Comparative Analysis of Circulating Metabolomic Profiles Identifies Shared Metabolic Alterations Across Distinct Multi-Stressor Military Training Operations.

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 types 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 three-week survival school course (ST, n=36), a four-day arctic cross country ski march (AT, n=24), and a 28-day controlled diet- and exercise-induced energy deficit (CED, n=26). Log2-fold changes of >±1 in 191, 121 and 64 metabolites were identified in the ST, AT and CED datasets, respectively. Most metabolite changes were within 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 acylcarnitine, fatty acid, ketone, and glutathione metabolism pathways, whereas the largest decreases were in 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 unique physiological demands of military training.

Longitudinal changes in adverse effects reporting in multiple dietary supplement classifications: The US military dietary supplement use study.

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.

Temporal changes in micronutrient intake among United States Adults, NHANES 2003 through 2018: A cross-sectional study.

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 %

Effects of testosterone enanthate on aggression, risk-taking, competition, mood, and other cognitive domains during 28 days of severe energy deprivation.

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.

Prevalence and adverse effects of sport-related nutritional supplements (sport drinks, bars, and gels) in the military before and during the COVID-19 pandemic: the US Military Dietary Supplement Use Study.

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.

The Medical Burden of Obesity and Overweight in the US Military: Association of BMI with Clinically Diagnosed Medical Conditions in United States Military Service Members.

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/height2 (kg/m2). The prevalence of CDMCs was compared among normal weight (<25.0 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30 kg/m2) 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.

Biomarkers of oxidative stress, diet and exercise distinguish soldiers selected and non-selected for special forces training.

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.

Caffeine consumption and sleep in a submarine environment: An observational study.

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; X2 (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.

Associations between clinically diagnosed medical conditions and dietary supplement use: the US military dietary supplement use study.

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.

Amino Acid Intake and Conformance With the Dietary Reference Intakes in the United States: Analysis of the National Health and Nutrition Examination Survey, 2001-2018.

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.

Effects of energy balance on cognitive performance, risk-taking, ambulatory vigilance and mood during simulated military sustained operations (SUSOPS).

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.

Effect of exogenous testosterone in the context of energy deficit on risky choice: Behavioural and neural evidence from males.

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.

Short sleep duration is associated with a wide variety of medical conditions among United States military service members.

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.

Metabolomics of testosterone enanthate administration during severe-energy deficit.

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.

Prescription medication use of United States military service members by therapeutic classification.

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.

Iodine and Iodine Deficiency: A Comprehensive Review of a Re-Emerging Issue.

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.

Testosterone undecanoate administration prevents declines in fat-free mass but not physical performance during simulated multi-stressor military operations.

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.

Effects of acute arginine supplementation on neuroendocrine, metabolic, cardiovascular, and mood outcomes in younger men: A double-blind, placebo-controlled trial.

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/m2) 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.

Effects of Testosterone on Mixed-Muscle Protein Synthesis and Proteome Dynamics During Energy Deficit.

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.

Dietary Supplement and Prescription Medication Use Among US Military Service Members With Clinically Diagnosed Medical Conditions: The US Military Dietary Supplement Use Study.

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, χ2 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.