Comparative analysis of circulating metabolomic profiles identifies shared metabolic alterations across distinct multistressor military training exercises.

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). Log2-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.

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.

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.

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.

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.

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.

Stress and the gut-brain axis: Cognitive performance, mood state, and biomarkers of blood-brain barrier and intestinal permeability following severe physical and psychological stress.

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.

Prevalence of caffeine consumers, daily caffeine consumption, and factors associated with caffeine use among active duty United States military personnel.

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.

Effects of testosterone administration on fMRI responses to executive function, aggressive behavior, and emotion processing tasks during severe exercise- and diet-induced energy deficit.

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.

Prevalence of and Factors Associated with Dietary Supplement Use in a Stratified, Random Sample of US Military Personnel: The US Military Dietary Supplement Use Study.

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.

Cellular dehydration acutely degrades mood mainly in women: a counterbalanced, crossover trial.

It is unclear if mild-to-moderate dehydration independently affects mood without confounders like heat exposure or exercise. This study examined the acute effect of cellular dehydration on mood. Forty-nine adults (55 % female, age 39 (sd 8) years) were assigned to counterbalanced, crossover trials. Intracellular dehydration was induced with 2-h (0·1 ml/kg per min) 3 % hypertonic saline (HYPER) infusion or 0·9 % isotonic saline (ISO) as a control. Plasma osmolality increased in HYPER (pre 285 (sd 3), post 305 (sd 4) mmol/kg; P < 0·05) but remained unchanged in ISO (pre 285 (sd 3), post 288 (sd 3) mmol/kg; P > 0·05). Mood was assessed with the short version of the Profile of Mood States Questionnaire (POMS). The POMS sub-scale (confusion-bewilderment, depression-dejection, fatigue-inertia) increased in HYPER compared with ISO (P < 0·05). Total mood disturbance score (TMD) assessed by POMS increased from 10·3 (sd 0·9) to 16·6 (sd 1·7) in HYPER (P < 0·01), but not in ISO (P > 0·05). When TMD was stratified by sex, the increase in the HYPER trial was significant in females (P < 0·01) but not in males (P > 0·05). Following infusion, thirst and copeptin (surrogate for vasopressin) were also higher in females than in males (21·3 (sd 2·0), 14·1 (sd 1·4) pmol/l; P < 0·01) during HYPER. In conclusion, cellular dehydration acutely degraded specific aspects of mood mainly in women. The mechanisms underlying sex differences may be related to elevated thirst and vasopressin.

Associations between urinary hydration markers and metabolic dysfunction: a cross-sectional analysis of NHANES data, 2008-2010.

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 (USG, 2007-2008 cohort) or urine osmolality (UOsm, 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 USG but not UOsm 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 USG but not UOsm 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 USG > 1.013 or UOsm > 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, USG remained positively associated with FPG (P < 0.01) and elevated FPG (P < 0.05). CONCLUSION: These analyses provide population-based evidence that USG as a proxy for hydration is associated with glucose homeostasis in NHANES 2007-2008. The same association was not significant when UOsm 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.

Hydration for health hypothesis: a narrative review of supporting evidence.

PURPOSE: An increasing body of evidence suggests that excreting a generous volume of diluted urine is associated with short- and long-term beneficial health effects, especially for kidney and metabolic function. However, water intake and hydration remain under-investigated and optimal hydration is poorly and inconsistently defined. This review tests the hypothesis that optimal chronic water intake positively impacts various aspects of health and proposes an evidence-based definition of optimal hydration. METHODS: Search strategy included PubMed and Google Scholar using relevant keywords for each health outcome, complemented by manual search of article reference lists and the expertise of relevant practitioners for each area studied. RESULTS: The available literature suggest the effects of increased water intake on health may be direct, due to increased urine flow or urine dilution, or indirect, mediated by a reduction in osmotically -stimulated vasopressin (AVP). Urine flow affects the formation of kidney stones and recurrence of urinary tract infection, while increased circulating AVP is implicated in metabolic disease, chronic kidney disease, and autosomal dominant polycystic kidney disease. CONCLUSION: In order to ensure optimal hydration, it is proposed that optimal total water intake should approach 2.5 to 3.5 L day-1 to allow for the daily excretion of 2 to 3 L of dilute (< 500 mOsm kg-1) urine. Simple urinary markers of hydration such as urine color or void frequency may be used to monitor and adjust intake.

Clinically-diagnosed vitamin deficiencies and disorders in the entire United States military population, 1997-2015.

BACKGROUND: This study examined incidence rates, temporal trends, and demographic factors associated with vitamin deficiencies/disorders in all United States military personnel from 1997 to 2015 (mean N = 1,382,266/year). METHODS: Employing an ecological study design, the Defense Medical Epidemiological Database and specific International Classification of Diseases codes were used to determine incidence rates for clinically-diagnosed vitamin deficiencies/disorders. Associations with demographic factors were examined. RESULTS: The overall incidence rate of vitamin deficiencies/disorders was 92.7 cases/100,000 person-years (p-yr). Highest rates were for vitamin D (53.7 cases/100,000 p-yr), other B-complex vitamins (20.2 cases, 100,000 p-yr), vitamin B12 anemia (7.6 cases/100,000 p-yr), deficiencies of "other vitamins" (5.9 cases/100,000 p-yr), and vitamin A (2.5 cases/100,000 p-yr). Thiamin, riboflavin, niacin, pyridoxine, folate, vitamin C, and vitamin K deficiencies and hypervitaminoses A and D had < 1 case/100,000 p-yr. Rates for vitamin D, other B-complex, "other vitamin", and thiamin deficiencies increased over time, while vitamin A and C deficiencies decreased. Women had higher incidence rates for all examined deficiencies/ disorders except niacin and vitamin C. Incidence rates rose with age in 8 of 15 deficiency/disorder categories and blacks had higher incidence rates in 9 of 15 deficiency/disorder categories. CONCLUSIONS: The overall rate of clinically-diagnosed vitamin deficiencies and disorders was low but higher in women and minority subgroups. As for most illnesses, the diagnosed incidence of such disorders may be an underestimate of the actual incidence. These findings can guide clinical decision making with regard to testing for nutritional deficiencies and delivering public health information to at risk populations. CLINICAL TRIAL REGISTRATION: (No. ISRCTN58987177 ). Registration date 9 October 2019.

Clinically diagnosed iron and iodine deficiencies and disorders in the entire population of US military service members from 1997 to 2015.

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).

Testosterone supplementation upregulates androgen receptor expression and translational capacity during severe energy deficit.

Testosterone supplementation during energy deficit promotes whole body lean mass accretion, but the mechanisms underlying that effect remain unclear. To elucidate those mechanisms, skeletal muscle molecular adaptations were assessed from muscle biopsies collected before, 1 h, and 6 h after exercise and a mixed meal (40 g protein, 1 h postexercise) following 14 days of weight maintenance (WM) and 28 days of an exercise- and diet-induced 55% energy deficit (ED) in 50 physically active nonobese men treated with 200 mg testosterone enanthate/wk (TEST) or placebo (PLA) during the ED. Participants (n = 10/group) exhibiting substantial increases in leg lean mass and total testosterone (TEST) were compared with those exhibiting decreases in both of these measures (PLA). Resting androgen receptor (AR) protein content was higher and fibroblast growth factor-inducible 14 (Fn14), IL-6 receptor (IL-6R), and muscle ring-finger protein-1 gene expression was lower in TEST vs. PLA during ED relative to WM (P < 0.05). Changes in inflammatory, myogenic, and proteolytic gene expression did not differ between groups after exercise and recovery feeding. Mechanistic target of rapamycin signaling (i.e., translational efficiency) was also similar between groups at rest and after exercise and the mixed meal. Muscle total RNA content (i.e., translational capacity) increased more during ED in TEST than PLA (P < 0.05). These findings indicate that attenuated proteolysis at rest, possibly downstream of AR, Fn14, and IL-6R signaling, and increased translational capacity, not efficiency, may drive lean mass accretion with testosterone administration during energy deficit.

Behavioral correlates of self-reported health status in US active duty military.

Trends and relationships between health behaviors and conditions in US active duty military and Coast Guard personnel are understudied. Self-reported data from the 2011 and 2015 Department of Defense Health Related Behaviors Surveys were analyzed to estimate associations between seven behaviors (reasons for not exercising; moderate, vigorous, and strength training exercise; alcohol intake; sleep; and smoking) and five health conditions (high blood pressure [BP], blood sugar [BG], cholesterol [CH]; overweight/obesity [OW]; or obesity [OB]). In 33,531 respondents, 14.8%, 1.7%, 13.6%, 65.5%, and 12.1% had high BP, BG, CH, OW, or OB, respectively. Respondents in 2015, versus 2011, had higher odds of BP, BG, OW, and OB. Compared to exercising as much as desired, citing a disability or injury, or work commitments as reasons for not exercising associated with higher odds of each condition. Longer sleep associated with lower odds of each condition except BG. Current and former smoking associated with higher odds of BP; former smoking also associated with higher odds of high CH and OW. Three behaviors contributing to the best predictive models of each condition resulted in associations of reasons for not exercising with all conditions; strength training for OW and OB; alcohol intake for BP and BG; sleep for BP and CH; and moderate exercise for BG. Disability and injury and time constraints limiting exercise were consistent markers of self-reported health conditions. Military-specific initiatives to promote strategies for overcoming barriers to exercising, continued emphasis on adequate sleep, and reduction of alcohol intake and smoking are warranted.

Severe negative energy balance during 21 d at high altitude decreases fat-free mass regardless of dietary protein intake: a randomized controlled trial.

In this 2-phase randomized controlled study, we examined whether consuming a higher-protein (HP) diet would attenuate fat-free mass (FFM) loss during energy deficit (ED) at high altitude (HA) in 17 healthy males (mean ± sd: 23 ± 6 yr; 82 ± 14 kg). During phase 1 at sea level (SL, 55 m), participants consumed a eucaloric diet providing standard protein (SP; 1.0 g protein/kg,) for 21 d. During phase 2, participants resided at HA (4300 m) for 22 d and were randomly assigned to either an SP or HP (2.0 g protein/kg) diet designed to elicit a 40% ED. Body composition, substrate oxidation, and postabsorptive whole-body protein kinetics were measured. Participants were weight stable during SL and lost 7.9 ± 1.9 kg ( P < 0.01) during HA, regardless of dietary protein intake. Decrements in whole-body FFM (3.6 ± 2.4 kg) and fat mass (3.6 ± 1.3 kg) were not different between SP and HP. HP oxidized 0.95 ± 0.32 g protein/kg per day more than SP and whole-body net protein balance was more negative for HP than for SP ( P < 0.01). Based on changes in body energy stores, the overall ED was 70% (-1849 ± 511 kcal/d, no group differences). Consuming an HP diet did not protect FFM during severe ED at HA.-Berryman, C. E., Young, A. J., Karl, J. P., Kenefick, R. W., Margolis, L. M., Cole, R. E., Carbone, J. W., Lieberman, H. R., Kim, I.-Y., Ferrando, A. A., Pasiakos, S. M. Severe negative energy balance during 21 d at high altitude decreases fat-free mass regardless of dietary protein intake: a randomized controlled trial.

Two days of calorie deprivation impairs high level cognitive processes, mood, and self-reported exertion during aerobic exercise: A randomized double-blind, placebo-controlled study.

Military personnel and emergency responders perform cognitively-demanding tasks during periods of sustained physical exertion and limited caloric intake. Cognitive function is preserved during short-term caloric restriction, but it is unclear if preservation extends to combined caloric restriction and physical exertion. According to the "reticular-activating hypofrontality" model, vigorous exertion impairs prefrontal cortex activity and associated functions. This double-blind, placebo-controlled, crossover study examined cognitive function during sustained exertion while volunteers were calorically-deprived. Twenty-three volunteers were calorie-depleted for two days on one occasion and fully-fed on another. They completed intermittent bouts of exercise at 40-65% VO2peak while prefrontal cortex-dependent tasks of cognitive control, mood, and perceived exertion were assessed. Calorie deprivation impaired accuracy on the task-switching task of set-shifting (p < .01) and decreased sensitivity on the go/no-go task of response inhibition (p < .05). Calorie deprivation did not affect risk taking on the Rogers risk task. During exercise, calorie deprivation, particularly on day 2, increased perceived exertion (p < .05) and impaired mood states of tension, depression, anger, vigor, fatigue, and confusion (all p < .01). Physical exertion during severe calorie deprivation impairs cognitive control, mood, and self-rated exertion. Reallocation of cerebral metabolic resources from the prefrontal cortex to structures supporting movement may explain these deficits.