Explorative Characterization of GI Complaints, General Physical and Mental Wellbeing, and Gut Microbiota in Trained Recreative and Competitive Athletes with or without Self-Reported Gastrointestinal Symptoms.

The current state of the literature lacks a clear characterization of gastrointestinal (GI) symptoms, gut microbiota composition, and general physical and mental wellbeing in well-trained athletes. Therefore, this study aimed to characterize differences in self-reported symptoms, gut microbiota composition, and wellbeing (i.e., sleep quality, mood, and physical (PHQ) and mental wellbeing) between athletes with and without GI symptoms. In addition, we assessed the potential impact of a 3-week multi-ingredient fermented whey supplement in the GI complaints group, without a control group, on the gut microbiota and self-reported GI symptoms and wellbeing. A total of 50 athletes (24.7 ± 4.5 years) with GI issues (GI group at baseline, GI-B) and 21 athletes (25.4 ± 5.3 years) without GI issues (non-GI group, NGI) were included. At baseline, there was a significant difference in the total gastrointestinal symptom rating scale (GSRS) score (24.1 ± 8.48 vs. 30.3 ± 8.82, p = 0.008) and a trend difference in PHQ (33.9 ± 10.7 vs. 30.3 ± 8.82, p = 0.081), but no differences (p > 0.05) were seen for other outcomes, including gut microbiota metrics, between groups. After 3-week supplementation, the GI group (GI-S) showed increased Bifidobacterium relative abundance (p < 0.05), reported a lower number of severe GI complaints (from 72% to 54%, p < 0.001), and PHQ declined (p = 0.010). In conclusion, well-trained athletes with GI complaints reported more severe GI symptoms than an athletic reference group, without showing clear differences in wellbeing or microbiota composition. Future controlled research should further investigate the impact of such multi-ingredient supplements on GI complaints and the associated changes in gut health-related markers.

Effects of Early and Late Time-Restricted Feeding on Parameters of Metabolic Health: An Explorative Literature Assessment.

Chrono-nutrition (meal timing) aligns food consumption with one's circadian rhythm. The first meal (e.g., breakfast) likely promotes synchronization of peripheral circadian clocks, thereby supporting metabolic health. Time-restricted feeding (TRF) has been shown to reduce body weight (BW) and/or improve cardiovascular biomarkers. In this explorative literature assessment, 13 TRF randomized controlled trials (RCTs) were selected from PubMed and Scopus to evaluate the effects of early (eTRF: first meal before 10:30 a.m.) and late TRF (lTRF: first meal after 11:30 a.m.) on parameters of metabolic health. Although distinct variations in study design were evident between reports, TRF consistently decreased energy intake (EI) and BW, and improved insulin resistance as well as systolic blood pressure. eTRF seemed to have a greater beneficial effect than lTRF on insulin resistance (HOMA-IR). Importantly, most studies did not appear to consider chronotype in their evaluation, which may have underestimated TRF effects. TRF intervention may be a promising approach for risk reduction of human metabolic diseases. To conclusively determine benefits of TRF and identify clear differences between eTRF and lTRF, future studies should be longer-term (≥8 weeks) with well-defined (differences in) feeding windows, include participants chronotypically matching the intervention, and compare outcomes to those of control groups without any dietary limitations.

Access to a pre-sleep protein snack increases daily energy and protein intake in surgical hospitalized patients.

BACKGROUND & AIM: In hospitalized patients, daily protein intake remains far below WHO requirements for healthy adults (0.8 g·kg-1·d-1) as well as ESPEN guidelines for patients (1.2-1.5 g·kg-1·d-1). Providing access to a pre-sleep protein dense snack between dinner and going to bed may serve as a great opportunity to increase daily energy and protein intake in hospitalized patients. However, it remains to be assessed whether protein provision prior to sleep effectively increases protein intake, or may reduce food intake throughout the remainder of the day(s). The present study evaluated the impact of giving access to a pre-sleep snack on daily energy and protein intake in patients throughout their hospitalization. METHODS: Patients admitted to the surgical wards of the Maastricht University Medical Centre+ were randomly allocated to usual care (n = 51) or given access to a pre-sleep snack (n = 50). The pre-sleep snack consisted of 103 g cheese cubes (30 g protein) provided between 7:30 and 9:30 PM, prior to sleep. All food provided and all food consumed was weighed and recorded throughout (2-7 days) hospitalization. Daily energy and protein intake and distribution were calculated. Data were analyzed by independent T-Tests with P < 0.05 considered as statistically significant. RESULTS: Daily energy intake was higher in the pre-sleep group (1353 ± 424 kcal d-1) when compared to the usual care group (1190 ± 402 kcal·d-1; P = 0.049). Providing patients access to a pre-sleep snack resulted in a 17% (11 ± 9 g) higher daily protein intake (0.81 ± 0.29 g·kg-1·d-1) when compared to the usual care group (0.69 ± 0.28 g·kg-1·d-1; P = 0.045). Protein intake at breakfast, lunch, and dinner did not differ between the pre-sleep and usual care groups (all P > 0.05). CONCLUSION: Providing access to a pre-sleep protein snack, in the form of protein dense food items such as cheese, represents an effective dietary strategy to increase daily energy and protein intake in hospitalized patients. Patients consuming pre-sleep protein snacks do not compensate by lowering energy or protein intake throughout the remainder of the days. Pre-sleep protein dense food provision should be implemented in hospital food logistics to improve the nutritional intake of patients. TRIAL REGISTER NO: NL8507 (https://trialsearch.who.int/).

Daily blood flow restriction does not preserve muscle mass and strength during 2 weeks of bed rest.

We measured the impact of blood flow restriction on muscle protein synthesis rates, muscle mass and strength during 2 weeks of strict bed rest. Twelve healthy, male adults (age: 24 ± 3 years, body mass index: 23.7 ± 3.1 kg/m2 ) were subjected to 14 days of strict bed rest with unilateral blood flow restriction performed three times daily in three 5 min cycles (200 mmHg). Participants consumed deuterium oxide and we collected blood and saliva samples throughout 2 weeks of bed rest. Before and immediately after bed rest, lean body mass (dual-energy X-ray absorptiometry scan) and thigh muscle volume (magnetic resonance imaging scan) were assessed in both the blood flow restricted (BFR) and control (CON) leg. Muscle biopsies were collected and unilateral muscle strength (one-repetition maximum; 1RM) was assessed for both legs before and after the bed rest period. Bed rest resulted in 1.8 ± 1.0 kg lean body mass loss (P < 0.001). Thigh muscle volume declined from 7.1 ± 1.1 to 6.7 ± 1.0 L in CON and from 7.0 ± 1.1 to 6.7 ± 1.0 L in BFR (P < 0.001), with no differences between treatments (P = 0.497). In addition, 1RM leg extension strength decreased from 60.2 ± 10.6 to 54.8 ± 10.9 kg in CON and from 59.2 ± 12.1 to 52.9 ± 12.0 kg in BFR (P = 0.014), with no differences between treatments (P = 0.594). Muscle protein synthesis rates during bed rest did not differ between the BFR and CON leg (1.11 ± 0.12 vs. 1.08 ± 0.13%/day, respectively; P = 0.302). Two weeks of bed rest substantially reduces skeletal muscle mass and strength. Blood flow restriction during bed rest does not modulate daily muscle protein synthesis rates and does not preserve muscle mass or strength. KEY POINTS: Bed rest, often necessary for recovery from illness or injury, leads to the loss of muscle mass and strength. It has been postulated that blood flow restriction may attenuate the loss of muscle mass and strength during bed rest. We investigated the effect of blood flow restriction on muscle protein synthesis rates, muscle mass and strength during 2 weeks of strict bed rest. Blood flow restriction applied during bed rest does not modulate daily muscle protein synthesis rates and does not preserve muscle mass or strength. Blood flow restriction is not effective in preventing muscle atrophy during a prolonged period of bed rest.

Graded Replacement of Carbohydrate-Rich Breakfast Products with Dairy Products: Effects on Postprandial Aminoacidemia, Glycemic Control, Bone Metabolism, and Satiety.

BACKGROUND: Postprandial metabolic responses following dairy consumption have mostly been studied using stand-alone dairy products or milk-derived nutrients. OBJECTIVE: Assessing the impact of ingesting dairy products as part of a common breakfast on postprandial aminoacidemia, glycemic control, markers of bone metabolism, and satiety. METHODS: In this randomized, crossover study, 20 healthy young males and females consumed on 3 separate occasions an iso-energetic breakfast containing no dairy (NO-D), 1 dairy (ONE-D), or 2 dairy (TWO-D) products. Postprandial concentrations of amino acids, glucose, insulin, glucagon-like peptide-1 (GLP-1), calcium, parathyroid hormone (PTH), and markers of bone formation (P1NP) and resorption (CTX-I) were measured before and up to 300 min after initiating the breakfast, along with VAS-scales to assess satiety. RESULTS: Plasma essential and branched-chained amino acids availability (expressed as total area under the curve (tAUC)) increased in a dose-dependent manner (P<0.05 for all comparisons). Plasma glucose tAUCs were lower in ONE-D and TWO-D compared with NO-D (P<0.05 for both comparisons). Plasma GLP-1 tAUC increased in a dose-dependent manner (P<0.05 for all comparisons), whereas no differences were observed in plasma insulin tAUC between conditions (P>0.05 for all comparisons). Serum calcium tAUCs were higher in ONE-D and TWO-D compared with NO-D (P<0.05 for both comparisons), along with lower PTH tAUCs in ONE-D and TWO-D compared with NO-D (P=0.001 for both comparisons). In accordance, serum CTX-I concentrations were lower in the late postprandial period in ONE-D and TWO-D compared with NO-D (P<0.01 for both comparisons). No differences were observed in P1NP tAUCs between conditions (P>0.05). The tAUC for satiety was higher in TWO-D compared with NO-D and ONE-D (P<0.05 for both comparisons). CONCLUSIONS: Iso-energetic replacement of a carbohydrate-rich breakfast component with one serving of dairy improves postprandial amino acid availability, glycemic control, and bone metabolism. Adding a second serving of dairy in lieu of carbohydrates augments postprandial amino acid and GLP-1 concentrations while further promoting satiety. This study was registered at https://doi.org/10.1186/ISRCTN13531586 with Clinical Trial Registry number ISRCTN13531586.

The anabolic response to protein ingestion during recovery from exercise has no upper limit in magnitude and duration in vivo in humans.

The belief that the anabolic response to feeding during postexercise recovery is transient and has an upper limit and that excess amino acids are being oxidized lacks scientific proof. Using a comprehensive quadruple isotope tracer feeding-infusion approach, we show that the ingestion of 100 g protein results in a greater and more prolonged (>12 h) anabolic response when compared to the ingestion of 25 g protein. We demonstrate a dose-response increase in dietary-protein-derived plasma amino acid availability and subsequent incorporation into muscle protein. Ingestion of a large bolus of protein further increases whole-body protein net balance, mixed-muscle, myofibrillar, muscle connective, and plasma protein synthesis rates. Protein ingestion has a negligible impact on whole-body protein breakdown rates or amino acid oxidation rates. These findings demonstrate that the magnitude and duration of the anabolic response to protein ingestion is not restricted and has previously been underestimated in vivo in humans.

The Postprandial Plasma Amino Acid Response Does Not Differ Following the Ingestion of a Solid Versus a Liquid Milk Protein Product in Healthy Adult Females.

Dietary protein digestion and amino acid absorption rates are modulated by numerous factors such as the food matrix. It has been speculated that protein ingested in liquid form is more rapidly digested and absorbed when compared with ingestion in solid form. Here, we assessed the postprandial plasma amino acid availability following ingestion of a single bolus of protein provided in either liquid or solid form. Twelve healthy, young females were included in this randomized cross-over study. On two separate test days, participants ingested 20-g milk protein concentrate in solid form (protein bar) or in liquid form (protein drink). Products were composed of matched ingredients and, thereby, had the same macro- and micronutrient composition. On both test days, arterialized blood samples were collected at regular time intervals for up to 4 hr following protein ingestion to assess the postprandial rise in plasma amino acid concentrations. Protein ingestion robustly elevated circulating plasma amino acid concentrations (p < .001), with no significant differences between treatments (p = .088). The incremental area under the curve of the postprandial rise in total plasma amino acid concentrations did not differ following bar versus drink consumption (160 ± 73 vs. 160 ± 71 mmol·L-1·240 min-1, respectively; 95% confidence interval [-37, 37]; Cohen's dz = 0.003; p = .992). Ingestion of protein in liquid or solid form does not modulate postprandial amino acid availability in healthy, female adults. Any differences in protein digestion and amino acid absorption due to differences in food matrix are not attributed to the protein being consumed as a bar or as a drink.

Pre-sleep Protein Ingestion Increases Mitochondrial Protein Synthesis Rates During Overnight Recovery from Endurance Exercise: A Randomized Controlled Trial.

BACKGROUND: Casein protein ingestion prior to sleep has been shown to increase myofibrillar protein synthesis rates during overnight sleep. It remains to be assessed whether pre-sleep protein ingestion can also increase mitochondrial protein synthesis rates. Though it has been suggested that casein protein may be preferred as a pre-sleep protein source, no study has compared the impact of pre-sleep whey versus casein ingestion on overnight muscle protein synthesis rates. OBJECTIVE: We aimed to assess the impact of casein and whey protein ingestion prior to sleep on mitochondrial and myofibrillar protein synthesis rates during overnight recovery from a bout of endurance-type exercise. METHODS: Thirty-six healthy young men performed a single bout of endurance-type exercise in the evening (19:45 h). Thirty minutes prior to sleep (23:30 h), participants ingested 45 g of casein protein, 45 g of whey protein, or a non-caloric placebo. Continuous intravenous L-[ring-13C6]-phenylalanine infusions were applied, with blood and muscle tissue samples being collected to assess overnight mitochondrial and myofibrillar protein synthesis rates. RESULTS: Pooled protein ingestion resulted in greater mitochondrial (0.087 ± 0.020 vs 0.067 ± 0.016%·h-1, p = 0.005) and myofibrillar (0.060 ± 0.014 vs 0.047 ± 0.011%·h-1, p = 0.012) protein synthesis rates when compared with placebo. Casein and whey protein ingestion did not differ in their capacity to stimulate mitochondrial (0.082 ± 0.019 vs 0.092 ± 0.020%·h-1, p = 0.690) and myofibrillar (0.056 ± 0.009 vs 0.064 ± 0.018%·h-1, p = 0.440) protein synthesis rates. CONCLUSIONS: Protein ingestion prior to sleep increases both mitochondrial and myofibrillar protein synthesis rates during overnight recovery from exercise. The overnight muscle protein synthetic response to whey and casein protein does not differ. CLINICAL TRIAL REGISTRATION: NTR7251 .

Acute Quark Ingestion Increases Muscle Protein Synthesis Rates at Rest with a Further Increase after Exercise in Young and Older Adult Males in a Parallel-Group Intervention Trial.

BACKGROUND: Ingestion of protein concentrates or isolates increases muscle protein synthesis rates in young and older adults. There is far less information available on the anabolic response following the ingestion of dairy wholefoods, which are commonly consumed in a normal diet. OBJECTIVES: This study investigates whether ingestion of 30 g protein provided as quark increases muscle protein synthesis rates at rest and whether muscle protein synthesis rates are further increased after resistance exercise in young and older adult males. METHODS: In this parallel-group intervention trial, 14 young (18-35 y) and 15 older (65-85 y) adult males ingested 30 g protein provided as quark after a single-legged bout of resistance exercise on leg press and leg extension machines. Primed, continuous intravenous L-[ring-13C6]-phenylalanine infusions were combined with the collection of blood and muscle tissue samples to assess postabsorptive and 4-h postprandial muscle protein synthesis rates at rest and during recovery from exercise. Data represent means ± SDs; η2 was used to measure the effect size. RESULTS: Plasma total amino acid and leucine concentrations increased after quark ingestion in both groups (both time: P < 0.001; η2 > 0.8), with no differences between groups (time × group: P = 0.127 and P = 0.172, respectively; η2<0.1). Muscle protein synthesis rates increased following quark ingestion at rest in both young (from 0.030 ± 0.011 to 0.051 ± 0.011 %·h-1) and older adult males (from 0.036 ± 0.011 to 0.062 ± 0.013 %·h-1), with a further increase in the exercised leg (to 0.071 ± 0.023 %·h-1 and to 0.078 ± 0.019 %·h-1, respectively; condition: P < 0.001; η2 = 0.716), with no differences between groups (condition × group: P = 0.747; η2 = 0.011). CONCLUSIONS: Quark ingestion increases muscle protein synthesis rates at rest with a further increase following exercise in both young and older adult males. The postprandial muscle protein synthetic response following quark ingestion does not differ between healthy young and older adult males when an ample amount of protein is ingested. This trial was registered at the Dutch Trial register, which is accessible via trialsearch.who.int www.trialregister.nl as NL8403.

Maternal dietary intake, nutritional status and macronutrient composition of human breast milk: systematic review.

Human breast milk (BM) is the best source of nutrition in early life, particularly during the first 6 months. Nevertheless, human BM composition is variable, and more insight in the exact factors contributing to this variability is warranted. In this review, we explored the impact of maternal dietary intake and nutritional status (e.g. anthropometric measures, BMI, bioimpedance) on human milk macronutrient composition. PubMed, Scopus and Cochrane were systematically searched till November 2019. In total, 4946 publications underwent title-abstract screening; 101 publications underwent full-text screening. Eventually, fifty publications were included in this review, investigating either associations between maternal dietary intake (n 29) and/or maternal nutritional status (n 29), and macronutrient composition of human BM. Reported energy composition ranged from 213 to 301 kJ/100 ml, and 67 % and 54 % of the studies reported associations between with maternal nutritional intake and status, respectively. Protein content ranged from 0·8 to 3·3 g/100 ml, and four studies suggested a negative association with nutritional status. Fat content ranged from 2·1 to 9·8 g/100 ml, and 68 % of the studies reported positive associations with nutritional status. Carbohydrate content ranged from 5·8 to 7·5 g/100 ml, and 67 % of the included studies did not report an association between intake and status. Literature investigating associations of maternal dietary intake and nutrition status with BM composition of macronutrients and energy content is diversified, both in terms of used methodology and results. Further studies using well-defined and standard parameters are essential to aid the formulation of scientific recommendations.

A Nitrate-Rich Vegetable Intervention Elevates Plasma Nitrate and Nitrite Concentrations and Reduces Blood Pressure in Healthy Young Adults.

BACKGROUND: Emerging evidence suggests that increasing dietary nitrate intake may be an effective approach to reduce blood pressure. Beetroot juice is often used to supplement dietary nitrate, whereas nitrate intake levels from habitual diet are low. An increase in the habitual intake of nitrate-rich vegetables may represent an alternative to nitrate supplementation. However, the effectiveness and acceptability of a nitrate-rich-vegetables diet remain to be established. OBJECTIVE: The aim was to investigate the effect and feasibility of two different intervention strategies to increase dietary nitrate intake, on plasma nitrate/nitrite concentrations and blood pressure. DESIGN: A randomized, crossover trial was used. PARTICIPANTS: Participants were healthy men and women (both n=15; age: 24±6 years) from the Netherlands. INTERVENTION: Participants were instructed to consume ∼400 mg nitrate at lunch, provided through nitrate-rich vegetables and dietary counseling, or beetroot juice supplementation. Both interventions lasted 1 week, with 1-week washout (January to April 2017). MAIN OUTCOME: Plasma nitrate and nitrite concentrations and resting systolic and diastolic blood pressure were measured in an overnight fasted state (before and after intervention) and ∼2.5 hours after lunch (before and throughout intervention on day 1, 4, and 7). STATISTICAL ANALYSIS: Two-factor (time × treatment) repeated-measures analyses of variance were performed. RESULTS: Mean plasma nitrate concentrations increased with both interventions, with a larger increase in beetroot juice vs nitrate-rich vegetables, both in a fasted state and ∼2.5 hours after lunch (day 1, beetroot juice: 2.31±0.56 mg/dL [373±90 µmol/L] vs nitrate-rich vegetables: 1.71±0.83 mg/dL [277±134 µmol/L]; P<0.001). Likewise, mean plasma nitrite concentrations increased with both interventions, but were higher after lunch in beetroot juice than in nitrate-rich vegetables (day 1: 2.58±1.52 µg/dL [560±331 nmol/L] vs 2.15±1.21 µg/dL [468±263 nmol/L]; P=0.020). Fasting mean systolic and diastolic blood pressure did not change, but mean systolic and diastolic blood pressure assessed ∼2.5 hours after lunch were significantly reduced throughout both intervention periods (P<0.05), with no differences between beetroot juice and nitrate-rich vegetables (day 1, systolic blood pressure: -5.1±9.5 mm Hg and diastolic blood pressure: -5.3±8.9 mm Hg). CONCLUSION: Short-term consumption of dietary nitrate in the form of nitrate-rich vegetables represents an effective means to increase plasma nitrate and nitrite concentrations, and reduces blood pressure to the same extent as beetroot juice supplementation.

Could intramuscular storage of dietary nitrate contribute to its ergogenic effect? A mini-review.

Extensive research performed over the past 10 years has resulted in dietary nitrate being considered a nutritional supplement that can improve exercise performance. However, there is still limited insight in the metabolic fate of dietary nitrate following the appearance of nitrate and nitrite in the circulation. Recent observations in humans suggest the storage of nitrate in skeletal muscle tissue. This short review discusses the possibility of nitrate being stored and utilized in human skeletal muscle tissue, and why confirming this may increase our understanding of how the nitrate-nitrite-NO pathway improves exercise performance. Further insight in skeletal muscle nitrate storage and metabolism may provide answers to current gaps in knowledge, such as the ergogenic benefit of acute vs multiday dietary nitrate supplementation, as well as the suggested muscle fiber-type specific effects on exercise performance. In this mini-review, specific questions that need further exploration are also discussed.

The glycation level of milk protein strongly modulates post-prandial lysine availability in humans.

Industrial heat treatment of milk results in protein glycation. A high protein glycation level has been suggested to compromise the post-prandial rise in plasma amino acid availability following protein ingestion. In the present study, we assessed the impact of glycation level of milk protein on post-prandial plasma amino acid responses in humans. Fifteen healthy, young men (age 26 (SEM 1) years, BMI 24 (SEM 1) kg/m2) participated in this randomised cross-over study and ingested milk protein powder with protein glycation levels of 3, 20 and 50 % blocked lysine. On each trial day, arterialised blood samples were collected at regular intervals during a 6-h post-prandial period to assess plasma amino acid concentrations using ultra-performance liquid chromatography. Plasma essential amino acid (EAA) concentrations increased following milk protein ingestion, with the 20 and 50 % glycated milk proteins showing lower overall EAA responses compared with the 3 % glycated milk protein (161 (SEM 7) and 142 (SEM 7) v. 178 (SEM 9) mmol/l × 6 h, respectively; P ≤ 0·011). The lower post-prandial plasma amino acid responses were fully attributed to an attenuated post-prandial rise in circulating plasma lysine concentrations. Plasma lysine responses (incremental AUC) following ingestion of the 20 and 50 % glycated milk proteins were 35 (SEM 4) and 92 (SEM 2) % lower compared with the 3 % glycated milk protein (21·3 (SEM 1·4) and 2·8 (SEM 0·7) v. 33·3 (SEM 1·7) mmol/l × 6 h, respectively; P < 0·001). Milk protein glycation lowers post-prandial plasma lysine availability in humans. The lower post-prandial availability of lysine following ingestion of proteins with a high glycation level may compromise the anabolic properties of a protein source.

Blood Flow Restriction Only Increases Myofibrillar Protein Synthesis with Exercise.

PURPOSE: Combining blood flow restriction (BFR) with exercise can stimulate skeletal muscle hypertrophy. Recent observations in an animal model suggest that BFR performed without exercise can also induce anabolic effects. We assessed the effect of BFR performed both with and without low-load resistance-type exercise (LLRE) on in vivo myofibrillar protein synthesis rates in young men. METHODS: Twenty healthy young men (age = 24 ± 1 yr, body mass index = 22.9 ± 0.6 kg·m) were randomly assigned to remain in resting condition (REST ± BFR; n = 10) or to perform LLRE (LLRE ± BFR at 20% one-repetition maximum; n = 10), combined with two 5-min cycles of single leg BFR. Myofibrillar protein synthesis rates were assessed during a 5-h post-BFR period by combining a primed continuous L-[ring-C6]phenylalanine infusion with the collection of blood samples, and muscle biopsies from the BFR leg and the contralateral control leg. The phosphorylation status of anabolic signaling (mammalian target of rapamycin pathway) and metabolic stress (acetyl-CoA carboxylase)-related proteins, as well as the mRNA expression of genes associated with skeletal muscle mass regulation, was assessed in the collected muscle samples. RESULTS: Under resting conditions, no differences in anabolic signaling or myofibrillar protein synthesis rates were observed between REST + BFR and REST (0.044% ± 0.004% vs 0.043% ± 0.004% per hour, respectively; P = 0.683). By contrast, LLRE + BFR increased myofibrillar protein synthesis rates by 10% ± 5% compared with LLRE (0.048% ± 0.005% vs 0.043% ± 0.004% per hour, respectively; P = 0.042). Furthermore, compared with LLRE, LLRE + BFR showed higher phosphorylation status of acetyl-CoA carboxylase and 4E-BP1 as well as the elevated mRNA expression of MuRF1 (all P < 0.05). CONCLUSION: BFR does not increase myofibrillar protein synthesis rates in healthy young men under resting conditions. When combined with LLRE, BFR increases postexercise myofibrillar protein synthesis rates in vivo in humans.

Arginine does not rescue p.Q188R mutation deleterious effect in classic galactosemia.

BACKGROUND: Classic galactosemia is a rare genetic metabolic disease with an unmet treatment need. Current standard of care fails to prevent chronically-debilitating brain and gonadal complications. Many mutations in the GALT gene responsible for classic galactosemia have been described to give rise to variants with conformational abnormalities. This pathogenic mechanism is highly amenable to a therapeutic strategy based on chemical/pharmacological chaperones. Arginine, a chemical chaperone, has shown beneficial effect in other inherited metabolic disorders, as well as in a prokaryotic model of classic galactosemia. The p.Q188R mutation presents a high prevalence in the Caucasian population, making it a very clinically relevant mutation. This mutation gives rise to a protein with lower conformational stability and lower catalytic activity. The aim of this study is to assess the potential therapeutic role of arginine for this mutation. METHODS: Arginine aspartate administration to four patients with the p.Q188R/p.Q188R mutation, in vitro studies with three fibroblast cell lines derived from classic galactosemia patients as well as recombinant protein experiments were used to evaluate the effect of arginine in galactose metabolism. This study has been registered at https://clinicaltrials.gov (NCT03580122) on 09 July 2018. Retrospectively registered. RESULTS: Following a month of arginine administration, patients did not show a significant improvement of whole-body galactose oxidative capacity (p = 0.22), erythrocyte GALT activity (p = 0.87), urinary galactose (p = 0.52) and urinary galactitol levels (p = 0.41). Patients' fibroblasts exposed to arginine did not show changes in GALT activity. Thermal shift analysis of recombinant p.Q188R GALT protein in the presence of arginine did not exhibit a positive effect. CONCLUSIONS: This short pilot study in four patients homozygous for the p.Q188R/p.Q188R mutation reveals that arginine has no potential therapeutic role for galactosemia patients homozygous for the p.Q188R mutation.

Relation between age and carotid artery intima-medial thickness: a systematic review.

Carotid artery intima-medial thickness (cIMT) represents a popular measure of atherosclerosis and is predictive of future cardiovascular and cerebrovascular events. Although older age is associated with a higher cIMT, little is known about whether this increase in cIMT follows a linear relationship with age or it is affected under influence of cardiovascular diseases (CVD) or CVD risk factors. We hypothesize that the relationship between cIMT and age is nonlinear and is affected by CVD or risk factors. A systematic review of studies that examined cIMT in the general population and human populations free from CVD/risk factors was undertaken. The literature search was conducted in PubMed, Scopus, and Web of Science. Seventeen studies with 32 unique study populations, involving 10,124 healthy individuals free from CVD risk factors, were included. Furthermore, 58 studies with 115 unique study populations were included, involving 65,774 individuals from the general population (with and without CVD risk factors). A strong positive association was evident between age and cIMT in the healthy population, demonstrating a gradual, linear increase in cIMT that did not differ between age decades (r = 0.91, P < 0.001). Although populations with individuals with CVD demonstrated a higher cIMT compared to populations free of CVD, a linear relation between age and cIMT was also present in this population. Our data suggest that cIMT is strongly and linearly related to age. This linear relationship was not affected by CVD or risk factors.

Sodium nitrate ingestion increases skeletal muscle nitrate content in humans.

Nitrate ([Formula: see text]) ingestion has been shown to have vasoactive and ergogenic effects that have been attributed to increased nitric oxide (NO) production. Recent observations in rodents suggest that skeletal muscle tissue serves as an endogenous [Formula: see text] "reservoir." The present study determined [Formula: see text] contents in human skeletal muscle tissue in a postabsorptive state and following ingestion of a sodium nitrate bolus (NaNO3). Seventeen male, type 2 diabetes patients (age 72 ± 1 yr; body mass index 26.5 ± 0.5 kg/m2; means ± SE) were randomized to ingest a dose of NaNO3 (NIT; 9.3 mg [Formula: see text]/kg body wt) or placebo (PLA; 8.8 mg NaCl/kg body wt). Blood and muscle biopsy samples were taken before and up to 7 h following [Formula: see text] or placebo ingestion to assess [Formula: see text] [and plasma nitrite ([Formula: see text])] concentrations. Additionally, basal plasma and muscle [Formula: see text] concentrations were assessed in 10 healthy young (CON-Y; age 21 ± 1 yr) and 10 healthy older (CON-O; age 75 ± 1 yr) control subjects. In all groups, baseline [Formula: see text] concentrations were higher in muscle (NIT, 57 ± 7; PLA, 61 ± 7; CON-Y, 80 ± 10; CON-O, 54 ± 6 µmol/l) than in plasma (NIT, 35 ± 3; PLA, 32 ± 3; CON-Y, 38 ± 3; CON-O, 33 ± 3 µmol/l; P ≤ 0.011). Ingestion of NaNO3 resulted in a sustained increase in plasma [Formula: see text], plasma [Formula: see text], and muscle [Formula: see text] concentrations (up to 185 ± 25 µmol/l) in the NIT group (time effect P < 0.001) compared with PLA (treatment effect P < 0.05). In conclusion, basal [Formula: see text] concentrations are substantially higher in human skeletal muscle tissue compared with plasma. Ingestion of a bolus of dietary [Formula: see text] increases both plasma and muscle [Formula: see text] contents in humans.NEW & NOTEWORTHY Literature of the pharmacokinetics following dietary nitrate ingestion is usually limited to the changes observed in plasma nitrate and nitrite concentrations. The present investigation assessed the skeletal muscle nitrate content in humans during the postabsorptive state, as well as following dietary nitrate ingestion. We show that basal nitrate content is higher in skeletal muscle tissue than in plasma and that ingestion of a dietary nitrate bolus strongly increases both plasma and muscle nitrate concentrations.

Beetroot Juice Supplementation Improves High-Intensity Intermittent Type Exercise Performance in Trained Soccer Players.

It has been shown that nitrate supplementation can enhance endurance exercise performance. Recent work suggests that nitrate ingestion can also increase intermittent type exercise performance in recreational athletes. We hypothesized that six days of nitrate supplementation can improve high-intensity intermittent type exercise performance in trained soccer players. Thirty-two male soccer players (age: 23 ± 1 years, height: 181 ± 1 m, weight: 77 ± 1 kg, playing experience: 15.2 ± 0.5 years, playing in the first team of a 2nd or 3rd Dutch amateur league club) participated in this randomized, double-blind cross-over study. All subjects participated in two test days in which high-intensity intermittent running performance was assessed using the Yo-Yo IR1 test. Subjects ingested nitrate-rich (140 mL; ~800 mg nitrate/day; BR) or a nitrate-depleted beetroot juice (PLA) for six subsequent days, with at least eight days of wash-out between trials. The distance covered during the Yo-Yo IR1 was the primary outcome measure, while heart rate (HR) was measured continuously throughout the test, and a single blood and saliva sample were collected just prior to the test. Six days of BR ingestion increased plasma and salivary nitrate and nitrite concentrations in comparison to PLA (p < 0.001), and enhanced Yo-Yo IR1 test performance by 3.4 ± 1.3% (from 1574 ± 47 to 1623 ± 48 m; p = 0.027). Mean HR was lower in the BR (172 ± 2) vs. PLA trial (175 ± 2; p = 0.014). Six days of BR ingestion effectively improves high-intensity intermittent type exercise performance in trained soccer players.