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Methods: We examined whether immune cell profiles differ between healthy women (n = 38) and breast cancer survivors (n = 27) within 2 years of treatment, and whether any group-differences were influenced by age, cytomegalovirus infection, cardiorespiratory fitness and body composition. Using flow cytometry, CD4+ and CD8+ T cell subsets, including naïve (NA), central memory (CM) and effector cells (EM and EMRA) were identified using CD27/CD45RA. Activation was measured by HLA-DR expression. Stem cell-like memory T cells (TSCMs) were identified using CD95/CD127. B cells, including plasmablasts, memory, immature and naïve cells were identified using CD19/CD27/CD38/CD10. Effector and regulatory Natural Killer cells were identified using CD56/CD16. Results: Compared to healthy women, CD4+ CM were +Δ21% higher among survivors (p = 0.028) and CD8+ NA were -Δ25% lower (p = 0.034). Across CD4+ and CD8+ subsets, the proportion of activated (HLA-DR+) cells was +Δ31% higher among survivors: CD4+ CM (+Δ25%), CD4+ EM (+Δ32%) and CD4+ EMRA (+Δ43%), total CD8+ (+Δ30%), CD8+ EM (+Δ30%) and CD8+ EMRA (+Δ25%) (p < 0.046). The counts of immature B cells, NK cells and CD16+ NK effector cells were higher among survivors (+Δ100%, +Δ108% and +Δ143% respectively, p < 0.04). Subsequent analyses examined whether statistically significant differences in participant characteristics, influenced immunological differences between groups. Compared to healthy women, survivors were older (56 ± 6 y vs. 45 ± 11 y), had lower cardiorespiratory fitness (VËO2max mL kg-1 min-1: 28.8 ± 5.0 vs. 36.2 ± 8.5), lower lean mass (42.3 ± 5.0 kg vs. 48.4 ± 15.8 kg), higher body fat (36.3% ± 5.3% vs. 32.7% ± 6.4%) and higher fat mass index (FMI kg/m2: 9.5 ± 2.2 vs. 8.1 ± 2.7) (all p < 0.033). Analysis of covariance revealed divergent moderating effects of age, CMV serostatus, cardiorespiratory fitness and body composition on the differences in immune cell profiles between groups, depending on the cell type examined. Moreover, across all participants, fat mass index was positively associated with the proportion of HLA-DR+ CD4+ EMRA and CD8+ EM/EMRA T cells (Pearson correlation: r > 0.305, p < 0.019). The association between fat mass index and HLA-DR+ CD8+ EMRA T cells withstood statistical adjustment for all variables, including age, CMV serostatus, lean mass and cardiorespiratory fitness, potentially implicating these cells as contributors to inflammatory/immune-dysfunction in overweight/obesity.
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Methods: This study examined the effects of exercise training for 8 weeks on blood immune cell characteristics among 20 breast cancer survivors (age 56 ± 6 years, Body Mass Index 25.4 ± 3.0â kg m2) within two years of treatment. Participants were randomly allocated to a partly-supervised or a remotely-supported exercise group (n = 10 each). The partly supervised group undertook 2 supervised (laboratory-based treadmill walking and cycling) and 1 unsupervised session per week (outdoor walking) progressing from 35 to 50â min and 55% to 70% VËO2max. The remotely-supported group received weekly exercise/outdoor walking targets (progressing from 105 to 150â min per week 55% to 70% VËO2max) via weekly telephone calls discussing data from a fitness tracker. Immune cell counts were assessed using flow cytometry: CD4+ and CD8+ T cells (Naïve, NA; Central memory, CM; and Effector cells, EM and EMRA; using CD27/CD45RA), Stem cell-like memory T cells (TSCMs; using CD95/CD127), B cells (plasmablasts, memory, immature and naïve cells using CD19/CD27/CD38/CD10) and Natural Killer cells (effector and regulatory cells, using CD56/CD16). T cell function was assessed by unstimulated HLA-DR expression or interferon gamma (IFN-γ) production with Enzyme-linked ImmunoSpot assays following stimulation with virus or tumour-associated antigens. Results: Total leukocyte counts, lymphocytes, monocytes and neutrophils did not change with training (p > 0.425). Most CD4+ and CD8+ T cell subtypes, including TSCMs, and B cell and NK cell subtypes did not change (p > 0.127). However, across groups combined, the CD4+ EMRA T cell count was lower after training (cells/µl: 18 ± 33 vs. 12 ± 22, p = 0.028) and these cells were less activated on a per cell basis (HLA-DR median fluorescence intensity: 463 ± 138 vs. 420 ± 77, p = 0.018). Furthermore, the partly-supervised group showed a significant decrease in the CD4+/CD8+ ratio (3.90 ± 2.98 vs. 2.54 ± 1.29, p = 0.006) and a significant increase of regulatory NK cells (cells/µl: 16 ± 8 vs. 21 ± 10, p = 0.011). T cell IFN-γ production did not change with exercise training (p > 0.515). Discussion: In summary, most immune cell characteristics are relatively stable with 8 weeks of exercise training among breast cancer survivors. The lower counts and activation of CD4+ EMRA T cells, might reflect an anti-immunosenescence effect of exercise.
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The idea that increasing physical activity directly adds to TEE in humans (additive model) has been challenged by the energy constrained hypothesis (constrained model). This model proposes that increased physical activity decreases other components of metabolism to constrain TEE. There is a logical evolutionary argument for trade-offs in metabolism, but, to date, evidence supporting constraint is subject to several limitations, including cross-sectional and correlational studies with potential methodological issues from extreme differences in body size/composition and lifestyle, potential statistical issues such as regression dilution and spurious correlations, and conclusions drawn from deductive inference rather than direct observation of compensation. Addressing these limitations in future studies, ideally, randomized controlled trials should improve the accuracy of models of human energy expenditure. The available evidence indicates that in many scenarios, the effect of increasing physical activity on TEE will be mostly additive although some energy appears to "go missing" and is currently unaccounted for. The degree of energy balance could moderate this effect even further.
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Metabolismo Energético , Exercício Físico , Humanos , Exercício Físico/fisiologia , Estudos Transversais , Metabolismo Energético/fisiologia , Estilo de Vida , Composição Corporal/fisiologiaRESUMO
PURPOSE: To determine the effects of dietary sugar or carbohydrate restriction on physical activity energy expenditure, energy intake, and physiological outcomes across 24 h. METHODS: In a randomized, open-label crossover design, twenty-five healthy men (n = 10) and women (n = 15) consumed three diets over a 24-h period: moderate carbohydrate and sugar content (MODSUG = 50% carbohydrate [20% sugars], 15% protein, 35% fat); low sugar content (LOWSUG = 50% carbohydrate [< 5% sugars], 15% protein, 35% fat); and low carbohydrate content (LOWCHO = 8% carbohydrate [< 5% sugars], 15% protein, 77% fat). Postprandial metabolic responses to a prescribed breakfast (20% EI) were monitored under laboratory conditions before an ad libitum test lunch, with subsequent diet and physical activity monitoring under free-living conditions until blood sample collection the following morning. RESULTS: The MODSUG, LOWSUG and LOWCHO diets resulted in similar mean [95%CI] rates of both physical activity energy expenditure (771 [624, 919] vs. 677 [565, 789] vs. 802 [614, 991] kcal·d-1; p = 0.29] and energy intake (2071 [1794, 2347] vs. 2195 [1918, 2473] vs. 2194 [1890, 2498] kcal·d-1; P = 0.34), respectively. The LOWCHO condition elicited the lowest glycaemic and insulinaemic responses to breakfast (P < 0.01) but the highest 24-h increase in LDL-cholesterol concentrations (P < 0.001), with no differences between the MODSUG and LOWSUG treatments. Leptin concentrations decreased over 24-h of consuming LOWCHO relative to LOWSUG (p < 0.01). CONCLUSION: When energy density is controlled for, restricting either sugar or total dietary carbohydrate does not modulate physical activity level or energy intake over a 24-h period (~ 19-h free-living) despite substantial metabolic changes. CLINICAL TRIALS REGISTRATION ID: NCT03509610, https://clinicaltrials.gov/show/NCT03509610.
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Ingestão de Energia , Açúcares , Masculino , Humanos , Feminino , Estudos Cross-Over , Dieta , Carboidratos da Dieta , Metabolismo Energético , Exercício FísicoRESUMO
INTRODUCTION: Continuous exercise can increase postprandial gut hormone such as glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) responses, but it is unknown whether interrupting prolonged sitting with intermittent walking elicits this effect. METHOD: Ten participants with central overweight/obesity (7 men and 3 postmenopausal women, 51 ± 5 yr; mean ± SD) completed a randomized crossover study in which they consumed breakfast and lunch in the laboratory while either sitting continuously for the entire 5.5-h period (SIT) or the prolonged sitting interrupted every 20 min by walking briskly (6.4 km·h-1) for 2 min (BREAKS). Blood samples were collected at regular intervals to examine postprandial plasma GLP-1, PYY, and glucose-dependent insulinotropic polypeptide concentrations. Adipose tissue samples were collected at baseline and at the end of the trials to examine changes in net dipeptidyl peptidase 4 secretion from primary explants. RESULTS: Mean (95% confidence interval) postprandial GLP-1 and PYY incremental area under curve values were elevated by 26% and 31% in the BREAKS trial versus SIT (8.4 [0.7, 16.1] vs 6.7 [-0.8, 14.2], P = 0.001, and 26.9 [8.1, 45.6] vs 20.4 [5.1, 35.8] nmol·330 min·L-1, P = 0.024, respectively) but without any such effect on glucose-dependent insulinotropic polypeptide (P = 0.076) or net adipose tissue dipeptidyl peptidase 4 secretion (P > 0.05). CONCLUSIONS: Interrupting prolonged sitting with regular short bouts of brisk walking increases postprandial GLP-1 and PYY concentrations in healthy middle-age men and women with central adiposity.
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Glicemia , Dipeptidil Peptidase 4 , Estudos Cross-Over , Feminino , Peptídeo 1 Semelhante ao Glucagon , Humanos , Insulina , Masculino , Pessoa de Meia-Idade , Obesidade , Obesidade Abdominal , Peptídeo YY , Período Pós-Prandial , Caminhada/fisiologiaRESUMO
PURPOSE: To examine the influence of post-exercise protein feeding upon the adaptive response to endurance exercise training. METHODS: In a randomised parallel group design, 25 healthy men and women completed 6 weeks of endurance exercise training by running on a treadmill for 30-60 min at 70-75% maximal oxygen uptake (VO2max) 4 times/week. Participants ingested 1.6 g per kilogram of body mass (g kg BM-1) of carbohydrate (CHO) or an isocaloric carbohydrate-protein solution (CHO-P; 0.8 g carbohydrate kg BM-1 + 0.8 g protein kg BM-1) immediately and 1 h post-exercise. Expired gas, blood and muscle biopsy samples were taken at baseline and follow-up. RESULTS: Exercise training improved VO2max in both groups (p ≤ 0.001), but this increment was not different between groups either in absolute terms or relative to body mass (0.2 ± 0.2 L min-1 and 3.0 ± 2 mL kg-1 min-1, respectively). No change occurred in plasma albumin concentration from baseline to follow-up with CHO-P (4.18 ± 0.18 to 4.23 ± 0.17 g dL-1) or CHO (4.17 ± 0.17 to 4.12 ± 0.22 g dL-1; interaction: p > 0.05). Mechanistic target of rapamycin (mTOR) gene expression was up-regulated in CHO-P (+ 46%; p = 0.025) relative to CHO (+ 4%) following exercise training. CONCLUSION: Post-exercise protein supplementation up-regulated the expression of mTOR in skeletal muscle over 6 weeks of endurance exercise training. However, the magnitude of improvement in VO2max was similar between groups.
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Adaptação Fisiológica/efeitos dos fármacos , Carboidratos da Dieta/farmacologia , Proteínas Alimentares/farmacologia , Treino Aeróbico/métodos , Adolescente , Adulto , Carboidratos da Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Feminino , Humanos , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Consumo de Oxigênio , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: Technological progress has enabled the provision of personalised feedback across multiple dimensions of physical activity that are important for health. Whether this multidimensional approach supports physical activity behaviour change has not yet been examined. Our objective was to examine the effectiveness of a novel digital system and app that provided multidimensional physical activity feedback combined with health trainer support in primary care patients identified as at risk of chronic disease. METHODS: MIPACT was a parallel-group, randomised controlled trial that recruited patients at medium (≥10 and < 20%) or high (≥20%) risk of cardiovascular disease and/or type II diabetes from six primary care practices in the United Kingdom. Intervention group participants (n = 120) received personal multidimensional physical activity feedback using a customised digital system and web-app for 3 months plus five health trainer-led sessions. All participants received standardised information regarding physical activity. Control group participants (n = 84) received no further intervention. The primary outcome was device-based assessment of physical activity at 12 months. RESULTS: Mean intervention effects were: moderate-vigorous physical activity: -1.1 (95% CI, - 17.9 to 15.7) min/day; moderate-vigorous physical activity in ≥10-min bouts: 0.2 (- 14.2 to 14.6) min/day; Physical Activity Level (PAL): 0.00 (- 0.036 to 0.054); vigorous physical activity: 1.8 (- 0.8 to 4.2) min/day; and sedentary time: 10 (- 19.3 to 39.3) min/day. For all of these outcomes, the results showed that the groups were practically equivalent and statistically ruled out meaningful positive or negative effects (>minimum clinically important difference, MCID). However, there was profound physical activity multidimensionality, and only a small proportion (5%) of patients had consistently low physical activity across all dimensions. CONCLUSION: In patients at risk of cardiovascular disease and/or type II diabetes, MIPACT did not increase mean physical activity. Using a sophisticated multidimensional digital approach revealed enormous heterogeneity in baseline physical activity in primary care patients, and practitioners may need to screen for low physical activity across dimensions rather than rely on disease-risk algorithms that are heavily influenced by age. TRIAL REGISTRATION: This trial is registered with the ISRCTN registry ( ISRCTN18008011 ; registration date 31 July 2013).
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Biorretroalimentação Psicológica , Tecnologia Biomédica/instrumentação , Exercício Físico , Doenças Cardiovasculares/prevenção & controle , Doença Crônica/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Metabolismo Energético , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Aplicativos Móveis , Monitorização Ambulatorial/métodos , Motivação , Reino Unido/epidemiologia , Dispositivos Eletrônicos VestíveisRESUMO
Breast cancer is the most common malignancy among women worldwide. Over the last four decades, diagnostic and therapeutic procedures have improved substantially, giving patients with localized disease a better chance of cure, and those with more advanced cancer, longer periods of disease control and survival. However, understanding and managing heterogeneity in the clinical response exhibited by patients remains a challenge. For some treatments, biomarkers are available to inform therapeutic options, assess pathological response and predict clinical outcomes. Nevertheless, some measurements are not employed universally and lack sensitivity and specificity, which might be influenced by tissue-specific alterations associated with aging and lifestyle. The first part of this article summarizes available and emerging biomarkers for clinical use, such as measurements that can be made in tumor biopsies or blood samples, including so-called liquid biopsies. The second part of this article outlines underappreciated factors that could influence the interpretation of these clinical measurements and affect treatment outcomes. For example, it has been shown that both adiposity and physical activity can modify the characteristics of tumors and surrounding tissues. In addition, evidence shows that inflammaging and immunosenescence interact with treatment and clinical outcomes and could be considered prognostic and predictive factors independently. In summary, changes to blood and tissues that reflect aging and patient characteristics, including lifestyle, are not commonly considered clinically or in research, either for practical reasons or because the supporting evidence base is developing. Thus, an aim of this article is to encourage an integrative phenomic approach in oncology research and clinical management.
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Envelhecimento , Biomarcadores Tumorais , Neoplasias da Mama , Estilo de Vida , Feminino , Perfilação da Expressão Gênica , Humanos , Fenômica , Fatores de Risco , TranscriptomaRESUMO
PURPOSE: To determine whether physical performance adaptation is impaired in smokers during early stages of military training and to examine some of the putative mechanistic candidates that could explain any impairment. METHODS: We examined measures of oxidative stress (malondialdehyde [MDA], lipid hydroperoxides), inflammation (C-reactive protein, interleukin-6), antioxidants (vitamins A and E and carotenes) and hormones (cortisol, testosterone, insulin-like growth factor-1) in 65 male British Army Infantry recruits (mean ± SD age, 21 ± 3 yr; mass, 75.5 ± 8.4 kg; height, 1.78 ± 0.07 m) at week 1, week 5, and week 10 of basic training. Physical performance (static lift, grip strength, jump height, 2.4 km run time, and 2-min press up and sit up scores) was examined and lower-leg muscle and adipose cross-sectional area and density measured by peripheral Quantitative Computed Tomography. RESULTS: Basic military training, irrespective of smoking status, elicited improvement in all physical performance parameters (main time effect; P < 0.05) except grip strength and jump height, and resulted in increased muscle area and decreased fat area in the lower leg (P < 0.05). MDA was higher in smokers at baseline, and both MDA and C-reactive protein were greater in smokers during training (main group effect; P < 0.05) than nonsmokers. Absolute performance measures, muscle characteristics of the lower leg and other oxidative stress, antioxidant, endocrine, and inflammatory markers were similar in the two groups. CONCLUSIONS: Oxidative stress and inflammation were elevated in habitual smokers during basic military training, but there was no clear evidence that this was detrimental to physical adaptation in this population over the timescale studied.
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Adaptação Fisiológica , Militares , Músculo Esquelético/fisiologia , Condicionamento Físico Humano/fisiologia , Aptidão Física/fisiologia , Fumar/fisiopatologia , Antioxidantes/metabolismo , Biomarcadores/sangue , Distribuição da Gordura Corporal , Humanos , Hidrocortisona/sangue , Inflamação/fisiopatologia , Fator de Crescimento Insulin-Like I/metabolismo , Perna (Membro)/fisiologia , Masculino , Força Muscular , Músculo Esquelético/diagnóstico por imagem , Estresse Oxidativo , Fumar/sangue , Adulto JovemRESUMO
PURPOSE: To examine whether calcium type and co-ingestion with protein alter gut hormone availability. METHODS: Healthy adults aged 26 ± 7 years (mean ± SD) completed three randomized, double-blind, crossover studies. In all studies, arterialized blood was sampled postprandially over 120 min to determine GLP-1, GIP and PYY responses, alongside appetite ratings, energy expenditure and blood pressure. In study 1 (n = 20), three treatments matched for total calcium content (1058 mg) were compared: calcium citrate (CALCITR); milk minerals rich in calcium (MILK MINERALS); and milk minerals rich in calcium plus co-ingestion of 50 g whey protein hydrolysate (MILK MINERALS + PROTEIN). In study 2 (n = 6), 50 g whey protein hydrolysate (PROTEIN) was compared to MILK MINERALS + PROTEIN. In study 3 (n = 6), MILK MINERALS was compared to the vehicle of ingestion (water plus sucralose; CONTROL). RESULTS: MILK MINERALS + PROTEIN increased GLP-1 incremental area under the curve (iAUC) by ~ ninefold (43.7 ± 11.1 pmol L-1 120 min; p < 0.001) versus both CALCITR and MILK MINERALS, with no difference detected between CALCITR (6.6 ± 3.7 pmol L-1 120 min) and MILK MINERALS (5.3 ± 3.5 pmol L-1 120 min; p > 0.999). MILK MINERALS + PROTEIN produced a GLP-1 iAUC ~ 25% greater than PROTEIN (p = 0.024; mean difference: 9.1 ± 6.9 pmol L-1 120 min), whereas the difference between MILK MINERALS versus CONTROL was small and non-significant (p = 0.098; mean difference: 4.2 ± 5.1 pmol L-1 120 min). CONCLUSIONS: When ingested alone, milk minerals rich in calcium do not increase GLP-1 secretion compared to calcium citrate. Co-ingesting high-dose whey protein hydrolysate with milk minerals rich in calcium increases postprandial GLP-1 concentrations to some of the highest physiological levels ever reported. Registered at ClinicalTrials.gov: NCT03232034, NCT03370484, NCT03370497.
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Cálcio/farmacologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Leite/química , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacologia , Proteínas do Soro do Leite/química , Adulto , Animais , Estudos Cross-Over , Método Duplo-Cego , Ingestão de Alimentos , Humanos , Minerais/farmacologia , Período Pós-Prandial , Adulto JovemRESUMO
BACKGROUND: This study sought to test the effectiveness of a 12-week, novel online intervention (Evolife) aiming to increase physical activity level (PAL) and reduce energy intake (EI) among overweight/obese adults. The intervention used an evolutionary mismatch message to frame health information in an engaging way, incorporating evidence-based behaviour change techniques to promote autonomous motivation, self-efficacy and self-regulatory skills. METHOD: Men and women aged 35-74 years with a BMI of 25-40 kg/m2 were eligible. Participants were randomised to receive either the intervention (comprising a face-to-face introductory session, 12 weeks' access to the Evolife website and a pedometer) or a control condition (face-to-face introductory session and NHS online health resources). PAL was measured objectively and EI was self-reported using 3-day weighed food records. Secondary measures included BMI, waist circumference and blood pressure. RESULTS: Sixty people met inclusion criteria; 59 (30 intervention) completed the trial (mean age = 50; 56% male). Differences between groups' change scores for PAL and EI were of small effect size but did not reach significance (d = 0.32 and d = - 0.49, respectively). Improvements were found in both groups for PAL (int: d = 0.33; control: d = 0.04), EI (int: d = - 0.81; control: d = - 0.16), waist circumference (int: d = - 0.30; control: d = - 0.17) and systolic blood pressure (int: d = - 0.67; control: d = - 0.28). CONCLUSION: The intervention did not lead to significantly greater improvement in PAL or reduction in EI than a minimal intervention control, although the changes in the intervention group were of meaningful effect size and comparable with positive outcomes in larger intervention trials. TRIAL REGISTRATION: This trail was registered on www.clinicaltrials.gov on 16 January 2017 (appeared online 26 January 2017), reference NCT03032731.
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Terapia Comportamental/métodos , Dieta Redutora/psicologia , Exercício Físico/psicologia , Intervenção Baseada em Internet , Obesidade/terapia , Sobrepeso/terapia , Adulto , Idoso , Pressão Sanguínea , Ingestão de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Obesidade/psicologia , Sobrepeso/psicologia , Autoeficácia , Autorrelato , Resultado do TratamentoRESUMO
BACKGROUND: Short-term overfeeding combined with reduced physical activity impairs metabolic function and alters the expression of key genes within adipose tissue. We have shown that daily vigorous-intensity running can prevent these changes independent of any net effect on energy imbalance. However, which type, intensity and/or duration of exercise best achieves these benefits remains to be ascertained. METHODS/DESIGN: Forty-eight healthy young men will be recruited and randomly allocated to one of four experimental conditions for 1 week: (1) to ingest 50% more energy than normal by over-consuming their habitual diet whilst simultaneously restricting their physical activity below 4000 steps day-1 (i.e. energy surplus; SUR group); (2) the same regimen but with a daily 45-min bout of vigorous-intensity arm crank ergometry at 70% of maximum oxygen uptake (SUR + ARM group); (3) the same regimen but with a daily 45-min bout of moderate-intensity treadmill walking at 50% of maximum oxygen uptake (SUR + MOD group); (4) the same regimen but with the addition of intermittent short bouts of walking during waking hours (SUR + BREAKS group). Critically, all exercise groups will receive additional dietary energy intake to account for the energy expended by exercise, thus maintaining a matched energy surplus. At baseline and follow-up, fasted blood samples, abdominal subcutaneous adipose tissue and skeletal muscle biopsies will be obtained and oral glucose tolerance tests conducted. DISCUSSION: This study will establish the impact of different forms of daily exercise on metabolic function at the whole-body level as well as within adipose tissue and skeletal muscle in the context of a standardised energy surplus. TRIAL REGISTRATION: ISRCTN, ISRCTN18311163 . Registered on 24 June 2015.
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Metabolismo Energético , Terapia por Exercício/métodos , Exercício Físico , Estado Nutricional , Hipernutrição/terapia , Comportamento Sedentário , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Adolescente , Adulto , Fatores Etários , Ingestão de Energia , Inglaterra , Voluntários Saudáveis , Humanos , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Hipernutrição/metabolismo , Hipernutrição/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Performing regular exercise is known to manifest a number of health benefits that mainly relate to cardiovascular and muscular adaptations to allow for greater oxygen extraction and utilization. There is increasing evidence that nutrient intake can affect the adaptive response to a single exercise bout, and that protein feeding is important to facilitate this process. Thus, the exercise-nutrient interaction may potentially lead to a greater response to training. The role of post-exercise protein ingestion in enhancing the effects of running-based endurance exercise training relative to energy-matched carbohydrate intervention remains to be established. Additionally, the influence of immediate versus overnight protein ingestion in mediating these training effects is currently unknown. The current protocol aims to establish whether post-exercise nutrient intake and timing would influence the magnitude of improvements during a prescribed endurance training program. METHODS/DESIGN: The project involves two phases with each involving two treatment arms applied in a randomized investigator-participant double-blind parallel group design. For each treatment, participants will be required to undergo six weeks of running-based endurance training. Immediately post-exercise, participants will be prescribed solutions providing 0.4 grams per kilogram of body mass (g · kg(-1)) of whey protein hydrolysate plus 0.4 g · kg(-1) sucrose, relative to an isocaloric sucrose control (0.8 g · kg(-1); Phase I). In Phase II, identical protein supplements will be provided (0.4 + 0.4 g · kg(-1) · h(-1) of whey protein hydrolysate and sucrose, respectively), with the timing of ingestion manipulated to compare immediate versus overnight recovery feedings. Anthropometric, expired gas, venous blood and muscle biopsy samples will be obtained at baseline and following the six-week training period. DISCUSSION: By investigating the role of nutrition in enhancing the effects of endurance exercise training, we will provide novel insight regarding nutrient-exercise interactions and the potential to help and develop effective methods to maximize health or performance outcomes in response to regular exercise. TRIAL REGISTRATION: Current Controlled Trials registration number: ISRCTN27312291 (date assigned: 4 December 2013). The first participant was randomized on 11 December 2013.
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Dieta , Sacarose Alimentar/administração & dosagem , Exercício Físico , Proteínas do Leite/administração & dosagem , Contração Muscular , Músculo Esquelético/fisiologia , Resistência Física , Projetos de Pesquisa , Adaptação Fisiológica , Adolescente , Adulto , Biomarcadores/sangue , Biópsia , Testes Respiratórios , Protocolos Clínicos , Sacarose Alimentar/metabolismo , Método Duplo-Cego , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Leite/metabolismo , Músculo Esquelético/metabolismo , Estado Nutricional , Recuperação de Função Fisiológica , Respiração , Corrida , Fatores de Tempo , Resultado do Tratamento , Proteínas do Soro do Leite , Adulto JovemRESUMO
BACKGROUND: Popular beliefs that breakfast is the most important meal of the day are grounded in cross-sectional observations that link breakfast to health, the causal nature of which remains to be explored under real-life conditions. OBJECTIVE: The aim was to conduct a randomized controlled trial examining causal links between breakfast habits and all components of energy balance in free-living humans. DESIGN: The Bath Breakfast Project is a randomized controlled trial with repeated-measures at baseline and follow-up in a cohort in southwest England aged 21-60 y with dual-energy X-ray absorptiometry-derived fat mass indexes ≤11 kg/m² in women (n = 21) and ≤7.5 kg/m² in men (n = 12). Components of energy balance (resting metabolic rate, physical activity thermogenesis, energy intake) and 24-h glycemic responses were measured under free-living conditions with random allocation to daily breakfast (≥700 kcal before 1100) or extended fasting (0 kcal until 1200) for 6 wk, with baseline and follow-up measures of health markers (eg, hematology/biopsies). RESULTS: Contrary to popular belief, there was no metabolic adaptation to breakfast (eg, resting metabolic rate stable within 11 kcal/d), with limited subsequent suppression of appetite (energy intake remained 539 kcal/d greater than after fasting; 95% CI: 157, 920 kcal/d). Rather, physical activity thermogenesis was markedly higher with breakfast than with fasting (442 kcal/d; 95% CI: 34, 851 kcal/d). Body mass and adiposity did not differ between treatments at baseline or follow-up and neither did adipose tissue glucose uptake or systemic indexes of cardiovascular health. Continuously measured glycemia was more variable during the afternoon and evening with fasting than with breakfast by the final week of the intervention (CV: 3.9%; 95% CI: 0.1%, 7.8%). CONCLUSIONS: Daily breakfast is causally linked to higher physical activity thermogenesis in lean adults, with greater overall dietary energy intake but no change in resting metabolism. Cardiovascular health indexes were unaffected by either of the treatments, but breakfast maintained more stable afternoon and evening glycemia than did fasting.
Assuntos
Regulação do Apetite , Desjejum , Comportamento Alimentar , Promoção da Saúde , Atividade Motora , Termogênese , Regulação para Cima , Adulto , Biomarcadores/sangue , Glicemia/análise , Estudos de Coortes , Ingestão de Energia , Metabolismo Energético , Feminino , Seguimentos , Humanos , Hiperglicemia/sangue , Hiperglicemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Inflammation plays a major role in diabetes-associated cardiovascular disease (CVD). There is uncertainty whether diet and physical activity interventions can be successfully integrated into healthcare settings and reduce markers of inflammation and risk of CVD in patients with type 2 diabetes (T2D). METHODS AND RESULTS: Systemic markers of inflammation were determined in a 12-month, real-world, multicenter, randomized, controlled trial that investigated the effect of diet, diet plus physical activity, and usual care in 593 individuals with newly diagnosed T2D. During the first 6 months, serum C-reactive protein (CRP) improved by -21 (-36 to -1.4)% and -22 (-38 to -3.1)% in diet and diet plus physical activity arms versus usual care. There were also improvements in adiponectin and soluble intercellular adhesion molecule-1 (sICAM-1). Though medication-adjusted CRP was improved between 6 and 12 months for usual care, both interventions were more successful in reducing the relative risk of a high-risk CRP level of >3 mg/L (risk ratios of 0.72 [0.55 to 0.95] for diet versus usual care and 0.67 [0.50 to 0.90] for diet plus activity versus usual care). Furthermore, sICAM-1 (a marker of vascular risk), remained substantially lower than usual care in both intervention arms at 12 months. CONCLUSIONS: Motivational, unsupervised diet and/or diet plus physical activity interventions given soon after diagnosis in real-world healthcare settings improve markers of inflammation and cardiovascular risk in patients with T2D, even after accounting for the effect of adjustments to medication to try and control blood pressure, glycated hemoglobin, and lipids. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com/. Unique identifier: ISRCTN92162869.
Assuntos
Diabetes Mellitus Tipo 2/terapia , Inflamação/sangue , Adiponectina/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Terapia Combinada , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/dietoterapia , Terapia por Exercício , Humanos , Inflamação/prevenção & controle , Molécula 1 de Adesão Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Atividade MotoraRESUMO
BACKGROUND: Muscle glycogen has been well established as the primary metabolic energy substrate during physical exercise of moderate- to high-intensity and has accordingly been implicated as a limiting factor when such activity is sustained for a prolonged duration. However, the role of this substrate during repeated exercise after limited recovery is less clear, with ongoing debate regarding how recovery processes can best be supported via nutritional intervention. The aim of this project is to examine the causes of fatigue during repeated exercise bouts via manipulation of glycogen availability through nutritional intervention, thus simultaneously informing aspects of the optimal feeding strategy for recovery from prolonged exercise. METHODS/DESIGN: The project involves two phases with each involving two treatment arms administered in a repeated measures design. For each treatment, participants will be required to exercise to the point of volitional exhaustion on a motorised treadmill at 70% of previously determined maximal oxygen uptake, before a four hour recovery period in which participants will be prescribed solutions providing 1.2 grams of sucrose per kilogram of body mass per hour of recovery (g.kg-1.h-1) relative to either a lower rate of sucrose ingestion (that is, 0.3 g.kg-1. h-1; Phase I) or a moderate dose (that is, 0.8 g.kg-1.h-1) rendered isocaloric via the addition of 0.4 g.kg-1.h-1 whey protein hydrolysate (Phase II); the latter administered in a double blind manner as part of a randomised and counterbalanced design. Muscle biopsies will be sampled at the beginning and end of recovery for determination of muscle glycogen resynthesis rates, with further biopsies taken following a second bout of exhaustive exercise to determine differences in substrate availability relative to the initial sample taken following the first exercise bout. DISCUSSION: Phase I will inform whether a dose-response relationship exists between carbohydrate ingestion rate and muscle glycogen availability and/or the subsequent capacity for physical exercise. Phase II will determine whether such effects are dependent on glycogen availability per se or energy intake, potentially via protein mediated mechanisms. TRIAL REGISTRATION: ISRCTN87937960.
Assuntos
Proteínas Alimentares/administração & dosagem , Sacarose Alimentar/administração & dosagem , Metabolismo Energético , Exercício Físico , Contração Muscular , Fadiga Muscular , Músculo Esquelético/metabolismo , Projetos de Pesquisa , Adolescente , Adulto , Biópsia , Protocolos Clínicos , Estudos Cross-Over , Método Duplo-Cego , Inglaterra , Teste de Esforço , Feminino , Glicogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Estado Nutricional , Consumo de Oxigênio , Recuperação de Função Fisiológica , Corrida , Fatores de Tempo , Adulto JovemRESUMO
Physical activity can affect many aspects of metabolism but it is unclear to what extent this relies on manipulation of energy balance. Twenty-six active men age 25 ± 7 years (mean ± SD) were randomly assigned either to consume 50% more energy than normal by over-consuming their habitual diet for 7 days whilst simultaneously restricting their physical activity below 4000 steps day(-1) to induce an energy surplus (SUR group; n = 14) or to the same regimen but with 45 min of daily treadmill running at 70% of maximum oxygen uptake (SUR+EX group; n = 12). Critically, the SUR+EX group received additional dietary energy intake to account for the energy expended by exercise, thus maintaining a matched energy surplus. At baseline and follow-up, fasted blood samples and abdominal subcutaneous adipose tissue biopsies were obtained and oral glucose tolerance tests conducted. Insulinaemic responses to a standard glucose load increased 2-fold from baseline to follow-up in the SUR group (17 ± 16 nmol (120 min) l(-1); P = 0.002) whereas there was no change in the SUR+EX group (1 ± 6 nmol (120 min) l(-1)). Seven of 17 genes within adipose tissue were differentially expressed in the SUR group; expression of SREBP-1c, FAS and GLUT4 was significantly up-regulated and expression of PDK4, IRS2, HSL and visfatin was significantly down-regulated (P ≤ 0.05). The pAMPK/AMPK protein ratio in adipose tissue was significantly down-regulated in the SUR group (P = 0.005). Vigorous-intensity exercise counteracted most of the effects of short-term overfeeding and under-activity at the whole-body level and in adipose tissue, even in the face of a standardised energy surplus.
Assuntos
Ingestão de Energia , Metabolismo Energético , Exercício Físico , Tecido Adiposo/metabolismo , Adolescente , Adulto , Regulação para Baixo , Jejum/metabolismo , Intolerância à Glucose , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Homeostase , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Consumo de Oxigênio , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil , Esterol Esterase/genética , Esterol Esterase/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Receptor fas/genética , Receptor fas/metabolismoRESUMO
Measurement of steroid hormones in saliva is increasingly common in elite sport settings. However, this environment may enforce handling and storage practices that introduce error in measurement of hormone concentrations. We assessed the influence of storage temperature and duration on reproducibility of salivary steroid levels. Nine healthy adults provided morning and afternoon saliva samples on two separate occasions. Each sample was divided into identical saliva aliquots which were stored long-term (i.e. 28 and 84 days) at - 80°C or - 20°C (testing day 1), and short-term (i.e. 1, 3, 7 and 14 days) at 4°C or 20°C (testing day 2). Samples were analyzed for cortisol, testosterone and estradiol using ELISA. In non-freezer conditions, there was a decrease from baseline to 7 days in testosterone (- 26 ± 15%) and estradiol (- 58 ± 17%) but not cortisol concentrations (p < 0.001). This decrease was larger in samples stored at room temperature than in the refrigerator (p ≤ 0.01). There were small but significant changes in measured concentrations of all hormones after 28 and/or 84 days of storage in freezer conditions (p ≤ 0.01), but these were generally within 12% of baseline concentrations, and may be partly explained by inter-assay variability. Whole saliva samples to be analyzed for cortisol, testosterone and estradiol should be frozen at - 20°C or below within 24 h of collection, and analyzed within 28 days. Storage of samples for measurement of testosterone and estradiol at temperatures above - 20°C can introduce large error variance to measured concentrations.
Assuntos
Estradiol/metabolismo , Hidrocortisona/metabolismo , Saliva/química , Manejo de Espécimes/métodos , Testosterona/metabolismo , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Congelamento , Hormônios , Humanos , Masculino , Reprodutibilidade dos Testes , Temperatura , Fatores de TempoRESUMO
OBJECTIVES: An experimental reduction in physical activity is a useful tool for exploring the health benefits of physical activity. This study investigated whether similarly-active overweight men show a more pronounced response to reduced physical activity than their lean counterparts because of their atherogenic phenotype (i.e., greater abdominal adiposity). METHODS: From 115 active men aged 45-64years, we recruited nine active lean (waist circumference <84cm) and nine active central overweight men (waist circumference >94cm). Fasting blood samples and responses to an oral glucose tolerance test (OGTT) were measured at baseline and following one week of reduced physical activity to simulate sedentary levels (removal of structured exercise and reduced habitual physical activity). RESULTS: Glucose and insulin areas under the curve (AUC), CRP, ALT, TAG were all higher in the overweight group and remained so throughout (P<0.05). Insulin and glucose AUC responses to an OGTT, as well as fasting triglyceride (TAG) concentrations, increased in both groups as a result of the intervention (P<0.05). There was no change in interleukin-6, C-reactive protein (CRP), Tumour Necrosis Factor-α, soluble intracellular adhesion molecule 1, or alanine transaminase (ALT). CONCLUSION: One-week of reduced activity similarly-impaired glucose control and increased fasting TAG in both lean and overweight men. Importantly, in spite of very similar (high) levels of habitual physical activity, central overweight men displayed a poorer profile for various inflammatory and metabolic outcomes (CRP, ALT, TAG, glucose AUC and insulin AUC).
Assuntos
Exercício Físico/fisiologia , Sobrepeso/fisiopatologia , Alanina Transaminase/sangue , Área Sob a Curva , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Molécula 1 de Adesão Intercelular/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Sobrepeso/sangue , Sobrepeso/metabolismo , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue , Circunferência da Cintura/fisiologiaRESUMO
There is no consensus regarding the effects of mixed antioxidant vitamin C and/or vitamin E supplementation on oxidative stress responses to exercise and restoration of muscle function. Thirty-eight men were randomly assigned to receive either placebo group (n = 18) or mixed antioxidant (primarily vitamin C & E) supplements (n = 20) in a double-blind manner. After 6 weeks, participants performed 90 min of intermittent shuttle-running. Peak isometric torque of the knee flexors/extensors and range of motion at this joint were determined before and after exercise, with recovery of these variables tracked for up to 168 h post-exercise. Antioxidant supplementation elevated pre-exercise plasma vitamin C (93 ± 8 µmol l(-1)) and vitamin E (11 ± 3 µmol l(-1)) concentrations relative to baseline (P < 0.001) and the placebo group (P ≤ 0.02). Exercise reduced peak isometric torque (i.e. 9-19% relative to baseline; P ≤ 0.001), which persisted for the first 48 h of recovery with no difference between treatment groups. In contrast, changes in the urine concentration of F(2)-isoprostanes responded differently to each treatment (P = 0.04), with a tendency for higher concentrations after 48 h of recovery in the supplemented group (6.2 ± 6.1 vs. 3.7 ± 3.4 ng ml(-1)). Vitamin C & E supplementation also affected serum cortisol concentrations, with an attenuated increase from baseline to the peak values reached after 1 h of recovery compared with the placebo group (P = 0.02) and serum interleukin-6 concentrations were higher after 1 h of recovery in the antioxidant group (11.3 ± 3.4 pg ml(-1)) than the placebo group (6.2 ± 3.8 pg ml(-1); P = 0.05). Combined vitamin C & E supplementation neither reduced markers of oxidative stress or inflammation nor did it facilitate recovery of muscle function after exercise-induced muscle damage.