No Measurable Transfer of Oxytocin-Receptor Agonist Merotocin Detected in Human Breast Milk.

Objective: The study aimed to assess the transfer of merotocin from systemic circulation to breast milk in early postpartum women and women with established lactation. Methods: This was a two-part, multicenter, open-label, parallel-group study. Merotocin was administered as a single 90-minute intravenous (iv) infusion mimicking the intranasal pharmacokinetic profile. In Part A, 12 early postpartum women received doses of either 4 µg (n = 6) or 16 µg (n = 6) of merotocin within 4 days of delivery. In Part B, six women with established lactation received 20 µg of merotocin. The total concentration of merotocin in plasma and breast milk and its metabolites excreted in breast milk were measured at various time points. Adverse events (AEs) were also assessed for both parts of the study. Results: In both early postpartum and established lactation groups (mean age, 26.3 years; 83.3% Caucasian), merotocin and its metabolites in breast milk were below the limit of quantification (25.0 pg/mL) at all time points. Sixteen treatment-emergent AEs occurred in early postpartum women only, including seven events of uterine spasm and three of breast engorgement. There was one moderate event, whereas all the other events were considered mild. Conclusion: Merotocin was undetectable in breast milk after single iv administration of up to 20 µg in early postpartum women and women with established lactation.

A Randomized, Double-Blind, Placebo-Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss.

OBJECTIVE: This study aims to assess the efficacy and safety of Gelesis100, a novel, nonsystemic, superabsorbent hydrogel to treat overweight or obesity. METHODS: The Gelesis Loss Of Weight (GLOW) study was a 24-week, multicenter, randomized, double-blind, placebo-controlled study in patients with BMI ≥  27 and ≤ 40 kg/m2 and fasting plasma glucose ≥ 90 and ≤ 145 mg/dL. The co-primary end points were placebo-adjusted weight loss (superiority and 3% margin super-superiority) and at least 35% of patients in the Gelesis100 group achieving ≥ 5% weight loss. RESULTS: Gelesis100 treatment caused greater weight loss over placebo (6.4% vs. 4.4%, P = 0.0007), achieving 2.1% superiority but not 3% super-superiority. Importantly, 59% of Gelesis100-treated patients achieved weight loss of ≥ 5%, and 27% achieved ≥ 10% versus 42% and 15% in the placebo group, respectively. Gelesis100-treated patients had twice the odds of achieving ≥ 5% and ≥ 10% weight loss versus placebo (adjusted OR: 2.0, P = 0.0008; OR: 2.1, P = 0.0107, respectively), with 5% responders having a mean weight loss of 10.2%. Patients with prediabetes or drug-naive type 2 diabetes had six times the odds of achieving ≥ 10% weight loss. Gelesis100 treatment had no apparent increased safety risks. CONCLUSIONS: Gelesis100 is a promising new nonsystemic therapy for overweight and obesity with a highly desirable safety and tolerability profile.

Personalized nutrition: pretreatment glucose metabolism determines individual long-term weight loss responsiveness in individuals with obesity on low-carbohydrate versus low-fat diet.

BACKGROUND/OBJECTIVES: The interaction between fasting plasma glucose (FPG) and fasting insulin (FI) concentrations and diets with different carbohydrate content were studied as prognostic markers of weight loss as recent studies up to 6 months of duration have suggested the importance of these biomarkers. SUBJECTS/METHODS: This was a retrospective analysis of a clinical trial where participants with obesity were randomized to an ad libitum low-carbohydrate diet or a low-fat diet with low energy content (1200-1800 kcal/day [≈ 5.0-7.5 MJ/d]; ≤ 30% calories from fat) for 24 months. Participants were categorized (pretreatment) as normoglycemic (FPG < 5.6 mmol/L) or prediabetic (FPG ≥ 5.6-6.9 mmol/L) and further stratified by median FI. Linear mixed models were used to examine outcomes by FPG and FI values. RESULTS: After 2 years, participants with prediabetes and high FI lost 7.2 kg (95% CI 2.1;12.2, P = 0.005) more with the low-fat than low-carbohydrate diet, whereas those with prediabetes and low FI tended to lose 6.2 kg (95% CI -0.9;13.3, P = 0.088) more on the low-carbohydrate diet than low-fat diet [mean difference: 13.3 kg (95% CI 4.6;22.0, P = 0.003)]. No differences between diets were found among participants with normoglycemia and either high or low FI (both P ≥ 0.16). CONCLUSIONS: Fasting plasma glucose and insulin are strong predictors of the weight loss response to diets with different macronutrient composition and might be a useful approach for personalized weight management.

Effect of a nonsystemic, orally administered hydrogel, GS100, on metformin pharmacokinetics.

Overweight and obesity are major health concerns worldwide, and are major predisposing factors for type 2 diabetes. This single-centre, Phase I, randomised, open-label, single-dose, 4-arm crossover, device-drug interaction study on 24 healthy volunteers with a body mass index of 25-40 kg/m2 tested the effect of a novel, nonsystemic, orally administered hydrogel (GS100) on the pharmacokinetics of an oral antidiabetic drug, metformin. When administered in both the fed and fasted states, the effect of GS100 on metformin pharmacokinetic characteristics was found to be similar to that of food. The type, frequency, and intensity of adverse events observed when GS100 was co-administered with metformin were similar to those observed with metformin alone. This study demonstrates that GS100 can be taken by patients receiving metformin, without altering the administration of metformin.

Weight loss in videoconference and in-person iDiet weight loss programs in worksites and community groups.

OBJECTIVE: To examine the association of program delivery factors with weight loss (WL) in enrollees in iDiet® , a commercial WL program. METHODS: Data were from 644 adults enrolling in an 11-week group WL program and 461 who reported weight to 11 weeks (complete reporters). Predictors of %WL were analyzed using ANCOVA, including meeting type (in-person vs. videoconference), participant type (worksite employees vs. community members), age, gender, BMI, and payment structure. RESULTS: Mean starting BMI was 32.4 ± 7.1 (mean ± SD); WL was 6.1 ± 3.9% in all enrollees in an intention-to-treat analysis and 7.4 ± 3.4% in complete reporters. Videoconference participants, older adults, and enrollees in incentivized programs were more likely to be complete reporters (P < 0.004). %WL at 11 weeks was not associated with gender, starting BMI, or videoconference versus in-person groups. Worksite participants had greater %WL than community participants (+1.2%, P < 0.001), and there was no significant difference in %WL between programs paid by the employee or employer. Greater %WL was achieved by individuals ≥30 versus < 30 years (+2.2%, P < 0.001) and by those enrolling in January-March versus April-June (+1.4%, P = 0.02). CONCLUSIONS: iDiet participants had clinically impactful mean WL. The observed high mean WL in worksites and videoconference-delivered programs broadens options for scalable WL program implementation.

Association of nutrition club membership with markers of health: a cross sectional study.

BACKGROUND: Nutrition clubs (NC) operate in community settings and provide members with nutrition education and meal replacements for weight management. NC are owned and operated by distributors of Herbalife products. There are over 6200 NC in the US, but there has been no independent assessment of the association of these NC with biomarkers of health. METHODS: We conducted a cross-sectional pilot study to compare the health status of 100 NC members to 100 community-matched controls (CC) in the greater Boston area. Each CC was matched to a NC member for community of residence (zip code), age category, gender, BMI category, race/ethnicity, education level (category), and readiness to make health changes. Measures obtained included cardio-metabolic risk factors, body composition, markers of nutritional status, reported health status, dietary intake, physical activity, sleep and depression. RESULTS: Participants were predominantly female (64%) and Hispanic (73%). NC members had significantly lower fasting insulin (P < 0.001) and lower HbA1c (P = 0.008), higher levels of 25 hydroxy-vitamin D (P = 0.001), and vitamin E:cholesterol ratio (P < 0.001), and lower prevalence of metabolic syndrome (P = 0.02) compared to CC. In addition, most of the NC members (99%) were satisfied with Herbalife NC membership for themselves and their families. A higher percentage of NC members (86%) compared to CC (32%) reported being in much better or somewhat better health compared to a year ago (P < 0.001); and they reported significantly better physical health (P = 0.03), and fewer sleep problems (P = 0.03). CONCLUSION: Herbalife NC membership was positively associated with perceived health and measured cardiometabolic benefits. However, causality cannot be inferred from these findings.

Energy Contents of Frequently Ordered Restaurant Meals and Comparison with Human Energy Requirements and U.S. Department of Agriculture Database Information: A Multisite Randomized Study.

BACKGROUND: Excess energy intake from meals consumed away from home is implicated as a major contributor to obesity, and ∼50% of US restaurants are individual or small-chain (non-chain) establishments that do not provide nutrition information. OBJECTIVE: To measure the energy content of frequently ordered meals in non-chain restaurants in three US locations, and compare with the energy content of meals from large-chain restaurants, energy requirements, and food database information. DESIGN: A multisite random-sampling protocol was used to measure the energy contents of the most frequently ordered meals from the most popular cuisines in non-chain restaurants, together with equivalent meals from large-chain restaurants. SETTING: Meals were obtained from restaurants in San Francisco, CA; Boston, MA; and Little Rock, AR, between 2011 and 2014. MAIN OUTCOME MEASURES: Meal energy content determined by bomb calorimetry. STATISTICAL ANALYSIS PERFORMED: Regional and cuisine differences were assessed using a mixed model with restaurant nested within region×cuisine as the random factor. Paired t tests were used to evaluate differences between non-chain and chain meals, human energy requirements, and food database values. RESULTS: Meals from non-chain restaurants contained 1,205±465 kcal/meal, amounts that were not significantly different from equivalent meals from large-chain restaurants (+5.1%; P=0.41). There was a significant effect of cuisine on non-chain meal energy, and three of the four most popular cuisines (American, Italian, and Chinese) had the highest mean energy (1,495 kcal/meal). Ninety-two percent of meals exceeded typical energy requirements for a single eating occasion. CONCLUSIONS: Non-chain restaurants lacking nutrition information serve amounts of energy that are typically far in excess of human energy requirements for single eating occasions, and are equivalent to amounts served by the large-chain restaurants that have previously been criticized for providing excess energy. Restaurants in general, rather than specific categories of restaurant, expose patrons to excessive portions that induce overeating through established biological mechanisms.

Independent, additive effects of five dietary variables on ad libitum energy intake in a residential study.

OBJECTIVE: To examine the relationship between dietary characteristics of self-selected foods and energy balance in a cafeteria-style dining hall. METHODS: Ad libitum dietary intake from a self-selection menu was measured over two days in 151 adults (70% female, mean age 41 years, mean BMI 24.9 kg/m(2) ). The associations of dietary variables with energy balance (calculated as measured energy intake/predicted energy requirements, pER) were assessed. RESULTS: Measured energy intake was significantly correlated with pER (R(2) =0.83, P < 0.001). In mixed multiple regression models, percent energy from protein was negatively associated with energy balance (R(2) =0.04, P = 0.02), and percent energy from liquid sources (R(2) = 0.02, P = 0.05), total dietary variety in females (R(2) = 0.39, P < 0.001), and energy density (R(2) = 0.57, P < 0.001) were positively associated with energy balance. In addition, glycemic index was inversely associated with energy balance in normal-weight individuals (R(2) = 0.14, P < 0.001) but not in overweight or obese individuals. CONCLUSIONS: There are independent associations of dietary protein, liquid calories, energy density, dietary variety, and glycemic index with energy balance, indicating additive effects of these dietary factors on energy intake and energy balance. Intervention studies are needed to determine whether dietary prescriptions combining these dietary factors facilitate long-term prevention of weight gain.

Effects of dietary factors on energy regulation: consideration of multiple- versus single-dietary-factor models.

While short-term studies demonstrate consistent effects of dietary protein, fiber, glycemic index and energy density on energy intake, long-term effectiveness trials typically indicate small or non-significant effects of these dietary factors on long-term weight change. In consequence, most lifestyle interventions for weight control typically focus on a single dietary factor, such as low energy density, to achieve reductions in energy intake. This paper proposes a multiple-dietary-factor model for the effects of dietary factors on energy intake and the regulation of energy balance that assumes additive effects of different dietary factors. The model is consistent with emerging evidence from recent studies examining pairs of dietary factors. Randomized clinical trials are now needed to determine whether multiple-dietary-factor prescriptions combined with standard behavior modification techniques lead to improved sustainability of weight loss in lifestyle interventions compared to conventional single-dietary-factor prescriptions.

Sodium, saturated fat, and trans fat content per 1,000 kilocalories: temporal trends in fast-food restaurants, United States, 2000-2013.

INTRODUCTION: Intakes of sodium, saturated fat, and trans fat remain high despite recommendations to limit these nutrients for cardiometabolic risk reduction. A major contributor to intake of these nutrients is foods prepared outside the home, particularly from fast-food restaurants. METHODS: We analyzed the nutrient content of frequently ordered items from 3 US national fast-food chains: fried potatoes (large French fries), cheeseburgers (2-oz and 4-oz), and a grilled chicken sandwich. We used an archival website to obtain data on sodium, saturated fat, and trans fat content for these items from 2000 through 2013. The amount of each nutrient per 1,000 kcal was calculated to determine whether there were trends in product reformulation. RESULTS: Sodium content per 1,000 kcal differed widely among the 3 chains by food item, precluding generalizations across chains. During the 14-year period, sodium content per 1,000 kcal for large French fries remained high for all 3 chains, although the range narrowed from 316-2,000 mg per 1,000 kcal in 2000 to 700-1,420 mg per 1,000 kcal in 2013. Among the items assessed, cheeseburgers were the main contributor of saturated fat, and there was little change in content per 1,000 kcal for this item during the 14-year period. In contrast, there was a sharp decline in saturated and trans fat content of large French fries per 1,000 kcal. Post-2009, the major contributor of trans fat per 1,000 kcal was cheeseburgers; trans fat content of this item remained stable during the 14-year period. CONCLUSION: With the exception of French fries, little evidence was found during the 14-year period of product reformulation by restaurants to become more consistent with dietary guidance to reduce intakes of sodium and saturated fat.

Temporal trends in fast-food restaurant energy, sodium, saturated fat, and trans fat content, United States, 1996-2013.

INTRODUCTION: Excess intakes of energy, sodium, saturated fat, and trans fat are associated with increased risk for cardiometabolic syndrome. Trends in fast-food restaurant portion sizes can inform policy decisions. We examined the variability of popular food items in 3 fast-food restaurants in the United States by portion size during the past 18 years. METHODS: Items from 3 national fast-food chains were selected: French fries, cheeseburgers, grilled chicken sandwich, and regular cola. Data on energy, sodium, saturated fat, and trans fat content were collated from 1996 through 2013 using an archival website. Time trends were assessed using simple linear regression models, using energy or a nutrient component as the dependent variable and the year as the independent variable. RESULTS: For most items, energy content per serving differed among chain restaurants for all menu items (P ≤ .04); energy content of 56% of items decreased (ß range, -0.1 to -5.8 kcal) and the content of 44% increased (ß range, 0.6-10.6 kcal). For sodium, the content of 18% of the items significantly decreased (ß range, -4.1 to -24.0 mg) and the content for 33% increased (ß range, 1.9-29.6 mg). Absolute differences were modest. The saturated and trans fat content, post-2009, was modest for French fries. In 2013, the energy content of a large-sized bundled meal (cheeseburger, French fries, and regular cola) represented 65% to 80% of a 2,000-calorie-per-day diet, and sodium content represented 63% to 91% of the 2,300-mg-per-day recommendation and 97% to 139% of the 1,500-mg-per-day recommendation. CONCLUSION: Findings suggest that efforts to promote reductions in energy, sodium, saturated fat, and trans fat intakes need to be shifted from emphasizing portion-size labels to additional factors such as total calories, frequency of eating, number of items ordered, menu choices, and energy-containing beverages.

The energy content of restaurant foods without stated calorie information.

IMPORTANCE: National recommendations for the prevention and treatment of obesity emphasize reducing energy intake through self-monitoring food consumption. However, little information is available on the energy content of foods offered by nonchain restaurants, which account for approximately 50% of restaurant locations in the United States. OBJECTIVE: To measure the energy content of foods from independent and small-chain restaurants that do not provide stated information on energy content. DESIGN: We used bomb calorimetry to determine the dietary energy content of the 42 most frequently purchased meals from the 9 most common restaurant categories. Independent and small-chain restaurants were randomly selected, and 157 individual meals were analyzed. SETTING: Area within 15 miles of downtown Boston. PARTICIPANTS: A random sample of independent and small-chain restaurants. MAIN OUTCOMES AND MEASURES: Dietary energy. RESULTS: All meal categories provided excessive dietary energy. The mean energy content of individual meals was 1327 (95% CI, 1248-1406) kcal, equivalent to 66% of typical daily energy requirements. We found a significant effect of food category on meal energy (P ≤ .05), and 7.6% of meals provided more than 100% of typical daily energy requirements. Within-meal variability was large (average SD, 271 kcal), and we found no significant effect of restaurant establishment or size. In addition, meal energy content averaged 49% greater than those of popular meals from the largest national chain restaurants (P < .001) and in subset analyses contained 19% more energy than national food database information for directly equivalent items (P < .001). CONCLUSIONS AND RELEVANCE: National chain restaurants have been criticized for offering meals with excess dietary energy. This study finds that independent and small-chain restaurants, which provide no nutrition information, also provide excessive dietary energy in amounts apparently greater than popular meals from chain restaurants or information in national food databases. A national requirement for accurate calorie labeling in all restaurants may discourage menus offering unhealthy portions and would allow consumers to make informed choices about ordering meals that promote weight gain and obesity.

Lifestyle intervention reduces body weight and improves cardiometabolic risk factors in worksites.

BACKGROUND: Worksites are potentially effective locations for obesity control because they provide opportunities for group intervention and social support. Studies are needed to identify effective interventions in these settings. OBJECTIVE: We examined the effects of a multicomponent lifestyle intervention on weight loss and prevention of regain in 4 worksites (2 intervention and 2 control sites). DESIGN: Overweight and obese employees (n = 133) enrolled in this pilot worksite-randomized controlled trial with a 0-6-mo weight-loss phase and a 6-12-mo structured weight-maintenance phase. The intervention combined recommendations to consume a reduced-energy, low-glycemic load, high-fiber diet with behavioral change education. Outcome measurements included changes in body weight and cardiometabolic risk factors. RESULTS: The mean ± SEM weight loss was substantial in intervention participants, whereas control subjects gained weight (-8.0 ± 0.7 compared with +0.9 ± 0.5 kg, respectively; P < 0.001), and 89% of participants completed the weight-loss phase. Intervention effects were not significant at the 0.05 level but would have been at the 0.10 level (P = 0.08) in a mixed model in which the worksite nested within group was a random factor. There were also significant improvements in cardiometabolic risk factors in intervention compared with control subjects regarding fasting total cholesterol, glucose, systolic blood pressure, and diastolic blood pressure (P ≤ 0.02 for each). No significant weight regain was observed in participants who enrolled in the structured weight-maintenance program (0.5 ± 0.7 kg; P = 0.65), and overweight and obese employees in intervention worksites who were not enrolled in the weight-loss program lost weight compared with subjects in control worksites (-1.3 ± 0.5 compared with +0.7 ± 0.2 kg, respectively; P = 0.02). CONCLUSION: Worksites can be effective for achieving clinically important reductions in body weight and improved cardiometabolic risk factors. This trial was registered at clinicaltrials.gov as NCT01470222.

Accuracy of stated energy contents of restaurant foods.

CONTEXT: National recommendations for the prevention and treatment of obesity emphasize reducing energy intake. Foods purchased in restaurants provide approximately 35% of the daily energy intake in US individuals but the accuracy of the energy contents listed for these foods is unknown. OBJECTIVE: To examine the accuracy of stated energy contents of foods purchased in restaurants. DESIGN AND SETTING: A validated bomb calorimetry technique was used to measure dietary energy in food from 42 restaurants, comprising 269 total food items and 242 unique foods. The restaurants and foods were randomly selected from quick-serve and sit-down restaurants in Massachusetts, Arkansas, and Indiana between January and June 2010. MAIN OUTCOME MEASURE: The difference between restaurant-stated and laboratory-measured energy contents, which were corrected for standard metabolizable energy conversion factors. RESULTS: The absolute stated energy contents were not significantly different from the absolute measured energy contents overall (difference of 10 kcal/portion; 95% confidence interval [CI], -15 to 34 kcal/portion; P = .52); however, the stated energy contents of individual foods were variable relative to the measured energy contents. Of the 269 food items, 50 (19%) contained measured energy contents of at least 100 kcal/portion more than the stated energy contents. Of the 10% of foods with the highest excess energy in the initial sampling, 13 of 17 were available for a second sampling. In the first analysis, these foods contained average measured energy contents of 289 kcal/portion (95% CI, 186 to 392 kcal/portion) more than the stated energy contents; in the second analysis, these foods contained average measured energy contents of 258 kcal/portion (95% CI, 154 to 361 kcal/portion) more than the stated energy contents (P <.001 for each vs 0 kcal/portion difference). In addition, foods with lower stated energy contents contained higher measured energy contents than stated, while foods with higher stated energy contents contained lower measured energy contents (P <.001). CONCLUSIONS: Stated energy contents of restaurant foods were accurate overall. However, there was substantial inaccuracy for some individual foods, with understated energy contents for those with lower energy contents.

The accuracy of stated energy contents of reduced-energy, commercially prepared foods.

The accuracy of stated energy contents of reduced-energy restaurant foods and frozen meals purchased from supermarkets was evaluated. Measured energy values of 29 quick-serve and sit-down restaurant foods averaged 18% more than stated values, and measured energy values of 10 frozen meals purchased from supermarkets averaged 8% more than originally stated. These differences substantially exceeded laboratory measurement error but did not achieve statistical significance due to considerable variability in the degree of underreporting. Some individual restaurant items contained up to 200% of stated values and, in addition, free side dishes increased provided energy to an average of 245% of stated values for the entrees they accompanied. These findings suggest that stated energy contents of reduced-energy meals obtained from restaurants and supermarkets are not consistently accurate, and in this study averaged more than measured values, especially when free side dishes were taken into account. If widespread, this phenomenon could hamper efforts to self-monitor energy intake to control weight, and could also reduce the potential benefit of recent policy initiatives to disseminate information on food energy content at the point of purchase.