Epidermal tyrosine catabolism is crucial for metabolic homeostasis and survival against high-protein diets in Drosophila.

The insect epidermis forms the exoskeleton and determines the body size of an organism. How the epidermis acts as a metabolic regulator to adapt to changes in dietary protein availability remains elusive. Here, we show that the Drosophila epidermis regulates tyrosine (Tyr) catabolism in response to dietary protein levels, thereby promoting metabolic homeostasis. The gene expression profile of the Drosophila larval body wall reveals that enzymes involved in the Tyr degradation pathway, including 4-hydroxyphenylpyruvate dioxygenase (Hpd), are upregulated by increased protein intake. Hpd is specifically expressed in the epidermis and is dynamically regulated by the internal Tyr levels. Whereas basal Hpd expression is maintained by insulin/IGF-1 signalling, Hpd induction on high-protein diet requires activation of the AMP-activated protein kinase (AMPK)-forkhead box O subfamily (FoxO) axis. Impairment of the FoxO-mediated Hpd induction in the epidermis leads to aberrant increases in internal Tyr and its metabolites, disrupting larval development on high-protein diets. Taken together, our findings uncover a crucial role of the epidermis as a metabolic regulator in coping with an unfavourable dietary environment.

Dietary cysteine and methionine promote peroxisome elevation and fat loss by induction of CG33474 expression in Drosophila adipose tissue.

The high-protein diet (HPD) has emerged as a potent dietary approach to curb obesity. Peroxisome, a highly malleable organelle, adapts to nutritional changes to maintain homeostasis by remodeling its structure, composition, and quantity. However, the impact of HPD on peroxisomes and the underlying mechanism remains elusive. Using Drosophila melanogaster as a model system, we discovered that HPD specifically increases peroxisome levels within the adipose tissues. This HPD-induced peroxisome elevation is attributed to cysteine and methionine by triggering the expression of CG33474, a fly homolog of mammalian PEX11G. Both the overexpression of Drosophila CG33474 and human PEX11G result in increased peroxisome size. In addition, cysteine and methionine diets both reduce lipid contents, a process that depends on the presence of CG33474. Furthermore, CG33474 stimulates the breakdown of neutral lipids in a cell-autonomous manner. Moreover, the expression of CG33474 triggered by cysteine and methionine requires TOR signaling. Finally, we found that CG33474 promotes inter-organelle contacts between peroxisomes and lipid droplets (LDs), which might be a potential mechanism for CG33474-induced fat loss. In summary, our findings demonstrate that CG33474/PEX11G may serve as an essential molecular bridge linking HPD to peroxisome dynamics and lipid metabolism.

FoxO transcription factors regulate urea cycle through Ass1.

When amino acids are plentiful in the diet, the liver upregulates most enzymes responsible for amino acid degradation. In particular, the activity of urea cycle enzymes increases in response to high-protein diets to facilitate the excretion of excess nitrogen. KLF15 has been established as a critical regulator of amino acid catabolism including ureagenesis and we have recently identified FoxO transcription factors as an important upstream regulator of KLF15 in the liver. Therefore, we explored the role of FoxOs in amino acid metabolism under high-protein diet. Our findings revealed that the concentrations of two urea cycle-related amino acids, arginine and ornithine, were significantly altered by FoxOs knockdown. Additionally, using KLF15 knockout mice and an in vivo Ad-luc analytical system, we confirmed that FoxOs directly regulate hepatic Ass1 expression under high-protein intake independently from KLF15. Moreover, ChIP analysis showed that the high-protein diet increased FoxOs DNA binding without altering the nuclear protein amount. Therefore, FoxOs play a direct role in regulating ureagenesis via a KLF15-independent pathway in response to high-protein intake.

Quantifying Protein Shape to Elucidate Its Influence on Solution Viscosity in High-Concentration Electrolyte Solutions.

Therapeutic proteins with a high concentration and low viscosity are highly desirable for subcutaneous and certain local injections. The shape of a protein is known to influence solution viscosity; however, the precise quantification of protein shape and its relative impact compared to other factors like charge-charge interactions remains unclear. In this study, we utilized seven model proteins of varying shapes and experimentally determined their shape factors (v) based on Einstein's viscosity theory, which correlate strongly with the ratios of the proteins' surface area to the 2/3 power of their respective volumes, based on protein crystal structures resolved experimentally or predicted by AlphaFold. This finding confirms the feasibility of computationally estimating protein shape factors from amino acid sequences alone. Furthermore, our results demonstrated that, in high-concentration electrolyte solutions, a more spherical protein shape increases the protein's critical concentration (C*), the transition concentration beyond which protein viscosity increases exponentially relative to concentration increases. In summary, our work elucidates protein shape as a key determinant of solution viscosity through quantitative analysis and comparison with other contributing factors. This provides insights into molecular engineering strategies to optimize the molecular design of therapeutic proteins, thus optimizing their viscosity.

Long-term personalized high-protein, high-fat diet in pediatric patients with glycogen storage disease type IIIa: Evaluation of myopathy, metabolic control, physical activity, growth, and dietary compliance.

Dietary lipid manipulation has recently been proposed for managing glycogen storage disease (GSD) type IIIa. This study aimed to evaluate the myopathic, cardiac, and metabolic status, physical activity, growth, and dietary compliance of a personalized diet high in protein and fat for 24 months. Of 31 patients with type IIIa GSD, 12 met the inclusion criteria. Of these, 10 patients (mean age 11.2 ± 7.4 years) completed the study. Patients were prescribed a personalized high-protein, high-fat diet, comprising 3.0-3.5 g/kg/day of protein and 3.0-4.5 g/kg/day of fat, constituting 18.5%-28% and 70.5%-75.7% of daily energy, respectively. Dietary compliance was ensured and assessed via the regular administration of questionnaires. Our results revealed consistent and significant decreases of 22%, 54%, and 30% in the creatinine kinase, creatine kinase-myocardial band, and lactate dehydrogenase levels, respectively. Echocardiography revealed improvements in the Z-scores of the left ventricular mass and interventricular septum thickness. A significant increase in body muscle mass was observed, and a higher score was achieved using the Daily Activity Questionnaire. Growth monitoring revealed an arrest in the height-SDS at the 6th and 12th months, followed by subsequent improvement at the end of the second year. A gradual and persistent decline in the periods of hypo- and hyperglycemia has been reported. Biotinidase activity decreased, whereas hepatosteatosis increased and then decreased by the end of the study. Implementing a high-protein, high-fat diet and monitoring key parameters in patients with type IIIa GSD can lead to myopathic and cardiac improvements and increased physical activity.

High-fat and carbohydrate diet caused chronic kidney damage by disrupting kidney function, caspase-3, oxidative stress and inflammation.

The study aimed to compare the effects of a diet rich in fat, carbohydrates and protein on rat kidneys. The study was conducted on 40 Wistar albino rats bred at Inönü University Faculty of Medicine after the approval of the ethics committee. Rats were randomly divided into 4 groups: Control group, and the groups where the animals were fed with high carbohydrate, fat and protein rich feed. After the applications, the rat kidney tissues were removed by laparoscopy under anesthesia and blood samples were collected. 13 weeks long fat-rich and carbohydrate feed application had negative effects on oxidant-antioxidant balance, oxidative stress index, inflammation markers, kidney functions tests, histopathology and immunohistochemistry caspase-3 findings in rat kidney tissues, especially in the carbohydrate group when compared to the controls. Protein-rich feed, there were no significant difference in biochemical and histopathology compared to the control group. Fat and carbohydrate rich feed led to an increase in oxidative stress in rat kidney tissues. Oxidative stress led to nephrotoxicity, which in turn led to chronic kidney tissue damages. A more balanced and protein-rich diet instead of excessive sugar and fatty food intake could be suggested to prevent chronic kidney damage.

A comprehensive approach to lifestyle intervention based on a calorie-restricted diet ameliorates liver fat in overweight/obese patients with NAFLD: a multicenter randomized controlled trial in China.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a globally increasing health epidemic. Lifestyle intervention is recommended as the main therapy for NAFLD. However, the optimal approach is still unclear. This study aimed to evaluate the effects of a comprehensive approach of intensive lifestyle intervention (ILI) concerning enhanced control of calorie-restricted diet (CRD), exercise, and personalized nutrition counseling on liver steatosis and extrahepatic metabolic status in Chinese overweight and obese patients with NAFLD. METHODS: This study was a multicenter randomized controlled trial (RCT) conducted across seven hospitals in China. It involved 226 participants with a body mass index (BMI) above 25. These participants were randomly assigned to two groups: the ILI group, which followed a low carbohydrate, high protein CRD combined with exercise and intensive counseling from a dietitian, and a control group, which adhered to a balanced CRD along with exercise and standard counseling. The main measure of the study was the change in the fat attenuation parameter (FAP) from the start of the study to week 12, analyzed within the per-protocol set. Secondary measures included changes in BMI, liver stiffness measurement (LSM), and the improvement of various metabolic indexes. Additionally, predetermined subgroup analyses of the FAP were conducted based on variables like gender, age, BMI, ethnicity, hyperlipidemia, and hypertension. RESULTS: A total of 167 participants completed the whole study. Compared to the control group, ILI participants achieved a significant reduction in FAP (LS mean difference, 16.07 [95% CI: 8.90-23.25] dB/m) and BMI (LS mean difference, 1.46 [95% CI: 1.09-1.82] kg/m2) but not in LSM improvement (LS mean difference, 0.20 [95% CI: -0.19-0.59] kPa). The ILI also substantially improved other secondary outcomes (including ALT, AST, GGT, body fat mass, muscle mass and skeletal muscle mass, triglyceride, fasting blood glucose, fasting insulin, HbA1c, HOMA-IR, HOMA-ß, blood pressure, and homocysteine). Further subgroup analyses showed that ILI, rather than control intervention, led to more significant FAP reduction, especially in patients with concurrent hypertension (p < 0.001). CONCLUSION: In this RCT, a 12-week intensive lifestyle intervention program led to significant improvements in liver steatosis and other metabolic indicators in overweight and obese Chinese patients suffering from nonalcoholic fatty liver disease. Further research is required to confirm the long-term advantages and practicality of this approach. TRIAL REGISTRATION: This clinical trial was registered on ClinicalTrials.gov (registration number: NCT03972631) in June 2019.

Nutritional value and environmental aspects of high-protein ultra-processed foods on the German market.

OBJECTIVE: To compare nutritional value and aspects with environmental impact of high-protein (HP) and 'normal-protein' (NP) ultra-processed foods (UPF). DESIGN: 299 HP and 286 NP products were evaluated regarding aspects of nutritional value, energy density, Nutri-Score, number of additives as well as hyper-palatability and price. Environmental impact of HP UPF was addressed by analysing protein sources and the use of environmentally persistent non-nutritive artificial sweeteners. SETTING: Cross-sectional market analysis in German supermarkets and online shops. PARTICIPANTS: 299 HP and 286 NP UPF products. RESULTS: HP compared to NP UPF had a lower energy density, a lower content of sugar, total and saturated fat, whereas fibre and protein content (62·2 % animal protein) were higher (all P < 0·001). HP products therefore had a higher prevalence of Nutri-Score A (67·2 % v. 21·7 %) and a lower prevalence of Nutri-Score E (0·3 % v. 11·2 %) labelling (both P < 0·001). By contrast, salt content and the number of additives (environmentally persistent sweeteners, sugar alcohols, flavourings) were higher in HP compared to NP UPF (P < 0·001). When compared to HP products, twice as many NP were identified as hyper-palatable (82·5 % v. 40·5 %; P < 0·001). The price of HP was on average 132 % higher compared to NP UPF (P < 0·001). CONCLUSIONS: While major adverse aspects of UPF regarding nutritional profile and hyper-palatability are less pronounced in HP compared to NP products, higher salt content, increased number of additives and negative environmental effects from frequent use of animal protein and environmentally persistent sweeteners are major drawbacks of HP UPF.

High-protein diet scores, macronutrient substitution, and breast cancer risk: insights from substitution analysis.

BACKGROUND: Evidence from recent studies suggested that variation in the quantity and quality of macronutrients in the diet may potentially play a role in predicting the risk of breast cancer (BC). In the current study, we aimed to assess the association of different high-protein diet scores and replacing fats and carbohydrate (CHO) with protein in the diet with the BC risk among Iranian women. METHODS: The current hospital-based case-control study was conducted on 401 participants, aged ≥ 30 years old, including 134 women in the case group who had been diagnosed with histologically confirmed BC and 267 women in the control group. Dietary intake data was collected using a validated food frequency questionnaire, and high protein diet scores were determined. Logistic regression models were used to determine the odds ratios (OR) and 95% confidence interval (CI) of BC across tertiles of high protein diet scores. Also, we assessed how substituting protein with other macronutrients affected BC odds while adjusting for the various confounding variables. RESULTS: Participants' mean ± SD of age and body mass index were 47.9 ± 10.3 years and 29.4 ± 5.5 kg/m2, respectively. The scores of high-protein-low-CHO and fat diet, high-protein and CHO-low-fat diet, and high-protein and fat-low-CHO diet in participants were 16.5 ± 3.8, 16.5 ± 6.7, and 16.4 ± 5.9, respectively. In the multivariable model, individuals in the highest tertile of high-protein-low-CHO and fat diet score (OR:0.71;95%CI:0.56-0.90) and high-protein and CHO-low-fat diet (OR:0.76;95%CI:0.60-0.97) had lower odds of BC compared to those in the lowest tertile (P < 0.05). However, no significant association was found between high-protein and fat-low-CHO diet and BC risk. Our results showed that replacing fat by protein (ORdifferences:-0.40;95%CI:-0.73,-0.07) and also replacing refined-CHO by plant protein (ORdifferences:-0.66;95%CI:-1.26,-0.07) in the diet are associated inversely with risk of BC(P < 0.05). CONCLUSIONS: The results of our study suggested that higher adherence to a high-protein-low-CHO and fat diet, characterized by a higher intake of plant proteins and a lower intake of refined grains and saturated fat can play a protective role against the odds of BC.

High-Protein Mulberry Leaves Improve Glucose and Lipid Metabolism via Activation of the PI3K/Akt/PPARα/CPT-1 Pathway.

High-Protein Mulberry is a novel strain of mulberry. High-Protein Mulberry leaves (HPM) were the subject of this study, which aimed to investigate its efficacy and underlying mechanisms in modulating glucose and lipid metabolism. A six-week intervention using db/db mice was carried out to assess the effects of HPM on serum lipid levels, liver function, and insulin (INS) levels. qRT-PCR and Western Blotting were employed to measure key RNA and protein expressions in the PI3K/Akt and PPARα/CPT-1 pathways. UHPLC-MS and the Kjeldahl method were utilized to analyze the component content and total protein. Additionally, network pharmacology was employed to predict regulatory mechanism differences between HPM and Traditional Mulberry leaves. The results of the study revealed significant improvements in fasting blood glucose, glucose tolerance, and insulin resistance in mice treated with HPM. HPM notably reduced serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and INS, while increasing high-density lipoprotein cholesterol (HDL-C) levels. The treatment also effectively mitigated liver fatty lesions, inflammatory infiltration, and islet atrophy. HPM activation of the PI3K/Akt/PPARα/CPT-1 pathway suggested its pivotal role in the regulation of glucose and lipid metabolism. With its rich composition and pharmacodynamic material basis, HPM displayed a greater number of targets associated with glucose and lipid metabolism pathways, underscoring the need for further research into its potential therapeutic applications.

Efficacy of a High-Protein Diet to Lower Glycemic Levels in Type 2 Diabetes Mellitus: A Systematic Review.

Diabetes is a metabolic disease with a high worldwide prevalence and an important factor in mortality and disability in the population. Complications can be reduced or prevented with lifestyle changes in physical activity, dietary habits, and smoking cessation. High-protein diets (HPDs, >30% or >1.0 g/Kg/day) decrease hyperglycemia in part due to their content of branched-chain amino acids (BCAAs), mainly leucine. Leucine (and other BCAAs) improve glucose metabolism by directly signaling in the medio-basal hypothalamus (MBH), increasing liver insulin sensitivity. To determine the effectiveness of an HPD to lower hyperglycemia, we analyzed the results of published clinical studies focusing on the levels of fasting plasma glucose and/or glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM). We carried out a systematic search for clinical studies using HPDs. We searched five databases (Scopus, Web of Science, PubMed, Epistemonikos, and Cochrane), collecting 179 articles and finally selecting 8 articles to analyze their results. In conclusion, HPDs are an effective alternative to reduce hyperglycemia in patients with T2DM, especially so-called Paleolithic diets, due to their higher-quality protein from animal and vegetal sources and their exclusion of grains, dairy products, salt, refined fats, and added sugars.

Gluten-free lentil cakes with optimal technological and nutritional characteristics.

BACKGROUND: The celiac population usually struggle finding nutritive gluten-free (GF) baked goods. GF foods can be improved using legume flours. Eleven GF cake formulations were elaborated according to different percentages of lentil flour (LF), corn flour (CF) and rice flour (RF) using a simplex lattice design. Water holding capacity and particle size of flours were evaluated. Moisture, aw, pH, specific volume, texture profile, relaxation, color and alveolar characteristics were determined for crumbs of all formulations. An optimization process was used to enhance the technological and nutritional attributes, selecting the three best formulations containing LF: 46% LF + 54% RF (CLF+RF); 49% LF + 51% CF (CLF+CF); and 100% LF (CLF), evaluated in their proximal composition and sensory characteristics. Linear and quadratic models for predicting the behavior of GF lentil cakes were obtained. RESULTS: LF and CF could favor water incorporation and show more resistance to enzymatic digestion than RF. Formulations with LF showed an improvement in specific volume and alveolar parameters, while use of RF led to better cohesiveness, elasticity and resilience but with a deterioration in chewiness and firmness. CLF can be labeled as high in protein and fiber and presented the lowest amounts of lipids, carbohydrates and energy content. Consumer preference leaned towards CLF+RF. CONCLUSION: It was possible to elaborate GF cakes using LF, obtaining nutritive products that can be offered to people intolerant to gluten ingestion. © 2024 Society of Chemical Industry.

Effects of hyperprotein diet on anxiety, haemodynamics and morphofunctional aspects of the heart of Wistar rats.

NEW FINDINGS: What is the central question of this study? The consumption of a high-protein diet has been associated with an anxiogenic factor that can influence anxiety and possible cardiovascular changes: does the consumption of a high-protein diet interfere with anxiety, haemodynamics and morphofunctional aspects of the heart of Wistar rats? What is the main finding and its importance? Our study showed that the high-protein diet did not interfere with anxiety and haemodynamics. The animals in the hyperproteic group showed positive heart adaptations characterized by less work and lower heart rate without impairing ejection fraction and systemic blood pressure. ABSTRACT: Anxiety is a mechanism preparatory to a response in situations of threat and danger, involving behavioural, affective and physiological factors. Protein-based foods have a high concentration of amino acids which perform multiple functions, including in the biosynthesis of excitatory transmitters for the central nervous system. In recent years, adherence to high-protein diets has been gaining ground in society, on the basis that it brings benefits to the musculoskeletal system and cardiovascular health. The aim of the present study was to investigate the effect of a high-protein diet in a state of anxiety and to investigate morphofunctional cardiovascular effects of a high-protein diet in Wistar rats. The experiment lasted 8 weeks and two groups of male rats were submitted to either a normoproteic or a hyperproteic diet. Anxiety was assessed using the plus maze test and cardiovascular morphofunctional aspects using transthoracic echocardiography and invasive measurements of femoral blood pressure. There was no statistically significant difference in the anxiety test, but the hyperproteic group was more agitated, with greater displacement during the test. Changes were found in systolic and end-diastolic volume, left ventricular diameter in systole and heart rate, which were significantly lower in the hyperproteic group, and there was an increase in the thickness of the interventricular septum in diastole. The results showed no influence of the higher protein diet on the animals' anxiety, body weight and haemodynamics.

Role of liver AMPK and GCN2 kinases in the control of postprandial protein metabolism in response to mid-term high or low protein intake in mice.

PURPOSE: Protein synthesis and proteolysis are known to be controlled through mammalian target of rapamycin, AMP-activated kinase (AMPK) and general control non-derepressible 2 (GCN2) pathways, depending on the nutritional condition. This study aimed at investigating the contribution of liver AMPK and GCN2 on the adaptation to high variations in protein intake. METHODS: To evaluate the answer of protein pathways to high- or low-protein diet, male wild-type mice and genetically modified mice from C57BL/6 background with liver-specific AMPK- or GCN2-knockout were fed from day 25 diets differing in their protein level as energy: LP (5%), NP (14%) and HP (54%). Two hours after a 1 g test meal, protein synthesis rate was measured after a 13C valine flooding dose. The gene expression of key enzymes involved in proteolysis and GNC2 signaling pathway were quantified. RESULTS: The HP diet but not the LP diet was associated with a decrease in fractional synthesis rate by 29% in the liver compared to NP diet. The expression of mRNA encoding ubiquitin and Cathepsin D was not sensitive to the protein content. The deletion of AMPK or GCN2 in the liver did not affect nor protein synthesis rates and neither proteolysis markers in the liver or in the muscle, whatever the protein intake. In the postprandial state, protein level alters protein synthesis in the liver but not in the muscle. CONCLUSIONS: Taken together, these results suggest that liver AMPK and GCN2 are not involved in this adaptation to high- and low-protein diet observed in the postprandial period.

High-protein home parenteral nutrition in malnourished oncology patients: a systematic literature review.

INTRODUCTION: Up to 83% of oncology patients are affected by cancer-related malnutrition, depending on tumour location and patient age. Parenteral nutrition can be used to manage malnutrition, but there is no clear consensus as to the optimal protein dosage. The objective of this systematic literature review (SLR) was to identify studies on malnourished oncology patients receiving home parenteral nutrition (HPN) where protein or amino acid delivery was reported in g/kg bodyweight/day, and to compare outcomes between patients receiving low (< 1 g/kg bodyweight/day), standard (1-1.5 g/kg/day), and high-protein doses (> 1.5 g/kg/day). METHODS: Literature searches were performed on 5th October 2021 in Embase, MEDLINE, and five Cochrane Library and Centre for Reviews and Dissemination databases. Searches were complemented by hand-searching of conference proceedings, a clinical trial registry, and bibliographic reference lists of included studies and relevant SLRs/meta-analyses. RESULTS: Nineteen publications were included; sixteen investigated standard protein, two reported low protein, and one included both, but none assessed high-protein doses. Only one randomised controlled trial (RCT) was identified; all other studies were observational studies. The only study to compare two protein doses reported significantly greater weight gain in patients receiving 1.15 g/kg/day than those receiving 0.77 g/kg/day. CONCLUSION: At present, there is insufficient evidence to determine the optimal protein dosage for malnourished oncology patients receiving HPN. Data from non-HPN studies and critically ill patients indicate that high-protein interventions are associated with increased overall survival and quality of life; further studies are needed to establish whether the same applies in malnourished oncology patients.

The effect of a low-calorie, high-protein diet on psychometric variables in obese individuals: a Randomized Clinical Trial.

INTRODUCTION: The last decade has seen the increased prevalence of obesity as a public health challenge, particularly in low- and middle-income countries. At the same time, studies have shown that there is a two-way relationship between low-calorie diets and depression in obese individuals. This study was designed and implemented to investigate the effect of a low-calorie high-protein diet on psychometric variables in obese individuals. MATERIALS AND METHODS: The present study is a Randomized Clinical Trial. Individuals meeting the inclusion criteria were randomly assigned to either the intervention group (low-calorie diet with increased protein percentage) or the control group (standard protein percentage) using block stratification. Psychometric characteristics of the participants were evaluated using the DASS-21 questionnaire. RESULTS: There were no significant differences in enrollment between the two groups with respect to anthropometric variables, body composition, and physical activity (p-value > .05). Similarly, no significant differences were observed between the two groups in terms of psychological variables (depression, anxiety and stress) (p-value > .05). However, the intervention groups had significantly lower depression and anxiety scores 15 days into the intervention (p-value < .05). After 30 and 60 days of intervention, significant differences were observed between the 2 groups in terms of depression, stress, and anxiety (p-value < .05), indicating a relative improvement in psychometric variables in the intervention group (p-value < .05). CONCLUSION: The results of this study showed that low-calorie diets with a high-protein percentage can significantly improve psychometric variables in obese people.Trial registration: Iranian Registry of Clinical Trials identifier: IRCT20221101056371N1..

High Protein Whole Food Snack and Albumin Outcomes in Patients With Dialysis-Dependent Chronic Kidney Disease.

OBJECTIVE: Protein-energy wasting is common among patients on hemodialysis (HD). This study sought to define effects that a novel, post-HD, high-calorie, high-protein whole food snack had on patients' serum albumin (serum alb), serum phosphorus and equilibrated normalized protein catabolic rate (enPCR). METHODS: A 12-month (6 months intervention, 6 months pre/post data collection), single-center, unblinded study was conducted. Participants (n = 67) consumed, ad libitum, a whole food snack post-HD for 6 treatments each month. Upon analysis, regression models identified relationships between serum alb and whole food snack consumption across follow up. Predefined effect size anticipated was + 0.2 g/dL. Patients were stratified by high (≥4 g/dL) or low (<4 g/dL) mean serum alb during a 3-month baseline period. Paired t-tests compared mean per patient difference in serum alb, enPCR and serum phosphorus from baseline to each month of follow up, stratified by high (≥640 g) or low (<640 g) consumption of the whole food snack (a priori caloric estimation). RESULTS: Linear regression models showed positive associations between higher serum alb and enPCR with higher whole food snack consumption across follow up (all P < .05). Assessments from baseline to each follow-up month show some increases in serum alb, yet t test comparisons were not significant. No significant changes were seen in serum phosphorus levels during follow-up. CONCLUSION: Albeit the catabolic effects of HD are well-known, effective nutritional interventions are scarce. Results showed that providing a whole food snack post-HD to individuals with serum alb <4.0 g/dL may be beneficial but further studies are recommended.

Comparison of micellar casein isolate and nonfat dry milk for use in the production of high-protein cultured milk products.

High protein levels in yogurt, as well as the presence of denatured whey proteins in the milk, lead to the development of firm gels that can make it difficult to formulate a fluid beverage. We wanted to prepare high-protein yogurts and explore the effects of using micellar casein isolate (MCI), which was significantly depleted in whey protein by microfiltration. Little is known about the use of whey protein-depleted milk protein powders for high-protein yogurt products. Microfiltration also depletes soluble ions, in addition to whey proteins, and so alterations to the ionic strength of rehydrated MCI dispersions were also explored, to understand their effects on a high-protein yogurt gel system. Yogurts were prepared at 8% protein (wt/wt) from MCI or nonfat dry milk (NDM). The NDM was dispersed in water, and MCI powders were dispersed in water (with either low levels of added lactose to allow fermentation to achieve the target pH, or a high level to match the lactose content of the NDM sample) or in ultrafiltered (UF) milk permeate to align its ionic strength with that of the NDM dispersion. Dispersions were then heated at 85°C for 30 min while stirring, cooled to 40°C in an ice bath, and fermented with yogurt cultures to a final pH of 4.3. The stiffness of set-style yogurt gels, as determined by the storage modulus, was lowest in whey protein-depleted milk (i.e., MCI) prepared with a high ionic strength (UF permeate). Confocal laser scanning microscopy and permeability measurements revealed no large differences in the gel microstructure of MCI samples prepared in various dispersants. Stirred yogurt made from MCI that was prepared with low ionic strength showed slow rates of elastic bond reformation after stirring, as well as slower increases in cluster particle size throughout the ambient storage period. Both the presence of denatured whey proteins and the ionic strength of milk dispersions significantly affected the properties of set and stirred-style yogurt gels. Results from this study showed that the ionic strength of the heated milk dispersion before fermentation had a large influence on the gelation pH and strength of acid milk gels, but only when prepared at high (8%) protein levels. Results also showed that depleting milk of whey proteins before fermentation led to the development of weak yogurt gels, which were slow to rebody and may be better suited for preparing cultured milk beverages where low viscosities are desirable.

High-protein diets and testosterone.

A recent meta-analysis found low-carbohydrate, high-protein diets (> 3.4 g/kg of bodyweight/day) (g/kg/day) decreased men's total testosterone (∼5.23 nmol/L) [Whittaker and Harris (2022) Low-carbohydrate diets and men's cortisol and testosterone: systematic review and meta-analysis. Nutrition and Health. DOI: 10.1177/02601060221083079]. This finding has generated substantial discussion, however, it has often lacked clarity and context, with the term 'high-protein' being used unqualified. Firstly, diets < 3.4 g/kg/day are not associated with a consistent decrease in testosterone. Secondly, the average protein intake is ∼1.3 g/kg/day, conventional 'high-protein' diets are ∼1.8-3 g/kg/day and the vast majority of athletes are < 3.4 g/kg/day; meaning very few individuals will ever surpass 3.4 g/kg/day. To avoid such confusion in the future, the following definitions are proposed: very high (> 3.4 g/kg/day), high (1.9-3.4 g/kg/day), moderate (1.25-1.9 g/kg/day) and low (<1.25 g/kg/day). Using these, very high-protein diets (> 3.4 g/kg/day) appear to decrease testosterone, however high- and moderate-protein diets (1.25-3.4 g/kg/day) do not.

Effects of a High-Protein Diet on Kidney Injury under Conditions of Non-CKD or CKD in Mice.

Considering the prevalence of obesity and global aging, the consumption of a high-protein diet (HPD) may be advantageous. However, an HPD aggravates kidney dysfunction in patients with chronic kidney disease (CKD). Moreover, the effects of an HPD on kidney function in healthy individuals are controversial. In this study, we employed a remnant kidney mouse model as a CKD model and aimed to evaluate the effects of an HPD on kidney injury under conditions of non-CKD and CKD. Mice were divided into four groups: a sham surgery (sham) + normal diet (ND) group, a sham + HPD group, a 5/6 nephrectomy (Nx) + ND group and a 5/6 Nx + HPD group. Blood pressure, kidney function and kidney tissue injury were compared after 12 weeks of diet loading among the four groups. The 5/6 Nx groups displayed blood pressure elevation, kidney function decline, glomerular injury and tubular injury compared with the sham groups. Furthermore, an HPD exacerbated glomerular injury only in the 5/6 Nx group; however, an HPD did not cause kidney injury in the sham group. Clinical application of these results suggests that patients with CKD should follow a protein-restricted diet to prevent the exacerbation of kidney injury, while healthy individuals can maintain an HPD without worrying about the adverse effects.