Are high-protein, vegetable-based diets safe for kidney function? A review of the literature

In individuals with chronic kidney disease, high-protein diets have been shown to accelerate renal deterioration, whereas low-protein diets increase the risk of protein malnutrition. Vegetarian diets have been promoted as a way to halt progression of kidney disease while maintaining adequate nutrition. We review the literature to date comparing the effects of animal and vegetable protein on kidney function in health and disease. Diets with conventional amounts of protein, as well as high-protein diets, are reviewed. The literature shows that in short-term clinical trials, animal protein causes dynamic effects on renal function, whereas egg white, dairy, and soy do not. These differences are seen both in diets with conventional amounts of protein and those with high amounts of protein. The long-term effects of animal protein on normal kidney function are not known. Although data on persons with chronic kidney disease are limited, it appears that high intake of animal and vegetable proteins accelerates the underlying disease process not only in physiologic studies but also in short-term interventional trials. The long-term effects of high protein intake on chronic kidney disease are still poorly understood. Several mechanisms have been suggested to explain the different effects of animal and vegetable proteins on normal kidney function, including differences in postprandial circulating hormones, sites of protein metabolism, and interaction with accompanying micronutrients.     

The Effects of High Protein Diets on Thermogenesis,Satiety and Weight Loss: A Critical Review

For years, proponents of some fad diets have claimed that higher amounts of protein facilitate weight loss. Only in recent years have studies begun to examine the effects of high protein diets on energy expenditure, subsequent energy intake and weight loss as compared to lower protein diets. In this study, we conducted a systematic review of randomized investigations on the effects of high protein diets on dietary thermogenesis, satiety, body weight and fat loss. There is convincing evidence that a higher protein intake increases thermogenesis and satiety compared to diets of lower protein content. The weight of evidence also suggests that high protein meals lead to a reduced subsequent energy intake. Some evidence suggests that diets higher in protein result in an increased weight loss and fat loss as compared to diets lower in protein, but findings have not been consistent. In dietary practice, it may be beneficial to partially replace refined carbohydrate with protein sources that are low in saturated fat. Although recent evidence supports potential benefit, rigorous longer-term studies are needed to investigate the effects of high protein diets on weight loss and weight maintenance.     

The effects of high protein diets on thermogenesis, satiety and weight loss: a critical review

For years, proponents of some fad diets have claimed that higher amounts of protein facilitate weight loss. Only in recent years have studies begun to examine the effects of high protein diets on energy expenditure, subsequent energy intake and weight loss as compared to lower protein diets. In this study, we conducted a systematic review of randomized investigations on the effects of high protein diets on dietary thermogenesis, satiety, body weight and fat loss. There is convincing evidence that a higher protein intake increases thermogenesis and satiety compared to diets of lower protein content. The weight of evidence also suggests that high protein meals lead to a reduced subsequent energy intake. Some evidence suggests that diets higher in protein result in an increased weight loss and fat loss as compared to diets lower in protein, but findings have not been consistent. In dietary practice, it may be beneficial to partially replace refined carbohydrate with protein sources that are low in saturated fat. Although recent evidence supports potential benefit, rigorous longer-term studies are needed to investigate the effects of high protein diets on weight loss and weight maintenance.     

Action and interaction of growth hormone and the beta-agonist, clenbuterol, on growth, body composition and protein turnover in dwarf mice

The responses of dwarf mice to dietary administration of clenbuterol (3 mg/kg diet), daily injections of growth hormone (15 micrograms/mouse per d) or both treatments combined were investigated and their actions, and any interactions, on whole-body growth, composition and protein metabolism, and muscle, liver and heart growth and protein metabolism, were studied at days 0, 4 and 8 of treatment. Growth hormone, with or without clenbuterol, induced an increase in body-weight growth and tail length growth; clenbuterol alone did not affect body-weight or tail length. Both growth hormone and clenbuterol reduced the percentage of whole-body fat and increased the protein:fat ratio. They also increased protein synthesis rates of whole body and muscle, although the magnitude of the increase was greater in response to growth hormone than to clenbuterol. Clenbuterol specifically induced growth of muscle, with a decrease in liver protein content, whereas growth hormone exhibited more general anabolic effects on tissue protein. Previous reports have suggested that effects of clenbuterol on skeletal muscle are mediated, at least in part, via decreased rates of protein degradation; we could find little evidence of any decrease in whole-body or tissue protein degradation and anabolic effects were largely due to increases in protein synthesis rates. However, small increases in muscle protein degradation rate were observed in response to growth hormone. Growth hormone induced a progressive increase in serum insulin-like growth factor-1 concentration, whereas there was no change with clenbuterol administration. Anabolic effects on whole-body and skeletal muscle protein metabolism, therefore, appear to be initially via independent mechanisms but are finally mediated by a common response (increased protein synthesis) in dwarf mice.     

Effects of acute and chronic protein deprivation on ornithine decarboxylase levels in rat liver and colon

The effects of protein intake on the levels of total and holo‐ornithine decarboxylase (ODC) in colon and liver have been examined in male Sprague‐Dawley rats fed varying amounts of casein in a defined purified diet. Pair‐feeding was used to eliminate effects of food intake per se. In the colon, both total and holo‐ODC activity increased in animals fed a low‐protein diet (1% casein). In the liver, on the other hand, both total and holo‐ODC activity decreased with protein deprivation. The observed changes in both colon and liver appeared to be maximal within several days after institution of the dietary regimen. Refeeding with a high‐protein diet (20% casein) led to a dramatic rise in ODC activity in the liver in animals previously fed a low‐protein diet. These results may be important in sorting out the effects of diet on the tumorigenic process.     

The role of protein in weight management

Several studies have shown that high protein meals and foods are more satiating than high carbohydrate or high fat meals when assessed by subjective ratings of satiety. Few of these studies were able to control for potentially confounding variables. Test meals differ widely in physical and sensory properties so it cannot be concluded that it is protein conferring these effects. When sensory properties are controlled up to 10-30% more calories are eaten at a subsequent meal with a high carbohydrate liquid meal than a high protein liquid meal with no difference in protein sources or BMI status. Weight loss studies examining the metabolic effects of isocaloric high protein energy restricted diets with high carbohydrate structured diets have not shown differences in kilojoule intake and weight loss despite expected satiety differences. Such studies do not allow the effects of increased satiety attributable to protein to be expressed as the dietary protocols have required all foods to be consumed. However, several longer term studies have noted improvements in body composition on a higher protein pattern despite similar weight loss. An interaction between protein intake and exercise on improved lean mass retention has also been observed. Studies comparing ad libitun high protein diets to high carbohydrate diets have usually shown greater weight loss on the high protein pattern and that enhanced satiety was the most important factor in the weight loss.     

Effect of thiamin deficiency on pancreatic acinar cell function

The aim of the present study was to determine the effect of thiamin deficiency on pancreatic acinar cell function. Weight-matched triplets of Sprague-Dawley rats were fed a purified thiamin-deficient diet ad libitum, isocaloric amount of purified thiamin-sufficient diet or rat feed ad libitum for a mean of 33 (+/- 0.5 SEM) days. Effect of diets on body weight, pancreas weight, DNA, RNA, protein and amylase content, synthesis of protein and secretion were determined. Controls diet effect was considered when fed ad libitum controls were different from isocaloric controls. Thiamin effect was considered when thiamin-deficient diet treatment resulted in effects similar to control diet effects in addition to specific effects that included reduced body weight, total protein, and amylase. Basal and bethanechol (10-4 M) stimulated secretion of protein and amylase were increased. It is concluded from this study that thiamin deficiency per se induced a reduction in body weight, pancreatic protein and digestive enzyme content and increased protein and digestive enzyme secretion due to metabolic derangements leading probably to altered redox state of pancreatic acinar cell.     

Dietary soy beta-conglycinin (7S globulin) inhibits atherosclerosis in mice

Although beta-conglycinin (7S globulin), a major soy storage protein, stimulates the expression of LDL receptors and the degradation of LDL by hepatocytes in vitro, the in vivo effects of dietary beta-conglycinin on the cardiovascular system are unknown. We assessed the effects of dietary beta-conglycinin and other soy peptide fractions on the development of atherosclerosis in atherosclerosis-susceptible mice. At 6 wk of age, male and ovariectomized female apolipoprotein (apo) E-null mice and LDL receptor-null, apoB transgenic mice were assigned randomly to treatment groups that differed only in the source of dietary protein: 1) casein/lactalbumin, 2) isoflavone-containing soy protein isolate, 3) beta-conglycinin, 4) glycinin (11S globulin, another major soy storage protein), 5) beta-conglycinin-devoid soy protein, and 6) W008 (a peptide fraction produced by hydrolysis and precipitation of soy protein isolate). After 4 mo, aortic atherosclerosis (cholesteryl ester content) and plasma lipoprotein cholesterol concentrations were quantified using GLC. Relative to mice fed casein/lactalbumin-based diets, the extent of atherosclerosis was reduced in ovariectomized female mice fed all soy protein-containing diets. Relative to mice fed isoflavone-containing soy protein isolate, atherosclerosis was reduced only in mice fed the beta-conglycinin-containing diet. Mean reductions were 39 and 67% (all P <0.05) in male and ovariectomized female apoE null mice and 66% (P < 0.05) in male LDL receptor null mice. These effects were unrelated to variation in isoflavone content of the protein source and only minimally related to plasma lipoprotein cholesterol concentrations. We conclude that a diet rich in beta-conglycinin has atheroprotective effects that greatly exceed those of isoflavone-containing soy protein isolate and do not depend on LDL receptors or influences on plasma lipoproteins.     

Leucine and protein synthesis: mTOR and beyond

The effects of amino acid intake on protein synthesis in the intact rat appear to be mediated almost entirely by a single amino acid: leucine. The effect of leucine on protein synthesis appears to be closely associated with eIF4G phosphorylation and its association with eIF4E, but whether eIF4G phosphorylation actually mediates the effects of leucine or is merely associated with these events has not been elucidated. Additional research is needed to determine whether leucine effects eIF4G phosphorylation, whether eIF4G phos-phorylation is essential for the effect of leucine on protein synthesis, and whether mTOR (mammalian target of rapamycin) or another component of the mTOR complex is somehow involved in leucine-specific signaling.     

Effects of diets high in whey, soy, red meat and milk protein on body weight maintenance in diet-induced obesity in mice

This study examined the effects of different food sources of protein on energy intake, body weight maintenance, and on the responses of plasma leptin, insulin and adiponectin in chronic high-fat diet-induced obese mice. Obesity was induced in 47 mice with a high-fat diet for 20 weeks. They were divided into five diet groups to test the effects of a higher protein proportion (30% energy), achieved at the expense of carbohydrate. For the next eight weeks, four of the groups were fed diets of chow formulated with whey, soy, red meat or milk while the control group continued on their high-fat diet. The results showed that: (i) increasing the protein : carbohydrate ratio (both at 30% energy) in a high-fat diet did not reduce the level of obesity; (ii) the type of protein added, however, did have a significant effect on the level of obesity attained; (iii) whey protein stabilised weight gain the most, had the strongest satiety effects and also stimulated the highest production of adiponectin; and (iv) whey protein also was associated with the lowest insulin values among all proteins tested. Plasma leptin levels were not affected by any of the diets. Dietary fat remains a potent factor in weight management, but the type and amount of protein may also be important through its effects on food intake. In particular, the apparent decreased appetite associated with increased adiponectin in the whey-based high-protein diet may contribute to stabilised body mass in chronic high-fat diet-induced obesity.     

Dietary protein and bone health

The effects of dietary protein on bone health are paradoxical and need to be considered in context of the age, health status and usual diet of the population. Over the last 80 years numerous studies have demonstrated that a high protein intake increases urinary Ca excretion and that on average 1 mg Ca is lost in urine for every 1 g rise in dietary protein. This relationship is primarily attributable to metabolism of S amino acids present in animal and some vegetable proteins, resulting in a greater acid load and buffering response by the skeleton. However, many of these early studies that demonstrated the calciuric effects of protein were limited by low subject numbers, methodological errors and the use of high doses of purified forms of protein. Furthermore, the cross-cultural and population studies that showed a positive association between animal-protein intake and hip fracture risk did not consider other lifestyle or dietary factors that may protect or increase the risk of fracture. The effects of protein on bone appear to be biphasic and may also depend on intake of Ca- and alkali-rich foods, such as fruit and vegetables. At low protein intakes insulin-like growth factor production is reduced, which in turn has a negative effect on Ca and phosphate metabolism, bone formation and muscle cell synthesis. Although growth and skeletal development is impaired at very low protein intakes, it is not known whether variations in protein quality affect the achievement of optimal peak bone mass in adolescents and young adults. Prospective studies in the elderly in the USA have shown that the greatest bone losses occur in elderly men and women with an average protein intake of 16-50 g/d. Although a low protein intake may be indicative of a generally poorer diet and state of health, there is a need to evaluate whether there is a lower threshold for protein intake in the elderly in Europe that may result in increased bone loss and risk of osteoporotic fracture.     

The effect of dietary protein intake on coronary heart disease risk

There is cumulative evidence that there is a relationship between diet and coronary heart disease (CHD) risk. The majority of studies have focused on the role of carbohydrate and fat on CHD risk; yet the role of protein has, until recently, been neglected. The effects of dietary protein on modulating CHD risk factors are still unclear. The aim of this review is to summarise available data from epidemiological and randomised control trials on the effects of animal and vegetable protein intake on markers of CHD risk; that is, obesity, hyperlipidaemia, glucose intolerance, diabetes and hypertension. Regarding the management of body weight, reviewed data suggest that there is no convincing evidence that higher protein (HP) diets enhance weight loss compared with low protein (LP) diets, but there is some evidence that HP diets may lead to better weight maintenance. Moreover, HP diets seem to have a more favourable effect on triglyceride levels than LP diets, but on the other hand, there is no convincing evidence that there is a significant beneficial effect on total and low‐density lipoprotein cholesterol levels. In the literature, there is also a concern that higher protein intakes may increase blood glucose levels and may aggravate glycaemic control. Currently, data suggest that HP diets may have a favourable effect on postprandial glucose and glycated haemoglobin levels, whereas there is no convincing evidence on their effects on fasting glucose and insulin levels. There has also been concern that higher protein intakes may increase arterial blood pressure because of higher levels of sodium in protein‐rich foods. The data we reviewed suggest that HP diets may be more beneficial in ameliorating hypertension than LP diets. Finally, the effect of a higher protein intake on kidney function has been debated.     

Soy products and the human diet

This review focuses upon the nutritional significance of soy products in the human diet. The impact of the consumption of soy foods on a range of diet and health issues are discussed, including protein quality and growth promoting effects of soy protein, allergies in children, hypocholesterolemic effects of soy protein and soy fiber, effects of soy products upon glucose tolerance, and the bioavailability of zinc and iron from soy foods. Recent research reports involving humans and relevant animal studies are reviewed.     

Effects of Dietary Protein Source and Quantity during Weight Loss on Appetite,Energy Expenditure,and Cardio-Metabolic Responses

Higher protein meals increase satiety and the thermic effect of feeding (TEF) in acute settings, but it is unclear whether these effects remain after a person becomes acclimated to energy restriction or a given protein intake. This study assessed the effects of predominant protein source (omnivorous, beef/pork vs. lacto-ovo vegetarian, soy/legume) and quantity (10%, 20%, or 30% of energy from protein) on appetite, energy expenditure, and cardio-metabolic indices during energy restriction (ER) in overweight and obese adults. Subjects were randomly assigned to one protein source and then consumed diets with different quantities of protein (4 weeks each) in a randomized crossover manner. Perceived appetite ratings (free-living and in-lab), TEF, and fasting cardio-metabolic indices were assessed at the end of each 4-week period. Protein source and quantity did not affect TEF, hunger, or desire to eat, other than a modestly higher daily composite fullness rating with 30% vs. 10% protein diet (p = 0.03). While the 20% and 30% protein diets reduced cholesterol, triacylglycerol, and APO-B vs. 10% protein (p < 0.05), protein source did not affect cardio-metabolic indices. In conclusion, diets varying in protein quantity with either beef/pork or soy/legume as the predominant source have minimal effects on appetite control, energy expenditure and cardio-metabolic risk factors during ER-induced weight loss.     

Dietary animal proteins and cholesterol metabolism in rats

The effects on cholesterol metabolism in rats of diets containing various animal proteins or soy protein were studied. The animal proteins tested were casein, whey protein, fish protein, hemoglobin, plasma proteins, ovalbumin, egg-yolk protein, beef protein and chicken-meat protein. The semi-purified diets were isonitrogenous and balanced for residual fat and cholesterol in the protein preparations. The nature of the dietary protein had no effect on serum cholesterol concentration. Group mean liver cholesterol concentration was increased and fecal excretion of bile acids was decreased by all animal proteins when compared with soy protein. This study suggests that carefully balancing diets for components other than protein in the protein preparations prevents protein effects on serum cholesterol in rats but not on liver cholesterol and bile acid excretion.     

钙、镁和蛋白质摄入量对氟中毒及氟耐受量影响的研究

研究了一个典型的饮水型氟中毒病区人群钙、镁、蛋白质摄入量及其对氟中毒和人群氟耐受量的影响。结果表明，在暴露区中儿童的平均钙、镁、蛋白质人均日摄入量分别为３９２ｍｇ、４４２ｍｇ和４４．２ｇ；成人平均钙、镁、蛋白质日摄入量分别为４８８ｇ、５６６ｍｇ和５３．６ｇ，二者之间存在显著性差异。对上述数据进行Ｌｏｇｉｓｔｉｃ回归分析表明，钙、镁与氟斑牙呈明显的负相关关系，钙、镁、蛋白质均与氟中毒的症状和体征呈负相关关系。提示钙、镁、蛋白质对氟斑牙、成人氟中毒的症状与体征具有拮抗作用。在同一患病率下，钙、镁、蛋白质对氟中毒的拮抗作用镁＞钙＞蛋白质。增加钙、镁、蛋白质摄入量可以提高人群氟耐受量     

Do protein and phosphorus cause calcium loss?

The widespread opinion that both protein and phosphorus cause calcium loss is examined. Controlled human studies show that commonly used complex dietary proteins, which have a high phosphorus content, do not cause calcium loss in adult humans. Similarly, a phosphorus intake of up to 2000 mg/d does not have adverse effects on calcium metabolism; however, the type of phosphate contained in carbonated beverages may not behave in the same manner. In contrast, a diet low in protein and phosphorus may have adverse effects on calcium balance in the elderly. Studies with adults suggest that high protein foods do not cause calcium loss.     

Long-chain polyunsaturated fatty acids upregulate LDL receptor protein expression in fibroblasts and HepG2 cells

The objective of this study was to investigate the effect of individual PUFAs on LDL receptor (LDLr) expression in human fibroblasts and HepG2 cells, and to evaluate whether acyl CoA:cholesterol acyltransferase (ACAT) and sterol regulatory element-binding protein 1 (SREBP-1) were involved in the regulation of LDLr expression by fatty acids. When fibroblasts and HepG2 cells were cultured with serum-free defined medium for 48 h, there was a 3- to 5-fold (P < 0.05) increase in LDLr protein and mRNA levels. Incubation of fibroblasts and HepG2 cells in serum-free medium supplemented with 25-hydroxycholesterol (25OH-cholesterol, 5 mg/L) for 24 h decreased LDLr protein and mRNA levels by 50-90% (P < 0.05). Arachidonic acid [AA, 20:4(n-6)], EPA [20:5(n-3)], and DHA [22:6(n-3)] antagonized the depression of LDLr gene expression by 25OH-cholesterol and increased LDLr protein abundance 1- to 3-fold (P < 0.05), but had no significant effects on LDLr mRNA levels. Oleic (18:1), linoleic (18:2), and alpha-linolenic acids [18:3(n-3)] did not significantly affect LDLr expression. ACAT inhibitor (58-035, 1 mg/L) attenuated the regulatory effect of AA on LDLr protein abundance by approximately 40% (P < 0.05), but did not modify the regulatory effects of other unsaturated fatty acids in HepG2 cells. The present results suggest that AA, EPA, and DHA increase LDLr protein levels, and that ACAT plays a role in modulating the effects of AA on LDLr protein levels. Furthermore, the effects of the fatty acids appeared to be independent of any change in SREBP-1 protein.     

Does Cry1Ab protein affect learning performances of the honey bee Apis mellifera L. (Hymenoptera, Apidae)?

Genetically modified Bt crops are increasingly used worldwide but side effects and especially sublethal effects on beneficial insects remain poorly studied. Honey bees are beneficial insects for natural and cultivated ecosystems through pollination. The goal of the present study was to assess potential effects of two concentrations of Cry1Ab protein (3 and 5000 ppb) on young adult honey bees. Following a complementary bioassay, our experiments evaluated effects of the Cry1Ab on three major life traits of young adult honey bees: (a) survival of honey bees during sub-chronic exposure to Cry1Ab, (b) feeding behaviour, and (c) learning performance at the time that honey bees become foragers. The latter effect was tested using the proboscis extension reflex (PER) procedure. The same effects were also tested using a chemical pesticide, imidacloprid, as positive reference. The tested concentrations of Cry1Ab protein did not cause lethal effects on honey bees. However, honey bee feeding behaviour was affected when exposed to the highest concentration of Cry1Ab protein, with honey bees taking longer to imbibe the contaminated syrup. Moreover, honey bees exposed to 5000 ppb of Cry1Ab had disturbed learning performances. Honey bees continued to respond to a conditioned odour even in the absence of a food reward. Our results show that transgenic crops expressing Cry1Ab protein at 5000 ppb may affect food consumption or learning processes and thereby may impact honey bee foraging efficiency. The implications of these results are discussed in terms of risks of transgenic Bt crops for honey bees.