An Intervention of Four Weeks of Time-Restricted Eating (16/8) in Male Long-Distance Runners Does Not Affect Cardiometabolic Risk Factors.

Timing of nutrient intake for athletes may affect exercise performance and cardiometabolic factors. Our objective was to examine the effect of time-restricted eating (TRE) on cardiometabolic health. Using a cross-over study design, 15 endurance-trained male runners were randomized to either a normal dietary pattern (ND) first (12 h eating/fasting times) followed by time-restricted eating (TRE) pattern (16 h fast; 8 h eating) or the reverse, with a 4-week washout period between interventions. Body composition, resting energy expenditure, blood pressure and serum insulin, glucose and lipids were measured using standard laboratory methods. Exercise training and dietary intake (calories and macronutrients) were similar across interventions. No significant differences were observed in resting energy expenditure, markers of insulin resistance, serum lipids or blood pressure. Body composition did change significantly (p < 0.05) with whole body fat mass (-0.8 ± 1.3 kg with TRE vs. +0.1 ± 4.3 kg with ND), leg fat mass (-0.3 ± 0.5 kg with TRE vs. +0.1 ± 0.4 kg with ND), and percent body fat (-1.0 ± 1.5% with TRE vs. +0.1 ± 1.3% with ND) declining more in the TRE intervention, with no change in fat-free mass. This study is one of a few to investigate the effects of an isocaloric 16/8 TRE eating pattern in trained endurance athletes and confirms no change in cardiometabolic risk factors. In conclusion, TRE is not detrimental to cardiometabolic health in endurance-trained male runners but could be beneficial on exercise performance by reducing fat mass.

Adolescent Endurance Runners Exhibit Suboptimal Energy Availability and Intakes of Key Nutrients.

Backgroud: Despite the evidence of an elevated prevalence of low bone mass in adolescent endurance runners, reports on dietary intake in this population is limited.Objectives: This study aimed to evaluate energy availability (EA) and dietary intake among 72 (n = 60 female, n = 12 male) high school cross-country runners.Methods: The sample consisted of a combined dataset of two cohorts. In both cohorts, the Block Food Frequency Questionnaire (FFQ; 2005 & 2014 versions) assessed dietary intake. Fat free mass was assessed using dual-energy x-ray absorptiometry or bioelectrical impedance analysis.Results: Mean EA was less than recommended (45 kcal/kgFFM/day) among male (35.8 ± 14.4 kcal/kg FFM/day) and female endurance runners (29.6 ± 17.4 kcal/kgFFM/day), with 30.0% of males and 60.0% of females meeting criteria for low EA (<30 kcal/kgFFM/day). Calorie intake for male (2,614.2 ± 861.8 kcal/day) and female (1,879.5 ± 723.6 kcal/day) endurance runners fell below the estimated energy requirement for "active" boys (>3,100 kcal/day) and girls (>2,300 kcal/day). Female endurance runners' relative carbohydrate intake (4.9 ± 2.1 g/kg/day) also fell below recommended levels (6-10 g/kg/day). Male and female endurance runners exhibited below-recommended intakes of calcium, vitamin D, potassium, fruit, vegetables, grains, and dairy. Compared to male endurance runners, female endurance runners demonstrated lower relative intakes of energy (kcal/kg/day), protein (g/kg/day), fat (g/kg/day), fiber, vegetables, total protein, and oils.Conclusion: This study provides evidence of the nutritional risk of adolescent endurance runners and underscores the importance of nutritional support efforts in this population.

Four Weeks of 16/8 Time Restrictive Feeding in Endurance Trained Male Runners Decreases Fat Mass, without Affecting Exercise Performance.

BACKGROUND: Time restricted Feeding (TRF) is a dietary pattern utilized by endurance athletes, but there is insufficient data regarding its effects on performance and metabolism in this population. The purpose of this investigation was to examine the effects of a 16/8 TRF dietary pattern on exercise performance in trained male endurance runners. METHODS: A 4-week randomized crossover intervention was used to compare an 8-h TRF to a 12-h normal diet (ND) feeding window. Exercise training and dietary intake were similar across interventions. Runners completed a dual-energy X-ray absorptiometry (DXA) scan to assess body composition, a graded treadmill running test to assess substrate utilization, and ran a 10 km time trial to assess performance. RESULTS: There was a significant decrease in fat mass in the TRF intervention (-0.8 ± 1.3 kg with TRF (p = 0.05), vs. +0.1 ± 4.3 kg with ND), with no significant change in fat-free mass. Exercise carbon dioxide production (VCO2) and blood lactate concentration were significantly lower with the TRF intervention (p ≤ 0.02). No significant changes were seen in exercise respiratory exchange ratio or 10 km time trial performance (-00:20 ± 3:34 min:s TRF vs. -00:36 ± 2:57 min:s ND). CONCLUSION: This investigation demonstrated that adherence to a 4-week 16/8 TRF dietary intervention decreased fat mass and maintained fat-free mass, while not affecting running performance, in trained male endurance runners.

Disordered Eating, Development of Menstrual Irregularity, and Reduced Bone Mass Change After a 3-Year Follow-Up In Female Adolescent Endurance Runners.

This prospective study evaluated the 3-year change in menstrual function and bone mass among 40 female adolescent endurance runners (age 15.9 ± 1.0 years) according to baseline disordered eating status. Three years after initial data collection, runners underwent follow-up measures including the Eating Disorder Examination Questionnaire and a survey evaluating menstrual function, running training, injury history, and prior sports participation. Dual-energy X-ray absorptiometry was used to measure bone mineral density and body composition. Runners with a weight concern, shape concern, or global score ≥4.0 or reporting >1 pathologic behavior in the past 28 days were classified with disordered eating. Compared with runners with normal Eating Disorder Examination Questionnaire scores at baseline, runners with disordered eating at baseline reported fewer menstrual cycles/year (6.4 ± 4.5 vs. 10.5 ± 2.8, p = .005), more years of amenorrhea (1.6 ± 1.4 vs. 0.3 ± 0.5, p = .03), and a higher proportion of menstrual irregularity (75.0% vs. 31.3%, p = .02) and failed to increase lumbar spine or total hip bone mineral density at the 3-year follow-up. In a multivariate model including body mass index and menstrual cycles in the past year at baseline, baseline shape concern score (B = -0.57, p value = .001) was inversely related to the annual number of menstrual cycles between assessments. Weight concern score (B = -0.40, p value = .005) was inversely associated with lumbar spine bone mineral density Z-score change between assessments according to a multivariate model adjusting for age and body mass index. These finding support associations between disordered eating at baseline and future menstrual irregularities or reduced accrual of lumbar spine bone mass in female adolescent endurance runners.

Weight Loss, but Not Dairy Composition of Diet, Moderately Affects Satiety and Postprandial Gut Hormone Patterns in Adults.

BACKGROUND: Inclusion of dairy in diet patterns has been shown to have mixed effects on weight loss. A prevailing hypothesis is that dairy improves weight loss by influencing endocrine systems associated with satiety and food intake regulation. OBJECTIVES: The objective of the current study was to evaluate the effect of weight loss with or without adequate dietary dairy on subjective and objective appetitive measures. METHODS: Men and women who were habitual low dairy consumers (n = 65, 20-50 y) participated in a 12-wk randomized controlled feeding weight loss trial. During the 12-wk intervention, a low-dairy (<1 serving dairy/d) was compared with an adequate-dairy (3-4 servings dairy/d) diet, both with a 500-kcal deficit/d. Test days, before and at the end of the intervention, began with 2 fasting blood draws and visual analog scale (VAS) measures, followed by a standard breakfast (25% of prescribed restricted calories), 5 postbreakfast blood draws and VASs, a standard lunch (40% of restricted energy amount), and 12 postlunch blood draws and VASs. Blood samples were used for satiety hormone measurements. On a separate day when matching standard meals were consumed, an ad libitum buffet meal was provided as dinner, at a self-selected time. Meal duration and intermeal interval were recorded. RESULTS: Weight loss (-6.1 kg), irrespective of dairy, resulted in reduced fasting insulin (-20%) and leptin (-25%), and increased fasting acylated ghrelin (+25%) and VAS desire to eat (+18%) (P < 0.05). There were no effects of dairy on objective or subjective satiety measures. Weight loss marginally reduced the intermeal interval (289 min compared with 276 min, P = 0.059) between lunch and the ad libitum buffet. CONCLUSIONS: These results do not support the hypothesis that inclusion of dairy in long-term dietary patterns influences appetite during weight loss. Weight loss per se has a modest impact on select systems that regulate hunger and satiety.This trial was registered at clinicaltrials.gov as NCT00858312.

Cognitive dietary restraint score is associated with lower energy, carbohydrate, fat, and grain intake among female adolescent endurance runners.

This cross-sectional study investigated associations between cognitive dietary restraint (CDR), energy, macronutrient and food group intake, menstrual function, and bone density in female adolescent endurance runners. Participants were forty female adolescent endurance runners. The independent variable was CDR, as assessed by the Three Factor Eating Questionnaire (TFEQ). Runners with CDR subscale scores ≥11 were classified with elevated CDR. The main outcomes measured were dietary intake measured by 24-hour recall for 7 days, menstrual history, and bone mineral density (BMD). Twelve of 40 participants (30.0%) met criteria for elevated CDR. Compared to runners with normal CDR, runners with elevated CDR scores reported consuming lower energy (kcal/kg/day) (37.5 ± 8.6 vs. 44.0 ± 9.6, p = 0.052), lower carbohydrate (g/kg/day) (5.3 ± 1.3 vs. 6.3 ± 1.3, p = 0.042), more fiber (g/day) (24.9 ± 6.7 vs. 20.0 ± 5.3, p = 0.018), more servings of fruit (3.3 ± 1.4 vs. 1.9 ± 1.2, p = 0.003), more servings of vegetables (2.7 ± 1.4 vs. 1.7 ± 0.7, p = 0.004), and fewer servings of grain (7.6 ± 2.4 vs. 9.8 ± 2.4, p = 0.009) per day. Runners with elevated CDR exhibited significantly lower lumbar spine BMD Z-scores (adjusting for BMI) (-0.78 ± 0.19 vs. -0.22 ± 0.12, p = 0.016) than runners with normal CDR. Menstrual history did not significantly differ based on CDR status. Elevated CDR may increase risk of dietary patterns associated with consuming inadequate levels of energy, key nutrients, and developing low BMD in endurance runners. Trial Registration:ClinicalTrials.gov Identifier: NCT01059968.

Circulating 25-Hydroxyvitamin D Concentrations in Overweight and Obese Adults Are Explained by Sun Exposure, Skin Reflectance, and Body Composition.

BACKGROUND: Obese individuals are known to be at higher risk for vitamin D deficiency than normal-weight individuals. Cutaneous synthesis is a major source of vitamin D; however, objective measurements of sun exposure are lacking in this population. OBJECTIVE: To assess the validity of a regression model using sun exposure in lean individuals to estimate serum 25-hydroxyvitamin D [25(OH)D] in overweight and obese individuals, and to develop a prediction equation for serum 25(OH)D in overweight and obese adults. METHODS: This study was a secondary analysis of a 15-wk controlled feeding study investigating the effects of dairy consumption on body composition. Information regarding sun exposure, including day, hour, time outside, and clothing, were self-assessed in sun exposure diaries. Personal sun exposure energy (joules) was assessed by downloading time-specific ultraviolet B energy data from climate stations. Skin reflectance was measured using a Minolta 2500d spectrophotometer. Dietary intake of vitamin D was known. Serum 25(OH)D concentration was measured by radioimmunoassay. Body composition was determined from whole-body dual energy x-ray absorptiometry and computed tomography scans. RESULTS: Sun exposure was positively related to serum 25(OH)D (r = 0.26; P ≤ 0.05) and inversely related to total fat mass, android fat, and BMI (r = -0.25, -0.30, and -0.32, respectively). The modified Hall model significantly overestimated serum 25(OH)D in overweight and obese adults by 27.33-80.98 nmol/L, depending on the sun exposure calculation. A new regression model was developed for overweight and obese persons that explained 29.1% of the variance in postintervention 25(OH)D concentrations and included sun exposure, skin reflectance, total fat mass, total lean mass, and intra-abdominal adipose tissue as predictors. CONCLUSION: Major determinants of serum 25(OH)D concentration in healthy overweight and obese individuals include sun exposure, skin reflectance, and adiposity. Addition of adiposity terms to the prior model significantly improved predictive ability in overweight and obese men and women. (clinicaltrials.gov: NCT00858312).

Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults With Human Immunodeficiency Virus Infection Being Treated With Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial.

Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized that vitamin D3 (VITD3) would increase BMD in youth receiving TDF. Methods: This was a randomized, double-blind, placebo-controlled trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth aged 16-24 years with HIV, RNA load <200 copies/mL, taking TDF-containing combination antiretroviral therapy (TDF-cART) for ≥180 days. Participants (N = 214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg, plus monthly randomized VITD3 50000 IU (n = 109) or placebo (n = 105). Outcome was change from baseline to week 48 in lumbar spine BMD (LSBMD). Data presented are median (Q1, Q3). Results: Participants were aged 22.0 (21.0, 23.0) years, 84% were male, and 74% were black/African American. At baseline, 62% had 25-hydroxy vitamin D (25-OHD) <20 ng/mL. Multivitamin adherence was 49% (29%, 69%), and VITD3/placebo adherence 100% (100%, 100%). Vitamin D intake was 2020 (1914, 2168) and 284 (179, 394) IU/day, and serum 25-OHD concentration was 36.9 (30.5, 42.4) and 20.6 (14.4, 25.8) ng/mL at 48 weeks in VITD3 and placebo groups, respectively (P < .001). From baseline to week 48, LSBMD increased by 1.15% (-0.75% to 2.74%) in the VITD3 group (n = 99; P < .001) and 0.09% (-1.49% to 2.61%) in the placebo group (n = 89; P = .25), without between-group difference (P = .12). VITD3 group changes occurred with baseline 25-OHD <20 ng/mL (1.17% [-.82% to 2.90%]; P = .004) and ≥20 ng/mL (0.93% [-.26% to 2.15%]; P = .033). Conclusions: For youth taking TDF-cART, LSBMD increased through 48 weeks with VITD3 plus multivitamin, but not with placebo plus multivitamin, independent of baseline vitamin D status. Clinical Trials Registration: NCT01751646.

The role of a dairy fraction rich in milk fat globule membrane in the suppression of postprandial inflammatory markers and bone turnover in obese and overweight adults: an exploratory study.

BACKGROUND: Inflammation is associated with increased bone resorption; the role of inflammation in postprandial bone turnover has not been explored. Consumption of milk fat globule membrane (MFGM) reduces inflammation in animal models. This study aimed to measure postprandial changes in bone turnover after intake of high saturated fat test meals, with- and without the anti-inflammatory ingredient MFGM. METHODS: Subjects (n = 36 adults) were obese (BMI 30-39.9 kg/m2) or overweight (BMI 25-29.9 kg/m2) with two traits of Metabolic Syndrome. Subjects consumed a different test meal on four occasions at random; blood draws were taken at baseline and 1, 3, and 6 h postprandial. Test meals included whipping cream (WC), WC + MFGM, palm oil (PO) and PO + MFGM. Biomarkers of bone turnover and inflammation were analyzed from all four time points. RESULTS: Test meal (treatment) by time interactions were significant for bone resorption marker C-telopeptide of type 1 collagen (CTX) (p < 0.0001) and inflammatory marker interleukin 10 (IL-10) (p = 0.012). Significant differences in overall postprandial response among test meals were found for CTX and soluble intercellular adhesion molecule (sICAM), with the greatest overall postprandial suppression of CTX occurring in meals containing MFGM. However, test meal by MFGM interactions were non- significant for bone and inflammatory markers. Correlations between CTX and inflammatory markers were non-significant. CONCLUSION: This exploratory analysis advances the study of postprandial suppression of bone turnover by demonstrating differing effects of high SFA meals that contained MFGM; however MFGM alone did not directly moderate the difference in postprandial CTX response among test meals in this analysis. These observations may be useful for identifying foods and ingredients which maximize the suppression of bone resorption, and for generating hypotheses to test in future studies examining the role of inflammation in postprandial bone turnover. TRIAL REGISTRATION: Clinicaltrials.gov NCT01811329. Registered 11 March 2013.

Decline in Bone Mass With Tenofovir Disoproxil Fumarate/Emtricitabine Is Associated With Hormonal Changes in the Absence of Renal Impairment When Used by HIV-Uninfected Adolescent Boys and Young Men for HIV Preexposure Prophylaxis.

BACKGROUND: We aimed to define the relative importance of renal and endocrine changes in tenofovir disoproxil fumarate (TDF)-related bone toxicity. METHODS: In a study of daily TDF/emtricitabine (FTC) preexposure prophylaxis (PrEP) in human immunodeficiency virus (HIV)-uninfected young men who have sex with men, we measured changes from baseline in blood and urine markers of the parathyroid hormone (PTH)-vitamin D-fibroblast growth factor 23 (FGF23) axis, creatinine, and renal tubular reabsorption of phosphate (TRP). We explored the relationship of those variables to changes in bone mineral density (BMD). Tenofovir-diphosphate (TFV-DP) in red blood cells was used to categorize participants into high and low drug exposure groups. RESULTS: There were 101 participants, median age 20 years (range 15 to 22). Compared with low drug exposure, high-exposure participants showed increase from baseline in PTH and decline in FGF23 by study week 4, with no differences in creatinine, phosphate, or TRP. At 48 weeks, the median (interquartile range) percent decline in total hip BMD was greater in those with high- compared to low- exposure (-1.59 [2.77] vs +1.54 [3.34] %, respectively; P = .001); in high-exposure participants, this correlated with week 4 TFV-DP (inversely; r = -0.60, P = .002) and FGF23 (directly; r = 0.42; P = .039) but not other variables. CONCLUSIONS: These findings support the short-term renal safety of TDF/FTC PrEP in HIV-seronegative young men and suggest that endocrine disruption (PTH-FGF23) is a primary contributor to TDF-associated BMD decline in this age group. CLINICAL TRIALS REGISTRATION: NCT01769469.

Is bone equally responsive to calcium and vitamin D intake from food vs. supplements? Use of (41)calcium tracer kinetic model.

BACKGROUND: Few interventions directly compare equivalent calcium and vitamin D from dairy vs. supplements on the same bone outcomes. The radioisotope calcium-41 ((41)Ca) holds promise as a tracer method to directly measure changes in bone resorption with differing dietary interventions. OBJECTIVE: Using (41)Ca tracer methodology, determine if 4 servings/day of dairy foods results in greater (41)Ca retention than an equivalent amount of calcium and vitamin D from supplements. Secondary objective was to evaluate the time course for the change in (41)Ca retention. METHODS: In this crossover trial, postmenopausal women (n = 12) were dosed orally with 100 nCi of (41)Ca and after a 180 day equilibration period received dairy (4 servings/day of milk or yogurt; ~ 1300 mg calcium, 400 IU cholecalciferol (vitamin D3/day)) or supplement treatments (1200 mg calcium carbonate/day and 400 IU vitamin D3/day) in random order. Treatments lasted 6 weeks separated by a 6 week washout (WO). Calcium was extracted from weekly 24 h urine collections; accelerator mass spectrometry (AMS) was used to determine the (41/40)Ca ratio. Primary outcome was change in (41/40)Ca excretion. Secondary outcome was the time course for change in (41)Ca excretion during intervention and WO periods. RESULTS: The (41/40)Ca ratio decreased significantly over time during both treatments; there was no difference between treatments. Both treatments demonstrated a significant retention of (41)Ca within 1-2 weeks (p = 0.0007 and p < 0.001 for dairy and supplements, respectively). WO demonstrated a significant decrease (p = 0.0024) in (41)Ca retention within 1-2 weeks, back to pre-intervention levels. CONCLUSION: These data demonstrate that urinary (41)Ca retention is increased with an increase in calcium and vitamin D intake regardless of the source of calcium, and the increased retention occurs within 1-2 weeks.

Addition of a dairy fraction rich in milk fat globule membrane to a high-saturated fat meal reduces the postprandial insulinaemic and inflammatory response in overweight and obese adults.

Meals high in SFA, particularly palmitate, are associated with postprandial inflammation and insulin resistance. Milk fat globule membrane (MFGM) has anti-inflammatory properties that may attenuate the negative effects of SFA-rich meals. Our objective was to examine the postprandial metabolic and inflammatory response to a high-fat meal composed of palm oil (PO) compared with PO with an added dairy fraction rich in MFGM (PO+MFGM) in overweight and obese men and women (n 36) in a randomised, double-blinded, cross-over trial. Participants consumed two isoenergetic high-fat meals composed of a smoothie enriched with PO with v. without a cream-derived complex milk lipid fraction ( dairy fraction rich in MFGM) separated by a washout of 1-2 weeks. Serum cytokines, adhesion molecules, cortisol and markers of inflammation were measured at fasting, and at 1, 3 and 6 h postprandially. Glucose, insulin and lipid profiles were analysed in plasma. Consumption of the PO + MFGM v. PO meal resulted in lower total cholesterol (P = 0·021), LDL-cholesterol (P = 0·046), soluble intracellular adhesion molecule (P = 0·005) and insulin (P = 0·005) incremental AUC, and increased IL-10 (P = 0·013). Individuals with high baseline C-reactive protein (CRP) concentrations (≥3 mg/l, n 17) had higher (P = 0·030) insulin at 1 h after the PO meal than individuals with CRP concentrations <3 mg/l (n 19). The addition of MFGM attenuated this difference between CRP groups. The addition of a dairy fraction rich in MFGM attenuated the negative effects of a high-SFA meal by reducing postprandial cholesterol, inflammatory markers and insulin response in overweight and obese individuals, particularly in those with elevated CRP.

Consumption of a high-fat meal containing cheese compared with a vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomised controlled cross-over study.

Dietary recommendations suggest decreased consumption of SFA to minimise CVD risk; however, not all foods rich in SFA are equivalent. To evaluate the effects of SFA in a dairy food matrix, as Cheddar cheese, v. SFA from a vegan-alternative test meal on postprandial inflammatory markers, a randomised controlled cross-over trial was conducted in twenty overweight or obese adults with metabolic abnormalities. Individuals consumed two isoenergetic high-fat mixed meals separated by a 1- to 2-week washout period. Serum was collected at baseline, and at 1, 3 and 6 h postprandially and analysed for inflammatory markers (IL-6, IL-8, IL-10, IL-17, IL-18, TNFα, monocyte chemotactic protein-1 (MCP-1)), acute-phase proteins C-reactive protein (CRP) and serum amyloid-A (SAA), cellular adhesion molecules and blood lipids, glucose and insulin. Following both high-fat test meals, postprandial TAG concentrations rose steadily (P < 0·05) without a decrease by 6 h. The incremental AUC (iAUC) for CRP was significantly lower (P < 0·05) in response to the cheese compared with the vegan-alternative test meal. A treatment effect was not observed for any other inflammatory markers; however, for both test meals, multiple markers significantly changed from baseline over the 6 h postprandial period (IL-6, IL-8, IL-18, TNFα, MCP-1, SAA). Saturated fat in the form of a cheese matrix reduced the iAUC for CRP compared with a vegan-alternative test meal during the postprandial 6 h period. The study is registered at clinicaltrials.gov under NCT01803633.

Habitual physical activity and plasma metabolomic patterns distinguish individuals with low vs. high weight loss during controlled energy restriction.

BACKGROUND: Total weight loss induced by energy restriction is highly variable even under tightly controlled conditions. Identifying weight-loss discriminants would provide a valuable weight management tool and insights into body weight regulation. OBJECTIVE: This study characterized responsiveness to energy restriction in adults from variables including the plasma metabolome, endocrine and inflammatory markers, clinical indices, body composition, diet, and physical activity. METHODS: Data were derived from a controlled feeding trial investigating the effect of 3-4 dairy product servings in an energy-restricted diet (2092 kJ/d reduction) over 12 wk. Partial least squares regression was used to identify weight-loss discriminants in 67 overweight and obese adults. Linear mixed models were developed to identify discriminant variable differences in high- vs. low-weight-loss responders. RESULTS: Both pre- and postintervention variables (n = 127) were identified as weight-loss discriminants (root mean squared error of prediction = 1.85 kg; Q(2) = 0.43). Compared with low-responders (LR), high-responders (HR) had greater decreases in body weight (LR: 2.7 ± 1.6 kg; HR: 9.4 ± 1.8 kg, P < 0.01), BMI (in kg/m(2); LR: 1.0 ± 0.6; HR: 3.3 ± 0.5, P < 0.01), and total fat (LR: 2.2 ± 1.1 kg; HR: 8.0 ± 2.1 kg, P < 0.01). Significant group effects unaffected by the intervention were determined for the respiratory exchange ratio (LR: 0.86 ± 0.05; HR: 0.82 ± 0.03, P < 0.01), moderate physical activity (LR: 127 ± 52 min; HR: 167 ± 68 min, P = 0.02), sedentary activity (LR: 1090 ± 99 min; HR: 1017 ± 110 min, P = 0.02), and plasma stearate [LR: 102,000 ± 21,000 quantifier ion peak height (QIPH); HR: 116,000 ± 24,000 QIPH, P = 0.01]. CONCLUSIONS: Overweight and obese individuals highly responsive to energy restriction had accelerated reductions in adiposity, likely supported in part by higher lipid mobilization and combustion. A novel observation was that person-to-person differences in habitual physical activity and magnitude of weight loss were accompanied by unique blood metabolite signatures. This trial was registered at clinicaltrials.gov as NCT00858312.

Ethnicity and acculturation: do they predict weight status in a longitudinal study among Asian, Hispanic, and non-Hispanic White early adolescent females?

BACKGROUND: The prevalence of overweight and obesity among adolescents has increased over the past decade. Prevalence rates are disparate among certain racial and ethnic groups. This study sought to longitudinally examine the relationship between overweight status (≥85th percentile according to the Centers for Disease Control and Prevention growth charts) and ethnic group, as well as acculturation (generation and language spoken in the home) in a sample of adolescent females. METHODS: Asian (n=160), Hispanic (n=217), and non-Hispanic White (n=304) early adolescent girls participating in the multistate calcium intervention study with complete information on weight, ethnicity, and acculturation were included. Multiple methods of assessing longitudinal relationships (binary logistic regression model, linear regression model, Cox proportional-hazards regression analysis, and Kaplan-Meier survival analysis) were used to examine the relationship. RESULTS: The total proportion of girls overweight at baseline was 36%. When examining by ethnic group, the proportion varied with Hispanic girls having the highest percentage (46%) in comparison to their Asian (23%) and Non-Hispanic White (35%) counterparts. Although the total proportion of overweight was 36% at 18 months, the variation across the ethnic groups remained with the proportion of Hispanic girls becoming overweight (55%) being greater than their Asian (18%) and non-Hispanic White (34%) counterparts. However, regardless of the statistical approach used, there were no significant associations between overweight status and acculturation over time. CONCLUSION: These unexpected results warrant further exploration into factors associated with overweight, especially among Hispanic girls, and further investigation of acculturation's role is warranted. Identifying these risk factors will be important for developing targeted obesity prevention initiatives.

Soy Isoflavones for Reducing Bone Loss Study: effects of a 3-year trial on hormones, adverse events, and endometrial thickness in postmenopausal women.

OBJECTIVE: This study aims to assess the overall safety and potential endometrium-stimulating effects of soy isoflavone tablets consumed (3 y) by postmenopausal women and to determine endometrial thickness response to treatment among compliant women, taking into account hormone concentrations and other hypothesized modifying factors. METHODS: We randomized healthy postmenopausal women (aged 45.8-65.0 y) to placebo control or two doses (80 or 120 mg/d) of soy isoflavones at two sites. We used intent-to-treat analysis (N = 224) and compliant analysis (>95%; N = 208) to assess circulating hormone concentrations, adverse events, and endometrial thickness (via transvaginal ultrasound). RESULTS: Median values for endometrial thickness (mm) declined from baseline through 36 months. Nonparametric analysis of variance for treatment differences among groups showed no differences in absolute (or percentage of change) endometrial thickness (χ(2) P ranged from 0.12 to 0.69) or in circulating hormones at any time point. A greater number of adverse events in the genitourinary system (P = 0.005) were noted in the 80 mg/day group compared with the 120 mg/day group, whereas other systems showed no treatment effects. The model predicting endometrial thickness response (using natural logarithm) to treatment among compliant women across time points was significant (P ≤ 0.0001), indicating that estrogen exposure (P = 0.0013), plasma 17ß-estradiol (P = 0.0086), and alcohol intake (P = 0.023) contributed significantly to the response. Neither the 80 mg/day dose (P = 0.57) nor the 120 mg/day dose (P = 0.43) exerted an effect on endometrial thickness across time. CONCLUSIONS: Our randomized controlled trial verifies the long-term overall safety of soy isoflavone tablet intake by postmenopausal women who display excellent compliance. We find no evidence of treatment effects on endometrial thickness, adverse events, or circulating hormone concentrations, most notably thyroid function, across a 3-year period.

Associations among endocrine, inflammatory, and bone markers, body composition and weight loss induced bone loss.

INTRODUCTION: Weight loss reduces co-morbidities of obesity, but decreases bone mass. PURPOSE: Our aims were to (1) determine if adequate dairy intake attenuates weight loss-induced bone loss; (2) evaluate the associations of endocrine, inflammatory and bone markers, anthropometric and other parameters to bone mineral density and content (BMD, BMC) pre- and post-weight loss; and (3) model the contribution of these variables to post weight-loss BMD and BMC. METHODS: Overweight/obese women (BMI: 28-37 kg/m2) were enrolled in an energy reduced (-500 kcal/d; -2092 kJ/d) diet with adequate dairy (AD: 3-4 servings/d; n=25, 32.2±8.8 years) or low dairy (LD: ≤1 serving/d; n=26, 31.7±8.4 years). BMD, BMC and body composition were measured by DXA. Bone markers (CTX, PYD, BAP, OC), endocrine (PTH, vitamin D, leptin, adiponectin, ghrelin, amylin, insulin, GLP-1, PAI-1, HOMA) and inflammatory markers (CRP, IL1-ß, IL-6, IL-8, TNF-α, cortisol) were measured in serum or plasma. PA was assessed by accelerometry. RESULTS: Following weight loss, AD intake resulted in significantly greater (p=0.004) lumbar spine BMD and serum osteocalcin (p=0.004) concentration compared to LD. Pre- and post-body fat was negatively associated with hip and lumbar spine BMC (r=-0.28, p=0.04 to -0.45, p=0.001). Of note were the significant negative associations among bone markers and IL-1ß, TNFα and CRP ranging from r = -0.29 (p=0.04) to r = -0.34 (p=0.01); magnitude of associations did not change with weight loss. Adiponectin was negatively related to change in osteocalcin. Factor analysis resulted in 8 pre- and post-weight loss factors. Pre-weight loss factors accounted for 13.7% of the total variance in pre-weight loss hip BMD; post-weight loss factors explained 19.6% of the total variance in post-weight loss hip BMD. None of the factors contributed to the variance in lumbar spine BMD. CONCLUSION: AD during weight loss resulted in higher lumbar spine BMD and osteocalcin compared to LD. Significant negative associations were observed between bone and inflammatory markers suggesting that inflammation suppresses bone metabolism. Using factor analysis, 19.6% of total variance in post-weight loss hip BMD could be explained by endocrine, immune, and anthropometric variables, but not lumbar spine BMD.

Serum biomarkers of bone metabolism in castration-resistant prostate cancer patients with skeletal metastases: results from SWOG 0421.

BACKGROUND: Prior studies suggest that elevated markers of bone turnover are prognostic for poor survival in castration-resistant prostate cancer (CRPC). The predictive role of these markers relative to bone-targeted therapy is unknown. We prospectively evaluated the prognostic and predictive value of bone biomarkers in sera from CRPC patients treated on a placebo-controlled phase III trial of docetaxel with or without the bone targeted endothelin-A receptor antagonist atrasentan (SWOG S0421). METHODS: Markers for bone resorption (N-telopeptide and pyridinoline) and formation (C-terminal collagen propeptide and bone alkaline phosphatase) were assayed in pretreatment and serial sera. Cox proportional hazards regression models were fit for overall survival. Models were fit with main effects for marker levels and with/without terms for marker-treatment interaction, adjusted for clinical variables, to assess the prognostic and predictive value of atrasentan. Analysis was adjusted for multiple comparisons. Two-sided P values were calculated using the Wald test. RESULTS: Sera from 778 patients were analyzed. Elevated baseline levels of each of the markers were associated with worse survival (P < .001). Increasing marker levels by week nine of therapy were also associated with subsequent poor survival (P < .001). Patients with the highest marker levels (upper 25th percentile for all markers) not only had a poor prognosis (hazard ratio [HR] = 4.3; 95% confidence interval [CI] = 2.41 to 7.65; P < .001) but also had a survival benefit from atrasentan (HR = 0.33; 95% CI = 0.15 to 0.71; median survival = 13 [atrasentan] vs 5 months [placebo]; P interaction = .005). CONCLUSIONS: Serum bone metabolism markers have statistically significant independent prognostic value in CRPC. Importantly, a small group of patients (6%) with highly elevated markers of bone turnover appear to preferentially benefit from atrasentan therapy.

Vitamin D3 supplementation increases fibroblast growth factor-23 in HIV-infected youths treated with tenofovir disoproxil fumarate.

BACKGROUND: Tenofovir (TDF) is associated with phosphaturia and elevated 1,25 dihydroxy vitamin D (1,25-OH(2)D). Fibroblast growth factor 23 (FGF23) causes phosphaturia and increases in response to elevated 1,25-OH(2)D. Vitamin D-binding protein (VDBP) binds to 1,25-OH(2)D, decreasing its biological activity, and is elevated in individuals with higher plasma tenofovir concentrations. We compared FGF23 and VDBP before and after vitamin D3 (VITD) supplementation in youths treated with combination antiretroviral therapy (cART) containing or not containing TDF. METHODS: A randomized controlled trial in HIV-positive youths aged 18-25 years enrolled participants based on cART treatment with TDF (TDF; n=118) or without TDF (no-TDF; n=85), and randomized within those groups to VITD (50,000 IU every 4 weeks) or placebo (PL). We measured FGF23 and VDBP and calculated free 1,25-OH(2)D at baseline and week 12, and compared changes by TDF treatment and VITD randomized group. RESULTS: At baseline, serum FGF23 concentration showed a quadratic relationship with 1,25-OH(2)D most pronounced in the TDF group. At week 12, total and free 1,25-OH(2)D increased in the VITD but not PL groups, independent of TDF use. FGF23 increased in the TDF group receiving VITD, but there was no FGF23 change in the no-TDF group receiving VITD or the PL groups. The adjusted mean change in FGF23 from baseline to week 12 was 7.7 pg/ml in the TDF/VITD group, compared with -1.7 (no-TDF/VITD, P=0.010), -1.3 (TDF/PL, P=0.006) and 1.1 (no-TDF/PL, P=0.035). CONCLUSIONS: These results suggest that TDF-containing cART may alter the FGF23 response to vitamin D supplementation in HIV-infected youths. Clinical trials number: NCT00490412.

Association between subcutaneous white adipose tissue and serum 25-hydroxyvitamin D in overweight and obese adults.

Cholecalciferol is known to be deposited in human adipose tissue, but it is not known whether 25-hydroxyvitamin D (25(OH)D) is found in detectable concentrations. Therefore, our objective was to determine whether 25(OH)D is detectable in subcutaneous white adipose tissue (SWAT) in overweight and obese persons enrolled in a twelve week energy restricted diet. Baseline and post-intervention gluteal SWAT biopsies were collected from 20 subjects participating in a larger clinical weight loss intervention. LC-MS/MS was utilized to determine SWAT 25(OH)D concentrations. Serum 25(OH)D and 1,25(OH)2D were measured by RIA. Body composition was assessed by dual energy x-ray absorptiometry. SWAT 25(OH)D concentrations were 5.8 ± 2.6 nmol/kg tissue and 6.2 ± 2.7 nmol/kg tissue pre- and post-intervention SWAT, respectively. There was a significant positive association between SWAT 25(OH)D concentration and serum 25(OH)D concentration (r = 0.52, P < 0.01). Both SWAT and serum 25(OH)D concentrations did not significantly change after a twelve-week period of energy restriction with approximately 5 kg of fat loss. In conclusion, we have demonstrated our LC-MS/MS method can detect 25(OH)D3 in human subcutaneous fat tissue from overweight and obese individuals and is consistent with previously reported concentrations in swine. Additionally, our findings of no significant changes in SWAT 25(OH)D3 or serum 25(OH)D after a 6% loss of total body weight and 13% reduction in total fat provides the first human evidence that adipose 25(OH)D does not likely contribute to serum 25(OH)D with moderate weight loss; whether this is also the case with larger amounts of weight loss is unknown. Weight loss alone is not sufficient to increase serum 25(OH)D and increases in dietary or dermal biosynthesis of vitamin D appear to be the most critical contributors to in vitamin D status.