Translational Significance of the LINE-1 Jumping Gene in Skeletal Muscle.

Retrotransposons are gene segments that proliferate in the genome, and the Long INterspersed Element 1 (LINE-1 or L1) retrotransposon is active in humans. Although older mammals show enhanced skeletal muscle L1 expression, exercise generally reverses this trend. We hypothesize skeletal muscle L1 expression influences muscle physiology, and additional innovative investigations are needed to confirm this hypothesis.

Effects of an external pneumatic compression device vs static compression garment on peripheral circulation and markers of sports performance and recovery.

PURPOSE: To identify the effects of a single 30 min partial lower leg external pneumatic compression (EPC) treatment compared to a static compression (SC) garment or a no treatment control (CTL) on markers of recovery and performance following a muscle damaging protocol. METHODS: Thirty healthy, active males (23 ± 3 years; 180.2 ± 9.0 cm; 81.6 ± 11.3 kg) performed 100 drop jumps from a 0.6 m box followed by a randomized, single 30 min treatment of either a partial lower leg EPC device worn below the knee and above the ankle (110 mmHg), SC garment (20-30 mmHg) covering the foot and calf just below the knee, or no treatment CTL, and then returned 24 and 48 h later. Participants were assessed for measures of muscle soreness, fatigue, hemodynamics, blood lactate, muscle thickness, circumferences, and performance assessments. RESULTS: The drop jump protocol significantly increased muscle soreness (p < 0.001), fatigue (p < 0.001), blood flow (p < 0.001), hemoglobin (p < 0.001), and muscle oxygen saturation (SMO2; p < 0.001). Countermovement jump and squat jump testing completed after treatment with either EPC, SC, or CTL revealed no differences for jump height between any condition. However, EPC treatment maintained consistent braking force and propulsive power measures across all timepoints for countermovement jump testing. EPC and SC treatment also led to better maintenance of squat jump performance for average relative propulsive force and power variables at 24 and 48 h compared to CTL. CONCLUSIONS: A single 30 min partial leg EPC treatment may lead to more consistent jump performance following a damaging bout of exercise.

Molecular Differences in Skeletal Muscle After 1 Week of Active vs. Passive Recovery From High-Volume Resistance Training.

ABSTRACT: Vann, CG, Haun, CT, Osburn, SC, Romero, MA, Roberson, PA, Mumford, PW, Mobley, CB, Holmes, HM, Fox, CD, Young, KC, and Roberts, MD. Molecular differences in skeletal muscle after 1 week of active vs. passive recovery from high-volume resistance training. J Strength Cond Res 35(8): 2102-2113, 2021-Numerous studies have evaluated how deloading after resistance training (RT) affects strength and power outcomes. However, the molecular adaptations that occur after deload periods remain understudied. Trained, college-aged men (n = 30) performed 6 weeks of whole-body RT starting at 10 sets of 10 repetitions per exercise per week and finishing at 32 sets of 10 repetitions per exercise per week. After this period, subjects performed either active (AR; n = 16) or passive recovery (PR; n = 14) for 1 week where AR completed ∼15% of the week 6 training volume and PR ceased training. Variables related to body composition and recovery examined before RT (PRE), after 6 weeks of RT (POST), and after the 1-week recovery period (DL). Vastus lateralis (VL) muscle biopsies and blood samples were collected at each timepoint, and various biochemical and histological assays were performed. Group × time interactions (p < 0.05) existed for skeletal muscle myosin heavy chain (MHC)-IIa mRNA (AR > PR at POST and DL) and 20S proteasome activity (post-hoc tests revealed no significance in groups over time). Time effects (P < 0.05) existed for total mood disturbance and serum creatine kinase and mechano growth factor mRNA (POST > PRE &D L), VL pressure to pain threshold and MHC-IIx mRNA (PRE&DL > POST), Atrogin-1 and MuRF-1 mRNA (PRE < POST < DL), MHC-I mRNA (PRE < POST & DL), myostatin mRNA (PRE & POST < DL), and mechanistic target of rapamycin (PRE > POST & DL). No interactions or time effects were observed for barbell squat velocity, various hormones, histological metrics, polyubiquitinated proteins, or phosphorylated/pan protein levels of 4E-BP1, p70S6k, and AMPK. One week of AR after a high-volume training block instigates marginal molecular differences in skeletal muscle relative to PR. From a practical standpoint, however, both paradigms elicited largely similar responses.

Five months of voluntary wheel running downregulates skeletal muscle LINE-1 gene expression in rats.

Transposable elements (TEs) are mobile DNA and constitute approximately half of the human genome. LINE-1 (L1) is the only active autonomous TE in the mammalian genome and has been implicated in a number of diseases as well as aging. We have previously reported that skeletal muscle L1 expression is lower following acute and chronic exercise training in humans. Herein, we used a rodent model of voluntary wheel running to determine whether long-term exercise training affects markers of skeletal muscle L1 regulation. Selectively bred high-running female Wistar rats (n = 11 per group) were either given access to a running wheel (EX) or not (SED) at 5 wk of age, and these conditions were maintained until 27 wk of age. Thereafter, mixed gastrocnemius tissue was harvested and analyzed for L1 mRNA expression and DNA content along with other L1 regulation markers. We observed significantly (P < 0.05) lower L1 mRNA expression, higher L1 DNA methylation, and less L1 DNA in accessible chromatin regions in EX versus SED rats. We followed these experiments with 3-h in vitro drug treatments in L6 myotubes to mimic transient exercise-specific signaling events. The AMP-activated protein kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR; 4 mM) significantly decreased L1 mRNA expression in L6 myotubes. However, this effect was not facilitated through increased L1 DNA methylation. Collectively, these data suggest that long-term voluntary wheel running downregulates skeletal muscle L1 mRNA, and this may occur through chromatin modifications. Enhanced AMPK signaling with repetitive exercise bouts may also decrease L1 mRNA expression, although the mechanism of action remains unknown.

Skeletal muscle LINE-1 retrotransposon activity is upregulated in older versus younger rats.

Long interspersed element-1 (LINE-1) is a retrotransposon capable of replicating and inserting LINE-1 copies into the genome. Others have reported skeletal muscle LINE-1 markers are higher in older versus younger mice, but data are lacking in other species. Herein, gastrocnemius muscle from male Fischer 344 rats that were 3, 12, and 24 mo old (n = 9 per group) were analyzed for LINE-1 mRNA, DNA, promoter methylation and DNA accessibility. qPCR primers were designed for active (L1.3) and inactive (L1.Tot) LINE-1 elements as well as part of the ORF1 sequence. L1.3, L1.Tot, and ORF1 mRNAs were higher (P < 0.05) in 12/24 versus 3-mo-old rats. L1.3 DNA was higher in the 24-mo-old rats versus other groups, and ORF1 DNA was greater in 12/24 versus 3-mo-old rats. ORF1 protein was higher in 12/24 versus 3-mo-old rats. RNA-sequencing indicated mRNAs related to DNA methylation (Tet1) and histone acetylation (Hdac2) were lower in 24 versus 3-mo-old rats. L1.3 DNA accessibility was higher in 24-mo-old versus 3-mo-old rats. No age-related differences in nuclear histone deacetylase (HDAC) activity existed, although nuclear DNA methyltransferase (DNMT) activity was lower in 12/24 versus 3-mo-old rats (P < 0.05). In summary, markers of skeletal muscle LINE-1 activity increase across the age spectrum of rats, and this may be related to deficits in DNMT activity and/or increased LINE-1 DNA accessibility.

Acute and chronic resistance training downregulates select LINE-1 retrotransposon activity markers in human skeletal muscle.

Herein, we examined if acute or chronic resistance exercise affected markers of skeletal muscle long interspersed nuclear element-1 (LINE-1) retrotransposon activity. In study 1, 10 resistance-trained college-aged men performed three consecutive daily back squat sessions, and vastus lateralis biopsies were taken before (Pre), 2 h following session 1 (Post1), and 3 days following session 3 (Post2). In study 2, 13 untrained college-aged men performed a full-body resistance training program (3 days/wk), and vastus lateralis biopsies were taken before ( week 0) and ~72 h following training cessation ( week 12). In study 1, LINE-1 mRNA decreased 42-48% at Post1 and 2 ( P < 0.05), and reverse transcriptase (RT) activity trended downward at Post2 (-37%, P = 0.067). In study 2, LINE-1 mRNA trended downward at week 12 (-17%, P = 0.056) while LINE-1 promoter methylation increased (+142%, P = 0.041). Open reading frame (ORF)2p protein expression (-24%, P = 0.059) and RT activity (-26%, P = 0.063) also trended downward by week 12. Additionally, changes in RT activity versus satellite cell number were inversely associated ( r = -0.725, P = 0.008). Follow-up in vitro experiments demonstrated that 48-h treatments with lower doses (1 µM and 10 µM) of efavirenz and nevirapine (non-nucleoside RT inhibitors) increased myoblast proliferation ( P < 0.05). However, we observed a paradoxical decrease in myoblast proliferation with higher doses (50 µM) of efavirenz and delavirdine. This is the first report suggesting that resistance exercise downregulates markers of skeletal muscle LINE-1 activity. Given our discordant in vitro findings, future research is needed to thoroughly assess whether LINE-1-mediated RT activity enhances or blunts myoblast, or primary satellite cell, proliferative capacity.

Skeletal muscle amino acid transporter and BCAT2 expression prior to and following interval running or resistance exercise in mode-specific trained males.

Endurance (END)- and resistance (RES)-trained males performed interval running or resistance exercise during three consecutive days (bouts 1-3). Muscle biopsies were obtained at baseline, 2 h post-bout 1, and 72 h post-bout 3. Amino acid transporter SNAT2 mRNA was 75% greater in END (group p = 0.008), and increased ~ 70% 2 h post in both groups (time p = 0.023). Amino acid transporter PAT1 mRNA was 2.7-fold greater in RES (group p = 0.002). Baseline protein levels of the mitochondrial aminotransferase BCAT2 were 79% greater in END (p = 0.015).

Effect of 1-week betalain-rich beetroot concentrate supplementation on cycling performance and select physiological parameters.

PURPOSE: Betalains are indole-derived pigments found in beet root, and recent studies suggest that they may exert ergogenic effects. Herein, we examined if supplementation for 7 days with betalain-rich beetroot concentrate (BLN) improved cycling performance or altered hemodynamic and serum analytes prior to, during and following a cycling time trial (TT). METHODS: Twenty-eight trained male cyclists (29 ± 10 years, 77.3 ± 13.3 kg, and 3.03 ± 0.62 W/kg) performed a counterbalanced crossover study whereby BLN (100 mg/day) or placebo (PLA) supplementation occurred over 7 days with a 1-week washout between conditions. On the morning of day seven of each supplementation condition, participants consumed one final serving of BLN or PLA and performed a 30-min cycling TT with concurrent assessment of several physiological variables and blood markers. RESULTS: BLN supplementation improved average absolute power compared to PLA (231.6 ± 36.2 vs. 225.3 ± 35.8 W, p = 0.050, d = 0.02). Average relative power, distance traveled, blood parameters (e.g., pH, lactate, glucose, NOx) and inflammatory markers (e.g., IL-6, IL-8, IL-10, TNFα) were not significantly different between conditions. BLN supplementation significantly improved exercise efficiency (W/ml/kg/min) in the last 5 min of the TT compared to PLA (p = 0.029, d = 0.45). Brachial artery blood flow in the BLN condition, immediately post-exercise, tended to be greater compared to PLA (p = 0.065, d = 0.32). CONCLUSIONS: We report that 7 days of BLN supplementation modestly improves 30-min TT power output, exercise efficiency as well as post-exercise blood flow without increasing plasma NOx levels or altering blood markers of inflammation, oxidative stress, and/or hematopoiesis.

Concomitant external pneumatic compression treatment with consecutive days of high intensity interval training reduces markers of proteolysis.

PURPOSE: To compare the effects of external pneumatic compression (EPC) and sham when used concurrently with high intensity interval training (HIIT) on performance-related outcomes and recovery-related molecular measures. METHODS: Eighteen recreationally endurance-trained male participants (age: 21.6 ± 2.4 years, BMI: 25.7 ± 0.5 kg/m2, VO2peak: 51.3 ± 0.9 mL/kg/min) were randomized to balanced sham and EPC treatment groups. Three consecutive days of HIIT followed by EPC/sham treatment (Days 2-4) and 3 consecutive days of recovery (Days 5-7) with EPC/sham only on Days 5-6 were employed. Venipuncture, flexibility and pressure-to-pain threshold (PPT) measurements were made throughout. Vastus lateralis muscle was biopsied at PRE (i.e., Day 1), 1-h post-EPC/sham treatment on Day 2 (POST1), and 24-h post-EPC/sham treatment on Day 7 (POST2). 6-km run time trial performance was tested at PRE and POST2. RESULTS: No group × time interaction was observed for flexibility, PPT, or serum measures of creatine kinase (CK), hsCRP, and 8-isoprostane. However, there was a main effect of time for serum CK (p = 0.005). Change from PRE in 6-km run times at POST2 were not significantly different between groups. Significant between-groups differences existed for change from PRE in atrogin-1 mRNA (p = 0.018) at the POST1 time point (EPC: - 19.7 ± 8.1%, sham: + 7.7 ± 5.9%) and atrogin-1 protein concentration (p = 0.013) at the POST2 time point (EPC: - 31.8 ± 7.5%, sham: + 96.0 ± 34.7%). In addition, change from PRE in poly-Ub proteins was significantly different between groups at both the POST1 (EPC: - 26.0 ± 10.3%, sham: + 34.8 ± 28.5%; p = 0.046) and POST2 (EPC: - 33.7 ± 17.2%, sham: + 21.4 ± 14.9%; p = 0.037) time points. CONCLUSIONS: EPC when used concurrently with HIIT and in subsequent recovery days reduces skeletal muscle markers of proteolysis.

Whey protein-derived exosomes increase protein synthesis and hypertrophy in C2-C12 myotubes.

We sought to examine potential amino acid independent mechanisms whereby hydrolyzed whey protein (WP) affects muscle protein synthesis (MPS) and anabolism in vitro. Specifically, we tested (1) whether 3-h and 6-h treatments of WP, essential amino acids, or l-leucine (Leu) affected MPS, and whether 6-h treatments with low-, medium-, or high doses of WP versus Leu affected MPS; (2) whether knockdown of the primary Leu transporter affected WP- and Leu-mediated changes in MPS, mammalian target of rapamycin (mTOR) signaling responses, or both, following 6-h treatments; (3) whether exosomes isolated from WP (WP-EXO) affected MPS, mTOR signaling responses, or both, compared with untreated (control) myotubes, following 6-h, 12-h, and 24-h treatments, and whether they affected myotube diameter following 24-h and 48-h treatments. For all treatments, 7-d post-differentiated C2C12 myotubes were examined. In experiment 1, 6-h WP treatments increased MPS compared with control (+46%), Leu (+24%), and essential amino acids (+25%). Moreover, the 6-h low-, medium-, and high WP treatments increased MPS by approximately 40 to 50% more than corresponding Leu treatments. In experiment 2 (LAT short hairpin RNA-transfected myotubes), 6-h WP treatments increased MPS compared with control (+18%) and Leu (+19%). In experiment 3, WP-EXO treatments increased MPS over controls at 12h (+18%) and 24h (+45%), and myotube diameters increased with 24-h (+24%) and 48-h (+40%) WP-EXO treatments compared with controls. The WP-EXO treatments did not appear to operate through mTOR signaling; instead, they increased mRNA and protein levels o eukaryotic initiation factor 4A. Bovine-specific microRNA following 24-h WP-EXO treatments were enriched in myotubes (chiefly miR-149-3p, miR-2881), but were not related to hypertrophic gene targets. To summarize, hydrolyzed WP-EXO increased skeletal MPS and anabolism in vitro, and this may be related to an unknown mechanism that increases translation initiation factors rather than enhancing mTOR signaling or the involvement of bovine-specific microRNA.

Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running.

We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley rats (∼9-10 wk of age) exercised with resistance-loaded voluntary running wheels (EX; wheels loaded with 20-60% body mass) or remained sedentary (SED) over 6 wk. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7-42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n = 8-10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency were lowest in KD rats, independent of exercise (P < 0.05). Absolute and relative (body mass-adjusted) omental adipose tissue (OMAT) masses were greatest in WD rats (P < 0.05), and OMAT adipocyte diameters were lowest in KD-fed rats (P < 0.05). None of the assayed OMAT or subcutaneous (SQ) protein markers were affected by the diets [total acetyl coA carboxylase (ACC), CD36, and CEBPα or phosphorylated NF-κB/p65, AMPKα, and hormone-sensitive lipase (HSL)], although EX unexpectedly altered some OMAT markers (i.e., higher ACC and phosphorylated NF-κB/p65, and lower phosphorylated AMPKα and phosphorylated HSL). Liver triglycerides were greatest in WD rats (P < 0.05), and liver phosphorylated NF-κB/p65 was lowest in KD rats (P < 0.05). Serum insulin, glucose, triglycerides, and total cholesterol were greater in WD and/or SC rats compared with KD rats (P < 0.05), and serum ß-hydroxybutyrate was greater in KD vs. SC rats (P < 0.05). In conclusion, KD rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss.

A Pilot Study Examining the Effects of 8-Week Whey Protein versus Whey Protein Plus Creatine Supplementation on Body Composition and Performance Variables in Resistance-Trained Women.

AIMS: We performed a pilot study examining the effects of whey protein and creatine supplementation (PRO + CRE group) versus whey protein supplementation (PRO group) alone on body composition and performance variables in a limited number of resistance-trained women. METHODS: Seventeen resistance-trained women (21 ± 3 years, 64.7 ± 8.2 kg, 23.5 kg/m2, 26.6 ± 4.8% body fat, >6 months of training) performed a 4-day per week split-body resistance training program for 8 weeks. Subjects ingested either 24 g PRO (n = 9) or 24 g whey plus 5 g creatine monohydrate (PRO + CRE, n = 8) following each exercise bout. At baseline (T1), 4 weeks (T2) and 8 weeks (T3), body composition was measured by dual X-ray absorptiometry (DXA), strength measures (leg press and bench press one repetition maximum) and lower-body power measures were determined. RESULTS: DXA lean mass increased from T1 to T3 in both groups (PRO: +2.5 kg, p < 0.001; PRO + CRE: +2.5 kg, p < 0.001), although no differences between groups were observed. Compared to T1 values, performance measures similarly increased in both groups from T1 to T3 although, no between-group differences were observed. CONCLUSIONS: PRO + CRE did not enhance training adaptations compared to PRO, albeit studies employing longer-term interventions with larger sample sizes are needed in order to confirm or disprove our findings.

Milk or Kefir, in Comparison to Water, Do Not Enhance Running Time-Trial Performance in Endurance Master Athletes.

This study compared flavored kefir (KFR) and flavored milk (MLK) as a recovery drink in endurance master athletes. Using a randomized, placebo-controlled, non-blinded crossover design, 11 males and females completed three testing visits whilst acutely ingesting either KFR, MLK, or water as a placebo (PLA). KFR supplementation occurred for 14 days before the KFR-testing day, followed by a 3-week washout period. Testing visits consisted of an exhausting-exercise (EE) bout, a 4-h rest period where additional carbohydrate feeding was provided, and a treadmill 5 km time trial (TT). The Gastrointestinal Symptom Rating Scale (GSRS) survey was assessed at four timepoints. Blood was collected at baseline and after the TT and was analyzed for I-FABP levels. No significant difference (PLA: 33:39.1 ± 6:29.0 min, KFR: 33:41.1 ± 5:44.4 min, and MLK: 33:36.2 ± 6:40.5 min, p = 0.99) was found between the groups in TT performance. The KFR GSRS total score was significantly lower than the PLA after EE (p = 0.005). No differences in I-FABP were observed between conditions. In conclusion, acute KFR supplementation did not impact TT performance or I-FABP levels but may have reduced subjective GI symptoms surrounding exercise when compared to MLK or PLA.

A Dose-Response Study to Examine Paraxanthine's Impact on Energy Expenditure, Hunger, Appetite, and Lipolysis.

This study investigated if paraxanthine (PX) impacts energy expenditure, lipolysis and perceptual responses. In a randomized, double-blind, placebo-controlled, crossover fashion, 21 adults (13 M, 8 F; 26.0 ± 6.4 years, 174.9 ± 11.5 cm, 81.0 ± 15.7 kg body mass, 26.3 ± 3.4 kg/m2) consumed a placebo (PLA), 100 mg (PX100), 200 mg (PX200), and 300 mg of PX (PX300, enfinity®, Ingenious Ingredients, L.P. Lewisville, TX, USA). Venous blood was collected 0, 30, 60, 90, 120 and 180 min (min) after ingestion and analyzed for glycerol and free fatty acids. Resting hemodynamics, metabolic rate and perceptual indicators of hunger, appetite and anxiety were evaluated. Mixed factorial analysis of variance were used to evaluate changes time within and between groups. Heart rate decreased in PX100 compared to PLA 60 (p = .022) and 180 min (p = .001). Blood pressure did not change. Hunger ratings in PLA increased 30 (p = .05), 60 (p = .04), 90 (p = .02), and 180 min (p = .05) after ingestion when compared to PX200. PX200 increased energy expenditure (all p < .05) when compared to PLA. Rates of fat oxidation tended to increase 90 (p = .056) and 120 min (p = .066) in PX200 compared to PLA. Free fatty acids increased in PX300 compared to PLA (p = .002). Glycerol did not change. Ingestion of PX200 augmented energy expenditure and hunger ratings when compared to PLA without impacting hemodynamics or lipolysis.

Peripheral quantitative computed tomography is a valid imaging technique for tracking changes in skeletal muscle cross-sectional area.

Peripheral quantitative computed tomography (pQCT) has recently expanded to quantifying skeletal muscle, however its validity to determine muscle cross-sectional area (mCSA) compared to magnetic resonance imaging (MRI) is unknown. Eleven male participants (age: 22 ± 3 y) underwent pQCT and MRI dual-leg mid-thigh imaging before (PRE) and after (POST) 6 weeks of resistance training for quantification of mid-thigh mCSA and change in mCSA. mCSA agreement at both time points and absolute change in mCSA across time was assessed using Bland-Altman plots for mean bias and 95% limits of agreement (LOA), as well as Lin's concordance correlation coefficients (CCC). Both pQCT and MRI mCSA increased following 6 weeks of resistance training (∆mCSApQCT: 6.7 ± 5.4 cm2, p < 0.001; ∆mCSAMRI: 6.0 ± 6.4 cm2, p < 0.001). Importantly, the change in mCSA was not different between methods (p = 0.39). Bland-Altman analysis revealed a small mean bias (1.10 cm2, LOA: -6.09, 8.29 cm2) where pQCT tended to overestimate mCSA relative to MRI when comparing images at a single time point. Concordance between pQCT and MRI mCSA at PRE and POST was excellent yielding a CCC of 0.982. For detecting changes in mCSA, Bland-Altman analysis revealed excellent agreement between pQCT and MRI (mean bias: -0.73 cm2, LOA: -8.37, 6.91 cm2). Finally, there was excellent concordance between pQCT and MRI mCSA change scores (CCC = 0.779). Relative to MRI, pQCT imaging is a valid technique for measuring both mid-thigh mCSA at a single time point and mCSA changes following a resistance training intervention.

Dose-Response Absorption Kinetics of Oral L-Beta-Aminoisobutyric Acid (L-BAIBA) Supplementation in Healthy Men and Women.

L-Beta-amino isobutyric acid (L-BAIBA) is a myokine produced in skeletal muscle during exercise and has been shown to impact carbohydrate and fat metabolism in both animals and humans. This study was designed to determine the rate and extent to which L-BAIBA appeared in human plasma after oral ingestion. In a randomized, double-blind, placebo-controlled, crossover fashion, six males and 6 females (N = 12; 24 ± 5 yrs; 173.6 ± 12.0 cm; 72.3 ± 11.3 kg; 21.0 ± 7.0 body fat %) completed a single-dose supplementation protocol of placebo (PLA), L-BAIBA at 250 mg (B250), 500 mg (B500), 1,500mg (B1500), and 1,500mg of valine (V1500). Participants fasted overnight (8-10 h) and consumed their dose with 8-12 fluid ounces of cold water. Venous blood samples were collected 0, 30, 60, 90, 120, 180, 240 and 300 min after ingestion and analyzed for L-BAIBA. Complete blood counts and comprehensive metabolic panels were analyzed 0 and 300 min after ingestion. Peak concentration (CMax) and area under the curve (AUC) were calculated for all variables. Baseline L-BAIBA levels were not different between conditions (p = 0.46). The observed AUC for B1500 (30,513 ± 9190 µM•300 min) was significantly higher than B500 (11,087 ± 3378 µM•300 min, p < 0.001), B250 (7081 ± 2535 µM•300 min, p < 0.001), V1500 (2837 ± 2107 µM•300 min, p < 0.001), and PLA (2836 ± 2061 µM•300 min, p < 0.001). Similarly, L-BAIBA CMax for B1500 (278.1 ± 52.1 µM) was significantly higher than all other supplement conditions: B500 (95.4 ± 33.5 µM, p < 0.001), B250 (63.3 ± 61.1 µM, p < 0.001), V1500 (10.1 ± 7.2 µM, p < 0.001), PLA (11.0 ± 7.1 µM, p = 0.001). AUC and CMax for B500 was significantly higher than B250 (p < 0.001), V1500 (p < 0.001), and PLA (p < 0.001). BAIBA AUC for B250 was significantly higher than V1500 (p < 0.001) and PLA (p < 0.001). No clinically significant changes in blood-based markers of health or adverse events were observed across the study protocol. L-BAIBA doses of 250 mg, 500 mg, and 1500 mg produced significantly greater concentrations of plasma L-BAIBA across a five-hour measurement window when compared to a 1500 mg dose of valine or a placebo. Follow-up efficacy studies on resting and exercise metabolism should be completed to assess the impact of L-BAIBA supplementation in normal weight and overweight individuals. Retrospectively registered on April 22, 2022 at ClinicalTrials.gov as NCT05328271.

Naturally Bicarbonated Water Supplementation Does Not Improve Anaerobic Cycling Performance or Blood Gas Parameters in Active Men and Women.

The completion of high-intensity exercise results in robust perturbations to physiologic homeostasis, challenging the body's natural buffering systems to mitigate the accumulation of metabolic by-products. Supplementation with bicarbonate has previously been used to offset metabolic acidosis, leading to improvements in anaerobic exercise performance. PURPOSE: The purpose of this study was to investigate the presence of ergogenic properties in naturally occurring low-dose bicarbonated water and their effects on anaerobic cycling performance and blood gas kinetics in recreationally active men and women. METHODS: Thirty-nine healthy, recreationally active men and women (28.1 ± 8.0 years, 169.8 ± 11.7 cm, 68.9 ± 10.8 kg, 20.1 ± 7.9% fat, V˙O2peak: 42.8 ± 7.6 mL/kg/min) completed two separate testing sessions consisting of 15 cycling sprints (10 s sprint, 20 s active rest) against 7.5% of their body mass. Using a randomized, double-blind, placebo-controlled, parallel group study design, study participants consumed a 10 mL/kg dose of either spring water (SW) or bicarbonated mineral water (BMW) (delivering ~3 g/day of bicarbonate) for 7 days. Venous blood was collected before, immediately after, and 5 and 10 min after the sprint protocol and was analyzed for lactate and a series of blood gas components. After the completion of 15 cycling sprints, averages of peak and mean power for bouts 1-5, 6-10, and 11-15, along with total work for the entire cycling protocol, were calculated. All performance and blood gas parameters were analyzed using a mixed-factorial ANOVA. RESULTS: pH was found to be significantly higher in the BMW group immediately after (7.17 ± 0.09 vs. 7.20 ± 0.11; p = 0.05) and 10 min post exercise (7.21 ± 0.11 vs. 7.24 ± 0.09; p = 0.04). A similar pattern of change was observed 5 min post exercise wherein pH levels in the SW group were lower than those observed in the BMW group; however, this difference did not achieve statistical significance (p = 0.09). A statistical trend (p = 0.06) was observed wherein lactate in the BMW group tended to be lower than in the SW group 5 min post exercise. No significant main effect for time (p > 0.05) or group × time interactions (p > 0.05) for the total work, average values of peak power, or average values of mean power were observed, indicating performance was unchanged. CONCLUSION: One week of consuming water with increased bicarbonate (10 mL/kg; ~3 g/day bicarbonate) showed no effect on anaerobic cycling performance. BMW decreased blood lactate concentrations 5 min after exercise and increased blood pH immediately and 10 min after exercise.

Corrigendum: A randomized controlled trial to examine the impact of a multi-strain probiotic on self-reported indicators of depression, anxiety, mood, and associated biomarkers.

[This corrects the article DOI: 10.3389/fnut.2023.1219313.].

A randomized controlled trial to examine the impact of a multi-strain probiotic on self-reported indicators of depression, anxiety, mood, and associated biomarkers.

Objective: To examine the efficacy of supplementing with a multi-strain probiotic (MSP) on changes associated with mood, anxiety, and neurotransmitter levels. Method: In a randomized, double-blind, placebo-controlled fashion, 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented with a single capsule of MSP (a total daily dose of 4 × 109 colony forming units [CFU] comprised of a 1 × 109 CFU dose from each of the following strains: Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04, Probiotical S.p.A., Novara, Italy) or a maltodextrin placebo (PLA). After 0, 2, 4, and 6 weeks of supplementation and 3 weeks after ceasing supplementation, study participants completed the Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), and Leiden Index of Depression Sensitivity (LEIDS-R) questionnaires and had plasma concentrations of cortisol, dopamine, serotonin, and C-reactive protein determined. Results: BDI, STAI, and total LEIDS-R scores were reduced from baseline (p < 0.05) with MSP supplementation after 4 and 6 weeks of supplementation and 3 weeks after supplementation while no changes (p > 0.05) were reported in PLA. When compared to PLA, MSP scores for state anxiety, trait anxiety, and LEIDS-R (hopeless, aggression, rumination, and total score) were significantly lower (p < 0.05) after supplementation. Plasma serotonin concentrations in MSP were increased from baseline after 6 weeks of supplementation and 3 weeks after ceasing supplementation. No changes (p > 0.05) in plasma dopamine, C-reactive protein, or cortisol concentrations were observed between groups. Conclusion: MSP supplementation resulted in widespread improvements in several questionnaires evaluating mood, anxiety, and depression in young, healthy men and women. MSP supplementation increased serotonin increased after 6 weeks of MSP supplementation with no change in dopamine, C-reactive protein, or cortisol. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT05343533, NCT05343533.