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The metabolic response to nutrient ingestion and the rate of digestion and absorption of nutrient molecules in bowel physiology plays an important role in the metabolic control of some human chronic non-infectious diseases. This experimentally-controlled designed nutritional study which lasted eight weeks aimed to determine the effects of proportional high-protein/low-carbohydrate (HP/LC) formulated diet on glycemic tolerance, glycemic control, body weight, organ weight and organ morphometry in healthy and diabetic adult male Wistar rats. Twenty-four male Wistar rats purchased from a disease-free stock were randomly categorized into four groups (n = 6, each) after two weeks acclimatization period in raised stainless steel cages with 6 [mm.sup.2] mesh floor and replaceable numbered blotters papers placed under each cage in a well-ventilated animal house. Animal groups include: Healthy control group (HC), Healthy treated group (HT), Diabetic control group (DC) and Diabetic treated group (DT). The animals were fed according to the experimental design with water ad libitum for eight weeks. Diabetes was inducted with freshly prepared alloxan monohydrate solution (150 mg/kg bw, intraperitoneally). Body weights and fasting blood sugar concentrations were measured twice weekly, while oral glucose tolerance test was conducted on the last day of the eighth-week study and subsequently followed by organs extraction after anesthesia for weight and gross assessment. Proportional high-protein/low-carbohydrate formulated diet caused significant reduction in mean body weight of treated diabetic (DT: 22.6%; P = .001) and healthy (HT: 5.8%; P = .007) rats while the control animals on control diet recorded significant (P < .05) increase in body weight gain (DC: 12.4%; HC: 11.2%). Glycemic tolerance and control improved significantly in diabetic treated rats over that of the healthy treated rats. Gross morphometry of the extracted organs (kidneys, liver, heart, lungs, spleen and testes) revealed sustained normal morphological features without any visible lesion. In conclusion, consumption of proportional high-protein/low-carbohydrate formulated diet enhanced body weight reduction and sustained normal organ morphological features with good glycemic tolerance and control in experimental rats, suggesting its dietary potentiality, safety and suitability to ameliorate obesity-related diabetes. Key words: Body weight, diabetes, formulated-diet, glycemic control, obesity, Wistar rats, alloxan monohydrate, INTRODUCTION Metabolic response to carbohydrate and protein ingestion plays an important role in health and disease states [1,2]. Diabetes and obesity are chronic non-infectious diseases with related pathogenesis. Diabetic individuals, [...]

INTRODUCTION In recent years, diet methods for weight control and their impact on health and survival have received much attention. Particularly, controversial are the carbohydrate-restricted diets that run counter to [...], BACKGROUND/OBJECTIVE: Long-term effects of carbohydrate-restricted diets are unclear. We examined a low-carbohydrate, high-protein (LCHP) score in relation to mortality. SUBJECTS/METHODS: This is a population-based cohort study on adults in the northern Swedish county of Vasterbotten. In 37 639 men (1460 deaths) and 39 680 women (923 deaths) from the population-based Vasterbotten Intervention Program, deciles of energy-adjusted carbohydrate (descending) and protein (ascending) intake were added to create an LCHP score (2-20 points). Sex-specific hazard ratios (HR) were calculated by Cox regression. RESULTS: Median intakes of carbohydrates, protein and fat in subjects with LCHP scores 2-20 ranged from 61.0% to 38.6%, 11.3% to 19.2% and 26.6% to 41.5% of total energy intake, respectively. High LCHP score (14-20 points) did not predict all-cause mortality compared with low LCHP score (2-8 points), after accounting for saturated fat intake and established risk factors (men: HR for high vs low 1.03 (95% confidence interval (CI) 0.88-1.20), P for continuous = 0.721; women: HR for high vs low 1.10 (95% CI 0.91-1.32), P for continuous = 0.229). For cancer and cardiovascular disease, no clear associations were found. Carbohydrate intake was inversely associated with all-cause mortality, though only statistically significant in women (multivariate HR per decile increase 0.95 (95% CI 0.91-0.99), P = 0.010). CONCLUSION: Our results do not support a clear, general association between LCHP score and mortality. Studies encompassing a wider range of macronutrient consumption may be necessary to detect such an association. European Journal of Clinical Nutrition (2012) 66, 694-700; doi: 10.1038/ejcn.2012.9; published online 15 February 2012 Keywords: diet; survival; macronutrients; protein intake; carbohydrate intake; cohort study

We had previously observed that drastic increases in protein consumption greatly modified hepatic protein anabolism in rats, but the confounding effects of other macronutrient changes or a moderate protein increase to generate the same modifications have not yet been established. This study examined the metabolic and hormonal responses of rats subjected to 14-day isoenergetic diets containing normal, intermediate, or high-protein levels (NP: 14% of energy, IP: 33%, HP: 50%) and different carbohydrate (CHO) to fat ratios within each protein level. Fasted or fed rats (n = 104) were killed after the injection of a flooding dose of 13C-valine. The hepatic protein content increased in line with the dietary protein level (P < 0.05). The hepatic fractional synthesis rates (FSR) of protein were significantly influenced by both the protein level and the nutritional state (fasted vs. fed) (P < 0.0001) but not by the CHO level, reaching on average 110%/day, 92%/day, and 83%/day in rats fed the NP, IP, and HP diets, respectively. The FSR of plasma albumin and muscle did not differ between diets, while feeding tended to increase muscle FSR. Proteolysis, especially the proteasome-dependent system, was down-regulated in the fed state in the liver when protein content increased. Insulin decreased with the CHO level in the diet. Our results reveal that excess dietary protein lowers hepatic constitutive, but not exported, protein synthesis rates, independently of the other macronutrients, and related changes in insulin levels. This response was observed at the moderate levels of protein intake (33%) that are plausible in a context of human consumption. high-protein diet; liver; energy nutrients doi: 10.1152/aj pregu.00497.2010

The Diet, Obesity and Genes (Diogenes) study is a pan-European, multicenter, randomized, dietary-intervention study that is designed for assessing the efficacy of moderate-fat diets that vary in protein content and glycemic index for preventing weight regain and obesity-related risk factors after weight loss. The results have shown that a modest increase in protein content and a modest reduction in the glycemic index have led to an improvement in study completion and maintenance of weight loss.

Hyperproteic diets are used in human nutrition to obtain body weight reduction. Although increased protein ingestion results in an increased transfer of proteins from the small to the large intestine, there is little information on the consequences of the use of such diets on the composition of large intestine content and on epithelial cell morphology and metabolism. Rats were fed for 15 days with either a normoproteic (NP, 14% protein) or a hyperproteic isocaloric diet (HP, 53% protein), and absorptive colonocytes were observed by electron microscopy or isolated for enzyme activity studies. The colonic luminal content was recovered for biochemical analysis. Absorbing colonocytes were characterized by a 1.7-fold reduction in the height of the brush-border membranes (P = 0.0001) after HP diet consumption when compared with NP. This coincided in the whole colon content of HP animals with a 1.8-fold higher mass content (P = 0.0020), a 2.2-fold higher water content (P = 0.0240), a 5.2-fold higher protease activity (P = 0.0104), a 5.5-fold higher ammonia content (P = 0.0008), and a more than twofold higher propionate, valerate, isobutyrate, and isovalerate content (P < 0.05). The basal oxygen consumption of colonocytes was similar in the NP and HP groups, but ammonia was found to provoke a dose-dependent decrease of oxygen consumption in the isolated absorbing colonocytes. The activity of glutamine synthetase (which condenses ammonia and glutamate) was found to be much higher in colonocytes than in small intestine enterocytes and was 1.6-fold higher (P = 0.0304) in colonocytes isolated from HP animals than NP. Glutaminase activity remained unchanged. Thus hyperproteic diet ingestion causes marked changes both in the luminal environment of colonocytes and in the characteristics of these cells, demonstrating that hyperproteic diet interferes with colonocyte metabolism and morphology. Possible causal relationships between energy metabolism, reduced height of colonocyte brush-border membranes, and reduced water absorption are discussed. hyperproteic diet; colonic epithelial cells; ammonia; glutamine synthetase doi: 10.1152/ajpgi.00149.2010.

High-protein diets have been advocated for weight loss and the treatment of diabetes. Yet animal protein sources are often high in saturated fat and cholesterol. Vegetable protein sources, by contrast, are low in saturated fat and without associated cholesterol. We have therefore assessed the effect on serum lipids of raising the protein intake by 5% using a cereal protein, barley protein, as part of a standard therapeutic diet. Twenty-three hypercholesterolemic men and postmenopausal women completed a randomized crossover study comparing a bread enriched with either barley protein or calcium caseinate [30 g protein, 8374 kJ (2000 kcal)] taken separately as two 1-mo treatment phases with a minimum 2-wk washout. Body weight and diet history were collected weekly during each treatment. Fasting blood samples were obtained at wk 0, 2, and 4. Palatability, satiety, and compliance were similar for both the barley protein- and casein- enriched breads, with no differences between the treatments in effects on serum LDL cholesterol or C-reactive protein, measures of oxidative stress, or blood pressure. Nevertheless, because no adverse effects were observed on cardiovascular risk factors, barley protein remains an additional option for raising the protein content of the diet. J. Nutr. 140: 1633-1637, 2010. doi: 10.3945/jn.110.123224.

Little attention has been given to the association of dietary patterns with plasma homocysteine. Our objective in this study was to identify major dietary patterns and investigate their association with plasma homocysteine. In a cross-sectional survey, 872 healthy adults (355 males, 517 females; aged 18-60 y) were enrolled from an urban population in Karachi. Dietary intake was assessed by a FFQ. We used factor analysis to define major dietary patterns. Fasting concentrations of plasma or serum homocysteine, folate, pyridoxal-phosphate (PLP; coenzyme form of vitamin B-6), and vitamin B-12 were measured. Three major dietary patterns were identified and labeled as 'prudent diet,' 'high animal-protein diet,' and 'high plant-protein diet.' We observed a protective effect of the prudent dietary pattern for the highest quartile of intake compared with the lowest quartile of hyperhomocysteinemia when the model was adjusted for age, gender, household income, BMI, tobacco chewing, and smoking [OR = 0.52 (95% CI = 0.30-0.90); P = 0.01]. The high plant-protein diet pattern was inversely related to hyperhomocysteinemia, with a higher intake being protective. Compared with the 1st quartile, the adjusted OR was 0.42 (95% CI = 0.25-0.69; P = 0.001) for the 4th quartile. The high animal-protein diet was positively associated with hyperhomocysteinemia, with participants in the highest quartile of intake having the greatest increase in risk [OR = 2.10 (95% CI = 1.22-3.60); P = 0.007]. Plasma homocysteine concentrations appeared to be correlated more with circulating folate (r = -0.25; P < 0.001) than with PLP (r = -0.02; P = 0.663) or vitamin B-12 (r = -0.16; P < 0.001). A diet rich in fruits and uncooked vegetables decreased the risk of hyperhomocysteinemia, whereas diets rich in red meat, chicken, and tea with milk were positively associated with hyperhomocysteinemia. doi: 10.3945/jn.109.120477

Introduction Prevalence of type 2 diabetes (DM2) is reaching epidemic proportions worldwide. Although nutrition has always had an integral role in diabetes management, the optimal diet for people with diabetes [...], Background/Objectives: There is controversy over dietary protein's effects on cardiovascular disease risk factors in diabetic subjects. It is unclear whether observed effects are due to increased protein or reduced carbohydrate content of the consumed diets. The aim of this study was to compare the effects of two diets differing in protein to fat ratios on cardiovascular disease risk factors. Subjects/Methods: A total of 17 obese (body mass index (BMI) ranging from 31 to 45 kg/m2) volunteers with type 2 diabetes (DM2), aged 46 ± 3 years, consumed two diets, each for 4 weeks, with 3 weeks of washout period in a random, blind, crossover design. The diets were: (1) a high-protein low-fat diet (HP-LF, with 30% protein, 50% carbohydrates and 20% fat) and (2) a low-protein high-fat diet (LP-HF, with 15% protein, 50% carbohydrates and 35% fat). Their effects on fasting glycemic control, lipid levels and blood pressure, and on postprandial glucose and insulin responses after a standard test meal at the beginning and end of each dietary intervention were analyzed. Results: Both diets were equally effective in promoting weight loss and fat loss and in improving fasting glycemic control, total cholesterol and low-density lipoprotein (LDL) cholesterol, but the HP-LF diet decreased to a greater extent triglyceride (TG) levels (P = 0.04) when compared with the LP-HF diet. HP-LF diet improved significantly both systolic and diastolic blood pressure when compared with the LP-HF diet (P< 0.001 and P Conclusions: A protein to fat ratio of 1.5 in diets significantly improves blood pressure and TG concentrations in obese individuals with DM2. European Journal of Clinical Nutrition (2010) 64, 595-602; doi: 10.1038/ejcn.2010.29; published online 10 March 2010 Keywords: diet; protein; coronary heart disease; diabetes; obesity

The apparent digestibility of energy-yielding nutrients (carbohydrate, protein, and fat) was predicted in the human upper digestive tract and large bowel separately for 4 diverse diets containing either a single dietary fiber source [wheat bran and pectin (PE) diets] or mixed fiber sources [low-fiber (LF) and high-fiber (HF) diets). A human balance study was undertaken to determine fecal energy and nutrient excretion and a rat model was used to predict human ileal energy and nutrient excretion. Total tract energy digestibility ranged from 92 (HF diet) to 96% (PE diet and LF diet), while at the ileal level it ranged from 79 to 86% for the HF diet to the LF diet. The predicted upper-tract digestion of starch, sugars, and fat was high, with ileal digestibilities exceeding 90% for all diets. Nonstarch polysaccharides were poorly digested in the upper tract for all diets except in the PE diet. The daily quantity of protein excreted at the ileal level was between 2 (HF diet) and 5 (PE diet) times higher than that at the fecal level. The large differences between fecal and ileal nutrient loss highlight that fecal digestibility data alone provide incomplete information on nutrient loss. There is a need to be able to routinely determine the uptake of energy in the upper and lower digestive tracts separately. doi: 10.3945/jn.109.116293.

Chotechuang N, Azzout-Marniche D, Bos C, Chaumontet C, Gausser/s N, Steiler T, Gaudichon C, Tome D. mTOR, AMPK, and GCN2 coordinate the adaptation of hepatic energy metabolic pathways in response to protein intake in the rat. Am J Physiol Endocrinol Metab 297: E 1313-E 1323, 2009. First published September 8, 2009; doi: 10.1152/ajpendo.91000.2008.--Three transduction pathways are involved in amino acid (AA) sensing in liver: mammalian target of rapamycin (roTOR), AMP-activated protein kinase (AMPK), and general control nondepressible kinase 2 (GCN2). However, no study has investigated the involvement of these signaling pathways in hepatic AA sensing. To address the question of liver AA sensing and signaling in response to a high-protein (HP) dietary supply, we investigated the changes in the phosphorylation state of hepatic mTOR (p-mTOR), AMPK[alpha] (p-AMPK[alpha]), and GCN2 (p-GCN2) by Western blotting. In rats fed a HP diet for 14 days, the hepatic p-AMPK[alpha] and p-GCN2 were lower (P < 0.001), and those of both the p-roTOR and eukaryotic initiation factor 4E-binding protein-1 phosphorylation (p-4E-BP1) were higher (P < 0.01) compared with rats receiving a normal protein (NP) diet. In hepatocytes in primary culture, high AA concentration decreased AMPK[alpha] phosphorylation whether insulin was present or not (P < 0.01). Either AAs or insulin can stimulate p-roTOR, but this is not sufficient for 4E-BP1 phosphorylation that requires both (P < 0.01). As expected, branchedchain AAs (BCAA) or leucine stimulated the phosphorylation of mTOR, but both insulin and BCAA or leucine are required for 4E-BP1 phosphorylation. GCN2 phosphorylation was reduced by both AAs and insulin(P < 0.01), suggesting for the first time that the translation inhibitor GCN2 senses not only the AA deficiency but also the AA increase in the liver. The present findings demonstrate that AAs and insulin exert a coordinated action on translation and involved mTOR, AMPK, and GCN2 transduction pathways. mammalian target of rapamycin; adenosine 5'-monophosphate-activated protein kinase; general control nondepressible kinase 2; transduction pathways; translation; high-protein diet doi: 10.1152/ajpendo.91000.2008

Diets with increased protein and reduced carbohydrates (PRO) are effective for weight loss, but the long-term effect on maintenance is unknown. This study compared changes in body weight and composition and blood lipids after short-term weight loss (4 mo) followed by weight maintenance (8 mo) using moderate PRO or conventional high-carbohydrate (CHO) diets. Participants (age = 45.4 [+ or -] 1.2 y; BMI = 32.6 [+ or -] 0.8 kg/[m.sup.2]; n = 130) were randomized to 2 energy-restricted diets (-500 kcal/d of -2093 k J/d): PRO with 1.6 g x [kg.sup.-1] x [d.sup.-1] protein and 220 g/d carbohydrates. At 4 mo, the PRO group had lost 22% more fat mass (FM) (-5.6 [+ or -] 0.4 kg) than the CHO group (-4.6 [+ or -] 0.3 kg) but weight loss did not differ between groups (-8.2 [+ or -] 0.5 kg vs. -7.0 [+ or -] 0.5 kg; P = 0.10). At 12 mo, the PRO group had more participants complete the study (64 vs. 45%, P < 0.05) with greater improvement in body composition; however, weight loss did not differ between groups (-10.4 [+ or -] 1.2 kg vs. -8.4 [+ or -] 0.9 kg; P = 0.18). Using a compliance criterion of participants attaining >10% weight loss, the PRO group had more participants (31 vs. 21%) lose more weight (-16.5 [+ or -] 1.5 vs. -12.3 [+ or -] 0.9 kg; P < 0.01)and FM (-11.7 [+ or -] 1.0 vs. -7.9 [+ or -] 0.7 kg; P< 0.01) than the CHO group. The CHO diet reduced serum cholesterol and LDL cholesterol compared with PRO (P < 0.01 ) at 4 mo, but the effect did not remain at 12 mo. PRO had sustained favorable effects on serum triacylglycerol (TAG), HDL cholesterol (HDL-C), and TAG:HDL-C compared with CHO at 4 and 12 mo (P < 0.01). The PRO diet was more effective for FM loss and body composition improvement during initial weight loss and long-term maintenance and produced sustained reductions in TAG and increases in HDL-C compared with the CHO diet.

Decline in muscle mass, protein synthesis, and mitochondrial function occurs with age, and amino acids are reported to enhance both muscle protein synthesis and mitochondrial function. It is unclear whether increasing dietary protein intake corrects postabsorptive muscle changes in aging. We determined whether a 10-day diet of high [HP; 3.0 g protein x kg fat-free mass [(FFM).sup.-1] x [day.sup.-1]] vs. usual protein intake (UP; 1.5 g protein x kg [FFM.sup.-1] x [day.sup.-1]) favorably affects mitochondrial function, protein metabolism, and nitrogen balance or adversely affects insulin sensitivity and glomerular filtration rate (GFR) in 10 healthy younger (24 [+ or -] 1 yr) and 9 older (70 [+ or -] 2 yr) participants in a randomized crossover study. Net daily nitrogen balance increased equally in young and older participants, but postabsorptive catabolic state also increased, as indicated by higher whole body protein turnover and leucine oxidation with no change in protein synthesis. Maximal muscle mitochondrial ATP production rate was lower in older people, with no change occurring in diet. GFR was lower in older people, and response to HP was significantly different between the two groups, with a significant increase occurring only in younger people, thus widening the differences in GFR between the young and older participants. In conclusion, a short-term high-protein diet increased net daily nitrogen balance but increased the postabsorptive use of protein as a fuel. HP did not enhance protein synthesis or muscle mitochondrial function in either young or older participants. Additionally, widening differences in GFR between young and older patients is a potential cause of concern in using HP diet in older people. dietary protein; protein metabolism; mitochondrial function; kidney function; aging

Sickle cell disease is associated with hypermetabolism and a consequent shortage of substrates for normal growth and healthy immune response. The protein:energy ratio is a major determinant of dietary adequacy; the requirement for optimal growth of control mice is 20% of energy from dietary protein. This study investigated the efficacy of increased dietary protein for improving weight gain and reducing inflammation in the Berkeley sickle cell mouse model (S). The study examined the effect of diet on weight gain and circulating levels of 2 inflammatory proteins, C-reactive protein (CRP), and cytokine interleukin-6 (IL-6). Male C57BL/6 (C) control (n = 8) and S mice (n = 8) were randomized at weaning to 40 d of isoenergetic diets containing 20% (normal) and 35% (high) of energy from protein (C20, C35, S20, S35), replacing dextrin. Rate of weight gain was calculated and plasma CRP and IL-6 concentrations determined by ELISA. Liver mRNA expression of these proteins was measured by real-time PCR and L-arginase by colorimetric assay. S35 mice tended to gain weight more rapidly than S20 mice (P = 0.06) and more rapidly than C35 mice (P < 0.01). Circulating CRP and IL-6 levels were also lower in S35 mice than in S20 mice (P < 0.05), as was liver CRP mRNA expression (P < 0.01). These results demonstrate that introducing a high protein diet at weaning attenuates the steady-state inflammation in this S mouse model. Dietary L-arginine availability was investigated as a possible mechanism for increased nitric oxide production and consequent reduced inflammation.

Weight loss causes bone mineral loss. Higher protein diets continue to be criticized for further potential harmful bone effects, including elevated urinary calcium, but may promote bone health if protein sources include dairy. Overweight middle-aged subjects (n = 130, 59 males) were randomized to a diet providing 1.4 g x [kg.sup.-1] x [d.sup.-1] protein and 3 daily servings of dairy (PRO) or 0.8 g x [kg.sup.-1] x [d.sup.-1] protein and 2 daily servings of dairy (CARB) for 4 mo of weight loss plus 8 mo of weight maintenance. Diets prescribed 6276 kJ/d for females and 7113 kJ/d for males. Bone mineral content and density (BMD) for whole body (WB), lumbar spine (LS) and total hip (TH) were measured using dual X-ray absorptiometry, and dietary intake using 3-d weighed food records. Urinary calcium was measured using 24-h collection at 0 and 8 mo for a sub- sample (n = 42). Participants lost body weight (mean, 95% Cl) of 8.2% (7.5-8.9%) at 4 mo, 10.6% (9.5-11.8%) at 8 mo, and 10.5% (8.9-12.0%) at 12 mo without differences between groups at any time (P = 0.64). At 12 mo, PRO BMD was higher by 1.6% (0.3-3.0%) at WB, 2.1% (0.6-3.7%) at LS, and 1.4% (0.2-2.5%) at TH compared with CARB. PRO calcium intake was higher (PRO: 1140 [+ or -] 58 mg/d, CARB: 766 [+ or -] 46; P < 0.01 ), as was urinary calcium (PRO: 163 [+ or -] 15 mg/d, CARB: 100 [+ or -] 9.2; P < 0.01). A reduced-energy diet supplying 1.4 g x [kg.sup.-1] x [d.sup.-1] protein and 3 dairy servings increased urinary calcium excretion but provided improved calcium intake and attenuated bone loss over 4 mo of weight loss and 8 additional mo of weight maintenance.

High dietary protein intake generates endogenous acid production, which may adversely affect bone health. Alkaline potassium citrate (Kcit) may contribute to the neutralization of the protein-induced metabolic acidosis. We investigated the impact of 2 levels of protein intake and Kcit supplementation on acid-base metabolism and bone status in rats. Two-monthold Wistar male rats were randomly assigned to 4 groups (n = 30 per group). Two groups received a normal-protein content (13%) (NP) or a high-protein (HP) content diet (26%) for 19 mo. The 2 other groups received identical diets supplemented with Kcit (3.60%) (N PKcit and H PKcit). Rats were pair-fed based on the ad libitum intake of the H P group. At 9, 16, and 21 mo of age, 10 rats of each group were killed. The HP diet induced a metabolic acidosis characterized by hypercalciuria, hypermagnesuria, and hypocitraturia at all ages. Kcit supplementation neutralized this effect, as evidenced by decreased urinary calcium and magnesium excretion by the HPKcit rats. Femoral bone mineral density, biomechanical properties, bone metabolism biomarkers (osteocalcin and deoxypyridinoline), and plasma insulin-like growth factor 1 levels were not affected by the different diets. Nevertheless, at 21 mo of age, calcium retention was reduced in the HP group. This study suggests that lifelong excess of dietary protein results in low-grade metabolic acidosis without affecting the skeleton, which may be protected by an adequate calcium supply.

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. J Am Diet Assoc. 2007;107:644-650.

Maternal low-protein diet during pregnancy is a risk factor for cardiovascular disease of the offspring in later life. The impact of high-protein diet during pregnancy on the cardiovascular phenotype of the offspring, however, is still unknown. We examined the influence of a high-protein diet during pregnancy and lactation on the renal, hemodynamic, and metabolic phenotype of the F1 generation. Female Wistar rats were either fed a normal protein diet (20% protein: NP) or an isocaloric high-protein diet (40% protein: HP) throughout pregnancy and lactation. At weaning, the offspring were fed with standard diet, and they were allocated according to sex and maternal diet to four groups: normal-protein male (NPm, n = 25), normal-protein female (NPf, n = 19), high-protein male (HPm, n = 24), high-protein female (HPf, n = 29). During the experiment (22 wk), the animals were characterized by repeated measurement of body weight, food intake, blood pressure, glucose tolerance, energy expenditure, and kidney function. At the end of the study period histomorphological analyses of the kidneys and weight measurement of reproductive fat pads were conducted. There were no differences in birth weight between the study groups. No influence of maternal diet on energy expenditure, glucose tolerance, and plasma lipid levels was detected. Blood pressure and glomerulosclerosis were elevated in male offspring only, whereas female offspring were characterized by an increased food efficiency, higher body weight, and increased fat pads. Our study demonstrates that a high-protein diet during pregnancy and lactation in rats programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner. fetal programming; hypertension; thrifty phenotype hypothesis; maternal diet

We recently reported that in subjects with untreated type 2 diabetes a 5-wk diet of 30:30:40 carbohydrate/protein/fat ratio resulted in a significant decrease in 24-h integrated glucose, total %glycohemoglobin, and total cholesterol compared with a control diet of 55:15:30 carbohydrate/ protein/fat given at the beginning of the 5-wk period. Body weight was stable and insulin was unchanged. We now present data on other hormones and metabolites considered to be affected by dietary macronutrient changes. The test diet resulted in an elevated fasting plasma total IGF-I, but not growth hormone. Urinary free cortisol was increased. Serum renin and urinary aldosterone remained unchanged. Blood pressure was stable. Serum creatinine and uric acid were increased. Urinary microalbumin was decreased. Creatinine clearance, serum [B.sub.12], folate, homocysteine, TSH, and free thyroxine were unchanged. Total triiodothyronine was decreased. Plasma [alpha]-amino nitrogen, urea nitrogen, and serum albumin were increased. Urea production rate was increased such that a new steady state was present. The calculated urea production rate accounted for 84% of protein ingested on the control diet but only 68% on the test diet, suggesting net nitrogen retention on the latter. Overall, the lack of negative effects, the improved glucose control, and the positive nitrogen balance suggest such a diet will be beneficial for older subjects with type 2 diabetes. Nevertheless, the long-term effects and general applicability of the diet remain to be determined. low biologically available glucose-30 diet; high-protein diet; glycemic index; diabetes; thyroid hormone; protein balance

Renal cortical cyclooxygenase-2 (COX-2) is restricted to the macula densa and adjacent cortical thick ascending limbs (MD/cTALH). Renal cortical COX-2 increases in response to diabetes and renal ablation, both of which are characterized by hyperfiltration and reduced NaCl delivery to the MD due to increased proximal NaCl reabsorption. High-protein intake also induces hyperfiltration and decreases NaCl delivery to the MD due to increased NaCl reabsorption proximally. We investigated whether high protein induces cortical COX-2 and whether cortical COX-2 contributes to high protein-induced hyperfiltration and increased intrarenal renin biosynthesis. Cortical COX-2 increased after protein loading but decreased after protein restriction. COX-2 inhibition attenuated high protein-induced hyperfiltration but had no effect on high protein-induced intrarenal renin elevation. Therefore, induction of cortical COX-2 contributed to high protein-induced hyperfiltration but not intrarenal renin elevation. In the kidney cortex, neuronal nitric oxide synthase (nNOS) is also localized to the MD, and interactions between intrarenal nNOS and COX-2 systems have been proposed. Cortical COX-2 elevation seen in salt restriction was blocked by nNOS inhibiton. Cortical nNOS expression also increased after protein loading, and inhibition of nNOS activity completely reversed high protein-induced cortical COX-2 elevation and hyperfiltration. These results indicate that NO is a mediator of high protein-induced cortical COX-2 elevation and suggest that both intrarenal nNOS and COX-2 systems appear to regulate afferent arteriolar tone and subsequent hyperfiltration seen in high-protein intake. prostaglandin synthase [G.sub.2]/[H.sub.2]; glomerular filtration rate; protein diet doi:10.1152/ajprenal.00500.2005

A study compares a training diet recommended for endurance athletes (high carbohydrate, or h-CHO) with an isoenergetic high protein (whey supplemented), moderate carbohydrate (H-Pro) diet on endurance cycling performance. Results indicate an ergolytic effect of a seven-day high protein diet on self-paced endurance cycling performance.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jada.2005.06.025 Byline: Sharon M. Nickols-Richardson, Mary Dean Coleman, Joanne J. Volpe, Kathy W. Hosig Abstract: The impact of a low-carbohydrate/high-protein diet compared with a high-carbohydrate/low-fat diet on ratings of hunger and cognitive eating restraint were examined. Overweight premenopausal women consumed a low-carbohydrate/high-protein (n=13) or high-carbohydrate/low-fat diet (n=15) for 6 weeks. Fasting body weight (BW) was measured and the Eating Inventory was completed at baseline, weeks 1 to 4, and week 6. All women experienced a reduction in BW (P<.01), although relative BW loss was greater in the low-carbohydrate/high-protein vs high-carbohydrate/low-fat group at week 6 (P<.05). Based on Eating Inventory scores, self-rated hunger decreased (P<.03) in women in the low-carbohydrate/high-protein but not in the high-carbohydrate/low-fat group from baseline to week 6. In both groups, self-rated cognitive eating restraint increased (P<.01) from baseline to week 1 and remained constant to week 6. Both diet groups reported increased cognitive eating restraint, facilitating short-term weight loss; however, the decrease in hunger perception in the low-carbohydrate/high-protein group may have contributed to a greater percentage of BW loss.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jada.2005.01.004 Byline: Mary Dean Coleman, Sharon M. Nickols-Richardson Abstract: This study examined the effect of a low-carbohydrate/high-protein diet on serum and urine ketone body concentrations. Thirteen overweight premenopausal women aged 32 to 45 years consumed [less than or equal to]20 g carbohydrate/day with liberal intakes of protein and fat for 2 weeks; thereafter, carbohydrate intake increased 5 g/week for 10 weeks. Women were weighed and provided fasting urine and blood samples to detect urinary ketones and quantify serum ketone concentrations, respectively, at baseline and weeks 1 to 4, 6, and 12. Women lost 8.3%[+ or -]2.8% of initial body weight by week 12. Serum [beta]-hydroxybutyrate production was highest at week 1 and declined weekly, with all values higher than baseline (P<.05). Each week, serum [beta]-hydroxybutyrate was correlated with presence of urinary ketones (P<.05), but no relationship was found between weekly weight change and serum ketone production. Urinary ketones are detected in premenopausal women complying with a low-carbohydrate/high-protein diet and are associated with serum ketone concentration. However, serum ketones do not reflect weight loss.

We showed previously that rats adapted to a high-protein (70%), carbohydrate-free (HP) diet have reduced lipolytic activity. To clarify the underlying biochemical mechanisms, several metabolic processes involved in adipose tissue lipolysis were investigated. The experiments were performed in rats adapted for 15 d to an HP or a balanced diet. In agreement with previous results, microdialysis experiments showed that the concentrations of adipose tissue interstitial and arterial plasma glycerol were lower in rats adapted to the HP diet. Under nonstimulated conditions, rates of lipolysis, estimated by glycerol release to the incubation medium, were reduced in adipocytes from HP rats. Under the same conditions, there was a small, but significant (17%) reduction in the activity of hormone sensitive lipase (HSL), with no change in the content of the enzyme. Upon stimulation with isoproterenol, the percentage of the enzyme in the adipocyte cytosol translocated to the fat droplet was 20-25% in HP rats and 40-50% in rats fed the balanced diet. Adipocytes from HP diet-adapted rats had a significantly reduced response (~40%) to the lipolytic action of nonspecific (norepinephrine, epinephrine, isoproterenol) and specific (CL316,243, BRL37,344, dobutamine, clenbuterol) [beta]-adrenergic agonists. Adipocytes from HP rats also had a reduced lipolytic response to the intracellular agents, dibutyryl cAMP (44%), forskolin (46%), and isobutyl-methylxanthine (29%). The data suggest that the main mechanism responsible for the reduced basal and stimulated lipolysis in HP diet-adapted rats is an impairment in the intracellular process of lipolysis activation, with a deficient translocation of HSL to the fat droplet. J. Nutr. 134: 2919-2923, 2004. KEY WORDS: * hormone sensitive lipase (HSL) * HSL content and activity * HSL translocation * [beta]-adrenergic agonists * intracellular lipolytic agents

It is appropriate to characterize the nutritional value of dietary proteins in humans through the specific study of dietary nitrogen metabolism during the postprandial period. However, the influence of the habitual protein intake on this variable has not been studied. We aimed to describe the influence of prior protein intake on the specific metabolic utilization of dietary nitrogen in humans. Healthy men and women were adapted for 7 d to two diets with a normal [NP, 1 g/(kg * d)] and high protein content [HP, 2 g/(kg * d)]. After each period, they were studied for an 8-h postmeal period after ingesting a single [sup.15]N-labeled mixed meal (0.41 g/kg protein) containing either milk (n = 12) or soy protein (n = 8). The HP diet reduced the peak of dietary N incorporation into free serum amino acids in the soy group but had no effect in the milk group. The incorporation of dietary N into plasma protein was higher after soy than after milk protein, but habitual protein level had no effect. The postprandial retention of milk protein was reduced by the HP diet compared with the NP diet by only 5% and that of soy protein was diminished by 13% (protein source: P < 0.0001, protein level: P < 0.0001, interaction: P < 0.001). In conclusion, the efficiency of the meal N postprandial retention was lower after HP adaptation, but this decrease was much more pronounced for soy than for milk protein, indicating that increasing the habitual protein intake accentuates differences in metabolic utilization among dietary proteins. KEY WORDS: * dietary protein * high protein diets * protein quality * nitrogen retention * humans

Claims about the merits or risks of carbohydrate (CHO) vs. protein for weight loss diets are extensive, yet the ideal ratio of dietary carbohydrate to protein for adult health and weight management remains unknown. This study examined the efficacy of two weight loss diets with modified CHO/protein ratios to change body composition and blood lipids in adult women. Women (n = 24; 45 to 56 y old) with body mass indices >26 kg/[m.sup.2] were assigned to either a CHO Group consuming a diet with a CHO/protein ratio of 3.5 (68 g protein/d) or a Protein Group with a ratio of 1.4 (125 g protein/d). Diets were isoenergetic, providing 7100 k J/d, and similar amounts of fat (~50 g/d). After consuming the diets for 10 wk, the CHO Group lost 6.96 [+ or -] 1.36 kg body weight and the Protein Group lost 7.53 [+ or -] 1.44 kg. Weight loss in the Protein Group was partitioned to a significantly higher loss of fat/lean (6.3 [+ or -] 1.2 g/g) compared with the CHO Group (3.8 [+ or -] 0.9). Both groups had significant reductions in serum cholesterol (~10%), whereas the Protein Group also had significant reductions in triacylglycerols (TAG) (21%) and the ratio of TAG/HDL cholesterol (23%). Women in the CHO Group had higher insulin responses to meals and postprandial hypoglycemia, whereas women in the Protein Group reported greater satiety. This study demonstrates that increasing the proportion of protein to carbohydrate in the diet of adult women has positive effects on body composition, blood lipids, glucose homeostasis and satiety during weight loss. KEY WORDS: * obesity * body fat * blood lipids * insulin

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

The objective of this study was to determine consumer reaction to boar (BO), barrow (BA), and gilt (G) meat from pigs grown and finished on high- (HI) and low- (LO) protein diets and slaughtered at 100 and 110 kg BW. Within each of two trials, 54 BO, BA, and G were allotted within sexes to HI or LO protein sequences for growing and finishing: 19 and 17% (BOHI), 18 and 16% (BOLO), 17 and 15% (GHI), 16 and 14% (GLO), 15 and 13% (BAHI), and 14 and 12% (BALO). Backfat skatole and salivary gland 16-androstene concentrations were measured from samples taken at slaughter. Longissimus (LM) and semitendinosus (ST) chops from 24 pigs (with equal representation across diet and sex groups) were evaluated by trained panelists for tenderness, juiciness, and off-flavor. Consumer panelists evaluated acceptability of LM chops. In the 100-kg trial, HI diets improved (P < .05) carcass leanness in BO and BA but not in G. In both trials, BO were leaner (P < .05) than G, and both were leaner (P < .05) than BA. Skatole and 16-androstene concentrations were similar (P > .05) among sexes in both trials. In the 100-kg trial, trained panelists found BOLO chops had more (P < .05) off-flavor. In the 110-kg trial, all BO had more off-flavor (P < .05) than BAHI, BALO, and GHI but were similar (P > .05) to GLO. In both trials, BA chops were more tender (P < .05) than G and BO chops and LM chops had less off-flavor (P < .05) than ST chops. In the 110-kg trial, skatole was correlated (r = .28, P < .001) to off-flavor. A relationship may exist among diet, skatole deposition, and off-flavor. Untrained consumers reported all chops were equally acceptable (P > .05). Key Words: Boar Taint, Skatole, Sensory Evaluation, Protein, Pigs

The effects of diabetes on dietary amino acid retention were analyzed in normal and diabetic subjects after a high protein diet followed by a mixed test meal (MTM) and after a protein-deficient diet. Postprandial urea production was reduced in normal subjects and insulin-dependent diabetes mellitus patients under extensive insulin treatment after a five day regimen of protein-deficient diet preceded by MTM. Furthermore, diabetic subjects exhibited higher rates of protein catabolism due to energy deficiency and suboptimal insulin provision.