Dietary Protein Restriction Research Articles

Effect of the content of microbial proteins and the poly-β-hydroxybutyric acid in biofloc on the performance and health of Nile tilapia (Oreochromis niloticus) fingerlings fed on a protein-restricted diet

A 112-day experiment was conducted to investigate the influence of the content of microbial protein and poly-β-hydroxybutyrate (PHB) in biofloc on the growth, productive performance, and hemato-biochemical parameters of Nile tilapia (Oreochromis niloticus) fingerlings. The fish cultivated using the biofloc technology system (BFT) were reared at two stocking densities (40 and 80 fish m−3) and fed with a gradual protein-restriction diet (LPBFT). Two clear-water controls (CW) were used for the estimation of the density: High protein control (HP) and Low protein control (LP). The fish from HP (HPCW) were fed with commercial pellets containing 45% crude protein (CP) during the initial seven weeks and 35% CP during the final nine weeks. The fish from LP (LPCW) and LPBFT were fed with 35% CP during the initial seven weeks and 25% CP until harvest. The BFT microbial proteins were observed to compensate for the restriction of the dietary proteins. A 22.2% net reduction in the CP given to fish of 4.29 ± 0.25 g to 40.5 ± 5.4 g BW, and by 28.6% to fish of 40.5 ± 5.4 g to 182.6 ± 5.2 g BW did not negatively affect the survival, growth, and health of the fingerlings. Weight gain was significantly higher in LPBFT than LPCW at both stocking densities, and no significant differences were observed between the fish raised in CW and those fed on a high protein diet. The net yield of LPBFTs was increased by 27.9–29.5% compared to LP controls, while FCR was improved by 1.6% with the incorporation of BFT. When the concentration of heterotrophic bacteria (HB) reached 5.06 × 105 and 5.66 × 105 CFU mL−1, the maximum value of microbial proteins was 33.0 ± 5.9% for LPBFT-L and 32.5 ± 6.2% for LPBFT-H, respectively. The variables associated with the cumulative variance in the percentage of microbial protein were the concentration of HB (84.3%), followed by total organic carbon (8.6%) and NO3-N (4.6%). The PHB increased significantly with an increase in the concentration of HB (R = 80%) and showed a 75% correlation with the microbial protein content. During the final week of the culture, 1 mL of floc containing an average of 5.22 ± 1.78 × 105 CFU mL−1 produced 18.57 ± 2.22 nmol 100 g−1 DW of PBH. The blood biochemistry profile from LPBFT was similar to the high protein controls. Our data confirm the potential of the application of BFT during the early stages of tilapia growth, without affecting the survival, productive parameters, or the overall health of the organisms.

385 Feed efficiency of beef cattle in low-protein diets is driven by nitrogen use efficiency

Abstract Performance of cattle in rangeland systems is driven by the ability to efficiently use nutrients during periods of restricted availability. Thirty Bos indicus steers (398 ± 24 kg BW) were used to evaluate the relationship between feed efficiency (FE) and nitrogen use efficiency (NUE). The hypothesis was that FE would be related to NUE in protein restricted diets, but not in high-protein diets. Steers used in a completely randomized block design were classified by residual gain in low (LFE), medium (MFE) and highly feed efficient (HFE), after being fed for periods of 70 days with diets supplying either 70% (LP) or 100% (HP) of their rumen degradable protein requirements. After each 70-day period, animals were adapted to metabolism crates for two days, and NUE was measured for five days. About 10% of daily faecal and urine output of each animal was collected for N analysis. Results of N intake from LFE, MFE and HFE in the LP diet were 21.6, 21.2 and 22.2 g N/100 kg BW (P = 0.63), while the total N excretion was 20.3, 18.0 and 19.0 g N/100 kg BW (P = 0.45) for LFE, MFE and HFE, respectively. NUE values were 11.1, 26.9 and 28.0 g retained N/100 g of digested N (P = 0.04). In the HP diet, N intake was 31.6, 30.8 and 26.8 g/100 kg BW (P = 0.12) for LFE, MFE, and HFE, respectively. Total N excretion was 26.9, 28.8 and 27.5 g N/100 kg BW (P = 0.83), respectively. NUE in the HP diet was 21.0, 5.2 and -6.3 g retained N/100 g of digested N (P = 0.04). These results support the hypothesis that FE is dependent on NUE in protein restricted diets; whereas when evaluated in protein abundant diets, FE is not related to NUE.

Prospects for Cell-Directed Curative Therapy of Phenylketonuria (PKU).

Phenylketonuria (PKU) due to recessively inherited phenylalanine hydroxylase (PAH) deficiency is among the most common inborn errors of metabolism. Dietary therapy begun early in infancy prevents the major manifestations of the disease but shortcomings to treatment continue to exist including lifelong commitment to a complicated and unpalatable diet, poor adherence to diet in adolescence and adulthood, and consequently a range of unsatisfactory outcomes, including neuropsychiatric disorders, frequently develop. Novel treatments that do not strictly depend upon dietary protein restriction are actively sought. This review discusses the potential for and the limitations of permanently curative cell-directed treatment of PKU, including liver-directed gene therapy and gene editing, if initiated during early infancy. A fictional but realistic vignette of a family with a new baby girl recently diagnosed with PKU is presented. What is needed to permanently cure her?

Vitamin D Levels and Bone Mineral Density in Inborn Errors of Metabolism Requiring Specialised Diets.

To evaluate vitamin D levels and bone mineral density in patients with dietary limitations due to inborn errors of metabolism (IEM) and its correlation with diets. Retrospective study. Department of Pediatrics, Division of Pediatric Metabolism and Nutrition, Gazi University Hospital, Turkey, from March to Semtember 2016. The study is a retrospective review of 115 patients. Information about vitamin D status, bone mineral density (BMD) measurement and anthropometric parametres were collected. Patients were divided into two major groups, receiving protein-restricted diets (n=83) and lactose-restricted diets (n=32). Data of 110 healthy children were used as the control group. Mean vitamin D level of patients with special diets 28.1 ±14.9 ng/ml while mean level of healthy controls was 26.6 ±12.27 ng/ml. Levels of 26.8% (n=26/97) patients were found to be deficient and 34% (n=33/97) were found to be insufficient. No statistically significant differences were found between vitamin D levels and BMD of patients and healthy controls. BMD was not influenced by vitamin D levels. Low BMD may be encountered in IEM, independent of vitamin D levels and revision of diet for adequacy of essential nutrients; and follow-up for dietary compliance is inevitable.

Dietary protein insufficiency: an important consideration in fatty liver disease?

Dietary protein insufficiency has been linked to excessive TAG storage and non-alcoholic fatty liver disease (NAFLD) in developing countries. Hepatic TAG accumulation following a low-protein diet may be due to altered peroxisomal, mitochondrial and gut microbiota function. Hepatic peroxisomes and mitochondria normally mediate metabolism of nutrients to provide energy and substrates for lipogenesis. Peroxisome biogenesis and activities can be modulated by odd-chain fatty acids (OCFA) and SCFA that are derived from gut bacteria, for example, propionate and butyrate. Also produced during amino acid metabolism by peroxisomes and mitochondria, propionate and butyrate concentrations correlate inversely with risk of obesity, insulin resistance and NAFLD. In this horizon-scanning review, we have compiled available evidence on the effects of protein malnutrition on OCFA production, arising from loss in mitochondrial, peroxisomal and gut microbiota function, and its association with lipid accumulation in the liver. The methyl donor amino acid composition of dietary protein is an important contributor to liver function and lipid storage; the presence and abundance of dietary branched-chain amino acids can modulate the composition and metabolic activity of the gut microbiome and, on the other hand, can affect protective OCFA and SCFA production in the liver. In preclinical animal models fed with low-protein diets, specific amino acid supplementation can ameliorate fatty liver disease. The association between low dietary protein intake and fatty liver disease is underexplored and merits further investigation, particularly in vulnerable groups with dietary protein restriction in developing countries.

Urea Cycle Related Amino Acids Measured in Dried Bloodspots Enable Long-Term In Vivo Monitoring and Therapeutic Adjustment.

Background: Dried bloodspots are easy to collect and to transport to assess various metabolites, such as amino acids. Dried bloodspots are routinely used for diagnosis and monitoring of some inherited metabolic diseases. Methods: Measurement of amino acids from dried blood spots by liquid chromatography-tandem mass spectrometry. Results: We describe a novel rapid method to measure underivatised urea cycle related amino acids. Application of this method enabled accurate monitoring of these amino acids to assess the efficacy of therapies in argininosuccinate lyase deficient mice and monitoring of these metabolites in patients with urea cycle defects. Conclusion: Measuring urea cycle related amino acids in urea cycle defects from dried blood spots is a reliable tool in animal research and will be of benefit in the clinic, facilitating optimisation of protein-restricted diet and preventing amino acid deprivation.

NEURONAL FGF-21 SIGNALING: A SENSOR OF DIETARY PROTEIN

Our data demonstrates that dietary protein restriction increases energy expenditure and improves glucose homeostasis, and that this effect is largely mediated by the metabolic hormone fibroblast growth factor 21(FGF21). Considering that the central nervous system (CNS) is acknowledged as a major regulator of both energy and glucose homeostasis, we have extended our studies to identify the tissue site mediating these FGF21-dependent effects via dietary protein restriction. In this study, mice with dysfunctional FGF21-signaling in either the CNS or adipose tissue were fed a control or low protein (LP)-diet to assess changes in body weight and metabolic endpoints. Our data show that LP diet increased energy expenditure and reduced body weight in control littermates, but these effects were lost in mice bearing CNS-specific deletion of Klb. These data highlight a liver to brain FGF21-signal as the first known neuroendocrine mechanism to explain the coordinated metabolic changes induced by dietary protein restriction.

Dietary protein restriction throughout intrauterine and postnatal life results in potentially beneficial myocardial tissue remodeling in the adult mouse heart

Diet composition impacts metabolic and cardiovascular health with high caloric diets contributing to obesity related disorders. Dietary interventions such as caloric restriction exert beneficial effects in the cardiovascular system, but alteration of which specific nutrient is responsible is less clear. This study investigates the effects of a low protein diet (LPD) on morphology, tissue composition and function of the neonatal and adult mouse heart. Mice were subjected to LPD (8.8% protein) or standard protein diet (SPD, 22% protein) throughout intrauterine and postnatal life. At birth LPD female but not male offspring exhibit reduced body weight whereas heart weight was unchanged in both sexes. Cardiomyocyte cross sectional area was increased in newborn LPD females compared to SPD, whereas proliferation, cellular tissue composition and vascularization were unaffected. Adult female mice on LPD exhibit reduced body weight but normal heart weight compared to SPD controls. Echocardiography revealed normal left ventricular contractility in LPD animals. Histology showed reduced interstitial fibrosis, lower cardiomyocyte volume and elevated numbers of cardiomyocyte and non-myocyte nuclei per tissue area in adult LPD versus SPD myocardium. Furthermore, capillary density was increased in LPD hearts. In conclusion, pre- and postnatal dietary protein restriction in mice causes a potentially beneficial myocardial remodeling.

Resilience to acute kidney injury in offspring of maternal protein restriction.

Protein restriction (PR) during pregnancy induces morphofunctional alterations related to deficient nephrogenesis. We studied the renal functional and morphological significance of PR during pregnancy and/or lactation in adult male rat offspring and the repercussions on acute kidney injury (AKI) severity. Female rats were randomly assigned to the following groups: control diet during pregnancy and lactation (CC), control diet during pregnancy and PR diet during lactation (CR), PR during pregnancy and control diet during lactation (RC), and PR during pregnancy and lactation (RR). Three months after birth, at least 12 male offspring of each group randomly underwent either bilateral renal ischemia for 45 min [ischemia-reperfusion (IR)] or sham surgery. Thus, eight groups were studied 24 h after reperfusion: CC, CC + IR, CR, CR + IR, RC, RC + IR, RR, and RR + IR. Under basal conditions, the CR, RC, and RR groups exhibited a significant reduction in nephron number that was associated with a reduction in renal blood flow. Glomerular hyperfiltration was present as a compensatory mechanism to maintain normal renal function. mRNA levels of several vasoactive, antioxidant, and anti-inflammatory molecules were decreased. After IR, renal function was similarly reduced in all of the studied groups. Although all of the offspring from maternal PR exhibited renal injury, the magnitude was lower in the RC and RR groups, which were associated with faster renal blood flow recovery, differential vasoactive factors, and hypoxia-inducible factor-1α signaling. Our results show that the offspring from maternal PR are resilient to AKI induced by IR that was associated with reduced tubular injury and a differential hemodynamic response.

The Effects of Restricted Protein Diet Supplemented With Ketoanalogue on Renal Function, Blood Pressure, Nutritional Status, and Chronic Kidney Disease-Mineral and Bone Disorder in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis

To systemically review the meta-analysis exploring the effectiveness and safety of restricted protein diet supplemented with ketoanalogues (KAs) when compared with regular diet or low protein diet (LPD) without KAs in chronic kidney disease (CKD) patients. We conducted electronic searches in PubMed, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from January 1960 to May 2018 to identify randomized controlled clinical trials that explored the effects of restricted protein diet including vegetarian and mixed type of protein with KAs on kidney endpoints including the changes in estimated glomerular filtration rate (eGFR) and proteinuria, nutritional status, and CKD-mineral bone disorder. Seventeen RCTs with 1,459 participants were included in our meta-analysis. Restricted protein diet with KAs significantly preserved eGFR and reduced proteinuria, serum phosphate, parathyroid hormone (PTH) level, systolic blood pressure, diastolic blood pressure, and serum cholesterol. By subgroup analysis, very low protein diet (VLPD) with KAs was plausibly superior to LPD with KAs in slowing the decline in eGFR. Only VLPD with KAs significantly improved serum PTH, systolic blood pressure, and diastolic blood pressure while both regimens significantly decreased serum phosphate. Only LPD with KAs significantly raised serum albumin and serum calcium. Restricted protein diet supplemented with KAs could effectively improve kidney endpoints including preserving eGFR and diminishing proteinuria, blood pressure levels, and CKD-mineral bone disorder parameters without causing malnutrition. VLPD with KAs appears to provide more effectiveness in slowing the decline in eGFR, lowering blood pressure, reducing serum PTH, and less increasing serum calcium level.

Effects of low protein diets with amino acids supplementation on biochemical and faeces parameters in weaned piglets

Effects of low protein diets with amino acids supplementation on biochemical and faeces parameters in weaned piglets

Psychiatric and Cognitive Aspects of Phenylketonuria: The Limitations of Diet and Promise of New Treatments.

Phenylketonuria (PKU) is a recessive disorder of phenylalanine metabolism due to mutations in the gene for phenylalanine hydroxylase (PAH). Reduced PAH activity results in significant hyperphenylalaninemia, which leads to alterations in cerebral myelin and protein synthesis, as well as reduced levels of serotonin, dopamine, and noradrenaline in the brain. When untreated, brain development is grossly disrupted and significant intellectual impairment and behavioral disturbance occur. The advent of neonatal heel prick screening has allowed for diagnosis at birth, and the institution of a phenylalanine restricted diet. Dietary treatment, particularly when maintained across neurodevelopment and well into adulthood, has resulted in markedly improved outcomes at a cognitive and psychiatric level for individuals with PKU. However, few individuals can maintain full dietary control lifelong, and even with good control, an elevated risk remains of—in particular—mood, anxiety, and attentional disorders across the lifespan. Increasingly, dietary recommendations focus on maintaining continuous dietary treatment lifelong to optimize psychiatric and cognitive outcomes, although the effect of long-term protein restricted diets on brain function remains unknown. While psychiatric illness is very common in adult PKU populations, very little data exist to guide clinicians on optimal treatment. The advent of new treatments that do not require restrictive dietary management, such as the enzyme therapy Pegvaliase, holds the promise of allowing patients a relatively normal diet alongside optimized mental health and cognitive functioning.

Ketoacid Analogues Supplementation in Chronic Kidney Disease and Future Perspectives

Diet is a key component of care during chronic kidney disease (CKD). Nutritional interventions, and, specifically, a restricted protein diet has been under debate for decades. In order to reduce the risk of nutritional disorders in very-low protein diets (VLDP), supplementation by nitrogen-free ketoacid analogues (KAs) have been proposed. The aim of this review is to summarize the potential effects of this dietary therapy on renal function, uremic toxins levels, and nutritional and metabolic parameters and propose future directions. The purpose of this paper is also to select all experimental and randomized clinical studies (RCTs) that have compared VLDP + KA to normal diet or/and low protein diet (LPD). We reviewed the SCOPUS, WEB of SCIENCES, CENTRAL, and PUBMED databases from their inception to 1 January, 2019. Following duplicate removal and application of exclusion criteria, 23 RCTs and 12 experimental studies were included. LPD/VLPD + KAs appear nutritionally safe even if how muscle protein metabolism adapts to an LPD/VLPD + KAs is still largely unknown. VLPD + KAs seem to reduce uremic toxins production but the impact on intestinal microbiota remains unexplored. All studies observed a reduction of acidosis, phosphorus, and possibly sodium intake, while still providing adequate calcium intake. The impact of this diet on carbohydrate and bone parameters are only preliminary and need to be confirmed with RCTs. The Modification of Diet in Renal Disease study, the largest RCTs, failed to demonstrate a benefit in the primary outcome of the decline rate for the glomerular filtration rate. However, the design of this study was challenged and data were subsequently reanalyzed. However, when adherent patients were selected, with a rapid rate of progression and a long-term follow up, more recent meta-analysis and RCTs suggest that these diets can reduce the loss of the glomerular filtration rate in addition to the beneficial effects of renin-angiotensin-aldosterone system (RAAS) inhibitors. The current evidence suggests that KAs supplemented LPD diets should be included as part of the clinical recommendations for both the nutritional prevention and metabolic management of CKD. More research is needed to examine the effectiveness of KAs especially on uremic toxins. A reflection about the dose and composition of the KAs supplement, the cost-effective features, and their indication to reduce the frequency of dialysis needs to be completed.

P: 20 EID-UL-AZHA (Muslim's Festival of Sacrifice): Increased Frequency of Spontaneous Encephalopathy, Whether This Is Secondary to Consumption of High Protein Diet?

BACKGROUND: Protein restricted diet once was the cornerstone of the management of Hepatic encephalopathy, latter no evidence showed significant benefits. However sub group of cirrhotics are intolerant to dietary proteins, especially animal proteins. We compared precipitants of encephalopathy and effect of animal proteins consumption during the festival of EID-UL-AZHA METHODS: A retrospective comparative cross sectional study was conducted and analyzed hospital data of AIMS (Asian institute of medical sciences, Hyderabad, Pak.). Patients of cirrhosis were enrolled with clinically diagnosed hepatic encephalopathy in two groups. Group A was categories with patients admitted 15 days before EID-Ul-AZHA and Group B includes patients admitted on EID UL AZHA day and up to 15 days afterward. Patients with neurological deficit and suspected CNS infection were excluded. Patient of both groups were assessed to compare precipitant factors for encephalopathy that includes infections, electrolytes imbalance, upper GI bleed, constipation, AKI and drugs. Dietary history regarding normal protein diet and high protein diet (animal proteins > 1.5 g/kg/day) were also collected and compared in both groups. RESULTS: Out of 378 screened patients, 92 were presented with encephalopathy. All patients were Muslims with mean age 54.36 ± 11 yrs. Majority 66.3% were males and 33.7% were females. Precipitating factors were identified in 70.2% and 62.9% in group A and B respectively. Precipitating factor remain unidentified in 29.8% patients in group A and 37.1% in group B. 98.2% patients in group A were taking usual diet, only 1.8% consumed high (animal) protein diet, while in group B 51.4% patients were on usual diet and 48.6% consumed high (animal) protein diet. A comparable rise in frequency of spontaneous hepatic encephalopathy (without an identified precipitating factors) was observed in group B and 76.9% patients out of them were consuming high (animal) protein diet. CONCLUSIONS: A comparable rise in frequency spontaneous hepatic encephalopathy was observed during and/or post event of EID-UL-AZHA, majority had consumed high (animal) proteins. Consumption of meat (animal proteins) could be the possible contributing factor. Generally protein restriction is not recommended in cirrhotics but, still in sub group of cirrhotics who are protein intolerant, protein restriction or substitution of source of protein is inevitable. A further multicenter study is necessary at a larger scale to find out characteristic of patients who are intolerant to animal proteins.

Low‐Protein Diets with Fixed Carbohydrate Content Promote Hyperphagia and Sympathetically Mediated Increase in Energy Expenditure

Dietary protein restriction elicits hyperphagia and increases energy expenditure; however, less is known of whether these responses are a consequence of increasing carbohydrate content. The effects of protein-diluted diets with fixed carbohydrate content on energy balance, hormones, and key markers of protein sensing and thermogenesis in tissues are determined. Obesity-prone rats (n = 13-16 per group) are randomized to diets containing fixed carbohydrate (52% calories) and varying protein concentrations: 15% (control), 10% (mild protein restriction), 5% (moderate protein restriction) or 1% (severe protein restriction) protein calories, or protein-matched to 5% protein, for 21 days. Propranolol and ondansetron are administered to interrogate the roles of sympathetic and serotonergic systems, respectively, in diet-induced changes in energy expenditure. It is found that mild-to-moderate protein restriction promotes transient hyperphagia, whereas severe protein restriction induces hypophagia, with alterations in meal patterns. Protein restriction enhances energy expenditure that is partly attenuated by propranolol, but not ondansetron. Moderate to severe protein restriction decreases gains in body weight, lean and fat mass, decreased postprandial glucose and leptin, but increased fibroblast growth factor-21 concentrations. Protein-matching retains lean mass suggesting that intake of dietary protein, but not calories, is important for preserving lean mass. Notably, protein restriction increases the protein and/or transcript abundance of key amino acid sensing molecules in liver and intestine (PERK, eIF2α, ATF2, CHOP, 4EBP1, FGF21), and upregulated thermogenic markers (β2AR, Klotho, HADH, UCP-1) in brown adipose tissue. Low-protein diets promote hyperphagia and sympathetically mediated increase in energy expenditure, prevent gains in tissue reserves, and concurrently upregulate hepatic and intestinal amino acid sensing intermediaries and thermogenic markers in brown adipose tissue.

Expanding the genetic and phenotypic spectrum of branched-chain amino acid transferase 2 deficiency.

The first step in branched-chain amino acid (BCAA) catabolism is catalyzed by the two BCAA transferase isoenzymes, cytoplasmic branched-chain amino acid transferase (BCAT) 1, and mitochondrial BCAT2. Defects in the second step of BCAA catabolism cause maple syrup urine disease (MSUD), a condition which has been far more extensively investigated. Here, we studied the consequences of BCAT2 deficiency, an ultra-rare condition in humans. We present genetic, clinical, and functional data in five individuals from four different families with homozygous or compound heterozygous BCAT2 mutations which were all detected following abnormal biochemical profile results or familial mutation segregation studies. We demonstrate that BCAT2 deficiency has a recognizable biochemical profile with raised plasma BCAAs and, in contrast with MSUD, low-normal branched-chain keto acids (BCKAs) with undetectable l-allo-isoleucine. Interestingly, unlike in MSUD, none of the individuals with BCAT2 deficiency developed acute encephalopathy even with exceptionally high BCAA levels. We observed wide-ranging clinical phenotypes in individuals with BCAT2 deficiency. While one adult was apparently asymptomatic, three individuals had presented with developmental delay and autistic features. We show that the biochemical characteristics of BCAT2 deficiency may be amenable to protein-restricted diet and that early treatment may improve outcome in affected individuals. BCAT2 deficiency is an inborn error of BCAA catabolism. At present, it is unclear whether developmental delay and autism are parts of the variable phenotypic spectrum of this condition or coincidental. Further studies will be required to explore this.

Dietary protein restriction increases hepatic leptin receptor mRNA and plasma soluble leptin receptor in male rodents.

Leptin is an adipokine that regulates adipose tissue mass through membrane-anchored leptin receptor (Ob-R). Extracellular domain of Ob-R in plasma is called soluble leptin receptor (sOb-R), and is the main leptin-binding protein. Based on a previous DNA microarray analysis that showed induction of hepatic Ob-R mRNA in low-protein diet-fed mice, this study aimed to clarify the effect of dietary protein restriction on hepatic Ob-R mRNA and plasma sOb-R levels. First, the effect of protein restriction on hepatic Ob-R mRNA level was examined together with fasting and food restriction using male rats as common experimental model for nutritional research. Hepatic Ob-R mRNA level was increased by feeding low-protein diet for 7 d, although not significantly influenced by 12-h fasting and sixty percent restriction in food consumption. Then, effect of protein restriction on liver Ob-R and plasma sOb-R was investigated using male mice because specific sOb-R ELISA was more available for mice. Hepatic Ob-R mRNA level was also increased in protein restricted-mice although it did not increase in hypothalamus. Hepatic Ob-R protein was decreased, whereas plasma sOb-R was increased by protein restriction. Because the concentration of sOb-R increased without changing plasma leptin concentration, free leptin in plasma was significantly reduced. The direct effect of amino acid deprivation on Ob-R mRNA level was not observed in rat hepatoma cells H4IIE cultured in amino acid deprived medium. In conclusion, dietary protein restriction increased hepatic Ob-R mRNA, resulting in increased plasma sOb-R concentration, which in turn, reduces plasma free leptin level and may modulate leptin activity.

SAT-270 Results from the Chronic Kidney Disease Observational Database (CKDOD), India

Protein restricted diets (PRD) with or without ketoanalogue (KA) supplementation are an established treatment option in chronic kidney disease (CKD). Although their efficacy for slowing down decline of CKD has been shown in randomized controlled trials, implementation to clinical practice has not been investigated in detail in developing countries like India. The aim of this study was to examine utilization and effectiveness of PRD with or without KA supplementation in a real world setting. This observational study was a subcohort of eight Indian centers that participated in the CKDOD study (Shah et al. BMC Nephrol 2015;16:215). Data from routine care were documented between Jun 2010 and Dec 2017. Dietary patterns were analyzed in their relationship with progression of CKD assessed by eGFR decline over time using a mixed effects regression model. 1383 patients were enrolled. The most common dietary interventions were low protein diet (LPD, 0.6-0.8 g/kg) with or without KA supplementation (n = 412, 42%) and no PRD (n = 576, 58%). These patients (LPD or no PRD) were on average 56+/-14 years old (median 58 [47; 66]). 66% were male, 34% female. Most of them were in CKD stage 4 (339, 34%) and 5 (265, 27%). Their main underlying causes of CKD were diabetes mellitus (353, 36%) and hypertension (473, 48%). 54 LPD patients received KA supplementation at enrollment. Figure 1 shows the distribution of dietary protocols stratified by CKD stages (n per stage: 1:10, 2:22, 3A:85, 3B:225, 4:339, 5:265).eGFR changeView Large Image Figure ViewerDownload Hi-res image Download (PPT) The most common PRD in this selected cohort of Indian CKD patients was LPD. LPD was supplemented with KA for some but not all patients in later stages of CKD. Analysis of eGFR decline suggests that a potential beneficial effect of a KA-supplemented LPD might be applicable to routine care in India.

Abstract 1611: Caloric restriction potentiates the therapeutic benefit of androgen deprivation therapy and alters macrophage polarization when combined with PD1 inhibition in murine models of prostate cancer

Abstract Background: Data from epidemiological studies have linked dietary intake to the development of prostate cancer (CaP). We have previously shown that dietary protein restriction inhibits tumor growth by modulating PI3K/mTOR signaling in vivo. Additionally we have shown that dietary methionine restriction influence macrophage polarization which enhances the ability of the immune system to fight cancer. In this study we hypothesize that caloric restriction is capable of restricting tumor growth and potentiating the antitumor effect of androgen deprivation therapy (ADT) and PD1 inhibition. Methods: We utilized two prostate cancer models for our in vivo studies; castrate resistant LuCaP 23.1 AI prostate cancer model and MYC-Driven prostate cancer model in C57BL/6 mice. Caloric restriction was carried out by exposing mice to alternating fasting either as a single intervention (in LuCaP 23.1 model) or in combination with ADT (enzalutamide or surgical castration) or PD-1 inhibition in Myc-CaP model. Tumor sizes and weights were blindly assessed during the study and upon study termination respectively. IHC staining for both Ki-67 and mTOR phosphorylation was done to assess the impact of fasting+/- ADT on tumor growth and mTOR signaling. Macrophage polarization/distribution in tumors was assessed using immunofluorescence. Blood was collected at the end of the study for future comprehensive analysis of PBMCS. Results: In both models, alternating fasting was associated with significant decrease in tumor weight at the end of study in comparison to control group (*p<0.05). In Myc-CaP model, tumor weight was significantly decreased in combined fasting and enzalutamide/castration group in comparison to the control condition (**p<0.001) but was not significantly better than either intervention alone. Similarly, fasting potentiated the therapeutic benefit of PD-1 inhibition yet it was not significant. Combined fasting and ADT was associated with significant reduction in Ki-67 nuclear expression (****p<0.0001), however it was not significantly less than either agent alone. Combined fasting and ADT was associated with significant decrease in P-mTOR expression in comparison to control mice (****p<0.0001). Although we did not observe significant change in tumor weight with combined fasting and PD-1 inhibition; fasting potentiated the influence of PD-1 on macrophage polarization. M2 macrophages were significantly less in combined treatment compared to either single intervention alone (**p<0.01). Conclusions: Caloric restriction can hinder prostate cancer growth and potentiate the therapeutic effect of ADT. Our results provide basis for the translational use of dietary modification both as preventive measure as well as a therapeutic intervention that can improve the benefit of current standard treatments. Citation Format: May Elbanna, Justin Budka, Paige Dausinas, Remi Adelaiye-Ogala, Nur Damayanti, Ashley Orillion, Eri Banno, Luigi Fontana, Roberto Pili. Caloric restriction potentiates the therapeutic benefit of androgen deprivation therapy and alters macrophage polarization when combined with PD1 inhibition in murine models of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1611.

Ketogenic diet: a promising alternative nonpharmacology treatment for pediatric epilepsy

Epilepsy is a syndrome of brain dysfunction induced by the aberrant excitability of certain neurons. Despite advances in surgical technique and anti-epileptic drug in recent years, recurrent epileptic seizures remain intractable and lead to a serious morbidity in the world. The ketogenic diet (KD) is a nonpharmacologic treatment that has been used for refractory epilepsy since 1921. The KD is a high-fat, low-carbohydrate, and restricted protein diet, which is calculated and weighed for each individual patient. The goal of the KD treatment is to bring the brain into a state of ketosis to control seizures. Many studies have shown that ketogenic diet was very useful in controlling refractory epilepsy.