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Introduction: β-alanine (BA) supplementation may improve cognition and mitigate symptoms of anxiety and depression associated with aging, neurological disorders, and physical exertion, which has been attributed to increases in brain carnosine and/or brain-derived neurotropic factor (BDNF). BA also provides beneficial effects on cognition, mood, and physical performance during military operations; however, whether BA can attenuate mood disruptions and cognitive dysfunction associated with the anticipatory stress prior to simulated military operations is unknown. Purpose: The present study examined the effects of 14 days of BA (12 g·day -1 ) supplementation on cognitive function, mood, and circulating BDNF concentrations in recreationally-active, healthy males with limited inflammation and oxidative stress prior to a 24h simulated military operation. Methods: Participants were randomized into BA ( n  = 10) or placebo ( n  = 9; PL) for 14 days. Cognitive function, mood, and circulating BDNF were assessed before (PRE) and after (POST) supplementation. Cognition was assessed via multiple object tracking (Neurotracker™), visuomotor reaction time (Dynavision™), mathematical processing (Serial Subtraction Test), and neuropsychological assessments (ANAM™). Mood was assessed using the Profile of Mood States (POMS) questionnaire. After POST testing, subjects underwent a 24h simulated military operation. Results: No change in measures of cognitive function or BDNF concentrations were observed ( p  > 0.05). However, BA experienced significant reductions ( p  = 0.046) in subjective feelings of depression, while PL experienced significant reductions ( p  = 0.021) in feelings of vigor from PRE to POST. Conclusions: High-dose, short-duration BA supplementation does not appear to affect cognitive function or circulating BDNF, but may mitigate the onset of negative mood states in healthy, recreationally-active males prior to a simulated military operation.

Wells, AJ, Varanoske, AN, Coker, NA, Kozlowski, GJ, Frosti, CL, Boffey, D, Harat, I, Jahani, S, Gepner, Y, and Hoffman, JR. Effect of β-alanine supplementation on monocyte recruitment and cognition during a 24-hour simulated military operation. J Strength Cond Res 34(11): 3042-3054, 2020-Sustained military operations (SUSOPs) result in psychological stress and cognitive dysfunction, which may be related to the recruitment of classical monocytes into the brain. This study examined the effect of beta-alanine (BA) on cognition and monocyte recruitment during a simulated 24-hour SUSOP. Nineteen healthy men ingested 12-g/d BA or placebo for 14 days before an SUSOP. Monocyte chemoattractant protein-1 (MCP-1), C-C chemokine receptor-2 (CCR2), and macrophage-1-antigen (CD11b) expression were assessed through multiplex assay and flow cytometry. Psychological stress and cognition were assessed through Automated Neuropsychological Assessment Metrics (ANAM). A composite measure of cognition (COGcomp) was generated from throughput scores extracted from 7 ANAM cognitive tests. Assessments occurred at baseline (0H), 12 hours (12H), 18 hours (18H), and 24 hours (24H). Significance was accepted at p ≤ 0.05. No significant effect of BA was noted for any variable (p's > 0.05). The frequency and severity of symptoms of psychological stress increased significantly at 18 and 24H compared with 0 and 12H (p's < 0.05). COGcomp decreased significantly at 18 and 24H compared with 0 and 12H (p's ≤ 0.001). MCP-1 peaked at 18H was significantly lower at 24H compared with 18H but remained elevated at 24H compared with 0H (p's < 0.001). CCR2 expression was significantly lower at 12 (p = 0.031), 18, and 24H (p's < 0.001). CD11b expression was significantly higher at 12H (p = 0.039) and 24H (p's = 0.003). MCP-1 was negatively associated with COGcomp (β = -0.395, p = 0.002, r2 = 0.174). Neither CCR2 or CD11b was related to COGcomp (p's > 0.05). Cognitive dysfunction during SUSOPs is related to serum concentrations of MCP-1 but is not influenced by BA supplementation.

Introduction: Intense military operations during deployment or training are associated with elevations in inflammatory cytokine markers. However, the influence of an inflammatory response on military-specific skills is unclear. This study examined the association between brain-derived neurotrophic factor (BDNF), glial fibrillar acidic protein, markers of inflammation, marksmanship and cognitive function following a week of intense military field training., Methods: Twenty male soldiers (20.1±0.6 years; 1.78±0.05m; 74.1±7.9kg) from the same elite combat unit of the Israel Defense Forces volunteered to participate in this study. Soldiers completed a five-day period of intense field training including navigation of 27.8km/day with load carriages of ~50% of their body mass. Soldiers slept approximately fivehours per day and were provided with military field rations. Following the final navigational exercise, soldiers returned to their base and provided a blood sample. In addition, cognitive function assessment and both dynamic and static shooting (15 shots each) were performed following a 200 m gauntlet, in which soldiers had to use hand-to-hand combat skills to reach the shooting range., Results: Results revealed that tumour necrosis factor-α (TNF-α) concentrations were inversely correlated with dynamic shooting (r=-0.646, p=0.005). In addition, a trend (r=0.415, p=0.098) was noted between TNF-α concentrations and target engagement speed (ie, time to complete the shooting protocol). BDNF concentrations were significantly correlated with the Serial Sevens Test performance (r=0.672, p=0.012)., Conclusion: The results of this investigation indicate that elevated TNF-α concentrations and lower BDNF concentrations in soldiers following intense military training were associated with decreases in marksmanship and cognitive function, respectively., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Sustained military operations (SUSOPs) are associated with performance decrements and cognitive dysfunction. β-Alanine (BA) supplementation may have a role in increasing soldier resiliency by enhancing muscle-buffering capacity and reducing oxidative stress. The purpose of this study was to examine the effects of BA on physical performance, cognition, endocrine function, and inflammation during a 24 h simulated SUSOP. Nineteen males were randomized into one of two groups: BA (n = 10) or placebo (n = 9; PLA) (12 g/day) for 14 days preceding the 24 h SUSOP. Assessments were performed at 0 h (0H), 12 h (12H), and 24 h (24H) during the SUSOP. No changes in visual tracking ability, jump power, or upper-body muscular endurance were observed between groups or time points (P's > 0.05). Increases in subjective feelings of soreness and fatigue were noted at 12H compared to 0H (P < 0.05) in PLA, but not in BA. Visual reaction time for PLA was slower at 24H compared to 0H (P = 0.035), and PLA made more errors on reaction time testing at 12H compared to BA (P = 0.048), but motor reaction time was faster (P = 0.016) for PLA. Simulated litter carry and 1 km run completion times increased at 24H compared to 0H in both groups (P < 0.05), however, PLA had a longer 1 km time compared to BA at 24H (P = 0.050). Increases in inflammatory and endocrine markers were observed over the SUSOP, with no differences between groups. BA supplementation appears to maintain some aspects of cognition and physical performance during a 24 h SUSOP, with no effects on endocrine function or inflammation., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Hoffman, JR, Gepner, Y, Hoffman, M, Zelicha, H, Shapira, S, and Ostfeld, I. Effect of high dose, short-duration β-alanine supplementation on circulating IL-10 concentrations during intense military training. J Strength Cond Res 32(10): 2978-2981, 2018-This study examined the effect of β-alanine as a potential anti-inflammatory agent during intense military training. Twenty soldiers (20.1 ± 0.6 years) from an elite combat unit were randomly assigned to either a β-Alanine (BA) or placebo (PL) group. Soldiers were provided with 12 g·d of either BA or PL for 7 days between 2 intensive periods of navigational training and restricted sleep. During the initial training period, soldiers navigated on average 27.8 km·d with ∼50% of their body mass in their packs for 5 days. Soldiers returned to base and began a 7-day supplementation program before departing for an additional period of intense field training. During the second period of field training, soldiers navigated 10 km·d for an additional 5 days, carrying similar loading as the initial week, performed tactical missions, and slept approximately 5 hours per day. Blood samples were obtained after the initial training period and after the second training period and analyzed for IL-10. Magnitude-based inferences that were used to provide inferences on the true effect BA may have had on IL-10 concentrations compared with PL, calculated from 90% confidence intervals. Data analysis indicated that changes in circulating IL-10 concentrations (mean difference 0.86 pg·ml) were possibly greater (57%) for BA than PL. Results of this study suggest that 1 week of high-dose BA ingestion may enhance the anti-inflammatory response during intense military training, suggesting a potential therapeutic role of BA during intense training.

The purpose of this study was to compare the coadministration of the probiotic Bacillus coagulans GBI-30, 6086 (BC30) with β-hydroxy-β-methylbutyrate (HMB) calcium (CaHMB) to CaHMB alone on inflammatory response and muscle integrity during 40 days of intense military training. Soldiers were randomly assigned to one of two groups: CaHMB with BC30 (CaHMBBC30; n = 9) or CaHMB with placebo (CaHMBPL, n = 9). A third group of participants served as a control (CTL; n = 8). During the first 28 days soldiers were garrisoned on base and participated in the same training tasks. During the final 2 wk soldiers navigated 25-30 km per night in difficult terrain carrying ~35 kg of equipment. All assessments (blood draws and diffusion tensor imaging to assess muscle integrity) were conducted before and ~12 h after final supplement consumption. Analysis of covariance was used to analyze all blood and muscle measures. Significant attenuations were noted in IL-1β, IL-2, IL-6, CX3CL1, and TNF-α for both CaHMBBC30 and CaHMBPL compared with CTL. Plasma IL-10 concentrations were significantly attenuated for CaHMBBC30 compared with CTL only. A significant decrease in apparent diffusion coefficients was also observed for CaHMBBC30 compared with CaHMBPL. Results provide further evidence that HMB supplementation may attenuate the inflammatory response to intense training and that the combination of the probiotic BC30 with CaHMB may be more beneficial than CaHMB alone in maintaining muscle integrity during intense military training. NEW & NOTEWORTHY β-Hydroxy-β-methylbutyrate (HMB) in its free acid form was reported to attenuate inflammation and maintain muscle integrity during military training. However, this formulation was difficult to maintain in the field. In this investigation, soldiers ingested HMB calcium (CaHMB) with Bacillus coagulans (BC30) or CaHMB alone during 40 days of training. Results indicated that CaHMB attenuated the inflammatory response and that BC30 combined with CaHMB may be more beneficial than CaHMB alone in maintaining muscle integrity during intense military training., (Copyright © 2017 the American Physiological Society.)

Objective: Insulin-like growth factor-I (IGF-I) is a metabolic and anabolic biomarker that has been proposed to reflect physiological adaptations resulting from multistressor environments. The bioactivity of IGF-I is regulated by seven different insulin-like growth factor binding proteins (IGFBPs) which act not only as carriers of IGF-1, but also function as a modulator of IGF-I availability and activity. Supplementing with β-hydroxy-β-methylbutyrate (HMB) has been shown to enhance physiological outcomes associated with intense training, and has been reported to augment the IGF-1 response. The purpose of this study was to examine the effect of 23days of HMB supplementation on circulating levels of IGF-I and IGFBPs in combat soldiers during highly intense military training., Methods: Thirteen male soldiers from an elite infantry unit volunteered to participate in this double-blind, parallel design study. Soldiers were provided 3g·day -1 of either HMB (n=6) or placebo (PL; n=7). During the study soldiers performed advanced military training with periods of restricted sleep and severe environmental stressors. Blood samples were obtained prior to (PRE) and approximately 18h following the final supplement consumption (POST)., Results: No significant differences were observed for circulating IGF-1 concentrations between HMB and PL (p=0.568). In addition, no differences were seen between the groups for IGFBP-1 (p=1.000), IGFBP-2 (p=0.855), IGFBP-3 (p=0.520), IGFBP-4 (p=0.103), IGFBP-5 (p=0.886), or IGFBP-6 (p=0.775). A significant difference was noted between HMB (169.9±23.0ng·ml -1 ) and PL (207.2±28.0ng·ml -1 ) for IGFBP-7 at POST (p=0.042)., Conclusions: Although the results of this study do not support the influence of HMB supplementation on circulating concentrations of IGF-1 or IGFBPs1-6 during high intensity military training, it does present initial evidence that it may lower circulating IGFBP-7 concentrations. This may provide some indication of a reduced stress response, but further investigation on the physiological role of IGFBP-7 and military training is needed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This study tested the hypothesis that of 23 days of β-hydroxy-β-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., (Copyright © 2016 Elsevier Inc. All rights reserved.)