High-fat ketogenic diets and ketone monoester supplements differentially affect substrate metabolism during aerobic exercise.

Chronically adhering to high-fat ketogenic diets or consuming ketone monoester supplements elicits ketosis. Resulting changes in substrate metabolism appear to be drastically different between ketogenic diets and ketone supplements. Consuming a ketogenic diet increases fatty acid oxidation with concomitant decreases in endogenous carbohydrate oxidation. Increased fat oxidation eventually results in an accumulation of circulating ketone bodies, which are metabolites of fatty acids that serve as an alternative source of fuel. Conversely, consuming ketone monoester supplements rapidly increases circulating ketone body concentrations that typically exceed those achieved by adhering to ketogenic diets. Rapid increases in ketone body concentrations with ketone monoester supplementation elicit a negative feedback inhibition that reduces fatty acid mobilization during aerobic exercise. Supplement-derived ketosis appears to have minimal impact on sparing of muscle glycogen or minimizing of carbohydrate oxidation during aerobic exercise. This review will discuss the substrate metabolic and associated aerobic performance responses to ketogenic diets and ketone supplements.

Performance nutrition for cold-weather military operations.

.High daily energy expenditure without compensatory increases in energy intake results in severe energy deficits during cold-weather military operations. The severity of energy deficits has been proportionally linked to declines in body mass, negative protein balance, suppression of androgen hormones, increases in systemic inflammation and degraded physical performance. Food availability does not appear to be the predominant factor causing energy deficits; providing additional rations or supplement snack bars does not reduce the severity of the energy deficits. Nutrition interventions that allow greater energy intake could be effective for reducing energy deficits during cold-weather military operations. One potential intervention is to increase energy density (i.e. energy per unit mass of food) by increasing dietary fat. Our laboratory recently reported that self-selected higher energy intakes and reductions in energy deficits were primarily driven by fat intake (r = 0.891, r2 = 0.475), which, of the three macronutrients. Further, soldiers who ate more fat lost less body mass, had lower inflammation, and maintained net protein balance compared to those who ate less fat. These data suggest that consuming high-fat energy-dense foods may be a viable nutritional intervention that mitigates the negative physiological effects of energy deficit and sustains physical performance during cold-weather military operations.

Ketone Monoester Plus Carbohydrate Supplementation Does Not Alter Exogenous and Plasma Glucose Oxidation or Metabolic Clearance Rate During Exercise in Men Compared with Carbohydrate Alone.

BACKGROUND: Increasing ß-hydroxybutyrate (ßHB) availability through ketone monoester (KE) plus carbohydrate supplementation is suggested to enhance physical performance by sparing glucose use during exercise. However, no studies have examined the effect of ketone supplementation on glucose kinetics during exercise. OBJECTIVES: This exploratory study primarily aimed to determine the effect of KE plus carbohydrate supplementation on glucose oxidation during steady-state exercise and physical performance compared with carbohydrate alone. METHODS: Using a randomly assigned, crossover design, 12 men consumed 573 mg KE/kg body mass plus 110 g glucose (KE+CHO) or 110 g glucose (CHO) before and during 90 min of steady-state treadmill exercise [54 ± 3% peak oxygen uptake (V˙O2peak)] wearing a weighted vest (30% body mass; 25 ± 3 kg). Glucose oxidation and turnover were determined using indirect calorimetry and stable isotopes. Participants performed an unweighted time to exhaustion (TTE; 85% V˙O2peak) after steady-state exercise and a weighted (25 ± 3 kg) 6.4 km time trial (TT) the next day after consuming a bolus of KE+CHO or CHO. Data were analyzed by paired t-tests and mixed model ANOVA. RESULTS: ßHB concentrations were higher (P < 0.05) after exercise [2.1 mM (95% CI: 1.6, .6)] and the TT [2.6 mM (2.1, 3.1)] in KE+CHO compared with CHO. TTE was lower [-104 s (-201, -8)], and TT performance was slower [141 s (19,262)] in KE+CHO than in CHO (P < 0.05). Exogenous [-0.01 g/min (-0.07, 0.04)] and plasma [-0.02 g/min (-0.08, 0.04)] glucose oxidation and metabolic clearance rate {MCR [0.38 mg·kg-1·min-1 (-0.79, 1.54)]} were not different, and glucose rate of appearance [-0.51 mg·kg-1·min-1 (-0.97, -0.04)], and disappearance [-0.50 mg·kg-1·min-1 (-0.96, -0.04)] were lower (P < 0.05) in KE+CHO compared with CHO during steady-state exercise. CONCLUSIONS: In the current study, rates of exogenous and plasma glucose oxidation and MCR were not different between treatments during steady-state exercise, suggesting blood glucose utilization is similar between KE+CHO and CHO. KE+CHO supplementation also results in lower physical performance compared with CHO alone. This trial was registered at www. CLINICALTRIALS: gov as NCT04737694.

Essential amino acid-enriched whey enhances post-exercise whole-body protein balance during energy deficit more than iso-nitrogenous whey or a mixed-macronutrient meal: a randomized, crossover study.

BACKGROUND: The effects of ingesting varying essential amino acid (EAA)/protein-containing food formats on protein kinetics during energy deficit are undetermined. Therefore, recommendations for EAA/protein food formats necessary to optimize both whole-body protein balance and muscle protein synthesis (MPS) during energy deficit are unknown. We measured protein kinetics after consuming iso-nitrogenous amounts of free-form essential amino acid-enriched whey (EAA + W; 34.7 g protein, 24 g EAA sourced from whey and free-form EAA), whey (WHEY; 34.7 g protein, 18.7 g EAA), or a mixed-macronutrient meal (MEAL; 34.7 g protein, 11.4 g EAA) after exercise during short-term energy deficit. METHODS: Ten adults (mean ± SD; 21 ± 4 y; 25.7 ± 1.7 kg/m2) completed a randomized, double-blind crossover study consisting of three, 5 d energy-deficit periods (- 30 ± 3% of total energy requirements), separated by 14 d. Whole-body protein synthesis (PS), breakdown (PB), and net balance (NET) were determined at rest and in response to combination exercise consisting of load carriage treadmill walking, deadlifts, and box step-ups at the end of each energy deficit using L-[2H5]-phenylalanine and L-[2H2]-tyrosine infusions. Treatments were ingested immediately post-exercise. Mixed-muscle protein synthesis (mixed-MPS) was measured during exercise through recovery. RESULTS: Change (Δ postabsorptive + exercise to postprandial + recovery [mean treatment difference (95%CI)]) in whole-body (g/180 min) PS was 15.8 (9.8, 21.9; P = 0.001) and 19.4 (14.8, 24.0; P = 0.001) greater for EAA + W than WHEY and MEAL, respectively, with no difference between WHEY and MEAL. ΔPB was - 6.3 (- 11.5, - 1.18; P = 0.02) greater for EAA + W than WHEY and - 7.7 (- 11.9, - 3.6; P = 0.002) greater for MEAL than WHEY, with no difference between EAA + W and MEAL. ΔNET was 22.1 (20.5, 23.8; P = 0.001) and 18.0 (16.5, 19.5; P = 0.00) greater for EAA + W than WHEY and MEAL, respectively, while ΔNET was 4.2 (2.7, 5.6; P = 0.001) greater for MEAL than WHEY. Mixed-MPS did not differ between treatments. CONCLUSIONS: While mixed-MPS was similar across treatments, combining free-form EAA with whey promotes greater whole-body net protein balance during energy deficit compared to iso-nitrogenous amounts of whey or a mixed-macronutrient meal. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier no. NCT04004715 . Retrospectively registered 28 June 2019, first enrollment 6 June 2019.

Utility of Ketone Supplementation to Enhance Physical Performance: A Systematic Review.

Ingesting exogenous ketone bodies has been touted as producing ergogenic effects by altering substrate metabolism; however, research findings from recent studies appear inconsistent. This systematic review aimed to aggregate data from the current literature to examine the impact of consuming ketone supplements on enhancing physical performance. A systematic search was performed for randomized controlled trials that measured physical performance outcomes in response to ingesting exogenous ketone supplements compared with a control (nutritive or non-nutritive) in humans. A total of 161 articles were screened. Data were extracted from 10 eligible studies (112 participants; 109 men, 3 women ) containing 16 performance outcomes [lower-body power (n = 8) and endurance performance (n = 8)]. Ketone supplements were grouped as ketone esters (n = 8) or ketone salts/precursors (n = 8). Of the 16 performance outcomes identified by the systematic review, 3 reported positive, 10 reported null, and 3 reported negative effects of ketone supplementation on physical performance compared with controls. Heterogeneity was detected for lower-body power ( Q = 40, I2 = 83%, P < 0.01) and endurance performance (Q = 95, I2 = 93%, P < 0.01) between studies. Similarly high levels of heterogeneity were detected in studies providing ketone esters (Q = 111, I2 = 93%, P < 0.01), and to a lesser extent studies with ketone salts/precursors (Q = 25, I2 = 72%, P < 0.01). Heterogeneity across studies makes it difficult to conclude any benefit or detriment to consuming ketone supplements on physical performance. This systematic review discusses factors within individual studies that may contribute to discordant outcomes across investigations to elucidate if there is sufficient evidence to warrant recommendation of consuming exogenous ketone supplements to enhance physical performance.

Effects of testosterone supplementation on body composition and lower-body muscle function during severe exercise- and diet-induced energy deficit: A proof-of-concept, single centre, randomised, double-blind, controlled trial.

BACKGROUND: Severe energy deficits during military operations, produced by significant increases in exercise and limited dietary intake, result in conditions that degrade lean body mass and lower-body muscle function, which may be mediated by concomitant reductions in circulating testosterone. METHODS: We conducted a three-phase, proof-of-concept, single centre, randomised, double-blind, placebo-controlled trial (CinicalTrials.gov, NCT02734238) of non-obese men: 14-d run-in, free-living, eucaloric diet phase; 28-d live-in, 55% exercise- and diet-induced energy deficit phase with (200 mg testosterone enanthate per week, Testosterone, n = 24) or without (Placebo, n = 26) exogenous testosterone; and 14-d recovery, free-living, ad libitum diet phase. Body composition was the primary end point; secondary endpoints included lower-body muscle function and health-related biomarkers. FINDINGS: Following energy deficit, lean body mass increased in Testosterone and remained stable in Placebo, such that lean body mass significantly differed between groups [mean difference between groups (95% CI), 2.5 kg (3.3, 1.6); P < .0001]. Fat mass decreased similarly in both treatment groups [0.2 (-0.4, 0.7), P = 1]. Change in lean body mass was associated with change in total testosterone (r = 0.71, P < .0001). Supplemental testosterone had no effect on lower-body muscle function or health-related biomarkers. INTERPRETATION: Findings suggest that supplemental testosterone may increase lean body mass during short-term severe energy deficit in non-obese, young men, but it does not appear to attenuate lower-body functional decline. FUNDING: Collaborative Research to Optimize Warfighter Nutrition projects I and II, Joint Program Committee-5, funded by the US Department of Defence.

Pilot Study Examining the Influence of Potassium Bicarbonate Supplementation on Nitrogen Balance and Whole-Body Ammonia and Urea Turnover Following Short-Term Energy Restriction in Older Men.

With aging there is a chronic low-grade metabolic-acidosis that may exacerbate negative protein balance during weight loss. The objective of this randomized pilot study was to assess the impact of 90 mmol∙day-1 potassium bicarbonate (KHCO3) versus a placebo (PLA) on 24-h urinary net acid excretion (NAE), nitrogen balance (NBAL), and whole-body ammonia and urea turnover following short-term diet-induced weight loss. Sixteen (KHCO3; n = 8, PLA; n = 8) older (64 ± 4 years) overweight (BMI: 28.5 ± 2.1 kg∙day-1) men completed a 35-day controlled feeding study, with a 7-day weight-maintenance phase followed by a 28-day 30% energy-restriction phase. KHCO3 or PLA supplementation began during energy restriction. NAE, NBAL, and whole-body ammonia and urea turnover (15N-glycine) were measured at the end of the weight-maintenance and energy-restriction phases. Following energy restriction, NAE was -9.8 ± 27.8 mmol∙day-1 in KHCO3 and 43.9 ± 27.8 mmol∙day-1 in PLA (p < 0.05). No significant group or time differences were observed in NBAL or ammonia and urea turnover. Ammonia synthesis and breakdown tended (p = 0.09) to be higher in KHCO3 vs. PLA following energy restriction, and NAE was inversely associated (r = -0.522; p < 0.05) with urea synthesis in all subjects. This pilot study suggests some benefit may exist with KHCO3 supplementation following energy restriction as lower NAE indicated higher urea synthesis.

Effects of Potassium Bicarbonate Supplements on Circulating microRNA Expression.

Several studies suggest that neutralizing acid load in the diet with alkali had favorable effects on intermediate markers of musculoskeletal health. We examined whether alkali supplementation with potassium bicarbonate [(KHCO3); 81 mmol/d; n = 12] vs placebo (n = 12) for 84 days altered serum microRNAs, potential biomarkers associated with innumerable biological processes including bone and muscle metabolism. Serum microRNAs, urinary net acid excretion (UNAE), urinary N-telopeptide (UNTX), urinary calcium (UCa), urinary nitrogen (UN), glomerular filtration rate, serum procollagen type 1 amino-terminal propeptide (P1NP), serum insulin-like growth factor-1 (IGF-1), and its serum binding protein IGFBP3 were measured at baseline and day 84. Baseline characteristics and measurements were similar in the two treatment groups. Eighty-four-day changes in UNAE differed by group (KHCO3, -47 ± 9 mmol; placebo, -5 ± 5 mmol; P < 0.01). KHCO3 significantly reduced UNTX, UCa, and serum P1NP but did not affect UN, serum IGF-1, or IGFBP3 levels compared with placebo over 84 days. Fold change in serum circulating microRNA (c-miR)-133b differed significantly by group (KHCO3, 2.26 ± 0.85; placebo, -1.23 ± 0.69; P < 0.01); there was a similar trend in c-miR-21-5p. Fold changes in c-miR-133b and c-miR-21-5p were inversely associated with changes in UNAE and UNTX; fold change in c-miR-21-5p was inversely associated with change in UCa, with a similar trend with c-miR-133b. In summary, reducing renal acid load with KHCO3 was associated with increased expressions of c-miR-133b and c-miR-21-5p. Furthermore, increases in c-miRNA-133b and c-miR-21-5p were inversely associated with bone resorption markers UNTX and UCa consistent with potential beneficial effects on bone in older adults. However, the broader significance of c-miRNAs as musculoskeletal biomarkers is still under investigation, and larger studies are needed to verify these preliminary results.

Effects of Combat Deployment on Anthropometrics and Physiological Status of U.S. Army Special Operations Forces Soldiers.

INTRODUCTION: U.S. Army Special Operations Forces (SOF) soldiers deploy frequently and conduct military operations through special warfare and surgical strike capabilities. Tasks required to execute these capabilities may induce physical and mental stress and have the potential to degrade soldier physiological status. No investigations have longitudinally characterized whether combat deployment alters anthropometrics or biochemical markers of physiological status in a SOF population of frequent deployers. MATERIALS AND METHODS: Effects of modern combat deployment on longitudinal changes in anthropometrics and physiological status of elite U.S. Army SOF soldiers (n = 50) were assessed. Changes in measures of body composition, grip strength, physiological status, and health behaviors from baseline to postdeployment were determined with paired t test and McNemar's statistic. Baseline measures were obtained between 4 and 8 weeks before deployment. Deployment length was a uniform duration of time between 3 and 6 months (all soldiers completed the same length of deployment). Post hoc analyses determined change in body mass within quartiles of baseline body mass with paired t test and associations between change in sex hormone-binding globulin (SHBG) and change in body mass with correlation coefficient. The study was approved by the Human Use Review Committee at the U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts. RESULTS: In response to deployment, increases in lean mass (77.1 ± 7.6 to 77.8 ± 7.5 kg), maximum grip strength (57.9 ± 7.2 to 61.6 ± 8.8 kg), and conduct of aerobic (156 ± 106 to 250 ± 182 minutes/week) and strength training (190 ± 101 to 336 ± 251 minutes/week) exercise were observed (p < 0.05). Increases in serum SHBG (35.42 ± 10.68 to 38.77 ± 12.26 nmol/L) and decreases in serum cortisol (443.2 ± 79.3 to 381.9 ± 111.6 nmol/L) were also observed (p < 0.05). Body mass changes were dependent on baseline body mass. Soldiers in the lowest quartile of baseline body mass increased body mass (75.6 ± 2.6 vs. 76.6 ± 2.8 kg, p = 0.03), as did those in the second quartile (81.6 ± 2.0 vs. 83.7 ± 3.5 kg, p = 0.02). Those in the third quartile also tended to increase body mass (89.2 ± 2.6 vs. 90.9 ± 3.3 kg, p = 0.05), while those in the upper quartile tended to decrease body mass (98.5 ± 3.6 vs. 96.7 kg, p = 0.06). Change in SHBG was inversely correlated with change in body mass (r = -0.33, p = 0.02). There were no changes in fat mass, body fat percentage, waist circumference, neck circumference, total testosterone, calculated bioavailable or free testosterone, high-sensitivity C-reactive protein, tumor necrosis factor-α, interleukin-1ß, or interleukin-6. Inflammatory markers were skewed toward lower values. CONCLUSIONS: Overall, physiological status of elite SOF soldiers characterized by multiple prior deployments was minimally impacted by combat deployment, in the absence of major unit casualties. The majority experienced some adaptive changes, including increased lean mass, grip strength, time spent engaged in exercise, and decreased levels of the stress hormone cortisol. Mechanisms contributing to inverse correlations between change in SHBG and change in body mass may be further clarified. Future investigations may also more fully characterize the degradation and optimization of health and physiological status of SOF training and deployment cycles with in-theater data collection and repeated measures.

Effects of exercise mode, energy, and macronutrient interventions on inflammation during military training.

Load carriage (LC) exercise may exacerbate inflammation during training. Nutritional supplementation may mitigate this response by sparing endogenous carbohydrate stores, enhancing glycogen repletion, and attenuating negative energy balance. Two studies were conducted to assess inflammatory responses to acute LC and training, with or without nutritional supplementation. Study 1: 40 adults fed eucaloric diets performed 90-min of either LC (treadmill, mean ± SD 24 ± 3 kg LC) or cycle ergometry (CE) matched for intensity (2.2 ± 0.1 VO2peak L min(-1)) during which combined 10 g protein/46 g carbohydrate (223 kcal) or non-nutritive (22 kcal) control drinks were consumed. Study 2: 73 Soldiers received either combat rations alone or supplemented with 1000 kcal day(-1) from 20 g protein- or 48 g carbohydrate-based bars during a 4-day, 51 km ski march (~45 kg LC, energy expenditure 6155 ± 515 kcal day(-1) and intake 2866 ± 616 kcal day(-1)). IL-6, hepcidin, and ferritin were measured at baseline, 3-h post exercise (PE), 24-h PE, 48-h PE, and 72-h PE in study 1, and before (PRE) and after (POST) the 4-d ski march in study 2. Study 1: IL-6 was higher 3-h and 24-h post exercise (PE) for CE only (mode × time, P < 0.05), hepcidin increased 3-h PE and recovered by 48-h, and ferritin peaked 24-h and remained elevated 72-h PE (P < 0.05), regardless of mode and diet. Study 2: IL-6, hepcidin and ferritin were higher (P < 0.05) after training, regardless of group assignment. Energy expenditure (r = 0.40), intake (r = -0.26), and balance (r = -0.43) were associated (P < 0.05) with hepcidin after training. Inflammation after acute LC and CE was similar and not affected by supplemental nutrition during energy balance. The magnitude of hepcidin response was inversely related to energy balance suggesting that eating enough to balance energy expenditure might attenuate the inflammatory response to military training.

Effects of Supplemental Energy on Protein Balance during 4-d Arctic Military Training.

UNLABELLED: Soldiers often experience negative energy balance during military operations that diminish whole-body protein retention, even when dietary protein is consumed within recommended levels (1.5-2.0 g·kg·d). PURPOSE: The objective of this study is to determine whether providing supplemental nutrition spares whole-body protein by attenuating the level of negative energy balance induced by military training and to assess whether protein balance is differentially influenced by the macronutrient source. METHODS: Soldiers participating in 4-d arctic military training (AMT) (51-km ski march) were randomized to receive three combat rations (CON) (n = 18), three combat rations plus four 250-kcal protein-based bars (PRO, 20 g protein) (n = 28), or three combat rations plus four 250-kcal carbohydrate-based bars daily (CHO, 48 g carbohydrate) (n = 27). Energy expenditure (D2O) and energy intake were measured daily. Nitrogen balance (NBAL) and protein turnover were determined at baseline (BL) and day 3 of AMT using 24-h urine and [N]-glycine. RESULTS: Protein and carbohydrate intakes were highest (P < 0.05) for PRO (mean ± SD, 2.0 ± 0.3 g·kg·d) and CHO (5.8 ± 1.3 g·kg·d), but only CHO increased (P < 0.05) energy intake above CON. Energy expenditure (6155 ± 515 kcal·d), energy balance (-3313 ± 776 kcal·d), net protein balance (NET) (-0.24 ± 0.60 g·d), and NBAL (-68.5 ± 94.6 mg·kg·d) during AMT were similar between groups. In the combined cohort, energy intake was associated (P < 0.05) with NET (r = 0.56) and NBAL (r = 0.69), and soldiers with the highest energy intake (3723 ± 359 kcal·d, 2.11 ± 0.45 g protein·kg·d, 6.654 ± 1.16 g carbohydrate·kg·d) achieved net protein balance and NBAL during AMT. CONCLUSION: These data reinforce the importance of consuming sufficient energy during periods of high energy expenditure to mitigate the consequences of negative energy balance and attenuate whole-body protein loss.

Human Muscle Protein Synthetic Responses during Weight-Bearing and Non-Weight-Bearing Exercise: A Comparative Study of Exercise Modes and Recovery Nutrition.

Effects of conventional endurance (CE) exercise and essential amino acid (EAA) supplementation on protein turnover are well described. Protein turnover responses to weighted endurance exercise (i.e., load carriage, LC) and EAA may differ from CE, because the mechanical forces and contractile properties of LC and CE likely differ. This study examined muscle protein synthesis (MPS) and whole-body protein turnover in response to LC and CE, with and without EAA supplementation, using stable isotope amino acid tracer infusions. Forty adults (mean ± SD, 22 ± 4 y, 80 ± 10 kg, VO 2peak 4.0 ± 0.5 L ∙ min(-1)) were randomly assigned to perform 90 min, absolute intensity-matched (2.2 ± 0.1 VO2 L ∙ m(-1)) LC (performed on a treadmill wearing a vest equal to 30% of individual body mass, mean ± SD load carried 24 ± 3 kg) or CE (cycle ergometry performed at the same absolute VO2 as LC) exercise, during which EAA (10 g EAA, 3.6 g leucine) or control (CON, non-nutritive) drinks were consumed. Mixed-muscle and myofibrillar MPS were higher during exercise for LC than CE (mode main effect, P < 0.05), independent of dietary treatment. EAA enhanced mixed-muscle and sarcoplasmic MPS during exercise, regardless of mode (drink main effect, P < 0.05). Mixed-muscle and sarcoplasmic MPS were higher in recovery for LC than CE (mode main effect, P < 0.05). No other differences or interactions (mode x drink) were observed. However, EAA attenuated whole-body protein breakdown, increased amino acid oxidation, and enhanced net protein balance in recovery compared to CON, regardless of exercise mode (P < 0.05). These data show that, although whole-body protein turnover responses to absolute VO2-matched LC and CE are the same, LC elicited a greater muscle protein synthetic response than CE.

Optimizing intramuscular adaptations to aerobic exercise: effects of carbohydrate restriction and protein supplementation on mitochondrial biogenesis.

Mitochondrial biogenesis is a critical metabolic adaptation to aerobic exercise training that results in enhanced mitochondrial size, content, number, and activity. Recent evidence has shown that dietary manipulation can further enhance mitochondrial adaptations to aerobic exercise training, which may delay skeletal muscle fatigue and enhance exercise performance. Specifically, studies have demonstrated that combining carbohydrate restriction (endogenous and exogenous) with a single bout of aerobic exercise potentiates the beneficial effects of exercise on markers of mitochondrial biogenesis. Additionally, studies have demonstrated that high-quality protein supplementation enhances anabolic skeletal muscle intracellular signaling and mitochondrial protein synthesis following a single bout of aerobic exercise. Mitochondrial biogenesis is stimulated by complex intracellular signaling pathways that appear to be primarily regulated by 5'AMP-activated protein kinase and p38 mitogen-activated protein kinase mediated through proliferator-activated γ receptor co-activator 1 α activation, resulting in increased mitochondrial DNA expression and enhanced skeletal muscle oxidative capacity. However, the mechanisms by which concomitant carbohydrate restriction and dietary protein supplementation modulates mitochondrial adaptations to aerobic exercise training remains unclear. This review summarizes intracellular regulation of mitochondrial biogenesis and the effects of carbohydrate restriction and protein supplementation on mitochondrial adaptations to aerobic exercise.

Persistence of Lactobacillus reuteri DSM17938 in the human intestinal tract: response to consecutive and alternate-day supplementation.

BACKGROUND: Probiotics may enhance gastrointestinal health and immune function. The efficacy of different probiotic dosing strategies on colonization and persistence of probiotics is undefined. OBJECTIVE: The authors assessed colonization and persistence of Lactobacillus reuteri (L. reuteri) DSM17938 (BioGaia AB, Stockholm, Sweden) after daily or alternate-day dosing. METHODS: Volunteers ate pudding with L. reuteri (10(9) CFU) daily (n = 9) or on alternate days (n = 9) over 7 days. Fecal samples were collected on dosing days (D1-7) and after dosing ended (D13-15 and D20-22) and were analyzed for the presence of L. reuteri. Results are reported in 3-day increments (D2-4, D5-7, D13-15, and D20-22). RESULTS: L. reuteri count rose in response to daily supplementation ([mean ± SD] D2-4: 4 × 104 ± 2 × 104 CFU, p < 0.01; D5-7: 10 × 104 ± 9 × 104 CFU, p < 0.01) and alternate-day supplementation (D2-4: 21 × 104 ± 20 × 104 CFU, p < 0.01; D5-7: 11 × 104 ± 15 × 104 CFU, p = 0.06) and fell in both groups 1 week after dosing ended (p < 0.01). Total volunteers with detectable L. reuteri 1 and 2 weeks after dosing ended was similar in response to daily feeding (4/9 and 2/9, respectively) and alternate-day feeding (3/9 and 2/9, respectively). L. reuteri count was higher D2-4 in response to alternate-day vs daily feeding (p < 0.05) but similar thereafter. CONCLUSIONS: Alternate-day probiotic intake achieves equivalent colonization to daily intake, but colonization declines rapidly once dosing stops. It is possible that, initially, responsiveness to probiotics may differ between individuals, but those differences do not persist with longer consumption.

Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis.

BACKGROUND: The effects of essential amino acid (EAA) supplementation during moderate steady state (ie, endurance) exercise on postexercise skeletal muscle metabolism are not well described, and the potential role of supplemental leucine on muscle protein synthesis (MPS) and associated molecular responses remains to be elucidated. OBJECTIVE: This randomized crossover study examined whether EAA supplementation with 2 different concentrations of leucine affected post-steady state exercise MPS, whole-body protein turnover, and mammalian target of rapamycin 1 (mTORC1) intracellular signaling. DESIGN: Eight adults completed 2 separate bouts of cycle ergometry [60 min, 60% VO(2)peak (peak oxygen uptake)]. Isonitrogenous (10 g EAA) drinks with different leucine contents [leucine-enriched (l)-EAA, 3.5 g leucine; EAA, 1.87 g leucine] were consumed during exercise. MPS and whole-body protein turnover were determined by using primed continuous infusions of [(2)H(5)]phenylalanine and [1-(13)C]leucine. Multiplex and immunoblot analyses were used to quantify mTORC1 signaling. RESULTS: MPS was 33% greater (P < 0.05) after consumption of L-EAA (0.08 ± 0.01%/h) than after consumption of EAA (0.06 ± 0.01%/h). Whole-body protein breakdown and synthesis were lower (P < 0.05) and oxidation was greater (P < 0.05) after consumption of L-EAA than after consumption of EAA. Regardless of dietary treatment, multiplex analysis indicated that Akt and mammalian target of rapamycin phosphorylation were increased (P < 0.05) 30 min after exercise. Immunoblot analysis indicated that phosphorylation of ribosomal protein S6 and extracellular-signal regulated protein kinase increased (P < 0.05) and phosphorylation of eukaryotic elongation factor 2 decreased (P < 0.05) after exercise but was not affected by dietary treatment. CONCLUSION: These findings suggest that increasing the concentration of leucine in an EAA supplement consumed during steady state exercise elicits a greater MPS response during recovery. This trial is registered at clinicaltrials.gov as NCT01366924.