverluste waren um 180% gesteigert. Gleichzeitig war die Ausscheidung des aktiven GCs Cortisol erhöht. Die Ingestion von KHCO3 bei hoher NaCl-Zufuhr hat die NaCl-induzierte Reduktion der systemischen Pufferbasen temporär vermindert. Eine konstante Kompensation der NaCl-induzierten latenten metabolischen Azidose durch KHCO3 wurde jedoch nicht beobachtet. Dennoch war die Ausscheidung der potentiell bioaktiven GCs und der Netto-Proteinabbau, gemessen als postabsorptive Hydroxylierungsrate von Phenylalanin, moderat vermindert. Dies hatte jedoch keinen Einfluss auf die Stickstoffbilanz. Die Ergebnisse führen zu folgenden Schlussfolgerungen: 1. Eine hohe NaCl-Zufuhr verstärkt immobilisationsbedingte Proteinverluste. Dies scheint durch eine Wechselwirkung aus Veränderungen des Säure-Basen Status und gesteigerter Aktivität des GCs Cortisol verursacht zu werden. 2. Die Supplementation von 3 x 30 mmol KHCO3/d war bei hoher NaCl-Zufuhr ungeeignet zur beständigen Kompensation der Veränderungen des Säure-Basen Status. Auch wenn bereits die temporäre Kompensation zu einer Reduktion von GC-Aktivität und Netto-Proteinabbau geführt hat, wurden NaCl-induzierte Stickstoffverluste innerhalb von zehn Tagen nicht vermindert. Influences of high dietary sodium chloride and potassium bicarbonate supplements on acid base status and protein metabolism Immobilisation induces muscle loss, mainly occurring in the lower-limb muscles. This atrophy is associated with protein degradation. In addition to the direct effect of reduced mechanical loading, protein losses may be exacerbated by dietary impacts. Thus, a high NaCl intake is dicussed as a risk factor for protein losses due to observed acidic properties. The first aim of the present work was therefore to investigate influences of a high dietary NaCl intake on acid base status and protein metabolism in healthy immobilized humans. In contrast, administration of alkaline salts during metabolic acidosis has been shown to act anticatabolic. Hence, the second object was a monitoring of both systems when potassium bicarbonate (KHCO3) was supplemented during high NaCl intake. Acid base status and protein metabolism were examined in the frame of two stationary interventional studies (Salty Life 7 and 8), performed in the metabolic lab of the Institute of Aerospace Medicine, Cologne, Germany. Each study was divided into two campaigns that were completed by eight male volunteers in a randomized crossover design. During the interventional phase of the Salty Life 7 subjects were immobilized in 6º head-down-tilt bed rest (HDTBR) for 14 days and received either a high (7.0 mmol NaCl/kgBM/d) or a low (0.7 mmol NaCl/kgBM/d) NaCl intake. During the ten days of ambulatory intervention of the Salty Life 8 the subjects received a high NaCl-diet (7.3 mmol NaCl/kgBM/d) that was supplemented by oral administration of 3 x 30 mmol KHCO3/d in one campaign. The intervention phases of each study were preceded by a stationary adaptation phase. Nutrient intake was standardized and strictly controlled for the whole duration of both studies. To assess systemic acid base status we analysed blood gases, parameters of differential diagnosis (anion gap, serum chloride) as well as pH and net acid excretion in 24h urine. Changes of whole body protein content were measured by nitrogen balance, calculated from nitrogen intake and excretion in 24h urine. During the Salty Life 8 whole body protein kinetics were measured by Tracer Dilution Technique in the postabsorptive state. Serum concentration of IGF-1 and 24h urinary excretion of potentially bioactive glucocorticoids (GCs), cortisol and cortisone, were also analysed. During HDTBR high NaCl intake led to hyperchloremic, low-grade metabolic acidosis. Disuse-induced renal nitrogen losses were exacerbated by 180% and cortisol activity was concomitantly increased. KHCO3 during high NaCl intake counteracted postprandial NaCl-induced reduction of buffer substance, but failed to consistently compensate NaCl-induced low-grade metabolic acidosis. Excretion of potentially bioactive GCs was reduced. Though rates of phenylalanine hydroxylation, a sensitive marker of whole body net protein catabolism, slightly decreased, nitrogen balance was insensitive to those changes. To conclude: 1. High NaCl intake exacerbates disuse-induced protein losses. Concomitant changes in acid base status and increased GC activity seem to mediate this effect. 2. Administration of 3 x 30 mmol KHCO3/d appeared inadequate to compensate for NaCl-induced low grade metabolic acidosis. Even though temporary compensating led to reduced GC activity and net protein catabolism, NaCl-induced nitrogen losses were not prevented during ten days of high NaCl intake

High sodium chloride intake might contribute to muscle wasting via low-grade metabolic acidosis

Osteoporosis is a multifactoral musculoskeletal issue: factors that influence muscle likewise affect bone metabolism. Anyway, muscle degradation is caused by mechanical unloading but also by several other environmental stimuli, e.g. in renal failure metabolic acidosis has been linked to muscle wasting. We have recently shown that a high sodium chloride (NaCl) intake induces low grade metabolic acidosis. We therefore hypothesized that high NaCl intake exacerbates disuse-induced protein losses. Eight healthy male subjects (mean age 26.25 ± 3.5; mean body weight: 78.5 ± 4.1 kg) participated in a 14-day crossover bed rest study in the metabolic ward of the DLR – Institute of Aerospace Medicine, Cologne, Germany. Each of the study phases lasted 22 days (5 days adaptation, 14 days bed rest and 3 days recovery). During the bed rest phases every subject received a low NaCl diet (0.7 mEq/kg/day) in one phase and a high NaCl diet (7.7 mEq/kg/day) in the other one. The diet was individually tailored and weight-maintaining with a constant protein intake of 1.3 g protein/kg/day. Blood gases were taken on predefined times. Nitrogen balance was calculated from the difference between nitrogen intake and excretion in 24h urine. The high NaCl intake during bed rest induced a low grade metabolic acidosis (pH: high NaCl: 7.419 ± 0.017; low NaCl: 7.426 ± 0.018, (p = 0.061); bicarbonate: high NaCl: 25.21 mmol/L ± 1.14; low NaCl: 26.4 mmol/L ± 1.36, (p<0.001)) and a more negative nitrogen balance (high NaCl: -1.26g/d ± 2.3; low NaCl: -0.47g/d ± 2.3, (p<0.001)). Our results indicate that high NaCl intake exacerbates disuse-induced protein losses. We conclude that a high NaCl intake is a risk factor for osteoporosis not only due to its influence on bone itself but also because it induces protein wasting, most likely from skeletal muscle. Currently we are investigating if the observed low grade metabolic acidosis with high NaCl intake might be the reason for increased protein losses