Safety of dietary conjugated linoleic acid (CLA) in a 12-weeks trial in healthy overweight Japanese male volunteers.

A study was conducted to investigate the short-term safety of dietary conjugated linoleic acid (CLA) in overweight Japanese male volunteers. The study design was a randomized, double-blind placebo-controlled trial including 60 healthy overweight volunteers (body mass index (BMI), 25 approximately 35 kg/m(2)). The subjects were randomly assigned to three groups: 5.4 g CLA-triacylglycerol (3.4 g as CLA), 10.8 g CLA-triacylglycerol (6.8 g as CLA) and placebo (10.8 g safflower oil) daily for 12 weeks. The CLA-triaclyglycerol contained 9c,11t- and 10t,12c-isomers at an equal proportion. The safety was evaluated by analyses of blood parameters and by clinical examinations at the baseline, and at 6 and 12 weeks, including vital signs and adverse effects. All subjects completed the study. The occurrence of adverse events tended to be higher in the CLA groups than in the placebo group, but all of the adverse events were mild to moderate, within normal ranges, and temporary. Serum aspartate aminotransferase (AST) activity did not differ significantly between the groups at 12 weeks, but in the high CLA group it was slightly increased from the baseline. Serum alanine aminotransferase (ALT) activity was higher in the high CLA group than in the placebo group after 12 weeks and was higher than at the baseline in both CLA groups. However, statistical analysis of the population of apparently healthy volunteers who had normal blood parameters at the baseline revealed that AST and ALT levels did not differ significantly among the 3 groups at 12 weeks. Moreover, no clinically significant changes in vital signs were observed in any of the groups. These results indicate that CLA at a dose of 3.4 g/day is a safe dietary level in healthy Japanese populations in terms of the parameters examined.

Orlistat for the management of overweight individuals and obesity: a review of potential for the 60-mg, over-the-counter dosage.

Orlistat, in the 60-mg over-the-counter dose, was recently approved by the FDA. This lipase inhibitor blocks absorption of ~25% of ingested fat and has ~85% of the efficacy of the 120-mg dose for weight loss. Over 16 weeks weight loss with diet and orlistat 60 mg averages ~5% of initial body weight. The 60-mg dose is better tolerated than the 120-mg dose and the gastrointestinal side effects are minimal when individuals consume < 30% of their energy from fat. In addition to facilitating modest weight loss, orlistat use decreases serum LDL-cholesterol values by ~10%. When taken three times daily before meals, orlistat 60 mg modifies lifestyle behavior, encourages lower fat-consumption and sets the stage for other healthy lifestyle changes.

Pharmacotherapeutic options for overweight adolescents.

OBJECTIVE: To evaluate the safety and efficacy of current pharmacotherapeutic options for weight loss in overweight adolescents. DATA SOURCES: Literature was obtained through MEDLINE Ovid (1996-April 2007) and EMBASE Drugs and Pharmacology (1991-2nd quarter 2007) searches and a bibliographic review of published articles. Key words included adolescents, overweight, obesity, anti-obesity agents, drug therapy, orlistat, sibutramine, and metformin. STUDY SELECTION AND DATA EXTRACTION: All studies published in the English language that evaluated the use of pharmacotherapy for the treatment of overweight adolescents were critically analyzed; pertinent articles were selected for this review. DATA SYNTHESIS: Orlistat has been approved for use in adolescents between the ages of 12 and 16 years. The most frequently reported adverse effects of orlistat were gastrointestinal; reduced concentrations of fat-soluble vitamins were also observed. Of the 6 clinical trials published, 5 have shown statistically significant reductions in body mass index (BMI) from baseline, ranging from 0.55 to 4.09 kg/m2; one small trial failed to demonstrate significant weight reduction compared with placebo. Sibutramine has also been evaluated for use in overweight adolescents in 6 trials. Trials demonstrated a statistically significant reduction in BMI up to 5.6 kg/m2 (from baseline). Of concern is evidence indicating that sibutramine therapy may be associated with elevated blood pressure, increased pulse rate, depression, and suicidal ideations. Lastly, metformin has recently been evaluated for weight loss in overweight adolescents; small, short-term trials demonstrate modest reductions in weight and BMI. CONCLUSIONS: Orlistat has been proven both safe and effective for weight reduction in overweight adolescents. Sibutramine has also been proven effective in reducing weight in this population; however, the potential for severe adverse effects requires further investigation. Metformin has demonstrated promising results in small trials; its role in the treatment of overweight adolescents will remain investigational until further research is conducted.

Topiramate-induced weight loss in schizophrenia: a retrospective case series study.

OBJECTIVE: Atypical antipsychotics have been associated with weight gain. This study examines the efficacy of adjunctive topiramate in patients with schizophrenia and schizoaffective disorder with antipsychotic-induced weight gain. METHODS: A 2-year retrospective case analysis was performed in all 300 patients of the outpatient Special Follow-up Clinic for chronic schizophrenia and related psychoses at the Allan Memorial Institute, McGill University Health Centre (Montreal, Canada), a tertiary care University teaching hospital. RESULTS: 10 patients met study inclusion criteria. Mean daily topiramate dose was 197.5 mg (A+/-77) (range, 125-400 mg). Topiramate produced continued weight loss throughout the study duration without tolerance. Patients treated for 6 months and more had significantly higher Body Mass Index (BMI) differences than those treated for shorter durations (BMI-d6 months=-4.7A+/-2.4; BMI-d2 months=-3.2A+/-2.3; P=0.015). BMI changes were similar across genders. CONCLUSION: This study supports topiramate use to target weight loss in stable overweight schizophrenic patients as a potential therapy that requires further investigation.

Effects of intravenous glucose on dopaminergic function in the human brain in vivo.

Dopamine is known to regulate food intake by modulating food reward via the mesolimbic circuitry of the brain. The objective of this study was to compare the effects of high energy input (i.v. glucose) on striatal and thalamic dopamine release in overweight and lean individuals. We hypothesized that glucose would induce dopamine release and positive ratings (e.g., satiety) in Behavioral Analog Scales, particularly in food-deprived lean subjects. [(11)C]raclopride PET was performed for 12 lean (mean BMI = 22 kg/m(2)) and 12 overweight (mean BMI = 33 kg/m(2)) healthy subjects. Each subject was imaged twice in a blinded counter-balanced setting, after 300 mg/kg i.v. glucose and after i.v. placebo. Dopamine D2 receptor binding potentials (BPs) were estimated. The voxel-based analysis of the baseline scans indicated lower striatal BPs in the overweight group and a negative correlation between BMIs and BPs. Intravenous glucose did not have a significant effect on BPs in overweight or lean subjects (male and female groups combined). However, BP changes were opposite in the two gender groups. In male subjects, significant BP reductions after glucose were seen in the right and left caudate nucleus, left putamen, and right thalamus. In female subjects, increases in BP secondary to glucose were seen in the right caudate nucleus and right and left putamen. The sexually dimorphic effect of glucose was seen in both overweight and lean subjects. Although gender differences were not among the a priori hypotheses of the present study and, therefore, they must be considered to be preliminary findings, we postulate that this observation is a reflection of an interaction between glucose, sex steroids (estrogen), leptin, and dopamine.

Histamine H1-receptors differentially mediate the action of amylin on hypothalamic neurons in control and in overweight rats.

The hypothalamic arcuate, dorsomedial and paraventricular nuclei are involved in regulation of body weight and food intake and contain binding sites for the anorexigenic amylin. Effects of amylin on medial arcuate and paraventricular neurons studied in adult rats overweight through early postnatal overfeeding in small litters (SL) differed from those of control litters (CL). Now we observed that also dorsomedial neurons respond differentially to this satiety signal. They were significantly inhibited by amylin in SL but not CL rats. Since the histaminergic system seems to be involved in mediating effects of amylin, we studied the role of histamine H(1)-receptors. Single unit activity was recorded in brain slices of CL and SL rats in each of the three hypothalamic nuclei. The histamine H(1)-receptor antagonist pyrilamine differentially altered or reduced responses to amylin, not depending on the kind of litter but on the functional effect of the peptide. Pyrilamine prevented significant inhibition of medial arcuate neurons in controls as well as inhibition of dorsomedial and paraventricular neurons in SL rats. Searching for further mechanisms possibly contributing to the change of neuronal responses we found that in the presence of a GABA(A)-receptor antagonist amylin induced a significant inhibition of medial arcuate neurons in SL rats similar to that in CL without antagonist. Activation of medial arcuate neurons expressing the orexigenic neuropeptide Y and inhibition of dorsomedial and paraventricular neurons in SL rats may in vivo contribute to hyperphagia and overweight. Histamine H(1)-receptors and GABA(A)-receptors seem to be differentially involved in mediation of these effects.

Does a high-protein diet improve weight loss in overweight and obese children?

OBJECTIVE: To evaluate the effect of a high-protein diet on anthropometry, body composition, subjective appetite, and mood sensations in overweight and obese children attending a residential weight-loss camp. RESEARCH METHODS AND PROCEDURES: Children (120; BMI, 33.1 +/- 5.5 kg/m(2); age, 14.2 +/- 1.9 years) were randomly assigned to either a standard or high-protein diet group (15% vs. 22.5% protein, respectively). All children were assessed at baseline and at the end of the camp for anthropometry, body composition, blood pressure, biochemical variables (n = 27), and subjective appetite and mood sensations (n = 50). RESULTS: Attendance at the weight-loss camp resulted in significant improvements in most measures. Campers lost 5.5 +/- 2.9 kg in body weight (p < 0.001) and 3.8 +/- 5.4 kg in fat mass (p < 0.001) and reduced their BMI standard deviation score by 0.27 +/- 0.1 (p < 0.001) and their waist circumference by 6.6 +/- 2.8 cm (p < 0.001). Subjective sensations of hunger increased significantly over the camp duration, but no other changes in appetite or mood were observed. There were no significant differences between the two diets on any physical or subjective measures. DISCUSSION: Weight-loss camps are effective in assisting children to lose weight and improve on a range of health outcomes, independently of the protein content of the diet. The implications of an increase in hunger associated with weight loss needs to be considered. Further work is warranted to investigate whether higher levels of dietary protein are feasible or effective in longer-term weight-loss interventions of this type.

Effects of combined oleoyl-estrone and rimonabant on overweight rats.

Oleoyl-estrone (OE) decreases appetite, maintains energy expediture, induces lipolysis (sparing protein), and decreases cholesterolemia and insulin resistance. Rimonabant (SR141716) is a cannabinoid-receptor inhibitor that decreases appetite and mobilizes fat. We studied whether their combination improves their slimming effects. Male overweight rats received daily gavages of 5.3 mg/kg OE, 10 mg/kg rimonabant, or both drugs during 10 days. Body weight and composition, energy balance, adipose tissue weight, and serum hormones and metabolites were measured. OE halved food intake and maintained energy expenditure at the expense of body fat. Rimonabant effects on appetite and energy balance were less marked, resulting in lower lipid mobilization. OE and rimonabant followed the OE pattern, with no additive or synergic effects. Glycemia was maintained, but OE decreased insulin, GLP-1, and cholesterol, whilst rimonabant increased cholecystokinin and cholesterol, and decreased NEFA. Both drugs decreased leptin and triacylglycerols; ghrelin was unchanged. The results hint at different mechanisms of action of both drugs: we can assume that OE effects do not involve the cannabinoid pathway. OE does not seem to act, either, after 10 days, through the secretion of ghrelin or the intestinal appetite-controlling peptides tested.

Drug treatment of the overweight patient.

Three medications with approval for long-term use in the treatment of obesity are currently available in the United States. Sibutramine (U.S. Food and Drug Administration [FDA] approved in 1997), orlistat (FDA approved in 1999), and rimonabant (available in Europe and given FDA approvable status in 2006 and expected to be marketed in 2007) represent modern approaches to medications used adjunctively for weight management. As demonstrated in large clinical trials of 2 to 4 years' duration, these medications significantly increase weight loss compared with placebo; weight loss with these drugs reaches a nadir between 20 and 28 weeks; weight loss, averaged 8%-10%, with the placebo contributing 4%-6% of that. Weight maintenance is demonstrated as long as adherence to medication continues. All medications have side effects that need to be considered. For sibutramine, there is a rise in blood pressure and heart rate that may require discontinuation of the drug in a small percent of patients. For orlistat, steatorrhea produces the principal gastrointestinal side effects. Rimonabant appears to have a favorable safety and tolerability profile. Nausea and gastrointestinal symptoms are the chief tolerability issue, but they are usually self-limited. In addition there are several drugs and drug combinations in phase 2 or phase 2 trials that will be reported on in the coming years.

[Cardiometabolic effects of rimonabant in obese/overweight subjects with dyslipidaemia or type 2 diabetes]. / Effets cardio-métaboliques du rimonabant chez le sujet obèse ou en surpoids avec dyslipidémie ou diabète de type 2.

Rimonabant (Acomplia) is the first selective CB1 receptor blocker of the endocannabinoid system. It has been evaluated in the RIO ("Rimonabant In Obesity and related disorders") programme including above 6.600 overweight/obese patients with or without comorbidities followed for 1 to 2 years. Compared to placebo, rimonabant 20 mg/day consistently increases weight loss, reduces waist circumference, increases HDL cholesterol, lowers triglyceride levels, diminishes insulin resistance, and reduces the prevalence of metabolic syndrome. In patients with type 2 diabetes, rimonabant also diminishes HbA1c levels, an effect confirmed in the recent SERENADE trial. Almost half of the metabolic effects occurs beyond weight loss, suggesting direct peripheral effects of rimonabant. Rimonabant is indicated in Europe as an adjunct to diet and exercise for the treatment of obese patients, or overweight patients with associated risk factor(s), such as type 2 diabetes or dyslipidaemia.

[A nursing experience in a patient with antipsychotics-induced overweight].

The purpose of this article is to describe a nursing experience with a patient with schizophrenia who had antipsychotics-induced overweight. The authors assessed the patient's health condition and provided weight management to reduce her hallucinations as well as her body weight between May 1 and June 10, 2004. Three nursing problems had been identified as follows: disturbed sensory perception, imbalanced nutrition, and ineffective health maintenance. During the nursing process, the authors established a rapport relationship with the patient and her mother, educated them in skills for reducing hallucinations, and designed an individual body weight management program. After the interventions, the patient was able to positively face her illness, effectively use methods to reduce the impact of hallucinations, and successfully lose 5.5 kg. From this perspective, an individual body weight management program can be an effective intervention for nurses to care for this group of patients.

A Dietary supplement containing standardized Phaseolus vulgaris extract influences body composition of overweight men and women.

BACKGROUND: More than one billion human adults worldwide are overweight and, therefore, are at higher risk of developing cardiovascular diseases, diabetes, and a variety of other chronic perturbations. Many believe that use of natural dietary supplements could aid in the struggle against obesity. So-called "starch blockers" are listed among natural weight loss supplements. Theoretically, they may promote weight loss by interfering with the breakdown of complex carbohydrates thereby reducing, or at least slowing, the digestive availability of carbohydrate-derived calories and/or by providing resistant starches to the lower gastrointestinal tract. AIMS: The present research study examines a dietary supplement containing 445 mg of Phaseolus vulgaris extract derived from the white kidney bean, previously shown to inhibit the activity of the digestive enzyme alpha amylase, on body composition of overweight human subjects. METHODS: A randomized, double-blinded, placebo-controlled study was conducted on 60 pre-selected, slightly overweight volunteers, whose weight had been essentially stable for at least six months. The volunteers were divided into two groups, homogeneous for age, gender, and body weight. The test product containing Phaseolus vulgaris extract and the placebo were taken one tablet per day for 30 consecutive days before a main meal rich in carbohydrates. Each subject's body weight, fat and non-fat mass, skin fold thickness, and waist/hip/thigh circumferences were measured. RESULTS: After 30 days, subjects receiving Phaseolus vulgaris extract with a carbohydrate-rich, 2000- to 2200-calorie diet had significantly (p<0.001) greater reduction of body weight, BMI, fat mass, adipose tissue thickness, and waist,/hip/ thigh circumferences while maintaining lean body mass compared to subjects receiving placebo. CONCLUSION: The results indicate that Phaseolus vulgaris extract produces significant decrements in body weight and suggest decrements in fat mass in the face of maintained lean body mass.

Six months supplementation with conjugated linoleic acid induces regional-specific fat mass decreases in overweight and obese.

Long-term supplementation with conjugated linoleic acid (CLA) reduces body fat mass (BFM) and increases or maintains lean body mass (LBM). However, the regional effect of CLA was not studied. The study aimed to evaluate the effect of CLA per region and safety in healthy, overweight and obese adults. A total of 118 subjects (BMI: 28-32 kg/m2) were included in a double blind, placebo-controlled trial. Subjects were randomised into two groups supplemented with either 3 x 4 g/d CLA or placebo for 6 months. CLA significantly decreased BFM at month 3 (Delta=- 0 x 9 %, P=0 x 016) and at month 6 (Delta=- 3 x 4 %, P=0 x 043) compared with placebo. The reduction in fat mass was located mostly in the legs (Delta=- 0 x 8 kg, P<0 x 001), and in women (Delta=-1 x 3 kg, P=0 x 046) with BMI >30 kg/m2 (Delta=-1 x 9 kg, P=0 x 011), compared with placebo. The waist-hip ratio decreased significantly (P=0 x 043) compared with placebo. LBM increased (Delta=+0 x 5 kg, P=0 x 049) within the CLA group. Bone mineral content was not affected (P=0 x 70). All changes were independent of diet and physical exercise. Safety parameters including blood lipids, inflammatory and diabetogenic markers remained within the normal range. Adverse events did not differ between the groups. It is concluded that supplementation with CLA in healthy, overweight and obese adults decreases BFM in specific regions and is well tolerated.

Overweight and obesity affect treatment response in major depression.

BACKGROUND: Epidemiologic and clinical studies suggest comorbidity between major depressive disorder (MDD) and obesity. To elucidate the impact of weight on the course of depression beyond comorbidity, we investigated psychopathology, attention, neuroendocrinology, weight change, and treatment response in MDD patients, depending on their weight. METHODS: Four hundred eight inpatients with MDD participated in the Munich Antidepressant Response Signature Study, designed to discover biomarkers and genotypes that are predictive for clinical outcome. Psychopathology and anthropometric parameters were monitored weekly in 230 patients. In subsamples, combined dexamethasone-corticotropin-releasing hormone and attention tests were conducted at admission and discharge. One thousand twenty-nine diagnosed matched controls served for morphometric comparisons. RESULTS: Patients with MDD had a significantly higher body mass index (BMI) compared with healthy controls. Patients with high BMI (> or =25) showed a significantly slower clinical response, less improvement in neuroendocrinology and attention, and less weight gain than did patients with normal BMI (18.5 < or = BMI < 25) during antidepressant treatment. CONCLUSIONS: Our findings suggest that overweight and obesity characterize a subgroup of MDD patients with unfavorable treatment outcome.

Plasma triacylglycerol and coagulation factor concentrations predict the anticoagulant effect of dietary fish oil in overweight subjects.

Fish oil, containing (n-3) PUFA, is associated with a moderate reduction in cardiovascular disease through a multifactorial mechanism involving a decrease in plasma lipids and anticoagulant activity. Two intervention studies on subjects at risk were performed to determine the relation of these 2 fish-oil effects. In study 1, 54 overweight subjects consumed 3.1 g (n-3) PUFA daily. In study 2, which involved 42 overweight patients with type 2 diabetes, 20 subjects consumed (n-3) PUFA, whereas 22 others ingested a preparation rich in (n-6) PUFA. Tissue factor-induced thrombin generation (thrombin potential) was determined as an integrated measure of plasma coagulant activity. In both studies, multivariate analysis indicated a strong clustering of fasting concentrations of triacylglycerols, prothrombin, factor V, factor VII, and factor X with one another at baseline. This cluster of factors determined partly the interindividual variation in thrombin generation, of which prothrombin and triacylglycerol concentrations were the main determinants. In both healthy subjects and diabetes patients, high triacylglycerol concentrations (>1.69 mmol/L) at baseline were closely linked to a strong fish oil-induced lowering of triacylglycerol and coagulation factor V, VII, and X concentrations, and thrombin generation. We conclude that high fasting triacylglycerol concentrations predict high procoagulant activity and a lowering of thrombin potential with dietary fish oil.

Antihypertensive and lipid lowering treatment in 70-74 year old individuals--predictors for treatment and blood-pressure control: a population based survey. The Hordaland Health Study (HUSK).

BACKGROUND: In an elderly, community based population we aimed at investigating antihypertensive and lipid lowering medication use in relation to own and familiar cardiovascular morbidity and diabetes mellitus, as well as to lifestyle factors and general health. We also examined levels of blood pressure in untreated and treated residents, to investigate factors correlating with blood pressure control. METHODS: A health survey carried out in 1997-9 in the county of Hordaland, Norway included a self-administered questionnaire mailed to 4,338 persons born in 1925-7. Drug use the day prior to filling in the questionnaire was reported. A health check-up was carried out, where their systolic and diastolic blood pressure (SBP and DBP), body mass index (BMI), and serum-cholesterol level were recorded. RESULTS: One third of respondents used one or more antihypertensive drugs, while 13% of men and women were treated with a statin. Diabetes mellitus, own or relatives'cardiovascular disease, having quit smoking, physical inactivity, and overweight correlated with antihypertensive treatment. Mean blood pressure was lower in respondents not on treatment. Among those on treatment, 38% of men and 29% of women had reached a target BP-level of lower than 140/90 mm Hg. Own cardiovascular disease and a low BMI correlated with good BP-control. CONCLUSION: One third of 70-74 year old individuals living in the community used one or more antihypertensive drugs. Only around one third of those treated had reached a target BP-level of less than 140/90 mm Hg. Own cardiovascular disease and a low BMI correlated with good BP-control.