A 6-month randomized,placebo-controlled,dose-ranging trial of topiramate for weight loss in obesity

OBJECTIVE: To evaluate the efficacy and safety of topiramate (TPM) for weight loss in healthy obese subjects. RESEARCH METHODS AND PROCEDURES: A randomized, double-blind, placebo-controlled, dose-ranging trial was conducted. Three hundred eighty-five subjects, 18 and 75 years of age, were randomized to receive either placebo or TPM at 64, 96, 192, or 384 mg daily. Dosing began at 16 mg once daily. In week 2, the dose was increased to 16 mg twice daily. Thereafter, the dose was raised every week by 32 mg/d (16 mg twice daily) until subjects reached their target dose. Twenty-four weeks after beginning treatment, all subjects were tapered off treatment by a dose reduction of 50% per week. All participants received the same lifestyle program. RESULTS: Mean percent weight loss from baseline to week 24 was -2.6% in placebo-treated patients vs. -5.0%, -4.8%, -6.3%, and -6.3% in the 64, 96, 192, and 384 mg/d TPM groups, respectively. Greater percentages of TPM-treated patients lost at least 5% or 10% of body weight compared with placebo. The most frequent adverse events were related to the central or peripheral nervous system, including paresthesia, somnolence, and difficulty with memory, concentration, and attention. Most events were dose-related, occurred early in treatment, and usually resolved spontaneously; only 21% receiving TPM withdrew due to adverse events compared with 11% on placebo. DISCUSSION: TPM produced significantly greater weight loss than placebo at all doses.     

Bupropion SR enhances weight loss: a 48-week double-blind,placebo- controlled trial

OBJECTIVE: To critically examine the efficacy of bupropion SR for weight loss. RESEARCH METHODS AND PROCEDURES: This 24-week multicenter, double-blind, placebo-controlled study randomized obese adults to placebo, bupropion SR 300, or 400 mg/d. Subjects were counseled on energy-restricted diets, meal replacements, and exercise. During a 24-week extension, placebo subjects were randomized to bupropion SR 300 or 400 mg/d in a double-blinded manner. RESULTS: Of 327 subjects enrolled, 227 completed 24 weeks; 192 completed 48 weeks. Percentage losses of initial body weight for subjects completing 24 weeks were 5.0%, 7.2%, and 10.1% for placebo, bupropion SR 300, and 400 mg/d, respectively. Compared with placebo, net weight losses were 2.2% (p = 0.0468) and 5.1% (p < 0.0001) for bupropion SR 300 and 400 mg/d, respectively. The percentages of subjects who lost >or=5% of initial body weight were 46%, 59%, and 83% (p vs. placebo < 0.0001) for placebo, bupropion SR 300, and 400 mg/d, respectively; weight losses of >or=10% were 20%, 33%, and 46% (p vs. placebo = 0.0008) for placebo, bupropion SR 300, and 400 mg/d, respectively. Withdrawals, changes in pulse and blood pressure did not differ significantly from placebo at 24 weeks. Subjects who completed 48 weeks maintained mean losses of initial body weight of 7.5% and 8.6% for bupropion SR 300 and 400 mg/d, respectively. DISCUSSION: Bupropion SR 300 and 400 mg/d were well-tolerated by obese adults and were associated with a 24-week weight loss of 7.2% and 10.1% and sustained weight losses at 48 weeks.     

Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study.

BACKGROUND: Long-term maintenance of weight loss remains a therapeutic challenge in obesity treatment. OBJECTIVE: This multicenter, double-blind, placebo-controlled study was designed to test the hypothesis that orlistat, a gastrointestinal lipase inhibitor, is significantly more effective than a placebo in preventing weight regain. DESIGN: Obese subjects who lost > or = 8% of their initial body weight during a 6-mo lead-in of a prescribed hypoenergetic diet (4180-kJ/d deficit) with no adjunctive pharmacotherapy were randomly assigned to receive placebo, 30 mg orlistat, 60 mg orlistat, or 120 mg orlistat 3 times daily for 1 y in combination with a maintenance diet to help prevent weight regain. Of 1313 recruited subjects [body mass index (in kg/m2): 28-43], 729 subjects lost > or =8% of their initial body weight during the 6-mo weight-loss lead-in period and were enrolled in the double-blind phase. RESULTS: After 1 y, subjects treated with 120 mg orlistat 3 times daily regained less weight than did placebo-treated subjects (32.8 +/- 4.5% compared with 58.7 +/- 5.8% regain of lost weight; P < 0.001). Moreover, more subjects in the 120-mg orlistat group than in the placebo group regained < or = 25% of lost weight (47.5% of subjects compared with 29.9%). In addition, orlistat treatment (120 mg 3 times daily) was associated with significantly greater reductions in total and LDL-cholesterol concentrations than was placebo (P < 0.001). CONCLUSION: The use of orlistat during periods of attempted weight maintenance minimizes weight readjustment and facilitates long-term improvement in obesity-related disease risk factors.     

Bupropion for weight loss: an investigation of efficacy and tolerability in overweight and obese women

OBJECTIVE: On the basis of the clinical observations that bupropion facilitated weight loss, we investigated the efficacy and tolerability of this drug in overweight and obese adult women. RESEARCH METHODS AND PROCEDURES: A total of 50 overweight and obese (body mass index: 28.0 to 52.6 kg/m(2)) women were included. The core component of the study was a randomized, double-blind, placebo-controlled comparison for 8 weeks. Bupropion or placebo was started at 100 mg/d with gradual dose increase to a maximum of 200 mg twice daily. All subjects were prescribed a 1600 kcal/d balanced diet and compliance was monitored with food diaries. Responders continued the same treatment in a double-blind manner for an additional 16 weeks to a total of 24 weeks. There was additional single-blind follow-up treatment for a total of 2 years. RESULTS: Subjects receiving bupropion achieved greater mean weight loss (last-observation-carried-forward analysis) over the first 8 weeks of the study (p = 0.0001): 4.9% +/- 3.4% (n = 25) for bupropion treatment compared with 1.3% +/- 2.4% (n = 25) for placebo treatment. For those who completed the 8 weeks, the comparison was 6.2% +/- 3.1% (n = 18) vs. 1.6% +/- 2.9% (n = 13), respectively(p = 0.0002), with 12 of 18 of the bupropion subjects (67%) losing over 5% of baseline body weight compared with 2 of 13 in the placebo group (15%; p = 0.0094). In the continuation phase, 14 bupropion responders who completed 24 weeks achieved weight loss of 12.9% +/- 5.6% with fat accounting for 73.5% +/- 3.7% of the weight lost and no change in bone mineral density as assessed by DXA. Bupropion was generally well-tolerated in this sample. DISCUSSION: Bupropion was more effective than placebo in achieving weight loss at 8 weeks in overweight and obese adult women in this preliminary study. Initial responders to bupropion benefited further in the continuation phase.     

Effects of green tea on weight maintenance after body-weight loss

The present study was conducted to investigate whether green tea may improve weight maintenance by preventing or limiting weight regain after weight loss of 5 to 10 % in overweight and moderately obese subjects. The study had a randomised, parallel, placebo-controlled design. A total of 104 overweight and moderately obese male and female subjects (age 18-60 years; BMI 25-35 kg/m(2)) participated. The study consisted of a very-low-energy diet intervention (VLED; 2.1 MJ/d) of 4 weeks followed by a weight-maintenance period of 13 weeks in which the subjects received green tea or placebo. The green tea contained caffeine (104 mg/d) and catechins (573 mg/d, of which 323 mg was epigallocatechin gallate). Subjects lost 6.4 (sd 1.9) kg or 7.5 (sd 2.2) % of their original body weight during the VLED (P<0.001). Body-weight regain was not significantly different between the green tea and the placebo group (30.5 (sd 61.8) % and 19.7 (sd 56.9) %, respectively). In the green tea treatment, habitual high caffeine consumption was associated with a higher weight regain compared with habitual low caffeine consumption (39 (sd 17) and 16 (sd 11) %, respectively; P<0.05). We conclude that weight maintenance after 7.5 % body-weight loss was not affected by green tea treatment and that habitual caffeine consumption affected weight maintenance in the green tea treatment.     

Bupropion SR vs. placebo for weight loss in obese patients with depressive symptoms

OBJECTIVE: This randomized, double-blind, placebo-controlled study evaluated the efficacy and tolerability of bupropion sustained-release (bupropion SR) in reducing weight and depressive symptoms in obese adults. RESEARCH METHODS AND PROCEDURES: Obese adults (body mass index, 30 to 44 kg/m(2)) not currently meeting criteria for major depression but with depressive symptoms (Beck Depression Inventory score 10-30) received bupropion SR 300 mg/d or placebo for 26 weeks with a 500 kcal/d-deficit diet. Patients who lost <5% of baseline weight at week 12 had bupropion SR dosage or placebo increased to 400 mg/d in a blinded fashion. RESULTS: The bupropion SR group (n = 193) lost an average of 4.4 kg (4.6% of baseline weight) vs. 1.7 kg (1.8% of baseline weight) on placebo (n = 191, p < 0.001, last-observation-carried-forward analysis). More patients in the bupropion SR group than in the placebo group (40% vs. 16% of intent-to-treat sample, 50% vs. 28% of completers, respectively) lost at least 5% of baseline weight (p < 0.05 at week 4, p < 0.001 at weeks 6 to 26). The percentage of patients reporting > or =50% decrease in depressive symptoms did not differ between groups, but depressive symptoms improved more with bupropion SR than with placebo among patients with a history of major depression (p < 0.05, weeks 4 to 26). In the sample as a whole, improvement in depressive symptoms was related to weight loss of > or =5% regardless of treatment (p < 0.0001). Bupropion SR was well-tolerated. DISCUSSION: Bupropion SR in combination with a 500 kcal/d-deficit diet facilitated weight loss. Weight loss of > or =5% may improve mood in obese patients with depressive symptoms.     

Calcium and dairy acceleration of weight and fat loss during energy restriction in obese adults

OBJECTIVE: Increasing 1,25-dihydroxyvitamin D in response to low-calcium diets stimulates adipocyte Ca2+ influx and, as a consequence, stimulates lipogenesis, suppresses lipolysis, and increases lipid accumulation, whereas increasing dietary calcium inhibits these effects and markedly accelerates fat loss in mice subjected to caloric restriction. Our objective was to determine the effects of increasing dietary calcium in the face of caloric restriction in humans. RESEARCH METHODS AND PROCEDURES: We performed a randomized, placebo-controlled trial in 32 obese adults. Patients were maintained for 24 weeks on balanced deficit diets (500 kcal/d deficit) and randomized to a standard diet (400 to 500 mg of dietary calcium/d supplemented with placebo), a high-calcium diet (standard diet supplemented with 800 mg of calcium/d), or high-dairy diet (1200 to 1300 mg of dietary calcium/d supplemented with placebo). RESULTS: Patients assigned to the standard diet lost 6.4 +/- 2.5% of their body weight, which was increased by 26% (to 8.6 +/- 1.1%) on the high-calcium diet and 70% (to 10.9 +/- 1.6% of body weight) on the high-dairy diet (p < 0.01). Fat loss was similarly augmented by the high-calcium and high-dairy diets, by 38% and 64%, respectively (p < 0.01). Moreover, fat loss from the trunk region represented 19.0 +/- 7.9% of total fat loss on the low-calcium diet, and this fraction was increased to 50.1 +/- 6.4% and 66.2 +/- 3.0% on the high-calcium and high-dairy diets, respectively (p < 0.001). DISCUSSION: Increasing dietary calcium significantly augmented weight and fat loss secondary to caloric restriction and increased the percentage of fat lost from the trunk region, whereas dairy products exerted a substantially greater effect.     

Randomized, double-blind trial of chitosan for body weight reduction.

BACKGROUND: Overweight and obesity is a prevalent and costly threat to public health. Compelling evidence links overweight and obesity with serious disorders such as cardiovascular diseases and diabetes. Dietary regimen are notoriously burdened with poor compliance. Chitosan is promoted in the US and other countries as an oral remedy to reduce fat absorption and has now been incorporated as a major constituent into several over-the-counter remedies. The primary aim of this study is to investigate the clinical effectiveness of oral chitosan for body weight reduction. METHODS: Thirty-four overweight volunteers were included in a randomized placebo-controlled double-blind trial. Subjects were assigned to receive either four capsules of chitosan or indistinguishable placebo twice daily for 28 consecutive days. Measurements were taken at baseline, after 14 and 28d of treatment. Subjects maintained their normal diet and documented the type and amount of food consumed. Adverse effects were assessed and compliance monitored. RESULTS: Data from 30 subjects were entered into an intention-to-treat analysis. After four weeks of treatment, body mass index, serum cholesterol, triglycerides, vitamin A, D, E and beta-carotene were not significantly different in subjects receiving chitosan compared to those receiving placebo. Vitamin K was significantly increased after four weeks in the chitosan group compared with placebo (P<0.05). Compliance was 91.5% and 96.0% for chitosan and placebo groups respectively. CONCLUSION: The above data suggest that chitosan in the administered dosage, without dietary alterations, does not reduce body weight in overweight subjects. No serious adverse effects were reported.     

Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation

OBJECTIVE: Investigation of the effect of a green tea-caffeine mixture on weight maintenance after body weight loss in moderately obese subjects in relation to habitual caffeine intake. RESEARCH METHODS AND PROCEDURES: A randomized placebo-controlled double blind parallel trial in 76 overweight and moderately obese subjects, (BMI, 27.5 +/- 2.7 kg/m2) matched for sex, age, BMI, height, body mass, and habitual caffeine intake was conducted. A very low energy diet intervention during 4 weeks was followed by 3 months of weight maintenance (WM); during the WM period, the subjects received a green tea-caffeine mixture (270 mg epigallocatechin gallate + 150 mg caffeine per day) or placebo. RESULTS: Subjects lost 5.9 +/-1.8 (SD) kg (7.0 +/- 2.1%) of body weight (p < 0.001). At baseline, satiety was positively, and in women, leptin was inversely, related to subjects' habitual caffeine consumption (p < 0.01). High caffeine consumers reduced weight, fat mass, and waist circumference more than low caffeine consumers; resting energy expenditure was reduced less and respiratory quotient was reduced more during weight loss (p < 0.01). In the low caffeine consumers, during WM, green tea still reduced body weight, waist, respiratory quotient and body fat, whereas resting energy expenditure was increased compared with a restoration of these variables with placebo (p < 0.01). In the high caffeine consumers, no effects of the green tea-caffeine mixture were observed during WM. DISCUSSION: High caffeine intake was associated with weight loss through thermogenesis and fat oxidation and with suppressed leptin in women. In habitual low caffeine consumers, the green tea-caffeine mixture improved WM, partly through thermogenesis and fat oxidation.     

Orlistat in the long-term treatment of obesity in primary care settings

OBJECTIVE: To evaluate the long-term efficacy and tolerability within primary care settings of orlistat, a gastrointestinal lipase inhibitor, for the treatment of obesity. DESIGN: Randomized, double-blind, placebo-controlled, multicenter study. PARTICIPANTS: A group of 796 obese patients (body mass index, 30-44 kg/m2), treated with placebo 3 times a day (TID), 60 mg of orlistat TID, or 120 mg of orlistat TID, in conjunction with a reduced-energy diet for the first year and a weight-maintenance diet during the second year. SETTING: Seventeen primary care centers in the United States. MAIN OUTCOME MEASURES: Changes in body weight and obesity-related disease risk factors. RESULTS: Patients treated with orlistat lost significantly more weight (7.08 +/- 0.54 and 7.94 +/- 0.57 kg for the 60-mg and 120-mg orlistat groups, respectively) than those treated with placebo (4.14 +/- 0.56 kg) in year 1 (P<.001) and sustained more of this weight loss during year 2 (P<.001). More patients treated with orlistat lost 5% or more of their initial weight in year 1 (48.8% and 50.5% of patients in the 60-mg and 120-mg groups, respectively) compared with placebo (30.7%; P<.001), and approximately 34% of patients in the orlistat groups sustained weight loss of 5% or greater over 2 years compared with 24% in the placebo group (P<.001). Orlistat produced greater improvements than placebo in serum lipid levels and blood pressure and was well tolerated, although treatment resulted in a higher incidence of gastrointestinal events. CONCLUSIONS: This long-term study indicates that orlistat is an effective adjunct to dietary intervention in the treatment of obesity in primary care settings.     

Effect of conjugated linoleic acid supplementation after weight loss on appetite and food intake in overweight subjects

OBJECTIVE: To study the effects of 13 weeks conjugated linoleic acid (CLA) supplementation in overweight subjects on body-weight maintenance, parameters of appetite and energy intake (EI) at breakfast after weight loss. DESIGN: This study had a double-blind, placebo-controlled randomized design. SUBJECTS: A total of 26 men and 28 women (age 37.8+/-7.7 y; body mass index 27.8+/-1.5 kg/m(2)). INTERVENTIONS: Subjects were first submitted to a very-low-calorie diet (VLCD; 2.1 MJ/day) for 3 weeks after which they started with the 13-week intervention period. They either received 1.8 g CLA or placebo per day or 3.6 g CLA or placebo per day. Additionally, subjects of the high dosage intervention replaced their habitual lunch by one meal of a protein-rich, low-energy supplement. EI was measured at breakfast and appetite profile after an overnight fast. RESULTS: The mean body weight loss was 6.9+/-1.7% of their original body weight. Multiple regression analysis showed that at the end of the 13-week intervention, CLA did not have an effect on body weight regain. Feelings of fullness and satiety were increased and feelings of hunger were decreased after 13 weeks intervention by CLA compared to placebo, independent of %body weight regain. However, EI measured at breakfast was not affected by CLA. CONCLUSION: Appetite (hunger, satiety and fullness) was favorably, dose-independently affected by a 13-week consumption of 1.8 or 3.6 g CLA/day. This did not result in a lower EI at breakfast or an improved body-weight maintenance after weight loss.     

Persons Successful at Long-term Weight Loss and Maintenance Continue to Consume a Low-energy, Low-fat Diet

Objectives To describe the dietary intakes of persons who successfully maintained weight loss and to determine if differences exist between those who lost weight on their own vs those who received assistance with weight loss (eg, participated in a commercial or self-help program or were seen individually by a dietitian). Intakes of selected nutrients were also compared with data from the third National Health and Nutrition Examination Survey (NHANES III) and the 1989 Recommended Dietary Allowances (RDAs).Subjects Subjects were 355 women and 83 men, aged 18 years or older, primarily white, who had maintained a weight loss of at least 13.6 kg for at least 1 year, and were the initial enrollees in the ongoing National Weight Control Registry. On average, the participants had lost 30 kg and maintained the weight loss for 5.1 years.Methods A cross-sectional study in which subjects in the registry completed demographic and weight history questionnaires as well as the Health Habits and History Questionnaire developed by Block et al. Subjects’ dietary intake data were compared with that of similarly aged men and women in the NHANES III cohort and to the RDAs. Adequacy of the diet was assessed by comparing the intake of selected nutrients (iron; calcium; and vitamins C, A, and E) in subjects who lost weight on their own or with assistance.Results Successful maintainers of weight loss reported continued consumption of a low-energy and low-fat diet. Women in the registry reported eating an average of 1,306 kcal/day (24.3% of energy from fat); men reported consuming 1,685 kcal (23.5% of energy from fat). Subjects in the registry reported consuming less energy and a lower percentage of energy from fat than NHANES III subjects did. Subjects who lost weight on their own did not differ from those who lost weight with assistance in regards to energy intake, percent of energy from fat, or intake of selected nutrients (iron; calcium; and vitamins C, A, and E). In addition, subjects who lost weight on their own and those who lost weight with assistance met the RDAs for calcium and vitamins C, A, and E for persons aged 25 years or older.Applications Because continued consumption of a low-fat, low-energy diet may be necessary for long-term weight control, persons who have successfully lost weight should be encouraged to maintain such a diet. J Am Diet Assoc. 1998;98:408–413.     

Effects of cardiac stress during a very-low-calorie diet and exercise program in obese women

To assess the safety of very-low-calorie diets (VLCDs), stress tests known to induce arrhythmias in susceptible patients were performed in 24 obese women on a VLCD (660-720 kcal/d) for 6 wk. Half of the subjects had diet only (DO) and half underwent supervised exercise (DE) four times weekly. Five control subjects ate a balanced, moderately low-calorie diet (approximately 1400 kcal/d). Stress tests included maximal and submaximal (85%) exercise, psychological stress, and isometric handgrip tests, all with constant electrocardiogram (ECG) monitoring. Twenty-four-hour Holter monitors at weeks 0 and 6 and weekly resting ECGs were obtained. DO and DE lost similar amounts of weight. There were no changes in QT intervals or in voltage or width of the QRS complex on resting ECG and no arrhythmias on Holter monitoring. These data support the safety of VLCDs containing greater than or equal to 650 kcal/d and adequate amounts of high-quality protein, vitamins, and minerals for use for periods of at least 6 wk in normal, healthy obese women.     

Long-term weight maintenance after an intensive weight-loss program

OBJECTIVE: This prospective study assessed long-term weight maintenance of patients completing an intensive very-low-calorie diet (VLCD) weight-loss program. SUBJECTS: Individuals who had completed the 12-week core education program and lost > or = 10 kg were recruited. RESULTS: Of 154 eligible subjects, follow-up weights were obtained at > or = 2 years in 112 subjects (72.7%, 72 women, 40 men). Subjects had an average initial body mass index of 37.3 kg/m2 and an average weight loss of 29.7 kg in five months. Six hundred and forty-five follow-up weights (median, five per subject) were obtained over two to seven years of follow-up from clinic visits (70%) and self-report by telephone or mail (30%). Subjects regained an average of 2.5% per month of their lost weight during the first two to three years of follow-up; however, their weight stabilized over the next four years. Subjects regained an average of 73.4% of their weight loss during the first three years. The average weight loss maintained for 112 subjects was 22.8% of initial weight loss after an average of 5.3 years of follow-up. When successful weight maintenance was defined as maintaining a weight loss of 5% or 10% of initial (pre-treatment) body weight, 40% were maintaining a 5% weight loss at five years and 25% were maintaining a weight loss of 10% at 7 years. Multiple regression analyses suggested that age had a significant (p=0.004) and positive effect on weight maintenance. CONCLUSIONS: This study suggests that weight maintenance after an intensive VLCD program is improving but still needs intensive efforts to enable most individuals to maintain a substantial percentage of their weight loss long-term.     

Effect of a dietary herbal supplement containing caffeine and ephedra on weight, metabolic rate, and body composition

OBJECTIVE: To evaluate the effect of a dietary supplement containing herbal caffeine (70 mg/dose) and ephedra (24 mg/dose; C&E) on metabolic rate, weight loss, body composition, and safety parameters. RESEARCH METHODS AND PROCEDURES: In phase I, 12 healthy subjects with a BMI of 25 to 35 kg/m2 had resting metabolic rate (RMR) measured for 2 hours after ingesting C&E or a placebo on two occasions 1 week apart, followed by a 1-week washout before phase II. In phase II, these 12 and 28 additional subjects were randomized to a 12-week, double-blind trial comparing C&E (3 times/day) to placebo. In phase III, the C&E group was given open-label C&E for 3 months, and the placebo group was given C&E for 6 months. RESULTS: In phase I, C&E gave an average 8 +/- 0.1% (SE) rise in RMR over 2 hours compared with placebo (p < 0.01). In phase II, weight loss at 12 weeks was 3.5 +/- 0.6 kg with C&E compared with 0.8 +/- 0.5 kg with placebo (p < 0.02). The percentage fat lost, shown by DXA, was 7.9 +/- 2.9% with C&E and 1.9 +/- 1.1% with placebo (p < 0.05). Pulse decreased more in the placebo group that in the C&E group (p < 0.03). There were no differences in lipid levels or blood pressure. In phase III, there was a 6-month loss of 7.3% and 7.8% of initial body weight for the groups on placebo and C&E during phase II, respectively. There were no serious adverse events. DISCUSSION: C&E increased RMR significantly by 8% compared with placebo, promoted more weight and fat loss than placebo, and was well tolerated.     

The long-term influence of orlistat on dietary intake in obese subjects with components of metabolic syndrome

Background:  Orlistat is a lipase inhibitor that reduces the intestinal absorption of fat and may enhance the effects of dietary and behavioural therapy on weight loss and maintenance. The present study examined the effect of orlistat on dietary intake, especially fat intake, during long-term weight maintenance.
Methods:  Subjects comprised 44 men and women (aged 18–63 years; body mass index 37.5 ± 4.3 kg m⁻²) included in the Scandinavian Multicenter study of Obese subjects with the metabolic syndrome, a 3-year clinical trial of orlistat or placebo following an 8-week, very low energy diet (VLED). Two months after the end of the trial when the use of orlistat was optional, 33 subjects remained in the study. A dietary interview based on a validated food frequency questionnaire was conducted before the VLED, after 1 year of treatment with orlistat or placebo and 2 months after the end of the trial.
Results:  At 1 year, dietary intake did not differ between the orlistat and placebo group. Energy percent (E%) fat was reduced and E% carbohydrate was increased within both groups. Two months after the end of the trial, E% fat was 32.6% (SD 6.2%) in subjects that chose to take orlistat and 27.7% (SD 5.5%) in subjects not taking orlistat [between group difference −5.0% (95% confidence interval −9.2 to −0.7); P  = 0.021].
Conclusions:  The use of orlistat compared with placebo in a lifestyle modification programme does not appear to influence dietary intake. Subjects that chose to take orlistat after the end of the programme did not comply with dietary recommendations and this may hamper the effect of the drug.     

Is DL-fenfluramine a potentially helpful drug therapy in overweight adolescent subjects?

We have studied the therapeutic effects of two different doses (30 mg and 60 mg, twice daily) of DL-fenfluramine (DL-F) in, respectively, prepuberal (11-13 years old) and adolescent subjects (14-17 years old). Sixty-eight obese subjects were recruited for this study (22 boys, 36 girls, aged 10-17 years old) with body mass index ranging from 24.5 to 44.0 kg/m2, absolute weight ranging from 37.0 to 119.5 kg and % over IBW ranging from 122% to 260%. Results were compared to a placebo treated group of obese adolescent patients (n = 17), 6 boys and 11 girls, aged 10-17 years old, BMI ranging from 26-44 kg/m2, absolute weight 53.1 to 96.5 kg, and with 129% to 253% over IBW. In the DL-F-treated subjects most patients (n = 41) had a continuous weight loss during 12 months but 27 individuals were unable to lose any additional weight after the initial 6 months of the trial. Taken together 65% of all patients lost weight during DL-F treatment (12 months) whereas only 17.4% of the placebo group lost a significant (> 10% BMI) amount of excess weight. Also the placebo group had a higher withdrawal rate (57%) as compared with the DL-F-treated group (24%). There was a significant (p < 0.05) decrease of the mean +/- SD of the BMI (at 6 and 12 months of therapy). No significant change of the BMI was observed for control group. Minor adverse side effects consisted of a brief period of drowsiness and dry mouth. Our findings indicated that the continuous administration of DL-Fenfluramine might help obese adolescent subjects adhere to a diet and to maintain the weight loss achieved without major or harmful adverse effects.     

Growth hormone favorably affects bone turnover and bone mineral density in patients with short bowel syndrome undergoing intestinal rehabilitation

BACKGROUND: Patients with short bowel syndrome (SBS) have a high prevalence of metabolic bone disease due to nutrient malabsorption and potential effects of parenteral nutrition (PN). Human growth hormone (hGH) has been shown in some studies to have anabolic effects on bone, but hGH effects on bone in patients with SBS are unknown. METHODS: Adults with PN-dependent SBS underwent a 7-day period of baseline studies while receiving usual oral diet and PN and then began receiving modified diets designed to improve nutrient absorption and daily oral calcium/vitamin D supplements (1500 mg elemental calcium and 600 IU vitamin D, respectively). Subjects were randomized to receive in a double-blind manner either subcutaneous (sc) saline placebo as the control or hGH (0.1 mg/kg/d for 3 weeks, then 0.1 mg/kg 3 days a week for 8 subsequent weeks). Open-label hGH was given from week 13 to week 24 in subjects who required PN after completion of the 12-week double-blind phase. Markers of bone turnover (serum osteocalcin and urinary N-telopeptide [NTX]), vitamin D nutriture (serum calcium, 25-hydroxyvitamin D [25-OH D] and parathyroid hormone [PTH] concentrations), and intestinal calcium absorption were measured at baseline and at weeks 4 and 12. Dual x-ray absorptiometry (DXA) of the hip and spine was performed to determine bone mineral density (BMD) at baseline and weeks 12 and 24. RESULTS: The majority of subjects in each group exhibited evidence of vitamin D deficiency at baseline (25-OH D levels<30 ng/mL; 78% and 79% of control and hGH-treated subjects, respectively). Subjects treated with hGH demonstrated a significant increase from baseline in serum osteocalcin levels at 12 weeks (+62%; p<.05). The levels of NTX were increased over time in the hGH-treated group; however, this did not reach statistical significance. Both NTX and osteocalcin remained unchanged in control subjects. BMD of the spine and total hip was unchanged in subjects treated with placebo or hGH at 24 weeks. However, femoral neck BMD was slightly but significantly decreased in the placebo group at this time point but remained unchanged from baseline in the hGH-treated subjects. CONCLUSIONS: hGH therapy significantly increased markers of bone turnover during the initial 3 months of therapy and stabilized femoral neck bone mass over a 6-month period in patients with severe SBS undergoing intestinal rehabilitation.     

The eating disorder inventory as a predictor of compliance in a behavioral weight-loss program

Eating Disorders Inventory (EDI) is a significant and meaningful predictor of adherence in a dietary program employing a very low-calorie diet. This study used multiple linear regression and discriminant analysis to examine the dietary adherence of 105 clients who were, on average, 91 pounds overweight. With three increasingly rigid standards of success, discriminant analysis successfully classified 74%, 71%, and 63% of clients as likely successes or failures using the EDI. Using the EDI scales as the independent variables, three significant multiple regressions equations were obtained that individually were predictive of total weight lost, percentage of weight lost, or weeks in treatment.     

Pantethine, a derivative of vitamin B5 used as a nutritional supplement, favorably alters low-density lipoprotein cholesterol metabolism in low- to moderate-cardiovascular risk North American subjects: a triple-blinded placebo and diet-controlled investigation

Safety and efficacy of a biologically active derivative of vitamin B₅ (pantethine) on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) metabolism was studied in North American subjects at conventional low to moderate cardiovascular disease (CVD) risk. A total of 120 subjects initiated a therapeutic lifestyle change (TLC) diet 4 weeks before randomization (baseline) and maintained the diet throughout a 16-week study period; at baseline, subjects were randomized in a triple-blinded manner to either pantethine (600 mg/d, baseline to week 8, and 900 mg/d, weeks 9-16) or identically labeled, nonbiologically active placebo (n = 60 per group). We hypothesized that pantethine would lower TC and low-density lipoprotein in low-CVD-risk North American subjects in a similar manner as reported in high-CVD-risk subjects studied mainly in Italy and Japan. While sustaining a TLC diet and in comparison with placebo, pantethine demonstrated significant (P < .005) and sustained reductions (from baseline to week 16) in TC (6 mg/dL, 0.16 mmol/L, 3%), LDL-C (4 mg/dL, 0.10 mmol/L, 4%), and apolipoprotein B (4 mg/dL, 0.04 g/L, 5%). Our data suggest that pantethine supplementation for 16 weeks (600 mg/d for weeks 1-8 then 900 mg/d for weeks 9-16) is safe and significantly lowers TC and LDL-C over and above the effect of TLC diet alone. Although the absolute magnitude of these effects was small in these low- to moderate-risk North Americans (4-6 mg/dL), the results are noteworthy as prior studies have shown that, for each 1 mg/dL (0.026 mmol/L) reduction in LDL-C, there is a concomitant 1% reduction in overall future CVD risk.