Nutrition, Immune Function, and Infectious Disease in Military Personnel: A Narrative Review.

Consuming a diet that meets energy demands and provides essential nutrients promotes a healthy immune system, while both under- and over-nutrition have been associated with immune dysfunction. Military personnel comprise a unique population who frequently endure multi-stressor environments, predisposing them to immune decrements. Additionally, 49% and 22% of active duty U.S. military personnel are classified as overweight and obese, respectively. A literature search on PubMed was conducted to identify studies, reports, review papers, and references within those sources relevant to the topic area. Military personnel experiencing either under- or over-nutrition can suffer from degraded health, readiness, and performance. Insufficient intake of nutrients during military operations increases infection risk and negatively impacts infection recovery. Energy, protein, iron, zinc, and vitamins C and D are nutritional areas of concern that may impact immune competence in a multi-stressor environment. Over-nutrition can promote accretion of excess body fat and obesity, which contributes to a chronic inflammatory state that coincides with immune impairments. Prioritizing efforts to optimize nutrient intake is one approach for reducing disease burden and improving readiness. This review discusses nutritional concerns concomitant to multi-stressor environments that impact immune function, and the relevance of obesity to infectious disease risk in the military population.

Severe, short-term sleep restriction reduces gut microbiota community richness but does not alter intestinal permeability in healthy young men.

Sleep restriction alters gut microbiota composition and intestinal barrier function in rodents, but whether similar effects occur in humans is unclear. This study aimed to determine the effects of severe, short-term sleep restriction on gut microbiota composition and intestinal permeability in healthy adults. Fecal microbiota composition, measured by 16S rRNA sequencing, and intestinal permeability were measured in 19 healthy men (mean ± SD; BMI 24.4 ± 2.3 kg/m2, 20 ± 2 years) undergoing three consecutive nights of adequate sleep (AS; 7-9 h sleep/night) and restricted sleep (SR; 2 h sleep/night) in random order with controlled diet and physical activity. α-diversity measured by amplicon sequencing variant (ASV) richness was 21% lower during SR compared to AS (P = 0.03), but α-diversity measured by Shannon and Simpson indexes did not differ between conditions. Relative abundance of a single ASV within the family Ruminococcaceae was the only differentially abundant taxon (q = 0.20). No between-condition differences in intestinal permeability or ß-diversity were observed. Findings indicated that severe, short-term sleep restriction reduced richness of the gut microbiota but otherwise minimally impacted community composition and did not affect intestinal permeability in healthy young men.

Characterizing Relationships Among the Cognitive, Physical, Social-emotional, and Health-related Traits of Military Personnel.

INTRODUCTION: Personnel engaged in high-stakes occupations, such as military personnel, law enforcement, and emergency first responders, must sustain performance through a range of environmental stressors. To maximize the effectiveness of military personnel, an a priori understanding of traits can help predict their physical and cognitive performance under stress and adversity. This work developed and assessed a suite of measures that have the potential to predict performance during operational scenarios. These measures were designed to characterize four specific trait-based domains: cognitive, health, physical, and social-emotional. MATERIALS AND METHODS: One hundred and ninety-one active duty U.S. Army soldiers completed interleaved questionnaire-based, seated task-based, and physical task-based measures over a period of 3-5 days. Redundancy analysis, dimensionality reduction, and network analyses revealed several patterns of interest. RESULTS: First, unique variable analysis revealed a minimally redundant battery of instruments. Second, principal component analysis showed that metrics tended to cluster together in three to five components within each domain. Finally, analyses of cross-domain associations using network analysis illustrated that cognitive, health, physical, and social-emotional domains showed strong construct solidarity. CONCLUSIONS: The present battery of metrics presents a fieldable toolkit that may be used to predict operational performance that can be clustered into separate components or used independently. It will aid predictive algorithm development aimed to identify critical predictors of individual military personnel and small-unit performance outcomes.

Changes in Immune Function during Initial Military Training.

PURPOSE: Initial military training (IMT) is a transitionary period wherein immune function may be suppressed and infection risk heightened due to physical and psychological stress, communal living, and sleep deprivation. This study characterized changes in biomarkers of innate and adaptive immune function, and potential modulators of those changes, in military recruits during IMT. METHODS: Peripheral leukocyte distribution and mitogen-stimulated cytokine profiles were measured in fasted blood samples, Epstein-Barr (EBV), varicella zoster (VZV), and herpes simplex 1 (HSV1) DNA was measured in saliva by quantitative polymerase chain reaction as an indicator of latent herpesvirus reactivation, and diet quality was determined using the healthy eating index measured by food frequency questionnaire in 61 US Army recruits (97% male) at the beginning (PRE) and end (POST) of 22-wk IMT. RESULTS: Lymphocytes and terminally differentiated cluster of differentiation (CD)4+ and CD8+ T cells increased PRE to POST, whereas granulocytes, monocytes, effector memory CD4+ and CD8+ T cells, and central memory CD8+ T cells decreased ( P ≤ 0.02). Cytokine responses to anti-CD3/CD28 stimulation were higher POST compared with PRE, whereas cytokine responses to lipopolysaccharide stimulation were generally blunted ( P < 0.05). Prevalence of EBV reactivation was higher at POST ( P = 0.04), but neither VZV nor HSV1 reactivation was observed. Diet quality improvements were correlated with CD8+ cell maturation and blunted proinflammatory cytokine responses to anti-CD3/CD28 stimulation. CONCLUSIONS: Lymphocytosis, maturation of T-cell subsets, and increased T-cell reactivity were evident POST compared with PRE IMT. Although EBV reactivation was more prevalent at POST, no evidence of VZV or HSV1 reactivation, which are more common during severe stress, was observed. Findings suggest increases in the incidence of EBV reactivation were likely appropriately controlled by recruits and immune-competence was not compromised at the end of IMT.

Supplemental Protein and a Multinutrient Beverage Speed Wound Healing after Acute Sleep Restriction in Healthy Adults.

BACKGROUND: Physiologic and psychologic stress slow healing from experimental wounds by impairing immune function. OBJECTIVES: We aimed to determine whether supplemental protein and multinutrient supplementation improved wound healing markers after acute stress induced by acute sleep restriction. METHODS: In this single-blind, crossover study in generally healthy young adults (18 males/2 females; mean ± SD age: 19.7 ± 2.30 y), experimental wounds were created by removing the top layer of forearm blisters induced via suction after 48 h of 72-h sleep restriction (2-h nightly sleep), a protocol previously shown to delay wound healing. Skin barrier restoration (measured by transepidermal water loss) assessed wound healing ≤10 d postblistering, and local immune responses were evaluated by serial measurement of cytokine concentrations in fluid collected at wound sites for 48 h postblistering. Participants consumed controlled, isocaloric diets with either 0.900 g · kg-1 · d-1 protein plus placebo (PLA) or 1.50 g · kg-1 · d-1 protein plus multinutrient beverage [l-arginine: 20.0 g/d; l-glutamine: 30.0 g/d; omega-3 (n-3) fatty acids: 1.00 g/d; zinc sulfate: 24.0 mg/d; cholecalciferol: 800 IU/d; and vitamin C: 400 mg/d] (NUT) during sleep restriction and for 4 d afterwards. RESULTS: Skin barrier restoration (primary outcome) was shorter for NUT (median: 3.98 d; IQR: 1.17 d) than for PLA (median: 5.25 d; IQR: 1.05 d) (P = 0.001). Cytokines from wound fluid (secondary outcome) increased over time (main effect of time P ≤ 0.001), except IL-13 (P = 0.07); however, no effects of treatment were observed. CONCLUSIONS: Supplemental nutrition may promote wound healing after sleep restriction in healthy adults including military personnel, the latter of which also have a high incidence of wounds and infection.This trial was registered at clinicaltrials.gov as NCT03525184.

A Food-Based Intervention in a Military Dining Facility Improves Blood Fatty Acid Profile.

Enhancing dietary omega-3 highly unsaturated fatty acids (n-3 HUFA) intake may confer neuroprotection, brain resiliency, improve wound healing and promote cardiovascular health. This study determined the efficacy of substituting a few common foods (chicken meat, chicken sausage, eggs, salad dressings, pasta sauces, cooking oil, mayonnaise, and peanut butter) lower in omega-6 polyunsaturated fatty acids (n-6 PUFA) and higher in n-3 HUFA in a dining facility on blood fatty acid profile. An eight-week prospective, between-subjects (n = 77), repeated measures, parallel-arm trial was conducted. Participants self-selected foods consumed from conventionally produced foods (control), or those lower n-6 PUFA and higher n-3 HUFA versions (intervention). Changes in blood omega-3 index, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), n-6 PUFA, lipid profile, and food satisfaction were main outcomes. Between-group differences over time were assessed using a linear mixed model to measure the effect of diet on blood serum fatty acids and inflammatory markers. The intervention group achieved a higher omega-3 index score (3.66 ± 0.71 vs. 2.95 ± 0.77; p < 0.05), lower total n-6 (10.1 ± 4.6 vs. 15.3 ± 6.7 µg/mL; p < 0.05), and higher serum concentration of EPA (5.0 ± 1.31 vs. 4.05 ± 1.56 µg/mL; p < 0.05) vs. controls. Satisfaction in intervention foods improved or remained consistent. Substitution of commonly eaten dining facility foods with like-items higher in DHA and EPA and lower in n-6 PUFA can favorably impact fatty acid status and the omega-3 index.

Severe sleep restriction suppresses appetite independent of effects on appetite regulating hormones in healthy young men without obesity.

OBJECTIVE: Several nights of moderate (4-5 hr/night) sleep restriction increases appetite and energy intake, and may alter circulating concentrations of appetite regulating hormones. Whether more severe sleep restriction has similar effects is unclear. This study aimed to determine the effects of severe, short-term sleep restriction on appetite, ad libitum energy intake during a single meal, appetite regulating hormones, and food preferences. METHODS: Randomized, crossover study in which 18 healthy men (mean ± SD: BMI 24.4 ± 2.3 kg/m2, 20 ± 2 yr) were assigned to three consecutive nights of sleep restriction (SR; 2 hr sleep opportunity/night) or adequate sleep (AS; 7-9 hr sleep opportunity/night) with controlled feeding and activity designed to maintain energy balance throughout the 3-day period. On day 4, participants consumed a standardized breakfast. Appetite, assessed by visual analogue scales, and circulating ghrelin, peptide-YY (PYY), glucagon-like peptide (GLP-1), insulin, and glucose concentrations were measured before and every 20-60 min for 4hr after the meal. Ad libitum energy and macronutrient intakes were then measured at a provided buffet lunch. Food preferences were measured by Leeds Food Preference Questionnaire (LFPQ) administered before and after the lunch. RESULTS: Area under the curve (AUC) of postprandial hunger (-23%), desire to eat (-23%), and prospective consumption (-18%) ratings were all lower, and postprandial fullness AUC (25%) was higher after SR relative to after AS (p ≤ 0.02). Ad libitum energy intake at the lunch meal was 332 kcal [95% CI: -479, -185] (p<0.001) lower after SR relative to after AS, but relative macronutrient intakes and LFPQ scores did not differ. Postprandial glucose, insulin, PYY, GLP-1, and ghrelin AUCs did not differ between phases. However, mean concentrations of PYY (-11%) and GLP-1 (-4%) over the 4-hr testing period were lower, and glucose concentrations were 6% higher, after SR relative to after AS (p ≤ 0.01). CONCLUSION: In contrast with reported effects of moderate sleep restriction, severe sleep restriction reduced appetite and energy intake, had no impact food preferences, and had little impact on appetite regulating hormones. Findings suggest that severe sleep restriction may suppress appetite and food intake, at least at a single meal, by a mechanism independent of changes in food preference or appetite regulating hormones.

Nutrition, Immune Function, and Infectious Disease.

Consuming a diet meeting energy demands and providing essential nutrients promotes a healthy immune system. Suboptimal nutritional status, resulting from either under- or overnutrition, disrupts immune health and compromises resistance to, and recovery from, infections. Multiple micronutrients contribute to immune health, for example vitamin D, iron, selenium and zinc. Inadequate intake and suboptimal micronutrient status have been observed in military personnel, which potentially increases the risk of acquiring, and recovering from, infectious diseases and may compromise readiness and lethality. This manuscript briefly reviews the relationship between nutrition, immune function, and infectious disease, and provides resources and future research directions.

Symptoms of depression, anxiety, and post-traumatic stress disorder and their relationship to health-related behaviors in over 12,000 US military personnel: Bi-directional associations.

Background Military personnel are at greater risk of psychological disorders and related symptoms than civilians. Limited participation in health-promoting behaviors may increase presence of these disorders. Alternatively, these symptoms may limit engagement in health-promoting behaviors. Methods Self-reported data from the 2015 Department of Defense Health Related Behaviors Survey were used to assess bi-directional relationships between health-related behaviors (obesity, physical activity [PA], alcohol, smoking, sleep) and self-reported psychological disorders (generalized anxiety disorder [GAD], depression, post-traumatic disorder [PTSD]) in U.S. military personnel. Outcomes Among 12 708 respondents (14.7% female; 28.2% 17-24 y; 13.7% obese), self-reported depression was reported by 9.2%, GAD by 13.9%, and PTSD by 8.2%. Obesity and short sleep were associated with self-reported depression, GAD, and PTSD; current smoking was associated with higher odds of GAD; higher levels of vigorous PA were associated with lower odds of GAD; higher levels of moderate PA associated with lower odds of PTSD; and higher alcohol intake associated with higher odds of depression and PTSD. Self-reported depression, GAD, and PTSD were associated with higher odds of short sleep, obesity, and low levels of PA. Interpretation Obesity, short sleep, and limited engagement in health-promoting behaviors are associated with higher likelihood of self-reported psychological disorders, and vice-versa. Encouraging and improving health-promoting behaviors may contribute to positive mental health in military personnel.

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.

Glycaemic regulation, appetite and ex vivo oxidative stress in young adults following consumption of high-carbohydrate cereal bars fortified with polyphenol-rich berries.

Consumption of certain berries appears to slow postprandial glucose absorption, attributable to polyphenols, which may benefit exercise and cognition, reduce appetite and/or oxidative stress. This randomised, crossover, placebo-controlled study determined whether polyphenol-rich fruits added to carbohydrate-based foods produce a dose-dependent moderation of postprandial glycaemic, glucoregulatory hormone, appetite and ex vivo oxidative stress responses. Twenty participants (eighteen males/two females; 24 (sd 5) years; BMI: 27 (sd 3) kg/m2) consumed one of five cereal bars (approximately 88 % carbohydrate) containing no fruit ingredients (reference), freeze-dried black raspberries (10 or 20 % total weight; LOW-Rasp and HIGH-Rasp, respectively) and cranberry extract (0·5 or 1 % total weight; LOW-Cran and HIGH-Cran), on trials separated by ≥5 d. Postprandial peak/nadir from baseline (Δmax) and incremental postprandial AUC over 60 and 180 min for glucose and other biochemistries were measured to examine the dose-dependent effects. Glucose AUC0-180 min trended towards being higher (43 %) after HIGH-Rasp v. LOW-Rasp (P=0·06), with no glucose differences between the raspberry and reference bars. Relative to reference, HIGH-Rasp resulted in a 17 % lower Δmax insulin, 3 % lower C-peptide (AUC0-60 min and 3 % lower glucose-dependent insulinotropic polypeptide (AUC0-180 min) P<0·05. No treatment effects were observed for the cranberry bars regarding glucose and glucoregulatory hormones, nor were there any treatment effects for either berry type regarding ex vivo oxidation, appetite-mediating hormones or appetite. Fortification with freeze-dried black raspberries (approximately 25 g, containing 1·2 g of polyphenols) seems to slightly improve the glucoregulatory hormone and glycaemic responses to a high-carbohydrate food item in young adults but did not affect appetite or oxidative stress responses at doses or with methods studied herein.

Bone turnover is altered during 72 h of sleep restriction: a controlled laboratory study.

PURPOSE: The objective of the study was to evaluate how controlled, short-term sleep restriction (SR; 72 h) alters markers of bone formation and resorption and urinary calcium (Ca) output. METHODS: Ten healthy, sleep-adequate, male soldiers were housed in the research facility one day prior to and for the duration of SR. Diet was controlled to provide adequate energy balance and macronutrient distribution, meeting the recommended dietary allowance (RDA) for Ca. Subjects engaged in light activities to maintain wakefulness and were allowed 2 h of sleep per night (0430-0630 hours). Blood samples were collected each morning at 0 h (baseline) and 24, 48, and 72 h of SR. Serum was assayed for parathyroid hormone (PTH), bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRAP), and C-terminal telopeptide of type I collagen (CTX). Urine was collected in 24 h increments during SR for measurement of Ca and creatinine (Cr). RESULTS: BAP was reduced at 24 h (P= 0.015) and resorption markers TRAP and CTX were increased after 48 and 72 h of SR compared to baseline (P < 0.05). The ratio of BAP:TRAP was significantly lower (P= 0.017) at 48 and 72 h of SR. In contrast, total 24 h urinary Ca and Ca/Cr excretion were unchanged. CONCLUSIONS: Markers of bone formation and resorption are uncoupled in response to as little as 48 h of SR even when Ca intake is at the RDA. Sleep deprivation may be a risk factor for reduced bone health due to perturbations in bone turnover.

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.

Self-reported health behaviors, including sleep, correlate with doctor-informed medical conditions: data from the 2011 Health Related Behaviors Survey of U.S. Active Duty Military Personnel.

BACKGROUND: Health behaviors and cardiometabolic disease risk factors may differ between military and civilian populations; therefore, in U.S. active duty military personnel, we assessed relationships between demographic characteristics, self-reported health behaviors, and doctor-informed medical conditions. METHODS: Data were self-reported by 27,034 active duty military and Coast Guard personnel who responded to the 2011 Department of Defense Health Related Behaviors Survey. Multivariate linear and logistic regressions were used to estimate cross-sectional associations between (1) demographic characteristics (age, sex, service branch, marital status, children, race/ethnicity, pay grade) and self-reported behaviors (exercise, diet, smoking, alcohol, sleep); (2) demographic characteristics and doctor-informed medical conditions (hypertension, hypercholesterolemia, low high density lipoprotein (HDL) cholesterol, hyperglycemia) and overweight/obesity; and (3) behaviors and doctor-informed medical conditions. RESULTS: Among respondents (age 29.9 ± 0.1 years, 14.7% female), females reported higher intake than men of fruit, vegetables, and dairy; those with higher education reported higher intakes of whole grains; those currently married and/or residing with children reported higher intake of starches. Older age and female sex were associated with higher odds (ORs 1.25 to 12.54 versus the youngest age group) of overweight/obesity. Older age and female sex were also associated with lower odds (ORs 0.29 to 0.65 versus male sex) of doctor-informed medical conditions, except for blood glucose, for which females had higher odds. Those currently married had higher odds of high cholesterol and overweight/obesity, and separated/divorced/widowed respondents had higher odds of high blood pressure and high cholesterol. Short sleep duration (< 5 versus 7-8 h/night) was associated with higher odds (ORs 1.36to 2.22) of any given doctor-informed medical condition. Strength training was associated with lower probability of high cholesterol, high triglycerides, and low HDL, and higher probability of overweight/obesity. Dietary factors were variably associated with doctor-informed medical conditions and overweight/obesity. CONCLUSIONS: This study observed pronounced associations between health behaviors-especially sleep-and medical conditions, thus adding to evidence that sleep is a critical, potentially modifiable behavior within this population. When possible, adequate sleep should continue to be promoted as an important part of overall health and wellness throughout the military community.

Impact of sleep restriction on local immune response and skin barrier restoration with and without "multinutrient" nutrition intervention.

Systemic immune function is impaired by sleep restriction. However, the impact of sleep restriction on local immune responses and to what extent any impairment can be mitigated by nutritional supplementation is unknown. We assessed the effect of 72-h sleep restriction (2-h nightly sleep) on local immune function and skin barrier restoration of an experimental wound, and determined the influence of habitual protein intake (1.5 g·kg-1·day-1) supplemented with arginine, glutamine, zinc sulfate, vitamin C, vitamin D3, and omega-3 fatty acids compared with lower protein intake (0.8 g·kg-1·day-1) without supplemental nutrients on these outcomes. Wounds were created in healthy adults by removing the top layer of less than or equal to eight forearm blisters induced via suction, after adequate sleep (AS) or 48 h of a 72-h sleep restriction period (SR; 2-h nightly sleep). A subset of participants undergoing sleep restriction received supplemental nutrients during and after sleep restriction (SR+). Wound fluid was serially sampled 48 h postblistering to assess local cytokine responses. The IL-8 response of wound fluid was higher for AS compared with SR [area-under-the-curve (log10), 5.1 ± 0.2 and 4.9 ± 0.2 pg/ml, respectively; P = 0.03]; and both IL-6 and IL-8 concentrations were higher for SR+ compared with SR ( P < 0.0001), suggestive of a potentially enhanced early wound healing response. Skin barrier recovery was shorter for AS (4.2 ± 0.9 days) compared with SR (5.0 ± 0.9 days) ( P = 0.02) but did not differ between SR and SR+ ( P = 0.18). Relatively modest sleep disruption delays wound healing. Supplemental nutrition may mitigate some decrements in local immune responses, without detectable effects on wound healing rate. NEW & NOTEWORTHY The data herein characterizes immune function in response to sleep restriction in healthy volunteers with and without nutrition supplementation. We used a unique skin wound model to show that sleep restriction delays skin barrier recovery, and nutrition supplementation attenuates decrements in local immune responses produced by sleep restriction. These findings support the beneficial effects of adequate sleep on immune function. Additional studies are necessary to characterize practical implications for populations where sleep restriction is unavoidable.

Body Mass Index at Accession and Incident Cardiometabolic Risk Factors in US Army Soldiers, 2001-2011.

Individuals entering US Army service are generally young and healthy, but many are overweight, which may impact cardiometabolic risk despite physical activity and fitness requirements. This analysis examines the association between Soldiers' BMI at accession and incident cardiometabolic risk factors (CRF) using longitudinal data from 731,014 Soldiers (17.0% female; age: 21.6 [3.9] years; BMI: 24.7 [3.8] kg/m2) who were assessed at Army accession, 2001-2011. CRF were defined as incident diagnoses through 2011, by ICD-9 code, of metabolic syndrome, glucose/insulin disorder, hypertension, dyslipidemia, or overweight/obesity (in those not initially overweight/obese). Multivariable-adjusted proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) between BMI categories at accession and CRF. Initially underweight (BMI<18.5 kg/m2) were 2.4% of Soldiers, 53.5% were normal weight (18.5-<25), 34.2% were overweight (25-<30), and 10.0% were obese (≥30). Mean age range at CRF diagnosis was 24-29 years old, with generally low CRF incidence: 228 with metabolic syndrome, 3,880 with a glucose/insulin disorder, 26,373 with hypertension, and 13,404 with dyslipidemia. Of the Soldiers who were not overweight or obese at accession, 5,361 were eventually diagnosed as overweight or obese. Relative to Soldiers who were normal weight at accession, those who were overweight or obese, respectively, had significantly higher risk of developing each CRF after multivariable adjustment (HR [95% CI]: metabolic syndrome: 4.13 [2.87-5.94], 13.36 [9.00-19.83]; glucose/insulin disorder: 1.39 [1.30-1.50], 2.76 [2.52-3.04]; hypertension: 1.85 [1.80-1.90], 3.31 [3.20-3.42]; dyslipidemia: 1.81 [1.75-1.89], 3.19 [3.04-3.35]). Risk of hypertension, dyslipidemia, and overweight/obesity in initially underweight Soldiers was 40%, 31%, and 79% lower, respectively, versus normal-weight Soldiers. BMI in early adulthood has important implications for cardiometabolic health, even within young, physically active populations.

Two Days of Calorie Deprivation Induced by Underfeeding and Aerobic Exercise Degrades Mood and Lowers Interstitial Glucose but Does Not Impair Cognitive Function in Young Adults.

BACKGROUND: In studies assessing the effects of acute undernutrition on cognitive function, volunteers are sedentary and findings are equivocal, even though glucose concentrations fall substantially. However, military personnel and endurance athletes often are underfed when physical demands, and consequently energy expenditure, are substantial. OBJECTIVE: The objective of this study was to determine whether 2 d of near-total calorie deprivation combined with aerobic exercise degraded cognitive performance and mood. METHODS: A double-blind, placebo-controlled, crossover design was used. Twenty-three volunteers [17 men (mean ± SD age: 20.5 ± 0.7 y) and 6 women (mean ± SD age: 23.3 ± 1.4 y); mean ± SD body mass index (in kg/m2): 25 ± 3] participated for 68 h, including a 51-h inpatient phase in a calorie-deprived or fully fed state during which behavioral testing was conducted and interstitial glucose was monitored continuously. Mood and cognitive performance, including psychomotor and visual vigilance, visual match-to-sample, repeated acquisition (motor learning), N-back (working memory), and grammatical reasoning, were repeatedly assessed. During each condition, individual daily energy intake and expenditure were controlled. During calorie deprivation, volunteers consumed 266 ± 61 kcal/d; during full feeding, they consumed 3935 ± 769 kcal/d. Participants engaged in identical exercise sessions for 4 h/d at 40-65% of peak volume of oxygen uptake attained. RESULTS: Calorie deprivation did not affect any aspect of cognitive performance, but produced robust effects on mood measured by the Profile of Mood States, including increased tension (P < 0.001), fatigue (P < 0.001), and total mood disturbance (from -0.80 ± 5.1 to 20.1 ± 6.1; P < 0.001), and decreased vigor (P = 0.002), as indicated by treatment × trial (time) effects on ANOVA. Interstitial glucose concentrations were lower during calorie deprivation than in the fully fed condition (P = 0.002, treatment × trial interaction) and declined to 61 mg/dL by the end of the treatment condition. CONCLUSION: In healthy young men and women, 2 d of severe calorie deprivation in combination with substantial aerobic exercise adversely affects multiple aspects of mood, but not cognition, in spite of substantial reductions in interstitial glucose concentrations. This trial was registered at clinicaltrials.gov as NCT01603550.

Interstitial glucose concentrations and hypoglycemia during 2 days of caloric deficit and sustained exercise: a double-blind, placebo-controlled trial.

Military personnel and some athlete populations endure short-term energy deficits from reduced energy intake and/or increased energy expenditure (EE) that may degrade physical and cognitive performance due to severe hypoglycemia (<3.1 mmol/l). The extent to which energy deficits alter normoglycemia (3.9-7.8 mmol/l) in healthy individuals is not known, since prior studies measured glucose infrequently, not continuously. The purpose of this study was to characterize the glycemic response to acute, severe energy deficit compared with fully fed control condition, using continuous glucose monitoring (CGM). For 2 days during a double-blind, placebo-controlled, crossover study, 23 volunteers (17 men/6 women; age: 21.3 ± 3.0 yr; body mass index: 25 ± 3 kg/m) increased habitual daily EE [2,300 ± 450 kcal/day [means ± SD)] by 1,647 ± 345 kcal/day through prescribed exercise (~3 h/day; 40-65% peak O2 consumption), and consumed diets designed to maintain energy balance (FED) or induce 93% energy deficit (DEF). Interstitial glucose concentrations were measured continuously by CGM (Medtronic Minimed). Interstitial glucose concentrations were 1.0 ± 0.9 mmol/l lower during DEF vs. FED (P < 0.0001). The percentage of time spent in mild (3.1-3.8 mmol/l) hypoglycemia was higher during DEF compared with FED [mean difference = 20.5%; 95% confidence interval (CI): 13.1%, 27.9%; P = 0.04], while time spent in severe (<3.1 mmol/l) hypoglycemia was not different between interventions (mean difference = 4.6%; 95% CI: -0.6%, 9.8%; P = 0.10). Three of 23 participants spontaneously reported symptoms (e.g., nausea) potentially related to hypoglycemia during DEF, and an additional participant reported symptoms during both interventions. These findings suggest that severe hypoglycemia rarely occurs in healthy individuals enduring severe, short-term energy deficit secondary to heavy exercise and inadequate energy intake.

Altered metabolic homeostasis is associated with appetite regulation during and following 48-h of severe energy deprivation in adults.

BACKGROUND: Military personnel frequently endure intermittent periods of severe energy deficit which can compromise health and performance. Physiologic factors contributing to underconsumption, and the subsequent drive to overeat, are not fully characterized. This study aimed to identify associations between appetite, metabolic homeostasis and endocrine responses during and following severe, short-term energy deprivation. METHODS: Twenty-three young adults (17M/6F, 21±3years, BMI 25±3kg/m(2)) participated in a randomized, controlled, crossover trial. During separate 48-h periods, participants increased habitual energy expenditure by 1647±345kcal/d (mean±SD) through prescribed exercise at 40-65% VO2peak, and consumed provided isovolumetric diets designed to maintain energy balance at the elevated energy expenditure (EB; 36±93kcal/d energy deficit) or to produce a severe energy deficit (ED; 3681±716kcal/d energy deficit). Appetite, markers of metabolic homeostasis and endocrine mediators of appetite and substrate availability were periodically measured. Ad libitum energy intake was measured over 36h following both experimental periods. RESULTS: Appetite increased during ED and was greater than during EB despite maintenance of diet volume (P=0.004). Ad libitum energy intake was 907kcal/36h [95% CI: 321, 1493kcal/36h, P=0.004] higher following ED compared to following EB. Serum beta-hydroxybutyrate, free fatty acids, branched-chain amino acids, dehydroepiandrosterone-sulfate (DHEA-S) and cortisol concentrations were higher (P<0.001 for all), whereas whole-body protein balance was more negative (P<0.001), and serum glucose, insulin, and leptin concentrations were lower (P<0.001 for all) during ED relative to during EB. Cortisol concentrations, but not any other hormone or metabolic substrate, were inversely associated with satiety during EB (R(2)=0.23, P=0.04). In contrast, serum glucose and DHEA-S concentrations were inversely associated with satiety during ED (R(2)=0.68, P<0.001). No associations between physiologic variables measured during EB and ad libitum energy intake following EB were observed. However, serum leptin and net protein balance measured during ED were inversely associated with ad libitum energy intake following ED (R(2)=0.48, P=0.01). CONCLUSION: These findings suggest that changes in metabolic homeostasis during energy deprivation modulate appetite independent of reductions in diet volume. Following energy deprivation, physiologic signals of adipose and lean tissue loss may drive restoration of energy balance. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov #NCT01603550.

Altered Appetite-Mediating Hormone Concentrations Precede Compensatory Overeating After Severe, Short-Term Energy Deprivation in Healthy Adults.

BACKGROUND: Adaptive responses of appetite-mediating hormones to negative energy balance are thought to contribute to a counterregulatory response that drives weight regain, but they have not been studied while controlling for reduced diet volume. OBJECTIVE: In this secondary analysis, we aimed to determine the effects of short-term, severe energy deprivation (ED) on appetite and appetite-mediating hormone concentrations. METHODS: Twenty-one adults with a mean ± SD age of 21 ± 3 y and body mass index of 25 ± 3 kg/m(2) consumed isovolumetric diets provided over separate 48-h periods while increasing habitual energy expenditure by 1683 ± 329 kcal/d through light- and moderate-intensity exercise. Energy intake was matched to energy expenditure to maintain energy balance (EB) (-44 ± 92 kcal/d) or was <10% of energy expenditure to generate a -3696 ± 742-kcal/d energy deficit. Postprandial appetite, glucose, insulin, acyl ghrelin, peptide YY, pancreatic polypeptide (PP), and glucagon-like peptide-1 (GLP-1) responses and ad libitum energy intake were measured as secondary outcomes after both experimental periods. RESULTS: Fasting insulin (-56% ± 42%) and acyl ghrelin (-60% ± 17%) concentrations decreased during ED but not during EB (condition-by-time interaction; P-interaction ≤ 0.01), whereas fasting leptin concentrations decreased more during ED compared with during EB (-47% ± 27% compared with -20% ± 27%; P-interaction = 0.05). Postprandial insulin (57% ± 63%; P < 0.001), GLP-1 (14% ± 28%; P = 0.04), and PP (54% ± 52%; P < 0.001) areas under the curve (AUCs) were higher, whereas the acyl ghrelin AUC was lower (-56% ± 13%; P < 0.001) after ED compared with after EB. After ED, self-rated appetite was greater, and ad libitum energy intake was 811 kcal/36 h (95% CI: 184, 1439 kcal/36 h) higher relative to after EB (P = 0.01). CONCLUSIONS: Short-term, severe ED suppressed acyl ghrelin concentrations and increased postprandial anorexigenic hormone concentrations. These effects preceded compensatory overeating, suggesting that in adults without obesity, altered sensitivity to appetite-mediating hormones may contribute to an adaptive counterregulatory response during the initial stages of negative EB. This trial was registered at clinicaltrials.gov as NCT01603550.