¿Cuál es el efecto de los impuestos a alimentos sólidos altos en nutrientes críticos sobre el consumo de ellos en la población general? / What is the effect of food taxes solids high in critical nutrients on the consumption of them in the general population?

INTRODUCCIÓN: La malnutrición por exceso, junto con las enfermedades crónicas no transmisibles, se han convertido en un importante problema de salud pública a nivel global. En el mundo, alrededor de un 39% de la población adulta presenta sobrepeso y un 13% obesidad (1). Una dieta insuficiente, alta en calorías, grasas y azúcares, está estrechamente relacionada con enfermedades crónicas no transmisibles (cáncer, diabetes, hipertensión, enfermedades cardiovasculares, entre otras) (2,3). Así mismo, se ha descrito que una dieta saludable podría prevenir una de cada cinco muertes a nivel mundial, independiente del sexo, edad o nivel socioeconómico (2). Chile presenta una de las prevalencias más altas de sobrepeso y obesidad en adultos a nivel mundial, con un 75%, según los datos de la última Encuesta Nacional de Salud (ENS) (4). Un 82% de la carga de enfermedad en Chile está dada por las enfermedades crónicas no transmisibles, como diabetes, cáncer, hipertensión y enfermedades cardiovasculares (5). Como ejemplo, la diabetes en Chile causó 3.426 muertes en el año 2014. La prevalencia de diabetes en personas mayores de 15 años alcanza al 10%, mientras que la prevalencia de hipertensión llega al 28% y las enfermedades cardiovasculares al 27% (5). El gasto público total relacionado con obesidad en Chile llega a un 3%, lo que equivale al 0,5% del Producto Interno Bruto (PIB) chileno, equivalente a 455 mil millones de pesos anuales (6,7). OBJETIVO DE ESTA SÍNTESIS: Informar la toma de decisiones respecto de los efectos que tendría la aplicación de un impuesto a alimentos sólidos "altos en" nutrientes críticos en la población general. Se presentan los principales hallazgos encontrados en la evidencia recopilada, además de algunas consideraciones sobre la implementación relacionadas a la intervención estudiada. RESUMEN DE HALLAZGOS: Esta síntesis busca aportar evidencia sobre el efecto que tendría un programa de impuestos a alimentos sólidos altos en nutrientes críticos (azúcar, grasas, grasas saturadas) o en calorías, sobre el consumo de ellos en la población general. Se utilizó como comparador el escenario donde no se implementan impuestos a nutrientes críticos en alimentos sólidos. Para esta síntesis, se considera la definición de alimentos sólidos del Reglamento Sanitario de los Alimentos, la que señala lo siguiente: "será sólido si su contenido neto está expresado en gramos u otra medida equivalente. En el caso de los productos alimenticios que se consuman reconstituidos, se entenderá como sólido o líquido según como sea el producto listo para consumir, de acuerdo a las instrucciones de reconstitución (17)". Al realizar la búsqueda, los títulos y resúmenes fueron seleccionados por dos revisoras independientes, discutiendo cada uno de los disensos encontrados. Se encontraron inicialmente 162 revisiones sistemáticas (RS). De éstas, se incluyeron sólo las RS que evaluaran el efecto de los impuestos sobre el consumo, independiente de si eran basadas en contextos reales o simulados. Se excluyen 150 RS por no responder a la pregunta. De esta forma, se utilizaron 12 revisiones sistemáticas (9,13,18­27) publicadas entre 2010 y 2020. De ellas, se seleccionaron los estudios primarios con intervenciones que consideraron estrategias de cambios de precios debido a los impuestos y que evaluaron el efecto del impuesto sobre el consumo de los alimentos gravados. CONSIDERACIONES DE IMPLEMENTACIÓN: Consideraciones de Aplicabilidad: La evidencia aquí contemplada se aplica solamente a impuestos a alimentos sólidos altos en los siguientes nutrientes críticos: azúcar, grasas, grasas saturadas y/o calorías y no evalúa el efecto sustitución que pudieran tener estos impuestos por sobre el consumo de otro tipo de alimentos o nutrientes (10,20,41). Del total de los estudios primarios incluidos en esta síntesis, cuatro fueron realizados en los Estados Unidos, 12 en Europa, y uno en México. La mayoría de los estudios contemplados en esta síntesis corresponden a modelos de simulaciones de impuestos ficticios o simulaciones de impuestos implementados recientemente. Solo tres de los estudios incluidos en esta síntesis mostraron resultados de impuestos reales. Consideraciones Económicas: Se ha descrito que los impuestos en alimentos y bebidas altos en nutrientes críticos muestran elasticidad en su consumo, lo que significa que la compra y consumo de estos disminuye en relación al aumento de su precio (21,22,25). Diversos estudios de costo-efectividad han mostrado que los impuestos a alimentos altos en nutrientes críticos podrían reducir los costos directos e indirectos en la salud individual, como por ejemplo disminuir el peso, disminuir la discapacidad, y mejorar la calidad de vida de las personas, además de los efectos a nivel gubernamental, como el aumento en los ingresos de las arcas fiscales (46­49). Consideraciones de Equidad: Es importante considerar el potencial impacto de las políticas fiscales en equidad. Se debe tener en cuenta si la propuesta de gravamen tendrá un impacto en restricciones de libertad de selección de productos o si aumentará inequidades, afectando de forma desproporcionadas a algunos grupos. Se ha descrito que los impuestos a alimentos y bebidas podrían tener un efecto regresivo por nivel socioeconómico (NSE), ya que las personas de menor ingreso, comparadas con las de mayor ingreso, gastan un mayor porcentaje de su sueldo en este tipo de productos. Desde una perspectiva ética, es necesario balancear el posible impacto en equidad, con la efectividad de la intervención y si la población más afectada por el aumento de impuestos es la que recibiría los mayores beneficios en salud, especialmente si las recaudaciones por los impuestos a estos alimentos son usadas para promover y sustentar programas de promoción de hábitos saludables y subvención de alimentos saludables en grupos más vulnerables (8,10,51). Consideraciones de Monitoreo y Evaluación: Es preciso considerar que existen diversos actores involucrados en la implementación de un programa de impuestos a alimentos sólidos altos en nutrientes críticos, entre los que se encuentran: Ministerio de Salud, Ministerio de Hacienda, Ministerio de Economía, Ministerio de Agricultura, productores de alimentos, industria alimentaria, sociedad de consumidores y sociedad civil. Para poder concretar un programa de impuestos exhaustivo y evaluar sus efectos es necesario incluir a todos los actores involucrados (8,10). Chile ya tiene experiencia con la implementación innovadora de impuestos a bebidas azucaradas (52,53), por lo que es crucial identificar cuáles han sido y siguen siendo los facilitadores, barreras y contratiempos que se identificaron en este proceso. Así mismo, y como lo plantea Caro et al (52), junto con Nakamura (53) et al, se recomienda efectuar evaluaciones a corto, mediano y largo plazo, desde el comienzo de la ejecución de los impuestos, idealmente, incluyendo un grupo control para comparaciones. La literatura también sugiere analizar las posibles diferencias en consumo por NSE (52­54). Finalmente, cabe destacar que el monitoreo y evaluación de impuestos a alimentos sólidos altos en nutrientes críticos debe ser de alta calidad, y libre de cualquier tipo de conflicto de interés, independiente de los desenlaces de la implementación de la estrategia (10).

Study on the new strategy and key techniques for accurate prevention and treatment of nonalcoholic steatohepatitis based on intestinal target bacteria.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has emerged as a major health problem worldwide; according to statistics, 10% to 25% of patients with NAFLD can progress to nonalcoholic steatohepatitis (NASH). A link between the composition and metabolites of intestinal microbiota and the development of NAFLD is becoming clearer. It is believed that microbiota factors are driving forces of hepatic steatosis and inflammation. The formulated food that contains prebiotics and dietary fiber may improve NAFLD by altering the intestinal flora and its metabolites. METHODS: The study plan to recruit adult patients (18-75 years, n = 120) with NAFLD, range of alanine aminotransferase is 1.5 to 5 times upper limit of normal (ULN) or liver biopsy is confirmed as NASH. Participants will be randomly allocated into 2 groups: formulated food (n = 80) and a placebo group (n = 40) for 24 weeks. Both groups will receive lifestyle and nutritional advice. The primary endpoint is a decrease in MRS-PDFF by more than 30% from baseline at 24 weeks. The secondary endpoints include the change of anthropometric, liver function, glycolipid metabolism, and systemic inflammation at 4, 12, and 24 weeks. In addition, we consider the changes in intestinal microbiota as an exploration to assess the abundance and diversity at 24 weeks. Weeks 24 to 36 are the follow-up period of drug withdrawal. DISCUSSION: This clinical trial will provide evidence of efficacy and safety of formulated food as a potential new therapeutic agent for NAFLD patients. TRIAL REGISTRATION: The trial is registered in the China Clinical Trial Center (ChiCTR1800016178).

Honokiol Alleviates Methionine-Choline Deficient Diet-Induced Hepatic Steatosis and Oxidative Stress in C57BL/6 Mice by Regulating CFLAR-JNK Pathway.

BACKGROUND: Honokiol (HNK) has been reported to possess various beneficial effects in the context of metabolic disorders, including fatty liver, insulin resistance, and oxidative stress which are closely related to nonalcoholic steatohepatitis (NASH), however with no particular reference to CFLAR or JNK. METHODS: C57BL/6 mice were fed methionine-choline-deficient (MCD) diet and administered simultaneously with HNK (10 and 20 mg/kg once a day, ig) for 6 weeks, and NCTC1469 cells were pretreated, respectively, by oleic acid (OA, 0.5 mmol/L) plus palmitic acid (PA, 0.25 mmol/L) for 24 h, and adenovirus-down Cflar for 24 h, then exposed to HNK (10 and 20 µmol/L) for 24 h. Commercial kits, H&E, MT, ORO staining, RT-qPCR, and Western blotting were used to detect the biomarkers, hepatic histological changes, and the expression of key genes involved in NASH. RESULTS: The in vivo results showed that HNK suppressed the phosphorylation of JNK (pJNK) by activating CFLAR; enhanced the mRNA expression of lipid metabolism-related genes Acox, Cpt1α, Fabp5, Gpat, Mttp, Pparα, and Scd-1; and decreased the levels of hepatic TG, TC, and MDA, as well as the levels of serum ALT and AST. Additionally, HNK enhanced the protein expression of oxidative stress-related key regulatory gene NRF2 and the activities of antioxidases HO-1, CAT, and GSH-Px and decreased the protein levels of prooxidases CYP4A and CYP2E1. The in vivo effects of HNK on the expression of CLFAR, pJNK, and NRF2 were proved by the in vitro experiments. Moreover, HNK promoted the phosphorylation of IRS1 (pIRS1) in both tested cells and increased the uptake of fluorescent glucose 2-NBDG in OA- and PA-pretreated cells. CONCLUSIONS: HNK ameliorated NASH mainly by activating the CFLAR-JNK pathway, which not only alleviated fat deposition by promoting the efflux and ß-oxidation of fatty acids in the liver but also attenuated hepatic oxidative damage and insulin resistance by upregulating the expression of NRF2 and pIRS1.

Reduction in Healthcare Utilization With Transition to Peptide-Based Diets in Intolerant Home Enteral Nutrition Patients.

BACKGROUND: Since the introduction of percutaneous endoscopic gastrostomy in the 1980s, the prevalence of home enteral nutrition (HEN) support has increased significantly. Despite these increases, many patients are unable to tolerate standard polymeric formulas (SPFs), resulting in significant healthcare resource utilization. Peptide-based diets (PBDs) have emerged as a viable option in SPF-intolerant patients; however, data in the HEN population are lacking. METHODS: Retrospective review of our prospectively maintained HEN database was conducted to assess tolerance, efficacy, and impact on healthcare utilization in patients on PBDs. RESULTS: From January 1, 2016, to May 1, 2018, 95 patients were placed on PBDs, with 53 patients being started directly and 42 patients being transitioned from SPFs. In patients transitioned to PBDs, symptoms of nausea and vomiting, diarrhea, abdominal pain, and distention improved significantly. Healthcare utilization also declined significantly, including mean number of phone calls (1.8 ± 1.6 to 1.1 ± 0.9, P = 0.006), mean number of emergency room visits (0.3 ± 0.6 to 0.09 ± 0.3, P = 0.015), and mean number of provider visits (1.3 ± 1.3 to 0.3 ± 0.5, P < 0.0001). CONCLUSIONS: Overall, PBDs were well tolerated and resulted in significant improvements in symptoms of gastrointestinal distress and healthcare utilization in patients intolerant to SPFs.

Helicobacter pylori antibiotic eradication coupled with a chemically defined diet in INS-GAS mice triggers dysbiosis and vitamin K deficiency resulting in gastric hemorrhage.

Infection with Helicobacter pylori causes chronic inflammation and is a risk factor for gastric cancer. Antibiotic treatment or increased dietary folate prevents gastric carcinogenesis in male INS-GAS mice. To determine potential synergistic effects, H. pylori-infected male INS-GAS mice were fed an amino acid defined (AAD) diet with increased folate and were treated with antibiotics after 18 weeks of H. pylori infection. Antibiotic therapy decreased gastric pathology, but dietary folate had no effect. However, the combination of antibiotics and the AAD diet induced anemia, gastric hemorrhage, and mortality. Clinical presentation suggested hypovitaminosis K potentially caused by dietary deficiency and dysbiosis. Based on current dietary guidelines, the AAD diet was deficient in vitamin K. Phylloquinone administered subcutaneously and via a reformulated diet led to clinical improvement with no subsequent mortalities and increased hepatic vitamin K levels. We characterized the microbiome and menaquinone profiles of antibiotic-treated and antibiotic-free mice. Antibiotic treatment decreased the abundance of menaquinone producers within orders Bacteroidales and Verrucomicrobiales. PICRUSt predicted decreases in canonical menaquinone biosynthesis genes, menA and menD. Reduction of menA from Akkermansia muciniphila, Bacteroides uniformis, and Muribaculum intestinale were confirmed in antibiotic-treated mice. The fecal menaquinone profile of antibiotic-treated mice had reduced MK5 and MK6 and increased MK7 and MK11 compared to antibiotic-free mice. Loss of menaquinone-producing microbes due to antibiotics altered the enteric production of vitamin K. This study highlights the role of diet and the microbiome in maintaining vitamin K homeostasis.

Oligomeric Enteral Nutrition in Undernutrition, due to Oncology Treatment-Related Diarrhea. Systematic Review and Proposal of An Algorithm of Action.

Oncology treatment-related diarrhea and malnutrition appear together in oncological patients because of the disease itself, or the treatments that are administered for it. Therefore it is essential to carry out a nutritional treatment. Enteral nutrition formulas, containing peptides and medium chain triglycerides, can facilitate absorption in cases of malabsorption. There are few references to the use of enteral nutrition in the clinical society guidelines of patient management with oncology treatment-related diarrhea (OTRD). A bibliographic review of the studies with oligomeric enteral nutrition in OTRD found only nine studies with chemotherapy (all with the same oligomeric formula in which oral mucositis improves, while the rest of the outcomes show different results), and eight studies with radiotherapy (with different products and very heterogeneous results). We hereby present our action algorithm to supplement the diet of OTRD patients with an oligomeric enteral nutrition formula. The first step is the nutritional assessment, followed by the assessment of the functional capacity of the patient's intestine. With these two aspects evaluated, the therapeutic possibilities available vary in degrees of complexity: These will range from the usual dietary recommendations, to supplementation with oral oligomeric enteral nutrition, along with complete enteral nutrition with oligomeric formula, and up to potentially total parenteral nutrition.

Hepatoprotective Effect of Jianpi Huoxue Formula on Nonalcoholic Fatty Liver Disease Induced by Methionine-Choline-Deficient Diet in Rat.

In parallel with the prevalence metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in most countries. It features a constellation of simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and even hepatocellular carcinoma. There are no approved drugs for effective management of NAFLD and NASH. Jianpi Huoxue formula (JPHX) mainly consists of Atractylodes macrocephal (Baizhu), Salvia miltiorrhiza (Danshen), Rasux Paeonia Alba (Baishao), Rhizoma Alismatis (Zexie), and Fructus Schisandrae Chinensis (Wuweizi), which may have beneficial effects on NAFLD. The aim of the study was to identify the effect of JPHX on NAFLD. A NAFLD model was induced by methionine-choline-deficient food (MCD) in Wistar rats and orally administered with simultaneous JPHX, once a day for 8 weeks. Hepatocellular injury, lipid profile, inflammation, fibrosis, and apoptosis were evaluated. The results showed that JPHX significantly decreased the abnormal serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the MCD model (P<0.05). Furthermore, JPHX protected MCD diet-fed rats from accumulation of hepatic triglycerides (TG) and total cholesterol (TC). Histological examination demonstrated that JPHX noticeably normalized the NAFLD activity score (NAS). Moreover, JPHX ameliorated liver inflammation by decreasing TNF-α levels and reduced collagen and matrix metalloproteinases in MCD diet-fed rats. In addition, JPHX prevented rats from MCD-induced cellular apoptosis, as suggested by TUNEL staining, and suppressed the activation of caspase 3 and 7 proteins. JPHX also inhibited the phosphorylation of JNK. In conclusion, JPHX exhibited a hepatoprotective effect against NAFLD in an MCD experimental model.

Weight management strategies for those with chronic kidney disease: A consensus report from the Asia Pacific Society of Nephrology and Australia and New Zealand Society of Nephrology 2016 renal dietitians meeting.

AIM: The aim of the present study was to develop a consensus report to guide dietetic management of overweight or obese individuals with chronic kidney disease (CKD). METHODS: Six statements relating to weight management in CKD guided a comprehensive review of the literature. A summary of the evidence was then presented at the renal nutrition meeting of the 2016 Asia Pacific Society of Nephrology and Australia and New Zealand Society of Nephrology. Majority agreement was defined as group agreement on a statement of between 50-74%, and consensus was considered ≥75% agreement. The recommendations were developed via a mini Delphi process. RESULTS: Two statements achieved group consensus: the current guidelines used by dietitians to estimate energy requirements for overweight and obese people with CKD are not relevant and weight loss medications may be unsafe or ineffective in isolation for those with CKD. One statement achieved group agreement: Meal replacement formulas are safe and efficacious in those with CKD. No agreement was achieved on the statements of whether there is strong evidence of benefit for weight loss prior to kidney transplantation; whether traditional weight loss strategies can be used in those with CKD and if bariatric surgery in those with end stage kidney disease is feasible and effective. CONCLUSION: There is a limited evidence base to guide the dietetic management of overweight and obese individuals with CKD. Medical or surgical strategies to facilitate weight loss are not recommended in isolation and require a multidisciplinary approach with the involvement of a skilled renal dietitian.

Prostaglandin I2 suppresses the development of diet-induced nonalcoholic steatohepatitis in mice.

Nonalcoholic steatohepatitis (NASH) is a hepatic manifestation of metabolic syndrome. Although the prostaglandin (PG)I2 receptor IP is expressed broadly in the liver, the role of PGI2-IP signaling in the development of NASH remains to be determined. Here, we investigated the role of the PGI2-IP system in the development of steatohepatitis using mice lacking the PGI2 receptor IP [IP-knockout (IP-KO) mice] and beraprost (BPS), a specific IP agonist. IP-KO and wild-type (WT) mice were fed a methionine- and choline-deficient diet (MCDD) for 2, 5, or 10 wk. BPS was administered orally to mice every day during the experimental periods. The effect of BPS on the expression of chemokine and inflammatory cytokines was examined also in cultured Kupffer cells. WT mice fed MCDD developed steatohepatitis at 10 wk. IP-KO mice developed steatohepatitis at 5 wk with augmented histologic derangements accompanied by increased hepatic monocyte chemoattractant protein-1 (MCP-1) and TNF-α concentrations. After 10 wk of MCDD, IP-KO mice had greater hepatic iron deposition with prominent oxidative stress, resulting in hepatocyte damage. In WT mice, BPS improved histologic and biochemical parameters of steatohepatitis, accompanied by reduced hepatic concentration of MCP-1 and TNF-α. Accordingly, BPS suppressed the LPS-stimulated Mcp-1 and Tnf-α mRNA expression in cultured Kupffer cells prepared from WT mice. PGI2-IP signaling plays a crucial role in the development and progression of steatohepatitis by modulating the inflammatory response, leading to augmented oxidative stress. We suggest that the PGI2-IP system is an attractive therapeutic target for treating patients with NASH.-Kumei, S., Yuhki, K.-I., Kojima, F., Kashiwagi, H., Imamichi, Y., Okumura, T., Narumiya, S., Ushikubi, F. Prostaglandin I2 suppresses the development of diet-induced nonalcoholic steatohepatitis in mice.

Metastatic mineralisation caused by vitamin D intoxication in hand-raised short-beaked echidnas (Tachyglossus aculeatus).

CASE REPORT: Two cases of metastatic mineralisation caused by dietary excess of vitamin D are reported in hand-raised short-beaked echidna (Tachyglossus aculeatus) puggles at the Australian Wildlife Health Centre. Oversupplementation was attributed to excessive levels of vitamin D in Wombaroo Echidna Milk Replacer fed to the puggles. No information exists regarding the naturally occurring vitamin D levels in echidna milk, but, given the low serum levels that have been observed in free-ranging animals, it is likely to be low. CONCLUSION: The vitamin D concentration in Wombaroo Echidna Milk Replacer has been reduced.

Elevation of liver endoplasmic reticulum stress in a modified choline-deficient l-amino acid-defined diet-fed non-alcoholic steatohepatitis mouse model.

Endoplasmic reticulum (ER) stress caused by accumulation of misfolded proteins is observed in several kinds of diseases. Since ER stress is reported to be involved in the progression of non-alcoholic steatohepatitis (NASH), highly sensitive and simple measurement methods are required for research into developing novel therapy for NASH. To investigate the involvement of ER stress in NASH pathogenesis in a mouse model, an assay for liver ER stress was developed using ER stress activated indicator-luciferase (ERAI-Luc) mice. To establish the assay method for detection of ER stress in the liver, tunicamycin (TM) (0.3 mg/kg i. p.) was administered to ERAI-Luc mice, and the luciferase activity was measured in ex vivo and in vivo. To evaluate ER stress in the NASH model, ERAI-Luc mice were fed a modified choline-deficient l-amino acid-defined (mCDAA) diet for 14 weeks. After measurement of ER stress by luminescence imaging, levels of liver lipids and pro-fibrotic and pro-inflammatory gene expression were measured as NASH-related indexes. In non-invasive whole-body imaging, TM elevated luciferase activity in the liver, induced by activation of ER stress. The highest luminescence in the liver was confirmed by ex vivo imaging of isolated tissues. In parallel with progression of NASH, elevated luminescence induced by ER stress in liver was observed in mCDAA diet-fed ERAI-Luc mice. Luciferase activity was significantly and positively correlated to levels of triglyceride and free cholesterol in the liver, as well as to the mRNA expression of type 1 collagen α1 chain and tumor necrosis factor α. These data indicated that the use of ERAI-Luc mice was effective in the detection of ER stress in the liver. Moreover, the NASH model using ERAI-Luc mice can be a useful tool to clarify the role of ER stress in pathogenesis of NASH and to evaluate effects of drugs targeted against ER stress.

p16 deficiency promotes nonalcoholic steatohepatitis via regulation of hepatic oxidative stress.

Nonalcoholic steatohepatitis (NASH) is characterized by excess accumulation of lipids in liver, accompanied with hepatocyte injury, cell death and inflammation. Although p16 is known as tumor suppressor in multiple cancer types, it remains unclear whether p16 plays a critical role in NASH. To determine whether p16 could play a role in the pathogenesis of NASH, wild-type mice and p16-/- mice were fed on a methionine and choline-deficient (MCD) diet for 3 weeks, and liver steatosis, fibrosis, and inflammation were evaluated. Our data show that p16-/- mice fed with MCD diet displayed more significant hepatic steatosis, hepatocyte damage, increased oxidative stress and inflammatory cell infiltration compared to MCD-fed WT mice. It was also clear that the increased ROS and the accumulation of lipid in BEL-7402 cells occurred when p16 expression was depleted with siRNA. These findings indicate that p16 may play a critical role in the development of NASH by reining in ROS production and by inhabiting inflammatory response.

Bone health assessment of food allergic children on restrictive diets: a practical guide.

BACKGROUND: Food allergy in childhood is on the rise globally and is managed with avoidance diets; recent case reports of food allergic children with nutritional rickets in the literature highlight the importance of close monitoring of bone health in this population. METHODS: There is no consensus as yet with regard to bone health evaluation in food allergic children; therefore, extensive literature search was performed and the existing evidence is presented, along with a relevant algorithm. RESULTS: Children allergic to cow's milk protein or presenting with allergy in more than three food items, as well as patients with severe allergic phenotypes or comorbidities known to affect the skeleton, seem to be at risk of metabolic bone disorders. As a practical guide, suspicious cases can be investigated with basic bone profile, whereas more severe cases (persistent bone pain and fractures) may undergo advanced bone health assessment, with bone mineral density (BMD) and metabolic bone markers' evaluation. Of note, these diagnostic steps call for further studies in the field of food allergy, as they are not performed as a routine. Evidence is accumulating with regard to vitamin D deficiency, osteopenia and imbalanced bone metabolism in those food allergic children who show poor dietary compliance or have inadequate medical supervision. CONCLUSIONS: Ensuring optimal bone accrual in a food allergic child is an important task for the clinician and requires close monitoring of the restrictive diet and prompt therapeutic intervention, in an effort to avoid rickets or osteopenia.

Methionine-Restricted Diet Increases miRNAs That Can Target RUNX2 Expression and Alters Bone Structure in Young Mice.

Dietary methionine restriction (MR) increases longevity and improves healthspan in rodent models. Young male C57BL/6J mice were placed on MR to assess effects on bone structure and formation. Mice were fed diets containing 0.86% or 0.12% methionine for 5 weeks. Fasting blood plasma was analyzed for metabolic and bone-related biomarkers. Tibiae were analyzed by histomorphometry, while femurs were analyzed by micro-CT and biomechanically using 4-point bending. MR mice had reduced plasma glucose and insulin, while FGF21 and FGF23 increased. Plasma levels of osteocalcin and osteoprotegrin were unaffected, but sclerostin and procollagen I decreased. MR induced bone marrow fat accretion, antithetical to the reduced fat depots seen throughout the body. Cortical bone showed significant decreases in Bone Tissue Density (BTD). In trabecular bone, mice had decreased BTD, bone surface, trabecula and bone volume, and trabecular thickness.. Biomechanical testing showed that on MR, bones were significantly less stiff and had reduced maximum load and total work, suggesting greater fragility. Reduced expression of RUNX2 occurred in bone marrow of MR mice. These results suggest that MR alters bone remodeling and apposition. In MR mice, miR-31 in plasma and liver, and miR-133a, miR-335-5p, and miR-204 in the bone marrow was elevated. These miRNAs were shown previously to target and regulate Osterix and RUNX2 in bone, which could inhibit osteoblast differentiation and function. Therefore, dietary MR in young animals alters bone structure by increasing miRNAs in bone and liver that can target RUNX2. J. Cell. Biochem. 118: 31-42, 2017. © 2016 Wiley Periodicals, Inc.

Hepatoprotective Effect and Synergism of Bisdemethoycurcumin against MCD Diet-Induced Nonalcoholic Fatty Liver Disease in Mice.

Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC) is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD)-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment), MCD diet (MCD diet only), MCD + silymarin (SIL) 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD-diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD-diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent against NAFLD.

Normal vitamin D levels and bone mineral density among children with inborn errors of metabolism consuming medical food-based diets.

A higher incidence of osteopenia is observed among children with inherited metabolic disorders (inborn errors of metabolism, or IEMs) who consume medical food-based diets that restrict natural vitamin D-containing food sources. We evaluated the vitamin D status of children with IEMs who live in the Pacific Northwest with limited sun exposure and determined whether bone mineral density (BMD) in children with phenylketonuria (PKU), the most common IEM, correlated with diet or biochemical markers of bone metabolism. We hypothesized that children with IEMs would have lower serum vitamin D concentrations than controls and that some children with PKU would have reduced bone mineralization. A retrospective record review of 88 patients with IEMs, and 445 children on unrestricted diets (controls) found the 25-hydroxyvitamin D concentrations were normal and not significantly different between groups (IEM patients, 27.1 ± 10.9; controls, 27.6 ± 11.2). Normal BMD at the hip or spine (-2

Effects of Immunonutrition for Cystectomy on Immune Response and Infection Rates: A Pilot Randomized Controlled Clinical Trial.

UNLABELLED: After radical cystectomy (RC), patients are at risk for complications including infections. The expansion of myeloid-derived suppressor cells (MDSCs) after surgery may contribute to the lower resistance to infection. Immune response and postoperative complications were compared in men consuming either specialized immunonutrition (SIM; n=14) or an oral nutrition supplement (ONS; n=15) before and after RC. MDSC count (Lin- CD11b+ CD33+) was significantly different between the groups over time (p=0.005) and significantly lower in SIM 2 d after RC (p<0.001). MDSC count expansion from surgery to 2 d after RC showed a weak association with an increase in infection rate 90 d after surgery (p=0.061). Neutrophil:lymphocyte ratio was significantly lower in SIM compared with ONS 3h after the first incision (p=0.039). Participants receiving SIM had a 33% reduction in postoperative complication rate (95% confidence interval [CI], 1-64; p=0.060) and a 39% reduction in infection rate (95% CI, 8-70; p=0.027) during late-phase recovery. The small sample size limits the study findings. PATIENT SUMMARY: Results show that the immune response to surgery and late infection rates differ between radical cystectomy patients receiving specialized immunonutrition versus oral nutrition supplement in the perioperative period. TRIAL REGISTRATION: ClinicalTrials.gov NCT01868087.

Effects of diet quality on vulnerability to mild subchronic social defeat stress in mice.

OBJECTIVES: The chronic social defeat stress (CSDS) mouse model is a potentially useful system for understanding stress responses to social environments. We previously developed a mouse model of subchronic and mild social defeat stress (sCSDS) that exhibits increased body weight gain and food intake following polydipsia-like features. sCSDS mice also show avoidance behavior in a social interaction test. In this study, we examined the effects of diet quality on susceptibility to sCSDS by feeding these mice semi- and non-purified diets. METHODS: Male C57BL/6J (B6; n = 82) mice were exposed to sCSDS using male ICR mice. The B6 mice were divided into four test groups: semi-purified pellet diet + sCSDS, non-purified pellet diet + sCSDS, semi-purified diet + control (no sCSDS), and non-purified diet + control. RESULTS: Although increased body weight, and food and water intake following sCSDS exposure were consistently observed in the groups that were fed semi- and non-purified diets, social avoidance behavior was influenced by food type (i.e., sCSDS mice fed semi-purified diet showed the greatest social avoidance behavior). In addition, the rates of stress susceptibility were estimated at 73.9 and 34.8% in sCSDS mice fed semi-purified and non-purified diets, respectively (P < 0.05). For comparison, the susceptible-like phenotype rates were estimated at 12.5 and 8.3% in healthy control mice fed semi-purified and non-purified diets, respectively. DISCUSSION: These results suggest that diet quality affects the vulnerability of mice to social defeat stress.

Gastric feeding intolerance is not caused by mucosal ischemia measured by intragastric air tonometry in the critically ill.

BACKGROUND: Gastric mucosal ischemia may be a risk factor for gastrointestinal intolerance to early feeding in the critically ill. AIMS: To study intragastric PCO2 air tonometry and gastric residual volumes (GRV) before and after the start of gastric feeding. METHODS: This is a two-center study in intensive care units of a university and teaching hospital. Twenty-nine critically ill, consecutive and consenting patients scheduled to start gastric feeding were studied after insertion of a gastric tonometry catheter and prior to and after start of gastric feeding (500 ml over 1 h), when clinically indicated. RESULTS: Blood gasometry and intragastric tonometry were performed prior to and 2 h after gastric feeding. The intragastric to arterial PCO2 gap (normal <8 mm Hg) was elevated in 41% of patients prior to feeding and measured (mean ± standard deviation) 13 ± 20 and 16 ± 23 mm Hg in patients with normal (<100 ml, 42 ± 34 ml, n = 19) and elevated GRV (250 ± 141 ml, n = 10, P = 0.75), respectively. After feeding, the gradient did not increase and measured 27 ± 25 and 23 ± 34 mm Hg, respectively (P = 0.80). CONCLUSION: Gastric mucosal ischemia is not a major risk factor for intolerance to early gastric feeding in the critically ill.