The Effect of Exercise on Neurogenesis in the Brain.

BACKGROUND: The connection between physical exercise and the brain has long been studied. The evidence showing that physical exercise plays a significant role on neurogenesis and cognitive function has primarily been based on research examining aerobic exercise. In this review, we described three exercise modalities: aerobic, anaerobic, and resistance exercise and their impact on brain plasticity and cognitive function. While each of these exercise modalities have been demonstrated to positively influence brain plasticity and cognitive function, the specific mechanism that stimulates these changes appear to differ to some degree between these training modalities. The effect of aerobic and anaerobic exercise appears to be primarily mediated by changes in expression of brain-derived neurotrophic factor (BDNF), lactate, vascular endothelial growth factor (VEGF), and several additional proteins within the brain. However, resistance exercise appears to influence brain plasticity by myokines such as irisin, insulin-growth factor-1 (IGF1), and BDNF that are secreted from skeletal tissue and stimulate neurogenesis within the brain. In addition to the various training modes, manipulation of various acute program variables such as intensity, volume, and rest intervals leads to numerous possible training paradigms that can provide a different stimulus for neurogenesis. This review focuses on the three primary training modes and their connection to neurogenesis and cognitive function.

Examination of Cognitive Function, Neurotrophin Concentrations, and both Brain and Systemic Inflammatory Markers Following a Simulated Game of American Football.

ABSTRACT: Hoffman, JR, Ostfeld, I, Zamir, A, Amedi, R, Fonville, TR, Horstemeyer, MF, and Gepner, Y. Examination of cognitive function, neurotrophin concentrations, and both brain and systemic inflammatory markers following a simulated game of American football. J Strength Cond Res 36(3): 686-694, 2022-This investigation examined the effect of a simulated American football game on cognitive function, neurotrophin concentrations, and markers of both systemic and brain inflammation. Members of the Israel national team (6 linemen and 9 skill position players) were examined 1 week before (PRE), immediately post (IP) and 24-hour post (24P) game. Blood was obtained, and cognitive function was measured at each assessment. No head injuries to any of the players participating in the study occurred. Significant (p < 0.001) decreases in acute memory, and a trend (p = 0.066) toward a decrease in delayed memory was noted at IP. Significant negative correlations were observed between playing time (number of plays) and concentration changes from PRE to IP (r = -0.801; p = 0.001) and from PRE to 24P (r = -0.549; p = 0.034). All cognitive function measures returned to PRE levels by 24P. Increases from PRE were noted in tumor necrosis factor-alpha (TNF-α) (p = 0.041) at IP and in brain-derived neurotrophic factor (p = 0.009) and C-reactive protein (CRP) (p = 0.019) concentrations at 24P. Circulating CRP concentrations and the cytokine markers, interleukin (IL)-4, IL-6, IL-10, and TNF-α, were significantly elevated in linemen compared with skill players. Brain inflammatory markers (S100B and glial fibrillary acidic protein) and total tau protein (a marker of brain injury) were not elevated from PRE. No change from PRE was noted in either myoglobin or creatine kinase-MM concentrations. In conclusion, muscle damage and inflammatory marker responses observed from the scrimmage game were consistent with muscle desensitization associated with football participation. In addition, the systemic inflammatory marker results observed in linemen were suggestive of chronic low-grade inflammation.

BDNF Val66Met Polymorphism, the Allele-Specific Analysis by qRT-PCR - a Novel Protocol.

Background: Alteration in brain-derived neurotrophic factor (BDNF) production is a marker of neuropathological conditions, which has led to the investigation of Val66Met polymorphism occurring in the human BDNF gene (BDNF). Presently, there are no reported methods available for the analysis of Val66Met impact on human BDNF functioning. Purpose: To develop a qRT-PCR protocol for the allele-specific expression evaluation of the Val66Met polymorphism in BDNF. Methods: Using RNA extracted from muscle samples of 9 healthy volunteers (32.9 ± 10.3 y) at rest and following a maximal effort aerobic capacity exercise test, a protocol was developed for the detection of Val66/Met66 allele-specific BDNF expression in Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) - relative to housekeeping genes - and validated by absolute quantification in Droplet Digital Polymerase Chain Reaction (ddPCR). Results: Differences in the relative values of BDNF mRNA were confirmed by ddPCR analysis. HPRT1 and B2M were the most stable genes expressed in muscle tissue among different metabolic conditions, while GAPDH revealed to be metabolic responsive. Conclusion: Our qRT-PCR protocol successfully determines the allele-specific detection and changes in BDNF expression regarding the Val66Met polymorphism.

The Effect of 2 Weeks of Inactivated Probiotic Bacillus coagulans on Endocrine, Inflammatory, and Performance Responses During Self-Defense Training in Soldiers.

Hoffman, JR, Hoffman, MW, Zelicha, H, Gepner, Y, Willoughby, DS, Feinstein, U, and Ostfeld, I. The Effect of 2-Weeks of Inactivated Probiotic Bacillus coagulans on Endocrine, Inflammatory and Performance Responses During Self-Defense Training in Soldiers. J Strength Cond Res 33(9): 2330-2337, 2019-The effect of 2 weeks of inactivated Bacillus coagulans (iBC) ingestion on performance and inflammatory cytokines was examined during a self-defense course in soldiers. Sixteen male soldiers were randomly assigned to either iBC (n = 8) or placebo (PL; n = 8) in this double-blind study. Participants were garrisoned on base and participated in the same training tasks. Assessments were conducted in a single day before (PRE) and after the supplementation period (POST). During each testing session, participants were assessed for vertical jump power (VJP), muscle endurance, simulated casualty drag, and 2 100-m shuttle runs. Resting blood measures for testosterone, cortisol, creatine kinase, and inflammatory cytokines were also assessed. Mann-Whitney analysis of change (Δ) scores indicated no significant change (p's > 0.05) in any of the performance or blood variables. However, a trend (p = 0.089) was noted in the Δ score for VJP in iBC compared with PL. In addition, trends were observed in the change in IL-10 (p = 0.057) and IFNγ (p = 0.057). Magnitude based inferential analysis indicated that changes in VJP and simulated casualty drag were likely beneficial (90.7 and 80.4% likelihood effect, respectively) for iBC. In addition, iBC supplementation very likely augmented IL-10 concentrations, but was possibly negative for changes in IL-6, and likely negative for changes in TNFα and IFNγ. Changes in all other performance and blood markers were unclear. Results indicated that 2 weeks of iBC supplementation appeared to be beneficial for maintaining power and short-term speed performance, while attenuating the inflammatory response during intense training in a military self-defense course.

ß-Alanine supplementation reduces anxiety and increases neurotrophin expression in both young and older rats.

The effect of 30 days of ß-alanine supplementation (100 mg/kg) on behavioral response and expression of brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY), and markers of inflammation was examined in both young (4 months) and older (14 months) rats. We hypothesized that animals fed ß-alanine would experience reduced inflammation and an enhanced neurotrophin and behavioral response. Animals were assigned to either a control group, in which young or older rats were fed regular chow and water, or a ß-alanine group, in which rats were fed regular chow and provided ß-alanine in their water. Behavior measures were conducted following the 30-day supplementation period, which included spatial learning, memory, and an anxiety index. Hippocampal expressions of BDNF, NPY, glial fibrillary acidic protein, nuclear factor-κB p50 and p65 subunits, tumor necrosis factor-α, and cyclooxygenase-2 were also analyzed. Learning ability was reduced (P = .001) and anxiety index was higher (P = .001) in older compared to young rats. Similarly, BDNF and NPY expressions were reduced and all inflammatory markers were elevated (P < .05) in the older animals. ß-Alanine increased BDNF expressions in the cornu ammonis area 1 (P = .003) and 3 (P < .001) subregions of the hippocampus. BDNF expression for younger rats in the ß-alanine group was also significantly greater than younger rats in the control group in cornu ammonis area 3. Learning for young animals fed ß-alanine was significantly better than all other groups. Significant reductions in anxiety were noted in both older and younger rats fed ß-alanine compared to age-matched controls. Results indicated that ß-alanine ingestion in both young and older rats was effective in attenuating anxiety and augmenting BDNF expression in the hippocampus.

Resistance Exercise Selectively Mobilizes Monocyte Subsets: Role of Polyphenols.

PURPOSE: To examine the impact of polyphenol supplementation on the recruitment, mobilization, and activation of monocyte subsets after resistance exercise. METHODS: Thirty-eight recreationally active males (22.1 ± 3.1 yr; 173.9 ± 7.9 cm; 77.8 ± 14.5 kg) were assigned to 28 d of polyphenol blend (PPB) supplementation, placebo (PL), or control (CON). Blood samples were obtained before (PRE) postresistance exercise, immediately (IP) postresistance exercise, 1 h (1H) postresistance exercise, 5 h (5H) postresistance exercise, 24 h (24H) postresistance exercise, and 48 h (48H) postresistance exercise (PPB/PL) or rest (CON). Fine-needle biopsies were obtained from the vastus lateralis at PRE, 1H, 5H, and 48H. Circulating concentrations of macrophage chemoattractant protein-1 (MCP-1) and fractalkine, as well as intramuscular MCP-1 were analyzed via multiplex assay. Changes in the proportions and expression of CD11b on monocyte subsets were assessed via flow cytometry. RESULTS: Circulating MCP-1 increased in PPB and PL at IP with further increases at 5H. Intramuscular MCP-1 was increased at 1H, 5H, and 48H in all groups. Classical monocyte proportions were reduced in PPB and PL at IP, and increased at 1H. Nonclassical monocytes were increased in PPB and PL at IP, whereas intermediate monocytes were increased at IP, and reduced at 1H. Intermediate monocytes were increased in PPB at 24H and 48H. CD11b expression was reduced on PPB compared with PL and CON at PRE on intermediate and nonclassical monocytes. CONCLUSIONS: Resistance exercise may elicit selective mobilization of intermediate monocytes at 24H and 48H, which may be mediated by tissue damage. Additionally, polyphenol supplementation may suppress CD11b expression on monocyte subsets at rest.

Polyphenol supplementation alters intramuscular apoptotic signaling following acute resistance exercise.

The purpose of this study was to examine the effects of 28-days of supplementation with an aqueous proprietary polyphenol blend (PPB) sourced from Camellia sinensis on intramuscular apoptotic signaling following an acute lower-body resistance exercise protocol and subsequent recovery. Untrained males (n = 38, 21.8 ± 2.7 years, 173.4 ± 7.9 cm, 77.6 ± 14.6 kg) were randomized to PPB (n = 14), placebo (PL; n = 14) or control (CON; n = 10). Participants completed a lower-body resistance exercise protocol comprised of the squat, leg press, and leg extension exercises. Skeletal muscle microbiopsies were obtained from the vastus lateralis preexercise (PRE), 1-h (1HR), 5-h (5HR), and 48-h (48HR) post-resistance exercise. Apoptotic signaling pathways were quantified using multiplex signaling assay kits to quantify total proteins (Caspase 3, 8, 9) and markers of phosphorylation status (JNK, FADD, p53, BAD, Bcl-2). Changes in markers of muscle damage and intramuscular signaling were analyzed via separate repeated measures analysis of variance (ANOVA). Change in Bcl-2 phosphorylation at 1H was significantly greater in PL compared to CON (P = 0.001). BAD phosphorylation was significantly elevated at 5H in PL compared to PPB (P = 0.015) and CON (P = 0.006). The change in JNK phosphorylation was significantly greater in PPB (P = 0.009), and PL (P = 0.017) compared to CON at 1H, while the change for PL was elevated compared to CON at 5H (P = 0.002). A main effect was observed (P < 0.05) at 1H, 5H, and 48H for p53 and Caspase 8, with Caspase 3 and Caspase 9 elevated at 48H. These data indicate that chronic supplementation with PPB alters apoptotic signaling in skeletal muscle following acute muscle-damaging resistance exercise.

Impact of Polyphenol Supplementation on Acute and Chronic Response to Resistance Training.

Beyer, KS, Stout, JR, Fukuda, DH, Jajtner, AR, Townsend, JR, Church, DD, Wang, R, Riffe, JJ, Muddle, TWD, Herrlinger, KA, and Hoffman, JR. Impact of polyphenol supplementation on acute and chronic response to resistance training. J Strength Cond Res 31(11): 2945-2954, 2017-This study investigated the effect of a proprietary polyphenol blend (PPB) on acute and chronic adaptations to resistance exercise. Forty untrained men were assigned to control, PPB, or placebo. Participants in PPB or placebo groups completed a 4-week supplementation period (phase I), an acute high-volume exercise bout (phase II), and a 6-week resistance training program (phase III); whereas control completed only testing during phase II. Blood draws were completed during phases I and II. Maximal strength in squat, leg press, and leg extension were assessed before and after phase III. The exercise protocol during phase II consisted of squat, leg press, and leg extension exercises using 70% of the participant's strength. The resistance training program consisted of full-body exercises performed 3 d·wk. After phase I, PPB (1.56 ± 0.48 mM) had greater total antioxidant capacity than placebo (1.00 ± 0.90 mM). Changes in strength from phase III were similar between PPB and placebo. Polyphenol blend supplementation may be an effective strategy to increase antioxidant capacity without limiting strength gains from training.

Tumor necrosis factor-alpha and soluble TNF-alpha receptor responses in young vs. middle-aged males following eccentric exercise.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) has been shown to be implicated in both muscle regeneration and muscle wasting. However, it remains unclear whether TNF-α is responsible for the age-related losses in muscle size and function. Also, due to the high clearance rate of TNF-α from circulation, analyzing the circulating levels of soluble TNF-α receptors 1 and 2 (STNFR1 and STNFR2) may provide a better indication of inflammatory events. The aim of this study was to examine changes in circulating concentrations of TNF-α, STNFR1, and STNFR2 following acute eccentric exercise in young (YA) and middle-aged (MA) men. METHODS AND MATERIALS: Nine YA (N=9, 21.8±2.2y, 179.5±4.9cm, 91.2±12.2kg, 21.8±4.3% body fat) and ten MA (N=10, 47.0±4.4y, 176.8±7.6cm; 96.0±21.5kg, 25.4±5.3% body fat) men completed an acute muscle damaging protocol (MDP). Blood samples were obtained at baseline (BL), immediately (IP), 30-minute (30P), 60-minute (60P), 120-minute (120P), 24-hour (24H), and 48-hour (48H) post-MDP. Lower body performance was assessed via isokinetic dynamometer at BL, IP, 120P, 24H, and 48H. RESULTS: YA displayed higher values of peak torque (p=0.023) and mean torque (p=0.036) at BL. No significant group differences were observed for markers of muscle damage or TNF-α. Plasma concentrations of TNF-α were unchanged following MDP. STNFR1 concentrations were significantly higher in the YA group compared to MA (p=0.036). Significant time effects were observed for STNFR1 (p<0.001) and STNFR2 (p=0.001). With both groups combined, serum STNFR1 was decreased at 30P (p=0.001), while STNFR2 was decreased at 30P (p=0.008), 60P (p=0.003), and 120P (p=0.002) relative to BL. CONCLUSIONS: The pro-inflammatory response to muscle damage does not appear to decline at middle age when individuals are recreationally trained. However, young men showed significantly higher serum STNFR1 concentrations than middle age men. This may suggest that natural inhibitors of TNF-α decline as early as middle age.

Comparison of Two ß-Alanine Dosing Protocols on Muscle Carnosine Elevations.

OBJECTIVE: ß-alanine (BA) is a nonproteogenic amino acid that combines with histidine to form carnosine. The amount taken orally in individual doses, however, is limited due to symptoms of paresthesia that are associated with higher doses. The use of a sustained-release formulation has been reported to reduce the symptoms of paresthesia, suggesting that a greater daily dose may be possible. The purpose of the present study was to determine whether increasing the daily dose of BA can result in a similar increase in muscle carnosine in a reduced time. METHODS: Eighteen men and twelve women were randomized into either a placebo (PLC), 6-g BA (6G), or 12-g BA (12G) groups. PLC and 6G were supplemented for 4 weeks, while 12G was supplemented for 2 weeks. A resting blood draw and muscle biopsy were obtained prior to (PRE) and following (POST) supplementation. Plasma and muscle metabolites were measured by high-performance liquid chromatography. The loss in peak torque (ΔPT) was calculated from maximal isometric contractions before and after 250 isokinetic kicks at 180°·sec-1 PRE and POST. RESULTS: Both 12G (p = 0.026) and 6G (p = 0.004) increased muscle carnosine compared to PLC. Plasma histidine was decreased from PRE to POST in 12G compared to PLC (p = 0.002) and 6G (p = 0.001), but no group x time interaction (p = 0.662) was observed for muscle histidine. No differences were observed for any hematological measure (e.g., complete blood counts) or in symptoms of paresthesia among the groups. Although no interaction was noted in ΔPT, a trend (p = 0.073) was observed. CONCLUSION: Results of this investigation indicate that a BA supplementation protocol of 12 g/d-1, using a sustained-release formulation, can accelerate the increase in carnosine content in skeletal muscle while attenuating paresthesia.

Comparisons in the Recovery Response From Resistance Exercise Between Young and Middle-Aged Men.

Gordon, JA III, Hoffman, JR, Arroyo, E, Varanoske, AN, Coker, NA, Gepner, Y, Wells, AJ, Stout, JR, and Fukuda, DH. Comparisons in the recovery response from resistance exercise between young and middle-aged men. J Strength Cond Res 31(12): 3454-3462, 2017-The purpose of this study was to compare the effects of a bout of high-volume isokinetic resistance exercise protocol (HVP) on lower-body strength and markers of inflammation and muscle damage during recovery between young and middle-aged adult men. Nineteen recreationally trained men were classified as either a young adult (YA: 21.8 ± 2.0 years; 90.7 ± 11.6 kg) or a middle-aged adult (MA: 47.0 ± 4.4 years; 96.0 ± 21.5 kg) group. The HVP consisted of 8 sets of 10 repetitions, with 1 minute of rest between each set, performed on an isokinetic dynamometer at 60°·s. Maximal voluntary isometric contractions and isokinetic peak torque (PKT) and average torque (AVGT) (measured at 240° and 60°·s, respectively) were assessed at baseline (BL), immediately post (IP), 120 minutes, 24, and 48 hours after HVP. Blood was obtained at BL, IP, 30, 60, 120 minute, 24, and 48 hours after HVP to assess muscle damage and inflammation. All performance data were analyzed using repeated measures analysis of covariance, whereas all inflammatory and muscle damage markers were analyzed using a 2-way (time × group) repeated measures analysis of variance. Results revealed no between-group differences for PKT, AVGT, or rate of torque development at 200 ms (RTD200). No between-group differences in myoglobin, creatine kinase, C-reactive protein, or interleukin-6 were observed. Although BL differences in muscle performance were observed between YA and MA, no between-group differences were noted in performance recovery measures from high-volume isokinetic exercise in recreationally trained men. These results also indicate that the inflammatory and muscle damage response from high-volume isokinetic exercise is similar between recreationally trained, young, and middle-aged adult men.

Post-resistance exercise ingestion of milk protein attenuates plasma TNFα and TNFr1 expression on monocyte subpopulations.

Attenuating TNFα/TNFr1 signaling in monocytes has been proposed as a means of mitigating inflammation. The purpose of this study was to examine the effects of a milk protein supplement on TNFα and monocyte TNFr1 expression. Ten resistance-trained men (24.7 ± 3.4 years; 90.1 ± 11.3 kg; 176.0 ± 4.9 cm) ingested supplement (SUPP) or placebo (PL) immediately post-exercise in a randomized, cross-over design. Blood samples were obtained at baseline (BL), immediately (IP), 30-min (30P), 1-h (1H), 2-h (2H), and 5-h (5H) post-exercise to assess plasma concentrations of myoglobin; tumor necrosis factor-alpha (TNFα); and expression of tumor necrosis factor receptor 1 (TNFr1) on classical, intermediate, and non-classical monocytes. Magnitude-based inferences were used to provide inferences on the true effects of SUPP compared to PL. Plasma TNFα concentrations were "likely attenuated" (91.6% likelihood effect) from BL to 30P in the SUPP group compared with PL (d = 0.87; mean effect: 2.3 ± 2.4 pg mL-1). TNFr1 expressions on classical (75.9% likelihood effect) and intermediate (93.0% likelihood effect) monocytes were "likely attenuated" from BL to 2H in the SUPP group compared with PL (d = 0.67; mean effect: 510 ± 670 RFU, and d = 1.05; mean effect: 2500 ± 2300 RFU, respectively). TNFr1 expression on non-classical monocytes was "likely attenuated" (77.6% likelihood effect) from BL to 1H in the SUPP group compared with PL (d = 0.69; mean effect: 330 ± 430 RFU). Ingestion of a milk protein supplement immediately post-exercise appears to attenuate both plasma TNFα concentrations and TNFr1 expression on monocyte subpopulations in resistance-trained men.

Comparison of the recovery response from high-intensity and high-volume resistance exercise in trained men.

PURPOSE: The purpose of this study was to compare the physiological responses of a high-volume (HV; 8 sets of 10 repetitions) versus high-intensity (HI; 8 sets of 3 repetitions) exercise protocol in resistance-trained men. METHODS: Twelve men (24.5 ± 4.2 years; 82.3 ± 8.4 kg; 175.2 ± 5.5 cm) with 6.3 ± 3.4 years of resistance training experience performed each protocol in a counterbalanced, randomized order. Performance [counter movement jump peak power (CMJP), isokinetic (ISOK) and isometric leg extension (MVIC), isometric mid-thigh pull (IMTP), and isometric squat (ISQ)] and muscle morphological [cross-sectional area (CSA) of vastus lateralis] assessments were performed at baseline (BL), 30-min (P-30 min), 24-h (P-24 h), 48-h (P-48 h), and 72-h (P-72 h) post-exercise for each testing session. In addition, endocrine (testosterone and cortisol), inflammatory [interleukin-6 (IL-6) and C-reactive protein (CRP)], and markers of muscle damage [creatine kinase (CK), lactate dehydrogenase (LDH), and myoglobin (Mb)] were assessed at the same time points. RESULTS: Significantly greater reductions in CMJP (p < 0.001), and peak torque during both ISOK (p = 0.003) and MVIC (p = 0.008) at P-30 min were detected in HV compared to HI protocol. MVIC was still impaired at P-72 h following the HV protocol, while no differences were noted following HI. Markers of muscle damage (LDH, CK, and Mb) were significantly elevated following both HV and HI (p < 0.05), while cortisol and IL-6 concentrations were significantly elevated at P-30 min following HV only (p < 0.001 and p < 0.05, respectively). CONCLUSIONS: Results indicate that high-volume resistance exercise results in greater performance deficits, and a greater extent of muscle damage, than a bout of high-intensity resistance exercise.

Castration alters protein balance after high-frequency muscle contraction.

Resistance exercise increases muscle mass by shifting protein balance in favor of protein accretion. Androgens independently alter protein balance, but it is unknown whether androgens alter this measure after resistance exercise. To answer this, male mice were subjected to sham or castration surgery 7-8 wk before undergoing a bout of unilateral, high-frequency, electrically induced muscle contractions in the fasted or refed state. Puromycin was injected 30 min before euthanasia to measure protein synthesis. The tibialis anterior was analyzed 4 h postcontraction. In fasted mice, neither basal nor stimulated rates of protein synthesis were affected by castration despite lower phosphorylation of mechanistic target of rapamycin in complex 1 (mTORC1) substrates [p70S6K1 (Thr389) and 4E-BP1 (Ser65)]. Markers of autophagy (LC3 II/I ratio and p62 protein content) were elevated by castration, and these measures remained elevated above sham values after contractions. Furthermore, in fasted mice, the protein content of Regulated in Development and DNA Damage 1 (REDD1) was correlated with LC3 II/I in noncontracted muscle, whereas phosphorylation of uncoordinated like kinase 1 (ULK1) (Ser757) was correlated with LC3 II/I in the contracted muscle. When mice were refed before contractions, protein synthesis and mTORC1 signaling were not affected by castration in either the noncontracted or contracted muscle. Conversely, markers of autophagy remained elevated in the muscles of refed, castrated mice even after contractions. These data suggest the castration-mediated elevation in baseline autophagy reduces the absolute positive shift in protein balance after muscle contractions in the refed or fasted states. NEW & NOTEWORTHY: In the absence of androgens, markers of autophagy were elevated, and these could not be normalized by muscle contractions. In the fasted state, REDD1 was identified as a potential contributor to autophagy in noncontracted muscle, whereas phosphorylation of ULK1 may contribute to this process in the contracted muscle. In the refed state, markers of autophagy remain elevated in both noncontracted and contracted muscles, but the relationship with REDD1 and ULK1 (Ser757) no longer existed.

ß-Hydroxy-ß-methylbutyrate attenuates cytokine response during sustained military training.

This study tested the hypothesis that of 23 days of ß-hydroxy-ß-methylbutyrate (HMB) supplementation can maintain muscle mass and attenuate the immune and inflammatory response in combat soldiers during highly intense military training. Soldiers were randomly assigned to either a HMB (n = 6) or placebo (PL; n = 7) group and provided with 3 g · day(-1) of either HMB or PL. During the final week of supplementation soldiers participated in extreme physical training, which included night navigation of 6-8 hours across difficult terrain carrying heavy loads combined with sleep deprivation (3.8 ± 3.0 h per night). Blood draws were performed prior to and following the supplementation period. Magnetic resonance imaging, which included diffusion tensor imaging sequence, was used for muscle fiber tracking analysis. Data was analyzed using a two-way mixed factorial analysis of variance. Magnitude-based inferences were used to provide inferences on the true effects that HMB may have had on the dependent variables compared to PL, calculated from 90% confidence intervals. Changes in tumor necrosis factor-α for HMB (-3.9 ± 8.2 pg · mL(-1)) were significantly lower (P = .043) compared to the change in PL (+4.0 ± 3.7 pg · mL(-1)). HMB ingestion was also very likely (92%-95% Likelihood) to lower granulocyte colony-stimulating factor and interleukin 10 compared to PL. In addition, HMB supplementation was likely (78%-87% likelihood) to reduce interferon-γ, interleukin 8, CX3CL1, and increase muscle volume for the adductor magnus (77% likelihood) compared to PL. In summary, the results of this study provides evidence that HMB supplementation may attenuate the inflammatory response to high intense military training, and maintain muscle quality.

Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome.

A variety of dietary interventions has been used in the management of chronic fatigue syndrome (CFS), yet no therapeutic modality has demonstrated conclusive positive results in terms of effectiveness. The main aim of this study was to evaluate the effects of orally administered guanidinoacetic acid (GAA) on multidimensional fatigue inventory (MFI), musculoskeletal soreness, health-related quality of life, exercise performance, screening laboratory studies, and the occurrence of adverse events in women with CFS. Twenty-one women (age 39.3 ± 8.8 years, weight 62.8 ± 8.5 kg, height 169.5 ± 5.8 cm) who fulfilled the 1994 Centers for Disease Control and Prevention criteria for CFS were randomized in a double-blind, cross-over design, from 1 September 2014 through 31 May 2015, to receive either GAA (2.4 grams per day) or placebo (cellulose) by oral administration for three months, with a two-month wash-out period. No effects of intervention were found for the primary efficacy outcome (MFI score for general fatigue), and musculoskeletal pain at rest and during activity. After three months of intervention, participants receiving GAA significantly increased muscular creatine levels compared with the placebo group (36.3% vs. 2.4%; p < 0.01). Furthermore, changes from baseline in muscular strength and aerobic power were significantly greater in the GAA group compared with placebo (p < 0.05). Results from this study indicated that supplemental GAA can positively affect creatine metabolism and work capacity in women with CFS, yet GAA had no effect on main clinical outcomes, such as general fatigue and musculoskeletal soreness.

Monocyte Recruitment after High-Intensity and High-Volume Resistance Exercise.

UNLABELLED: The innate immune response is generally considered to have an important role in tissue remodeling after resistance exercise. PURPOSE: The purpose of this study was to compare changes in markers of monocyte recruitment after an acute bout of high-intensity (HVY) versus high-volume (VOL) lower-body resistance exercise. METHODS: Ten resistance-trained men (24.7 ± 3.4 yr, 90.1 ± 11.3 kg, 176.0 ± 4.9 cm) performed each protocol in a randomized, counterbalanced order. Blood samples were collected at baseline, immediately (IP), 30 min (30P), 1 h (1H), 2 h (2H), and 5 h (5H) postexercise. Plasma concentrations of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α), myoglobin, and cortisol were measured via assay. Tumor necrosis factor receptor 1 (TNFr1), macrophage-1 antigen (cluster of differentiation 11b [CD11b]), and C-C chemokine receptor 2 (CCR2) expression levels were measured using flow cytometry. TNFr1 and CD11b were assessed on CD14CD16 monocytes, whereas CCR2 was assessed on CD14 monocytes. RESULTS: Plasma myoglobin concentrations were significantly greater after HVY compared with VOL (P < 0.001). Changes in plasma TNF-α, MCP-1, and expression levels of CCR2 and CD11b were similar between HVY and VOL. When collapsed across groups, TNF-α was significantly increased at IP, 30P, 1H, and 2H (P values < 0.05), whereas MCP-1 was significantly elevated at all postexercise time points (P values < 0.05). CCR2 expression on CD14 monocytes was significantly lower at IP, 1H, 2H, and 5H (P values < 0.05). CD11b expression on CD14 CD16 was significantly greater at IP (P < 0.014) and 1H (P = 0.009). TNFr1 expression did not differ from baseline at any time point. Plasma cortisol concentrations did not seem to be related to receptor expression. CONCLUSIONS: Results indicate that both HVY and VOL protocols stimulate a robust proinflammatory response. However, no differences were noted between resistance exercise training paradigms.

The effect of polyphenols on cytokine and granulocyte response to resistance exercise.

This study examined the effect of resistance exercise on the production, recruitment, percentage, and adhesion characteristics of granulocytes with and without polyphenol (PPB) supplementation. Thirty-eight untrained men were randomized into three groups: PPB (n = 13, 21.8 ± 2.5 years, 171.2 ± 5.5 cm, 71.2 ± 8.2 kg), placebo (PL; n = 15, 21.6 ± 2.5 years, 176.5 ± 4.9 cm, 84.0 ± 15.7 kg), or control (CON; n = 10, 23.3 ± 4.3 years, 173.7 ± 12.6 cm, 77.3 ± 16.3 kg). Blood samples were obtained pre (PRE), immediately (IP), 1 h (1H), 5 h (5H), 24 h (24H), 48 h (48H), and 96 h (96H) postresistance exercise (PPB/PL) or rest (CON). Fine-needle biopsies were obtained from the vastus lateralis at PRE, 1H, 5H, and 48H. Plasma concentrations and intramuscular content of interleukin-8 (IL-8), granulocyte (G-CSF), and granulocyte-macrophage colony stimulating factor (GM-CSF) were analyzed via multiplex assays. Changes in relative number of circulating granulocytes and adhesion receptor (CD11b) were assessed using flow cytometry. Intramuscular IL-8 was significantly elevated at 1H, 5H, and 48H (P < 0.001). Area under the curve analysis indicated a greater intramuscular IL-8 content in PL than PPB (P = 0.011). Across groups, circulating G-CSF was elevated from PRE at IP (P < 0.001), 1H (P = 0.011), and 5H (P = 0.025), while GM-CSF was elevated at IP (P < 0.001) and 1H (P = 0.007). Relative number of granulocytes was elevated at 1H (P < 0.001), 5H (P < 0.001), and 24H (P = 0.005, P = 0.006) in PPB and PL, respectively. Across groups, granulocyte CD11b expression was upregulated from PRE to IP (P < 0.001) and 1H (P = 0.015). Results indicated an increase in circulating CD11b on granulocytes, and IL-8 within the muscle following intense resistance exercise. Polyphenol supplementation may attenuate the IL-8 response, however, did not affect granulocyte percentage and adhesion molecule expression in peripheral blood following resistance exercise.

A Microbiopsy Method for Immunohistological and Morphological Analysis: A Pilot Study.

INTRODUCTION: The fine aspiration microbiopsy is a relatively new biopsy technique, which allows muscle physiologists to sample skeletal muscle less invasively. However, the small sample size obtained is often deemed insufficient for certain analyses. The aim of the current study was to develop procedures for muscle fiber morphology and immunohistological analysis from a microbiopsy technique. METHODS: Microbiopsies of the vastus lateralis were taken with a 14-gauge microbiopsy needle from four healthy men on two separate occasions. The tissue was oriented in a cryomold, embedded in Tissue-Tek® then frozen in liquid nitrogen cooled isopentane. The muscle sections were stained with hematoxylin and eosin, laminin, MHCI, MHCIIa, and Pax7 for fiber number, mean fiber area, muscle fiber typing, and satellite cell observation. RESULTS: The mean ± SD (range) microbiopsy sample weight was 18.3 ± 2.9 mg (14-22 mg). The mean fiber number within the microbiopsy specimens was 150.4 ± 120.6 (64-366). All viable fibers were measured in each sample, and the mean fiber area was 4385.1 ± 1265.8 µm2 (977.0-10,132.93 µm2). There was no significant time difference (P = 0.69) in mean fiber area. DISCUSSION: Results suggest the potential use of a "minimally invasive" muscle biopsy technique for immunohistological and morphological analysis. This could provide clinicians and investigators additional data in future research. Further investigations are needed to determine the usefulness and potential limiting factors of this technique.

Effects of l-Alanyl-l-Glutamine Ingestion on One-Hour Run Performance.

OBJECTIVE: To examine the efficacy of l-alanyl-l-glutamine ingestion with a commercially available sports drink compared to the sports drink only on time to exhaustion and physiological measures during prolonged endurance exercise. METHODS: Twelve endurance-trained men (23.5 ± 3.7 years; 175.5 ± 5.4 cm; 70.7 ± 7.6 kg) performed 4 trials, each consisting of a 1-hour treadmill run at 75% VO2peak followed by a run to exhaustion at 90% VO2peak. One trial consisted of no hydration (NHY), another required ingestion of only a sports drink (ED), and 2 trials required ingestion of a low dose (LD; 300 mg·500 ml(-1)) and high dose (HD) of l-alanyl-l-glutamine (1 g·500 ml(-1)) added to the sports drink. During the fluid ingestion trials, 250 ml was consumed every 15 minutes. Plasma glutamine, glucose, electrolytes, and osmolality were measured prior to the run (PRE) and at 30, 45, and 60 minutes. VO2, respiratory quotient (RQ), and heart rate (HR) were measured every 15 minutes. RESULTS: Time to exhaustion was significantly longer during the LD and HD trials compared to NHY. No differences were noted in time to exhaustion between ED and NHY. Plasma glutamine concentrations were significantly elevated at 45 minutes in LD and HD trials and remained elevated at 60 minutes during HD. Sodium concentrations increased from the beginning of exercise and remained stable for the duration of the 1-hour run. At 60 minutes, plasma sodium was significantly lower in all trials compared to NHY. CONCLUSIONS: Results indicated that ingestion of the alanine-glutamine dipeptide at either the low or high dose significantly improved time to exhaustion during high-intensity exercise compared to a no-hydration trial.