Vicia faba Peptide Network Supplementation Does Not Differ From Milk Protein in Modulating Changes in Muscle Size During Short-Term Immobilization and Subsequent Remobilization, but Increases Muscle Protein Synthesis Rates During Remobilization in Healthy Young Men.

BACKGROUND: Muscle mass and strength decrease during short periods of immobilization and slowly recover during remobilization. Recent artificial intelligence applications have identified peptides that appear to possess anabolic properties in in vitro assays and murine models. OBJECTIVES: This study aimed to compare the impact of Vicia faba peptide network compared with milk protein supplementation on muscle mass and strength loss during limb immobilization and regain during remobilization. METHODS: Thirty young (24 ± 5 y) men were subjected to 7 d of one-legged knee immobilization followed by 14 d of ambulant recovery. Participants were randomly allocated to ingest either 10 g of the Vicia faba peptide network (NPN_1; n = 15) or an isonitrogenous control (milk protein concentrate; MPC; n = 15) twice daily throughout the study. Single-slice computed tomography scans were performed to assess quadriceps cross-sectional area (CSA). Deuterium oxide ingestion and muscle biopsy sampling were applied to measure myofibrillar protein synthesis rates. RESULTS: Leg immobilization decreased quadriceps CSA (primary outcome) from 81.9 ± 10.6 to 76.5 ± 9.2 cm2 and from 74.8 ± 10.6 to 71.5 ± 9.8 cm2 in the NPN_1 and MPC groups, respectively (P < 0.001). Remobilization partially recovered quadriceps CSA (77.3 ± 9.3 and 72.6 ± 10.0 cm2, respectively; P = 0.009), with no differences between the groups (P > 0.05). During immobilization, myofibrillar protein synthesis rates (secondary outcome) were lower in the immobilized leg (1.07% ± 0.24% and 1.10% ± 0.24%/d, respectively) than in the non-immobilized leg (1.55% ± 0.27% and 1.52% ± 0.20%/d, respectively; P < 0.001), with no differences between the groups (P > 0.05). During remobilization, myofibrillar protein synthesis rates in the immobilized leg were greater with NPN_1 than those with MPC (1.53% ± 0.38% vs. 1.23% ± 0.36%/d, respectively; P = 0.027). CONCLUSION: NPN_1 supplementation does not differ from milk protein in modulating the loss of muscle size during short-term immobilization and the regain during remobilization in young men. NPN_1 supplementation does not differ from milk protein supplementation in modulating the myofibrillar protein synthesis rates during immobilization but further increases myofibrillar protein synthesis rates during remobilization.

Fermented soybean meal modified the rumen microbiome to enhance the yield of milk components in Holstein cows.

The study was conducted to evaluate the rumen microbiota as well as the milk composition and milk component yields of Holstein cows supplemented with fermented soybean meal (FSBM). Eighteen Holstein cows in their 2nd parity with 54.38 ± 11.12 SD days in milking (DIM) were divided into two dietary groups (CON and TRT) of nine cows per group. The cows in the TRT group received 300 g of FSBM per cow per day in addition to the conventional diet, while each cow in the CON group was supplemented with 350 g of soybean meal (SBM) in their diet daily throughout the 28-day feeding trial. Rumen bacterial composition was detected via 16S rRNA sequencing, and the functional profiles of bacterial communities were predicted. Milk composition, milk yield, as well as rumen fermentation parameters, and serum biochemistry were also recorded. The inclusion of FSBM into the diets of Holstein cows increased the milk urea nitrogen (MUN), milk protein yield, fat corrected milk (FCM), and milk fat yield while the milk somatic cell count (SCC) was decreased. In the rumen, the relative abundances of Fibrobacterota, and Spirochaetota phyla were increased in the TRT group, while the percentage of Proteobacteria was lower. In addition, the supplementation of FSBM to Holstein cows increased the acetate percentage, rumen pH, and acetate to propionate ratio, while the proportion of propionate and propionate % was observed to decrease in the TRT group. The KEGG pathway and functional prediction revealed an upregulation in the functional genes associated with the biosynthesis of amino acids in the TRT group. This enrichment in functional genes resulted in an improved synthesis of several essential amino acids including lysine, methionine, and branch chain amino acids (BCAA) which might be responsible for the increased milk protein yield. Future studies should employ shotgun metagenomics, transcriptomics, and metabolomics technology to investigate the effects of FSBM on other rumen microbiomes and milk protein synthesis in the mammary gland in Holstein cows. KEY POINTS: • The supplementation of fermented soybean meal (FSBM) to Holstein cows modified the proportion of rumen bacteria. • Predicted metabolic pathways and functional genes of rumen bacteria revealed an enrichment in pathway and genes associated with biosynthesis of amino acids in the group fed FSBM. • The cows supplemented with FSBM record an improved rumen fermentation. • Cows supplemented with FSBM recorded an increased yield of milk protein and milk fat.

Effect of 24-Week, Late-Evening Ingestion of a Calcium-Fortified, Milk-Based Protein Matrix on Biomarkers of Bone Metabolism and Site-Specific Bone Mineral Density in Postmenopausal Women with Osteopenia.

Dietary calcium intake is a modifiable, lifestyle factor that can affect bone health and the risk of fracture. The diurnal rhythm of bone remodelling suggests nocturnal dietary intervention to be most effective. This study investigated the effect of daily, bed-time ingestion of a calcium-fortified, milk-derived protein matrix (MBPM) or control (CON), for 24 weeks, on serum biomarkers of bone resorption (C-terminal telopeptide of type I collagen, CTX) and formation (serum pro-collagen type 1 N-terminal propeptide, P1NP), and site-specific aerial bone mineral density (BMD), trabecular bone score (TBS), in postmenopausal women with osteopenia. The MBPM supplement increased mean daily energy, protein, and calcium intake, by 11, 30, and 107%, respectively. 24-week supplementation with MBPM decreased CTX by 23%, from 0.547 (0.107) to 0.416 (0.087) ng/mL (p < 0.001) and P1NP by 17%, from 60.6 (9.1) to 49.7 (7.2) µg/L (p < 0.001). Compared to CON, MBPM induced a significantly greater reduction in serum CTX (mean (CI95%); −9 (8.6) vs. −23 (8.5)%, p = 0.025 but not P1NP −19 (8.8) vs. −17 (5.2)%, p = 0.802). No significant change in TBS, AP spine or dual femur aerial BMD was observed for CON or MBPM. This study demonstrates the potential benefit of bed-time ingestion of a calcium-fortified, milk-based protein matrix on homeostatic bone remodelling but no resultant treatment effect on site-specific BMD in postmenopausal women with osteopenia.

Effects of corn distillers grains with yeast bodies and manipulation of dietary cation and anion difference on production, nutrient digestibility, and gas emissions from manure in lactating cows.

In a randomized complete block design, 40 lactating Holstein cows (average 98 d in milk and 41 kg/d of milk yield) were randomly assigned to 1 of 4 diets: (1) containing soybean meal as the major protein supplement (CON diet); (2) CON diet with high-protein dried corn distillers grains at 20% on a dry matter (DM) basis by replacing mainly soybean meal (DG diet); (3) DG diet except that high-protein dried corn distillers grains with yeast bodies (extracted after corn ethanol production) was used (DGY diet); or (4) DG diet supplemented with sodium bicarbonate and potassium carbonate to elevate the dietary cation and anion difference (DCAD; DG-DCAD diet). The DCAD of CON, DG, DGY, and DG-DCAD were 185, 62, 67, and 187 mEq/kg of DM, respectively. The experiment began with a 10-d covariate period and then cows were fed the experimental diets for 5 wk (2-wk diet adaptation and 3-wk data collection periods). Dry matter intake and milk yield were measured daily, and spot urine and fecal samples were collected in the last week of the experiment to measure nutrient digestibility; N, S, and P utilization and excretion; and in vitro NH3 and H2S emissions from manure. All data were analyzed using the MIXED procedure of SAS (random effect: block; fixed effects: diets, repeated week, and interactions). During data collection, DM intake was not different among treatment groups, but milk yield tended to be lower (42.4 vs. 39.9 kg/d) for DG, DGY, and DG-DCAD versus CON, which could have been caused by decreases in organic matter and neutral detergent fiber digestibility. Milk protein yield tended to be lower (1.33 vs. 1.24 kg/d) for DG, DGY, and DG-DCAD versus CON. Milk fat yield was lower (1.26 vs. 1.55 kg/d) for DG and DGY versus CON, but that for DG-DCAD (1.43 kg/d) did not differ from CON. Similarly, energy-corrected milk was lower (38.0 vs. 43.3 kg/d) for cows on DG and DGY versus those on CON, but it did not differ between DG-DCAD (40.7 kg/d) and CON. Urinary and fecal N excretion were greater for DG, DGY, and DG-DCAD compared with CON due to greater dietary crude protein content and N intake. However, NH3 emissions did not differ across treatments. Intakes of dietary P and S were greater for DG, DGY, and DG-DCAD, resulting in greater excretion of those in manure and greater H2S emissions from manure compared with CON. These data suggest that the negative effects of feeding distillers grains on production of lactating cows can be partly explained by a decrease in nutrient digestibility (milk yield) and excessive anion load (milk fat). The milk fat response to DG-DCAD suggests that milk fat depression observed with a diet with high content of distillers grains can be partially alleviated by supplementation of cations. In the current study, we observed no beneficial effects of DG containing yeast bodies.

Camel milk protein hydrosylate alleviates hepatic steatosis and hypertension in high fructose-fed rats.

CONTEXT: Camel milk is used in traditional medicine to treat diabetes mellitus hypertension and other metabolic disorders. OBJECTIVE: This study evaluated the antisteatotic and antihypertensive effects of camel milk protein hydrolysate (CMH) in high fructose (HF)-fed rats and compared it with the effects afforded by the intact camel milk protein extract (ICM). MATERIALS AND METHODS: Adult male Wistar rats were divided into 6 groups (n = 8 each) as 1) control, 2) ICM (1000 mg/kg), 3) CMH (1000 mg/kg), 4) HF (15% in drinking water), 5) HF (15%) + ICM (1000 mg/kg), and 6) HF (15%) + CMH (1000 mg/kg). All treatments were given orally for 21 weeks, daily. RESULTS: Both ICM and CMH reduced fasting glucose and insulin levels, serum and hepatic levels of cholesterol and triglycerides, and serum levels of ALT and AST, angiotensin II, ACE, endothelin-1, and uric acid in HF-fed rats. In addition, both ICM and CMH reduced hepatic fat deposition in the hepatocytes and reduced hepatocyte damage. This was associated with an increase in the hepatic activity of AMPK, higher PPARα mRNA, reduced expression of fructokinase C, SREBP1, SREBP2, fatty acid synthase, and HMG-CoA-reductase. Both treatments lowered systolic and diastolic blood pressure. However, the effects of CMH on all these parameters were greater as compared to ICM. DISCUSSION AND CONCLUSIONS: The findings of this study encourage the use of CMH in a large-scale population and clinical studies to treat metabolic steatosis and hypertension.

Effects of Milk Protein in Resistance Training-Induced Lean Mass Gains for Older Adults Aged ≥ 60 y: A Systematic Review and Meta-Analysis.

This review evaluated the effects of milk-based protein supplementation on resistance training (RT)-induced gains in lean body mass or fat free mass (LBM/FFM) and muscle strength for older adults. A systematic search of PubMed, Scopus and EBSCOhost/SPORTDiscus was conducted. Eligibility criteria: Randomized controlled trials comparing all types of milk-based protein supplements with control supplements for the training older adults at mean age ≥ 60 y. Twenty studies were included in the qualitative synthesis, whilst seventeen studies were included in the quantitative synthesis. A dose of 10-15 g of milk protein supplementation was sufficient to augment RT-induced LBM/FFM. Intriguingly, four out of five studies show negative effect of whey protein supplementation at the same dose range (or even higher) compared with control supplementation (-0.49 kg, 95% CI: -0.69, -0.29, I2 = 14%, Z = 4.82, p < 0.001). For milk-based protein supplementation, RT-induced improvements in muscle strength were observed only when the protein doses ≥22 g (+0.66 kg, 95% CI: 0.07, 1.25, I2 = 0%, Z = 2.18, p = 0.03). Conclusion: Milk protein is superior to whey protein in enhancing RT-induced LBM/FFM gains for older adults. Optimal daily protein intake can dilute the protein supplementation effect.

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

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

The Effects of Cow-Milk Protein Supplementation in Elderly Population: Systematic Review and Narrative Synthesis.

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.

Short communication: Processed bovine colostrum milk protein concentrate increases epithelial barrier integrity of Caco-2 cell layers.

Colostrum plays an important role in initiating the development of the intestinal barrier in newborn mammals. Given its bioactivity, there is much interest in the potential use of bovine colostrum to improve human gastrointestinal health throughout the life span. There is evidence that bovine colostrum is effective at improving small intestinal barrier integrity and some indication that it may alter colonic motility. However, for colostrum to be used as a product to improve intestinal health, it needs to be bioactive after processing. The aim of this study was to determine whether industrial processing of bovine colostrum affects its ability to improve small intestinal barrier integrity or alter distal colon motility. Three colostrum sample types were compared; raw whole colostrum powder (WCP), raw skim colostrum powder (SCP), and industrially produced colostrum milk protein concentrate (CMPC). To determine whether these colostrum powders had different effects on small intestinal barrier integrity, their effects on the transepithelial electrical resistance across an in vitro intestinal epithelial layer (Caco-2 cells) were measured, both with and without a challenge from the proinflammatory cytokine tumor necrosis factor-α. These results showed that CMPC enhanced transepithelial electrical resistance across unchallenged epithelial cell layers, whereas the raw colostrum samples, WCP and SCP, did not have an effect. The colostrum samples were also compared to determine how they affect contractility in the distal colon isolated from the rat. Skim colostrum powder was the only sample to act directly on colonic tissue to modulate motility, increasing the amplitude of contractions. The results show that bovine colostrum is able to improve small intestinal barrier integrity and alter colon motility, and they implicate different components. The barrier integrity enhancement was apparent only in the industrial CMPC, which may have been due to the increase in protein concentration or the release of small peptides as a result of processing. The ability to alter colon motility was present in SCP but absent in WCP, again implying that an increase in protein concentration is responsible for the effect. However, this effect was not apparent for the industrially processed CMPC, suggesting denaturation or degradation of the active component. The beneficial effect of colostrum on small intestinal barrier integrity was present after processing, confirming that it is feasible to industrially produce an active product for gut health.

Dietary protein and bone health across the life-course: an updated systematic review and meta-analysis over 40 years.

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, I2 = 32%), animal (RR (random) = 0.98; 0.76 to 1.27, I2 = 46%) or vegetable protein (RR (fixed) = 0.97 (0.89 to 1.09, I2 = 15%). In total protein supplementation studies, pooled effect sizes were not statistically significant for LSBMD (total n = 255, MD(fixed) = 0.04 g/cm2 (0.00 to 0.08, P = 0.07), I2 = 0%) or FNBMD (total n = 435, MD(random) = 0.01 g/cm2 (-0.03 to 0.05, P = 0.59), I2 = 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.

The Impact of Dairy Protein Intake on Muscle Mass, Muscle Strength, and Physical Performance in Middle-Aged to Older Adults with or without Existing Sarcopenia: A Systematic Review and Meta-Analysis.

Sarcopenia is an age-related condition associated with a progressive loss of muscle mass and strength. Insufficient protein intake is a risk factor for sarcopenia. Protein supplementation is suggested to improve muscle anabolism and function in younger and older adults. Dairy products are a good source of high-quality proteins. This review evaluates the effectiveness of dairy proteins on functions associated with sarcopenia in middle-aged and older adults. Randomized controlled trials were identified using PubMed, CINAHL/EBSCO, and Web of Science databases (last search: 10 May 2017) and were quality assessed. The results of appendicular muscle mass and muscle strength of handgrip and leg press were pooled using a random-effects model. The analysis of the Short Physical Performance Battery is presented in narrative form. Adverse events and tolerability of dairy protein supplementation were considered as secondary outcomes. Fourteen studies involving 1424 participants aged between 61 and 81 y met the inclusion criteria. Dairy protein significantly increased appendicular muscle mass (0.13 kg; 95% CI: 0.01, 0.26 kg; P = 0.04); however, it had no effect on improvement in handgrip (0.84 kg; 95% CI: -0.24, 1.93 kg; P = 0.13) or leg press (0.37 kg; 95% CI: -4.79, 5.53 kg; P = 0.89). The effect of dairy protein on the Short Physical Performance Battery was inconclusive. Nine studies reported the dairy protein to be well tolerated with no serious adverse events. Although future high-quality research is required to establish the optimal type of dairy protein, the present systematic review provides evidence of the beneficial effect of dairy protein as a potential nutrition strategy to improve appendicular muscle mass in middle-aged and older adults.

Variable Glycemic Responses to Intact and Hydrolyzed Milk Proteins in Overweight and Obese Adults Reveal the Need for Precision Nutrition.

Background: Dietary modifications can contribute to improved pancreatic ß cell function and enhance glycemic control. Objectives: The objectives of this study were as follows: 1) to investigate the potential of milk protein hydrolysates to modulate postprandial glucose response; 2) to assess individual responses; and 3) to explore the inter- and intraindividual reproducibility of the response. Methods: A 14-d randomized crossover study investigated interstitial glucose levels of participants in response to 12% w/v milk protein drinks (intact caseinate and casein hydrolysate A and B) consumed in random order with a 2-d washout between treatments. Milk protein drinks were consumed immediately prior to study breakfast and evening meals. Twenty participants (11 men, 9 women) aged 50 ± 8 y with a body mass index (in kg/m2) of 30.2 ± 3.1 were recruited. Primary outcome was glucose levels assessed at 15-min intervals with the use of glucose monitors. Results: Repeated-measures ANOVA revealed that for breakfast there was a significant difference across the 3 treatment groups (P = 0.037). The ability to reduce postprandial glucose was specific to casein hydrolysate B in comparison with intact caseinate (P = 0.039). However, despite this significant difference, further examination revealed that only 3 out of 18 individuals were classified as responders (P < 0.05). High intraclass correlation coefficients were obtained for glucose response to study meals (intraclass correlation coefficient: 0.892 for breakfast with intact caseinate). The interindividual CVs were higher than the intraindividual CVs. Mean inter- and intraindividual CVs were 19.4% and 5.7%, respectively, for breakfast with intact caseinate. Conclusion: Ingestion of a specific casein hydrolysate successfully reduced the postprandial glucose response; however, at an individual level only 3 participants were classified as responders, highlighting the need for precision nutrition. Exploration of high interindividual responses to nutrition interventions is needed, in combination with the development of precision nutrition, potentially through an n-of-1 approach. This clinical trial was registered as ISRCTN61079365 (https://www.isrctn.com/).

Serenoa repens and N-acetyl glucosamine/milk proteins complex differentially affect the paracrine communication between endothelial and follicle dermal papilla cells.

Current treatments for hair follicle (HF) disruption are based on 5-α reductase inhibitors and prostaglandin modulators. Botanicals and nutraceutical compounds interfere with hair loss or stimulate its partial regrowth. Here, we used in vitro cocultures to investigate the activity of Serenoa repens ( SR) and N-acetyl glucosamine + milk proteins (NAG/Lac) on the paracrine interactions between human microvascular endothelial cells (HMVEC) and HF dermal papilla cells (FDPC). Both SR and NAG/Lac-induced endothelial tubulogenesis were enhanced by FDPC. SR promoted proliferation of both the cell types, while NAG/Lac was effective on endothelium. Vascular endothelial growth factor production, enhanced by SR, was further augmented by FDPC. In FDPC 5-α reductase-II and ß-catenin expressions were modified by SR and less by NAG/Lac, with no additional effect by HMVEC. SR and NAG/Lac prevented lipid peroxidation, whereas NAG/Lac was effective on interleukin 1ß production. Finally, SR and NAG/Lac differentially affected HMVEC permeability and tight junction proteins content. These data provide a mechanistic background for the potential use of these compounds as promoters of HF vascularization.

Ingestion of Insect Protein Isolate Enhances Blood Amino Acid Concentrations Similar to Soy Protein in A Human Trial.

BACKGROUND: Increased amino acid availability stimulates muscle protein synthesis (MPS), which is critical for maintaining or increasing muscle mass when combined with training. Previous research suggests that whey protein is superior to soy protein in regard to stimulating MPS and muscle mass. Nevertheless, with respect to a future lack of dietary protein and an increasing need for using eco-friendly protein sources it is of great interest to investigate the quality of alternative protein sources, like insect protein. OBJECTIVE: Our aim was to compare the postprandial amino acid (AA) availability and AA profile in the blood after ingestion of protein isolate from the lesser mealworm, whey isolate, and soy isolate. DESIGN: Six healthy young men participated in a randomized cross-over study and received three different protein supplementations (25 g of crude protein from whey, soy, insect or placebo (water)) on four separate days. Blood samples were collected at pre, 0 min, 20 min, 40 min, 60 min, 90 min, and 120 min. Physical activity and dietary intake were standardized before each trial, and participants were instructed to be fasting from the night before. AA concentrations in blood samples were determined using ¹H NMR spectroscopy. RESULTS: A significant rise in blood concentration of essential amino acids (EAA), branched-chain amino acids (BCAA) and leucine was detected over the 120 min period for all protein supplements. Nevertheless, the change in AA profile was significantly greater after ingestion of whey than soy and insect protein (p < 0.05). Area under the curve (AUC) analysis and AA profile revealed comparable AA concentrations for soy and insect protein, whereas whey promoted a ~97% and ~140% greater AUC value than soy and insect protein, respectively. A tendency towards higher AA concentrations beyond the 120 min period was observed for insect protein. CONCLUSION: We report that ingestion of whey, soy, and insect protein isolate increases blood concentrations of EAA, BCAA, and leucine over a 120 min period (whey > insect = soy). Insect protein induced blood AA concentrations similar to soy protein. However, a tendency towards higher blood AA concentrations at the end of the 120 min period post ingestion was observed for insect protein, which indicates that it can be considered a "slow" digestible protein source.

Impact of dairy protein during limb immobilization and recovery on muscle size and protein synthesis; a randomized controlled trial.

Muscle disuse results in the loss of muscular strength and size, due to an imbalance between protein synthesis (MPS) and breakdown (MPB). Protein ingestion stimulates MPS, although it is not established if protein is able to attenuate muscle loss with immobilization (IM) or influence the recovery consisting of ambulatory movement followed by resistance training (RT). Thirty men (49.9 ± 0.6 yr) underwent 14 days of unilateral leg IM, 14 days of ambulatory recovery (AR), and a further six RT sessions over 14 days. Participants were randomized to consume an additional 20 g of dairy protein or placebo with a meal during the intervention. Isometric knee extension strength was reduced following IM (-24.7 ± 2.7%), partially recovered with AR (-8.6 ± 2.6%), and fully recovered after RT (-0.6 ± 3.4%), with no effect of supplementation. Thigh muscle cross-sectional area decreased with IM (-4.1 ± 0.5%), partially recovered with AR (-2.1 ± 0.5%), and increased above baseline with RT (+2.2 ± 0.5%), with no treatment effect. Myofibrillar MPS, measured using deuterated water, was unaltered by IM, with no effect of protein. During AR, MPS was increased only with protein supplementation. Protein supplementation did not attenuate the loss of muscle size and function with disuse or potentiate recovery but enhanced myofibrillar MPS during AR. NEW & NOTEWORTHY Twenty grams of daily protein supplementation does not attenuate the loss of muscle size and function induced by 2 wk of muscle disuse or potentiate recovery in middle-age men. Average mitochondrial but not myofibrillar muscle protein synthesis was attenuated during immobilization with no effect of supplementation. Protein supplementation increased myofibrillar protein synthesis during a 2-wk period of ambulatory recovery following disuse but without group differences in phenotype recovery.

High dairy protein intake is associated with greater bone strength parameters at the distal radius and tibia in older men: a cross-sectional study.

Dairy protein but not plant protein was associated with bone strength of the radius and tibia in older men. These results are consistent with previous results in women and support similar findings related to fracture outcomes. Bone strength differences were largely due to thickness and area of the bone cortex. INTRODUCTION: Our objective was to determine the association of protein intake by source (dairy, non-dairy animal, plant) with bone strength and bone microarchitecture among older men. METHODS: We used data from 1016 men (mean 84.3 years) who attended the Year 14 exam of the Osteoporotic Fractures in Men (MrOS) study, completed a food frequency questionnaire (500-5000 kcal/day), were not taking androgen or androgen agonists, and had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal or diaphyseal tibia. Protein was expressed as percentage of total energy intake (TEI); mean ± SD for TEI = 1548 ± 607 kcal/day and for total protein = 16.2 ± 2.9%TEI. We used linear regression with standardized HR-pQCT parameters as dependent variables and adjusted for age, limb length, center, education, race/ethnicity, marital status, smoking, alcohol intake, physical activity level, corticosteroids use, supplement use (calcium and vitamin D), and osteoporosis medications. RESULTS: Higher dairy protein intake was associated with higher estimated failure load at the distal radius and distal tibia [radius effect size = 0.17 (95% CI 0.07, 0.27), tibia effect size = 0.13 (95% CI 0.03, 0.23)], while higher non-dairy animal protein was associated with higher failure load at only the distal radius. Plant protein intake was not associated with failure load at any site. CONCLUSION: The association between protein intake and bone strength varied by source of protein. These results support a link between dairy protein intake and skeletal health, but an intervention study is needed to evaluate causality.

Milk basic protein supplementation exerts an anti-inflammatory effect in a food-allergic enteropathy model mouse.

To examine novel functions of milk basic protein (MBP) in T-cell-related inflammatory diseases, such as autoimmune diseases and allergies, we evaluated the effects of MBP on the causative responses of ovalbumin (OVA)-specific T cells in a food-allergic enteropathy model, OVA23-3 mice, which express an OVA-specific T-cell receptor gene. The OVA-specific CD4+ T cells of the mesenteric lymph nodes (MLN) from OVA23-3 mice were cultured with CD11c+ dendritic cells of MLN from BALB/cA mice in the absence or presence of MBP following stimulation with OVA; then the levels of CD69 expression and the levels of cytokine production by CD4+ T cells were measured to evaluate activation. The effects of MBP supplementation of OVA 23-3 mice were assessed by feeding a diet containing OVA (OVA diet) with or without MBP for 28 d. Intestinal inflammation, together with activation and cytokine production of CD4+ T cells by MLN, as well as femoral bone mineral density, were measured. In in vitro culture, MBP inhibited excess activation and IL-4 production by CD4+ T cells. The supplementation of MBP to the OVA diet attenuated OVA-specific IgE production in OVA-diet-fed OVA23-3 mice and slightly resolved developing enteropathy caused by excess IL-4 production by CD4+ T cells. Feeding OVA diet to OVA23-3 mice exhibited bone loss accompanied with enteropathy, whereas MBP supplementation prevented bone loss and increased osteoprotegerin, an osteoclastogenesis inhibitory factor, in the mice. The inhibition of T-cell-activation in both MLN and bone marrow by MBP supplementation may help prevent increased IgE levels caused by excessive IL-4 production and bone loss accompanied by enteropathy. Our findings show that MBP may help attenuate both T-cell-related inflammation and bone loss.

Short-Communication: A Comparison of the In Vitro Angiotensin-1-Converting Enzyme Inhibitory Capacity of Dairy and Plant Protein Supplements.

The consumption of supplements based on dairy or plant proteins may be associated with bioactive potential, including angiotensin-1-converting enzyme inhibitory (ACE-1i) activity, which is linked with blood pressure reduction in vivo. To gain insight into this proposed mechanism, the ACE-1i potential of protein-based supplements, including a selection of dairy (n = 10) and plant (n = 5) proteins were in vitro digested. The total digest was filtered and permeate and retentate were obtained. ACE-1i activity was measured as the ability of proteins (pre-digestion, 'gastric', permeate, and retentate) to decrease the hydrolysis of furanacroloyl-Phe-Glu-Glu (FAPGG) substrate for the ACE-1 enzyme. Permeate and retentate of dairy proteins exerted a significantly higher ACE-1i activity (mean of 10 proteins: 27.05 ± 0.2% and 20.7 ± 0.2%, respectively) compared with pre-digestion dairy proteins (16.7 ± 0.3%). Plant protein exhibited high ACE-1i in 'gastric' and retentate fractions (mean of five proteins: 54.9 ± 0.6% and 35.7 ± 0.6%, respectively). The comparison of the in vitro ACE-1i activity of dairy and plant proteins could provide valuable knowledge regarding their specific bioactivities, which could inform their use in the formulation of specific functional supplements that would require testing for blood pressure control in human randomly-controlled studies.

Milk fat globule-epidermal growth factor-factor VIII-derived peptide MSP68 is a cytoskeletal immunomodulator of neutrophils that inhibits Rac1.

BACKGROUND: Prolonged neutrophil infiltration leads to exaggerated inflammation and tissue damage during sepsis. Neutrophil migration requires rearrangement of their cytoskeleton. Milk fat globule-epidermal growth factor-factor VIII-derived short peptide 68 (MSP68) has recently been shown to be beneficial in sepsis-induced tissue injury and mortality. We hypothesize that MSP68 inhibits neutrophil migration by modulating small GTPase Rac1-dependent cytoskeletal rearrangements. METHODS: Bone marrow-derived neutrophils (BMDNs) or whole lung digest isolated neutrophils were isolated from 8 to 10 wk old C57BL/6 mice by Percoll density gradient centrifugation. The purity of BMDN was verified by flow cytometry with CD11b/Gr-1 staining. Neutrophils were stimulated with N-formylmethionine-leucine-phenylalanine (f-MLP) (10 nM) in the presence or absence of MSP68 at 10 nM or cecal ligation and puncture (CLP) was used to induce sepsis, and MSP68 was administered at 1 mg/kg intravenously. Cytoskeletal organization was assessed by phalloidin staining, followed by analysis using fluorescence microscopy. Activity of the Rac1 GTPase in f-MLP or CLP-activated BMDN in the presence or absence of MSP68 was assessed by GTPase enzyme-linked immunosorbent assay. Mitogen-activated protein (MAP) kinase activity was determined by western blot densitometry. RESULTS: BMDN treatment with f-MLP increased cytoskeletal remodeling as revealed by the localization of filamentous actin to the periphery of the neutrophil. By contrast, cells pretreated with MSP68 had considerably reduced filamentous actin polymerization. Cytoskeletal spreading is associated with the activation of the small GTPase Rac1. We found BMDN-treated with f-MLP or that were exposed to sepsis by CLP had increased Rac1 signaling, whereas the cells pretreated with MSP68 had significantly reduced Rac1 activation (P < 0.05). MAP kinases related to cell migration including pp38 and pERK were upregulated by treatment with f-MLP. Upregulation of these MAP kinases was also significantly reduced after pretreatment with MSP68 (P < 0.05). CONCLUSIONS: MSP68 downregulates actin cytoskeleton-dependent, Rac1-MAP kinase-mediated neutrophil motility. Thus, MSP68 is a novel therapeutic candidate for regulating inflammation and tissue damage caused by excessive neutrophil migration in sepsis.

Inflammaging and Skeletal Muscle: Can Protein Intake Make a Difference?

Inflammaging is the chronic low-grade inflammatory state present in the elderly, characterized by increased systemic concentrations of proinflammatory cytokines. It has been shown that inflammaging increases the risk of pathologic conditions and age-related diseases, and that it also has been associated with increased skeletal muscle wasting, strength loss, and functional impairments. Experimental evidence suggests that the increased concentrations of proinflammatory cytokines and primary tumor necrosis factor α observed in chronic inflammation lead to protein degradation through proteasome activation and reduced skeletal muscle protein synthesis (MPS) via protein kinase B/Akt downregulation. Dairy and soy proteins contain all the essential amino acids, demonstrate sufficient absorption kinetics, and include other bioactive peptides that may offer nutritional benefits, in addition to those of stimulating MPS. Whey protein has antioxidative effects, primarily because of its ability to enhance the availability of reduced glutathione and the activity of the endogenous antioxidative enzyme system. Soy protein and isoflavone-enriched soy protein, meanwhile, may counteract chronic inflammation through regulation of the nuclear transcription factor κB signaling pathway and cytokine production. Although evidence suggests that whey protein, soy protein, and isoflavone-enriched soy proteins may be promising nutritional interventions against the oxidative stress and chronic inflammation present in pathologic conditions and aging (inflammaging), there is a lack of information about the anabolic potential of dietary protein intake and protein supplementation in elderly people with increased systemic inflammation. The antioxidative and anti-inflammatory effects, as well as the anabolic potential of protein supplementation, should be further investigated in the future with well-designed clinical trials focusing on inflammaging and its associated skeletal muscle loss.