Search

Emerging data indicate a substantial decrease in global physical activity levels during the period of social isolation adopted worldwide to contain the spread of the coronavirus disease 2019 (COVID-19). Confinement-induced decreases in physical activity levels and increases in sedentary behavior may provoke a rapid deterioration of cardiovascular health and premature deaths among populations with increased cardiovascular risk. Even short-term (1-4 wk) inactivity has been linked with detrimental effects in cardiovascular function and structure and increased cardiovascular risk factors. In this unprecedented and critical scenario, home-based physical activity programs arise as a clinically relevant intervention to promote health benefits to cardiac patients. Many studies have demonstrated the feasibility, safety, and efficacy of different models of home-based exercise programs in the primary and secondary prevention of cardiovascular diseases and major cardiovascular events among different populations. This body of knowledge can inform evidence-based policies to be urgently implemented to counteract the impact of increased physical inactivity and sedentary behavior during the COVID-19 outbreak, thereby alleviating the global burden of cardiovascular disease.

Objective: To evaluate the effects of a low-load resistance training program associated with partial blood-flow restriction in patients with rheumatoid arthritis (RA)., Methods: Forty-eight women with RA were randomized into 1 of 3 groups: high-load resistance training (HL-RT; 70% 1 repetition maximum [1RM]), low-load resistance training (30% 1RM) with partial blood-flow restriction training (BFRT), and a control group. Patients completed a 12-week supervised training program and were assessed for lower-extremity 1RM, quadriceps cross-sectional area (CSA), physical function (timed-stands test [TST], timed-up-and-go test [TUG], and Health Assessment Questionnaire [HAQ]), and quality of life (Short Form 36 health survey [SF-36]) at baseline and after the intervention., Results: BFRT and HL-RT were similarly effective in increasing maximum dynamic strength in both leg press (22.8% and 24.2%, respectively; P < 0.0001 for all) and knee extension (19.7% and 23.8%, respectively; P < 0.0001 for all). Quadriceps CSA was also significantly increased in both BFRT and HL-RT (9.5% and 10.8%, respectively; P < 0.0001 for all). Comparable improvements in TST (11.2% and 14.7%; P < 0.0001 for all) and TUG (-6.8% [P < 0.0053] and -8.7% [P < 0.0001]) were also observed in BFRT and HL-RT, respectively. Improvements in both groups were significantly greater than those of the control group (P < 0.05 for all). SF-36 role physical and bodily pain and HAQ scores were improved only in BFRT (45.7%, 22.5%, and -55.9%, respectively; P < 0.05 for all). HL-RT resulted in 1 case of withdrawal and several cases of exercise-induced pain, which did not occur in BFRT., Conclusion: BFRT was effective in improving muscle strength, mass, function, and health-related quality of life in patients with RA, emerging as a viable therapeutic modality in RA management., (© 2019, American College of Rheumatology.)

To investigate the association between food consumption stratified by processing level and cardiovascular risk factors in rheumatoid arthritis. In this cross-sectional study, 56 patients (age: 62.5 ± 7.9 years, BMI: 28.4 ± 5.1 kg/m 2 ) had food consumption evaluated according to the processing level (e.g., unprocessed or minimally processed foods, processed foods, and ultra-processed foods) and associated with cardiovascular risk factors. The most prevalent food processing level was unprocessed or minimally processed foods (42.6 ± 12.6% of total energy intake [TEI]), followed by processed (24.2 ± 11.9%TEI), ultra-processed (18.1 ± 11.8%TEI), and culinary ingredients (15.1 ± 6.4%TEI). Adjusted regression models showed that higher consumption of ultra-processed foods was positively associated with Framingham risk score (β = 0.06, CI: 95% 0.001, 0.11, p = 0.045) and glycated hemoglobin (β = 0.04, CI: 95% 0.01, 0.08, p = 0.021). In contrast, higher consumption of unprocessed or minimally processed foods was associated with lower 10-year risk of developing cardiovascular diseases (β = -0.05, CI: 95% - 0.09, -0.003, p = 0.021) and LDL (β = -1.09, CI: 95% - 1.94, -0.24, p = 0.013). Patients with rheumatoid arthritis consuming more ultra-processed foods showed worse metabolic profile, whereas those consuming more unprocessed or minimally processed foods had lower cardiovascular risks. A food pattern characterized by a high ultra-processed food consumption appears to emerge as a novel, modifiable risk factor for cardiovascular diseases in rheumatoid arthritis. Key-Points • Higher ultra-processed food consumption was associated with worse metabolic profile and increased cardiovascular risk, whereas higher unprocessed or minimally processed food consumption was associated with lower 10-year risk of developing cardiovascular diseases. • A food pattern characterized by a high ultra-processed food consumption appears to emerge as a novel, modifiable risk factor for cardiovascular diseases in rheumatoid arthritis.

Purpose: High-intensity activity is an important aspect of football performance during competitive match play. The aim of this study was to investigate the effect of beta-alanine supplementation throughout a short-duration intense football-specific training period prior to an international competition on measures of high-intensity running performance. Methods: Twenty-four elite international U20 female footballers (age 18 ± 1 y, height 1.67 ± 0.07 m, body mass 62.7 ± 7.4 kg) volunteered to perform the YoYo Intermittent Recovery Test Level 1 (YoYo IR1), the Running Anaerobic Sprint Test (RAST) and a 20-m maximal sprint test on two separate occasions, separated by 3 weeks of training and supplementation. Participants were randomly assigned to receive either 6.4 g·day -1 sustained-release beta-alanine (BA, N = 12) or an equivalent dose of maltodextrin (placebo, PL, N = 12) throughout a 3-week standardized training camp. Results: There was a main effect of group ( P = 0.05) and time ( P = 0.004) on YoYo IR1; overall values were lower in PL and distance covered was lower post- vs. pre-supplementation. There was no group × time interaction ( P = 0.07). There was an effect of sprint number for RAST, but no further main effects and there were no effect for the 20-m sprint. Conclusions: Top-level female footballers involved in this intense 3-week training period prior to a competition worsened their high-intensity intermittent exercise capacity, and this negative result was not attenuated by a short-duration BA supplementation protocol throughout the same period. Further work is necessary to elucidate whether adapted training protocols and BA dosing regimens could lead to better results., (Copyright © 2020 Ribeiro, Duarte, Guedes da Silva, Ramos, Rossi Picanço, Penna, Coswig, Barbalho, Gentil, Gualano and Saunders.)

Background: Creatine supplementation could be a nonexpensive, safe, and effective dietary intervention to counteract bone loss. The aim of this study was to investigate whether long-term creatine supplementation can improve bone health in older, postmenopausal women., Methods: A double-blind, placebo-controlled, parallel-group, randomized trial was conducted between November 2011 and December 2017 in Sao Paulo, Brazil. Two hundred postmenopausal women with osteopenia were randomly allocated to receive either creatine monohydrate (3 g/d) or placebo for 2 years. At baseline and after 12 and 24 months, we assessed areal bone mineral density (aBMD; primary outcome), lean and fat mass (through dual X-ray absorptiometry), volumetric BMD and bone microarchitecture parameters, biochemical bone markers, physical function and strength, and the number of falls and fractures. Possible adverse effects were self-reported., Results: Lumbar spine (p < .001), femoral neck (p < .001), and total femur aBMD (p = .032) decreased across time; however, no interaction effect was observed (all p > .050). Bone markers, microarchitecture parameters, and the number of falls/fractures were not changed with creatine (all p > .050). Lean mass and appendicular skeletal muscle mass increased throughout the intervention (p < .001), with no additive effect of creatine (p = .731 and p = .397, respectively). Creatine did not affect health-related laboratory parameters., Conclusion: Creatine supplementation more than 2 years did not improve bone health in older, postmenopausal women with osteopenia, nor did it affect lean mass or muscle function in this population. This refutes the long-lasting notion that this dietary supplement alone has osteogenic or anabolic properties in the long run., Clinical Trial Registry: Clinicaltrials.gov: NCT: 01472393., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To test whether high circulating insulin concentrations influence the transport of β-alanine into skeletal muscle at either saturating or subsaturating β-alanine concentrations, we conducted two experiments whereby β-alanine and insulin concentrations were controlled. In experiment 1 , 12 men received supraphysiological amounts of β-alanine intravenously (0.11 g·kg -1 ·min -1 for 150 min), with or without insulin infusion. β-Alanine and carnosine were measured in muscle before and 30 min after infusion. Blood samples were taken throughout the infusion protocol for plasma insulin and β-alanine analyses. β-Alanine content in 24-h urine was assessed. In experiment 2 , six men ingested typical doses of β-alanine (10 mg/kg) before insulin infusion or no infusion. β-Alanine was assessed in muscle before and 120 min following ingestion. In experiment 1 , no differences between conditions were shown for plasma β-alanine, muscle β-alanine, muscle carnosine and urinary β-alanine concentrations (all P > 0.05). In experiment 2 , no differences between conditions were shown for plasma β-alanine or muscle β-alanine concentrations (all P > 0.05). Hyperinsulinemia did not increase β-alanine uptake by skeletal muscle cells, neither when substrate concentrations exceed the V max of β-alanine transporter TauT nor when it was below saturation. These results suggest that increasing insulin concentration is not necessary to maximize β-alanine transport into muscle following β-alanine intake.

Carnosine is a dipeptide abundantly found in human skeletal muscle, cardiac muscle and neuronal cells having numerous properties that confers performance enhancing effects, as well as a wide-range of potential therapeutic applications. A reliable and valid method for tissue carnosine quantification is crucial for advancing the knowledge on biological processes involved with carnosine metabolism. In this regard, proton magnetic resonance spectroscopy (1H-MRS) has been used as a non-invasive alternative to quantify carnosine in human skeletal muscle. However, carnosine quantification by 1H-MRS has some potential limitations that warrant a thorough experimental examination of its validity. The present investigation examined the reliability, accuracy and sensitivity for the determination of muscle carnosine in humans using in vitro and in vivo experiments and comparing it to reference method for carnosine quantification (high-performance liquid chromatography - HPLC). We used in vitro 1H-MRS to verify signal linearity and possible noise sources. Carnosine was determined in the m. gastrocnemius by 1H-MRS and HPLC to compare signal quality and convergent validity. 1H-MRS showed adequate discriminant validity, but limited reliability and poor agreement with a reference method. Low signal amplitude, low signal-to-noise ratio, and voxel repositioning are major sources of error.

Background: Patients with rheumatoid arthritis spend most of their daily hours in sedentary behavior (sitting), a predisposing factor to poor health-related outcomes and all-cause mortality. Interventions focused on reducing sedentary time could be of novel therapeutic relevance. However, studies addressing this topic remain scarce. We aim to investigate the feasibility and efficacy of a newly developed intervention focused on reducing sedentary time, and potential clinical, physiological, metabolic and molecular effects in rheumatoid arthritis., Methods: The Take a STAND for Health study is a 4-month, parallel-group, randomized controlled trial, in which postmenopausal patients with rheumatoid arthritis will set individually tailored, progressive goals to replace their sedentary time with standing and light-intensity activities. Patients will be recruited from the Clinical Hospital (School of Medicine, University of Sao Paulo) and will be assessed at baseline and after a 4-month follow up. Outcomes will include objectively measured sedentary behavior (primary outcome) and physical activity levels, clinical parameters, anthropometric parameters and body composition; aerobic fitness, muscle function, blood pressure, cardiovascular autonomic function, vascular function and structure, health-related quality of life, and food intake. Blood and muscle samples will be collected for assessing potential mechanisms, through targeted and non-targeted approaches., Discussion: Findings will be of scientific and clinical relevance with the potential to inform new prescriptions focused on reducing sedentary behavior, a modifiable risk factor that thus far has been overlooked in patients with rheumatoid arthritis., Trial Registration: ClinicalTrials.gov, NCT03186924. Registered on 14 June 2017.

Purpose: To investigate the effects of chronic beta-alanine (BA) supplementation on muscle taurine content, blood clinical markers and sensory side-effects., Methods: Twenty-five healthy male participants (age 27 ± 4 years, height 1.75 ± 0.09 m, body mass 78.9 ± 11.7 kg) were supplemented with 6.4 g day -1 of sustained-release BA (N = 16; CarnoSyn™, NAI, USA) or placebo (PL; N = 9; maltodextrin) for 24 weeks. Resting muscle biopsies of the m. vastus lateralis were taken at 0, 12 and 24 weeks and analysed for taurine content (BA, N = 12; PL, N = 6) using high-performance liquid chromatography. Resting venous blood samples were taken every 4 weeks and analysed for markers of renal, hepatic and muscle function (BA, N = 15; PL, N = 8; aspartate transaminase; alanine aminotransferase; alkaline phosphatase; lactate dehydrogenase; albumin; globulin; creatinine; estimated glomerular filtration rate and creatine kinase)., Results: There was a significant main effect of group (p = 0.04) on muscle taurine, with overall lower values in PL, although there was no main effect of time or interaction effect (both p > 0.05) and no differences between specific timepoints (week 0, BA: 33.67 ± 8.18 mmol kg -1  dm, PL: 27.75 ± 4.86 mmol kg -1  dm; week 12, BA: 35.93 ± 8.79 mmol kg -1  dm, PL: 27.67 ± 4.75 mmol kg -1  dm; week 24, BA: 35.42 ± 6.16 mmol kg -1  dm, PL: 31.99 ± 5.60 mmol kg -1  dm). There was no effect of treatment, time or any interaction effects on any blood marker (all p > 0.05) and no self-reported side-effects in these participants throughout the study., Conclusions: The current study showed that 24 weeks of BA supplementation at 6.4 g day -1 did not significantly affect muscle taurine content, clinical markers of renal, hepatic and muscle function, nor did it result in chronic sensory side-effects, in healthy individuals. Since athletes are likely to engage in chronic supplementation, these data provide important evidence to suggest that supplementation with BA at these doses for up to 24 weeks is safe for healthy individuals.

Social distancing has been adopted worldwide to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Social isolation is likely to lead to a decline in physical activity, which could result in immune system dysfunction, thereby increasing infection susceptibility and exacerbating the pathophysiology of conditions that are common among older adults, including cardiovascular disease, cancer, and inflammatory disorders. Older adults and people living with these comorbidities are at a greater risk for complications during coronavirus disease 2019 (COVID-19). In this review, we discuss the negative impact of physical inactivity on immune function and showcase evidence that regular physical activity may be an effective strategy to counter some of the deleterious effects of social isolation. Furthermore, we briefly highlight key research questions in exercise immunology, with a focus on older adults in the context of COVID-19. Although it is worth emphasizing that there is no direct evidence that physical activity can prevent or treat -COVID-19, promoting an active lifestyle is a key intervention to counteract the effects of social isolation, especially in older adults and other at-risk individuals, such as those living with chronic diseases associated with ageing and lifestyle., (© 2020 S. Karger AG, Basel.)

The study investigated the influence of β-alanine supplementation during a high-intensity interval training (HIIT) program on repeated sprint ability (RSA) performance. This study was randomized, double-blinded, and placebo controlled. Eighteen men performed an incremental running test until exhaustion (T INC ) at baseline and followed by 4-wk HIIT (10 × 1-min runs 90% maximal T INC velocity [1-min recovery]). Then, participants were randomized into two groups and performed a 6-wk HIIT associated with supplementation of 6.4 g/day of β-alanine (Gβ) or dextrose (placebo group; GP). Pre- and post-6-wk HIIT + supplementation, participants performed the following tests: 1 ) T INC ; 2 ) supramaximal running test; and 3 ) 2 × 6 × 35-m sprints (RSA). Before and immediately after RSA, neuromuscular function was assessed by vertical jumps, maximal isometric voluntary contractions of knee extension, and neuromuscular electrical stimulations. Muscle biopsies were performed to determine muscle carnosine content, muscle buffering capacity in vitro (βm in vitro ), and content of phosphofructokinase (PFK), monocarboxylate transporter 4 (MCT4), and hypoxia-inducible factor-1α (HIF-1α). Both groups showed a significant time effect for maximal oxygen uptake (Gβ: 6.2 ± 3.6% and GP: 6.5 ± 4.2%; P > 0.01); only Gβ showed a time effect for total (-3.0 ± 2.0%; P = 0.001) and best (-3.3 ± 3.0%; P = 0.03) RSA times. A group-by-time interaction was shown after HIIT + Supplementation for muscle carnosine (Gβ: 34.4 ± 2.3 mmol·kg -1 ·dm -1 and GP: 20.7 ± 3.0 mmol·kg -1 ·dm -1 ; P = 0.003) and neuromuscular voluntary activation after RSA (Gβ: 87.2 ± 3.3% and GP: 78.9 ± 12.4%; P = 0.02). No time effect or group-by-time interaction was shown for supramaximal running test performance, βm, and content of PFK, MCT4, and HIF-1α. In summary, β-alanine supplementation during HIIT increased muscle carnosine and attenuated neuromuscular fatigue, which may contribute to an enhancement of RSA performance. NEW & NOTEWORTHY β-Alanine supplementation during a high-intensity interval training program increased repeated sprint performance. The improvement of muscle carnosine content induced by β-alanine supplementation may have contributed to an attenuation of central fatigue during repeated sprint. Overall, β-alanine supplementation may be a useful dietary intervention to prevent fatigue.

Objective: The aim of this study was to assess the impact of a real-world citywide intervention on physical activity and eating habits in a Latin American city with more than 50,000 inhabitants., Methods: This was a plausibility assessment of a real-life intervention. A probabilistic sample (n = 1,424) from Jaguariuna (Sao Paulo, Brazil) was assessed before and after a 7-month intervention aimed at increasing physical activity levels and improving eating habits at a city level. Primary outcomes were physical activity, sedentary behavior, and eating habits assessed by a valid telephone inquiry. The secondary outcome was body weight., Results: The proportion of individuals achieving the recommended intake of fruits and vegetables increased (18%; 95% CI: 2% to 36%; P = 0.031), whereas the number of individuals consuming soft drinks and exchanging main meals for snacks or junk food decreased (-35%; 95% CI: -45% to -22%; P < 0.001 and -16%; 95% CI: -29% to -1%; P = 0.037). The number of active individuals increased during leisure time (37%; 95% CI: 19% to 58%; P < 0.001), at work (17%; 95% CI: 4% to 32%; P = 0.009), and in the household (14%; 95% CI: 0% to 31%; P = 0.047). Body weight decreased among individuals with overweight or obesity., Conclusions: This intervention promoted pronounced lifestyle changes (i.e., increased physical activity and healthier food choices) in the entire city, providing scientific-based evidence on which to build effective public health policies in Latin America., (© 2019 The Obesity Society.)

Introduction/objectives: To assess the effects of exercise training on insulin resistance and β-cell function in patients with systemic autoimmune myopathies (SAMs)., Method: This quasi-experimental, prospective study includes 9 patients with SAMs (six with dermatomyositis, two with antisynthetase syndrome, and one with polymyositis). Patients were submitted to a 12-week, twice a week, exercise training program comprising aerobic and resistance exercises. Baseline and after the intervention, we evaluated disease status, aerobic capacity, muscle strength, body composition, insulin resistance, and β-cell function parameters., Results: The patients have a mean age of 46.7 years and stable disease. No clinical or laboratory parameter impairment was observed after the intervention. Compared with baseline, aerobic capacity, muscle strength, and function increased after 12 weeks (P < 0.05), while no changes were observed for body composition. Data from the oral glucose tolerance test showed that exercise did not change glucose area under the curve (AUC), whereas insulin and C-peptide AUC decreased significantly (P < 0.05). Furthermore, Matsuda index and HOMA2 percentage (both surrogates of insulin resistance) also improved (P < 0.05)., Conclusion: Exercise training improved aerobic capacity, muscle strength, and muscle function in patients with SAMs. In addition, exercise training led to an attenuation of insulin resistance and improvements in β-cell function parameters. These data indicate that exercise training can mitigate metabolic impairments, attenuating the cardiovascular risk in SAMs.Key Points• Exercise training improved aerobic capacity, muscle strength, and function without disease impairment• Exercise training was capable of improve insulin resistance and β-cell function in patients with SAM• These results suggest that exercise can mitigate metabolic impairments in patients with SAM, attenuating the cardiovascular risk.

Sarcopenia is characterized by a loss of muscle mass, quality, and function, and negatively impacts health, functionality, and quality of life for numerous populations, particularly older adults. Creatine is an endogenously produced metabolite, which has the theoretical potential to counteract many of the morphological and metabolic parameters underpinning sarcopenia. This can occur through a range of direct and indirect mechanisms, including temporal and spatial functions that accelerate ATP regeneration during times of high energy demand, direct anabolic and anti-catabolic functions, and enhanced muscle regenerating capacity through positively impacting muscle stem cell availability. Studies conducted in older adults show little benefit of creatine supplementation alone on muscle function or mass. In contrast, creatine supplementation as an adjunct to exercise training seems to augment the muscle adaptive response to the training stimulus, potentially through increasing capacity for higher intensity exercise, and/or by enhancing post-exercise recovery and adaptation. As such, creatine may be an effective dietary strategy to combat age-related muscle atrophy and sarcopenia when used to complement the benefits of exercise training., Competing Interests: The authors declare no conflict of interest.

Context: Bone loss after bariatric surgery potentially could be mitigated by exercise., Objective: To investigate the role of exercise training (ET) in attenuating bariatric surgery-induced bone loss., Design: Randomized, controlled trial., Setting: Referral center for bariatric surgery., Patients: Seventy women with severe obesity, aged 25 to 55 years, who underwent Roux-en-Y gastric bypass (RYGB)., Intervention: Supervised, 6-month, ET program after RYGB vs. standard of care (RYGB only)., Outcomes: Areal bone mineral density (aBMD) was the primary outcome. Bone microarchitecture, bone turnover, and biochemical markers were secondary outcomes., Results: Surgery significantly decreased femoral neck, total hip, distal radius, and whole body aBMD (P < 0.001); and increased bone turnover markers, including collagen type I C-telopeptide (CTX), procollagen type I N-propeptide (P1NP), sclerostin, and osteopontin (P < 0.05). Compared with RYGB only, exercise mitigated the percent loss of aBMD at femoral neck [estimated mean difference (EMD), -2.91%; P = 0.007;], total hip (EMD, -2.26%; P = 0.009), distal radius (EMD, -1.87%; P = 0.038), and cortical volumetric bone mineral density at distal radius (EMD, -2.09%; P = 0.024). Exercise also attenuated CTX (EMD, -0.20 ng/mL; P = 0.002), P1NP (EMD, -17.59 ng/mL; P = 0.024), and sclerostin levels (EMD, -610 pg/mL; P = 0.046) in comparison with RYGB. Exercise did not affect biochemical markers (e.g., 25(OH)D, calcium, intact PTH, phosphorus, and magnesium)., Conclusion: Exercise mitigated bariatric surgery-induced bone loss, possibly through mechanisms involving suppression in bone turnover and sclerostin. Exercise should be incorporated in postsurgery care to preserve bone mass., (Copyright © 2019 Endocrine Society.)

This study investigated the effect of open-placebo on cycling time-trial (TT) performance. Twenty-eight trained female cyclists completed a 1-km cycling TT following a control session or an open-placebo intervention. The intervention consisted of an individual presentation, provided by a medic, in which the concept of open-placebo was explained to the participant, before she ingested two red and white capsules containing flour; 15 min later, they performed the TT. In the control session, the participant sat quietly for 20 min. Heart rate and ratings of perceived exertion (RPE) were monitored throughout exercise, while blood lactate was determined pre- and post-exercise. Post-exercise questionnaires were employed to gain insight into the perceived influence of the supplement on performance. Open-placebo improved time-to-completion (P = 0.039, 103.6±5.0 vs. 104.4±5.1 s, -0.7±1.8 s, -0.7±1.7%) and mean power output (P = 0.01, 244.8±34.7 vs. 239.7±33.2, +5.1±9.5 W) during the TT. Individual data analysis showed that 11 individuals improved, 13 remained unchanged and 4 worsened their performance with open-placebo. Heart rate, RPE and blood lactate were not different between sessions (all P>0.05). Positive expectation did not appear necessary to induce performance improvements, suggesting unconscious processes occurred, although a lack of an improvement appeared to be associated with a lack of belief. Open-placebo improved 1-km cycling TT performance in trained female cyclists. Although the intervention was successful for some individuals, individual variation was high, and some athletes did not respond or even performed worse. Thus, open-placebo interventions should be carefully considered by coaches and practitioners, while further studies are warranted., Competing Interests: The authors have declared that no competing interests exist.

This study evaluated the effects of β-hydroxy-β-methylbutyrate free acid (HMB-FA) and calcium salt (HMB-Ca) on strength, hypertrophy, and markers of muscle damage. In this randomized, double-blind, placebo-controlled study, 44 resistance-trained men (age: 26 ± 4 years; body mass: 84.9 ± 12.0 kg) consuming ≥1.7 g·kg-1·day-1 of protein received HMB-FA (3 g/day; n = 14), HMB-Ca (3 g/day; n = 15), or placebo (PL; cornstarch, 3 g/day; n = 15) for 12 weeks, while performing a periodized resistance training program. Before and after intervention, lean body mass (measured with dual X-ray absorptiometry), maximal dynamic strength (one-repetition maximum), knee extension maximal isometric strength (maximal voluntary isometric contraction [MVIC]), cross-sectional area (measured with ultrasound), and muscle soreness were assessed. MVIC was also measured 48 hr after the first and the last training sessions. All groups increased lean body mass (main time effect: p < .0001; HMB-FA: 1.8 ± 1.8 kg; HMB-Ca: 0.8 ± 1.4 kg; PL: 0.9 ± 1.4 kg), cross-sectional area (main time effect: p < .0001; HMB-FA: 6.6 ± 3.8%; HMB-Ca: 4.7 ± 4.4%; PL: 6.9 ± 3.8%), one-repetition maximum bench press (main time effect: p < .0001; HMB-FA: 14.8 ± 8.4 kg; HMB-Ca: 11.8 ± 7.4 kg; PL: 11.2 ± 6.6 kg), MVIC (main time effect: p < .0001; HMB-FA: 34.4 ± 39.3%; HMB-Ca: 32.3 ± 27.4%; PL: 17.7 ± 20.9%) after the intervention, but no differences between groups were shown. HMB-FA group showed greater leg press strength after the intervention than HMB-Ca and PL groups (Group × Time interaction: p < .05; HMB-FA: 47.7 ± 31.2 kg; HMB-Ca: 43.8 ± 31.7 kg; PL: 30.2 ± 20.9 kg). MVIC measured 48 hr after the first and the last sessions showed no attenuation of force decline with supplementation. Muscle soreness following the first and last sessions was not different between groups. The authors concluded that neither HMB-Ca nor HMB-FA improved hypertrophy or reduced muscle damage in resistance-trained men undergoing resistance training ingesting optimal amounts of protein. HMB-FA but not HMB-Ca resulted in a statistically significant yet minor improvement on leg press one-repetition maximum.

Introduction: Health at Every Size (HAES) is a weight-neutral approach focused on promoting healthy behaviors in people with different body sizes and on enhancing pleasure derived from consuming food to achieve sustainable healthy eating outcomes. However, to the best of our knowledge, there are no studies in the literature assessing the effects of the HAES approach on perceptions of eating pleasure., Objective: We qualitatively investigated the perceptions of obese women about eating pleasure before and after a new interdisciplinary, nonprescriptive intervention based on the HAES approach., Design: The intervention was a randomized controlled clinical trial, designated as Health and Wellness in Obesity, conducted over 7 months at University of São Paulo (Brazil). We used a qualitative approach to data construction and analysis of perceptions about eating pleasure. Participants were randomized to either the intervention (I-HAES) group or the control (CTRL) group. The I-HAES group featured individual nutritional counseling, group practice of enjoyable physical activity, and philosophical workshops. The CTRL group was a traditional HAES intervention group (lecture-based model). Focus group discussions eliciting perceptions of pleasure around eating were conducted at baseline and post-study. Focus group transcripts were analyzed by exploratory content analysis., Participants: Forty-three women aged 25 to 50 years with body mass index (measured in kilograms per square meter) between 30 and 39. 9 completed the intervention and the focus groups, with 32 in the I-HAES group and 11 in the CTRL group., Results: Lack of guilt about experiencing pleasure while eating and increased reflection on their own desires increased in participants of both groups after the study. The I-HAES group also displayed a greater sense of autonomy related to eating, increased pleasure in commensality, familiarity with the practice of cooking, and decreased automatic eating., Conclusion: HAES-based intervention featuring nutritional counseling, appreciation for physical activity, and philosophical engagement was shown to stimulate pleasure around eating without leading to indiscriminate eating., (Copyright © 2019 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Histidine containing dipeptides (HCDs: carnosine, anserine and balenine) have numerous therapeutic and ergogenic properties, but there is a lack of consensus on the mechanistic pathways through which they function. Potential roles include intracellular buffering, neutralisation of reactive species, and calcium regulation. Comparative investigations of the HCD content of various species provide unique insight into their most likely mechanisms of action. This review chronologically describes how the comparative physiology studies, conducted since the beginning of the 20th century, have shaped our understanding of the physiological roles of HCDs. The investigation of a wide range of physiologically distinct species indicates that those species with a strong reliance on non-oxidative forms of energy production are abundant in HCDs. These include: whales who experience long periods of hypoxia while diving; racehorses and greyhound dogs who have highly developed sprint abilities, and chickens and turkeys whose limited capacity for flight is largely fuelled by their white, glycolytic, muscle. Additionally, a higher HCD content in the Type 2 muscle fibres of various species (which have greater capacity for non-oxidative metabolism) was consistently observed. The pKa of the HCDs render them ideally suited to act as intracellular physicochemical buffers within the pH transit range of the skeletal muscle. As such, their abundance in species which show a greater reliance on non-oxidative forms of energy metabolism, and which experience regular challenges to acid-base homeostasis, provides strong evidence that intracellular proton buffering is an important function of the HCDs in skeletal muscle., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Polycystic ovary syndrome (PCOS) is characterized by exacerbated inflammation, which is implicated in cardiometabolic dysfunction. This study aimed to examine the potential effects of acute exercise on inflammatory responses in obese/overweight PCOS women and their controls. Participants underwent a single bout of moderate-intensity aerobic exercise (30 min at ∼65% of VO 2peak ). Blood and muscle samples were collected immediately before (PRE) and 60 min after the exercise session. Cytokines (i.e., IL-1β, IL-6, IL-4, IL-10, TNF-α) were measured both in plasma and in skeletal muscle, and proteins related to inflammatory signaling (IKKα/β and JNK) were assessed in skeletal muscle. At PRE, PCOS showed elevated muscle TNF-α (+62%, p = 0.0012) and plasma IL-1β (+76%, p = 0.0010) compared to controls. In PCOS, exercise decreased plasma and muscle TNF-α (-14%, p = 0.0003 and -46%, p = 0.0003), as well as increased plasma and muscle IL-4 (+147%, p = 0.0018 and +62%, p = 0.0474) and plasma IL-10 (+38%, p = 0.0029). Additionally, IKKα/β and JNK phosphorylation in skeletal muscle, which was higher in PCOS at PRE, was significantly reduced by exercise (-58%, p < 0.0001 and -46%, p < 0.0001, respectively), approaching control levels. Person's correlations between PRE values and delta changes (i.e., exercise effect) showed significant, negative associations for plasma IL-1β (r = -0.92, p < 0.0001), TNF-α (r = -0.72, p = 0.0100) and IL-6 (r = -0.58, p = 0.05), and muscle TNF-α (r = -0.95, p < 0.0001), IKKα/β (r = -0.75, p = 0.005), and JNK (r = -0.94, p < 0.0001) in PCOS. In conclusion, exercise can mitigate the inflammatory milieu in women with PCOS. The anti-inflammatory role of exercise could underlie its cardiometabolic protection in PCOS., (Copyright © 2019. Published by Elsevier Ltd.)

β-Alanine supplementation is one of the world's most commonly used sports supplements, and its use as a nutritional strategy in other populations is ever-increasing, due to evidence of pleiotropic ergogenic and therapeutic benefits. Despite its widespread use, there is only limited understanding of potential adverse effects. To address this, a systematic risk assessment and meta-analysis was undertaken. Four databases were searched using keywords and Medical Subject Headings. All human and animal studies that investigated an isolated, oral, β-alanine supplementation strategy were included. Data were extracted according to 5 main outcomes, including 1) side effects reported during longitudinal trials, 2) side effects reported during acute trials, 3) effect of supplementation on circulating health-related biomarkers, 4) effect of supplementation on skeletal muscle taurine and histidine concentration, and 5) outcomes from animal trials. Quality of evidence for outcomes was ascertained using the Grading of Recommendations Assessment Development and Evaluation (GRADE) framework, and all quantitative data were meta-analyzed using multilevel models grounded in Bayesian principles. In total, 101 human and 50 animal studies were included. Paraesthesia was the only reported side effect and had an estimated OR of 8.9 [95% credible interval (CrI): 2.2, 32.6] with supplementation relative to placebo. Participants in active treatment groups experienced similar dropout rates to those receiving the placebo treatment. β-Alanine supplementation caused a small increase in circulating alanine aminotransferase concentration (effect size, ES: 0.274, CrI: 0.04, 0.527), although mean data remained well within clinical reference ranges. Meta-analysis of human data showed no main effect of β-alanine supplementation on skeletal muscle taurine (ES: 0.156; 95% CrI: -0.38, 0.72) or histidine (ES: -0.15; 95% CrI: -0.64, 0.33) concentration. A main effect of β-alanine supplementation on taurine concentration was reported for murine models, but only when the daily dose was ≥3% β-alanine in drinking water. The results of this review indicate that β-alanine supplementation within the doses used in the available research designs, does not adversely affect those consuming it., (Copyright © American Society for Nutrition 2019.)

Objectives: To evaluate the feasibility, safety and efficacy of exercise training in patients with immune-mediated necrotising myopathies (IMNM)., Methods: Eight consecutive sedentary patients with IMNM (5 anti-signal recognition particle and 3 anti-hydroxy-methyl-glutaryl coenzyme A reductase) were engaged in this study. Disease status was based on International Myositis Assessment and Clinical Studies Group (IMACS) core set measures. Physical performance was evaluated by cardiopulmonary exercise test, repetition maximum (RM) protocol, handgrip dynamometry, sit-to-stand (STS) and timed up-and-go (TUG) tests. All these parameters were measured at baseline and after a 12-week, twice-a-week, supervised exercise training comprising aerobic and strength exercises., Results: Patients (aged 61 years on average) were very disabled at the beginning of the disease (mean duration of 17.7 months), but after being aggressively treated with a treat-to-target approach, they presented only mild symptoms that were well-controlled with oral immunosuppression and low disease status scores by the time of the exercise intervention. No disease relapsing, worsening of the IMACS set scores or adverse events were observed throughout the training period. Patients also increased aerobic capacity (e.g. time to achieve anaerobic threshold and time to achieve exhaustion), muscle strength (e.g. 1RM bench press) and function (e.g. STS test)., Conclusions: Supervised exercise training did not impair disease status and seemed to be feasible, safe and effective in patients with IMNM. Moreover, exercise training increased aerobic capacity, muscle strength and function, suggesting that this could be a novel potential coadjuvant therapy in IMNM.

The ergogenic and therapeutic effects of increasing muscle creatine by supplementation are well-recognized. It appears that similar benefits to brain function and cognitive processing may also be achieved with creatine supplementation, however research in this area is more limited, and important knowledge gaps remain. The purpose of this review is to provide a comprehensive overview of the current state of knowledge about the influence of creatine supplementation on brain function in healthy individuals. It appears that brain creatine is responsive to supplementation, however higher, or more prolonged dosing strategies than those typically used to increase muscle creatine, may be required to elicit an increase in brain creatine. The optimal dosing strategy to induce this response, is currently unknown, and there is an urgent need for studies investigating this. When considering the influence of supplementation strategies on cognitive processes, it appears that creatine is most likely to exert an influence in situations whereby cognitive processes are stressed, e.g. during sleep deprivation, experimental hypoxia, or during the performance of more complex, and thus more cognitively demanding tasks. Evidence exists indicating that increased brain creatine may be effective at reducing the severity of, or enhancing recovery from mild traumatic brain injury, however, only limited data in humans are available to verify this hypothesis, thus representing an exciting area for further research.

β-Alanine (BA) supplementation may be ergogenic during high-intensity exercise, primarily due to the buffering of hydrogen cations, although the effects of beta-alanine supplementation on strength endurance are equivocal. The aim of the study was to determine the effects of 4 weeks of beta-alanine supplementation on skeletal muscle endurance using a battery of performance tests. This study employed a parallel group, repeated measures, randomised, double-blinded and placebo-controlled design. Twenty recreationally strength-trained healthy males completed tests of isotonic strength endurance (repeated bench and leg press), along with tests of isometric and isokinetic endurance conducted using an isokinetic dynamometer. Tests were performed before and after a 4 week intervention, comprising an intake of 6.4 g day -1 of BA (n = 9) or placebo (maltodextrin, n = 11). Time-to-exhaustion during the isometric endurance test improved by ~ 17% in the BA group (p < 0.01), while PL remained unchanged. No significant within-group differences (p > 0.1) were shown for any of the performance variables in the isokinetic test (peak torque, fatigue index, total work) nor for the total number of repetitions performed in the isotonic endurance tests (leg or bench press). Four weeks of BA supplementation (6.4 g day -1 ) improved isometric, but not isokinetic or isotonic endurance performance.

The effects of β-alanine (BA) and sodium bicarbonate (SB) on energy metabolism during work-matched high-intensity exercise and cycling time-trial performance were examined in 71 male cyclists. They were randomised to receive BA + placebo (BA, n = 18), placebo + SB (SB, n = 17), BA + SB (BASB, n = 19), or placebo + placebo (PLA, n = 18). BA was supplemented for 28 days (6.4 g day -1 ) and SB (0.3 g kg -1 ) ingested 60 min before exercise on the post-supplementation trial. Dextrose and calcium carbonate were placebos for BA and SB, respectively. Before (PRE) and after (POST) supplementation, participants performed a high-intensity intermittent cycling test (HICT-110%) consisting of four 60-s bouts at 110% of their maximal power output (60-s rest between bouts). The estimated contribution of the energy systems was calculated for each bout in 39 of the participants (BA: n = 9; SB: n = 10; BASB: n = 10, PLA: n = 10). Ten minutes after HICT-110%, cycling performance was determined in a 30-kJ time-trial test in all participants. Both groups receiving SB increased estimated glycolytic contribution in the overall HICT-110%, which approached significance (SB: + 23%, p = 0.068 vs. PRE; BASB: + 18%, p = 0.059 vs. PRE). No effects of supplementation were observed for the estimated oxidative and ATP-PCr systems. Time to complete 30 kJ was not significantly changed by any of the treatments, although a trend toward significance was shown in the BASB group (p = 0.06). We conclude that SB, but not BA, increases the estimated glycolytic contribution to high-intensity intermittent exercise when total work done is controlled and that BA and SB, either alone or in combination, do not improve short-duration cycling time-trial performance.

Purpose: Cross-sectional studies suggest that training can increase muscle carnosine (MCarn), although longitudinal studies have failed to confirm this. A lack of control for dietary β-alanine intake or muscle fiber type shifting may have hampered their conclusions. The purpose of the present study was to investigate the effects of high-intensity interval training (HIIT) on MCarn., Methods: Twenty vegetarian men were randomly assigned to a control (CON) (n = 10) or HIIT (n = 10) group. High-intensity interval training was performed on a cycle ergometer for 12 wk, with progressive volume (6-12 series) and intensity (140%-170% lactate threshold [LT]). Muscle carnosine was quantified in whole-muscle and individual fibers; expression of selected genes (CARNS, CNDP2, ABAT, TauT, and PAT1) and muscle buffering capacity in vitro (βmin vitro) were also determined. Exercise tests were performed to evaluate total work done, V˙O2max, ventilatory thresholds (VT) and LT., Results: Total work done, VT, LT, V˙O2max, and βmin vitro were improved in the HIIT group (all P < 0.05), but not in CON (P > 0.05). MCarn (in mmol·kg dry muscle) increased in the HIIT (15.8 ± 5.7 to 20.6 ± 5.3; P = 0.012) but not the CON group (14.3 ± 5.3 to 15.0 ± 4.9; P = 0.99). In type I fibers, MCarn increased in the HIIT (from 14.4 ± 5.9 to 16.8 ± 7.6; P = 0.047) but not the CON group (from 14.0 ± 5.5 to 14.9 ± 5.4; P = 0.99). In type IIa fibers, MCarn increased in the HIIT group (from 18.8 ± 6.1 to 20.5 ± 6.4; P = 0.067) but not the CON group (from 19.7 ± 4.5 to 18.8 ± 4.4; P = 0.37). No changes in gene expression were shown., Conclusions: In the absence of any dietary intake of β-alanine, HIIT increased MCarn content. The contribution of increased MCarn to the total increase in βmin vitro appears to be small.

Real-world interventions are fundamental to bridge the research-practice gap in healthy lifestyle promotion. This study aimed to assess the impact of a 7-month, intensive, city-wide intervention ("Life of Health") on tackling youth inactivity and sedentary behavior in an entire Latin-American city (Jaguariuna, Brazil). For youth, a program focused on tackling inactivity/sedentary behavior was delivered at every school ( n = 18). Plausibility assessments (pre-to-post design) were performed with 3,592 youth (out of 8,300 individuals at school age in the city) to test the effectiveness of the intervention. Primary outcomes were physical activity and sedentary behavior. Secondary outcome was BMI z -score. Physical activity did not change (0; 95%CI:-2.7-2.8 min/day; p = 0.976), although physically inactive sub-group increased physical activity levels (11.2; 95%CI:8.8-13.6 min/day; p < 0.001). Weekday television and videogame time decreased, whereas computer time increased. Participants with overweight and obesity decreased BMI z -score (-0.08; 95%CI:-0.11-0.05; p < 0.001; -0.15; 95%CI:-0.19-0.11; p < 0.001). This intervention was not able to change the proportion of physical inactivity and sedentary behavior in youth at a city level. Nonetheless, physically inactive individuals increased PA levels and participants with overweight and obesity experienced a reduction in BMI z -score, evidencing the relevance of the intervention. Education-based lifestyle programs should be supplemented with environmental changes to better tackle inactivity/sedentary behavior in the real-world.

Background/objective: Recent studies have indicated that cardiac autonomic dysfunction is an early sign of cardiovascular impairment in rheumatoid arthritis (RA). Previous studies have mainly focused on resting assessments; however, analysis of heart rate (HR) responses to exercise might provide additional information on cardiac autonomic dysfunction in this disease. Thus, we aimed to assess the HR responses during and after a maximal graded exercise test in patients with RA and healthy controls (CONs)., Methods: This was a cross-sectional study in which 27 female RA patients and 14 female CONs frequency matched by physical activity, age, and body mass index were compared for HR responses during and after a maximal graded exercise test., Results: Rheumatoid arthritis patients showed reduced chronotropic response (94.3% ± 16.3% vs. 106.1% ± 10.3%, p = 0.02) and lower HR recovery (HRR) at 30 seconds (8.6 ± 6.7 vs. 13.4 ± 5.2 beats/min [bpm], p = 0.02), 60 seconds (16.5 ± 7.8 vs. 24.0 ± 9.9 bpm, p = 0.01), 120 seconds (32.6 ± 9.9 vs. 40.7 ± 12.3 bpm, p = 0.03), and 180 seconds (46.5 ± 12.6 vs. 55.5 ± 13.4 bpm, p = 0.05) post-maximal exercise test when compared with CONs. Moreover, the prevalence of chronotropic incompetence (i.e., failure to reach 80% of the HR-predicted response) and abnormal HRR (i.e., HRR ≤12 bpm) were, respectively, 22.2% and 37.1% in RA patients., Conclusions: Patients with RA showed reduced chronotropic response to exercise and slower postexercise HRR. These abnormal autonomic responses to exercise indicate the presence of cardiac autonomic dysfunction and increased cardiovascular risk in this population.

Previous studies have demonstrated that exercise results in reactive aldehyde production and that β-alanine supplementation increases carnosine content in skeletal muscle. However, little is known about the influence exercise and β-alanine supplementation have on the formation of carnosine-aldehydes. The goal of the present study was to monitor the formation of carnosine-aldehyde adducts, following high-intensity intermittent exercise, before and after β-alanine supplementation. Vastus lateralis biopsy samples were taken from 14 cyclists, before and after a 28 day β-alanine supplementation, following 4 bouts of a 30 s all-out cycling test, and carnosine and CAR-aldehyde adducts [carnosine-acrolein, CAR-ACR (m/z 303), carnosine-4-hydroxy-2-hexenal, CAR-HHE (m/z 341) and carnosine-4-hydroxy-2-nonenal, CAR-HNE (m/z 383)] were quantified by HPLC-MS/MS. β-alanine supplementation increased muscle carnosine content by ~50% (p = 0.0001 vs. Pre-Supplementation). Interestingly, there was a significant increase in post-exercise CAR-ACR content following β-alanine supplementation (p < 0.001 vs. post-exercise before supplementation), whereas neither exercise alone nor supplementation alone increased CAR-ACR formation. These results suggest that carnosine functions as an acrolein-scavenger in skeletal muscle. Such a role would be relevant to the detoxification of this aldehyde formed during exercise, and appears to be enhanced by β-alanine supplementation. These novel findings not only have the potential of directly benefiting athletes who engage in intensive training regimens, but will also allow researchers to explore the role of muscle carnosine in detoxifying reactive aldehydes in diseases characterized by abnormal oxidative stress., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Exercise is the treatment of choice for fibromyalgia (FM), but little is known about resistance exercise prescription to modulate pain in this condition. This study aimed to compare the effects of different resistance exercise models, comprising self-selected or prescribed intensity, on pain in FM patients. In a cross-over fashion, 32 patients underwent the following sessions: (i) standard prescription (STD; 3 × 10 repetitions at 60% of maximal strength); (ii) self-selected load with fixed number of repetitions (SS); (iii) self-selected load with volume load (i.e., load × sets × repetitions) matched for STD (SS-VM); and (iv) self-selected load with a free number of repetitions until achieving score 7 of rating perceived exertion (SS-RPE). Pain, assessed by Visual Analogic Scale (VAS) and Short-Form McGill Pain Questionnaire (SF-MPQ), was evaluated before and 0, 24, 48, 72, and 96 h after the sessions. Load was significantly lower in SS, SS-VM, SS-RPE than in STD, whereas rating perceived exertion and volume load were comparable between sessions. VAS scores increased immediately after all sessions ( p < 0.0001), and reduced after 48, 72, 96 h ( p < 0.0001), remaining elevated compared to pre-values. SF-MPQ scores increased immediately after all exercise sessions ( p = 0.025), then gradually reduced across time, reaching baseline levels at 24 h. No significant differences between sessions were observed. Both prescribed and preferred intensity resistance exercises failed in reducing pain in FM patients. The recommendation that FM patients should exercise at preferred intensities to avoid exacerbated pain, which appears to be valid for aerobic exercise, does not apply to resistance exercise.

Health at Every Size® (HAES®) is a weight-neutral approach focused on promoting healthy behaviors in people with different body sizes. This study examined multiple physiological, attitudinal, nutritional, and behavioral effects of a newly developed, intensive, interdisciplinary HAES®-based intervention in obese women. This was a prospective, seven-month, randomized (2:1), controlled, mixed-method clinical trial. The intervention group (I-HAES®; n = 39) took part in an intensified HAES®-based intervention comprising a physical activity program, nutrition counseling sessions, and philosophical workshops. The control group (CTRL; n = 19) underwent a traditional HAES®-based intervention. Before and after the interventions, participants were assessed for physiological, psychological, and behavioral parameters (quantitative data) and took part in focus groups (qualitative data). Body weight, body mass index, and waist and hip circumferences did not significantly differ within or between groups (P > 0.05). I-HAES® showed increased peak oxygen uptake and improved performance in the timed-stand test (P = 0.004 and P = 0.004, between-group comparisons). No significant within- or between-group differences were observed for objectively measured physical activity levels, even though the majority of the I-HAES® participants indicated that they were engaged in or had plans to include physical activity in their routines. I-HAES® resulted in improvements in eating attitudes and practices. The I-HAES® group showed significantly improved all Body Attitude Questionnaire subscale and all Figure Rating Scale scores (P ≤ 0.05 for all parameters, within-group comparisons), whereas the CTRL group showed slight or no changes. Both groups had significant improvements in health-related quality of life parameters, although the I-HAES® group had superior gains in the "physical health," "psychological health," and "overall perception of quality of life and health" (P = 0.05, 0.03, and 0.02, respectively, between-group comparisons) domains. Finally, most of the quantitative improvements were explained by qualitative data. Our results show that this new intensified HAES®-based intervention improved participants' eating attitudes and practices, perception of body image, physical capacity, and health-related quality of life despite the lack of changes in body weight and physical activity levels, showing that our novel approach was superior to a traditional HAES®-based program., Competing Interests: The authors have declared that no competing interests exist.

The concept of personalized nutrition and exercise prescription represents a topical and exciting progression for the discipline given the large inter-individual variability that exists in response to virtually all performance and health related interventions. Appropriate interpretation of intervention-based data from an individual or group of individuals requires practitioners and researchers to consider a range of concepts including the confounding influence of measurement error and biological variability. In addition, the means to quantify likely statistical and practical improvements are facilitated by concepts such as confidence intervals (CIs) and smallest worthwhile change (SWC). The purpose of this review is to provide accessible and applicable recommendations for practitioners and researchers that interpret, and report personalized data. To achieve this, the review is structured in three sections that progressively develop a statistical framework. Section 1 explores fundamental concepts related to measurement error and describes how typical error and CIs can be used to express uncertainty in baseline measurements. Section 2 builds upon these concepts and demonstrates how CIs can be combined with the concept of SWC to assess whether meaningful improvements occur post-intervention. Finally, section 3 introduces the concept of biological variability and discusses the subsequent challenges in identifying individual response and non-response to an intervention. Worked numerical examples and interactive Supplementary Material are incorporated to solidify concepts and assist with implementation in practice.

Aerobic training (AT) is a promising intervention to improve cognitive functioning. However, its modulatory effects on brain networks are not yet entirely understood. Sixty-five subjects with mild cognitive impairment performed a moderate intensity, 24-week AT program. Differences in resting regional brain glucose metabolism (rBGM) with FDG-PET were assessed before and after AT on a voxel-by-voxel basis. Structural equation modeling was used to create latent variables based on regions with significant rBGM changes and to test a hypothetical model about the inter-relationships between these changes. There were significant rBGM reductions in both anterior temporal lobes (ATL), left inferior frontal gyrus, left anterior cingulate cortex, right hippocampus, left meddle frontal gyrus and bilateral caudate nuclei. In contrast, there was an increase in rBGM in the right precuneus and left inferior frontal gyrus. Latent variables reflecting the salience network and ATL were created, while the precuneus represented the default mode network. In the model, salience network rBGM was decreased after AT. In contrast, rBGM in the default mode network increased as a final outcome. This result suggested improved salience network efficacy and increased control over other brain functional networks. The ATL network decreased its rBGM and connected to the salience network and default mode network with positive and negative correlations, respectively. The model fit values reached statistical significance, demonstrating that this model explained the variance in the measured data. In mild cognitive impairment subjects, AT modulated rBGM in salience network and default mode network nodes. Such changes were in the direction of the normally expected resting-state metabolic patterns of these networks.

Purpose: Evaluate the effects of a low-intensity resistance training (LI-RT) program associated with partial blood flow restriction on selected clinical outcomes in patients with knee osteoarthritis (OA)., Methods: Forty-eight women with knee OA were randomized into one of the three groups: LI-RT (30% one repetition maximum [1-RM]) associated (blood flow restriction training [BFRT]) or not (LI-RT) with partial blood flow restriction, and high-intensity resistance training (HI-RT, 80% 1-RM). Patients underwent a 12-wk supervised training program and were assessed for lower-limb 1-RM, quadriceps cross-sectional area, functionality (timed-stands test and timed-up-and-go test), and disease-specific inventory (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) before (PRE) and after (POST) the protocol., Results: Similar within-group increases were observed in leg press (26% and 33%, all P < 0.0001), knee extension 1-RM (23% and 22%; all P < 0.0001) and cross-sectional area (7% and 8%; all P < 0.0001) in BFRT and HI-RT, respectively, and these were significantly greater (all P < 0.05) than those of LI-RT. The BFRT and HI-RT showed comparable improvements in timed-stands test (7% and 14%, respectively), with the latter showing greater increases than LI-RT. Timed-up-and-go test scores were not significantly changed within or between groups. WOMAC physical function was improved in BFRT and HI-RT (-49% and -42%, respectively; all P < 0.05), and WOMAC pain was improved in BFRT and LI-RT (-45% and -39%, respectively; all P < 0.05). Four patients (of 16) were excluded due to exercise-induced knee pain in HI-RT., Conclusions: Blood flow restriction training and HI-RT were similarly effective in increasing muscle strength, quadriceps muscle mass, and functionality in knee OA patients. Importantly, BFRT was also able to improve pain while inducing less joint stress, emerging as a feasible and effective therapeutic adjuvant in OA management.

Systemic lupus erythematosus (SLE) patients may show increased insulin resistance (IR) when compared with their healthy peers. Exercise training has been shown to improve insulin sensitivity in other insulin-resistant populations, but it has never been tested in SLE. Therefore, the aim of the present study was to assess the efficacy of a moderate-intensity exercise training program on insulin sensitivity and potential underlying mechanisms in SLE patients with mild/inactive disease. A 12-week, randomized controlled trial was conducted. Nineteen SLE patients were randomly assigned into two groups: trained (SLE-TR, n  = 9) and non-trained (SLE-NT, n  = 10). Before and after 12 weeks of the exercise training program, patients underwent a meal test (MT), from which surrogates of insulin sensitivity and beta-cell function were determined. Muscle biopsies were performed after the MT for the assessment of total and membrane GLUT4 and proteins related to insulin signaling [Akt and AMP-activated protein kinase (AMPK)]. SLE-TR showed, when compared with SLE-NT, significant decreases in fasting insulin [-39 vs. +14%, p  = 0.009, effect size (ES) = -1.0] and in the insulin response to MT (-23 vs. +21%, p  = 0.007, ES = -1.1), homeostasis model assessment IR (-30 vs. +15%, p  = 0.005, ES = -1.1), a tendency toward decreased proinsulin response to MT (-19 vs. +6%, p  = 0.07, ES = -0.9) and increased glucagon response to MT (+3 vs. -3%, p  = 0.09, ES = 0.6), and significant increases in the Matsuda index (+66 vs. -31%, p  = 0.004, ES = 0.9) and fasting glucagon (+4 vs. -8%, p  = 0.03, ES = 0.7). No significant differences between SLT-TR and SLT-NT were observed in fasting glucose, glucose response to MT, and insulinogenic index (all p  > 0.05). SLE-TR showed a significant increase in AMPK Thr 172 phosphorylation when compared to SLE-NT (+73 vs. -12%, p  = 0.014, ES = 1.3), whereas no significant differences between groups were observed in Akt Ser 473 phosphorylation, total and membrane GLUT4 expression, and GLUT4 translocation (all p  > 0.05). In conclusion, a 12-week moderate-intensity aerobic exercise training program improved insulin sensitivity in SLE patients with mild/inactive disease. This effect appears to be partially mediated by the increased insulin-stimulated skeletal muscle AMPK phosphorylation., Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01515163.

Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, n  = 11) or n-3 PUFA (ω-3, n  = 11) supplementation. Before (pre) and after (post) 16 weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ω-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. -12%, p  = 0.06, ES = 0.9; and +23 vs. -22%, p  = 0.02, ES = 1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels ( p  > 0.05). In addition, ω-3 group showed decreased circulating levels of interleukin-10 (-4 vs. +45%, p  = 0.04, ES = -0.9) and tumor necrosis factor (-13 vs. +0.3%, p  = 0.04, ES = -0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, p  = 0.1, ES = -0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16 weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an adjuvant therapy in APS. Registered at http://ClinicalTrials.gov as NCT01956188.

The role of plasma glutamine concentration and glutamine supplementation on immunosuppression was investigated in combat athletes. Twenty-three male athletes were randomly assigned to receive glutamine (21 g/day, n=12) or placebo (ovalbumin, n=11) for 10 days. Six athletes who did not lose weight served as controls. Athletes were assessed 21 days before (-21d), 1 day before (-1d) and 5 days after (+5d) a competition. Weight reduction was similar between glutamine (-8.2%± 4.1%) and placebo (-8.5%±2.4%) and negligible in control (-0.6%±1.4%). In both weight-loss groups, the majority of athletes reported symptoms of upper respiratory symptoms, as assessed by the Wisconsin upper respiratory symptom survey questionnaire. Only two athletes reported symptoms in the control group. Immune cell function remained unchanged throughout the study except for an increase in neutrophil phagocytic activity (placebo: -21d=5,251±2,986; -1d=17,428±22,374; +5d=21,125±21,934; glutamine: -21d=6,096±3,549; -1d=11,029±17,113; +5d=28,186±21,032 FI) and a minor change in monocyte phagocytic activity (placebo: -21d=4,421±3,634; -1d=3,329±6,283; +5d=3,243± 2,553; glutamine: -21d=4,051±3,186; -1d=3,106±2,625; +5d=4,981± 4,598) in both glutamine and placebo after weight loss. Plasma glutamine and cortisol remained unchanged across the study. creatine kinase levels were increased in placebo (-21d=125.2±54.1; -1d=187.2± 73.5; +5d=111.3±59.1 U/L) but not in glutamine (-21d=136.2±58.2; -1d= 168.8±65.0; +5d=129.7±64.0 U/L). Rapid weight loss increased the frequency and severity of infection symptoms, but this was neither associated with plasma glutamine depletion nor counteracted by glutamine supplementation., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported.

Objective: To assess insulin sensitivity in patients with systemic lupus erythematosus (SLE) in response to a meal tolerance test (MTT)., Methods: In this cross-sectional study, 33 adult females with mild/inactive SLE (SLE group) and 16 age- and body mass index-matched female healthy controls (CTRL group) underwent an MTT and were assessed for insulin sensitivity and beta cell function. Skeletal muscle protein expressions of total and membrane insulin-dependent glucose transporter 4 (GLUT-4) were also evaluated (SLE group: n = 10, CTRL group: n = 5); muscle biopsies were performed after MTT. Further measurements included inflammatory cytokines, adipocytokines, physical activity level, body composition, and food intake., Results: SLE and CTRL groups showed similar fasting glucose, glucose response, and skeletal muscle GLUT-4 translocation after MTT. However, the SLE group demonstrated higher fasting insulin levels (P = 0.01; effect size [ES] 1.2), homeostatic model assessment insulin resistance (IR) (P = 0.03; ES 1.1), insulin-to-glucose ratio response to MTT (P = 0.02; ES 1.2), fasting glucagon levels (P = 0.002; ES 2.7), glucagon response to MTT (P = 0.0001; ES 2.6), and a tendency toward lower Matsuda index of whole-body insulin sensitivity (P = 0.06; ES -0.5) when compared with the CTRL group. Fasting proinsulin-to-insulin ratio and proinsulin-to-insulin ratio response to MTT were similar between groups (P > 0.05), while the SLE group showed a higher insulinogenic index when compared with the CTRL group (P = 0.02; ES = 0.9)., Conclusion: We have identified that SLE patients had a bi-hormone metabolic abnormality characterized by increased IR and hyperglucagonemia despite normal glucose tolerance and preserved beta cell function and skeletal muscle GLUT-4 translocation. Strategies capable of ameliorating insulin sensitivity to reduce the risk of type 2 diabetes mellitus and cardiovascular disease in SLE may require more than targeting IR alone., (© 2017, American College of Rheumatology.)

Background: Frailty is a multifactorial geriatric syndrome characterized by progressive decline in health and associated with decreased muscle mass, strength, and functional capacity. Resistance training (RT) combined with protein or amino acids supplementation has been shown to be promising for mitigating age-related impairments., Aim: To investigate the chronic effects of different strategies of protein and derivatives supplementation in association with RT on selected health-related parameters in pre-frail and frail elderly., Methods: This is a series of double-blind, randomized, placebo-controlled, parallel-group clinical trials. Volunteers will be divided into nine groups, comprising four different sub-studies evaluating the effects of: isolated leucine supplementation (study 1); protein source (whey vs. soy - study 2); combination of whey protein and creatine (study 3); and sexual dimorphism on the response to protein intake and RT (males vs. females - study 4). Muscle cross-sectional area, fiber cross-sectional area, body composition, lower-limb maximal dynamic and isometric strength, functionality, lipid profile, biochemical parameters, renal function, quality of life, and nutritional status will be assessed before and after a 16-week intervention period. Data will be tested for normality and a mixed-model for repeated measures will be conducted to assess within- and between-group effects of the intervention on the dependent variables. Confidence intervals (95%), effect sizes, and relative changes will also be determined, with significance set at p < 0.05.

Background: This manuscript describes the design and rationale of a clinical trial that aims to investigate the multiple physiological, attitudinal, nutritional, and behavioral effects of a new interdisciplinary intervention based on the Health at Every Size® (HAES®) approach in obese women., Methods: This will be a prospective, 7-month, randomized (2:1), mixed-method clinical trial. Obese women will be recruited and randomly allocated into two groups. The intervention group (I-HAES®; proposed n = 40) will undertake a novel HAES®-based intervention. Participants will take part in an exercise program, nutrition counseling sessions, and philosophical workshops, all aligned with the principles of the HAES® approach. The control group (CTRL; proposed n = 20) will participate in a program using a traditional HAES®-based group format, characterized by bimonthly lectures about the same topics offered to the experimental group, encouraging the adoption of a healthy lifestyle. The following multiple quantitative outcomes will be assessed pre and post intervention: health-related quality of life, cardiovascular risk factors, anthropometric assessments, physical activity level, physical capacity and function, and psychological and behavioral assessments. Qualitative analysis will be used to evaluate the experiences of the participants throughout the intervention, as assessed by focus groups and semi-structured interviews., Conclusions: The interdisciplinary research team leading this study has varied and complementary expertise. The knowledge arising from this study will help to guide new interdisciplinary interventions with the potential to holistically improve the health of obese individuals. This trial is registered at Clinicaltrials.gov (NCT02102061).

Creatine/phosphorylcreatine (PCr) responses to creatine supplementation may be modulated by age, diet, and tissue, but studies assessing this possibility are lacking. Therefore we aimed to determine whether PCr responses vary as a function of age, diet, and tissue. Fifteen children, 17 omnivorous and 14 vegetarian adults, and 18 elderly individuals ("elderly") participated in this study. Participants were given placebo and subsequently creatine (0.3 g·kg -1 ·day -1 ) for 7 days in a single-blind fashion. PCr was measured through phosphorus magnetic resonance spectroscopy ( 31 P-MRS) in muscle and brain. Creatine supplementation increased muscle PCr in children ( P < 0.0003) and elderly ( P < 0.001), whereas the increase in omnivores did not reach statistically significant difference ( P = 0.3348). Elderly had greater PCr increases than children and omnivores ( P < 0.0001 for both), whereas children experienced greater PCr increases than omnivores ( P = 0.0022). In relation to diet, vegetarians ( P < 0.0001), but not omnivores, had significant increases in muscle PCr content. Brain PCr content was not affected by creatine supplementation in any group, and delta changes in brain PCr (-0.7 to +3.9%) were inferior to those in muscle PCr content (+10.3 to +27.6%; P < 0.0001 for all comparisons). PCr responses to a standardized creatine protocol (0.3 g·kg -1 ·day -1 for 7 days) may be affected by age, diet, and tissue. Whereas creatine supplementation was able to increase muscle PCr in all groups, although to different extents, brain PCr was shown to be unresponsive overall. These findings demonstrate the need to tailor creatine protocols to optimize creatine/PCr accumulation both in muscle and in brain, enabling a better appreciation of the pleiotropic properties of creatine. NEW & NOTEWORTHY A standardized creatine supplementation protocol (0.3 g·kg -1 ·day -1 for 7 days) effectively increased muscle, but not brain, phosphorylcreatine. Older participants responded better than younger participants whereas vegetarians responded better than omnivores. Responses to supplementation are thus dependent on age, tissue, and diet. This suggests that a single "universal" protocol, originally designed for increasing muscle creatine in young individuals, may lead to heterogeneous muscle responses in different populations or even no responses in tissues other than skeletal muscle., (Copyright © 2017 the American Physiological Society.)

Exercise has been overlooked as a potential therapy in chronic kidney disease (CKD), mainly because of a lack of understanding on its safety aspects. Notably, there are no data on renal function after exercise in CKD considering its stages. We investigated the acute effects of a 30-min moderate-intensity aerobic exercise bout on glomerular filtration rate (GFR) and albuminuria in 22 nondialysis CKD patients divided into: CKD stages 1 and 2 (CKD 1-2 ) and CKD stages 3 and 4 (CKD 3-4 ). Eleven body mass index-, age-, and sex-matched healthy individuals served as control (CON). Blood and urine samples were collected before, immediately after, and up to 90 min postexercise for creatinine and albumin assessments. GFR was determined by creatinine clearance (GFR Cr-Cl ). All CKD patients had significantly lower peak oxygen uptake than CON. CKD 1-2 and CKD 3-4 had increasingly higher serum creatinine than CON (9.6 ± 2.6, 25.6 ± 1.01, and 7.5 ± 1.4 mg/l, respectively); however, no within-group changes in serum or urinary creatinine were observed across time. GFR Cr-Cl was decreased in CKD 1-2 and CKD 3-4 compared with CON (91 ± 17 ml·min -1 ·1.73 m -2 ; 34 ± 15 ml·min -1 ·1.73 m -2 ; 122 ± 20 ml·min -1 ·1.73 m -2 , respectively). Most importantly, exercise did not affect GFR Cr-Cl in none of the groups across time. Albuminuria was significantly higher in CKD 3-4 (297 ± 284 µg/min) than in CON (5.4 ± 1.4 µg/min), but no within-group changes were observed after exercise. In conclusion, a single 30-min moderate-intensity aerobic exercise bout does not impair renal function in nondialysis CKD patients, regardless of disease stage, supporting the notion that exercise training can be safe in this disease., (Copyright © 2017 the American Physiological Society.)

This study investigates the influence of habitual caffeine intake on aerobic exercise-performance responses to acute caffeine supplementation. A double-blind, crossover, counterbalanced study was performed. Forty male endurance-trained cyclists were allocated into tertiles, according to their daily caffeine intake: low (58 ± 29 mg/d), moderate (143 ± 25 mg/d), and high (351 ± 139 mg/d) consumers. Participants completed three trials in which they performed simulated cycling time trials (TTs) in the fastest time possible following ingestion of the following: caffeine (CAF: 6 mg/kg body mass), placebo (PLA), and no supplement (CON). A mixed-model analysis revealed that TT performance was significantly improved in CAF compared with PLA and CON (29.92 ± 2.18 vs. 30.81 ± 2.67 and 31.14 ± 2.71 min, respectively; P = 0.0002). Analysis of covariance revealed no influence of habitual caffeine intake as a covariate on exercise performance ( P = 0.47). TT performance was not significantly different among tertiles ( P = 0.75). No correlation was observed between habitual caffeine intake and absolute changes (CAF - CON) in TT performance with caffeine ( P = 0.524). Individual analysis showed that eight, seven, and five individuals improved above the variation of the test in CAF in the low, moderate, and high tertiles, respectively. A Fisher's exact test did not show any significant differences in the number of individuals who improved in CAF among the tertiles ( P > 0.05). Blood lactate and ratings of perceived exertion were not different between trials and tertiles ( P > 0.05). Performance effects of acute caffeine supplementation during an ~30-min cycling TT performance were not influenced by the level of habitual caffeine consumption. NEW & NOTEWORTHY There has been a long-standing paradigm that habitual caffeine intake may influence the ergogenicity of caffeine supplementation. Low, moderate, and high caffeine consumers showed similar absolute and relative improvements in cycling time-trial performance following acute supplementation of 6 mg/kg body mass caffeine. Performance effects of acute caffeine were not influenced by the level of habitual caffeine consumption, suggesting that high habitual caffeine intake does not negate the benefits of acute caffeine supplementation., (Copyright © 2017 the American Physiological Society.)