Low-dose Exercise Research Articles

The dose-response effect of aerobic exercise on inflammation in colon cancer survivors.

Physical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer. In this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1:1:1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor necrosis factor-alpha receptor 2 (sTNFαR2). Mixed models for repeated measures were used to test the hypothesis that exercise was associated with dose-response reductions in inflammation; exploratory analyses examined treatment effects by cancer stage. In the overall population, aerobic exercise was not associated with dose-response reductions in hs-CRP, IL6, or sTNFαR2. Cancer stage modified the association between randomized group and hs-CRP (P=0.022) and IL6 (P<0.001) but not sTNFαR2 (P=0.39). In stage I-II disease, compared to control, exercise was not associated with inflammation outcomes. In stage III disease, compared to control, low-dose exercise reduced hs-CRP: -35.4% (95% CI: -70.1, -0.7) and IL6: -29.6% (95% CI: -58.4, -0.8) but not sTNFαR2: 2.7% (95% CI: sTNFαR2: -15.7, 21.1); high-dose exercise was not associated with inflammation outcomes in stage III disease. This exploratory analysis offers preliminary data to support the hypothesis that inflammation may mediate the association between physical activity and disease-free survival in colon cancer. clinicaltrials.gov, identifier NCT02250053.

Low-dose exercise protects the heart against established myocardial infarction via IGF-1-upregulated CTRP9 in male mice.

Regular exercise is recommended as an important component of therapy for cardiovascular diseases in clinical practice. However, there are still major challenges in prescribing an optimized exercise regimen to individual patients with established cardiac disease. Here, we tested the effects of different exercise doses on cardiac function in mice with established myocardial infarction (MI). Exercise was introduced to mice with MI after 4weeks of surgery. Low-dose exercise (15min/day for 8weeks) improved mortality and cardiac function by increasing 44.39% of ejection fractions while inhibiting fibrosis by decreasing 37.74% of distant region. Unlike higher doses of exercise, low-dose exercise consecutively upregulated cardiac expression of C1q complement/tumor necrosis factor-associated protein 9 (CTRP9) during exercise (>1.5-fold). Cardiac-specific knockdown of CTRP9 abolished the protective effects of low-dose exercise against established MI, while cardiac-specific overexpression of CTRP9 protected the heart against established MI. Mechanistically, low-dose exercise upregulated the transcription factor nuclear receptor subfamily 2 group F member 2 by increasing circulating insulin-like growth factor 1 (IGF-1), therefore, upregulating cardiac CTRP9 expression. These results suggest that low-dose exercise protects the heart against established MI via IGF-1-upregulated CTRP9 and may contribute to the development of optimized exercise prescriptions for patients with MI.

Primary mitral regurgitation: Toward a better quantification on left ventricular consequences.

Left ventricular end-systolic diameter (LVESD) and ejection fraction (LVEF) are the parameters to look for when discussing repair in asymptomatic patients with a primary mitral regurgitation (PMR). Loading conditions are altering LV-function quantification. LV-myocardial work (LVMW) is a method based on pressure-strain loops. We sought to evaluate the additive value of the LVMW for predicting clinical events in patients with PMR. 103 patients (66% men, median age 57 years) with asymptomatic severe PMR were explored at rest and during an exercise stress echocardiography. LV myocardial global work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were measured with speckle-tracking echocardiography at rest and low workload. The indication for surgery was based on the heart teams' decision. The median follow-up was 670 days. Clinical events occurred for 50 patients (48.5%) with a median of event-free survival distribution of 289 days. Systolic pulmonary artery pressure (sPAP) at rest was 32.61 ± 8.56 mmHg and did not predict the risk of event like LVEF and LVESD. Changes in, GLS (hazard ratio [HR] 0.55; 95% confidence interval (Cl): 0.36-0.83; p = .005), GWI (HR 1.01; 95% Cl: 1.00-1.02; p = .002) and GCW (HR 1.85; 95% Cl: 1.28-2.68; p = .001) in addition to Left Atrial Volume Index (HR 1.73; 95% CI: 1.28 - 2.33; p < 0,001) were independent predictors of events. Changes in myocardial work indices related to low-dose exercise are relevant to best predict PMR patient prognosis It might help to better select patient's candidate for "early-surgery."

Web Exclusive. Annals On Call - Exercise for Knee Osteoarthritis: Is More Better?

Web ExclusivesMarch 2023Annals On Call - Exercise for Knee Osteoarthritis: Is More Better?FREERobert M. Centor, MD and Patricia L. Perez, PT, DScPTRobert M. Centor, MDHuntsville Regional Medical Campus, University of Alabama Birmingham School of Medicine, Birmingham, Alabama (R.M.C.)Search for more papers by this author and Patricia L. Perez, PT, DScPTUniversity of Alabama at Birmingham, Birmingham, Alabama (P.L.P.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/A22-0006 CME/MOC SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In this episode of Annals On Call, Dr. Centor discusses the role of exercise in the treatment of knee osteoarthritis with Dr. Patricia Perez.Annals articles discussed include...High- Versus Low-Dose Exercise Therapy for Knee Osteoarthritis. A Randomized Controlled Multicenter Trial: https://www.acpjournals.org/doi/10.7326/M22-2348Effectiveness of an Unsupervised Online Yoga Program on Pain and Function in People With Knee Osteoarthritis. A Randomized Clinical Trial: https://www.acpjournals.org/doi/10.7326/M22-1761About Annals On CallAnnals On Call focuses on a clinically influential article published in Annals of Internal Medicine. Dr. Robert Centor shares his own perspective on the material and interviews topic area experts to discuss, debate, and share diverse insights about patient care and health care delivery.For more information on Annals On Call and for more episodes, visit go.annals.org/OnCall. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Huntsville Regional Medical Campus, University of Alabama Birmingham School of Medicine, Birmingham, Alabama (R.M.C.)University of Alabama at Birmingham, Birmingham, Alabama (P.L.P.)Disclosures: All relevant financial relationships have been mitigated. Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=A22-0006.Editors' Disclosures: The editors have no relevant financial relationships to disclose. Individual forms may be viewed at www.annals.org/editorsdisclosures. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEffectiveness of an Unsupervised Online Yoga Program on Pain and Function in People With Knee Osteoarthritis Kim L. Bennell , Sarah Schwartz , Pek Ling Teo , Stephanie Hawkins , Dave Mackenzie , Fiona McManus , Karen E. Lamb , Alexander J. Kimp , Ben Metcalf , David J. Hunter , and Rana S. Hinman High- Versus Low-Dose Exercise Therapy for Knee Osteoarthritis Tom Arild Torstensen , Håvard Østerås , Riccardo LoMartire , Georg Mørtvedt Rugelbak , Wilhelmus Johannes Andreas Grooten , and Björn Olov Äng Metrics Current IssueMarch 2023Volume 176, Issue 3 ePublished: 21 March 2023 Issue Published: March 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.Loading ...

Annals for Educators - February 2023.

Annals for Educators - February 2023.

130 Impact of Low-Dose High-Frequency &lt;i&gt;in situ&lt;/i&gt; Simulation on Inpatient Diabetes Management: A Pilot Study

Even in the presence of established institutional guidelines, failure of compliance by the clinical teams plays an important role in the control of diabetes. The identified gaps include contextual and biomedical knowledge, attitudes, clinical inertia, confidence and familiarity with existing hospital resources and guidelines with regards to hospital diabetes care We wanted to demonstrate the efficacy of low-dose high-frequency The exercise was a 15-minute session, delivered during working hours to individual nurses. This consisted of a 5-minute scenario, involving a standardized patient followed by a 10-minute debrief. Modified Diamond-model debrief with an advocacy-inquiry model was used by the debriefer, a trained fellow in simulation, and overseen by an expert. The scripted scenario involved a patient with Diabetic Ketoacidosis (DKA), with learning outcomes of recognizing DKA, managing the patient and adhering to the institutional guidelines including management of hypoglycaemia. The scenario was individualized based on the roles of the participants. Pre- and post-questionnaires were given to the participants. The simulation was repeated twice in the second week and once in the third week. This mixed-method study was conducted in a UK teaching hospital, in a ward designated for patients with diabetes, as a part of a quality improvement programme. In the first week, patients with diabetes, admitted for DKA, were chosen and their blood sugar recordings, dysglycaemic episodes and adherence to guidelines were noted. Every week data were collected as in the first week. GNU pspp 1.0.1 [version 3] free software was used. The confidence scores were given as mean and standard deviation with confidence interval (CI) of 98.75%. A p-value of &lt;0.0125 was considered significant based on the number of data points. The Dysglycemic episodes and protocol adherence from medical records Considering the T2 (increased recognition of diabetic emergencies and adherence to protocol) and T3 (improved patient outcomes) outcomes, the methodology was recommended as a modality of training the nursing staff involved in inpatient care of patients with diabetes. Future programmes including multi-disciplinary teams, to explore teamwork and communication, are planned.

Effect of exercise on inhibitory control is dose-dependent for adolescents

Adolescence is an important stage for brain maturation. To investigate the effect of different exercise doses on inhibitory control in adolescents aged 12 to 14-year old, an after-school exercise program was offered 5 days per week for 12 weeks during a school semester. Thirsty-four adolescents (17 boys) from the first six classes were randomly divided into low-dose exercise group (LE group, one 30-min aerobic exercise bout per day, n ​= ​16) and high-dose exercise group (HE group, two 30-min aerobic exercise bouts per day, n ​= ​18), while 23 adolescents (10 boys) in the control group (CON, zero 30-min exercise bout, n ​= ​23) were from the last two classes. All the participants in different classes received the same physical education with the same contents, duration, and intensity at class. All the participants completed flanker tests and cardiorespiratory tests before and after exercise intervention. The HE group showed more significant improvements on inhibitory control and V˙O2peak than CON (p ​< ​0.05). Changes in physical activity (PA) were significantly correlated with changes in interference scores (Spearman rho ​= ​-0.30, p ​< ​0.05), V˙O2peak (Spearman rho ​= ​0.31, p ​< ​0.05), and BF percentage (Spearman rho ​= ​-0.32, p ​< ​0.05). This study demonstrated that effect of exercise on inhibitory control in adolescents is dose-dependent, which highlights the need to focus on the exercise dose in daily life for improving cognition among adolescents.

Effect of Supervised Training Therapy on Pulmonary Arterial Compliance and Stroke Volume in Severe Pulmonary Arterial Hypertension and Inoperable or Persistent Chronic Thromboembolic Pulmonary Hypertension

Background: Pulmonary arterial compliance (PAC) is a prognostic parameter in pulmonary arterial hypertension (PAH) reflecting the elasticity of the pulmonary vessels. Objectives: The objective of this post hoc analysis of a prospective randomized controlled trial (RCT) was to assess the effect of exercise training on PAC and stroke volume (SV) in patients with PAH and persistent/inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Method: From the previous RCT, 43 out of 87 patients with severe PAH (n = 29) and CTEPH (n = 14) had complete haemodynamic examinations at baseline and after 15 weeks by right heart catheterization and were analysed (53% female, 79% World Health Organization functional class III/IV, 58% combination therapy, 42% on supplemental oxygen therapy, training group n = 24, and control group n = 19). Medication remained unchanged for all patients. Results: Low-dose exercise training at 4–7 days/week significantly improved PAC (training group 0.33 ± 0.65 mL/mm Hg vs. control group −0.06 ± 1.10 mL/mm Hg; mean difference 0.39 mL/mm Hg, 95% confidence interval [CI] 0.15–0.94 mL/mm Hg; p = 0.004) and SV (training group 9.9 ± 13.4 mL/min vs. control group −4.2 ± 11.0 mL/min; mean difference 14.2 mL, 95% CI 6.5–21.8 mL; p < 0.001) in the training versus control group. Furthermore, exercise training significantly improved cardiac output and pulmonary vascular resistance at rest, peak oxygen consumption, and oxygen pulse. Conclusions: Our findings suggest that supervised exercise training may improve right ventricular function and PAC at the same time. Further prospective studies are needed to evaluate these findings.

Increased Duration of Exercise Decreases Rate of Nonresponse to Exercise but May Not Decrease Risk for Cancer Mortality.

Previous studies have observed an inverse relationship between exercise and breast cancer risk. However, there is interindividual variability in response to exercise training interventions. We investigated whether increasing the dose of aerobic exercise (150 or 300 min·wk-1), while keeping intensity of exercise constant (70%-80% HRmax), decreases the number of exercise nonresponders and further decreases associated risk for cancer mortality in our study population of women genetically predisposed for breast cancer. Healthy premenopausal women at elevated risk of breast cancer were randomized into control (<75 min·wk-1, n = 47), low-dose exercise (150 min·wk-1, n = 39), and high-dose exercise groups (300 min·wk-1, n = 39) for approximately 6 months. We assessed 1) clinical effectiveness (CE), defined as an improvement in predicted V˙O2max of ≥1 mL·kg-1·min-1, and twice the typical error (2× TE) of V˙O2max as thresholds to classify exercise "nonresponders"; 2) CE and 2× TE relative to exercise adherence levels; and 3) related changes in V˙O2max to predicted cancer mortality risk. After our 6-month intervention, we observed that 23.5% of women in the low-dose group and 5.6% of women in the high-dose group were clinical nonresponders (P = 0.04). Clinical nonresponder status was independent of adherence level. Associated reduction in risk for cancer mortality was observed among 87.2% of women in the low-dose group and 94.9% in the high-dose group (P = 0.43). Increasing volume (not intensity) of exercise via time spent exercising significantly decreases the number of "nonresponders." True nonresponders were observed as some women did not improve their fitness capacity despite high exercise adherence levels. Lastly, it appears 150 min·wk-1 is sufficient to decrease the predicted risk of cancer mortality.

Exercising control over signs and symptoms of stress and depression

300 million people worldwide suffer from depression. A poorly understood stress‐related pathophysiology is compounded by frequent treatment‐resistance.Undertaking regular exercise has consistently shown to prevent, protect and increase resilience against the development of aberrant stress‐related responses seen in depression, whereas sedentary behaviour tends to heighten symptoms. Despite the promise shown by exercise its clinical use is undermined by poor understanding of how beneficial effects are produced.Stress exposure can dysregulate important physiological pathways such as the hypothalamic‐pituitary‐adrenal (HPA) axis and the sympathetic nervous system. Disruption of tryptophan metabolism, including increased metabolism along the kynurenine pathway, is a neurobiological hallmark of depressed patients. Recent studies have shown that the beneficial impact of exercise for mood and cognition may be linked to reduced kynurenine production.Aimto examine the benefits of a 12‐week exercise programme in healthy but sedentary adults across mood, stress, anxiety and depression were mediated by the regulation of tryptophan metabolism in a dose dependent manner.32 healthy sedentary participants (16 female) were analysed. To establish a baseline profile each participant undertook a battery of psychometric assessments, cognitive assessments and a cycle ergometer‐based incremental fitness assessment. Measures of oxygen uptake and capillary blood lactate levels were taken at the end of each stage during the fitness assessment.After the baseline assessment, participants were randomised into one of four groups (high, moderate, low dose exercise, or sedentary control group). Exercise was administered over 3 sessions/week based on individual fitness and group. Monthly fitness and psychometric assessments were performed throughout to monitor change across the 12‐week exercise programme. Analyses performed using SPSS.As expect, participants showed a positive increase in fitness and performance with an increase in maximal oxygen uptake (F(1,28)=14.62, p=.001, ηp2=.343) after 12‐weeks exercise training, accompanied by an increased relative peak power output (rPPO) (F(1,28)=16.93, p=.000, ηp2=.377) and an increased time to exhaustion (T2Ex) (F(1,28)=31.07, p=.000, ηp2=.526). Post hoc paired T‐tests revealed that the most pronounced effects on rPPO and T2Ex occurred in the moderate or high intensity groups There was a reduction in scores on the Beck Depression Inventory (BDI) (F(1,28)=6.50, p=.017, ηp2=.189) and the Perceived Stress Scale (PSS) (F(1,28)=4.09, p=.053, ηp2=.127) scores after 12 weeks of exercise.In sum, these results confirm that exercise training beneficially influences measures of stress and depression. Further work is required to understand the role of exercise‐induced alterations in tryptophan metabolism in mediating these effects.Support or Funding InformationAPC Microbiome Ireland is a research center funded by Science Foundation Ireland (SFI), through the Irish Government’s National Development Plan (grant no. 12/RC/2273). GC, JFC and TD are supported by the Irish Health Research Board (Grant number ILP‐POR‐2017‐013). CEG is supported by European Foundation for the Advancement in Neurosciences, Geneva, Switzerland.

Early treatment with ambrisentan of mildly elevated mean pulmonary arterial pressure associated with systemic sclerosis: a randomized, controlled, double-blind, parallel group study (EDITA study)

ObjectiveThe objective of this randomized, placebo-controlled, double-blind, parallel group, trial was to assess the effect of ambrisentan on mean pulmonary arterial pressure (mPAP) in patients with systemic sclerosis (SSc) and mildly elevated pulmonary hypertension (PH).MethodsThirty-eight SSc patients with mildly elevated mPAP at rest between 21 and 24 mmHg and/or > 30 mmHg during low-dose exercise were randomly assigned to treatment with either ambrisentan 5–10 mg/day or placebo. Right heart catheterization and further clinical parameters were assessed at baseline and after 6 months. The primary endpoint was the difference of mPAP change at rest between groups.ResultsAfter 6 months, the two groups did not differ in the primary endpoint (ambrisentan mPAP − 1 ± 6.4 mmHg vs. placebo − 0.73 ± 3.59 mmHg at rest, p = 0.884). However, three patients from the placebo group but none of the ambrisentan group progressed to SSc-associated pulmonary arterial hypertension. Furthermore, ambrisentan treatment showed significant improvements in the secondary endpoints cardiac index (CI) and pulmonary vascular resistance (PVR) at rest (CI 0.36 ± 0.66 l/min/m2 vs. − 0.31 ± 0.71 l/min/m2, p = 0.010; PVR − 0.70 ± 0.78 WU vs. 0.01 ± 0.71 WU, p = 0.012) and during exercise (CI 0.7 ± 0.81 l/min/m2 vs. − 0.45 ± 1.36 l/min/m2, p = 0.015; PVR − 0.84 ± 0.48 WU vs. − 0.0032 ± 0.34 WU, p < 0.0001).ConclusionThis is the first randomized, double-blind, placebo-controlled study testing the effect of ambrisentan in patients with mildly elevated mPAP and/or exercise PH. The primary endpoint change in mPAP did only tendentially improve in the ambrisentan group, but the significant improvement of other hemodynamic parameters points to a possible benefit of ambrisentan and will be helpful to design future trials.Trial registrationwww.ClinicalTrials.gov, unique identifier NCT: NCT02290613, registered 14th of November 2014.

The dosing of aerobic exercise therapy on experimentally-induced pain in healthy female participants

Knowledge of efficacious dosing respective to exercise type and pain condition is extremely limited in the literature. This study aimed to determine the impact of dose of moderate intensity treadmill walking on experimentally-induced pain in healthy human participants. Forty females were divided into 4 groups: control (no exercise), low dose exercise (3×/wk), moderate dose exercise (5×/wk) or high dose exercise (10×/wk). Over a 7-day period, subjects performed treadmill walking during assigned exercise days. Both qualitative and quantitative measures of pain were measured at baseline, during the trial, and 24 hrs post-final intervention session via sensitivity thresholds to painful thermal and painful pressure stimulation. Significant effects of treatment were found post-intervention for constant pressure pain intensity (p = 0.0016) and pain unpleasantness ratings (p = 0.0014). Post-hoc tests revealed significant differences between control and moderate and control and high dose groups for constant pressure pain intensity (p = 0.0015), (p = 0.0094), respectively and constant pressure pain unpleasantness (p = 0.0040), (p = 0.0040), respectively. Moderate and high dose groups had the greatest reductions in ratings of pain, suggesting that our lowest dose of exercise was not sufficient to reduce pain and that the moderate dose of exercise may be a sufficient starting dose for exercise-based adjuvant pain therapy.

Dose-dependent effect of aerobic exercise on inflammatory biomarkers in a randomized controlled trial of women at high risk of breast cancer.

Increased levels of inflammation are associated with many diseases, including cancer. Physical activity can lower breast cancer risk as well as levels of inflammation. The Women In Steady Exercise Research (WISER) Sister trial was a randomized controlled trial that investigated the effects of a dosed, moderate to vigorous, aerobic exercise intervention on levels of inflammation in premenopausal women who were at high risk of developing breast cancer. Participants were randomized to control (<75minutes per week; 41 patients), low-dose exercise (150minutes per week; 38 patients), or high-dose exercise (300minutes per week; 37 patients) groups. The 5-menstrual cycles-long, home-based treadmill exercise intervention gradually increased in minutes per week and intensity up to a maximum of 80% of the age-predicted maximum heart rate. Blood was collected at baseline and at follow-up and assayed for chemokine (C-C motif) ligand 2 (CCL2), interleukin 10 (IL-10), interleukin 12 (IL-12), and tumor necrosis factor α (TNF-α). A linear dose-response relationship was observed for the proinflammatory biomarkers CCL2 (%Δ of -5.44% in the control group, -0.03% in the low-dose exercise group, and 1.54% in the high-dose exercise group), IL-12 (%Δ of -21.5% in the control group, 38.2% in the low-dose exercise group, and 25.8% in the high-dose exercise group,) and TNF-α (%Δ of -4.69% in the control group, 9.51% in the low-dose exercise group, and 15.7% in the high-dose exercise group) but not for the anti-inflammatory biomarker IL-10 (%Δ of 5.05% in the control group, 6.05% in the low-dose exercise group, and 10.6% in the high-dose exercise group). For IL-12 and TNF-α, the percentage change was significantly higher in the low-dose (IL-12: P<.001; and TNF-α: P=.01) and high-dose (IL-12: P<.001; and TNF-α: P<.001) exercise groups compared with the control group. Moderate to vigorous aerobic exercise appeared to increase levels of proinflammatory biomarkers in a dose-dependent manner in a population of healthy women at high risk of developing breast cancer. The results of the current study suggest that for healthy premenopausal women, the mechanism of reduced breast cancer risk observed in physically active individuals may not be a result of reduced levels of inflammation.

A Systematic Review Comparing Dose Response of Exercise on Cardiovascular and All-Cause Mortality

It is well established that exercise improves cardiovascular and all-cause mortality, although an ideal dose of exercise is not known. The physical activity guidelines currently recommend 150 minutes per week of moderate-intensity exercise or 75 minutes of vigorous-intensity activity. Most individuals do not engage in adequate exercise, although a safe upper limit does not exist and a too much exercise hypothesis has recently emerged. This review of the literature analyzes studies that have evaluated exercise dose response on all-cause and cardiovascular mortality for the purpose of determining safe and effective exercise prescriptions. Searches were performed in PubMed and CINAHL between 2010 and 2018 to identify six studies that met inclusion criteria. Moderate-intensity exercise reduced all-cause mortality in five of six studies, whereas low-dose exercise most effectively improved all-cause mortality in three studies, and cardiovascular mortality in one study. Vigorous-intensity exercise or extreme doses demonstrated variable outcomes and remain controversial; two studies found vigorous-intensity exercise beneficial to improve health, two studies discouraged vigorous exercise, and two studies had less conclusive outcomes. It is not surprising that any amount of exercise improves health compared with none at all, with the greatest benefits observed when sedentary individuals began exercising. Low-dose exercise should be recommended to everyone with a goal of meeting the minimal requirements according to guidelines for decreased all-cause and cardiovascular mortality. Additional research to more thoroughly understand exercise dose response and motivate individuals to improve exercise engagement is currently warranted.

The influence of exercise training dose on fasting acylated ghrelin concentration in older women.

This study investigated if exercise dose affected acylated ghrelin response to exercise training, and how body weight or fat mass changes might affect the responses. Non-obese older women (n = 49) were randomly assigned to 4-month moderate-intensity aerobic exercise of one of two doses (8 or 14kcalkg-1 body weight weekly). Following exercise training, fasting acylated ghrelin concentrations changed differently between the two groups (p for group × time interaction = 0.050). It decreased in the moderate-dose (Cohen's d = 0.52, p = 0.019), but did not change in the low-dose exercise group. Adjustment for weight or fat changes did not affect these results. Therefore, exercise training dose can have specific effects on acylated ghrelin that are not dependent on weight or fat loss. However, whether the different acylated ghrelin changes are associated with differing degree of subsequent weight maintenance worth further investigation.

Impact of a daily exercise dose on knee joint cartilage – a systematic review and meta-analysis of randomised controlled trials in healthy animals

Purpose: To investigate the impact of a daily exercise dose on cartilage composition and thickness, by conducting a systematic review of randomized controlled trials (RCTs) involving healthy animals. Methods: A systematic literature search was performed within the databases MEDLINE, EMBASE, Web of Science and CINAHL for studies published prior to October 2015 with no restriction on publication year or language. We included randomized controlled trials of healthy animals assessing the impact of exercise on cartilage aggrecan content, collagen content and cartilage thickness. The following studies were excluded: non-RCTs, studies which did not investigate any of the outcomes of interest or knee joints, studies with genetically modified animals, comorbidities, non-English full text, and where treatment arms involved other interventions besides exercise. In dog studies, we used the British Kennel Club recommendations for exercise to categorize dogs into low, moderate or high dose of exercise. To classify the dose of exercise programs in rodents as low, moderate or high, we used the American Physiological Society guideline for the design of animal exercise protocols. To determine the dose of exercise in rabbits and sheep, we used the authors’ own classifications, since no existing exercise dosage classifications were found in the literature. A narrative synthesis of the effect of a daily exercise dose on knee cartilage aggrecan, collagen and thickness was performed. We classified the effect of exercise on knee cartilage aggrecan content, collagen content and thickness as: positive (‘+’) or negative (‘-’) when a significant difference (P<0.05) was reported in favor of the exercise (‘+’) or control (‘-’) group; and as similar (‘=’) when no significant difference between the intervention and control groups was reported. A subset of studies reporting sufficient data was combined in meta-analysis using a random-effects model. Meta-regression analyses were performed to investigate the impact of covariates. Results: The literature search resulted in 1,144 publications of which 112 individual studies were identified as potentially eligible and checked in full text. Ultimately, twenty-nine RCTs, involving 64 comparisons, were included. In the low dose exercise group, 21/25 comparisons reported decreased or no effect on cartilage aggrecan, collagen and thickness. In the moderate dose exercise group, all 12 comparisons reported either no or increased effect. In the high dose exercise group, 19/27 comparisons reported decreased effect. A meta-analysis of 14 studies investigating cartilage thickness showed no effect in the low dose exercise group (SMD -0.02; 95%CI -0.42 to 0.38; I2=0.0%), large but non-significant cartilage thickening in the moderate dose exercise group (SMD 0.95; 95%CI -0.33 to 2.23; I2=72.1%) and non-significant cartilage thinning in the high dose exercise group (SMD -0.19; 95%CI -0.49 to 0.12; I2=0.0%). Results were independent of analyzed covariates. Conclusions: Our results suggest that the relationship between daily exercise dose and cartilage composition and thickness is non-linear. While a low daily dose of exercise may have no effects and a high daily dose of exercise may have negative effects, a moderate daily dose of exercise may have positive effects on cartilage composition and thickness in healthy animals.

Impact of a daily exercise dose on knee joint cartilage - a systematic review and meta-analysis of randomized controlled trials in healthy animals.

To investigate the impact of a daily exercise dose on cartilage composition and thickness, by conducting a systematic review of randomized controlled trials (RCTs) involving healthy animals. A narrative synthesis of the effect of a daily exercise dose on knee cartilage aggrecan, collagen and thickness was performed. A subset of studies reporting sufficient data was combined in meta-analysis using a random-effects model. Meta-regression analyses were performed to investigate the impact of covariates. Twenty-nine RCTs, involving 64 comparisons, were included. In the low dose exercise group, 21/25 comparisons reported decreased or no effect on cartilage aggrecan, collagen and thickness. In the moderate dose exercise group, all 12 comparisons reported either no or increased effect. In the high dose exercise group, 19/27 comparisons reported decreased effect. A meta-analysis of 14 studies investigating cartilage thickness showed no effect in the low dose exercise group (SMD-0.02; 95% CI-0.42 to 0.38; I2=0.0%), large but non-significant cartilage thickening in the moderate dose exercise group (SMD 0.95; 95% CI-0.33 to 2.23; I2=72.1%) and non-significant cartilage thinning in the high dose exercise group (SMD-0.19; 95% CI-0.49 to 0.12; I2=0.0%). Results were independent of analyzed covariates. The overall quality of the studies was poor because of inadequate reporting of data and high risk of bias. Our results suggest that the relationship between daily exercise dose and cartilage composition, but not necessarily cartilage thickness, may be non-linear. While we found inconclusive evidence for a low daily dose of exercise, a high daily dose of exercise may have negative effects and a moderate daily dose of exercise may have positive effects on cartilage matrix composition in healthy animals.

Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer.

Dysregulation of adipokines, such as adiponectin and leptin, is associated with a variety of chronic diseases, including cancer. Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels. The WISER Sister Trial was a three-armed randomized controlled trial in premenopausal women (n = 137) with an elevated risk for breast cancer. A 5-menstrual-cycle-long dosed aerobic exercise intervention compared low-dose exercise (150 min/wk; n = 44) or high-dose exercise (300 min/wk; n = 48) with a control group asked to maintain usual activity levels (n = 45). Exercise intensity progressed to and was maintained at 70% to 80% of age predicted heart rate max. Body composition and adipokine levels were measured at baseline and follow-up. We observed significant linear trends for increased fitness capacity (Δ%: -2.0% control, 10.1% low dose, 13.1% high dose), decreased fat tissue-to-total tissue mass (Δ%: 0.7% control, -2.9% low dose, -3.7% high dose), increased body fat adjusted adiponectin (Δ%: -0.6% control, 0.6% low dose, 0.9% high dose), and decreased body fat adjusted leptin (Δ%: 0.7% control, -8.2% low dose, -10.2% high dose). In this randomized clinical trial of premenopausal women at risk for breast cancer, we demonstrate a dose-response effect of exercise on adiponectin and leptin and that dose response is dependent on changes in body fat. Improved adipokine levels, achieved by aerobic exercise training-induced decreases in body fat, may decrease breast cancer risk for high-risk premenopausal women. Cancer Epidemiol Biomarkers Prev; 25(8); 1195-200. ©2016 AACR.

Correlation Between Energy Balance And Body Composition Changes After 12 Weeks Of Exercise In Overweight Premenopausal Women

The national recommendation for the amount of physical activity (PA) needed to achieve and maintain a healthy body weight is 13-26 kcal/kg/day. The wide range in exercise dose is due partly to exercise studies that inadequately assessed energy balance components that either complement or compensate for experimental increases in exercise energy expenditure (ExEE). PURPOSE:To determine the energy balance correlates of changes in body composition resulting from a 12-week endurance training intervention. METHODS:Twenty-four previously sedentary, overweight women were randomly assigned to a high (26 kcal/kg/day) or low dose (13 kcal/kg/day) of endurance exercise. Twelve-week changes in weight, body composition estimates from air displacement plethysmography, waist circumference from anthropometry, 19-hour post-exercise resting energy expenditure (REE) from indirect calorimetry, energy intake (EI) from 7-day food diaries, and spontaneous physical activity (SPA) from 7-days of wearing piezoelectric pedometers were assessed. RESULTS:There were no mean differences between high- and low-dose exercise groups in the 12-week changes in average body weight (p=0.79), fat mass (p=0.44), fat-free mass (p=0.52), waist circumference (p=0.24), EI (p=0.94), or SPA (p=0.29). When groups were combined, there were significant 12-week changes in waist circumference (-1.0 ± 1.9 cm, p=0.02) and fat-free mass (+0.6 ± 1.2 kg, p=0.03). In addition, average ExEE was inversely correlated with changes in fat mass (r=-0.50, p=0.01) and waist circumference (r=-0.56, p<0.01), and positively correlated with post-exercise REE (r=0.42, p=0.04). Moreover, post-exercise REE was inversely correlated with changes in fat mass (r-0. 47, p=0.02) and waist circumference (r=-0.60, p<0.01), and positively correlated with changes in fat-free mass (r=0.47, p=0.02) and SPA (r=0.44, p=0.03). CONCLUSIONS:Exercise-related reductions in fat mass and waist circumference are correlated with higher ExEE and post-exercise REE. Furthermore, higher post-exercise REE is also correlated with greater exercise-related increases in fat-free mass and SPA. Our findings suggest that national physical activity recommendations aimed at improving body composition focus on effective ways to sustain increases in ExEE.

Dose-dependent changes in cognitive function with exercise augmentation for major depression: Results from the TREAD study

Cognitive dysfunction has been repeatedly observed in major depressive disorder (MDD), particularly in areas of attention, verbal and nonverbal learning and memory, and executive functioning. Exercise has been shown to improve cognitive outcomes in other populations, including age-associated cognitive decline, but has not to our knowledge been investigated as an augmentation strategy in depression. This study evaluated the effectiveness of exercise augmentation on cognitive performance in persons with MDD and residual symptoms that included cognitive complaints following initial treatment with a selective serotonin reuptake inhibitor (SSRI). Participants enrolled in the Treatment with Exercise Augmentation for Depression (TREAD) study were randomized to receive either a low or high dose exercise regimen. TREAD participants who provided informed consent for the current study completed Cambridge Neuropsychological Test Automated Battery measures assessing Attention, Visual Memory, Executive Function/Set-shifting and Working Memory, and Executive Function/Spatial Planning domains. Data were analyzed for 39 participants completing both baseline and Week 12 cognitive testing. Overall tests indicated a significant task×group×time interaction for the Executive Function/Set-shifting and Working Memory domain. Post-hoc tests indicated improvements in high dose exercisers׳ spatial working memory, but decreases in spatial working memory and set-shifting outcomes in low dose exercisers. Both groups improved on measures of psychomotor speed, attention, visual memory and spatial planning. This study suggests a dose–response effect of exercise in specific executive function and working memory tasks among depressed persons with a partial response to SSRI and cognitive complaints, with some cognitive functions improving regardless of exercise dose.