Abstract 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.

The effectiveness of whey protein plus potassium bicarbonate-enriched diet (WP+KHCO) in mitigating disuse-induced changes in muscle fiber oxidative capacity and capillarization was investigated in a 21-day crossover design bed rest study. Ten healthy men (31 ± 6 yr) once received WP+KHCO and once received a standardized isocaloric diet. Muscle biopsies were taken 2 days before and during the 19th day of bed rest (BR) from the soleus (SOL) and vastus lateralis (VL) muscle. Whole-body aerobic power (V̇o), 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 V̇o (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+KHCO attenuated the disuse-induced reduction in fiber oxidative capacity in both muscles (P < 0.01). In conclusion, following 19 days of bed rest, the decrement in fiber oxidative capacity is proportionally larger than the loss of capillaries. WP+KHCO appears to attenuate disuse-induced reductions in fiber oxidative capacity.

No abstract

Frings-Meuthen P, Buehlmeier J, Baecker N, Stehle P, Fimmers R, May F, Kluge G, Heer M. High sodium chloride intake exacerbates immobilization-induced bone resorption and protein losses.

ObjectivesThe present study evaluated the effectiveness of a short and versatile daily exercise regime, named locomotion replacement training (LRT), to maintain muscle size, isometric strength, power, and endurance capacity of the leg muscles following 5 days of head-down tilt (HDT) bed rest.Methods10 male subjects (age 29.4 ± 5.9 years; height 178.8 ± 3.7 cm; body mass 77.7 ± 4.1 kg) performed, in random order, 5 days of 6° head-down tilt bed rest (BR) with no exercise (CON), or BR with daily 25 min of upright standing (STA) or LRT.ResultsKnee extensor and plantar flexor cross-sectional area (CSA) were reduced by 2–3 % following bed rest (P < 0.01) for CON and STA, yet maintained for LRT. Knee extensor isometric strength (MVC) decreased by 8 % for CON (P < 0.05), was maintained for STA, and increased with 12 % for LRT (P < 0.05). Plantar flexor MVC remained unaltered during the study. Maximum jump height declined (~1.5 cm) for all conditions (P < 0.001). Neural activation and knee extensor fatigability did not change with bed rest. Bone resorption increased during BR and neither LRT nor STA was able to prevent or attenuate this increase.ConclusionLRT was adequate to maintain muscle size and to even increase knee extensor MVC, but not muscle power and bone integrity, which likely requires more intense and/or longer exercise regimes. However, with only some variables showing significant changes, we conclude that 5 days of BR is an inadequate approach for countermeasure assessments.

Low-grade metabolic acidosis (LGMA), as induced by high dietary acid load or sodium chloride (NaCl) intake, has been shown to increase bone and protein catabolism. Underlying mechanisms are not fully understood, but from clinical metabolic acidosis interactions of acid-base balance with glucocorticoid (GC) metabolism are known. We aimed to investigate GC activity/metabolism under alkaline supplementation and NaCl-induced LGMA. Eight young, healthy, normal-weight men participated in two crossover designed interventional studies. In Study A, two 10-day high NaCl diet (32 g/d) periods were conducted, one supplemented with 90 mmol KHCO3/day. In Study B, participants received a high and a low NaCl diet (31 vs. 3 g/day), each for 14 days. During low NaCl, the diet was moderately acidified by replacement of a bicarbonate-rich mineral water (consumed during high NaCl) with a non-alkalizing drinking water. In repeatedly collected 24-h urine samples, potentially bioactive-free GCs (urinary-free cortisol + free cortisone) were analyzed, as well as tetrahydrocortisol (THF), 5α-THF, and tetrahydrocortisone (THE). With supplementation of 90 mmol KHCO3, the marker of total adrenal GC secretion (THF + 5α-THF + THE) dropped (p = 0.047) and potentially bioactive-free GCs were reduced (p = 0.003). In Study B, however, GC secretion and potentially bioactive-free GCs did not exhibit the expected fall with NaCl-reduction as net acid excretion was raised by 30 mEq/d. Diet-induced acidification/alkalization affects GC activity and metabolism, which in case of long-term ingestion of habitually acidifying western diets may constitute an independent risk factor for bone degradation and cardiometabolic diseases.

The impact of effective exercise against bone loss during experimental bed rest appears to be associated with increases in bone formation rather than reductions of bone resorption. Sclerostin and dickkopf-1 are important inhibitors of osteoblast activity. We hypothesized that exercise in bed rest would prevent increases in sclerostin and dickkopf-1. Twenty-four male subjects performed resistive vibration exercise (RVE; n = 7), resistive exercise only (RE; n = 8), or no exercise (control n = 9) during 60 days of bed rest (2nd Berlin BedRest Study). We measured serum levels of BAP, CTX-I, iPTH, calcium, sclerostin, and dickkopf-1 at 16 time-points during and up to 1 year after bed rest. In inactive control, after an initial increase in both BAP and CTX-I, sclerostin increased. BAP then returned to baseline levels, and CTX-I continued to increase. In RVE and RE, BAP increased more than control in bed rest (p ≤ 0.029). Increases of CTX-I in RE and RVE did not differ significantly to inactive control. RE may have attenuated increases in sclerostin and dickkopf-1, but this was not statistically significant. In RVE there was no evidence for any impact on sclerostin and dickkopf-1 changes. Long-term recovery of bone was also measured and 6-24 months after bed rest, and proximal femur bone mineral content was still greater in RVE than control (p = 0.01). The results, while showing that exercise against bone loss in experimental bed rest results in greater bone formation, could not provide evidence that exercise impeded the rise in serum sclerostin and dickkopf-1 levels.

High sodium chloride (NaCl) intake can induce low-grade metabolic acidosis (LGMA) and may thus influence bone and protein metabolism. We hypothesized that oral potassium bicarbonate (KHCO(3)) supplementation may compensate for NaCl-induced, LGMA-associated bone resorption and protein losses. Eight healthy male subjects participated in a randomized trial with a crossover design. Each of two study campaigns consisted of 5 d of dietary and environmental adaptation followed by 10 d of intervention and 1.5 d of recovery. In one study campaign, 90 mmol KHCO(3)/d were supplemented to counteract NaCl-induced LGMA, whereas the other campaign served as a control with only high NaCl intake. When KHCO(3) was ingested during high NaCl intake, postprandial buffer capacity ([HCO(3)(-)]) increased (P = 0.002). Concomitantly, urinary excretion of free potentially bioactive glucocorticoids [urinary free cortisol (UFF) and urinary free cortisone (UFE)] was reduced by 14% [∑(UFF,UFE); P = 0.024]. Urinary excretion of calcium and bone resorption marker N-terminal telopeptide of type I collagen was reduced by 12 and 8%, respectively (calcium, P = 0.047; N-terminal bone collagen telopeptide, P = 0.044). There was a trend of declining net protein catabolism when high NaCl was combined with KHCO(3) (P = 0.052). We conclude that during high salt intake, the KHCO(3)-induced postprandial shift to a more alkaline state reduces metabolic stress. This leads to decreased bone resorption and protein degradation, which in turn might initiate an anticatabolic state for the musculoskeletal system in the long run.