Gymnastik- och idrottshögskolan, GIH

Background: Recently, it was shown that exogenously administered testosterone enhances endurance capacity in women. In this study, our understanding on the effects of exogenous testosterone on key determinants of oxygen transport and utilization in skeletal muscle is expanded.Methods: In a double-blinded, randomized, placebo-controlled trial, 48 healthy active women were randomized to 10 weeks of daily application of 10 mg of testosterone cream or placebo. Before and after the intervention, VO₂ max, body composition, total hemoglobin (Hb) mass and blood volumes were assessed. Biopsies from the vastus lateralis muscle were obtained before and after the intervention to assess mitochondrial protein abundance, capillary density, capillary-to-fiber (C/F) ratio, and skeletal muscle oxidative capacity.Results: Maximal oxygen consumption per muscle mass, Hb mass, blood, plasma and red blood cell volumes, capillary density, and the abundance of mitochondrial protein levels (i.e., citrate synthase, complexes I, II, III, IV-subunit 2, IV-subunit 4, and V) were unchanged by the intervention. However, the C/F ratio, specific mitochondrial respiratory flux activating complex I and linked complex I and II, uncoupled respiration and electron transport system capacity, but not leak respiration or fat respiration, were significantly increased following testosterone administration compared to placebo.Conclusion: This study provides novel insights into physiological actions of increased testosterone exposure on key determinants of oxygen diffusion and utilization in skeletal muscle of women. Our findings show that higher skeletal muscle oxidative capacity coupled to higher C/F ratio could be major contributing factors that improve endurance performance following moderately increased testosterone exposure.

OBJECTIVE: Human skeletal muscle consists of a mixture of slow- and fast-twitch fibers with distinct capacities for contraction mechanics, fermentation, and oxidative phosphorylation (OXPHOS). While the divergence in mitochondrial volume favoring slow-twitch fibers is well established, data on the fiber type-specific intrinsic mitochondrial function and morphology are highly limited with existing data mainly being generated in animal models. This highlights the need for more human data on the topic.

METHODS: Here, we utilized THRIFTY, a rapid fiber type identification protocol to detect, sort, and pool fast- and slow-twitch fibers within six hours of muscle biopsy sampling. Respiration of permeabilized fast- and slow-twitch fiber pools was then analyzed with high-resolution respirometry. Using standardized western blot procedures, muscle fiber pools were subsequently analyzed for control proteins and key proteins related to respiratory capacity.

RESULTS: Maximal complex I CI+II respiration was 25% higher in human slow-twitch fibers compared to fast-twitch fibers. However, per volume, the respiratory rate of mitochondria in fast-twitch fibers was approximately 50% higher for CI+II, which was primarily mediated through elevated CII respiration, but not CI or. Furthermore, the abundance of CII protein and proteins regulating cristae structure were disproportionally elevated in mitochondria of the fast-twitch fibers. The difference in intrinsic respiratory rate was not reflected in fatty acid- or complex I respiration.

CONCLUSION: Mitochondria of human fast-twitch muscle fibers compensate for their lack of volume by substantially elevating intrinsic respiratory rate through increased reliance on complex II.

På uppdrag av Försvarsmakten genomförde Militärmedicinska forskningsgruppen vid Åstandlaboratoriet vid Gymnastik- och idrottshögskolan Stockholm (GIH), en observationsstudie gällande fysiologisk/medicinsk belastning på 14 flygplatsjägare under en fältövning med beteckningen "F 17 - Flygvapenövning 2014".

Övningen var indelad i tre etapper, varav den första (c:a 42 tim) och sista (c:a 59 tim) planerades vara mer fysiskt och psykiskt krävande än den mellersta (c:a 114 tim). Registrering av hjärtfrekvens gjordes under hela övningen. Fysiologiska mätningar samt blodprov togs före och efter varje etapp samt efter c:a 12 timmars vila med sedvanliga kost efter övningens avslutande.

Beräkningar av energiomsättningen för de tre etapperna inklusive viloperioder var c:a 308, 185 respektive 369 kcal/tim, resulterande i totalt c:a 13 000, 21 100 respektive 21 600 kcal per etapp eller totalt c:a 55 700 kcal för hela övningen. De höga fysiska belastningarna i etapp ett och tre är klart högre än tidigare uppmätta data i svenska och utländska militära operationer. Vissa delar av etapp tre resulterade i fysiska belastningar som var på ungefär samma nivå som vid tävlingar i längre uthållighetsidrotter.

Den höga belastningen resulterade i stora förändringar i fysiologiska parametrar och medicinska markörer. Vissa mätningar av muskelstyrka i armar och ben liksom maximal syreupptagning försämrades. Testosteron sjönk under hela övningen kraftigt. Dessa och andra uppmätta data talar för att fysiska arbetsförmågan – i förlängningen "stridsvärdet" – blev klart försämrat under övningen.

Mätningen 12 timmar efter övningens avslut visade oväntade resultat. Den subjektiva ansträngningskänslan under standardiserat cykelarbete var klart förbättrat av 12-timmarsvilan efter övningen. Däremot var flertalet medicinska och fysiologiska värden oförändrade jämfört med värden vid testerna 12 timmar tidigare och därmed var de klart lägre än vid testet innan övningens start. Det är uppenbart att återhämtning av stridsvärdet inte kan bedömas subjektivt utan måste avgöras genom reliabla psykologiska och fysiologiska mätningar.

Undersökningen har gett underlag för fortsatta studier rörande bland annat typer av energitillskott under övning, olika strategier för snabb återhämtning samt försök att finna markörer för individuella reaktionsmönster på "stridsvärde" under långvariga militära operationer.

Exercise and exercise training induces several physiological adaptations that increase the oxidative capacity of the muscles and improve glucose regulation. While the positive metabolic adaptations and effects on glucose regulation after exercise and exercise training have been extensively studied, negative outcomes have not. This thesis aims to address these questions and investigate possible negative effects of intensified training on mitochondrial parameters and glucose regulation.

In two separate interventions, we studied these outcomes after progressive exercise training, and after different intensities of exercise. Mitochondrial respiration was assessed in muscle biopsies taken from m. vastus lateralis 14 hours after exercise and oral glucose tolerance tests were performed at the same time point.

In paper I, we demonstrate that there is an upper limit of training load that can be tolerated without the manifestation of negative outcomes. After administrating almost daily sessions of high-intensity interval training, mitochondrial function and glucose control were impaired. In paper II, we used mitochondrial function as a novel biomarker of maladaptive training loads and constructed a diagnostic model that can be used for the early detection of maladaptations to exercise training. In paper III, we further demonstrated that endurance-trained athletes can have decreased glucose tolerance and increased insulin resistance the day after three hours of continuous cycling whereas these responses were not accentuated in healthy controls. Our results indicate that a metabolic switch in favor of lipid metabolism is the probable cause of this phenomenon. In paper IV, we briefly commented on a publication that described changes in whole-body VO2 responses to work rates in the athlete with the highest recorded VO2max. We provided arguments that the observed changes in VO2 and gross efficiency can in part have their origin in the mitochondria.

We here combine measurements in muscle tissue with physiological measurements in an applied context. Using this integrated approach, we investigated the effects of intensified training on health-related and performance outcomes, thereby presenting insights into what maladaptations to exercise can constitute. We hope that our results and conclusions can help to further understand the complex relationship between exercise and health and to guide athletes and coaches to optimize training outcomes.

Blood glucose regulation has been studied for well over a century as it is intimately related to metabolic health. Research in glucose transport and uptake has also been substantial within the field of exercise physiology as glucose delivery to the working muscles affects exercise capacity and athletic achievements. However, although exceptions exist, less focus has been on blood glucose as a parameter to optimize training and competition outcomes in athletes with normal glucose control. During the last years, measuring glucose has gained popularity within the sports community and successful endurance athletes have been seen with skin-mounted sensors for continuous glucose monitoring (CGM). The technique offers real-time recording of glucose concentrations in the interstitium, which is assumed to be equivalent to concentrations in the blood. Although continuous measurements of a parameter that is intimately connected to metabolism and health can seem appealing, there is no current consensus on how to interpret measurements within this context. Well-defined approaches to use glucose monitoring to improve endurance athletes' performance and health are lacking. In several studies, blood glucose regulation in endurance athletes has been shown to differ from that in healthy controls. Furthermore, endurance athletes regularly perform demanding training sessions and can be exposed to high or low energy and/or carbohydrate availability, which can affect blood glucose levels and regulation. In this current opinion, we aim to discuss blood glucose regulation in endurance athletes and highlight the existing research on glucose monitoring for performance and health in this population.

Introduction

To predict endurance performance and evaluate adaption to training in endurance athletes a laboratory test for retrieving the anaerobic lactate threshold is often used. The maximal rate of oxidative metabolism that can be sustained during prolonged exercise indicates preserved homeostasis and thereby sets the upper limit for long term endurance. Exercise intensities above the anaerobic threshold require an additional input from anaerobic energy sources resulting in blood lactate accumulation and reduced time to fatigue. The threshold is therefore a reliable and powerful predictor of performance in aerobic exercise lasting approximately 40-60 min. The work rate that elicits a blood lactate of 4 mmol/l (e.g. LT4) is widely used to determine the threshold, but by using a fixed lactate concentration, flexibility to account for inter- and intra-individual differences in aerobic and anaerobic metabolism is lost. Our hypothesis was that our modified D-max method (D-maxmod) would provide a more accurate performance related value by calculating the individual anaerobic threshold (IAT).

Methods

20 males cyclists age 36 ± 5 years, weight 79.7 ± 5.8 kg, VO2max 4.4 ± 0.4 l/min performed an incremental test on a cycle ergometer for calculation of LT (D-maxmod, and LT4) at two occasions separated by 8 weeks. The test consisted of 5 minutes long stages separated by 1 min of rest were lactate was sampled. The increase in work rate was 30 W/stage starting at 100 W and ended above LT4. Short after, an incremental test to fatigue (start at LT4 power, increase 20 W/min) was performed for assessment of VO2max, calculation of maximal aerobic power (MAP) and maximal power achieved in the test (Wmax). On a separate day a 40 minutes time-trial (TT40) was performed for assessment of aerobic endurance performance. IAT D-maxmod was defined as the derivate to the exponential curve created from exponentially lactate increase, including maximal lactate concentration plotted at MAP. The increase in lactate relative to power was defined as the increase in blood lactate from the point where the exponential curve crossed the lactate baseline (See also Cheng et al. 1992 and Zhou & Weston 1997).

Results

IAT D-maxmod was calculated to 5.0 ± 0.8 mmol/l. Both D-maxmod and LT4 were highly significantly correlated with both TT40 and Wmax. Coefficients of determination were higher for D-maxmod compared to LT4 for both TT40 (r2 = 0.78 vs 0.69) and Wmax (r2 = 0.89 vs 0.64).

Conclusion

The calculated D-maxmod correlated better with performance than LT4 for parameters highly linked to performance in road- and mountain bike competitions.

References

Cheng B, Kuipers H, Snyder AC, et al. (1992). Int. J Sports Med. 13:518-22

Zhou S, Weston SB (1997). Physiol. Meas. 18: 145

Energistatus och förändring i fysiskt stridsvärde studerades i samband med en nästan 8 dygn långa grundmilitär slutövning (GMU) vid AMF-1 Berga Örlogsskolor i månadsskiftet oktober november 2013.

Totalt deltog 105 soldater i övningen, fördelat på 3 plutoner om vardera 35 soldater. En subgrupp på 24 soldater (8 kvinnor) bestående av 8 soldater från vardera pluton studerades mer ingående.

Medelhjärtfrekvensen för de 6 soldater (2 kvinnor) som hade i stort sett kompletta mätningar från den 187 timmar långa övningen, inklusive viloperioder, var 88 ± 7 slag/minut. Utifrån hjärtfrekvensdata beräknades den totala energiomsättningen till i genomsnitt 44 000 ± 6 600 kcal, vilket motsvarar 5 600 ± 840 kcal per dygn och 235 ± 35 kcal/tim. Total energiförbrukning var i genomsnitt 39 000 kcal för kvinnorna och 46 500 kcal för männen. I övrigt noterades inte några betydande skillnader mellan kvinnor och män. Däremot var det stora individuella variationer i energiutgift, vilka till ca hälften berodde på skillnader i kroppsvikt. Med hänsyn till kroppsvikt och buren vikt var energiförbrukningen ca 3,1 ± 0,23 kcal per timme per kg totalvikt. Den individuella variationen beror på skillnad i buren vikt, på olika uppgifter och på individuella fysiologiska skillnader.

Utifrån beräknat energiintag blev det totala energiunderskottet under övningen 12 000-15 000 kcal, vilket är ca 1 500-2 000 kcal per dygn. Viktminskningen under övningen var 2,9 kg för kvinnor och 3,7 kg för män. Denna viktminskning på >4 % leder troligen till försämrad uthållighetsförmåga.

Den maximala muskelstyrkan i armar och ben var i stort sett oförändrade efter övningen, liksom den beräknade maximala syreupptagningsförmågan. Däremot upplevdes ett lågintensivt cykelarbete som betydligt tyngre efter övningen. Muskeluthållighet mättes inte i denna studie.

Ett skjutprov om 5 skott i liggande på 100 m mot en tredjedelsfigur visade 64 deltagande soldater på en försämrad träffprocent från 90,5% före till 79,4 % efter övningen. Alla soldater hade minst en träff före medan 6 soldater hade alla bom efter övningen.

Slutsatsen från studien är att GMU-övningen resulterade i ett stort energiunderskott. Stridsvärdet, bedömt från skjutprovet var klart försämrat. Maximala fysiologiska parametrar var i stort sett oförändrade, medan skattad ansträngning och därmed uthållighetsförmåga, försämrades.

Denna observationsstudie av militär grundutbildning för kadetter visar mycket tydligt att förflyttning i fjällmiljö leder till stort energiunderskott, till viss del beroende på ökade energiutgifter i och med bärande av utrustning, men framför beroende på otillräckligt energiintag.

Den genomsnittliga energiförbrukningen över övningens 100 timmarna och ca 78 km förflyttning var ca 260 kcal/h, medan energiintaget endast 135 kcal/h. Även om en typ av rations (mjukkonserv) gav i genomsnitt högre energiintag än två rations av frystorkat blev det genomsnittliga energiunderskottet för samtliga rations nästan 50 %.

Mätningarna visade stora variationer mellan olika deltagare vilket dock endast delvis kan förklaras med tekniken av att bära tungt.

Skjutprov (precision) visade att stridsvärdet påverkats negativt, genom en klart försämrad träffbild efter övningen. De fysiologiska testerna visar ökad hjärtfrekvens och upplevd ansträngning på submaximala belastningar, medan de maximala nivåerna av de fysiologiska kapaciteterna kondition, muskelstyrka i hand och ben i stort sett var oförändrade.

Kommande undersökningar på motsvarande övningar bör inriktas på interventionsstudier på fördelning av utrustningsvikter, samt hur kostintaget bör förbättras för att nå ökat energiintag.

På längre sikt bör träningsmodeller för att förbättra förmågan att bära tung utrustning utvärderas.

Dose-response relationship between exercise load and mitochondrial function

Flockhart M, Nilsson L, Bergman K, Apro W, Ekblom B, Larsen FJ

A dose-dependent relationship exists between exercise load and muscular adaptation. Mitochondria adapt to the increased ATP-demand by alterations in mass and/or quality. How mitochondrial mass and quality changes as a function of exercise load is not well investigated and we have previously found mitochondrial dysfunction after short-term intensive exercise. We therefore aimed to study mitochondrial function by altering exercise load during a three week interval training regimen to understand the dose-response relationship between exercise load and mitochondrial function. We took four muscle biopsies throughout the study, and as expected, mitochondrial function was positively affected during the first two weeks. After the third week, a dramatic mitochondrial dysfunction was evident as mitochondrial intrinsic respiration was reduced by 26% despite a 32% increase in mitochondrial yield. We hereby present evidence of a striking exercise-induced reduction in mitochondrial function after a period of very intense interval training.

Background: The concept of overreaching and super compensation is widely in use by athletes and coaches seeking to maximize performance and adaptations to exercise training. The physiological aspects of acute fatigue, overreaching and non-functional overreaching are, however, not well understood, and well-defined negative physiological outcomes are missing. Instead, the concept relies heavily on performance outcomes for differentiating between the states. Recent advancements in the field of integrated exercise physiology have associated maladaptations in muscular oxidative function to high loads of exercise training.

Method: Eleven female and male subjects that exercised regularly but did not engage in high-intensity interval training (HIIT) were recruited to a 4-week long training intervention where the responses to different training loads were studied. Highly monitored HIIT sessions were performed on a cycle ergometer in a progressive fashion with the intent to accomplish a training overload. Throughout the intervention, physiological and psychological responses to HIIT were assessed, and the results were used to construct a diagnostic model that could indicate maladaptations during excessive training loads.

Results: We here use mitochondrial function as an early marker of excessive training loads and show the dynamic responses of several physiological and psychological measurements during different training loads. During HIIT, a loss of mitochondrial function was associated with reduced glycolytic, glucoregulatory and heart rate responses and increased ratings of perceived exertion in relation to several physiological measurements. The profile of mood states was highly affected after excessive training loads, whereas performance staled rather than decreased. By implementing five of the most affected and relevant measured parameters in a diagnostic model, we could successfully, and in all the subjects, identify the training loads that lead to maladaptations.

Conclusions: As mitochondrial parameters cannot be assessed without donating a muscle biopsy, this test can be used by coaches and exercise physiologists to monitor adaptation to exercise training for improving performance and optimizing the health benefits of exercise. Clinical trial registry number NCT04753021 . Retrospectively registered 2021-02-12.

Exercise training positively affects metabolic health through increased mitochondrial oxidative capacity and improved glucose regulation and is the first line of treatment in several metabolic diseases. However, the upper limit of the amount of exercise associated with beneficial therapeutic effects has not been clearly identified. Here, we used a training model with a progressively increasing exercise load during an intervention over 4 weeks. We closely followed changes in glucose tolerance, mitochondrial function and dynamics, physical exercise capacity, and whole-body metabolism. Following the week with the highest exercise load, we found a striking reduction in intrinsic mitochondrial function that coincided with a disturbance in glucose tolerance and insulin secretion. We also assessed continuous blood glucose profiles in world-class endurance athletes and found that they had impaired glucose control compared with a matched control group.

Oxidative stress plays a vital role for the adaptive responses to physical training. However, excessive oxidative stress can precipitate cellular damage, necessitating protective mechanisms to mitigate this effect. Glucosinolates, found predominantly in cruciferous vegetables, can be converted into isothiocyanates, known for their antioxidative properties. These compounds activate crucial antioxidant defence pathways and support mitochondrial function and protein integrity under oxidative stress, in both Nrf2-dependent and independent manners. We here administered glucosinolate-rich broccoli sprouts (GRS), in a randomized double-blinded cross-over fashion to 9 healthy subjects in combination with daily intense exercise training for 7 days. We found that exercise in combination with GRS significantly decreased the levels of carbonylated proteins in skeletal muscle and the release of myeloperoxidase into blood. Moreover, it lowered lactate accumulation during submaximal exercise, and attenuated the severe nocturnal hypoglycaemic episodes seen during the placebo condition. Furthermore, GRS in combination with exercise improved physical performance, which was unchanged in the placebo condition.

BACKGROUND

It is well accepted that exercise training improves glucose uptake and insulin sensitivity, and that endurance trained athletes in general show a high capacity for these parameters and excellent metabolic control. However, some studies fail to observe positive effects on glucose regulation in healthy, trained subjects the day after exercise. These, often unexpected, results have been postulated to be caused by excessive training loads, muscle damage, energy deficit, differences in glucose uptake in the exercised and non-exercised musculature and a metabolic interaction through increased fatty acid metabolism which suppresses glucose oxidation and uptake. The mode or volume of exercise that can lead to glucose intolerance in trained athletes as well as mechanistic insights and its relevance for health and performance are, however, not fully understood.

AIM

We studied the metabolic response to a glucose load the day after a session of high intensity interval training (HIIT) or three hours of continuous exercise (3h) in endurance trained athletes and compared the results with measurements during rest.

METHOD

Nine endurance trained athletes (5 females, 4 males) underwent oral glucose tolerance tests (OGTT) after rest and ~14 hours after exercise on a cycle ergometer (HIIT 5x4 minutes at ~95% of VO2max or 3h at 65% of VO2max). Venous blood was sampled at 15-minute intervals for 120 minutes and concentrations of glucose, insulin, free fatty acids (FFA) and ketones (β-hydroxybutyrate) were measured. Statistical analysis was performed using a RM one-way ANOVA with the Giesser-Greenhouse correction and Dunnett’s test was used to compare the exercise conditions to the resting condition.

RESULTS

The area under the curve (AUC) during the OGTT increased greatly after 3h (668±124 mM · min) (p<0.01) compared to rest (532±89) but was found to be unchanged after HIIT (541±96). Resting values of FFA and ketones were increased after 3h (p<0.01 and p<0.05, respectively) but not after HIIT. Insulin was found to be unaltered during all conditions.

CONCLUSIONS AND RELEVANCE

Here, we show manifestation of glucose intolerance in endurance trained athletes together with concomitant increases in plasma concentrations of FFA and ketones the day after a session of prolonged exercise training but not after HIIT. This could be a protective response for securing glucose delivery to the brain and therefore have a positive effect on endurance. It also has the potential to reduce the recovery of glycogen depots, glucose uptake during exercise and performance at higher work rates.

AIM: The purpose of this study was to 1. investigate if glucose tolerance is affected after one acute bout of different types of exercise; 2. assess if potential differences between two exercise paradigms are related to changes in mitochondrial function; and 3. determine if endurance athletes differ from nonendurance-trained controls in their metabolic responses to the exercise paradigms.

METHODS: Nine endurance athletes (END) and eight healthy nonendurance-trained controls (CON) were studied. Oral glucose tolerance tests (OGTT) and mitochondrial function were assessed on three occasions: in the morning, 14 h after an overnight fast without prior exercise (RE), as well as after 3 h of prolonged continuous exercise at 65% of VO₂ max (PE) or 5 × 4 min at ~95% of VO₂ max (HIIT) on a cycle ergometer.

RESULTS: Glucose tolerance was markedly reduced in END after PE compared with RE. END also exhibited elevated fasting serum FFA and ketones levels, reduced insulin sensitivity and glucose oxidation, and increased fat oxidation during the OGTT. CON showed insignificant changes in glucose tolerance and the aforementioned measurements compared with RE. HIIT did not alter glucose tolerance in either group. Neither PE nor HIIT affected mitochondrial function in either group. END also exhibited increased activity of 3-hydroxyacyl-CoA dehydrogenase activity in muscle extracts vs. CON.

CONCLUSION: Prolonged exercise reduces glucose tolerance and increases insulin resistance in endurance athletes the following day. These findings are associated with an increased lipid load, a high capacity to oxidize lipids, and increased fat oxidation.

Energistatus, muskelfysiologiska data och fysiskt stridsvärde studerades före och efter en 8 dygn långa grundmilitär slutövning (GMU) vid AMF-1 Berga Örlogsskolor i månadsskiftet oktober november 2013.

Totalt deltog 105 soldater i övningen, fördelat på 3 plutoner om vardera 35 soldater. En subgrupp på 24 soldater (8 kvinnor) bestående av 8 soldater från vardera pluton studerades mer ingående.

Medelhjärtfrekvensen för de 6 soldater (2 kvinnor) som hade i stort sett kompletta mätningar från den 187 timmar långa övningen, inklusive viloperioder, var 88 ± 7 slag/minut. Utifrån hjärtfrekvensdata beräknades den totala energiomsättningen till i genomsnitt 44 000 ± 6 600 kcal, vilket motsvarar 5 600 ± 840 kcal per dygn och 235 ± 35 kcal/tim. Total energiförbrukning var i genomsnitt 39 000 kcal för kvinnorna och 46 500 kcal för männen. I övrigt noterades inte några betydande skillnader mellan kvinnor och män. Däremot var det stora individuella variationer i energiutgift, vilka till ca hälften berodde på skillnader i kroppsvikt. Med hänsyn till kroppsvikt och buren vikt var energiförbrukningen ca 3,1 ± 0,23 kcal per timme per kg totalvikt. Den individuella variationen beror på skillnad i buren vikt, på olika uppgifter och på individuella fysiologiska skillnader.

Utifrån beräknat energiintag blev det totala energiunderskottet under övningen 12 000-15 000 kcal, vilket är ca 1 500-2 000 kcal per dygn. Viktminskningen under övningen var 2,9 kg för kvinnor och 3,7 kg för män. Denna viktminskning på >4 % leder troligen till försämrad uthållighetsförmåga.

Den maximala muskelstyrkan i armar och ben var i stort sett oförändrade efter övningen, liksom den beräknade maximala syreupptagningsförmågan. Däremot upplevdes ett lågintensivt cykelarbete som betydligt tyngre efter övningen. Muskeluthållighet mättes inte i denna studie.

Ett skjutprov om 5 skott i liggande på 100 m mot en tredjedelsfigur visade 64 deltagande soldater på en försämrad träffprocent från 90,5% före till 79,4 % efter övningen. Alla soldater hade minst en träff före medan 6 soldater hade alla bom efter övningen.

Slutsatsen från studien är att GMU-övningen resulterade i ett stort energiunderskott. Stridsvärdet, bedömt från skjutprovet var klart försämrat. Maximala fysiologiska parametrar var i stort sett oförändrade, medan skattad ansträngning och därmed uthållighetsförmåga, försämrades.

Introduction

It is well known that ultra-endurance exercise, such as Adventure racing and military operations, often induce substantial energy deficits. This suggests a catabolic state, but the exact effects on protein turnover have not yet been sufficiently investigated. The aim of this study was to examine several markers involved in muscle protein turnover before and after a multi-day physically demanding military training operation.

Methods

Seven female (age 21 ± 5 years, weight 71.2 ± 6.6 kg) and seventeen male (age 20 ± 1 years, weight 76.6 ± 6.2 kg) performed a 185 hours military training operation. Energy intake was estimated from food supply and energy expenditure was calculated from continuous heart rate and accelerometer recordings. Muscle biopsies were taken from M Vastus Lateralis before and after the operation.

Results

A negative energy balance of 1,500-2,000 kcal/24 hours was estimated. Body weight declined 3.4 (95% CI 3.0-3.8) kg and muscle explosive strength, evaluated from squad and counter movement jumps, was reduced 5 and 6 %, respectively, after the operation with no difference between genders. Muscle glycogen content was reduced from 269 ± 58 to 181 ± 44 mmol/kg dry muscle (p<0.05) with no difference between genders. Muscle content of mTOR and p70 as well as MAFbx were unchanged while the protein content of MuRF-1 was significantly down regulated in both genders.

Discussion

The study indicated that prolonged low intensity exercise with substantial energy deficit reduces muscle function and muscle glycogen content. Proteins for muscle synthesis mTOR and p70 were unchanged while the down regulation of MuRF-1 indicates a protection against muscle break down during the energy deficit situation, preserving the muscle mass.

Little is known about the molecular regulation of skeletal muscle protein turnover during exercise in field conditions where energy is intake inadequate. Here, 17 male and 7 female soldiers performed an 8 day long field based military operation. Vastus lateralis muscle biopsies, in which autophagy, the ubiquitin-proteasome system and the mTORC1 signaling pathway where studied, were collected before and after the operation. The 187 h long operation resulted in a 15% and 29% negative energy balance as well as a 4.1% and 4.6% loss of body mass in women and men respectively. After the operation protein levels of ULK1 as well as the phosphorylation of ULK1^Ser317 and ULK1^Ser555 had increased by 11%, 39% and 13%, respectively, and this was supported by a 17% increased phosphorylation of AMPK^Thr172 (P<0.05). The LC3b-I/II ratio was 3-fold higher after compared to before the operation (P<0.05), whereas protein levels of p62/SQSTM1 were unchanged. The β1, β2, and β5 activity of the proteasome and protein levels of MAFbx did not change, while levels of MuRF-1 were slightly reduced (6%, P<0.05). Protein levels and phosphorylation status of key components in the mTORC1 signaling pathway remained at basal levels after the operation. Muscle levels of glycogen decreased from 269±12 to 181±9 mmol ∙ kg dry muscle^-1 after the exercise period (P<0.05). In conclusion, the 8 days of field based exercise resulted in induction of autophagy without any increase in proteasome activity or protein ubiquitination. Simultaneously, the regulation of protein synthesis through the mTORC1 signaling pathway was maintained.

Human muscles are tailored towards ATP synthesis. When exercising at high work rates muscles convert glucose to lactate, which is less nutrient efficient than respiration. There is hence a trade-off between endurance and power. Metabolic models have been developed to study how limited catalytic capacity of enzymes affects ATP synthesis. Here we integrate an enzyme-constrained metabolic model with proteomics data from muscle fibers. We find that ATP synthesis is constrained by several enzymes. A metabolic bypass of mitochondrial complex I is found to increase the ATP synthesis rate per gram of protein compared to full respiration. To test if this metabolic mode occurs in vivo, we conduct a high resolved incremental exercise tests for five subjects. Their gas exchange at different work rates is accurately reproduced by a whole-body metabolic model incorporating complex I bypass. The study therefore shows how proteome allocation influences metabolism during high intensity exercise.

Biphasic relationship between training load and glucose tolerance

Nilsson, L, Flockhart M, Bergman K, Apro W, Ekblom B, Larsen FJ

There is a well-established construct regarding the positive effects of exercise on glucose tolerance and insulin sensitivity, as well as muscle glycogen storage. In insulin resistance, physical activity is an essential part of the treatment. However, the optimal dose is unknown. Reduced muscular glycogen stores, resulting from exercise, should stimulate an increased uptake of blood glucose. In this study we investigated the relation between training load, glucose tolerance and insulin sensitivity during three weeks of increasing interval training. Three times during the intervention, oral glucose tests were conducted to investigate the rate of glucose uptake. We found a biphasic dose-response relationship between training load and glucose tolerance, where an excessive training load led to a paradoxical reduction in glucose tolerance and impaired insulin release despite an unchanged amount of muscle glycogen. In light of these results, an upper limit of physical exercise exist where the negative effects overpowers the positive.

The molecular signaling of mitochondrial biogenesis is enhanced when resistance exercise is added to a bout of endurance exercise. The purpose of the present study was to examine if this mode of concurrent training translates into increased mitochondrial content and improved endurance performance. Moderately trained cyclists performed 8 weeks (two sessions per week) of endurance training only (E, n = 10; 60-min cycling) or endurance training followed by strength training (ES, n = 9; 60-min cycling + leg press). Muscle biopsies were obtained before and after the training period and analyzed for enzyme activities and protein content. Only the ES group increased in leg strength (+19%, P < 0.01), sprint peak power (+5%, P < 0.05), and short-term endurance (+9%, P < 0.01). In contrast, only the E group increased in muscle citrate synthase activity (+11%, P = 0.06), lactate threshold intensity (+3%, P < 0.05), and long-term endurance performance (+4%, P < 0.05). Content of mitochondrial proteins and cycling economy was not affected by training. Contrary to our hypothesis, the results demonstrate that concurrent training does not enhance muscle aerobic capacity and endurance performance in cyclists.

Recent studies suggest that carbohydrate restriction can improve the training-induced adaptation of muscle oxidative capacity. However, the importance of low muscle glycogen on the molecular signaling of mitochondrial biogenesis remains unclear. Here, we compare the effects of exercise with low (LG) and normal (NG) glycogen on different molecular factors involved in the regulation of mitochondrial biogenesis. Ten highly trained cyclists (VO(2max) 65 ± 1 ml/kg/min, W (max) 387 ± 8 W) exercised for 60 min at approximately 64 % VO(2max) with either low [166 ± 21 mmol/kg dry weight (dw)] or normal (478 ± 33 mmol/kg dw) muscle glycogen levels achieved by prior exercise/diet intervention. Muscle biopsies were taken before, and 3 h after, exercise. The mRNA of peroxisome proliferator-activated receptor-γ coactivator-1 was enhanced to a greater extent when exercise was performed with low compared with normal glycogen levels (8.1-fold vs. 2.5-fold increase). Cytochrome c oxidase subunit I and pyruvate dehydrogenase kinase isozyme 4 mRNA were increased after LG (1.3- and 114-fold increase, respectively), but not after NG. Phosphorylation of AMP-activated protein kinase, p38 mitogen-activated protein kinases and acetyl-CoA carboxylase was not changed 3 h post-exercise. Mitochondrial reactive oxygen species production and glutathione oxidative status tended to be reduced 3 h post-exercise. We conclude that exercise with low glycogen levels amplifies the expression of the major genetic marker for mitochondrial biogenesis in highly trained cyclists. The results suggest that low glycogen exercise may be beneficial for improving muscle oxidative capacity.

Aim

The aim of this study was to establish a method to create a difference between groups in muscle glycogen content as well as to investigate the effect of training in low muscle glycogen state on metabolic and physiological parameters.

Method

During two trials, a subject group of ten highly trained male road or mountain bike cyclists ((mean±SD) age, hight, body weight, VO₂max, and VO₂max·kg^-1 was 28±5 years, 74.7±6.3 kg, 183±6 cm, 4876±332 mL min^-1, 64.4±2.8 mL·kg^-1 min^-1), performed a glycogen depletion exercise followed by a night’s rest and a second exercise session. In the study, which was a crossover design, the subjects were randomly chosen to perform the first trial on a carbohydrate rich diet or a diet with no of carbohydrates. All the testing was performed on a Monark 839E ergometer bike and muscle biopsy sampling was collected before depletion exercise, before the exercise the following day and three hours post exercise. Plasma FFA and glucose was analyzed from venous blood collected at rest.

Results

Muscle glycogen pre depletion exercise was 623±180 and 645±133 mmol·kg dw^-1 glycosyl units for non-CHO and CHO trials respectively. The depletion exercise followed by 13 hours of rest resulted in a significant decrease in muscle glycogen in the non-CHO (p<0.0001), and CHO trials (p<0.01) to 166±71 and 478±111 mmol·kg dw^-1 respectively. In the non-CHO trial net glycogen depletion correlated positively with pre depletion glycogen storage.  After the completion of exercise 2 and the following three hour rest period, glycogen content in non-CHO and CHO-trial was 130±52 and477±97 mmol·kg dw^-1, respectively. In low glycogen state, the non-CHO trial resulted in an increase in FFA measured in blood plasma at rest and in an increase in Borg rating of perceived exertion (RPE) as well as a reduction in blood glucose during exercise. 

Conclusion

The protocol used in the present study was successful in creating a difference in muscle glycogen storage and training in low glycogen state was associated with an increase of several physiological parameters indicating a possible impairment of endurance exercise performance.