Amino acid supplementation counteracts negative effects of low protein diets on tail biting in pigs more than extra environmental enrichment.

Low protein (LP) diets may increase the occurrence of damaging behaviours, like tail biting, in pigs. We investigated the effect of supplementing a LP diet with indispensable amino acids (IAA) or environmental enrichment on tail biting. Undocked pigs (n = 48 groups of 12) received either a normal protein diet (NP), a LP, LP with supplemented IAA (LP+), or LP diet with extra environmental enrichment (LP-E+) during the starter, grower, and finisher phase. Performance, activity, behaviour, and body damage were recorded. LP and LP-E+ had a lower feed intake, growth, and gain-to-feed ratio, and were more active than NP and LP+ pigs. LP-E+ pigs interacted most often with enrichment materials, followed by LP, LP+, and NP pigs. LP pigs showed more tail biting than all other groups during the starter phase and the finisher phase (tendency) compared to NP and LP+ pigs. Thus, LP-E+ only reduced tail biting in the starter phase, whereas LP+ tended to do so throughout. Tail damage was more severe in LP pigs than in NP and LP+, with LP-E+ in between. In conclusion, IAA supplementation was more effective than extra environmental enrichment in countering the negative effects of a low protein diet on tail biting in pigs.

A Low-Protein, Plant-Dominant Gluten-Free Diet for Immunoglobulin A Nephropathy and Focal Segmental Glomerulosclerosis.

Immunoglobulin A nephropathy is the most common glomerulonephritis syndrome in the world, yet there is currently no cure. While blood pressure control, renin-angiotensin-aldosterone system inhibition, and immunosuppression may slow disease progression, low-protein diets, defined as a daily dietary protein intake of 0.6 to 0.8 g/kg body weight, may also decrease immune complex deposition and disease severity, as evidenced in animal models. The link between secondary immunoglobulin A nephropathy and celiac disease has also led to the rise of gluten-free diets and zinc supplementation as potential lifestyle modifications to help manage common immunoglobulin A nephropathy symptoms such as proteinuria and hematuria. In addition, case reports and prospective studies suggest that patients with focal segmental glomerulosclerosis, which manifests as steroid-resistant nephrotic syndrome may also benefit from a gluten-free diet. We highlight the example of a gluten-free, plant-dominant low-protein diet (a different type of low-protein diet that addresses both protein quantity and quality) for patients with immunoglobulin A nephropathy or focal segmental glomerulosclerosis.

Effects of perinatal protein restriction on the oxidative balance in the hypothalamus of 60-day-old rats / Efeitos da restrição proteica perinatal sobre o balanço oxidativo no hipotálamo de ratos de 60 dias de idade

ABSTRACT Objective Evaluate the effects of maternal low-protein diet on the oxidative stress in the hypothalamus of 60-day-old rats. Methods Male Wistar rats were divided into two experimental groups according to the mother's diet during pregnancy and lactation; control group (NP:17% casein n=6) and a malnourished group (LP:8% casein n=6). At 60 days of life, the rats were sacrificed for the collection of the hypothalamus for further biochemical analysis. Results Our results showed an increase in oxidative stress in malnourished group, observed through an increase in carbonyl content (p=0.0357), a reduction in the activity of the glutathione-S-transferase enzyme (p=0.0257), and a reduction in the non-enzymatic antioxidant capacity evidenced by the decrease in the ratio reduced glutathione/oxidized glutathione (p=0.0406) and total thiol levels (p=0.0166). Conclusion A low-protein diet during pregnancy and lactation is closely associated with increased oxidative stress and reduced antioxidant capacity in the hypothalamus of sixty-day-old rats.

RESUMO Objetivo Avaliar os efeitos da restrição proteica materna sobre o estresse oxidativo no hipotálamo de ratos de 60 dias de idade. Métodos Ratos Wistar machos foram divididos em dois grupos experimentais de acordo com a dieta da mãe durante a gestação e lactação: grupo controle (NP: 17% caseína n=6) e grupo desnutrido (LP: 8% caseína n=6). Aos 60 dias de vida, os ratos foram sacrificados para coleta do hipotálamo para posterior análise bioquímica. Resultados Os resultados demonstraram aumento do estresse oxidativo no grupo desnutrido, observado através do aumento do conteúdo de cabonilas (p=0,0357) e redução da atividade da enzima glutationa-S-transferase (p=0,0257) e da capacidade antioxidante não enzimática, evidenciada pela queda da razão glutationa reduzida/glutationa oxidada (p=0,0406) e dos níveis de tióis totais (p=0,0166). Conclusão Uma dieta com baixo teor de proteínas durante a gestação e lactação está intimamente associada ao aumento do estresse oxidativo e à redução da capacidade antioxidante no hipotálamo de ratos de 60 dias de vida.

Ketoanalogues Supplemental Low Protein Diet Safely Decreases Short-Term Risk of Dialysis among CKD Stage 4 Patients.

Background: Rigid dietary controls and pill burden make a very-low protein (0.3−0.4 g/kg body weight per day), vegetarian diet supplemented with ketoanalogues of amino acids (sVLPD) hard to follow in the long-term. This study aimed to evaluate whether a ketoanalogue supplemental low-protein diet (sLPD) (0.6 g/kg body weight per day) could also reduce the risks of dialysis among CKD stage 4 patients. Methods: Patients aged >20 years with a diagnosis of stage 4 CKD who subsequently received ketosteril treatment, which is the most commonly used ketoanalogue of essential amino acids, between 2003 and 2018 were identified from the Chang Gung Research Database (CGRD). Then, these individuals were divided into two groups according to the continuation of ketosteril for more than three months or not. The primary outcome was ESKD requiring maintenance dialysis. Results: With one-year follow-up, the continuation group (n = 303) exhibited a significantly lower incidence of new-onset end-stage kidney disease (ESKD) requiring maintenance dialysis (6.8% vs. 10.4%, hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.41−0.94) in comparison to the discontinuation group (n = 238). Conclusions: This study demonstrated that initiating sLPDs since CKD stage 4 may additionally reduce the short-term risks of commencing dialysis without increasing CV events, infections, or mortality.

[Soy protein as part of a low-protein diet is a new direction in cardio- and nephroprotection in patients with 3B-4 stages of chronic kidney disease: prospective, randomized, controlled clinical study].

BACKGROUND: It has been established that the use of a low-protein diet (LPD) in combination with ketoanalogues (KA) of essential amino acids can contribute to cardio- and nephroprotection in chronic kidney disease (CKD). Moreover, it has been shown that replacing part of the animal protein with soy protein (SP) in the diet contributed to more pronounced nephro- and cardioprotection in CKD, however, the data, available in the literature, are mainly represented by experimental studies. AIM: To compare the effects of 2 types of diets on the main parameters of nephro- and cardioprotection in patients with CKD. MATERIALS AND METHODS: We have conducted a prospective, randomized, controlled clinical study which included 85 patients with 3B4 stages of CKD, compliant to LPD (0.6 g of protein/kg body weight) + KA (1 tablet/5 kg body weight). 43 patients (Group 1) received LPD with replacing animal protein with soy (60% soy protein + 40% another vegetable proteins) + KA, and 42 patients (control group, Group 2) received LPD (60% animal protein + 40% vegetable protein) + KA, within 12 months. RESULTS: The dietary substitution of animal protein with SP to a greater extent delayed the decrease in glomerular filtration rate (-5.9% vs -13.3%; p=0.048), the increase in left ventricular hypertrophy (+4.7% vs +12.3%; p=0.042), as well as the increase in central systolic blood pressure (+2.6% vs +13.0%; p=0.021), augmentation index (+7.6% vs +23.3%; p=0.010), slowed down the decrease in lean body mass in men (+0.9% vs -11.2%; p=0.017) and women (-1.8% vs -10.3%; p=0.024), increase in phosphorus (-10.3% vs +13.0%; p=0.029), cholesterol (-10.7% vs -3.4%; p=0.047) and urea (+6.3% vs +19.6%; p=0.035) serum levels. CONCLUSION: The use of LPD with substitution of animal protein with soy protein + KA provides a more pronounced effect on nephro- and cardioprotection as well as maintenance of nutritional status, than conventional LPD + KA in patients with 3B4 stages of CKD.

Nutrition and Obesity Impacts on Kidney Health.

Clinical Background and Epidemiology: Nutrition and obesity are both important and common clinical issues in chronic kidney disease (CKD). Protein-energy wasting predicts adverse clinical outcomes in CKD. Obesity is associated with poor health outcomes. Nutrition management, specifically a protein-restricted diet, has been shown to ameliorate glomerular injury and progressive CKD by reducing glomerular hyperfiltration and hypertension. A protein-restricted diet has favorable metabolic and hemodynamic effects and effects on CKD-mineral bone disease that may favorably impact patients' outcomes. On the other hand, obesity may adversely affect kidney function both directly by placing an increased metabolic demand on the kidneys and indirectly through various humoral mechanisms mediated via adiponectin, leptin, and resistin that lead to hyperinsulinemia, insulin resistance, abnormal lipid metabolism, activation of renin-angiotensin aldosterone system, chronic inflammation, and oxidative stress, and could result in the development of obesity-related glomerulopathy. It is therefore important to raise more awareness of the two clinical issues and promote a healthy lifestyle with proper nutrition and exercise in CKD management. Challenges and Solutions: There are global shortage of dietitians and challenges in accessibility and availability of renal dietitians in many emerging countries as well as lack of reimbursement of dietitians' consultations. Many patients may not have the opportunity to be monitored and reviewed by dieticians on a regular basis. In addition, there are practical challenges in enforcing patients' adherence to a protein-restricted diet. Patients and nephrologists from developed countries may\not appreciate the need to adopt a protein restricted diets as dialysis is readily available. Furthermore, keto-analogues or nutrition supplements are not reimbursed in many parts of the world. Increased government advocacy, prioritization of renal nutrition care, and more trained renal dietitians are required in many parts of the world. More government resource allocation is required to increase renal dietitians' manpower in nephrology centers so to enable multidisciplinary nutrition management in CKD and end-stage kidney disease. On the other hand, prevention and treatment of obesity require lifestyle modifications including calorie restriction and adequate exercise, and they need to be maintained lifelong. Such changes may be difficult in modern societies with the "fast food culture" and increasing prevalence of sedentary lifestyles. Changes in lifestyle may become even more difficult as long-term complications such as diabetes and cardiovascular disease set in, which may further limit patients' mobility. To tackle the obesity epidemic, we need a global action plan to prevent and control non-communicable diseases. We need a concerted population-wide intervention by national governments, health policy planners, and professional organizations to target obesity and CKD by promoting healthy lifestyle factors and healthy diets. Pharmacologic and surgical interventions such as bariatric surgery for obesity require further evaluation in CKD.

Severe protein deficiency induces hepatic expression and systemic level of FGF21 but inhibits its hypothalamic expression in growing rats.

To study, in young growing rats, the consequences of different levels of dietary protein deficiency on food intake, body weight, body composition, and energy balance and to assess the role of FGF21 in the adaptation to a low protein diet. Thirty-six weanling rats were fed diets containing 3%, 5%, 8%, 12%, 15% and 20% protein for three weeks. Body weight, food intake, energy expenditure and metabolic parameters were followed throughout this period. The very low-protein diets (3% and 5%) induced a large decrease in body weight gain and an increase in energy intake relative to body mass. No gain in fat mass was observed because energy expenditure increased in proportion to energy intake. As expected, Fgf21 expression in the liver and plasma FGF21 increased with low-protein diets, but Fgf21 expression in the hypothalamus decreased. Under low protein diets (3% and 5%), the increase in liver Fgf21 and the decrease of Fgf21 in the hypothalamus induced an increase in energy expenditure and the decrease in the satiety signal responsible for hyperphagia. Our results highlight that when dietary protein decreases below 8%, the liver detects the low protein diet and responds by activating synthesis and secretion of FGF21 in order to activate an endocrine signal that induces metabolic adaptation. The hypothalamus, in comparison, responds to protein deficiency when dietary protein decreases below 5%.

Protection of Residual Renal Function and Nutritional Treatment: First Step Strategy for Reduction of Uremic Toxins in End-Stage Kidney Disease Patients.

The retention of uremic toxins and their pathological effects occurs in the advanced phases of chronic kidney disease (CKD), mainly in stage 5, when the implementation of conventional thrice-weekly hemodialysis is the prevalent and life-saving treatment. However, the start of hemodialysis is associated with both an acceleration of the loss of residual kidney function (RKF) and the shift to an increased intake of proteins, which are precursors of uremic toxins. In this phase, hemodialysis treatment is the only way to remove toxins from the body, but it can be largely inefficient in the case of high molecular weight and/or protein-bound molecules. Instead, even very low levels of RKF are crucial for uremic toxins excretion, which in most cases are protein-derived waste products generated by the intestinal microbiota. Protection of RKF can be obtained even in patients with end-stage kidney disease (ESKD) by a gradual and soft shift to kidney replacement therapy (KRT), for example by combining a once-a-week hemodialysis program with a low or very low-protein diet on the extra-dialysis days. This approach could represent a tailored strategy aimed at limiting the retention of both inorganic and organic toxins. In this paper, we discuss the combination of upstream (i.e., reduced production) and downstream (i.e., increased removal) strategies to reduce the concentration of uremic toxins in patients with ESKD during the transition phase from pure conservative management to full hemodialysis treatment.

Paternal low protein diet and the supplementation of methyl-donors impact fetal growth and placental development in mice.

INTRODUCTION: Paternal low-protein diet can alter sperm methylation status, fetal growth and program offspring ill-health, however its impact on the placenta remains poorly defined. Here we examine the influence paternal low-protein diet has on fetal and placental development and the additional impact of supplementary methyl-donors on fetoplacental physiology. METHODS: Male C57BL/6J mice were fed a control normal protein diet (NPD; 18% protein), a low-protein diet (LPD; 9% protein) or LPD with methyl-donor supplementation (MD-LPD; choline chloride, betaine, methionine, folic acid, vitamin B12) for a minimum of 8 weeks. Males were mated with 8-11 week old female C57BL/6J mice and fetal and placental tissue collected on embryonic day 17.5. RESULTS: Paternal LPD was associated with increased fetal weights compared to NPD and MD-LPD with 22% fetuses being above the 90th centile for fetal weight. However, LPD and MD-LPD placental weights were reduced when compared to NPD. Placentas from LPD fathers demonstrated a reduced junctional zone area and reduced free-fatty acid content. MD-LPD placentas did not mirror these finding, demonstrating an increased chorion area, a reduction in junctional-specific glycogen staining and reduced placental Dnmt3bexpression, none of which were apparent in either NPD or LPD placentas. DISCUSSION: A sub-optimal paternal diet can influence fetal growth and placental development, and dietary methyl-donor supplementation alters placental morphology and gene expression differentially to that observed with LPD alone. Understanding how paternal diet and micro-nutrient supplementation influence placental development is crucial for determining connections between paternal well-being and future offspring health.

Maternal Protein Restriction in Rats Alters the Expression of Genes Involved in Mitochondrial Metabolism and Epitranscriptomics in Fetal Hypothalamus.

Fetal brain development is closely dependent on maternal nutrition and metabolic status. Maternal protein restriction (PR) is known to be associated with alterations in the structure and function of the hypothalamus, leading to impaired control of energy homeostasis and food intake. The objective of this study was to identify the cellular and molecular systems underlying these effects during fetal development. We combined a global transcriptomic analysis on the fetal hypothalamus from a rat model of maternal PR with in vitro neurosphere culture and cellular analyses. Several genes encoding proteins from the mitochondrial respiratory chain complexes were overexpressed in the PR group and mitochondrial metabolic activity in the fetal hypothalamus was altered. The level of the N6-methyladenosine epitranscriptomic mark was reduced in the PR fetuses, and the expression of several genes involved in the writing/erasing/reading of this mark was indeed altered, as well as genes encoding several RNA-binding proteins. Additionally, we observed a higher number of neuronal-committed progenitors at embryonic day 17 (E17) in the PR fetuses. Together, these data strongly suggest a metabolic adaptation to the amino acid shortage, combined with the post-transcriptional control of protein expression, which might reflect alterations in the control of the timing of neuronal progenitor differentiation.

Impact of reduced dietary crude protein levels and phytase enzyme supplementation on growth response, slurry characteristics, and gas emissions of growing pigs.

This experiment was carried out to evaluate the effect of reduced dietary crude protein (CP) levels supplemented with or without exogenous phytase on growing pigs. Six dietary treatments arranged in a 3 × 2 factorial arrangements of 3 CP levels (containing 14%, 16%, and 18% CP) supplemented each with or without 5,000 FTU/g phytase enzyme. Thirty growing pigs (average weight of 17.80 ± 0.10 kg) were allotted to the six dietary treatments in a complete randomized design. The final weight, daily weight gain, and feed conversion ratio (FCR) increased significantly with increasing CP levels. While, phytase supplementation improved (p = .044) FCR in pigs. Total solid and volatile solid content of the slurry were higher (p = .001) in pigs fed 14% and 16% CP diets supplemented with phytase when compared with other treatment groups. Concentration of methane gas emitted was lowest (p = .001) in the slurry of pigs fed 14% CP diet with or without phytase and those fed 16% CP diet with phytase supplementation. In conclusion, reduction in dietary CP levels resulted in reduced weight gain and poor FCR. While, reduced CP with phytase supplementation reduced concentration of methane gas emitted.

Dietary Cystine Ameliorates Defects in Spermatogenesis via Testosterone Production Induced by Protein Deficiency and Darkness in Rats.

Nutrition and light-dark cycle influence rat testicular development. With 9% casein diet (low protein diet) under normal 12 h-12 h lighting cycles (9P), juvenile rat testes undergo normal growth. On the other hand, a low protein diet with constant darkness (D9P) results in a growth arrest of rat testes. Supplementation of cystine to the low protein diet under constant darkness (D9PC) had a tendency to increase testes weight, suggesting an improvement in growth suppression. Whether the growth suppression of testes in D9P is associated with suppression of spermatogenesis has not yet been shown. We aimed to determine the effect of a low protein diet and constant darkness with or without dietary cystine in testes using a histological technique. In the histological assessment, D9P testes showed a decreased number of seminiferous tubules with elongated spermatids, indicating a functional testicular defect in this group. However, cystine supplementation resulted in enhanced spermatogenesis versus control animals (D9PC vs. D9P) implying the importance of cystine to testicular development in this condition. Furthermore, serum testosterone concentration was increased in D9PC suggesting contribution of testosterone to ameliorate spermatogenesis. From these results, we conclude that cystine supplementation to a low protein diet under constant darkness promoted an increase in testosterone which in turn benefitted spermatogenesis.

Maternal curcumin supplementation ameliorates placental function and fetal growth in mice with intrauterine growth retardation†.

Intrauterine growth retardation (IUGR) is a serious reproductive problem in humans. The objective of this study was to investigate the effects of daily maternal curcumin supplementation during pregnancy on placental function and fetal growth in a mouse model of IUGR fed the low-protein (LP) diet. Pregnant mice were divided into four groups: (1) normal protein (19% protein) diet (NP); (2) LP (8% protein) diet; (3) LP diet + 100 mg/kg curcumin (LPL); (4) LP diet +400 mg/kg curcumin (LPH). The results showed that the LP group decreased fetal weight, placental weight, placental efficiency, serum progesterone level, placental glutathione peroxidase activity activity, blood sinusoids area, and antioxidant gene expression of placenta. In addition, in comparison with the NP group, LP diet increased serum corticosterone level, placental malondialdehyde content, and apoptotic index. Daily curcumin administration decreased the placental apoptosis, while it increased placental efficiency, placental redox balance, blood sinusoids area, and antioxidant-related protein expression in fetal liver. The antioxidant gene expression of placenta and fetal liver was normalized to the NP level after curcumin administration. In conclusion, daily curcumin supplementation could improve maternal placental function and fetal growth in mice with IUGR.

Biomarkers of Micronutrients in Regular Follow-Up for Tyrosinemia Type 1 and Phenylketonuria Patients.

Phenylketonuria (PKU) is treated with dietary restrictions and sometimes tetrahydrobiopterin (BH4). PKU patients are at risk for developing micronutrient deficiencies, such as vitamin B12 and folic acid, likely due to their diet. Tyrosinemia type 1 (TT1) is similar to PKU in both pathogenesis and treatment. TT1 patients follow a similar diet, but nutritional deficiencies have not been investigated yet. In this retrospective study, biomarkers of micronutrients in TT1 and PKU patients were investigated and outcomes were correlated to dietary intake and anthropometric measurements from regular follow-up measurements from patients attending the outpatient clinic. Data was analyzed using Kruskal-Wallis, Fisher's exact and Spearman correlation tests. Furthermore, descriptive data were used. Overall, similar results for TT1 and PKU patients (with and without BH4) were observed. In all groups high vitamin B12 concentrations were seen rather than B12 deficiencies. Furthermore, all groups showed biochemical evidence of vitamin D deficiency. This study shows that micronutrients in TT1 and PKU patients are similar and often within the normal ranges and that vitamin D concentrations could be optimized.

Dietary Lectin exclusion: The next big food trend?

Until recently, with the exception of coeliac disease, gastroenterologists have not been particularly interested in the role of diet in the management of gastrointestinal disorders. However, patients have always felt that diet must play a part in their symptoms and, in the absence of any medical interest, have turned to alternative dietary practitioners for help, which can often have no evidence base. Fortunately, with the advent of the FODMAP diet (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) and the realisation that diet can have a profound effect on the microbiome, medical opinion is now changing. Nevertheless, research on the various diets that are now available is often completely lacking. Lectins are carbohydrate binding proteins which are widely distributed in nature and are found in a whole variety of commonly consumed foods. It seems likely that the exclusion of lectins from the diet could become the next "food fashion" for alternative practitioners to promote, especially as there is some evidence to suggest that certain lectins may be harmful to health. It is, therefore, the purpose of this viewpoint to try and stimulate research on the dietary effects of lectins, which is currently minimal, so that we can pre-empt a situation where we are unable to give patients or the public evidence based advice on this topic.

Prenatal Adversity Modulates the Quality of Maternal Care Via the Exposed Offspring.

Adversities in pregnancy, including poor diet and stress, are associated with increased risk of developing both metabolic and mental health disorders later in life, a phenomenon described as fetal programming or developmental origins of disease. Predominant hypotheses proposed to explain this relationship suggest that the adversity imposes direct changes to the developing fetus which are maintained after birth resulting in an increased susceptibility to ill health. However, during pregnancy the mother, the developing fetus, and the placenta are all exposed to the adversity. The same adversities linked to altered offspring outcome can also result in suboptimal maternal care, which is considered an independent adverse exposure for the offspring. Recent key experiments in mice reveal the potential of prenatal adversity to drive alterations in maternal care through abnormal maternal-pup interactions and via alterations in placental signaling. Together, these data highlight the critical importance of viewing fetal programming holistically paying attention to the intimate, bidirectional, and reiterative relationship between mothers and their offspring.

Perinatal free-choice of a high-calorie low-protein diet affects leptin signaling through IRS1 and AMPK dephosphorylation in the hypothalami of female rat offspring in adulthood.

AIM: We aimed to investigate whether a dysregulated maternal diet during gestation and lactation induces long-lasting changes in the hypothalamic control of feeding behavior in the offspring and whether this effect is sex specific. METHODS: The study included an analysis of appetite-regulating metabolic hormones and hypothalamic signaling in male and female offspring in adulthood after exposure to a free-choice high-calorie palatable low-protein (P) diet or standard chow (C) during (pre)gestation/lactation (maternal) and/or postweaning (offspring). RESULTS: Maternal exposure to the P diet resulted in decreased protein intake and body weight gain in dams and decreased body weight gain in offspring during lactation. The maternal P diet (PC) specifically increased feed efficacy and decreased body weight and cholesterol levels in the female offspring in adulthood, but no changes in adiposity or leptin levels were found. In contrast, P diet exposure after weaning (CP and PP) increased caloric intake, adiposity and circulating levels of leptin in the male and female offspring in adulthood. The hypothalami of the female offspring exposed to the maternal P diet (PC and PP) expressed high levels of the phospho-leptin receptor and low levels of SOCS3, phospho-IRS1 and phospho-AMPK, regardless of the postweaning diet. The hypothalami of the female rats in the PC group also showed increased levels of STAT3 and the orexigenic neuropeptide Agrp. CONCLUSIONS: Maternal exposure to a free-choice high-calorie low-protein diet induces a long-term feed efficacy associated with changes in leptin signaling through IRS-1 and AMPK dephosphorylation in the hypothalami of female offspring in adulthood.

Exploring Drivers of Liking of Low-Phenylalanine Products in Subjects with Phenyilketonuria Using Check-All-That-Apply Method.

The aim of the present study was to apply the Check-all-that-apply (CATA) method in an ambulatory context involving subjects with phenylketonuria (PKU) to obtain a sensory description and to find the drivers of liking of low-phenylalanine products (Glycomacropeptide vs. L-amino acids formulas). 86 subjects with PKU (age range: 8⁻55 years) evaluated 8 samples: 4 L-amino acid formulas and 4 Glycomacropeptide (GMP) formulas, flavored with neutral, chocolate, strawberry and tomato aromas. Participants were asked to indicate which sensory attributes characterized each formulations and to score the overall liking. Significant differences were found regarding liking scores (F = 65.29; p < 0.001). GMP samples flavored with chocolate and strawberry, described as sweets, with a mild and natural taste and odor, were the most appreciated. Overall, GMP formulas obtained higher liking scores compared to L-amino acid formulas. Tomato flavored samples, described as bitter, salty, with artificial color, with strong taste and odor, obtained the lowest scores. In conclusion, CATA questionnaire seems to be a suitable method also in ambulatory context since this approach suggested that different foods and beverages with GMP could be developed to improve dietary treatment compliance of subjects with PKU from school age onwards.

Long-Term Effects of Dietary Protein and Branched-Chain Amino Acids on Metabolism and Inflammation in Mice.

Aging is the main factor involved in the onset of degenerative diseases. Dietary protein restriction has been shown to increase the lifespan of rodents and improve metabolic phenotype. Branched-chain amino acids (BCAA) can act as nutrient signals that increase the lifespan of mice after prolonged supplementation. It remains unclear whether the combination of protein restriction and BCAA supplementation improves metabolic and immunological profiles during aging. Here, we investigated how dietary protein levels and BCAA supplementation impact metabolism and immune profile during a 12-month intervention in adult male C57BL/6J mice. We found that protein restriction improved insulin tolerance and increased hepatic fibroblast growth factor 21 mRNA, circulating interleukin (IL)-5 concentration, and thermogenic uncoupling protein 1 in subcutaneous white fat. Surprisingly, BCAA supplementation conditionally increased body weight, lean mass, and fat mass, and deteriorated insulin intolerance during protein restriction, but not during protein sufficiency. BCAA also induced pro-inflammatory gene expression in visceral adipose tissue under both normal and low protein conditions. These results suggest that dietary protein levels and BCAA supplementation coordinate a complex regulation of metabolism and tissue inflammation during prolonged feeding.

Low-Protein Diets Decrease Porcine Nitrogen Excretion but with Restrictive Effects on Amino Acid Utilization.

Reducing dietary crude protein (CP) intake effectively decreases nitrogen excretion in growing-finishing pigs but at the expense of poor growth when dietary CP content is reduced by ≥3%. In this study, we investigated the main disadvantages of low-protein diets supplemented with lysine, methionine, threonine, and tryptophan in pigs. First, changes in the nitrogen balance in response to differences in dietary CP content (18%, 15%, and 13.5%) were investigated in barrows (40 kg). Then, barrows (40 kg) surgically fitted with catheters in the mesenteric vein, portal vein, hepatic vein, and carotid artery were used to investigate changes in amino acid (AA) metabolism in the portal-drained viscera and liver in response to differences in dietary CP content. The results showed that low-protein diets reduced fecal and urinary nitrogen excretion ( P < 0.05) meanwhile resulted in significant decreases in nitrogen retention ( P < 0.05). Moreover, a reduction in the dietary CP content from 18% to 13.5% resulted in decreases in the net portal fluxes of NH3, glycine, and alanine as well as in the urea production in the liver ( P < 0.05), whereas their values as a percentage of nitrogen intake did not decline ( P > 0.05). The net portal fluxes of nonessential AA (NEAA) were reduced in the low-protein diet groups ( P < 0.05), while essential AA consumption in the liver increased ( P < 0.05). Thus, low-protein diets result in reductions in both nitrogen excretion and retention, and NEAA deficiency may be a major disadvantage of low-protein diets.