Hyperglycaemia and central obesity disrupt conditioned pain modulation: A single-blind cross-over randomised controlled trial.

Hyperglycaemia and high adiposity are risk factors for pain in diabetes. To clarify these links with pain, the effects of a glucose load on sensory detection, pain sensitivity, conditioned pain modulation (primary aims), and autonomic and endothelial functions (secondary aims) were examined in 64 pain-free participants: 22 with normal adiposity (determined by dual-energy X-ray absorptiometry), 29 with high adiposity, and 13 with combined high adiposity and elevated glycated haemoglobin (HbA1c; including prediabetes and type 2 diabetes). Participants ingested either 37.5-g glucose or 200-mg sucralose (taste-matched) in the first session and crossed over to the other substance in the second session one month later. At baseline, painful temple cooling (the conditioning stimulus) inhibited pressure- and heat-pain in the ipsilateral arm (the test stimuli) immediately after cooling ceased (partial η2's >.32). Glucose ingestion weakened pressure-pain inhibition irrespective of HbA1c levels (partial η2 =.11). However, a larger reduction in pressure-pain inhibition after ingesting glucose was associated with a higher waist/hip ratio (r =.31), suggesting a role of central obesity. Heat-pain inhibition was absent at baseline in unmedicated participants with elevated HbA1c, and these participants reported more occlusion-induced pain after ingesting glucose (partial η2's >.17). Glucose ingestion interfered with parasympathetic activity in all participants (partial η2 =.11) but did not affect endothelial function (measured by reactive hyperaemia) or alter other sensations (e.g., feet vibration detection). The disruptive effect of hyperglycaemia on conditioned pain modulation increases in line with central obesity, which might facilitate pain in diabetes. PERSPECTIVE: Ingesting 37.5-g glucose (approximately 350-mL soft drink) interfered with pain modulation in pain-free adults with normal adiposity or with combined high adiposity and HbA1c levels. The interference was stronger alongside increasing central obesity, suggesting that controlling blood glucose and body fat mass might help preserve pain modulation.

Exploring the efficacy and safety of a novel standardized ashwagandha (Withania somnifera) root extract (Witholytin®) in adults experiencing high stress and fatigue in a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Stress is a state of homeostasis in the body being challenged, resulting in a systemic response. It has become more prevalent in recent years and affects mental and physical health. AIMS: Evaluate the effects of ashwagandha on stress, fatigue, and sex hormones in overweight or mildly obese men and women with self-reported stress and fatigue. METHODS: Two-arm, parallel-group, 12-week, randomized, double-blind, placebo-controlled trial on overweight or mildly obese men and women aged 40-75 years, supplementing with 200 mg of an ashwagandha root extract (Witholytin®) twice daily. RESULTS/OUTCOMES: Supplementation with ashwagandha was associated with a significant reduction in stress levels based on the Perceived Stress Scale (primary outcome); however, the improvements were not significantly different to the placebo group (p = 0.867). Based on the Chalder Fatigue Scale, there was a statistically significant reduction in fatigue symptoms in the ashwagandha group compared to the placebo group (p = 0.016), and participants taking ashwagandha also experienced a significant increase in heart rate variability (p = 0.003). However, there were no significant between-group differences in other self-report outcome measures. In the men taking ashwagandha, there was a significant increase in the blood concentrations of free testosterone (p = 0.048) and luteinizing hormone (p = 0.002) compared to the placebo group. CONCLUSIONS/INTERPRETATION: The results of this study suggest that in overweight middle-to-older age adults experiencing high stress and fatigue, compared to the placebo, ashwagandha did not have a significantly greater impact on perceived stress levels. However, based on secondary outcome measures, it may have anti-fatigue effects. This may be via its impact on the autonomic nervous system. However, further research is required to expand on these current findings.

Old muscle, new tricks: a clinician perspective on sarcopenia and where to next.

PURPOSE OF REVIEW: This review offers a contemporary clinical approach to the recognition, prevention and management of sarcopenia, and discusses recent clinically relevant advances in the aetiopathogenesis of muscle ageing that may lead to future therapeutic targets. RECENT FINDINGS: The key recent directions for sarcopenia are in the diagnosis, understanding molecular mechanisms and management. Regarding the recognition of the condition, it has become increasingly clear that different definitions hamper progress in understanding. Therefore, the Global Leadership in Sarcopenia has been established in 2022 to develop a universally accepted definition. Moreover, substantial work is occurring to understand the various roles and contribution of inflammation, oxidative stress, mitochondrial dysfunction and metabolic dysregulation on skeletal muscle function and ageing. Finally, the role of resistance-based exercise regimes has been continually emphasised. However, the role of protein supplementation and hormone replacement therapy (HRT) are still under debate, and current clinical trials are underway. SUMMARY: With the global ageing of our population, there is increasing emphasis on maintaining good health. Maintenance of skeletal muscle strength and function are key to preventing frailty, morbidity and death.

Examining the associations between testosterone and biomarkers as men age.

OBJECTIVES: Testosterone concentrations in men decline with advancing age. However, the cause of the decline is yet to be fully elucidated. Therefore, the aims of this study were to examine the associations between chronic diseases such as obesity and type 2 diabetes mellitus (T2DM) with total testosterone (TT) and sex hormone-binding globulin (SHBG), using a large nationally-representative data set (National Health and Nutrition Examination Survey; NHANES). METHODS: NHANES is a cross-sectional survey, physical examination, and laboratory evaluation of a nationally-representative sample of a non-institutionalized United States population. Male participants aged ≥18 years during the NHANES 2013-2014 and NHANES 2015-2016 survey periods were selected for this analysis. The analysis included the following data: body mass index (BMI), oral glucose tolerance test (OGTT), homeostatic model assessment of insulin resistance (HOMA-IR), insulin, glucose, and age. RESULTS: An overweight or obese condition was significantly inversely associated with TT and SHBG, even after adjusting for other variables. Several variables associated with T2DM (OGTT, HOMA-IR, insulin, and glucose) were also inversely associated with TT; however, only the associations between OGTT and insulin with TT remained significant after adjusting for the other variables. Insulin and HOMA-IR levels were significantly inversely associated with SHBG; however, only the association between SHBG and pre-diabetic HOMA-IR levels remained significant after adjusting for the other variables. OGTT became significantly associated with SHBG after adjusting for the other variables. Age was significantly inversely associated with TT, but positively associated with SHBG, even after adjusting for other variables. CONCLUSION: The results of the present study, which is the largest to date, indicate that a marker of obesity, BMI, and some markers of T2DM are both independently and significantly inversely associated with TT and SHBG.

Testosterone treatment combined with exercise to improve muscle strength, physical function and quality of life in men affected by inclusion body myositis: A randomised, double-blind, placebo-controlled, crossover trial.

INTRODUCTION: Inclusion body myositis (IBM) is the most commonly acquired skeletal muscle disease of older adults involving both autoimmune attack and muscle degeneration. As exercise training can improve outcomes in IBM, this study assessed whether a combination of testosterone supplementation and exercise training would improve muscle strength, physical function and quality of life in men affected by IBM, more than exercise alone. METHODS: This pilot study was a single site randomised, double-blind, placebo-controlled, crossover study. Testosterone (exercise and testosterone cream) and placebo (exercise and placebo cream) were each delivered for 12 weeks, with a two-week wash-out between the two periods. The primary outcome measure was improvement in quadriceps isokinetic muscle strength. Secondary outcomes included assessment of isokinetic peak flexion force, walk capacity and patient reported outcomes, and other tests, comparing results between the placebo and testosterone arms. A 12-month Open Label Extension (OLE) was offered using the same outcome measures collected at 6 and 12-months. RESULTS: 14 men completed the trial. There were no significant improvements in quadriceps extension strength or lean body mass, nor any of the secondary outcomes. Improvement in the RAND Short Form 36 patient reported outcome questionnaire 'emotional wellbeing' sub-category was reported during the testosterone arm compared to the placebo arm (mean difference [95% CI]: 6.0 points, [95% CI 1.7,10.3]). The OLE demonstrated relative disease stability over the 12-month period but with a higher number of testosterone-related adverse events. CONCLUSIONS: Adding testosterone supplementation to exercise training did not significantly improve muscle strength or physical function over a 12-week intervention period, compared to exercise alone. However, the combination improved emotional well-being over this period, and relative stabilisation of disease was found during the 12-month OLE. A longer duration trial involving a larger group of participants is warranted.

Exercise-induced responses in matrix metalloproteinases and osteopontin are not moderated by exercise format in males with overweight or obesity.

PURPOSE: Matrix metalloproteinase-2 (MMP-2) and -3 (MMP-3), and osteopontin (OPN) are associated with adipose-tissue expansion and development of metabolic disease. The purpose of the current study was to assess the circulating concentration of these markers, along with adiponectin and glucose concentrations, in response to acute exercise in individuals with overweight or obesity. METHODS: Fourteen sedentary males with overweight or obesity (29.0 ± 3.1 kg/m2) completed two separate, 3-day trials in randomised and counterbalanced order. An oral glucose tolerance test (OGTT) was performed on each day of the trial. Day two of each trial consisted of a single 30 min workload-matched bout of either high-intensity interval exercise (HIIE; alternating 100% and 50% of peak pulmonary oxygen uptake, [Formula: see text]O2peak) or continuous moderate intensity (CME; 60% [Formula: see text]O2peak) cycling completed 1 h prior to the OGTT. Glucose and physical activity were continuously monitored, while MMP-2, MMP-3, OPN and adiponectin were measured pre-, 0 h post-, 1 h post- and 25 h post-exercise. RESULTS: Exercise transiently increased MMP-3 and decreased OPN (both p < 0.01), but not MMP-2 or adiponectin. There were no differences in the response of inflammatory markers to the different exercise formats. Exercise increased mean daily glucose concentration and area under the glucose curve during the OGTT on Day 2 and Day 3 (main effect of time; p < 0.05). CONCLUSION: Acute cycling exercise decreased OPN, which is consistent with longer term improvements in cardiometabolic health and increased MMP-3, which is consistent with its role in tissue remodelling. Interestingly, exercise performed prior to the morning OGTT augmented the glucose concentrations in males. TRIAL REGISTRATION: ACTRN12613001086752.

Temple cooling increases parasympathetic activity and decreases pressure pain on the hand.

BACKGROUND: Applying an ice cube to the temple (the conditioning stimulus) inhibits electrically evoked pain in the forearm. The present study aimed to determine whether temple cooling also inhibits pressure- and heat-pain test stimuli in the upper limb and, if so, to investigate the intra-session test-retest reliability of this response. Additional aims were to establish whether pain inhibition evoked by temple cooling was associated with parasympathetic activity; and to explore sex differences in response. METHODS: The sample consisted of 40 healthy adults (24 females). Heart rate was recorded continuously throughout the session. An ice cube (3 × 4 cm contact area) was applied for 1 min to the temple on the dominant side. Before and immediately afterwards, the pressure pain threshold was measured from the dorsal hand and sensitivity to heat (individually adjusted at baseline to elicit moderate pain) was measured from the ventral forearm. The procedures were repeated 15 min later. RESULTS: Temple cooling inhibited pressure pain on the hand but not heat pain on the forearm. However, test-retest reliability of pressure pain inhibition was poor. Heart rate decreased during temple cooling, consistent with a "diving" reflex. Males had stronger pressure pain inhibition, lower heart rate and higher overall autonomic activity than females. However, cardiac parasympathetic activation during temple cooling was comparable in both sexes and was unrelated to pain inhibition. CONCLUSIONS: These findings indicate that temple cooling evokes pain inhibition that is stronger in males than in females. Cardiac parasympathetic activity does not appear to mediate this response. SIGNIFICANCE: The conditioning stimulus in the conditioned pain modulation paradigm is often applied to the upper or lower limbs. This may confound pain-inhibitory effects in people with peripheral neuropathy who typically have enhanced or diminished sensation in the extremities. Applying an ice cube at the temple area induces pain-inhibitory effects on the upper limb after the ice is removed. Future research examining pain modulation in people with peripheral neuropathy may consider adopting temple cooling as the conditioning stimulus.

High Blood Glucose and Excess Body fat Enhance Pain Sensitivity and Weaken Pain Inhibition in Healthy Adults: A Single-blind Cross-over Randomized Controlled Trial.

To investigate links between blood glucose, body fat mass and pain, the effects of acute hyperglycaemia on pain sensitivity and pain inhibition were examined in healthy adults with normal (n = 24) or excess body fat (n = 20) determined by dual-energy X-ray absorptiometry. Effects of hyperglycaemia on heart rate variability and reactive hyperaemia were also explored. For the overall sample, ingesting 75-g glucose enhanced pain sensitivity during 1-minute cold-water immersion of both feet (conditioning stimulus) and weakened the pain inhibitory effect of cold water on pressure pain thresholds (test stimulus). Exploratory subgroup analyses not adjusted for multiple comparisons suggested that this effect was limited to people with excess fat mass. In addition, acute hyperglycaemia suppressed resting heart rate variability only in people with excess fat mass. Furthermore, regardless of blood glucose levels, people with excess fat mass had weaker pain inhibition for pinprick after cold water and reported more pain during 5-minutes of static blood flow occlusion. Neither high blood glucose nor excess body fat affected pinprick-temporal summation of pain or reactive hyperaemia. Together, these findings suggest that hyperglycaemia and excess fat mass interfere with pain processing and autonomic function. PERSPECTIVE: Ingesting 75-g glucose (equivalent to approximately 2 standard cans of soft drink) interfered with pain-processing and autonomic function, particularly in people with excess body fat mass. As both hyperglycaemia and overweight are risk factors for diabetes, whether these are sources of pain in people with diabetes should be further explored.

Immunoregulatory effects of testosterone supplementation combined with exercise training in men with Inclusion Body Myositis: a double-blind, placebo-controlled, cross-over trial.

Objectives: Sporadic Inclusion Body Myositis (IBM) is an inflammatory muscle disease affecting individuals over the age of 45, leading to progressive muscle wasting, disability and loss of independence. Histologically, IBM is characterised by immune changes including myofibres expressing major histocompatibility complex molecules and invaded by CD8+ T cells and macrophages, and by degenerative changes including protein aggregates organised in inclusion bodies, rimmed vacuoles and mitochondrial abnormalities. There is currently no cure, and regular exercise is currently the only recognised treatment effective at limiting muscle weakening, atrophy and loss of function. Testosterone exerts anti-inflammatory effects, inhibiting effector T-cell differentiation and pro-inflammatory cytokine production. Methods: We conducted a double-blind, placebo-controlled, cross-over trial in men with IBM, to assess whether a personalised progressive exercise training combined with application of testosterone, reduced the inflammatory immune response associated with this disease over and above exercise alone. To assess intervention efficacy, we immunophenotyped blood immune cells by flow cytometry, and measured serum cytokines and chemokines by Luminex immunoassay. Results: Testosterone supplementation resulted in modest yet significant count reduction in the classical monocyte subset as well as eosinophils. Testosterone-independent immunoregulatory effects attributed to exercise included altered proportions of some monocyte, T- and B-cell subsets, and reduced IL-12, IL-17, TNF-α, MIP-1ß and sICAM-1 in spite of interindividual variability. Conclusion: Overall, our findings indicate anti-inflammatory effects of exercise training in IBM patients, whilst concomitant testosterone supplementation provides some additional changes. Further studies combining testosterone and exercise would be worthwhile in larger cohorts and longer testosterone administration periods.

The effect of the inclusion of trunk-strengthening exercises to a multimodal exercise program on physical activity levels and psychological functioning in older adults: secondary data analysis of a randomized controlled trial.

BACKGROUND: Engaging in multimodal exercise program helps mitigate age-related decrements by improving muscle size, muscle strength, balance, and physical function. The addition of trunk-strengthening within the exercise program has been shown to significantly improve physical functioning outcomes. Whether these improvements result in improved psychological outcomes associated with increased physical activity levels requires further investigation. We sought to explore whether the inclusion of trunk-strengthening exercises to a multimodal exercise program improves objectively measured physical activity levels and self-reported psychological functioning in older adults. METHOD: We conducted a secondary analysis within a single-blinded parallel-group randomized controlled trial. Sixty-four healthy older (≥ 60 years) adults were randomly allocated to a 12-week walking and balance exercise program with (n = 32) or without (n = 32) inclusion of trunk strengthening exercises. Each program involved 12 weeks of exercise training, followed by a 6-week walking-only program (identified as detraining). Primary outcome measures for this secondary analysis were physical activity (accelerometry), perceived fear-of-falling, and symptoms of anxiety and depression. RESULTS: Following the 12-week exercise program, no significant between-group differences were observed for physical activity, sedentary behaviour, fear-of-falling, or symptoms of anxiety or depression. Significant within-group improvements (adjusted mean difference [95%CI]; percentage) were observed in moderate-intensity physical activity (6.29 [1.58, 11.00] min/day; + 26.3%) and total number of steps per min/day (0.81 [0.29 to 1.33] numbers or + 16.3%) in trunk-strengthening exercise group by week 12. With respect to within-group changes, participants in the walking-balance exercise group increased their moderate-to-vigorous physical activity (MVPA) (4.81 [0.06 to 9.56] min/day; + 23.5%) and reported reduction in symptoms of depression (-0.26 [-0.49 to -0.04] points or -49%) after 12 weeks of the exercise program. The exercise-induced increases in physical activity levels in the trunk-strengthening exercise group were abolished 6-weeks post-program completion. While improvements in physical activity levels were sustained in the walking-balance exercise group after detraining phase (walking only). CONCLUSIONS: The inclusion of trunk strengthening to a walking-balance exercise program did not lead to statistically significant between-group improvements in physical activity levels or psychological outcomes in this cohort following completion of the 12-week exercise program. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12613001176752), registered on 28/10/2013.

The role of glucose in cognition, risk of dementia, and related biomarkers in individuals without type 2 diabetes mellitus or the metabolic syndrome: A systematic review of observational studies.

BACKGROUND: Excessive blood glucose promotes neuropathological cognitive decline in individuals with type 2 diabetes mellitus and the metabolic syndrome, but no systematic synthesis of the evidence for the same association exists in individuals without these conditions. OBJECTIVES: To systematically review studies exploring the role of glucose on cognition, dementia risk, and related biomarkers in adults without diabetes or metabolic syndrome. DATA SOURCES: We searched databases from inception until July 2021 and manually searched the reference lists of included studies. Risk of bias was assessed using the Joanna Briggs Institute tool. RESULTS: We found 46 observational studies including approximately 98,216 participants. Substantial heterogeneity in study results precluded drawing definitive conclusion whether blood glucose levels are associated with cognition or dementia risk. Higher blood glucose, however, was associated with greater amyloid burden, brain atrophy, and reduced cortical thickness. CONCLUSIONS AND IMPLICATIONS: High glucose concentrations in blood may exacerbate dementia-related neuropathology but whether this translates into pathological cognitive decline or elevate dementia risk later in life remains unclear.

Examining the effects of calorie restriction on testosterone concentrations in men: a systematic review and meta-analysis.

CONTEXT: Testosterone concentrations decline with age, and lower testosterone concentrations are associated with several morbidities, including sexual dysfunction, obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. OBJECTIVE: Because dietary habits play a critical role in weight regulation and T2DM management, the aim of this systematic review and meta-analysis was to summarize and critically evaluate the evidence from randomized controlled trials to determine the effects of calorie restriction (CR) on testosterone concentrations in men. DATA SOURCES: A literature search was conducted across 4 databases, from their inception until March 2020. DATA EXTRACTION: The screening and data extraction were completed by 2 authors independently, and in a blinded manner, according to a priori inclusion and exclusion criteria. DATA ANALYSIS: Of the 4198 studies identified from the initial search, 7 randomized controlled trials were included for data extraction. Significant increases in total testosterone concentrations were reported in 3 of 4 studies in which CR was examined with overweight or obese men, compared with the control groups. Significant decreases in total testosterone concentrations were reported in 2 of 3 studies in which the effects of CR were examined with normal-weight, healthy men, compared with the control groups. In all 4 studies that examined the effect of CR on sex hormone-binding globulin concentrations, the intervention significantly increased sex hormone-binding globulin concentrations compared with that of the control groups irrespective of body composition. CONCLUSION: This systematic review and meta-analysis provide some evidence that CR affects testosterone concentrations in men and this effect depends on their body mass index. PROSPERO registration no. CRD42020173102.

Painful diabetic peripheral neuropathy: Role of oxidative stress and central sensitisation.

AIMS: Diabetic peripheral neuropathy (DPN) occurs in about half of people with diabetes, of whom a quarter may develop chronic pain. Pain may remain for years yet be difficult to treat because the underlying mechanisms remain unclear. There is consensus that processing excessive glucose leads to oxidative stress, interfering with normal metabolism. In this narrative review, we argue that oxidative stress may also contribute to pain. METHODS: We reviewed literature in PubMed published between January 2005 and August 2021. RESULTS AND CONCLUSIONS: In diabetes, hyperglycaemia and associated production of reactive species can directly increase pain signalling and activate sensory neurons; or the effects can be indirect, mediated by mitochondrial damage and enhanced inflammation. Furthermore, pain processing in the central nervous system is compromised in painful DPN. This is implicated in central sensitisation and dysfunctional pain modulation. However, central pain modulatory function is understudied in diabetes. Future research is required to clarify whether central sensitisation and/or disturbances in central pain modulation contribute to painful DPN. Positive results would facilitate early detection and future treatment.

Vigorous physical activity is important in maintaining a favourable health trajectory in active children: the CHAMPS Study-DK.

Physical activity (PA) is critical to improving health factors such as weight, adiposity, and aerobic fitness. However, children who meet PA guideline recommendations demonstrate developmental differences in health-related outcomes. To investigate prospective associations between PA behaviour (overall PA and PA intensity) and trajectories of health-related factors among physically active children. This prospective study (2.5 years) included 391 children (baseline age: 8.1 ± 1.4 years; girls 36.3%) from ten public schools. All children performed 60-min or more of moderate-to-vigorous physical activity (MVPA) per day objectively measured. Trajectories of BMI, waist circumference, and aerobic fitness were constructed with a group-based multi-trajectory model. Three trajectory subgroups were identified: 'high fitness/normal weight' (48.4% of children), 'moderate fitness /normal weight' (42.5% of children), and 'low fitness/overweight-obese' (9.1% of children). Children performing higher overall PA, were less likely of being classified as members of the 'Low Fitness/Overweight-Obese' [Relative Risk Ratio (RRR and 95% CI) = 0.56 (0.37 to 0.85) compared to 'high fitness/normal weight' subgroup. Each additional 5% in light PA time was associated with approximately twofold [RRR 2.12 (1.24-3.61)] increased risk of being in the 'low fitness/overweight-obese' trajectory relative to the 'high fitness/normal weight' trajectory. Each additional 2% in vigorous-PA time was associated with a 42% and 85% reduced risk (relative to 'high fitness/normal weight') of being in the 'moderate fitness/normal weight' [RRR 0.58 (0.38-0.96)] and 'low fitness/overweight-obesity' [RRR 0.15 (0.06-0.37)] trajectory, respectively. Overall PA and additional time in vigorous-PA was associated with improved health-related outcomes, while light PA was negatively associated with health-related outcomes among children who adhere to PA guideline recommendations. Vigorous PA was the strongest predictor of the health trajectories. All PA guidelines for children should place greater emphasis on the importance of vigorous PA.

Effects of diurnal exercise timing on appetite, energy intake and body composition: A parallel randomized trial.

OBJECTIVE: To determine the effect of diurnal exercise timing on appetite, energy intake and body composition in individuals with overweight or obesity. METHODS: Forty sedentary, individuals with overweight or obesity (17 males, 23 females; age: 51 ± 13 years; BMI: 30.9 ± 4.2 kg/m2) were randomly allocated to complete a 12-week supervised multi-modal exercise training program performed either in the morning (amEX) or evening (pmEX). Outcome measures included appetite in response to a standardised test meal, daily energy intake (EI), body weight and body composition. Measures of dietary behaviour were assessed at baseline and post-intervention, along with habitual physical activity, sleep quality and sleep quantity. Significance was set at p ≤ .05 and Hedge's g effect sizes were calculated. RESULTS: Regardless of timing, exercise training increased perceived fullness (AUC; g = 0.82-1.67; both p < .01), decreased daily EI (g = 0.73-0.93; both p < .01) and body-fat (g = 0.29-0.32; both p <. 01). The timing of exercise did not change the daily EI or body-fat response to training (all p ≥ .27), however, perceived fullness increased in the amEX group (p ≤ .01). DISINHIBITION: (g = 0.35-1.95; p ≤ .01) and Hunger (g = 0.05-0.4; p = .02) behaviours decreased following exercise training, with Disinhibition demonstrating greater improvements in the pmEX group (p = .01). Objective and subjective sleep quantity increased with training (all p ≤ .01), but sleep quality was not reported to change. CONCLUSIONS: Multi-modal exercise training improved body composition and some appetite outcomes, although changes were inconsistent and largely independent of exercise-timing. In the absence of dietary manipulation, the effect of diurnal exercise timing on appetite and body composition appear trivial compared to the overall benefits of exercise participation.

Examining the Effects of Herbs on Testosterone Concentrations in Men: A Systematic Review.

Testosterone concentrations in males tend to decline with advancing age. Low testosterone, also known as androgen deficiency (AD), is associated with an increased risk of morbidity and mortality. Currently, the primary treatment for AD is testosterone replacement therapy (TRT), which may exacerbate pre-existing medical conditions. Therefore, the use of alternative options, such as herbs, spices, plants, or their extracts, has been explored as a potential treatment option for AD. The aim of this systematic review was to summarize and critically evaluate randomized controlled trials published on the efficacy of single herbal ingredients on testosterone concentrations, in addition to its fractions or binding proteins, in men (≥18 y). From the 4 databases searched, there were 13 herbs identified in 32 studies, published between 2001 and 2019. The main findings of this review indicate that 2 herbal extracts, fenugreek seed extracts and ashwagandha root and root/leaf extracts, have positive effects on testosterone concentrations in men. Also, some evidence exists for another herb and herbal extract, Asian red ginseng and forskohlii root extract. Overall, 9 out of 32 studies demonstrated statistically significant increases in testosterone concentrations. Moreover, 6 studies out of 32 were judged as having a low risk of bias. Current evidence is largely based on young, nonclinical populations, with 16 out of 32 studies using men <40 y of age. Conclusions are moderated by the paucity of research for many herbs, the variation in dosages and extracts used, small sample sizes, and the heterogeneity of study characteristics. Also, further research is required before definitive conclusions on efficacy and safety can be made. This systematic review was registered at PROSPERO as CRD42020173623.

Branched-chain amino acid supplementation improves cycling performance in untrained cyclists.

OBJECTIVES: To investigate the effects of acute branched-chain amino acid (BCAA) supplementation on cycling performance and neuromuscular fatigue during a prolonged, self-paced cycling time-trial. DESIGN: Randomised double-blind counterbalanced crossover. METHODS: Eighteen recreationally active men (mean±SD; age: 24.7±4.8 years old; body-weight, BW: 67.1±6.1kg; height: 171.7±4.9cm) performed a cycling time-trial on an electromagnetically-braked cycle ergometer. Participants were instructed to complete the individualised total work in the shortest time possible, while ingesting either BCAAs (pre-exercise: 0.084gkg-1 BW; during exercise: 0.056gkg-1h-1) or a non-caloric placebo solution. Rating of perceived exertion, power, cadence and heart rate were recorded throughout, while maximal voluntary contraction, muscle voluntary activation level and electrically evoked torque using single and doublet stimulations were assessed at baseline, immediately post-exercise and 20-min post-exercise. RESULTS: Supplementation with BCAA reduced (287.9±549.7s; p=0.04) time-to-completion and ratings of perceived exertion (p≤0.01), while concomitantly increasing heart rate (p=0.02). There were no between-group differences (BCAA vs placebo) in any of the neuromuscular parameters, but significant decreases (All p≤0.01) in maximal voluntary contraction, muscle voluntary activation level and electrically evoked torque (single and doublet stimulations) were recorded immediately following the trial, and these did not recover to pre-exercise values by the 20min recovery time-point. CONCLUSIONS: Compared to a non-caloric placebo, acute BCAA supplementation significantly improved performance in cycling time-trial among recreationally active individuals without any notable changes in either central or peripheral factors. This improved performance with acute BCAA supplementation was associated with a reduced rating of perceived exertion.

Correction to: Bilingualism Is Associated with a Delayed Onset of Dementia but Not with a Lower Risk of Developing it: a Systematic Review with Meta-Analyses.

The original version of this article unfortunately contained the following mistakes.

Bilingualism Is Associated with a Delayed Onset of Dementia but Not with a Lower Risk of Developing it: a Systematic Review with Meta-Analyses.

Some studies have linked bilingualism with a later onset of dementia, Alzheimer's disease (AD), and mild cognitive impairment (MCI). Not all studies have observed such relationships, however. Differences in study outcomes may be due to methodological limitations and the presence of confounding factors within studies such as immigration status and level of education. We conducted the first systematic review with meta-analysis combining cross-sectional studies to explore if bilingualism might delay symptom onset and diagnosis of dementia, AD, and MCI. Primary outcomes included the age of symptom onset, the age at diagnosis of MCI or dementia, and the risk of developing MCI or dementia. A secondary outcome included the degree of disease severity at dementia diagnosis. There was no difference in the age of MCI diagnosis between monolinguals and bilinguals [mean difference: 3.2; 95% confidence intervals (CI): -3.4, 9.7]. Bilinguals vs. monolinguals reported experiencing AD symptoms 4.7 years (95% CI: 3.3, 6.1) later. Bilinguals vs. monolinguals were diagnosed with dementia 3.3 years (95% CI: 1.7, 4.9) later. Here, 95% prediction intervals showed a large dispersion of effect sizes (-1.9 to 8.5). We investigated this dispersion with a subgroup meta-analysis comparing studies that had recruited participants with dementia to studies that had recruited participants with AD on the age of dementia and AD diagnosis between mono- and bilinguals. Results showed that bilinguals vs. monolinguals were 1.9 years (95% CI: -0.9, 4.7) and 4.2 (95% CI: 2.0, 6.4) older than monolinguals at the time of dementia and AD diagnosis, respectively. The mean difference between the two subgroups was not significant. There was no significant risk reduction (odds ratio: 0.89; 95% CI: 0.68-1.16) in developing dementia among bilinguals vs. monolinguals. Also, there was no significant difference (Hedges' g = 0.05; 95% CI: -0.13, 0.24) in disease severity at dementia diagnosis between bilinguals and monolinguals, despite bilinguals being significantly older. The majority of studies had adjusted for level of education suggesting that education might not have played a role in the observed delay in dementia among bilinguals vs. monolinguals. Although findings indicated that bilingualism was on average related to a delayed onset of dementia, the magnitude of this relationship varied across different settings. This variation may be due to unexplained heterogeneity and different sources of bias in the included studies. Registration: PROSPERO CRD42015019100.