The redox signal: A physiological perspective.

A signal in biology is any kind of coded message sent from one place in an organism to another place. Biology is rich in claims that reactive oxygen and nitrogen species transmit signals. Therefore, we define a "redox signal as an increase/decrease in the level of reactive species". First, as in most biology disciplines, to analyze a redox signal you need first to deconstruct it. The essential components that constitute a redox signal and should be characterized are: (i) the reactivity of the specific reactive species, (ii) the magnitude of change, (iii) the temporal pattern of change, and (iv) the antioxidant condition. Second, to be able to translate the physiological fate of a redox signal you need to apply novel and bioplausible methodological strategies. Important considerations that should be taken into account when designing an experiment is to (i) assure that redox and physiological measurements are at the same or similar level of biological organization and (ii) focus on molecules that are at the highest level of the redox hierarchy. Third, to reconstruct the redox signal and make sense of the chaotic nature of redox processes, it is essential to apply mathematical and computational modeling. The aim of the present study was to collectively present, for the first time, those elements that essentially affect the redox signal as well as to emphasize that the deconstructing, decoding and reconstructing of a redox signal should be acknowledged as central to design better studies and to advance our understanding on its physiological effects.

Skeletal muscle and cerebral oxygenation levels during and after submaximal concentric and eccentric isokinetic exercise.

The aim was to investigate the potential differences in muscle (vastus lateralis) and cerebral (prefrontal cortex) oxygenation levels as well as in the number of repetitions and total work output between isokinetic eccentric and concentric exercise at a moderate relative intensity until exhaustion. Ten recreationally active young men underwent two isokinetic exercise sessions either concentric or eccentric, one on each randomly selected leg. The protocols were performed at 60°/s and an intensity corresponding to 60% of the maximal voluntary contraction (MVC) of each contraction type. Concentric torque was significantly lower compared to eccentric torque in both peak values and at values corresponding to 60% of MVC [230 ± 18 Nm vs. 276 ± 19 Nm (P = .014) and 137 ± 12 Nm vs. 168 ± 11 Nm, respectively (P = .010)]. The participants performed 40% more contractions during eccentric compared to concentric exercise [122 ± 15 vs. 78 ± 7, respectively]. No differences were found in the levels of oxyhaemoglobin, deoxyhemoglobin, total haemoglobin and tissue saturation index when eccentric and eccentric exercise regimes were compared (all P > .05). Our results demonstrate that eccentric exercise of moderate intensity leads to greater resistance to fatigue and more work output compared to concentric exercise, despite the comparable muscle and cerebral oxygenation levels.

Eccentric exercise per se does not affect muscle damage biomarkers: early and late phase adaptations.

PURPOSE: Acute high-intensity unaccustomed eccentric exercise performed by naive subjects is accompanied by disturbances in muscle damage biomarkers. The aim of the study was to investigate whether a causal relationship indeed exists between eccentric exercise and muscle damage. METHODS: Twenty-four men randomly assigned into a concentric only or an eccentric-only training group and performed 10 weeks of isokinetic resistance exercise (one session/week of 75 maximal knee extensors actions). Physiological markers of muscle function and damage (i.e., range of motion, delayed onset muscle soreness, isometric, concentric and eccentric peak torque) were assessed prior to and 1-3 and 5 days post each session. Biochemical markers of muscle damage (creatine kinase) and inflammation (C-reactive protein) were measured prior and 2 days post each session. RESULTS: After the first bout, eccentric exercise induced greater muscle damage compared to concentric exercise; however, during the nine following sessions, this effect progressively diminished, while after the 10th week of training, no alterations in muscle damage biomarkers were observed after either exercise protocol. Additionally, strength gains at the end of the training period were comparable between the two groups and were mode-specific. CONCLUSION: (1) eccentric exercise per se does not affect muscle damage biomarkers; (2) muscle damage occurs as a result of muscle unaccustomedness to this action type; (3) exercise-induced muscle damage is not a prerequisite for increased muscle strength. Collectively, we believe that muscle unaccustomedness to high-intensity eccentric exercise, and not eccentric exercise per se, is the trigger for muscle damage as indicated by muscle damage biomarkers.

Dietary Cysteine Intake is Associated with Blood Glutathione Levels and Isometric Strength.

Glutathione is the most abundant cellular antioxidant and regulates redox homeostasis. Healthy individuals with certain antioxidant inadequacies/deficiencies exhibit impairments in physiological functions. The aim was to investigate whether low levels of dietary cysteine intake are associated with a) lower erythrocyte glutathione, b) increased plasma F2-isoprostanes, and c) impaired muscle function. Towards this aim, we recorded the dietary intake of the three amino acids that synthesize glutathione (i. e., glutamic acid, cysteine, and glycine) in forty-one healthy individuals, and subsequently measured erythrocyte glutathione levels. Maximal isometric strength and fatigue index were also assessed using an electronic handgrip dynamometer. Our findings indicate that dietary cysteine intake was positively correlated with glutathione levels (r=0.765, p<0.001). In addition, glutathione levels were negatively correlated with F2-isoprostanes (r=- 0.311, p=0.048). An interesting finding was that glutathione levels and cysteine intake were positively correlated with maximal handgrip strength (r=0.416, p=0.007 and r=0.343, p=0.028, respectively). In conclusion, glutathione concentration is associated with cysteine intake, while adequate cysteine levels were important for optimal redox status and muscle function. This highlights the importance of proper nutritional intake and biochemical screening with the goal of personalized nutrition.

Effect of body composition on redox homeostasis at rest and in response to exercise: The case of underfat women.

Underfat individuals have been neglected as a malnourished population in terms of redox homeostasis. The aim of the present study was to evaluate the effect of body composition on redox homeostasis at rest and in response to exercise. Underfat, lean and overfat women, classified according to their BMI and body fat percentage, participated in the study and were subjected to an acute session of eccentric exercise. With regard to muscle function and damage, a significant group × time interaction was found for range of motion (P < .01), isometric peak torque at 90° (P < .01), delayed onset muscle soreness (P < .01) and creatine kinase (P < .05), with the lean group generally exhibiting faster recovery compared to the underfat and overfat groups. With regard to redox homeostasis, a significant group × time interaction was found for F2-isoprostanes, protein carbonyls and glutathione (P < .01 for all biomarkers), with the underfat and overfat groups exhibiting increased resting oxidative stress levels and lower exercise-induced reactive species production . In conclusively, our data underline the importance of normal body composition for redox homeostasis, since underfat and overfat women demonstrate a similar pattern of redox disturbances both at rest and in response to exercise.

Beetroot Increases Muscle Performance and Oxygenation During Sustained Isometric Exercise, but Does Not Alter Muscle Oxidative Efficiency and Microvascular Reactivity at Rest.

OBJECTIVE: To examine the effects of beetroot juice (BRJ) on (i) in vivo skeletal muscle O2 consumption (mVO2) and microvascular reactivity at rest and (ii) muscle performance, muscle oxygenation, and mVO2 during sustained isometric handgrip exercise (IHG). METHODS: Sixteen young males consumed, randomly, a nitrate-rich (8.1 mmol BRJnitrate) or nitrate-depleted (BRJplacebo) BRJ. After 2.5 hours, they performed an occlusion-reperfusion maneuver at rest, a 3-minute sustained IHG, and a sustained IHG to exhaustion with arterial occlusion. Changes in muscle oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), microvascular red blood cell content (tHb), and mVO2 were measured using near-infrared spectroscopy. Force output was recorded. RESULTS: During occlusion, the O2Hb decline did not differ between BRJnitrate and BRJplacebo (magnitude: -30.3 ± 1.6 vs. -31.1 ± 1.5 ΔµΜ; slope: -0.107 ± 0.007 vs. -0.111 ± 0.007 µΜ second-1). During reperfusion, all microvascular reactivity indices were not altered after BRJnitrate (e.g., O2Hbslope: 1.584 ± 0.093 vs. 1.556 ± 0.072 µΜ second-1). During the second and third minute of IHG, O2Hb and tHb were higher in BRJnitrate versus BRJplacebo (p < 0.05), and force output was higher during the third minute (10.8 ± 0.7 vs. 9.5 ± 1.2 kg; p < 0.05); HHb did not differ between trials. In IHG with arterial occlusion, BRJnitrate prolonged the time to fatigue (94.1 ± 5.8 vs. 80.1 ± 3.3 seconds; p < 0.01), with no effects on O2Hb decline (O2Hbslope: -0.226 ± 0.015 vs. -0.230 ± 0.026 µΜ s-1) and mVO2 (14.1 ± 1.0 vs. 14.3 ± 1.6 µmol l-1 minute-1). CONCLUSION: Acute BRJ ingestion in moderately trained individuals (i) did not alter in vivo skeletal muscle microvascular reactivity (index of microvascular function at rest) and basal oxidative efficiency, (ii) increased muscle oxygenation during IHG (possibly via enhanced O2 delivery), and (iii) provided ergogenic benefits during sustained IHG with no effects on muscle oxidative efficiency. The ergogenic effects of BRJ appeared independent of its tissue perfusion benefits.

A Novel Swimming Performance Test in Rats.

Swimming is an advantageous exercise modality since it induces limited muscle damage. Performance is a crucial endpoint measurement of physiological relevance in exercise physiology and clinical settings alike. To our knowledge, the literature lacks a comprehensive and widely accepted swimming performance protocol without suffering from high variability in time to exhaustion. Thus, the present study presents an easily carried out, two-phased swimming performance incremental test exhibiting low variability in the time to exhaustion among rats. All nine rats managed to complete the first 12 min-part of the test (phase 1) with gradually increased loads attached at the base of their tails equal to 2%, 3.5% and 5% (for 4 min each). All rats reached exhaustion at the 10% final load (phase 2). The mean swimming time until exhaustion, as a measure for defining exercise performance, was 865 ± 59 s. In conclusion, we have presented in detail a novel protocol for practically and satisfactorily measuring swimming performance in rats characterized by low variability in the time to exhaustion. This protocol, with the appropriate modifications, can be applied to a wide spectrum of experimental treatments.

Global Metabolic Stress of Isoeffort Continuous and High Intensity Interval Aerobic Exercise: A Comparative 1H NMR Metabonomic Study.

The overall metabolic/energetic stress that occurs during an acute bout of exercise is proposed to be the main driving force for long-term training adaptations. Continuous and high-intensity interval exercise protocols (HIIE) are currently prescribed to acquire the muscular and metabolic benefits of aerobic training. We applied 1H NMR-based metabonomics to compare the overall metabolic perturbation and activation of individual bioenergetic pathways of three popular aerobic exercises matched for effort/strain. Nine men performed continuous, long-interval (3 min), and short-interval (30 s) bouts of exercise under isoeffort conditions. Blood was collected before and after exercise. The multivariate PCA and OPLS-DA models showed a distinct separation of pre- and postexercise samples in three protocols. The two models did not discriminate the postexercise overall metabolic profiles of the three exercise types. Analysis focused on muscle bioenergetic pathways revealed an extensive upregulation of carbohydrate-lipid metabolism and the TCA cycle in all three protocols; there were only a few differences among protocols in the postexercise abundance of molecules when long-interval bouts were performed. In conclusion, continuous and HIIE exercise protocols, when performed with similar effort/strain, induce comparable global metabolic response/stress despite their marked differences in work-bout intensities. This study highlights the importance of NMR metabonomics in comprehensive monitoring of metabolic consequences of exercise training in the blood of athletes and exercising individuals.

Exaggerated haemodynamic and neural responses to involuntary contractions induced by whole-body vibration in normotensive obese versus lean women.

What is the central question of this study? In obesity, the exaggerated blood pressure response to voluntary exercise is linked to hypertension, yet the mechanisms are not fully elucidated. We examined whether involuntary contractions elicit greater haemodynamic responses and altered neural control of blood pressure in normotensive obese versus lean women. What is the main finding and its importance? During involuntary contractions induced by whole-body vibration, there were augmented blood pressure and spontaneous baroreflex responses in obese compared with lean women. This finding is suggestive of an overactive mechanoreflex in the exercise-induced hypertensive response in obesity. Passive contractions did not elicit differential heart rate responses in obese compared with lean women, implying other mechanisms for the blunted heart rate response reported during voluntary exercise in obesity. In obesity, the exaggerated blood pressure (BP) response to exercise is linked to hypertension, yet the mechanisms are not fully elucidated. In this study, we examined whether involuntary mechanical oscillations, induced by whole-body vibration (WBV), elicit greater haemodynamic responses and altered neural control of BP in obese versus lean women. Twenty-two normotensive, premenopausal women (12 lean and 10 obese) randomly underwent a passive WBV (25 Hz) and a control protocol (similar posture without WVB). Beat-by-beat BP, heart rate, stroke volume, systemic vascular resistance, cardiac output, parasympathetic output (evaluated by heart rate variability) and spontaneous baroreceptor sensitivity (sBRS) were assessed. We found that during WBV, obese women exhibited an augmented systolic BP response compared with lean women that was correlated with body fat percentage (r = 0.77; P < 0.05). The exaggerated BP rise was driven mainly by the greater increase in cardiac output index in obese versus lean women, associated with a greater stroke volume index in obese women. Involuntary contractions did not elicit a differential magnitude of responses in heart rate, heart rate variability indices and systemic vascular resistance in obese versus lean women; however, they did result in greater sBRS responses (P < 0.05) in obese women. In conclusion, involuntary contractions elicited an augmented BP and sBRS response in normotensive obese versus lean women. The greater elevations in circulatory haemodynamics in obese women are suggestive of an overactive mechanoreflex in the exercise-induced hypertensive response in obesity.

Spectrophotometric assays for measuring redox biomarkers in blood.

The assessment of redox status is most frequently performed by measuring redox biomarkers. The spectrophotometer is the most commonly used analytical instrument in biochemistry. There is a huge number of spectrophotometric redox biomarkers and assays, thus distinguishing the most appropriate biomarkers and protocols is overwhelming. The aim of the present review is to propose valid and reliable spectrophotometric assays for measuring redox biomarkers in blood. It is hoped that this work will help researchers to select the most suitable redox biomarkers and assays.

Low vitamin C values are linked with decreased physical performance and increased oxidative stress: reversal by vitamin C supplementation.

PURPOSE: It has been suggested that part of the failure of antioxidant supplementation to reduce oxidative stress and promote health is that it has been administered in humans with normal levels of antioxidants. METHODS: To test this hypothesis, we screened 100 males for vitamin C baseline values in blood. Subsequently, the 10 individuals with the lowest and the 10 with the highest vitamin C values were assigned in two groups. Using a placebo-controlled crossover design, the 20 selected subjects performed aerobic exercise to exhaustion (oxidant stimulus) before and after vitamin C supplementation for 30 days. RESULTS: The low vitamin C group had lower VO2max values than the high vitamin C group. Vitamin C supplementation in this group marginally increased VO2max. Baseline concentration of F2-isoprostanes and protein carbonyls was higher in the low vitamin C group compared to the high vitamin C group. Vitamin C supplementation decreased the baseline concentration of F2-isoprostanes and protein carbonyls in both groups, yet the decrease was greater in the low vitamin C group. Before vitamin C supplementation, F2-isoprostanes and protein carbonyls were increased to a greater extent after exercise in the high vitamin C group compared to the low vitamin C group. Interestingly, after vitamin C supplementation, this difference was narrowed. CONCLUSION: We show for the first time that low vitamin C concentration is linked with decreased physical performance and increased oxidative stress and that vitamin C supplementation decreases oxidative stress and might increase exercise performance only in those with low initial concentration of vitamin C.

The rat closely mimics oxidative stress and inflammation in humans after exercise but not after exercise combined with vitamin C administration.

PURPOSE: The purpose of the present study was to directly compare oxidative stress and inflammation responses between rats and humans. METHODS: We contrasted rat and human oxidative stress and inflammatory responses to exercise (pro-oxidant stimulus) and/or vitamin C (anti-oxidant stimulus) administration. Vitamin C was administered orally in both species (16 mg kg(-1) of body weight). Twelve redox biomarkers and seven inflammatory biomarkers were determined in plasma and erythrocytes pre- and post-exercise or pre- and post-exercise combined with vitamin C administration. RESULTS: Exercise increased oxidative stress and induced an inflammatory state in rats and humans. There were only 1/19 significant species × exercise interactions (catalase), indicating similar responses to exercise between rats and humans in redox and inflammatory biomarkers. Vitamin C decreased oxidative stress and increased antioxidant capacity only in humans and did not affect the redox state of rats. In contrast, vitamin C induced an anti-inflammatory state only in rats and did not affect the inflammatory state of humans. There were 10/19 significant species × vitamin C interactions, indicating that rats poorly mimic human oxidative stress and inflammatory responses to vitamin C administration. Exercise after acute vitamin C administration altered redox state only in humans and did not affect the redox state of rats. On the contrary, inflammation biomarkers changed similarly after exercise combined with vitamin C in both rats and humans. CONCLUSIONS: The rat adequately mimics human responses to exercise in basic blood redox/inflammatory profile, yet this is not the case after exercise combined with vitamin C administration.

Blood reflects tissue oxidative stress: a systematic review.

We examined whether the levels of oxidative stress biomarkers measured in blood reflect the tissue redox status. Data from studies that measured redox biomarkers in blood, heart, liver, kidney and skeletal muscle were analyzed. In seven out of nine investigated redox biomarkers (malondialdehyde, reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase, vitamin C and E) there was generally good qualitative and quantitative agreement between the blood and tissues. In contrast, oxidized glutathione and the reduced to oxidized glutathione ratio showed poor agreement between the blood and tissues. This study suggests that most redox biomarkers measured in blood adequately reflect tissue redox status.

Passive smoking reduces and vitamin C increases exercise-induced oxidative stress: does this make passive smoking an anti-oxidant and vitamin C a pro-oxidant stimulus?

The current interpretative framework states that, for a certain experimental treatment (usually a chemical substance) to be classified as "anti-oxidant", it must possess the property of reducing (or even nullifying) exercise-induced oxidative stress. The aim of the study was to compare side by side, in the same experimental setup, redox biomarkers responses to an identical acute eccentric exercise session, before and after chronic passive smoking (considered a pro-oxidant stimulus) or vitamin C supplementation (considered an anti-oxidant stimulus). Twenty men were randomly assigned into either passive smoking or vitamin C group. All participants performed two acute eccentric exercise sessions, one before and one after either exposure to passive smoking or vitamin C supplementation for 12 days. Vitamin C, oxidant biomarkers (F2-isoprostanes and protein carbonyls) and the non-enzymatic antioxidant (glutathione) were measured, before and after passive smoking, vitamin C supplementation or exercise. It was found that chronic exposure to passive smoking increased the level of F2-isoprostanes and decreased the level of glutathione at rest, resulting in minimal increase or absence of oxidative stress after exercise. Conversely, chronic supplementation with vitamin C decreased the level of F2-isoprostanes and increased the level of glutathione at rest, resulting in marked exercise-induced oxidative stress. Contrary to the current scientific consensus, our results show that, when a pro-oxidant stimulus is chronically delivered, it is more likely that oxidative stress induced by subsequent exercise is decreased and not increased. Reversely, it is more likely to find greater exercise-induced oxidative stress after previous exposure to an anti-oxidant stimulus. We believe that the proposed framework will be a useful tool to reach more pragmatic explanations of redox biology phenomena.

Circulating angiogenic biomolecules at rest and in response to upper-limb exercise in individuals with spinal cord injury.

OBJECTIVE: Individuals with spinal cord injury (SCI) show structural and functional vascular maladaptations and muscle loss in their lower limbs. Angiogenic biomolecules play important roles in physiological and pathological angiogenesis, and are implicated in the maintenance of muscle mass. This study examined the responses of angiogenic molecules during upper-limb aerobic exercise in patients with SCI and in able-bodied (AB) individuals. METHODS: Eight SCI patients with thoracic lesions (T6-T12, ASIA A) and eight AB individuals performed an arm-cranking exercise for 30 minutes at 60% of their VO2max. Plasma concentrations of vascular endothelial growth factor (VEGF-A165), VEGF receptor 1 (sVEGFr-1), VEGF receptor 2 (sVEGFr-2), metalloproteinase 2 (MMP-2), and endostatin were measured at rest, after exercise, and at 1.5 and 3.0 hours during recovery. RESULTS: The two-way analysis of variance showed non-significant main effects of "group" and significant main effects of "time/exercise" for all angiogenic biomolecules examined (P < 0.01-0.001). The arm-cranking exercise significantly increased plasma concentrations of VEGF, sVEGFr-1, sVEGFr-2, MMP-2, and endostatin in both groups (P < 0.001-0.01). The magnitude of the increase was similar in both patients with SCI and AB individuals, as shown by the non-significant group × time interaction for all angiogenic parameters. CONCLUSIONS: Upper-limb exercise (arm-cranking for 30 minutes at 60% of VO2max) is a sufficient stimulus to trigger a coordinated circulating angiogenic response in patients with SCI. The response of angiogenic molecules to upper-limb aerobic exercise in SCI appears relatively similar to that observed in AB individuals.

Erythrocyte metabolism.

Our aim is to present an updated overview of the erythrocyte metabolism highlighting its richness and complexity. We have manually collected and connected the available biochemical pathways and integrated them into a functional metabolic map. The focus of this map is on the main biochemical pathways consisting of glycolysis, the pentose phosphate pathway, redox metabolism, oxygen metabolism, purine/nucleoside metabolism, and membrane transport. Other recently emerging pathways are also curated, like the methionine salvage pathway, the glyoxalase system, carnitine metabolism, and the lands cycle, as well as remnants of the carboxylic acid metabolism. An additional goal of this review is to present the dynamics of erythrocyte metabolism, providing key numbers used to perform basic quantitative analyses. By synthesizing experimental and computational data, we conclude that glycolysis, pentose phosphate pathway, and redox metabolism are the foundations of erythrocyte metabolism. Additionally, the erythrocyte can sense oxygen levels and oxidative stress adjusting its mechanics, metabolism, and function. In conclusion, fine-tuning of erythrocyte metabolism controls one of the most important biological processes, that is, oxygen loading, transport, and delivery.

Determinants of muscle metaboreflex and involvement of baroreflex in boys and young men.

This study aimed to assess the arterial pressure (AP) determinants during the muscle metaboreflex in boys and men and to investigate the contribution of baroreflex and sympathovagal function to the metaboreflex-induced responses. Fourteen pre-adolescent boys and 13 men performed a protocol involving: baseline, isometric handgrip exercise, circulatory occlusion, and recovery. The same protocol was repeated without occlusion. During baseline, boys had lower beat-to-beat AP, higher heart rate (HR), and lower low/high frequency HR variability. During exercise, a parasympathetic withdrawal was evident in both groups. In adults, HR was the key contributor to the pressure response, with no changes in stroke volume, whereas in boys, the lower HR increase was counterbalanced by an increase in stroke volume, resulting in similar relative increases in AP in both groups. In recovery, boys exhibited a faster rate of HR-decay, rapid vagal reactivation, and greater decrease in TPR than men. An overshoot in baroreceptor sensitivity was observed in men. The isolated metaboreflex resulted in a similar AP elevation in both age groups (by ~15 mmHg), and attenuated spontaneous baroreceptor sensitivity. However, during the metaboreflex, pre-adolescent males exhibited a lower increase in peripheral resistance and a greater bradycardic response than adults, and a fast restoration of vagal activity to non-occlusion levels. During metaboreflex, boys were capable of eliciting a pressure response similar to the one elicited by men; however, the interplay of the mechanisms underlying the rise in AP differed between the two groups with the vagal contribution being greater in the younger participants.

Inter-individual variability in redox and performance responses after antioxidant supplementation: A randomized double blind crossover study.

AIM: We aimed to investigate the inter-individual variability in redox and physiological responses of antioxidant-deficient subjects after antioxidant supplementation. METHODS: Two hundred individuals were sorted by plasma vitamin C levels. A low vitamin C group (n = 22) and a control group (n = 22) were compared in terms of oxidative stress and performance. Subsequently, the low vitamin C group received for 30 days vitamin C (1 g) or placebo, in randomized, double-blind, crossover fashion, and the effects were examined through a mixed-effects model, while individual responses were calculated. RESULTS: The low vitamin C group exhibited lower vitamin C (-25 µmol/L; 95%CI[-31.7, -18.3]; p < 0.001), higher F2 -isoprostanes (+17.1 pg/mL; 95%CI[6.5, 27.7]; p = 0.002), impaired VO2max (-8.2 mL/kg/min; 95%CI[-12.8, -3.6]; p < 0.001) and lower isometric peak torque (-41.5 Nm; 95%CI[-61.8, -21.2]; p < 0.001) compared to the control group. Regarding antioxidant supplementation, a significant treatment effect was found in vitamin C (+11.6 µmol/L; 95%CI[6.8, 17.1], p < 0.001), F2 -isoprostanes (-13.7 pg/mL; 95%CI[-18.9, -8.4], p < 0.001), VO2max (+5.4 mL/kg/min; 95%CI[2.7, 8.2], p = 0.001) and isometric peak torque (+18.7; 95%CI[11.8, 25.7 Nm], p < 0.001). The standard deviation for individual responses (SDir) was greater than the smallest worthwhile change (SWC) for all variables indicating meaningful inter-individual variability. When a minimal clinically important difference (MCID) was set, inter-individual variability remained for VO2max , but not for isometric peak torque. CONCLUSION: The proportion of response was generally high after supplementation (82.9%-95.3%); however, a few participants did not benefit from the treatment. This underlines the potential need for personalized nutritional interventions in an exercise physiology context.

Redox biology of exercise: an integrative and comparative consideration of some overlooked issues.

The central aim of this review is to address the highly multidisciplinary topic of redox biology as related to exercise using an integrative and comparative approach rather than focusing on blood, skeletal muscle or humans. An attempt is also made to re-define 'oxidative stress' as well as to introduce the term 'alterations in redox homeostasis' to describe changes in redox homeostasis indicating oxidative stress, reductive stress or both. The literature analysis shows that the effects of non-muscle-damaging exercise and muscle-damaging exercise on redox homeostasis are completely different. Non-muscle-damaging exercise induces alterations in redox homeostasis that last a few hours post exercise, whereas muscle-damaging exercise causes alterations in redox homeostasis that may persist for and/or appear several days post exercise. Both exhaustive maximal exercise lasting only 30 s and isometric exercise lasting 1-3 min (the latter activating in addition a small muscle mass) induce systemic oxidative stress. With the necessary modifications, exercise is capable of inducing redox homeostasis alterations in all fluids, cells, tissues and organs studied so far, irrespective of strains and species. More importantly, 'exercise-induced oxidative stress' is not an 'oddity' associated with a particular type of exercise, tissue or species. Rather, oxidative stress constitutes a ubiquitous fundamental biological response to the alteration of redox homeostasis imposed by exercise. The hormesis concept could provide an interpretative framework to reconcile differences that emerge among studies in the field of exercise redox biology. Integrative and comparative approaches can help determine the interactions of key redox responses at multiple levels of biological organization.

Exercise as a model to study redox homeostasis in blood: the effect of protocol and sampling point.

Twenty males ran either on a level treadmill (nonmuscle-damaging condition) or on a downhill treadmill (muscle-damaging condition). Blood and urine samples were collected before and after exercise (immediately after, 1h, 4h, 24h, 48h, and 96h). The following assays were performed: F(2)-isoprostanes in urine, protein carbonyls in plasma, glutathione, superoxide dismutase, glutathione peroxidase, and catalase in erythrocytes. The main finding was that monophasic redox responses were detected after nonmuscle-damaging exercise compared to the biphasic responses detected after muscle-damaging exercise. Based on these findings, muscle-damaging exercise may be a more appropriate experimental model to induce physiological oxidative stress.