Recommendations for increased consumption of protein are among the most common approaches of popular or fad diets. This review summarizes the effects of dietary protein on satiety, energy intake, thermogenesis, and weight loss, as well as its effect on a variety of health outcomes in adults. In short-term studies, dietary protein modulates energy intake via the sensation of satiety and increases total energy expenditure by increasing the thermic effect of feeding. Whereas these effects did not contribute to weight and fat loss in those studies in which energy intake was fixed, one ad libitum study does suggest that a high-protein diet results in a greater decrease in energy intake, and therefore greater weight and fat loss. In terms of safety, there is little long-term information on the health effects of high-protein diets. From the available data, however, it is evident that the consumption of protein greater than two to three times the U.S. Recommended Daily Allowance contributes to urinary calcium loss and may, in the long term, predispose to bone loss. Caution with these diets is recommended in those individuals who may be predisposed to nephrolithiasis or kidney disease, and particularly in those with diabetes mellitus. Key Words: dietary protein, energy intake, thermogenesis, weight loss, high-protein diet, urinary calcium loss, bone loss

(c) 2002 International Life Sciences Institute

Introduction

The prevalence of obesity in the United States and other industrialized countries continues to rise despite increased public awareness and efforts to control weight.1 However, there remains no scientific consensus on dietary and other causes of the rising prevalence of obesity, or on optimal methods for weight loss and prevention of weight regain. In the absence of scientific unity on this issue, non-scientific prescriptions for weight loss have flourished and are frequently attempted by individuals wishing to lose weight. Many of these have focused on dietary protein and have advocated consumption of highprotein or high-protein, high-fat diets. The purported benefits of such diets include weight loss, amelioration of hunger, and prevention, reduction, or even resolution of several chronic diseases. This review focuses on evidence for the safety and effects of high dietary protein on energy regulation and is the fourth2-4 in a series from our laboratory on the influence of different dietary factors on weight gain and weight control.

The current recommended dietary allowance (RDA) for protein is 0.8 g/kg,5 although the typical U.S. American consumes approximately 1.2 g/kg protein daily or 15% of total energy intake.6 There are no standard definitions for high-protein diets, but based on the data summarized in this review, we propose that intakes of >=25% energy in weight-stable individuals or >= 1.6 g/kg ideal body weight in those in negative energy balance be defined as high, and >=35% energy in weight-stable individuals or >=2.4 g/kg ideal body weight in those in negative energy balance be considered extremely high.

Effects of Protein on Satiety and Energy Intake

A number of studies have been conducted to examine the effects of dietary protein on hunger, satiety, energy intake, and body fatness.7-34 Of eight preload studies that compared subjective hunger and satiety in the hours following consumption of a single high-protein meal and/or a control meal,9-16 six reported increased satiety with the high-protein diet compared with at least one control diet.9-12,14,16 Of the two studies that found no subjective difference between a high-protein preload and a control, one15 used liquid breakfasts instead of solid food, which may have influenced the results, and in another study13 the higher-protein meal was rated more palatable and thus may have influenced subjective satiety. Although not conclusive, the body of evidence from these studies of dietary protein and perceived hunger and satiety suggests that higher-protein meals have the potential to suppress hunger to a greater degree and result in enhanced sensations of satiety. However, it should be noted that not all of these studies controlled for dietary factors other than protein that have the potential to influence hunger and satiety, including fiber content,4 glycemic index, energy density,3 variety,35 and palatability.36 Whereas all preloads within each study were similar with regard to energy and variety, only a subset used preloads that controlled for energy density 10-12,14 or palatability.11,16 None of the studies controlled for fiber content or glycemic index. Stubbs et al.,11 whose study was possibly the most tightly controlled, identified a greater satiety effect of protein, but noted no difference in subsequent energy intake.

In addition to the above studies, changes in the satiety effects of protein over time have been studied. Long et al.37 reported that the satiety effect of dietary protein varied inversely with regular protein intake over a 13-day dietary manipulation period that compared 0.75 g X kg^sup -1^ X day^sup -1^ with 1.96 g X kg^sup -1^ X day^sup -1^ protein intake. Whereas there appears to be evidence for effects on perceived satiety, there is a paucity of evidence for longer-term effects and the stability of such effects.

The question of whether dietary protein influences short-term ad libitum energy intake has also been examined. Ten studies measured energy intake after consuming higher-protein and control preloads (Table 1). Studies were included in the analysis only if time from preload to the test meal was > 1 hour (range 1.5-7 hours); this is because the amount of a test meal consumed within 1 hour from the time of the preload may be dictated by the cephalic response to a meal.38 Energy intake following the higher-protein preload was lower in eight out of ten of the studies reviewed, and mean energy intake was nine percent less than with the lower-protein preload (P = 0.03). In many of these studies, however, the higher-protein preloads contained a proportion of protein energy that was extremely high (>=5%), and the relevance of the findings to diets that are typically consumed is therefore uncertain.

Three studies with a control group have also assessed the influence of protein on ad libitum energy intake beyond a single meal (Table 2). In two of the studies17,18 (conducted for 24 hours and 3 days, respectively) there was no effect of protein level on energy intake, and mean values were very similar. The other study19 was conducted for 6 months, and observed a significant 18% lower energy intake with the higher-- protein diet. The reasons for the differences between the studies are not known, although it is possible that study duration was important. In addition, there may have been unmeasured differences between groups in some of the studies that could have influenced the results. For example, the study design for the long-term study allowed the subjects to choose foods consistent with their group randomization from a store set up by the investigators. It is possible that the nature of the available foods reduced dietary variety in the high-protein group, which could have had an independent effect on energy intake.35

Thermogenesis

In this analysis, which combined studies using isolated macronutrients with those using mixed meals, protein contributed approximately twice as much to the estimated TEF as fat or carbohydrate. In addition, because the contribution of fat and carbohydrate to the TEF was similar, for any fixed protein level, TEF was essentially unaffected by the proportions of fat and carbohydrate. Although confirmatory studies are needed, this initial analysis suggests that protein exerts a more significant effect on energy expenditure. For example, if an individual consuming a 2000 kcal/day weight-loss diet was to substitute a high-protein diet (30% protein, 30% fat, 40% carbohydrate) for a typical recommended U.S. diet (15% protein, 30% fat, 55% carbohydrate), the above equation predicts an increase in energy expenditure of 23 kcal/day, which is approximately equivalent to an increase of 0.8% of the total energy expenditure (TEE) for a typical individual. On theoretic grounds, this small increase in energy expenditure would result in additional weight loss of 0.09 kg/month. These observations and calculations demonstrate that high-protein diets are associated with a significant increase in TEF, but it is quantitatively small and as such is expected to have only a limited influence on body weight even if energy intake is unaffected by the increase in energy expenditure. Other studies, although not providing enough information to calculate TEF, corroborate the finding that protein has a higher thermogenic effect.40,41