A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations

BACKGROUND: Ad libitum, low-carbohydrate diets decrease caloric intake and cause weight loss. It is unclear whether these effects are due to the reduced carbohydrate content of such diets or to their associated increase in protein intake. OBJECTIVE: We tested the hypothesis that increasing the protein content while maintaining the carbohydrate content of the diet lowers body weight by decreasing appetite and spontaneous caloric intake. DESIGN: Appetite, caloric intake, body weight, and fat mass were measured in 19 subjects placed sequentially on the following diets: a weight-maintaining diet (15% protein, 35% fat, and 50% carbohydrate) for 2 wk, an isocaloric diet (30% protein, 20% fat, and 50% carbohydrate) for 2 wk, and an ad libitum diet (30% protein, 20% fat, and 50% carbohydrate) for 12 wk. Blood was sampled frequently at the end of each diet phase to measure the area under the plasma concentration versus time curve (AUC) for insulin, leptin, and ghrelin. RESULTS: Satiety was markedly increased with the isocaloric high-protein diet despite an unchanged leptin AUC. Mean (+/-SE) spontaneous energy intake decreased by 441 +/- 63 kcal/d, body weight decreased by 4.9 +/- 0.5 kg, and fat mass decreased by 3.7 +/- 0.4 kg with the ad libitum, high-protein diet, despite a significantly decreased leptin AUC and increased ghrelin AUC. CONCLUSIONS: An increase in dietary protein from 15% to 30% of energy at a constant carbohydrate intake produces a sustained decrease in ad libitum caloric intake that may be mediated by increased central nervous system leptin sensitivity and results in significant weight loss. This anorexic effect of protein may contribute to the weight loss produced by low-carbohydrate diets.     

Calcium and dairy products inhibit weight and fat regain during ad libitum consumption following energy restriction in Ap2-agouti transgenic mice

We demonstrated previously that dietary calcium suppression of calcitriol reduces adipocyte Ca(2+), suppresses lipogenesis, and increases lipid utilization during energy restriction. Notably, dairy calcium sources exert markedly greater effects. To determine the effects of dietary calcium and dairy products on energy partitioning during subsequent refeeding, we induced obesity in aP2-agouti transgenic mice with a high-fat/high-sucrose diet, then restricted energy intake from a high-calcium (1.3%) diet for 6 wk to induce fat loss, and then provided free access to a low-calcium (0.4%) diet or to high-calcium (1.3%) diets that utilized either calcium-fortified foods or dairy products (milk or yogurt) for 6 wk. Refeeding the low-calcium diet caused the regain of all weight and fat, whereas all high-calcium diets reduced fat gain by 55% (P < 0.01). All high-calcium diets stimulated adipose tissue uncoupling protein (UCP)2 and skeletal muscle UCP3 expression (P < 0.001) and slightly increased core temperature (P = 0.136), but only the dairy-based diets elicited a marked (>10-fold, P < 0.001) increase in skeletal muscle peroxisome proliferator-activated receptor-alpha expression. All 3 high-calcium diets produced significant increases in lipolysis, decreases in fatty acid synthase expression and activity, and reduced fat regain (P < 0.03), but the 2 dairy-containing high-calcium diets exerted significantly greater effects on regain (P < 0.01). Thus, high-Ca diets elicit a shift in energy partitioning and reduction of weight gain during refeeding, with dairy Ca sources exerting markedly greater effects.     

Effects of dietary protein, fat and restriction on body composition and energy balance in lactating rats

Isoenergetic diets formulated at three levels of dietary protein using 12,24 and 40% casein and at two levels of fat using 2.26 and 13.82% corn oil were fed at five levels of intake, ad libitum, 75, 62.5, 50 and 37.5% of average ad libitum intake, to 90 lactating rats from d 7 to 14 of lactation. Regression equations developed from lactating rats killed on d 7 of lactation were used to calculate initial body composition and energy of rats killed on d 14 of lactation. Changes in body weight and body water were significantly (P less than 0.05) affected by dietary fat and protein, but change in dry lean body mass was affected only by level of dietary fat, whereas body nitrogen and fat and lean body energy were not affected by level of dietary fat or protein. However, restricted intake significantly increased loss of all these. Likewise, restricted intake decreased milk production. Changes in weights of heart and liver were not affected by diet or intake, whereas intestinal weight decreased with intake restriction. Liver enzyme activities were markedly affected by intake restriction, whereas responses to dietary protein and fat were marginal.     

Lean mass loss is associated with low protein intake during dietary-induced weight loss in postmenopausal women

The health and quality-of-life implications of overweight and obesity span all ages in the United States. We investigated the association between dietary protein intake and loss of lean mass during weight loss in postmenopausal women through a retrospective analysis of a 20-week randomized, controlled diet and exercise intervention in women aged 50 to 70 years. Weight loss was achieved by differing levels of caloric restriction and exercise. The diet-only group reduced caloric intake by 2,800 kcal/week, and the exercise groups reduced caloric intake by 2,400 kcal/week and expended approximately 400 kcal/week through aerobic exercise. Total and appendicular lean mass was measured using dual energy x-ray absorptiometry. Linear regression analysis was used to examine the association between changes in lean mass and appendicular lean mass and dietary protein intake. Average weight loss was 10.8+/-4.0 kg, with an average of 32% of total weight lost as lean mass. Protein intake averaged 0.62 g/kg body weight/day (range=0.47 to 0.8 g/kg body weight/day). Participants who consumed higher amounts of dietary protein lost less lean mass and appendicular lean mass (r=0.3, P=0.01 and r=0.41, P<0.001, respectively). These associations remained significant after adjusting for intervention group and body size. Therefore, inadequate protein intake during caloric restriction may be associated with adverse body-composition changes in postmenopausal women.     

Contribution of different mechanisms to compensation for energy restriction in the mouse

OBJECTIVE: Restriction of energy intake produces weight loss, but the rate of loss is seldom sustained. This is presumed to be a consequence of compensatory reductions in energy expenditure, although the exact contributions of different components to the energy budget remain uncertain. We examined the compensatory responses of mice to a 20% dietary restriction. RESEARCH METHODS AND PROCEDURES: We measured body mass, body fatness, body temperature, and the components of daily energy expenditure for 50 MF1 mice. Forty mice were then placed on a restricted diet at 80% of their ad libitum intake for 50 days. The remaining 10 mice continued to feed ad libitum. Ten days before the end of the restriction period, the same measurements were taken. RESULTS: There were no significant differences between the control and restricted groups in any parameters before restriction. During the restriction period, body mass increased in both the control and restricted groups, but at a slower rate in the restricted mice. The control group increased in both fat and fat free mass; however, although the restricted group increased fat to the same extent as the controls, fat free mass increased to a lesser extent. The contributions of the different components of the expended energy to compensate for the reduced energy intake were energy deposition, 2.2%; resting metabolic rate, 22.3%; and activity, 75.5%. DISCUSSION: Mice were able to compensate almost completely for the restricted energy intake that was achieved by altering the amount of energy required for each component of the energy budget except digestive efficiency.     

High dietary fat promotes syndrome X in nonobese rats

High fat, low carbohydrate diets are popularly advocated for weight loss and improvement in metabolic Syndrome X, a constellation of risk factors for type 2 diabetes mellitus and cardiovascular disease. The effects of an energy-restricted (to prevent weight gain in excess of normal growth) high fat (60% of energy), low carbohydrate (15%) diet were assessed in both lean rats and in rats previously rendered obese through ad libitum consumption of the same high fat diet. In obese rats, restriction of intake failed to improve impaired glucose tolerance, hyperinsulinemia, and hypertriglyceridemia, although it lowered visceral fat mass, liver lipid content and in vitro insulin hypersecretion compared with rats continuing to consume the high fat diet ad libitum. In lean rats, restricted intake of the high fat diet impaired glucose tolerance and increased visceral fat mass and liver lipid content. These findings support the conclusion that, in the absence of weight loss, a high fat, low carbohydrate diet not only may be ineffective in decreasing risk factors for cardiovascular disease and type 2 diabetes but may promote the development of disease in previously lower risk, nonobese individuals.     

Fructose and metabolic diseases: New findings,new questions

There has been much concern regarding the role of dietary fructose in the development of metabolic diseases. This concern arises from the continuous increase in fructose (and total added caloric sweeteners consumption) in recent decades, and from the increased use of high-fructose corn syrup (HFCS) as a sweetener. A large body of evidence shows that a high-fructose diet leads to the development of obesity, diabetes, and dyslipidemia in rodents. In humans, fructose has long been known to increase plasma triglyceride concentrations. In addition, when ingested in large amounts as part of a hypercaloric diet, it can cause hepatic insulin resistance, increased total and visceral fat mass, and accumulation of ectopic fat in the liver and skeletal muscle. These early effects may be instrumental in causing, in the long run, the development of the metabolic syndrome. There is however only limited evidence that fructose per se, when consumed in moderate amounts, has deleterious effects. Several effects of a high-fructose diet in humans can be observed with high-fat or high-glucose diets as well, suggesting that an excess caloric intake may be the main factor involved in the development of the metabolic syndrome. The major source of fructose in our diet is with sweetened beverages (and with other products in which caloric sweeteners have been added). The progressive replacement of sucrose by HFCS is however unlikely to be directly involved in the epidemy of metabolic disease, because HFCS appears to have basically the same metabolic effects as sucrose. Consumption of sweetened beverages is however clearly associated with excess calorie intake, and an increased risk of diabetes and cardiovascular diseases through an increase in body weight. This has led to the recommendation to limit the daily intake of sugar calories.     

Effects of calcium and dairy on body composition and weight loss in African-American adults

OBJECTIVE: Our objective was to determine the effects of dairy consumption on adiposity and body composition in obese African Americans. RESEARCH METHODS AND PROCEDURES: We performed two randomized trials in obese African-American adults. In the first (weight maintenance), 34 subjects were maintained on a low calcium (500 mg/d)/low dairy (<1 serving/d) or high dairy (1200 mg Ca/d diet including 3 servings of dairy) diet with no change in energy or macronutrient intake for 24 weeks. In the second trial (weight loss), 29 subjects were similarly randomized to the low or high dairy diets and placed on a caloric restriction regimen (-500 kcal/d). RESULTS: In the first trial, body weight remained stable for both groups throughout the maintenance study. The high dairy diet resulted in decreases in total body fat (2.16 kg, p < 0.01), trunk fat (1.03 kg, p < 0.01), insulin (18.7 pM, p < 0.04), and blood pressure (6.8 mm Hg systolic, p < 0.01; 4.25 mm Hg diastolic, p < 0.01) and an increase in lean mass (1.08 kg, p < 0.04), whereas there were no significant changes in the low dairy group. In the second trial, although both diets produced significant weight and fat loss, weight and fat loss on the high dairy diet were approximately 2-fold higher (p < 0.01), and loss of lean body mass was markedly reduced (p < 0.001) compared with the low dairy diet. DISCUSSION: Substitution of calcium-rich foods in isocaloric diets reduced adiposity and improved metabolic profiles in obese African Americans without energy restriction or weight loss and augmented weight and fat loss secondary to energy restriction.     

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.     

Effect of Overeating Dietary Protein at Different Levels on Circulating Lipids and Liver Lipid: The PROOF Study

Background: During overeating, a low protein diet slowed the rate of weight gain and increased the energy cost of the added weight, suggesting that low protein diets reduced energy efficiency. The Protein Overfeeding (PROOF) study explored the metabolic changes to low and high protein diets, and this sub-study examined the changes in body composition and blood lipids when eating high and low protein diets during overeating. Methods: Twenty-three healthy volunteers (M = 14; F = 9) participated in an 8-week, parallel arm study where they were overfed by ~40% with diets containing 5% (LPD = low protein diet), 15% (NPD = normal protein diet), or 25% (HPD = high protein diet) protein. Dual energy X-ray absorptiometry (DXA) and computer tomography (CT) were used to quantify whole body and abdominal fat and intrahepatic lipid, respectively. Metabolites were measured by standard methods. Results: Protein intake and fat intake were inversely related since carbohydrate intake was fixed. Although overeating the LPD diet was associated with a significant increase in high density lipoprotein (HDL)-cholesterol (p < 0.001) and free fatty acids (p = 0.034), and a significant decrease in fat free mass (p < 0.0001) and liver density (p = 0.038), statistical models showed that dietary protein was the main contributor to changes in fat free mass (p = 0.0040), whereas dietary fat was the major predictor of changes in HDL-cholesterol (p = 0.014), free fatty acids (p = 0.0016), and liver fat (p = 0.0007). Conclusions: During 8 weeks of overeating, the level of dietary protein intake was positively related to the change in fat free mass, but not to the change in HDL-cholesterol, free fatty acids, and liver fat which were, in contrast, related to the intake of dietary fat.     

HIGH FAT DIET FOR WEIGHT REDUCTION

Low calorie diets promote weight loss whether caloric reduction is achieved by restriction of carbohydrate or of fat. More weight is lost initially on a diet severely restricted in carbohydrate.     

Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia

BACKGROUND: Low-carbohydrate diets have been used to manage obesity and its metabolic consequences. OBJECTIVE: The objective was to study the effects of moderate carbohydrate restriction on atherogenic dyslipidemia before and after weight loss and in conjunction with a low or high dietary saturated fat intake. DESIGN: After 1 wk of consuming a basal diet, 178 men with a mean body mass index (in kg/m(2)) of 29.2 +/- 2.0 were randomly assigned to consume diets with carbohydrate contents of 54% (basal diet), 39%, or 26% of energy and with a low saturated fat content (7-9% of energy); a fourth group consumed a diet with 26% of energy as carbohydrate and 15% as saturated fat. After 3 wk, the mean weight loss (5.12 +/- 1.83 kg) was induced in all diet groups by a reduction of approximately 1000 kcal/d for 5 wk followed by 4 wk of weight stabilization. RESULTS: The 26%-carbohydrate, low-saturated-fat diet reduced triacylglycerol, apolipoprotein B, small LDL mass, and total:HDL cholesterol and increased LDL peak diameter. These changes were significantly different from those with the 54%-carbohydrate diet. After subsequent weight loss, the changes in all these variables were significantly greater and the reduction in LDL cholesterol was significantly greater with the 54%-carbohydrate diet than with the 26%-carbohydrate diet. With the 26%-carbohydrate diet, lipoprotein changes with the higher saturated fat intakes were not significantly different from those with the lower saturated fat intakes, except for LDL cholesterol, which decreased less with the higher saturated fat intake because of an increase in mass of large LDL. CONCLUSIONS: Moderate carbohydrate restriction and weight loss provide equivalent but nonadditive approaches to improving atherogenic dyslipidemia. Moreover, beneficial lipid changes resulting from a reduced carbohydrate intake were not significant after weight loss.     

Enteral feeding in burn hypermetabolism: nutritional and metabolic effects of different levels of calorie and protein intake

Enteral nutrition was provided by continuous pump-controlled gastrostomy tube feeding for 14 days in 97 guinea pigs bearing a 30% full thickness burn. Seven defined combinations of caloric and protein intake were studied. With a caloric intake of 175 kcal/kg/day, equaling the measured energy expenditure, the animals receiving 10% of calories as protein had a significantly greater postburn weight loss (p less than 0.05) and muscle mass depletion (p less than 0.05), and a significantly lower muscle nitrogen concentration (p less than 0.05), serum albumin level (p less than 0.01) and liver nitrogen content (p less than 0.01). With the same caloric intake but with more than 20% of calories as protein, the weight loss and the muscle wasting were reduced, but not abolished, and the serum albumin level and liver nitrogen content were normalized. Also with the diets containing 200 kcal/kg/day the muscle tissue depletion could not be abolished. However, with this caloric intake, the animals given 20% of calories as protein had a lower weight loss and a higher serum albumin level (p less than 0.01), but also a greater fat infiltration of the liver (p less than 0.01). At both levels of caloric intake, the nitrogen balance correlated significantly with the level of nitrogen intake but did not correlate with the changes of body weight. The incidence of diarrhea was lowest in animals fed 20% protein calories at a caloric intake of 175 kcal/kg/day. All things considered, the best metabolic and nutritional results were obtained with diets containing 20 to 30% of calories as protein and providing a caloric intake that paralleled the measured energy expenditure.     

Dietary management of obesity

BACKGROUND: The optimal diet for prevention of weight gain, obesity, metabolic syndrome, and type 2 diabetes is fat-reduced, fiber-rich, high in low-energy density carbohydrates (fruit, vegetables, and whole grain products), and intake of energy-containing drinks is restricted. RESULTS ON DIETARY FAT: The reduction of the total fat content of ad libitum diets produces weight loss in both the short term and over periods as long as 7 years. A fat-reduced diet, combined with physical activity, reduces almost all risk factors for cardiovascular disease and reduces the incidence of type 2 diabetes. The combination of reduction of dietary fat and energy, and increased physical activity has been shown to reduce the incidence of diabetes by 58% in 2 major trials. In post hoc analyses, the reduction in dietary fat (energy density) and increase in fiber were the strongest predictors of weight loss and diabetes-protective effects. LOW-GLYCEMIC INDEX AND HIGH-PROTEIN DIETS: It remains to be shown whether a low-glycemic index diet provides any benefit to weight control beyond this. Low-carbohydrate diets may be an option for inducing weight loss in obese patients, but a very low intake of carbohydrate-rich foods is not commensurate with a healthy and palatable diet in the long term. However, there is evidence that increasing the protein content of the diet from 15% up to 20%-30%, at the expense of carbohydrates, increases the satiating effect of the diet, and induces a spontaneous weight loss, and this could turn out to be a preferred option for patients with metabolic syndrome and type 2 diabetes.     

Altered brown adipose tissue and Na,K pump activities during diet-induced obesity and weight loss in rats

Brown adipose tissue (BAT) thermogenesis is an uncoupled ATPase-independent thermogenic mechanism. Ion transport by the Na,K pump is an ATPase-dependent thermogenic mechanism. Both have been proposed as mechanisms of altered energy expenditure during states of dietary energy surfeit and deficit. Our aim was to study these mechanisms during diet-induced obesity and weight loss. Over 36 weeks rats were fed lard- or tallow-based diets (63% energy as fat), or a control diet (12% energy as fat). During periods of restriction rats were fed 50% of the energy intake of controls in the form of a control diet. Several components of thermogenic response increased in rats eating high fat diets and decreased following dietary restriction. BAT activation occurred, particularly with a lard-based diet, as indicated by increased GDP binding and uncoupling protein (UCP) content. Na,K pump activity in thymocytes increased with the feeding of both high fat diets at some time points. Plasma T3 level increased in rats eating the lard-based diet and decreased with dietary restriction regardless of previous diet. Resting metabolic rate (RMR) of the animals was unchanged despite increases in these thermogenic components and was decreased in all groups following dietary restriction. Our results indicate a lack of any major role for activated BAT thermogenesis in mitigating the extent of the obesity induced by the high fat diets. The reasons for the differences in response to the two different sources of saturated fat, lard, and tallow, are not clear.