Marleen A. van Baak

Diets with high or low protein content and glycemic index for weight-loss maintenance

BACKGROUND Studies of weight-control diets that are high in protein or low in glycemic index have reached varied conclusions, probably owing to the fact that the studies had insufficient power. METHODS We enrolled overweight adults from eight European countries who had lost at least 8% of their initial body weight with a 3.3-MJ (800-kcal) low-calorie diet. Participants were randomly assigned, in a two-by-two factorial design, to one of five ad libitum diets to prevent weight regain over a 26-week period: a low-protein and low-glycemic-index diet, a low-protein and high-glycemic-index diet, a high-protein and low-glycemic-index diet, a high-protein and high-glycemic-index diet, or a control diet. RESULTS A total of 1209 adults were screened (mean age, 41 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 34), of whom 938 entered the low-calorie-diet phase of the study. A total of 773 participants who completed that phase were randomly assigned to one of the five maintenance diets; 548 completed the intervention (71%). Fewer participants in the high-protein and the low-glycemic-index groups than in the low-protein-high-glycemic-index group dropped out of the study (26.4% and 25.6%, respectively, vs. 37.4%; P=0.02 and P=0.01 for the respective comparisons). The mean initial weight loss with the low-calorie diet was 11.0 kg. In the analysis of participants who completed the study, only the low-protein-high-glycemic-index diet was associated with subsequent significant weight regain (1.67 kg; 95% confidence interval [CI], 0.48 to 2.87). In an intention-to-treat analysis, the weight regain was 0.93 kg less (95% CI, 0.31 to 1.55) in the groups assigned to a high-protein diet than in those assigned to a low-protein diet (P=0.003) and 0.95 kg less (95% CI, 0.33 to 1.57) in the groups assigned to a low-glycemic-index diet than in those assigned to a high-glycemic-index diet (P=0.003). The analysis involving participants who completed the intervention produced similar results. The groups did not differ significantly with respect to diet-related adverse events. CONCLUSIONS In this large European study, a modest increase in protein content and a modest reduction in the glycemic index led to an improvement in study completion and maintenance of weight loss. (Funded by the European Commission; ClinicalTrials.gov number, NCT00390637.).

Systemic β-Adrenergic Stimulation of Thermogenesis Is Not Accompanied by Brown Adipose Tissue Activity in Humans

Brown adipose tissue (BAT) is currently considered as a target to combat obesity and diabetes in humans. BAT is densely innervated by the sympathetic nervous system (SNS) and can be stimulated by β-adrenergic agonists, at least in animals. However, the exact role of the β-adrenergic part of the SNS in BAT activation in humans is not known yet. In this study, we measured BAT activity by 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) positron emission tomography/computed tomography imaging in 10 lean men during systemic infusion of the nonselective β-agonist isoprenaline (ISO) and compared this with cold-activated BAT activity. ISO successfully mimicked sympathetic stimulation as shown by increased cardiovascular and metabolic activity. Energy expenditure increased to similar levels as during cold exposure. Surprisingly, BAT was not activated during β-adrenergic stimulation. We next examined whether the high plasma free fatty acid (FFA) levels induced by ISO competed with glucose ([18F]FDG) uptake in BAT locations by blocking lipolysis with acipimox (ACI). ACI successfully lowered plasma FFA, but did not increase [18F]FDG-uptake in BAT. We therefore conclude that systemic nonselective β-adrenergic stimulation by ISO at concentrations that increase energy expenditure to the same extent as cold exposure does not activate BAT in humans, indicating that other tissues are responsible for the increased β-adrenergic thermogenesis.

Effects of Weight Loss and Long-Term Weight Maintenance With Diets Varying in Protein and Glycemic Index on Cardiovascular Risk Factors The Diet, Obesity, and Genes (DiOGenes) Study: A Randomized, Controlled Trial

Background— We sought to separately examine the effects of either weight loss or diets varying in protein content and glycemic index without further changes in body weight on cardiovascular risk factors within the Diet, Obesity, and Genes study (DiOGenes). Methods and Results— DiOGenes is a pan-European controlled dietary intervention study in 932 overweight adults who first lost body weight on an 8-week low-calorie diet and were then randomized to 1 of 5 ad libitum diets for 26 weeks. The diets were either high or low protein or high or low glycemic index in 4 combinations or control. Weight loss (−11.23 kg; 95% confidence interval, −11.54 to −10.92; P<0.001) reduced high-sensitivity C-reactive protein (−1.15 mg/L; 95% confidence interval, −1.30 to −0.41; P<0.001), low- and high-density lipoprotein cholesterol, triglycerides, and blood pressure. During the 26-week weight maintenance period in the intention-to-treat analysis, the further decrease of high-sensitivity C-reactive protein blood levels was −0.46 mg/L greater (95% confidence interval, −0.79 to −0.13) in the groups assigned to low-glycemic-index diets than in those on high-glycemic-index diets (P<0.001). Groups on low-protein diets achieved a −0.25 mg/L greater reduction in high-sensitivity C-reactive protein (95% confidence interval, −0.59 to −0.17) than those on high-protein diets (P<0.001), whereas lipid profiles and blood pressure were not differently affected. Conclusions— This large-scale intervention study clearly separates weight loss from dietary composition–related effects. Low-glycemic-index carbohydrates and, to a lesser extent, low-protein intake may specifically reduce low-grade inflammation and associated comorbidities in overweight/obese adults. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT00390637.

Dietary Protein and Blood Pressure: A Systematic Review

Background Elevated blood pressure (BP), which is a major risk factor for cardiovascular disease, is highly prevalent worldwide. Recently, interest has grown in the role of dietary protein in human BP. We performed a systematic review of all published scientific literature on dietary protein, including protein from various sources, in relation to human BP. Methodology/Principal Findings We performed a MEDLINE search and a manual search to identify English language studies on the association between protein and blood pressure, published before June 2010. A total of 46 papers met the inclusion criteria. Most observational studies showed no association or an inverse association between total dietary protein and BP or incident hypertension. Results of biomarker studies and randomized controlled trials indicated a beneficial effect of protein on BP. This beneficial effect may be mainly driven by plant protein, according to results in observational studies. Data on protein from specific sources (e.g. from fish, dairy, grain, soy, and nut) were scarce. There was some evidence that BP in people with elevated BP and/or older age could be more sensitive to dietary protein. Conclusions/Significance In conclusion, evidence suggests a small beneficial effect of protein on BP, especially for plant protein. A blood pressure lowering effect of protein may have important public health implications. However, this warrants further investigation in randomized controlled trials. Furthermore, more data are needed on protein from specific sources in relation to BP, and on the protein-BP relation in population subgroups.

Starches, sugars and obesity.

The rising prevalence of obesity, not only in adults but also in children and adolescents, is one of the most important public health problems in developed and developing countries. As one possible way to tackle obesity, a great interest has been stimulated in understanding the relationship between different types of dietary carbohydrate and appetite regulation, body weight and body composition. The present article reviews the conclusions from recent reviews and meta-analyses on the effects of different starches and sugars on body weight management and metabolic disturbances, and provides an update of the most recent studies on this topic. From the literature reviewed in this paper, potential beneficial effects of intake of starchy foods, especially those containing slowly-digestible and resistant starches, and potential detrimental effects of high intakes of fructose become apparent. This supports the intake of whole grains, legumes and vegetables, which contain more appropriate sources of carbohydrates associated with reduced risk of cardiovascular and other chronic diseases, rather than foods rich in sugars, especially in the form of sugar-sweetened beverages.

Brown adipose tissue activity after a high-calorie meal in humans

BACKGROUND Studies in rodents have shown that brown adipose tissue (BAT) is activated on food intake, thereby reducing metabolic efficiency. OBJECTIVE The current study investigated whether a single high-calorie, carbohydrate-rich meal activates BAT in lean human adults. DESIGN BAT activity was studied in 11 lean adult men [age: 23.6 ± 2.1 y; body mass index (BMI; in kg/m(2)): 22.4 ± 2.1] after consumption of a high-calorie, carbohydrate-rich meal (1622 ± 222 kcal; 78% carbohydrate, 12% protein, 10% fat). BAT activity during 2 h of mild cold exposure served as a positive control experiment. BAT activity was assessed by [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography. Energy expenditure was measured by indirect calorimetry. RESULTS Postprandial [(18)F]FDG uptake was significantly higher in BAT [1.65 ± 0.99 mean standard uptake value (SUVmean)] than in subcutaneous (0.35 ± 0.15 SUVmean; P < 0.05) and visceral (0.49 ± 0.24 SUVmean; P < 0.05) white adipose tissue and liver (0.95 ± 0.28 SUVmean; P < 0.05). Postprandial BAT activity was lower than cold-induced BAT activity (7.19 ± 2.09 SUVmean). However, postprandial BAT activity may have been underestimated because of high postprandial [(18)F]FDG uptake in skeletal muscle compared with cold (1.36 ± 0.31 compared with 0.59 ± 0.07 SUVmean, P < 0.05), which reduces [(18)F]FDG bioavailability for BAT and other tissues. No direct relation was found between BAT and diet-induced thermogenesis (DIT). CONCLUSIONS Glucose uptake in BAT increases after a meal in humans, which indicates a role for BAT in reducing metabolic efficiency. However, the quantitative contribution of BAT to DIT relative to other tissues, such as skeletal muscle, remains to be investigated. This trial was registered at www.controlled-trials.com as ISRCTN21413505.

Dietary acid load and risk of hypertension: the Rotterdam Study

BACKGROUND Mild metabolic acidosis, which can be caused by diet, may result in elevated blood pressure (BP). DESIGN The analyses included 2241 participants aged ≥55 y who were free of hypertension at baseline (1990-1993) and who had complete dietary and BP data. Dietary data were obtained from a 170-item food-frequency questionnaire. We used 2 measures to characterize dietary acid load: (1) potential renal acid load (PRAL) by using an algorithm including protein, phosphorus, potassium, calcium, and magnesium, and (2) estimated net endogenous acid production (NEAP) based on protein and potassium. HRs for 6-y incidence of hypertension were obtained in tertiles of PRAL and NEAP with adjustment for age, sex, BMI, smoking, education, and intakes of alcohol, fiber, and total energy. RESULTS We identified 1113 incident cases of hypertension during 8707 person-years of follow-up. The median dietary acid load ranged from -14.6 to 19.9 mEq/d across categories of PRAL. Hypertension risk was not significantly associated with dietary acid load. The multivariate HRs (95% CIs) in consecutive tertiles of PRAL were 1.00 (reference), 1.01 (0.87, 1.17), and 1.02 (0.88, 1.18) (P trend = 0.83). The median dietary acid loads were 30.4, 36.7, and 43.7 mEq/d, respectively, in consecutive tertiles of NEAP. Corresponding HRs for NEAP were 1.00 (reference), 0.92 (0.80, 1.07), and 0.94 (0.81, 1.10) (P-trend = 0.46). CONCLUSION The findings from this prospective cohort study provided no evidence of an association between dietary acid load and risk of hypertension in older adults.

Meal-induced activation of the sympathetic nervous system and its cardiovascular and thermogenic effects in man

The postprandial activation of the peripheral sympathetic nervous system is crucial to maintain cardiovascular homeostasis. A contribution of postprandial sympathetic activation to the thermic effect of food is not always evident and depends on the size and composition of the meal, with carbohydrates having the clearest effect. Signals related to food intake from various origins (e.g. gut, hepatoportal area, baroreceptors) are integrated in the brain and result in increased peripheral sympathetic outflow. It is of interest to further explore the role of diet composition in the level of sympathetic activation during the day in view of the potential role of adrenergic overactivity in the pathogenesis of obesity and its cardiovascular and metabolic comorbidities.The postprandial activation of the peripheral sympathetic nervous system is crucial to maintain cardiovascular homeostasis. A contribution of postprandial sympathetic activation to the thermic effect of food is not always evident and depends on the size and composition of the meal, with carbohydrates having the clearest effect. Signals related to food intake from various origins (e.g. gut, hepatoportal area, baroreceptors) are integrated in the brain and result in increased peripheral sympathetic outflow. It is of interest to further explore the role of diet composition in the level of sympathetic activation during the day in view of the potential role of adrenergic overactivity in the pathogenesis of obesity and its cardiovascular and metabolic comorbidities.

Endocrine Role of the Renin-Angiotensin System in Human Adipose Tissue and Muscle. Effect of {beta}-Adrenergic Stimulation

The renin-angiotensin system has been implicated in obesity-related hypertension and insulin resistance. We examined whether locally produced components of the renin-angiotensin system in adipose tissue and skeletal muscle play an endocrine role in vivo in humans. Furthermore, the effects of &bgr;-adrenergic stimulation on plasma concentrations and tissue release of renin-angiotensin system components were investigated. Systemic renin-angiotensin system components and arteriovenous differences of angiotensin II (Ang II) and angiotensinogen (AGT) across abdominal subcutaneous adipose tissue and skeletal muscle were assessed in combination with measurements of tissue blood flow before and during systemic &bgr;-adrenergic stimulation in 13 lean and 10 obese subjects. Basal plasma Ang II and AGT concentrations were not significantly different between lean and obese subjects. Ang II concentrations were increased in obese compared with lean subjects during &bgr;-adrenergic stimulation (12.6±1.5 versus 8.1±1.0 pmol/L; P=0.04), whereas AGT concentrations remained unchanged. Plasma renin activity increased to a similar extent in lean and obese subjects during &bgr;-adrenergic stimulation (both P<0.01). No net Ang II release across adipose tissue and skeletal muscle could be detected in both groups of subjects. However, AGT was released from adipose tissue and muscle during &bgr;-adrenergic stimulation in obese subjects (both P<0.05). In conclusion, locally produced Ang II in adipose tissue and skeletal muscle exerts no endocrine role in lean and obese subjects. In contrast, AGT is released from adipose tissue and muscle in obese subjects during &bgr;-adrenergic stimulation, which may contribute to the increased plasma Ang II concentrations during &bgr;-adrenergic stimulation in obese subjects.

Glucagon and insulin responses after ingestion of different amounts of intact and hydrolysed proteins

Ingestion of dietary protein is known to induce both insulin and glucagon secretion. These responses may be affected by the dose and the form (intact or hydrolysed) in which protein is ingested. The aim of the study was to investigate the effect of different amounts of intact protein and protein hydrolysate of a vegetable (soya) and animal (whey) protein on insulin and glucagon responses and to study the effect of increasing protein loads for both intact protein and protein hydrolysate in man. The study employed a repeated-measures design with Latin-square randomisation and single-blind trials. Twelve healthy non-obese males ingested three doses (0.3, 0.4 and 0.6 g/kg body weight) of intact soya protein (SPI) and soya protein hydrolysate (SPH). Another group of twelve healthy male subjects ingested three doses (0.3, 0.4 and 0.6 g/kg body weight) of intact whey protein (WPI) and whey protein hydrolysate (WPH). Blood was sampled before (t = 0) and 15, 30, 60, 90 and 120 min after protein ingestion for insulin, glucagon and glucose determination. SPI induced a higher total area under the curve for insulin and glucagon than SPH while no difference between WPI and WPH was found. Insulin and glucagon responses increased with increasing protein load for SPI, SPH, WPI and WPH, but the effect was more pronounced for glucagon. A higher dose of protein or its hydrolysate will result in a lower insulin:glucagon ratio, an important parameter for the control of postprandial substrate metabolism. In conclusion, insulin and glucagon responses were protein and hydrolysate specific.