Gymnastik- och idrottshögskolan, GIH

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  • 1.
    Björkman, Frida
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Edin, Fredrik
    University of Gothenburg.
    Mattsson, C Mikael
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Larsen, Filip
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Regular moist snuff dipping does not affect endurance exercise performance.2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 7, article id e0181228Article in journal (Refereed)
    Abstract [en]

    Physiological and medical effects of snuff have previously been obtained either in cross-sectional studies or after snuff administration to non-tobacco users. The effects of snuff cessation after several years of daily use are unknown. 24 participants with >2 years of daily snuff-use were tested before and after >6 weeks snuff cessation (SCG). A control group (CO) of 11 snuff users kept their normal habits. Resting heart rate (HR) and blood pressure (BP) were significantly lower in SCG after snuff cessation, and body mass was increased by 1.4 ± 1.7 kg. Total cholesterol increased from 4.12 ± 0.54 (95% CI 3.89-4.35) to 4.46 ± 0.70 (95% CI 4.16-4.75) mM L-1 in SCG, due to increased LDL, and this change was significantly different from CO. Resting values of HDL, C-reactive protein, and free fatty acids (FFA) remained unchanged in both groups. In SCG group, both HR and BP were reduced during a four-stage incremental cycling test (from 50 to 80% of VO2max) and a prolonged cycling test (60 min at 50% of VO2max). Oxygen uptake (VO2), respiratory exchange ratio, blood lactate (bLa) and blood glucose (bGlu) concentration, and rate of perceived exertion (RPE) were unchanged. In CO group, all measurements were unchanged. During the prolonged cycling test, FFA was reduced, but with no significant difference between groups. During the maximal treadmill running test peak values of VO2, pulmonary ventilation (VE), time to exhaustion and bLa were unchanged in both groups. In conclusion, endurance exercise performance (VO2max and maximal endurance time) does not seem to be affected by prolonged snuff use, while effects on cardiovascular risk factors are contradictory. HR and BP during rest and submaximal exercise are reduced after cessation of regular use of snuff. Evidently, the long-time adrenergic stress on circulation is reversible.

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  • 2.
    Björkman, Frida
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's and Mats Börjesson's research group.
    Edin, Fredrik
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's and Mats Börjesson's research group.
    Mattsson, C. Mikael
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's and Mats Börjesson's research group.
    Larsen, Filip
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's and Mats Börjesson's research group.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's and Mats Börjesson's research group.
    Regular oral moist snuff dipping does not impair physical performanceArticle in journal (Refereed)
  • 3.
    Blackwood, Sarah J
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Horwath, Oscar
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Moberg, Marcus
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Pontén, Marjan
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Apro, William
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden..
    Ekblom, Maria
    Swedish School of Sport and Health Sciences, GIH, Department of Physical Activity and Health. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden..
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Katz, Abram
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Extreme Variations in Muscle Fiber Composition Enable Detection of Insulin Resistance and Excessive Insulin Secretion.2022In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 107, no 7, p. e2729-e2737, article id dgac221Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Muscle fiber composition is associated with peripheral insulin action.

    OBJECTIVE: We investigated whether extreme differences in muscle fiber composition are associated with alterations in peripheral insulin action and secretion in young, healthy subjects who exhibit normal fasting glycemia and insulinemia.

    METHODS: Relaxation time following a tetanic contraction was used to identify subjects with a high or low expression of type I muscle fibers: group I (n=11), area occupied by type I muscle fibers = 61.0 ± 11.8%; group II (n=8), type I area = 36.0 ± 4.9% (P<0.001). Biopsies were obtained from the vastus lateralis muscle and analyzed for mitochondrial respiration on permeabilized fibers, muscle fiber composition and capillary density. An intravenous glucose tolerance test was performed and indices of glucose tolerance, insulin sensitivity and secretion were determined.

    RESULTS: Glucose tolerance was similar between groups, whereas whole-body insulin sensitivity was decreased by ~50% in group II vs group I (P=0.019). First phase insulin release (area under the insulin curve during 10 min after glucose infusion) was increased by almost 4-fold in group II vs I (P=0.01). Whole-body insulin sensitivity was correlated with % area occupied by type I fibers (r=0.54; P=0.018) and capillary density in muscle (r=0.61; P=0.005), but not with mitochondrial respiration. Insulin release was strongly related to % area occupied by type II fibers (r=0.93; P<0.001).

    CONCLUSIONS: Assessment of muscle contractile function in young healthy subjects may prove useful in identifying individuals with insulin resistance and enhanced glucose stimulated insulin secretion prior to onset of clinical manifestations.

  • 4.
    Blackwood, Sarah J
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Horwath, Oscar
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Moberg, Marcus
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden..
    Pontén, Marjan
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Apro, William
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Ekblom, Maria
    Swedish School of Sport and Health Sciences, GIH, Department of Physical Activity and Health. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden..
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Katz, Abram
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Insulin resistance after a 3-day fast is associated with an increased capacity of skeletal muscle to oxidize lipids.2023In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 324, no 5, p. E390-E401Article in journal (Refereed)
    Abstract [en]

    There is a debate on whether lipid-mediated insulin resistance derives from an increased or decreased capacity of muscle to oxidize fats. Here we examine the involvement of muscle fiber composition in the metabolic responses to a 3-day fast (starvation, which results in increases in plasma lipids and insulin resistance) in two groups of healthy young subjects: 1, area occupied by type I fibers = 61.0 ± 11.8%; 2, type I area = 36.0 ± 4.9% (P<0.001). Muscle biopsies and intravenous glucose tolerance tests were performed after an overnight fast and after starvation. Biopsies were analyzed for muscle fiber composition and mitochondrial respiration. Indices of glucose tolerance and insulin sensitivity were determined. Glucose tolerance was similar in both groups after an overnight fast and deteriorated to a similar degree in both groups after starvation. In contrast, whole-body insulin sensitivity decreased markedly after starvation in group 1 (P<0.01), whereas the decrease in group 2 was substantially smaller (P=0.06). Non-esterified fatty acids and β-hydroxybutyrate levels in plasma after an overnight fast were similar between groups and increased markedly and comparably in both groups after starvation, demonstrating similar degrees of lipid load. The capacity of permeabilized muscle fibers to oxidize lipids was significantly higher in group 1 vs. 2, whereas there was no significant difference in pyruvate oxidation between groups. The data demonstrate that loss of whole-body insulin sensitivity after short-term starvation is a function of muscle fiber composition and is associated with an elevated rather than a diminished capacity of muscle to oxidize lipids.

  • 5. Boushel, Robert
    et al.
    Gnaiger, E
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Helge, J W
    González-Alonso, J
    Ara, I
    Munch-Andersen, T
    van Hall, G
    Søndergaard, H
    Saltin, Bengt
    Calbet, J A L
    Maintained peak leg and pulmonary VO2 despite substantial reduction in muscle mitochondrial capacity.2015In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 25, no Suppl 4, p. 135-143Article in journal (Refereed)
    Abstract [en]

    We recently reported the circulatory and muscle oxidative capacities of the arm after prolonged low-intensity skiing in the arctic (Boushel et al., 2014). In the present study, leg VO2 was measured by the Fick method during leg cycling while muscle mitochondrial capacity was examined on a biopsy of the vastus lateralis in healthy volunteers (7 male, 2 female) before and after 42 days of skiing at 60% HR max. Peak pulmonary VO2 (3.52 ± 0.18 L.min(-1) pre vs 3.52 ± 0.19 post) and VO2 across the leg (2.8 ± 0.4L.min(-1) pre vs 3.0 ± 0.2 post) were unchanged after the ski journey. Peak leg O2 delivery (3.6 ± 0.2 L.min(-1) pre vs 3.8 ± 0.4 post), O2 extraction (82 ± 1% pre vs 83 ± 1 post), and muscle capillaries per mm(2) (576 ± 17 pre vs 612 ± 28 post) were also unchanged; however, leg muscle mitochondrial OXPHOS capacity was reduced (90 ± 3 pmol.sec(-1) .mg(-1) pre vs 70 ± 2 post, P < 0.05) as was citrate synthase activity (40 ± 3 μmol.min(-1) .g(-1) pre vs 34 ± 3 vs P < 0.05). These findings indicate that peak muscle VO2 can be sustained with a substantial reduction in mitochondrial OXPHOS capacity. This is achieved at a similar O2 delivery and a higher relative ADP-stimulated mitochondrial respiration at a higher mitochondrial p50. These findings support the concept that muscle mitochondrial respiration is submaximal at VO2max , and that mitochondrial volume can be downregulated by chronic energy demand.

  • 6.
    Bovard, Joshua
    et al.
    Univ British Columbia, Vancouver, BC, Canada..
    Cardinale, Daniele A.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Reiter, Emma
    Univ British Columbia, Vancouver, BC, Canada..
    Jensen-Urstad, Mads
    Karolinska Inst, Stockholm, Sweden..
    Rullman, Erik
    Karolinska Inst, Stockholm, Sweden..
    Morales-Alamo, David
    Univ Las Palmas Gran Canaria, Las Palmas Gran Canaria, Spain..
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH.
    Calbet, Jose A. L.
    Univ Las Palmas Gran Canaria, Las Palmas Gran Canaria, Spain..
    Boushel, Robert
    Univ British Columbia, Vancouver, BC, Canada..
    Sex-differences In Exercising Hemodynamics: Role Of Exercising Muscle Mass2020In: MEDICINE AND SCIENCE IN SPORTS AND EXERCISE. 52:17. Suppl. Meeting Abstract: 924, Lippincott Williams & Wilkins, 2020, Vol. 52, no 17, p. 224-224Conference paper (Other academic)
  • 7.
    Cardinale, Daniele A.
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. Elite Performance Centre, Bosön, Lidingö, Sweden.
    Gejl, Kasper D
    University of Southern Denmark, Odense, Denmark..
    Petersen, Kristine Grøsfjeld
    University of Southern Denmark, Odense, Denmark..
    Nielsen, Joachim
    University of Southern Denmark, Odense, Denmark..
    Ørtenblad, Niels
    University of Southern Denmark, Odense, Denmark..
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Short term intensified training temporarily impairs mitochondrial respiratory capacity in elite endurance athletes.2021In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 131, no 1, p. 388-400Article in journal (Refereed)
    Abstract [en]

    AIM: The maintenance of healthy and functional mitochondria is the result of a complex mitochondrial turnover and herein quality-control program which includes both mitochondrial biogenesis and autophagy of mitochondria. The aim of this study was to examine the effect of an intensified training load on skeletal muscle mitochondrial quality control in relation to changes in mitochondrial oxidative capacity, maximal oxygen consumption and performance in highly trained endurance athletes.

    METHODS: 27 elite endurance athletes performed high intensity interval exercise followed by moderate intensity continuous exercise 3 days per week for 4 weeks in addition to their usual volume of training. Mitochondrial oxidative capacity, abundance of mitochondrial proteins, markers of autophagy and antioxidant capacity of skeletal muscle were assessed in skeletal muscle biopsies before and after the intensified training period.

    RESULTS: The intensified training period increased several autophagy markers suggesting an increased turnover of mitochondrial and cytosolic proteins. In permeabilized muscle fibers, mitochondrial respiration was ~20 % lower after training although some markers of mitochondrial density increased by 5-50%, indicative of a reduced mitochondrial quality by the intensified training intervention. The antioxidative proteins UCP3, ANT1, and SOD2 were increased after training, whereas we found an inactivation of aconitase. In agreement with the lower aconitase activity, the amount of mitochondrial LON protease that selectively degrades oxidized aconitase, was doubled.

    CONCLUSION: Together, this suggests that mitochondrial respiratory function is impaired during the initial recovery from a period of intensified endurance training while mitochondrial quality control is slightly activated in highly trained skeletal muscle.

  • 8.
    Cardinale, Daniele A
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll. Elite Performance Centre, Bosön.
    Gejl, Kasper D
    University of Southern Denmark.
    Ørtenblad, Niels
    University of Southern Denmark.
    Ekblom, Bjorn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Blomstrand, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Eva Blomstrand's research group.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Reliability of maximal mitochondrial oxidative phosphorylation in permeabilized fibers from the vastus lateralis employing high-resolution respirometry.2018In: Physiological Reports, E-ISSN 2051-817X, Vol. 6, no 4, article id e13611Article in journal (Refereed)
    Abstract [en]

    The purpose was to assess the impact of various factors on methodological errors associated with measurement of maximal oxidative phosphorylation (OXPHOS) in human skeletal muscle determined by high-resolution respirometry in saponin-permeabilized fibers. Biopsies were collected from 25 men to assess differences in OXPHOS between two muscle bundles and to assess the correlation between OXPHOS and the wet weight of the muscle bundle. Biopsies from left and right thighs of another five subjects were collected on two occasions to compare limbs and time-points. A single muscle specimen was used to assess effects of the anesthetic carbocaine and the influence of technician. The difference in OXPHOS between two fiber-bundles from the same biopsy exhibited a standard error of measurement (SEM) of 10.5 pmol · s-1  · mg-1 and a coefficient of variation (CV) of 15.2%. The differences between left and right thighs and between two different time-points had SEMs of 9.4 and 15.2 pmol · s-1  · mg-1 and CVs of 23.9% and 33.1%, respectively. The average (±SD) values obtained by two technicians monitoring different bundles of fibers from the same biopsy were 31.3 ± 7.1 and 26.3 ± 8.1 pmol · s-1  · mg-1 . The time that elapsed after collection of the biopsy (up to a least 5 h in preservation medium), wet weight of the bundle (from 0.5 to 4.5 mg) and presence of an anesthetic did not influence OXPHOS. The major source of variation in OXPHOS measurements is the sample preparation. The thigh involved, time-point of collection, size of fiber bundles, and time that elapsed after biopsy had minor or no effect.

  • 9.
    Cardinale, Daniele A.
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. Elite Performance Centre, Bosön. Swedish Sports Confederation, Lidingö, Sweden.
    Horwath, Oscar
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Elings-Knutsson, Jona
    Karolinska Institutet, Stockholm, Sweden,.
    Helge, Torbjörn
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Godhe, Manne
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Bermon, Stéphane
    LAMHESS, Université Côte d’Azur, Nice, France.
    Moberg, Marcus
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Flockhart, Mikael
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Hirschberg, Angelica Lindén
    Karolinska institutet, Stockholm, Sweden.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Enhanced Skeletal Muscle Oxidative Capacity and Capillary-to-Fiber Ratio Following Moderately Increased Testosterone Exposure in Young Healthy Women2020In: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 11, article id 585490Article in journal (Refereed)
    Abstract [en]

    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, VO<sub>2</sub> 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.

  • 10.
    Cardinale, Daniele A.
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Jensen-Urstad, M
    Karolinska institutet.
    Rullman, E
    Karolinska institutet.
    Søndergaard, H
    Rigshospitalet, Köpenhamn, Danmark.
    Morales-Alamo, D
    University of Las Palmas de Gran Canaria, Spanien.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Calbet, J A L
    University of Las Palmas de Gran Canaria, Spanien.
    Boushel, Robert
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology. University of British Columbia, Vancouver, British Columbia, Canada.
    Muscle mass and inspired oxygen influence oxygen extraction at maximal exercise: role of mitochondrial oxygen affinity.2019In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 225, no 1, article id e13110Article in journal (Refereed)
    Abstract [en]

    AIM:We examined the Fick components together with mitochondrial O2 affinity (p50mito ) in defining O2 extraction and O2 uptake during exercise with large and small muscle mass during normoxia (NORM) and hyperoxia (HYPER).

    METHODS:Seven individuals performed two incremental exercise tests to exhaustion on a bicycle ergometer (BIKE) and two on a one-legged knee extension ergometer (KE) in NORM or HYPER. Leg blood flow and VO2 were determined by thermodilution and the Fick method. Maximal ADP-stimulated mitochondrial respiration (OXPHOS) and p50mito were measured ex vivo in isolated mitochondria. Mitochondrial excess capacity in the leg was determined from OXPHOS in permeabilized fibers and muscle mass measured with magnetic resonance imaging in relation to peak leg O2 delivery.

    RESULTS:The ex vivo p50mito increased from 0.06±0.02 to 0.17±0.04 kPa with varying substrate supply and O2 flux rates from 9.84±2.91 to 16.34±4.07 pmol O2 ·s-1 ·μg-1 respectively. O2 extraction decreased from 83% in BIKE to 67% in KE as a function of a higher O2 delivery, and lower mitochondrial excess capacity. There was a significant relationship between O2 extraction and mitochondrial excess capacity and p50mito that was unrelated to blood flow and mean transit time.

    CONCLUSION:O2 extraction varies with mitochondrial respiration rate, p50mito and O2 delivery. Mitochondrial excess capacity maintains a low p50mito which enhances O2 diffusion from microvessels to mitochondria during exercise. This article is protected by copyright. All rights reserved.

  • 11.
    Cardinale, Daniele A.
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Lindholm, Peter
    Karolinska Institutet, Stockholm, Sweden..
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Boushel, Robert
    Univ British Columbia, Vancouver, BC, Canada..
    Effects Of Hyperoxic-Supplemented High Intensity Interval Training On Endurance Performance, Maximal Oxygen Consumption And Mitochondrial Function In Trained Cyclists2019In: MEDICINE AND SCIENCE IN SPORTS AND EXERCISE Vol 51(2019):6. Supplement: S, Meeting Abstract: 1753, Lippincott Williams & Wilkins, 2019, Vol. 51, no 6, p. 463-464Conference paper (Other academic)
  • 12.
    Cardinale, Daniele A.
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Lännerström, Johan
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Manselin, Tom
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Södergård, Olof
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Mijwel, Sara
    Karolinska institutet, Sweden.
    Lindholm, P
    Karolinska institutet, Sweden.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Boushel, Robert
    University of British Columbia, Vancouver, BC, Canada..
    Influence of Hyperoxic-Supplemented High-Intensity Interval Training on Hemotological and Muscle Mitochondrial Adaptations in Trained Cyclists.2019In: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 10, article id 730Article in journal (Refereed)
    Abstract [en]

    Background: Hyperoxia (HYPER) increases O2 carrying capacity resulting in a higher O2 delivery to the working muscles during exercise. Several lines of evidence indicate that lactate metabolism, power output, and endurance are improved by HYPER compared to normoxia (NORM). Since HYPER enables a higher exercise power output compared to NORM and considering the O2 delivery limitation at exercise intensities near to maximum, we hypothesized that hyperoxic-supplemented high-intensity interval training (HIIT) would upregulate muscle mitochondrial oxidative capacity and enhance endurance cycling performance compared to training in normoxia. Methods: 23 trained cyclists, age 35.3 ± 6.4 years, body mass 75.2 ± 9.6 kg, height 179.8 ± 7.9 m, and VO2max 4.5 ± 0.7 L min-1 performed 6 weeks polarized and periodized endurance training on a cycle ergometer consisting of supervised HIIT sessions 3 days/week and additional low-intensity training 2 days/week. Participants were randomly assigned to either HYPER (FIO2 0.30; n = 12) or NORM (FIO2 0.21; n = 11) breathing condition during HIIT. Mitochondrial respiration in permeabilized fibers and isolated mitochondria together with maximal and submaximal VO2, hematological parameters, and self-paced endurance cycling performance were tested pre- and posttraining intervention. Results: Hyperoxic training led to a small, non-significant change in performance compared to normoxic training (HYPER 6.0 ± 3.7%, NORM 2.4 ± 5.0%; p = 0.073, ES = 0.32). This small, beneficial effect on the self-paced endurance cycling performance was not explained by the change in VO2max (HYPER 1.1 ± 3.8%, NORM 0.0 ± 3.7%; p = 0.55, ES = 0.08), blood volume and hemoglobin mass, mitochondrial oxidative phosphorylation capacity (permeabilized fibers: HYPER 27.3 ± 46.0%, NORM 16.5 ± 49.1%; p = 0.37, ES = 3.24 and in isolated mitochondria: HYPER 26.1 ± 80.1%, NORM 15.9 ± 73.3%; p = 0.66, ES = 0.51), or markers of mitochondrial content which were similar between groups post intervention. Conclusions: This study showed that 6 weeks hyperoxic-supplemented HIIT led to marginal gain in cycle performance in already trained cyclists without change in VO2max, blood volume, hemoglobin mass, mitochondrial oxidative phosphorylation capacity, or exercise efficiency. The underlying mechanisms for the potentially meaningful performance effects of hyperoxia training remain unexplained and may raise ethical questions for elite sport.

  • 13.
    Cardinale, Daniele A.
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Schiffer, Tomas A
    Karolinska Institute.
    Morales-Alamo, David
    University of Las Palmas de Gran Canaria.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Calbet, Jose A L
    University of Las Palmas de Gran Canaria.
    Holmberg, Hans-Christer
    Mid Sweden University, Östersund, The University of British Columbia, Vancouver, BC, Canada..
    Boushel, Robert
    The University of British Columbia, Vancouver, BC, Canada..
    Superior Intrinsic Mitochondrial Respiration in Women Than in Men.2018In: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 9, article id 1133Article in journal (Refereed)
    Abstract [en]

    Sexual dimorphism is apparent in humans, however, to date no studies have investigated mitochondrial function focusing on intrinsic mitochondrial respiration (i.e., mitochondrial respiration for a given amount of mitochondrial protein) and mitochondrial oxygen affinity (p50mito) in relation to biological sex in human. A skeletal muscle biopsy was donated by nine active women, and ten men matched for maximal oxygen consumption (VO2max) and by nine endurance trained men. Intrinsic mitochondrial respiration, assessed in isolated mitochondria, was higher in women compared to men when activating complex I (CIP) and complex I+II (CI+IIP) (p < 0.05), and was similar to trained men (CIP, p = 0.053; CI+IIP, p = 0.066). Proton leak and p50mito were higher in women compared to men independent of VO2max. In conclusion, significant novel differences in mitochondrial oxidative function, intrinsic mitochondrial respiration and p50mito exist between women and men. These findings may represent an adaptation in the oxygen cascade in women to optimize muscle oxygen uptake to compensate for a lower oxygen delivery during exercise.

  • 14.
    Cardinale, Daniele A.
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll. Elite Performance Centre, Bosön.
    Lilja, Mats
    Karolinska institutet.
    Mandic, Mirko
    Karolinska institutet.
    Gustafsson, Thomas
    Karolinska institutet.
    Larsen, Filip J.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Lundberg, Tommy R.
    Karolinska institutet.
    Resistance Training with Co-ingestion of Anti-inflammatory Drugs Attenuates Mitochondrial Function2017In: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 8, article id 1074Article in journal (Refereed)
    Abstract [en]

    Aim: The current study aimed to examine the effects of resistance exercise with concomitant consumption of high versus low daily doses of non-steroidal anti-inflammatory drugs (NSAIDs) on mitochondrial oxidative phosphorylation in skeletal muscle. As a secondary aim, we compared the effects of eccentric-overload with conventional training. Methods: Twenty participants were randomized to either a group taking high doses (3 x 400 mg/day) of ibuprofen (IBU; 27±5 yr; n=11) or a group ingesting a low dose (1 x 75 mg/day) of acetylsalicylic acid (ASA; 26±4 yr; n=9) during 8 weeks of supervised knee extensor resistance training. Each of the subject’s legs were randomized to complete the training program using either a flywheel (FW) device emphasizing eccentric-overload, or a traditional weight stack machine (WS). Maximal mitochondrial oxidative phosphorylation (CI+IIP) from permeabilized skeletal muscle bundles was assessed using high-resolution respirometry. Citrate synthase (CS) activity was assessed using spectrophotometric techniques and mitochondrial protein content using western blotting. Results: After training, CI+IIP decreased (P<0.05) in both IBU (23%) and ASA (29%) with no difference across medical treatments. Although CI+IIP decreased in both legs, the decrease was greater (interaction p = 0.015) in WS (33%, p = 0.001) compared with FW (19%, p = 0.078). CS activity increased (p = 0.027) with resistance training, with no interactions with medical treatment or training modality. Protein expression of ULK1 increased with training in both groups (p < 0.001). The increase in quadriceps muscle volume was not correlated with changes in CI+IIP (R=0.16). Conclusion: These results suggest that 8 weeks of resistance training with co-ingestion of anti-inflammatory drugs reduces mitochondrial function but increases mitochondrial content. The observed changes were not affected by higher doses of NSAIDs consumption, suggesting that the resistance training intervention was the prime mediator of the decreased mitochondrial phosphorylation. Finally, we noted that flywheel resistance training, emphasizing eccentric overload, rescued some of the reduction in mitochondrial function seen with conventional resistance training.

  • 15.
    Cardinale, Daniele
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Lilja, Mats
    Karolinska Institutet, Stockholm, Sweden..
    Mandic, Mirko
    Karolinska Institutet, Stockholm, Sweden..
    Gustafsson, Thomas
    Karolinska Institutet, Stockholm, Sweden..
    Larsen, Filip J.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Lundberg, Tommy R.
    Karolinska Institutet Stockholm, Sweden..
    Resistance Exercise Attenuates Mitochondrial Function: Effects Of NSAID Intake And Eccentric-Overload Training2017In: Medicine & Science in Sports & Exercise. 49(5S):329, MAY 2017, 2017, Vol. 49, no 5, p. 329-329Conference paper (Refereed)
    Abstract [en]

    Although nonsteroidal antiinflammatorydrugs (NSAIDs) have been shown to modulate skeletal muscle adaptations and protein metabolism in response toresistance exercise, little is known about the effects of NSAIDs on mitochondrial function. Thus, the current study aimed to examine the effects of resistanceexercise with concomitant NSAID consumption on mitochondrial oxidative phosphorylation in skeletal muscle. Twenty participants were randomized in asingleblindedfashion to either an experimental group receiving ibuprofen (IBU: 27±5 yr; n=11; 1200 mg/d) or a control group receiving a lowdoseacetylsalicylic acid (CON: 26±4 yr; n=9; 75 mg/d) During this period, subjects performed 8 weeks of supervised resistance exercise involving the kneeextensors muscles. Each of the subject’s legs were randomized to complete the training program using either a flywheel (FW) device emphasizing eccentricoverload,or a traditional weight stack machine (WS). Maximal mitochondrial oxidative phosphorylation (OXPHOS) from permeabilized skeletal muscle bundleswas assessed using high resolution respirometry before and after the training intervention. Citrate synthase activity was assessed using spectrophotometrictechniques. After training, OXPHOS decreased (P<0.05) in both IBU (23%) and CON (29%) with no difference across medical treatments. Although OXPHOSdecreased in both legs, the decrease was greater (interaction P= 0.015) in WS (33%, P= 0.015) than in FW (19%, P= 0.078). Citrate synthase (CS) did notchange after the intervention. The increase in quadriceps muscle volume was not significantly correlated with the change in OXPHOS (R=0.15). These resultssuggest that 1) eight weeks of resistance training reduces mitochondrial function but not mitochondrial content, 2) The decreased mitochondrial function withresistance exercise was not affected by ibuprofen consumption, 3) flywheel resistance training, emphasizing eccentric overload, rescues some of thereduction in mitochondrial function seen with conventional resistance training.

  • 16.
    Carlström, Mattias
    et al.
    Karolinska Institutet.
    Larsen, Filip J
    Karolinska Institutet.
    Nyström, Thomas
    Hezel, Michael
    Borniquel, Sara
    Weitzberg, Eddie
    Lundberg, Jon O
    Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice.2010In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 41, p. 17716-20Article in journal (Refereed)
    Abstract [en]

    The metabolic syndrome is a clustering of risk factors of metabolic origin that increase the risk for cardiovascular disease and type 2 diabetes. A proposed central event in metabolic syndrome is a decrease in the amount of bioavailable nitric oxide (NO) from endothelial NO synthase (eNOS). Recently, an alternative pathway for NO formation in mammals was described where inorganic nitrate, a supposedly inert NO oxidation product and unwanted dietary constituent, is serially reduced to nitrite and then NO and other bioactive nitrogen oxides. Here we show that several features of metabolic syndrome that develop in eNOS-deficient mice can be reversed by dietary supplementation with sodium nitrate, in amounts similar to those derived from eNOS under normal conditions. In humans, this dose corresponds to a rich intake of vegetables, the dominant dietary nitrate source. Nitrate administration increased tissue and plasma levels of bioactive nitrogen oxides. Moreover, chronic nitrate treatment reduced visceral fat accumulation and circulating levels of triglycerides and reversed the prediabetic phenotype in these animals. In rats, chronic nitrate treatment reduced blood pressure and this effect was also present during NOS inhibition. Our results show that dietary nitrate fuels a nitrate-nitrite-NO pathway that can partly compensate for disturbances in endogenous NO generation from eNOS. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against cardiovascular disease and type 2 diabetes.

  • 17.
    Edman, Sebastian
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Flockhart, Mikael
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Apro, William
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Need for Speed: Human fast-twitch mitochondria favor power over efficiency.2024In: Molecular Metabolism, ISSN 2212-8778, Vol. 79, article id 101854Article in journal (Refereed)
    Abstract [en]

    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.

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  • 18.
    Edman, Sebastian
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Flockhart, Mikael
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Apro, William
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Need for Speed: Human fast-twitch mitochondria favour power over efficiencyManuscript (preprint) (Other academic)
  • 19.
    Flockhart, Mikael
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Continuous Glucose Monitoring in Endurance Athletes: Interpretation and Relevance of Measurements for Improving Performance and Health.2023In: Sports Medicine, ISSN 0112-1642, E-ISSN 1179-2035Article in journal (Refereed)
    Abstract [en]

    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.

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  • 20.
    Flockhart, Mikael
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Physiological adaptation of aerobic efficiency: when less is more.2019In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 127, no 6, article id 1821Article in journal (Other academic)
  • 21.
    Flockhart, Mikael
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Nilsson, Lina
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Apro, William
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Dose-response relationship between exercise load and mitochondrial function2019Conference paper (Other academic)
    Abstract [en]

    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.

  • 22.
    Flockhart, Mikael
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Nilsson, Lina C
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    A simple model for diagnosis of maladaptations to exercise training2022In: Sports Medicine Open, E-ISSN 2198-9761, Vol. 8, no 1, article id 136Article in journal (Refereed)
    Abstract [en]

    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.

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  • 23.
    Flockhart, Mikael
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Nilsson, Lina C.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Tais, Senna
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Apro, William
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. Karolinska Institutet, Stockholm, Sweden.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Excessive exercise training causes mitochondrial functional impairment and decreases glucose tolerance in healthy volunteers.2021In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 33, no 5, p. 957-970, article id S1550-4131(21)00102-9Article in journal (Refereed)
    Abstract [en]

    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.

  • 24.
    Flockhart, Mikael
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Nilsson, Lina
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Tillqvist, E N
    Linnaeus University, Kalmar, Sweden..
    Vinge, Fredrik
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Millbert, F
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Lännerström, Johan
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Nilsson, P H
    Linnaeus University, Kalmar, Sweden..
    Samyn, D
    Örebro University, Örebro, Sweden.
    Apro, William
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Sundqvist, Michaela L
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Glucosinolate-rich broccoli sprouts protect against oxidative stress and improve adaptations to intense exercise training.2023In: Redox Biology, E-ISSN 2213-2317, Vol. 67, article id 102873Article in journal (Refereed)
    Abstract [en]

    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.

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  • 25.
    Flockhart, Mikael
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Tischer, Dominik
    School of Health Sciences, Örebro University, Örebro, Sweden.
    Nilsson, Lina
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Blackwood, Sarah J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Physical Activity and Health.
    Katz, Abram
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Apro, William
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    THREE HOURS OF MODERATE INTENSITY EXERCISE TRAINING REDUCES GLUCOSE TOLERANCE IN ENDURANCE TRAINED ATHLETES2022Conference paper (Other academic)
    Abstract [en]

    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.

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    THREE HOURS OF MODERATE INTENSITY EXERCISE TRAINING REDUCES GLUCOSE TOLERANCE IN ENDURANCE TRAINED ATHLETES
  • 26.
    Flockhart, Mikael
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Tischer, Dominik
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Nilsson, Lina
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Blackwood, Sarah J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Katz, Abram
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Apro, William
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Three hours of moderate intensity exercise training reduces glucose tolerance in endurance trained athletes2022In: Svensk idrottsmedicin 2022:2, Svensk förening för fysisk aktivitet och idrottsmedicin , 2022, p. 28-Conference paper (Other academic)
  • 27.
    Flockhart, Mikael
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Tischer, Dominik
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Nilsson, Lina C.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Blackwood, Sarah J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Katz, Abram
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Apro, William
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Reduced glucose tolerance and insulin sensitivity after prolonged exercise in endurance athletes.2023In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 238, no 4, article id e13972Article in journal (Refereed)
    Abstract [en]

    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.

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  • 28.
    Gejl, Kasper Degn
    et al.
    University of Southern Denmark.
    Thams, Line
    University of Southern Denmark.
    Hansen, Mette
    Aarhus University, Aarhus, Denmark.
    Rokkedal-Lausch, Torben
    Aalborg University, Aalborg, Denmark.
    Plomgaard, Peter
    Rigshospitalet, Copenhagen, Denmark.
    Nybo, Lars
    University of Copenhagen, Copenhagen Denmark.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll. Karolinska Institute.
    Cardinale, Daniele A
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Jensen, Kurt
    University of Southern Denmark.
    Holmberg, Hans-Christer
    Mid Sweden University, Östersund, Sweden.
    Vissing, Kristian
    Aarhus University, Aarhus, Denmark.
    Ørtenblad, Niels
    University of Southern Denmark.
    No Superior Adaptations to Carbohydrate Periodization in Elite Endurance Athletes.2017In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 49, no 12, p. 2486-2497Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The present study investigated the effects of periodic CHO restriction on endurance performance and metabolic markers in elite endurance athletes.

    METHODS: Twenty-six male elite endurance athletes (VO2max: 65.0 ml O2[BULLET OPERATOR]kg[BULLET OPERATOR]min) completed 4 weeks of regular endurance training, while matched and randomized into two groups training with (Low) or without (High) carbohydrate (CHO) manipulation three days a week. The CHO manipulation days consisted of a 1-hr high intensity bike session in the morning, recovery for 7 hrs while consuming isocaloric diets containing either high CHO (414±2.4 g) or low CHO (79.5±1.0 g), and a 2-hr moderate bike session in the afternoon with or without CHO. VO2max, maximal fat oxidation and power output during a 30-min time trial (TT) were determined before and after the training period. The TT was undertaken after 90 mins of intermittent exercise with CHO provision before the training period and both CHO and placebo after the training period. Muscle biopsies were analyzed for glycogen, citrate synthase (CS) and β-hydroxyacyl-coenzyme A dehydrogenase (HAD) activity, carnitine palmitoyltransferase (CPT1b) and phosphorylated acetyl-CoA carboxylase (pACC).

    RESULTS: The training effects were similar in both groups for all parameters. On average, VO2max and power output during the 30-min TT increased by 5 ± 1% (P<0.05) and TT performance was similar after CHO and placebo during the preload phase. Training promoted overall increases in glycogen content (18 ± 5%), CS activity (11 ± 5%) and pACC (38 ± 19%) (P<0.05) with no differences between groups. HAD activity and CPT1b protein content remained unchanged.

    CONCLUSION: Superimposing periodic CHO restriction to 4 weeks of regular endurance training had no superior effects on performance and muscle adaptations in elite endurance athletes.

  • 29.
    Horwath, Oscar
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Edman, Sebastian
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. Åstrand Laboratory.
    Andersson, Alva
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Apro, William
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden..
    THRIFTY: a novel high-throughput method for rapid fibre type identification of isolated skeletal muscle fibres.2022In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 600, no 20, p. 4421-4438Article in journal (Refereed)
    Abstract [en]

    Fibre type-specific analyses are required for broader understanding of muscle physiology, but such analyses are difficult to conduct due to the extreme time requirements of dissecting and fibre typing individual fibres. Investigations are often confined to a small number of fibres from few participants with low representativeness of the entire fibre population and the participant population. To increase the feasibility of conducting large-scale fibre type-specific studies, a valid and rapid method for high-throughput fibre typing of individually dissected fibres was developed and named THRIFTY (for high-THRoughput Immunofluorescence Fibre TYping). Employing THRIFTY, 400 fibre segments were fixed onto microscope slides with a pre-printed coordinated grid system, probed with antibodies against myosin heavy chain (MyHC)-I and MyHC-II and classified using a fluorescence microscope. The validity and speed of THRIFTY was compared to a previously validated protocol (dot blot) on a fibre-to-fibre basis. Fibre pool purity was evaluated using 'gold standard' SDS-PAGE and silver staining. A modified THRIFTY-protocol using fluorescence western blot equipment was also validated. THRIFTY displayed excellent agreement with the dot blot protocol, κ = 0.955 (95% CI: 0.928, 0.982), P < 0.001. Both the original and modified THRIFTY protocols generated type I and type II fibre pools of absolute purity. Using THRIFTY, 400 fibres were typed just under 11 h, which was approximately 3 times faster than dot blot. THRIFTY is a novel and valid method with high versatility for very rapid fibre typing of individual fibres. THRIFTY can therefore facilitate the generation of large fibre pools for more extensive mechanistic studies into skeletal muscle physiology. KEY POINTS: Skeletal muscle is composed of different fibre types, each with distinct physiological properties. To fully understand how skeletal muscle adapts to external cues such as exercise, nutrition and ageing, fibre type-specific investigations are required. Such investigations are very difficult to conduct due to the extreme time requirements related to classifying individually isolated muscle fibres. To bypass this issue, we have developed a rapid and reliable method named THRIFTY which is cheap as well as versatile and which can easily be implemented in most laboratories. THRIFTY increases the feasibility of conducting larger fibre type-specific studies and enables time-sensitive assays where measurements need to be carried out in close connection with tissue sampling. By using THRIFTY, new insights into fibre type-specific muscle physiology can be gained which may have broad implications in health and disease.

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  • 30.
    Horwath, Oscar
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Moberg, Marcus
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Philp, Andrew
    Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
    Apro, William
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. Karolinska institutet, Sweden.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Influence of sex- and fiber type on the satellite cell pool in human skeletal muscle.2021In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 31, no 2, p. 303-312Article in journal (Refereed)
    Abstract [en]

    The repair, remodeling and regeneration of myofibers is dependent on satellite cells (SCs), although, the distribution of SCs in different fiber types of human muscle remains inconclusive. There is also a paucity of research comparing muscle fiber characteristics in a sex-specific manner. Therefore, the aim of this study was to investigate fiber type-specific SC content in men and women. Muscle biopsies from vastus lateralis were collected from 64 young (mean age 27 ± 5), moderately trained men (n=34) and women (n=30). SCs were identified by Pax7-staining together with immunofluorescent analyses of fiber type composition, fiber size and myonuclei content. In a mixed population, comparable number of SCs were associated to type I and type II fibers (0.07 ± 0.02 vs 0.07 ± 0.02 SCs per fiber, respectively). However, unlike men, women displayed a fiber type-specific distribution, with SC content being lower in type II than type I fibers (P=0.041). Sex-based differences were found specifically for type II fibers, where women displayed lower SC content compared to men (P<0.001). In addition, positive correlations (r-values between 0.36-0.56) were found between SC content and type I and type II fiber size in men (P=0.03 and P<0.01, respectively), whereas similar relationships could not be detected in women. Sex-based differences were also noted for fiber type composition and fiber size, but not for myonuclei content. We hereby provide evidence for sex-based differences present at the myocellular level, which may have important implications when studying exercise- and training induced myogenic responses in skeletal muscle.

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  • 31.
    Larsen, Filip
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Effects of dietary nitrate on oxygen cost during exercise2007In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 191, no 1, p. 59-66Article in journal (Refereed)
    Abstract [en]

    AIM: Nitric oxide (NO), synthesized from l-arginine by NO synthases, plays a role in adaptation to physical exercise by modulating blood flow, muscular contraction and glucose uptake and in the control of cellular respiration. Recent studies show that NO can be formed in vivo also from the reduction of inorganic nitrate (NO(3) (-)) and nitrite (NO(2) (-)). The diet constitutes a major source of nitrate, and vegetables are particularly rich in this anion. The aim of this study was to investigate if dietary nitrate had any effect on metabolic and circulatory parameters during exercise. METHOD: In a randomized double-blind placebo-controlled crossover study, we tested the effect of dietary nitrate on physiological and metabolic parameters during exercise. Nine healthy young well-trained men performed submaximal and maximal work tests on a cycle ergometer after two separate 3-day periods of dietary supplementation with sodium nitrate (0.1 mmol kg(-1) day-1) or an equal amount of sodium chloride (placebo). RESULTS: The oxygen cost at submaximal exercise was reduced after nitrate supplementation compared with placebo. On an average Vo(2) decreased from 2.98 +/- 0.57 during CON to 2.82 +/- 0.58 L min(-1) during NIT (P < 0.02) over the four lowest submaximal work rates. Gross efficiency increased from 19.7 +/- 1.6 during CON to 21.1 +/- 1.3% during NIT (P < 0.01) over the four lowest work rates. There was no difference in heart rate, lactate [Hla], ventilation (VE), VE/Vo(2) or respiratory exchange ratio between nitrate and placebo during any of the submaximal work rates. CONCLUSION: We conclude that dietary nitrate supplementation, in an amount achievable through a diet rich in vegetables, results in a lower oxygen demand during submaximal work. This highly surprising effect occurred without an accompanying increase in lactate concentration, indicating that the energy production had become more efficient. The mechanism of action needs to be clarified but a likely first step is the in vivo reduction of dietary nitrate into bioactive nitrogen oxides including nitrite and NO.

  • 32.
    Larsen, Filip
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    The low intracellular oxygen tension during exercise is a function of limited oxygen supply and high mitochondrial oxygen affinity: A letter to the editor2012In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 112, no 11, p. 3935-3936Article in journal (Other academic)
    Abstract [en]

    A letter to the editor is presented in response to an article on muscle intracellular oxygenation during exercise published in a previous issue of the journal.

  • 33.
    Larsen, Filip
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Mitochondrial oxygen affinity predicts basal metabolic rate in humans2011In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 25, no 8, p. 2843-52Article in journal (Refereed)
    Abstract [en]

    The basal metabolic rate (BMR) is referred to as the minimal rate of metabolism required to support basic body functions. It is well known that individual BMR varies greatly, even when correcting for body weight, fat content, and thyroid hormone levels, but the mechanistic determinants of this phenomenon remain unknown. Here, we show in humans that mass-related BMR correlates strongly to the mitochondrial oxygen affinity (p50(mito); R(2)=0.66, P=0.0004) measured in isolated skeletal muscle mitochondria. A similar relationship was found for oxygen affinity and efficiency during constant-load submaximal exercise (R(2)=0.46, P=0.007). In contrast, BMR did not correlate to overall mitochondrial density or to proton leak. Mechanistically, part of the p50(mito) seems to be controlled by the excess of cytochrome c oxidase (COX) protein and activity relative to other mitochondrial proteins. This is illustrated by the 5-fold increase in p50(mito) after partial cyanide inhibition of COX at doses that do not affect maximal mitochondrial electron flux through the ETS. These data suggest that the interindividual variation in BMR in humans is primarily explained by differences in mitochondrial oxygen affinity. The implications of these findings are discussed in terms of a trade-off between aerobic efficiency and power.

  • 34.
    Larsen, Filip
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Weitzberg, Eddie
    Lundberg, Jon
    Effects of dietary nitrate on blood pressure in healthy volunteers2006In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 28, no 355(26), p. 2792-3Article in journal (Refereed)
    Abstract [en]

    To the Editor:

    Nitric oxide, generated by nitric oxide synthase, is a key regulator of vascular integrity. This system is dysfunctional in many cardiovascular disorders, including hypertension. A fundamentally different pathway for the generation of nitric oxide was recently described in which the anions nitrate (NO3 ) and nitrite (NO2 ) are converted into nitric oxide and other bioactive nitrogen oxides.1-3 Nitrate is abundant in our diet, and particularly high levels are found in many vegetables.3

    We examined the effect of 3-day dietary supplementation with either sodium nitrate (at a dose of 0.1 mmol per kilogram of body weight per day) or placebo (sodium chloride, at a dose of 0.1 mmol per kilogram per day) on blood pressure in 17 physically active, healthy volunteers, none of whom smoked (15 men and 2 women; mean age, 24 years). The study had a randomized, double-blind, crossover design with two different treatment periods during which the subjects received either nitrate or placebo; the treatment periods were separated by a washout period of at least 10 days. The compounds were dissolved in water and could not be distinguished by taste or appearance. During the two treatment periods, the subjects were instructed to avoid all foods with a moderate or high nitrate content.3

    Systolic blood pressure Effects of 3-Day Dietary Supplementation with Inorganic Nitrate or Placebo on Systolic (Panel A) and Diastolic (Panel B) Blood Pressure in 17 Healthy Volunteers.) and pulse rate did not change significantly after nitrate supplementation, as compared with placebo supplementation. However, the diastolic blood pressure was on average 3.7 mm Hg lower after nitrate supplementation than after placebo supplementation (P<0.02) (Figure 1B), and the mean arterial pressure was 3.2 mm Hg lower (P<0.03). Plasma nitrate levels were higher after nitrate ingestion than after placebo ingestion (mean [±SD], 178±51 and 26±11 μM, respectively; P<0.001), as were plasma nitrite levels (219±105 and 138±38 nM, respectively; P<0.01).

    The daily nitrate dose used in the study corresponds to the amount normally found in 150 to 250 g of a nitrate-rich vegetable such as spinach, beetroot, or lettuce. It is clear from earlier studies, such as the Dietary Approaches to Stop Hypertension (DASH) trial, that a diet rich in fruits and vegetables can reduce blood pressure,4,5 but attempts to modify single nutrients have been inconsistent. Therefore, it has been argued that the effect of any individual nutrient is too small to detect in trials. In our study, reduced blood pressure was associated with nitrate supplementation alone; this effect was evident in young normotensive subjects. In fact, it was similar to that seen in the healthy control group in the DASH study.4 The exact mechanism behind the blood-pressure–lowering effect of nitrate needs to be clarified in future studies.

    We conclude that short-term dietary supplementation with inorganic nitrate reduces diastolic blood pressure in healthy young volunteers.

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  • 35.
    Larsen, Filip J.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Dietary inorganic nitrate: role in exercise physiology, cardiovascular and metabolic regulation2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Nitric oxide (NO) is a ubiquitous signaling molecule with a vast number of tasks in the body, including regulation of cardiovascular and metabolic function. A decreased bioavailability of NO is a central event in disorders such as hypertension and metabolic syndrome. NO is also important in the regulation of blood flow and metabolism during exercise. The production of NO has previously been thought to be under the exclusive control of the nitric oxide synthases (NOS) but this view is now being seriously challenged. Recent lines of research suggest the existence of an NO-synthase independent pathway in which the supposedly inert NO oxidation products nitrate (NO3-) and nitrite (NO2-) can be reduced back to NO in blood and tissues. An important additional source of nitrate is our everyday diet and certain vegetables are particularly rich in this anion. In this thesis the possibility that dietary derived nitrate is metabolized in vivo to form reactive nitrogen oxides with NO-like bioactivity has been explored. It is shown that nitrate in amounts easily achieved via the diet, increases the systemic levels of nitrite and reduces blood pressure in healthy humans. Moreover, nitrate reduces whole body oxygen cost during submaximal and maximal exercise; a surprising effect involving improvement in mitochondrial efficiency and reduced expression of specific mitochondrial proteins regulating proton conductance. Alterations in the mitochondrial affinity for oxygen can explain this reduction in both submaximal and maximal oxygen consumption and predicts basal metabolic rate in humans. Finally, in mice lacking endothelial NO synthase, dietary supplementation with nitrate could reverse several features of the metabolic syndrome that develop in these animals. These studies demonstrate that dietary nitrate can fuel a nitrate-nitrite-NO pathway with important implications for cardiovascular and metabolic functions in health and disease.

  • 36.
    Larsen, Filip J
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Anderson, Martin
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Nyström, Thomas
    Cardiorespiratory fitness predicts insulin action and secretion in healthy individuals.2012In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 61, no 1, p. 12-6Article in journal (Refereed)
    Abstract [en]

    Long-term cardiorespiratory fitness (CRF) and the development of type 2 diabetes mellitus are inversely correlated. Here, we examined the relationships between peak oxygen uptake (VO(2)peak), on the one hand, and glucose infusion rate at rest (GIR(rest)) and during exercise (GIR(exercise)), as well as insulin secretion (both the early and late phases of response [area under the curve {AUC}(insulin)]), on the other. Eight male and 4 female healthy, lean, nonsmoking volunteers were recruited. The VO(2)peak was measured during graded exercise on a cycle ergometer until exhaustion was reached. The GIR(rest) and GIR(exercise) were determined using a euglycemic-hyperinsulinemic clamp, and insulin secretion at rest was evaluated with an intravenous glucose tolerance test. The VO(2)peak correlated positively to GIR(rest) (r = 0.81, P = .001) and GIR(exercise) (r = 0.87, P < .001) and negatively to AUC(insulin) (r = -0.64, P = .03). The respiratory exchange ratio (RER) during insulin infusion was positively correlated to GIR(rest) (r = 0.83, P < .001) and GIR(exercise) (r = 0.86, P < .01) and negatively correlated to both the early insulin response (r = -0.86, P < .0001) and AUC(insulin) (r = -0.87, P = .001). The VO(2)peak accounted for 45% of the variability in RER (R(2) = 0.45, P = .035). In this healthy population, CRF and RER were highly correlated to insulin sensitivity and secretion, as well as to the ability to alter the substrate being oxidized during exercise. These findings highlight the importance of good CRF to maintaining normal insulin action.

  • 37.
    Larsen, Filip J
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Schiffer, T A
    Karolinska insitutet, Stockholm, Sweden.
    Zinner, C
    University of Applied Sciences for Police and Administration of Hesse, Wiesbaden, Germany.
    Willis, S J
    University of Lausanne, Lausanne, Switzerland.
    Morales-Alamo, D
    University of Las Palmas de Gran Canaria, Gran Canaria, Spain.
    Calbet, Jal
    University of Las Palmas de Gran Canaria, Gran Canaria, Spain.
    Boushel, R
    The University of British Columbia, Vancouver, BC, Canada..
    Holmberg, H C
    Mid Sweden University, Östersund, Sweden..
    Mitochondrial oxygen affinity increases after sprint interval training and is related to the improvement in peak oxygen uptake.2020In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 229, no 3, article id e13463Article in journal (Refereed)
    Abstract [en]

    AIMS: The body responds to exercise training by profound adaptations throughout the cardiorespiratory and muscular systems, which may result in improvements in maximal oxygen consumption (VO2 peak) and mitochondrial capacity. By convenience, mitochondrial respiration is often measured at supra-physiological oxygen levels, an approach that ignores any potential regulatory role of mitochondrial affinity for oxygen (p50mito ) at physiological oxygen levels.

    METHODS: In this study, we examined the p50mito of mitochondria isolated from the Vastus lateralis and Triceps brachii in 12 healthy volunteers before and after a training intervention with 7 sessions of sprint interval training using both leg cycling and arm cranking. The changes in p50mito were compared to changes in whole-body VO2 peak.

    RESULTS: We here show that p50mito is similar in isolated mitochondria from the Vastus (40 ± 3.8 Pa) compared to Triceps (39 ± 3.3) but decreases (mitochondrial oxygen affinity increases) after 7 sessions of sprint interval training (to 26 ± 2.2 Pa in Vastus and 22 ± 2.7 Pa in Triceps, both p<0.01). The change in VO2 peak modeled from changes in p50mito was correlated to actual measured changes in VO2 peak (R2 =0.41, p=0.002).

    CONCLUSION: Together with mitochondrial respiratory capacity, p50mito is a critical factor when measuring mitochondrial function, it can decrease with sprint interval training and should be considered in the integrative analysis of the oxygen cascade from lung to mitochondria.

  • 38.
    Larsen, Filip J
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's and Mats Börjesson's research group.
    Schiffer, Tomas A
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's and Mats Börjesson's research group.
    Mattsson, Mathias P
    Checa, Antonio
    Wheelock, Craig E
    Nyström, Thomas
    Lundberg, Jon O
    Weitzberg, Eddie
    Dietary nitrate reduces resting metabolic rate: a randomized, crossover study in humans.2014In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 99, no 4, p. 843-50Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Nitrate, which is an inorganic anion abundant in vegetables, increases the efficiency of isolated human mitochondria. Such an effect might be reflected in changes in the resting metabolic rate (RMR) and formation of reactive oxygen species. The bioactivation of nitrate involves its active accumulation in saliva followed by a sequential reduction to nitrite, nitric oxide, and other reactive nitrogen species.

    OBJECTIVE: We studied effects of inorganic nitrate, in amounts that represented a diet rich in vegetables, on the RMR in healthy volunteers.

    DESIGN: In a randomized, double-blind, crossover study, we measured the RMR by using indirect calorimetry in 13 healthy volunteers after a 3-d dietary intervention with sodium nitrate (NaNO3) or a placebo (NaCl). The nitrate dose (0.1 mmol · kg(-1) · d(-1)) corresponded to the amount in 200-300 g spinach, beetroot, lettuce, or other vegetable that was rich in nitrate. Effects of direct nitrite exposure on cell respiration were studied in cultured human primary myotubes.

    RESULTS: The RMR was 4.2% lower after nitrate compared with placebo administration, and the change correlated strongly to the degree of nitrate accumulation in saliva (r(2) = 0.71). The thyroid hormone status, insulin sensitivity, glucose uptake, plasma concentration of isoprostanes, and total antioxidant capacity were unaffected by nitrate. The administration of nitrite to human primary myotubes acutely inhibited respiration.

    CONCLUSIONS: Dietary inorganic nitrate reduces the RMR. This effect may have implications for the regulation of metabolic function in health and disease.

  • 39.
    Larsen, Filip J
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Schiffer, Tomas A
    Ørtenblad, Niels
    Zinner, Christoph
    Morales-Alamo, David
    Willis, Sarah J
    Calbet, Jose A
    Holmberg, Hans-Christer
    Boushel, Robert
    High-intensity sprint training inhibits mitochondrial respiration through aconitase inactivation.2016In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 30, no 1, p. 417-427Article in journal (Refereed)
    Abstract [en]

    Intense exercise training is a powerful stimulus that activates mitochondrial biogenesis pathways and thus increases mitochondrial density and oxidative capacity. Moderate levels of reactive oxygen species (ROS) during exercise are considered vital in the adaptive response, but high ROS production is a serious threat to cellular homeostasis. Although biochemical markers of the transition from adaptive to maladaptive ROS stress are lacking, it is likely mediated by redox sensitive enzymes involved in oxidative metabolism. One potential enzyme mediating such redox sensitivity is the citric acid cycle enzyme aconitase. In this study, we examined biopsy specimens of vastus lateralis and triceps brachii in healthy volunteers, together with primary human myotubes. An intense exercise regimen inactivated aconitase by 55-72%, resulting in inhibition of mitochondrial respiration by 50-65%. In the vastus, the mitochondrial dysfunction was compensated for by a 15-72% increase in mitochondrial proteins, whereas H2O2 emission was unchanged. In parallel with the inactivation of aconitase, the intermediary metabolite citrate accumulated and played an integral part in cellular protection against oxidative stress. In contrast, the triceps failed to increase mitochondrial density, and citrate did not accumulate. Instead, mitochondrial H2O2 emission was decreased to 40% of the pretraining levels, together with a 6-fold increase in protein abundance of catalase. In this study, a novel mitochondrial stress response was highlighted where accumulation of citrate acted to preserve the redox status of the cell during periods of intense exercise.-Larsen, F. J., Schiffer, T. A., Ørtenblad, N., Zinner, C., Morales-Alamo, D., Willis, S. J., Calbet, J. A., Holmberg, H.-C., Boushel, R. High-intensity sprint training inhibits mitochondrial respiration through aconitase inactivation.

  • 40.
    Larsen, Filip J
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Weitzberg, Eddie
    Lundberg, Jon O
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise.2010In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 48, no 2, p. 342-7Article in journal (Refereed)
    Abstract [en]

    The anion nitrate-abundant in our diet-has recently emerged as a major pool of nitric oxide (NO) synthase-independent NO production. Nitrate is reduced stepwise in vivo to nitrite and then NO and possibly other bioactive nitrogen oxides. This reductive pathway is enhanced during low oxygen tension and acidosis. A recent study shows a reduction in oxygen consumption during submaximal exercise attributable to dietary nitrate. We went on to study the effects of dietary nitrate on various physiological and biochemical parameters during maximal exercise. Nine healthy, nonsmoking volunteers (age 30+/-2.3 years, VO(2max) 3.72+/-0.33 L/min) participated in this study, which had a randomized, double-blind crossover design. Subjects received dietary supplementation with sodium nitrate (0.1 mmol/kg/day) or placebo (NaCl) for 2 days before the test. This dose corresponds to the amount found in 100-300 g of a nitrate-rich vegetable such as spinach or beetroot. The maximal exercise tests consisted of an incremental exercise to exhaustion with combined arm and leg cranking on two separate ergometers. Dietary nitrate reduced VO(2max) from 3.72+/-0.33 to 3.62+/-0.31 L/min, P<0.05. Despite the reduction in VO(2max) the time to exhaustion trended to an increase after nitrate supplementation (524+/-31 vs 563+/-30 s, P=0.13). There was a correlation between the change in time to exhaustion and the change in VO(2max) (R(2)=0.47, P=0.04). A moderate dietary dose of nitrate significantly reduces VO(2max) during maximal exercise using a large active muscle mass. This reduction occurred with a trend toward increased time to exhaustion implying that two separate mechanisms are involved: one that reduces VO(2max) and another that improves the energetic function of the working muscles.

  • 41.
    Larsen, Filip
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Schiffer, TA
    Borniquel, S
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Lundberg, JO
    Weitzberg, E
    Dietary inorganic nitrate improves mitochondrial efficiency in humans.2011In: Cell Metabolism, ISSN 1550-4131, Vol. 13, no 2, p. 149-159Article in journal (Refereed)
    Abstract [en]

    Nitrate, an inorganic anion abundant in vegetables, is converted in vivo to bioactive nitrogen oxides including NO. We recently demonstrated that dietary nitrate reduces oxygen cost during physical exercise, but the mechanism remains unknown. In a double-blind crossover trial we studied the effects of a dietary intervention with inorganic nitrate on basal mitochondrial function and whole-body oxygen consumption in healthy volunteers. Skeletal muscle mitochondria harvested after nitrate supplementation displayed an improvement in oxidative phosphorylation efficiency (P/O ratio) and a decrease in state 4 respiration with and without atractyloside and respiration without adenylates. The improved mitochondrial P/O ratio correlated to the reduction in oxygen cost during exercise. Mechanistically, nitrate reduced the expression of ATP/ADP translocase, a protein involved in proton conductance. We conclude that dietary nitrate has profound effects on basal mitochondrial function. These findings may have implications for exercise physiology- and lifestyle-related disorders that involve dysfunctional mitochondria.

  • 42.
    Lundberg, Jon O
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden..
    Schiffer, Tomas
    Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden..
    Weitzberg, Eddie
    Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden..
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    The Tortoise and the Hare.2023In: Trends in endocrinology and metabolism, ISSN 1043-2760, E-ISSN 1879-3061, Vol. 34, no 6, p. 317-318Article in journal (Other academic)
    Abstract [en]

    Distance running requires a high absolute oxygen consumption, while for a breath-hold diver the opposite is preferable. We compared physiological exercise parameters and mitochondrial function in a competitive triathlete with those seen in an accomplished breath-hold diver and notice some remarkable differences, possibly explaining why both have become successful.

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  • 43.
    Lännerström, Johan
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Nilsson, Lina C
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Cardinale, Daniele A.
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. The Swedish Sports Confederation, Stockholm, Sweden.
    Björklund, Glenn
    Mid Sweden University, Östersund, Sweden; The Swedish Sports Confederation, Stockholm, Sweden.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Effects of Plyometric Training on Soft and Hard Surfaces for Improving Running Economy.2021In: Journal of Human Kinetics, ISSN 1640-5544, E-ISSN 1899-7562, Vol. 79, no 1, p. 187-196Article in journal (Refereed)
    Abstract [en]

    The present study investigated the effects of plyometric jump training on hard and soft surfaces on running economy (RE), maximal oxygen uptake (VO2max), running performance and the rate of force development in orienteers. Nineteen orienteers (11 women and 8 men, body mass 61.1 ± 7.3 kg, age 21 ± 5.8 yrs) were randomly stratified based on sex, age, VO2max and RE to plyometric jumping training (8 sessions over 4 weeks) on either a hard or a soft surface. RE, VO2max and running performance were assessed on a treadmill and outdoor on- and off-trail loops. Moreover, ground reaction forces and force development were assessed during a one leg drop-jump test. The training intervention led to an overall 2-7% improvement in treadmill and off-trail RE, independent of the jumping surface and running velocity assessed. These improvements were not explained by force development during drop jump tests, which remained unchanged following the intervention. The changes in time-trial performance were associated with changes in RE. Plyometric training improved RE with no difference between the hard or the soft training surface and improved RE was also independent of the running speed assessed. Furthermore, improved running performance was associated with changes in RE after the intervention.

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  • 44.
    Manselin, Tom A
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Södergård, Olof
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Lindholm, Peter
    Karolinska institutet.
    Aerobic efficiency is associated with the improvement in maximal power output during acute hyperoxia.2017In: Physiological Reports, E-ISSN 2051-817X, Vol. 5, no 2, article id e13119Article in journal (Refereed)
    Abstract [en]

    This study investigated the relationship between aerobic efficiency during cycling exercise and the increase in physical performance with acute hyperoxic exposure (FiO2 ~31%) (HOX) and also tested the hypothesis that fat oxidation could be increased by acute hyperoxia. Fourteen males and four females were recruited for two sessions, where they exercised for 2 × 10 min at 100 W to determine efficiency. HOX and normoxia (NOX) were administered randomly on both occasions to account for differences in nitrogen exchange. Thereafter, a progressive ramp test was performed to determine VO2max and maximal power output (Wmax). After 30 min rest, workload was set to 80% of maximal power output (Wmax) for a time to exhaustion test (TTE). At 100W gross efficiency was reduced from 19.4% during NOX to 18.9% during HOX (P ≤ 0.0001). HOX increased fat oxidation at 100 W by 52% from 3.41 kcal min(-1) to 5.17 kcal min(-1) (P ≤ 0.0001) with a corresponding reduction in carbohydrate oxidation. Wmax increased by 2.4% from 388.8 (±82.1) during NOX to 397.8 (±83.5) during HOX (P ≤ 0.0001). SaO2 was higher in HOX both at the end of the maximal exercise test and TTE. Subjects with a high level of efficiency in NOX had a larger improvement in Wmax with HOX, in agreement with the hypothesis that an optimum level of efficiency exists that maximizes power production. No association between mitochondrial excess capacity and endurance performance was found; increases in oxygen supply seemed to increase maximal aerobic power production and maintain/increase endurance capacity at the same relative workload.

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  • 45.
    Mattsson, C. Mikael
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Björkman, Frida
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Edin, Fredrik
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Larsen, Filip
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Regular moist snuff dipping does not affect endurance exercise performance2013Conference paper (Refereed)
    Abstract [en]

    Physiological and medical effects of snuff have previously been obtained either in cross-sectional studies or after snuff administration to non-tobacco users, but the effects of snuff cessation (SC) after several years of daily use on individual level are unknown. 24 participants with >2 years of daily snuff-use were tested before and after >6 weeks SC (SCG), together with a control group (CO) of 11 snuff users who kept their normal habits. Resting heart rate (HR) was significantly lower in SCG after SC. Body mass in SCG group increased by 1.4 ± 1.7 kg and blood pressure (BP) were reduced, but without significant differences between groups. Total cholesterol increased from 4.12 ± 0.54 (95% CI 3.89–4.35) to 4.46 ± 0.70 (95% CI 4.16–4.75) mM/L in SCG, due to increased LDL, and this change was significantly different from CO. Resting values of HDL, C-reactive protein, and free fatty acids (FFA) remained unchanged in both groups. During a four-stage incremental (from 50 to 80% of VO2max) and a prolonged (60 min at 50% of VO2max) cycling test HR and BP were reduced in SCG, while oxygen uptake (VO2), respiratory exchange ratio, blood lactate (bLa) and blood glucose (bGlu) concentration, and rate of perceived exertion were unchanged. All measurements were unchanged in CO. During the prolonged exercise FFA was reduced but there was no significant difference between groups. During the maximal treadmill running test peak values of VO2, pulmonary ventilation (VE), time to exhaustion and bLa were unchanged in both groups. In conclusion, endurance exercise performance (VO2max and maximal endurance time) does not seem to be affected by prolonged snuff use, while effects on cardiovascular risk factors are contradictory.

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    Presentationsposter
  • 46.
    Mattsson, C. Mikael
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Larsen, Filip
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's and Mats Börjesson's research group.
    Kondition och uthållighet: För träning, tävling och hälsa2013Book (Other (popular science, discussion, etc.))
    Abstract [sv]

    Vilken intervallform är den mest effektiva i syfte att förbättra konditionen? Är det viktigt att ett träningsupplägg styrs av individualisering? Vilka positiva hälsoeffekter medför en förbättrad kondition? Och vad händer i framtiden – kommer drömgränsen under två timmar på maraton, att sprängas?

    En sammanställning och tolkning av den kunskap vi i nuläget har om fysiologi och träningslära.

    Boken Kondition och uthållighet är en sammanställning och tolkning av den kunskap vi i nuläget har om fysiologi och träningslära. Den beskriver en mängd faktorer och situationer kopplade till träning, prestation, utveckling och hälsa. Den vägleder dig som planerar och genomför träningen - aktiv eller tränare – att välja rätt träningsupplägg med hänsyn till träningsgrad och ambitionsnivå.

    Hälsoeffekter och ofattbara prestationer

    Att träna sin kondition medför en lång rad positiva hälsoeffekter såsom ökad livslängd, förbättrad livskvalitet och minskad risk för en mängd sjukdomar. Vid ökad träningsdos genomgår kroppen en rad förändringar för att anpassa sig till de krav som belastningen kräver. Kroppen är lyckligtvis enormt anpassningsbar och får den bara tillräckligt mycket träning kan den lära sig att tåla stora påfrestningar. Detta bidrar till att idrottare som specialiserar sig, och tränar mycket under lång tid, kan uppnå häpnadsväckande prestationer. Ju sämre kondition och uthållighet du har, desto mindre krävs för att du ska förbättra dig. Ju bättre kondition och uthållighet du har, desto hårdare belastning krävs för att du ska förbättra dig ytterligare.

    Pulsträning

    Ett sätt att mäta träningsbelastning är att använda puls och pulsklocka. Författarna, som även har skrivit träningshäftet Pulsträning (SISU Idrottsböcker 2011), förordar en indelning med sex intensitetszoner som baseras på beräkningar av individuella värden på vilo-, tröskel- och maxpuls. Beroende på hur vältränad man är kommer de olika zonerna att hamna mellan olika pulsnivåer. I den här boken beskrivs vad som tränas i de olika zonerna och varför man utför denna träning, samt hur man ska fördela träningsmängden mellan de olika zonerna.

    Intervallträning och individualisering

    Intervallträning innebär att man delar upp ett träningspass i mindre bitar med viloperioder i mellan, vilket möjliggör att hårda träningspass kan genomföras med en större mängd arbete på hög intensitet. Forskning tyder på att högintensiv intervallträning behövs för att man ska få ut så mycket som möjligt av sin konditionsträning. Vid intervallträning är det extra tydligt att man för bästa effekt bör utgå från sin egen förmåga; att man strävar efter en relativ belastning och upplevelse av trötthet, under och efter intervallpassen.

    Bokens upplägg

    Bokens första del går igenom grunderna i fysiologi och den andra delen handlar om vad som händer och vad man behöver tänka på vid planering, utförande och utvärdering av träning och tävling i konditions- och uthållighetsidrotter. Kondition och uthållighet tar också upp områden som återhämtning, skador, olika riskfaktorer och näringslära, vilka har en direkt betydelse för konditionsträning, oavsett om det handlar om att vinna OS eller träning för hälsa och ett långt aktivt liv.

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  • 47.
    Mattsson, C. Mikael
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's and Mats Börjesson's research group.
    Larsen, Filip
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's and Mats Börjesson's research group.
    Pulsträning2011Book (Other (popular science, discussion, etc.))
    Abstract [sv]

    Att träna pulsbaserat skapar perfekta förutsättningarna för en positiv utveckling av din kondition eftersom du tränar utifrån din egen förmåga. Pulsen hjälper dig att träna på rätt nivå på de enskilda träningspassen och kan användas vid all form av konditionsträning. I häftet Pulsträning lär du dig grunderna för att träna med puls och hur du genom att använda olika belastningar kan uppnå olika effekter av din träning.  Du får också förslag på olika tester som både hjälper dig att träna effektivare och skapar motivation.

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  • 48.
    Mattsson, C. Mikael
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Larsen, Filip
    Karolinska insitutet.
    Holmberg, Hans Christer
    Mittuniversitetet.
    Den nödvändiga distansträningen2014In: Svensk Idrottsforskning: Organ för Centrum för Idrottsforskning, ISSN 1103-4629, Vol. 23, no 3, p. 8-13Article in journal (Other academic)
    Abstract [sv]

    Korta och intensiva intervallpass är ett trendigt sätt att förbättra sin kondition. Men för att bli en bra löpare, längdåkare eller cyklist måste man träna många långa pass i ett lägre tempo. Forskning har visat att högintensiv intervallträning är tidseffektiv och ger bra effekt på många parametrar som är viktiga för konditionsidrottare. Tanken att ersätta nötandet i spåret med kort och snabb träning kan därför låta lockande. Men fullt så enkelt är det inte. Idrottsfysiologerna Mikael Mattsson, Filip Larsen och H-C Holmberg har studerat den forskning som finns om distansträning. Den visar att det inte går att komma runt den lågintensiva träningen om man vill bli en riktigt bra löpare, orienterare, längdskidåkare eller cyklist. På maraton finns till exempel ett nästan linjärt förhållande mellan träningsmängd och prestation. Ju fler mil löparen tränar i veckan desto bättre blir tiden. Kanske räcker det med att studera hur eliten tränar för att förstå distansträningens betydelse. Visserligen är den intensiva intervallträningen viktig även för dem, särskilt inför viktiga tävlingar. Men upp till 90 procent av den totala träningstiden eller minst 3-4 timmar per dag ägnar de åt mer lågintensiva pass.

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  • 49.
    Mattsson, C. Mikael
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Ståhlberg, Marcus
    Institutionen för Medicin, Enheten för kardiologi, Karolinska Universitetssjukhuset.
    Larsen, Filip
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Braunschweig, Frieder
    Institutionen för Medicin, Enheten för kardiologi, Karolinska Universitetssjukhuset.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Late cardiovascular drift observable during ultra endurance exercise.2011In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 43, no 7, p. 1162-1168Article in journal (Refereed)
    Abstract [en]

    Introduction: The present study investigates the adaptation of the central circulation to ultraenduranceexercise, including the relative contributions of changes in stroke volume (SV) andarterio-venous oxygen difference (a-v O2 diff) to the increased oxygen pulse (VO2/HR).Methods: We evaluated subjects undergoing 12h of mixed exercise at controlled intensity(n=8) and a 53h Adventure race (n=20). Heart rate (HR), oxygen uptake (VO2), and cardiacoutput determined using non-invasive gas rebreathing (CORB) were measured during cyclingat fixed work rate after 0, 4, 8, 12 hours, and 0, 20, and 53 hours of continuous exercise in the12 and 53 h protocol, respectively.Results and Conclusion: The central circulation changed in several steps in response to ultraenduranceexercise. Compared to initial levels, VO2 was increased at every time-point measured.The increase was attributed to peripheral adaptations, confirmed by a close correlation betweenchange in VO2 and change in a-v O2 diff. The first step of the circulatory response was typical ofnormal (early) cardiovascular drift, with increased HR and concomitantly decreased SV andVO2/HR, occurring over the first 4-6 h. The second step, which continued until approximately 12h, included reversed HR-drift, with normalization of SV and VO2/HR. When exercise continueduntil 50 h late cardiovascular drift was noted, characterized by increased VO2/HR, (indicatingmore efficient energy distribution), decreased peripheral resistance, increased stroke volume, anddecreased work of the heart. Since cardiac output was maintained at all time points we interpretthe changes as physiologically appropriate adaptations to ultra-endurance exercise.

  • 50.
    Mattsson, Mikael
    et al.
    Karolinska institutet.
    Larsen, Filip J
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Ashley, Euan
    Stanford University.
    Montgomery, Darren
    Waggot, Daryl
    Individen i idrotten2019In: Idrott och Kunskap, ISSN 1652-6961, Vol. 5, no 5, p. 14-21Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Sedan urminnes tider har det varit känt att olika träningsupplägg fungerar bättre för vissa idrottare än för andra. Med modern datainsamling och analytiska tekniker kan vi integrera mätvärden från träning, prestation och resultat, samt subjektiva och biologiska markörer så att de från en sammantagen bild kan ge rekommendationer anpassade till den specifika individen. Detta gör att idrottarna inte bara kan träna, återhämta sig mer effektivt och prestera bättre, utan även undvika skador och sjukdomar.

    Artikeln belyser att många professionella team samlar in så mycket mätvärden att de lider av en ”data-tsunami”, och hur den senaste vetenskapen och analytiska metoder, inklusive AI och djupinlärning, kan optimera datainsamling och analys för att minimera skador och förbättra prestationen.

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