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Branched-chain amino acids (BCAA) and carbohydrate (CHO) are commonly recommended postexercise supplements. However, no study has examined the interaction of CHO and BCAA ingestion on myofibrillar protein synthesis (MyoPS) rates following exercise. We aimed to determine the response of MyoPS to the co-ingestion of BCAA and CHO following an acute bout of resistance exercise. Ten resistance-trained young men completed two trials in counterbalanced order, ingesting isocaloric drinks containing either 30.6-g CHO plus 5.6-g BCAA (B + C) or 34.7-g CHO alone following a bout of unilateral, leg resistance exercise. MyoPS was measured postexercise with a primed, constant infusion of L-[ring13C6] phenylalanine and collection of muscle biopsies pre- and 4 hr postdrink ingestion. Blood samples were collected at time points before and after drink ingestion. Serum insulin concentrations increased to a similar extent in both trials (p > .05), peaking at 30 min postdrink ingestion. Plasma leucine (514 ± 34 nmol/L), isoleucine (282 ± 23 nmol/L), and valine (687 ± 33 nmol/L) concentrations peaked at 0.5 hr postdrink in B + C and remained elevated for 3 hr during exercise recovery. MyoPS was ∼15% greater (95% confidence interval [−0.002, 0.028], p = .039, Cohen’s d = 0.63) in B + C (0.128%/hr ± 0.011%/hr) than CHO alone (0.115%/hr ± 0.011%/hr) over the 4 hr postexercise period. Co-ingestion of BCAA and CHO augments the acute response of MyoPS to resistance exercise in trained young males.

The importance of carbohydrate as a fuel source for exercise and athletic performance is well established. Equally well developed are dietary carbohydrate intake guidelines for endurance athletes seeking to optimize their performance. This narrative review provides a contemporary perspective on research into the role of, and application of, carbohydrate in the diet of endurance athletes. The review discusses how recommendations could become increasingly refined and what future research would further our understanding of how to optimize dietary carbohydrate intake to positively impact endurance performance. High carbohydrate availability for prolonged intense exercise and competition performance remains a priority. Recent advances have been made on the recommended type and quantity of carbohydrates to be ingested before, during and after intense exercise bouts. Whilst reducing carbohydrate availability around selected exercise bouts to augment metabolic adaptations to training is now widely recommended, a contemporary view of the so-called train-low approach based on the totality of the current evidence suggests limited utility for enhancing performance benefits from training. Nonetheless, such studies have focused importance on periodizing carbohydrate intake based on, among other factors, the goal and demand of training or competition. This calls for a much more personalized approach to carbohydrate recommendations that could be further supported through future research and technological innovation (e.g., continuous glucose monitoring). Despite more than a century of investigations into carbohydrate nutrition, exercise metabolism and endurance performance, there are numerous new important discoveries, both from an applied and mechanistic perspective, on the horizon.

Purpose This study aimed to investigate whether carbohydrate ingestion during 3 h long endurance exercise in highly trained cyclists at a rate of 120 g h−1 in 0.8:1 ratio between fructose and glucose-based carbohydrates would result in higher exogenous and lower endogenous carbohydrate oxidation rates as compared to ingestion of 90 g h−1 in 1:2 ratio, which is the currently recommended approach for exercise of this duration. Methods Eleven male participants (V̇O2peak 62.6 ± 7 mL kg−1 min−1, gas exchange threshold (GET) 270 ± 17 W and Respiratory compensation point 328 ± 32 W) completed the study involving 4 experimental visits consisting of 3 h cycling commencing after an overnight fast at an intensity equivalent to 95% GET. During the trials they received carbohydrates at an average rate of 120 or 90 g h−1 in 0.8:1 or 1:2 fructose-maltodextrin ratio, respectively. Carbohydrates were naturally high or low in 13C stable isotopes enabling subsequent calculations of exogenous and endogenous carbohydrate oxidation rates. Results Exogenous carbohydrate oxidation rates were higher in the 120 g h−1 condition (120–180 min: 1.51 ± 0.22 g min−1) as compared to the 90 g h−1 condition (1.29 ± 0.16 g min−1; p = 0.026). Endogenous carbohydrate oxidation rates did not differ between conditions (2.15 ± 0.30 and 2.20 ± 0.33 g min−1 for 120 and 90 g h−1 conditions, respectively; p = 0.786). Conclusions The results suggest that carbohydrate ingestion at 120 g h−1 in 0.8:1 fructose-maltodextrin ratio as compared with 90 g h−1 in 1:2 ratio offers higher exogenous carbohydrate oxidation rates but no additional sparing of endogenous carbohydrates. Further studies should investigate potential performance effects of such carbohydrate ingestion strategies.

Mitochondria are critical to skeletal muscle contractile function and metabolic health. Short-term periods of step reduction (SR) are associated with alterations in muscle protein turnover and mass. However, the effects of SR on mitochondrial metabolism/muscle oxidative metabolism and insulin-mediated signaling are unclear. We tested the hypothesis that the total and/or phosphorylated protein content of key skeletal muscle markers of mitochondrial/oxidative metabolism, and insulin-mediated signaling would be altered over 7 days of SR in young healthy males. Eleven, healthy, recreationally active males (means ± SE, age: 22 ± 1 yr, BMI: 23.4 ± 0.7 kg·m

Purpose Whole-body fat oxidation during exercise can be measured non-invasively during athlete profiling. Gaps in understanding exist in the relationships between fat oxidation during incremental fasted exercise and skeletal muscle parameters, endurance performance, and fat oxidation during prolonged fed-state exercise. Methods Seventeen endurance-trained males underwent a (i) fasted, incremental cycling test to assess peak whole-body fat oxidation (PFO), (ii) resting vastus lateralis microbiopsy, and (iii) 30-min maximal-effort cycling time-trial preceded by 2-h of fed-state moderate-intensity cycling to assess endurance performance and fed-state metabolism on separate occasions within one week. Results PFO (0.58 ± 0.28 g.min−1) was associated with vastus lateralis citrate synthase activity (69.2 ± 26.0 μmol.min−1.g−1 muscle protein, r = 0.84, 95% CI 0.58, 0.95, P

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; V̇osub2peak/sub, 58.1 (7.0) mL·kgsup-1/sup·minsup-1/sup] 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.minsup-1/supgalactose (GAL), 0.8 g.minsup-1/supglucose (GLU), and on two occasions 0.8 g.minsup-1/suptotal galactose-glucose (GAL + GLU; 1:1 ratio). Single-monosaccharidesup13/supC-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;iP/ilt; 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·minsup-1/sup; 95% CL: 0.28, 0.35) was marginally reduced (contrast: 0.05 g·minsup-1/sup; 95% CL: -0.09, 0.00007;iP/i= 0.01) when combined with glucose (GAL* + GLU 0.27 g·minsup-1/sup; 0.24, 0.30). Total combined exogenous-carbohydrate oxidation (COMBINE: 0.57 g·minsup-1/sup; 95% CL: 0.49, 0.64) was similar (contrast: 0.02 g·minsup-1/sup; 95% CL: -0.05, 0.09;iP/i= 0.63) when compared with isoenergetic GLU (0.55 g·minsup-1/sup; 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.bNEWamp; NOTEWORTHY/bGlucose 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.

The impact of resistance exercise frequency on muscle protein synthesis rates remains unknown. The aim of this study was to compare daily myofibrillar protein synthesis rates over a 7-day period of low-frequency (LF) versus high-frequency (HF) resistance exercise training. Nine young men (21 ± 2 years) completed a 7-day period of habitual physical activity (BASAL). This was followed by a 7-day exercise period of volume-matched, LF (10 × 10 repetitions at 70% one-repetition maximum, once per week) or HF (2 × 10 repetitions at ∼70% one-repetition maximum, five times per week) resistance exercise training. The participants had one leg randomly allocated to LF and the other to HF. Skeletal muscle biopsies and daily saliva samples were collected to determine myofibrillar protein synthesis rates using 2H2O, with intracellular signaling determined using Western blotting. The myofibrillar protein synthesis rates did not differ between the LF (1.46 ± 0.26%/day) and HF (1.48 ± 0.33%/day) conditions over the 7-day exercise training period (p > .05). There were no significant differences between the LF and HF conditions over the first 2 days (1.45 ± 0.41%/day vs. 1.25 ± 0.46%/day) or last 5 days (1.47 ± 0.30%/day vs. 1.50 ± 0.41%/day) of the exercise training period (p > .05). Daily myofibrillar protein synthesis rates were not different from BASAL at any time point during LF or HF (p > .05). The phosphorylation status and total protein content of selected proteins implicated in skeletal muscle ribosomal biogenesis were not different between conditions (p > .05). Under the conditions of the present study, resistance exercise training frequency did not modulate daily myofibrillar protein synthesis rates in young men.

Background: Prolonged sitting is associated with increased risk of obesity, type 2 diabetes and cardiovascular disease. Occupational sitting accounts for up to 50 hours per week for employees. This pilot study assessed 1) the acceptability of stair climbing as an interruption to sitting throughout working hours, 2) provide preliminary data of the effects on glucose and lipid profiles. Methods: Participants (n = 16) were randomised to intervention and control groups. For the intervention, a continuous 4-floor stair climb and descent at self-selected pace was performed eight times.day-1 spread evenly over the working day. A prompt to climb was presented on the participant’s computer 8-times.day-1. A log sheet recorded floors climbed in response to each prompt and total weekly steps were measured with pedometers. Blood samples were collected pre and post intervention to test effects on fasting glucose and OGTT, triglycerides, and total (TC), LDL and HDL cholesterol. Experimental participants were interviewed at the end of the study. The Wilcoxon signed rank test was used to compare the median changes (pre-post) of the dependent variables. Results: On average, the experimental group climbed 121 floors.week-1 when prompted. There were significant reductions in fasting blood glucose, TC and LDL, as well as the derived measures of ‘bad’ cholesterol and the TC/HDL ratio in the experimental group. Post-experimental interviews indicated that the interruption to sitting was well tolerated. Conclusion: Prompted stair climbing activity had impacts on health outcomes and was found acceptable to employees at work.Trial registration: Ethics for this study was approved by Science, Technology, Engineering and Mathematics Ethical Review Committee, University of Birmingham with ethics reference number ERN_15_0491.

Key points Acute nicotinamide riboside (NR) supplementation does not alter substrate metabolism at rest, during or in recovery from endurance exercise. NR does not alter NAD+ -sensitive signalling pathways in human skeletal muscle. NR supplementation and acute exercise influence the NAD+ metabolome. Abstract Oral supplementation of the NAD+ precursor nicotinamide riboside (NR) has been reported to alter metabolism alongside increasing sirtuin (SIRT) signalling and mitochondrial biogenesis in rodent skeletal muscle. However, whether NR supplementation can elicit a similar response in human skeletal muscle is unclear. This study assessed the effect of 7-day NR supplementation on whole-body metabolism and exercise-induced mitochondrial biogenic signalling in skeletal muscle. Eight male participants (age: 23 ± 4 years, V O 2 peak 46.5 ± 4.4 ml kg-1 min-1 ) received 1 week of NR or cellulose placebo (PLA) supplementation (1000 mg day-1 ). Muscle biopsies were collected from the medial vastus lateralis prior to supplementation and pre-, immediately post- and 3 h post-exercise (1 h of 60% Wmax cycling) performed following the supplementation period. There was no effect of NR supplementation on substrate utilisation at rest or during exercise or on skeletal muscle mitochondrial respiration. Global acetylation, auto-PARylation of poly ADP-ribose polymerase 1 (PARP1), acetylation of Tumour protein 53 (p53)Lys382 and Manganese superoxide dismutase (MnSOD)Lys122 were also unaffected by NR supplementation or exercise. NR supplementation did not increase skeletal muscle NAD+ concentration, but it did increase the concentration of deaminated NAD+ precursors nicotinic acid riboside (NAR) and nicotinic acid mononucleotide (NAM) and methylated nicotinamide breakdown products (Me2PY and Me4PY), demonstrating the skeletal muscle bioavailability of NR supplementation. In summary, 1 week of NR supplementation does not alter whole-body metabolism or skeletal muscle signal transduction pathways implicated in the mitochondrial adaptation to endurance exercise.

The benefits of high exogenous glucose availability for endurance exercise performance are well-established. Exogenous glucose oxidation rates are thought to be limited by intestinal glucose transport. Extracellular calcium in rodent intestine increases the translocation of the intestinal glucose transporter GLUT2 which, if translated to humans, could increase the capacity for exogenous glucose availability during exercise. Therefore, this pilot study aimed to explore the effect of calcium co-ingestion during endurance exercise on exogenous glucose oxidation in healthy men. Eight healthy men cycled for 2 h at 50% peak power output, ingesting either 1.2 g min −1 dextrose alone (GLU) or with the addition of 2000 mg calcium (GLU + CAL), in a randomised crossover design. Expired breath samples were collected to determine whole-body and exogenous glucose oxidation. Peak exogenous glucose oxidation during GLU was 0.83 ± 0.15 g min −1, and was not enhanced during GLU + CAL (0.88 ± 0.11 g min −1, p = 0.541). The relative contributions of exogenous carbohydrate (19 ± 3% vs. 20 ± 2%, p = 0.434), endogenous carbohydrate (65 ± 3% vs. 65 ± 3%, p = 0.822) and fat (16 ± 3% vs. 15 ± 3%, p = 0.677) to total substrate utilisation did not differ between trials. These results suggest the addition of calcium to glucose ingestion, at saturating glucose ingestion rates, does not appear to alter exogenous glucose oxidation during endurance exercise in healthy men.

Purpose Maximizing carbohydrate availability is important for many endurance events. Combining pectin and sodium alginate with ingested maltodextrin-fructose (MAL + FRU + PEC + ALG) has been suggested to enhance carbohydrate delivery via hydrogel formation, but the influence on exogenous carbohydrate oxidation remains unknown. The primary aim of this study was to assess the effects of MAL + FRU + PEC + ALG on exogenous carbohydrate oxidation during exercise compared with a maltodextrin-fructose mixture (MAL + FRU). MAL + FRU has been well established to increase exogenous carbohydrate oxidation during cycling compared with glucose-based carbohydrates (MAL + GLU). However, much evidence focuses on cycling, and direct evidence in running is lacking. Therefore, a secondary aim was to compare exogenous carbohydrate oxidation rates with MAL + FRU versus MAL + GLU during running. Methods Nine trained runners completed two trials (MAL + FRU and MAL + FRU + PEC + ALG) in a double-blind, randomized crossover design. A subset (n = 7) also completed a MAL + GLU trial to address the secondary aim, and a water trial to establish background expired CO2 enrichment. Participants ran at 60% V˙O2peak for 120 min while ingesting either water only or carbohydrate solutions at a rate of 1.5 g carbohydrate per minute. Results At the end of 120 min of exercise, exogenous carbohydrate oxidation rates were 0.9 (SD 0.5) g·min with MAL + GLU ingestion. MAL + FRU ingestion increased exogenous carbohydrate oxidation rates to 1.1 (SD 0.3) g·min (P = 0.038), with no further increase with MAL + FRU + PEC + ALG ingestion (1.1 (SD 0.3) g·min; P = 1.0). No time-treatment interaction effects were observed for plasma glucose, lactate, insulin, or nonesterified fatty acids, or for ratings of perceived exertion or gastrointestinal symptoms (all, P > 0.05). Conclusion To maximize exogenous carbohydrate oxidation during moderate-intensity running, athletes may benefit from consuming glucose(polymer)-fructose mixtures over glucose-based carbohydrates alone, but the addition of pectin and sodium alginate offers no further benefit.

Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases1-5. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear6. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis of Lac-Phe from lactate and phenylalanineoccurs in CNDP2+ cells, including macrophages,monocytes and otherimmune and epithelial cells localized to diverse organs. In diet-induced obese mice, pharmacological-mediated increases in Lac-Phe reduces food intake without affecting movement or energy expenditure. Chronic administration of Lac-Phe decreases adiposity and body weight and improves glucose homeostasis. Conversely, genetic ablation of Lac-Phe biosynthesis in mice increases food intake and obesity following exercise training. Last, large activity-inducible increases in circulating Lac-Phe are alsoobserved in humans and racehorses, establishing this metabolite as a molecular effector associated with physical activity across multiple activity modalities and mammalian species. These data define a conserved exercise-inducible metabolite that controls food intake and influences systemic energy balance.

PURPOSE OF REVIEW: The present review summarized evidence on the role of carbohydrates in recovery from exercise within the context of acute and chronic effects on metabolism and performance. RECENT FINDINGS: Recent studies demonstrate that, in contrast to recovery of muscle glycogen stores, the recovery of liver glycogen stores can be accelerated by the co-ingestion of fructose with glucose-based carbohydrates. Three recent studies suggest this can extend time-to-exhaustion during endurance exercise tests. However, periodically restricting carbohydrate intakes during recovery from some training sessions to slow the recovery of liver and muscle glycogen stores may, over time, result in a modest increase in the ability to oxidize fat during exercise in a fasted state. Whether this periodized strategy translates into a performance advantage in the fed state remains to be clearly demonstrated. SUMMARY: To maximize recovery of glycogen stores and the capacity to perform in subsequent endurance exercise, athletes should consider ingesting at least 1.2 g carbohydrate per kilogram body mass per hour - for the first few hours of recovery - as a mixture of fructose and glucose-based carbohydrates. However, if a goal is increased capacity for fat oxidation, athletes should consider restricting carbohydrate intakes during recovery from some key training sessions. VIDEO ABSTRACT: http://links.lww.com/COCN/A15.

Altering dietary carbohydrate (CHO) intake modulates fuel utilization during exercise. However, there has been no systematic evaluation of metabolic responses to graded changes in short-term (< 1 week) dietary CHO intake. Thirteen active men performed interval running exercise combined with isocaloric diets over 3 days before evaluation of metabolic responses to 60-min running at 65% V̇O2max on three occasions. Diets contained lower (LOW, 2.40 ± 0.66 g CHO.kg-1.d-1, 21.3 ± 0.5% of energy intake [EI]), moderate (MOD, 4.98 ± 1.31 g CHO.kg-1.d-1, 46.3 ± 0.7% EI), or higher (HIGH, 6.48 ± 1.56 g CHO.kg-1.d-1, 60.5 ± 1.6% EI) CHO. Pre-exercise muscle glycogen content was lower in LOW (54.3 ± 26.4 mmol.kg-1 wet weight [ww]) compared to MOD (82.6 ± 18.8 mmol.kg-1 ww) and HIGH (80.4 ± 26.0 mmol.kg-1 ww, P

The present review summarized evidence on the role of carbohydrates in recovery from exercise within the context of acute and chronic effects on metabolism and performance.Recent studies demonstrate that, in contrast to recovery of muscle glycogen stores, the recovery of liver glycogen stores can be accelerated by the co-ingestion of fructose with glucose-based carbohydrates. Three recent studies suggest this can extend time-to-exhaustion during endurance exercise tests. However, periodically restricting carbohydrate intakes during recovery from some training sessions to slow the recovery of liver and muscle glycogen stores may, over time, result in a modest increase in the ability to oxidize fat during exercise in a fasted state. Whether this periodized strategy translates into a performance advantage in the fed state remains to be clearly demonstrated.To maximize recovery of glycogen stores and the capacity to perform in subsequent endurance exercise, athletes should consider ingesting at least 1.2 g carbohydrate per kilogram body mass per hour - for the first few hours of recovery - as a mixture of fructose and glucose-based carbohydrates. However, if a goal is increased capacity for fat oxidation, athletes should consider restricting carbohydrate intakes during recovery from some key training sessions.http://links.lww.com/COCN/A15.

Endurance athletes are frequently exposed to environmental heat stress during training. We investigated whether exposure to 33°C during training would improve endurance performance in temperate conditions and stimulate mitochondrial adaptations. Seventeen endurance‐trained males were randomly assigned to perform a 3‐week training intervention in 18°C (TEMP) or 33°C (HEAT). An incremental test and 30‐min time‐trial preceded by 2‐h low‐intensity cycling were performed in 18°C pre‐ and post‐intervention, along with a resting vastus lateralis microbiopsy. Training was matched for relative cardiovascular demand using heart rates measured at the first and second ventilatory thresholds, along with a weekly “best‐effort” interval session. Perceived training load was similar between‐groups, despite lower power outputs during training in HEAT versus TEMP (p, We observed that 3 weeks of endurance training performed in 33°C improved endurance performance in temperate conditions to a significantly greater extent than matched training performed in 18°C. We also observed a significant increase in vastus lateralis citrate synthase activity in response to training performed in 33°C, but not matched training performed in 18°C.

ObjectiveTo investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses.DesignTwelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period.ResultsBoth IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose.ConclusionThese data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.

Purpose Ingesting readily oxidized carbohydrates (CHO) such as sucrose during exercise can improve endurance performance. Whether lactose can be utilized as a fuel source during exercise is unknown. The purpose of this study was to investigate the metabolic response to lactose ingestion during exercise, compared with sucrose or water. Methods Eleven participants (age, 22 ± 4 yr; V[Combining Dot Above]O2peak, 50.9 ± 4.7 mL·min·kg) cycled at 50% Wmax for 150 min on five occasions. Participants ingested CHO beverages (lactose or sucrose; 48 g·h, 0.8 g·min) or water throughout exercise. Total substrate and exogenous CHO oxidation was estimated using indirect calorimetry and stable isotope techniques (naturally high C-abundance CHO ingestion). Naturally low C-abundance CHO trials were conducted to correct background shifts in breath CO2 production. Venous blood samples were taken to determine plasma glucose, lactate, and nonesterified fatty acid concentrations. Results Mean exogenous CHO oxidation rates were comparable with lactose (0.56 ± 0.19 g·min) and sucrose (0.61 ± 0.10 g·min; P = 0.49) ingestion. Endogenous CHO oxidation contributed less to energy expenditure in lactose (38% ± 14%) versus water (50% ± 11%, P = 0.01) and sucrose (50% ± 7%, P ≤ 0.05). Fat oxidation was higher in lactose (42% ± 8%) than in sucrose (28% ± 6%; P ≤ 0.01); CHO conditions were lower than water (50% ± 11%; P ≤ 0.05). Plasma glucose was higher in lactose and sucrose than in water (P ≤ 0.01); plasma lactate was higher in sucrose than in water (P ≤ 0.01); plasma nonesterified fatty acids were higher in water than in sucrose (P ≤ 0.01). Conclusions Lactose and sucrose exhibited similar exogenous CHO oxidation rates during exercise at moderate ingestion rates. Compared with sucrose ingestion, lactose resulted in higher fat and lower endogenous CHO oxidation.

Background: Current sports nutrition guidelines recommend athletes ingest carbohydrates at 1.0–1.2 g·kg−1·h−1 to optimize repletion of muscle glycogen during short-term recovery from endurance exercise. However, they do not provide specific advice on monosaccharides (e.g., fructose or glucose) other than to ingest carbohydrates of moderate to high glycaemic index. Recent evidence suggests that combined ingestion of fructose and glucose in recovery leads to enhanced liver glycogen synthesis and that this translates into improvement of subsequent endurance capacity. Purpose: The purpose of the present study was to investigate whether consuming a combination of fructose and glucose as opposed to glucose alone during short-term recovery (i.e., 4 h) from exhaustive exercise would also improve subsequent pre-loaded cycle time trial (TT) performance. Methods: Eight participants (seven men, one woman; V∙O2peak: 56.8 ± 5.0 mLO2·min−1·kg−1; Wmax: 352 ± 41 W) participated in this randomized double-blind study. Each experimental session involved a glycogen reducing exercise bout in the morning, a 4-h recovery period and 1-h of steady state (SS) exercise at 50% Wmax followed by a ~40-min simulated TT. During recovery carbohydrates were ingested at a rate of 1.2 g·kg−1·h−1 in the form of fructose and maltodextrin (FRU + MD) or dextrose and maltodextrin (GLU + MD) (both in 1:1.5 ratio). Substrate oxidation rates, including ingested carbohydrate oxidation, were determined during the steady state (SS). Blood samples were collected during recovery, during the SS exercise and at the end of the TT for determination of glucose and lactate concentrations. Results: There were no differences in TT performance [37.41 ± 3.45 (GLU + MD); 37.96 ± 5.20 min (FRU + MD), p = 0.547]. During the first 45-min of SS oxidation of ingested carbohydrates was greater in FRU + MD (1.86 ± 0.41 g−1·min−1 and 1.51 ± 0.37 g−1·min−1 for FRU + MD and GLU + MD, respectively; time x condition interaction p = 0.003) and there was a trend toward higher overall carbohydrate oxidation rates in FRU + MD (2.50 ± 0.36 g−1·min−1 and 2.31 ± 0.37 g−1·min−1 for FRU + MD and GLU + MD, respectively; p = 0.08). However, at 60-min of SS, differences in substrate oxidation disappeared. Conclusion: Ingestion of combined fructose and glucose compared to glucose only during recovery from an exhaustive exercise bout increased the ingested carbohydrate oxidation rate during subsequent exercise. Under the conditions studied, subsequent TT performance was not improved with fructose-glucose.

Training with low carbohydrate availability enhances endurance training adaptations but training volume may be compromised. We explored whole-body metabolism and performance with delayed carbohydrate feeding during exercise undertaken following acute sleep-low training. We hypothesised this strategy would not suppress fat oxidation and would maintain exercise performance. The study involved three experimental trials and included 9 men and 1 woman (⩒O

Maximizing carbohydrate availability is important for many endurance events. Combining pectin and sodium alginate with ingested maltodextrin-fructose (MAL + FRU + PEC + ALG) has been suggested to enhance carbohydrate delivery via hydrogel formation, but the influence on exogenous carbohydrate oxidation remains unknown. The primary aim of this study was to assess the effects of MAL + FRU + PEC + ALG on exogenous carbohydrate oxidation during exercise compared with a maltodextrin-fructose mixture (MAL + FRU). MAL + FRU has been well established to increase exogenous carbohydrate oxidation during cycling compared with glucose-based carbohydrates (MAL + GLU). However, much evidence focuses on cycling, and direct evidence in running is lacking. Therefore, a secondary aim was to compare exogenous carbohydrate oxidation rates with MAL + FRU versus MAL + GLU during running.Nine trained runners completed two trials (MAL + FRU and MAL + FRU + PEC + ALG) in a double-blind, randomized crossover design. A subset (n = 7) also completed a MAL + GLU trial to address the secondary aim, and a water trial to establish background expired CO2 enrichment. Participants ran at 60% V˙O2peak for 120 min while ingesting either water only or carbohydrate solutions at a rate of 1.5 g carbohydrate per minute.At the end of 120 min of exercise, exogenous carbohydrate oxidation rates were 0.9 (SD 0.5) g·min with MAL + GLU ingestion. MAL + FRU ingestion increased exogenous carbohydrate oxidation rates to 1.1 (SD 0.3) g·min (P = 0.038), with no further increase with MAL + FRU + PEC + ALG ingestion (1.1 (SD 0.3) g·min; P = 1.0). No time-treatment interaction effects were observed for plasma glucose, lactate, insulin, or nonesterified fatty acids, or for ratings of perceived exertion or gastrointestinal symptoms (all, P0.05).To maximize exogenous carbohydrate oxidation during moderate-intensity running, athletes may benefit from consuming glucose(polymer)-fructose mixtures over glucose-based carbohydrates alone, but the addition of pectin and sodium alginate offers no further benefit.

Lactose is a disaccharide of glucose and galactose, found exclusively in milk. Carbohydrates represent an important fuel for endurance and prolonged exercise. Recommendations for athletes include high carbohydrate diets to maximise performance, especially before, during and after exercise. However, lactose does not feature in guidelines for carbohydrate intake for athletes, despite athletes likely consuming nutritionally relevant amounts. This review explores possible applications for lactose in a sports nutrition context. These include lactose as a fuel source, for before and during exercise, where maximising availability of readily oxidisable carbohydrate can optimise performance. Lactose could play a role in a post-exercise recovery setting, as a vehicle for the delivery of glucose and galactose, for the optimisation of muscle and liver glycogen. Lactose may also act as a prebiotic, possibly promoting beneficial changes to gut microbiota. A discussion of the possible risks associated with lactose over-consumption and intolerance will also be considered.

Background: Substantial interindividual variability exists in the maximal rate of fat oxidation (MFO) during exercise with potential implications for metabolic health. Although the diet can affect the metabolic response to exercise, the contribution of a self-selected diet to the interindividual variability in the MFO requires further clarification.Objective: We sought to identify whether recent, self-selected dietary intake independently predicts the MFO in healthy men and women.Design: The MFO and maximal oxygen uptake ([Formula: see text]O2 max) were determined with the use of indirect calorimetry in 305 healthy volunteers [150 men and 155 women; mean ± SD age: 25 ± 6 y; body mass index (BMI; in kg/m2): 23 ± 2]. Dual-energy X-ray absorptiometry was used to assess body composition with the self-reported physical activity level (SRPAL) and dietary intake determined in the 4 d before exercise testing. To minimize potential confounding with typically observed sex-related differences (e.g., body composition), predictor variables were mean-centered by sex. In the analyses, hierarchical multiple linear regressions were used to quantify each variable's influence on the MFO.Results: The mean absolute MFO was 0.55 ± 0.19 g/min (range: 0.19-1.13 g/min). A total of 44.4% of the interindividual variability in the MFO was explained by the [Formula: see text]O2 max, sex, and SRPAL with dietary carbohydrate (carbohydrate; negative association with the MFO) and fat intake (positive association) associated with an additional 3.2% of the variance. When expressed relative to fat-free mass (FFM), the MFO was 10.8 ± 3.2 mg · kg FFM-1 · min-1 (range: 3.5-20.7 mg · kg FFM-1 · min-1) with 16.6% of the variability explained by the [Formula: see text]O2 max, sex, and SRPAL; dietary carbohydrate and fat intakes together explained an additional 2.6% of the variability. Biological sex was an independent determinant of the MFO with women showing a higher MFO [men: 10.3 ± 3.1 mg · kg FFM-1 · min-1 (3.5-19.9 mg · kg FFM-1 · min-1); women: 11.2 ± 3.3 mg · kg FFM-1 · min-1 (4.6-20.7 mg · kg FFM-1 · min-1); P < 0.05].Conclusion: Considered alongside other robust determinants, dietary carbohydrate and fat intake make modest but independent contributions to the interindividual variability in the capacity to oxidize fat during exercise. This trial was registered at clinicaltrials.gov as NCT02070055.

Regular physical activity (PA) promotes musculoskeletal health in older adults. However, the majority of older individuals do not meet current PA guidelines and are also highly sedentary. Emerging evidence indicates that large amounts of sedentary time accelerate the loss of skeletal muscle mass (i.e., sarcopenia) and physical function with advancing age. However, current PA recommendations for sedentary time are non-specific (i.e., keep sedentary time to a minimum). Research indicates that physical inactivity and large amounts of sedentary time accelerate sarcopenic muscle loss by inducing skeletal muscle 'anabolic resistance'. These findings suggest a critical interaction between engaging in 'sufficient' levels of PA, minimising sedentary time, and consuming 'adequate' nutrition to promote optimal musculoskeletal health in older adults. However, current PA recommendations do not take into account the important role that nutrition plays in ensuring older adults can maximise the benefits from the PA in which they engage. The aim of this narrative review is: (1) to briefly summarise the evidence used to inform current public health recommendations for PA and sedentary time in older adults; and (2) to discuss the presence of 'anabolic resistance' in older adults, highlighting the importance of regular PA and minimising sedentary behaviour. It is imperative that the synergy between PA, minimising sedentary behaviour and adequate nutrition is integrated into future PA guidelines to promote optimal musculoskeletal health and metabolic responses in the growing ageing population.

Context Pre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness. Objective To assess acute and chronic effects of exercise performed before versus after nutrient ingestion on whole-body and intramuscular lipid utilization and postprandial glucose metabolism. Design (1) Acute, randomized, crossover design (Acute Study); (2) 6-week, randomized, controlled design (Training Study). Setting General community. Participants Men with overweight/obesity (mean ± standard deviation, body mass index: 30.2 ± 3.5 kg⋅m-2 for Acute Study, 30.9 ± 4.5 kg⋅m-2 for Training Study). Interventions Moderate-intensity cycling performed before versus after mixed-macronutrient breakfast (Acute Study) or carbohydrate (Training Study) ingestion. Results Acute Study—exercise before versus after breakfast consumption increased net intramuscular lipid utilization in type I (net change: –3.44 ± 2.63% versus 1.44 ± 4.18% area lipid staining, P < 0.01) and type II fibers (–1.89 ± 2.48% versus 1.83 ± 1.92% area lipid staining, P < 0.05). Training Study—postprandial glycemia was not differentially affected by 6 weeks of exercise training performed before versus after carbohydrate intake (P > 0.05). However, postprandial insulinemia was reduced with exercise training performed before but not after carbohydrate ingestion (P = 0.03). This resulted in increased oral glucose insulin sensitivity (25 ± 38 vs –21 ± 32 mL⋅min-1⋅m-2; P = 0.01), associated with increased lipid utilization during exercise (r = 0.50, P = 0.02). Regular exercise before nutrient provision also augmented remodeling of skeletal muscle phospholipids and protein content of the glucose transport protein GLUT4 (P < 0.05). Conclusions Experiments investigating exercise training and metabolic health should consider nutrient-exercise timing, and exercise performed before versus after nutrient intake (ie, in the fasted state) may exert beneficial effects on lipid utilization and reduce postprandial insulinemia.

SUMMARYNAD+ is modulated by conditions of metabolic stress and has been reported to decline with aging, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome, and questioned if tissue NAD+ levels are depressed with aging. We supplemented 12 aged men with NR 1g per day for 21-days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways. NR also depressed levels of circulating inflammatory cytokines. In an additional study, 31P magnetic resonance spectroscopy-based NAD+ measurement in muscle and brain showed no difference between young and aged individuals. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR, while suggesting that NAD+ decline is not associated with chronological aging per se in human muscle or brain.

Supplementation with inulin-propionate ester (IPE), which delivers propionate to the colon, suppresses ad libitum energy intake and stimulates the release of satiety hormones acutely in humans, and prevents weight gain. In order to determine whether IPE remains effective when incorporated into food products (FP), IPE needs to be added to a widely accepted food system. A bread roll and fruit smoothie were produced. Twenty-one healthy overweight and obese humans participated. Participants attended an acclimatisation visit and a control visit where they consumed un-supplemented food products (FP). Participants then consumed supplemented-FP, containing 10 g/d inulin or IPE for six days followed by a post-supplementation visit in a randomised crossover design. On study visits, supplemented-FP were consumed for the seventh time and ad libitum energy intake was assessed 420 min later. Blood samples were collected to assess hormones and metabolites. Resting energy expenditure (REE) was measured using indirect calorimetry. Taste and appearance ratings were similar between FP. Ad libitum energy intake was significantly different between treatments, due to a decreased intake following IPE-FP. These observations were not related to changes in blood hormones and metabolites. There was an increase in REE following IPE-FP. However, this effect was lost after correcting for changes in fat free mass. Our results suggest that IPE suppresses appetite and may alter REE following its incorporation into palatable food products.

Purpose Across the lifespan, physical activity levels decrease and time spent sedentary typically increases. However, little is known about the impact that these behavioral changes have on skeletal muscle mass regulation. The primary aim of this study was to use a step reduction model to determine the impact of reduced physical activity and increased sedentary time on daily myofibrillar protein synthesis rates in healthy young men. Methods Eleven men (22 +/- 2 yr) completed 7 d of habitual physical activity (HPA) followed by 7 d of step reduction (SR). Myofibrillar protein synthesis rates were determined during HPA and SR using the deuterated water ((H2O)-H-2) method combined with the collection of skeletal muscle biopsies and daily saliva samples. Gene expression of selected proteins related to muscle mass regulation and oxidative metabolism were determined via real time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results Daily step count was reduced by approximately 91% during SR (from 13,054 +/- 2763 steps per day to 1192 +/- 330 steps per day; P

The aim of this study was to characterize postprandial glucose flux after exercise in the fed versus overnight fasted state and to investigate the potential underlying mechanisms. In a randomized order, twelve men underwent breakfast-rest [(BR) 3 h semirecumbent], breakfast-exercise [(BE) 2 h semirecumbent before 60 min of cycling (50% peak power output)], and overnight fasted exercise [(FE) as per BE omitting breakfast] trials. An oral glucose tolerance test (OGTT) was completed after exercise (after rest on BR). Dual stable isotope tracers ([U-13C] glucose ingestion and [6,6-2H2] glucose infusion) and muscle biopsies were combined to assess postprandial plasma glucose kinetics and intramuscular signaling, respectively. Plasma intestinal fatty acid binding (I-FABP) concentrations were determined as a marker of intestinal damage. Breakfast before exercise increased postexercise plasma glucose disposal rates during the OGTT, from 44 g/120 min in FE {35 to 53 g/120 min [mean (normalized 95% confidence interval)] to 73 g/120 min in BE [55 to 90 g/120 min; P = 0.01]}. This higher plasma glucose disposal rate was, however, offset by increased plasma glucose appearance rates (principally OGTT-derived), resulting in a glycemic response that did not differ between BE and FE ( P = 0.11). Plasma I-FABP concentrations during exercise were 264 pg/ml (196 to 332 pg/ml) lower in BE versus FE ( P = 0.01). Breakfast before exercise increases postexercise postprandial plasma glucose disposal, which is offset (primarily) by increased appearance rates of orally ingested glucose. Therefore, metabolic responses to fed-state exercise cannot be readily inferred from studies conducted in a fasted state.

Summary Nicotinamide adenine dinucleotide (NAD+) is modulated by conditions of metabolic stress and has been reported to decline with aging in preclinical models, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome and if it can alter muscle mitochondrial bioenergetics. We supplemented 12 aged men with 1 g NR per day for 21 days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways, without altering mitochondrial bioenergetics. NR also depressed levels of circulating inflammatory cytokines. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR., Graphical Abstract, Highlights • NR supplementation in aged subjects augments the skeletal muscle NAD+ metabolome • NR supplementation does not affect skeletal muscle mitochondrial bioenergetics • NR supplementation reduces levels of circulating inflammatory cytokines, Elhassan et al. show that oral nicotinamide riboside increases the NAD+ metabolome in aged human skeletal muscle, without apparently altering mitochondrial bioenergetics. Measures of muscle and whole-body metabolism are also unchanged. Nicotinamide riboside reduces the levels of circulating inflammatory cytokines. Studies in relevant human disease models are warranted.

The objective of this review paper is to evaluate the impact of undertaking aerobic exercise in the overnight-fastedv.fed-state, in the context of optimising the health benefits of regular physical activity. Conducting a single bout of aerobic exercise in the overnight-fastedv.fed-state can differentially modulate the aspects of metabolism and energy balance behaviours. This includes, but is not limited to, increased utilisation of fat as a fuel source, improved plasma lipid profiles, enhanced activation of molecular signalling pathways related to fuel metabolism in skeletal muscle and adipose tissue, and reductions in energy intake over the course of a day. The impact of a single bout of overnight-fastedv.fed-state exercise on short-term glycaemic control is variable, being affected by the experimental conditions, the time frame of measurement and possibly the subject population studied. The health response to undertaking overnight-fastedv.fed-state exercise for a sustained period of time in the form of exercise training is less clear, due to a limited number of studies. From the extant literature, there is evidence that overnight-fasted exercise in young, healthy men can enhance training-induced adaptations in skeletal muscle metabolic profile, and mitigate against the negative consequences of short-term excess energy intake on glucose tolerance compared with exercising in the fed-state. Nonetheless, further long-term studies are required, particularly in populations at-risk or living with cardio-metabolic disease to elucidate if feeding status prior to exercise modulates metabolism or energy balance behaviours to an extent that could impact upon the health or therapeutic benefits of exercise.

Disturbances in fat oxidation have been associated with an increased risk of obesity and metabolic disorders such as insulin resistance. There is large intersubject variability in the capacity to oxidize fat when a person is physically active, although the significance of this for metabolic health is unclear. We investigated whether the maximal capacity to oxidize fat during exercise is related to 24-h fat oxidation and insulin sensitivity. Maximal fat oxidation (MFO; indirect calorimetry during incremental exercise) and insulin sensitivity (Quantitative Insulin Sensitivity Check Index) were measured in 53 young, healthy men (age 24 ± 7 yr, V̇o2max 52 ± 6 ml·kg−1·min−1). Fat oxidation over 24 h (24-h FO; indirect calorimetry) was assessed in 16 young, healthy men (age 26 ± 8 yr, V̇o2max 52 ± 6 ml·kg−1·min−1) during a 36-h stay in a whole-room respiration chamber. MFO (g/min) was positively correlated with 24-h FO (g/day) ( R = 0.65, P = 0.003; R = 0.46, P = 0.041 when controlled for V̇o2max [l/min]), 24-h percent energy from FO ( R = 0.58, P = 0.009), and insulin sensitivity ( R = 0.33, P = 0.007). MFO (g/min) was negatively correlated with 24-h fat balance (g/day) ( R = −0.51, P = 0.021) but not significantly correlated with 24-h respiratory quotient ( R = −0.29, P = 0.142). Although additional investigations are needed, our data showing positive associations between MFO and 24-h FO, and between MFO and insulin sensitivity in healthy young men suggests that a high capacity to oxidize fat while one is physically active could be advantageous for the maintenance of metabolic health.

The ingestion of intact protein or essential amino acids (EAA) stimulates mechanistic target of rapamycin complex-1 (mTORC1) signaling and muscle protein synthesis (MPS) following resistance exercise. The purpose of this study was to investigate the response of myofibrillar-MPS to ingestion of branched-chain amino acids (BCAAs) only (i.e., without concurrent ingestion of other EAA, intact protein, or other macronutrients) following resistance exercise in humans. Ten young (20.1 ± 1.3 years), resistance-trained men completed two trials, ingesting either 5.6 g BCAA or a placebo (PLA) drink immediately after resistance exercise. Myofibrillar-MPS was measured during exercise recovery with a primed, constant infusion of L-[ring13C6] phenylalanine and collection of muscle biopsies pre and 4 h-post drink ingestion. Blood samples were collected at time-points before and after drink ingestion. Western blotting was used to measure the phosphorylation status of mTORC1 signaling proteins in biopsies collected pre, 1-, and 4 h-post drink. The percentage increase from baseline in plasma leucine (300 ± 96%), isoleucine (300 ± 88%), and valine (144 ± 59%) concentrations peaked 0.5 h-post drink in BCAA. A greater phosphorylation status of S6K1Thr389 (P = 0.017) and PRAS40 (P = 0.037) was observed in BCAA than PLA at 1 h-post drink ingestion. Myofibrillar-MPS was 22% higher (P = 0.012) in BCAA (0.110 ± 0.009%/h) than PLA (0.090 ± 0.006%/h). Phenylalanine Ra was ~6% lower in BCAA (18.00 ± 4.31 μmol·kgBM-1) than PLA (21.75 ± 4.89 μmol·kgBM-1; P = 0.028) after drink ingestion. We conclude that ingesting BCAAs alone increases the post-exercise stimulation of myofibrillar-MPS and phosphorylation status mTORC1 signaling.

AimsDiet-derived short chain fatty acids (SCFAs) improve glucose homeostasis in vivo, but the role of individual SCFAs and their mechanisms of action have not been defined. This study evaluated the effects of increasing colonic delivery of the SCFA propionate on β-cell function in humans and the direct effects of propionate on isolated human islets in vitro.Materials and MethodsFor 24 weeks human subjects ingested an inulin-propionate ester that delivers propionate to the colon. Acute insulin, GLP-1 and non-esterified fatty acid (NEFA) levels were quantified pre- and post-supplementation in response to a mixed meal test. Expression of the SCFA receptor FFAR2 in human islets was determined by western blotting and immunohistochemistry. Dynamic insulin secretion from perifused human islets was quantified by radioimmunoassay and islet apoptosis was determined by quantification of caspase 3/7 activities.ResultsColonic propionate delivery in vivo was associated with improved β-cell function with increased insulin secretion that was independent of changes in GLP-1 levels. Human islet β-cells expressed FFAR2 and propionate potentiated dynamic glucose-stimulated insulin secretion in vitro, an effect that was dependent on signalling via protein kinase C. Propionate also protected human islets from apoptosis induced by the NEFA sodium palmitate and inflammatory cytokines.ConclusionsOur results indicate that propionate has beneficial effects on β-cell function in vivo, and in vitro analyses demonstrated that it has direct effects to potentiate glucose-stimulated insulin release and maintain β-cell mass through inhibition of apoptosis. These observations support ingestion of propiogenic dietary fibres to maintain healthy glucose homeostasis.

Summary: Nicotinamide adenine dinucleotide (NAD+) is modulated by conditions of metabolic stress and has been reported to decline with aging in preclinical models, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome and if it can alter muscle mitochondrial bioenergetics. We supplemented 12 aged men with 1 g NR per day for 21 days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways, without altering mitochondrial bioenergetics. NR also depressed levels of circulating inflammatory cytokines. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR. : Elhassan et al. show that oral nicotinamide riboside increases the NAD+ metabolome in aged human skeletal muscle, without apparently altering mitochondrial bioenergetics. Measures of muscle and whole-body metabolism are also unchanged. Nicotinamide riboside reduces the levels of circulating inflammatory cytokines. Studies in relevant human disease models are warranted. Keywords: nicotinamide adenine dinucleotide, metabolism, aging, inflammation, cell adhesion

The extent to which dietary supplementation with the nitric oxide synthase (NOS) substrate, l-arginine (ARG), impacts on NO production and NO-mediated physiological responses is controversial. This randomised, double blinded, cross-over study investigated the effects of acute ARG supplementation on NO biomarkers, O2 cost of exercise and exercise tolerance in humans. In one experiment, 15 subjects completed moderate- and severe-intensity running bouts after acute supplementation with 6 g ARG or placebo (PLA). In another experiment, eight subjects completed moderate- and severe-intensity cycling bouts after acute supplementation with 6 g ARG plus 25 g of carbohydrate (ARG + CHO) or an energy-matched dose of carbohydrate alone (CHO). The plasma nitrite concentration was not different after ARG (Pre: 204 ± 79; Post: 241 ± 114 nM; P > 0.05) or ARG + CHO consumption (Pre: 304 ± 57; Post: 335 ± 116 nM; P > 0.05). During moderate-intensity exercise, the steady-state pulmonary $$ \dot{V}{\text{O}}_{2} $$ was not different, relative to the respective placebo conditions, after ARG (PLA: 2,407 ± 318, ARG: 2,422 ± 333 mL min−1) or ARG + CHO (CHO: 1,695 ± 304, ARG + CHO: 1,712 ± 312 mL min−1) ingestion (P > 0.05). The tolerable duration of severe exercise was also not significantly different (P > 0.05) after ingesting ARG (PLA: 551 ± 140, ARG: 552 ± 150 s) or ARG + CHO (CHO: 457 ± 182, ARG + CHO: 441 ± 221 s). In conclusion, acute dietary supplementation with ARG or ARG + CHO did not alter biomarkers of NO synthesis, O2 cost of exercise or exercise tolerance in healthy subjects.

The currently accepted amount of protein required to achieve maximal stimulation of myofibrillar protein synthesis (MPS) following resistance exercise is 20-25 g. However, the influence of lean body mass (LBM) on the response of MPS to protein ingestion is unclear. Our aim was to assess the influence of LBM, both total and the amount activated during exercise, on the maximal response of MPS to ingestion of 20 or 40 g of whey protein following a bout of whole-body resistance exercise. Resistance-trained males were assigned to a group with lower LBM (≤65 kg; LLBM n = 15) or higher LBM (≥70 kg; HLBM n = 15) and participated in two trials in random order. MPS was measured with the infusion of (13)C6-phenylalanine tracer and collection of muscle biopsies following ingestion of either 20 or 40 g protein during recovery from a single bout of whole-body resistance exercise. A similar response of MPS during exercise recovery was observed between LBM groups following protein ingestion (20 g - LLBM: 0.048 ± 0.018%·h(-1); HLBM: 0.051 ± 0.014%·h(-1); 40 g - LLBM: 0.059 ± 0.021%·h(-1); HLBM: 0.059 ± 0.012%·h(-1)). Overall (groups combined), MPS was stimulated to a greater extent following ingestion of 40 g (0.059 ± 0.020%·h(-1)) compared with 20 g (0.049 ± 0.020%·h(-1); P = 0.005) of protein. Our data indicate that ingestion of 40 g whey protein following whole-body resistance exercise stimulates a greater MPS response than 20 g in young resistance-trained men. However, with the current doses, the total amount of LBM does not seem to influence the response.

The maximal capacity to oxidize fat during exercise (MFO) is associated with 24-h fat balance and insulin sensitivity. Understanding factors that influence MFO could have implications for metabolic health. We investigated relationships between selected plasma metabolites, hormones and overnight-fasted resting fat oxidation rates (Resting), with MFO. Resting fat oxidation and MFO was measured in 57 men with blood collected at rest and during exercise. Plasma glycerol (R=0.39, P=0.033), non-esterified fatty acids (NEFA: R=0.27, P=0.030) and insulin (R=− 0.36, P=0.007) measured at MFO correlated with MFO; only glycerol remained correlated when controlled for resting concentrations (R=0.36, P=0.008). The change in glycerol from rest to MFO correlated with exercise-induced fat oxidation (R=0.32, P=0.012). V˙O 2max correlated with resting fat oxidation (R=0.44, P=0.001) and MFO (R=0.52, P

For unknown reasons, interval training often reduces body weight more than energy-expenditure matched continuous training. We compared the acute effects of time-duration and oxygen-consumption matched interval- vs. continuous exercise on excess post-exercise oxygen consumption (EPOC), substrate oxidation rates and lipid metabolism in the hours following exercise in subjects with type 2 diabetes (T2D).Following an overnight fast, ten T2D subjects (M/F: 7/3; age=60.3±2.3years; body mass index (BMI)=28.3±1.1kg/m(2)) completed three 60-min interventions in a counterbalanced, randomized order: 1) control (CON), 2) continuous walking (CW), 3) interval-walking (IW - repeated cycles of 3min of fast and 3min of slow walking). Indirect calorimetry was applied during each intervention and repeatedly for 30min per hour during the following 5h. A liquid mixed meal tolerance test (MMTT, 450kcal) was consumed by the subjects 45min after completion of the intervention with blood samples taken regularly.Exercise interventions were successfully matched for total oxygen consumption (CW=1641±133mL/min; IW=1634±126mL/min, P0.05). EPOC was higher after IW (8.4±1.3l) compared to CW (3.7±1.4l, P0.05). Lipid oxidation rates were increased during the MMTT in IW (1.03±0.12mg/kg per min) and CW (0.87±0.04mg/kg per min) compared with CON (0.73±0.04mg/kg per min, P0.01 and P0.05, respectively), with no difference between IW and CW. Moreover, free fatty acids and glycerol concentrations, and glycerol kinetics were increased comparably during and after IW and CW compared to CON.Interval exercise results in greater EPOC than oxygen-consumption matched continuous exercise during a post-exercise MMTT in subjects with T2D, whereas effects on substrate oxidation and lipid metabolism are comparable.