Oxidative capacity and ageing in human muscle. Improving the vitamin D status of vitamin D deficient adults is associated with improved mitochondrial oxidative function in skeletal muscle. The Effect of Neoadjuvant Chemoradiotherapy on Whole-Body Physical Fitness and Skeletal Muscle Mitochondrial Oxidative Phosphorylation In Vivo in Locally Advanced Rectal Cancer Patients – An Observational Pilot Study Higher mitochondrial respiration and uncoupling with reduced electron transport chain content in vivo in muscle of sedentary versus active subjects. Large energetic adaptations of elderly muscle to resistance and endurance training. Combined training enhances skeletal muscle mitochondrial oxidative capacity independent of age. Effects of Dietary n-3 Fatty Acids on Hepatic and Peripheral Insulin Sensitivity in Insulin-Resistant Humans Effect of Iron Isomaltoside on Skeletal Muscle Energetics in Patients With Chronic Heart Failure and Iron Deficiency. Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM. Mitochondrial Capacity in Skeletal Muscle Is Not Stimulated by Weight Loss Despite Increases in Insulin Action and Decreases in Intramyocellular Lipid Content Oxidative capacity and glycogen content increase more in arm than leg muscle in sedentary women after intense training. Effect of exercise training on insulin sensitivity, mitochondria and computed tomography muscle attenuation in overweight women with and without polycystic ovary syndrome Effect of carbohydrate ingestion on glycogen resynthesis in human liver and skeletal muscle, measured by (13)C MRS. Idebenone in patients with Friedreich ataxia Ultrastructural modification of human skeletal muscle tissue with 6-month moderate-intensity exercise training. Issues related to the conduct of systematic reviews: a focus on the nutrition field. (-)-Epicatechin enhances fatigue resistance and oxidative capacity in mouse muscle. Skeletal muscle phosphocreatine recovery in exercise-trained humans is dependent on O2 availability. Effects of endurance training on mitochondrial ultrastructure and fiber type distribution in skeletal muscle of patients with stable chronic heart failure. Effect of resistance training on physical disability in chronic heart failure. Grape consumption's effects on fitness, muscle injury, mood, and perceived health. Skeletal muscle mitochondrial function and lean body mass in healthy exercising elderly The effect of physical training on skeletal muscle in patients with chronic heart failure.
This study determined the decline in oxidative capacity per volume of human vastus lateralis muscle between nine adult ( mean age 38.8 years ) and 40 elderly ( mean age 68.8 years ) human subjects ( age range 25 - 80 years ) . We based our oxidative capacity estimates on the kinetics of changes in creatine phosphate content ( [ PCr ] ) during recovery from exercise as measured by (31)P magnetic resonance ( MR ) spectroscopy . A matched muscle biopsy sample permitted determination of mitochondrial volume density and the contribution of the loss of mitochondrial content to the decline in oxidative capacity with age . The maximal oxidative phosphorylation rate or oxidative capacity was estimated from the PCr recovery rate constant ( k(PCr ) ) and the [ PCr ] in accordance with a simple electrical circuit model of mitochondrial respiratory control . Oxidative capacity was 50 % lower in the elderly vs. the adult group ( 0.61 + /- 0.04 vs. 1.16 + /- 0.147 mM ATP s(-1 ) ) . Mitochondrial volume density was significantly lower in elderly compared with adult muscle ( 2.9 + /- 0.15 vs. 3.6 + /- 0.11 % ) . In addition , the oxidative capacity per mitochondrial volume ( 0.22 + /- 0.042 vs. 0.32 + /- 0.015 mM ATP ( s % ) ( -1 ) ) was reduced in elderly vs. adult subjects . This study showed that elderly subjects had nearly 50 % lower oxidative capacity per volume of muscle than adult subjects . The cellular basis of this drop was a reduction in mitochondrial content , as well as a lower oxidative capacity of the mitochondria with age OBJECTIVE Suboptimal mitochondrial function has been implicated in several disorders in which fatigue is a prominent feature . Vitamin D deficiency is a well-recognized cause of fatigue and myopathy . The aim of this study was to examine the effects of cholecalciferol therapy on skeletal mitochondrial oxidative function in symptomatic , vitamin D-deficient individuals . DESIGN This longitudinal study assessed mitochondrial oxidative phosphorylation in the gastrosoleus compartment using phosphorus-31 magnetic resonance spectroscopy measurements of phosphocreatine recovery kinetics in 12 symptomatic , severely vitamin D-deficient subjects before and after treatment with cholecalciferol .  All subjects had serum assays before and after cholecalciferol therapy to document serum 25-hydroxyvitamin D ( 25OHD ) and bone profiles . Fifteen healthy controls also underwent (31)P-magnetic resonance spectroscopy and serum 25OHD assessment . RESULTS The phosphocreatine recovery half-time ( τ1/2PCr ) was significantly reduced after cholecalciferol therapy in the subjects indicating an improvement in maximal oxidative phosphorylation ( 34.44 ± 8.18 sec to 27.84 ± 9.54 sec , P < .001 ) . This was associated with an improvement in mean serum 25OHD levels ( 8.8 ± 4.2 nmol/L to 113.8 ± 51.5 nmol/L , P < .001 ) . There was no difference in phosphate metabolites at rest . A linear regression model showed that decreasing serum 25OHD levels was associated with increasing τ1/2PCr ( r = -0.41 , P = .009 ) . All patients reported an improvement in fatigue  after cholecalciferol therapy . CONCLUSIONS Cholecalciferol therapy augments muscle mitochondrial maximal oxidative phosphorylation after exercise in symptomatic , vitamin D-deficient individuals . This finding suggests that changes in mitochondrial oxidative phosphorylation in skeletal muscle could at least be partly responsible for the fatigue experienced by these patients . For the first time , we demonstrate a link between vitamin D and the mitochondria in human skeletal muscle Background In the United Kingdom , patients with locally advanced rectal cancer routinely receive neoadjuvant chemoradiotherapy . However , the effects of this on physical fitness are unclear . This pilot study is aim ed to investigate the effect of neoadjuvant chemoradiotherapy on objective ly measured in vivo muscle mitochondrial function and whole-body physical fitness . Methods We prospect ively studied 12 patients with rectal cancer who completed st and ardized neoadjuvant chemoradiotherapy , recruited from a large tertiary cancer centre , between October 2012 and July 2013 . All patients underwent a cardiopulmonary exercise test and a phosphorus magnetic resonance spectroscopy quadriceps muscle exercise-recovery study before and after neoadjuvant chemoradiotherapy . Data were analysed and reported blind to patient identity and clinical course . Primary variables of interest were the two physical fitness measures ; oxygen uptake at estimated anaerobic threshold and oxygen uptake at Peak exercise ( ml.kg−1.min−1 ) , and the post-exercise phosphocreatine recovery rate constant ( min−1 ) , a measure of muscle mitochondrial capacity in vivo .  Results Median age was 67 years ( IQR 64–75 ) . Differences ( 95%CI ) in all three primary variables were significantly negative post-NACRT : Oxygen uptake at estimated anaerobic threshold −2.4 ml.kg−1.min−1 ( −3.8 , −0.9 ) , p = 0.004 ; Oxygen uptake at Peak −4.0 ml.kg−1.min−1 ( −6.8 , −1.1 ) , p = 0.011 ; and post-exercise phosphocreatine recovery rate constant −0.34 min−1 ( −0.51 , −0.17 ) , p<0.001 . Conclusion The significant decrease in both whole-body physical fitness and in vivo muscle mitochondrial function raises the possibility that muscle mitochondrial mechanisms , no doubt multifactorial , may be important in deterioration of physical fitness following neoadjuvant chemoradiotherapy . This may have implication s for targeted interventions to improve physical fitness pre-surgery . Trial Registration Clinical trials.gov registration OBJECTIVE This study investigated the disparity between muscle metabolic rate and mitochondrial metabolism in human muscle of sedentary vs. active individuals . RESEARCH DESIGN AND METHODS Chronic activity level was characterized by a physical activity question naire and a triaxial accelerometer as well as a maximal oxygen uptake test . The ATP and O(2 ) fluxes and mitochondrial coupling ( ATP/O(2 ) or P/O ) in resting muscle as well as mitochondrial capacity ( ATP(max ) ) were determined in vivo in human vastus lateralis muscle using magnetic resonance and optical spectroscopy on 24 sedentary and seven active subjects . Muscle biopsies were analyzed for electron transport chain content ( using complex III as a representative marker ) and mitochondrial proteins associated with antioxidant protection . RESULTS Sedentary muscle had lower electron transport chain complex content ( 65 % of the active group ) in proportion to the reduction in ATP(max ) ( 0.69 ± 0.07 vs. 1.07 ± 0.06 mM sec(-1 ) ) as compared with active subjects . This lower ATP(max ) paired with an unchanged O(2 ) flux in resting muscle between groups result ed in a doubling of O(2 ) flux per ATP(max ) ( 3.3 ± 0.3 vs. 1.7 ± 0.2 μM O(2 ) per mM ATP ) that reflected mitochondrial uncoupling ( P/O = 1.41 ± 0.1 vs. 2.1 ± 0.3 ) and greater UCP3/complex III ( 6.0 ± 0.7 vs. 3.8 ± 0.3 ) in sedentary vs. active subjects . CONCLUSION A smaller mitochondrial pool serving the same O(2 ) flux result ed in elevated mitochondrial respiration in sedentary muscle . In addition , uncoupling contributed to this higher mitochondrial respiration . This finding resolves the paradox of stable muscle metabolism but greater mitochondrial respiration in muscle of inactive vs. active subjects This study determined the cellular energetic and structural adaptations of elderly muscle to exercise training .  Forty male and female subjects ( 69.2 + /- 0.6 yr ) were assigned to a control group or 6 mo of endurance ( ET ) or resistance training ( RT ) . We used magnetic resonance spectroscopy and imaging to characterize energetic properties and size of the quadriceps femoris muscle . The phosphocreatine and pH changes during exercise yielded the muscle oxidative properties , glycolytic ATP synthesis , and contractile ATP dem and . Muscle biopsies taken from the same site as the magnetic resonance measurements were used to determine myosin heavy chain isoforms , metabolite concentrations , and mitochondrial volume densities . The ET group showed changes in all energetic pathways : oxidative capacity ( + 31 % ) , contractile ATP dem and ( -21 % ) , and glycolytic ATP supply ( -56 % ) . The RT group had a large increase in oxidative capacity ( 57 % ) . Only the RT group exhibited change in structural properties : a rise in mitochondrial volume density ( 31 % ) and muscle size ( 10 % ) . These results demonstrate large energetic , but smaller structural , adaptations by elderly muscle with exercise training . The rise in oxidative properties with both ET and RT suggests that the aerobic pathway is particularly sensitive to exercise training in elderly muscle . Thus elderly muscle remains adaptable to chronic exercise , with large energetic changes accompanying both ET and RT CONTEXT Skeletal muscle from sedentary older adults exhibits reduced mitochondrial abundance and oxidative capacity . OBJECTIVE The primary objective was to determine whether 8 weeks of combined training ( CT ) has a more robust effect than endurance training ( ET ) or resistance training ( RT ) on mitochondrial physiology in healthy young ( 18 - 30 years ) and older ( ≥ 65 years ) adults . INTERVENTION Thirty-four young and 31 older adults were r and omly assigned to 8 weeks of ET , RT , and control/CT .  Control subjects completed 8 weeks of no exercise ( control ) followed by 8 weeks of CT  . Body composition , skeletal muscle strength , and peak oxygen uptake were measured before and after the intervention . Vastus lateralis muscle biopsy sample s were obtained before and 48 hours after the intervention . Mitochondrial physiology was evaluated by high-resolution respirometry and expression of mitochondrial proteins and transcription factors by quantitative PCR and immunoblotting . RESULTS ET and CT significantly increased oxidative capacity and expression of mitochondrial proteins and transcription factors . All training modalities improved body composition , cardiorespiratory fitness , and skeletal muscle strength . CT induced the most robust improvements in mitochondria-related outcomes and physical characteristics despite lower training volumes for the ET and RT components . Importantly , most of the adaptations to training occurred independent of age . CONCLUSION Collectively , these results demonstrate that both ET and CT increase muscle mitochondrial abundance and capacity although CT induced the most robust improvements in the outcomes measured . In conclusion , CT provides a robust exercise regimen to improve muscle mitochondrial outcomes and physical characteristics independent of age OBJECTIVE Dietary n-3 polyunsaturated fatty acids , including eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , prevent insulin resistance and stimulate mitochondrial biogenesis in rodents , but the findings of translational studies in humans are thus far ambiguous . The aim of this study was to evaluate the influence of EPA and DHA on insulin sensitivity , insulin secretion , and muscle mitochondrial function in insulin-resistant , nondiabetic humans using a robust study design and gold-st and ard measurements . RESEARCH DESIGN AND METHODS Thirty-one insulin-resistant adults received 3.9 g/day  EPA+DHA or placebo for 6 months in a r and omized double-blind study . Hyperinsulinemic-euglycemic clamp with somatostatin was used to assess hepatic and peripheral insulin sensitivity . Postpr and ial glucose disposal and insulin secretion were measured after a meal . Measurements were performed at baseline and after 6 months of treatment . Abdominal fat distribution was evaluated by MRI . Muscle oxidative capacity was measured in isolated mitochondria using high-resolution respirometry and noninvasively by magnetic resonance spectroscopy . RESULTS Compared with placebo , EPA+DHA did not alter peripheral insulin sensitivity , postpr and ial glucose disposal , or insulin secretion . Hepatic insulin sensitivity , determined from the suppression of endogenous glucose production by insulin , exhibited a small but significant improvement with EPA+DHA compared with placebo .  Muscle mitochondrial function was unchanged by EPA+DHA or placebo . CONCLUSIONS This study demonstrates that dietary EPA+DHA does not improve peripheral glucose disposal , insulin secretion , or skeletal muscle mitochondrial function in insulin-resistant nondiabetic humans . There was a modest improvement in hepatic insulin sensitivity with EPA+DHA , but this was not associated with any improvements in clinical ly meaningful outcomes BACKGROUND Iron repletion augments exercise capacity in chronic heart failure ( HF ) , but there is a lack of mechanistic data explaining how iron could augment exercise performance despite minimal changes in hemoglobin ( Hb ) . Besides Hb , iron is an obligate component of mitochondrial enzymes that generate cellular energy in the form of adenosine triphosphate and phosphocreatine ( PCr ) . Dynamic phosphorus magnetic resonance spectroscopy is a noninvasive tool that quantifies in vivo muscle energetics by measuring the kinetics of PCr recovery after exertion . We tested the hypothesis that intravenous iron repletion in chronic HF enhances skeletal muscle energetics as reflected by shorter PCr recovery half-times ( PCr t1/2 ) on phosphorus magnetic resonance spectroscopy . METHODS We enrolled 40 patients ( 50 % anemic ) with chronic HF , New York Heart Association class ≥II , left ventricular ejection fraction ≤45 % , and iron deficiency ( ferritin<100 μg/L or 100 - 300 μg/L with transferrin saturation < 20 % ) . Subjects underwent stratified ( anemic versus nonanemic ) r and omization ( 1:1 ) to a single , double-blinded , total dose infusion of iron isomaltoside or saline placebo with end points reassessed early at 2 weeks posttreatment to minimize confounding from exercise adaptation . The primary end point was PCr t1/2 at 2 weeks . Secondary end points included ADP recovery half-time ( ADP t1/2 ; energetic marker ) , iron status , symptoms , Hb , exercise capacity , and safety . RESULTS In the total population , treatment groups were similar at baseline . At 2 weeks , iron isomaltoside  improved PCr t1/2 ( adjusted difference , -6.8 s ; 95 % CI , 11.5 to -2.1 ; P=0.006 ) , ADP t1/2 ( -5.3 s ; 95 % CI , -9.7 to -0.9 ; P=0.02 ) , ferritin ( 304 ng/mL ; 95 % CI , 217 - 391 ; P<0.0001 ) , transferrin saturation ( 6.8 % ; 95 % CI , 2.7 - 10.8 ; P=0.002 ) , New York Heart Association class ( -0.23 ; 95 % CI , -0.46 to -0.01 ; P=0.04 ) , resting respiratory rate ( -0.7 breaths/min ; 95 % CI , -1.2 to -0.2 ; P=0.009 ) , and postexercise Borg dyspnea score ( -2.0 ; 95 % CI , -3.7 to -0.3 ; P=0.04 ) , but not Hb ( 2.4 g/L ; 95 % CI , -3.5 to 8.4 ; P=0.41 ) . Adverse events were similar between groups . In subgroup analyses , iron isomaltoside improved PCr t1/2 in anemic ( -8.4 s ; 95 % CI , -16.7 to -0.2 ; P=0.04 ) and nonanemic ( -5.2 s ; 95 % CI , -10.6 to 0.2 ; P=0.06 ) cohorts . CONCLUSIONS In patients with chronic HF and iron deficiency , a total repletion dose of iron isomaltoside given at a single sitting is well tolerated and associated with faster skeletal muscle PCr t1/2 at 2 weeks , implying better mitochondrial function . Augmented skeletal muscle energetics might therefore be an important mechanism via which iron repletion confers benefits in chronic HF despite minimal Hb changes . CLINICAL TRIAL REGISTRATION URL : https://www . clinical trialsregister.eu/ctr- search /trial/2012 - 005592 - 13/GB . Unique identifier : EudraCT 2012 - 005592 - 13 The insulin resistance of skeletal muscle in glucose-tolerant obese individuals is associated with reduced activity of oxidative enzymes and a disproportionate increase in activity of glycolytic enzymes . Because non-insulin-dependent diabetes mellitus ( NIDDM ) is a disorder characterized by even more severe insulin resistance of skeletal muscle and because many individuals with NIDDM are obese , the present study was undertaken to examine whether decreased oxidative and increased glycolytic enzyme activities are also present in NIDDM .  Percutaneous biopsy of vatus lateralis muscle  was obtained in eight lean ( L ) and eight obese ( O ) nondiabetic subjects and in eight obese NIDDM subjects and was assayed for marker enzymes of the glycolytic [ phosphofructokinase , glyceraldehyde phosphate dehydrogenase , hexokinase ( HK ) ] and oxidative pathways [ citrate synthase ( CS ) , cytochrome-c oxidase ] , as well as for a glycogenolytic enzyme ( glycogen phosphorylase ) and a marker of anaerobic ATP re synthesis ( creatine kinase ) . Insulin sensitivity was measured by using the euglycemic clamp technique .  Activity for glycolytic enzymes ( phosphofructokinase , glyceraldehye phosphate dehydrogenase , HK ) was highest in subjects with subjects with NIDDM , following the order of NIDDM > O > L , whereas maximum velocity for oxidative enzymes ( CS , cytochrome-c oxidase ) was lowest in subjects with NIDDM . The ratio between glycolytic and oxidative enzyme activities within skeletal muscle correlated negatively with insulin sensitivity . The HK/CS ratio had the strongest correlation ( r = -0.60 , P < 0.01 ) with insulin sensitivity . In summary , an imbalance between glycolytic and oxidative enzyme capacities is present in NIDDM subjects and is more severe than in obese or lean glucose-tolerant subjects . The altered ratio between glycolytic and oxidative enzyme activities found in skeletal muscle of individuals with NIDDM suggests that a dysregulation between mitochondrial oxidative capacity and capacity for glycolysis is an important component of the expression of insulin resistance OBJECTIVE — In obesity and type 2 diabetes , exercise combined with weight loss increases skeletal muscle mitochondrial capacity . It remains unclear whether mitochondrial capacity increases because of weight loss , improvements in insulin resistance , or physical training . In this study , we examined the effects of an intervention of weight loss induced by diet and compared these with those of a similar intervention of weight loss by diet with exercise . Both are known to improve insulin resistance , and we tested the hypothesis that physical activity , rather than improved insulin resistance , is required to increase mitochondrial capacity of muscle . RESEARCH DESIGN AND METHODS — Sixteen sedentary overweight/obese volunteers were r and omized to a 16-week intervention of diet ( n = 7 ) or diet plus exercise ( n = 9 ) . Insulin sensitivity was measured using euglycemic clamps . Mitochondria were examined in muscle biopsies before and after intervention . We measured mitochondrial content and size by electron microscopy , electron transport chain ( ETC ) activity , cardiolipin content , and mitochondrial DNA content . Intramyocellular content of lipid ( IMCL ) and fiber-type distribution were determined by histology . RESULTS — The diet-only and diet plus exercise groups achieved similar weight loss ( 10.8 and 9.2 % , respectively ) ; only the diet plus exercise group improved aerobic capacity . Insulin sensitivity improved similarly in both groups . Mitochondrial content and ETC activity increased following the diet plus exercise intervention but remained unchanged following the diet-only intervention , and mitochondrial size decreased with weight loss despite improvement in insulin resistance . IMCL decreased in the diet-only but not in the diet plus exercise intervention . CONCLUSIONS — Despite similar effects to improve insulin resistance , these interventions had differential effects on mitochondria . Clinical ly significant weight loss in the absence of increased physical activity ameliorates insulin resistance and IMCL but does not increase muscle mitochondrial capacity in obesity The hypothesis that the adaptive capacity is higher in human upper- than lower-body skeletal muscle was tested . Furthermore , the hypothesis that more pronounced adaptations in upper-body musculature can be achieved by " low-volume high-intensity " compared with " high-volume low-intensity " exercise training was evaluated . A group of sedentary premenopausal women aged 45 ± 6 yr ( ± SD ) with expected high adaptive potential in both upper- and lower-extremity muscle groups participated . After r and om allocation to high-intensity swimming ( HIS , n = 21 ) , moderate-intensity swimming ( MOS , n = 21 ) , soccer ( SOC , n = 21 ) or a nontraining control group ( CON , n = 20 ) , the training groups completed three workouts per week for 15 wk . Resting muscle biopsies were obtained from the vastus lateralis muscle and deltoideus muscle before and after the intervention . After the training intervention , a larger ( P < 0.05 ) increase existed in deltoideus muscle of the HIS group compared with vastus lateralis muscle of the SOC group for citrate synthase maximal activity ( 95 ± 89 vs. 27 ± 34 % ) , citrate synthase protein expression ( 100 ± 29 vs. 31 ± 44 % ) , 3-hydroxyacyl-CoA dehydrogenase maximal activity ( 35 ± 43 vs. 3 ± 25 % ) , muscle glycogen content ( 63 ± 76 vs. 20 ± 51 % ) , and expression of mitochondrial complex II , III , and IV . Additionally , HIS caused higher ( P < 0.05 ) increases than MOS in deltoideus muscle citrate synthase maximal activity , citrate synthase protein expression , and muscle glycogen content . In conclusion , the deltoideus muscle has a higher adaptive potential than the vastus lateralis muscle in sedentary women , and " high-intensity low-volume " training is a more efficient regime than " low-intensity high-volume " training for increasing the aerobic capacity of the deltoideus muscle Aims /hypothesisPolycystic ovary syndrome ( PCOS ) is an insulin resistant ( IR ) state . Increased skeletal muscle lipid content and impaired mitochondrial biogenesis have been implicated in the pathogenesis of IR . We investigated whether differences in these variables explain the IR of women affected by PCOS and whether improvements in IR with exercise are reflected by changes in these variables . Methods Sixteen PCOS and 13 non-PCOS overweight women were assessed , and eight PCOS and seven non-PCOS women were reassessed after 12 weeks of moderate and vigorous exercise training . Outcomes included insulin sensitivity ( glucose infusion rate [ GIR ] ) , skeletal muscle gene expression and protein abundance , enzyme activity of selected mitochondrial components , and computed tomography ( CT ) attenuation-estimated muscle lipid . Results GIR was lower in women with PCOS versus those without ( p = 0.01 ) and increased with exercise in both groups . Baseline CT muscle attenuation suggested a trend to less muscle lipid in PCOS , which increased with exercise training , with a difference in the change in muscle lipid ( p = 0.01 , age-corrected ) , compared with non-PCOS women . GIR correlated with PGC1A gene expression across the whole group ; skeletal muscle expression of mitochondrial biogenesis markers was not different between groups at baseline , or after training . Neither lipid changes nor mitochondrial changes correlated with changes in GIR . Conclusions /interpretationDifferences in IR in women with and without PCOS were not explained by differences in skeletal muscle lipid or mitochondrial parameters . Improvements in IR with exercise were dissociated from mitochondrial parameters . CT muscle attenuation suggested a differential capacity of PCOS muscle to store lipid compared with non-PCOS.Trial registration : Clinical trials.gov IS RCT N84763265 Funding : National Health & Medical Research Council ( Grant number 606553 ) , Monash University and The Jean Hailes Foundation This study investigated the effect of carbohydrate ( CHO ) ingestion on postexercise glycogen re synthesis , measured simultaneously in liver and muscle ( n = 6 ) by (13)C magnetic resonance spectroscopy , and subsequent exercise capacity ( n = 10 ) . Subjects cycled at 70 % maximal oxygen uptake for 83 + /- 8 min on six separate occasions . At the end of exercise , subjects ingested 1 g/kg body mass ( BM ) glucose , sucrose , or placebo ( control ) . Re synthesis of glycogen over a 4-h period after treatment ingestion was measured on the first three occasions , and subsequent exercise capacity was measured on occasions four through six . No glycogen was resynthesized during the control trial . Liver glycogen re synthesis was evident after glucose ( 13 + /- 8 g ) and sucrose ( 25 + /- 5 g ) ingestion , both of which were different from control ( P < 0.01 ) . No significant differences in muscle glycogen re synthesis were found among trials . A relationship between the CHO load ( g ) and change in liver glycogen content ( g ) was evident after 30 , 90 , 150 , and 210 min of recovery ( r = 0.59 - 0 . 79 , P < 0.05 ) . Furthermore , a modest relationship existed between change in liver glycogen content ( g ) and subsequent exercise capacity ( r = 0.53 , P < 0.05 ) . However , no significant difference in mean exercise time was found ( control : 35 + /- 5 , glucose : 40 + /- 5 , and sucrose : 46 + /- 6 min ) . Therefore , 1 g/kg BM glucose or sucrose is sufficient to initiate postexercise liver glycogen re synthesis , which contributes to subsequent exercise capacity , but not muscle glycogen re synthesis Friedreich ataxia ( FA ) , the most common form of degenerative ataxia , is thought to be caused by respiratory deficiency due to mitochondrial iron accumulation and oxidative stress . Idebenone , a free-radical scavenger , protects mitochondrial function in in vitro models of FA . In a placebo-controlled crossover trial we studied the effect of idebenone on respiratory function in nine ambulant FA patients . (31)P magnetic resonance spectroscopy demonstrated mitochondrial impairment in vivo in skeletal muscle of all FA patients , but no recovery with idebenone . No effects were seen in clinical scores . Echocardiography did not confirm a preliminary study reporting improvement of FA-associated cardiomyopathy with idebenone The study was aim ed at investigating if endurance training of moderate intensity and longer duration , intended to promote health rather than performance , evokes ultrastructural changes in skeletal muscle tissue comparable to those observed after high-intensity protocol s. Twenty healthy , middle-aged men enrolled in a 6-month , home-based jogging program of 120 min/wk at 75 % VO2max . Only 12 men showed a sufficient exercise adherence  over the 6 months ( > or = 60 min/wk on average ) and were included into statistical analysis . Their average training activity was 105 + /- 31 min/wk . The results revealed significant increases in VO2max ( + 8.4 % , p < 0.01 ) and submaximal power output ( + 18.1 % , p < 0.01 ) . Total mitochondrial volume density in M. vastus lateralis increased by 20 % ( p < 0.05 ) with a larger increase in subsarcolemmal volume compared to central volume ( 50 % vs 15 % ) . No changes in volume of intracellular lipid droplets , capillary density , capillary per fiber ratio , fiber mean cross-sectional area and muscle fiber type could be observed . Body composition analysis showed a decrease in trunk fat mass ( -7.3 % , p < 0.05 ) and an increase in trunk lean mass ( + 1.7 % , p < 0.05 ) , while changes in the legs were not significant . It can be concluded that a moderate-intensity , health oriented endurance training beneficially affected cardiovascular and muscle oxidation capacity as well as body composition in the trunk area . No adaptations in capillaries or lipid metabolism could be demonstrated . The results support the hypothesis of thresholds for induction of adaptation processes in muscle skeletal tissue depending on the intensity of the exercise stimulus Systematic review s ( SRs ) are an increasingly popular evidence -based tool and are often used to answer complex research questions across many different research domains . Early SR methodology was advanced by social scientists , and the term meta- analysis was coined by a social scientist who also conducted research in psychology . SRs have recently become popular in healthcare and are likely to be beneficial in any field . The aim of this report is to highlight issues in SR conduct with a focus on the field of nutrition and to make recommendations on improving SR conduct in this area . Development of the research question is probably the most important step in conducting an SR . The 4 main components of an answerable question are 1 ) the patient , population , or problem ; 2 ) the intervention , independent variable , or exposure ; 3 ) the comparators ; and 4 ) the dependent variables or outcomes of interest . The question will be used to determine the optimal methods for conducting the SR . SRs often include study design s beyond r and omized trials and do not always include a meta- analysis of the results . Other topics explored include underst and ing and interpreting discordant review s and the importance of reporting tools [ eg , QUality Of Reporting Of Meta-analyses ( QUOROM Statement ) or CONsoli date d St and ards Of Reporting of Trials ( CONSORT Statement ) ] . Recommendations are then provided , such as developing a capacity-building program , search ing the primary literature for research gaps , and extending reporting tools such as the QUOROM Statement to the field of nutrition The flavanol (-)-epicatechin , a component of cacao ( cocoa ) , has been shown to have multiple health benefits in humans . Using 1-year-old male mice , we examined the effects of 15 days of (-)-epicatechin treatment and regular exercise on : ( 1 ) exercise performance , ( 2 ) muscle fatigue , ( 3 ) capillarity , and ( 4 ) mitochondrial biogenesis in mouse hindlimb and heart muscles . Twenty-five male mice ( C57BL/6N ) were r and omized into four groups : ( 1 ) water , ( 2 ) water-exercise ( W-Ex ) , ( 3 ) (-)-epicatechin ( (-)-Epi ) , and ( 4 ) (-)-epicatechin-exercise ( (-)-Epi-Ex ) . Animals received 1 mg kg(-1 ) of (-)-epicatechin or water ( vehicle ) via oral gavage ( twice daily ) . Exercise groups underwent 15 days of treadmill exercise . Significant increases in treadmill performance ( ∼50 % ) and enhanced in situ muscle fatigue resistance ( ∼30 % ) were observed with (-)-epicatechin . Components of oxidative phosphorylation complexes , mitofilin , porin , nNOS , p-nNOS , and Tfam as well as mitochondrial volume and cristae abundance were significantly higher with (-)-epicatechin treatment for hindlimb and cardiac muscles than exercise alone . In addition , there were significant increases in skeletal muscle capillarity . The combination of (-)-epicatechin and exercise result ed in further increases in oxidative phosphorylation-complex proteins , mitofilin , porin and capillarity than (-)-epicatechin alone . These findings indicate that (-)-epicatechin alone or in combination with exercise induces an integrated response that includes structural and metabolic changes in skeletal and cardiac muscles result ing in greater endurance capacity . These results , therefore , warrant the further evaluation of the underlying mechanism of action of (-)-epicatechin and its potential clinical application as an exercise mimetic In skeletal muscle , phosphocreatine ( PCr ) recovery from submaximal exercise has become a reliable and accepted measure of muscle oxidative capacity . During exercise , O2 availability plays a role in determining maximal oxidative metabolism , but the relationship between O2 availability and oxidative metabolism measured by 31P-magnetic resonance spectroscopy ( MRS ) during recovery from exercise has never been studied . We used 31P-MRS to study exercising human gastrocnemius muscle under conditions of varied fractions of inspired O2 ( FIO2 ) to test the hypothesis that varied O2 availability modulates PCr recovery from submaximal exercise . Six male subjects performed three bouts of 5-min steady-state submaximal plantar flexion exercise followed by 5 min of recovery in a 1.5-T magnet while breathing three different FIO2 concentrations ( 0.10 , 0 . 21 , and 1.00 ) . Under each FIO2 treatment , the PCr recovery time constants were significantly different , being longer in hypoxia [ 33 . 5 + /- 4.1 s ( SE ) ] and shorter in hyperoxia ( 20.0 + /- 1.8 s ) than in normoxia ( 25.0 + /- 2.7 s ) ( P < /= 0.05 ) . End-exercise pH was not significantly different among the three treatments ( 7.08 + /- 0.01 for 0.10 , 7.04 + /- 0.01 for 0.21 , and 7.04 + /- 0.02 for 1.00 ) . These results demonstrate that PCr recovery is significantly altered by FIO2 and suggest that , after submaximal exercise , PCr recovery , under normoxic conditions , is limited by O2 availability OBJECTIVES The present study was design ed to evaluate the effects of an ambulatory training program in patients with chronic heart failure ( CHF ) on the ultrastructural morphology of mitochondria and fiber type distribution of skeletal muscle and its relation to peripheral perfusion . BACKGROUND Recent studies in patients with CHF have suggested that intrinsic abnormalities in skeletal muscle can contribute to the development of early lactic acidosis and fatigue during exercise . METHODS ; Patients were prospect ively r and omized to either a training group ( n = 9 ; mean [ + /- SD ] left ventricular ejection fraction [ LVEF ] 26 + /- 10 ) participating in an ambulatory training program or to a physically inactive control group ( n = 9 ; LVEF 28 + /- 10 % ) . At baseline and after 6 months , patients underwent symptom-limited bicycle exercise testing with measurement of central and peripheral hemodynamic variables as well as percutaneous needle biopsies of the vastus lateralis muscle . The mitochondrial ultrastructure of skeletal muscle was analyzed by ultrastructural morphometry ; cytochrome c oxidase activity was visualized by histochemistry and subsequently quantitated by morphometry . The fiber type distribution was determined by adenosine triphosphatase staining . RESULTS After 6 months of exercise training there was a significant increase of 41 % in the surface density of cytochrome c oxidase-positive mitochondria ( SVMOcox+ ) ( p < 0.05 vs. control ) and of 43 % in the surface density of mitochondrial cristae ( SVMC ) ( p < 0.05 vs. control ) . Furthermore , exercise training induced a 92 % increase in the surface density of the mitochondrial inner border membrane ( p < 0.05 vs. control ) . In contrast , the total number of cytochrome c oxidase-positive mitochondria remained essentially unchanged . Exercise-induced improvement in peak oxygen uptake was closely linked to changes in SVMOcox+ ( p < 0.01 , r = 0.66 ) . After exercise training , changes in submaximal femoral venous lactate levels were not related to changes in submaximal leg blood flow ( r = -0.4 ) , but were inversely related to changes in the volume density of mitochondria ( p = 0.01 ; r = -0.6 ) as well as to changes in SVMC ( p < 0.05 ; r = -0.5 ) . After exercise training there was a " reshift " from type II to type I fibers ( p < 0.05 vs. control ) . CONCLUSIONS Patients with CHF who engage in regular physical exercise show enhanced oxidative enzyme activity in the working skeletal muscle and a concomitant reshift to type I fibers . These exercise-induced changes in oxidative capacity appear to be unrelated to changes in peripheral perfusion PURPOSE Patients with chronic heart failure ( CHF ) report difficulty performing activities of daily living . To our knowledge , however , no study has directly measured performance in activities of daily living in these patients to systematic ally assess their level of physical disability . Moreover , the contribution of skeletal muscle weakness to physical disability in CHF remains unclear . Thus , we measured performance in activities of daily living in CHF patients and controls , its relationship to aerobic capacity and muscle strength , and the effect of resistance exercise training to improve muscle strength and physical disability . METHODS Patients and controls were assessed for performance in activities of daily living , self-reported physical function , peak aerobic capacity , body composition , and muscle strength before and after an 18-wk resistance training program . To remove the confounding effects of several disease-related factors ( muscle disuse , hospitalization , acute illness ) , we recruited controls with similar activity levels as CHF patients and tested patients > 6 months after any disease exacerbation/hospitalization . RESULTS Performance in activities of daily living was 30 % lower ( P < 0.05 ) in CHF patients versus controls and was related to both reduced aerobic capacity ( P < 0.001 ) and muscle strength ( P < 0.01 ) . Moreover , resistance training improved ( P < 0.05 to P < 0.001 ) physical function and muscle strength in patients and controls similarly , without altering aerobic capacity . CONCLUSIONS CHF patients are characterized by marked physical disability compared with age- and physical activity-matched controls , which is related to reduced aerobic capacity and muscle strength . CHF patients respond to resistance training with normal strength/functional adaptations . Our results support muscle weakness as a determinant of physical disability in CHF and show that interventions that increase muscle strength  ( resistance training ) reduce physical disability Compounds found in the skins of grapes , including catechins , quercetin , and resveratrol , have been added to the diet of rodents and improved run time to exhaustion , fitness , and skeletal-muscle mitochondrial function . It is unknown if such effects occur in humans . The purpose of this experiment was to investigate whether 6 wk of daily grape consumption influenced maximal oxygen uptake ( VO(2max ) ) , work capacity , mood , perceived health status , inflammation , pain , and arm-function responses to a mild eccentric-exercise-induced arm-muscle injury . Forty recreationally active young adults were r and omly assigned to consume a grape or placebo drink for 45 consecutive days . Before and after 42 d of supplementation , assessment s were made of treadmill-running VO(2max ) , work capacity ( treadmill performance time ) , mood ( Profile of Mood States ) , and perceived health status ( SF-36 Health Survey ) . The day after posttreatment treadmill tests were completed , 18 high-intensity eccentric actions of the nondominant elbow flexors were performed . Arm-muscle inflammation , pain , and function ( isometric strength and range of motion ) were measured before and on 2 consecutive days after the eccentric exercise . Mixed-model ANOVA showed no significant effect of grape consumption on any of the outcomes . Six weeks of supplemental grape consumption by recreationally active young adults has no effect on VO(2max ) , work capacity , mood , perceived health status , inflammation , pain , or physical-function responses to a mild injury induced by eccentric exercise BACKGROUND The decline in muscle mass ( sarcopenia ) with aging may be related to a decline in mitochondrial function . However , investigators have yet to reach a consensus as to whether a decline in mitochondrial function can be attenuated by physical activity has yet to reach a consensus . METHODS Using dynamic 31PMRS to measure mitochondrial function , we measured baseline Phosphocreatine ( PCr ) , inorganic phosphate ( Pi ) , phosphodiester ( PDE ) , [ ADP ] , pH and recovery times ( t(1/2 ) ) for PCr and [ ADP ] following exercise , in 45 older ( 73+/-4 years , SD ) , and 20 younger subjects ( 25+/-4 years , SD ) who were matched for body mass across high and low activity levels and within age and sex groupings . RESULTS Baseline PCr , and Pi , were lower , and PDE higher in the older subjects compared to younger subjects ( all P<0.01 ) . The t(1/2)(ADP ) was longer in older subjects ( P<0.001 ) controlling for age and sex in the low activity group ( P=0.02 ) . In the older low activity groups , t(1/2)(PCr ) was longer than high activity groups . Higher PDE levels were positively correlated with longer t(1/2)(PCr ) in the older low activity females ( both P<0.05 ) . CONCLUSIONS Our data suggests that mitochondrial function declines with age in healthy , exercising elderly adults and that the decline appears to be influenced by the level of physical activity BACKGROUND The improvement of exercise capacity in patients with chronic heart failure ( CHF ) by physical training has been connected with reversal of the abnormalities in muscle fiber distribution and with the reduced activity of the enzymes of oxidative metabolism in skeletal muscle . However , the change in fiber type distribution induced by training is controversial and in previous studies the activities of the rate-limiting enzymes of the metabolic pathways have not been measured . AIMS To examine the effect of dynamic training on percentage distribution of muscle fibers , on activities of the rate-limiting enzymes of the metabolic pathways and on electrophysiology in skeletal muscle . METHODS A total of 27 patients with stable CHF ( NYHA class II-III ) were r and omized to a training ( N=12 ) or a control ( N=15 ) group . The training group exercised on a bicycle ergometer for 30 min three times a week for 3 months using a load corresponding to 50 - 60 % of their peak oxygen consumption . This was followed by a 3-month training period at home according to personal instructions . The control group did not change its physical activities . We studied muscle histology and measured the activities of the rate-limiting enzymes of anaerobic glycolysis ( phosphofructokinase , PFK ) , glycogenolysis ( phosphorylase ) , citric acid cycle ( alpha-ketoglurate dehydrogenase , KGDH ) and fatty acid oxidation ( carnitinepalmitoyl transferase I and II , CPT I and II ) from biopsies of the vastus lateralis muscle at baseline and after 3 and 6 months . Muscle strength and strength endurance with surface EMG and macro EMG of the right knee extensors were also determined . RESULTS Exercise capacity , particularly submaximal , improved in the training group . The activity of PFK rose significantly but that of the other enzymes did not when compared with the change in the controls . Training had no effect on the percentage distribution of slow-twitch and fast-twitch muscle fibers or on capillary density around these fibers in skeletal muscle . Maximum voluntary force , strength endurance and the function of motor units remained unaffected . CONCLUSIONS Dynamic training results in improved exercise endurance in CHF . In skeletal muscle , the capacity of anaerobic glycolysis is increased but that of the citric acid cycle and fatty acid oxidation is not . Furthermore , the improvement in exercise endurance seems to be independent of changes in the percentage distribution of muscle fibers , capillarity or electrophysiological factors
This analysis indicates that the current body of literature does not support a de facto decrease of in vivo muscle oxidative capacity in old age .
The heterogeneity of study results and identification of significant moderators provide clarity regarding apparent discrepancies in the literature , and indicate the importance of accounting for these variables when examining purported age-related differences in muscle oxidative capacity
Despite intensive efforts to underst and the extent to which skeletal muscle mitochondrial capacity changes in older humans , the answer to this important question remains unclear .
To determine what the preponderance of evidence from in vivo studies suggests , we conducted a systematic review and meta- analysis of the effects of age on muscle oxidative capacity as measured noninvasively by magnetic resonance spectroscopy .
A secondary aim was to examine potential moderators contributing to differences in results across studies , including muscle group , physical activity status , and sex .