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Background: Doubly labeled water is gold standard for measuring total energy expenditure (TEE). Measurements using the method are sensitive to the isotope dilution space ratio (DSR). Accuracy and precision of the method might be improved if we could identify factors influencing DSR., Objectives: We evaluated the potential associations of age, sex, ethnicity, anthropometry, body composition, turnover rates of the isotopes, and geographical elevation with DSR., Methods: We used univariate regression analysis to explore the relationships between the continuous variables and analysis of variance to test the relationships between the categorical variables with DSR. Subsequently, we used general linear model (GLM) and 1-way analysis of variance to evaluate the simultaneous associations of age, sex, ethnicity, fat-free mass (FFM) and fat mass (FM) on DSR., Results: From 5678 measurements complied from studies around the world with diverse ethnicity and living at various elevations, the mean DSR was 1.0364 ± 0.0141. No meaningful physiologic effect of any of the continuous and categorical variable on DSR was detected. General linear model analysis revealed no effect of FFM and FM (P > 0.33) on DSR, but DSR decreased with age (P < 0.001) among those aged 60 y and older regardless of sex. Among the Whites who were younger than 60 y, DSR was not related to FFM and FM (P = 0.73) but was affected by both age and sex (P < 0.001)., Conclusions: Previous estimates of age-related decline in TEE may have overestimated TEE at age 90 y. Validation studies on older participants are required to confirm this finding., Competing Interests: Conflict of interest WWW reports administrative support was provided by Baylor College of Medicine. JRS reports administrative support and article publishing charges were provided by University of Aberdeen. MLN is a Deputy Editor of the Journal of Nutrition but played no role in the Journal’s evaluation of the manuscript. The other authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

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

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

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.

Introduction/purpose: The effects of testosterone on energy and substrate metabolism during energy deficit are unknown. The objective of this study was to determine the effects of weekly testosterone enanthate (TEST; 200 mg·wk -1 ) injections on energy expenditure, energy substrate oxidation, and related gene expression during 28 d of energy deficit compared with placebo (PLA)., Methods: After a 14-d energy balance phase, healthy men were randomly assigned to TEST ( n = 24) or PLA ( n = 26) for a 28-d controlled diet- and exercise-induced energy deficit (55% below total energy needs by reducing energy intake and increasing physical activity). Whole-room indirect calorimetry and 24-h urine collections were used to measure energy expenditure and energy substrate oxidation during balance and deficit. Transcriptional regulation of energy and substrate metabolism was assessed using quantitative reverse transcription-polymerase chain reaction from rested/fasted muscle biopsy samples collected during balance and deficit., Results: Per protocol design, 24-h energy expenditure increased ( P < 0.05) and energy intake decreased ( P < 0.05) in TEST and PLA during deficit compared with balance. Carbohydrate oxidation decreased ( P < 0.05), whereas protein and fat oxidation increased ( P < 0.05) in TEST and PLA during deficit compared with balance. Change (∆; deficit minus balance) in 24-h energy expenditure was associated with ∆activity factor ( r = 0.595), but not ∆fat-free mass ( r = 0.147). Energy sensing (PRKAB1 and TP53), mitochondria (TFAM and COXIV), fatty acid metabolism (CD36/FAT, FABP, CPT1b, and ACOX1) and storage (FASN), and amino acid metabolism (BCAT2 and BCKHDA) genes were increased ( P < 0.05) during deficit compared with balance, independent of treatment., Conclusions: These data demonstrate that increased physical activity and not exogenous testosterone administration is the primary determinate of whole-body and skeletal muscle metabolic adaptations during diet- and exercise-induced energy deficit., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Physical performance decrements observed during multi-stressor military operations may be attributed, in part, to cellular membrane dysfunction, which is quantifiable using phase angle (PhA) derived from bioelectrical impedance analysis (BIA). Positive relationships between PhA and performance have been previously reported in cross-sectional studies and following longitudinal exercise training programs, but whether changes in PhA are indicative of acute decrements in performance during military operations is unknown. Data from the Optimizing Performance for Soldiers II study, a clinical trial examining the effects of exogenous testosterone administration on body composition and performance during military stress, was used to evaluate changes in PhA and their associations with physical performance. Recreationally active, healthy males (n = 34; 26.6 ± 4.3 years; 77.9 ± 12.4 kg) were randomized to receive testosterone undecanoate or placebo before a 20-day simulated military operation, which was followed by a 23-day recovery period. PhA of the whole-body (Whole) and legs (Legs) and physical performance were measured before (PRE) and after (POST) the simulated military operation as well as in recovery (REC). Independent of treatment, PhA Whole and PhA Legs decreased from PRE to POST (p < 0.001), and PhA Legs , but not PhA Whole , remained lower at REC than PRE. PhA Whole at PRE and REC were associated with vertical jump height and Wingate peak power (p < 0.001-0.050), and PhA Whole at PRE was also associated with 3-RM deadlift mass (p = 0.006). However, PhA at POST and changes in PhA from PRE to POST were not correlated with any performance measure (p > 0.05). Additionally, PhA was not associated with aerobic performance at any timepoint. In conclusion, reduced PhA from PRE to POST provides indirect evidence of cellular membrane disruption. Associations between PhA and strength and power were only evident at PRE and REC, suggesting PhA may be a useful indicator of strength and power, but not aerobic capacity, in non-stressed conditions, and not a reliable indicator of physical performance during severe physiological stress., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

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

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

Background: Food processing alters diet digestibility and composition, thereby influencing interactions between host biology, diet, and the gut microbiota. The fecal metabolome offers insight into those relations by providing a readout of diet-microbiota interactions impacting host health., Objectives: The aims were to determine the effects of consuming a processed diet on the fecal metabolome and to explore relations between changes in the fecal metabolome with fecal microbiota composition and gastrointestinal health markers., Methods: This was a secondary analysis of a randomized controlled trial wherein healthy adults [94% male; 18-61 y; BMI (kg/m 2 ): 26 ± 3] consumed their usual diet [control (CON), n = 27] or a Meal, Ready-to-Eat TM (Ameriqual Packaging) military ration diet composed of processed, shelf-stable, ready-to-eat items for 21 d (MRE; n = 27). Fecal metabolite profiles, fecal microbiota composition, biomarkers of intestinal barrier function, and gastrointestinal symptoms were measured before and after the intervention. Between-group differences and associations were assessed using nonparametric t tests, partial least-squares discriminant analysis, correlation, and redundancy analysis., Results: Fecal concentrations of multiple dipeptides [Mann-Whitney effect size (ES) = 0.27-0.50] and long-chain SFAs (ES = 0.35-0.58) increased, whereas plant-derived compounds (ES = 0.31-0.60) decreased in MRE versus CON (P < 0.05; q < 0.20). Changes in dipeptides correlated positively with changes in fecal concentrations of Maillard-reaction products (ρ = 0.29-0.70; P < 0.05) and inversely with changes in serum prealbumin (ρ = -0.30 to -0.48; P ≤ 0.03). Multiple bile acids, coffee and caffeine metabolites, and plant-derived compounds were associated with both fecal microbiota composition and gastrointestinal health markers, with changes in fecal microbiota composition explaining 26% of the variability within changes in gastrointestinal health-associated fecal metabolites (P = 0.001)., Conclusions: Changes in the fecal metabolomes of adults consuming a Meal, Ready-to-Eat TM diet implicate interactions between diet composition, diet digestibility, and the gut microbiota as contributing to variability within gastrointestinal responses to the diet. Findings underscore the need to consider both food processing and nutrient composition when investigating the impact of diet-gut microbiota interactions on health outcomes. This trial was registered at www., Clinicaltrials: gov as NCT02423551., (Copyright © 2022 American Society for Nutrition.)

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

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

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

Aims: To examine whether changes in objectively measured physical activity (PA) are associated with weight loss and changes in body composition and fat distribution in response to weight-loss diet interventions., Methods: This study included 535 participants with overweight/ obesity, who were randomly assigned to four weight-loss diets varying in macronutrients. PA was measured objectively with pedometers, and body composition and fat distribution were measured using dual-energy X-ray absorptiometry and computed tomography scans at baseline, 6 months and 24 months., Results: From baseline to 6 months, when the maximum weight loss was achieved, each 1000-steps/d increment in PA was associated with a greater reduction in body weight (β[SE] = -0.48[0.11]) and waist circumference (β[SE] = -0.49[0.12]). Similar inverse associations were found in changes in body composition and fat distribution (P < 0.05 and false discovery rate qvalue < 0.1 for all). The trajectory of the above adiposity measures across the 24-month intervention period differed between the patterns of PA change. Participants with the largest increase in PA maintained their weight loss from 6 months to 24 months, while those with a smaller increase in PA regained their weight. In addition, dietary fat or protein intake significantly modified the associations between changes in PA and changes in body weight and waist circumference over 24 months (P ∆PA*diet  < 0.05)., Conclusions: Changes in objectively measured PA were inversely related to changes in body weight, body composition and fat distribution in response to weight-loss diets, and such associations were more evident in people on a high-fat or average-protein diet compared with a low-fat or high-protein diet., (© 2022 John Wiley & Sons Ltd.)

A successful randomized clinical trial of the effect of dietary supplements on a chosen endpoint begins with developing supporting data in preclinical studies while paying attention to easily overlooked details when planning the related clinical trial. In this perspective, we draw on our experience studying the effect of an ethanolic extract from Artemisia dracunculus L. (termed PMI-5011) on glucose homeostasis as a potential therapeutic option in providing resilience to metabolic syndrome (MetS). Decisions on experimental design related to issues ranging from choice of mouse model to dosing levels and route of administration in the preclinical studies will be discussed in terms of translation to the eventual human studies. The more complex considerations in planning the clinical studies present different challenges as these studies progress from testing the safety of the dietary supplement to assessing the effect of the dietary supplement on a predetermined clinical outcome. From the vantage point of hindsight, we will outline potential pitfalls when translating preclinical studies to clinical studies and point out details to address when designing clinical studies of dietary supplements., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Floyd, Ribnicky, Raskin, Hsia, Rood and Gurley.)

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

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

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.

Rating of perceived exertion (RPE) and respiratory exchange ratio (RER) have previously been associated with acute exercise compensation. This study examined adaptations in the RPE and RER with long-term exercise training in individuals who did (noncompensators) and did not (compensators) lose the expected amount of weight. Participants ( n = 110, 71.8% women, means ± SD; age 49 ± 12 yr) completed 24 wk of supervised exercise training at 65-85% V̇o 2peak to achieve a prescribed dose of 8 kcal·kg body wt -1 ·wk -1 (8 KKW) or 20 KKW. Participants were categorized as noncompensators ( n = 55) or compensators ( n = 55) based on the percent of expected weight loss (%EWL) achieved. Changes in RPE and RER during exercise over time (baseline, week 12 , week 24 ) were compared by weight compensation category. Individual %EWL in relation to RPE, RER, and training intensity (%V̇o 2peak ) was evaluated over the same time period. RPE and RER for a given workload decreased from baseline to week 12 and stabilized through week 24 , regardless of weight compensation (time P < 0.0001). Noncompensators had a higher RPE relative to heart rate, which was partly explained by higher %V̇o 2peak . RPE and %V̇o 2peak both positively predicted %EWL, independent of age, sex, and exercise dose. Training intensity and RPE were positively associated with weight loss on the individual level, warranting further investigation into self-selection in exercise-based programs. Understanding individual heterogeneity in training intensity and behavioral responses may improve future weight management efforts that involve exercise. NEW & NOTEWORTHY In sedentary individuals with overweight and obesity, achievement of expected weight loss from long-term exercise training was associated with individual adaptations in perceived exertion. Contrary to our hypothesis, those with higher relative perceived exertion achieved a larger proportion of their expected weight loss, which was partly explained by a higher self-selected exercise training intensity.

Context: Severe energy deprivation markedly inhibits erythropoiesis by restricting iron availability for hemoglobin synthesis., Objective: The objective of this study was to determine whether testosterone supplementation during energy deficit increased indicators of iron turnover and attenuated the decline in erythropoiesis compared to placebo., Design: This was a 3-phase, randomized, double-blind, placebo-controlled trial., Setting: The study was conducted at the Pennington Biomedical Research Center., Patients or Other Participants: Fifty healthy young males., Intervention(s): Phase 1 was a 14-day free-living eucaloric controlled-feeding phase; phase 2 was a 28-day inpatient phase where participants were randomized to 200 mg testosterone enanthate/week or an isovolumetric placebo/week during an energy deficit of 55% of total daily energy expenditure; phase 3 was a 14-day free-living, ad libitum recovery period., Main Outcome Measure(s): Indices of erythropoiesis, iron status, and hepcidin and erythroferrone were determined., Results: Hepcidin declined by 41%, indicators of iron turnover increased, and functional iron stores were reduced with testosterone administration during energy deficit compared to placebo. Testosterone administration during energy deficit increased circulating concentrations of erythropoietin and maintained erythropoiesis, as indicated by an attenuation in the decline in hemoglobin and hematocrit with placebo. Erythroferrone did not differ between groups, suggesting that the reduction in hepcidin with testosterone occurs through an erythroferrone-independent mechanism., Conclusion: These findings indicate that testosterone suppresses hepcidin, through either direct or indirect mechanisms, to increase iron turnover and maintain erythropoiesis during severe energy deficit. This trial was registered at www.clinicaltrials.gov as #NCT02734238., (Published by Oxford University Press on behalf of the Endocrine Society 2020.)

Background: Severe energy deficits cause interrelated reductions in testosterone and fat free mass. Testosterone supplementation may mitigate those decrements, but could also reduce circulating concentrations of the orexigenic hormone ghrelin, thereby exacerbating energy deficit by suppressing appetite., Objective: To determine whether testosterone supplementation during severe energy deficit influences fasting and postprandial ghrelin concentrations and appetite., Design and Methods: Secondary analysis of a randomized, double-blind trial that determined the effects of testosterone supplementation on body composition changes during and following severe energy deficit in nonobese, eugonadal men. Phase 1 (PRE-ED): 14-day run-in; phase 2: 28 days, 55% energy deficit with 200 mg testosterone enanthate weekly (TEST; n = 24) or placebo (PLA; n = 26); phase 3: free-living until body mass recovered (end-of-study; EOS). Fasting and postprandial acyl ghrelin and des-acyl ghrelin concentrations and appetite were secondary outcomes measured during the final week of each phase., Results: Fasting acyl ghrelin concentrations, and postprandial acyl and des-acyl ghrelin concentrations increased in PLA during energy deficit then returned to PRE-ED values by EOS, but did not change in TEST (phase-by-group, P  < 0.05). Correlations between changes in free testosterone and changes in fasting acyl ghrelin concentrations during energy deficit (ρ = -0.42, P  = 0.003) and body mass recovery (ρ = -0.38; P  = 0.01) were not mediated by changes in body mass or body composition. Transient increases in appetite during energy deficit were not affected by testosterone treatment., Conclusions: Testosterone supplementation during short-term, severe energy deficit in healthy men prevents deficit-induced increases in circulating ghrelin without blunting concomitant increases in appetite., Clinical Trials Registration: www.clinicaltrials.gov NCT02734238 (registered 12 April 2016)., (Published by Oxford University Press on behalf of the Endocrine Society 2020.)

Interactions between gut microbes and dietary components modulate intestinal permeability (IP) and inflammation. Recent studies have reported altered fecal microbiota composition together with increased IP and inflammation in individuals consuming military food rations in austere environments, but could not isolate effects of the diet from environmental factors. To determine how the U.S. Meal, Ready-to-Eat food ration affects fecal microbiota composition, IP and inflammation, 60 adults (95% male,18-61 years) were randomized to consume their usual ad libitum diet for 31 days (CON) or a strictly controlled Meal, Ready-to-Eat-only diet for 21 days followed by their usual diet for 10 days (MRE). In both groups, fecal microbiota composition was measured before, during (INT, days 1-21) and after the intervention period. IP and inflammation [high-sensitivity C-reactive protein (hsCRP)] were measured on days 0, 10, 21 and 31. Longitudinal changes in fecal microbiota composition differed between groups (P=.005), and fecal samples collected from MRE during INT were identified with 88% accuracy using random forest models. The genera making the strongest contribution to that prediction accuracy included multiple lactic acid bacteria (Lactobacillus, Lactococcus, Leuconostoc), which demonstrated lower relative abundance in MRE, and several genera known to dominate the ileal microbiota (Streptococcus, Veillonella, Clostridium), the latter two demonstrating higher relative abundance in MRE. IP and hsCRP were both lower (34% and 41%, respectively) in MRE relative to CON on day 21 (P<.05) but did not differ otherwise. Findings demonstrate that a Meal, Ready-to-Eat ration diet alters fecal microbiota composition and does not increase IP or inflammation., (Published by Elsevier Inc.)

Background: Exercise is recommended for weight management, yet exercise produces less weight loss than expected, which is called weight compensation. The mechanisms for weight compensation are unclear., Objective: The aim of this study was to identify the mechanisms responsible for compensation., Methods: In a randomized controlled trial conducted at an academic research center, adults (n = 198) with overweight or obesity were randomized for 24 wk to a no-exercise control group or 1 of 2 supervised exercise groups: 8 kcal/kg of body weight/wk (KKW) or 20 KKW. Outcome assessment occurred at weeks 0 and 24. Energy intake, activity, and resting metabolic rate (RMR) were measured with doubly labeled water (DLW; with and without adjustments for change in RMR), armband accelerometers, and indirect calorimetry, respectively. Appetite and compensatory health beliefs were measured by self-report., Results: A per-protocol analysis included 171 participants (72.5% women; mean ± SD baseline body mass index: 31.5 ± 4.7 kg/m2). Significant (P < 0.01) compensation occurred in the 8 KKW (mean: 1.5 kg; 95% CI: 0.9, 2.2 kg) and 20 KKW (mean: 2.7 kg; 95% CI: 2.0, 3.5 kg) groups, and compensation differed significantly between the exercise groups (P = 0.01). Energy intake by adjusted DLW increased significantly (P < 0.05) in the 8 KKW (mean: 90.7 kcal/d; 95% CI: 35.1, 146.4 kcal/d) and 20 KKW (mean: 123.6 kcal/d; 95% CI: 64.5, 182.7 kcal/d) groups compared with control (mean: -2.3 kcal/d; 95% CI: -58.0, 53.5 kcal/d). Results were similar without DLW adjustment. RMR and physical activity (excluding structured exercise) did not differentially change among the 3 groups. Participants with higher compared with lower compensation reported increased appetite ratings and beliefs that healthy behaviors can compensate for unhealthy behaviors. Furthermore, they increased craving for sweet foods, increased sleep disturbance, and had worsening bodily pain., Conclusions: Compensation resulted from increased energy intake and concomitant increases in appetite, which can be treated with dietary or pharmacological interventions. Compensation was not due to activity or metabolic changes. This trial was registered at clinicaltrials.gov as NCT01264406., (Copyright © American Society for Nutrition 2019.)

Background: Severe energy deficits during military operations, produced by significant increases in exercise and limited dietary intake, result in conditions that degrade lean body mass and lower-body muscle function, which may be mediated by concomitant reductions in circulating testosterone., Methods: We conducted a three-phase, proof-of-concept, single centre, randomised, double-blind, placebo-controlled trial (CinicalTrials.gov, NCT02734238) of non-obese men: 14-d run-in, free-living, eucaloric diet phase; 28-d live-in, 55% exercise- and diet-induced energy deficit phase with (200 mg testosterone enanthate per week, Testosterone, n = 24) or without (Placebo, n = 26) exogenous testosterone; and 14-d recovery, free-living, ad libitum diet phase. Body composition was the primary end point; secondary endpoints included lower-body muscle function and health-related biomarkers., Findings: Following energy deficit, lean body mass increased in Testosterone and remained stable in Placebo, such that lean body mass significantly differed between groups [mean difference between groups (95% CI), 2.5 kg (3.3, 1.6); P < .0001]. Fat mass decreased similarly in both treatment groups [0.2 (-0.4, 0.7), P = 1]. Change in lean body mass was associated with change in total testosterone (r = 0.71, P < .0001). Supplemental testosterone had no effect on lower-body muscle function or health-related biomarkers., Interpretation: Findings suggest that supplemental testosterone may increase lean body mass during short-term severe energy deficit in non-obese, young men, but it does not appear to attenuate lower-body functional decline., Funding: Collaborative Research to Optimize Warfighter Nutrition projects I and II, Joint Program Committee-5, funded by the US Department of Defence., (Copyright © 2019. Published by Elsevier B.V.)

Hypobaric hypoxia and dietary protein and fat intakes have been independently associated with an altered gastrointestinal (GI) environment and gut microbiota, but little is known regarding host-gut microbiota interactions at high altitude (HA) and the impact of diet macronutrient composition. This study aimed to determine the effect of dietary protein:fat ratio manipulation on the gut microbiota and GI barrier function during weight loss at high altitude (HA) and to identify associations between the gut microbiota and host responses to HA. Following sea-level (SL) testing, 17 healthy males were transported to HA (4,300 m) and randomly assigned to consume provided standard protein (SP; 1.1 g·kg -1 ·day -1 , 39% fat) or higher protein (HP; 2.1 g·kg -1 ·day -1 , 23% fat) carbohydrate-matched hypocaloric diets for 22 days. Fecal microbiota composition and metabolites, GI barrier function, GI symptoms, and acute mountain sickness (AMS) severity were measured. Macronutrient intake did not impact fecal microbiota composition, had only transient effects on microbiota metabolites, and had no effect on increases in small intestinal permeability, GI symptoms, and inflammation observed at HA. AMS severity was also unaffected by diet but in exploratory analyses was associated with higher SL-relative abundance of Prevotella, a known driver of interindividual variability in human gut microbiota composition, and greater microbiota diversity after AMS onset. Findings suggest that the gut microbiota may contribute to variability in host responses to HA independent of the dietary protein:fat ratio but should be considered preliminary and hypothesis generating due to the small sample size and exploratory nature of analyses associating the fecal microbiota and host responses to HA. NEW & NOTEWORTHY This study is the first to examine interactions among diet, the gut microbiota, and host responses to weight loss at high altitude (HA). Observed associations among the gut microbiota, weight loss at HA, and acute mountain sickness provide evidence that the microbiota may contribute to variability in host responses to HA. In contrast, dietary protein:fat ratio had only minimal, transient effects on gut microbiota composition and bacterial metabolites which were likely not of clinical consequence.

Background: Young adulthood is a critical period for excessive weight gain. The extent to which young adults' sedentary time (ST) and moderate-to-vigorous physical activity (MVPA) relate to adiposity and weight gain remains unclear., Objective: The purpose of this study was to examine the relation of ST and MVPA with adiposity and change in adiposity in healthy, nonobese young adults over a 2-y period., Design: Participants were 71 adults aged 20-35 y. Measurements included ST and MVPA by accelerometry and reported energy intake at baseline, and anthropometry (%FM) and fat mass (FM) by dual-energy X-ray absorptiometry at baseline, year 1, and year 2. Associations of baseline ST and MVPA with adiposity were examined with the use of repeated-measures linear regression models, controlling for age, sex, and reported energy intake. The Benjamini-Hochberg procedure was used to adjust for multiple comparisons., Results: Participants [mean ± SD body mass index (BMI; kg/m2): 22.6 ± 2.4] engaged in 8.5 ± 1.5 h ST/d and 0.4 ± 0.3 h MVPA/d. At baseline, adults who engaged in ST for ≥8 h/d had higher FM, %FM, and lower MVPA, whereas those who engaged in MVPA for ≥30 min/d had lower FM and %FM. In fully adjusted models, ST was significantly associated with baseline body weight, hip circumference, BMI, FM, and %FM and with year-1 body weight, waist and hip circumference, FM, and %FM, but not with any year-2 adiposity indicators. MVPA was not significantly associated with any adiposity indicators at baseline, year 1, or year 2 in fully adjusted models. Over 2 y, participants significantly increased waist circumference, BMI, FM, and %FM (all P-values <0.05), but there were no associations among baseline ST and MVPA with change in adiposity., Conclusions: Among nonobese young adults, high ST and low MVPA were related to elevated adiposity but did not predict change in adiposity over time. This trial was registered at clinicaltrials.gov as NCT00945633.

This study investigated how high-altitude (HA, 4300 m) acclimatization affected exogenous glucose oxidation during aerobic exercise. Sea-level (SL) residents ( n = 14 men) performed 80-min, metabolically matched exercise ( V ˙ O 2 ∼ 1.7 L/min) at SL and at HA < 5 h after arrival (acute HA, AHA) and following 22-d of HA acclimatization (chronic HA, CHA). During HA acclimatization, participants sustained a controlled negative energy balance (-40%) to simulate the "real world" conditions that lowlanders typically experience during HA sojourns. During exercise, participants consumed carbohydrate (CHO, n = 8, 65.25 g fructose + 79.75 g glucose, 1.8 g carbohydrate/min) or placebo (PLA, n = 6). Total carbohydrate oxidation was determined by indirect calorimetry and exogenous glucose oxidation by tracer technique with 13 C. Participants lost ( P ≤ 0.05, mean ± SD) 7.9 ± 1.9 kg body mass during the HA acclimatization and energy deficit period. In CHO, total exogenous glucose oxidized during the final 40 min of exercise was lower ( P < 0.01) at AHA (7.4 ± 3.7 g) than SL (15.3 ± 2.2 g) and CHA (12.4 ± 2.3 g), but there were no differences between SL and CHA. Blood glucose and insulin increased ( P ≤ 0.05) during the first 20 min of exercise in CHO, but not PLA. In CHO, glucose declined to pre-exercise concentrations as exercise continued at SL, but remained elevated ( P ≤ 0.05) throughout exercise at AHA and CHA. Insulin increased during exercise in CHO, but the increase was greater ( P ≤ 0.05) at AHA than at SL and CHA, which did not differ. Thus, while acute hypoxia suppressed exogenous glucose oxidation during steady-state aerobic exercise, that hypoxic suppression is alleviated following altitude acclimatization and concomitant negative energy balance.

Karl, J. Philip, Renee E. Cole, Claire E. Berryman, Graham Finlayson, Patrick N. Radcliffe, Matthew T. Kominsky, Nancy E. Murphy, John W. Carbone, Jennifer C. Rood, Andrew J. Young, and Stefan M. Pasiakos. Appetite suppression and altered food preferences coincide with changes in appetite-mediating hormones during energy deficit at high altitude, but are not affected by protein intake. High Alt Med Biol. 19:156-169, 2018.-Anorexia and unintentional body weight loss are common during high altitude (HA) sojourn, but underlying mechanisms are not fully characterized, and the impact of dietary macronutrient composition on appetite regulation at HA is unknown. This study aimed to determine the effects of a hypocaloric higher protein diet on perceived appetite and food preferences during HA sojourn and to examine longitudinal changes in perceived appetite, appetite mediating hormones, and food preferences during acclimatization and weight loss at HA. Following a 21-day level (SL) period, 17 unacclimatized males ascended to and resided at HA (4300 m) for 22 days. At HA, participants were randomized to consume measured standard-protein (1.0 g protein/kg/d) or higher protein (2.0 g/kg/d) hypocaloric diets (45% carbohydrate, 30% energy restriction) and engaged in prescribed physical activity to induce an estimated 40% energy deficit. Appetite, food preferences, and appetite-mediating hormones were measured at SL and at the beginning and end of HA. Diet composition had no effect on any outcome. Relative to SL, appetite was lower during acute HA (days 0 and 1), but not different after acclimatization and weight loss (HA day 18), and food preferences indicated an increased preference for sweet- and low-protein foods during acute HA, but for high-fat foods after acclimatization and weight loss. Insulin, leptin, and cholecystokinin concentrations were elevated during acute HA, but not after acclimatization and weight loss, whereas acylated ghrelin concentrations were suppressed throughout HA. Findings suggest that appetite suppression and altered food preferences coincide with changes in appetite-mediating hormones during energy deficit at HA. Although dietary protein intake did not impact appetite, the possible incongruence with food preferences at HA warrants consideration when developing nutritional strategies for HA sojourn.

We evaluated the performance of a semiquantitative food frequency questionnaire (SFFQ), the Automated Self-Administered 24-Hour Dietary Recall (ASA24), and 7-day dietary records (7DDRs), in comparison with biomarkers, in the estimation of nutrient intakes among 627 women in the Women's Lifestyle Validation Study (United States, 2010-2012). Two paper SFFQs, 1 Web-based SFFQ, 4 ASA24s (beta version), 2 7DDRs, 4 24-hour urine samples, 1 doubly labeled water measurement (repeated among 76 participants), and 2 fasting blood samples were collected over a 15-month period. The dietary variables evaluated were energy, energy-adjusted intakes of protein, sodium, potassium, and specific fatty acids, carotenoids, α-tocopherol, retinol, and folate. In general, relative to biomarkers, averaged ASA24s had lower validity than the SFFQ completed at the end of the data-collection year (SFFQ2); SFFQ2 had slightly lower validity than 1 7DDR; the averaged SFFQs had validity similar to that of 1 7DDR; and the averaged 7DDRs had the highest validity. The deattenuated correlation of energy-adjusted protein intake assessed by SFFQ2 with its biomarker was 0.46, similar to its correlation with 7DDRs (deattenuated r = 0.54). These data indicate that the SFFQ2 provides reasonably valid measurements of energy-adjusted intake for most of the nutrients assessed in our study, consistent with earlier conclusions derived using 7DDRs as the comparison method. The ASA24 needs further evaluation for use in large population studies, but an average of 3 days of measurement will not be sufficient for some important nutrients.

Objectives: 1. Evaluate the effect of washing and cooking iron-fortified rice on iron retention and bioavailability. 2. Evaluate the effect of iron-fortified rice on women with iron deficiency anemia., Methods: 1. Iron-fortified rice (18 mg/100 g as FeSO 4 ) was cooked in Baton Rouge, Louisiana (C), rinsed and cooked (RC), fried and cooked (FC), cooked with extra water (CW), or soaked and cooked with extra water (SCW), and iron retention was determined. 2. Rice samples were cooked in Kampala, Uganda in a lab (C-Uganda) and households using traditional cooking method (TC-Uganda) and iron retention were determined. 3. Seventeen women with iron deficiency (low iron and/or low ferritin) anemia were randomized to 100 g/d of rice (two cooked 0.75 cup servings) for two weeks containing 18 mg/d iron (supplemented) or 0.5 mg/d iron (un-supplemented). Hemoglobin and hematocrit were evaluated at baseline and 2 weeks with other measures of iron metabolism., Results: 1. Iron retention, from highest to lowest, was (C), (RC), (FC), (C-Uganda), (CW), (SCW) and (TC-Uganda). 2. Seventeen women were randomized and 15 completed the study (hemoglobin 10.6 ± 1.6 g, hematocrit 33.7 ± 4.1%), 9 in the iron-fortified rice group and 6 in the un-fortified rice group. The iron-fortified group had a greater increase in hemoglobin (0.82 g, p = 0.0035) and Hematocrit (1.83%, p = 0.0248) with directional differences in other measures of iron metabolism favoring the iron-fortified group., Conclusions: Iron-fortified rice increased hemoglobin and hematocrit in women with iron-deficient anemia. Iron deficiency and anemia are widespread in Southeast Asia and Africa and undermine development in these regions.

Background: The physiological consequences of severe energy deficit include hypogonadism and the loss of fat-free mass. Prolonged energy deficit also impacts physical performance, mood, attentiveness, and decision-making capabilities. This study will determine whether maintaining a eugonadal state during severe, sustained energy deficit attenuates physiological decrements and maintains mental performance. This study will also assess the effects of normalizing testosterone levels during severe energy deficit and recovery on gut health and appetite regulation., Methods: Fifty physically active men will participate in a 3-phase, randomized, placebo-controlled study. After completing a 14-d, energy-adequate, diet acclimation phase (protein: 1.6g∙kg -1 ∙d -1 ; fat: 30% total energy intake), participants will be randomized to undergo a 28-d, 55% energy deficit phase with (DEF+TEST: 200mg testosterone enanthate per week) or without (DEF) exogenous testosterone. Diet and physical activity will be rigorously controlled. Recovery from the energy deficit (ad libitum diet, no testosterone) will be assessed until body mass has been recovered within ±2.5% of initial body mass. Body composition, stable isotope methodologies, proteomics, muscle biopsies, whole-room calorimetry, molecular biology, activity/sleep monitoring, personality and cognitive function assessments, functional MRI, and comprehensive biochemistries will be used to assess physiological and psychological responses to energy restriction and recovery feeding while volunteers are in an expected hypogonadal versus eugonadal state., Discussion: The Optimizing Performance for Soldiers (OPS) study aims to determine whether preventing hypogonadism will mitigate declines in physical and mental function that typically occur during prolonged energy deficit, and the efficacy of testosterone replacement on recovery from severe underfeeding., Trial Registration: NCT02734238., (Copyright © 2017. Published by Elsevier Inc.)

Activity monitors such as the Actical accelerometer, the Sensewear armband, and the Intelligent Device for Energy Expenditure and Activity (IDEEA) are commonly validated against gold standards (e.g., doubly labeled water, or DLW) to determine whether they accurately measure total daily energy expenditure (TEE) or activity energy expenditure (AEE). However, little research has assessed whether these parameters or others (e.g., posture allocation) predict body weight change over time. The aims of this study were to (i) test whether estimated energy expenditure or posture allocation from the devices was associated with weight change during and following a low-calorie diet (LCD) and (ii) compare free-living TEE and AEE predictions from the devices against DLW before weight change. Eighty-seven participants from 2 clinical trials wore 2 of the 3 devices simultaneously for 1 week of a 2-week DLW period. Participants then completed an 8-week LCD and were weighed at the start and end of the LCD and 6 and 12 months after the LCD. More time spent walking at baseline, measured by the IDEEA, significantly predicted greater weight loss during the 8-week LCD. Measures of posture allocation demonstrated medium effect sizes in their relationships with weight change. Bland-Altman analyses indicated that the Sensewear and the IDEEA accurately estimated TEE, and the IDEEA accurately measured AEE. The results suggest that the ability of energy expenditure and posture allocation to predict weight change is limited, and the accuracy of TEE and AEE measurements varies across activity monitoring devices, with multi-sensor monitors demonstrating stronger validity.

Physiological consequences of winter military operations are not well described. This study examined Norwegian soldiers (n = 21 males) participating in a physically demanding winter training program to evaluate whether short-term military training alters energy and whole-body protein balance, muscle damage, soreness, and performance. Energy expenditure (D2(18)O) and intake were measured daily, and postabsorptive whole-body protein turnover ([(15)N]-glycine), muscle damage, soreness, and performance (vertical jump) were assessed at baseline, following a 4-day, military task training phase (MTT) and after a 3-day, 54-km ski march (SKI). Energy intake (kcal·day(-1)) increased (P < 0.01) from (mean ± SD (95% confidence interval)) 3098 ± 236 (2985, 3212) during MTT to 3461 ± 586 (3178, 3743) during SKI, while protein (g·kg(-1)·day(-1)) intake remained constant (MTT, 1.59 ± 0.33 (1.51, 1.66); and SKI, 1.71 ± 0.55 (1.58, 1.85)). Energy expenditure increased (P < 0.05) during SKI (6851 ± 562 (6580, 7122)) compared with MTT (5480 ± 389 (5293, 5668)) and exceeded energy intake. Protein flux, synthesis, and breakdown were all increased (P < 0.05) 24%, 18%, and 27%, respectively, during SKI compared with baseline and MTT. Whole-body protein balance was lower (P < 0.05) during SKI (-1.41 ± 1.11 (-1.98, -0.84) g·kg(-1)·10 h) than MTT and baseline. Muscle damage and soreness increased and performance decreased progressively (P < 0.05). The physiological consequences observed during short-term winter military training provide the basis for future studies to evaluate nutritional strategies that attenuate protein loss and sustain performance during severe energy deficits.