Resveratrol Does Not Influence Metabolic Risk Markers Related to Cardiovascular Health in Overweight and Slightly Obese Subjects: A Randomized,Placebo-Controlled Crossover Trial

Background

In vitro and animal studies have shown positive effects of resveratrol on lipid and lipoprotein metabolism, but human studies specifically designed to examine these effects are lacking.

Objective

The primary outcome parameter of this study in overweight and slightly obese subjects was the effect of resveratrol on apoA-I concentrations. Secondary outcome parameters were effects on other markers of lipid and lipoprotein metabolism, glucose metabolism, and markers for inflammation and endothelial function.

Design

This randomized, placebo-controlled crossover study was conducted in 45 overweight and slightly obese men (n = 25) and women (n = 20) with a mean age of 61 ± 7 years. Subjects received in random order resveratrol (150 mg per day) or placebo capsules for 4 weeks, separated by a 4-week wash-out period. Fasting blood samples were collected at baseline and at the end of each intervention period.

Results

Compliance was excellent as indicated by capsule count and changes in resveratrol and dihydroresveratrol concentrations. No difference between resveratrol and placebo was found in any of the fasting serum or plasma metabolic risk markers (mean ± SD for differences between day 28 values of resveratrol vs. placebo: apoA-I; 0.00 ± 0.12 g/L (P = 0.791), apoB100; -0.01 ± 0.11 g/L (P = 0.545), HDL cholesterol; 0.00 ± 0.09 mmol/L (P = 0.721), LDL cholesterol -0.03 ± 0.57 mmol/L (P = 0.718), triacylglycerol; 0.10 ± 0.54 mmol/L (P = 0.687), glucose; -0.08 ± 0.28 mmol/L (P = 0.064), insulin; -0.3 ± 2.5 mU/L (P = 0.516)). Also, no effects on plasma markers for inflammation and endothelial function were observed. No adverse events related to resveratrol intake were observed.

Conclusion

150 mg of daily resveratrol intake for 4 weeks does not change metabolic risk markers related to cardiovascular health in overweight and slightly obese men and women. Effects on glucose metabolism warrant further study.

Trial Registration

ClinicalTrials.gov NCT01364961     

Caffeine Intake,Short Bouts of Physical Activity,and Energy Expenditure: A Double-Blind Randomized Crossover Trial

PA energy expenditure (PAEE) is the most variable component of Total Energy Expenditure (TEE) and largely due to the balance of sedentary time (SedT) and low intensity physical activity (LIPA). There has been an emergence for seeking an understanding of factors which determine variations in SedT, LIPA, and PAEE. Sedentary behavior and physical activity are relatively resistant to change by experimental dietary treatments and significant body weight changes. Although caffeine (Caf) is by far the most heavily used nutritional agent ingested to promote a sense of vigor/alertness, it is still unknown if Caf is effective in increasing PAEE and physical activity. The aim of the study was to test the hypothesis that 2 daily doses of Caf (as a capsule to blind the treatment and divided equally during breakfast and lunch) increase PAEE and TEE, and it would do so through increasing the frequent and brief bouts of physical activity (~1-5 min long) through the day as measured by accelerometry. In 21 low Caf users (<100 mg day^-1), we used a double-blind crossover trial (ClinicalTrials.govID;{"type":"clinical-trial","attrs":{"text":"NCT01477294","term_id":"NCT01477294"}}NCT01477294) with two conditions (4-day each with a 3-day washout period) randomly ordered as 5 mg kg^-1 day^-1 of Caf and maltodextrin as placebo (Plc). Resting energy expenditure (REE) by indirect calorimetry, total energy expenditure (TEE) from doubly labeled water, PAEE calculated as TEE-(REE+0.1TEE), and accelerometry measurements of both LIPA and MVPA were not different between conditions. However, regardless of caffeine or placebo, there were several significant relationships between brief bouts of LIPA and MVPA with PAEE. In conclusion, this double-blind study found that low and moderate-vigorous activity as well as the total volume of PAEE in free-living conditions is resistant to dietary caffeine intake that was equivalent to 5 cups of espresso or 7 cups of tea.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01477294","term_id":"NCT01477294"}}NCT01477294     

Reducing Anti‐Fat Prejudice in Preservice Health Students: A Randomized Trial

Anti‐fat sentiment is increasing, is prevalent in health professionals, and has health and social consequences. There is no evidence for effective obesity prejudice reduction techniques in health professionals. The present experiment sought to reduce implicit and explicit anti‐fat prejudice in preservice health students. Health promotion/public health bachelor degree program students (n = 159) were randomized to one of three tutorial conditions. One condition presented an obesity curriculum on the controllable reasons for obesity (i.e., diet/exercise). A prejudice reduction condition presented evidence on the uncontrollable reasons for obesity (i.e., genes/environment); whereas a neutral (control) curriculum focused on alcohol use in young people. Measures of implicit and explicit anti‐fat prejudice, beliefs about obese people, and dieting, were taken at baseline and postintervention. Repeated measures analyses showed decreases in two forms of implicit anti‐fat prejudice (decreases of 27 and 12%) in the genes/environment condition relative to other conditions. The diet/exercise condition showed a 27% increase in one measure of implicit anti‐fat prejudice. Reductions in explicit anti‐fat prejudice were also seen in the genes/environment condition (P = 0.006). No significant changes in beliefs about obese people or dieting control beliefs were found across conditions. The present results show that anti‐fat prejudice can be reduced or exacerbated depending on the causal information provided about obesity. The present results have implications for the training of health professionals, especially given their widespread negativity toward overweight and obesity.     

The Biphasic Effects of Moderate Alcohol Consumption with a Meal on Ambiance-Induced Mood and Autonomic Nervous System Balance: A Randomized Crossover Trial

Background

The pre-drinking mood state has been indicated to be an important factor in the mood effects of alcohol. However, for moderate alcohol consumption there are no controlled studies showing this association. Also, the mood effects of consuming alcohol combined with food are largely unknown. The aim of this study was to investigate the effects of moderate alcohol combined with a meal on ambiance-induced mood states. Furthermore effects on autonomic nervous system activity were measured to explore physiological mechanisms that may be involved in changes of mood state.

Methods

In a crossover design 28 women (age 18–45 y, BMI 18.5–27 kg/m²) were randomly allocated to 4 conditions in which they received 3 glasses of sparkling white wine (30 g alcohol) or alcohol-free sparkling white wine while having dinner in a room with either a pleasant or unpleasant created ambiance. Subjects filled out questionnaires (B-BAES, POMS and postprandial wellness questionnaire) at different times. Skin conductance and heart rate variability were measured continuously.

Results

Moderate alcohol consumption increased happiness scores in the unpleasant, but not in the pleasant ambiance. Alcohol consumption increased happiness and stimulation feelings within 1 hour and increased sedative feelings and sleepiness for 2.5 hour. Skin conductance was increased after alcohol within 1 hour and was related to happiness and stimulation scores. Heart rate variability was decreased after alcohol for 2 hours and was related to mental alertness.

Conclusion

Mood inductions and autonomic nervous system parameters may be useful to evaluate mood changes by nutritional interventions. Moderate alcohol consumption elevates happiness scores in an unpleasant ambiance. However, drinking alcohol during a pleasant mood results in an equally positive mood state.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01426022","term_id":"NCT01426022"}}NCT01426022.     

Bioavailability of Orally Administered rhGM-CSF: A Single-Dose,Randomized, Open-Label,Two-Period Crossover Trial

Background

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is usually administered by injection, and its oral administration in a clinical setting has been not yet reported. Here we demonstrate the bioavailability of orally administered rhGM-CSF in healthy volunteers. The rhGM-CSF was expressed in Bombyx mori expression system (BmrhGM-CSF).

Methods and Findings

Using a single-dose, randomized, open-label, two-period crossover clinical trial design, 19 healthy volunteers were orally administered with BmrhGM-CSF (8 µg/kg) and subcutaneously injected with rhGM-CSF (3.75 µg/kg) respectively. Serum samples were drawn at 0.0h, 0.5h ,0.75h,1.0h,1.5h,2.0h ,3.0h,4.0h,5.0h,6.0h,8.0h,10.0h and 12.0h after administrations. The hGM-CSF serum concentrations were determined by ELISA. The AUC was calculated using the trapezoid method. The relative bioavailability of BmrhGM-CSF was determined according to the AUC ratio of both orally administered and subcutaneously injected rhGM-CSF. Three volunteers were randomly selected from 15 orally administrated subjects with ELISA detectable values. Their serum samples at the 0.0h, 1.0h, 2.0h, 3.0h and 4.0h after the administrations were analyzed by Q-Trap MS/MS TOF. The different peaks were revealed by the spectrogram profile comparison of the 1.0h, 2.0h, 3.0h and 4.0h samples with that of the 0.0h sample, and further analyzed using both Enhanced Product Ion (EPI) scanning and Peptide Mass Fingerprinting Analysis. The rhGM-CSF was detected in the serum samples from 15 of 19 volunteers administrated with BmrhGM-CSF. Its bioavailability was observed at an average of 1.0%, with the highest of 3.1%. The rhGM-CSF peptide sequences in the serum samples were detected by MS analysis, and their sizes ranging from 2,039 to 7,336 Da.

Conclusions

The results demonstrated that the oral administered BmrhGM-CSF was absorbed into the blood. This study provides an approach for an oral administration of rhGM-CSF protein in clinical settings.

Trial Registration

www.chictr.org ChiCTR-TRC-00000107     

The Effect of Electronic Self‐Monitoring on Weight Loss and Dietary Intake: A Randomized Behavioral Weight Loss Trial

Technology may improve self‐monitoring adherence and dietary changes in weight loss treatment. Our study aimed to investigate whether using a personal digital assistant (PDA) with dietary and exercise software, with and without a feedback message, compared to using a paper diary/record (PR), results in greater weight loss and improved self‐monitoring adherence. Healthy adults (N = 210) with a mean BMI of 34.01 kg/m² were randomized to one of three self‐monitoring approaches: PR (n = 72), PDA with self‐monitoring software (n = 68), or PDA with self‐monitoring software and daily feedback messages (PDA+FB, n = 70). All participants received standard behavioral treatment. Self‐monitoring adherence and change in body weight, waist circumference, and diet were assessed at 6 months; retention was 91%. All participants had a significant weight loss (P < 0.01) but weight loss did not differ among groups. A higher proportion of PDA+FB participants (63%) achieved ≥5% weight loss in comparison to the PR group (46%) (P < 0.05) and PDA group (49%) (P = 0.09). Median percent self‐monitoring adherence over the 6 months was higher in the PDA groups (PDA 80%; PDA+FB 90%) than in the PR group (55%) (P < 0.01). Waist circumference decreased more in the PDA groups than the PR group (P = 0.02). Similarly, the PDA groups reduced energy and saturated fat intake more than the PR group (P < 0.05). Self‐monitoring adherence was greater in the PDA groups with the greatest weight change observed in the PDA+FB group.     

Effects of Exercise on Metabolic Risk Variables in Overweight Postmenopausal Women: A Randomized Clinical Trial

Objective: This study examined the effects of exercise on metabolic risk variables insulin, leptin, glucose, and triglycerides in overweight/obese postmenopausal women. Research Methods and Procedures: Sedentary women (n = 173) who were overweight or obese (BMI ≥ 25 kg/m² or ≥24 kg/m² with ≥33% body fat), 50 to 75 years of age, were randomized to 12 months of exercise (≥45 minutes of moderate‐intensity aerobic activity 5 d/wk) or to a stretching control group. Body composition (DXA) and visceral adiposity (computed tomography) were measured at baseline and 12 months. Insulin, glucose, triglycerides, and leptin were measured at baseline and 3 and 12 months. Insulin resistance was evaluated by the homeostasis model assessment formula. Differences from baseline to follow‐up were calculated and compared across groups. Results: Exercisers had a 4% decrease and controls had a 12% increase in insulin concentrations from baseline to 12 months (p = 0.0002). Over the same 12‐month period, leptin concentrations decreased by 7% among exercisers compared with remaining constant among controls (p = 0.03). Homeostasis model assessment scores decreased by 2% among exercisers and increased 14% among controls from baseline to 12 months (p = 0.0005). The exercise effect on insulin was modified by changes in total fat mass (trend, p = 0.03), such that the exercise intervention abolished increases in insulin concentrations associated with gains in total fat mass. Discussion: Regular moderate‐intensity exercise can be used to improve metabolic risk variables such as insulin and leptin in overweight/obese postmenopausal women. These results are promising for health care providers providing advice to postmenopausal women for lifestyle changes to reduce risk of insulin resistance, coronary heart disease, and diabetes.     

Lack of Functional Benefit with Glutamine versus Placebo in Duchenne Muscular Dystrophy: A Randomized Crossover Trial

Background

Oral glutamine decreases whole body protein breakdown in Duchenne muscular dystrophy (DMD). We evaluated the functional benefit of 4 months oral glutamine in DMD.

Methodology/Principal Findings

30 ambulant DMD boys were included in this double-blind, randomized crossover trial with 2 intervention periods: glutamine (0.5 g/kg/d) and placebo, 4 months each, separated by a 1-month wash-out, at 3 outpatient clinical investigation centers in France. Functional benefit was tested by comparing glutamine versus placebo on change in walking speed at 4 months. Secondary outcome measures were: 2-minute walk test, work, power, muscle mass (urinary creatinine), markers of myofibrillar protein breakdown (urinary 3-methyl-histidine/creatinine), serum creatine phospho-kinase, body composition (fat free mass, fat mass percentage), safety and oral nutrient intake. There was no improvement in the primary end point (walking speed) or in secondary measures of muscle function (2-minute walk test, work, power) in the glutamine group compared with placebo. However, subjects receiving glutamine or placebo showed no deterioration in functional measures over the course of the 9-month trial. No differences in muscle mass, markers of protein breakdown or serum creatine phosho-kinase were observed, except for a blunted increase in fat free mass in the glutamine group which led to a greater increase in fat mass percentage. Glutamine was safe and well-tolerated.

Conclusions

This trial did not identify additional benefit of 4 months oral glutamine over placebo on muscle mass or function in ambulatory DMD boys. Although apparently safe, current data cannot support routine supplementation in this population as a whole, until further research proves otherwise.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00296621","term_id":"NCT00296621"}}NCT00296621     

Insulin Lispro with Continuous Subcutaneous Insulin Infusion is Safe and Effective in Patients With Type 2 Diabetes: A Randomized Crossover Trial of Insulin Lispro Versus Insulin Aspart

ObjectiveThis study provides clinical information regarding the use of insulin lispro versus insulin aspart in continuous subcutaneous insulin infusion (CSII) in adult patients with type 2 diabetes mellitus (T2D).MethodsAfter a 2-week lead-in period, 122 subjects treated with CSII therapy were randomized to 32 weeks of treatment during 2 separate 16-week treatment periods (TPs) with crossover beginning with insulin lispro (n = 60) or insulin aspart (n = 62). Glycated hemoglobin A1c (HbA1c), total daily insulin dose, and weight were recorded at the end of TP1 and TP2. Adverse events (AEs) and hypoglycemic events (overall, documented symptomatic, nocturnal, or severe) were recorded throughout the TPs. Data were analyzed using statistical methods that accounted for repeated measurements.ResultsA total of 107 subjects completed the study; 7 discontinued in TP1 and 8 discontinued in TP2. Insulin lispro was noninferior to insulin aspart in endpoint (weeks 16 and 32) HbA1c over TP1 and TP2 combined. Total daily insulin dose, weight change, and incidence and rates of hypoglycemia were not statistically significantly different between treatments. One case of severe hypoglycemia and 1 of diabetic ketoacidosis was observed with insulin aspart. One case of severe infusion site abscess was noted with insulin lispro. Overall, both insulin lispro and insulin aspart were well tolerated with similar AEs reported.ConclusionInsulin lispro and insulin aspart performed similarly after 16 weeks of treatment, with non-inferiority for HbA1c and no significant difference in parameters measured. These findings indicate that insulin lispro and insulin aspart can both be used safely and effectively in patients with T2D using CSII. (Endocr Pract. 2015;21:247-257)     

Effect of Acetazolamide on Obesity-Induced Glomerular Hyperfiltration: A Randomized Controlled Trial

Aims

Obesity is an important risk factor for the development of chronic kidney disease. One of the major factors involved in the pathogenesis of obesity-associated kidney disease is glomerular hyperfiltration. Increasing salt-delivery to the macula densa is expected to decrease glomerular filtration rate (GFR) by activating tubuloglomerular feedback. Acetazolamide, a carbonic anhydrase inhibitor which inhibits salt reabsorption in the proximal tubule, increases distal salt delivery. Its effects on obesity-related glomerular hyperfiltration have not previously been studied. The aim of this investigation was to evaluate whether administration of acetazolamide to obese non diabetic subjects reduces glomerular hyperfiltration.

Materials and Methods

The study was performed using a randomized double-blind crossover design. Obese non-diabetic men with glomerular hyperfiltration were randomized to receive intravenously either acetazolamide or furosemide at equipotent doses. Twelve subjects received the allocated medications. Two weeks later, the same subjects received the drug which they had not received during the first study. Inulin clearance, p-aminohippuric acid clearance and fractional lithium excretion were measured before and after medications administration. The primary end point was a decrease in GFR, measured as inulin clearance.

Results

GFR decreased by 21% following acetazolamide and did not decrease following furosemide. Renal vascular resistance increased by 12% following acetazolamide, while it remained unchanged following furosemide administration. Natriuresis increased similarly following acetazolamide and furosemide administration. Sodium balance was similar in both groups.

Conclusions

Intravenous acetazolamide decreased GFR in obese non-diabetic men with glomerular hyperfiltration. Furosemide, administered at equipotent dose, did not affect GFR, suggesting that acetazolamide reduced glomerular hyperfiltration by activating tubuloglomerular feedback.

Trial Registration

ClinicalTrials.gov NCT01146288     

Web‐based Weight Loss in Primary Care: A Randomized Controlled Trial

Evidence is lacking regarding effective and sustainable weight loss approaches for use in the primary care setting. We conducted a 12-week randomized controlled trial to evaluate the short-term efficacy of a web-based weight loss intervention among 101 primary care patients with obesity and hypertension. Patients had access to a comprehensive website that used a moderate-intensity weight loss approach designed specifically for web-based implementation. Patients also participated in four (two in-person and two telephonic) counseling sessions with a health coach. Intent-to-treat analysis showed greater weight loss at 3 months (−2.56 kg; 95% CI −3.60, −1.53) among intervention participants (−2.28 ± 3.21 kg), relative to usual care (0.28 ± 1.87 kg). Similar findings were observed among intervention completers (−3.05 kg; 95% CI −4.24, −1.85). High rates of participant retention (84%) and website utilization were observed, with the greatest weight loss found among those with a high frequency of website logins (quartile 4 vs. 1: −4.16 kg; 95% CI −1.47, −6.84). The intervention's approach promoted moderate weight loss at 12 weeks, though greater weight loss was observed among those with higher levels of website utilization. Efficacious web-based weight loss interventions can be successfully offered in the primary care setting.     

Safety,Tolerability, Pharmacodynamics and Pharmacokinetics of Umeclidinium and Vilanterol Alone and in Combination: A Randomized Crossover Trial

Umeclidinium bromide (GSK573719; UMEC), a new long-acting muscarinic receptor antagonist (LAMA), is in development with vilanterol ({"type":"entrez-nucleotide","attrs":{"text":"GW642444","term_id":"290522278","term_text":"GW642444"}}GW642444; VI), a selective long-acting β₂ agonist (LABA), as a once-daily inhaled combination therapy for the treatment of chronic obstructive pulmonary disease (COPD). A single dose healthy volunteer study was conducted to assess the safety and tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of inhaled umeclidinium (500 µg) and vilanterol (50 µg) when administered separately and in combination using a novel dry powder inhaler (NDPI). Co-administration of single inhaled doses of umeclidinium and vilanterol to healthy Japanese subjects was well tolerated and not associated with meaningful changes in systemic exposure or PD effects compared with administration of either compound individually. Pharmacokinetic assessments showed rapid absorption for both drugs (Tmax = 5 min for both umeclidinium and vilanterol) followed by rapid elimination with median tlast of 4–5 h for umeclidinium and median tlast of 1.5–2.0 h for vilanterol. Assessments of pharmacokinetic interaction were inconclusive since for umeclidinium, Cmax following combination was higher than umeclidinium alone but not AUC whereas for vilanterol, AUC following combination was higher than vilanterol alone but not Cmax. There were no obvious trends observed between individual maximum supine heart rate and umeclidinium Cmax or vilanterol Cmax when delivered as umeclidinium 500 µg and vilanterol 50 µg combination or when delivered as umeclidinium or vilanterol alone.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00976144","term_id":"NCT00976144"}}NCT00976144