A real-world cross-sectional study evaluating the role of an oral amino acid-based supplement in nutrient intake by preschoolers on a cow's milk elimination diet.

INTRODUCTION AND OBJECTIVES: Food allergy has several negative nutritional consequences and may persist beyond the first year of lives. This study aimed to assess the role of a complete oral amino acid-based supplement in the diet of children on cow's milk protein elimination diet because of food allergy. MATERIALS AND METHODS: This study included two groups of children aged 1-5 years paired by age and socioeconomic status: (1) study group, on cow's milk protein elimination diet plus an oral amino acid-based supplement, and (2) control group, on cow's milk protein elimination diet. Sociodemographic, clinical, anthropometric, and dietary data were obtained through online interviews. Two 24-h dietary recalls were collected on nonconsecutive days. Both groups comprised mostly boys. RESULTS: The study group presented lower values of body mass index. The frequency of feeding difficulties was similar between groups. The study group had a higher intake of energy, protein, carbohydrates, calcium, iron, zinc, phosphorus, magnesium, copper, selenium, vitamins D, E, B1, B2, B6, and B12, niacin, and folic acid compared to the control group. A higher proportion of children in the study group had adequate intake according to the recommendations made for energy, carbohydrates, iron, phosphorus, selenium, vitamins A, D, E, B1, B2, and B6, and folic acid. CONCLUSIONS: The use of a complete oral amino acid-based supplement has a positive effect on the diet quality of preschoolers on cow's milk elimination diet because of food allergy, promoting higher intake of energy, calcium, vitamin D, and other essential nutrients.

Ingestion of a variety of non-animal-derived dietary protein sources results in diverse postprandial plasma amino acid responses which differ between young and older adults.

Whole-body tissue protein turnover is regulated, in part, by the postprandial rise in plasma amino acid concentrations, although minimal data exist on the amino acid response following non-animal-derived protein consumption. We hypothesised that the ingestion of novel plant- and algae-derived dietary protein sources would elicit divergent plasma amino acid responses when compared with vegan- and animal-derived control proteins. Twelve healthy young (male (m)/female (f): 6/6; age: 22 ± 1 years) and 10 healthy older (m/f: 5/5; age: 69 ± 2 years) adults participated in a randomised, double-blind, cross-over trial. During each visit, volunteers consumed 30 g of protein from milk, mycoprotein, pea, lupin, spirulina or chlorella. Repeated arterialised venous blood samples were collected at baseline and over a 5-h postprandial period to assess circulating amino acid, glucose and insulin concentrations. Protein ingestion increased plasma total and essential amino acid concentrations (P < 0·001), to differing degrees between sources (P < 0·001), and the increase was further modulated by age (P < 0·001). Postprandial maximal plasma total and essential amino acid concentrations were highest for pea (2828 ± 106 and 1480 ± 51 µmol·l-1) and spirulina (2809 ± 99 and 1455 ± 49 µmol·l-1) and lowest for chlorella (2053 ± 83 and 983 ± 35 µmol·l-1) (P < 0·001), but were not affected by age (P > 0·05). Postprandial total and essential amino acid availabilities were highest for pea, spirulina and mycoprotein and lowest for chlorella (all P < 0·05), but no effect of age was observed (P > 0·05). The ingestion of a variety of novel non-animal-derived dietary protein sources elicits divergent plasma amino acid responses, which are further modulated by age.

Vitamin D supplementation and increased dairy protein intake do not affect muscle strength or physical function in healthy 6-8-year-old children: the D-pro randomized trial.

PURPOSE: To investigate separate and combined effects of vitamin D supplementation during the extended winter and increased dairy protein intake on muscle strength and physical function in children, and furthermore to explore potential sex differences. METHODS: In a 2 × 2-factorial, randomized winter trial, 183 healthy, 6-8-year-old children received blinded tablets with 20 µg/day vitamin D3 or placebo, and substituted 260 g/day dairy with yogurts with high (HP, 10 g protein/100 g) or normal protein content (NP, 3.5 g protein/100 g) for 24 weeks during winter at 55° N. We measured maximal isometric handgrip and leg press strength, and physical function by jump tests and a 30 s sit-to-stand test. Physical activity was measured by 7-day accelerometry. RESULTS: Baseline (mean ± SD) serum 25-hydroxyvitamin D was 80.8 ± 17.2 nmol/L, which increased to 88.7 ± 17.6 nmol/L with vitamin D supplementation and decreased to 48.4 ± 19.2 nmol/L with placebo. Baseline protein intake was 15.5 ± 2.4 E%, which increased to 18.4 ± 3.4 E% with HP and was unchanged with NP. We found no separate or combined effects of vitamin D supplementation and/or increased dairy protein intake on muscle strength or physical function (all P > 0.20). There was an interaction on the sit-to-stand test (Pvitamin×yogurt = 0.02), which however disappeared after adjusting for physical activity (P = 0.16). Further, vitamin D supplementation increased leg press strength relatively more in girls compared to boys (mean [95% CI] 158 [17, 299] N; Pvitamin×sex = 0.047). CONCLUSION: Overall, vitamin D and dairy protein supplementation during the extended winter did not affect muscle strength or physical function in healthy children. Potential sex differences of vitamin D supplementation should be investigated further. REGISTERED AT CLINICALTRIALS.GOV: NCT0395673.

From Mum to Bum: An Observational Study Protocol to Follow Digestion of Human Milk Oligosaccharides and Glycoproteins from Mother to Preterm Infant.

The nutritional requirements of preterm infants are challenging to meet in neonatal care, yet crucial for their growth, development and health. Aberrant maturation of the gastrointestinal tract and the microbiota could affect the digestion of human milk and its nutritional value considerably. Therefore, the main objective of the proposed research is to investigate how the intestinal microbiota of preterm and full-term infants differ in their ability to extract energy and nutrients from oligosaccharides and glycoproteins in human milk. This pilot study will be an observational, single-center study performed at the Neonatal Intensive Care Unit at Isala Women and Children's Hospital (Zwolle, The Netherlands). A cohort of thirty mother-infant pairs (preterm ≤30 weeks of gestation, n = 15; full-term 37-42 weeks of gestation, n = 15) will be followed during the first six postnatal weeks with follow-up at three- and six-months postnatal age. We will collect human milk of all mothers, gastric aspirates of preterm infants and fecal samples of all infants. A combination of 16S rRNA amplicon sequencing, proteomics, peptidomics, carbohydrate analysis and calorimetric measurements will be performed. The role of the microbiota in infant growth and development is often overlooked yet offers opportunities to advance neonatal care. The 'From Mum to Bum' study is the first study in which the effect of a preterm gut microbiota composition on its metabolic capacity and subsequent infant growth and development is investigated. By collecting human milk of all mothers, gastric aspirates of preterm infants and fecal samples of all infants at each timepoint, we can follow digestion of human milk from the breast of the mother throughout the gastrointestinal tract of the infant, or 'From Mum to Bum'.

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.

The effect of milk and rapeseed protein on growth factors in 7-8 year-old healthy children - A randomized controlled trial.

OBJECTIVE: Milk protein may stimulate linear growth through insulin-like growth factor-1 (IGF-1). However, the effect of plant proteins on growth factors is largely unknown. This study assesses the effect of combinations of milk and rapeseed protein versus milk protein alone on growth factors in children. DESIGN: An exploratory 3-armed randomized, double-blind, controlled trial was conducted in 129 healthy 7-8 year-old Danish children. Children received 35 g milk and rapeseed protein (ratio 54:46 or 30:70) or 35 g milk protein per day for 4 weeks. The primary outcome was difference in IGF-1 changes between intervention groups after 4 weeks. Secondary outcomes included changes in IGF-1 after 1 week and changes in insulin-like growth factor binding protein-3 (IGFBP-3), IGF-1/IGFBP-3, insulin, height, weight and body composition after 1 and 4 weeks. Results were analysed by multiple linear mixed-effect models. RESULTS: There were no differences in changes of plasma IGF-1, insulin-like growth factor binding protein-3 (IGFBP-3), IGF-1/IGFBP-3 ratio or insulin between groups after 1 or 4 weeks based on 89 complete cases (P > 0.10). IGF-1 increased by 13.7 (95% CI 9.7;17.7) ng/mL and 18.0 (14.0;22.0) ng/mL from baseline to week 1 and 4, respectively, a 16% increase during the intervention. Similarly, insulin increased by 31% (14; 50) and 33% (16; 53) from baseline to week 1 and 4. Fat-free mass index (FFMI) increments were higher with milk alone than rapeseed blends (P < 0.05), coinciding with a trend towards a lower height increment. Body mass index increased within all groups (P < 0.05), mainly due to an increase in FFMI (P < 0.01). CONCLUSION: There were no differences in changes of growth factors between the combinations of milk and rapeseed protein and milk protein alone in healthy, well-nourished children with a habitual intake of milk. Within groups, growth factors increased considerably. Future studies are needed to investigate how intakes of plant and animal proteins affect childhood growth.

Protein nanoparticles in drug delivery: animal protein, plant proteins and protein cages, albumin nanoparticles.

In this article, we will describe the properties of albumin and its biological functions, types of sources that can be used to produce albumin nanoparticles, methods of producing albumin nanoparticles, its therapeutic applications and the importance of albumin nanoparticles in the production of pharmaceutical formulations. In view of the increasing use of Abraxane and its approval for use in the treatment of several types of cancer and during the final stages of clinical trials for other cancers, to evaluate it and compare its effectiveness with conventional non formulations of chemotherapy Paclitaxel is paid. In this article, we will examine the role and importance of animal proteins in Nano medicine and the various benefits of these biomolecules for the preparation of drug delivery carriers and the characteristics of plant protein Nano carriers and protein Nano cages and their potentials in diagnosis and treatment. Finally, the advantages and disadvantages of protein nanoparticles are mentioned, as well as the methods of production of albumin nanoparticles, its therapeutic applications and the importance of albumin nanoparticles in the production of pharmaceutical formulations.

Insects are a viable protein source for human consumption: from insect protein digestion to postprandial muscle protein synthesis in vivo in humans: a double-blind randomized trial.

BACKGROUND: Insects have recently been identified as a more sustainable protein-dense food source and may represent a viable alternative to conventional animal-derived proteins. OBJECTIVES: We aimed to compare the impacts of ingesting lesser mealworm- and milk-derived protein on protein digestion and amino acid absorption kinetics, postprandial skeletal muscle protein synthesis rates, and the incorporation of dietary protein-derived amino acids into de novo muscle protein at rest and during recovery from exercise in vivo in humans. METHODS: In this double-blind randomized controlled trial, 24 healthy, young men ingested 30 g specifically produced, intrinsically l-[1-13C]-phenylalanine and l-[1-13C]-leucine labeled lesser mealworm- or milk-derived protein after a unilateral bout of resistance-type exercise. Primed continuous l-[ring-2H5]-phenylalanine, l-[ring-3,5-2H2]-tyrosine, and l-[1-13C]-leucine infusions were applied, with frequent collection of blood and muscle tissue samples. RESULTS: A total of 73% ± 7% and 77% ± 7% of the lesser mealworm and milk protein-derived phenylalanine was released into the circulation during the 5 h postprandial period, respectively, with no significant differences between groups (P < 0.05). Muscle protein synthesis rates increased after both lesser mealworm and milk protein concentrate ingestion from 0.025 ± 0.008%/h to 0.045 ± 0.017%/h and 0.028 ± 0.010%/h to 0.056 ± 0.012%/h at rest and from 0.025 ± 0.012%/h to 0.059 ± 0.015%/h and 0.026 ± 0.009%/h to 0.073 ± 0.020%/h after exercise, respectively (all P < 0.05), with no differences between groups (both P > 0.05). Incorporation of mealworm and milk protein-derived l-[1-13C]-phenylalanine into de novo muscle protein was greater after exercise than at rest (P < 0.05), with no differences between groups (P > 0.05). CONCLUSIONS: Ingestion of a meal-like amount of lesser mealworm-derived protein is followed by rapid protein digestion and amino acid absorption and increases muscle protein synthesis rates both at rest and during recovery from exercise. The postprandial protein handling of lesser mealworm does not differ from ingesting an equivalent amount of milk protein concentrate in vivo in humans.This trial was registered at www.trialregister.nl as NL6897.

Functional constipation related to cow's milk allergy in children: A management proposal.

Functional constipation (FC) is one of the most common disorders in childhood and has a negative impact on the quality of life of children. Scientific evidence regarding a causal relationship between FC and cow's milk allergy is controversial, as it is also reported by the latest European Society for Paediatric Gastroenterology, Hepatology and Nutrition-North American Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN-NASPGHAN) recommendations. In the case of FC, routine allergometric tests are not recommended and the cows' milk-free diet is only proposed in the case of laxative-resistant constipation and only following the advice of an expert. Instead, after a careful review of the literature and in view of the many clinical cases encountered in our clinical practice, we believe that it is useful to propose cows' milk-free diet as first line for the treatment of FC at least in pre-school children and in children with a personal or family history of atopy or with a previous diagnosis of cow's milk protein allergy.

Whole and Isolated Protein Fractions Differentially Affect Gastrointestinal Integrity Markers in C57Bl/6 Mice Fed Diets with a Moderate-Fat Content.

Various proteins or protein fractions reportedly positively affect gastrointestinal integrity and inflammation in diets providing >45% energy as fat. This study tested whether benefits were seen in diets providing 30% of energy as fat. Purified diets (PD) with isolated soy protein (ISP), dried whole milk powder (DWMP), milk fat globule membrane (MFGM), or milk protein concentrate (MPC) as protein sources were fed to C57BL/6J mice (n = 15/diet group) for 13 weeks. MFGM-fed mice were heaviest (p < 0.005) but remained within breeder norms. Growth rates and gut motility were similar for all PD-fed mice. FITC-dextran assessed gut permeability was lowest in DWMP and MFGM (p = 0.054); overall, plasma endotoxin and unprovoked circulating cytokines indicated a non-inflammatory state for all PD-fed mice. Despite differences in cecal butyrate and intestinal gene expression, all PDs supported gastrointestinal health. Whole milk provided more positive effects compared to its fractions. However, ISP-fed mice showed a >370%, (p < 0.006) increase in colonic myeloperoxidase activity indicative of tissue neutrophil infiltration. Surprisingly, FITC-dextran and endotoxin outcomes were many folds better in PD-fed mice than mice (strain, vendor, age and sex matched) fed a "chow-type" nutritionally adequate non-PD. Additional variables within a diet's matrix appear to affect routine indicators or gastrointestinal health.

A Human Milk-Based Protein Concentrate Developed for Preterm Infants Retains Bioactive Proteins and Supports Growth of Weanling Rats.

BACKGROUND: Bovine milk-based protein modulars are currently available to nutrient-enrich enteral feedings; however, they have limitations for use in very-low-birth-weight infants. OBJECTIVES: Our objectives were to develop a human milk-based protein (HMP) concentrate and to conduct a preclinical assessment of the HMP concentrate in weanling rats. METHODS: An HMP concentrate was produced from donor milk using pressure-driven membrane filtration processes and high hydrostatic pressure processing. Protein and lactoferrin concentrations and lysozyme activity were determined by Kjeldahl, HPLC, and turbidimetric assay, respectively. Male Sprague Dawley rats 24 d old (n = 30) were randomly assigned to 1 of 3 isocaloric AIN-93G diets for 4 wk containing 100% casein (control) or with 50% of the casein replaced with the HMP concentrate (treatment) or a bovine whey protein isolate (treatment). Body weight, food intake, fat mass, plasma amino acid profiles, and organ weights were measured. Data were analyzed using linear regression models. RESULTS: Raw donor milk contained (mean ± SD) 101 ± 6 g protein/kg and 5 ± 1 g lactoferrin/kg of milk solids. Postprocessing, protein and lactoferrin concentrations were 589 ± 3 g/kg and 29 ± 10 g/kg, respectively. Lysozyme activity was initially 209 ± 4 U/kg and increased to 959 ± 39 U/kg in the HMP concentrate. There were no statistically significant differences in body weight, food intake, fat mass, or plasma amino acid profiles between rats fed diets containing the HMP concentrate and the control diet. Full cecum weights were higher in rats fed the HMP concentrate than in those fed control diets (mean difference: 5.59 g; 95% CI: 4.50, 6.68 g; P < 0.0001), likely reflecting the concentration of human milk oligosaccharides. No differences were found for other organ weights. CONCLUSIONS: The HMP concentrate retained important bioactive proteins and supported normal rat growth in the preclinical assessment.

Daily protein supplementation attenuates immobilization-induced blunting of postabsorptive muscle mTORC1 activation in middle-aged men.

Disuse-induced muscle atrophy is accompanied by a blunted postprandial response of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Conflicting observations exist as to whether postabsorptive mTORC1 pathway activation is also blunted by disuse and plays a role in atrophy. It is unknown whether changes in habitual protein intake alter mTORC1 regulatory proteins and how they may contribute to the development of anabolic resistance. The primary objective of this study was to characterize the downstream responsiveness of skeletal muscle mTORC1 activation and its upstream regulatory factors, following 14 days of lower limb disuse in middle-aged men (45-60 yr). The participants were further randomized to receive daily supplementation of 20 g/d of protein (n = 12; milk protein concentrate) or isocaloric carbohydrate placebo (n = 13). Immobilization reduced postabsorptive skeletal muscle phosphorylation of the mTORC1 downstream targets, 4E-BP1, P70S6K, and ribosomal protein S6 (RPS6), with phosphorylation of the latter two decreasing to a greater extent in the placebo, compared with the protein supplementation groups (37% ± 13% vs. 14% ± 11% and 38% ± 20% vs. 25% ± 8%, respectively). Sestrin2 protein was also downregulated following immobilization irrespective of supplement group, despite a corresponding increase in its mRNA content. This decrease in Sestrin2 protein was negatively correlated with the immobilization-induced change in the in silico-predicted regulator miR-23b-3p. No other measured upstream proteins were altered by immobilization or supplementation. Immobilization downregulated postabsorptive mTORC1 pathway activation, and 20 g/day of protein supplementation attenuated the decrease in phosphorylation of targets regulating muscle protein synthesis.

The Use of Bovine Colostrum in Medical Practice and Human Health: Current Evidence and Areas Requiring Further Examination.

Colostrum is produced by the mammary gland for the first few days following birth and is a rich natural source of macro- and micro-nutrients, immunoglobulins, and peptides with anti-microbial, immune modulatory and/or growth-factor activity [...].

Effects of slow- v. fast-digested protein supplementation combined with mixed power training on muscle function and functional capacities in older men.

Ageing leads to a progressive loss of muscle function (MF) and quality (MQ: muscle strength (MS)/lean muscle mass (LM)). Power training and protein (PROT) supplementation have been proposed as efficient interventions to improve MF and MQ. Discrepancies between results appear to be mainly related to the type and/or dose of proteins used. The present study aimed at determining whether or not mixed power training (MPT) combined with fast-digested PROT (F-PROT) leads to greater improvements in MF and MQ in elderly men than MPT combined with slow-digested PROT (S-PROT) or MPT alone. Sixty elderly men (age 69 (sd 7) years; BMI 18-30 kg/m2) were randomised into three groups: (1) placebo + MPT (PLA; n 19); (2) F-PROT + MPT (n 21) and (3) S-PROT + MPT (n 20) completed the intervention. LM, handgrip and knee extensor MS and MQ, functional capacity, serum metabolic markers, skeletal muscle characteristics, dietary intake and total energy expenditure were measured. The interventions consisted in 12 weeks of MPT (3 times/week; 1 h/session) combined with a supplement (30 g:10 g per meal) of F-PROT (whey) or S-PROT (casein) or a placebo. No difference was observed among groups for age, BMI, number of steps and dietary intake pre- and post-intervention. All groups improved significantly their LM, lower limb MS/MQ, functional capacity, muscle characteristics and serum parameters following the MPT. Importantly, no difference between groups was observed following the MPT. Altogether, adding 30 g PROT/d to MPT, regardless of the type, does not provide additional benefits to MPT alone in older men ingesting an adequate (i.e. above RDA) amount of protein per d.

MFG-E8 attenuates inflammation in subarachnoid hemorrhage by driving microglial M2 polarization.

Increasing evidence suggests that microglial polarization plays an important role in the pathological processes of neuroinflammation following subarachnoid hemorrhage (SAH). Previous studies indicated that milk fat globule-epidermal growth factor-8 (MFG-E8) has potential anti-apoptotic and anti-inflammatory effects in cerebral ischemia. However, the effects of MFG-E8 on microglial polarization have not been evaluated after SAH. Therefore, the aim of this study was to explore the role of MFG-E8 in anti-inflammation, and its effects on microglial polarization following SAH. We established the SAH model via prechiasmatic cistern blood injection in mice. Double-immunofluorescence staining, western blotting and quantitative real-time polymerase chain reaction (q-PCR) were performed to investigate the expression and cellular distribution of MFG-E8. Two different dosages (1 and 5 µg) of recombinant human MFG-E8 (rhMFG-E8) were injected intracerebroventricularly (i.c.v.) at 1 h after SAH. Brain water content, neurological scores, beam-walking score, Fluoro-Jade C (FJC), and terminal deoxynucleotidyl transferase dUTP nick endlabeling staining (TUNEL) were measured at 24 h. Suppression of MFG-E8, integrin ß3 and phosphorylation of STAT3 were achieved by specific siRNAs (500 pmol/5 µl) and the STAT3 inhibitor Stattic (5 µM). The potential signaling pathways and microglial polarization were measured by immunofluorescence labeling and western blotting. SAH induction increased the levels of inflammatory mediators and the proportion of M1 cells, and caused neuronal apoptosis in mice at 24 h. Treatment with rhMFG-E8 (5 µg) remarkably decreased brain edema, improved neurological functions, reduced the levels of proinflammatory factors, and promoted the microglial to shift to M2 phenotype. However, knockdown of MFG-E8 and integrin ß3 via siRNA abolished the effects of MFG-E8 on anti-inflammation and M2 phenotype polarization. The STAT3 inhibitor Stattic further clarified the role of rhMFG-E8 in microglial polarization by regulating the protein levels of the integrin ß3/SOCS3/STAT3 pathway. rhMFG-E8 inhibits neuronal inflammation by transformation the microglial phenotype toward M2 and its direct protective effect on neurons after SAH, which may be mediated by modulation of the integrin ß3/SOCS3/STAT3 signaling pathway, highlighting rhMFG-E8 as a potential therapeutic target for the treatment of SAH patients.

Fermented Maillard reaction products attenuate stress-induced testicular dysfunction in mice.

Chronic stress can cause psychological diseases and affect male fertility and the reproductive system. Maillard reaction of milk proteins improves their functional and nutritional properties through modification of proteins. Previously, we determined that Maillard reaction product (MRP) from milk casein and MRP fermented (FMRP) with Lactobacillus rhamnosus 4B15 (4B15) had anti-anxiolytic effects in mice under chronic stress. Therefore, we aimed to investigate the effects of MRP and FMRP on chronic stress-induced testicular dysfunction in mice through quantitative real-time PCR (qRT-PCR) and in situ hybridization analysis. Mice were pretreated with MRP and FMRP for 10 wk; simultaneously, from the third week of the experimental period, they were exposed to unpredictable chronic mild stress (UCMS) for 7 wk. The expression levels of the luteinizing hormone subunit ß (Lhb) and follicle-stimulating hormone subunit ß (Fshb) were remarkably reduced after exposure to UCMS. However, treatment with MRP and FMRP inhibited the UCMS-induced reduction, with FMRP showing especially significant inhibition. Moreover, the expression of steroidogenesis-related genes [luteinizing hormone receptor (Lhr), follicle-stimulating hormone (Fshr), 3-ß hydroxysteroid dehydrogenase 2 (Hsd3b2), and steroidogenic acute regulatory protein (StAR)] were significantly reduced in response to UCMS. In contrast, the transcript levels of these genes were highest in the MRP-treated mice. Mice pretreated with FMRP also exhibited higher levels of gene expression compared with the nonstressed mice. Moreover, UCMS significantly downregulated the expression of genes associated with testicular function [i.e., a disintegrin and metallopeptidase domain 5 (Adam5), Adam29, bone morphogenetic protein 2 (Bmp2), tektin 3 (Tekt3), and sperm adhesion molecule 1 (Spam1)]. However, the administration of MRP and FMRP prevented the UCMS-induced reduction in the expressions of above genes. The localization of Lhr, Srd5a2, Adam29, and Spam1 was confirmed by in situ hybridization analysis and the results were consistent with those of qRT-PCR. Consequently, these results indicated that MRP and FMRP, manufactured by the heat treatment of milk casein and fermentation with probiotic 4B15, have the potential to prevent chronic stress-induced testicular dysfunction.

Impact of food supplements on early child development in children with moderate acute malnutrition: A randomised 2 x 2 x 3 factorial trial in Burkina Faso.

BACKGROUND: Lipid-based nutrient supplements (LNS) and corn-soy blends (CSBs) with varying soy and milk content are used in treatment of moderate acute malnutrition (MAM). We assessed the impact of these supplements on child development. METHODS AND FINDINGS: We conducted a randomised 2 × 2 × 3 factorial trial to assess the effectiveness of 12 weeks' supplementation with LNS or CSB, with either soy isolate or dehulled soy, and either 0%, 20%, or 50% of protein from milk, on child development among 6-23-month-old children with MAM. Recruitment took place at 5 health centres in Province du Passoré, Burkina Faso between September 2013 and August 2014. The study was fully blinded with respect to soy quality and milk content, while study participants were not blinded with respect to matrix. This analysis presents secondary trial outcomes: Gross motor, fine motor, and language development were assessed using the Malawi Development Assessment Tool (MDAT). Of 1,609 children enrolled, 54.7% were girls, and median age was 11.3 months (interquartile range [IQR] 8.2-16.0). Twelve weeks follow-up was completed by 1,548 (96.2%), and 24 weeks follow-up was completed by 1,503 (93.4%); follow-up was similar between randomised groups. During the study, 4 children died, and 102 children developed severe acute malnutrition (SAM). There was no difference in adverse events between randomised groups. At 12 weeks, the mean MDAT z-scores in the whole cohort had increased by 0.33 (95% CI: 0.28, 0.37), p < 0.001 for gross motor; 0.26 (0.20, 0.31), p < 0.001 for fine motor; and 0.14 (0.09, 0.20), p < 0.001 for language development. Children had larger improvement in language z-scores if receiving supplements with milk (20%: 0.09 [-0.01, 0.19], p = 0.08 and 50%: 0.11 [0.01, 0.21], p = 0.02), although the difference only reached statistical significance for 50% milk. Post hoc analyses suggested that this effect was specific to boys (interaction p = 0.02). The fine motor z-scores were also improved in children receiving milk, but only when 20% milk was added to CSB (0.18 [0.03, 0.33], p = 0.02). Soy isolate over dehulled soy increased language z-scores by 0.07 (-0.01, 0.15), p = 0.10, although not statistically significant. Post hoc analyses suggested that LNS benefited gross motor development among boys more than did CSB (interaction p = 0.04). Differences between supplement groups did not persist at 24 weeks, but MDAT z-scores continued to increase post-supplementation. The lack of an unsupplemented control group limits us from determining the overall effects of nutritional supplementation for children with MAM. CONCLUSIONS: In this study, we found that child development improved during and after supplementation for treatment of MAM. Milk protein was beneficial for language and fine motor development, while suggested benefits related to soy quality and supplement matrix merit further investigation. Supplement-specific effects were not found post-intervention, but z-scores continued to improve, suggesting a sustained overall effect of supplementation. TRIAL REGISTRATION: ISRCTN42569496.

Role of Bioactive Peptide Sequences in the Potential Impact of Dairy Protein Intake on Metabolic Health.

For years, there has been an increasing move towards elucidating the complexities of how food can interplay with the signalling networks underlying energy homeostasis and glycaemic control. Dairy foods can be regarded as the greatest source of proteins and peptides with various health benefits and are a well-recognized source of bioactive compounds. A number of dairy protein-derived peptide sequences with the ability to modulate functions related to the control of food intake, body weight gain and glucose homeostasis have been isolated and characterized. Their being active in vivo may be questionable mainly due to expected low bioavailability after ingestion, and hence their real contribution to the metabolic impact of dairy protein intake needs to be discussed. Some reports suggest that the differential effects of dairy proteins-in particular whey proteins-on mechanisms underlying energy balance and glucose-homeostasis may be attributed to their unique amino acid composition and hence the release of free amino acid mixtures enriched in essential amino acids (i.e., branched-chain-amino acids) upon digestion. Actually, the research reports reviewed in this article suggest that, among a number of dairy protein-derived peptides isolated and characterized as bioactive compounds in vitro, some peptides can be active in vivo post-oral administration through a local action in the gut, or, alternatively, a systemic action on specific molecular targets after entering the systemic circulation. Moreover, these studies highlight the importance of the enteroendocrine system in the cross talk between food proteins and the neuroendocrine network regulating energy balance.

Comparison of different protein concentrations of human milk fortifier for promoting growth and neurological development in preterm infants.

BACKGROUND: Human milk alone may provide inadequate amounts of protein to meet the growth requirements of preterm infants because of restrictions in the amount of fluid they can tolerate. It has become common practice to feed preterm infants with breast milk fortified with protein and other nutrients but there is debate about the optimal concentration of protein in commercially available fortifiers. OBJECTIVES: To compare the effects of different protein concentrations in human milk fortifier, fed to preterm infants, on growth and neurodevelopment. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search CENTRAL (2019, Issue 8), Ovid MEDLINE and CINAHL on 15 August 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: We included all published and unpublished randomised, quasi-randomised and cluster-randomised trials comparing two different concentrations of protein in human milk fortifier. We included preterm infants (less than 37 weeks' gestational age). Participants may have been exclusively fed human milk or have been supplemented with formula. The concentration of protein was classified as low (< 1g protein/100 mL expressed breast milk (EBM)), moderate (≥ 1g to < 1.4g protein/100 mL EBM) or high (≥ 1.4g protein/100 mL EBM). We excluded trials that compared two protein concentrations that fell within the same category. DATA COLLECTION AND ANALYSIS: We undertook data collection and analyses using the standard methods of Cochrane Neonatal. Two review authors independently evaluated trials. Primary outcomes included growth, neurodevelopmental outcome and mortality. Data were synthesised using risk ratios (RR), risk differences and mean differences (MD), with 95% confidence intervals (CI). We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We identified nine trials involving 861 infants. There is one trial awaiting classification, and nine ongoing trials. The trials were mostly conducted in infants born < 32 weeks' gestational age or < 1500 g birthweight, or both. All used a fortifier derived from bovine milk. Two trials fed infants exclusively with mother's own milk, three trials gave supplementary feeds with donor human milk and four trials supplemented with preterm infant formula. Overall, trials were small but generally at low or unclear risk of bias. High versus moderate protein concentration of human milk fortifier There was moderate certainty evidence that a high protein concentration likely increased in-hospital weight gain compared to moderate concentration of human milk fortifier (MD 0.66 g/kg/day, 95% CI 0.51 to 0.82; trials = 6, participants = 606). The evidence was very uncertain about the effect of high versus moderate protein concentration on length gain (MD 0.01 cm/week, 95% CI -0.01 to 0.03; trials = 5, participants = 547; very low certainty evidence) and head circumference gain (MD 0.00 cm/week, 95% CI -0.01 to 0.02; trials = 5, participants = 549; very low certainty evidence). Only one trial reported neonatal mortality, with no deaths in either group (participants = 45). Moderate versus low protein concentration of human milk fortifier A moderate versus low protein concentration fortifier may increase weight gain (MD 2.08 g/kg/day, 95% CI 0.38 to 3.77; trials = 2, participants = 176; very low certainty evidence) with little to no effect on head circumference gain (MD 0.13 cm/week, 95% CI 0.00 to 0.26; I² = 85%; trials = 3, participants = 217; very low certainty evidence), but the evidence is very uncertain. There was low certainty evidence that a moderate protein concentration may increase length gain (MD 0.09 cm/week, 95% CI 0.05 to 0.14; trials = 3, participants = 217). Only one trial reported mortality and found no difference between groups (RR 0.48, 95% CI 0.05 to 5.17; participants = 112). No trials reported long term growth or neurodevelopmental outcomes including cerebral palsy and developmental delay. AUTHORS' CONCLUSIONS: Feeding preterm infants with a human milk fortifier containing high amounts of protein (≥ 1.4g/100 mL EBM) compared with a fortifier containing moderate protein concentration (≥ 1 g to < 1.4 g/100 mL EBM) results in small increases in weight gain during the neonatal admission. There may also be small increases in weight and length gain when infants are fed a fortifier containing moderate versus low protein concentration (< 1 g protein/100 mL EBM). The certainty of this evidence is very low to moderate; therefore, results may change when the findings of ongoing studies are available. There is insufficient evidence to assess the impact of protein concentration on adverse effects or long term outcomes such as neurodevelopment. Further trials are needed to determine whether modest increases in weight gain observed with higher protein concentration fortifiers are associated with benefits or harms to long term growth and neurodevelopment.

Hydrolyzed Rice Protein-Based Formulas, a Vegetal Alternative in Cow's Milk Allergy.

Formulas adapted to infant feeding, although most of the time made from cow's milk proteins, can be made from hydrolyzed rice protein but they must be classified as "formulas for specific medical needs", according to European regulations. The nutritional quality of rice proteins is thus suitable to be used in infant formulas giving that it is supplemented by certain amino acids which can be lacking. Besides, hydrolysis is required to facilitate their water solubility and digestibility. Owing to a low allergenicity of rice and to the absence of the cross-allergy between milk proteins and rice proteins, these formulas are adapted to the diet of children with cow's milk protein allergy (CMPA), which explains their growing use in some countries. However, CMPA, an expanding disorder, has consequences for growth, bone mineralization, and often has an association with allergy to other foods, including cow's milk extensive hydrolysate, so that a surveillance of the adaption of hydrolyzed rice protein formulas (HRPF) to CMPA, the absence of unexpected side effects, and the appropriate response to its various health hazards seems mandatory. This paper analyses the health problem deriving from CMPA, the industrial development of hydrolyzed rice protein formulas, and the limited number of clinical studies, which confirms, at the moment, a good allergic tolerance and safety. The goal is to better advise heath care professionals on their use of HRPFs during CMPA.