Dietary interventions have established that high-protein diets can induce weight loss. As reviewed [1••], several of the popular high-protein diets are high in fat. Most investigations of high-protein diets, including a recent study [2••], have relied primarily on animal sources of protein as indicated by typical menus [1••] and reported high content of cholesterol and saturated fat [2••]. The high content of cholesterol and saturated fat in popular high-protein diets raises concerns regarding the long-term impact of such diets on cardiovascular disease as well as other chronic diseases. Importantly, no randomized, controlled clinical trial has demonstrated the long-term safety of high-protein diets. Just as the long-term safety of high-protein diets remains to be established, the long-term impact of the source of dietary protein remains to be determined. However, accumulating evidence suggests that plant proteins, particularly legumes, may be valuable components of high-protein diets.
Popular high-protein, low carbohydrate diets are based on the assumption that lowering carbohydrate to the point of ketosis is desirable or even necessary to reduce food intake. However, recent work not only demonstrates that induction of ketosis may not be necessary to inhibit food intake but also provides additional evidence that prolonged intake of a ketogenic diet can have negative health consequences. Prior work had established that under most conditions, protein induces greater satiety than isoenergetic intake of carbohydrate or fat . Recent work in rats fed diets with increased levels of protein without a corresponding increase in fat showed that both acute and habitual increase in protein content of the diet reduced food intake . Importantly, that study, which evaluated changes in brain activation, demonstrated that the reduction in food intake by the high-protein diet was associated with increased activation of the noradrenergic/adrenergic neurons involved in cholecystokinin-induced satiety and did not involve the activation of brain centers indicative of nonphysiological anorexia. A recent study in children with intractable epilepsy treated with a ketogenic diet documented the progressive loss of whole-body and spine bone mineral density during 15 months [5•]. As a decline in bone mineral density over 15 months was observed even without a change in BMI, it seems possible that adverse skeletal changes reported in some weight loss studies in adults may be even greater in persons following high-protein diets that are sufficiently low in carbohydrate to induce ketosis.
Several recent reports have provided increasing evidence for adverse consequences of higher dietary intake of animal food sources high in fat or cholesterol. A recent report from the Physicians' Health Study [6•] demonstrated that though increasing consumption of eggs was not associated with increased risk of myocardial infarction or stroke, increasing consumption of eggs was associated with a stepwise increase in all-cause mortality. This increased risk remained significant after multivariate adjustment for relevant demographic, lifestyle, dietary, and medical risk factors, as well as randomization assignment. As weight loss is often indicated in persons with diabetes, it is important that the authors found the risk of death with increasing egg consumption to be substantially higher among those with prevalent diabetes than without diabetes. A recent report from the Atherosclerosis Risk in Communities (ARIC) study [7•] also found egg consumption to have a negative health impact and additionally implicated high fat dairy products. In that study, the investigators found increased intake of eggs to be associated with increased risk of incident heart failure. Increased intake of high fat dairy products was also associated with increased risk of incident heart failure. These associations persisted after multivariate adjustment for relevant covariates, including other food groups, and were altered only slightly by adjustment for follow-up BMI and incident comorbidities. A recent report from the European Prospective Investigation into Cancer and Nutrition [8••] provided evidence that dietary saturated fat, but not total fat, monounsaturated fat, or polyunsaturated fat, was associated with increased risk of breast cancer. Interestingly, and relevant to the aging population, in postmenopausal women the association between saturated fat and risk of breast cancer was limited to those who were not using hormone replacement therapy. Overall, these recent studies suggest that long-term consumption of diets enriched in animal sources of protein has multiple adverse health consequences and provides further support for the possibility that such adverse effects may be accounted for at least in part by the saturated fat that is present in many foods of animal origin.
Intact plant sources of protein are typically low in fat, particularly saturated fat, and high in dietary fiber . The low saturated fat content of many plant proteins would be expected to improve lipids whereas the high fiber content of plant proteins would be expected to improve lipids and blood pressure and increase satiety, facilitating weight loss and limiting weight gain. Several recent reports provide increasing support for the notion that a specific source of plant protein, legumes, may be a particularly relevant component of high-protein diets aiming to reduce weight or cardiovascular risk factors and promote long-term health. A recent analysis [10•] of data collected as part of the National Health and Nutrition Examination Survey reported on differences between physiological measures and dietary composition for persons who consumed beans compared with those who did not consume beans. Interestingly, both weight and waist circumference were lower in those who consumed beans compared with those who did not, even though total energy intake was higher in the former. In addition, a number of measures of dietary status, including saturated fat, dietary fiber, phosphorus, magnesium, and folate, were more favorable in those who consumed beans. A recent crossover study investigated the influence of incorporating chickpeas, a legume high in dietary fiber and polyunsaturated fatty acids, on lipids and measures of glycemia . In that study, daily chickpea intake representing 119 kcal per day for 12 weeks reduced plasma total and LDL cholesterol, fasting insulin, and insulin resistance as assessed by the homeostasis model, with a trend for reduced weight. A recent study in a rat model of carcinogenesis [12•] demonstrated that incorporating increasing amounts of small red beans into the diet while holding total protein, crude fiber, and carbohydrate constant resulted in a dose-dependent reduction in mammary tumor incidence, cancer multiplicity, and tumor burden. That study also demonstrated dietary red bean to induce a dose-dependent reduction in plasma glucose, insulin, insulin-like growth factor, and the inflammatory markers C-reactive protein and IL-6. Overall, these studies suggest that increasing legume intake to increase dietary protein may provide most, if not all, of the benefits associated with typical high-protein diets while promoting better long-term health outcomes.
In summary, though long-term clinical trials evaluating the safety of high-protein diets are lacking and not likely to ever be completed, recent evidence provides increasing support for greater potential health benefits of plant proteins, particularly legumes, both for weight reduction and control of obesity and for minimizing chronic disease. There is much opportunity for research in the area of high-protein diets emphasizing plant protein. The Optimal Macronutrient Intake Trial to Prevent Heart Disease (OmniHeart) protein diet included some plant sources of protein [1••,13] and has been demonstrated to effectively improve cardiovascular risk factors [13,14••,15]. As the protein content of the OmniHeart protein diet did not reach the levels of popular high-protein diets [1••], it seems possible that modifying the OmniHeart protein diet by partial replacement of sources of carbohydrate with legumes may result in a diet that induces even more beneficial changes in cardiovascular risk factors. As the existing positive information for dietary plant protein concerns primarily plant protein consumed within the relatively intact vegetable ‘protein package’, rich in dietary fiber, vitamins, and minerals which may contribute to the health benefits of these vegetable sources of protein, it is recommended that future research focuses on the entire vegetable ‘protein package’ rather than on proteins isolates. Most dietary interventions that included plant sources of protein have provided very limited information concerning the amounts of specific types of plant protein that were included. The value of future research on dietary protein and health outcomes will be enhanced by detailed description of the specific types of plant (and animal) protein that are included in experimental diets, ideally in somewhat more detail than the best example to date . Relatively few head-to-head comparisons of the health implications of different plant sources of protein have been conducted; such studies will be valuable to increase understanding of the differences among plant proteins and to suggest hypotheses concerning mechanism(s) by which plant proteins confer health benefits.
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
1•• deSouza RJ, Swain JF, Appel LJ, Sacks FM. Alternatives for macronutrient intake and chronic disease: a comparison of the OmniHeart diets with popular diets and with dietary recommendations. Am J Clin Nutr 2008; 88:1–11. This report will be of interest to readers for comparative information for dietary guidelines from the Institute of Medicine, the American Heart Association, the American Diabetes Association, and the American Cancer Society. This report will also be of interest for the comparative information concerning menus and macronutrient profiles for five popular diets as well as for the Dietary Approaches to Stop Hypertension (DASH) Diet and the OmniHeart diets.
2•• Shai I, Schwarzfuchs D, Henkin Y, et al
. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. New Eng J Med 2008; 359:229–241. This report will be of interest to readers for the comparative data for the impact of three dietary interventions, a low-fat diet, a Mediterranean diet, and a high-protein low carbohydrate diet, on weight loss and cardiovascular risk factors. Of particular interest, this report provides information for cardiovascular risk factors after both 6 and 24 months of intervention with more frequent measures of weight. This report is also of interest as a model of implementation of a weight loss intervention at the work site.
3 Paddon-Jones D, Westman E, Mattes RD, et al
. Protein, weight management, and satiety. Am J Clin Nutr 2008; 87:1558S–1561S.
4 Faipoux R, Tome D, Gougis S, et al
. Proteins activate satiety-related neuronal pathways in the brainstem and hypothalamus of rats. J Nutr 2008; 138:1172–1178.
5• Bergqvist AGC, Schall JI, Stallings VA, Zemel BS. Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. Am J Clin Nutr 2008; 88:1678–1684. This study will be of interest to readers for the serial measures of bone mineral content during the 15-month study.
6• Djousse L, Gaziano JM. Egg consumption in relation to cardiovascular disease and mortality: the Physicians' Health Study. Am J Clin Nutr 2008; 87:964–969. This study will be of interest to readers because of the prospective design, long (20-year) follow-up, and the large study cohort (21 327 participants), derived from the Physicians' Health Study I. In addition, of interest will be the comparative data for risk of myocardial infarction, stroke, and all-cause mortality, as well as comparative data for persons with and without prevalent diabetes.
7• Nettleton JA, Steffen LM, Loehr LR, et al
. Incident heart failure is associated with lower whole-grain intake and greater high-fat dairy and egg intake in the Atherosclerosis Risk in Communities (ARIC) Study. J Am Diet Assoc 2008; 108:1881–1887. This report will be of interest to readers because of the large (14 153) population-based sample from the ARIC study, including both African–Americans and white adults, the prospective design, and the long (13-year) follow-up.
8•• Sieri S, Krogh V, Ferrari P, et al
. Dietary fat and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr 2008; 88:1304–1312. This report will be of interest due to the large (319 826) and geographically and culturally heterogeneous cohort. In addition, of particular interest are the comparative data for four different methods of energy adjustment.
10• Papanikolaou Y, Fulgoni VL. Bean consumption is associated with greater nutrient intake, reduced systolic blood pressure, lower body weight, and a smaller waist circumference in adults: results from the National Health and Nutrition Examination Survey 1999–2002. J Am Coll Nutr 2008; 27:569–576. This report will be of interest to readers as it presents data for a representative sample of 9965 and 11 039 noninstitutionalized Americans responding to the National Health and Nutrition Examination Survey (NHANES) in 1999–2000 and 2001–2002, respectively. Data are presented for three categories of bean consumers: those who consumed beans only as baked beans, those consuming other specific types of beans, including pinto beans, kidney beans, etc., and those consuming any type of bean. Data are presented for all ages and for ages 20–40 years compared with 40 years and older.
11 Pittaway JK, Robertson IK, Ball MJ. Chickpeas may influence fatty acid and fiber intake in an ad libitum diet, leading to small improvements in serum lipid profile and glycemic control. J Am Diet Assoc 2008; 108:1009–1013.
12• Thompson MD, Thompson HJ, Brick MA, et al
. Mechanisms associated with dose-dependent inhibition of rat mammary carcinogenesis by dry bean (Phaseolus vulgaris, L
.). J Nutr 2008; 138:2091–2097. This study is of particular interest because unlike many studies of dietary protein in animal models, the red bean incorporated into the diet was representative of red bean products consumed in the USA, including prior cooking and packing in brine by a major commercial supplier of canned beans to the market for human consumption. This study is also distinguished by the formulation of the diets containing different amounts of red bean to contain equivalent levels of crude fiber, dietary protein, and dietary carbohydrate. In addition, of relevance, the bean content of each experimental diet is related to the corresponding human dose on a caloric basis.
13 Swain JF, McCarron PB, Hamilton EF, et al
. Characteristics of the diet patterns tested in the Optimal Macronutrient Intake Trial to Prevent Heart Disease (OmniHeart): options for a heart-healthy diet. J Am Diet Assoc 2008; 108:257–265.
14•• Furtado JD, Campos H, Appel LJ, et al
. Effect of protein, unsaturated fat, and carbohydrate intakes on plasma apolipoprotein B and VL DL and LDL containing apolipoprotein C-III: results from the OmniHeart Trial. Am J Clin Nutr 2008; 87:1623–1630. This article will be of interest to readers as it provides comparative data for the three OmniHeart diets: healthy diets emphasizingcarbohydrate, nonmeat protein, and unsaturated fat. This article is also of particular interest due to the comprehensive information for lipoprotein subfractions. Shown are the changes from baseline for these three diets for the following: plasma concentrations of cholesterol, triglycerides, apoprotein B, apoprotein C-III, and apoprotein E as well as similar compositional information for apoprotein B containing lipoproteins stratified by presence of apoprotein C-III. Comparisons between the three diets are also presented.
15 Appel LJ, Sacks FM, Carey VJ, et al
. Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids. Results of the OmniHeart Randomized Trial. JAMA 2005; 294:2455–2464.
Further recommended reading
• Pencharz PB, Elango R, Ball RO. An approach to defining the upper safe limits of amino acid intake. J Nutr 2008; 138:1996S–2002S. This article will be of interest to readers as it presents approaches to assess dietary requirements, safe upper limits, and toxic levels of protein.