Whey Protein Augments Leucinemia and Postexercise p70S6K1 Activity Compared With a Hydrolyzed Collagen Blend When in Recovery From Training With Low Carbohydrate Availability.

We examined the effects of whey versus collagen protein on skeletal muscle cell signaling responses associated with mitochondrial biogenesis and protein synthesis in recovery from an acute training session completed with low carbohydrate availability. In a repeated-measures design (after adhering to a 36-hr exercise-dietary intervention to standardize preexercise muscle glycogen), eight males completed a 75-min nonexhaustive cycling protocol and consumed 22 g of a hydrolyzed collagen blend (COLLAGEN) or whey (WHEY) protein 45 min prior to exercise, 22 g during exercise, and 22 g immediately postexercise. Exercise decreased (p < .05) muscle glycogen content by comparable levels from pre- to postexercise in both trials (≈300-150 mmol/kg·dry weight). WHEY protein induced greater increases in plasma branched chain amino acids (p = .03) and leucine (p = .02) than COLLAGEN. Exercise induced (p < .05) similar increases in PGC-1α (fivefold) mRNA at 1.5 hr postexercise between conditions, although no effect of exercise (p > .05) was observed for p53, Parkin, and Beclin1 mRNA. Exercise suppressed (p < .05) p70S6K1 activity in both conditions immediately postexercise (≈25 fmol·min-1·mg-1). Postexercise feeding increased p70S6K1 activity at 1.5 hr postexercise (p < .05), the magnitude of which was greater (p < .05) in WHEY (180 ± 105 fmol·min-1·mg-1) versus COLLAGEN (73 ± 42 fmol·min-1·mg-1). We conclude that protein composition does not modulate markers of mitochondrial biogenesis when in recovery from a training session deliberately completed with low carbohydrate availability. By contrast, whey protein augments postexercise p70S6K activity compared with hydrolyzed collagen, as likely mediated via increased leucine availability.

Leucine-enriched protein feeding does not impair exercise-induced free fatty acid availability and lipid oxidation: beneficial implications for training in carbohydrate-restricted states.

Given that the enhanced oxidative adaptations observed when training in carbohydrate (CHO)-restricted states is potentially regulated through free fatty acid (FFA)-mediated signalling and that leucine-rich protein elevates muscle protein synthesis, the present study aimed to test the hypothesis that leucine-enriched protein feeding enhances circulating leucine concentration but does not impair FFA availability or whole body lipid oxidation during exercise. Nine males cycled for 2 h at 70% VO2peak when fasted (PLACEBO) or having consumed a whey protein solution (WHEY) or a leucine-enriched whey protein gel (GEL), administered as 22 g 1 h pre-exercise, 11 g/h during and 22 g 30 min post-exercise. Total leucine administration was 14.4 g and 6.3 in GEL and WHEY, respectively. Mean plasma leucine concentrations were elevated in GEL (P = 0.001) compared with WHEY and PLACEBO (375 ± 100, 272 ± 51, 146 ± 14 µmol L(-1), respectively). No differences (P = 0.153) in plasma FFA (WHEY 0.53 ± 0.30, GEL 0.45 ± 0.25, PLACEBO 0.65 ± 0.30, mmol L(-1)) or whole body lipid oxidation during exercise (WHEY 0.37 ± 0.26, GEL 0.36 ± 0.24, PLACEBO 0.34 ± 0.24 g/min) were apparent between trials, despite elevated (P = 0.001) insulin in WHEY and GEL compared with PLACEBO (38 ± 16, 35 ± 16, 22 ± 11 pmol L(-1), respectively). We conclude that leucine-enriched protein feeding does not impair FFA availability or whole body lipid oxidation during exercise, thus having practical applications for athletes who deliberately train in CHO-restricted states to promote skeletal muscle adaptations.

Vitamin D supplementation does not improve human skeletal muscle contractile properties in insufficient young males.

PURPOSE: Vitamin D may be a regulator of skeletal muscle function, although human trials investigating this hypothesis are limited to predominantly elderly populations. We aimed to assess the effect of oral vitamin D3 in healthy young males upon skeletal muscle function. METHODS: Participants (n = 29) received an oral dose of 10,000 IU day(-1) vitamin D3 (VITD) or a visually identical placebo (PLB) for 3 months. Serum 25[OH]D and intact parathyroid hormone (iPTH) were measured at baseline and at week 4, 8 and 12. Muscle function was assessed in n = 22 participants by isokinetic dynamometry and percutaneous isometric electromyostimulation at baseline and at week 6 and 12. RESULTS: Baseline mean total serum 25[OH]D was 40 ± 17 and 41 ± 20 nmol L(-1) for PLB and VITD, respectively. VITD showed a significant improvement in total 25[OH]D at week 4 (150 ± 31 nmol L(-1)) that remained elevated throughout the trial (P < 0.005). Contrastingly, PLB showed a significant decrease in 25[OH]D at week 12 (25 ± 15 nmol L(-1)) compared with baseline. Despite marked increases in total serum 25[OH]D in VITD and a decrease in PLB, there were no significant changes in any of the muscle function outcome measures at week 6 or 12 for either group (P > 0.05). CONCLUSIONS: Elevating total serum 25[OH]D to concentrations > 120 nmol L(-1) has no effect on skeletal muscle function. We postulate that skeletal muscle function is only perturbed in conditions of severe deficiency (<12.5 nmol L(-1)).

Oxidation of independent and combined ingested galactose and glucose during exercise.

Coingestion of glucose and galactose has been shown to enhance splanchnic extraction and metabolism of ingested galactose at rest; effects during exercise are unknown. This study examined whether combined ingestion of galactose and glucose during exercise enhances exogenous galactose oxidation. Fourteen endurance-trained male and female participants [age, 27 (5) yr; V̇o2peak, 58.1 (7.0) mL·kg-1·min-1] performed cycle ergometry for 150 min at 50% peak power on four occasions, in a randomized counterbalanced manner. During exercise, they ingested beverages providing carbohydrates at rates of 0.4 g.min-1 galactose (GAL), 0.8 g.min-1 glucose (GLU), and on two occasions 0.8 g.min-1 total galactose-glucose (GAL + GLU; 1:1 ratio). Single-monosaccharide 13C-labeling (*) was used to calculate independent (GAL, GLU, GAL* + GLU, and GAL + GLU*) and combined (GAL* + GLU*, COMBINE) exogenous-monosaccharide oxidation between exercise. Plasma galactose concentrations with GAL + GLU [0.4 mmol.L; 95% confidence limits (CL): 0.1, 0.6] were lower (contrast: 0.5 mmol.L; 95% CL: 0.2, 0.8; P < 0.0001) than when GAL alone (0.9 mmol.L; 95% CL: 0.7, 1.2) was ingested. Exogenous carbohydrate oxidation with GAL alone (0.31 g·min-1; 95% CL: 0.28, 0.35) was marginally reduced (contrast: 0.05 g·min-1; 95% CL: -0.09, 0.00007; P = 0.01) when combined with glucose (GAL* + GLU 0.27 g·min-1; 0.24, 0.30). Total combined exogenous-carbohydrate oxidation (COMBINE: 0.57 g·min-1; 95% CL: 0.49, 0.64) was similar (contrast: 0.02 g·min-1; 95% CL: -0.05, 0.09; P = 0.63) when compared with isoenergetic GLU (0.55 g·min-1; 95% CL: 0.52, 0.58). In conclusion, coingestion of glucose and galactose did not enhance exogenous galactose oxidation during exercise. When combined, isoenergetic galactose-glucose ingestion elicited similar exogenous-carbohydrate oxidation to glucose suggesting galactose-glucose blends are a valid alternative for glucose as an exogenous-carbohydrate source during exercise.NEW & NOTEWORTHY Glucose and galactose coingestion blunted the galactosemia seen with galactose-only ingestion during exercise. Glucose and galactose coingestion did not enhance the oxidation of ingested galactose during exercise. Combined galactose-glucose (1:1 ratio) ingestion was oxidized to a similar extent as isoenergetic glucose-only ingestion during exercise. Galactose-glucose blends are a viable exogenous carbohydrate energy source for ingestion during exercise.

A pilot sequential multiple assignment randomized trial (SMART) protocol for developing an adaptive coaching intervention around a mobile application for athletes to improve carbohydrate periodization behavior.

BACKGROUND: It has recently been identified that manipulating carbohydrate availability around exercise activity can enhance training-induced metabolic adaptations. Despite this approach being accepted in the athletic populations, athletes do not systematically follow the guidelines. Digital environments appear to allow nutritionists to deliver this intervention at scale, reducing expensive human coaching time. Yet, digitally delivered dietary behavior change interventions for athletes and the coaching strategy to support them are still novel concepts within sports nutrition. METHODS/DESIGN: We aim to recruit 900 athletes across the UK. 500 athletes will be recruited to test the feasibility of a novel menu planner mobile application with coaching for 6 weeks. 250 athletes with pre-existing nutritionist support will also be recruited as control. We will then conduct a 4-week pilot sequential multiple assignment randomized trial (SMART) with an additional 150 athletes. In the SMART, athletes will be given the application and additional coaching according to their engagement responses. The primary outcomes are the mobile application and coach uptake, retention, engagement, and success in attaining carbohydrate periodization behavior. Secondary outcomes are changes in goal, weight, carbohydrate periodization self-efficacy, and beliefs about consequences. Due to the high attrition nature of digital interventions, all quantitative analyses will be carried out based on both the intention-to-treat and per-protocol principles. DISCUSSION: This study will be the first to investigate improving carbohydrate periodization using a digital approach and tailored coaching strategies under this context. Foundational evidence from this study will provide insights into the feasibility of the digital approach.

Glycogen Utilization during Running: Intensity, Sex, and Muscle-Specific Responses.

PURPOSE: This study aimed to quantify net glycogen utilization in the vastus lateralis (VL) and gastrocnemius (G) of male (n = 11) and female (n = 10) recreationally active runners during three outdoor training sessions. METHODS: After 2-d standardization of carbohydrate intakes (6 g·kg body mass per day), glycogen was assessed before and after 1) a 10-mile road run (10-mile) at lactate threshold, 2) 8 × 800-m track intervals (8 × 800 m) at velocity at V˙O2max, and 3) 3 × 10-min track intervals (3 × 10 min) at lactate turnpoint. RESULTS: Resting glycogen concentration was lower in the G of female compared with males (P < 0.001) runners, although no sex differences were apparent in the VL (P = 0.40). Within the G and VL of male runners, net glycogen utilization differed between training sessions where 10 miles was greater than both track sessions (all comparisons, P < 0.05). In contrast, net glycogen utilization in female runners was not different between training sessions in either muscle (all comparisons, P > 0.05). Net glycogen utilization was greater in male than in female runners in both VL (P = 0.02) and G (P = 0.07) during the 10-mile road run. With the exception of male runners during the 3 × 10-min protocol (P = 0.28), greater absolute glycogen utilization was observed in the G versus the VL muscle in both male and female runners and during all training protocols (all comparisons, P < 0.05). CONCLUSION: Data demonstrate that 1) prolonged steady-state running necessitates a greater glycogen requirement than shorter but higher-intensity track running sessions, 2) female participants display evidence of reduced resting muscle glycogen concentration and net muscle glycogen utilization when compared with male participants, and 3) net glycogen utilization is higher in the G muscle compared with the VL.

Fuel for the Work Required: A Theoretical Framework for Carbohydrate Periodization and the Glycogen Threshold Hypothesis.

Deliberately training with reduced carbohydrate (CHO) availability to enhance endurance-training-induced metabolic adaptations of skeletal muscle (i.e. the 'train low, compete high' paradigm) is a hot topic within sport nutrition. Train-low studies involve periodically training (e.g., 30-50% of training sessions) with reduced CHO availability, where train-low models include twice per day training, fasted training, post-exercise CHO restriction and 'sleep low, train low'. When compared with high CHO availability, data suggest that augmented cell signalling (73% of 11 studies), gene expression (75% of 12 studies) and training-induced increases in oxidative enzyme activity/protein content (78% of 9 studies) associated with 'train low' are especially apparent when training sessions are commenced within a specific range of muscle glycogen concentrations. Nonetheless, such muscle adaptations do not always translate to improved exercise performance (e.g. 37 and 63% of 11 studies show improvements or no change, respectively). Herein, we present our rationale for the glycogen threshold hypothesis, a window of muscle glycogen concentrations that simultaneously permits completion of required training workloads and activation of the molecular machinery regulating training adaptations. We also present the 'fuel for the work required' paradigm (representative of an amalgamation of train-low models) whereby CHO availability is adjusted in accordance with the demands of the upcoming training session(s). In order to strategically implement train-low sessions, our challenge now is to quantify the glycogen cost of habitual training sessions (so as to inform the attainment of any potential threshold) and ensure absolute training intensity is not compromised, while also creating a metabolic milieu conducive to facilitating the endurance phenotype.

Acute high-intensity interval running increases markers of gastrointestinal damage and permeability but not gastrointestinal symptoms.

The purpose of this study was to investigate the effects of high-intensity interval running on markers of gastrointestinal (GI) damage and permeability alongside subjective symptoms of GI discomfort. Eleven male runners completed an acute bout of high-intensity interval training (HIIT) (eighteen 400-m runs at 120% maximal oxygen uptake) where markers of GI permeability, intestinal damage, and GI discomfort symptoms were assessed and compared with resting conditions. Compared with rest, HIIT significantly increased serum lactulose/rhamnose ratio (0.051 ± 0.016 vs. 0.031 ± 0.021, p = 0.0047; 95% confidence interval (CI) = 0.006 to 0.036) and sucrose concentrations (0.388 ± 0.217 vs. 0.137 ± 0.148 mg·L-1; p < 0.001; 95% CI = 0.152 to 0.350). In contrast, urinary lactulose/rhamnose (0.032 ± 0.005 vs. 0.030 ± 0.005; p = 0.3; 95% CI = -0.012 to 0.009) or sucrose concentrations (0.169% ± 0.168% vs. 0.123% ± 0.120%; p = 0.54; 95% CI = -0.199 to 0.108) did not differ between HIIT and resting conditions. Plasma intestinal-fatty acid binding protein (I-FABP) was significantly increased (p < 0.001) during and in the recovery period from HIIT whereas no changes were observed during rest. Mild symptoms of GI discomfort were reported immediately and at 24 h post-HIIT, although these symptoms did not correlate to GI permeability or I-FABP. In conclusion, acute HIIT increased GI permeability and intestinal I-FABP release, although these do not correlate with symptoms of GI discomfort. Furthermore, by using serum sampling, we provide data showing that it is possible to detect changes in intestinal permeability that is not observed using urinary sampling over a shorter time-period.

A Ketone Ester Drink Increases Postexercise Muscle Glycogen Synthesis in Humans.

INTRODUCTION: Physical endurance can be limited by muscle glycogen stores, in that glycogen depletion markedly reduces external work. During carbohydrate restriction, the liver synthesizes the ketone bodies, D-ß-hydroxybutyrate, and acetoacetate from fatty acids. In animals and in the presence of glucose, D-ß-hydroxybutyrate promotes insulin secretion and increases glycogen synthesis. Here we determined whether a dietary ketone ester, combined with plentiful glucose, can increase postexercise glycogen synthesis in human skeletal muscle. METHODS: After an interval-based glycogen depletion exercise protocol, 12 well-trained male athletes completed a randomized, three-arm, blinded crossover recovery study that consisted of consumption of either a taste-matched, zero-calorie control or a ketone monoester drink, followed by a 10-mM glucose clamp or saline infusion for 2 h. The three postexercise conditions were control drink then saline infusion, control drink then hyperglycemic clamp, or ketone ester drink then hyperglycemic clamp. Skeletal muscle glycogen content was determined in muscle biopsies of vastus lateralis taken before and after the 2-h clamps. RESULTS: The ketone ester drink increased blood D-ß-hydroxybutyrate concentrations to a maximum of 5.3 versus 0.7 mM for the control drink (P < 0.0001). During the 2-h glucose clamps, insulin levels were twofold higher (31 vs 16 mU·L, P < 0.01) and glucose uptake 32% faster (1.66 vs 1.26 g·kg, P < 0.001). The ketone drink increased by 61 g, the total glucose infused for 2 h, from 197 to 258 g, and muscle glycogen was 50% higher (246 vs 164 mmol glycosyl units per kilogram dry weight, P < 0.05) than after the control drink. CONCLUSION: In the presence of constant high glucose concentrations, a ketone ester drink increased endogenous insulin levels, glucose uptake, and muscle glycogen synthesis.

Metabolic demands and replenishment of muscle glycogen after a rugby league match simulation protocol.

OBJECTIVES: The metabolic requirements of a rugby league match simulation protocol and the timing of carbohydrate provision on glycogen re-synthesis in damaged muscle were examined. DESIGN: Fifteen (mean±SD: age 20.9±2.9 year, body-mass 87.3±14.1kg, height 177.4±6.0cm) rugby league (RL) players consumed a 6gkgday-1 CHO diet for 7-days, completed a time to exhaustion test (TTE) and a glycogen depletion protocol on day-3, a RL simulated-match protocol (RLMSP) on day-5 and a TTE on day-7. Players were prescribed an immediate or delayed (2-h-post) re-feed post-simulation. METHODS: Muscle biopsies and blood samples were obtained post-depletion, before and after simulated match-play, and 48-h after match-play with PlayerLoad and heart-rate collected throughout the simulation. Data were analysed using effects sizes±90% CI and magnitude-based inferences. RESULTS: PlayerLoad (8.0±0.7 AUmin-1) and %HRpeak (83±4.9%) during the simulation were similar to values reported for RL match-play. Muscle glycogen very likely increased from immediately after to 48-h post-simulation (272±97 cf. 416±162mmolkg-1d.w.; ES±90%CI) after immediate re-feed, but changes were unclear (283±68 cf. 361±144mmolkg-1d.w.; ES±90%CI) after delayed re-feed. CK almost certainly increased by 77.9±25.4% (0.75±0.19) post-simulation for all players. CONCLUSIONS: The RLMSP presents a replication of the internal loads associated with professional RL match-play, although difficulties in replicating the collision reduced the metabolic demands and glycogen utilisation. Further, it is possible to replete muscle glycogen in damaged muscle employing an immediate re-feed strategy.

Fuel for the work required: a practical approach to amalgamating train-low paradigms for endurance athletes.

Using an amalgamation of previously studied "train-low" paradigms, we tested the effects of reduced carbohydrate (CHO) but high leucine availability on cell-signaling responses associated with exercise-induced regulation of mitochondrial biogenesis and muscle protein synthesis (MPS). In a repeated-measures crossover design, 11 males completed an exhaustive cycling protocol with high CHO availability before, during, and after exercise (HIGH) or alternatively, low CHO but high protein (leucine enriched) availability (LOW + LEU). Muscle glycogen was different (P < 0.05) pre-exercise (HIGH: 583 ± 158, LOW + LEU: 271 ± 85 mmol kg(-1) dw) but decreased (P < 0.05) to comparable levels at exhaustion (≈100 mmol kg(-1) dw). Despite differences (P < 0.05) in exercise capacity (HIGH: 158 ± 29, LOW + LEU: 100 ± 17 min), exercise induced (P < 0.05) comparable AMPKα2 (3-4-fold) activity, PGC-1α (13-fold), p53 (2-fold), Tfam (1.5-fold), SIRT1 (1.5-fold), Atrogin 1 (2-fold), and MuRF1 (5-fold) gene expression at 3 h post-exercise. Exhaustive exercise suppressed p70S6K activity to comparable levels immediately post-exercise (≈20 fmol min(-1) mg(-1)). Despite elevated leucine availability post-exercise, p70S6K activity remained suppressed (P < 0.05) 3 h post-exercise in LOW + LEU (28 ± 14 fmol min(-1) mg(-1)), whereas muscle glycogen resynthesis (40 mmol kg(-1) dw h(-1)) was associated with elevated (P < 0.05) p70S6K activity in HIGH (53 ± 30 fmol min(-1) mg(-1)). We conclude: (1) CHO restriction before and during exercise induces "work-efficient" mitochondrial-related cell signaling but; (2) post-exercise CHO and energy restriction maintains p70S6K activity at basal levels despite feeding leucine-enriched protein. Our data support the practical concept of "fuelling for the work required" as a potential strategy for which to amalgamate train-low paradigms into periodized training programs.

Postexercise High-Fat Feeding Suppresses p70S6K1 Activity in Human Skeletal Muscle.

PURPOSE: This study aimed to examine the effects of reduced CHO but high postexercise fat availability on cell signaling and expression of genes with putative roles in regulation of mitochondrial biogenesis, lipid metabolism, and muscle protein synthesis. METHODS: Ten males completed a twice per day exercise model (3.5 h between sessions) comprising morning high-intensity interval training (8 × 5 min at 85% V˙O2peak) and afternoon steady-state (SS) running (60 min at 70% V˙O2peak). In a repeated-measures design, runners exercised under different isoenergetic dietary conditions consisting of high-CHO (HCHO: 10 g·kg CHO, 2.5 g·kg protein, and 0.8 g·kg fat for the entire trial period) or reduced-CHO but high-fat availability in the postexercise recovery periods (HFAT: 2.5 g·kg CHO, 2.5 g·kg protein, and 3.5 g·kg fat for the entire trial period). RESULTS: Muscle glycogen was lower (P < 0.05) at 3 h (251 vs 301 mmol·kg dry weight) and 15 h (182 vs 312 mmol·kg dry weight) post-SS exercise in HFAT compared with HCHO. Adenosine monophosphate-activated protein kinase α2 activity was not increased post-SS in either condition (P = 0.41), although comparable increases (all P < 0.05) in PGC-1α, p53, citrate synthase, Tfam, peroxisome proliferator-activated receptor, and estrogen-related receptor α mRNA were observed in HCHO and HFAT. By contrast, PDK4 (P = 0.003), CD36 (P = 0.05), and carnitine palmitoyltransferase 1 (P = 0.03) mRNA were greater in HFAT in the recovery period from SS exercise compared with HCHO. Ribosomal protein S6 kinase activity was higher (P = 0.08) at 3 h post-SS exercise in HCHO versus HFAT (72.7 ± 51.9 vs 44.7 ± 27 fmol·min·mg). CONCLUSION: Postexercise high-fat feeding does not augment the mRNA expression of genes associated with regulatory roles in mitochondrial biogenesis, although it does increase lipid gene expression. However, postexercise ribosomal protein S6 kinase 1 activity is reduced under conditions of high-fat feeding, thus potentially impairing skeletal muscle remodeling processes.

Muscle glycogen utilisation during Rugby match play: Effects of pre-game carbohydrate.

OBJECTIVES: Although the physical demands of Rugby League (RL) match-play are well-known, the fuel sources supporting energy-production are poorly understood. We therefore assessed muscle glycogen utilisation and plasma metabolite responses to RL match-play after a relatively high (HCHO) or relatively low CHO (LCHO) diet. DESIGN: Sixteen (mean±SD age; 18±1 years, body-mass; 88±12kg, height 180±8cm) professional players completed a RL match after 36-h consuming a non-isocaloric high carbohydrate (n=8; 6gkgday-1) or low carbohydrate (n=8; 3gkgday-1) diet. METHODS: Muscle biopsies and blood samples were obtained pre- and post-match, alongside external and internal loads quantified using Global Positioning System technology and heart rate, respectively. Data were analysed using effects sizes ±90% CI and magnitude-based inferences. RESULTS: Differences in pre-match muscle glycogen between high and low carbohydrate conditions (449±51 and 444±81mmolkg-1d.w.) were unclear. High (243±43mmolkg-1d.w.) and low carbohydrate groups (298±130mmolkg-1d.w.) were most and very likely reduced post-match, respectively. For both groups, differences in pre-match NEFA and glycerol were unclear, with a most likely increase in NEFA and glycerol post-match. NEFA was likely lower in the high compared with low carbohydrate group post-match (0.95±0.39mmoll-1 and 1.45±0.51mmoll-1, respectively), whereas differences between the 2 groups for glycerol were unclear (98.1±33.6mmoll-1 and 123.1±39.6mmoll-1) in the high and low carbohydrate groups, respectively. CONCLUSIONS: Professional RL players can utilise ∼40% of their muscle glycogen during a competitive match regardless of their carbohydrate consumption in the preceding 36-h.