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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 (

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 randomly assigned to 4 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 (DEXA) scans and computed tomography (CT) scans at baseline, 6 months, and 24 months. RESULTS: From baseline to 6 months, when the maximum weight loss was achieved, each 1000 daily steps 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

The effects of testosterone on energy and substrate metabolism during energy deficit is unknown. The objective of this study was to determine the effects of weekly testosterone enanthate (TEST; 200 mg/wk) injections on energy expenditure, energy substrate oxidation, and related gene expression during 28 days of energy deficit compared to placebo (PLA).After a 14-day energy balance phase, healthy men were randomly assigned to TEST (n = 24) or PLA (n = 26) for a 28-day 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-hour 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 RT-qPCR from rested/fasted muscle biopsy samples collected during balance and deficit.Per protocol design 24-hour energy expenditure increased (P0.05) and energy intake decreased (P0.05) in TEST and PLA during deficit compared to balance. Carbohydrate oxidation decreased (P0.05), while protein and fat oxidation increased (P0.05) in TEST and PLA during deficit compared to balance. Change (∆, deficit minus balance) in 24-hour 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 (P0.05) during deficit compared to balance, independent of treatment.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.

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 Conclusion Testosterone administration altered androgenic steroid, acylcarnitine, and amino acid metabolites, which were associated with changes in body composition during SED.

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 relationships by providing a readout of diet-microbiota interactions impacting host health.To determine the effects of consuming a processed diet on the fecal metabolome, and to explore relationships between changes in the fecal metabolome with fecal microbiota composition and gastrointestinal health markers.Secondary analysis of a randomized-controlled trial wherein healthy adults (94% male; 18-61 yr; BMI 26 ± 3 kg.m-2) consumed their usual diet (CON, n = 27) or a Meal, Ready-to-EatTM military ration diet comprised of processed, shelf-stable, ready-to-eat items for 21d (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.Fecal levels of multiple dipeptides (Mann-Whitney effect size (ES) = 0.27-0.50) and long-chain saturated fatty acids (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 levels of Maillard-reaction products (ρ = 0.29-0.70; P 0.05) and inversely with changes in serum prealbumin (ρ = -0.30 - -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).Changes in the fecal metabolomes of adults consuming a Meal, Ready-to-EatTM 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. Clinical trials registration: clinicaltrials.gov NCT02423551.

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 0.05). Muscle mass was unchanged during energy deficit but was greater in TEST than PLA during recovery (P 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.

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.

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.Thirty physically active, healthy men (age 18-39 y; body mass index: 18.5-25 kg/mArginine 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 (P0.05) 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 (P0.05), 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%; P0.05). 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 (P0.05).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.

BACKGROUND AND AIMS Primary bile acids (BAs) are synthesized in the liver and secondary BAs result from intestinal microbial activity. Different subtypes of BAs may be involved in regulating adiposity and energy homeostasis. We examined how changes in circulating BA subtypes induced by weight-loss diets were associated with improvements in adiposity, regional fat deposition and energy metabolism among overweight and obese adults. METHODS The study included 551 subjects who participated in a 2-year weight-loss diet intervention trial. Circulating 14 BA subtypes (primary and secondary unconjugated BAs and their taurine-/glycine-conjugates) were measured at baseline and 6 months. Associations of changes in BAs with changes in weight, waist circumference, resting energy expenditure (REE), body fat composition and fat distribution were evaluated. RESULTS Greater decreases in primary BAs (cholate and chenodeoxycholate) and secondary BAs (deoxycholate and lithocholate) and their conjugates (except for glycolithocholate) were associated with more decreases in weight and waist circumference at 6 months (P-after-false-discovery-rate-correction [PFDR ]

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.

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

Introduction: Bile acids (BAs) are synthesized in the liver from cholesterol, and gut microbiota transform the host-derived primary BAs into secondary BAs in the intestine. Emerging evidence suggests that different types of circulating BAs may play pivotal roles in regulating energy metabolism and body adiposity. Hypothesis: We comprehensively examined whether changes in different BA subtypes after consuming weight-loss diets were associated with improvements in energy metabolism and body adiposity among patients with obesity. Methods: This study included 551 overweight and obese adults who participated in a 2-year weight-loss dietary intervention, the POUNDS Lost trial. Blood levels of 14 types of BAs (primary and secondary unconjugated BAs and their taurine-/glycine-conjugates) were measured at baseline and 6 months after the intervention; changes in BAs from baseline to 6 months after the intervention were calculated. We evaluated changes in resting energy expenditure, weight, and waist circumference. Also, body composition was assessed by the dual-energy X-ray absorptiometry (DEXA) scans, and fat distribution was assessed by computed tomography (CT) scans. Results: At baseline, higher primary and secondary BAs were related to greater degrees of adiposity and energy expenditure. At 6 months after the intervention, greater decreases in primary BAs (cholic acid [CA] and chenodeoxycholic acid) and secondary BAs (deoxycholic acid [DCA] and lithocholic acid [LCA]) and their conjugated subtypes (except for glycolithocholic acid) were significantly associated with more decreases in weight and waist circumference at 6 months after the intervention (P values after controlling for the multiple testing, P FDR P FDR Conclusions: Weight-loss diet-induced changes in circulating various BAs may be involved in improving general and central adiposity and energy metabolism. Changes in specific BA subtypes would be potential targets for improving regional adiposity and achieving successful weight-loss among patients with obesity.

Sustained periods of severe energy deficit during military operations, produced by significant increases in aerobic-type physical work and limited dietary intake, result in conditions that degrade lean body mass (LBM) and lower-body muscle function, which may be mediated by concomitant reductions in circulating testosterone. Therefore, we studied the effects of restoring testosterone by supplementation (200 mg testosterone enanthate/wk, TEST), compared to placebo (1 mL sesame seed oil/wk, PLA), on body composition and lower-body muscular strength and endurance during 28 d of severe exercise- and diet-induced energy deficit in non-obese, young men. Following energy deficit, concentrations of free testosterone decreased, total testosterone remained unchanged, and sex-hormone binding globulin (SHBG) increased in PLA; whereas, total and free testosterone increased and SHBG was unchanged in TEST, such that, total and free testosterone were greater and SHBG concentrations were lower in TEST than PLA. During energy deficit, TEST attenuated weight loss and increased DXA-derived LBM compared to PLA, but both groups had a similar increase in type I slow twitch myosin heavy chain cross-sectional area (CSA) and decrease in type II fast twitch myosin heavy chain CSA. Lower-body muscle function declines and adverse event rates did not differ by group during energy deficit. Supplemental testosterone may be an effective pharmacological LBM enhancement strategy during short-term periods of exercise- and diet-induced energy deficit in non-obese, young men, but does not appear to mitigate lower-body functional decline. Funding:The research reported in this publication is supported by the Collaborative Research to Optimize Warfighter Nutrition II and III projects and the Joint Program Committee-5, funded by the US Department of Defense. Declaration of Interest: J.C.W., O.T.C., and K.M.G. reported that their institution received funding from the US Department of Defense for work associated with this publication. H.R.L. reported receiving personal fees from Pfizer, Inc., for work outside this publication. All remaining authors declare 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. Ethical Approval: This study was approved by the Pennington Biomedical Research Center (PBRC) Institutional Review Board and the Human Research Protection Office of the US Army Medical Research and Materiel Command.

An ethanolic extract of Artemisia scoparia (SCO) has metabolically favorable effects on adipocyte development and function in vitro and in vivo. In diet-induced obese mice, SCO supplementation significantly reduced fasting glucose and insulin levels. Given the importance of adipocyte lipolysis in metabolic health, we hypothesized that SCO modulates lipolysis in vitro and in vivo. Free fatty acids and glycerol were measured in the sera of mice fed a high-fat diet with or without SCO supplementation. In cultured 3T3-L1 adipocytes, the effects of SCO on lipolysis were assessed by measuring glycerol and free fatty acid release. Microarray analysis, qPCR, and immunoblotting were used to assess gene expression and protein abundance. We found that SCO supplementation of a high-fat diet in mice substantially reduces circulating glycerol and free fatty acid levels, and we observed a cell-autonomous effect of SCO to significantly attenuate tumor necrosis factor-α (TNFα)-induced lipolysis in cultured adipocytes. Although several prolipolytic and antilipolytic genes were identified by microarray analysis of subcutaneous and visceral adipose tissue from SCO-fed mice, regulation of these genes did not consistently correlate with SCO’s ability to reduce lipolytic metabolites in sera or cell culture media. However, in the presence of TNFα in cultured adipocytes, SCO induced antilipolytic changes in phosphorylation of hormone-sensitive lipase and perilipin. Together, these data suggest that the antilipolytic effects of SCO on adipose tissue play a role in the ability of this botanical extract to improve whole body metabolic parameters and support its use as a dietary supplement to promote metabolic resiliency.

OBJECTIVE A common variant rs236918 in the PCSK7 gene has the strongest association with iron homeostasis and is related to insulin resistance. Dietary carbohydrate (CHO) modulates the genetic effect on insulin resistance. We examined whether 2-year weight-loss diets modify the effect of PCSK7 genetic variants on changes in fasting insulin levels and insulin resistance in a randomized, controlled trial. RESEARCH DESIGN AND METHODS Data were analyzed in the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial, which is a randomized, controlled 2-year weight-loss trial using diets that differed in macronutrient proportions. PCSK7 rs236918 was genotyped in 730 overweight or obese adults (80% whites) in this trial. We assessed the progression in fasting insulin and glucose levels, and insulin resistance by genotypes. RESULTS During the 6-month weight-loss phase, the PCSK7 rs236918 G allele was significantly associated with greater decreases in fasting insulin levels in the high–dietary CHO group (P for interaction = 0.04), while the interaction for changes in HOMA-insulin resistance (HOMA-IR) (P for interaction = 0.06) did not reach significant levels in white subjects. The G allele was significantly associated with a greater decrease in fasting insulin levels and HOMA-IR in response to high dietary CHO levels (P = 0.02 and P = 0.03, respectively). From 6 months to 2 years (weight-regain phase), the interactions became attenuated due to the regaining of weight (P for interactions = 0.08 and 0.06, respectively). In addition, we observed similar and even stronger results in the whole-study samples from the trial. CONCLUSIONS Our data suggest that PCSK7 genotypes may interact with dietary CHO intake on changes in insulin sensitivity in the white Americans.

The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown. To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight loss setting. Data analysis was conducted among 569 overweight and obese participants aged 30–70 years with normal thyroid function participating in the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine (T3), free thyroxine (T4), total T3, total T4 and thyroid-stimulating hormone (TSH)), anthropometric measurements and biochemical parameters were assessed at baseline, 6 months and 24 months. Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6 to 24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P

Release of home health testing kits into the market has enabled people to take care of their own health. Misinterpretation of results and delays in treatments are the major concerns of the doctors. In the present study, two cholesterol test kits, Accuchek ® Instant plus ® and Home Access ® Instant Cholesterol Test, were compared on the basis of user performance, accuracy, and the patient’s future medical decisions based on the test results. The study was conducted with 30 participants, 15 men and 15 women. Participants tested their overall cholesterol level with both kits. In addition, a clinical cholesterol evaluation, the medical gold standard, was performed. The usability of both test kits was evaluated through questionnaires, user task performance, and comparison with the clinical evaluation. Participants were questioned on how they would use the information once they had seen the result from the first test kit. Results of the study found that regardless of the kit used, participants always found the first kit used as the more usable kit. When participants were asked to provide a decision on future healthcare, a predominate number of participants said they would change their lifestyle rather than visit a doctor regardless of their cholesterol level. This finding highlights physicians’ concerns that patients may delay treatment for potentially serious conditions even when they have the available results. Relevance to industry The results of this study indicate the importance of conducting thorough usability assessments to ensure patients can effectively use products. In addition, this study shows the value of understanding how a product is used in its environment.

A home health test kit is a medical test approved by the United States Food and Drug Administration that can be purchased without a prescription and used in the privacy of the house. Release of home health testing kits into the market has enabled people to take care of their own health. Misinterpretation of results and delays in treatments are the major concerns of the doctors. In the present study, two cholesterol test kits, Accuchek® Instant plus® and Home Access® Instant Cholesterol Test, were compared. This research focused on user errors and clinical accuracy of the kits. The study was conducted with 30 participants, 15 men and 15 women. Participants tested their overall cholesterol level with both kits. In addition, a clinical cholesterol evaluation, the medical gold standard, was performed. The accuracy of both test kits was evaluated by comparing each of the test kit results with the clinical evaluation. The results of the study showed that inaccuracy of the test kit results did not depend on the type of the test kit used; however, the Accuchek® Instant plus® resulted in a greater correlation between the clinical results and test kit results regardless of the number of user errors.

Background: Nuts appear to have cardiovascular benefits but their effect in diabetic patients is unclear. Objective: The objective was to assess effects of almond-enriched diets on insulin sensitivity and lipids in patients with normoglycemia or type 2 diabetes. Design: Study 1 assessed the effect of almonds on insulin sensitivity in 20 free-living healthy volunteers who received 100 g almonds/d for 4 wk. Study 2 was a randomized crossover study that compared 4 diets in 30 volunteers with type 2 diabetes: 1) high-fat, high-almond (HFA; 37% total fat, 10% from almonds); 2) low-fat, high-almond (LFA; 25% total fat, 10% from almonds); 3) high-fat control (HFC; 37% total fat, 10% from olive or canola oil); and 4) low-fat control (LFC; 25% total fat, 10% from olive or canola oil). After each 4-wk diet, serum lipids and oral glucose tolerance were measured. Results: In study 1, almond consumption did not change insulin sensitivity significantly, although body weight increased and total and LDL cholesterol decreased by 21% and 29%, respectively (P < 0.05). In study 2, total cholesterol was lowest with the HFA diet (4.46 ± 0.14, 4.52 ± 0.14, 4.63 ± 0.14, and 4.63 ± 0.14 mmol/L with the HFA, HFC, LFA, and LFC diets, respectively; P = 0.0004 for fat level). HDL cholesterol was significantly lower with the almond diets (P = 0.002); however, no significant effect of fat source on LDL:HDL was observed. Glycemia was unaffected. Conclusions: Almond-enriched diets do not alter insulin sensitivity in healthy adults or glycemia in patients with diabetes. Almonds had beneficial effects on serum lipids in healthy adults and produced changes similar to high monounsaturated fat oils in diabetic patients. Am J Clin Nutr 2002;76:1000‐6.

Objective: Both ethnicity and menopause appear to influence intra-abdominal fat distribution. This study evaluated intra-abdominal fat distribution and obesity-related health risks in perimenopausal white and African American women. Research Methods and Procedures: Baseline data from a longitudinal study of changes in body composition and energy balance during menopause are reported. Healthy women (55 African Americans and 103 whites) who were on no medication and had at least five menstrual cycles in the previous 6 months were recruited. Body composition was assessed by DXA, and visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were assessed by computed tomography scan. SAT was divided into deep and superficial layers demarcated by the fascia superficialis. Results: African American women were slightly younger (46.7 ± 0.2 vs. 47.7 ± 0.2 years, p = 0.002) and fatter (42.4% ± 1.0% vs. 39.4% ± 0.8% body fat, p = 0.02) than white women. In unadjusted data, African Americans had significantly more total abdominal fat and total, deep, and superficial SAT than whites. After adjustment for percent body fat and age, only total and superficial SAT remained significantly higher in African Americans. VAT although slightly less in African American women, did not differ significantly by race. In multiple regression analysis, VAT was the strongest predictor of serum lipids, glucose, and insulin in women of both races, although superficial SAT was significantly associated with fasting glucose in whites. Conclusions: Middle-aged African American women have larger SAT depots, adjusted for total body fatness, but do not differ from white women with regard to VAT. The complexity of the relationship between abdominal fat and metabolic risk is increased by ethnic differences in such associations.

Decrements in muscle strength as a result of prolonged bed rest are well defined, but little is known about potential countermeasures for preventing loss of strength under this condition. The purpose of this study was to determine whether testosterone administration would preserve protein balance and muscle strength during prolonged bed rest. Ten healthy men (age, 36 ± 2 yr; height, 177.2 ± 3.4 cm; weight, 80.5 ± 3.9 kg; mean ± se) were admitted to our in-patient metabolic unit. After a 1-week ambulatory run-in period, each subject was confined to bed for 28 days at 6° head-down tilt while receiving a daily oral dose of T3 (50 μg/day). During the bed rest/T3 period, six of the men were randomized to receive testosterone enanthate by im injection (T; 200 mg/week) while four received placebo in a double blind fashion. Nitrogen balance was determined throughout, and whole body[ 13C]leucine kinetics were assessed at baseline and on day 26 of bed rest. Before bed rest and on the third day of reambulation, the muscle strength of the knee extensors and flexors and shoulder extensors and flexors was determined at 60°/s on a Cybex isokinetic dynamometer. Despite improved [13C]leucine kinetics and maintenance of nitrogen balance and lean body mass in T-treated subjects, little preservation of muscle strength, particularly in the knee extensors, was noted. Muscle strength[ reported as the best work repetition in foot-pounds (FtLb)] for right knee extensors declined (P = 0.011) similarly in both groups; from 165 ± 15 to 126 ± 18 FtLb in T-treated men and from 179 ± 22 to 149 ± 13 FtLb in placebo-treated men. Overall, there was less of a decline in extension and flexion strength of the shoulder compared to the knee, with no benefit from T. These results suggest that in the absence of daily ambulatory activity, T administration will not increase or, in the case of this bed rest model, preserve muscle strength.

Although triiodothyronine (T3) exerts major regulatory actions in both animals and humans, most clinical studies of T3 administration have been relatively short-term. The present study examined the effects of more than 2 months (63 days) of low-dose T3 treatment on overnight pulsatile growth hormone (GH) secretion, short-term insulin secretion, and of sex steroid levels in seven healthy, lean men studied at an inpatient metabolic unit. At baseline, there were strong correlations between sex hormone-binding globulin (SHBG) and several measures of GH production, including total GH production (r = .99), GH interburst interval (r = -.75), and GH mass (r = .82). SHBG was also inversely correlated with basal insulin secretion (r = -.74). There was a 42% increase in serum levels of total testosterone (18.5 +/- 1.3 to 26.3 +/- 1.8 nmol/L, P = .005) and a 150% increase in SHBG (18.0 +/- 2.2 to 44.9 +/- 7.0 nmol/L, P = .008) following T3 treatment. Estradiol and free testosterone levels were unchanged by treatment, although free testosterone decreased from 142.8 +/- 18.4 to 137.3 +/- 19.5 pmol/L. T3 treatment significantly reduced the GH interburst interval (P < .05) and produced slight increases in the measures of GH secretion. There were no statistically significant effects of T3 treatment on insulin secretion, although insulin peak amplitude, mass secreted per burst, and total production all decreased. We conclude that experimentally induced T3 excess in healthy men produces significant and sustained changes in sex hormone levels and GH secretion. Furthermore, there are strong associations between SHBG and both GH and insulin secretion independent of thyroid hormone excess that require additional study.

Abdominal fat distribution is influenced by androgen levels in both men and women. The purpose of this study was to assess the effects on fat distribution of administering nandrolone decanoate (ND; an anabolic steroid with weak androgenic activity) or spironolactone (SP; an antiandrogen) in obese postmenopausal women. The design was a randomized, placebo-controlled, 9-month trial with simultaneous calorie restriction for weight loss. Women in all three groups lost comparable amounts of weight, but the ND-treated women gained lean mass relative to the other two groups (P < 0.0005) and lost more body fat than women in the SP group (P < 0.01). The resting metabolic rate also increased slightly in the ND group. ND treatment produced a gain in visceral fat, as determined by computed tomography scan, and a relatively greater loss of sc abdominal fat. SP-treated women lost significantly less sc fat than the other two groups. Serum cholesterol decreased in the placebo group, but increased slightly in the other two groups (significant for SP vs. placebo, P < 0.05). High density lipoprotein cholesterol decreased significantly in the ND-treated women. There were no significant changes in fasting glucose or insulin sensitivity. We conclude that administration of exogenous androgens modulates body composition in obese postmenopausal women and independently affects visceral and sc abdominal fat.

Overweight and obesity are associated with increased high-sensitivity C-reactive protein (hsCRP) levels. The purpose of this study was to determine if weight loss diets differing in fat, protein, or carbohydrate composition differentially reduce hsCRP.POUNDS (preventing overweight using novel dietary strategies) LOST was a 2-year trial of overweight and obese adults randomly allocated to one of four weight loss diets with targeted percentages of energy derived from fat, protein, and carbohydrates (20, 15, 65%; 20, 25, 55%; 40, 15, 45%; 40, 25, 35%, respectively). hsCRP was measured at baseline, 6, and 24 months among 710 participants, and adiposity as measured by dual X-ray absorptiometry (N = 340) or abdominal computed tomography (N = 126) was correlated with hsCRP change.At 6 months, hsCRP was reduced in all trial participants by -24.7% (Interquartile range (IQR) +7%, -50%), weight by -6.7% (IQR -3%, -11%), and waist circumference by -6.0% (IQR -3%, -10%) (all P0.002), with no significant differences according to dietary composition. The percent change in hsCRP at 6 and 24 months correlated modestly with change in weight, waist circumference, fasting insulin, fasting glucose, HOMA, and most lipid levels. Reductions in hsCRP persisted despite ∼ 50% regain of weight by 24 months. The percent change in hsCRP at 24 months significantly correlated with changes in total body fat (r = 0.42), total abdominal adiposity (r = 0.52), subcutaneous abdominal adiposity (r = 0.52), visceral adiposity (r = 0.47), and hepatic tissue density (r = -0.34) (all P0.0006).Weight loss decreased hsCRP by similar magnitude, irrespective of dietary composition. Clinicians concerned about inflammation and cardiovascular risk should recommend weight loss diets most likely to succeed for their patients.

Energy density (ED) and eating rate (ER) influence energy intake; their combined effects on intake and on postprandial pancreatic and gut hormone responses are undetermined. To determine the combined effects of ED and ER manipulation on voluntary food intake, subjective appetite, and postprandial pancreatic and gut hormone responses.Twenty nonobese volunteers each consumed high (1.6 kcal g(-1) ; HED) and low (1.2 kcal g(-1) ; LED) ED breakfasts slowly (20 g min(-1) ; SR) and quickly (80 g min(-1) ; FR) ad libitum to satiation. Appetite, and pancreatic and gut hormone concentrations were measured periodically over 3 h. Ad libitum energy intake during the subsequent lunch was then measured.Main effects of ED and ER on energy intake and a main effect of ER, but not ED, on mass of food consumed were observed, FR and HED being associated with increased intake (P0.05). Across all conditions, energy intake was highest during FR-HED (P ≤ 0.01). Area under the curve (AUC) of appetite ratings was not different between meals. Main effects of ED and ER on insulin, peptide-YY, and glucagon-like peptide-1 AUC (P0.05) were observed, FR and HED being associated with larger AUC. No effects on active or total ghrelin AUC were documented. Total energy intake over both meals was highest during the FR-HED trial with the greatest difference between FR-HED and SR-LED trials (P ≤ 0.01).Consuming an energy dense meal quickly compounds independent effects of ER and ED on energy intake. Energy compensation at the following meal may not occur despite altered gut hormone responses.

Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures.Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m(2)) were randomized to "control (CO)" = 100% energy requirements; "CR" = 25%; "caloric restriction and increased structured exercise (CR+EX)"= 12.5% CR + 12.5% increase in energy expenditure through exercise; or "low-calorie diet (LCD)" = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood.At baseline, increased liver lipid content (by MRS) correlated (P0.05) with elevated fasting triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation.CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD.