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Background: Changes in tryptophan metabolism through the kynurenine pathway (KP) are observed in several disorders and coupled with pathophysiological deviations. Methods: This study retrospectively compared the KP in serum in healthy subjects (108) with subjects with obesity (141), depression (49), and chronic obstructive pulmonary disease (COPD) (22) participating in four clinical studies and explored predictors of the changes in the KP metabolites. Results: Compared with the healthy group, the KP was upregulated in the disease groups with high kynurenine, quinolinic acid (QA), kynurenine/tryptophan-ratio and QA/xanthurenic acid-ratio and low kynurenic acid/QA-ratio. Tryptophan and xanthurenic acid were upregulated in the depressed group compared with the groups with obesity and COPD. The covariates BMI, smoking, diabetes, and C-reactive protein explained the significant differences between the healthy group and the group with obesity but not between the healthy group and the groups with depression and COPD, indicating that different pathophysiological conditions result in the same changes in the KP. Conclusions: The KP was significantly upregulated in the disease groups compared with the healthy group, and there were significant differences between the disease groups. Different pathophysiological abnormalities seemed to result in the same deviations in the KP. [ABSTRACT FROM AUTHOR]

Obesity and physical inactivity have a profound impact on skeletal muscle metabolism. In the present work, we have investigated differences in protein expression and energy metabolism in primary human skeletal muscle cells established from lean donors (BMI<25 kg/m2) and individuals with obesity (BMI>30 kg/m2). Furthermore, we have studied the effect of fatty acid pretreatment on energy metabolism in myotubes from these donor groups. Alterations in protein expression were investigated using proteomic analysis, and energy metabolism was studied using radiolabeled substrates. Gene Ontology enrichment analysis showed that glycolytic, apoptotic, and hypoxia pathways were upregulated, whereas the pentose phosphate pathway was downregulated in myotubes from donors with obesity compared to myotubes from lean donors. Moreover, fatty acid, glucose, and amino acid uptake were increased in myotubes from individuals with obesity. However, fatty acid oxidation was reduced, glucose oxidation was increased in myotubes from subjects with obesity compared to cells from lean. Pretreatment of myotubes with palmitic acid (PA) or eicosapentaenoic acid (EPA) for 24 h increased glucose oxidation and oleic acid uptake. EPA pretreatment increased the glucose and fatty acid uptake and reduced leucine fractional oxidation in myotubes from donors with obesity. In conclusion, these results suggest that myotubes from individuals with obesity showed increased fatty acid, glucose, and amino acid uptake compared to cells from lean donors. Furthermore, myotubes from individuals with obesity had reduced fatty acid oxidative capacity, increased glucose oxidation, and a higher glycolytic reserve capacity compared to cells from lean donors. Fatty acid pretreatment enhances glucose metabolism, and EPA reduces oleic acid and leucine fractional oxidation in myotubes from donor with obesity, suggesting increased metabolic flexibility after EPA treatment. [ABSTRACT FROM AUTHOR]

Purpose: The primary purpose was to test the effect of heat suit training on hemoglobin mass (Hbmass) in elite cross‐country (XC) skiers. Methods: Twenty‐five male XC‐skiers were divided into a group that added 5 × 50 min weekly heat suit training sessions to their regular training (HEAT; n = 13, 23 ± 5 years, 73.9 ± 5.2 kg, 180 ± 6 cm, 76.8 ± 4.6 ml·min−1·kg−1) or to a control group matched for training volume and intensity distribution (CON; n = 12, 23 ± 4 years, 78.4 ± 5.8 kg, 184 ± 4 cm, 75.2 ± 3.4 ml·min−1·kg−1) during the five‐week intervention period. Hbmass, endurance performance and factors determining endurance performance were assessed before and after the intervention. Results: HEAT led to 30 g greater Hbmass (95% CI: [8.5, 51.7], p = 0.009) and 157 ml greater red blood cell volume ([29, 285], p = 0.018) post‐intervention, compared to CON when adjusted for baseline values. In contrast, no group differences were observed for changes in work economy, running velocity, and fractional utilization of maximal oxygen uptake (V̇O2max) at 4 mmol·L−1 blood lactate, V̇O2max or 15‐min running distance performance trial during the intervention. Conclusion: HEAT induced a larger increase in Hbmass and red blood cell volume after five weeks with five weekly heat suit training sessions than CON, but with no detectable group differences on physiological determinants of endurance performance or actual endurance performance in elite CX skiers. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the effects of 12 weeks load-matched block periodization (BP, n = 14), using weekly concentration of high- (HIT), moderate- (MIT), and low- (LIT) intensity training, with traditional periodization (TP, n = 16) using a weekly, cyclic progressive increase in training load of HIT-, MIT-, and LIT-sessions in trained cyclists (peak oxygen uptake: 58 ± 8 ml·kg−1·min−1). Red blood cell volume increased 10 ± 16% (p = 0.029) more in BP compared to TP, while capillaries around type I fibers increased 20 ± 12% (p = 0.002) more in TP compared to BP from Pre to Post12. No other group differences were found in time-trial (TT) performances or muscular-, or hematological adaptations. However, both groups improved 5 and 40-min TT power by 9 ± 9% (p < 0.001) and 8 ± 9% (p < 0.001), maximal aerobic power (Wmax) and power output (PO) at 4 mmol·L−1 blood lactate (W4mmol), by 6 ± 7 (p = 0.001) and 10 ± 12% (p = 0.001), and gross efficiency (GE) in a semi-fatigued state by 0.5 ± 1.1%-points (p = 0.026). In contrast, GE in fresh state and VO2peak were unaltered in both groups. The muscle protein content of β-hydroxyacyl (HAD) increased by 55 ± 58% in TP only, while both TP and BP increased the content of cytochrome c oxidase subunit IV (COXIV) by 72 ± 34%. Muscle enzyme activities of citrate synthase (CS) and phosphofructokinase (PFK) were unaltered. TP increased capillary-to-fiber ratio and capillary around fiber (CAF) type I by 36 ± 15% (p < 0.001) and 17 ± 8% (p = 0.025), respectively, while BP increased capillary density (CD) by 28 ± 24% (p = 0.048) from Pre to Post12. The present study shows no difference in performance between BP and "best practice"-TP of endurance training intensities using a cyclic, progressively increasing training load in trained cyclists. However, hematological and muscle capillary adaptations may differ. [ABSTRACT FROM AUTHOR]

The main goal of the current study was to compare the effects of volume-equated training frequency on gains in muscle mass and strength. In addition, we aimed to investigate whether the effect of training frequency was affected by the complexity, concerning the degrees of freedom, of an exercise. Participants were randomized to a moderate training frequency group (two weekly sessions) or high training frequency group (four weekly sessions). Twenty-one participants (male: 11, female: 10, age: 25.9 ± 4.0) completed the 9-week whole-body progressive heavy resistance training intervention with moderate (n = 13) or high (n = 8) training frequency. Whole-body and regional changes in lean mass were measured using dual-energy x-ray absorptiometry, while the vastus lateralis thickness was measured by ultrasound. Changes in muscle strength were measured as one repetition maximum for squat, hack squat, bench press, and chest press. No differences between groups were observed for any of the measures of muscle growth or muscle strength. Muscle strength increased to a greater extent in hack squat and chest press than squat and bench press for both moderate (50 and 21% vs. 19 and 14%, respectively) and high-frequency groups (63 and 31% vs. 19 and 16%, respectively), with no differences between groups. These results suggest that training frequency is less decisive when weekly training volume is equated. Further, familiarity with an exercise seems to be of greater importance for strength adaptations than the complexity of the exercise. [ABSTRACT FROM AUTHOR]

Background: Lifestyle therapy with resistance training is a potent measure to counteract age‐related loss in muscle strength and mass. Unfortunately, many individuals fail to respond in the expected manner. This phenomenon is particularly common among older adults and those with chronic diseases (e.g. chronic obstructive pulmonary disease, COPD) and may involve endocrine variables such as vitamin D. At present, the effects of vitamin D supplementation on responses to resistance training remain largely unexplored. Methods: Ninety‐five male and female participants (healthy, n = 71; COPD, n = 24; age 68 ± 5 years) were randomly assigned to receive either vitamin D3 or placebo supplementation for 28 weeks in a double‐blinded manner (latitude 61°N, September–May). Seventy‐eight participants completed the RCT, which was initiated by 12 weeks of supplementation‐only (two weeks with 10 000 IU/day, followed by 2000 IU/day), followed by 13 weeks of combined supplementation (2000 IU/day) and supervised whole‐body resistance training (twice weekly), interspersed with testing and measurements. Outcome measures included multiple assessments of muscle strength (nvariables = 7), endurance performance (n = 6), and muscle mass (n = 3, legs, primary), as well as muscle quality (legs), muscle biology (m. vastus lateralis; muscle fibre characteristics, transcriptome), and health‐related variables (e.g. visceral fat mass and blood lipid profile). For main outcome domains such as muscle strength and muscle mass, weighted combined factors were calculated from the range of singular assessments. Results: Overall, 13 weeks of resistance training increased muscle strength (13% ± 8%), muscle mass (9% ± 8%), and endurance performance (one‐legged, 23% ± 15%; whole‐body, 8% ± 7%), assessed as weighted combined factors, and were associated with changes in health variables (e.g. visceral fat, −6% ± 21%; [LDL]serum, −4% ± 14%) and muscle tissue characteristics such as fibre type proportions (e.g. IIX, −3% points), myonuclei per fibre (30% ± 65%), total RNA/rRNA abundances (15%/6–19%), and transcriptome profiles (e.g. 312 differentially expressed genes). Vitamin D3 supplementation did not affect training‐associated changes for any of the main outcome domains, despite robust increases in [25(OH)D]serum (∆49% vs. placebo). No conditional effects were observed for COPD vs. healthy or pre‐RCT [25(OH)D]serum. In secondary analyses, vitamin D3 affected expression of gene sets involved in vascular functions in muscle tissue and strength gains in participants with high fat mass, which advocates further study. Conclusions: Vitamin D3 supplementation did not affect muscular responses to resistance training in older adults with or without COPD. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Do haemoglobin mass and red blood cell volume increase in elite cyclists training in a hot environment compared to a control group training at normal temperature?What is the main finding and its importance?Five weeks of heat training increases haemoglobin mass in elite cyclists. There are small to intermediate effect sizes for exercise parameters favouring heat training. In this study we tested the hypothesis that performing 1 h of regular light exercise in a heat chamber (HEAT; 37.8 ± 0.5°C; 65.4 ± 1.8% humidity) 5 times week−1 for a total of 5 weeks increases haemoglobin mass (Hbmass) and exercise performance in elite cyclists (V̇O2max = 76.2 ± 7.6 ml min−1 kg−1). Twenty‐three male volunteers were assigned to HEAT (n = 11) or CON (n = 12; 15.5 ± 0.1°C; 25.1 ± 0.0% humidity) training groups. Hbmass was determined before and after the intervention period in conjunction with an extensive exercise test protocol (conducted at 16–19°C). HEAT increased (P < 0.05) Hbmass by 42 g from 893 ± 78 to 935 ± 108 g whereas Hbmass remained unchanged (+6 g) in CON. Furthermore, statistical analysis revealed a time–group interaction (P < 0.05). The greater increase in Hbmass in HEAT, however, did not manifest in a greater increase in V̇O2max (225 ± 274 ml min−1 in HEAT and 161 ± 202 ml min−1 in CON). While HEAT reduced (P < 0.05) lactate levels during some of the submaximal exercise tests, there was no statistical difference between other performance parameters. There were, however, small to intermediate effect sizes favouring HEAT for lactate threshold power output (2.8 ± 3.9 vs. −0.4 ± 5.1% change, effect size (ES) = 0.34), gross economy in the fatigued state (0.19 ± 0.42 vs. −0.12 ± 0.49%‐point change, ES = 0.52) and 15 min mean power (6.9 ± 8.4 vs. 3.4 ± 5.1% increase, ES = 0.22). This study demonstrates an increase in Hbmass and small to intermediate effect sizes on exercise variables in elite cyclists following a 5‐week heat training intervention. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate the effect of an arduous 1-wk military course on measures of physical performance, body composition, and blood biomarkers. Methods: Participants were apprentices in an annual selection course for the Norwegian Special Forces. Fifteen soldiers (23 ± 4 yr, 1.81 ± 0.06 m, 78 ± 7 kg) completed a hell week consisting of rigorous activity only interspersed by 2 to 3 h of sleep per day. Testing was conducted before and 0, 1, 3, 7, and 14 d after the hell week. Physical performance was measured as muscle strength and jump performance. Body composition was measured by bioelectrical impedance and blood samples were collected and analyzed for hormones, creatine kinase, and C-reactive protein. Results: Body mass was reduced by 5.3 ± 1.9 kg during the hell week and returned to baseline within 1 wk. Fat mass was reduced by 2.1 ± 1.7 kg and muscle mass by 1.9 ± 0.9 kg. Muscle strength in leg press and bench press was reduced by 20% ± 9% and 9% ± 7%, respectively, and both were approximately 10% lower than baseline after 1 wk of recovery. Jump-height was reduced by 28% ± 13% and was still 14% ± 5% below baseline after 2 wk of recovery. Testosterone was reduced by 70% ± 12% and recovered gradually within a week. Cortisol was increased by 154% ± 74% and did not fully recover during the next week. Insulin-like growth factor 1 was reduced by 51% ± 10% and triiodothyronine and thyroxine by 12% to 30%, all recovered within a week. Conclusions: One-week arduous military exercise resulted in reductions in body mass and performance, as well as considerable hormonal disturbances. Our most important observation was that whereas the hormonal systems was normalized within 1 wk of rest and proper nutrition, lower body strength and jump performance were still depressed after 2 wk. [ABSTRACT FROM AUTHOR]

Background: Protein intake is essential to maximally stimulate muscle protein synthesis, and the amino acid leucine seems to possess a superior effect on muscle protein synthesis compared to other amino acids. Native whey has higher leucine content and thus a potentially greater anabolic effect on muscle than regular whey (WPC-80). This study compared the acute anabolic effects of ingesting 2 × 20 g of native whey protein, WPC-80 or milk protein after a resistance exercise session. Methods: A total of 24 young resistance trained men and women took part in this double blind, randomized, partial crossover, controlled study. Participants received either WPC-80 and native whey (n = 10), in a crossover design, or milk (n = 12). Supplements were ingested immediately (20 g) and two hours after (20 g) a bout of heavy-load lower body resistance exercise. Blood samples and muscle biopsies were collected to measure plasma concentrations of amino acids by gas-chromatography mass spectrometry, muscle phosphorylation of p70S6K, 4E–BP1 and eEF-2 by immunoblotting, and mixed muscle protein synthesis by use of [2H5]phenylalanine-infusion, gas-chromatography mass spectrometry and isotope-ratio mass spectrometry. Being the main comparison, differences between native whey and WPC-80 were analysed by a one-way ANOVA and comparisons between the whey supplements and milk were analysed by a two-way ANOVA. Results: Native whey increased blood leucine concentrations more than WPC-80 and milk (P < 0.05). Native whey ingestion induced a greater phosphorylation of p70S6K than milk 180 min after exercise (P = 0.03). Muscle protein synthesis rates increased 1–3 h hours after exercise with WPC-80 (0.119%), and 1–5 h after exercise with native whey (0.112%). Muscle protein synthesis rates were higher 1–5 h after exercise with native whey than with milk (0.112% vs. 0.064, P = 0.023). Conclusions: Despite higher-magnitude increases in blood leucine concentrations with native whey, it was not superior to WPC-80 concerning effect on muscle protein synthesis and phosphorylation of p70S6K during a 5-h post-exercise period. Native whey increased phosphorylation of p70S6K and muscle protein synthesis rates to a greater extent than milk during the 5-h post exercise period. Trial registration: This study was retrospectively registered at clinicaltrials.gov as NCT02968888. [ABSTRACT FROM AUTHOR]

Background: High-intensity exercise induces many metabolic responses. In is unknown whether the response in the peripheral blood mononuclear cells (PBMCs) reflects the response in skeletal muscle and whether mRNA expression after exercise can be modulated by nutritional intake. The aims were to (i) investigate the effect of dairy proteins on acute responses to exercise in skeletal muscle and PBMCs measuring gene expression and (ii) compare this response in young and older subjects. Methods: We performed two separate studies in young (20-40 years) and older subjects (≥70 years). Subjects were randomly allocated to a milk group or a whey group. Supplements were provided immediately after a standardized exercise session. We measured mRNA expression of selected genes after a standardized breakfast and 60/120 min after finishing the exercise, using RT-qPCR. Results: We observed no significant differences in mRNA expression between the milk and the whey group; thus, we merged both groups for further analysis. The mRNA expression of IL6, TNF, and CCL2 in skeletal muscle increased significantly after exercise compared with smaller or no increase, in mRNA expression in PBMCs in all participants. The mRNA expression of IL1RN, IL8, and IL10 increased significantly in skeletal muscle and PBMCs. Some mRNA transcripts were differently regulated in older compared to younger participants in PBMCs. Conclusions: An acute bout of heavy-load strength exercise, followed by protein supplementation, caused overlapping, but also unique, responses in skeletal muscle and PBMCs, suggesting tissue-specific functions in response to exercise. However, no different effects of the different protein supplements were observed. Altered mRNA expressions in PBMCs of older participants may affect regenerative mechanisms. [ABSTRACT FROM AUTHOR]

Aging is associated with reduced specific strength, defined as strength normalized to the cross-sectional area of a given muscle or muscle group. Dysregulated autophagy, impairing removal of dysfunctional proteins and organelles, is suggested as one of the underlying mechanisms. The aim of this study was to investigate levels of autophagic markers in skeletal muscle in groups known to differ in specific strength. Sixty-two volunteers were assigned to the following study groups: young, old non-frail, old pre-frail, and old frail individuals. Leg lean mass was assessed with dual-energy X-ray absorptiometry and quadriceps femoris muscle strength by isometric maximal voluntary contraction. The abundance of autophagic proteins within skeletal muscle cytosolic and membrane sub-fractions were determined by western blotting. In addition, the level of heat shock proteins and proteins involved in the regulation of protein synthesis were measured. The abundance of LC3-I was higher in old frail compared to young individuals. If the three elderly groups were pooled, the level of LC3-II was higher in old compared to young subjects. Pre-frail and frail elderly also displayed higher levels of certain heat shock proteins. No between-group differences were observed for p62, LC3-II/LC3-I ratio, or any of the anabolic signaling molecules. A negative correlation was observed between cytosolic LC3-I and specific strength. Higher levels of LC3-I in the frail elderly might represent attenuated autophagosome formation. However, higher LC3-II levels indicate an increased abundance of autophagosomes. These findings may therefore imply that both the process of autophagosome formation and autophagosome-lysosome fusion are affected in frail elderly. Higher levels of heat shock proteins might represent an auto-protective mechanism against increased levels of misfolded proteins, possibly due to inefficient degradation. In conclusion, the reduction in specific strength with aging and frailty may partly be caused by alterations in muscle protein quality control. • Certain autophagic markers and heat shock proteins change with aging and frailty. • Differences may reflect alterations in protein quality control. • Altered protein quality control may contribute to reductions in specific strength. [ABSTRACT FROM AUTHOR]

Background: Large amounts of protein (40 g) or supplementing suboptimal servings of protein with leucine are able to overcome the anabolic resistance in elderly muscle. Our aim was to compare the effects of supplementation of native whey, high in leucine, with milk on gains in muscle mass and strength during a period of strength training, in elderly individuals. Methods: In this double-blinded, randomized, controlled study, a total of 30 healthy men and women received two daily servings of 20 g of either milk protein or native whey, during an 11-week strength training intervention. Muscle strength, lean mass, m. vastus lateralis thickness, muscle fiber area, and resting and post-exercise phosphorylation of p70S6K, 4E-BP1, and eEF-2 were assessed prior to and after the intervention period. Results: Muscle mass and strength increased, by all measures applied in both groups (p < 0.001), with no differences between groups (p > 0.25). p70S6K phosphorylation increased (~1000%, p < 0.045) 2 h after exercise in the untrained and trained state, with no differences between supplements. Total and phosphorylated mTORC-1 decreased after training. Conclusion: Supplementation with milk or native whey during an 11-week strength training period increased muscle mass and strength similarly in healthy elderly individuals. [ABSTRACT FROM AUTHOR]

Heat exercise training may increase exercise performance in athletes. The underlying mechanisms remain partly unresolved, and it is unknown if female and male athletes may experience comparable gains. The aims were to investigate whether heat training (HEAT) increases hemoglobin mass (Hb mass ), skeletal muscle fiber characteristics, and thermoneutral exercise performance in elite female and male endurance athletes. Female ( n = 20; V̇o 2max = 58.2 ± 6.7 mL·min -1 ·kg -1 ) and male ( n = 27; V̇o 2max = 76.4 ± 7.8 mL·min -1 ·kg -1 ) cyclists were studied before and after 5 wk of randomized control or HEAT consisting of five weekly sessions each of 50 min duration, which were included in their normal training regimes. Overall, the observed relative responses to HEAT were largely similar in female and male study participants. HEAT increased ( P < 0.05) Hb mass in females from 650 ± 77 to 675 ± 76 g (4.0 ± 1.6%) and from 1,008 ± 155 to 1,041 ± 147 g (3.5 ± 2.3%) in males. In contrast, skeletal muscle citrate synthase activity, fiber type distribution, and capillary density remained unchanged with HEAT. Lactate threshold, V̇o 2max , and mean power output during 15-min all-out testing were all enhanced ( P < 0.05) following HEAT in female and male study participants. In conclusion, 5 wk of HEAT increases Hb mass in female and male elite cyclists and improves exercise performance in a thermoneutral environment. Based on this, heat training may be recommended to elite female and male athletes aiming to perform in a thermoneutral environment. NEW & NOTEWORTHY We demonstrate in elite female and male cyclists that heat exercise training (5 × 50 min sessions/wk for 5 wk) facilities Hb mass and other hematological parameters more than control exercise training, whereas skeletal muscle properties remain unaltered. Collectively, this coincided with improvements in lactate threshold, V̇o 2max , and 15-min all-out cycling performance.

Background: Lifestyle therapy with resistance training is a potent measure to counteract age-related loss in muscle strength and mass. Unfortunately, many individuals fail to respond in the expected manner. This phenomenon is particularly common among older adults and those with chronic diseases (e.g. chronic obstructive pulmonary disease, COPD) and may involve endocrine variables such as vitamin D. At present, the effects of vitamin D supplementation on responses to resistance training remain largely unexplored., Methods: Ninety-five male and female participants (healthy, n = 71; COPD, n = 24; age 68 ± 5 years) were randomly assigned to receive either vitamin D 3 or placebo supplementation for 28 weeks in a double-blinded manner (latitude 61°N, September-May). Seventy-eight participants completed the RCT, which was initiated by 12 weeks of supplementation-only (two weeks with 10 000 IU/day, followed by 2000 IU/day), followed by 13 weeks of combined supplementation (2000 IU/day) and supervised whole-body resistance training (twice weekly), interspersed with testing and measurements. Outcome measures included multiple assessments of muscle strength (n variables  = 7), endurance performance (n = 6), and muscle mass (n = 3, legs, primary), as well as muscle quality (legs), muscle biology (m. vastus lateralis; muscle fibre characteristics, transcriptome), and health-related variables (e.g. visceral fat mass and blood lipid profile). For main outcome domains such as muscle strength and muscle mass, weighted combined factors were calculated from the range of singular assessments., Results: Overall, 13 weeks of resistance training increased muscle strength (13% ± 8%), muscle mass (9% ± 8%), and endurance performance (one-legged, 23% ± 15%; whole-body, 8% ± 7%), assessed as weighted combined factors, and were associated with changes in health variables (e.g. visceral fat, -6% ± 21%; [LDL] serum , -4% ± 14%) and muscle tissue characteristics such as fibre type proportions (e.g. IIX, -3% points), myonuclei per fibre (30% ± 65%), total RNA/rRNA abundances (15%/6-19%), and transcriptome profiles (e.g. 312 differentially expressed genes). Vitamin D 3 supplementation did not affect training-associated changes for any of the main outcome domains, despite robust increases in [25(OH)D] serum (∆49% vs. placebo). No conditional effects were observed for COPD vs. healthy or pre-RCT [25(OH)D] serum . In secondary analyses, vitamin D 3 affected expression of gene sets involved in vascular functions in muscle tissue and strength gains in participants with high fat mass, which advocates further study., Conclusions: Vitamin D 3 supplementation did not affect muscular responses to resistance training in older adults with or without COPD., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Antioxidant supplementation has recently been demonstrated to be a double-edged sword, because small to moderate doses of exogenous antioxidants are essential or beneficial, while high doses may have adverse effects. The adverse effects can be manifested in attenuated effects of exercise and training, as the antioxidants may shut down some redox-sensitive signaling in the exercised muscle fibers. However, conditions such as age may potentially modulate the need for antioxidant intake. Therefore, this paper describes experiments for testing the hypothesis that high dosages of vitamin C (1000 mg/day) and E (235 mg/day) have negative effects on adaptation to resistance exercise and training in young volunteers, but positive effects in older men., Methods/design: We recruited a total of 73 volunteers. The participants were randomly assigned to receiving either vitamin C and E supplementation or a placebo. The study design was double-blinded, and the participants followed an intensive training program for 10-12 weeks. Tests and measurements aimed at assessing changes in physical performance (maximal strength) and physiological characteristics (muscle mass), as well as biochemical and cellular systems and structures (e.g., cell signaling and morphology)., Discussion: Dietary supplements, such as vitamin C and E, are used by many people, especially athletes. The users often believe that high dosages of supplements improve health (resistance to illness and disease) and physical performance. These assumptions are, however, generally not supported in the scientific literature. On the contrary, some studies have indicated that high dosages of antioxidant supplements have negative effects on exercise-induced adaptation processes. Since this issue concerns many people and few randomized controlled trials have been conducted in humans, further studies are highly warranted., Trial Registration: ACTRN12614000065695.