| 1. |
- Andersson, Eva A, et al.
(författare)
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Improving Strength, Power, Muscle Aerobic Capacity, and Glucose Tolerance through Short-term Progressive Strength Training Among Elderly People.
- 2017
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Ingår i: Journal of Visualized Experiments. - : MyJove Corporation. - 1940-087X. ; :125
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Tidskriftsartikel (refereegranskat)abstract
- This protocol describes the simultaneous use of a broad span of methods to examine muscle aerobic capacity, glucose tolerance, strength, and power in elderly people performing short-term resistance training (RET). Supervised progressive resistance training for 1 h three times a week over 8 weeks was performed by RET participants (71±1 years, range 65-80). Compared to a control group without training, the RET showed improvements on the measures used to indicate strength, power, glucose tolerance, and several parameters of muscle aerobic capacity. Strength training was performed in a gym with only robust fitness equipment. An isokinetic dynamometer for knee extensor strength permitted the measurement of concentric, eccentric, and static strength, which increased for the RET group (8-12% post- versus pre-test). The power (rate of force development, RFD) at the initial 0-30 ms also showed an increase for the RET group (52%). A glucose tolerance test with frequent blood glucose measurements showed improvements only for the RET group in terms of blood glucose values after 2 h (14%) and the area under the curve (21%). The blood lipid profile also improved (8%). From muscle biopsy samples prepared using histochemistry, the amount of fiber type IIa increased, and a trend towards a decrease in IIx in the RET group reflected a change to a more oxidative profile in terms of fiber composition. Western blot (to determine the protein content related to the signaling for muscle protein synthesis) showed a rise of 69% in both Akt and mTOR in the RET group; this also showed an increase in mitochondrial proteins for OXPHOS complex II and citrate synthase (both ~30%) and for complex IV (90%), in only the RET group. We demonstrate that this type of progressive resistance training offers various improvements (e.g., strength, power, aerobic capacity, glucose tolerance, and plasma lipid profile).
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| 2. |
- Apró, William, 1980-, et al.
(författare)
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Endurance Exercise Does Not Impair mTOR Signalling After Resistance Exercise : D-58 Thematic Poster - Skeletal Muscle Cell Signaling: JUNE 2, 2011 3:15 PM - 5:15 PM: ROOM: 304
- 2011
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Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 43:5, s. 52-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Resistance exercise is known to stimulate muscle hypertrophy and this effect is mainly mediated by the mammalian target of rapamycin (mTOR) pathway. In contrast, endurance exercise results in a divergent phenotypic response which to a large extent is mediated by adenosine monophosphate-activated protein kinase (AMPK). Research indicates that molecular interference may exist, possibly through an inhibitory effect on mTOR signalling by AMPK, when these two modes of exercise are combined. PURPOSE: To investigate the impact of subsequent endurance exercise on resistance exercise induced mTOR signalling. METHODS: In a randomized and cross-over fashion, ten male subjects performed either heavy resistance exercise (R) or heavy resistance exercise followed by endurance exercise (RE) on two separate occasions. The R protocol consisted of thirteen sets of leg press exercise with 3 minutes of recovery allowed between each set. In the RE session, resistance exercise was followed by 15 minutes recovery after which 30 min of cycling was initiated at an intensity equal to 70 % of the subjects' maximal oxygen consumption. Muscle biopsies were collected before, 1 and 3 hours after resistance exercise in both trials. Samples were analyzed for several signalling proteins in the mTOR pathway using western blot technique. RESULTS: Phosphorylation of mTOR increased approx. twofold at 1 h post resistance exercise and remained elevated at the 3 h time point (p< 0.01) with no difference between the two trials. Phosphorylation of p70S6k, a downstream target of mTOR, was increased about 6-and18-fold at 1 h and 3 h post resistance exercise (p< 0.01). There was no difference in p70S6k phosphorylation at any time point between the two trials. Phosphorylation of the eukaryotic elongation factor eEF2 was decreased 3- to 4-fold at both time points post resistance exercise (p< 0.01) with no difference between trials. Phosphorylation of AMPK was unchanged at the 1 h time point but decreased approximately 30 % from pre-exercise values in both trials at 3 h post resistance exercise (p< 0.01). CONCLUSIONS: The signalling response following heavy resistance exercise is not blunted by subsequent endurance exercise. Supported by the Swedish National Centre for Research in Sports.
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| 3. |
- Apró, William, et al.
(författare)
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Resistance exercise induced mTORC1 signaling is not impaired by subsequent endurance exercise in human skeletal muscle.
- 2013
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 305:1, s. E22-32
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Tidskriftsartikel (refereegranskat)abstract
- The current dogma is that the muscle adaptation to resistance exercise is blunted when combined with endurance exercise. The suggested mechanism (based on rodent experiments) is that activation of adenosine monophosphate-activated protein kinase (AMPK) during endurance exercise impairs muscle growth through inhibition of the mechanistic target of rapamycin complex 1 (mTORC1). The purpose of this study was to investigate potential interference of endurance training on the signaling pathway of resistance training [mTORC1 phosphorylation of ribosomal protein S6 kinase 1 (S6K1)] in human muscle. Ten healthy and moderately trained male subjects performed on two separate occasions either acute high-intensity and high-volume resistance exercise (leg press, R) or R followed by 30 min of cycling (RE). Muscle biopsies were collected before and 1 and 3 h post resistance exercise. Phosphorylation of mTOR (Ser(2448)) increased 2-fold (P < 0.05) and that of S6K1 (Thr(389)) 14-fold (P < 0.05), with no difference between R and RE. Phosphorylation of eukaryotic elongation factor 2 (eEF2, Thr(56)) was reduced ∼70% during recovery in both trials (P < 0.05). An interesting finding was that phosphorylation of AMPK (Thr(172)) and acetyl-CoA carboxylase (ACC, Ser(79)) decreased ∼30% and ∼50%, respectively, 3 h postexercise (P < 0.05). Proliferator-activated receptor-γ coactivator-1 (PGC-1α) mRNA increased more after RE (6.5-fold) than after R (4-fold) (RE vs. R: P < 0.01) and was the only gene expressed differently between trials. These data show that the signaling of muscle growth through the mTORC1-S6K1 axis after heavy resistance exercise is not inhibited by subsequent endurance exercise. It is also suggested that prior activation of mTORC1 signaling may repress subsequent phosphorylation of AMPK.
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| 4. |
- Bakkman, L., et al.
(författare)
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Quantitative and qualitative adaptation of human skeletal muscle mitochondria to hypoxic compared to normoxic training at the same relative work rate
- 2007
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Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X .- 1748-1708 .- 1748-1716. ; 190:3, s. 243-251
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate if training during hypoxia (H) improves the adaptation of muscle oxidative function compared with normoxic (N) training performed at the same relative intensity.Method: Eight untrained volunteers performed one-legged cycle training during 4 weeks in a low-pressure chamber. One leg was trained under N conditions and the other leg under hypobaric hypoxia (526 mmHg) at the same relative intensity as during N (65% of maximal power output, Wmax). Muscle biopsies were taken from vastus lateralis before and after the training period. Muscle samples were analysed for the activities of oxidative enzymes [citrate synthase (CS) and cytochrome c oxidase (COX)] and mitochondrial respiratory function.Results: W max increased with more than 30% over the training period during both N and H. CS activity increased significantly after training during N conditions (+20.8%, P < 0.05) but remained unchanged after H training (+4.5%, ns) with a significant difference between conditions (P < 0.05 H vs. N). COX activity was not significantly changed by training and was not different between exercise conditions [+14.6 (N) vs. -2.3% (H), ns]. Maximal ADP stimulated respiration (state 3) expressed per weight of muscle tended to increase after N (+31.2%, P < 0.08) but not after H training (+3.2%, ns). No changes were found in state four respiration, respiratory control index, P/O ratio, mitochondrial Ca2+ resistance and apparent Km for oxygen.Conclusion: The training-induced increase in muscle oxidative function observed during N was abolished during H. Altitude training may thus be disadvantageous for adaptation of muscle oxidative function.
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| 5. |
- Berthelson, Per, et al.
(författare)
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Acute exercise and starvation induced insulin resistance
- 2012
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Ingår i: Medicine & Science In Sports & Exercise, 2012, S498 Vol. 44 No. 5 Supplement. 2661.. ; , s. 2661-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- It is well known that starvation causes insulin resistance. The mechanism is unclear but may relate disturbances in lipid metabolism i.e. incomplete mitochondrial FA oxidation and/or accumulation of lipid intermediates. Exercise results in increased substrate oxidation and may thus remove interfering lipid metabolites and reverse starvation-induced insulin resistance. However, the effect of acute exercise and starvation on insulin sensitivity is not known.Purpose: The aim of this study was to investigate the effect of exercise on starvation-induced insulin resistance and to elucidate potential mechanisms.Methods: Nine healthy lean subjects underwent 84h starvation on two occasions separated by at least 2 weeks. The starvation period was followed by either exercise (EX; 5x10 min intervals with 2-4 min rest, starting at 70 %VO2 max) or an equal period of rest (NE). Before and after the starvation period (3h after exercise/rest) subjects were investigated with muscle biopsies, bloo samples and an intravenous glucose tolerance test. Muscle samples were used for measurement of mitochondrial respiration in permeabilized muscle fibers (Oroboros oxygraph), glycogen content and activation of signaling proteins.Results: Insulin sensitivity was significantly higher in the EX group compared to the NE group (p<0.05). After starvation mitochondrial respiration was lower in both groups with complex I substrates whereas respiration with complex I+II substrates was higher in EX (p<0.05 vs. basal and NE). Muscle glycogen was decreased to 73% (NE) and 31% (EX) of the basal values. The EX group had a significant increased activation of AS160. Plasma FA increased 3-4 fold to 1.39±0.32(NE) and 1.80±0.49 (EX) (mmol/l) after starvation and plasma beta-hydroxybutyrate increased about 50-fold to 6.43±2.01(NE) and 7.12±1.59 (EX)(mmol/l).Conclusion: Acute exercise reverses starvation-induced insulin resistance. Plasma FA and BOH were increased to similar extent after NE and EX and cannot explain the changes in insulin sensitivity. However, an increased substrate oxidation together with the observed increased capacity for mitochondrial FA oxidation after EX may be involved in the activation of AS160 and the reversal of starvation-induced insulin resistance.
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| 6. |
- Bishop, David J, et al.
(författare)
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Sodium bicarbonate ingestion prior to training improves mitochondrial adaptations in rats.
- 2010
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 299:2, s. E225-33
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Tidskriftsartikel (refereegranskat)abstract
- We tested the hypothesis that reducing hydrogen ion accumulation during training would result in greater improvements in muscle oxidative capacity and time to exhaustion (TTE). Male Wistar rats were randomly assigned to one of three groups (CON, PLA, and BIC). CON served as a sedentary control, whereas PLA ingested water and BIC ingested sodium bicarbonate 30 min prior to every training session. Training consisted of seven to twelve 2-min intervals performed five times/wk for 5 wk. Following training, TTE was significantly greater in BIC (81.2 +/- 24.7 min) compared with PLA (53.5 +/- 30.4 min), and TTE for both groups was greater than CON (6.5 +/- 2.5 min). Fiber respiration was determined in the soleus (SOL) and extensor digitorum longus (EDL), with either pyruvate (Pyr) or palmitoyl carnitine (PC) as substrates. Compared with CON (14.3 +/- 2.6 nmol O(2).min(-1).mg dry wt(-1)), there was a significantly greater SOL-Pyr state 3 respiration in both PLA (19.6 +/- 3.0 nmol O(2).min(-1).mg dry wt(-1)) and BIC (24.4 +/- 2.8 nmol O(2).min(-1).mg dry wt(-1)), with a significantly greater value in BIC. However, state 3 respiration was significantly lower in the EDL from both trained groups compared with CON. These differences remained significant in the SOL, but not the EDL, when respiration was corrected for citrate synthase activity (an indicator of mitochondrial mass). These novel findings suggest that reducing muscle hydrogen ion accumulation during running training is associated with greater improvements in both mitochondrial mass and mitochondrial respiration in the soleus.
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| 7. |
- Boushel, Robert, et al.
(författare)
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Mitochondrial plasticity with exercise training and extreme environments.
- 2014
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Ingår i: Exercise and sport sciences reviews. - 0091-6331 .- 1538-3008. ; 42:4, s. 169-74
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondria form a reticulum in skeletal muscle. Exercise training stimulates mitochondrial biogenesis, yet an emerging hypothesis is that training also induces qualitative regulatory changes. Substrate oxidation, oxygen affinity, and biochemical coupling efficiency may be regulated differentially with training and exposure to extreme environments. Threshold training doses inducing mitochondrial upregulation remain to be elucidated considering fitness level.
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| 8. |
- Fernström, Maria, et al.
(författare)
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Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle.
- 2004
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Ingår i: Journal of Physiology. - 0022-3751 .- 1469-7793. ; 554, s. 755-763
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial proteins such as uncoupling protein 3 (UCP3) and adenine nucleotide translocase (ANT) may mediate back-leakage of protons and serve as uncouplers of oxidative phosphorylation. We hypothesized that UCP3 and ANT increase after prolonged exercise and/or endurance training, resulting in increased uncoupled respiration (UCR). Subjects were investigated with muscle biopsies before and after acute exercise (75 min of cycling at 70% of .VO2peak) or 6 weeks endurance training. Mitochondria were isolated and respiration measured in the absence (UCR or state 4) and presence of ADP (coupled respiration or state 3). Protein expression of UCP3 and ANT was measured with Western blotting. After endurance training, .VO2peak, citrate synthase activity (CS), state 3 respiration and ANT increased by 24, 47, 40 and 95%, respectively (all P < 0.05), whereas UCP3 remained unchanged. When expressed per unit of CS (a marker of mitochondrial volume) UCP3 and UCR decreased by 54% and 18%(P < 0.05). CS increased by 43% after acute exercise and remained elevated after 3 h of recovery (P < 0.05), whereas the other muscle parameters remained unchanged. An intriguing finding was that acute exercise reversibly enhanced the capacity of mitochondria to accumulate Ca2+(P < 0.05) before opening of permeability transition pores. In conclusion, UCP3 protein and UCR decrease after endurance training when related to mitochondrial volume. These changes may prevent excessive basal thermogenesis. Acute exercise enhances mitochondrial resistance to Ca2+ overload but does not influence UCR or protein expression of UCP3 and ANT. The increased Ca2+ resistance may prevent mitochondrial degradation and the mechanism needs to be further explored.
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| 9. |
- Fernström, Maria, et al.
(författare)
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Effects of acute and chronic exercise on mitochondrial uncoupling in human skeletal muscle
- 2004
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Ingår i: Journal of Physiology. - 0022-3751 .- 1469-7793. ; 554:3, s. 755-763
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial proteins such as uncoupling protein 3 (UCP3) and adenine nucleotide translocase (ANT) may mediate back-leakage of protons and serve as uncouplers of oxidative phosphorylation. We hypothesized that UCP3 and ANT increase after prolonged exercise and/or endurance training, resulting in increased uncoupled respiration (UCR). Subjects were investigated with muscle biopsies before and after acute exercise (75 min of cycling at 70% of ) or 6 weeks endurance training. Mitochondria were isolated and respiration measured in the absence (UCR or state 4) and presence of ADP (coupled respiration or state 3). Protein expression of UCP3 and ANT was measured with Western blotting. After endurance training , citrate synthase activity (CS), state 3 respiration and ANT increased by 24, 47, 40 and 95%, respectively (all P< 0.05), whereas UCP3 remained unchanged. When expressed per unit of CS (a marker of mitochondrial volume) UCP3 and UCR decreased by 54% and 18%(P < 0.05). CS increased by 43% after acute exercise and remained elevated after 3 h of recovery (P < 0.05), whereas the other muscle parameters remained unchanged. An intriguing finding was that acute exercise reversibly enhanced the capacity of mitochondria to accumulate Ca2+(P < 0.05) before opening of permeability transition pores. In conclusion, UCP3 protein and UCR decrease after endurance training when related to mitochondrial volume. These changes may prevent excessive basal thermogenesis. Acute exercise enhances mitochondrial resistance to Ca2+ overload but does not influence UCR or protein expression of UCP3 and ANT. The increased Ca2+ resistance may prevent mitochondrial degradation and the mechanism needs to be further explored.
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| 10. |
- Fernström, Maria
(författare)
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Effects of endurance exercise on mitochondrial efficiency, uncoupling and lipid oxidation in human skeletal muscle
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the last years the importance of muscle mitochondria, and mitochondrial function, not only for performance but also for health has been highlighted. The main function of the mitochondria is to produce ATP by oxidative phosphorylation (coupled respiration). In skeletal muscle a substantial part of the energy is lost in non-coupled reactions, it has been estimated that non-coupled respiration accounts for as much as 20-25% of the total energy expenditure. It is now almost 10 years since the discovery of uncoupling protein 3 (UCP3), but the functional role of UCP3 in non-coupled respiration is not completely understood. The aim of this thesis was to investigate mitochondrial efficiency (P/O ratio), mitochondrial fat oxidation, non-coupled respiration (state 4) and protein expression of UCP3 in response to exercise and training in human skeletal muscle.In study I eight healthy subjects endurance trained for 6 weeks and 9 subjects performed one exercise session (75 min). In the cycling efficiency study II, and in the study on mitochondrial lipid oxidation III, 9 healthy trained and 9 healthy untrained men participated. In study IV mitochondrial function and reactive oxygen species (ROS) production was studied in 9 elite athletes after extreme exercise, 24 hours of cycling, running and paddling.Endurance training increased whole body oxygen uptake (VO2 peak) by 24% and muscle citrate synthase (CS) activity (marker of mitochondrial volume) by 47% (P< 0.05), but non-coupled respiration and UCP3 adjusted for mitochondrial volume were reduced (P< 0.05). One session of exercise did not affect non-coupled respiration or UCP3.Cycling efficiency (expressed as work efficiency) was inversely related to protein expression of UCP3 (r= 0.57) and correlated to type 1 fibers (r= 0.58). Work efficiency was not influenced by training status or correlated to mitochondrial efficiency. UCP3 was 52% higher in the untrained men (P< 0.05). Mitochondrial capacity for fat oxidation was not influenced by training status, but related to fiber type composition. The hypothesis that mitochondrial fat oxidation is related to whole body lipid oxidation during low-intensity exercise was confirmed (r= 0.62).Mitochondrial capacity for fat oxidation increased after 24 hours of exercise, whereas mitochondrial efficiency (P/O ratio) decreased. P/O ratio remained reduced also after 28 hours of recovery. Formation of ROS by isolated mitochondria increased after exercise. Non-coupled respiration (state 4), however, decreased and UCP3 tended to be reduced after recovery from ultra-endurance exercise (P= 0.07).In conclusion: UCP3 does not follow exercise induced mitochondrial biogenesis. UCP3 is reduced by endurance training and lower in trained men compared with untrained men. Non-coupled respiration, measured in isolated mitochondria was reduced by endurance training and reduced after recovery from ultra-endurance exercise, but similar in trained and untrained men. In these studies UCP3 and non-coupled respiration follow the same pattern but are not correlated. Further studies are needed to understand the complex role of UCP3 in skeletal muscle metabolism.
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| 11. |
- Fernström, Maria, et al.
(författare)
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Four weeks of speed endurance training reduces energy expenditure during exercise and maintains muscle oxidative capacity despite a reduction in training volume
- 2009
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Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 106:1, s. 73-80
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Tidskriftsartikel (refereegranskat)abstract
- We studied the effect of an alteration from regular endurance to speed endurance training on muscle oxidative capacity, capillarization, as well as energy expenditure during submaximal exercise and its relationship to mitochondrial uncoupling protein 3 (UCP3) in humans. Seventeen endurance-trained runners were assigned to either a speed endurance training (SET; n = 9) or a control (Con; n = 8) group. For a 4-wk intervention (IT) period, SET replaced the ordinary training (∼45 km/wk) with frequent high-intensity sessions each consisting of 8–12 30-s sprint runs separated by 3 min of rest (5.7 ± 0.1 km/wk) with additional 9.9 ± 0.3 km/wk at low running speed, whereas Con continued the endurance training. After the IT period, oxygen uptake was 6.6, 7.6, 5.7, and 6.4% lower ( P < 0.05) at running speeds of 11, 13, 14.5, and 16 km/h, respectively, in SET, whereas remained the same in Con. No changes in blood lactate during submaximal running were observed. After the IT period, the protein expression of skeletal muscle UCP3 tended to be higher in SET (34 ± 6 vs. 47 ± 7 arbitrary units; P = 0.06). Activity of muscle citrate synthase and 3-hydroxyacyl-CoA dehydrogenase, as well as maximal oxygen uptake and 10-km performance time, remained unaltered in both groups. In SET, the capillary-to-fiber ratio was the same before and after the IT period. The present study showed that speed endurance training reduces energy expenditure during submaximal exercise, which is not mediated by lowered mitochondrial UCP3 expression. Furthermore, speed endurance training can maintain muscle oxidative capacity, capillarization, and endurance performance in already trained individuals despite significant reduction in the amount of training.
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| 12. |
- Fernström, Maria, et al.
(författare)
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Reduced efficiency, but increased fat oxidation, in mitochondria from human skeletal muscle after 24-h ultraendurance exercise.
- 2007
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 102:5, s. 1844-1849
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Tidskriftsartikel (refereegranskat)abstract
- The hypothesis that ultraendurance exercise influences muscle mitochondrial function has been investigated. Athletes in ultraendurance performance performed running, kayaking, and cycling at 60% of their peak O(2) consumption for 24 h. Muscle biopsies were taken preexercise (Pre-Ex), postexercise (Post-Ex), and after 28 h of recovery (Rec). Respiration was analyzed in isolated mitochondria during state 3 (coupled to ATP synthesis) and state 4 (noncoupled respiration), with fatty acids alone [palmitoyl carnitine (PC)] or together with pyruvate (Pyr). Electron transport chain activity was measured with NADH in permeabilized mitochondria. State 3 respiration with PC increased Post-Ex by 39 and 41% (P < 0.05) when related to mitochondrial protein and to electron transport chain activity, respectively. State 3 respiration with Pyr was not changed (P > 0.05). State 4 respiration with PC increased Post-Ex but was lower than Pre-Ex at Rec (P < 0.05 vs. Pre-Ex). Mitochondrial efficiency [amount of added ADP divided by oxygen consumed during state 3 (P/O ratio)] decreased Post-Ex by 9 and 6% (P < 0.05) with PC and PC + Pyr, respectively. P/O ratio remained reduced at Rec. Muscle uncoupling protein 3, measured with Western blotting, was not changed Post-Ex but tended to decrease at Rec (P = 0.07 vs. Pre-Ex). In conclusion, extreme endurance exercise decreases mitochondrial efficiency. This will increase oxygen demand and may partly explain the observed elevation in whole body oxygen consumption during standardized exercise (+13%). The increased mitochondrial capacity for PC oxidation indicates plasticity in substrate oxidation at the mitochondrial level, which may be of advantage during prolonged exercise.
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| 13. |
- Fernström, Maria, et al.
(författare)
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Skeletal muscle mitochondrial function and ROS production in response to extreme endurance exercise in athletes.
- 2006
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Ingår i: 14 European bioenergetic conference, Moscow, Russia, 22-27 July, 2006.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Although it is well known that endurance exercise induces oxidative stress (1) there is no evidence of deteriorated mitochondrial function after 1-2 hours intensive exercise (2). However, the effects of extreme endurance exercise on mitochondrial function and mitochondrial ROS production have not been investigated previously. Nine healthy well-trained men (age 27.1 ± 0.87 (mean ± SE), BMI 24.2 ± 0.64 and VO2 peak 62.5 ± 1.78 ml/kg. min) performed 24 hours exercise, consisting of equal parts running, cycling and paddling. Muscle biopsies were taken from vastus lateralis pre-exercise (PreEx), immediately post-exercise (PostEx) and after 28 hours of recovery (PostEx-28). Mitochondria were isolated and mitochondrial respiration was analyzed with palmitoyl-carnitine (PC) and pyruvate (Pyr). Mitochondrial H2O2 release was measured with the Amplex Red-horseradish peroxide method. The reaction was initiated by addition of succinate with following addition of antimycin A (reversed electron flow). UCP3 protein expression, evaluated with western blot technique, was not changed by exercise. Both state 3 (Pyr and PC) and state 4 (PC) rates of oxygen consumption (estimated per maximal ETC-activity) were increased PostEx (+29%, +11% and +18%). State 3 remained elevated PostEx-28, whereas state 4 (Pyr) decreased below that at PreEx (-18%). Mitochondrial efficiency (P/O) decreased PostEx (Pyr -8.9%, PC -6.1%) and remained reduced PostEx-28. The relative substrate oxidation (state 3 PC/Pyr) increased after exercise PreEx: (0.71 ± 0.06 vs. PostEx (0.90 ±0.04) and (0.77 ±0.06) PostEx-28. Mitochondrial H2O2 release (succinate) increased dramatically after exercise (+189 ± 64%). Treatment with Antimycin A resulted in a twofold-increased rate of mitochondrial H2O2 release PreEx but a decreased rate in PostEx samples. The exercise-induced changes in mitochondrial ROS production was totally abolished PostEx-28. In conclusion extreme endurance exercise decreases mitochondrial efficiency and increases mitochondrial ROS production. Both of these changes would increase the oxygen demand during exercise. Relative fatty acid oxidation as measured in isolated mitochondria increased after exercise indicating that the capacity to oxidize fat is improved during prolonged exercise.1. Mastaloudis, A., S.W. Leonard, and M.G. Traber, Oxidative stress in athletes during extreme endurance exercise. Free Radic Biol Med, 2001. 31(7): p. 911-22.2. Tonkonogi, M., et al., Mitochondrial function and antioxidative defence in human muscle: effects of endurance training and oxidative stress. J Physiol, 2000. 528 Pt 2: p. 379-88.
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| 14. |
- Fernström, Maria, et al.
(författare)
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The potential for mitochondrial fat oxidation in human skeletal muscle influences whole body fat oxidation during low-intensity exercise
- 2007
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 292:1, s. E223-30
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate fatty acid (FA) oxidation in isolated mitochondrial vesicles (mit) and its relation to training status, fiber type composition, and whole body FA oxidation. Trained (Vo(2 peak) 60.7 +/- 1.6, n = 8) and untrained subjects (39.5 +/- 2.0 ml.min(-1).kg(-1), n = 5) cycled at 40, 80, and 120 W, and whole body relative FA oxidation was assessed from respiratory exchange ratio (RER). Mit were isolated from muscle biopsies, and maximal ADP stimulated respiration was measured with carbohydrate-derived substrate [pyruvate + malate (Pyr)] and FA-derived substrate [palmitoyl-l-carnitine + malate (PC)]. Fiber type composition was determined from analysis of myosin heavy-chain (MHC) composition. The rate of mit oxidation was lower with PC than with Pyr, and the ratio between PC and Pyr oxidation (MFO) varied greatly between subjects (49-93%). MFO was significantly correlated to muscle fiber type distribution, i.e., %MHC I (r = 0.62, P = 0.03), but was not different between trained (62 +/- 5%) and untrained subjects (72 +/- 2%). MFO was correlated to RER during submaximal exercise at 80 (r = -0.62, P = 0.02) and 120 W (r = -0.71, P = 0.007) and interpolated 35% Vo(2 peak) (r = -0.74, P = 0.004). ADP sensitivity of mit respiration was significantly higher with PC than with Pyr. It is concluded that MFO is influenced by fiber type composition but not by training status. The inverse correlation between RER and MFO implies that intrinsic mit characteristics are of importance for whole body FA oxidation during low-intensity exercise. The higher ADP sensitivity with PC than that with Pyr may influence fuel utilization at low rate of respiration.
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| 15. |
- Frank, Per, et al.
(författare)
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Acute exercise during starvation improves insulin sensitivity and increases mitochondrial FA oxidation
- 2012
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To investigate if exercise can reverse starvation-induced insulin resistance and to elucidate the mechanism. Methods: Nine subjects underwent 87 h of starvation with (EX) or without (NE) one exercise session at the end. Before and after starvation (3 h post-exercise) subjects underwent an intravenous glucose tolerance test and muscle biopsy. Results: Insulin sensitivity decreased after starvation (NE) but increased after exercise (EX). Glycogen stores were reduced and plasma FA and β-Hydroxybutyrate increased in both conditions. Mitochondrial respiration with FA substrate increased in EX but was unchanged in NE. RCR and mitochondrial ROS production decreased in both conditions. Phosphorylation of Acetyl-CoA carboxylase (ACC) and Akt substrate of 160 kDA (AS160) proteins increased in EX. Conclusion: Exercise improves starvation induced insulin resistance, probably by increased mitochondrial FA oxidation, reduced glycogen stores and alterations in signaling proteins involved in glucose uptake and FA metabolism.
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| 16. |
- Frank, Per, et al.
(författare)
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Acute exercise reverses starvation-mediated insulin resistance in humans.
- 2013
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 304:4, s. E436-43
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Tidskriftsartikel (refereegranskat)abstract
- Within 2-3 days of starvation, pronounced insulin resistance develops, possibly mediated by increased lipid load. Here, we show that one exercise bout increases mitochondrial fatty acid (FA) oxidation and reverses starvation-induced insulin resistance. Nine healthy subjects underwent 75-h starvation on two occasions: with no exercise (NE) or with one exercise session at the end of the starvation period (EX). Muscle biopsies were analyzed for mitochondrial function, contents of glycogen, and phosphorylation of regulatory proteins. Glucose tolerance and insulin sensitivity, measured with an intravenous glucose tolerance test (IVGTT), were impaired after starvation, but in EX the response was attenuated or abolished. Glycogen stores were reduced, and plasma FA was increased in both conditions, with a more pronounced effect in EX. After starvation, mitochondrial respiration decreased with complex I substrate (NE and EX), but in EX there was an increased respiration with complex I + II substrate. EX altered regulatory proteins associated with increases in glucose disposal (decreased phosphorylation of glycogen synthase), glucose transport (increased phosphorylation of Akt substrate of 160 kDa), and FA oxidation (increased phosphorylation of acetyl-CoA carboxylase). In conclusion, exercise reversed starvation-induced insulin resistance and was accompanied by reduced glycogen stores, increased lipid oxidation capacity, and activation of signaling proteins involved in glucose transport and FA metabolism.
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| 17. |
- Frank, Per
(författare)
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Exercise strategies to improve aerobic capacity, insulin sensitivity and mitochondrial biogenesis
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Regular exercise plays a key role in the maintenance of health and physical capabilities. Extensive research shows that exercise is an efficient method to prevent diabetes. Both resistance and aerobic exercise training are well known countermeasures for insulin resistance. However, depending on factors like purpose, capability and accessibility, different exercise modes need to be evaluated on both applied and molecular levels. In addition, exercise is the means to improve performance. New training strategies have emerged, like training with low glycogen stores or combining strength with endurance training, and guidelines based on empirical data are needed. Although knowledge of exercise physiology has advanced, much more needs to be learned before we can exploit the full potential of exercise with regard to health and performance. Therefore, the overall aim of this thesis is to provide knowledge of how different exercise strategies improve performance and insulin sensitivity. The mitochondria represent a central part of this thesis considering their key role in both health and performance. Study I was an acute crossover investigation of the effect of exercise with low glycogen levels on markers of mitochondrial biogenesis. Study II investigated the effect of concurrent resistance and endurance training on mitochondrial density and endurance performance. Study III investigated the acute effect of exercise on starvation-induced insulin resistance. In Study IV, the effect of resistance exercise training on health and performance in the elderly was investigated. The main findings were:Training with low glycogen levels enhanced the response in markers of mitochondrial biogenesis.Adding resistance training to endurance training did not improve mitochondrial density or endurance performance in trained individuals. Resistance training for only eight weeks is an efficient strategy to improve strength, heart rate (HR) during submaximal cycling and glucose tolerance in elderly. It also improves muscular quality by increasing mitochondrial and hypertrophy signaling proteins. Starvation-induced insulin resistance is attenuated by exercise. Mitochondrial respiration and reactive oxygen species (ROS) production is reduced during starvation. Exercise during starvation reduced glycogen stores and resulted in the activation of enzymes involved in glucose metabolism.When exercise was performed during starvation there was an increase in markers for mitochondrial lipid oxidation.
In conclusion, training with low glycogen stores seems to be a promising strategy to increase mitochondrial density. In contrast to our previous acute findings, concurrent training had no effect on mitochondrial biogenesis or endurance performance. Exercise can reverse yet another mode of insulin resistance (starvation) which strengthens its role in the treatment for other states of insulin resistance, e.g. Type 2 diabetes (T2D). Resistance exercise training is an efficient and safe strategy for the elderly to improve health and performance.
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| 18. |
- Frank, Per, et al.
(författare)
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Strength training improves muscle aerobic capacity and glucose tolerance in elderly
- 2016
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 26:7, s. 764-773
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Tidskriftsartikel (refereegranskat)abstract
- The primary aim of this study was to investigate the effect of short-term resistance training (RET) on mitochondrial protein content and glucose tolerance in elderly. Elderly women and men (age 71 ± 1, mean ± SEM) were assigned to a group performing 8 weeks of resistance training (RET, n = 12) or no training (CON, n = 9). The RET group increased in (i) knee extensor strength (concentric +11 ± 3%, eccentric +8 ± 3% and static +12 ± 3%), (ii) initial (0-30 ms) rate of force development (+52 ± 26%) and (iii) contents of proteins related to signaling of muscle protein synthesis (Akt +69 ± 20 and mammalian target of rapamycin +69 ± 32%). Muscle fiber type composition changed to a more oxidative profile in RET with increased amount of type IIa fibers (+26.9 ± 6.8%) and a trend for decreased amount of type IIx fibers (-16.4 ± 18.2%, P = 0.068). Mitochondrial proteins (OXPHOS complex II, IV, and citrate synthase) increased in RET by +30 ± 11%, +99 ± 31% and +29 ± 8%, respectively. RET resulted in improved oral glucose tolerance measured as reduced area under curve for glucose (-21 ± 26%) and reduced plasma glucose 2 h post-glucose intake (-14 ± 5%). In CON parameters were unchanged or impaired. In conclusion, short-term resistance training in elderly not only improves muscular strength, but results in robust increases in several parameters related to muscle aerobic capacity.
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| 19. |
- Gejl, K. D., et al.
(författare)
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Muscle glycogen content modifies SR Ca2+ release rate in elite endurance athletes
- 2014
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Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 46:3, s. 496-505
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of the present study was to investigate the influence of muscle glycogen content on sarcoplasmic reticulum (SR) function and peak power output (Wpeak) in elite endurance athletes. Methods: Fourteen highly trained male triathletes (V̇O2max = 66.5 ± 1.3 mL O2·kg·min), performed 4 h of glycogen-depleting cycling exercise (HRmean = 73% ± 1% of maximum). During the first 4 h of recovery, athletes received either water (H2O) or carbohydrate (CHO), separating alterations in muscle glycogen content from acute changes affecting SR function and performance. Thereafter, all subjects received CHO-enriched food for the remaining 20-h recovery period. Results: Immediately after exercise, muscle glycogen content and SR Ca release rate was reduced to 32% ± 4% (225 ± 28 mmol·kg dw) and 86% ± 2% of initial levels, respectively (P < 0.01). Glycogen markedly recovered after 4 h of recovery with CHO (61% ± 2% of preexercise) and SR Ca release rate returned to preexercise level. However, in the absence of CHO during the first 4 h of recovery, glycogen and SR Ca release rate remained depressed, with the normalization of both parameters at the end of the 24 h of recovery after receiving a CHO-enriched diet. Linear regression demonstrated a significant correlation between SR Ca release rate and muscle glycogen content (P < 0.01, r = 0.30). The 4 h of cycling exercise reduced Wpeak by 5.5%-8.9% at different cadences (P < 0.05), and Wpeak was normalized after 4 h of recovery with CHO, whereas Wpeak remained depressed (P < 0.05) after water provision. Wpeak was fully recovered after 24 h in both the H2O and the CHO group. Conclusion: In conclusion, the present results suggest that low muscle glycogen depresses muscle SR Ca release rate, which may contribute to fatigue and delayed recovery of Wpeak 4 h postexercise. © 2014 by the American College of Sports Medicine.
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| 20. |
- Hawke, Emma, et al.
(författare)
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Effects of induced changes in acid-base balance on mitochondrial adaptations to training
- 2014
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Ingår i: Book of Abstracts of the 19th annual congress of the European College of Sport Science – ECSS Amsterdam 2014. - European College of Sport Science.
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Konferensbidrag (refereegranskat)abstract
- IntroductionEndurance training leads to an improved ability of muscle to utilize oxygen. This is related to an increased density and function of mitochondria. The biogenesis and adaptation of mitochondria is a complex process mediated by various signalling pathways and seems to be highly sensitive to the type of exercise and the local environment in the muscle. Changes in the muslce environment in terms of altered metabolism and substrate accumulation are affected by changes in acid/base balance in response to exercise. Recent studies have shown that changes in acid/base balance may affect the regulation of mitochondrial adaptation to acute exercise; however, how this responds to training and relates to performance adaptations in humans is unclear. Similarly, the effect of acid/base balance on mechanisms underlying mitochondrial biogenesis is unclear. The objectives of this study were to examine the relationship between acid/base balance, mitochondrial biogenesis and adaptation.MethodsNineteen recreationally active men undertook a six-week periodised high-intensity interval training programme, a protocol known to produce increases in mitochondrial biogenesis. Participants were matched for aerobic fitness and randomly assigned to one of two different training groups. One group ingested sodium bicarbonate (alkaline) and the other group ingested a placebo prior to each training session. Performance test results, blood samples and muscle biopsies were collected before and after the six week training period and assessed for changes in aerobic fitness, blood metabolites and muscle markers of mitochondrial function and biogenesis. Changes in gene expression associated with mitochondrial biogenesis were also examined. ResultsAfter the training period, there were significant (P < 0.05) improvements in TTF, Wmax and LT in both groups, citrate synthase activity in the alkaline group and VO2peak in the placebo group. Improvements were also seen in citrate synthase activity in the placebo group and VO2peak in the alkaline group, however these did not reach significance (P = 0.089 and 0.066 respectively).Despite these significant changes within groups in response to training, there were no significant differences between groups.DiscussionBoth training groups showed substantial changes in performance and physiological measures following the training period, however, suppressing exercise-induced acidosis during training did not significantly improve mitochondrial adaptations or performance in comparison to the placebo condition. However, there was a large degree of individual variation in the response and there were trends towards greater adaptations when exercise-induced acidosis was attenuated.
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| 21. |
- Hey-Mogensen, M, et al.
(författare)
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Effect of physical training on mitochondrial respiration and reactive oxygen species release in skeletal muscle in patients with obesity and type 2 diabetes.
- 2010
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 53:9, s. 1976-85
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Tidskriftsartikel (refereegranskat)abstract
- AIM/HYPOTHESIS: Studies have suggested a link between insulin resistance and mitochondrial dysfunction in skeletal muscles. Our primary aim was to investigate the effect of aerobic training on mitochondrial respiration and mitochondrial reactive oxygen species (ROS) release in skeletal muscle of obese participants with and without type 2 diabetes. METHODS: Type 2 diabetic men (n = 13) and control (n = 14) participants matched for age, BMI and physical activity completed 10 weeks of aerobic training. Pre- and post-training muscle biopsies were obtained before a euglycaemic-hyperinsulinaemic clamp and used for measurement of respiratory function and ROS release in isolated mitochondria. RESULTS: Training significantly increased insulin sensitivity, maximal oxygen consumption and muscle mitochondrial respiration with no difference between groups. When expressed in relation to a marker of mitochondrial density (intrinsic mitochondrial respiration), training resulted in increased mitochondrial ADP-stimulated respiration (with NADH-generating substrates) and decreased respiration without ADP. Intrinsic mitochondrial respiration was not different between groups despite lower insulin sensitivity in type 2 diabetic participants. Mitochondrial ROS release tended to be higher in participants with type 2 diabetes. CONCLUSIONS/INTERPRETATION: Aerobic training improves muscle respiration and intrinsic mitochondrial respiration in untrained obese participants with and without type 2 diabetes. These adaptations demonstrate an increased metabolic fitness, but do not seem to be directly related to training-induced changes in insulin sensitivity.
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| 22. |
- Jensen, Line, et al.
(författare)
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Carbohydrate restricted recovery from long term endurance exercise does not affect gene responses involved in mitochondrial biogenesis in highly trained athletes
- 2015
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to determine if the metabolic adaptations, particularly PGC-1a and downstream metabolic genes were affected by restricting CHO following an endurance exercise bout in trained endurance athletes. A second aim was to compare baseline expression level of these genes to untrained. Elite endurance athletes (VO2max 66 ± 2 mL·kg-1·min-1, n = 15) completed 4 h cycling at ~56% VO2max. During the first 4 h recovery subjects were provided with either CHO or only H2O and thereafter both groups received CHO. Muscle biopsies were collected before, after, and 4 and 24 h after exercise. Also, resting biopsies were collected from untrained subjects (n = 8). Exercise decreased glycogen by 67.7 ± 4.0% (from 699 ± 26.1 to 239 ± 29.5 mmol·kg-1·dw-1) with no difference between groups. Whereas 4 h of recovery with CHO partly replenished glycogen, the H2O group remained at post exercise level; nevertheless, the gene expression was not different between groups. Glycogen and most gene expression levels returned to baseline by 24 h in both CHO and H2O. Baseline mRNA expression of NRF-1, COX-IV, GLUT4 and PPAR-α gene targets were higher in trained compared to untrained. Additionally, the proportion of type I muscle fibers positively correlated with baseline mRNA for PGC-1α, TFAM, NRF-1, COX-IV, PPAR-α, and GLUT4 for both trained and untrained. CHO restriction during recovery from glycogen depleting exercise does not improve the mRNA response of markers of mitochondrial biogenesis. Further, baseline gene expression of key metabolic pathways is higher in trained than untrained.
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| 23. |
- Jeppesen, Jacob, et al.
(författare)
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FAT/CD36 is localized in sarcolemma and in vesicle-like structures in subsarcolemma regions but not in mitochondria.
- 2010
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 51:6, s. 1504-12
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Tidskriftsartikel (refereegranskat)abstract
- The primary aim of the present study was to investigate in which cellular compartments fatty acid trans-locase CD36 (FAT/CD36) is localized. Intact and fully functional skeletal muscle mitochondria were isolated from lean and obese female Zucker rats and from 10 healthy male individuals. FAT/CD36 could not be detected in the isolated mitochondria, whereas the mitochondrial marker F(1)ATPase-beta was clearly detected using immunoblotting. Lack of markers for other membrane structures indicated that the mitochondria were not contaminated with membranes known to contain FAT/CD36. In addition, fluorescence immunocytochemistry was performed on single muscle fibers dissected from soleus muscle of lean and obese Zucker rats and from the vastus lateralis muscle from humans. Costaining against FAT/CD36 and MitoNEET clearly show that FAT/CD36 is highly present in sarcolemma and it also associates with some vesicle-like intracellular compartments. However, FAT/CD36 protein was not detected in mitochondrial membranes, supporting the biochemical findings. Based on the presented data, FAT/CD36 seems to be abundantly expressed in sarcolemma and in vesicle-like structures throughout the muscle cell. However, FAT/CD36 is not present in mitochondria in rat or human skeletal muscle. Thus, the functional role of FAT/CD36 in lipid transport seems primarily to be allocated to the plasma membrane in skeletal muscle.
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| 24. |
- Larsen, Filip, 1977-, et al.
(författare)
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Dietary inorganic nitrate improves mitochondrial efficiency in humans.
- 2011
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 13:2, s. 149-159
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 25. |
- Larsen, Filip, et al.
(författare)
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Effects of dietary nitrate on blood pressure in healthy volunteers
- 2006
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 28:355(26), s. 2792-3
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Tidskriftsartikel (refereegranskat)abstract
- 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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