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Background: Infant growth trajectories reflect current health status and may predict future obesity and metabolic diseases. Human milk is tailored to support optimal infant growth. However, nutrient intake rather than milk composition more accurately predicts growth outcomes. Although the role of protein leverage in infant growth is unclear, protein intake is important for early infancy growth., Materials and Methods: This study of exclusively breastfeeding mothers with allergies ( n = 161) from the Infant Fish Oil Supplementation Study assessed relationships between intake of human milk macronutrients and infant growth. Human milk fat, protein and lactose concentrations were measured at 3 months postpartum, and infant daily intakes were estimated using an average milk intake of 800 mL/day., Results: Higher human milk protein:energy ratio was associated with higher weight-for-age z-score at 2.5 years compared to 3 months and higher body mass index-for-age z-score change (6 months to 1 year compared to 3-6 months). Maternal atopy and birth season (summer) were negatively associated with human milk lactose concentration. Passive smoke exposure was associated with reduced energy and fat concentrations and increased lactose:energy ratio., Conclusions: Our results indicate that intake of human milk macronutrients may impact early childhood growth.

Purpose: Disproportional fat-free mass loss often occurs post-bariatric surgery, partly due to insufficient protein intake during the post-surgery recovery phase. We compared five protein-enhancing strategies (PES) on patient tolerability, satisfaction and protein intake., Materials and Methods: Ninety-four participants, scheduled for bariatric surgery, were enrolled and allocated to either of the following: (1) whey powder, (2) hydrolysed collagen powder, (3) plant-based powder, (4) protein-rich products, (5) protein gel, or control. PES groups were instructed to add 30 g of powder or 2 gels or protein products to their diet. Patient satisfaction and tolerability were evaluated with questionnaires. Dietary intake was assessed prior to and during PES use., Results: Seven patients dropped out (i.e. loss of contact, personal reasons or post-surgery complications) yielding an analytical cohort of 87 participants. The majority of patients (61%) did not experience dietary complaints from PES and could use PES ≥ 5 days of the week. PES non-usage was mainly related to taste dislike (58%). Hydrolysed collagen scored highest on tolerability and satisfaction: 86% of the participants could use HC ≥ 5 days and 71% were satisfied with the product. PES increased protein intake from 54.7 ± 21.5 g/day to 64.7 ± 23.4 g/day during the intervention (p = 0.002), which differed from the control group (+ 10.1 ± 24.5 g/day vs. - 6.3 ± 23.8 g/day for controls, p = 0.019). Whey showed the highest increase, namely + 18.3 ± 16.3 g/day (p = 0.009)., Conclusion: PES were tolerated by the majority of participants, and an improved protein intake with PES use was seen. However, the taste of the products could be improved to further enhance satisfaction and tolerability., (© 2024. The Author(s).)

Background: Uncertainties still existed about the effect of high-quality protein supplementation on cardiovascular disease (CVD) risk factors, although high-quality proteins such as soy and milk proteins have proposed to be beneficial for cardiometabolic health., Methods: A systematic search in PubMed, Web of Science, Cochrane Library, Scopus, and Embase was conducted to quantify the impact of high-quality protein on CVD risk factors., Results: 63 RCTs on 4 types of high-quality protein including soy protein, milk protein, whey, and casein were evaluated. Soy protein supplementation decreased systolic blood pressure (SBP, -1.42 [-2.68, -0.17] mmHg), total cholesterol (TC, -0.18 [-0.30, -0.07] mmol/L), and low-density lipoprotein cholesterol (LDL-C, -0.16 [-0.27, -0.05] mmol/L). Milk protein supplementation decreased SBP (-2.30 [-3.45, -1.15] mmHg) and total cholesterol (-0.27 [-0.51, -0.03] mmol/L). Whey supplementation decreased SBP (-2.20 [-3.89, -0.51] mmHg), diastolic blood pressure (DBP, -1.07 [-1.98, -0.16] mmHg), triglycerides (-0.10 [-0.17, -0.03] mmol/L), TC (-0.18 [-0.35, -0.01] mmol/L), LDL-C (-0.09 [-0.16, -0.01] mmol/L) and fasting blood insulin (FBI, -2.02 [-3.75, -0.29] pmol/L). Casein supplementation decreased SBP (-4.10 [-8.05, -0.14] mmHg). In the pooled analysis of four high-quality proteins, differential effects were seen in individuals with different health status. In hypertensive individuals, high-quality proteins decreased both SBP (-2.69 [-3.50, -1.87] mmHg) and DBP (-1.34 [-2.09, -0.60] mmHg). In overweight/obese individuals, high-quality proteins improved SBP (-1.40 [-2.22, -0.59] mmHg), DBP (-2.59 [-3.20, -1.98] mmHg), triglycerides (-0.09 [-0.15, -0.02] mmol/L), TC (-0.14 [-0.22, -0.05] mmol/L), LDL-C (-0.12 [-0.16, -0.07] mmol/L), and HDL-C levels (0.02 [0.01, 0.04] mmol/L). According to the benefits on CVD risks factors, whey ranked top for improving cardiometabolic health in hypertensive or overweight/obese individuals., Conclusion: Our study supports a beneficial role of high-quality protein supplementation to reduce CVD risk factors. Further studies are still warranted to investigate the effects of different high-quality proteins on CVD risks in individuals with cardiometabolic disorders., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Sepsis-associated encephalopathy (SAE) impairs hippocampal microglial efferocytosis, causing cognitive deficits. Previous research found that milk fat globule epidermal growth factor 8 protein (MFGE8) stimulates efferocytosis, reducing hippocampal inflammation in SAE rats. In this study, we explore MFGE8's role in alleviating cognitive impairment and its impact on neural activity using functional magnetic resonance imaging (fMRI)., Methods: Sixty male Sprague Dawley rats were divided into four groups: Sham, cecal ligation and puncture (CLP), CLP+MFGE8, and CLP+MFGE8+CGT (Cilengitide). After CLP, CLP+MFGE8 rats received intracerebroventricular MFGE8 (3.3 µg), while CLP+MFGE8+CGT rats received intraperitoneal Cilengitide (10 mg/kg). We assessed cognitive function with the Morris water maze and open field test over five days. Eight days post-surgery, rats underwent T2-weighted magnetic resonance imaging (MRI) and resting state (rs)-fMRI scans. Brain tissues were collected for western blot, hematoxylin-eosin (HE) staining, and immunofluorescence. Statistical analysis employed one-way analysis of variance (ANOVA) followed by Tukey's post-test for multiple comparisons., Results: MFGE8 improved neurobehavioral performance in open field task (OFT) and morris water maze (MWM) tests. fMRI indicated a significant reduction in abnormal neural activity in the right hippocampal CA1, CA3, and dentate gyrus of SAE rats following MFGE8 treatment. Voxel-based morphometry (VBM) analysis revealed decreased high-signal areas in the hippocampus, along with reduced hippocampal volume due to alleviated neural edema. Western blot analysis demonstrated that MFGE8 enhanced ras-related C3 botulinum toxin substrate 1 (Rac1) and microtubule-associated protein 1A/1B-light chain 3 (LC3) expression in the rat hippocampus, while CGT reduced these protein levels. Behavioral experiments and fMRI results confirmed that CGT reversed the cognitive effects of MFGE8 by inhibiting microglial αVβ3/αVβ5 integrin receptors., Conclusions: Our findings show that MFGE8 reduced amplitude of low-frequency fluctuations (ALFF) values in the right hippocampal CA1, CA3, and the dentate gyrus, mitigating abnormal neural activity and decreasing hippocampal volume. This led to an improvement in cognitive dysfunction in SAE rats. These results suggest that MFGE8 enhances microglial efferocytosis by activating αVβ3 and αVβ5 integrin receptors on microglial surfaces, ultimately improving cognitive function in SAE rats., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

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.

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., Competing Interests: Adriana Sanudo, Vanessa Cristina de Castro Rodrigues, and Mauro Batista de Morais received personal fees to develop this study. Thaysa Maués Cezar works the Medical Affairs Division of Danone Nutricia Brazil, and Camila Leonel Mendes de Abreu was working in the Medical Affairs Division of Danone Nutricia Brazil when this study was developed.

Despite the widely recommended usage of partially hydrolyzed formula (PHF) or extensively hydrolyzed formula (EHF) of milk protein for preventing allergic diseases (ADs), clinical studies have been inconclusive regarding their efficacy compared with that of cow's milk formula (CMF) or breast milk (BM). We aimed to systematically evaluate the effects of PHF or EHF compared with those of CMF or BM on risk of ADs (cow's milk allergy, allergic rhinitis, eczema, asthma, wheeze, food allergy, and sensitization) in children. We searched PubMed, Embase, Cochrane Library, and Web of Science for clinical trials published from inception to 21 October, 2022. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to grade the strength of evidence. Overall, 24 trials (10,950 infants) were included, 17 of which specifically included high-risk infants. GRADE was low for the evidence that, compared with CMF, infants early fed with EHF had lower risk of cow's milk allergy at age 0-2 y [relative risk (RR): 0.62; 95% CI: 0.39, 0.99]. Moderate evidence supported that PHF and EHF reduced risk of eczema in children aged younger or older than 2 y, respectively (RR: 0.71; 95% CI: 0.52, 0.96; and RR: 0.79; 95% CI: 0.67, 0.94, respectively). We also identified moderate systematic evidence indicating that PHF reduced risk of wheeze at age 0-2 y compared with CMF (RR: 0.50; 95% CI: 0.29, 0.85), but PHF and EHF increased the risk compared with BM (RR: 1.61; 95% CI: 1.11, 2.31; and RR: 1.64; 95% CI: 1.26, 2.14). Neither PHF nor EHF had significant effects on other ADs in children of any age. In conclusion, compared with CMF, PHF, or EHF had different preventive effect on cow's milk allergy, eczema, and wheeze. Compared with BM, both PHF and EHF may increase risk of wheeze but not other ADs. Given that most trials included only high-risk infants, more research on non-high-risk infants is warranted before any generalization is attempted. This protocol was registered at PROSPERO as CRD42022320787., Competing Interests: Conflict of interest TH, SD, GF, FL, and IM-YS are employed by Inner Mongolia Yili Industrial Group, Yili Maternal and Infant Nutrition Institute (YMINI), Beijing. WY and BL are employed by Inner Mongolia Yili Industrial Group, Hohhot. All other authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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 D 3 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 (P vitamin×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; P vitamin×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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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'.

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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.

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.

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.

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., Competing Interests: The authors declare no conflicts of interest.

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.

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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.

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 β3 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 β3 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 β3/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 β3/SOCS3/STAT3 signaling pathway, highlighting rhMFG-E8 as a potential therapeutic target for the treatment of SAH patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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 β (Lhb) and follicle-stimulating hormone subunit β (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-β 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., (Copyright © 2021 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: For other research, KFM has received research grants from US Dairy Export Council and the Danish Dairy Research Foundation, and also has research collaboration with Nutriset, a producer of LNS products, and patent owner; HF has received research grants from ARLA Food for Health Centre, AFH (a consortium between U of Copenhagen, U of Aarhus, and the dairy company ARLA) and Danish Dairy Research Foundation, and also has research collaboration with Nutriset, a producer of LNS products, and patent owner; AB was the inventor of LNS, for which Nutriset has the patent, but abandoned claims to royalties in 2003. Other authors declare no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, and declare no other relationships or activities that could appear to have influenced the submitted work.

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.

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., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction and Objectives: The diagnosis of IgE-mediated cow's milk allergy (CMA) is often based on clinical history and on specific IgE levels and/or skin-prick tests (SPT), both of which are sensitive but not specific. The gold standard, oral food challenge (OFC), is expensive and time-consuming and involves a risk of severe allergic reactions. This study aimed to determine the value of specific IgEs, ratios of specific IgEs for cow's milk and its components to total IgE, and wheal size on SPT for predicting a positive OFC for CMA., Material and Methods: We retrospectively studied 72 patients [median age, four years; age range 0.75-15 years] sensitized to cow's milk who underwent OFCs to milk. predictive variables between patients with positive and negative OFCs were compared. Receiver operator characteristic (ROC) curves were uses to assess variables' discriminatory capacity and Youden's index to determine the best cut-offs for predicting CMA., Results: The OFC was positive in 39 (54%) patients. Wheal size on SPT and all specific IgEs and specific-to-total IgE ratios were significantly different between patients with positive OFCs and those with negative OFCs (p<0.001). The variable with the greatest area under the ROC curve was casein-specific IgE (0.98), followed by β-lactoglobulin-specific IgE (0.923), casein-specific-to-total-IgE ratio (0.919), and α-lactalbumin-specific IgE (0.908). Casein-specific IgE ≥0.95kU/L yielded 88.9% sensitivity and 90.9% specificity., Conclusions: In our center, casein-specific IgE >0.95kU/L can obviate an OFC to cow's milk for the diagnosis of CMA in patients sensitized to cow's milk with a compatible history., (Copyright © 2020 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

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.

Background: To review currently available evidence on the effect of cow-milk proteins supplementation (CPS) on health in the elderly., Methods: Five electronic databases (Pubmed, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov) were searched for studies about CPS among older people. All types of publications were included, with the exception of systematic reviews, meta-analyses, opinion letters, editorials, case reports, conference abstracts and comments. An additional search in Google Scholar and a manual review of the reference lists were performed., Results: Overall, 103 studies were included. Several studies explored the role of CPS in the preservation or improvement of muscle mass among healthy subjects (40 studies) and pre-frail, frail or sarcopenic patients (14), with evidence of beneficial effects. Other studies assessed the effect of CPS on bones (12), cardiovascular disease (8), inflamm-aging (7), chronic pulmonary disease (4), neurocognitive function (4), and vaccines (2), with weak evidence of positive effects. Seven studies in the field of protein metabolism investigated the role of CPS as an important contributor to nutritional needs. Other investigational areas are considered in the last five studies., Conclusions: The beneficial effects of CPS in achieving aged-related nutritional goals, in preserving muscle mass and in recovering after hospitalization may be particularly relevant in the elderly.

This cohort study aimed to identify the associations of dairy protein intake with the risk of developing a low muscle mass during a 12-year follow-up period, using data from 4412 middle-aged Korean Genome and Epidemiology Study participants with a normal baseline muscle mass. Dairy protein intake at baseline was assessed using a semi-quantitative Food Frequency Questionnaire. Skeletal muscle mass index (SMI), defined as the weight-adjusted skeletal muscle mass, was measured biennially using multi-frequency bioelectrical impedance analyses. Cox proportional hazards regression analysis was used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Overall, 395 subjects developed a low SMI (%) during an average follow-up of 141 (19-152) months. The average consumption of milk and other dairy products was 73.6 and 104.1 g/day, respectively. In men, a higher dairy protein intake was associated with a decreased risk of developing a low SMI (tertile 3 [T3] vs. T1, HR: 0.63; 95% CI: 0.42, 0.94; p for trend = 0.029). In a stratified analysis according to a total protein intake, this association was stronger in the lower-protein intake group (HR: 0.59; 95% CI: 0.35, 0.99; p for trend = 0.036) but not detected in the higher-protein intake group. Men who consumed milk ≥1 time/day had a significantly lower risk of developing a low SMI (HR: 0.62; 95% CI: 0.39, 0.98; p for trend = 0.023). No significant associations were observed in women. In summary, dairy consumption appears to be beneficial for decreasing the risk of developing a low muscle mass in middle-aged Korean men.

Background: IgE-mediated food allergy remains a significant and growing worldwide problem. Sublingual immunotherapy (SLIT) shows an excellent safety profile for food allergy, but the clinical efficacy needs to be improved. This study assessed the effects of the Toll-like receptor 4 agonist outer membrane protein (Omp) 16 from Brucella abortus combined with cow´s milk proteins (CMP) through the sublingual route to modulate cow's milk allergy in an experimental model., Methods: Mice sensitized with cholera toxin and CMP were orally challenged with the allergen to elicit hypersensitivity reactions. Then, mice were treated with a very low amount of CMP along with Omp16 as a mucosal adjuvant, and finally, animals were re-exposed to CMP. Systemic and mucosal immune parameters were assessed in vivo and in vitro., Results: We found that the sublingual administration of Omp16 + CMP induced a buccal Th1 immune response that modulated the intestinal allergic response with the suppression of symptoms, reduction of IgE and IL-5, and up-regulation of IgG2a and IFN-γ. The adoptive transfer of submandibular IFN-γ-producing α4β7 + CD4 + and CD8 + cells conferred protection against allergic sensitization. The use of Omp16 + CMP promoted enhanced protection compared to CMP alone., Conclusion: In conclusion, Omp16 represents a promising mucosal adjuvant that can be used to improve the clinical and immune efficacy of SLIT for food allergy., (© 2020 John Wiley & Sons Ltd.)

Background: It is unknown whether protein supplementation can enhance recovery of exercise-induced muscle damage in older adults who have a disturbed muscle protein synthetic response. We assessed whether protein supplementation could attenuate exercise-induced muscle damage and soreness after prolonged moderate-intensity walking exercise in older adults., Methods: In a double-blind, placebo-controlled intervention study, 104 subjects (81% male, ≥65 years) used either a protein (n = 50) or placebo supplement (n = 54) during breakfast and directly after exercise. Within a walking event, study subjects walked 30/40/50 km per day on three consecutive days. Muscle soreness and fatigue were determined with a numeric rating scale, and creatine kinase (CK) concentrations and serum inflammation markers were obtained., Results: Habitual protein intake was comparable between the protein (0.92 ± 0.27 g/kg/d) and placebo group (0.97 ± 0.23 g/kg/d, p = 0.31). At baseline, comparable CK concentrations were found between the protein and the placebo group (110 (IQR: 84-160 U/L) and 115 (IQR: 91-186 U/L), respectively, p = 0.84). Prolonged walking (protein: 32 ± 9 km/d, placebo: 33 ± 6 km/d) resulted in a cumulative increase of CK in both the protein (∆283 (IQR: 182-662 U/L)) and placebo group (∆456 (IQR: 209-885 U/L)) after three days. CK elevations were not significantly different between groups ( p = 0.43). Similarly, no differences in inflammation markers, muscle soreness and fatigue were found between groups., Conclusions: Protein supplementation does not attenuate exercise-induced muscle damage, muscle soreness or fatigue in older adults performing prolonged moderate-intensity walking exercise., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

The mechanisms that are responsible for sarcopenia are numerous, but the altered muscle protein anabolic response to food intake that appears with advancing age plays an important role. Dietary protein quality needs to be optimized to counter this phenomenon. Blending different plant proteins is expected to compensate for the lower anabolic capacity of plant-based when compared to animal-based protein sources. The objective of this work was to evaluate the nutritional value of pasta products that were made from a mix of wheat semolina and faba bean, lentil, or split pea flour, and to assess their effect on protein metabolism as compared to dietary milk proteins in old rats. Forty-three old rats have consumed for six weeks isoproteic and isocaloric diets containing wheat pasta enriched with 62% to 79% legume protein (depending on the type) or milk proteins, i.e., casein or soluble milk proteins (SMP). The protein digestibility of casein and SMP was 5% to 14% higher than legume-enriched pasta. The net protein utilization and skeletal muscle protein synthesis rate were equivalent either in rats fed legume-enriched pasta diets or those fed casein diet, but lower than in rats fed SMP diet. After legume-enriched pasta intake, muscle mass, and protein accretion were in the same range as in the casein and SMP groups. Mixed wheat-legume pasta could be a nutritional strategy for enhancing the protein content and improving the protein quality, i.e., amino acid profile, of this staple food that is more adequate for maintaining muscle mass, especially for older individuals., Competing Interests: The authors declare no competing interests.

Spinal cord injury (SCI) is a common disease and a major cause of paralysis, carrying much burden around the world. Despite the progress made with growth factors therapy, the response rate of acute SCI treatment still remains unsatisfactory, due largely to complex and severe inflammatory reactions. Herein, we prepare a MFG-E8-loaded copolymer system-based anti-inflammation therapy for SCI treatment. It is shown that the MFG-E8-loaded copolymer system can decrease pro-inflammatory cytokine expression and neuron death. In a rat model of crush-caused SCI, the copolymer system shows significant therapeutic efficacy by ameliorating inflammation, decreasing fibrotic scar, promoting myelin regeneration and suppressing overall SCI severity., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary, or financial interest in the products or companies described in this article., (Copyright © 2020 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Unhealthy Western-style eating patterns (WSEP) predominate, adversely affecting health. Resistance to improving dietary patterns prompts interest to incorporate a potentially health-promoting ingredient into typical WSEP foods and beverages. We assessed the effect of incorporating isocalorically matched carbohydrates versus milk protein isolate (MPI) into a WSEP on weight loss-induced changes in cardiometabolic health and body composition. In a randomized, double-blind, parallel-design study, 44 participants (age 52 ± 1 years, body mass index (BMI) 31.4 ± 0.5 kg/m 2 , mean ± standard error) consumed a weight maintenance WSEP (0.8 g total protein/kg/day) for 3 weeks (baseline). After, participants consumed an energy-restricted (750 kcal/day below estimated requirement) WSEP for 16 weeks, randomly assigned to contain either an additional 0.7 g carbohydrate/kg/d (CON: n = 23, 0.8 g total protein/kg/day) or 0.7 g protein/kg/d from MPI (MPI: n = 21, 1.5 g total protein/kg/day) incorporated into foods and beverages. Compared to CON, the MPI favored reductions in average 24 h and sleeping systolic and diastolic blood pressures (BP), waking hours systolic BP, and fasting plasma triglyceride concentrations. Reductions in fasting plasma insulin, glucose, total cholesterol, and low-density lipoprotein cholesterol concentrations were not different between groups. Among all participants, whole body mass, lean mass, fat mass, and thigh muscle area, each decreased over time. For adults finding it difficult to deviate from a WSEP, replacing a portion of their carbohydrate with foods and beverages containing MPI may be an effective dietary strategy to reduce BP after weight loss.

Industrial heat treatment of milk results in protein glycation. A high protein glycation level has been suggested to compromise the post-prandial rise in plasma amino acid availability following protein ingestion. In the present study, we assessed the impact of glycation level of milk protein on post-prandial plasma amino acid responses in humans. Fifteen healthy, young men (age 26 (SEM 1) years, BMI 24 (SEM 1) kg/m2) participated in this randomised cross-over study and ingested milk protein powder with protein glycation levels of 3, 20 and 50 % blocked lysine. On each trial day, arterialised blood samples were collected at regular intervals during a 6-h post-prandial period to assess plasma amino acid concentrations using ultra-performance liquid chromatography. Plasma essential amino acid (EAA) concentrations increased following milk protein ingestion, with the 20 and 50 % glycated milk proteins showing lower overall EAA responses compared with the 3 % glycated milk protein (161 (SEM 7) and 142 (SEM 7) v. 178 (SEM 9) mmol/l × 6 h, respectively; P ≤ 0·011). The lower post-prandial plasma amino acid responses were fully attributed to an attenuated post-prandial rise in circulating plasma lysine concentrations. Plasma lysine responses (incremental AUC) following ingestion of the 20 and 50 % glycated milk proteins were 35 (SEM 4) and 92 (SEM 2) % lower compared with the 3 % glycated milk protein (21·3 (SEM 1·4) and 2·8 (SEM 0·7) v. 33·3 (SEM 1·7) mmol/l × 6 h, respectively; P < 0·001). Milk protein glycation lowers post-prandial plasma lysine availability in humans. The lower post-prandial availability of lysine following ingestion of proteins with a high glycation level may compromise the anabolic properties of a protein source.

Background: Microthrombosis after subarachnoid hemorrhage has an adverse effect on prognosis. Milk fat globule-epidermal growth factor 8 promotes phagocytosis of phagocytic cells and may reduce microthrombosis. This study investigated the effects of recombinant human milk fat globule-epidermal growth factor 8 on microthrombosis and neurological function after subarachnoid hemorrhage., Methods: Rats subarachnoid hemorrhage model was induced by intravascular puncture method. Western blot was performed to measure the expression of endogenous milk fat globule-epidermal growth factor 8 after subarachnoid hemorrhage. Microthrombosis was quantified by microthrombi count using immunohistochemistry and immunofluorescence. The neuroprotective effect of recombinant human milk fat globule-epidermal growth factor 8 administration was evaluated by modified Garcia score, beam balance, Rotarod test, and Morris water maze., Results: Endogenous milk fat globule-epidermal growth factor 8 protein level increased after subarachnoid hemorrhage. Microthrombosis was significantly increased in subarachnoid hemorrhage rats brain, while recombinant human milk fat globule-epidermal growth factor 8 dramatically reduced microthrombosis as well as improve short- and long- term neurobehavior after subarachnoid hemorrhage., Conclusions: Recombinant human milk fat globule-epidermal growth factor 8 reduces microthrombosis and improves neurological function after subarachnoid hemorrhage, which may be an effective strategy for treating subarachnoid hemorrhage., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Epicutaneous immunotherapy (EPIT) involving the skin's immune system is easy to use, painless and has a low risk of systemic side effects; it can be applied to food allergies that have a high morbidity rate in children. In this study, we evaluated the safety and efficacy of hydrophilic gel patch (HG) for EPIT., Methods: Milk protein concentrate (MPC)-containing HG was applied to the skin that maintained a barrier function or formed puncture holes with microneedle, and MPC-specific antibodies were measured. The clinical study was conducted involving patients with severe milk allergy., Results: No specific immune response was induced when immunizing to intact skin, and antibody production was observed by forming puncture holes. It was suggested that MPC contained in HG has immunogenicity and a very small amount of MPC was delivered to intact skin. In the clinical study, the symptom induction threshold increased in four of eight subjects, allowing them to consume milk and switch to oral immunotherapy. Although local skin reactions and temporary elevation of specific IgE antibodies were observed, no systemic side effects appeared throughout the study., Conclusions: EPIT using HG is a safe method to enable oral administration even in patients with severe milk allergies.

Tackling the global burden of acute malnutrition in children remains a major public health challenge and is essential for achieving sustainable development. Despite having effective treatment options, most wasted children go untreated; treatment coverage for severe acute malnutrition (SAM) children is only about 20%. Milk is currently an essential component of effective SAM treatment, incorporated into ready-to-use therapeutic food (RUTF). Reaching the untreated children, as well as preventing SAM, requires investment in innovative and cost-efficient approaches. To date, attempts to replace or remove milk from RUTF have been either unsuccessful or unpersuasive. This is likely because milk provides the highest protein quality and density of all typical RUTF ingredients. However, alternative protein sources could provide cost savings. Alternative protein sources, especially plant-based protein alternatives, have had shown more promising progress for the treatment of children with moderate acute malnutrition. Acknowledging that cost is a major barrier to the scale-up of treatment of acute malnutrition and that alternative protein sources are a practical means to reduce cost, continued research focusing on alternative proteins is necessary., (© 2020 Nestlé Nutrition Institute, Switzerland/S. Karger AG, Basel.)

Necrotizing enterocolitis (NEC) is one of the most widespread and devastating gastrointestinal diseases in neonates. Destruction of the intestinal barrier is the main underlying cause of NEC. The aim of this study was to determine the role of lactadherin in preventing NEC in a neonatal rat model and investigate the molecular mechanism of lactadherin-mediated protection of the intestinal barrier. Neonatal rats were divided into three groups: dam feeding (DF), NEC (NEC), and NEC supplemented with 10 μg/(g·day) recombinant human lactadherin (NEC+L). Intestinal permeability, tissue damage, and cell junction protein expression and localization were evaluated. We found that lactadherin reduced weight loss caused by NEC, reduced the incidence of NEC from 100% to 46.7%, and reduced the mean histological score for tissue damage to 1.40 compared with 2.53 in the NEC group. Intestinal permeability of lactadherin-treated rats was significantly reduced when compared with that of the NEC group. In addition, the expression levels of JAM-A, claudin 3, and E-calcium in the ileum of NEC group animals increased compared with those in the ileum of DF group animals, and these levels decreased in the NEC+L group. Lactadherin changed the localization of claudin 3, occludin, and E-cadherin in epithelial cells. The mechanism underlying lactadherin-mediated protection of the intestinal barrier might be restoring the correct expression levels and localization of tight junction and adherent junction proteins. These findings suggest a new candidate agent for the prevention of NEC in newborns., (© 2019 Wiley Periodicals, Inc.)

Objectives: The objective of this study was to show the effects of routine vs. selective fortification of human milk (HM) on short-term growth and metabolic parameters., Methods: Single-centre retrospective pre-post cohort study in India. Preterm infants ≤32 weeks' gestation and weighing ≤1500 g were included. Routine fortification: pre-fixed feed volume (100 ml/kg/day in our unit) at which fortification was done. Selective fortification: feed volume was gradually optimized till 180-200 ml/kg/day. If weight gain was below the expected threshold (<10 g/kg/day), then fortification was considered. Primary outcome measure was rate of growth till discharge., Results: The median rate of weight gain (g/kg/day) in the routine fortification group [10.8 (3.3, 17.1)] was comparable with that in the selective fortification group [8.4 (0, 14.2), p = 0.6]. Serum phosphorus showed a significantly higher value (5.9 vs. 4.8, p = 0.03), while rest of the metabolic parameters showed a trend towards a favourable outcome in the selective fortification group. Adverse outcomes showed a trend towards decreased feed intolerance, necrotizing enterocolitis, and sepsis in the selective fortification group., Conclusions: Selective fortification had a comparable growth rate and showed a trend towards better metabolic parameters and lesser adverse outcomes compared with routine fortification of HM., (© The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Resistance exercise and dietary protein stimulate muscle protein synthesis (MPS). The rate at which proteins are digested and absorbed into circulation alters peak plasma amino acid concentrations and may modulate postexercise MPS. A novel mineral modified milk protein concentrate (mMPC), with identical amino acid composition to standard milk protein concentrate (MPC), was formulated to induce rapid aminoacidemia., Objectives: The aim of this study was to determine whether rapid aminoacidemia and greater peak essential amino acid (EAA) concentrations induced by mMPC would stimulate greater postresistance exercise MPS, anabolic signaling, and ribosome biogenesis compared to standard dairy proteins, which induce a small but sustained plasma essential aminoacidemia., Methods: Thirty healthy young men (22.5 ± 3.0 y; BMI 23.8 ± 2.7 kg/m2) received primed constant infusions of l-[ring-13C6]-phenylalanine and completed 3 sets of leg presses and leg extensions at 80% of 1 repetition. Afterwards, participants were randomly assigned in a double-blind fashion to consume 25 g mMPC, MPC, or calcium caseinate (CAS). Vastus lateralis biopsies were collected at rest, and 2 and 4 h post exercise., Results: Plasma EAA concentrations, including leucine, were 19.2-26.6% greater in the mMPC group 45-90 min post ingestion than in MPC and CAS groups (P < 0.001). Myofibrillar fractional synthetic rate from baseline to 4 h was increased by 82.6 ± 64.8%, 137.8 ± 72.1%, and 140.6 ± 52.4% in the MPC, mMPC, and CAS groups, respectively, with no difference between groups (P = 0.548). Phosphorylation of anabolic signaling targets (P70S6KThr389, P70S6KThr421/Ser424, RPS6Ser235/236, RPS6Ser240/244, P90RSKSer380, 4EBP1) were elevated by <3-fold at both 2 and 4 h post exercise in all groups (P < 0.05)., Conclusions: The amplitude of plasma leucine and EAA concentrations does not modulate the anabolic response to resistance exercise after ingestion of 25 g dairy protein in young men. This trial was registered at http://www.anzctr.org.au/ as ACTRN12617000393358., (Copyright © American Society for Nutrition 2019.)

The objective of this study was to evaluate the effects of incorporating 2 commonly used additives or spray-dried porcine plasma in calf milk replacer (CMR) on calf performance and health. Male Holstein calves (n = 158) transported from auction barns and local dairy farms were randomly assigned to receive 1 of 3 decoquinate-containing CMR for the first 49 d of the experiment: all milk protein and no additives (CONT); 15% of crude protein (CP) replaced with spray-dried porcine plasma, no additives (PLM); or all milk protein and an added combination of sodium butyrate (rate 1.4 kg of butyric acid/Mt) and Bacillus subtilis (1.28 million cfu/g of feed; BB). All milk replacers were formulated to contain 26% CP and 17% fat, 2.4% Lys, and 0.8% Met, and were bucket-fed at daily feeding rates of 520 g during wk 1 and 2, 650 g during wk 3, and 900 g during wk 4 and 5, in a total of 4, 5, and 6 L of solution, respectively. Calves were offered texturized calf starter (18% CP) upon arrival until wk 3 and transitioned to a corn and pellet ration with 2% straw (18.1% CP). No prophylactic administration of antibiotics occurred. All calves were gradually weaned over a 2-wk period. Calves were individually housed until weaned and then housed in groups of 5 in a mechanically ventilated facility in southwestern Ontario, Canada. Fecal scores, treatments administered (antibiotic or supportive therapy), and mortalities were recorded daily. Body weight was measured using a digital scale at arrival and at 14, 49, 56, and 78 d after arrival. No differences were found among the groups with respect to growth, feed efficiency, or incidence of diarrhea or respiratory infection treatment. Calves supplemented with BB had a greater hazard of mortality over the growing period compared with CONT. An interaction was found between the BB group and the level of total serum protein, with the BB group having a lower proportion of days with a fecal score of 3 when the calves had a higher total serum protein level. Calves fed PLM had a lower proportion of d with a fecal score of 3 relative to CONT but no difference in the proportion of d with a fecal score of 2 or higher. This study found that the addition of spray-dried plasma in CMR reduced diarrhea severity; however, supplementing BB was associated with a higher hazard of calf mortality and had a varying response on fecal score., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Milk proteins have been hypothesized to protect against type 2 diabetes (T2DM) by beneficially modulating glycemic response, predominantly in the postprandial status. This potential is, amongst others, attributed to the high content of whey proteins, which are commonly a product of cheese production. However, native whey has received substantial attention due to its higher leucine content, and its postprandial glycemic effect has not been assessed thus far in prediabetes. In the present study, the impact of a milk protein hydrolysate of native whey origin with alpha-glucosidase inhibiting properties was determined in prediabetics in a randomized, cross-over trial. Subjects received a single dose of placebo or low- or high-dosed milk protein hydrolysate prior to a challenge meal high in carbohydrates. Concentration-time curves of glucose and insulin were assessed. Incremental areas under the curve (iAUC) of glucose as the primary outcome were significantly reduced by low-dosed milk peptides compared to placebo ( p = 0.0472), and a minor insulinotropic effect was seen. A longer intervention period with the low-dosed product did not strengthen glucose response but significantly reduced HbA 1c values ( p = 0.0244). In conclusion, the current milk protein hydrolysate of native whey origin has the potential to modulate postprandial hyperglycemia and hence may contribute in reducing the future risk of developing T2DM., Competing Interests: C.S., A.W., T.D., T.S.: employees of contracted research organization. M.W. is an independent statistician supporting with data analysis. The study was financially supported by Ingredia S.A., France. The sponsors contributed to the discussion about the study design and selection of outcome measures prior to the study start. Planning and organization of the study and its realization, data analysis and report generating were independently undertaken solely by BioTeSys GmbH and M.W. The authors from BioTeSys GmbH and M.W. declare no conflict of interest regarding the publication of this paper.

The diurnal rhythm of bone remodeling suggests nocturnal dietary intervention to be most effective. This study investigated the effect of bedtime ingestion of a calcium-fortified, milk-derived protein matrix (MBPM) or maltodextrin (CON) on acute (0-4 h) blood and 24-h urinary change in biomarkers of bone remodeling in postmenopausal women with osteopenia. In CON, participants received 804 ± 52 mg calcium, 8.2 ± 3.2 µg vitamin D and 1.3 ± 0.2 g/kg BM protein per day. MBPM increased calcium intake to 1679 ± 196 mg, vitamin D to 9.2 ± 3.1 µg and protein to 1.6 ± 0.2 g/kg BM. Serum C-terminal cross-linked telopeptide of type I collagen (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), and urinary N-telopeptide cross-links of type I collagen (NTX), pyridinoline (PYD) and deoxypyridinoline (DPD) was measured. Analyzed by AUC and compared to CON, a -32% lower CTX ( p = 0.011, d = 0.83) and 24% ( p = 0.52, d = 0.2) increase in P1NP was observed for MBPM. Mean total 24 h NTX excreted in MBPM was -10% ( p = 0.035) lower than CON. Urinary PYD and DPD were unaffected by treatment. This study demonstrates the acute effects of bedtime ingestion of a calcium-fortified, milk-based protein matrix on bone remodeling.

The influence of types of human milk (HM)-raw own mother's milk (OMM), pasteurized OMM, and donor milk (DM)-was evaluated for growth in premature infants fed exclusively HM with controlled nutritional intakes using daily individualized HM fortification (IHMF). Growth and nutritional intakes were prospectively collected in preterm infants (<32 weeks) fed IHMF and compared in infants fed predominantly (≥75%) OMM and DM. The influence of HM types (raw OMM, pasteurized OMM, and DM) on growth were also evaluated in the whole population. One-hundred and one preterm infants (birth weight 970 ± 255 g, gestational age 27.8 ± 1.9 weeks) were included. Energy (143 ± 8 vs. 141 ± 6 kcal/kg/day; p = 0.15) and protein intakes (4.17 ± 0.15 vs. 4.15 ± 0.14 g/kg/day; p = 0.51) were similar in both groups. Infants receiving predominantly OMM ( n = 37), gained significantly more weight (19.8 ± 2.0 vs. 18.2 ± 2.2 g/kg/day; p = 0.002) and length (1.17 ± 0.26 vs. 0.99 ± 0.36 cm/week; p = 0.020) than those fed predominantly DM ( n = 33). Stepwise multivariate analysis ( n = 101) suggests that raw OMM was the major determinant of growth, contributing 22.7% of weight gain. Length gain was also related to OMM (raw + pasteurized) intakes, explaining 4.0% of length gain. In conclusion, at daily controlled similar protein and energy intakes, OMM had significant beneficial effects on weight and length versus DM in VLBW infants. This difference could be partially explained by the use of raw OMM.

We undertook a systematic review and meta-analysis of published papers assessing dietary protein and bone health. We found little benefit of increasing protein intake for bone health in healthy adults but no indication of any detrimental effect, at least within the protein intakes of the populations studied. This systematic review and meta-analysis analysed the relationship between dietary protein and bone health across the life-course. The PubMed database was searched for all relevant human studies from the 1st January 1976 to 22nd January 2016, including all bone outcomes except calcium metabolism. The searches identified 127 papers for inclusion, including 74 correlational studies, 23 fracture or osteoporosis risk studies and 30 supplementation trials. Protein intake accounted for 0-4% of areal BMC and areal BMD variance in adults and 0-14% of areal BMC variance in children and adolescents. However, when confounder adjusted (5 studies) adult lumbar spine and femoral neck BMD associations were not statistically significant. There was no association between protein intake and relative risk (RR) of osteoporotic fractures for total (RR (random)  = 0.94; 0.72 to 1.23, I 2  = 32%), animal (RR (random)  = 0.98; 0.76 to 1.27, I 2  = 46%) or vegetable protein (RR (fixed)  = 0.97 (0.89 to 1.09, I 2  = 15%). In total protein supplementation studies, pooled effect sizes were not statistically significant for LSBMD (total n = 255, MD (fixed)  = 0.04 g/cm 2 (0.00 to 0.08, P = 0.07), I 2  = 0%) or FNBMD (total n = 435, MD (random)  = 0.01 g/cm 2 (-0.03 to 0.05, P = 0.59), I 2  = 68%). There appears to be little benefit of increasing protein intake for bone health in healthy adults but there is also clearly no indication of any detrimental effect, at least within the protein intakes of the populations studied (around 0.8-1.3 g/Kg/day). More studies are urgently required on the association between protein intake and bone health in children and adolescents.

Background: Whey and micellar casein are high-quality dairy proteins that can stimulate postprandial muscle protein synthesis rates. How whey and casein compare with milk protein in their capacity to stimulate postprandial myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis rates during postexercise recovery is currently unknown., Objective: The objective of this study was to compare postprandial MyoPS and MitoPS rates after protein-carbohydrate co-ingestion with milk protein, whey, or micellar casein during recovery from a single bout of concurrent resistance- and endurance-type exercise in young healthy men., Methods: In a randomized, double-blind, parallel-group design, 48 healthy, young, recreationally active men (mean ± SEM age: 23 ± 0.3 y) received a primed continuous infusion of L-[ring-13C6]-phenylalanine and L-[ring-3,5-2H2]-tyrosine and ingested 45 g carbohydrate with 0 g protein (CHO), 20 g milk protein (MILK), 20 g whey protein (WHEY), or 20 g micellar casein protein (CASEIN) after a sequential bout of resistance- and endurance-type exercise (i.e., concurrent exercise). Blood and muscle biopsies were collected over 360 min during recovery from exercise to assess MyoPS and MitoPS rates and signaling through mammalian target of rapamycin complex 1 (mTORC1)., Results: Despite temporal differences in postprandial plasma leucine concentrations between treatments (P < 0.001), MyoPS rates over 360 min of recovery did not differ between treatments (CHO: 0.049% ± 0.003%/h; MILK: 0.059% ± 0.003%/h; WHEY: 0.054% ± 0.002%/h; CASEIN: 0.059% ± 0.005%/h; P = 0.11). When MILK, WHEY, and CASEIN were pooled into a single group (PROTEIN), protein co-ingestion resulted in greater MyoPS rates compared with CHO (PROTEIN: 0.057% ± 0.002%/h; CHO: 0.049% ± 0.003%/h; P = 0.04). MitoPS rates and signaling through the mTORC1 pathway were similar between treatments., Conclusion: MyoPS and MitoPS rates do not differ after co-ingestion of either milk protein, whey protein, or micellar casein protein with carbohydrate during recovery from a single bout of concurrent resistance- and endurance-type exercise in recreationally active young men. Co-ingestion of protein with carbohydrate results in greater MyoPS, but not MitoPS rates, when compared with the ingestion of carbohydrate only during recovery from concurrent exercise. This trial was registered at Nederlands Trial Register: NTR5098., (© 2019 American Society for Nutrition.)

Background: Protein ingestion during recovery from resistance-type exercise increases postexercise muscle protein synthesis rates. Whey protein has been reported to have greater anabolic properties than soy protein, an effect which may be attributed to the higher leucine content of whey., Objective: The objective of this study was to compare postprandial myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis rates after ingestion of carbohydrate with whey, soy, or soy protein enriched with free leucine (to match the leucine content of whey) during recovery from a single bout of concurrent resistance- and endurance-type exercise in young healthy men., Methods: In a randomized, double-blind, parallel-group design, 36 healthy young recreationally active men (mean ± SEM age: 23 ± 0.4 y) received a primed continuous infusion of l-[ring-13C6]-phenylalanine and l-[ring-3,5-2H2]-tyrosine and ingested 45 g carbohydrate with 20 g protein from whey (WHEY), soy (SOY), or leucine-enriched soy (SOY + LEU) after concurrent resistance- and endurance-type exercise. Blood and muscle biopsies were collected over a 360 min postexercise recovery period to assess MyoPS and MitoPS rates, and associated signaling through the mammalian target of rapamycin complex 1 (mTORC1)., Results: Postprandial peak plasma leucine concentrations were significantly higher in WHEY (mean ± SEM: 322 ± 10 μmol/L) and SOY + LEU (328 ± 14 μmol/L) compared with SOY (216 ± 6 μmol/L) (P < 0.05). Despite the apparent differences in plasma leucinemia, MyoPS (WHEY: 0.054 ± 0.002; SOY: 0.053 ± 0.004; SOY + LEU: 0.056 ± 0.004%·h-1; P = 0.83), and MitoPS (WHEY: 0.061 ± 0.004; SOY: 0.061 ± 0.006; SOY + LEU: 0.063 ± 0.004%·h-1; P = 0.96) rates over the entire 360 min recovery period did not differ between treatments. Similarly, signaling through mTORC1Ser2448, p70S6kThr389, 4E-BP1Thr37/46, and rpS6Ser235/236 was similar between treatments., Conclusion: Postexercise MyoPS and MitoPS rates do not differ after co-ingestion of carbohydrate with 20 g protein from whey, soy, or leucine-enriched soy protein during 360 min of recovery from concurrent resistance- and endurance-type exercise in young, recreationally active men. This trial was registered at Nederlands Trial Register as NTR5098., (© 2019 American Society for Nutrition.)

Milk and dairy products are known to contain various bioactives with potential anti-inflammatory and immune modulating effects. Previous research has indicated that milk produced from hyperimmunized cows provided meaningful health benefits to individuals suffering from varying degrees of osteoarthritis and rheumatoid arthritis. PURPOSE: To examine the impact of MicroLactin®, a proprietary milk protein concentrate, on joint discomfort and physical function, exercise performance, quality of life and various measures of affect. METHODS: Non-osteoarthritic men (42.5 ± 8.9 years, 176.7 ± 6.7 cm, 89.9 ± 11.5 kg, 28.8 ± 3.5 kg/m², n = 30) and women (46.4 ± 9.6 years, 163.1 ± 8.2 cm, 72.2 ± 13.1 kg, 27.2 ± 5.3 kg/m², n = 28) with mild to moderate knee pain during physical activity were randomized in a double-blind, placebo-controlled fashion to consume daily either a placebo (PLA) or MicroLactin® (ML) for a period of 8 weeks. Participants completed a functional capacity test pre and post-supplementation and completed visual analog scales (VAS), a 6-min walking test, WOMAC and profile of mood states (POMS) to assess changes in joint health, discomfort, physical function, exercise performance and affect. Mixed factorial ANOVA was used for all statistical analysis and significance was set a priori at p ≤ 0.05. RESULTS: Distance covered in the 6-min walking significantly improved 9% in ML versus 2% in PLA (mean difference: 110 ± 43 m, p = 0.012) in addition to 11 WOMAC components and 5 VAS reflective of ML improving joint health, discomfort and joint stability (all p < 0.05 vs. PLA). Additionally, ML also improved overall perceptions of neck and back health compared to PLA. Serum and whole blood indicators of clinical safety remained within normal ranges throughout the study. CONCLUSIONS: In comparison to placebo, daily doses of MicroLactin ® yielded improvements in several components of the WOMAC, multiple visual analog scales indicative of joint health and stability, discomfort and pain, as well as significant improvements in distance covered during a 6-min walking test. Supplementation was well tolerated with no significant changes in whole-blood or serum markers of clinical safety.

Background: A rapid digestibility and high leucine content are considered important for maximal stimulation of muscle protein synthesis. Consequently, with these properties, native whey may hold greater anabolic potential than milk, when supplemented in combination with strength training. Our aim was to compare the effects of supplementation with milk or native whey, during a 12-wk strength training period, on gains in muscle mass and strength in young adults., Methods: In this double-blinded, randomized, controlled study a total of 40 untrained young men and women received two daily servings of either milk or native whey containing 20 g of protein, during a 12-wk strength training intervention. Muscle strength, lean mass, thigh muscle cross-sectional area, m. vastus lateralis thickness and muscle fiber cross-sectional area were assessed before and after the training period. In addition, the acute phosphorylation of the anabolic kinases p70S6K, 4E-BP1 and eEF-2 in response to a standardized workout and supplementation was investigated before and after the 12-wk training period., Results: Muscle mass and strength increased, by all measures applied (5%-16%, P < 0.001), with no differences between groups (P > 0.25). p70S6K phosphorylation increased (~1000%, P < 0.02) 2 h after exercise in the untrained and trained state, but no differences in anabolic signaling were observed between supplements (P > 0.40). No correlation between these acute measures and changes in muscle mass or strength were observed., Conclusion: Supplementation with milk or native whey during a 12-wk strength training period did not differentially affect muscle mass and strength in young untrained individuals.