Søren Toubro

Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity.

OBJECTIVE: To study the effect on weight loss in obese subjects by replacement of carbohydrate by protein in ad libitum consumed fat-reduced diets.DESIGN: Randomized dietary intervention study over six months comparing two ad libitum fat reduced diets (30% of total energy) strictly controlled in composition: High-carbohydrate (HC, protein 12% of total energy) or high-protein (HP, protein 25% of total energy).SETTING AND PARTICIPANTS: Subjects were 65 healthy, overweight and obese subjects (50 women, 15 men, aged 18–55 y) randomly assigned to HC (n=25), HP (n=25) or a control group (C, n=15). All food was provided by self-selection in a shop at the department, and compliance to the diet composition was evaluated by urinary nitrogen excretion.MAIN OUTCOME MEASURE: Change in body weight, body composition and blood lipids.RESULTS: More than 90% completed the trial. Weight loss after six months was 5.1 kg in the HC group and 8.9 kg in the HP group (difference 3.7 kg, 95% confidence interval (CI)(1.3–6.2 kg) P<0.001), and fat loss was 4.3 kg and 7.6 kg, respectively (difference 3.3 kg (1.1–5.5 kg) P<0.0001), whereas no changes occurred in the control group. More subjects lost >10 kg in the HP group (35 %) than in the HC group (9 %). The HP diet only decreased fasting plasma triglycerides and free fatty acids significantly.CONCLUSIONS: Replacement of some dietary carbohydrate by protein in an ad libitum fat-reduced diet, improves weight loss and increases the proportion of subjects achieving a clinically relevant weight loss. More freedom to choose between protein-rich and complex carbohydrate-rich foods may allow obese subjects to choose more lean meat and dairy products, and hence improve adherence to low-fat diets in weight reduction programs.

The role of postprandial releases of insulin and incretin hormones in meal-induced satiety—effect of obesity and weight reduction

BACKGROUND: Previous studies have indicated that the secretion of the intestinal satiety hormone glucagon-like peptide-1 (GLP-1) is attenuated in obese subjects.OBJECTIVE: To compare meal-induced response of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in obese and lean male subjects, to investigate the effect of a major weight reduction in the obese subjects, and to look for an association between these hormones and ad libitum food intake.METHOD: Plasma concentrations of intestinal hormones and appetite sensations were measured prior to, and every 30 min for 180 min after, ingestion of a 2.5 MJ solid test meal. Gastric emptying was estimated scintigraphically. An ad libitum lunch was served 3 h after the test meal.SUBJECTS: Nineteen non-diabetic obese (body mass index (BMI) 34.1–43.8 kg/m2) and 12 lean (BMI 20.4–24.7 kg/m2) males. All obese subjects were re-examined after a mean stabilised weight loss of 18.8 kg (95% CI 14.4–23.2).RESULTS: Total area under the GLP-1 response curve (AUCtotal, GLP-1) was lower in obese before and after the weight loss compared to lean subjects (P<0.05), although weight loss improved the response from 80 to 88% of that of the lean subjects (P=0.003). The GIP response was similar in obese and lean subjects. However, after the weight loss both AUCtotal, GIP and AUCincremental, GIP were lowered (P<0.05). An inverse correlation was observed between AUCincremental, GIP and energy intake at the subsequent ad libitum meal in all groups. In lean subjects ad libitum energy intake was largely predicted by the insulin response to the preceding meal (r 2=0.67, P=0.001).CONCLUSION: Our study confirmed previous findings of a reduced postprandial GLP-1 response in severely obese subjects. Following weight reduction, GLP-1 response in the obese subjects apparently rose to a level between that of obese and lean subjects. The data suggests that postprandial insulin and GIP responses are key players in short-term appetite regulation.

Effect of normal-fat diets, either medium or high in protein, on body weight in overweight subjects: a randomised 1-year trial

BACKGROUND: We have previously reported that a fat-reduced high-protein diet had more favourable effects on body weight loss over 6 months than a medium-protein diet.OBJECTIVE: To extend this observation by a further 6–12 months less stringent intervention and a 24 months follow-up.DESIGN: A randomised 6 months strictly controlled dietary intervention followed by 6–12 months dietary counselling period, and a subsequent 24 months follow-up, comparing an ad libitum, fat-reduced diet (30% of energy) either high in protein (25% of energy, HP) or medium in protein (12% of energy, MP).SUBJECTS: A total of 50 overweight and obese subjects (age: 19–55 y; BMI: 26–34 kg/m2).MEASUREMENTS: Change in body weight, body composition and blood parameters.RESULTS: After 6 months, the HP group (n=23) achieved a greater weight loss than the MP group (n=23) (9.4 vs 5.9 kg) (P<0.01). After 12 months, 8% had dropped out in the HP vs 28% in the MP group (P<0.07). After 12 months, the weight loss was not significantly greater among the subjects in the HP group (6.2 and 4.3 kg), but they had a 10% greater reduction in intra-abdominal adipose tissue and more in the HP group (17%) lost >10 kg than in the MP (P<0.09). At 24 months, both groups tended to maintain their 12 months weight loss, but more than 50% were lost to follow-up.CONCLUSION: A fat-reduced diet high in protein seems to enhance weight loss and provide a better long-term maintenance of reduced intra-abdominal fat stores.

PPARgamma agonists in the treatment of type II diabetes: is increased fatness commensurate with long-term efficacy?

The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the PPAR family. The endogenous activators of all members of the PPAR family are a variety of fatty acids, which suggests that the PPARs are highly involved in lipid metabolism. In the present paper, the current understanding of the involvement of PPARγ in adipocyte proliferation and adipose tissue formation is extensively reviewed, and it is stressed that PPARγ seems to be a major regulator in the differentiation of adipocytes. Thiazoledinediones (TZDs) are a group of PPARγ-agonists used in the treatment of type 2 diabetes (T2D) since 1997. They are characterized by their ability to decrease insulin resistance, and have been suggested to slow down the progression of insulin resistance. Treatment with TZD requires several weeks of treatment to decrease plasma glucose levels, but in addition they markedly decrease plasma triglycerides and free fatty acids. A major drawback of treatment with TZD is body fat gain, but some evidence suggests that the fat is redistributed in a favourable direction, that is, from visceral to subcutaneous depots. However, the effect of long-term treatment on weight gain following TZD treatment is unknown, and it may be questioned whether the use of these ‘adipogenic compounds’ is appropriate, considering that excess body fat is almost a prerequisite for the development of type 2 diabetes.

Efficacy and safety of dietary supplements containing CLA for the treatment of obesity evidence from animal and human studies

Dietary supplements containing conjugated linoleic acid (CLA) are widely promoted as weight loss agents available over the counter and via the Internet. In this review, we evaluate the efficacy and safety of CLA supplementation based on peer-reviewed published results from randomized, placebo-controlled, human intervention trials lasting more than 4 weeks. We also review findings from experimental studies in animals and studies performed in vitro. CLA appears to produce loss of fat mass and increase of lean tissue mass in rodents, but the results from 13 randomized, controlled, short-term (<6 months) trials in humans find little evidence to support that CLA reduces body weight or promotes repartitioning of body fat and fat-free mass in man. However, there is increasing evidence from mice and human studies that the CLA isomer trans-10, cis-12 may produce liver hypertrophy and insulin resistance via a redistribution of fat deposition that resembles lipodystrophy. CLA also decreases the fat content of both human and bovine milk. In conclusion, although CLA appears to attenuate increases in body weight and body fat in several animal models, CLA isomers sold as dietary supplements are not effective as weight loss agents in humans and may actually have adverse effects on human health.

Randomised comparison of diets for maintaining obese subjects' weight after major weight loss: ad lib, low fat, high carbohydrate diet v fixed energy intake.

Abstract Objectives: To compare importance of rate of initial weight loss for long term outcome in obese patients and to compare efficacy of two different weight maintenance programmes. Design: Subjects were randomised to either rapid or slow initial weight loss. Completing patients were re-randomised to one year weight maintenance programme of ad lib diet or fixed energy intake diet. Patients were followed up one year later. Setting: University research department in Copenhagen, Denmark. Subjects: 43 (41 women) obese adults (body mass index 27-40) who were otherwise healthy living in or around Copenhagen. Interventions: 8 weeks of low energy diet (2 MJ/day) or 17 weeks of conventional diet (5 MJ/day), both supported by an anorectic compound (ephedrine 20 mg and caffeine 200 mg thrice daily); one year weight maintenance programme of ad lib, low fat, high carbohydrate diet or fixed energy intake diet (≤7.8 MJ/day), both with reinforcement sessions 2-3 times monthly. Main outcome measures: Mean initial weight loss and proportion of patients maintaining a weight loss of >5 kg at follow up. Results: Mean initial weight loss was 12.6 kg (95% confidence interval 10.9 to 14.3 kg) in rapid weight loss group and 12.6 (9.9 to 15.3) kg in conventional diet group. Rate of initial weight loss had no effect on weight maintenance after 6 or 12 months of weight maintenance or at follow up. After weight maintenance programme, the ad lib group had maintained 13.2 (8.1 to 18.3) kg of the initial weight loss of 13.5 (11.4 to 15.5) kg, and the fixed energy intake group had maintained 9.7 (6.1 to 13.3) kg of the initial 13.8 (11.8 to 15.7) kg weight loss (group difference 3.5 (-2.4 to 9.3) kg). Regained weight at follow up was greater in fixed energy intake group than in ad lib group (11.3 (7.1 to 15.5) kg v 5.4 (2.3 to 8.6) kg, group difference 5.9 (0.7 to 11. 1) kg, P<0.03). At follow up, 65% of ad lib group and 40% of fixed energy intake group had maintained a weight loss of >5 kg (P<0.07). Conclusion: Ad lib, low fat, high carbohydrate diet was superior to fixed energy intake for maintaining weight after a major weight loss. The rate of the initial weight loss did not influence long term outcome. Key messages Obesity has reached epidemic proportions in the Western world, but weight loss reverses almost all the health hazards of obesity Obese patients lose weight when they keep strictly to an energy restricted diet, but weight losses tend not to be maintained in the long term We conducted an intensive one year weight maintenance programme (comparing an ad lib, low fat, high carbohydrate diet with a fixed energy intake diet) after a major weight loss (eight weeks of low energy diet or 17 weeks of conventional diet) The rate of initial weight loss did not influence the long term outcome The ad lib, low fat diet was superior in maintaining weight loss during weight maintenance programme and at one year follow up

The effect of sibutramine on energy expenditure and appetite during chronic treatment without dietary restriction.

OBJECTIVE: To assess the contribution of a thermogenic effect to weight loss induced by eight weeks treatment with sibutramine (15mg/d) vs placebo in obese subjects.DESIGN: Randomised, placebo controlled, double blind study.SUBJECTS: Thirty-two (7 male, 25 female) healthy obese body mass index (BMI) 33.9±0.5 kg/m2 subjects completed the trial.MEASUREMENTS: Energy expenditure (EE) was measured by indirect calorimetry during a 32 h stay in a respiration chamber before and after 8 weeks treatment. Visual analogue scales were completed for assessment of appetite sensation. No dietary restriction was given.RESULTS: Sibutramine caused a significant weight loss compared with placebo (−2.4 kg vs+0.3 kg, P<0.001). Despite the larger weight loss after 8 weeks, 24-h EE did not decrease more in the sibutramine than in the placebo group (−2.6% vs −2.5%, P=ns). When the changes in 24-h EE were adjusted for changes in body weight, 24-h EE decreased significantly less in the sibutramine group than in the placebo group (0.8% vs 3.8%, P<0.02). Sibutramine significantly decreased both hunger and anticipated food consumption, and increased satiety scores.CONCLUSIONS: The weight reducing effect of sibutramine in humans is caused by a dual mechanism: reduction of energy intake by increasing satiety and decreasing hunger and prevention of the decline in EE that follows weight loss.

Changes in renal function during weight loss induced by high vs low-protein low-fat diets in overweight subjects

BACKGROUND: Due to the high satiating effect of protein, a high-protein diet may be desirable in the treatment of obesity. However the long-term effect of different levels of protein intake on renal function is unclear.OBJECTIVE: To assess the renal effects of high vs low protein contents in fat-reduced diets.DESIGN: Randomized 6 months dietary intervention study comparing two controlled ad libitum diets with 30 energy (E%) fat content: high-protein (HP; 25 E%) or low-protein, (LP, 12 E% protein). All food was provided by self-selection in a shop at the department, and high compliance to the diet composition was confirmed by measurements of urinary nitrogen excretion.SUBJECTS: 65 healthy, overweight and obese (25<body mass index (BMI)<34 kg/m2).RESULTS: Dietary protein intake changed from 91.1 g/d to a 6 months intervention average of 70.4 g/d (P<0.05) in the LP group and from 91.4 g/d to 107.8 g/d (P<0.05) in the HP group, producing changes in glomular filtration rate (GFR) of −7.1 ml/min in the LP group and +5.2 ml/min in the HP group (group effect: P<0.05). Kidney volume decreased by −6.2 cm3 in the LP group and increased by +9.1 cm3 in the HP group (P<0.05), whereas albuminuria remained unchanged in all groups.CONCLUSION: Moderate changes in dietary protein intake cause adaptive alterations in renal size and function without indications of adverse effects.

THERMOGENIC SYNERGISM BETWEEN EPHEDRINE AND CAFFEINE IN HEALTHY VOLUNTEERS: A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

Animal and human studies have suggested a thermogenic synergism between ephedrine (E), a beta-agonist, and caffeine (C), an adenosine antagonist, which may be suitable for the treatment of obesity. To study this phenomenon, the thermogenic effect of single doses of oral placebo, E 10 mg, E 20 mg, C 100 mg, and C 200 mg were compared with the effects of three different combinations of E + C, 10 mg/200 mg, 20 mg/100 mg, and 20 mg/200 mg, measured by indirect calorimetry in six healthy, lean subjects. The thermogenic effect after E + C 20 mg/200 mg was larger than that of any of the other combinations. In this dose ratio, ephedrine and caffeine exerted a supra-additive synergism, whereas the thermogenic effects of the other two combinations were only additive. The 3-hour postintake increase in systolic blood pressure after all three combinations averaged 5 to 7 mm Hg more than placebo (P less than .01), which exceeded the predicted additive effect fivefold to sevenfold. Diastolic blood pressure was not increased by E + C 20 mg/200 mg, whereas the other two combinations increased it by approximately 4 mm Hg more than placebo. E + C 20 mg/100 mg and 20 mg/200 mg increased heart rate more than placebo, while E + C 10 mg/200 mg had no effect on heart rate. As expected, all combinations increased plasma glucose, insulin, and C-peptide from their ephedrine content. No significant effects of the combinations were found on plasma lactate, glycerol, nonesterified fatty acids (NEFA), triglyceride, potassium, or sodium.(ABSTRACT TRUNCATED AT 250 WORDS)

Whole Grain Compared with Refined Wheat Decreases the Percentage of Body Fat Following a 12-Week, Energy-Restricted Dietary Intervention in Postmenopausal Women

Observational studies show inverse associations between intake of whole grain and adiposity and cardiovascular risk; however, only a few dietary intervention trials have investigated the effect of whole-grain consumption on health outcomes. We studied the effect of replacing refined wheat (RW) with whole-grain wheat (WW) for 12 wk on body weight and composition after a 2-wk run-in period of consumption of RW-containing food intake. In this open-label randomized trial, 79 overweight or obese postmenopausal women were randomized to an energy-restricted diet (deficit of ~1250 kJ/d) with RW or WW foods providing 2 MJ/d. Body weight and composition, blood pressure, and concentration of circulating risk markers were measured at wk 0, 6, and 12. Fecal output and energy excretion were assessed during run-in and wk 12. Plasma alkylresorcinol analysis indicated good compliance with the intervention diets. Body weight decreased significantly from baseline in both the RW (-2.7 ± 1.9 kg) and WW (-3.6 ± 3.2 kg) groups, but the decreases did not differ between the groups (P = 0.11). The reduction in body fat percentage was greater in the WW group (-3.0%) than in the RW group (-2.1%) (P = 0.04). Serum total and LDL cholesterol increased by ~5% (P < 0.01) in the RW group but did not change in the WW group; hence, the changes differed between the groups (P = 0.02). In conclusion, consumption of whole-grain products resulted in a greater reduction in the percentage fat mass, whereas body weight changes did not differ between the RW and WW groups. Serum total and LDL cholesterol, two important risk factors of cardiovascular disease, increased with RW but not WW consumption, which may suggest a cardioprotective role for whole grain.