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PURPOSE: The US Marine Corps (USMC) is an elite military organization. Marine recruit training (RT) is a physically and psychologically intense 13-wk-long course designed to transform civilians into Marines through shared hardship and arduous training. Our laboratory conducted a study of female recruits in USMC RT that assessed the nature and the extent of cognitive, nutritional, and physical changes that occur during this unique period of structured mental and physical training. METHODS: During RT, mood state was assessed every 4 wk with a standardized questionnaire, the POMS. Body composition was assessed with dual-energy x-ray absorptiometry every 4 wk, and blood samples were collected for assessing metabolic status at the start and at the completion of training. RESULTS: At the beginning of RT, approximately 1 wk after arrival at the training facility, levels of several negative mood states assessed by the POMS, depression, anxiety, fatigue, anger, and confusion, were considerably higher than POMS norms for age-matched, female college students. However, over the course of RT, these mood states gradually declined until, by the completion of training, they were substantially lower than college norms. Body composition changed dramatically, with muscle mass increasing by 2.5 +/- 0.2 kg on average and fat declining by 4.7 +/- 0.4 kg. There were also significant changes in several biochemical parameters associated with nutritional and physical status, particularly LDL cholesterol, free fatty acids, and cortisol. Other factors, such as total cholesterol, HDL cholesterol, and glucose, were more stable. CONCLUSIONS: Over the course of USMC RT, mood and body composition improved substantially and dramatically, an indication of the effectiveness of USMC RT for altering the physical and the cognitive status of trainees. [ABSTRACT FROM AUTHOR]

PURPOSE: The characteristics of U.S. military personnel who use dietary supplements have not been well described. This study aimed to determine whether deployment experience and physical activity were associated with the use of bodybuilding, energy, or weight-loss supplement among U.S. military personnel. METHODS: Self-reported data from active-duty, Reserve, and National Guard participants of the Millennium Cohort Study collected from 2007-2008 (n = 106,698) on supplement use, physical activity, and other behavioral data were linked with deployment and demographic data. We used multivariable logistic regression sex-stratified models to compare the adjusted odds of each type of supplement use among those with deployment experience in support of operations in Iraq or Afghanistan and those engaged in aerobic or strength-training activities. RESULTS: Overall, 46.7% of participants reported using at least one type of supplement, and 22.0% reported using multiple supplements. Male deployers were more likely to use bodybuilding supplements, whereas female deployers were more likely to use weight-loss supplements. Physically active and younger subjects reported all types of supplement use. Men and women reporting 5 or less hours of sleep per night were more likely to use energy supplements. CONCLUSIONS: The high prevalence of supplement use and important characteristics found to be associated with their use, including deployment, physical activity, and suboptimal sleep, suggest focus areas for future research and adverse event monitoring. [ABSTRACT FROM AUTHOR]

Objective: The goal of this project was to evaluate the effects of energy supplementation, as liquid carbohydrate (CHO), on facilitating recovery of cognitive function in soldiers who have been exposed to sustained psychological and physical stress during Survival School Training. PROJECT DESIGN: A double-blind, placebo-controlled design was used. Healthy, male volunteers attending survival training were recruited for participation in the study. At the conclusion of the mock captivity phase of survival training and before a recovery night of sleep, subjects participated in cognitive testing. After this, subjects were randomly assigned to one of three treatment groups. Subjects received either a 6% CHO (35.1 kJ/kg), 12% CHO (70.2 kJ/kg), or placebo beverage in four isovolemic doses. In the morning of the following day, all subjects participated in a second assessment of cognitive functioning.Results: Compared to subjects who received placebo, those who received supplemental CHO beverages exhibited significantly improved performance on a complex cognitive task (i.e., Stroop Test) involving concentration effectiveness associated with selective attention and response inhibition. No differences were observed on a variety of cognitive tasks of lesser complexity.Discussion: These data suggest nutritional interventions enhance the rapid recovery of complex cognitive functions impaired by exposure to significant or sustained stressful conditions. In addition to enhancing speed of recovery of function between operational intervals, the current data suggest that dietary supplement strategies may hold promise for enhancing field performance and a capacity to assist in sustaining operations by military personnel over time. [ABSTRACT FROM AUTHOR]

This study evaluated whether Special Forces (SF) soldiers training in garrison would meet nutrient intake recommendations using the available garrison dining facility. Dietary intakes were obtained by a visual estimation method and self-reported food records from 32 SF and 13 support soldiers for 9 days. Total energy expenditure (TEE) was measured in nine soldiers from each group using doubly labeled water. Mean (+/- SD) total energy expenditure of SF (4,099 +/- 740 kcal/day) was higher than support soldiers (3,361 +/- 939 kcal/day, p < 0.01). Energy intake did not differ between groups. Median energy intake for all soldiers was 3,204 kcal/day. The nutrient intake goals of SF soldiers were not fully met by eating in the dining facility. Extending meal times and providing additional meals or "take out" foods may allow energy needs of SF soldiers (approximately 4,200 kcal/day) to be met, while reducing the reliance on potentially less nutritious outside foods. [ABSTRACT FROM AUTHOR]

This is the first study to provide valuable insights into the effects of the Israeli Navy's 20-h rotating watch schedule on submariners' alertness, mood states, risk-taking behaviours, and sleep. Specifically, we assessed the impact of the non-circadian-aligned schedule on cognitive performance, mood, and behavioural outcomes in a highly controlled submarine environment. A total of 20 male submariners participated in an at-sea mission, where their cognitive performance, mood states, risk-taking propensity, and caffeine consumption were measured. A psychomotor vigilance task (PVT) assessed alertness, the propensity for risky behaviour (Evaluation of Risks Scale) measured risk-taking behaviours, and the Profile of Mood States evaluated mood disturbances. Actigraphy was used to monitor sleep times. Data were analysed according to seven watch schedule segments. Submariners slept a mean (standard error of the mean [SEM]) of 8.3 (0.2) h/24 h, fragmented into 3.7 (0.8) h epochs. Caffeine consumption decreased at sea (mean [SEM] 149.3 [6.0] mg) compared to land (mean [SEM] 205.5 [7.2] mg; p = 0.027). In the PVT, premature responses significantly increased during Watch VI (5:00-8:00 p.m.) and Watch VII (8:00 p.m.-12:00 a.m.; p = 0.014). In the mood subscales, tension was significantly higher during Watch II (4:00-8:00 a.m.; p = 0.002), indicating greater stress. Risk-taking propensity significantly increased during afternoon shifts (p = 0.050). The 20-h watch schedule led to fragmented sleep, reduced alertness in the evening, worsened mood states in the early morning, and increased risk-taking propensity in the afternoon. These findings suggest the need for the Israeli Navy to establish evidence-based caffeine guidelines and optimise the watch schedule to improve submariners' sleep, performance, and overall well-being., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objectives: This retrospective cohort study examined clinically diagnosed insomnia and sleep apnea and analyzed associations with deployment and combat exposure in active-duty soldiers (n=1,228,346) from 2010 to 2019., Methods: Retrospective data were obtained from the Soldier Performance, Health, and Readiness database., Results: Overseas soldier deployments peaked in 2010, decreasing thereafter as soldiers were withdrawn from Iraq and Afghanistan. From 2010 to 2012 insomnia incidence increased at a rate of 6.7 cases/1000 soldier-years, then decreased after 2012 at 5.3 cases/1000 soldier-years. Sleep apnea increased 2010-2016 at 1.9 cases/1000 soldier-years and generally declined thereafter. Risk of insomnia increased with deployment (hazard ratio=1.51; 95% confidence interval=1.49-1.52) and combat exposure (hazard ratio=1.15; 95% confidence interval=1.13-1.17). Risk of sleep apnea was increased by deployment (hazard ratio=1.89; 95% confidence interval, 1.86-1.92) and combat exposure (hazard ratio=1.09; 95% confidence interval, 1.07-1.11). Most relationships remained after accounting for other factors in multivariable analyses, except that the association between sleep apnea and combat exposure was reduced (hazard ratio=0.94; 95% confidence interval=0.92-0.97)., Conclusions: Insomnia risk decreased in the period nearly in parallel with a reduction in the number of deployments; nonetheless deployment and combat exposure increased insomnia risk in the period examined. Risk of sleep apnea increased in the period and was related to deployment but not combat exposure after accounting for demographics and comorbid conditions. Despite reductions in insomnia incidence and a slowing in sleep apnea incidence, sleep disorders remain highly prevalent, warranting continued emphasis on sleep-disorder screening and improving the soldier sleep habits., Competing Interests: Declaration of conflicts of interest None., (Published by Elsevier Inc.)

The purpose of this study was to determine the difference between estimated energy expenditure (EE) and self-reported dietary intake (EI), and factors associated with energy balance in deployed U.S. Army Special Operations Forces (SOF) Soldiers., Methods: Forty-six SOF Soldiers (age: 30.1 ± 3.5 yrs, body mass index: 27.7 ± 4.1 kg/m 2 ) completed surveys on demographic data, mission activity characteristics, gastrointestinal issues, ration consumption, resilience, mood state, and dietary intake using a 127-question food frequency questionnaire at the end of a six-month deployment. EE was estimated using a SOF-specific prediction equation with a physical activity factor of 2.1. A paired t -test compared reported energy intake (EI) with estimated energy expenditure (EE). Pearson correlations identified significant variables associated with energy balance, which were then incorporated into a multiple linear regression model. The regression analysis included Profile of Mood States (POMS) anger and POMS depression as predictor variables to determine their influence on energy balance., Results: Reported mean EI was 2512 ± 1059 kcal·d -1 , while estimated mean EE was 5272 ± 525 kcal·d -1 . The mean energy imbalance was -2854 kcal/d (95% CI: -2655 to -3055, p < 0.001), with all participants in negative energy balance (range: -492 to -3813 kcal/d). POMS depression (r = 0.517, p < 0.01) and POMS anger (r = 0.363, p = 0.020) were associated with energy balance. The regression model was significant (R 2 = 0.23, F (2, 38) = 7.02, p < 0.01), with POMS depression significantly predicting energy balance (β = 50.76, p = 0.011)., Conclusions: Deployed SOF Soldiers reported high EE and limited EI, which may negatively impact performance. Higher POMS depression scores were associated with lower energy deficits. Future studies should investigate the relationship between mood and energy balance, using direct measures of EI and EE.

Background: Variation in cognitive, emotional and physical performance in response to stress is attributable to environmental and genetic factors. Ability to adapt to stress is resilience., Objectives: This study investigated genetic factors associated with resilience in soldiers exposed to severe stress due to intense physical and mental demands at Survive, Evade, Resist and Escape school, a unique environment to study acute stress and resiliency in real-world circumstances., Design: A preliminary correlational study was conducted to identify genetic markers for resilience to stress., Methods: Mood state, resiliency and dissociative state of 73 soldiers were assessed using: Connor-Davidson Resilience Scale (CD-RISC); Profile of Mood States (POMS); and Clinician-Administered Dissociative States Scale (CADSS). Change scores for resilience-related stress markers were computed; 116 single nucleotide polymorphisms (SNPs) associated with stress, depression, anxiety, sleep, or psychiatric disorders were assessed., Results: A significant association between change in CD-RISC score and SNP rs4251417, present in an intron of SLC6A4, the serotonin transporter gene, was observed., Conclusions: Individuals with the minor allele of SNP rs4251417 had a greater positive change in CD-RISC, indicating increased self-assessed resilience. This study suggests the minor allele of SNP rs4251417 of SLC6A4 is associated with resilience when individuals are exposed to high stress.

Previous studies investigating temporal changes in dietary supplement (DS) use have used representative samples but have not followed the same cohort over time. This study investigated longitudinal patterns of changes in DS use and factors associated with discontinuing DS use in a single group of active-duty United States military service members (SMs). SMs (n = 5778) completed two identical questionnaires on their DS use and demographic/lifestyle characteristics an average ± standard deviation 1.3 ± 0.2 years apart. Prevalences of reported DS use ≥1 times/week in the baseline (BL) and follow-up (FU) phases were: any DS, BL = 77%, FU = 78%; multivitamins/multiminerals (MVM), BL = 50%, FU = 48%; individual vitamins/minerals, BL = 33%, FU 35%; proteins/amino acids, BL = 43%, FU = 39%; combination products, BL = 44%, FU = 37%; prohormones, BL = 5%, FU = 4%; herbal products, BL = 23%, FU = 21%; joint health products, BL = 12%, FU = 12%; fish oils, BL = 25%, FU = 23%; other DSs, BL = 17%, FU = 17%. Among BL users, the proportions reporting use in the FU phase were: any DS 88%, MVM 74%, protein/amino acids 70%, individual vitamin/minerals 62%, combination products 62%, fish oils 61%, joint health products 57%, herbal products 50%, other DSs 50%, and prohormones 37%. Higher odds of discontinuing any DS use in the follow-up were associated with female gender, younger age, higher BMI, and less weekly resistance training. Overall, prevalence of DS use was relatively consistent in the two phases; however, the cohort changed their use patterns in the follow-up with some discontinuing use and others initiating use, thus maintaining use prevalence over the period. These findings have implications for repeated cross-sectional DS studies where different samples are followed over time.

This longitudinal study examined associations between chronic medical conditions (CMCs) and persistent dietary supplement (DS) use. On two separate occasions, 1.3 ± 0.2 years apart, military service members (SMs) ( n = 5778) completed identical questionnaires concerning their DS use in the past 6 months and their demographic and lifestyle characteristics. Medical conditions were obtained from a medical surveillance system six months before the first questionnaire and during the period between questionnaires. Diagnoses were grouped into 19 major (largely systemic) and 9 specific CMCs. Conditions diagnosed in both periods (CMCs) were examined in relation to DS use reported on both questionnaires (persistent DS use). After adjustment for demographic and lifestyle factors, higher odds of persistent DS use were found in 7 of the 19 major CMCs and 5 of the 9 specific CMCs. SMs with a CMC had 1.25 (95% confidence interval [95%CI] = 1.10-1.41) higher adjusted odds of persistent DS use. The three specific CMCs with the highest adjusted odds of persistent DS use were anxiety (odds ratio [OR] = 2.30, 95%CI = 1.36-3.89), depression (OR = 2.12, 95%CI = 1.20-3.73), and gastroesophageal reflux disease (OR = 2.02, 95%CI = 1.02-4.04). Among DS categories, participants with a CMC had higher adjusted odds of persistent vitamins or mineral use (OR = 1.31, 95% CI = 1.12-1.53). Participants with CMCs had a higher prevalence of persistent DS use, especially individual vitamin and mineral use.

Military training provides insight into metabolic responses under unique physiological demands that can be comprehensively characterized by global metabolomic profiling to identify potential strategies for improving performance. This study identified shared changes in metabolomic profiles across three distinct military training exercises, varying in magnitude and type of stress. Blood samples collected before and after three real or simulated military training exercises were analyzed using the same untargeted metabolomic profiling platform. Exercises included a 2-wk survival training course (ST, n = 36), a 4-day cross-country ski march arctic training (AT, n = 24), and a 28-day controlled diet- and exercise-induced energy deficit (CED, n = 26). Log 2 -fold changes of greater than ±1 in 191, 121, and 64 metabolites were identified in the ST, AT, and CED datasets, respectively. Most metabolite changes were within the lipid (57-63%) and amino acid metabolism (18-19%) pathways and changes in 87 were shared across studies. The largest and most consistent increases in shared metabolites were found in the acylcarnitine, fatty acid, ketone, and glutathione metabolism pathways, whereas the largest decreases were in the diacylglycerol and urea cycle metabolism pathways. Multiple shared metabolites were consistently correlated with biomarkers of inflammation, tissue damage, and anabolic hormones across studies. These three studies of real and simulated military training revealed overlapping alterations in metabolomic profiles despite differences in environment and the stressors involved. Consistent changes in metabolites related to lipid metabolism, ketogenesis, and oxidative stress suggest a potential common metabolomic signature associated with inflammation, tissue damage, and suppression of anabolic signaling that may characterize the unique physiological demands of military training. NEW & NOTEWORTHY The extent to which metabolomic responses are shared across diverse military training environments is unknown. Global metabolomic profiling across three distinct military training exercises identified shared metabolic responses with the largest changes observed for metabolites related to fatty acids, acylcarnitines, ketone metabolism, and oxidative stress. These changes also correlated with alterations in markers of tissue damage, inflammation, and anabolic signaling and comprise a potential common metabolomic signature underlying the unique physiological demands of military training.

Background: The relationships between habitual essential amino acid (EAA) intake and body composition, muscle strength, and physical function in older US adults are not well defined., Objectives: This cross-sectional study evaluated associations between usual EAA intakes and body composition, muscle strength, and physical function in US adults ≥65 y., Methods: The Food and Nutrient Database for Dietary Studies (FNDDS) 2001-2018 was linked to the US Department of Agriculture Standard Reference database to access existing amino acid composition data for FNDDS ingredients. FNDDS ingredients without existing amino acid composition data were matched to similar ingredient codes with available data. Usual EAA, leucine, lysine, and sulfur-containing amino acid (SAA; methionine + cysteine) intakes (g/d) from National Health and Nutrition Examination Survey 2001-2018 were calculated for individuals ≥65 y ( n = 10,843). Dependent variables included muscle strength measured by isometric grip test, body mass index (BMI), waist circumference, dual-energy X-ray absorptiometry-measured appendicular lean mass and whole-body fat mass, and self-reported physical function (that is, tasks of daily living). Regression analyses were used to determine covariate-adjusted relationships between EAA, leucine, lysine, and SAA intake and functional health outcomes. P < 0.0013 was considered significant., Results: EAA, leucine, lysine, and SAA intakes, covaried with physical activity level and usual protein intake, were not associated with muscle strength or self-reported physical function in males or females or with body composition in males. EAA intakes were positively associated with waist circumference in females (β ± SEM, 2.1 ± 0.6 cm, P = 0.0007). Lysine intakes were positively associated with BMI (3.0 ± 0.7 kg/m 2 , P < 0.0001) and waist circumference (7.0 ± 1.7 cm, P = 0.0001) in females., Conclusions: Habitual EAA, leucine, lysine, and SAA intakes, covaried with physical activity level and usual protein intake, were not associated with lean mass, muscle strength, or physical function in adults ≥65 y. However, EAA intakes, particularly lysine, were positively associated with measures of adiposity in older females.This trial was registered with the Open Science Framework (https://doi.org/10.17605/OSF.IO/25V63) as osf.io/25v63)., (© 2024 The Author(s).)

Introduction: This observational study investigated the effects of sleep deprivation and ad libitum caffeine consumption on cognitive performance, risk behavior, and mood among 28 Israeli Special Forces (SF) soldiers (mean age: 20.57 ± 0.92 years) during a 96-hour combat exercise., Methods: Actigraphy was used to monitor sleep and activity; cognitive function, risk-taking propensity, mood states, and self-reported sleepiness were assessed using the Psychomotor Vigilance Task (PVT), Evaluation of Risks Scale (EVAR), Profile of Mood States (POMS), Karolinska Sleepiness Scale (KSS); and caffeine consumption by questionnaire at 0, 50, and 96 hours. For analyses, participants were divided into Low (<400 mg) and High (≥400 mg) caffeine consumption groups., Results: The soldiers hiked 108.5 ± 0.52 km and slept for 12.7 ± 0.5 h, with a notable transition from multiple short sleep epochs in the initial 50 hours to a consolidated 5-hour sleep period subsequently. In the High caffeine group, PVT reaction time was faster ( p  = 0.024) compared to the Low caffeine group, with fewer premature response errors ( p  = 0.026). However, this group showed increased risk-taking ( p  = 0.037), particularly reduced Self-Control ( p  = 0.010). No significant impact of ad libitum caffeine intake on mood was observed. However, degradation over the course of the exercise in both groups in mood states, including anger, fatigue, tension, and vigor, was noted ( p  < 0.05). KSS scores increased significantly at 50 and 96 h ( p  < 0.001)., Discussion: These results suggest that while caffeine enhances cognitive function, its ad libitum consumption did not consistently improve these measures in this cohort of SF soldiers. The study highlights the complex relationship between sleep deprivation and caffeine intake and their combined effects on soldiers' cognitive and behavioral functions, indicating a need for evidence-based caffeine use guidelines for using caffeine in military settings., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could potentially create a conflict of interest., (Copyright © 2024 Erez, Lieberman, Baum, Ketko and Moran.)

Over 70% of United States military service members (SMs) regularly use dietary supplements (DSs) and about 18% have reported adverse effects (AEs) associated with use. This investigation examined longitudinal changes in AEs reporting among DS users. On two separate occasions 1.3 ± 0.2 years apart (mean ± standard deviation), 5778 SMs completed identical questionnaires on DS use and associated AEs. Among SMs reporting DS use ≥1 time/week, ≥1 AE was reported by 19% and 15% in the baseline and follow-up phases, respectively. The risk of reporting DS use at follow-up was similar among those reporting and not reporting AEs at baseline for most DS categories including prohormones, proteins/amino acids, individual vitamins and minerals, multivitamin/multiminerals, herbals, fish oils, joint health products, and other DSs. An exception was combination products where those reporting AEs at baseline had an increased risk of use at follow-up (risk ratio = 1.13, 95% confidence interval = 1.06-1.09). Those reporting AEs at baseline and continuing DS use in the follow-up were more likely to report AEs at follow-up compared to those not reporting baseline AEs. In conclusion, AEs reported at baseline did not deter many participants from using DSs in the follow-up period, and many SMs reporting AEs at baseline continued reporting them at follow-up., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Harris Lieberman reports financial support was provided by Department of Defense Center Alliance for Nutrition and Dietary Supplement Research of the Defense Medical Research and Development Program, the U.S. Army Medical Research and Development Command (USAMRDC). The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Changes in the United States food supply and food choices make examination of temporal changes in micronutrient intake and their effect on meeting nutrient recommendations necessary., Objectives: This study aimed to examine 15-year trends of the contribution of foods and beverages (FB) and dietary supplements (DSs) to meeting nutrient recommendations among United States adults aged 19 y or older and compare usual mean intake distributions of FB alone with those of FB+DSs with dietary reference intakes [percentage below the estimated average requirement (%AI)]., Methods: This cross-sectional study used food, beverage, and DSs intake data from NHANES 2003-2018 (N = 39,925) to determine usual mean intakes for 21 micronutrients. Changes in intakes from FB and from FB+DSs, by sex, were compared in a time-trend analysis of 2-y cycles. Changes in mean intake as %AI were determined., Results: Over the time studied, United States adults underconsumed vitamins A, C, D, E, and K; calcium; potassium; magnesium; and choline, even when DSs intake was included. Sodium was overconsumed. In males, there were significant increases in %

Rationale: Behavioral effects of testosterone depend on dose, acute versus sustained formulation, duration of administration, personality, genetics, and endogenous levels of testosterone. There are also considerable differences between effects of endogenous and exogenous testosterone., Objectives: This study was the secondary behavioral arm of a registered clinical trial designed to determine if testosterone protects against loss of lean body mass and lower-body muscle function induced by a severe energy deficit typical of sustained military operations., Methods: Behavioral effects of repeated doses of testosterone on healthy young men whose testosterone was reduced by severe energy deficit were examined. This was a double-blind, placebo-controlled, between-group study. Effects of four weekly intramuscular injections of testosterone enanthate (200 mg/week, N = 24) or matching placebo (N = 26) were evaluated. Determination of sample size was based on changes in lean body mass. Tasks assessing aggression, risk-taking, competition, social cognition, vigilance, memory, executive function, and mood were repeatedly administered., Results: During a period of artificially induced, low testosterone levels, consistent behavioral effects of administration of exogenous testosterone were not observed., Conclusions: Exogeneous testosterone enanthate (200 mg/week) during severe energy restriction did not reliably alter the measures of cognition. Study limitations include the relatively small sample size compared to many studies of acute testosterone administration. The findings are specific to healthy males experiencing severe energy deficit and should not be generalized to effects of other doses, formulations, or acute administration of endogenous testosterone or studies conducted with larger samples using tests of cognitive function designed to detect specific effects of testosterone., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Hand-to-hand combat training, known as combatives, instructs Soldiers in close-quarters combat techniques and how to cope with stress, understand controlled physical aggression, and develop self-confidence when engaged in such activities. Limited research in combat sports suggests men and women may respond to combatives stress differently. Given the increasing integration of women into close combat roles in the military, investigation of sex differences in the physiological and psychological response to combatives among military-trained personnel is warranted., Purpose: This study was designed to identify sex differences in stress and gonadal hormones, mucosal immunity, and mood states in a military combatives training course., Methods: U.S. Military Academy Cadets (men = 144, women = 37) enrolled in a 2-month Combat Applications Course at West Point completed the Profile of Mood States and Competitive State Anxiety Inventory-2 and provided salivary samples at baseline prior to the course, and immediately prior to their midterm and final combat matches. Combat matches were gender- and weight-matched. Additional salivary samples were collected immediately following the first midterm and final matches. Salivary cortisol, testosterone, secretory immunoglobulin A (SIgA) and estradiol (women only) were measured via immunoassay. Men and women were compared over time with linear mixed effects models., Results: In both men and women, confusion, tension, anger, cognitive anxiety, somatic anxiety, and self-confidence increased throughout the course whereas friendliness and SIgA secretion rate decreased (all p < 0.05). Compared to women, men had a greater acute increase in cortisol from pre- to post-match (p = 0.043). Prior to the final match, women displayed higher ratings of tension (20.5 ± 9.3 vs. 16.0 ± 8.6) and cortisol (0.6 ± 0.3 vs. 0.4 ± 0.3 µg/dL) than men (all p < 0.05). After controlling for previous combative experience, ratings of tension did not differ by sex but remained elevated prior to midterm and final compared to baseline., Conclusion: Combatives training elicited significant psychological and physiological stress and decreased mucosal immunity in both men and women. Women exhibited higher tension at the final match, likely due to lack of previous combative experience. Self-confidence increased from baseline suggesting that the skills learned may help Cadets prepare for combatives and other activities that require controlled aggression., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier Ltd.)

Background: Sport-related nutritional supplements (SRNS) include sport drinks, sport bars, and sport gels. This investigation examined temporal patterns in SRNS use and adverse effects (AEs) reported by a single cohort of United States active-duty service members (SMs) surveyed before and during the coronavirus disease 2019 (COVID-19) pandemic., Methods: A stratified random sample ( n  = 22,858) of SMs (Air Force, Army, Navy, and Marine Corps) who completed a questionnaire on their SRNS use and AE experiences and were still on active duty were asked to complete the identical questionnaire on a second occasion. Twenty-five percent of successfully contacted SMs completed both questionnaires ( n  = 5,778) and were included in this investigation. The average ± standard deviation time between questionnaires was 1.3 ± 0.2 years., Results: Prevalence of reported SRNS use ≥1 time/week in the baseline (BL) and follow-up (FU) phases were as follows: any SRNS: BL = 46%, FU = 41%; sport drinks: BL = 31%, FU = 28%; sport bars: BL = 30%, FU = 24%; sport gels: BL = 4%, FU = 4%. Reported weekly aerobic and resistance training durations were reduced in the FU period (8% and 26%, respectively). The proportion of SMs reporting SRNS use in both study phases was as follows: any SRNS = 62%, sport drinks = 54%, sport bars = 50%, sport gels = 35%. Prevalence of reported AEs in the BL and FU phases were as follows: any SRNS: BL = 1.9%, FU = 1.9%; sport drinks: BL = 1.0%, FU = 1.3%; sport bars: BL = 1.7%, FU = 1.4%; sport gels: BL = 3.3%, FU = 2.5%. The proportion of SMs reporting AEs in both phases was as follows: any SRNS = 14%, sport drinks = 11%, sport bars = 17%, sport gels = 0%., Conclusions: Overall SRNS use prevalence decreased slightly in the FU period, possibly because of reduced physical training related to military restrictions imposed during the emergence of COVID-19 between surveys. A large proportion of SMs reported changing their use patterns in the FU with some discontinuing use and others initiating use. The AE incidence was similarly low in the BL and FU phases, and few SMs reported AEs in both phases suggesting AEs were transitory. AE reporting for SRNSs was much lower than previously found for dietary supplements, possibly because of greater government regulatory control over SRNSs.

Background: A high BMI is associated with various medical conditions, notably type 2 diabetes, cardiovascular disease, and mental health disorders. In the US military, BMI increased linearly between 1975 and 2015., Objective: This cross-sectional study investigated the associations between BMI and a comprehensive range of clinically diagnosed medical conditions (CDMCs) in US military service members (SMs)., Methods: A stratified random sample of SMs (n=26,177) completed an online questionnaire reporting their height, weight, and demographic/lifestyle characteristics. Medical conditions for 6 mo before questionnaire completion were obtained from a comprehensive military electronic medical surveillance system and grouped into 39 CDMCs covering both broad (largely systemic) and specific medical conditions. BMI was calculated as weight/height 2 (kg/m 2 ). The prevalence of CDMCs was compared among normal weight (<25.0 kg/m 2 ), overweight (25.0-29.9 kg/m 2 ), and obese (≥30 kg/m 2 ) SMs., Results: After multivariable adjustment for demographic/lifestyle characteristics, higher BMI was associated with higher odds of a diagnosed medical condition in 30 of 39 CDMCs, with all 30 displaying dose-response relationships. The 5 major CDMCs with the largest odds ratios comparing obese to normal weight were endocrine/nutritional/metabolic diseases (OR=2.67, 95%CI=2.24-3.15), nervous system diseases (odds ratio [OR]=2.59, 95%CI=2.32-2.90), circulatory system diseases (OR=2.56, 95%CI=2.15-3.06), musculoskeletal system diseases (OR=1.92, 95%CI=1.76-2.09), and mental/behavioral disorders (OR=1.69, 95%CI=1.51-1.90). Compared with normal weight SMs, overweight or obese SMs had a higher number of CDMCs (1.8±1.9 vs. 2.0±2.0 and 2.5±2.3, mean ± standard deviation, respectively, P<0.01)., Conclusions: In a young, physically active population, higher BMI was associated with a host of medical conditions, even after adjustment for demographic/lifestyle characteristics. The US Department of Defense should improve nutrition education and modify other factors that contribute to overweight and obesity. This study demonstrates that the medical burden of obesity is substantial in overweight and obese SMs., (Published by Elsevier Inc.)

Submariners face many environmental and operational challenges to maintaining good sleep, including suboptimal lighting, shift work, and frequent interruptions. Anecdotally, many Sailors consume caffeine to alleviate the effects of poor sleep on alertness, mood, and performance; however, caffeine itself may also degrade sleep quantity and/or quality. This study provides the first exploration of the potential relationship between caffeine use and sleep onboard submarines. Objective measures (wrist actigraphy, available from 45 participants), self-report sleep metrics, and self-reported caffeine consumption were collected from 58 US Navy Sailors before and during a routine submarine underway at sea lasting 30 days. Contrary to expectations, less caffeine was reportedly consumed at sea (232.8 ± 241.1 mg) than on land prior to the underway (M = 284.4 ± 251.7 mg; X 2 (1) = 7.43, p = 0.006), positive rather than negative relationships were observed between caffeine consumption and sleep efficiency (F = 6.11, p = 0.02), and negative relationships were observed between caffeine consumption and wake after sleep onset (F = 9.36, p = 0.004) and sleep fragmentation (F = 24.73, p < 0.0001). However, in contrast, higher caffeine consumption was also negatively related to self-reported sleep duration while at sea (F = 4.73, p = 0.03). This observational study is the first to measure relationships between caffeine consumption and sleep quantity and/or quality in a submarine environment. We propose that the unique submarine environment and the unique caffeine consumption patterns of submariners should be considered in the development of potential countermeasures for sleepiness., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Objective: This study examined associations between multiple dietary supplement (DS) categories and medical conditions diagnosed by health professionals., Design: Cross-sectional., Setting: Volunteers completed an online questionnaire on DS use and demographic/lifestyle factors. Medical diagnoses were obtained from a comprehensive military electronic medical surveillance system and grouped into twenty-four clinically diagnosed medical conditions (CDMC)., Participants: A stratified random sample of US service members (SM) from all military services ( n 26 680)., Results: After adjustment for demographic/lifestyle factors (logistic regression), higher risk was found for 92 % (22/24) of CDMC among individual vitamins/minerals users, 58 % (14/24) of CDMC among herbal users, 50 % (12/24) of CDMC among any DS users and 46 % (11/24) of CDMC among multivitamins/multiminerals (MVM) users. Among protein/amino acid (AA) users, risk was lower in 25 % (6/24) of CDMC. For combination products, risk was higher in 13 % (3/24) of CDMC and lower in 8 % (2/24). The greater the number of CDMC, the higher the prevalence of DS use in most DS categories except proteins/AA where prevalence decreased., Conclusions: Users in many DS categories had a greater number of CDMC, but protein/AA users had fewer CDMC; results for combination products were mixed. These data indicate those with certain CDMC were also users in some DS categories, especially individual vitamins/minerals, herbals and MVM. Data are consistent with the perception that use of DS enhances health, especially in those with CDMC. Protein/AA and combination product users were more likely to be younger, more physically active men, factors that likely reduced CDMC.

Introduction: The metabolomic profiles of Soldiers entering the U.S. Special Forces Assessment and Selection course (SFAS) have not been evaluated., Objectives: To compare pre-SFAS blood metabolomes of Soldiers selected during SFAS versus those not selected, and explore the relationships between the metabolome, physical performance, and diet quality., Methods: Fasted blood samples and food frequency questionnaires were collected from 761 Soldiers prior to entering SFAS to assess metabolomic profiles and diet quality, respectively. Physical performance was assessed throughout SFAS., Results: Between-group differences (False Discovery Rate < 0.05) in 108 metabolites were detected. Selected candidates had higher levels of compounds within xenobiotic, pentose phosphate, and corticosteroid metabolic pathways, while non-selected candidates had higher levels of compounds potentially indicative of oxidative stress (i.e., sphingomyelins, acylcarnitines, glutathione, amino acids). Multiple compounds higher in non-selected versus selected candidates included: 1-carboxyethylphenylalanine; 4-hydroxy-nonenal-glutathione; α-hydroxyisocaproate; hexanoylcarnitine; sphingomyelin and were associated with lower diet quality and worse physical performance.  CONCLUSION: Candidates selected during SFAS had higher pre-SFAS levels of circulating metabolites that were associated with resistance to oxidative stress, higher physical performance and higher diet quality. In contrast, non-selected candidates had higher levels of metabolites potentially indicating elevated oxidative stress. These findings indicate that Soldiers who were selected for continued Special Forces training enter the SFAS course with metabolites associated with healthier diets and better physical performance. Additionally, the non-selected candidates had higher levels of metabolites that may indicate elevated oxidative stress, which could result from poor nutrition, non-functional overreaching/overtraining, or incomplete recovery from previous physical activity., (© 2023. The Author(s).)

Background: The lack of complete amino acid composition data in food composition databases has made determining population-wide amino acid intake difficult., Objectives: This cross-sectional study characterizes habitual intakes of each amino acid and adherence to dietary requirements for each essential amino acid (EAA) in the US population., Methods: Food and Nutrient Database for Dietary Studies ingredient codes with missing amino acid composition data were matched to similar ingredients with available data so that amino acid composition could be determined for 100% of foods reported in the dietary intake assessment component of NHANES. Amino acid intakes during NHANES 2001-2018 (n = 72,831; ≥2 y) were calculated as relative (mg·kg of ideal body weight -1 ·d -1 ) intakes. Data from NHANES 2011-2018 were used to determine the percentage of population consuming less than that recommended by the DRIs for each EAA by age, sex, and race/ethnicity., Results: Relative intakes of EAAs and NEAAs were greatest in those 2-3 y and lowest in older individuals (≥71 y or ≥80 y). In females aged 2-18 y, relative intakes of EAAs were lowest in non-Hispanic White (NHW; histidine, lysine, threonine, methionine, and cysteine) and non-Hispanic Black (NHB; valine, isoleucine, leucine, phenylalanine, tryptophan, and tyrosine) populations and highest in the Asian population. In females aged ≥19 y, relative intakes were lowest in NHW (lysine and methionine only) and NHB populations and highest in the Asian population. In males aged 2-18 y, relative intakes of EAAs were lowest in the NHB population and highest in the Asian population. In males ≥19 y, relative intakes were lowest in NHB and NHW (lysine only) populations and highest in the Hispanic population. Less than 1% of individuals aged ≥19 y did not meet the Estimated Average Requirements for each EAA., Conclusions: EAA intakes in the US population exceed recommended minimum population requirements. Future studies can use the method described here to quantify amino acid intake and examine relationships with health and disease., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Previous research has shown greater risk aversion when people make choices about lives than cash. We tested the hypothesis that compared to placebo, exogenous testosterone administration would lead to riskier choices about cash than lives, given testosterone's association with financial risk-taking and reward sensitivity. A double-blind, placebo-controlled, randomized trial was conducted to test this hypothesis (Clinical Trials Registry: NCT02734238, www.clinicaltrials.gov). We collected functional magnetic resonance imaging (fMRI) data from 50 non-obese males before and shortly after 28 days of severe exercise-and-diet-induced energy deficit, during which testosterone (200 mg testosterone enanthate per week in sesame oil) or placebo (sesame seed oil only) was administered. Because we expected circulating testosterone levels to be reduced due to severe energy deficit, testosterone administration served a restorative function to mitigate the impact of energy deficit on testosterone levels. The fMRI task involved making choices under uncertainty for lives and cash. We also manipulated whether the outcomes were presented as gains or losses. Consistent with prospect theory, we observed the reflection effect such that participants were more risk averse when outcomes were presented as gains than losses. Brain activation in the thalamus covaried with individual differences in exhibiting the reflection effect. Testosterone did not impact choice, but it increased sensitivity to negative feedback following risky choices. These results suggest that exogenous testosterone administration in the context of energy deficit can impact some aspects of risky choice, and that individual differences in the reflection effect engage a brain structure involved in processing emotion, reward and risk., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Objectives: This cross-sectional study investigated self-reported sleep duration and its association with a comprehensive range of clinically-diagnosed medical condition categories (CDMCs), as well as the relationship between short sleep duration (≤6 h) and demographic/lifestyle factors, among United States military service members (SMs)., Methods: A stratified random sample of SMs (n = 20,819) completed an online questionnaire on usual daily hours of sleep and demographic/lifestyle characteristics. CDMCs for a six-month period prior to questionnaire completion were obtained from a comprehensive military electronic medical surveillance system and grouped into 33 CDMCs covering both broad and specific medical conditions. Prevalence of CDMCs was compared among three sleep duration categories (≤4, 5-6 and ≥7 h)., Results: SMs reported a mean ± standard deviation of 6.3 ± 1.4 h of sleep per day. After adjustment for demographic/lifestyle characteristics, shorter sleep duration was associated with higher odds of a medical condition in 25 of 33 CDMCs, with most (n = 20) demonstrating a dose-response relationship. The five CDMCs with the largest differences between ≤4 vs ≥ 7 h sleep were: diseases of the nervous system (odds ratio [OR] = 2.9, 95% confidence interval [95%CI] = 2.4-3.4), mental/behavioral diseases (OR = 2.7, 95%CI = 2.3-3.2), diseases of the musculoskeletal system (OR = 1.9, 95%CI = 1.6-2.1), diseases of the circulatory system (OR = 1.7, 95%CI = 1.3-2.2), and diseases of the digestive system (OR = 1.6, 95%CI = 1.2-2.0). Six hours of sleep or less was independently associated with older age, less formal education, race, Hispanic ethnicity, higher body mass index, smoking, and military service branch., Conclusions: In this young, physically active population, reporting shorter sleep duration was associated with a higher risk of multiple CDMCs., (Published by Elsevier B.V.)

Sustained operations (SUSOPS) require military personnel to conduct combat and training operations while experiencing physical and cognitive stress and limited sleep. These operations are often conducted in a state of negative energy balance and are associated with degraded cognitive performance and mood. Whether maintaining energy balance can mitigate these declines is unclear. This randomized crossover study assessed the effects of energy balance on cognitive performance, risk-taking propensity, ambulatory vigilance, and mood during a simulated 72-h SUSOPS., Methods: Ten male Soldiers (mean ± SE; 22.4 ± 1.7 y; body weight 87.3 ± 1.1 kg) completed two, 72-h simulated SUSOPS in random order, separated by 7 days of recovery. Each SUSOPS elicited ∼4500 kcal/d total energy expenditure and restricted sleep to 4 h/night. During SUSOPS, participants consumed either an energy-balanced or restricted diet that induced a 43 ± 3% energy deficit. A cognitive test battery was administered each morning and evening to assess: vigilance, working memory, grammatical reasoning, risk-taking propensity, and mood. Real-time ambulatory vigilance was assessed each morning, evening, and night via a wrist-worn monitoring device., Results: Participants exhibited heightened risk-taking propensity (p = 0.047) with lower self-reported self-control (p = 0.021) and fatigue (p = 0.013) during energy deficit compared to during energy balance. Vigilance accuracy (p < 0.001) and working memory (p = 0.040) performance decreased, and vigilance lapses increased (p < 0.001) during SUSOPS, but did not differ by diet. Percentage of correct responses to ambulatory vigilance stimuli varied during SUSOPS (p = 0.019) independent of diet, with generally poorer performance during the morning and night. Total mood disturbance (p = 0.001), fatigue (p < 0.001), tension (p = 0.003), and confusion (p = 0.036) increased whereas vigor decreased (p < 0.001) during SUSOPS, independent of diet., Conclusion: Prolonged physical activity combined with sleep restriction is associated with impaired vigilance, memory, and mood state. Under such conditions, maintaining energy balance prevents increased risk-taking and improves self-control, but does not improve other aspects of cognitive function or mood. Given the small sample in the present study, replication in a larger cohort is warranted., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Testosterone administration attenuates reductions in total body mass and lean mass during severe energy deficit (SED)., Objectives: This study examined the effects of testosterone administration on the serum metabolome during SED., Methods: In a double-blind, placebo-controlled clinical trial, non-obese men were randomized to receive 200-mg testosterone enanthate/wk (TEST) (n = 24) or placebo (PLA) (n = 26) during a 28-d inpatient, severe exercise- and diet-induced energy deficit. This study consisted of three consecutive phases. Participants were free-living and provided a eucaloric diet for 14-d during Phase 1. During Phase 2, participants were admitted to an inpatient unit, randomized to receive testosterone or placebo, and underwent SED for 28-d. During Phase 3, participants returned to their pre-study diet and physical activity habits. Untargeted metabolite profiling was conducted on serum samples collected during each phase. Body composition was measured using dual-energy X-ray absorptiometry after 11-d of Phase 1 and after 25-d of Phase 2 to determine changes in fat and lean mass., Results: TEST had higher (Benjamini-Hochberg adjusted, q < 0.05) androgenic steroid and acylcarnitine, and lower (q < 0.05) amino acid metabolites after SED compared to PLA. Metabolomic differences were reversed by Phase 3. Changes in lean mass were associated (Bonferroni-adjusted, p < 0.05) with changes in androgenic steroid metabolites (r = 0.42-0.70), acylcarnitines (r = 0.37-0.44), and amino acid metabolites (r = - 0.36-- 0.37). Changes in fat mass were associated (p < 0.05) with changes in acylcarnitines (r = - 0.46-- 0.49) and changes in urea cycle metabolites (r = 0.60-0.62)., Conclusion: Testosterone administration altered androgenic steroid, acylcarnitine, and amino acid metabolites, which were associated with changes in body composition during SED., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Anthropometrics and body composition characteristics differentiate many types of athletes and are related to performance on fitness tests and tasks in military personnel. Soldiers competing to enter elite units must demonstrate physical fitness and operational competence across multiple events. Therefore, this study determined whether anthropometrics and body composition predicted physical performance and selection for special forces training among soldiers attending the rigorous Special Forces Assessment and Selection (SFAS) course., Materials and Methods: Soldiers attending the SFAS course between May 2015 and March 2017 were enrolled in a longitudinal, observational study. Anthropometrics (height, body mass, and body mass index [BMI]; n = 795) and body composition measured by dual-energy X-ray absorptiometry (percentage body fat, fat mass, lean mass, bone mineral content [BMC], and bone mineral density [BMD]; n = 117) were assessed before the course start. Associations with physical performance were determined with correlation coefficients. Associations with selection were determined with analyses of variance and t-tests; effect sizes were calculated as Cohen's d. The U.S. Army Research Institute of Environmental Medicine Institutional Review Board (IRB) initially approved this study, and the U.S. Army Medical Research and Development Command IRB approved the continuing review., Results: Lower percentage body fat and fat mass predicted better performance on all assessments: Army Physical Fitness Test (APFT), pull-ups, SFAS run, loaded road march, obstacle course, and land navigation (P ≤ .05). Higher lean mass predicted better performance on the loaded road march (P ≤ .05). Lower body mass and BMI predicted better performance on APFT, pull-ups, run, and obstacle course; higher body mass and BMI predicted better performance on the loaded road march (P ≤ .05). Shorter stature predicted better performance on push-ups (APFT) and pull-ups; taller stature predicted better performance on SFAS run and loaded road march (P ≤ .05). On average, the selected soldiers were taller (179.0 ± 6.6 vs. 176.7 ± 6.7 cm), had higher body mass (85.8 ± 8.8 vs. 82.1 ± 9.6 kg), BMI (26.8 ± 2.2 vs. 26.3 ± 2.6 kg/m2), lean mass (67.2 ± 7.3 vs. 61.9 ± 7.6 kg), BMC (3.47 ± 0.40 vs. 3.29 ± 0.56 kg), and BMD (1.34 ± 0.10 vs. 1.28 ± 0.10 g/cm2), and lower percentage body fat (17.3 ± 3.4 vs. 20.1 ± 4.5%) and fat mass (14.2 ± 3.7 vs. 15.8 ± 4.4 kg) (P ≤ .05). Effect sizes were largest for lean mass (Cohen's d = 0.71) and percentage body fat (d = 0.70), followed by BMD (d = 0.60), body mass (d = 0.40), fat mass (d = 0.39), BMC (d = 0.37), height (d = 0.35), and BMI (d = 0.21). Body mass adjustment attenuated associations between height and selection., Conclusions: Anthropometrics and body composition are predictors of physical performance and SFAS success. Since these measures are modifiable (excluding height), they may be the focus of intervention studies aiming to improve performance in arduous military training courses, sports that require competition in multiple events, and occupations that have varied physical demands, such as firefighting, law enforcement, and construction., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: About 50% of Americans and 70% of US military service members (SMs) regularly use dietary supplements (DSs) and some are associated with adverse effects (AEs). SMs are more likely to use unsafe DSs than civilians., Objective: The aim of this investigation was to examine the prevalence of, and factors associated with, AEs., Design: Cross-sectional., Participants: A stratified random sample of 200,000 US SMs from the Air Force, Army, Marine Corps, and Navy were obtained from military workforce records. Eighteen percent (n = 26,681) of successfully contacted SMs (n = 146,365) volunteered to participate between December 2018 and August 2019. Participants completed a detailed online questionnaire on demographic characteristics, lifestyle factors, and AEs associated with DS use., Main Outcome Measure: Prevalence of, and factors associated with, AEs among DS users., Statistical Analysis: Prevalence of AEs was calculated by DS categories. Linear trends, χ 2 statistics, and multivariable logistic regression examined associations between AEs and demographic characteristics, lifestyle factors, and number DSs consumed., Results: Proportion of DS users (≥ 1 time /week) reporting ≥1 AE was 18% overall, 20% for combination products (ie, weight loss, muscle building, and before/after workout supplements), 8% for purported prohormones, 6% for protein/amino acid products, 6% for multivitamin/multiminerals, 6% for individual vitamins/minerals, 4% for herbal products, and 2% for joint health products. Combination products are very popular in military personnel with nearly half of SMs regularly taking them. In multivariable analysis, reporting AEs were independently associated with female gender, younger age, higher body mass index, smoking, higher alcohol intake, service in the Army, Navy, or Marine Corps (compared with Air Force), and consumption of a greater number of DSs., Conclusions: A large proportion of SMs report experiencing AEs, especially users of combination products and purported prohormone supplements. This study presents contemporary data collected from a very large at-risk population on potentially hazardous categories of DSs., (Copyright © 2022 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: Use of prescription medications (PMs) with dietary supplements (DSs) can be hazardous because of potential adverse interactions, but patterns of dual use in military service members (SMs) has not been examined., Objective: Investigate dual use of filled PMs (FPMs) and DSs, factors associated with dual use, and dual use among SMs with clinically diagnosed medical conditions (CDMCs)., Design: Cross-sectional. Data on FPMs and CDMCs were obtained from medical surveillance records. Between December 2018 and August 2019, participants completed a questionnaire on DS use in the previous 6 months., Participants: A stratified random sample of 26,880 SMs from all military services., Main Outcome Measures: Prevalence of dual use of FPMs with DSs within a 6-month period, demographic/lifestyle factors associated with dual use, and prevalence of dual use among SMs with CDMCs., Statistical Analysis: Prevalences were calculated as percents, χ 2 statistics examined differences across various strata of demographic and lifestyle characteristics, and univariable and multivariable logistic regression determined the odds of using FPMs with DSs for various CDMCs., Results: About one-half (49%) of SMs had dual use of FPMs with DSs in the 6-month period. Dual use was higher among women; increased with older age, more formal education, higher body mass index, and more physical activity; was highest among American Indian SMs and lowest among Asian SMs; was higher among former tobacco users; and was highest among Army personnel and lowest among Marine Corps personnel. The overall prevalence of dual use in the 6-month period was higher among those with a CDMC than those without (62% vs 19%), and this relationship was maintained for 20 International Classification of Diseases, Revision 10, code groupings covering virtually all CDMCs., Conclusion: This is the first study to document a high prevalence of dual FPMs and DSs in SMs, especially among those with CDMCs., (Copyright © 2022 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: This cross-sectional study investigated the prevalence of, and factors associated with, filled prescription medications (FPMs) among United States (US) service members (SMs). Methods: A stratified random sample of active duty SMs from the Air Force, Army, Marine Corps, and Navy was obtained from military workforce records. Participants ( n = 26,680) completed a questionnaire on demographics, physical characteristics, and lifestyle factors and approved access to their FPM for the previous 6 months. FPMs were obtained from the military Pharmacy Data Transaction Service that included all prescription medications dispensed at military medical treatment facilities, abroad, at retail pharmacies in the US, and/or through mail-order programs. Results: About two-thirds (65%) of SMs had ≥1 FPM in the 6 months surveillance period. Central nervous system (CNS) agents had the highest prevalence (41%), followed by anti-infective agents (20%), eye/ear/nose/throat preparations (20%), gastrointestinal drugs (18%), autonomic drugs (17%), skin and mucous membrane agents (13%), antihistamine drugs (12%), respiratory tract agents (12%) and cardiovascular drugs (9%). Among CNS agents, overall prevalence of dispensed non-steroidal anti-inflammatory drug (NSAIDs) was 30%. The odds of any FPM was independently associated with female gender, older age, higher body mass index, former tobacco use (smoking and smokeless tobacco), lower alcohol consumption, and was highest among Army, lowest among Marine Corps personnel. Conclusion: In this sample of SMs, dispensing of prescription medication was high, especially NSAIDs, but dispensing of cardiovascular drugs was much lower compared to the general US population, likely because of the younger age and higher level of physical activity of SMs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Knapik, Trone, Steelman, Farina and Lieberman.)

Objectives: Arginine is an amino-acid supplement and precursor for nitric-oxide synthesis, which affects various biologic processes. The objective of this study was to determine the effects of arginine supplementation on growth hormone (GH) and metabolic parameters., Methods: Thirty physically active, healthy men (age 18-39 y; body mass index: 18.5-25 kg/m 2 ) were randomized in a double-blind, placebo-controlled, crossover trial. Arginine (10 g) and placebo (0 g) beverages were consumed after an overnight fast. Blood samples were collected at baseline and 1.5, 3.0, and 24 h after supplementation. The primary outcomes were serum GH and metabolomics. Also, amino acids, glucose, insulin, triacylglycerols, thyroid hormones, testosterone, cortisol, dehydroepiandrosterone, and mood state were assessed. Individuals with detectable increases in GH were analyzed separately (responders: n = 16; < 0.05 ng/mL at 1.5 h). Repeated-measure analyses of variance estimated the treatment effects at each timepoint., Results: Arginine levels increased at 1.5 h (146%) and 3.0 h (95%; P ≤ 0.001) and GH (193%) and thyroid-stimulating hormone (TSH; 10%) levels at 24 h (P < 0.05) after arginine versus placebo consumption. Arginine versus placebo increased glucose levels at 1.5 h (5%) and 3.0 h (3%; P ≤ 0.001). Arginine versus placebo did not affect other dependent measures, including mood state (P > 0.05), but changes in the urea, glutamate, and citric-acid pathways were observed. Among responders, arginine versus placebo increased GH at 1.5 h (37%), glucose at 1.5 h (4%) and 3.0 h (4%), and TSH at 24 h (9%; P < 0.05). Responders had higher levels of benzoate metabolites at baseline and 1.5 h, and an unknown compound (X-16124) at baseline, 1.5 h, and 24 h that corresponds to a class of gut microbes (P < 0.05)., Conclusions: Arginine supplementation modestly increased GH, glucose, and TSH levels in younger men. Responders had higher benzoate metabolites and an unknown analyte attributed to the gut microbiome. Future studies should examine whether the increased prevalence of these gut microorganisms corresponds with GH response after arginine supplementation., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Iodine is a mineral nutrient essential for the regulation of a variety of key physiological functions including metabolism and brain development and function in children and adults. As such, iodine intake and status within populations is an area of concern and research focus. This paper will review recently published studies that focus on the re-emerging issue of iodine deficiency as a global concern and declining intake among populations in developed countries. Historically, the implementation of salt-iodization programs worldwide has reduced the incidence of iodine deficiency, but 30% of the world's population is still at risk. Iodine nutrition is a growing issue within industrialized countries including the U.S. as a result of declining iodine intake, in part due to changing dietary patterns and food manufacturing practices. Few countries mandate universal salt iodization policies, and differing agriculture and industry practices and regulations among countries have resulted in inconsistencies in supplementation practices. In the U.S., in spite of salt-iodization policies, mild-to-moderate iodine deficiency is common and appears to be increasing. European countries with the highest incidence of deficiency lack iodization programs. Monitoring the iodine status of at-risk populations and, when appropriate, public health initiatives, appear to be warranted.

Male military personnel conducting strenuous operations experience reduced testosterone concentrations, muscle mass, and physical performance. Pharmacological restoration of normal testosterone concentrations may attenuate performance decrements by mitigating muscle mass loss. Previously, administering testosterone enanthate (200 mg/wk) during 28 days of energy deficit prompted supraphysiological testosterone concentrations and lean mass gain without preventing isokinetic/isometric deterioration. Whether administering a practical dose of testosterone protects muscle and performance during strenuous operations is undetermined. The objective of this study was to test the effects of a single dose of testosterone undecanoate on body composition and military-relevant physical performance during a simulated operation. After a 7-day baseline phase ( P1 ), 32 males (means ± SD; 77.1 ± 12.3 kg, 26.5 ± 4.4 yr) received a single dose of either testosterone undecanoate (750 mg; TEST) or placebo (PLA) before a 20-day simulated military operation ( P2 ), followed by a 23-day recovery ( P3 ). Assessments included body composition and physical performance at the end of each phase and circulating endocrine biomarkers throughout the study. Total and free testosterone concentrations in TEST were greater than PLA throughout most of P2 ( P < 0.05), but returned to P1 values during P3 . Fat-free mass (FFM) was maintained from P1 to P2 in TEST (means ± SE; 0.41 ± 0.65 kg, P = 0.53), but decreased in PLA (-1.85 ± 0.69 kg, P = 0.01) and recovered in P3 . Regardless of treatment, total body mass and fat mass decreased from P1 to P2 ( P < 0.05), but did not fully recover by P3 . Physical performance decreased during P2 ( P < 0.05) and recovered by P3 , regardless of treatment. In conclusion, administering testosterone undecanoate before a simulated military operation protected FFM but did not prevent decrements in physical performance. NEW & NOTEWORTHY This study demonstrated that a single intramuscular dose of testosterone undecanoate (750 mg) administered to physically active males before a 20-day simulated, multi-stressor military operation increased circulating total and free testosterone concentrations within normal physiological ranges and spared FFM. However, testosterone administration did not attenuate decrements in physical performance across multiple measures of power, strength, anaerobic or aerobic capacity.

Context: Effects of testosterone on integrated muscle protein metabolism and muscle mass during energy deficit are undetermined., Objective: The objective was to determine the effects of testosterone on mixed-muscle protein synthesis (MPS), proteome-wide fractional synthesis rates (FSR), and skeletal muscle mass during energy deficit., Design: This was a randomized, double-blind, placebo-controlled trial., Setting: The study was conducted at Pennington Biomedical Research Center., Participants: Fifty healthy men., Intervention: The study consisted of 14 days of weight maintenance, followed by a 28-day 55% energy deficit with 200 mg testosterone enanthate (TEST, n = 24) or placebo (PLA, n = 26) weekly, and up to 42 days of ad libitum recovery feeding., Main Outcome Measures: Mixed-MPS and proteome-wide FSR before (Pre), during (Mid), and after (Post) the energy deficit were determined using heavy water (days 1-42) and muscle biopsies. Muscle mass was determined using the D3-creatine dilution method., Results: Mixed-MPS was lower than Pre at Mid and Post (P < 0.0005), with no difference between TEST and PLA. The proportion of individual proteins with numerically higher FSR in TEST than PLA was significant by 2-tailed binomial test at Post (52/67; P < 0.05), but not Mid (32/67; P > 0.05). Muscle mass was unchanged during energy deficit but was greater in TEST than PLA during recovery (P < 0.05)., Conclusions: The high proportion of individual proteins with greater FSR in TEST than PLA at Post suggests exogenous testosterone exerted a delayed but broad stimulatory effect on synthesis rates across the muscle proteome during energy deficit, resulting in muscle mass accretion during subsequent recovery., (Published by Oxford University Press on behalf of the Endocrine Society 2022.)

Background: Although representative data on caffeine intake in Americans are available, these data do not include US service members (SMs). The few previous investigations in military personnel largely involve convenience samples. This cross-sectional study examined prevalence of caffeine consumers, daily caffeine consumption, and factors associated with caffeine use among United States active duty military service members (SMs)., Methods: A stratified random sample of SMs were asked to complete an on-line questionnaire on their personal characteristics and consumption of caffeinated products (exclusive of dietary supplements). Eighteen percent (n = 26,680) of successfully contacted SMs (n = 146,365) completed the questionnaire., Results: Overall, 87% reported consuming caffeinated products ≥1 time/week. Mean ± standard error per-capita consumption (all participants) was 218 ± 2 and 167 ± 3 mg/day for men and women, respectively. Caffeine consumers ingested 243 ± 2 mg/day (251 ± 2 mg/day men, 195 ± 3 mg/day women). On a body-weight basis, men and women consumed respectively similar caffeine amounts (2.93 vs 2.85 mg/day/kg; p = 0.12). Among individual caffeinated products, coffee had the highest use (68%), followed by sodas (42%), teas (29%), energy drinks (29%) and gums/candy/medications (4%). In multivariable logistic regression, characteristics independently associated with caffeine use (≥1 time/week) included female gender, older age, white race/ethnicity, higher body mass index, tobacco use or former use, greater alcohol intake, and higher enlisted or officer rank., Conclusion: Compared to National Health and Nutrition Examination Survey data, daily caffeine consumption (mg/day) by SMs was higher, perhaps reflecting higher mental and physical occupational demands on SMs., (© 2022. The Author(s).)

Background: Physical and psychological stress alter gut-brain axis activity, potentially causing intestinal barrier dysfunction that may, in turn, induce cognitive and mood impairments through exacerbated inflammation and blood brain barrier (BBB) permeability. These interactions are commonly studied in animals or artificial laboratory environments. However, military survival training provides an alternative and unique human model for studying the impacts of severe physical and psychological stress on the gut-brain axis in a realistic environment., Purpose: To determine changes in intestinal barrier and BBB permeability during stressful military survival training and identify relationships between those changes and markers of stress, inflammation, cognitive performance, and mood state., Materials and Methods: Seventy-one male U.S. Marines (25.2 ± 2.6 years) were studied during Survival, Evasion, Resistance, and Escape (SERE) training. Measurements were conducted on day 2 of the 10-day classroom phase of training (PRE), following completion of the 7.5-day field-based simulation phase of the training (POST), and following a 27-day recovery period (REC). Fat-free mass (FFM) was measured to assess the overall physiologic impact of the training. Biomarkers of intestinal permeability (liposaccharide-binding protein [LBP]) and BBB permeability (S100 calcium-binding protein B [S100B]), stress (cortisol, dehydroepiandrosterone sulfate [DHEA-S] epinephrine, norepinephrine) and inflammation (interleukin-6 [IL-6], high-sensitivity C-reactive protein [hsCRP]) were measured in blood. Cognitive performance was assessed by psychomotor vigilance (PVT) and grammatical reasoning (GR) tests, and mood state by the Profile of Mood States (total mood disturbance; TMD), General Anxiety Disorder-7 (GAD-7), and Patient Health (PHQ-9) questionnaires., Results: FFM, psychomotor vigilance, and LBP decreased from PRE to POST, while TMD, anxiety, and depression scores, and S100B, DHEA-S, IL-6, norepinephrine, and epinephrine concentrations all increased (all p ≤ 0.01). Increases in DHEA-S were associated with decreases in body mass (p = 0.015). Decreases in FFM were associated with decreases in LBP concentrations (p = 0.015), and both decreases in FFM and LBP were associated with increases in TMD and depression scores (all p < 0.05) but not with changes in cognitive performance. Conversely, increases in S100B concentrations were associated with decreases in psychomotor vigilance (p < 0.05) but not with changes in mood state or LBP concentrations., Conclusions: Evidence of increased intestinal permeability was not observed in this military survival training-based model of severe physical and psychological stress. However, increased BBB permeability was associated with stress and cognitive decline, while FFM loss was associated with mood disturbance, suggesting that distinct mechanisms may contribute to decrements in cognitive performance and mood state during the severe physical and psychological stress experienced during military survival training., (Published by Elsevier Inc.)

Dietary supplements (DSs) are used by 50% of Americans and 70% of United States military service members (SMs); some have adverse effects (AEs). This cross-sectional investigation examined AEs associated with specific DSs. A stratified random sample of SMs from the Air Force, Army, Marine Corps, and Navy was obtained. Volunteers completed a questionnaire reporting AEs for 96 generic and 62 specific DSs. The highest prevalence (≥1 AE) in specific DS categories was 35% prohormones, 33% weight loss supplements, 26% pre/post workout supplements, 14% herbal products, 12% multivitamin/multiminerals, 11% protein/amino acids, 9% muscle building supplements, 7% other DSs, 6% joint health products, and 5% individual vitamins/minerals. Specific DSs of concern (with proportion reporting AEs) included: Libido Max® (35%), Hydroxycut Hardcore® (33%), OxyElite® (33%), Roxylean® (31%), Growth Factor 9® (30%), Super HD® (29%), Hydroxycut Advanced® (29%), Lipo 6® (28%), The Ripper® (27%), Test Booster® (27%), Xenadrine Xtreme Thermogenic® (27%), C4 Extreme® (26%), and C4 Original® (25%). Products marketed for weight loss, use before/after workout, and prohormones had the highest AE prevalence. DSs can contain substances with independent/additive AEs and/or interact with other ingredients or prescribed medications. Methods described here could provide a continuous surveillance system detecting dangerous DSs entering the market., (Published by Elsevier Ltd.)

Purpose: Growing evidence suggests hydration plays a role in metabolic dysfunction, however data in humans are scarce. This study examined the cross-sectional association between hydration and metabolic dysfunction in a representative sample of the US population., Methods: Data from 3961 adult NHANES (National Health and Nutrition Examination Survey) participants (49.8% female; age 46.3 ± 0.5 years) were grouped by quartile of urine specific gravity (U SG , 2007-2008 cohort) or urine osmolality (U Osm , 2009-2010 cohort) as measures of hydration. Metabolic dysfunction was assessed by glycemic and insulinemic endpoints and by components of the metabolic syndrome. Multivariate-adjusted linear and logistic regression models were used., Results: Increasing quartiles of U SG but not U Osm was associated with higher fasting plasma glucose (FPG), glycated hemoglobin (all P < 0.01), HOMA-IR and elevated insulin (all P < 0.05). Compared with the lowest quartile, those with the highest U SG but not U Osm had greater risk of metabolic syndrome (Q4 vs. Q1, OR (99% CI): 1.6 (1.0, 2.7), P = 0.01) and diabetes (Q4 vs. Q1, OR: 1.8 (1.0, 3.4), P < 0.05). Additionally, those with U SG  > 1.013 or U Osm  > 500 mOsm/kg, common cut-off values for optimal hydration based on retrospective analyses of existing data, had less favorable metabolic markers. In a subset of participants free from diabetes mellitus, impaired kidney function, hypertension and diuretic medication, U SG remained positively associated with FPG (P < 0.01) and elevated FPG (P < 0.05)., Conclusion: These analyses provide population-based evidence that U SG as a proxy for hydration is associated with glucose homeostasis in NHANES 2007-2008. The same association was not significant when U Osm was used as a proxy for hydration in the 2009-2010 wave., Clinical Trial Registry: Not applicable, as this was a reanalysis of existing NHANES data., (© 2021. The Author(s).)

Background: About 50% of Americans and 70% of US military service members use dietary supplements (DSs)., Objectives: This cross-sectional survey examined current prevalence of and factors associated with DS use in service members., Methods: A stratified random sample of 200,000 service members from the Air Force, Army, Marine Corps, and Navy was obtained from military manpower records, and these service members were asked to complete a questionnaire on their DS use and personal characteristics. Chi-square statistics and multivariable logistic regression examined differences across various strata of demographic, lifestyle, and military characteristics., Results: About 18% of successfully contacted service members (n = 26,681) completed the questionnaire between December 2018 and August 2019 (mean ± SD age: 33 ± 8 y, 86% male). Overall, 74% reported using ≥1 DS/wk. Multivitamins/multiminerals were the most commonly used DSs (45%), followed by combination products (44%), proteins/amino acids (42%), individual vitamins/minerals (31%), herbals (20%), joint health products (9%), and purported prohormones (5%). In multivariable analysis, factors independently associated with DS use included female gender [OR (female/male): 1.91; 95% CI: 1.73, 2.11], older age [OR (≥40/18-24 y): 1.25; 95% CI: 1.08, 1.44], higher education level [OR (college degree/high school or less): 1.35; 95% CI: 1.19, 1.53], higher BMI [OR (≥30/<25 kg/m2): 1.37; 95% CI: 1.25, 1.52], more weekly resistance training [OR (>300/≤45 min/wk): 5.05; 95% CI: 4.55, 5.61], smokeless tobacco use [OR (user/nonuser): 1.30; 95% CI: 1.17, 1.44], higher alcohol intake [OR (≥72/0 mL/wk): 1.41; 95% CI: 1.29, 1.54], and higher military rank [OR (senior officer/junior enlisted): 1.26; 95% CI: 1.06, 1.51]., Conclusions: Compared with civilian data from the NHANES, service members were much more likely to use DSs and used different types of DSs, especially combination products and proteins/amino acids often used to purportedly enhance physical performance. Comparisons with previous military data suggest DS use has increased over time., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Clinical administration of testosterone is widely used due to a variety of claimed physical and cognitive benefits. Testosterone administration is associated with enhanced brain and cognitive function, as well as mood, in energy-balanced males, although such relationships are controversial. However, the effects of testosterone administration on the brains of energy-deficient males, whose testosterone concentrations are likely to be well below normal, have not been investigated., Methods: This study collected functional magnetic resonance imaging (fMRI) data from 50 non-obese young men before (PRE) and shortly after (POST) 28 days of severe exercise-and-diet-induced energy deficit during which testosterone (200 mg testosterone enanthate per week in sesame oil, TEST) or placebo (sesame seed oil only, PLA) were administered. Scans were also collected after a post-energy-deficit weight regain period (REC). Participants completed five fMRI tasks that assessed aspects of: 1) executive function (Attention Network Task or ANT; Multi-Source Interference Task or MSIT; AXE Continuous Processing Task or AXCPT); 2) aggressive behavior (Provoked Aggression Task or AGG); and 3) latent emotion processing (Emotional Face Processing or EMO)., Results: Changes over time in task-related fMRI activation in a priori defined task-critical brain regions during performance of 2 out of 5 tasks were significantly different between TEST and PLA, with TEST showing greater levels of activation during ANT in the right anterior cingulate gyrus at POST and during MSIT in several brain regions at REC. Changes over time in objective task performance were not statistically significant; testosterone-treated volunteers had greater self-reported anger during AGG at POST., Conclusions: Testosterone administration can alter some aspects of brain function during severe energy deficit and increase levels of anger., (Copyright © 2021. Published by Elsevier Inc.)

Background: Sport-related nutritional supplements (SRNSs) include sport drinks, sport bars, and sport gels. Previous studies indicate that 25-35 % of athletes and 25-50 % of military personnel report using these supplements. This study examined prevalence, factors associated with use, and adverse effects (AEs) of SRNSs among United States military service members (SMs)., Methods: A stratified random sample of 200,000 SMs was obtained from military workforce records, and asked to complete a survey on demographics, SRNS use, and AEs experienced. About 18 % (n = 26,681) of contacted SMs (n = 146,365) completed the survey between December 2018 and August 2019., Results: Overall, 45 % of SMs used ≥ 1 SRNS at least once per week in the past 6 months. Prevalence of use (± standard error) for sport drinks, bars, and gels were 32 ± 0.3, 27 ± 0.3, and 3 ± 0.1 %, respectively. Use of 1, 2, or 3 SRNSs was 28.9 ± 0.5, 13.6 ± 0.6, and 2.2 ± 0.6 %, respectively. Multivariable logistic regression indicated greater use of any SRNS was independently associated with male gender, younger age, single marital status, more weekly aerobic or resistance training, tobacco use, higher alcohol intake, officer status, combat arms occupations, and service in the Marine Corps or Navy (compared to the Air Force). Overall, the proportion of users reporting ≥ 1 AE was 2.0 ± 0.1 %, with 1.3 ± 0.1 % for sport drinks, 1.6 ± 0.2 % for sport bars, and 2.8 ± 0.6 % for sport gels., Conclusions: This large study of a stratified random sample of SMs found that nearly half of SMs consumed SRNSs weekly, and self-reported AEs were comparatively low. The AE incidence for SRNSs was much lower than typically found for dietary supplements, possibly because of more rigorous regulatory oversight for SRNSs., (© 2021. The Author(s).)

Objective: Iron and/or iodine deficiencies can have multiple serious adverse health outcomes, but examination of incidence rates of these deficiencies has rarely been conducted in any large population. This study examined incidence rates, temporal trends and demographic factors associated with medically diagnosed iron and iodine deficiencies/disorders in US military service members (SM)., Design: The Defense Medical Epidemiological Database (DMED) was queried for medical visits of active duty SM to obtain specific International Classification of Diseases, Version 9, codes involving clinically diagnosed iron and iodine deficiencies/disorders., Setting: Analysis of existing database (DMED)., Participants: Entire population of US military SM from 1997 to 2015 (average n per year = 1 382 266, 15 % women)., Results: Overall incidence rates for iron and iodine were 104 and 36 cases/100 000 person-years, respectively. Over the 19-year period, rates for iron disorders increased steadily (108 % for men, 177 % for women). Rates for iodine disorders also increased steadily for men (91 %), but, for women, there was an initial rise followed by a later decline. Overall, women's rates were 12 and 10 times higher than men's for iron and iodine, respectively. Compared with whites, blacks and those of other races had higher rates of deficiencies of both minerals. Incidence rates for iodine deficiency increased substantially with age., Conclusions: The overall incidence of clinically diagnosed iron and iodine deficiency among SM was low, but increased over the 19 years examined, and certain demographic groups were at significantly greater risk. Given the unexpected increases in incidence of these mineral disorders, increased surveillance may be appropriate.Clinical Trial Registration No. ISRCTN58987177 (http//:www.isrctn.com/ISRCTN58987177).

Background: Previously, young males administered 200 mg/week of testosterone enanthate during 28 days of energy deficit (EDef) gained lean mass and lost less total mass than controls (Optimizing Performance for Soldiers I study, OPS I). Despite that benefit, physical performance deteriorated similarly in both groups. However, some experimental limitations may have precluded detection of performance benefits, as performance measures employed lacked military relevance, and the EDef employed did not elicit the magnitude of stress typically experienced by Soldiers conducting operations. Additionally, the testosterone administered required weekly injections, elicited supra-physiological concentrations, and marked suppression of endogenous testosterone upon cessation. Therefore, this follow-on study will address those limitations and examine testosterone's efficacy for preserving Solder performance during strenuous operations., Methods: In OPS II, 32 males will participate in a randomized, placebo-controlled, double-blind trial. After baseline testing, participants will be administered either testosterone undecanoate (750 mg) or placebo before completing four consecutive, 5-day cycles simulating a multi-stressor, sustained military operation (SUSOPS). SUSOPS will consist of two low-stress days (1000 kcal/day exercise-induced EDef; 8 h/night sleep), followed by three high-stress days (3000 kcal/day and 4 h/night). A 23-day recovery period will follow SUSOPS. Military relevant physical performance is the primary outcome. Secondary outcomes include 4-comparment body composition, muscle and whole-body protein turnover, intramuscular mechanisms, biochemistries, and cognitive function/mood., Conclusions: OPS II will determine if testosterone undecanoate safely enhances performance, while attenuating muscle and total mass loss, without impairing cognitive function, during and in recovery from SUSOPS., Trial Registration: ClinicalTrials.gov Identifier: NCT04120363., Competing Interests: The authors declare that they have no competing interests. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Army or the Department of Defense. Any citations of commercial organizations and trade names in this report do not constitute an official Department of the Army endorsement of approval of the products or services of these organizations., (© 2021 Published by Elsevier Inc.)