Are there sex differences in the variability of fasting metabolism?

There is evidence across species and across many traits that males display greater between-individual variance. In contrast, (premenopausal) females display large within-individual variance in sex hormone concentrations, which can increase within-individual variance in many other parameters. The latter may contribute to the lower representation of females in metabolic research. This study is a pooled secondary analysis of data from seven crossover studies to investigate the between-individual and the within-individual variance in fasting plasma metabolites, resting metabolic rate (RMR), and body mass. Females demonstrated higher within-individual variability of plasma 17ß-estradiol [coefficient of variation (CV): 15 ± 15% for males vs. 38 ± 34% for females, P < 0.001] and progesterone concentrations (CV: 13 ± 11% for males vs. 52 ± 51% for females, P < 0.001) but there were no meaningful differences in the variability of plasma glucose (CV: 4 ± 3% for males vs. 5 ± 5% for females), insulin, lactate, triglycerides (CV: 15 ± 9% for males vs. 15 ± 10% for females), and esterified fatty acid concentrations or in RMR and body mass (CV: 0.43 ± 0.34% for males vs. for 0.42 ± 0.33% females; P > 0.05 for all outcomes). Males displayed higher between-individual variance in RMR compared with females (SD: 224 kcal·day-1 for males vs. 151 kcal·day-1 for females). In conclusion, these data do not provide evidence that females show greater within-individual variability in many fasting metabolic variables, RMR, or body mass compared with males. We conclude that including females in metabolic research is unlikely to introduce greater within-individual variance when using the recruitment and control procedures described in these studies.NEW & NOTEWORTHY To investigate the within-individual variability in metabolic parameters in males and females, we performed a pooled secondary analysis of fasting blood samples, resting metabolic rate, and body mass from seven crossover studies. We found a greater day-to-day variation in 17ß-estradiol and progesterone in females compared with males but no meaningful difference in within-individual variability of fasting plasma glucose, insulin, lactate, triglycerides, NEFA, resting metabolic rate, or body mass between females and males.

Postprandial Metabolic Mesponses to High-fat Feeding in Healthy Adults Following Ingestion of Oolong Tea-Derived Polymerized Polyphenols: A Randomized, Double-blinded, Placebo-controlled Crossover Study.

BACKGROUND: Polymerized polyphenols (PP) found in oolong tea can inhibit pancreatic lipase activity in vitro, and pilot work indicates that this may reduce postprandial lipemia. Since tea contains caffeine and catechins, the interactions between these ingredients and PP warrant investigation. OBJECTIVES: To assess whether PP ingested alone or with caffeine and catechins lowers postprandial lipemia. METHODS: Fifty healthy adults [mean (SD) age: 26 (7) y; BMI (in kg/m2): 24.0 (2.7); female: n = 16] completed 4 oral lipid tolerance tests in a placebo-controlled randomized, crossover design. Participants ingested 40 g of fat with either 1) placebo, 2) 100 mg PP, 3) 150 mg PP, or 4) 100 mg PP plus 50 mg caffeine and 63 mg catechins (PP + CC). Blood was sampled for 3 h postprandially to assess concentrations of serum and plasma triacylglycerol and plasma markers of lipid (NEFA; glycerol; LDL and HDL cholesterol; and ApoA-I, A-II, B, C-II, C-III, and E) and glucose metabolism (glucose, insulin, and C-peptide). RESULTS: Serum and plasma triacylglycerol concentrations and lipid metabolism variables generally increased following any test drink ingestion (main effect of time, p < 0.001). Nevertheless, for the lipid metabolism responses, there were no statistically significant condition-time interactions and no statistically significant differences in incremental or total area under the curve between conditions, apart from HDL cholesterol (p = 0.021). Ingesting 100 mg PP + CC lowered peak plasma glucose, insulin, and C-peptide concentrations compared with all other conditions 30 min postingestion (p < 0.001), with persistent alterations in glucose concentrations observed for 90 min compared with placebo and 100 mg PP conditions. CONCLUSIONS: PP ingested at doses ≤150 mg does not clearly alter early-phase postprandial triacylglycerol concentrations in healthy adults, irrespective of the presence or absence of caffeine and catechins. Nevertheless, caffeine and catechins added to PP lowered postprandial glucose and insulin concentrations. This trial was registered in ClinicalTrials.gov as NCT03324191 (https://clinicaltrials.gov/ct2/show/NCT03324191).

Restricting sugar or carbohydrate intake does not impact physical activity level or energy intake over 24 h despite changes in substrate use: a randomised crossover study in healthy men and women.

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.

Interrupting Prolonged Sitting with Intermittent Walking Increases Postprandial Gut Hormone Responses.

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.

Effect of carbohydrate-protein supplementation on endurance training adaptations.

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.

The day-to-day reliability of peak fat oxidation and FATMAX.

PURPOSE: Prior studies exploring the reliability of peak fat oxidation (PFO) and the intensity that elicits PFO (FATMAX) are often limited by small samples. This study characterised the reliability of PFO and FATMAX in a large cohort of healthy men and women. METHODS: Ninety-nine adults [49 women; age: 35 (11) years; [Formula: see text]O2peak: 42.2 (10.3) mL·kg BM-1·min-1; mean (SD)] completed two identical exercise tests (7-28 days apart) to determine PFO (g·min-1) and FATMAX (%[Formula: see text]O2peak) by indirect calorimetry. Systematic bias and the absolute and relative reliability of PFO and FATMAX were explored in the whole sample and sub-categories of: cardiorespiratory fitness, biological sex, objectively measured physical activity levels, fat mass index (derived by dual-energy X-ray absorptiometry) and menstrual cycle status. RESULTS: No systematic bias in PFO or FATMAX was found between exercise tests in the entire sample (- 0.01 g·min-1 and 0%[Formula: see text]O2peak, respectively; p > 0.05). Absolute reliability was poor [within-subject coefficient of variation: 21% and 26%; typical errors: ± 0.06 g·min-1 and × / ÷ 1.26%[Formula: see text]O2peak; 95% limits of agreement: ± 0.17 g·min-1 and × / ÷ 1.90%[Formula: see text]O2peak, respectively), despite high (r = 0.75) and moderate (r = 0.45) relative reliability for PFO and FATMAX, respectively. These findings were consistent across all sub-groups. CONCLUSION: Repeated assessments are required to more accurately determine PFO and FATMAX.

Physiological responses to maximal eating in men.

This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until 'comfortably full' (ad libitum) and on the other, until they 'could not eat another bite' (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine-tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.

Frequent Carbohydrate Ingestion Reduces Muscle Glycogen Depletion and Postpones Fatigue Relative to a Single Bolus.

The timing of carbohydrate ingestion and how this influences net muscle glycogen utilization and fatigue has only been investigated in prolonged cycling. Past findings may not translate to running because each exercise mode is distinct both in the metabolic response to carbohydrate ingestion and in the practicalities of carbohydrate ingestion. To this end, a randomized, cross-over design was employed to contrast ingestion of the same sucrose dose either at frequent intervals (15 × 5 g every 5 min) or at a late bolus (1 × 75 g after 75 min) during prolonged treadmill running to exhaustion in six well-trained runners (V˙O2max 61 ± 4 ml·kg-1·min-1). The muscle glycogen utilization rate was lower in every participant over the first 75 min of running (Δ 0.51 mmol·kg dm-1·min-1; 95% confidence interval [-0.02, 1.04] mmol·kg dm-1·min-1) and, subsequently, all were able to run for longer when carbohydrate had been ingested frequently from the start of exercise compared with when carbohydrate was ingested as a single bolus toward the end of exercise (105.6 ± 3.0 vs. 96.4 ± 5.0 min, respectively; Δ 9.3 min, 95% confidence interval [2.8, 15.8] min). A moderate positive correlation was apparent between the magnitude of glycogen sparing over the first 75 min and the improvement in running capacity (r = .58), with no significant difference in muscle glycogen concentrations at the point of exhaustion. This study indicates that failure to ingest carbohydrates from the outset of prolonged running increases reliance on limited endogenous muscle glycogen stores-the ergolytic effects of which cannot be rectified by subsequent carbohydrate ingestion late in exercise.

Co-ingestion of whey protein hydrolysate with milk minerals rich in calcium potently stimulates glucagon-like peptide-1 secretion: an RCT in healthy adults.

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.

The effects of different forms of daily exercise on metabolic function following short-term overfeeding and reduced physical activity in healthy young men: study protocol for a randomised controlled trial.

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.

An investigation into the relationship between plain water intake and glycated Hb (HbA1c): a sex-stratified, cross-sectional analysis of the UK National Diet and Nutrition Survey (2008-2012).

The aim of this study was to analyse the association between plain water intake and glycated Hb (HbA1c) in the National Diet and Nutrition Survey (2008-2012) rolling survey. These data included diet (4-d diaries) and HbA1c (fasted blood sample) measures of 456 men and 579 women aged 44 (sd 18) years with full information on covariates of interest (age, ethnicity, BMI, smoking status, education, other beverage intake, energy intake and fibre). Data were analysed using sex-stratified linear and logistic regressions modelling the associations of cups per d (240 ml) of plain water with HbA1c, and odds of HbA1c≥5·5 %, respectively. Substitution analyses modelled the replacement of sugar-sweetened beverages, fruit juice and artificially sweetened beverages with plain water. After adjustment, 1 cup/d of plain water was associated with a -0·04 % lower HbA1c (95 % CI -0·07, -0·02) in men. In logistic regression, men had a 22 % (95 % CI 10, 32 %) reduced odds of HbA1c≥5·5 %/cup per d of plain water. There was no evidence of an association with either HbA1c or odds of HbA1c≥5·5 % in women. None of the substitution models was associated with a change in odds of HbA1c≥5·5 %. Plain water intake was associated with lower HbA1c in men but not in women. Substituting water for specific beverages was not associated with a reduced odds of HbA1c≥5·5 %, suggesting that the addition of water is the more pertinent factor. Future trials should test whether the relationships between water intake and HbA1c is causal as this could be a cost-effective and simple health intervention.

Post-Exercise Protein Trial: Interactions between Diet and Exercise (PEPTIDE): study protocol for randomized controlled trial.

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.

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

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.

Exploring mechanisms of fatigue during repeated exercise and the dose dependent effects of carbohydrate and protein ingestion: study protocol for a randomised controlled trial.

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.

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

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.

Oxidative stress, inflammation and recovery of muscle function after damaging exercise: effect of 6-week mixed antioxidant supplementation.

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.

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.

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.

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.