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Obesity is a risk factor for chronic diseases and moderate weight loss is generally recommended. Energy restriction results in the loss of hip bone mineral density (BMD) in older adults, but there is no consistent decline at the lumbar spine (LS), possibly due to vertebral abnormalities although this may also be dependent on the amount of weight loss. In this secondary analysis of weight loss trials investigating BMD and trabecular bone score (TBS) changes over 12-18 months, 92 postmenopausal women (60.8 ± 5.8 years; body mass index 32.7 ± 4.4 kg/m

In menopausal and postmenopausal women, the risk for obesity, cardiovascular disease, osteoporosis, and gut dysbiosis are elevated by the depletion of 17β-estradiol. A diet that is high in omega-6 polyunsaturated fatty acids (PUFAs), particularly linoleic acid (LA), and low in saturated fatty acids (SFAs) found in coconut oil and omega-3 PUFAs may worsen symptoms of estrogen deficiency. To investigate this hypothesis, ovariectomized C57BL/6J and transgenic fat-1 mice, which lower endogenous omega-6 polyunsaturated fatty acids, were treated with either a vehicle or estradiol benzoate (EB) and fed a high-fat diet with a high or low PUFA:SFA ratio for ~15 weeks. EB treatment reversed obesity, glucose intolerance, and bone loss in ovariectomized mice. fat-1 mice fed a 1% LA diet experienced reduced weight gain and adiposity, while those fed a 22.5% LA diet exhibited increased energy expenditure and activity in EB-treated ovariectomized mice. Coconut oil SFAs and omega-3 FAs helped protect against glucose intolerance without EB treatment. Improved insulin sensitivity was observed in wild-type and fat-1 mice fed 1% LA diet with EB treatment, while fat-1 mice fed 22.5% LA diet was protected against insulin resistance without EB treatment. The production of short-chain fatty acids by gut microbial microbiota was linked to omega-3 FAs production and improved energy homeostasis. These findings suggest that a balanced dietary fatty acid profile containing SFAs and a lower ratio of omega-6:omega-3 FAs is more effective in alleviating metabolic disorders during E2 deficiency.

Dietary protein alters circulating amino acid (AAs) levels and higher protein intake (HP) is one means of losing weight. We examined 34 overweight and obese women (57 ± 4 years) during 6 months of energy restriction (7.3 ± 3.8% weight loss) divided into groups consuming either normal protein (NP; 18.6 energy% protein) or HP (24.3 energy% protein). There was a reduction in fasting serum glucogenic AAs (p = 0.015) that also associated with greater weight loss (p

To evaluate total and free vitamin D metabolites and hormone-to-prohormone [1,25(OH)2D/25(OH)D] “activation ratio” in PHPT patients with low or insufficient vitamin D status. Thirty female patients with primary hyperparathyroidism (PHPT) and 30 age and body mass index (BMI) matched healthy controls were enrolled. Serum levels of calcium, intact parathyroid hormone (iPTH), vitamin D binding protein (DBP), albumin, total 25(OH)D and 1,25(OH)2D were measured. The activation ratio of vitamin D was calculated as total 1,25(OH)2D/25(OH)D. Calculated serum-free 25(OH)D and 1,25(OH)2D levels were also reported. Compared to the control subject, patients with PHPT had a lower total 25(OH)D and DBP levels (p

When taken with a meal, α-glucosidase inhibitors (α-GI) reduce the rise in postprandial glucose and increase glucagon-like peptide-1 (GLP-1), and this may lower bone turnover. In this study, a salacinol-type α-GI increased GLP-1 and markedly reduced postprandial bone resorption compared to placebo, suggesting it could have implications for bone health. Animal and clinical trials indicate that α-glucosidase inhibitors attenuate postprandial glycemic indices and increase secretion of GLP-1. In addition, GLP-1 acts on bone by inhibiting resorption. The goal in this study was to determine if a salacinol α-GI alters postprandial bone turnover and can be explained by changes in serum GLP-1. In this double-blind, placebo-controlled crossover study, healthy overweight/obese adults (body mass index 29.0 ± 3.8 kg/m2; 21–59 years; n = 21) received a fixed breakfast and, in random order, were administered Salacia chinensis (SC; 500 mg) or placebo. A fasting blood sample was taken before and at regular intervals for 3 h after the meal. Serum was measured for bone turnover markers, C-terminal telopeptide of type I collagen (CTX) and osteocalcin, and for glycemic indices and gut peptides. Compared to placebo, SC attenuated the bone resorption marker, CTX, at 60, 90, and 120 min (p < 0.05) after the meal, and decreased osteocalcin, at 180 min (p < 0.05). As expected, SC attenuated the postprandial rise in glucose compared with placebo, whereas GLP-1 was increased at 60 min (p < 0.05) with SC. Serum GLP-1 explained 41% of the variance for change in postprandial CTX (p < 0.05). This study indicates that attenuating postprandial glycemic indices, with an α-GI, markedly decreases postprandial bone resorption and can be explained by the rise in GLP-1. Future studies should determine whether longer term α-GI use benefits bone health.

Training to ensure good documentation practices and adherence to regulatory requirements in human nutrition randomized controlled trials has not been given sufficient attention. Furthermore, it is difficult to find this information conveniently organized or in a form relevant to nutrition protocols. Current gaps in training and research surveillance exist in clinical nutrition research because training modules emphasize drugs and devices, promote reliance on monitoring boards, and lack nutrition expertise on human nutrition research teams. Additionally, because eating is essential, ongoing, and highly individualized, it is difficult to distinguish risks associated with interventions from eating under free-living conditions. Controlled-feeding trials provide an option to gain more experimental control over food consumed, but at a price of less external validity, and may pose human behavior issues that are unrelated to the intervention. This paper covers many of the expected practices for documentation and regulation that may be encountered in planning and conducting nutrition intervention trials with examples and references that should be useful to clinical nutrition researchers, funders of research, and research institutions. Included are definitions and guidance on clinical nutrition research oversight (institutional review boards, data safety and monitoring boards, US FDA); participant safety; standard operating procedures; training of investigators, staff, and students; and local culture and reporting requirements relevant to diet-related clinical research conduct and documentation.

BACKGROUND: Hip fractures are associated with a high rate of morbidity and mortality, and successful ambulation after surgery is an important outcome in this patient population. OBJECTIVE: This study aims to determine whether 25-hydroxyvitamin D [25(OH)D] concentration or the Geriatric Nutritional Risk Index (GNRI) is associated with mortality or rates of walking in a patient cohort after hip fracture surgery. METHODS: Patients undergoing hip fracture repair from a multisite study in North America were included. Mortality and mobility were assessed at 30 and 60 d after surgery. Serum albumin, 25(OH)D, and intact parathyroid hormone were measured. Patients were characterized according to 25(OH)D

To investigate Klotho level and its association with biochemical indices of primary hyperparathyroidism (PHPT). Fifty PHPT patients and fifty-two age- and body mass index-(BMI) matched healthy control subjects were recruited. In addition, twenty-five PHPT patients underwent parathyroidectomy (PTX) and had 4-month follow-up visits. Intact parathyroid hormone (iPTH), 25-hydroxyvitamin D [25(OH)D], calcium, albumin, corrected calcium, and Klotho levels were determined. There was no significant difference in age and BMI between PHPT subjects and controls (p > 0.05). PHPT patients had Klotho levels (15.4 ± 1.2 ng/mL) about 23% higher compared with those of the controls (11.9 ± 0.8 ng/mL), but this difference was not significant (p = 0.063). However, postmenopausal PHPT patients had 45% higher Klotho levels (17.6 ± 1.5 ng/ml) compared with postmenopausal controls (12.1 ± 0.9 ng/mL, p = 0.008). For postmenopausal subjects, Klotho levels had positive correlation with levels of iPTH (r = 0.25, p = 0.026) and corrected calcium (r = 0.34, p = 0.003), but negative correlation with 25(OH)D (r = −0.23, p = 0.042). After PTX, levels of iPTH and corrected calcium decreased and 25(OH)D levels increased to normal range (p

Objective: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevated parathyroid hormone (PTH) levels with persistently normal calcium levels. The diagnosis of NPHPT assumes the absence of secondary causes of elevated PTH levels. The objective of the current study was to examine levels of free 25-hydroxyvitamin D (25[OH]D) in NPHPT subjects and healthy controls. Methods: Ten NPHPT subjects and 20 controls who were age, sex, race, and body mass index (BMI) matched were examined. The diagnosis of NPHPT was made if subjects had (1) a serum calcium level of 8.6 to 10.4 mg/dL, total 25(OH)D 30 to 40 ng/mL, and intact PTH (iPTH) ≥66 pg/mL; and (2) normal renal and liver function. Serum total 25(OH)D levels were measured by radioimmunoassay, and free 25(OH)D levels were determined using an enzyme-linked immunoassay. Results: Mean age of NPHPT subjects was 59.9 ± 5.4 years, and mean BMI was 28.4 ± 2.3 kg/m2, which was not significantly different from the mean age and BMI of the control subjects. Mean total 25(OH)D level was 31.9 ± 1.7 ng/mL in NPHPT subjects and did not differ from that of the controls (32.7 ± 3.3 ng/mL; P = .52). However, mean free 25(OH)D was 5.0 ± 0.9 pg/mL in NPHPT subjects, which was 20% lower compared to the mean of the controls (6.2 ± 1.3 pg/mL; P = .013). Serum iPTH levels were inversely correlated with levels of measured free 25(OH)D (r = -0.42; P .10). Conclusion: Measured free 25(OH)D levels are lower in NPHPT subjects than in healthy control subjects. We suggest that some NPHPT subjects may actually have secondary hyperparathyroidism based on their free 25(OH) D levels. Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; CV = coefficient of variation; DBP = vitamin D-binding protein; iPTH = intact parathyroid hormone; NPHPT = normocalcemic primary hyperparathyroidism.

Higher protein intake during weight loss is associated with better health outcomes, but whether this is because of improved diet quality is not known. The purpose of this study was to examine how the change in self-selected protein intake during caloric restriction (CR) alters diet quality and lean body mass (LBM).In this analysis of pooled data from multiple weight loss trials, 207 adults with overweight or obesity were examined before and during 6 months of CR (approximately 10 food records/person). Body composition was measured by dual-energy x-ray absorptiometry. Diet quality was assessed using the Healthy Eating Index in 2 groups: lower (LP) and higher (HP) protein intake.Participants (mean [SD], 54 [11] years; 29 [4] kg/mIncreasing dietary protein during CR improves diet quality and may be another reason for reduced LBM, but it requires further study.

OBJECTIVE This study aimed to examine change in bone mineral density (BMD) and trabecular bone score among older adult weight regainers (WR) and weight maintainers (WM). METHODS Observational data come from 77 older adults (mean age: 67 [SD 5] years; 69% women; 70% white) with obesity (mean BMI: 33.6 [SD 3.7] kg/m2 ) who lost weight during an 18-month weight loss intervention. Total body mass and body composition, along with regional (total hip, femoral neck, lumbar spine) BMD and trabecular bone score, were measured at baseline, 18 months, and 30 months. WR (n = 36) and WM (n = 41) categories were defined as a ≥ 5% or

Fruit and vegetables (FV) have been a cornerstone of healthy dietary recommendations; the 2015-2020 U.S. Dietary Guidelines for Americans recommend that FV constitute one-half of the plate at each meal. FV include a diverse collection of plant foods that vary in their energy, nutrient, and dietary bioactive contents. FV have potential health-promoting effects beyond providing basic nutrition needs in humans, including their role in reducing inflammation and their potential preventive effects on various chronic disease states leading to decreases in years lost due to premature mortality and years lived with disability/morbidity. Current global intakes of FV are well below recommendations. Given the importance of FV for health, public policies that promote dietary interventions to help increase FV intake are warranted. This externally commissioned expert comprehensive narrative, umbrella review summarizes up-to-date clinical and observational evidence on current intakes of FV, discusses the available evidence on the potential health benefits of FV, and offers implementation strategies to help ensure that public health messaging is reflective of current science. This review demonstrates that FV provide benefits beyond helping to achieve basic nutrient requirements in humans. The scientific evidence for providing public health recommendations to increase FV consumption for prevention of disease is strong. Current evidence suggests that FV have the strongest effects in relation to prevention of CVDs, noting a nonlinear threshold effect of 800 g per day (i.e., about 5 servings a day). A growing body of clinical evidence (mostly small RCTs) demonstrates effects of specific FV on certain chronic disease states; however, more research on the role of individual FV for specific disease prevention strategies is still needed in many areas. Data from the systematic reviews and mostly observational studies cited in this report also support intake of certain types of FV, particularly cruciferous vegetables, dark-green leafy vegetables, citrus fruits, and dark-colored berries, which have superior effects on biomarkers, surrogate endpoints, and outcomes of chronic disease.

Vitamin D may affect cognitive performance, but previous studies are either short term or observational. We conducted a randomized controlled trial of vitamin D supplementation on domain-specific cognitive measures in postmenopausal women. Overweight/obese women with serum 25-hydroxyvitamin D (25OHD) levels less than 30 ng/mL were recruited. Vitamin D3 supplementation (600, 2,000, or 4,000 IU/d) was randomly assigned in a double-blinded manner for 1 year. Serum 25-hydroxyvitamin D, osteocalcin (total and undercarboxylated), amyloid beta, parathyroid hormone, and estradiol were analyzed before and after supplementation. Cognitive tests were administered after treatment. The women (58 ± 6 years; body mass index, 30.0 ± 3.5 kg/m2) had a baseline serum 25-hydroxyvitamin D level of 22.6 ± 5.8 ng/mL that increased to 30.2 ± 5.6, 36.0 ± 4.9, and 40.8 ± 7.0 ng/mL in the 600, 2,000, and 4,000 IU/d groups, respectively (p < .001). Participants taking 2,000 IU/d compared to other doses performed better in learning and memory tests (p < .05), yet the 4,000 IU/d group had a slower reaction time compared to the 600 IU/d group. Multiple regression indicated that serum undercarboxylated osteocalcin predicted tasks associated with reaction time and executive function, whereas body mass index and parathyroid hormone negatively predicted reaction time and executive function (p ≤ .01). These data suggest that vitamin D has differential effects on domain-specific cognitive measures and that a higher dose may negatively affect reaction time.

BACKGROUND: Dietary protein and micronutrients are important to the maintenance of bone health and may be an effective countermeasure to weight-loss–associated bone loss. OBJECTIVES: We aimed to determine the effect of a 6-mo hypocaloric, nutritionally complete, higher-protein meal plan on change in bone density and quality as compared with weight stability in older adults using a randomized post-test design. We hypothesized that participants randomly assigned to this meal plan would maintain similar bone density and quality to weight-stable controls, despite significant reductions in body mass. METHODS: Ninety-six older adults (aged 70.3 ± 3.7 y, 74% women, 27% African American) with obesity [body mass index (kg/m(2)): 35.4 ± 3.3] were randomly assigned to a 6-mo hypocaloric, nutritionally complete, higher-protein meal plan targeting ≥1.0 g protein · kg body weight(–1) · d(–1) [weight-loss (WL) group; n = 47] or to a weight-stability (WS) group targeting 0.8 g protein · kg body weight(–1) · d(–1), the current Recommended Dietary Allowance (n = 49). The primary outcome was total hip bone mineral density (BMD), with femoral neck BMD, lumbar spine BMD, and lumbar spine trabecular bone score (TBS) as secondary outcomes, all assessed at baseline and 3 and 6 mo with dual-energy X-ray absorptiometry. RESULTS: Baseline total hip, femoral neck, and lumbar spine BMDs were 1.016 ± 0.160, 0.941 ± 0.142, and 1.287 ± 0.246 g/cm(2), respectively; lumbar TBS was 1.398 ± 0.109. Despite significant weight loss achieved in the WL group (6.6 ± 0.4 kg; 8.6% ± 0.4% of baseline weight), 6-mo regional BMD estimates were similar to those in the WS group (all P > 0.05). Lumbar spine TBS significantly increased at 6 mo in the WL group (mean: 1.421; 95% CI: 1.401, 1.441) compared with the WS group (1.390: 95% CI: 1.370, 1.409; P = 0.02). CONCLUSIONS: Older adults following a hypocaloric, nutritionally complete, higher-protein meal plan maintained similar bone density and quality to weight-stable controls. Our data suggest that adherence to this diet does not produce loss of hip and spine bone density in older adults and may improve bone quality. This trial was registered at clinicaltrials.gov as NCT02730988.

In the mouse, the osteoblast-derived hormone Lipocalin-2 (LCN2) suppresses food intake and acts as a satiety signal. We show here that meal challenges increase serum LCN2 levels in persons with normal or overweight, but not in individuals with obesity. Postprandial LCN2 serum levels correlate inversely with hunger sensation in challenged subjects. We further show through brain PET scans of monkeys injected with radiolabeled recombinant human LCN2 (rh-LCN2) and autoradiography in baboon, macaque, and human brain sections, that LCN2 crosses the blood-brain barrier and localizes to the hypothalamus in primates. In addition, daily treatment of lean monkeys with rh-LCN2 decreases food intake by 21%, without overt side effects. These studies demonstrate the biology of LCN2 as a satiety factor and indicator and anorexigenic signal in primates. Failure to stimulate postprandial LCN2 in individuals with obesity may contribute to metabolic dysregulation, suggesting that LCN2 may be a novel target for obesity treatment., eLife digest Obesity has reached epidemic proportions worldwide and affects more than 40% of adults in the United States. People with obesity have a greater likelihood of developing type 2 diabetes, cardiovascular disease or chronic kidney disease. Changes in diet and exercise can be difficult to follow and result in minimal weight loss that is rarely sustained overtime. In fact, in people with obesity, weight loss can lower the metabolism leading to increased weight gain. New drugs may help some individuals achieve 5 to 10% weight loss but have side effects that prevent long-term use. Previous studies in mice show that a hormone called Lipocalin-2 (LCN2) suppresses appetite. It also reduces body weight and improves sugar metabolism in the animals. But whether this hormone has the same effects in humans or other primates is unclear. If it does, LCN2 might be a potential obesity treatment. Now, Petropoulou et al. show that LCN2 suppressed appetite in humans and monkeys. In human studies, LCN2 levels increased after a meal in individuals with normal weight or overweight, but not in individuals with obesity. Higher levels of LCN2 in a person’s blood were also associated with a feeling of reduced hunger. Using brain scans, Petropoulou et al. showed that LCN2 crossed the blood-brain barrier in monkeys and bound to the hypothalamus, the brain center regulating appetite and energy balance. LCN2 also bound to human and monkey hypothalamus tissue in laboratory experiments. When injected into monkeys, the hormone suppressed food intake and lowered body weight without toxic effects in short-term studies. The experiments lay the initial groundwork for testing whether LCN2 might be a useful treatment for obesity. More studies in animals will help scientists understand how LCN2 works, which patients might benefit, how it would be given to patients and for how long. Clinical trials would also be needed to verify whether it is an effective and safe treatment for obesity.

Persons with neurologically motor‐complete spinal cord injury (SCI) have a marked loss of bone mineral density (BMD) of the long bones of the lower extremities, predisposing them to fragility fractures, especially at the knee. Denosumab, a commercially available human monoclonal IgG antibody to receptor activator of nuclear factor‐κB ligand (RANKL), may provide an immunopharmacological solution to the rapid progressive deterioration of sublesional bone after SCI. Twenty‐six SCI participants with subacute motor‐complete SCI were randomized to receive either denosumab (60 mg) or placebo at baseline (BL), 6, and 12 months. Areal bone mineral density (aBMD) by dual energy x‐ray absorptiometry (DXA) at 18 months at the distal femur was the primary outcome and aBMD of the proximal tibia and hip were the secondary outcomes analyzed in 18 of the 26 participants (denosumab, n = 10 and placebo, n = 8). The metrics of peripheral QCT (pQCT) were the exploratory outcomes analyzed in a subsample of the cohort (denosumab, n = 7 and placebo n = 7). The mean aBMD (±95% CI) for the denosumab versus the placebo groups demonstrated a significant group × time interactions for the following regions of interest at BL and 18 months: distal femoral metaphysis = mean aBMD 1.187; 95% CI, 1.074 to 1.300 and mean aBMD 1.202; 95% CI, 1.074 to 1.329 versus mean aBMD 1.162; 95% CI, 0.962 to 1.362 and mean aBMD 0.961; 95% CI, 0.763 to 1.159, respectively (p

During the prosecution and defence of drink-driving cases, forensic practitioners are often required to engage in various blood-alcohol calculations, such as whether or not the statutory limit was exceeded (e.g. 80mg/100mL, 0.08g/100mL or 0.80g/L). For this purpose, most forensic scientists utilize the Widmark equation, or some modification thereof, to calculate a person's blood alcohol concentration (BAC) based on information about the amount of ethanol consumed and the pattern of drinking. This equation comes in two main forms; one of which incorporates the apparent volume of distribution of ethanol (V) and the other a person's total body water (TBW). In this study, we utilised two independent data sets, one involving the determination of V for ethanol in 173 men and 63 women, and the other TBW determined for 582 men and 884 women. Those subjects included in the TBW group represented various racial groups (Caucasians, African Americans, Hispanics, Asians and Puerto Ricans), with body mass index (BMI) ranging from 17 to 80kg/m2. Both versions of the Widmark equation were evaluated in relation to their accuracy and precision in predicting TBW and/or V using the two most common anthropometric equations; those of Watson et al. and Forrest. Both anthropometric equations exhibited good accuracy (

Background: Vitamin D3 is metabolized to 25-hydroxyvitamin D [25(OH)D] in liver, and only after it goes to kidney is it converted to its biologically active form, 1,25-dihydroxyvitamin D [1,25(OH)2D]. Also, the majority of both total 25(OH)D and 1,25(OH)2D are tightly bound to vitamin D bind protein (DBP) and only a small portion remains in free form. In certain patient populations, like primary hyperparathyroidism (PHPT), concentrations of free vitamin D metabolites may be affected by altered levels of binding protein. Objective: To evaluate total and free 1,25(OH)2D levels in PHPT patients and healthy controls. Methods: Thirty female patients with PHPT and 30 healthy age and body mass index (BMI) matched controls were enrolled (57.1 ± 9.8 years and BMI of 32.2 ± 7.2 kg/m2). Serum levels of calcium, intact parathyroid hormone (iPTH), DBP, total 25(OH)D and 1,25(OH)2D levels were examined. Serum free 25(OH)D and 1,25(OH)2D levels were calculated using equations adapted from Bikle et al. Results: There were no significant differences in age and BMI between groups. Compared to controls, patients with PHPT had lower total 25(OH)D (25.2 ± 7.5 vs. 19.3 ± 6.4 ng/mL; p Conclusion: Postmenopausal patients with PHPT had lower serum total 25(OH)D, but similar free 25(OH)D levels. In contrast, total 1,25(OH)2D levels did not differ between patients and controls; however, patients had higher free 1,25(OH)2D. Because total 25(OH)D and 1,25(OH)2D levels do not reflect free levels, standard clinical measures of circulating vitamin D may not be an accurate estimate of true vitamin D status in patients with PHPT. References: Bikle et al. Serum Protein Binding of 1,25-Dihydroxyvitamin D: A Reevaluation by Direct Measurement of Free Metabolite Levels. JCEM 1985;61:969-75.

The objective of this study was to determine the ability of either aerobic or resistance training to counter weight loss associated bone loss in older adults. 187 older adults (67 years, 70% women, 64% Caucasian) with obesity (body mass index: 34.5±3.7 kg/m2) and cardiovascular disease and/or metabolic syndrome were randomized to participate in an 18 month, community-based trial, with a follow-up assessment occurring at 30 months. Intervention arms included: weight loss alone (WL; 7–10% baseline weight), WL plus aerobic training (WL+AT), and WL plus resistance training (WL+RT). Dual energy x-ray absorptiometry (DXA) acquired total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD) and trabecular bone score (TBS); and biomarkers of bone turnover (Procollagen Type 1 N-Terminal Propeptide, C-Terminal Telopeptide of Type 1 Collagen) were measured at baseline, six, 18, and 30 (aBMD and TBS, only) months. Computed tomography (CT) acquired hip and spine volumetric BMD (vBMD), cortical thickness, and bone strength was measured in a subset at baseline (n=55) and 18 months. Total hip aBMD was reduced by 2% in all groups at 18 months, with primary analysis showing no significant treatment effects for any DXA, biomarker, or CT outcome. After adjustment for weight loss and followed to 30 months, secondary analyses reveal total hip [−0.018 (−0.023 to −0.012) g/cm2 vs −0.025 (−0.031 to −0.019) g/cm2; p=0.05] and femoral neck [−0.01 (−0.009 to 0.008) g/cm2 vs −0.011 (−0.020 to −0.002) g/cm2; p=0.06] aBMD estimates were modestly attenuated in WL+RT compared to WL. Additionally, lumbar spine aBMD was increased in WL [0.015 (0.007 to 0.024) g/cm2] and WL+RT [0.009 (0.000 to 0.017) g/cm2] compared to WL+AT [−0.003 (−0.012 to 0.005) g/cm2]; both p≤0.01. Community-based exercise does not prevent bone loss during active weight loss in older adults; however, adding resistance training may help minimize long-term hip bone loss. Trial Registration: clinicaltrials.gov Identifier:{"type":"clinical-trial","attrs":{"text":"NCT01547182","term_id":"NCT01547182"}}NCT01547182.

Background Menopause is associated with fatty liver, glucose dysregulation, increased body fat, and impaired bone quality. Previously, it was demonstrated that single sessions of high-intensity interval exercise (HIIE) are more effective than distance- and duration-matched continuous exercise (CE) on altering hepatic triglyceride (TG) metabolism and very-low density lipoprotein-TG (VLDL-TG) secretion. Methods Six weeks training using these modalities was examined for effects on hepatic TG metabolism/secretion, glucose tolerance, body composition, and bone mineral density (BMD) in ovariectomized (OVX) and sham-operated (SHAM) mice. OVX and SHAM were assigned to distance- and duration-matched CE and HIIE, or sedentary control. Results Energy expenditure during exercise was confirmed to be identical between CE and HIIE and both similarly reduced post-exercise absolute carbohydrate oxidation and spontaneous physical activity (SPA). OVX vs. SHAM displayed impaired glucose tolerance and greater body fat despite lower hepatic TG, and these outcomes were not affected by training. Only HIIE increased hepatic AMPK in OVX and SHAM, but neither training type impacted VLDL-TG secretion. As expected, BMD was lower in OVX, and training did not affect long bones. Conclusions The results reveal intensity-dependent effects on hepatic AMPK expression and general exercise effects on subsequent SPA and substrate oxidation that is independent of estrogen status. These findings support the notion that HIIE can impact aspects of liver physiology in females while the effects of exercise on whole body substrate selection appear to be independent of training intensity. However, neither exercise approach mitigated the impairment in glucose tolerance and elevated body fat occurring in OVX mice.

In vivo studies measuring true fractional calcium (Ca) absorption have shown that dietary fat is a significant predictor of absorption and is influenced by luminal pH levels. However, whether changes in Ca bioaccessibility (CaB) can explain the effects on absorption has not been examined. In the current study, we examined two high fat diets enriched in either monounsaturated fatty acids or saturated fatty acids (SFA), and a low-fat diet (LFD), each with 50 mg Ca, and measured CaB at different intestinal regions during normal acidic or higher (pH = 7) gastrointestinal conditions using an in vitro gastrointestinal model. During normal pH conditions in the jejunum, there was an interaction between diet and time for CaB (P < 0.02), and CaB during the SFA diet was higher than LFD (P = 0.05). CaB was reduced by 90 ± 3% during higher compared with normal pH under all dietary conditions (P < 0.001). These findings indicate that fat intake, especially SFA enriched, is associated with a greater CaB in the jejunum, and may explain the higher Ca absorption in previous studies. In addition, the marked reduction in CaB under higher pH conditions could have implications in persons taking medications to reduce gastric acid.

BACKGROUND: Alternate day fasting (ADF) is a novel diet therapy that reduces body weight, but its effect on bone health remains unknown. OBJECTIVE: This study examined the impact of ADF versus traditional daily calorie restriction (CR) on markers of bone metabolism in a 6-month randomized controlled trial. METHODS: Overweight and obese subjects (n = 100) were randomized to 1 of 3 groups for 6 months: 1) ADF (25% energy intake fast day, alternated with 125% intake feast day; 2) CR (75% intake every day); or 3) control (usual intake every day). RESULTS: Body weight decreased similarly (P

Background The importance of vitamin D in general health as well as in human reproductive success has been an area of focus. A better understanding of vitamin D metabolism, particularly vitamin D binding protein, is important when elucidating this relationship. Methods This case control trial seeks to characterize vitamin D metabolism in infertile patients undergoing natural cycle IVF as compared to normally cycling premenopausal women with proven fertility matched for age and body mass index (BMI). A total of 68 subjects were examined; 39 were infertile premenopausal women and 29 were regularly cycling fertile controls. Their 25-hydroxy vitamin D (25OHD), vitamin D binding protein (DBP), and albumin were measured and free and bioavailable 25OHD calculated. Between group comparisons were conducted with an unpaired t-test. A stepwise regression using age, BMI, 25OHD, estradiol & albumin in the model were used to determine predictors of DBP. Results Age, BMI, and total 25OHD did not differ between the two groups. However, vitamin D binding protein, free and bioavailable vitamin D were significantly different in the infertile patients as compared to the regularly cycling fertile controls (p

Low circulating 25-hydroxyvitamin D (25OHD) is commonly found in obese individuals and is often attributed to a volume dilution effect of adipose tissue. However, low vitamin D (LD) intake may contribute to the obesity itself. In this study, we examine whether low vitamin D status contributes to increased food intake and weight gain and can be explained by altered brain serotonin metabolism in 8-month-old female C57BL/6J mice. In a first experiment, mice were fed a 45% high-fat diet (HFD) containing different amounts of vitamin D at low (100 IU/kg), normal (1,000 IU/kg) or high (10,000 IU/kg) intake. After 10 weeks, mice fed LD had greater energy intake, weight gain, total and hepatic fat than the higher vitamin D groups (P < .05). In a second experiment, mice were examined for the central serotonin regulation of food intake after a 10% normal-fat diet (NFD) or 45% HFD containing low (100 IU/kg) or normal (1000 IU/kg) vitamin D. After 10 weeks, both HFD and LD diets attenuated circulating 25OHD concentration. Additionally, LD intake lowered cortical serotonin level, regardless of dietary fat intake (P < .05). In the arcuate and raphe nuclei, gene expression of vitamin D 1α-hydroxylase was lower due to LD during HFD feeding (P < .05). Tryptophan hydroxylase-2 and serotonin reuptake transporter gene expression was not altered due to LD. Overall, these findings suggest that a LD diet alters peripheral 25OHD, reduces central serotonin, and may contribute to weight gain in an obesogenic environment.

OBJECTIVES: Hip fractures are associated with a high rate of morbidity and mortality, and successful ambulation after surgery is an important outcome in this patient population. This study aims to determine whether 25-hydroxyvitamin D (25(OH)D) or the Geriatric Nutritional Risk Index (GNRI) is associated with short term mortality or ability to walk after hip fracture surgery. METHODS: Patients undergoing hip fracture repair were included in this study. Mortality and walking ability were assessed at 30 and 60 days after hip fracture surgery. Pre-operative serum albumin and 25(OH)D were measured. Patients were characterized with 25(OH)D

Objective: To evaluate vitamin D binding protein and free 25-hydroxyvitamin D [25(OH)D] levels in healthy controls compared to primary hyperparathyroidism (PHPT) patients, and to examine PHPT before and after surgery.Methods: Seventy-five PHPT patients and 75 healthy age, gender, and body mass index (BMI) -matched control subjects were examined. In addition, 25 PHPT patients underwent parathyroidectomy and had a 3-month follow up visit. Levels of total and free 25(OH)D, DBP, and intact parathyroid hormone (iPTH) were determined before and 3 months after surgery.Results: There was no significant difference in age and BMI between PHPT patients and controls. Levels of 25(OH)D and DBP were lower in PHPT patients compared to controls (p < 0.01). There was no significant difference in calculated free and bioavailable 25(OH)D levels between PHPT patients and controls. Calcium and iPTH levels decreased to normal but DBP and DBP-bound-25(OH)D increased (P < 0.001) after parathyroidectomy. Levels of DBP were inversely correlated with iPTH (r = −0.406, P < 0.001) and calcium levels (r = −0.423, P < 0.001).Conclusion: Serum DBP levels were lower in patients with PHPT and parathyroidectomy restored DBP levels. We suggest that lower DBP levels is one of contributing mechanisms of low total 25(OH)D in PTHP patients and the total 25(OH)D levels might not reflect true vitamin D status in PHPT patients.

Background Despite evidence of the endocrine disrupting properties of zearalenone (ZEN) and alpha-zearalanol (zeranol, α-ZAL), they have been minimally studied in human populations. In previous cross-sectional analyses, we demonstrated that 9–10 years old girls with detectable urinary ZEN were of shorter stature and less likely to have reached the onset of breast development than girls with undetectable urinary ZEN. The aim of this study was to examine baseline concentrations of ZEN, (α-ZAL), and their phase-1 metabolites in relation to subsequent growth and timing of menarche using 10 years of longitudinal data. Methods Urine samples were collected from participants in the Jersey Girl Study at age 9–10 (n = 163). Unconjugated ZEN, (α-ZAL), and their metabolites were analyzed using high performance liquid chromatography and tandem mass spectrometry. Information on height, weight, and pubertal development was collected at a baseline visit with annual follow-up by mail thereafter. Cox regression was used to evaluate time to menarche in relation to baseline ZEN, (α-ZAL), and total mycoestrogen exposure. Z-scores for height and weight were used in mixed models to assess growth. Results Mycoestrogens were detectable in urine in 78.5% of the girls (median ZEN: 1.02 ng/ml, range 0–22.3). Girls with detectable urinary concentrations of (α-ZAL) and total mycoestrogens (sum of ZEN, (α-ZAL) and their metabolites) at baseline were significantly shorter at menarche than girls with levels below detection (p = 0.04). ZEN and total mycoestrogen concentrations were inversely associated with height- and weight-z-scores at menarche (adjusted β = − 0.18, 95% CI: -0.29, − 0.08, and adjusted β = − 0.10, 95% CI: -0.21, 0.01, respectively). Conclusion This study supports and extends our previous results suggesting that exposure to ZEN, (α-ZAL), and their metabolites is associated with slower growth and pubertal development in adolescent girls.

OBJECTIVES: Serum calcidiol is inversely associated with BMI in obese individuals and murine research has shown that vitamin D deficient diets (VDD) increase body weight. Alcohol intake doesn't necessarily increase body weight despite its caloric density but has been associated with VDD. The objective of this study was to determine the effect of vitamin D deficiency with or without alcohol on body weight, body composition, glucose tolerance, and energy expenditure in seven-month-old female mice. METHODS: Seven-month-old female retired breeder C57BL/6J mice (n = 40) were weight-matched and randomized to one of four diets: control (normal purified AIN-93 diet), vitamin D deficient (VDD, 0 intake of vitamin D), alcohol (Alc, 10% ethanol), or vitamin D deficient and alcohol (VDD + Alc). Mice were fed ad libitum for 8 weeks. Body weight and food intake were recorded weekly and body composition was measured at baseline and final time points using EchoMRI. Glucose tolerance and energy expenditure (EE) were assessed by an oral glucose tolerance test (OGTT) and Oxymax/CLAMS unit at week 8. RESULTS: Body weight at baseline was 27.4 ± 1.8 g and did not differ between groups. Mice drinking alcohol had a decreased food intake (p

Diet induced obesity has been shown to reduce bone mineral density (BMD) and Ca absorption. However, previous experiments have not examined the effect of high fat diet (HFD) in the absence of obesity or addressed the type of dietary fatty acids. The primary objective of this study was to determine the effects of different types of high fat feeding, without obesity, on fractional calcium absorption (FCA) and bone health. It was hypothesized that dietary fat would increase FCA and reduce BMD. Mature 8-month-old female C57BL/6J mice were fed one of three diets: a HFD (45% fat) enriched either with monounsaturated fatty acids (MUFAs) or with saturated fatty acids (SFAs), and a normal fat diet (NFD; 10% fat). Food consumption was controlled to achieve a similar body weight gain in all groups. After 8wk, total body bone mineral content and BMD as well as femur total and cortical volumetric BMD were lower in SFA compared with NFD groups (P < 0.05). In contrast, femoral trabecular bone was not affected by the SFAs, whereas MUFAs increased trabecular volume fraction and thickness. The rise over time in FCA was greater in mice fed HFD than NFD and final FCA was higher with HFD (P < 0.05). Intestinal calbindin-D9k gene and hepatic cytochrome P450 2r1 protein levels were higher with the MUFA than the NFD diet (P < 0.05). In conclusion, HFDs elevated FCA overtime; however, an adverse effect of HFD on bone was only observed in the SFA group, while MUFAs show neutral or beneficial effects.

To evaluate the measured free 25-hydroxyvitamin D [25(OH)D] levels in patients with hyperparathyroidism (PHPT) and healthy controls. Eighty patients with PHPT(n = 40) and age and BMI matched controls (n = 40) were examined. Serum levels of total or free 25(OH)D, vitamin D binding protein (DBP), intact parathyroid hormone (iPTH) and calcium were measured. There was no significant difference in age (61.2 ± 11.9 vs 60.2 ± 7.0 years) and BMI (30.0 ± 6.1 vs 30.0 ± 2.2 kg/m2) between PHPT patients and healthy subjects. Levels of total 25(OH)D were about 20 % lower in PHPT patients (26.4 ± 7.7 ng/mL) compared to controls (31.0 ± 7.8 ng/mL, P < 0.05). There were no significant differences in calculated or measured free 25(OH)D levels between PHPT patients (4.9 ± 1.8 or 4.9 ± 1.6 pg/mL, respectively) and control subjects (5.1 ± 1.2 or 5.3 ± 1.6 pg/mL, respectively). Levels of free 25(OH)D were positively associated with levels of total 25(OH)D (r = 0.28, P < 0.05) but negatively correlated with iPTH and calcium levels (r=-0.22 and -0.23 respectively, P < 0.05). Serum total 25(OH)D levels were lower but the calculated or measured free 25(OH)D levels in patients with PHPT did not differ from healthy subjects. We suggest that total 25(OH)D levels may not reflect true vitamin D nutritional status in patients with PHPT.

Obesity induced by high-fat diets (HFDs) is inversely associated with vitamin D status and bone health. However, the associations and effects of excessive fat intake on hepatic and renal vitamin D metabolism have not been addressed. The primary objective was to determine if excessive energy and fat intake, or the type of fat, affects serum 25-hydroxycholecalciferol concentration and whether this can be explained by an alteration of vitamin D-regulating enzymes in older mice. The second objective was a follow up of our recent findings that a high intake of monounsaturated fatty acids (MUFA) is not detrimental to bone in lean mice and whether this is also true under conditions of diet-induced obesity. In the study, twenty-one 8-month-old female C57BL/6 J mice were fed ad libitum for 10 weeks with a 10% normal-fat diet (NFD) or 45% HFD enriched with MUFA or saturated fatty acids (SFA). We found that the HFD, compared with NFD, resulted in greater energy intake, weight gain, total body fat, and liver fat (P < .05). Only the high SFA feeding resulted in higher mRNA but lower protein abundance of hepatic Cyp2r1 and lower renal Cyp24a1 mRNA expression than the NFD group (P < .05). Moreover, although bone mineral density did not differ among groups, the percent difference compared with NFD was significantly lower for SFA (P < .05) but not MUFA. Also, femoral trabecular bone volume fraction was lower (P < .05) only in the SFA compared with the NFD group. In conclusion, high SFA and MUFA feeding differentially affected gene and protein expressions of major vitamin D hydroxylases compared with NFD, but this was unrelated to the lower circulating 25-hydroxycholecalciferol concentration. In addition, only the SFA diet alters vitamin D metabolism and bone changes, indicating the importance of dietary fat composition.

The environmental estrogen, zearalenone (ZEA), is found in the food supply from Fusarium fungal contamination in grains and sometimes used as a growth promoter for beef cattle. Long-term exposure to ZEA and its metabolites may present health risk due to higher estrogenic activity. Serum ZEA metabolites were measured to determine the exposure and the association with food intake in 48 overweight/obese women (52 ± 9 years). The free and conjugated ZEA indicated the highest detection rate of all the metabolites. Conjugated ZEA and total ZEA metabolites were lower (p = 0.02) in overweight/obese than normal weight women, and free metabolites were either the same or showed a trend to be higher. In addition, those with highest (280-480 g/d) compared those with lowest (