James A. Betts

Time course of changes in inflammatory markers during a 6-mo exercise intervention in sedentary middle-aged men: a randomized-controlled trial.

Regular exercise may improve systemic markers of chronic inflammation, but direct evidence and dose-response information is lacking. The objective of this study was to examine the effect and time course of changes in markers of chronic inflammation in response to progressive exercise training (and subsequent detraining). Forty-one sedentary men 45-64 yr of age completed either a progressive 24-wk exercise intervention or control followed by short-term removal of the intervention (2-wk detraining). Serum IL-6 fell by -0.4 pg/ml (SD 0.6) after 12 wk and responded to moderate-intensity exercise. Serum alanine aminotransferase (ALT) activity fell -7 U/l (SD 11) at 24 wk although there was no evidence of any change by week 12 (and therefore ALT required more vigorous-intensity activity and/or a more prolonged intervention). The effect on IL-6 was lost after 2-wk detraining whereas the change in ALT was retained. The temporal fall and rise in IL-6 with training and subsequent detraining in men with high IL-6 at baseline provided a retrospective opportunity to examine parallel genomic changes in peripheral mononuclear cells. A subset of 53 probes was differentially regulated by at least twofold after training with 31 of these changes being lost after detraining (n = 6). IL-6 responded quickly to the carefully monitored exercise intervention (within weeks) and required only moderate-intensity exercise, whereas ALT took longer to change and/or required more vigorous-intensity exercise. Further work is required to determine whether any of the genes that temporally changed in parallel with changes in IL-6 are a cause or consequence of this response.

The causal role of breakfast in energy balance and health: a randomized controlled trial in obese adults

Background: The causal nature of associations between breakfast and health remain unclear in obese individuals. Objective: We sought to conduct a randomized controlled trial to examine causal links between breakfast habits and components of energy balance in free-living obese humans. Design: The Bath Breakfast Project is a randomized controlled trial with repeated measures at baseline and follow-up among a cohort in South West England aged 21–60 y with dual-energy X-ray absorptiometry–derived fat mass indexes of ≥13 kg/m2 for women (n = 15) and ≥9 kg/m2 for men (n = 8). Components of energy balance (resting metabolic rate, physical activity thermogenesis, diet-induced thermogenesis, and energy intake) 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 (e.g., hematology/adipose biopsies). Results: Breakfast resulted in greater physical activity thermogenesis during the morning than when fasting during that period (difference: 188 kcal/d; 95% CI: 40, 335) but without any consistent effect on 24-h physical activity thermogenesis (difference: 272 kcal/d; 95% CI: −254, 798). Energy intake was not significantly greater with breakfast than fasting (difference: 338 kcal/d; 95% CI: −313, 988). Body mass increased across both groups over time but with no treatment effects on body composition or any change in resting metabolic rate (stable within 8 kcal/d). Metabolic/cardiovascular health also did not respond to treatments, except for a reduced insulinemic response to an oral-glucose-tolerance test over time with daily breakfast relative to an increase with daily fasting (P = 0.05). Conclusions: In obese adults, daily breakfast leads to greater physical activity during the morning, whereas morning fasting results in partial dietary compensation (i.e., greater energy intake) later in the day. There were no differences between groups in weight change and most health outcomes, but insulin sensitivity increased with breakfast relative to fasting. This trial was registered at www.isrctn.org as ISRCTN31521726.

Short-term recovery from prolonged exercise: exploring the potential for protein ingestion to accentuate the benefits of carbohydrate supplements.

This review considers aspects of the optimal nutritional strategy for recovery from prolonged moderate to high intensity exercise. Dietary carbohydrate represents a central component of post-exercise nutrition. Therefore, carbohydrate should be ingested as early as possible in the post-exercise period and at frequent (i.e. 15- to 30-minute) intervals throughout recovery to maximize the rate of muscle glycogen resynthesis. Solid and liquid carbohydrate supplements or whole foods can achieve this aim with equal effect but should be of high glycaemic index and ingested following the feeding schedule described above at a rate of at least 1 g/kg/h in order to rapidly and sufficiently increase both blood glucose and insulin concentrations throughout recovery. Adding ≥0.3 g/kg/h of protein to a carbohydrate supplement results in a synergistic increase in insulin secretion that can, in some circumstances, accelerate muscle glycogen resynthesis. Specifically, if carbohydrate has not been ingested in quantities sufficient to maximize the rate of muscle glycogen resynthesis, the inclusion of protein may at least partially compensate for the limited availability of ingested carbohydrate. Some studies have reported improved physical performance with ingestion of carbohydrate-protein mixtures, both during exercise and during recovery prior to a subsequent exercise test. While not all of the evidence supports these ergogenic benefits, there is clearly the potential for improved performance under certain conditions, e.g. if the additional protein increases the energy content of a supplement and/or the carbohydrate fraction is ingested at below the recommended rate. The underlying mechanism for such effects may be partly due to increased muscle glycogen resynthesis during recovery, although there is varied support for other factors such as an increased central drive to exercise, a blunting of exercise-induced muscle damage, altered metabolism during exercise subsequent to recovery, or a combination of these mechanisms.

The influence of carbohydrate and protein ingestion during recovery from prolonged exercise on subsequent endurance performance

Abstract Ingesting carbohydrate plus protein following prolonged exercise may restore exercise capacity more effectively than ingestion of carbohydrate alone. The objective of the present study was to determine whether this potential benefit is a consequence of the protein fraction per se or simply due to the additional energy it provides. Six active males participated in three trials, each involving a 90-min treadmill run at 70% maximal oxygen uptake (run 1) followed by a 4-h recovery. At 30-min intervals during recovery, participants ingested solutions containing: (1) 0.8 g carbohydrate · kg body mass (BM)−1 · h−1 plus 0.3 g · kg−1 · h−1 of whey protein isolate (CHO-PRO); (2) 0.8 g carbohydrate · kg BM−1 · h−1 (CHO); or (3) 1.1 g carbohydrate · kg BM−1 · h−1 (CHO-CHO). The latter two solutions matched the CHO-PRO solution for carbohydrate and for energy, respectively. Following recovery, participants ran to exhaustion at 70% maximal oxygen uptake (run 2). Exercise capacity during run 2 was greater following ingestion of CHO-PRO and CHO-CHO than following ingestion of CHO (P ≤ 0.05) with no significant difference between the CHO-PRO and CHO-CHO treatments. In conclusion, increasing the energy content of these recovery solutions extended run time to exhaustion, irrespective of whether the additional energy originated from sucrose or whey protein isolate.

Nonprescribed physical activity energy expenditure is maintained with structured exercise and implicates a compensatory increase in energy intake

BACKGROUND Exercise interventions elicit only modest weight loss, which might reflect a compensatory reduction in nonprescribed physical activity energy expenditure (PAEE). OBJECTIVE The objective was to investigate whether there is a reduction in nonprescribed PAEE as a result of participation in a 6-mo structured exercise intervention in middle-aged men. DESIGN Sedentary male participants [age: 54 ± 5 y; body mass index (in kg/m²): 28 ± 3] were randomly assigned to a 6-mo progressive exercise (EX) or control (CON) group. Energy expenditure during structured exercise (prescribed PAEE) and nonprescribed PAEE were determined with the use of synchronized accelerometry and heart rate before the intervention, during the intervention (2, 9, and 18 wk), and within a 2-wk period of detraining after the intervention. RESULTS Structured prescribed exercise increased total PAEE and had no detrimental effect on nonprescribed PAEE. Indeed, there was a trend for greater nonprescribed PAEE in the EX group (P = 0.09). Weight loss in the EX group (-1.8 ± 2.2 kg compared with +0.2 ± 2.2 kg in the CON group, P < 0.02) reflected only ≈40% of the 300-373 kcal/kg body mass potential energy deficit from prescribed exercise. Serum leptin concentration decreased by 24% in the EX group (compared with 3% in the CON group, P < 0.03), and we estimate that this was accompanied by a compensatory increase in energy intake of ≈100 kcal/d. CONCLUSIONS The adoption of regular structured exercise in previously sedentary, middle-aged, and overweight men does not result in a negative compensatory reduction in nonprescribed physical activity. The less-than-predicted weight loss is likely to reflect a compensatory increase in energy intake in response to a perceived state of relative energy insufficiency.

The impact of adiposity on adipose tissue-resident lymphocyte activation in humans

Background/objectives:The presence of T lymphocytes in human adipose tissue has only recently been demonstrated and relatively little is known of their potential relevance in the development of obesity-related diseases. We aimed to further characterise these cells and in particular to investigate how they interact with modestly increased levels of adiposity typical of common overweight and obesity.Subjects/methods:Subcutaneous adipose tissue and fasting blood samples were obtained from healthy males aged 35–55 years with waist circumferences in lean (<94 cm), overweight (94–102 cm) and obese (>102 cm) categories. Adipose tissue-resident CD4+ and CD8+ T lymphocytes together with macrophages were identified by gene expression and flow cytometry. T lymphocytes were further characterised by their expression of activation markers CD25 and CD69. Adipose tissue inflammation was investigated using gene expression analysis and tissue culture.Results:Participants reflected a range of adiposity from lean to class I obesity. Expression of CD4 (T-helper cells) and CD68 (macrophage), as well as FOXP3 RNA transcripts, was elevated in subcutaneous adipose tissue with increased levels of adiposity (P<0.001, P<0.001 and P=0.018, respectively). Flow cytometry revealed significant correlations between waist circumference and levels of CD25 and CD69 expression per cell on activated adipose tissue-resident CD4+ and CD8+ T lymphocytes (P-values ranging from 0.053 to <0.001). No such relationships were found with blood T lymphocytes. This increased T lymphocyte activation was related to increased expression and secretion of various pro- and anti-inflammatory cytokines from subcutaneous whole adipose tissue explants.Conclusions:This is the first study to demonstrate that even modest levels of overweight/obesity elicit modifications in adipose tissue immune function. Our results underscore the importance of T lymphocytes during adipose tissue expansion, and the presence of potential compensatory mechanisms that may work to counteract adipose tissue inflammation, possibly through an increased number of T-regulatory cells.

Exercise counteracts the effects of short-term overfeeding and reduced physical activity independent of energy imbalance in healthy young men.

•  Physical exercise significantly improves health but to what extent these benefits depend on altered energy balance remains unclear. •  In a human experimental model, we investigated whether daily exercise could counteract the effects of short‐term overfeeding and under‐activity independent of its impact on energy imbalance in healthy young men. •  Short‐term positive energy balance from overfeeding and under‐activity resulted in impaired metabolic outcomes and alterations in the expression of several key genes within adipose tissue involved in nutritional balance, metabolism and insulin action. •  These changes were mostly prevented by the addition of a daily vigorous‐intensity exercise bout even in the face of a standardised energy surplus.

Increased carbohydrate oxidation after ingesting carbohydrate with added protein.

PURPOSE To examine the metabolic impact of including protein in a postexercise carbohydrate supplement when ingested between two bouts of prolonged running performed within the same day. METHODS Six healthy men participated in two trials separated by 14 d, each involving a 90-min treadmill run at 70% VO2max followed by 4 h of recovery and a subsequent 60-min run at the same intensity. At 30-min intervals during recovery, participants ingested either a solution containing 0.8 g.kg(-1)h(-1) of carbohydrate (CHO) or the same solution plus an additional 0.3 g.kg(-1)h(-1) of whey protein isolate (CHO-PRO). Muscle biopsies were obtained from the vastus lateralis at the beginning and end of the recovery period, with a third muscle biopsy taken following the second treadmill run. RESULTS Despite higher insulinemic responses to the CHO-PRO solution than to the CHO solution (P < 0.05), rates of muscle glycogen resynthesis during recovery were not different between treatments (CHO = 12.3 +/- 2.2 and CHO-PRO = 12.1 +/- 2.7 mmol glucosyl units per kilogram of dry mass per hour). Furthermore, there were no differences between treatments in muscle glycogen degradation during subsequent exercise (CHO = 2.2 +/- 0.3 and CHO-PRO = 2.0 +/- 0.1 mmol glucosyl units per kilogram of dry mass per minute). In contrast, whole-body carbohydrate oxidation during the second run was significantly greater with the CHO-PRO treatment than with the CHO treatment (48.4 +/- 2.2 and 41.7 +/- 2.6 mg.kg(-1)min(-1), respectively; P < 0.01). CONCLUSION These data show that the inclusion of protein in a carbohydrate-recovery supplement can increase the oxidation of extramuscular carbohydrate sources during subsequent exercise without altering the rate of muscle glycogen degradation.

Carbohydrate-rich breakfast attenuates glycaemic, insulinaemic and ghrelin response to ad libitum lunch relative to morning fasting in lean adults

Breakfast omission is associated with obesity and CVD/diabetes, but the acute effects of extended morning fasting upon subsequent energy intake and metabolic/hormonal responses have received less attention. In a randomised cross-over design, thirty-five lean men (n 14) and women (n 21) extended their overnight fast or ingested a typical carbohydrate-rich breakfast in quantities relative to RMR (i.e. 1963 (sd 238) kJ), before an ad libitum lunch 3 h later. Blood samples were obtained hourly throughout the day until 3 h post-lunch, with subjective appetite measures assessed. Lunch intake was greater following extended fasting (640 (sd 1042) kJ, P< 0·01) but incompletely compensated for the omitted breakfast, with total intake lower than the breakfast trial (3887 (sd 1326) v. 5213 (sd 1590) kJ, P< 0·001). Systemic concentrations of peptide tyrosine–tyrosine and leptin were greater during the afternoon following breakfast (both P< 0·05) but neither acylated/total ghrelin concentrations were suppressed by the ad libitum lunch in the breakfast trial, remaining greater than the morning fasting trial throughout the afternoon (all P< 0·05). Insulin concentrations were greater during the afternoon in the morning fasting trial (all P< 0·01). There were no differences between trials in subjective appetite during the afternoon. In conclusion, morning fasting caused incomplete energy compensation at an ad libitum lunch. Breakfast increased some anorectic hormones during the afternoon but paradoxically abolished ghrelin suppression by the second meal. Extending morning fasting until lunch altered subsequent metabolic and hormonal responses but without greater appetite during the afternoon. The present study clarifies the impact of acute breakfast omission and adds novel insights into second-meal metabolism.

Liver glycogen metabolism during and after prolonged endurance-type exercise

Carbohydrate and fat are the main substrates utilized during prolonged endurance-type exercise. The relative contribution of each is determined primarily by the intensity and duration of exercise, along with individual training and nutritional status. During moderate- to high-intensity exercise, carbohydrate represents the main substrate source. Because endogenous carbohydrate stores (primarily in liver and muscle) are relatively small, endurance-type exercise performance/capacity is often limited by endogenous carbohydrate availability. Much exercise metabolism research to date has focused on muscle glycogen utilization, with little attention paid to the contribution of liver glycogen. (13)C magnetic resonance spectroscopy permits direct, noninvasive measurements of liver glycogen content and has increased understanding of the relevance of liver glycogen during exercise. In contrast to muscle, endurance-trained athletes do not exhibit elevated basal liver glycogen concentrations. However, there is evidence that liver glycogenolysis may be lower in endurance-trained athletes compared with untrained controls during moderate- to high-intensity exercise. Therefore, liver glycogen sparing in an endurance-trained state may account partly for training-induced performance/capacity adaptations during prolonged (>90 min) exercise. Ingestion of carbohydrate at a relatively high rate (>1.5 g/min) can prevent liver glycogen depletion during moderate-intensity exercise independent of the type of carbohydrate (e.g., glucose vs. sucrose) ingested. To minimize gastrointestinal discomfort, it is recommended to ingest specific combinations or types of carbohydrates (glucose plus fructose and/or sucrose). By coingesting glucose with either galactose or fructose, postexercise liver glycogen repletion rates can be doubled. There are currently no guidelines for carbohydrate ingestion to maximize liver glycogen repletion.