Real-life data on the effectiveness of extensively hydrolyzed protein-based formula and amino acid–based formula in regaining weight and height in infants on a cow’s milk protein elimination diet

Objective: To compare the effectiveness of extensively hydrolyzed protein-based formula (EHF) or amino acid–based formula (AAF) in reversing the weight and height deficit in infants on a cow’s milk protein elimination diet. Methods: Infants from a retrospective cohort who were fed EHF (n = 17) or AAF (n = 16) for at least 2 months on a cow’s milk protein elimination diet were included. The weight and height values recorded in the infants’ medical records were obtained. Results: The mean age of the infants at the start of EHF and AAF were 5.8 ± 2.6 and 4.4 ± 2.5 months, respectively (P = 0.061). There was no difference between the groups in terms of the monthly weight gain (373.0 ± 212.2 and 453.1 ± 138.5 g, P = 0.223, respectively, for EHF and AAF), while the monthly increase in height was greater in the group fed with AAF (1.3 ± 0.5 and 1.8 ± 0.6, P = 0.030). A comparison between the difference in the initial z-score and in the oral challenge test of weight-for-age (+0.7 ± 1.2 and +1.3 ± 1.4, P = 0.262, respectively, for the EHF and AAF groups), height-for-age (+0.2 ± 1.1 and +1.2 ± 1.8, P = 0.090), and body mass index (BMI)-for-age (+0.7 ± 1.3 and +0.7 ± 1.5, P = 0.971) did not reveal a statistically significant difference between the groups. Correlation coefficients showed that the greater the initial nutritional deficit, the greater the positive variation between the beginning of each formula and the oral challenge test. Conclusion: EHF and AAF provided similar increases in the weight-for-age, height-for-age, and BMI-for-age z-scores in both groups. The monthly increase in height was greater in infants who received AAF (AU)

Hidrolizada con alto contenido de trigliceridos de cadena media en pacientes pediátricos con linfangiectasia intestinal primaria y alergia a la leche de vaca / Hydrolyzed with high content of medium chain triglycerides in pediatric patients with primary intestinal lymphangiectasia and allergy to cow's milk

ANTECEDENTES En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Institución de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen, el que expone la evaluación de la eficacia y seguridad de la fórmula extensamente hidrolizada con alto contenido de triglicéridos de cadena media en pacientes pediátricos con linfangiectasia intestinal primaria y alergia a la leche de vaca. Así, el Dr. Marco Antonio Morales Acosta, médico especialista en Pediatría del Servicio de Pediatría Especializada del Hospital Nacional Edgardo Rebagliati Martins de la Red Prestacional Rebagliati, siguiendo la Directiva N° 003-IETSI-ESSALUD-2016, envía al Instituto de Evaluación de Tecnologías en Salud e Investigación ­ IETSI la solicitud de uso fuera del petitorio del producto fórmula extensamente hidrolizada alta en triglicéridos de cadena media. ASPECTOS GENERALES La linfangiectasia intestinal primaria (LIP) es una enfermedad poco frecuente caracterizada por una dilatación de los vasos linfáticos de la mucosa o submucosa del intestino delgado. Debido a la estasis y, finalmente, a la rotura de los vasos linfáticos, el líquido linfático, rico en albúmina y otras proteínas, se filtra hacia el tracto gastrointestinal (Brownell and Piccoli 2021). La LIP afecta principalmente a niños y adultos jóvenes, y generalmente se diagnostica antes de los 3 años de edad. El síntoma principal es el edema predominantemente bilateral de miembros inferiores relacionado con la gastroenteropatía perdedora de proteínas. También puede haber fatiga, dolor abdominal, pérdida de peso, incapacidad para aumentar de peso, retraso del crecimiento en los niños, diarrea moderada, deficiencias de vitaminas liposolubles debido a malabsorción, o deficiencia de hierro con anemia moderada (Brownell and Piccoli 2021; Orphanet 2021). La etiología y la prevalencia de la LIP es desconocida. En todo el mundo, se han notificado menos de 500 casos (Orphanet 2021). Su diagnóstico se confirma por la observación endoscópica de los vasos linfáticos intestinales dilatados con la correspondiente histología de las muestras de biopsia intestinal (Orphanet 2021). Y los objetivos del tratamiento incluyen maximizar el estado nutricional y la calidad de vida de los pacientes, mediante la reducción de los síntomas y de las secuelas. El pilar de la terapia dietética es una dieta baja en grasas, alta en proteínas y alta en triglicéridos de cadena media (TCM) (Brownell and Piccoli 2021). METODOLOGÍA: Se realizó una búsqueda sistemática utilizando las bases de datos PubMed, Cochrane Library y LILACS. Además, se realizó una búsqueda dentro de bases de datos pertenecientes a grupos que realizan evaluaciones de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), incluyendo el Scottish Medicines Consortium (SMC), el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), la Haute Autorité de Santé (HAS), el Institute for Quality and Efficiency in Health Care (IQWiG), el Instituto de Evaluación Tecnológica en Salud de Colombia (IETS), la Comissáo Nacional de Incorporacáo de Tecnologias no Sistema Único de Saúde (CONITEC), entre otros. Asimismo, se revisó la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA) y páginas web de sociedades especializadas en nutrición en pediatría como la North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN), la European Society for Clinical Nutrition and Metabolism (ESPEN), y la American Society for Parenteral and Enteral Nutrition (ASPEN). De manera adicional, se hizo una búsqueda en la página web del registro de ensayos clínicos administrado por la Biblioteca Nacional de Medicina de los Estados Unidos (https://clinicaltrials.qov/) e International Clinical Trial Registry Platform (ICTRP) (https://apps.who.int/trialsearch/) para poder identificar ensayos clínicos en curso o cuyos resultados no hayan sido publicados. Las estrategias de búsqueda para identificar la evidencia de ensayos clínicos aleatorizados (ECA) se encuentran en las Tabla 1, 2 y 3 del Material Suplementario. ANÁLISIS DE LA EVIDENCIA: En la presente evaluación no se identificaron guías, consensos de expertos o estudios que ayudaran a responder la pregunta PICO establecida en este dictamen. En ese sentido la evaluación se centró en la evidencia descrita previamente por el IETSI para el uso de la FEH en niños con APLV y la fórmula con alto contenido de TCM en niños con LIP, la plausibilidad biológica de la eficacia de la intervención de interés, y la opinión de los expertos de EsSalud. CONCLUSIONES: Por todo lo expuesto, el IETSI recomienda el uso de la fórmula extensamente hidrolizada con alto contenido de TCM en pacientes pediátricos con LIP y alergia la leche de vaca. Dado que actualmente el producto farmacéutico fórmula extensamente hidrolizada con alto contenido de triglicéridos de cadena media no cuenta con registro sanitario en el mercado peruano; de requerirse la autorización de este producto farmacéutico se recomienda seguir el procedimiento TUPA 118 "Autorización excepcional para la importación y uso de productos farmacéuticos, dispositivos médicos o productos sanitarios para la prevención y tratamiento individual" en el marco de lo establecido en el artículo 16 de la Ley N° 29459 "Ley de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios".

Protective effects of bioactive peptides in foxtail millet protein hydrolysates against experimental colitis in mice.

It is of great significance to develop a dietary intervention strategy to prevent inflammatory bowel disease (IBD). A millet-rich diet can ameliorate IBD, but the active ingredients and mechanisms remain to be studied. Our results showed that the oral administration of foxtail millet protein hydrolysates (FMPH) reduced the disease activity index (DAI) score and improved the colon symptoms of dextran sulfate sodium (DSS)-induced colitis mice. FMPH reduced the serum LPS level, increased intestinal ZO-1 and occludin expression, inhibited NF-κB phosphorylation, and reduced the levels of TNF-α and IL-6. Further, FMPH inhibited Th17 cell differentiation, and inhibited inflammasome activation and IL-1ß expression through the NLRP3/ASC/caspase-1 pathway. The results on Caco-2 cells confirmed the role of FMPH on tight junction and inflammasomes activation. A total of 2620 peptides were identified in FMPH by UPLC-MS/MS, of which 22 peptides were predicted as potential biopeptides, and the key sequences were LPF, ANP, PY, YW, and IPP. This study supports the effect of a diet rich in millet on the improvement of IBD and provides a scientific basis for the use of millet protein as a functional food to improve intestinal inflammation.

Semi-Elemental and Elemental Formulas for Enteral Nutrition in Infants and Children with Medical Complexity-Thinking about Cow's Milk Allergy and Beyond.

Children with medical complexities, such as multi-system disorders and/or neurological impairments, often experience feeding difficulties and need enteral nutrition. They frequently have impaired motility and digestive-absorbing functions related to their underlying condition. If a cow's milk allergy (CMA) occurs as a comorbidity, it is often misdiagnosed, due to the symptoms' overlap. Many of the commercialized mixtures intended for enteral nutrition are composed of partially hydrolyzed cow's milk proteins, which are not suitable for the treatment of CMA; thus, the exclusion of a concomitant CMA is mandatory in these patients for obtaining symptoms relief. In this review, we focus on the use of elemental and semi-elemental formulas in children with neurological diseases and in preterm infants as clinical "models" of medical complexity. In children with neurodisabilities, when gastrointestinal symptoms persist despite the use of specific enteral formula, or in cases of respiratory and/or dermatological symptoms, CMA should always be considered. If diagnosis is confirmed, only an extensively hydrolyzed or amino-acid based formula, or, as an alternative, extensively hydrolyzed nutritionally adequate formulas derived from rice or soy, should be used. Currently, enteral formulas tailored to the specific needs of preterm infants and children with neurological impairment presenting concomitant CMA have not been marketed yet. For the proper monitoring of the health status of patients with medical complexity, multidisciplinary evaluation and involvement of the nutritional team should be promoted.

Measuring the oral bioavailability of protein hydrolysates derived from food sources: A critical review of current bioassays.

BACKGROUND: Food proteins are a source of hydrolysates with potentially useful biological attributes. Bioactive peptides from food-derived proteins are released from hydrolysates using exogenous industrial processes or endogenous intestinal enzymes. Current in vitro permeability assays have limitations in predicting the oral bioavailability (BA) of bioactive peptides in humans. There are also difficulties in relating the low blood levels of food-derived bioactive peptides detected in preclinical in vivo models to pharmacodynamic read-outs relevant for humans. SCOPE AND APPROACH: In this review, we describe in vitro assays of digestion, permeation, and metabolism as indirect predictors of the potential oral BA of hydrolysates and their constituent bioactive peptides. We discuss the relationship between industrial hydrolysis processes and the oral BA of hydrolysates and their peptide by-products. KEY FINDINGS: Hydrolysates are challenging for analytical detection methods due to capacity for enzymatic generation of peptides with novel sequences and also new modifications of these peptides during digestion. Mass spectrometry and peptidomics can improve the capacity to detect individual peptides released from complex hydrolysates in biological milieu.

Soybean protein hydrolysate stimulated cholecystokinin secretion and inhibited feed intake through calcium-sensing receptors and intracellular calcium signalling in pigs.

Although soybean protein is the major component in livestock feeds, its effect on pigs' appetites is largely unknown. Recently, the importance of gut nutrient-sensing for appetite modulation by regulating anorectic gut hormone release has been recognised. This study investigates the roles of soybean proteins in appetite regulation, anorectic gut hormone secretion, and underlying mechanisms. The duodenal-cannulated piglets were used to evaluate the effects of soybean protein hydrolysate (SPH) on feed intake and anorectic hormone release, including cholecystokinin (CCK), peptide YY (PYY), glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) in the hepatic vein by infusing SPH. Identifying which nutrient-sensing receptor in pig duodenum response to SPH stimulation for gut hormone release was conducted. Using its antagonist, the role of the identified receptor in feed intake and anorectic hormone release was also investigated. Combination with an ex vivo perfusion system, the possible mechanism by which SPH exerts the effects in porcine duodenum was further illustrated. Results in vivo showed that intraduodenal infusion of SPH inhibited short-term feed intake in pigs and promoted CCK, PYY, and GIP secretion in the hepatic vein. SPH also increased duodenum calcium-sensing receptor (CaSR) expression. Pre-treated with CaSR antagonist NPS 2143, the feed intake of pigs tended to be attenuated by SPH (P = 0.09), and CCK release was also suppressed (P < 0.05), indicating that CaSR was involved in SPH-stimulated CCK release and inhibited feed intake in pigs. The ex vivo perfused duodenum tissues revealed that SPH-triggered CCK secretion was likeliest due to the activation of the intracellular Ca2+/TRPM5 pathway. Overall, this study's result illustrates that the diet soybean protein might decrease appetite in pigs by triggering duodenum CCK secretion by activating CaSR and the intracellular Ca2+/TRPM5 pathway.

The Involvement of Macrophage Colony Stimulating Factor on Protein Hydrolysate Injection Mediated Hematopoietic Function Improvement.

Protein hydrolysate injection (PH) is a sterile solution of hydrolyzed protein and sorbitol that contains 17 amino acids and has a molecular mass of 185.0-622.0 g/mol. This study investigated the effect of PH on hematopoietic function in K562 cells and mice with cyclophosphamide (CTX)-induced hematopoietic dysfunction. In these myelosuppressed mice, PH increased the number of hematopoietic cells in the bone marrow (BM) and regulated the concentration of several factors related to hematopoietic function. PH restored peripheral blood cell concentrations and increased the numbers of hematopoietic stem cells and progenitor cells (HSPCs), B lymphocytes, macrophages, and granulocytes in the BM of CTX-treated mice. Moreover, PH regulated the concentrations of macrophage colony stimulating factor (M-CSF), interleukin (IL)-2, and other hematopoiesis-related cytokines in the serum, spleen, femoral condyle, and sternum. In K562 cells, the PH-induced upregulation of hematopoiesis-related proteins was inhibited by transfection with M-CSF siRNA. Therefore, PH might benefit the BM hematopoietic system via the regulation of M-CSF expression, suggesting a potential role for PH in the treatment of hematopoietic dysfunction caused by cancer therapy.

Hydrolysed Formulas in the Management of Cow's Milk Allergy: New Insights, Pitfalls and Tips.

An allergy to cow's milk requires the avoidance of cow's milk proteins and, in some infants, the use of a hypoallergenic formula. This review aims to summarize the current evidence concerning different types of hydrolysed formulas (HF), and recommendations for the treatment of IgE- and non-IgE-mediated cow's milk allergy and functional gastrointestinal disorders in infancy, for which some dietary intervention and HF may be of benefit to both immune and motor mechanisms. Current guidelines recommend cow's milk protein (i.e., whey or casein) extensively hydrolysed formula (eHF) as the first choice for cow's milk allergy treatment, and amino acid formulas for more severe cases or those with reactions to eHF. Rice hydrolysed formulas (rHF) have also become available in recent years. Both eHF and rHF are well tolerated by the majority of children allergic to cow's milk, with no concerns regarding body growth or adverse effects. Some hydrolysates may have a pro-active effect in modulating the immune system due to the presence of small peptides and additional components, like biotics. Despite encouraging results on tolerance acquisition, evidence is still not conclusive, thus hampering our ability to draw firm conclusions. In clinical practice, the choice of hypoallergenic formula should be based on the infant's age, the severity, frequency and persistence of symptoms, immune phenotype, growth pattern, formula cost, and in vivo proof of tolerance and efficacy.

Collagen-Containing Fish Sidestream-Derived Protein Hydrolysates Support Skin Repair via Chemokine Induction.

Restoring homeostasis following tissue damage requires a dynamic and tightly orchestrated sequence of molecular and cellular events that ensure repair and healing. It is well established that nutrition directly affects skin homeostasis, while malnutrition causes impaired tissue healing. In this study, we utilized fish sidestream-derived protein hydrolysates including fish collagen as dietary supplements, and investigated their effect on the skin repair process using a murine model of cutaneous wound healing. We explored potential differences in wound closure and histological morphology between diet groups, and analyzed the expression and production of factors that participate in different stages of the repair process. Dietary supplementation with fish sidestream-derived collagen alone (Collagen), or in combination with a protein hydrolysate derived from salmon heads (HSH), resulted in accelerated healing. Chemical analysis of the tested extracts revealed that Collagen had the highest protein content and that HSH contained the great amount of zinc, known to support immune responses. Indeed, tissues from mice fed with collagen-containing supplements exhibited an increase in the expression levels of chemokines, important for the recruitment of immune cells into the damaged wound region. Moreover, expression of a potent angiogenic factor, vascular endothelial growth factor-A (VEGF-A), was elevated followed by enhanced collagen deposition. Our findings suggest that a 5%-supplemented diet with marine collagen-enriched supplements promotes tissue repair in the model of cutaneous wound healing, proposing a novel health-promoting use of fish sidestreams.

Gastrointestinal Tolerance and Protein Absorption Markers with a New Peptide Enteral Formula Compared to a Standard Intact Protein Enteral Formula in Critically Ill Patients.

The aim of this exploratory study was to investigate gastrointestinal tolerance and protein absorption markers with a new enteral peptide formula (PF) compared to an isocaloric enteral intact protein standard formula (SF) containing the same amount of protein in ICU patients. Patients admitted to a cardio-thoracic intensive care unit expected to receive tube feeding for ≥5 days were randomized to receive either PF (1.5 kcal/mL) or SF in a double-blind manner for ≤14 days. Twenty-six patients were randomized (13 SF and 13 PF) and 23 (12 SF and 11 PF) completed at least 5 days of product administration. There were no statistically significant differences between the feeds during the first 5 days of intervention for diarrhea (SF:3 (23%); PF:5 (39%), p = 0.388), vomiting (SF:1 (8%); PF:2 (15%), p = 0.549), constipation (SF:7 (54%), PF:3 (23%), p = 0.115), and high gastric residual volume (>500 mL: SF:1 (8%); PF: 2 (15%), p = 0.535). There were no differences in plasma amino acids or urinary markers of protein absorption and metabolism. In conclusion, no major differences were found in tolerability and protein absorption markers between the standard intact protein formula and the peptide formula.

Fast Anxiolytic-Like Effect Observed in the Rat Conditioned Defensive Burying Test, after a Single Oral Dose of Natural Protein Extract Products.

Anxiety appears among the most frequent psychiatric disorders. During recent years, a growing incidence of anxiety disorders can be attributed, at least in part, to the modification of our eating habits. To treat anxiety disorders, clinicians use benzodiazepines, which unfortunately display many side effects. Herein, the anxiolytic-like properties of two natural products (αS1-casein hydrolysate and Gabolysat®) were investigated in rats and compared to the efficacy of benzodiazepine (diazepam). Thus, the conditioned defensive burying test was performed after a unique oral dose of 15 mg/kg, at two time-points (60 min and then 30 min post oral gavage) to show potential fast-onset of anxiolytic effect. Both natural products proved to be as efficient as diazepam to reduce the time rats spent burying the probe (anxiety level). Additionally, when investigated as early as 30 min post oral gavage, Gabolysat® also revealed a fast-anxiolytic activity. To date, identification of bioactive peptide, as well as how they interact with the gut-brain axis to sustain such anxiolytic effect, still remains poorly understood. Regardless, this observational investigation argues for the consideration of natural compounds in care pathway.

A Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy of a Hydrolyzed Chicken Collagen Type II Supplement in Alleviating Joint Discomfort.

Joint pain and disease affects more than one in four adults in the United States. We conducted a double-blind, randomized, placebo-controlled trial to investigate the efficacy of a hydrolyzed chicken collagen type II (HCII) supplement in reducing joint-related discomfort such as pain and stiffness, and in improving mobility. We enrolled adults aged 40-65 (65.5% were women) who had joint discomfort, but had no co-morbidities, and who were not taking pain medications. The participants were randomized to receive either the HCII supplement (n = 47) or a placebo (n = 43) for eight weeks. At the baseline, and at week 4 and week 8, we administered the Western Ontario and McMaster Universities Arthritis Index (WOMAC) survey with three additional wrist-related questions and the Visual Analog Scale for assessments of joint-related symptoms. In the WOMAC stiffness and physical activity domains and in the overall WOMAC score, the HCII group had a significant reduction in joint-related discomforts compared with the placebo group. For example, at week 4, the HCII group had a 36.9% reduction in the overall WOMAC score, compared with a 14.3% reduction in the placebo group (p = 0.027). This HCII product is effective in reducing joint pain and stiffness and in improving joint function among otherwise healthy adults.

Health Aspects, Growth Performance, and Meat Quality of Rabbits Receiving Diets Supplemented with Lettuce Fertilized with Whey Protein Hydrolysate Substituting Nitrate.

Lettuce (Lactuca sativa) was grown using a foliar spray with whey protein hydrolysate (WPH) as opposed to normal nitrate fertilization. Lettuce juice was prepared from lettuce cultivated without any fertilization, nitrate fertilization, or WPH. Sixty weaned, 4-week-old male V-line rabbits with an average 455 ± 6 g body weight were randomly divided into 4 groups (n = 15) and administered different lettuce juices. Rabbits administered WPH-fertilized lettuce showed significantly higher (n = 5, p < 0.05) body weight and carcass weight than those receiving nitrate-fertilized lettuce. Rabbits administered nitrate-fertilized lettuce were associated with significantly (p < 0.05) higher levels of liver enzyme activities (AST, ALT, and ALP), bilirubin (total, direct, and indirect), and kidney biomarkers (creatinine, urea, and uric acid). Rabbits administered WPH-fertilized lettuce avoided such increases and exhibited normal levels of serum proteins. Rabbits administered nitrate-fertilized lettuce manifested significantly (p < 0.05) lower RBCs and Hb levels than that of the other groups, while those receiving WPH-fertilized lettuce showed the highest levels. Liver and kidney sections of rabbits receiving WPH-fertilized lettuce witnessed the absence of the histopathological changes induced by feeding on nitrate-fertilized lettuce and produced higher quality meat. WPH-lettuce can substitute nitrate-fertilized lettuce in feeding rabbits for better performance and health aspects.

Strategies and Future Opportunities for the Prevention, Diagnosis, and Management of Cow Milk Allergy.

The prevalence of food allergy has increased over the last 20-30 years, including cow milk allergy (CMA) which is one of the most common causes of infant food allergy. International allergy experts met in 2019 to discuss broad topics in allergy prevention and management of CMA including current challenges and future opportunities. The highlights of the meeting combined with recently published developments are presented here. Primary prevention of CMA should start from pre-pregnancy with a focus on a healthy lifestyle and food diversity to ensure adequate transfer of inhibitory IgG- allergen immune complexes across the placenta especially in mothers with a history of allergic diseases and planned c-section delivery. For non-breastfed infants, there is controversy about the preventive role of partially hydrolyzed formulae (pHF) despite some evidence of health economic benefits among those with a family history of allergy. Clinical management of CMA consists of secondary prevention with a focus on the development of early oral tolerance. The use of extensive Hydrolysate Formulae (eHF) is the nutrition of choice for the majority of non-breastfed infants with CMA; potentially with pre-, probiotics and LCPUFA to support early oral tolerance induction. Future opportunities are, among others, pre- and probiotics supplementation for mothers and high-risk infants for the primary prevention of CMA. A controlled prospective study implementing a step-down milk formulae ladder with various degrees of hydrolysate is proposed for food challenges and early development of oral tolerance. This provides a more precise gradation of milk protein exposure than those currently recommended.

Postprandial amino acid availability after intake of intact or hydrolyzed meat protein in a mixed meal in healthy elderly subjects: a randomized, single blind crossover trial.

The absorption of dietary proteins affects the anabolic response, among others protein synthesis. For elderly, optimal amino acid absorption is warranted to preserve the amino acid pool of the body, especially skeletal muscle proteins. Therefore, the aim of this study was to characterize if hydrolyzing meat protein (HMP) would improve the amino acid absorption after ingestion of meat compared to equal amounts of the same meat proteins but present in a different structure; steak or minced meat. With a crossover study design on 12 healthy older adults (> 65 years of age, BMI 18.5-30), the amino acid absorption kinetics were explored by ingesting 0.55 g protein/kg LBM as a mixed meal together with intrinsically [2H5]phenylalanine labeled meat proteins prepared as a STEAK, MINCED meat, or HMP. Plasma [2H5]phenylalanine enrichment as well as AA concentrations were measured by mass spectrometry from blood samples drawn during a 5-h postprandial period. After HMP ingestion, [2H5]phenylalanine was faster absorbed in the initial 2 h compared to STEAK and MINCED. The peak time in AA concentrations was faster in HMP compared to STEAK and MINCED. However, the peak AA concentrations were not different between STEAK, MINCED, and HMP. Although HMP showed to have the fastest initial amino acid appearance in older adults, the peak EAA concentrations were similar after ingesting meal with either STEAK, MINCED, or HMP in the 5-h postprandial period.

Anti-hyperuricemic and nephroprotective effects of whey protein hydrolysate in potassium oxonate induced hyperuricemic rats.

BACKGROUND: Hyperuricemia (HUA) is a serious public health concern globally that needs to be solved. It is closely related to gout and other metabolic diseases. To develop a safe and effective dietary supplementation for alleviating HUA, we investigated the effects of whey protein hydrolysate (WPH) on HUA and associated renal dysfunction and explored their underlying mechanism. RESULTS: Potassium oxonate was used to induce HUA in model rats, who were then administered WPH for 21 days. The results showed that WPH significantly inhibited xanthine oxidase and adenosine deaminase activity in serum and liver, decreased uric acid (UA), creatinine, and blood urea nitrogen levels in serum, and increased the UA excretion in urine. In addition, WPH downregulated the expression of urate transporter 1 and upregulated the expression of organic anion transporter 1, adenosine triphosphate binding cassette subfamily G member 2, organic cation/carnitine transporters 1 and 2, and organic cation transporter 1 in kidneys. CONCLUSION: These findings demonstrated for the first time that WPH could alleviate HUA by inhibiting UA production and promoting UA excretion, and improve the renal dysfunction caused by HUA. Thus, WPH may be a potential functional ingredient for the prevention and treatment of HUA and associated renal dysfunction. © 2021 Society of Chemical Industry.

Protein Substitutes in PKU; Their Historical Evolution.

Protein substitutes developed for phenylketonuria (PKU) are a synthetic source of protein commonly based on L-amino acids. They are essential in the treatment of phenylketonuria (PKU) and other amino acid disorders, allowing the antagonistic amino acid to be removed but with the safe provision of all other amino acids necessary for maintaining normal physiological function. They were first formulated by a chemist and used experimentally on a 2-year-old girl with PKU and their nutritional formulations and design have improved over time. Since 2008, a bioactive macropeptide has been used as a base for protein substitutes in PKU, with potential benefits of improved bone and gut health, nitrogen retention, and blood phenylalanine control. In 2018, animal studies showed that physiomimic technology coating the amino acids with a polymer allows a slow release of amino acids with an improved physiological profile. History has shown that in PKU, the protein substitute's efficacy is determined by its nutritional profile, amino acid composition, dose, timing, distribution, and an adequate energy intake. Protein substitutes are often given little importance, yet their pharmacological actions and clinical benefit are pivotal when managing PKU.

Absorption Kinetics of Ethanolamine Plasmalogen and Its Hydrolysate in Mice.

Ethanolamine plasmalogen (PlsEtn), a subclass of ethanolamine glycerophospholipid (EtnGpl), has been reported to have many biological and dietary functions. In terms of PlsEtn absorption, some studies have reported that PlsEtn is re-esterized at the sn-2 position using lymph cannulation and the everted jejunal sac model. In this study, we aimed to better understand the uptake kinetics of PlsEtn and increase its absorption. We thus compared the uptake kinetics of PlsEtn with that of the lyso-form, in which the fatty acid at the sn-2 position was hydrolyzed enzymatically. Upon administration of EtnGpl (extracted from oysters or ascidians, 75.4 mol% and 88.4 mol% of PlsEtn ratio, respectively), the plasma PlsEtn species in mice showed the highest levels at 4 or 8 hours after administration. In the contrast, administration of the EtnGpl hydrolysate, which contained lysoEtnGpl and free fatty acids, markedly increased the plasma levels of PlsEtn species at 2 h after administration. The area under the plasma concentration-time curve (AUC), especially the AUC0-4 h of PlsEtn species, was higher with hydrolysate administration than that with EtnGpl administration. These results indicate that EtnGpl hydrolysis accelerated the absorption and metabolism of PlsEtn. Consequently, using a different experimental approach from that used in previous studies, we reconfirmed that PlsEtn species were absorbed via hydrolysis at the sn-2 position, suggesting that hydrolysis in advance could increase PlsEtn uptake.

Limited Benefit of Marine Protein Hydrolysate on Physical Function and Strength in Older Adults: A Randomized Controlled Trial.

Age-related muscle wasting can compromise functional abilities of the elderly. Protein intake stimulates muscle protein synthesis; however, ageing muscle is more resistant to stimuli. This double-blinded, randomized, controlled trial is one of the first registered studies to evaluate the effects of a supplement of marine protein hydrolysate (MPH) on measures of physical function and strength. Eighty-six older adults received nutritional supplements containing 3 g of MPH or a placebo for up to 12 months. Short Physical Performance Battery (SPPB), grip strength and gait speed were measured, and dietary intake was registered at baseline, 6 months, and 12 months. No difference was found between the intervention and control groups in mean change in SPPB (independent sample t-test, p = 0.41) or regarding time trend in SPPB, grip strength, or gait speed (linear mixed model). The participants in our study were well functioning, causing a ceiling effect in SPPB. Further, they had sufficient protein intake and were physically active. Differences in physical function between those completing the intervention and the dropouts might also have created bias in the results. We recommend that future studies of MPH be carried out on a more frail or malnourished population.

Glucagon-like peptide-1 regulation by food proteins and protein hydrolysates.

Glucagon-like peptide-1 (GLP-1) is an enterohormone with a key role in several processes controlling body homeostasis, including glucose homeostasis and food intake regulation. It is secreted by the intestinal cells in response to nutrients, such as glucose, fat and amino acids. In the present review, we analyse the effect of protein on GLP-1 secretion and clearance. We review the literature on the GLP-1 secretory effects of protein and protein hydrolysates, and the mechanisms through which they exert these effects. We also review the studies on protein from different sources that has inhibitory effects on dipeptidyl peptidase-4 (DPP4), the enzyme responsible for GLP-1 inactivation, with particular emphasis on specific sources and treatments, and the gaps there still are in knowledge. There is evidence that the protein source and the hydrolytic processing applied to them can influence the effects on GLP-1 signalling. The gastrointestinal digestion of proteins, for example, significantly changes their effectiveness at modulating this enterohormone secretion in both in vivo and in vitro studies. Nevertheless, little information is available regarding human studies and more research is required to understand their potential as regulators of glucose homeostasis.