Examining the Direct and Indirect Effects of Postprandial Amino Acid Responses on Markers of Satiety following the Acute Consumption of Lean Beef-Rich Meals in Healthy Women with Overweight.

The consumption of protein-rich foods stimulates satiety more than other macronutrient-rich foods; however, the underlying mechanisms-of-action are not well-characterized. The objective of this study was to identify the direct and indirect effects of postprandial amino acid (AA) responses on satiety. Seventeen women (mean ± SEM, age: 33 ± 1 year; BMI: 27.8 ± 0.1 kg/m2) consumed a eucaloric, plant-based diet containing two servings of lean beef/day (i.e., 7.5 oz (207 g)) for 7 days. During day 6, the participants completed a 12 h controlled-feeding, clinical testing day including repeated satiety questionnaires and blood sampling to assess pre- and postprandial plasma AAs, PYY, and GLP-1. Regression and mediation analyses were completed to assess AA predictors and hormonal mediators. Total plasma AAs explained 41.1% of the variance in perceived daily fullness (p < 0.001), 61.0% in PYY (p < 0.001), and 66.1% in GLP-1 (p < 0.001) concentrations, respectively. Several individual AAs significantly predicted fluctuations in daily fullness, PYY, and GLP-1. In completing mediation analyses, the effect of plasma leucine on daily fullness was fully mediated by circulating PYY concentrations (indirect effect = B: 0.09 [Boot 95% CI: 0.032, 0.17]) as no leucine-fullness direct effect was observed. No other mediators were identified. Although a number of circulating AAs predict satiety, leucine was found to do so through changes in PYY concentrations in middle-aged women.

Exogenous erythropoietin increases hematological status, fat oxidation, and aerobic performance in males following prolonged strenuous training.

This study investigated the effects of EPO on hemoglobin (Hgb) and hematocrit (Hct), time trial (TT) performance, substrate oxidation, and skeletal muscle phenotype throughout 28 days of strenuous exercise. Eight males completed this longitudinal controlled exercise and feeding study using EPO (50 IU/kg body mass) 3×/week for 28 days. Hgb, Hct, and TT performance were assessed PRE and on Days 7, 14, 21, and 27 of EPO. Rested/fasted muscle obtained PRE and POST EPO were analyzed for gene expression, protein signaling, fiber type, and capillarization. Substrate oxidation and glucose turnover were assessed during 90-min of treadmill load carriage (LC; 30% body mass; 55 ± 5% V̇O2peak) exercise using indirect calorimetry, and 6-6-[2H2]-glucose PRE and POST. Hgb and Hct increased, and TT performance improved on Days 21 and 27 compared to PRE (p < 0.05). Energy expenditure, fat oxidation, and metabolic clearance rate during LC increased (p < 0.05) from PRE to POST. Myofiber type, protein markers of mitochondrial biogenesis, and capillarization were unchanged PRE to POST. Transcriptional regulation of mitochondrial activity and fat metabolism increased from PRE to POST (p < 0.05). These data indicate EPO administration during 28 days of strenuous exercise can enhance aerobic performance through improved oxygen carrying capacity, whole-body and skeletal muscle fat metabolism.

Indices of Sleep Health Are Associated With Timing and Duration of Eating in Young Adults.

BACKGROUND: Limited data exist examining whether timing and/or duration of eating behaviors throughout the day affect sleep health. OBJECTIVE: The aim of this study was to identify the relationship between eating behaviors and sleep in young adults without chronic diseases or conditions. DESIGN: This was a cross-sectional study using 7 days of baseline data from a randomized crossover trial. PARTICIPANTS/SETTING: Participants included 52 young adults. The study took place in West Lafayette, Indiana, between April 2017 and May 2018. MAIN OUTCOME MEASURES: Timing and duration of eating were assessed via 3 nonconsecutive, 24-hour dietary recalls. Bedtime, wake time, total sleep time, sleep latency, sleep efficiency, and wake after sleep onset were measured over 7 days via wrist actigraphy and sleep diaries. STATISTICAL ANALYSES PERFORMED: Two-way analyses of variance were applied to assess group differences based on timing of consumption (early vs late eating) and duration of eating (long: >13 hours, short: <11 hours, or standard: 11-13 hours) with post-hoc pairwise comparisons. RESULTS: Main effects of timing of consumption, but not duration of eating, were detected for wake time, bedtime, and sleep efficiency (all, P < .05). Specifically, participants with later eating patterns that included breakfast skipping had later wake times and later bedtimes than those with earlier eating patterns. In addition, those who had later eating patterns that included breakfast skipping and nighttime eating experienced lower sleep efficiency (mean [SE], 77.0% [2.3%]) vs those who consumed breakfast and no nighttime eating (mean [SE], 84.6% [1.4%]; P < .001) and those who skipped breakfast but had no nighttime eating (mean [SE], 84.2% [2.5]; P < .05). Those who consumed breakfast but also had nighttime eating had a mean (SE) sleep efficiency of 82.4% (1.4%) (P = .09). CONCLUSIONS: The timing of eating was associated with sleep-wake onset and sleep efficiency. This study provides the preliminary characterization of eating behaviors relative to sleep-wake cycles and highlights the need for experimental studies to understand whether manipulating the timing of eating occasions to better align with sleep-wake cycles could improve sleep health.

Higher Expression of miR-15b-5p with Inclusion of Fresh, Lean Beef as Part of a Healthy Dietary Pattern Is Inversely Associated with Markers of Cardiometabolic Disease Risk.

BACKGROUND: Considerable controversy exists surrounding the consumption of red meat and its impacts on cardiometabolic health and if it may further impact risk factors at the molecular level. OBJECTIVE: The purpose of this study was to examine the acute effects of dietary patterns, varying in red meat quantity, on the expression of circulating microRNAs (miRNAs), which are emerging biomarkers of metabolic dysfunction and chronic disease severity. METHODS: Secondary analyses were performed on plasma samples collected within a randomized, crossover design study in 16 women with overweight (mean ± standard deviation, age = 33 ± 9.89 y; body mass index = 27.9 ± 1.66 kg/m2). Participants were provided with eucaloric, isonitrogenous diets (15% of daily intake as protein) containing either 2 servings of fresh, lean beef/day (BEEF) or 0 servings of fresh, lean beef/day (PLANT) for 7 d/pattern. Fasting blood samples were collected at the end of each dietary pattern for the assessment of 12 circulating metabolic miRNA expression levels (determined a priori by quantitative reverse transcriptase-polymerase chain reaction), plasma glucose, insulin, interleukin-6, tumor necrosis factor-α, C-reactive protein (CRP), adiponectin, glucagon-like peptide-1, and branched-chain amino acids. RESULTS: Of the 12 miRNAs, miR-15b-5p expression was higher following BEEF versus PLANT (P = 0.024). Increased miR-15b-5p expression correlated with decreased fasting CRP (r = -0.494; P = 0.086) and insulin concentrations (r = -0.670; P = 0.017). miR-15b-5p was inversely correlated with insulin resistance (r = -0.642; P = 0.024) and ß cell function (r = -0.646; P = 0.023) and positively correlated with markers of insulin sensitivity (r = 0.520; P = 0.083). However, the correlations were only observed following BEEF, not PLANT. CONCLUSIONS: These data indicate that the short-term intake of fresh, lean beef as part of a healthy dietary pattern impacts potential biomarkers of cardiometabolic health that are associated with cardiometabolic risk factors in women with overweight. This study was registered at clinicaltrials.gov as NCT02614729.

NSAIDs do not prevent exercise-induced performance deficits or alleviate muscle soreness: A placebo-controlled randomized, double-blinded, cross-over study.

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently consumed by athletes to manage muscle soreness, expedite recovery, or improve performance. Despite the prevalence of NSAID use, their effects on muscle soreness and performance, particularly when administered prophylactically, remain unclear. This randomized, double-blind, counter-balanced, crossover study examined the effect of consuming a single dose of each of three NSAIDs (celecoxib, 200 mg; ibuprofen, 800 mg; flurbiprofen, 100 mg) or placebo 2 h before on muscle soreness and performance following an acute plyometric training session. Twelve healthy adults, aged 18-42 years, completed a standardized plyometric exercise session consisting of 10 sets of 10 repetitions at 40 % 1-repetition maximum (1RM) on a leg press device. During exercise, total work, rating of perceived exertion, and heart rate were measured. Maximum voluntary contraction force (MVC), vertical jump height, and muscle soreness were measured before exercise and 4-h and 24-h post-exercise. We found no significant differences in total work, heart rate, or rating of perceived exertion between treatments. Additionally, no significant differences in muscle soreness or vertical jump were observed between treatments. Ibuprofen and flurbiprofen did not prevent decrements in MVC, but celecoxib attenuated decreases in MVC 4-h post exercise (p < 0.05). This study suggests that athletes may not benefit from prophylactic ibuprofen or flurbiprofen treatment to prevent discomfort or performance decrements associated with exercise, but celecoxib may mitigate short-term performance decrements.

Protein Source Influences Acute Appetite and Satiety but Not Subsequent Food Intake in Healthy Adults.

BACKGROUND: Although current recommendations encourage plant-based dietary patterns, data is limited as to whether the equivalent substitution of animal-based protein-rich foods with plant-based versions impacts ingestive behavior. OBJECTIVES: To compare higher-protein preloads, varying in protein source, on appetite, satiety, and subsequent energy intake. METHODS: Thirty-two adults (age: 25 ± 1 y; body mass index (BMI) measured in kg/m2: 24.2 ± 0.5 kg/m2) randomly consumed 250 kcal, protein-preload beverages (24 g protein), varying in protein source [whey, soy, and pea protein isolates (WHEY, SOY, and PEA) or micellar casein (CAS)] each morning for 3 acclimation days/preload. On day 4, participants completed a 4-h clinical testing day in which the respective preload was consumed, followed by blood sampling and questionnaires every 30 min for appetite and satiety. In addition, an ad libitum lunch was provided 4-h postpreload. On day 5, participants consumed the respective preload at home, followed by an ad libitum breakfast 30 min afterward. For normally-distributed data, repeated-measures analysis of variance (ANOVA) or Friedman nonparametric test were utilized to compare the main effects of protein source on study outcomes. Post hoc pairwise comparisons using least-significant differences (LSD) were then performed. RESULTS: CAS (-3330 ± 690 mm∗240 min) and PEA (-2840 ± 930mm∗240 min) reduced 4-h appetite compared with SOY (-1440 ± 936 mm∗240 min; both, P < 0.05). WHEY was not different (-2290 ± 930 mm∗240 min). CAS (3520 ± 84 pg/mL∗240 min) and PEA (3860 ± 864 pg/mL∗240 min) increased 4-h peptide YY concentrations compared with SOY (2200 ± 869 pg/mL∗240 min; both, P < 0.05). WHEY was not different (3870 ± 932 pg/mL∗240 min). No differences in ad libitum energy intake were observed. CONCLUSIONS: CAS and PEA, but not WHEY, elicited greater acute changes in appetite and satiety compared with SOY in healthy adults, supporting that not all protein sources are equivalent. This trial is registered at clinicaltrials.gov (NCT03154606).

Effects of energy balance on cognitive performance, risk-taking, ambulatory vigilance and mood during simulated military sustained operations (SUSOPS).

Sustained operations (SUSOPS) require military personnel to conduct combat and training operations while experiencing physical and cognitive stress and limited sleep. These operations are often conducted in a state of negative energy balance and are associated with degraded cognitive performance and mood. Whether maintaining energy balance can mitigate these declines is unclear. This randomized crossover study assessed the effects of energy balance on cognitive performance, risk-taking propensity, ambulatory vigilance, and mood during a simulated 72-h SUSOPS. METHODS: Ten male Soldiers (mean ± SE; 22.4 ± 1.7 y; body weight 87.3 ± 1.1 kg) completed two, 72-h simulated SUSOPS in random order, separated by 7 days of recovery. Each SUSOPS elicited ∼4500 kcal/d total energy expenditure and restricted sleep to 4 h/night. During SUSOPS, participants consumed either an energy-balanced or restricted diet that induced a 43 ± 3% energy deficit. A cognitive test battery was administered each morning and evening to assess: vigilance, working memory, grammatical reasoning, risk-taking propensity, and mood. Real-time ambulatory vigilance was assessed each morning, evening, and night via a wrist-worn monitoring device. RESULTS: Participants exhibited heightened risk-taking propensity (p = 0.047) with lower self-reported self-control (p = 0.021) and fatigue (p = 0.013) during energy deficit compared to during energy balance. Vigilance accuracy (p < 0.001) and working memory (p = 0.040) performance decreased, and vigilance lapses increased (p < 0.001) during SUSOPS, but did not differ by diet. Percentage of correct responses to ambulatory vigilance stimuli varied during SUSOPS (p = 0.019) independent of diet, with generally poorer performance during the morning and night. Total mood disturbance (p = 0.001), fatigue (p < 0.001), tension (p = 0.003), and confusion (p = 0.036) increased whereas vigor decreased (p < 0.001) during SUSOPS, independent of diet. CONCLUSION: Prolonged physical activity combined with sleep restriction is associated with impaired vigilance, memory, and mood state. Under such conditions, maintaining energy balance prevents increased risk-taking and improves self-control, but does not improve other aspects of cognitive function or mood. Given the small sample in the present study, replication in a larger cohort is warranted.

Initial military training modulates serum fatty acid and amino acid metabolites.

Initial military training (IMT) results in increased fat-free mass (FFM) and decreased fat mass (FM). The underlying metabolic adaptations facilitating changes in body composition during IMT are unknown. The objective of this study was to assess changes in body composition and the serum metabolome during 22-week US Army IMT. Fifty-four volunteers (mean ± SD; 22 ± 3 year; 24.6 ± 3.7 kg/m2 ) completed this longitudinal study. Body composition measurements (InBody 770) and blood samples were collected under fasting, rested conditions PRE and POST IMT. Global metabolite profiling was performed to identify metabolites involved in energy, carbohydrate, lipid, and protein metabolism (Metabolon, Inc.). There was no change in body mass (POST-PRE; 0.4 ± 5.1 kg, p = 0.59), while FM decreased (-1.7 ± 3.5 kg, p < 0.01), and FFM increased (2.1 ± 2.8 kg, p < 0.01) POST compared to PRE IMT. Of 677 identified metabolites, 340 differed at POST compared to PRE (p < 0.05, Q < 0.10). The majority of these metabolites were related to fatty acid (73%) and amino acid (26%) metabolism. Increases were detected in 41% of branched-chain amino acid metabolites, 53% of histidine metabolites, and 35% of urea cycle metabolites. Decreases were detected in 93% of long-chain fatty acid metabolites, while 58% of primary bile acid metabolites increased. Increases in amino acid metabolites suggest higher rates of protein turnover, while changes in fatty acid metabolites indicate increased fat oxidation, which likely contribute changes in body composition during IMT. Overall, changes in metabolomics profiles provide insight into metabolic adaptions underlying changes in body composition during IMT.

Mild to Moderate Food Deprivation Increases Hepcidin and Results in Hypoferremia and Tissue Iron Sequestration in Mice.

BACKGROUND: Short-term starvation and severe food deprivation (FD) reduce dietary iron absorption and restricts iron to tissues, thereby limiting the amount of iron available for erythropoiesis. These effects may be mediated by increases in the iron regulatory hormone hepcidin; however, whether mild to moderate FD has similar effects on hepcidin and iron homeostasis is not known. OBJECTIVES: To determine the effects of varying magnitudes and durations of FD on hepcidin and indicators of iron status in male and female mice. METHODS: Male and female C57BL/6J mice (14 wk old; n = 170) were randomly assigned to consume AIN-93M diets ad libitum (AL) or varying magnitudes of FD (10%, 20%, 40%, 60%, 80%, or 100%). FD was based on the average amount of food consumed by the AL males or females, and food was split into morning and evening meals. Mice were euthanized at 48 h and 1, 2, and 3 wk, and hepcidin and indicators of iron status were measured. Data were analyzed by Pearson correlation and one-way ANOVA. RESULTS: Liver hepcidin mRNA was positively correlated with the magnitude of FD at all time points (P < 0.05). At 3 wk, liver hepcidin mRNA increased 3-fold with 10% and 20% FD compared with AL and was positively associated with serum hepcidin (R = 0.627, P < 0.0001). Serum iron was reduced by ∼65% (P ≤ 0.01), and liver nonheme iron concentrations were ∼75% greater (P ≤ 0.01) with 10% and 20% FD for 3 wk compared with AL. Liver hepcidin mRNA at 3 wk was positively correlated with liver Bmp6 (R = 0.765, P < 0.0001) and liver gluconeogenic enzymes (R = >0.667, P < 0.05) but not markers of inflammation (P > 0.05). CONCLUSIONS: FD increases hepcidin in male and female mice and results in hypoferremia and tissue iron sequestration. These findings suggest that increased hepcidin with FD may contribute to the disturbances in iron homeostasis with undernutrition.

Circulating and skeletal muscle microRNA profiles are more sensitive to sustained aerobic exercise than energy balance in males.

MicroRNAs (miRNAs) regulate molecular processes governing muscle metabolism. Physical activity and energy balance influence both muscle anabolism and substrate metabolism, but whether circulating and skeletal muscle miRNAs mediate those effects remains unknown. This study assessed the impact of sustained physical activity with participants in energy balance (BAL) or deficit (DEF) on circulating and skeletal muscle miRNAs. Using a randomized cross-over design, 10 recreational active healthy males (mean ± SD, 22 ± 5 years, 87 ± 11 kg) completed 72 h of high aerobic exercise-induced energy expenditures in BAL (689 ± 852 kcal/day) or DEF (-2047 ± 920 kcal/day). Blood and muscle samples were collected under rested/fasted conditions before (PRE) and immediately after 120 min load carriage exercise bout at the end (POST) of the 72 h. Trials were separated by 7 days. Circulating and skeletal muscle miRNAs were measured using microarray RT-qPCR. Independent of energy status, 36 circulating miRNAs decreased (P < 0.05), while 10 miRNAs increased and three miRNAs decreased in skeletal muscle (P < 0.05) at POST compared to PRE. Of these, miR-122-5p, miR-221-3p, miR-222-3p and miR-24-3p decreased in circulation and increased in skeletal muscle. Two circulating (miR-145-5p and miR-193a-5p) and four skeletal muscle (miR-21-5p, miR-372-3p, miR-34a-5p and miR-9-5p) miRNAs had time-by-treatment effects (P < 0.05). These data suggest that changes in miRNA profiles are more sensitive to increased physical activity compared to energy status, and that changes in circulating miRNAs in response to high levels of daily aerobic exercise are not reflective of changes in skeletal muscle miRNAs. KEY POINTS: Circulating and skeletal muscle miRNA profiles are more sensitive to high levels of aerobic exercise-induced energy expenditure compared to energy status. Changes in circulating miRNA in response to high levels of daily sustained aerobic exercise are not reflective of changes in skeletal muscle miRNA.

Physiological Limitations of Protein Foods Ounce Equivalents and the Underappreciated Role of Essential Amino Acid Density in Healthy Dietary Patterns.

Protein quality is an important component of protein intake to support growth, development, and maintenance of essential body tissues and functions. Therefore, protein quality should be emphasized as a key characteristic during protein food selection within the larger context of healthy dietary patterns, especially when considering the wide variance of protein quality across animal- and plant-based foods. However, the USDA Dietary Guidelines for Americans (DGA) do not address specific protein quality recommendations within their protein foods ounce equivalents guidance or as a component of Healthy U.S. Style, Healthy Vegetarian, and Healthy Mediterranean Style dietary patterns. In addition, the protein foods ounce equivalents within the DGA are not established on any obvious metabolic equivalency characteristic [i.e., energy, protein, or essential amino acid (EAA) content], which creates misleading messaging of equivalent functional and metabolic benefit across protein foods. EAA content is a key characteristic of protein quality and can be a practical focal point for protein intake recommendations and achieving healthy dietary patterns. This review discusses the importance of protein quality, the state of messaging within DGA recommendations, and proposes EAA density (i.e., EAA content relative to total energy) as one practical approach to improve current dietary recommendations. Two recent publications that evaluated the DGA protein foods ounce equivalents based on metabolic effect and their application within DGA recommended dietary patterns are discussed.

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.

Effects of energy balance on appetite and physiological mediators of appetite during strenuous physical activity: secondary analysis of a randomised crossover trial.

Energy deficit is common during prolonged periods of strenuous physical activity and limited sleep, but the extent to which appetite suppression contributes is unclear. The aim of this randomised crossover study was to determine the effects of energy balance on appetite and physiological mediators of appetite during a 72-h period of high physical activity energy expenditure (about 9·6 MJ/d (2300 kcal/d)) and limited sleep designed to simulate military operations (SUSOPS). Ten men consumed an energy-balanced diet while sedentary for 1 d (REST) followed by energy-balanced (BAL) and energy-deficient (DEF) controlled diets during SUSOPS. Appetite ratings, gastric emptying time (GET) and appetite-mediating hormone concentrations were measured. Energy balance was positive during BAL (18 (sd 20) %) and negative during DEF (-43 (sd 9) %). Relative to REST, hunger, desire to eat and prospective consumption ratings were all higher during DEF (26 (sd 40) %, 56 (sd 71) %, 28 (sd 34) %, respectively) and lower during BAL (-55 (sd 25) %, -52 (sd 27) %, -54 (sd 21) %, respectively; Pcondition < 0·05). Fullness ratings did not differ from REST during DEF, but were 65 (sd 61) % higher during BAL (Pcondition < 0·05). Regression analyses predicted hunger and prospective consumption would be reduced and fullness increased if energy balance was maintained during SUSOPS, and energy deficits of ≥25 % would be required to elicit increases in appetite. Between-condition differences in GET and appetite-mediating hormones identified slowed gastric emptying, increased anorexigenic hormone concentrations and decreased fasting acylated ghrelin concentrations as potential mechanisms of appetite suppression. Findings suggest that physiological responses that suppress appetite may deter energy balance from being achieved during prolonged periods of strenuous activity and limited sleep.

Energy deficit increases hepcidin and exacerbates declines in dietary iron absorption following strenuous physical activity: a randomized-controlled cross-over trial.

BACKGROUND: Strenuous physical activity promotes inflammation and depletes muscle glycogen, which may increase the iron regulatory hormone hepcidin. Hepcidin reduces dietary iron absorption and may contribute to declines in iron status frequently observed following strenuous physical activity. OBJECTIVES: To determine the effects of strenuous physical activity on hepcidin and dietary iron absorption and whether energy deficit compared with energy balance modifies those effects. METHODS: This was a randomized, cross-over, controlled-feeding trial in healthy male subjects (n = 10, mean ± SD age: 22.4 ± 5.4 y, weight: 87.3 ± 10.9 kg) with sufficient iron status (serum ferritin 77.0 ± 36.7 ng/mL). Rest measurements were collected before participants began a 72-h simulated sustained military operation (SUSOPS), designed to elicit high energy expenditure, glycogen depletion, and inflammation, followed by a 7-d recovery period. Two 72-h SUSOPS trials were performed where participants were randomly assigned to consume either energy matched (±10%) to their individual estimated total daily energy expenditure (BAL) or energy at 45% of total daily energy expenditure to induce energy deficit (DEF). On the rest day and at the completion of BAL and DEF, participants consumed a beverage containing 3.8 mg of a stable iron isotope, and plasma isotope appearance was measured over 6 h. RESULTS: Muscle glycogen declined during DEF and was preserved during BAL (-188 ± 179 mmol/kg, P-adjusted < 0.01). Despite similar increases in interleukin-6, plasma hepcidin increased during DEF but not BAL, such that hepcidin was 108% greater during DEF compared with BAL (7.8 ± 12.2 ng/mL, P-adjusted < 0.0001). Peak plasma isotope appearance at 120 min was 74% lower with DEF (59 ± 38% change from 0 min) and 49% lower with BAL (117 ± 81%) compared with rest (230 ± 97%, P-adjusted < 0.01 for all comparisons). CONCLUSIONS: Strenuous physical activity decreases dietary iron absorption compared with rest. Energy deficit exacerbates both the hepcidin response to physical activity and declines in dietary iron absorption compared with energy balance. This trial was registered at clinicaltrials.gov as NCT03524690.

Effects of high versus standard essential amino acid intakes on whole-body protein turnover and mixed muscle protein synthesis during energy deficit: A randomized, crossover study.

BACKGROUND & AIMS: Consuming 0.10-0.14 g essential amino acids (EAA)/kg/dose (0.25-0.30 g protein/kg/dose) maximally stimulates muscle protein synthesis (MPS) during energy balance. Whether consuming EAA beyond that amount enhances MPS and whole-body anabolism following energy deficit is unknown. The aims of this study were to determine the effects of standard and high EAA ingestion on mixed MPS and whole-body protein turnover following energy deficit. DESIGN: Nineteen males (mean ± SD; 23 ± 5 y; 25.4 ± 2.7 kg/m2) completed a randomized, double-blind crossover study consisting of two, 5-d energy deficits (-30 ± 4% of total energy requirements), separated by 14-d. Following each energy deficit, mixed MPS and whole-body protein synthesis (PS), breakdown (PB), and net balance (NET) were determined at rest and post-resistance exercise (RE) using primed, constant L-[2H5]-phenylalanine and L-[2H2]-tyrosine infusions. Beverages providing standard (0.1 g/kg, 7.87 ± 0.87 g) or high (0.3 g/kg, 23.5 ± 2.54 g) EAA were consumed post-RE. Circulating EAA were measured. RESULTS: Postabsorptive mixed MPS (%/h) at rest was not different (P = 0.67) between treatments. Independent of EAA, postprandial mixed MPS at rest (standard EAA, 0.055 ± 0.01; high EAA, 0.061 ± 0.02) and post-RE (standard EAA, 0.055 ± 0.01; high EAA, 0.065 ± 0.02) were greater than postabsorptive mixed MPS at rest (P = 0.02 and P = 0.01, respectively). Change in (Δ postabsorptive) whole-body (g/180 min) PS and PB was greater for high than standard EAA [mean treatment difference (95% CI), 3.4 (2.3, 4.4); P = 0.001 and -15.6 (-17.8, -13.5); P = 0.001, respectively]. NET was more positive for high than standard EAA [19.0 (17.3, 20.7); P = 0.001]. EAA concentrations were greater in high than standard EAA (P = 0.001). CONCLUSIONS: These data demonstrate that high compared to standard EAA ingestion enhances whole-body protein status during underfeeding. However, the effects of consuming high and standard EAA on mixed MPS are the same during energy deficit. CLINICAL TRIAL REGISTRY: NCT03372928, https://clinicaltrials.gov.

Essential Amino Acids and Protein Synthesis: Insights into Maximizing the Muscle and Whole-Body Response to Feeding.

Ingesting protein-containing supplements and foods provides essential amino acids (EAA) necessary to increase muscle and whole-body protein synthesis (WBPS). Large variations exist in the EAA composition of supplements and foods, ranging from free-form amino acids to whole protein foods. We sought to investigate how changes in peripheral EAA after ingesting various protein and free amino acid formats altered muscle and whole-body protein synthesis. Data were compiled from four previous studies that used primed, constant infusions of L-(ring-2H5)-phenylalanine and L-(3,3-2H2)-tyrosine to determine fractional synthetic rate of muscle protein (FSR), WBPS, and circulating EAA concentrations. Stepwise regression indicated that max EAA concentration (EAACmax; R2 = 0.524, p < 0.001), EAACmax (R2 = 0.341, p < 0.001), and change in EAA concentration (ΔEAA; R = 0.345, p < 0.001) were the strongest predictors for postprandial FSR, Δ (change from post absorptive to postprandial) FSR, and ΔWBPS, respectively. Within our dataset, the stepwise regression equation indicated that a 100% increase in peripheral EAA concentrations increases FSR by ~34%. Further, we observed significant (p < 0.05) positive (R = 0.420-0.724) correlations between the plasma EAA area under the curve above baseline, EAACmax, ΔEAA, and rate to EAACmax to postprandial FSR, ΔFSR, and ΔWBPS. Taken together our results indicate that across a large variety of EAA/protein-containing formats and food, large increases in peripheral EAA concentrations are required to drive a robust increase in muscle and whole-body protein synthesis.

Muscle Protein Synthesis and Whole-Body Protein Turnover Responses to Ingesting Essential Amino Acids, Intact Protein, and Protein-Containing Mixed Meals with Considerations for Energy Deficit.

Protein intake recommendations to optimally stimulate muscle protein synthesis (MPS) are derived from dose-response studies examining the stimulatory effects of isolated intact proteins (e.g., whey, egg) on MPS in healthy individuals during energy balance. Those recommendations may not be adequate during periods of physiological stress, specifically the catabolic stress induced by energy deficit. Providing supplemental intact protein (20-25 g whey protein, 0.25-0.3 g protein/kg per meal) during strenuous military operations that elicit severe energy deficit does not stimulate MPS-associated anabolic signaling or attenuate lean mass loss. This occurs likely because a greater proportion of the dietary amino acids consumed are targeted for energy-yielding pathways, whole-body protein synthesis, and other whole-body essential amino acid (EAA)-requiring processes than the proportion targeted for MPS. Protein feeding formats that provide sufficient energy to offset whole-body energy and protein-requiring demands during energy deficit and leverage EAA content, digestion, and absorption kinetics may optimize MPS under these conditions. Understanding the effects of protein feeding format-driven alterations in EAA availability and subsequent changes in MPS and whole-body protein turnover is required to design feeding strategies that mitigate the catabolic effects of energy deficit. In this manuscript, we review the effects, advantages, disadvantages, and knowledge gaps pertaining to supplemental free-form EAA, intact protein, and protein-containing mixed meal ingestion on MPS. We discuss the fundamental role of whole-body protein balance and highlight the importance of comprehensively assessing whole-body and muscle protein kinetics when evaluating the anabolic potential of varying protein feeding formats during energy deficit.

Growing up strong: The importance of physical, mental, and emotional strength during childhood and adolescence with focus on dietary factors.

Childhood and adolescence are critical time periods for growth and development. Given the current physical and psychological health concerns affecting United States youth, an emerging area of interest exists supporting the importance of physical and psychological aspects of strength for health, resilience, and well-being through these life stages. This synopsis highlights the key concepts that were presented within the 2018 Strength Summit conference, entitled The Role of Strength in Optimal Health and Well-being. During the conference, strength was broadly defined as the ability to successfully respond to a challenge. Although much of the current research focuses on strength from a muscle function and performance perspective, mental and emotional strength are also important components of overall health and well-being, especially in children and adolescents. This paper provides a brief overview of the clinical and/or research-based strength outcomes, summarizes the relationship between strength and health, and discusses evidence-based dietary factors that promote strength in children and adolescents. Novelty Building physical, mental, and emotional strength during childhood and adolescence lays the foundation for health and well-being. Emerging evidence indicate positive associations between diet quality and strength in children and adolescents. Promising areas include the promotion of family-based meals, with focus on breakfast, for improved strength in United States youth.

Acute hypoxia reduces exogenous glucose oxidation, glucose turnover, and metabolic clearance rate during steady-state aerobic exercise.

BACKGROUND: Exogenous carbohydrate oxidation is lower during steady-state aerobic exercise in native lowlanders sojourning at high altitude (HA) compared to sea level (SL). However, the underlying mechanism contributing to reduction in exogenous carbohydrate oxidation during steady-state aerobic exercise performed at HA has not been explored. OBJECTIVE: To determine if alterations in glucose rate of appearance (Ra), disappearance (Rd) and metabolic clearance rate (MCR) at HA provide a mechanism for explaining the observation of lower exogenous carbohydrate oxidation compared to during metabolically-matched, steady-state exercise at SL. METHODS: Using a randomized, crossover design, native lowlanders (n = 8 males, mean ±â€¯SD, age: 23 ±â€¯2 yr, body mass: 87 ±â€¯10 kg, and VO2peak: SL 4.3 ±â€¯0.2 L/min and HA 2.9 ±â€¯0.2 L/min) consumed 145 g (1.8 g/min) of glucose while performing 80-min of metabolically-matched (SL: 1.66 ±â€¯0.14 V̇O2 L/min 329 ±â€¯28 kcal, HA: 1.59 ±â€¯0.10 V̇O2 L/min, 320 ±â€¯19 kcal) treadmill exercise in SL (757 mmHg) and HA (460 mmHg) conditions after a 5-h exposure. Substrate oxidation rates (g/min) and glucose turnover (mg/kg/min) during exercise were determined using indirect calorimetry and dual tracer technique (13C-glucose oral ingestion and [6,6-2H2]-glucose primed, continuous infusion). RESULTS: Total carbohydrate oxidation was higher (P < 0.05) at HA (2.15 ±â€¯0.32) compared to SL (1.39 ±â€¯0.14). Exogenous glucose oxidation rate was lower (P < 0.05) at HA (0.35 ±â€¯0.07) than SL (0.44 ±â€¯0.05). Muscle glycogen oxidation was higher at HA (1.67 ±â€¯0.26) compared to SL (0.83 ±â€¯0.13). Total glucose Ra was lower (P < 0.05) at HA (12.3 ±â€¯1.5) compared to SL (13.8 ±â€¯2.0). Exogenous glucose Ra was lower (P < 0.05) at HA (8.9 ±â€¯1.3) compared to SL (10.9 ±â€¯2.2). Glucose Rd was lower (P < 0.05) at HA (12.7 ±â€¯1.7) compared to SL (14.3 ±â€¯2.0). MCR was lower (P < 0.05) at HA (9.0 ±â€¯1.8) compared to SL (12.1 ±â€¯2.3). Circulating glucose and insulin concentrations were higher in response carbohydrate intake during exercise at HA compared to SL. CONCLUSION: Novel results from this investigation suggest that reductions in exogenous carbohydrate oxidation at HA may be multifactorial; however, the apparent insensitivity of peripheral tissue to glucose uptake may be a primary determinate.

Mitigation of Muscle Loss in Stressed Physiology: Military Relevance.

Military personnel may be exposed to circumstances (e.g., large energy deficits, sleep deprivation, cognitive demands, and environmental extremes) of external stressors during training and combat operations (i.e., operational stressors) that combine to degrade muscle protein. The loss of muscle protein is further exacerbated by frequent periods of severe energy deficit. Exposure to these factors results in a hypogonadal state that may contribute to observed decrements in muscle mass. In this review, lessons learned from studying severe clinical stressed states and the interventions designed to mitigate the loss of muscle protein are discussed in the context of military operational stress. For example, restoration of the anabolic hormonal status (e.g., testosterone, insulin, and growth hormone) in stressed physiological states may be necessary to restore the anabolic influence derived from dietary protein on muscle. Based on our clinical experiences, restoration of the normal testosterone status during sustained periods of operational stress may be advantageous. We demonstrated that in severe burn patients, pharmacologic normalization of the anabolic hormonal status restores the anabolic stimulatory effect of nutrition on muscle by improving the protein synthetic efficiency and limiting amino acid loss from skeletal muscle. Furthermore, an optimal protein intake, and in particular essential amino acid delivery, may be an integral ingredient in a restored anabolic response during the stress state. Interventions which improve the muscle net protein balance may positively impact soldier performance in trying conditions.