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1.
Oral lactate slows gastric emptying and suppresses appetite in young males.
Pedersen, MGB, Søndergaard, E, Nielsen, CB, Johannsen, M, Gormsen, LC, Møller, N, Jessen, N, Rittig, N
Clinical nutrition (Edinburgh, Scotland). 2022;(2):517-525
Abstract
BACKGROUND Lactate serves as an alternative energy fuel but is also an important signaling metabolite. We aimed to investigate whether oral lactate administration affects appetite-regulating hormones, slows gastric emptying rate, and dampens appetite. METHODS Ten healthy male volunteers were investigated on two separate occasions: 1) following oral ingestion of D/L-Na-lactate and 2) following oral ingestion of isotonic iso-voluminous NaCl and intravenous iso-lactemic D/L-Na-lactate infusions. Appetite was evaluated by questionnaires and ad libitum meal tests were performed at the end of each study day. Gastric emptying rate was evaluated using the acetaminophen test. RESULTS Plasma concentrations of growth differential factor 15 (GDF15, primary outcome) increased following oral and iv administration of lactate (p < 0.001) with no detectable difference between interventions (p = 0.15). Oral lactate administration lowered plasma concentrations of acylated ghrelin (p = 0.02) and elevated glucagon like peptide-1 (GLP-1, p = 0.045), insulin (p < 0.001), and glucagon (p < 0.001) compared with iv administration. Oral lactate administration slowed gastric emptying (p < 0.001), increased the feeling of being "full" (p = 0.008) and lowered the "anticipated future food intake" (p = 0.007) compared with iv administration. Food intake during the ad libitum meal test did not differ between the two study days. CONCLUSION Oral lactate administration has a direct effect on the upper gastrointestinal tract, affecting gut hormone secretion, motility and appetite sensations which cannot be mediated through lactate in the systemic circulation alone. These data suggest that compounds rich in lactate may be useful in the treatment of metabolic disease. CLINICAL TRIAL REGISTRY NUMBER NCT0429981, https://clinicaltrials.gov/ct2/show/NCT04299815.
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2.
Gluconeogenesis and protein-induced satiety.
Veldhorst, MA, Westerterp, KR, Westerterp-Plantenga, MS
The British journal of nutrition. 2012;(4):595-600
Abstract
Increased gluconeogenesis (GNG) has been suggested to contribute to protein-induced satiety via modulation of glucose homoeostasis. The objective was to determine GNG and appetite in healthy human subjects after a high-protein v. a normal-protein diet and to assess whether GNG contributes to protein-induced satiety. A total of twenty-two healthy subjects (ten men and twelve women: age 23 (sem 1) years, BMI 22·1 (sem 0·5) kg/m²) received an isoenergetic high-protein (30/0/70 % of energy from protein/carbohydrate/fat) or normal-protein diet (12/55/33 % of energy from protein/carbohydrate/fat) for 1·5 d in a randomised cross-over design. Appetite ratings were measured using visual analogue scales (VAS); endogenous glucose production and GNG were measured via infusion of [6,6-²H₂]glucose and ingestion of ²H₂O. Moreover, fasting glucose and β-hydroxybutyrate concentrations were measured. Glycogen stores were lowered at the start with a glycogen-lowering exercise test. During the high-protein compared with the normal-protein diet, GNG was increased and appetite was suppressed (GNG: 148 (sem 7) v. 133 (sem 6) g/24 h, P < 0·05; and 24 h area under the curve for hunger: 694 (sem 46) v. 1055 (sem 52) mm VAS × 24 h, P < 0·001; fullness: 806 (sem 59) v. 668 (sem 64) mm VAS × 24 h, P < 0·05; desire to eat: 762 (sem 48) v. 1004 (sem 66) mm VAS × 24 h, P < 0·001). There was no correlation between appetite ratings and GNG. Glucose concentration was lower (4·09 (sem 0·10) v. 4·89 (sem 0·06) mmol/l, P < 0·001) and β-hydroxybutyrate concentration was higher (1349 (sem 139) v. 234 (sem 25) μmol/l, P < 0·001) after the high-protein compared with the normal-protein diet. In conclusion, after a high-protein diet, GNG was increased and appetite was lower compared with a normal-protein diet; however, these were unrelated to each other. An increased concentration of β-hydroxybutyrate may have contributed to appetite suppression on the high-protein diet.
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3.
Dose-dependent suppression of hunger by a specific alginate in a low-viscosity drink formulation.
Peters, HP, Koppert, RJ, Boers, HM, Ström, A, Melnikov, SM, Haddeman, E, Schuring, EA, Mela, DJ, Wiseman, SA
Obesity (Silver Spring, Md.). 2011;(6):1171-6
Abstract
Addition of specific types of alginates to drinks can enhance postmeal suppression of hunger, by forming strong gastric gels in the presence of calcium. However, some recent studies have not demonstrated an effect of alginate/calcium on appetite, perhaps because the selected alginates do not produce sufficiently strong gels or because the alginates were not sufficiently hydrated when consumed. Therefore, the objective of the study was to test effects on appetite of a strongly gelling and fully hydrated alginate in an acceptable, low-viscosity drink formulation. In a balanced order crossover design, 23 volunteers consumed a meal replacement drink containing protein and calcium and either 0 (control), 0.6, or 0.8% of a specific high-guluronate alginate. Appetite (six self-report scales) was measured for 5 h postconsumption. Relevant physicochemical properties of the drinks were measured, i.e., product viscosity and strength of gel formed under simulated gastric conditions. Hunger was robustly reduced (20-30% lower area under the curve) with 0.8% alginate (P < 0.001, analysis of covariance), an effect consistent across all appetite scales. Most effects were also significant with 0.6% alginate, and a clear dose-response observed. Gastric gel strength was 1.8 and 3.8 N for the 0.6 and 0.8% alginate drinks, respectively, while product viscosity was acceptable (<0.5 Pa.s at 10 s(-1)). We conclude that strongly gastric-gelling alginates at relatively low concentrations in a low-viscosity drink formulation produced a robust reduction in hunger responses. This and other related studies indicate that the specific alginate source and product matrix critically impacts upon apparent efficacy.
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4.
[Clinical effectiveness of N-oleyl-phosphatidyl-ethanolamine (NOPE) in obesity: our experience].
Ciotta, L, Stracquadanio, M, Formuso, C, Di Leo, S, Andò, A, Pagano, I
Minerva gastroenterologica e dietologica. 2011;(3):323-31
Abstract
Adjustment and maintenance of body weight are the result of many process combination, that affect both the gastrointestinal system and other mechanisms in the central nervous system. Often a diet modification alone is not sufficient to guarantee significant changes in body weight. For this reason, it sometimes necessary to make other interventions, in order to help an individual to adhere to the diet as much as possible and to achieve the objectives established. The N-oleyl-phosphatidyl-ethanolamine (NOPE) is a phospholipid. It can be endogenous or exogenous, and it is present in cell membranes and in much of the food. Food intake increases its production; in fact, because of certain stimuli, it is sometimes produced by the epithelial intestine cells too. Another substance whose activity is comparable to NOPE is the epigallocatechin gallate (EGCG), an abundant catechin present in the green tea, which allows a lipid lowering and antioxidant action, and acts on energy consumption as well. The aim of our study was to evaluate the effectiveness of NOPE and EGCG pharmaceutical formulation in a population of obese women, administering the supplement twice daily before meals, for a period of 60 days. The comparison between the effectiveness of the results in a homogeneous group of patients treated with diet and placebo, allows to confirm the data reported in the literature regarding the effectiveness of the pharmaceutical formulation and the absence of side effects.
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5.
Sympathetic vasomotor tone determines blood pressure response to long-term sibutramine treatment.
Heusser, K, Engeli, S, Tank, J, Diedrich, A, Wiesner, S, Janke, J, Luft, FC, Jordan, J
The Journal of clinical endocrinology and metabolism. 2007;(4):1560-3
Abstract
CONTEXT The serotonin and norepinephrine transporter inhibitor sibutramine is a widely used antiobesity drug. In acute studies, the peripheral sympathomimetic effect of sibutramine was counteracted by a central sympatholytic action. OBJECTIVE The objective was to test the hypothesis that blood pressure responses to long-term sibutramine therapy may be related to sympathetic nerve traffic before treatment in a prospective open-label study in an academic clinical research center. PATIENTS This study comprised 20 obese subjects (body mass index, 30-40 kg/m2; age, 30-57 yr) receiving 5 d of placebo treatment followed by open-label 15 mg/d sibutramine and hypocaloric diet over 12 wk. MAIN OUTCOME MEASURES Body weight, blood pressure, heart rate, muscle sympathetic nerve activity (MSNA) (microneurography), plasma catecholamines, and adipose tissue gene expression were measured. RESULTS Open-label sibutramine treatment decreased body weight 4.1 kg (P<0.01) and MSNA 17 bursts per minute (P=0.001), and increased diastolic blood pressure 3 mm Hg (P<0.05) and heart rate 8 bpm (P<0.01). The change in blood pressure with sibutramine treatment was inversely correlated with initial MSNA (r2=0.34; P<0.01). Chronic sibutramine treatment increased adrenoreceptor gene expression and plasma catecholamines. CONCLUSIONS The blood pressure response to sibutramine treatment is related to initial MSNA so that subjects with higher MSNA exhibit a smaller increase or even a decrease in blood pressure. The phenomenon might be explained by a sustained reduction in central sympathetic activity with sibutramine treatment.
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6.
Effects of sibutramine on abdominal fat mass, insulin resistance and blood pressure in obese hypertensive patients.
Faria, AN, Ribeiro Filho, FF, Kohlmann, NE, Gouvea Ferreira, SR, Zanella, MT
Diabetes, obesity & metabolism. 2005;(3):246-53
Abstract
OBJECTIVE The objective of this study is to assess the effects of sibutramine on body weight, body fat distribution, insulin resistance, plasma leptin, lipid profile and blood pressure profiles in hypertensive obese patients. METHODS Eighty-six central obese hypertensive patients (BMI = 39 +/- 5 kg/m(2), 84% of women, 48 +/- 8.5 years old) were placed on a hypocaloric diet and placebo therapy for 4 weeks. They were then randomized to receive sibutramine (10 mg) or placebo for 24 weeks. Both, before therapy and at the end of the study, the waist and hip circumferences were measured and the waist/hip ratio (WHR) was calculated; abdominal ultrasonography was performed in order to estimate the amount of subcutaneous fat (SF) and visceral fat (VF), and the visceral/subcutaneous ratio. Beyond HOMA-r, another insulin resistance index (IRIp) was calculated by means of the formula: peak of blood glucose after oral glucose load x plasma insulin level/10(4). Fasting plasma leptin and lipid levels were also determined. RESULTS Sibutramine induced greater weight reduction than placebo (6.7 vs. 2.5%, p < 0.001). Reductions in WHR (0.97 +/- 0.08 vs. 0.94 +/- 0.07, p < 0.01), IRIp (0.11 +/- 0.07 vs. 0.09 +/- 0.06 mmol mu/l(2)) and VF (6.4 +/- 2.4-6.0 +/- 2.4 cm, p < 0.01) were observed only with sibutramine. Plasma leptin decreased with placebo (24 +/- 15 vs. 18 +/- 10 UI/l, p < 0.01), but not with sibutramine (18.8 +/- 8.4 vs. 18.2 +/- 13.2 UI/l). No clinically significant change in lipid profile was observed in both groups. Moreover, office and 24-h blood pressure values did not change during placebo or sibutramine therapy, whereas a significant increase in office heart rate, from 78.3 +/- 7.3-82 +/- 7.9 b.p.m., p = 0.02, was observed with sibutramine. CONCLUSIONS Sibutramine therapy induced greater body weight loss than placebo in hypertensive obese patients. This was associated with WHR reduction, decreases in VF and insulin resistance. The maintenance of leptin levels during sibutramine therapy may be important to avoid weight recovery, although this finding must be confirmed by other prospective studies.
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7.
A placebo controlled randomized trial of the effects of phenylpropanolamine and nicotine gum on cessation rates and postcessation weight gain in women.
Cooper, TV, Klesges, RC, Debon, MW, Zbikowski, SM, Johnson, KC, Clemens, LH
Addictive behaviors. 2005;(1):61-75
Abstract
With smoking prevalence rates beginning to decline, studies designed to promote cessation in more challenging populations, like weight-concerned smokers, warrant attention. This study assessed the efficacy of two forms of pharmacotherapy [nicotine and phenylpropanolamine (PPA) gums] in addition to a 13-week cognitive behavioral smoking cessation program targeted for women. Participants were 439 females who met rigorous screening criteria and were randomized to one of the three treatment intervention groups (PPA gum, nicotine gum, or placebo gum). All participants attended a 13-week cognitive behavioral smoking cessation program and were given specific instructions on gum chewing. At posttest (13 weeks), and 6- and 12-month follow-ups, body weight and point prevalence abstinence were assessed. Analyses to determine potential differences between treatment groups on weight change and cessation rates were performed. Results indicated that neither change in body weight nor cessation rates significantly differed between groups. Attendance to sessions did appear to consistently increase the likelihood of quitting smoking at posttest and at each of the follow-ups. These results suggest that although the pharmacological interventions had no effect on cessation rates and postcessation weight gain, the behavioral component of the intervention was effective in increasing the odds of quitting smoking in weight-concerned women. Future efforts should focus on increasing adherence to behavioral program components, particularly session attendance.
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8.
A double-blind, placebo-controlled trial of sibutramine for olanzapine-associated weight gain.
Henderson, DC, Copeland, PM, Daley, TB, Borba, CP, Cather, C, Nguyen, DD, Louie, PM, Evins, AE, Freudenreich, O, Hayden, D, et al
The American journal of psychiatry. 2005;(5):954-62
Abstract
OBJECTIVE Weight gain is commonly observed with olanzapine treatment and can increase the risk for obesity, cardiovascular disease, hypertension, and diabetes mellitus. This study examined the effectiveness of sibutramine, an approved weight loss agent, in overweight and obese subjects taking olanzapine for schizophrenia or schizoaffective disorder. METHOD Each subject had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder, had been taking a stable dose of olanzapine for at least 4 months, and had a body mass index of ≥30 kg/m(2) or ≥27 kg/m(2) plus at least one cardiovascular risk factor. In a 12-week double-blind, randomized, placebo-controlled study, 37 subjects received placebo or sibutramine (up to 15 mg/day). For the first 8 weeks all subjects participated in weekly group sessions focused on nutrition and behavioral modification. RESULTS The sibutramine and placebo groups had no significant baseline differences on age, gender, education, ethnicity, diagnosis, weight, body mass index, and blood pressure. At week 12 the sibutramine group had significantly greater losses than the placebo group in weight (mean=8.3 lb, SD=2.4, versus mean=1.8 lb, SD=1.6), waist circumference, body mass index, and hemoglobin A(1c). There were no significant differences on most side effects, although the sibutramine group exhibited a mean increase in systolic blood pressure of 2.1 mm Hg (SD=8.5), and anticholinergic side effects and sleep disturbances were at least twice as common in the sibutramine group. CONCLUSIONS Sibutramine was an effective and well-tolerated adjunct to behavior modification for weight loss in patients with schizophrenia and schizoaffective disorder being treated with olanzapine.
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9.
Psychobehavioral and nutritional predictors of weight loss in obese women treated with sibutramine.
Hainer, V, Kunesova, M, Bellisle, F, Hill, M, Braunerova, R, Wagenknecht, M
International journal of obesity (2005). 2005;(2):208-16
Abstract
OBJECTIVE To reveal whether baseline body mass index (BMI), and psychobehavioral and nutritional markers were significant predictors of the change in BMI observed after 4 and 12 months in obese women enrolled in a weight reduction program, including low-energy diet, increased physical activity, cognitive behavior therapy and sibutramine. The impact of changes in psychobehavioral and nutritional markers observed after 4 and 12 months of treatment on BMI changes was also investigated. DESIGN During a double-blind placebo-controlled 4-month period, subjects received either sibutramine (10 mg/day) or placebo. Then, an open phase with sibutramine administered to all patients continued until month 12. SUBJECTS In total, 80 obese women (age: 43.9+/-10.6 y, BMI: 36.7+/-4.8 kg/m(2)). MEASUREMENTS The dependent variable was change in BMI while baseline BMI, mode of treatment, the Beck depression score, the three items (dietary restraint, disinhibition and perceived hunger) of the Eating Inventory (EI), energy and macronutrient intakes were independent variables. At 1-week dietary records were analyzed using a computer software for assessing energy and macronutrient intake. RESULTS Multiple regression analysis revealed that the BMI loss at month 4 was significantly influenced by mode of treatment and initial BMI, whereas a borderline negative relationship was observed with the baseline restraint score. Baseline BMI, depression score, restraint score and total energy intake predicted weight loss at month 12. These predictive variables accounted for 43.8% of the variance in BMI loss at 12 months. When relationships between the BMI loss and changes in all included psychobehavioral and nutritional parameters were considered after 12 months of treatment, a drop in the disinhibition score of the EI appeared the only significant factor affecting the BMI decrease. CONCLUSIONS Our results suggest that psychobehavioral and nutritional characteristics can be used as predictors of weight loss in response to a comprehensive weight management program including pharmacological treatment with sibutramine.
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10.
The appetite-suppressant effect of nicotine is enhanced by caffeine.
Jessen, A, Buemann, B, Toubro, S, Skovgaard, IM, Astrup, A
Diabetes, obesity & metabolism. 2005;(4):327-33
Abstract
AIM: To test whether the anorectic effect of nicotine may be amplified by caffeine. METHODS Chewing gums with nicotine and caffeine were administered to 12 healthy young men of normal weight. Different combinations of 0, 1 or 2 mg of nicotine and 0, 50 or 100 mg of caffeine were applied during a 2-h period in a randomized, double blind, cross over design. Appetite sensations were measured using visual analogue scales. RESULTS Hunger and prospective food consumption were negatively associated with the increasing doses of nicotine, whereas satiety and fullness were positively associated with the increasing doses of nicotine (p < 0.05). Caffeine appeared to amplify the effects of nicotine on hunger and fullness as a caffeine x nicotine x time interaction was observed in these scores (p < 0.05). The 2-mg dose of nicotine in combination with the 100-mg dose of caffeine caused nausea in four of the non-smokers. However, the effects of nicotine and the caffeine x nicotine x time interaction persisted after the exclusion of these subjects. CONCLUSION Caffeine added to nicotine chewing gum appears to amplify its attenuating effects on appetite and the combinations of 1-mg of nicotine with caffeine seem to be well tolerated.