Co-Ingestion of Branched-Chain Amino Acids and Carbohydrate Stimulates Myofibrillar Protein Synthesis Following Resistance Exercise in Trained Young Men.

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.

Nicotinamide riboside supplementation does not alter whole-body or skeletal muscle metabolic responses to a single bout of endurance exercise.

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, V̇O2peak 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.

Pectin-Alginate Does Not Further Enhance Exogenous Carbohydrate Oxidation in Running.

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.

Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures.

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.

Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial.

OBJECTIVE: To 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. DESIGN: Twelve 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. RESULTS: Both 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. CONCLUSION: These 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.

Effects of Inulin Propionate Ester Incorporated into Palatable Food Products on Appetite and Resting Energy Expenditure: A Randomised Crossover Study.

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.

No effect of acute L-arginine supplementation on O2 cost or exercise tolerance.

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 VO2 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.