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Maternal nutrition during the dry period impacts colostrum quality, as well as cow and calf health. Despite the potential of biomarkers, in evaluating preventive interventions, their systematic identification remains limited. The objective of this study is to synthesize and identify biomarkers in colostrum and transition milk and, quantify the variation in response to dietary supplementation during the dry period. A comprehensive literature search was conducted across animal sciences interfaces, including studies from 1949 to 2024. Eligible studies focused on cows receiving dietary supplementation during late pregnancy measuring biomarkers in colostrum and transition milk. Study quality was assessed using a risk of bias tool. We identified 70 studies, all on experimental farms. The overall quality of the evidence was considered good, with 41 % of the studies had a low risk of bias. However, almost all studies lacked a plausible rationale for biomarkers selection. A total of 47 distinct biomarkers were identified, and categorized into biomarkers of dietary exposure (n = 38; e.g., lipids), health (n = 47; e.g., SCC), and status (e.g., protein). To explore the variation of colostrum IgG concentration in response to dry period supplementation, a random-effects meta-analysis was performed on 22 studies, including 19 in dairy cattle and 3 in beef cattle. Despite non-explicit pathways, we found a significant mean difference of 8.7 g/L of IgG between the treatment and control groups. In conclusion, in order to improve the selection of biomarkers in the longitudinal studies, we recommend to reflect on the supposed causal pathway. The link between exposure and health can be documented with appropriate biomarkers available in colostrum and milk matrices.

BACKGROUND: As dietary supplements play a crucial role in meeting the unique nutritional needs of soccer players, a growing body of studies are exploring the effects of dietary supplements on athletic performance in soccer players. The effectiveness of certain supplements, such as caffeine and creatine, remains debated due to inconsistent results across studies. Therefore, this systematic review and Bayesian network meta-analysis was conducted to tentatively identify the most effective dietary supplements for soccer players. METHODS: We searched PubMed, Web of Science, Cochrane, Embase, and SPORTDiscus from database establishment to 5 February 2024 to identify randomized controlled trials (RCTs) evaluating the effects of different dietary supplements on athletic performance in soccer players. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials. A Bayesian network meta-analysis was performed using the R software and Stata 18.0. A subgroup analysis was conducted based on the competitive level of the athletes. RESULTS: Eighty RCTs were included, with 1,425 soccer players randomly receiving 31 different dietary supplements or placebo. The network meta-analysis showed that compared with placebo, carbohydrate + protein (SMD: 2.2, very large), carbohydrate + electrolyte (SMD: 1.3, large), bovine colostrum (SMD: moderate) and caffeine (SMD: 0.29, small) were associated with a significant effect on increasing the distance covered. Kaempferia parviflora (SMD: 0.46, small) was associated with a significant effect on enhancing muscular strength. Beta-alanine (SMD: 0.83, moderate), melatonin (SMD: 0.75, moderate), caffeine (SMD: 0.37, small), and creatine (SMD: 0.33, small) were associated with a significant effect on enhancing jump height. Magnesium creatine chelate (SMD: -3.0, very large), melatonin (SMD: -1.9, large), creatine + sodium bicarbonate (SMD: -1.4, large), and arginine (SMD: -1.2, moderate) were associated with a significant effect on decreasing sprint time. Creatine + sodium bicarbonate (SMD: -2.3, very large) and caffeine (SMD: -0.38, small) were associated with a significant effect on improving agility. Sodium pyr

BACKGROUND: Increasing intestinal permeability causes chronic inflammation, which is one of the etiological factors of many diseases that presently constitute global challenges. AIMS: Considering the importance of developing therapies to eliminate the increased intestinal permeability, in this systematic review and meta-analysis, we analyze the impact of bovine colostrum (BC) on the gut barrier and its permeability. METHODS: Online databases, including PubMed, ISI Web of Science, and Scopus, were searched to find pertinent articles up to March 2022. Weighted mean difference (WMD) and 95% confidence intervals (CI) were considered as effect sizes. The random-effects model was used to pool the study results. RESULTS: A total of ten articles were included in the meta-analysis. The pooled effect revealed a significant reduction in the 5-h urinary lactulose/rhamnose ratio after BC consumption [mean difference (MD): -0.24; 95% CI -0.43 to -0.04; I2 = 99%] and urinary lactulose/mannitol ratio (MD: -0.01; 95% CI -0.02 to -0.001; I2 = 29.8%). No differences were observed in the plasma intestinal fatty acid-binding protein (I-FABP) between BC and control groups (MD: 2.30; 95% CI -293.9 to 298.5; I2 = 92%). CONCLUSIONS: BC supplementation significantly reduced intestinal permeability; however, to confirm the results, more randomized clinical trials considering different quality, dose, and duration are needed. © 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Precise protein supplementation strategies for muscle improvement are still lacking. The timing or type of protein supplementation has been debated as a window of opportunity to improve muscle mass, strength, and physical performance. We conducted a network meta-analysis of randomized controlled trials with protein supplements and resistance training. PubMed, Web of Science, Cochrane Library, and SPORTDiscus databases were searched until May 1, 2023. We included 116 eligible trials with 4,711 participants that reported on 11 timing and 14 types of protein supplementation. Compared with placebo, protein supplementation after exercise (mean difference [MD]: 0.54 kg [95% confidence intervals 0.10, 0.99] for fat-free mass, MD: 0.34 kg [95% confidence intervals 0.10, 0.58] for skeletal muscle mass) and at night (MD: 2.85 kg [0.49, 5.22] for handgrip strength, MD: 12.12 kg [3.26, 20.99] for leg press strength) was most effective in improving muscle mass and strength, respectively (moderate certainty). Milk proteins (milk, whey protein, yogurt, casein, and bovine colostrum), red meat, and mixed protein were effective for gains in both muscle mass and strength (moderate certainty). No timing or type of protein showed a significant enhancement in physical performance (timed up-to-go test, 6-min walk test, and gait speed). Pre/postexercise and Night are key recommended times of protein intake to increase muscle mass and strength, respectively. Milk proteins are the preferred types of protein supplements for improving muscle mass and strength. Future randomized controlled trials that directly compare the effects of protein timing or types are needed. This trial was registered at International Prospective Register of Systematic Reviews as CRD42022358766.

Vitamin E is an essential nutrient for cows, but the effect of vitamin E supplementation is often controversially discussed in the published literature. The main goal of this meta-analysis was to evaluate the effects of vitamin E supplementation on its serum and colostrum enrichment, milk yield (MY), and somatic cell counts (SCC), as well as on various reproductive variables of transition cows, by considering a large set of variables that might influence the responses to vitamin E supplementation. After a broad search in journals and databases with keywords related to transition cows supplemented with vitamin E and appropriate filtering of the results, 36 papers including 53 trials were selected, and their data were extracted into a database. A meta-analysis was conducted on the extracted data. The analysis showed enrichment of serum vitamin E both at parturition (effect size: 2.423) and postpartum (effect size: 0.473), but no effects of vitamin E supplementation on IgG concentration in colostrum (effect size: -0.05) were found. There was a tendency for supplemented cows to produce more milk (effect size: 1.29) during the first month of lactation. Because of large heterogeneity, a meta-regression was performed but none of the presumed influencing factors was identified as a potential variable affecting MY. Milk SCC, as an indicator of udder health, was unaffected by vitamin E supplementation. Vitamin E supplementation tended to decrease the calving to first estrus period (CFP), whereby supplementing Se and taking parity into account in the analysis significantly lowered the CFP. Cows receiving additional vitamin E had, on average, 6.1% fewer cases of retained placenta, whereby Se supplementation and breed were key factors improving the effect of vitamin E to reduce retained placenta. In this regard, breeds other than Holstein responded better and these cows showed a lower incidence of retained placenta. The supplemented cows showed fewer days open (effect size: -0.31), and this improvement was affected linearly by increasing the dosage administered. Also, cows showed fewer services per conception with increasing dosage of vitamin E. In conclusion, this analysis

Bovine colostrum (BC) is a promising natural product applied to improve immunological functions. However, there is very little evidence on the true benefits of BC treatment on the immune function of trained and physically active people; moreover, there is no consensus on the supplementation strategy. For this reason, the aim of this meta-analysis was to quantify the effects of BC supplementation on immunological outcomes in physically active people. Data from 10 randomised controlled trials (RCTs) investigating the effect of BC supplementation in athletes and physically active adults were analysed, involving 239 participants. The results show that BC supplementation has no or a fairly low impact on improving the concentration of serum immunoglobulins (IgA, IgG), lymphocytes and neutrophils, and saliva immunoglobulin (IgA) in athletes and physically active participants. Previous research has shown BC to reduce upper respiratory tract infections; nevertheless, there is a gap of scientific knowledge on the mechanisms underlying these effects. Future RCTs are needed to focus on finding these mechanisms, as well as on preparing a clear consensus on a BC supplementation strategy in trained athletes and the physically active population.

BACKGROUND: Lactoferrin, a normal component of human colostrum and milk, can enhance host defenses and may be effective for prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. OBJECTIVES: Primary objective 1. To assess the safety and effectiveness of lactoferrin supplementation to enteral feeds for prevention of sepsis and NEC in preterm neonates Secondary objectives 1. To determine the effects of lactoferrin supplementation to enteral feeds to prevent neonatal sepsis and/or NEC on duration of positive-pressure ventilation, development of chronic lung disease (CLD) or periventricular leukomalacia (PVL), length of hospital stay to discharge among survivors, and adverse neurological outcomes at two years of age or later2. To determine the adverse effects of lactoferrin supplementation for prophylaxis of neonatal sepsis and/or NECWhen data were available, we analyzed the following subgroups.1. Gestational age < 32 weeks and 32 to 36 weeks2. Birth weight < 1000 g (extremely low birth weight (ELBW) infants) and birth weight < 1500 g (very low birth weight (VLBW) infants)3. Type of feeding: breast milk versus formula milk SEARCH METHODS: We used the search strategy of the Cochrane Neonatal Review Group (CNRG) to update our search in December 2016. We searched the databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PREMEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), as well as trial registries and conference proceedings. SELECTION CRITERIA: Randomized controlled trials (RCTs) evaluating oral lactoferrin at any dose or duration to prevent sepsis or NEC in preterm neonates. DATA COLLECTION AND ANALYSIS: Review authors used standard methods of the CNRG. MAIN RESULTS: This review includes six RCTs. Trial results show that lactoferrin supplementation to enteral feeds decreased late-onset sepsis (typical risk ratio (RR) 0.59, 95% confidence interval (CI) 0.40 to 0.87; typical risk difference (RD) -0.06, 95% CI -0.10 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) 17, 95% CI 10 to 50; six trials, 886 participants; low-quality evidence) and NEC stage II or

Provision of good quality colostrum [i.e., immunoglobulin G (IgG) concentration ≥50g/L] is the first step toward ensuring proper passive transfer of immunity for young calves. Precise quantification of colostrum IgG levels cannot be easily performed on the farm. Assessment of the refractive index using a Brix scale with a refractometer has been described as being highly correlated with IgG concentration in colostrum. The aim of this study was to perform a systematic review of the diagnostic accuracy of Brix refractometry to diagnose good quality colostrum. From 101 references initially obtain ed, 11 were included in the systematic review meta-analysis representing 4,251 colostrum samples. The prevalence of good colostrum samples with IgG ≥50g/L varied from 67.3 to 92.3% (median 77.9%). Specific estimates of accuracy [sensitivity (Se) and specificity (Sp)] were obtained for different reported cut-points using a hierarchical summary receiver operating characteristic curve model. For the cut-point of 22% (n=8 studies), Se=80.2% (95% CI: 71.1-87.0%) and Sp=82.6% (71.4-90.0%). Decreasing the cut-point to 18% increased Se [96.1% (91.8-98.2%)] and decreased Sp [54.5% (26.9-79.6%)]. Modeling the effect of these Brix accuracy estimates using a stochastic simulation and Bayes theorem showed that a positive result with the 22% Brix cut-point can be used to diagnose good quality colostrum (posttest probability of a good colostrum: 94.3% (90.7-96.9%). The posttest probability of good colostrum with a Brix value <18% was only 22.7% (12.3-39.2%). Based on this study, the 2 cut-points could be alternatively used to select good quality colostrum (sample with Brix ≥22%) or to discard poor quality colostrum (sample with Brix <18%). When sample results are between these 2 values, colostrum supplementation should be considered.

BACKGROUND: Lactoferrin, a normal component of human colostrum and milk, can enhance host defense and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. OBJECTIVES: Primary objective To assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NEC in preterm neonates. Secondary objectives1. To determine the effects of oral lactoferrin used to prevent neonatal sepsis and/or NEC on duration of positive-pressure ventilation, development of chronic lung disease (CLD) or periventricular leukomalacia (PVL), length of hospital stay to discharge among survivors, and adverse neurological outcomes at two years of age or later.2. To determine the adverse effects of oral lactoferrin in the prophylaxis of neonatal sepsis and/or NEC.When data were available, we analyzed the following subgroups.1. Gestational age < 32 weeks and 32 to 36 weeks.2. Birth weight < 1000 g (extremely low birth weight (ELBW) infants) and birth weight < 1500 g (very low birth weight (VLBW) infants).3. Type of feeding: breast milk versus formula milk. SEARCH METHODS: We used the search strategy of the Cochrane Neonatal Review Group (CNRG) and updated our search in July 2014. We searched the databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PREMEDLINE, EMBASE, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), as well as trials registries and conference proceedings. SELECTION CRITERIA: Randomized controlled trials (RCTs) evaluating oral lactoferrin at any dose or duration to prevent sepsis or NEC in preterm neonates. DATA COLLECTION AND ANALYSIS: Review authors used standard methods of the CNRG. MAIN RESULTS: Four RCTs are included in this review. Oral lactoferrin supplementation decreased late-onset sepsis (typical risk ratio (RR) 0.49, 95% confidence interval (CI) 0.32 to 0.73; typical risk difference (RD) -0.09, 95% CI -0.14 to -0.04; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 7 to 25; four trials, 678 participants, moderate-quality evidence), NEC stage II or greater (typical RR 0.30, 95% CI 0.12 to 0.76; typical RD -0.05, 95% CI -0.08

INTRODUCTION: Bovine colostrum is a nutrient-dense first milk, rich in bioactive compounds such as immunoglobulins and growth factors, which may enhance athletic performance and immune function. Rugby union involves high-intensity training for both aerobic and muscular power, which could leave athletes vulnerable to opportunistic infections. PURPOSE: This double-blind, randomized study examined the effects of 8 weeks of bovine colostrum supplementation (38 g/day) versus soy protein in 29 club-level rugby players (three women) during the competitive season. METHODS: Muscular strength (1RM bench and leg press) and power (vertical jump), aerobic power (20 m shuttle run), body composition (DXA and ultrasound), and salivary immune and inflammatory markers (IgA, CRP, IL-6, IL-1β) were assessed at baseline and after 8 weeks of supplementation. RESULTS: Bovine colostrum supplementation significantly improved vertical jump height (+ 1.0 cm in the colostrum group; - 0.5 cm in the soy group; p = 0.0023), indicating enhanced lower body power. No significant changes were observed for upper (p = 0.38) or lower (p = 0.82) body strength, aerobic power (p = 0.16), body composition measures (p > 0.05), or salivary immune and inflammatory markers (p > 0.05) compared to the soy group. Reported incidences of illness were unaffected by bovine colostrum supplementation. CONCLUSION: Bovine colostrum may enhance neuromuscular performance, specifically lower body power, but provides limited benefits for other performance metrics, body composition, or immune/inflammatory function. Future research should explore bovine colostrum's potential during off-season training or under higher immune stress conditions. © 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

BACKGROUND: Accelerated recovery from bone injuries is a paramount health-care goal with substantial impacts on physical status and overall well-being. The aim of this study was to evaluate the impact of colostrum supplementation on bone healing in patients with a traumatic extracapsular hip fracture (ECF). METHODS: Patients with an ECF undergoing internal fixation were randomly assigned to receive either bovine colostrum or whey protein. Bone healing was assessed using the Radiographic Union Score for Hip (RUSH). Physical rehabilitation was evaluated using the Harris hip score (HHS) and the Short Musculoskeletal Functional Assessment (SMFA) within 3 months postoperatively. A generalized estimating equation (GEE) was used to assess the time-by-group interactions of these longitudinal variables. Patients were monitored for postoperative complications for 12 months, with the risk difference (RD) and risk ratio (RR) calculated. RESULTS: A total of 116 patients with an ECF were included in the final analysis (colostrum group, n = 59; whey group, n = 57). Baseline characteristics, including age, gender, ethnicity, and body mass index, were similar between the groups (p > 0.05 for all). The colostrum group had a significantly greater increase in the RUSH score (β = 0.88; p = 0.001) and HHS (β = 1.2; p = 0.001) over time compared with the whey group. SMFA dysfunction and bother indices demonstrated significantly greater decreases over time in the colostrum group compared with the whey group (β = -1.2 and -2.4, respectively; p < 0.001 for both). CONCLUSIONS: The present study provides preliminary evidence suggesting that colostrum may accelerate bone healing and enhance short-term physical rehabilitation outcomes more effectively than whey protein. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Very preterm infants (VPIs) are born with an immature gut and predisposed to gut microbiota dysbiosis-related diseases, for example, necrotizing enterocolitis. Although fortification of human milk is required for these infants, the optimal fortifier remains uncertain. Bovine colostrum (BC), rich in protein and bioactive components, could serve as an alternative to conventional fortifiers (CF). The gut microbiota (GM) of 225 VPIs fed human milk fortified with either BC or CF (FortiColos study, NCT03537365) was profiled by 16S rRNA gene amplicon sequencing of fecal samples collected before, and after 1 and 2 weeks of fortification. Birth mode exhibited transient effects on the microbial community structure shortly after birth, with cesarean section-born VPIs dominated by Firmicutes, whereas vaginally born VPIs were dominated by Proteobacteria. This birth mode-derived difference diminished with age and disappeared around 1 month after birth. Fortifier type affected the microbial community structure to a modest extent, but no specific taxa significantly differed between the BC and CF groups. Fecal pH, increased by BC, was positively correlated with Staphylococcus and Corynebacterium and negatively with Bifidobacterium abundance. Change in the relative abundance of Staphylococcus was negatively correlated with body weight gain. Collectively, fortification of human milk with BC or CF does influence the GM of VPIs but only to a modest extent during early life. Birth mode appears to have a significant, but temporary influence on the GM during this period.IMPORTANCEEarly life is a key period for gut microbiota (GM) establishment, where enteral feeding plays a significant role. This is also the case for infants born preterm, who, due to their immature gut, are at a high risk of developing GM dysbiosis-related diseases. Human milk is the optimal feed for preterm infants, but it requires fortification to reach adequate levels of especially protein. Only a few studies have investigated the impact of fortifiers on GM development in preterm infants. Here, we demonstrate that two different bovine milk-based fortifiers, bovine colostrum and a conventional fortifier based on matu

BACKGROUND: Severe acute malnutrition (SAM) is the most life-threatening form of undernutrition, and children hospitalised with complications have unacceptably high mortality. Complicated SAM is a multisystem disease characterised pathophysiologically by muscle wasting, systemic inflammation, metabolic dysfunction, and malnutrition enteropathy including epithelial barrier dysfunction. There is a clear need for novel interventions to address the underlying pathogenic perturbations of complicated SAM. METHODS: In this analysis of tertiary outcomes from a phase II multi-centre trial in Zambia and Zimbabwe, multiplex biomarkers were measured in 122 children (57% male) with SAM randomised following stabilisation ('baseline') to one of four interventions for 14 days to treat malnutrition enteropathy: budesonide, N-acetylglucosamine, colostrum, or teduglutide, compared with standard-of-care. Following measurement of 35 biomarkers from day 15 plasma samples using Luminex and ELISA, the dimensionality of biomarker data was reduced using principal component analysis. FINDINGS: Both budesonide and colostrum reduced systemic inflammation (as measured by CD14, IL1-ra, CRP, and LBP), while children receiving colostrum had higher GLP2 and angiopoietin, and lower circulating lipopolysaccharide, suggesting better restoration of epithelial barrier function. N-acetylglucosamine, a precursor for epithelial glycosaminoglycan synthesis, increased biomarkers of epithelial regeneration (EGF, VEGF), and circulating growth factors (angiopoietin, IGFBP-3, and GCSF). INTERPRETATION: Interventions aimed at ameliorating malnutrition enteropathy showed plausible effects on biomarkers of inflammation and epithelial regeneration, demonstrating an interdependence of systemic inflammation and enteropathy markers seen in structural analysis. Given the interplay between inflammation and tissue restoration in malnutrition, this mechanism of action supports larger trials to determine the clinical benefits of interventions, either alone or in combination, in children with complicated SAM. FUNDING: This analysis of tertiary outcomes for the TAME trial was funded by a Wellcome grant to JPS (220566/Z/20/

BACKGROUND & AIMS: Human milk is the optimal diet for very preterm infants (VPIs), but it requires nutrient fortification to support growth. Bovine colostrum (BC), rich in intact proteins and bioactive components, could serve as a novel fortifier with potential benefits to VPIs gut health. To evaluate a possible effect of feeding BC on intestinal metabolism, the gut microbiota, and their interaction, we studied the fecal metabolome of VPIs in the first month of life, as compared with a conventional fortifier (CF, based on infant formula ingredients). METHODS: Fecal samples were collected from VPIs recruited to the FortiColos trial (NCT03537365, BC, n = 107; CF, n = 112) before (FT0) and one (FT1) or two (FT2) weeks after start of fortification and analyzed using 1H NMR spectroscopy. Abundances of metabolites were compared between BC versus CF groups. Further, temporal changes in metabolite levels after start of fortification, as well as correlations with specific gut bacterial genera were explored. RESULTS: Infants in the BC group had higher levels of fecal acetoacetate, choline, methanol, uracil, creatine, creatinine, lysine and a lower leucine at both FT1 and FT2, relative to the CF group. Asparagine, tryptophan and phenylalanine levels were higher, and butyrate was lower in the BC group at FT1. At FT2, higher fecal succinate and lower isoleucine were found in the BC group. In addition, eight metabolites (asparagine, phenylalanine, tryptophan, lysine, creatinine, acetoacetate, methanol and uracil) had fortification-specific changes over time. Positive correlations were found between succinate and unclassified Enterobacteriaceae, butyrate and Clostridium, uracil and Staphylococcus, while negative correlation were found between uracil and unclassified Enterobacteriaceae members. CONCLUSION: Our study shows distinct fecal metabolome profiles in VPIs in the first weeks after fortification with BC versus CF. The fortification- and time-specific gut metabolite changes suggest that fortifiers influence luminal nutrient metabolism and microbiota activity in VPIs. Fortifier type for human milk affected gut health of VPIs via altered gut metabolite levels, interacting w

BACKGROUND: Bovine colostrum (COL) is assumed to be one of the strongest natural immune stimulants. Regular ingestion of COL may contribute to improved immune response in athletes exposed to high training loads. METHODS: Twenty-eight endurance-trained males aged 31.1 ± 10.2 years (body mass 81.9 ± 9.0 kg; height 1.82 ± 0.06 m) completed this randomized double-blind placebo(PLA)-controlled crossover study aimed at investigating the effect of 12-week COL supplementation (25gCOL·day-1) on resting (REST), exercise-induced (POST-EX), and short-term post-exercise recovery (REC; 1 h after test exercise) changes in selected saliva and blood immunoglobulins (Ig), white blood cell (WBC) count and differential; as well as blood hematological, nutritional status and muscle damage indices. The protocol assumed 4 study visits - before/after supplementation with COL (COLPRE and COLPOST ) and PLA (PLAPRE and PLAPOST ). During testing sessions, incremental rowing test to exhaustion and swimming-specific performance test were introduced as exercise stimuli. RESULTS: At COLPOST visit the secretory IgA (SIgA) concentration in saliva was significantly higher at POST-EX and REC compared to REST (p<0.05). COL supplementation had no effect on blood IgA, IgE, IgD, IgG, and IgM concentrations. Furthermore, after COL supplementation decrease of hematocrit at REC (p<0.05) was revealed. CONCLUSIONS: 12-week supplementation with 25 gCOL·day-1 in endurance-trained male athletes resulted in a favorable increase in post-exercise concentration of salivary SIgA. COL seems to be a potential stimulator of local immune defense after exercise-induced homeostasis disturbances. Nevertheless, the lack of effect on blood markers indicates the need for further research in the area of mechanisms underlying the effect of the supposed COL immunological capacity.

BACKGROUND: Bovine colostrum (BC) with liposomal delivery system (LDS) is a promising supplement to premature infant formula in absence of mother own milk. We propose that BC with LDS can target multiple etiological factors that threaten the developing retina, making premature infant less liable for retinopathy of prematurity (ROP). The aim of this study was to evaluate the effect of BC with LDS in the prevention of ROP. METHODS: This was a single center, randomized, controlled trial. Two hundred and eleven preterm infants of gestational age ≤ 32weeks were admitted to the NICU of Alexandria University Children Hospital, Egypt, and randomly allocated into either non-BC group (n = 105) or BC group (n = 106). Patients in BC group received 3.5 ml /kg/day of BC for 14 days. All patients were monitored for development of ROP, anemia, late onset sepsis (LOS), bronchopulmonary dysplasia (BPD), periventricular leukomalacia (PVL) and necrotizing enterocolitis (NEC), in addition to growth assessment. Multivariate binary logistic regression analysis was performed to determine factors predicting ROP development. RESULTS: Compared with the non-BC group, BC group was associated with a significantly lower incidence of ROP (5/100 vs. 16/100, respectively) with a p-value of 0.033. The administration of BC significantly decreased serum C- reactive protein (CRP) level and increased weight on day-14 of the study in comparison with the CRP level and birthweight at the beginning of study, with Cohen's D= -0.184, D = -2.246, respectively. Patients with suspected sepsis were significantly less in BC than non-BC group, p = 0.004. Patients with BC had significantly higher hemoglobin level on day-14 than non-BC-group, with median (IQR) 12.2 (11.0-13.9) and 11.7 (10.5-12.9), respectively. BC intake is one of factors that decreased development of ROP in univariate analysis. Nevertheless, weight gain and birth weight were the most significant factors affecting ROP development in multivariate-regression model. CONCLUSION: BC may reduce the incidence of ROP in preterm neonates aged ≤ 32 weeks. This might be due to keeping better Hb level and growth rate, as well as anti-inflammatory properties

BACKGROUND: For very preterm infants, human milk is often fortified with formula products based on processed bovine milk. Intact bovine colostrum (BC), rich in anti-inflammatory milk factors, is considered an alternative. We investigated if BC affects anti-inflammatory/TH2 immunity and infection risk in very preterm infants. METHODS: For a secondary analysis of a multicenter, randomized controlled trial (NCT03537365), very preterm infants (26-31 weeks gestation, 23% small for gestational age, SGA) were randomized to receive BC (ColoDan, Biofiber, Denmark, n = 113) or conventional fortifier (PreNAN, Nestlé, Switzerland, n = 116). Infection was defined as antibiotic treatment for five or more consecutive days and 29 cytokines/chemokines were measured in plasma before and after start of fortification. RESULTS: In general, infection risk after start of fortification was associated with low gestational age, SGA status and antibiotics use prior to fortification. Adjusted for confounders, infants fortified with BC showed more infection episodes (20 vs 12%, P < 0.05) and higher cumulative infection risk (hazard ratio, HR 1.9, P = 0.06), particularly for SGA infants (HR 3.6, P < 0.05). Additionally, BC-fortified infants had higher levels of TH2-related cytokines/chemokines (IL-10, MDC, MCP4) and reduced levels of cytokines related to TH1/TH17-responses (IL-15, IL-17, GM-CSF). The differences were most pronounced in SGA infants, displaying higher levels of TH2-related IL-4, IL-6, and IL-13, and lower interferon-γ and IL-1α levels in the BC group. CONCLUSION: Infants fortified with BC displayed a delayed shift from TH2- to TH1-biased systemic immunity, notably in SGA infants, possibly influenced by multiple confounding factors, alongside elevated antibiotic use, suggesting increased susceptibility to infection. © 2024. The Author(s).

Malnutrition underlies almost half of all child deaths globally. Severe Acute Malnutrition (SAM) carries unacceptable mortality, particularly if accompanied by infection or medical complications, including enteropathy. We evaluated four interventions for malnutrition enteropathy in a multi-centre phase II multi-arm trial in Zambia and Zimbabwe and completed in 2021. The purpose of this trial was to identify therapies which could be taken forward into phase III trials. Children of either sex were eligible for inclusion if aged 6-59 months and hospitalised with SAM (using WHO definitions: WLZ <-3, and/or MUAC <11.5 cm, and/or bilateral pedal oedema), with written, informed consent from the primary caregiver. We randomised 125 children hospitalised with complicated SAM to 14 days treatment with (i) bovine colostrum (n = 25), (ii) N-acetyl glucosamine (n = 24), (iii) subcutaneous teduglutide (n = 26), (iv) budesonide (n = 25) or (v) standard care only (n = 25). The primary endpoint was a composite of faecal biomarkers (myeloperoxidase, neopterin, α1-antitrypsin). Laboratory assessments, but not treatments, were blinded. Per-protocol analysis used ANCOVA, adjusted for baseline biomarker value, sex, oedema, HIV status, diarrhoea, weight-for-length Z-score, and study site, with pre-specified significance of P < 0.10. Of 143 children screened, 125 were randomised. Teduglutide reduced the primary endpoint of biomarkers of mucosal damage (effect size -0.89 (90% CI: -1.69,-0.10) P = 0.07), while colostrum (-0.58 (-1.4, 0.23) P = 0.24), N-acetyl glucosamine (-0.20 (-1.01, 0.60) P = 0.67), and budesonide (-0.50 (-1.33, 0.33) P = 0.32) had no significant effect. All interventions proved safe. This work suggests that treatment of enteropathy may be beneficial in children with complicated malnutrition. The trial was registered at ClinicalTrials.gov with the identifier NCT03716115. © 2024. The Author(s).

OBJECTIVES: The safety and feasibility of human milk fortification with bovine colostrum (BC) were investigated in very preterm infants (FortiColos trial, NCT03537365). The BC product contained lower calcium, phosphate, and iron levels compared to the conventional fortifier (CF). We tested whether fortification with BC plus extra phosphate was sufficient to support the infants' mineral status assessed by blood biochemistry. METHODS: In a randomised controlled trial (FortiColos, NCT03537365), mineral status was compared after fortification with BC versus CF. Blood calcium, phosphate, and haemoglobin were determined before and up to 3 weeks after the start of fortification (at the mean age of 8-9 days). The maximum supplemental doses of calcium, phosphate, and iron given were retrieved from patient medical records. Results were adjusted for gestational age, birth weight, and enteral nutrition with the mother's own milk and/or donor human milk. RESULTS: Blood values of calcium, phosphate, and haemoglobin were similar between groups. Infants in both groups required supplementation with calcium and phosphate, but infants fed BC required higher maximum doses of phosphate and calcium (p < 0.05) to maintain acceptable blood values. Regardless of fortification groups, the most immature (<29 weeks of gestation) and small for gestational age infants showed a higher risk for requiring additional phosphate (odds ratio [OR]: 3.9, p < 0.001; OR: 2.14, p = 0.07, respectively). CONCLUSIONS: The use of BC as a fortifier for human milk requires additional phosphate and calcium relative to a CF. Regardless of the fortification product, the most immature and small infants require additional mineral supplementation. © 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

RATIONALE: Non-small cell lung cancer (NSCLC) continues to impose a significant global mortality burden, due to limited therapies, drug resistance, and treatment-related toxicity. Exosomes offer promise for the targeted delivery of therapeutic agents. METHODS: Exosomes were isolated from bovine colostrum and characterized for size, polydispersity index, and surface charge. Celastrol (CEL) was loaded onto exosomes (ExoCEL), and Folic Acid (FA)-functionalized exosomes (FA-ExoCEL) and validated using fluorescence quenching and protease sensitivity assay. Anticancer activity was assessed in NSCLC cell lines using colony formation, cell migration and uptake assays. Transcriptomic (RNA-seq) and protein analysis were performed to analyze gene expression changes. Biodistribution, oral uptake and potential toxicity were evaluated in wild-type mice, while oral antitumor efficacy was tested in orthotopic lung tumor models comparing CEL, ExoCEL and FA-ExoCEL. Synergistic activity with paclitaxel was assessed in chemoresistant cells. RESULTS: Exosomes were isolated, characterized and efficiently loaded with CEL. ExoCEL demonstrated superior antiproliferative effects in NSCLC cell lines and enhanced potency in drug-resistant A549TR cells compared to free CEL. ExoCEL significantly inhibited colony formation and cell migration in a dose-dependent manner. RNA Seq and protein analyses showed that CEL and ExoCEL reversed TGF-β-induced EMT, restored epithelial markers, suppressed mesenchymal, oncogenic and extracellular matrix related markers. In orthotopic lung tumor models, FA-ExoCEL achieved approximately 80-90% tumor inhibition, outperforming both free CEL and ExoCEL. Oral delivery of FA-ExoCEL resulted in efficient gastrointestinal uptake, selective tumor targeting, recovery of exosomal markers in circulation and no observed systemic toxicity. CEL exhibited strong synergy with paclitaxel, with exosomal delivery further enhancing paclitaxel efficacy in resistant cells. CONCLUSIONS: FA-ExoCEL represents a safe, scalable, and effective oral therapeutic strategy for NSCLC. By combining exosome-mediated delivery with folate-targeted tumor accumulation, this platform enhances CEL bi

Clinical trials are reviewed, involving proteins and peptides derived from milk (predominantly bovine), with the exception of lactoferrin, which will be the subject of another article. The most explored milk fraction is α-lactalbumin (LA), which is often applied with glycomacropeptide (GMP) - a casein degradation product. These milk constituents are used in health-promoting infant and adult formulae as well as in a modified form (HAMLET) to treat cancer. Lactoperoxidase (LCP) is used as an additive to mouth hygiene products and as a salivary substitute. Casein derivatives are applied, in addition, in the dry mouth syndrome. On the other hand, casein hydrolysates, containing active tripeptides, found application in hypertension and in type 2 diabetes. Lysozyme is routinely used for food conservation and in pharmaceutical products. It was successfully used in premature infants with concomitant diseases to improve health parameters. When used as prophylaxis in patients with scheduled surgery, it significantly reduced the incidence of hepatitis resulting from blood transfusion. Lysozyme was also used in infected children as an antimicrobial agent showing synergistic effects in combination with different antibiotics. Proline-rich polypeptide (PRP) was introduced to therapy of Alzheimer's disease patients. The therapeutic value of PRP was proved in several clinical trials and supported by studies on its mechanism of action. Concentrated immunoglobulin preparations from colostrum and milk of hyperimmunized cows showed efficacy in prevention of infections by bacteria, viruses and protozoa. A nutrition formula with milk-derived TGF-β2 (Modulen IBD®) found application in treatment of pediatric Crohn's disease. In conclusion, the preparations containing milk-derived products are safe and effective measures in prevention and treatment of infections as well as autoimmune and neoplastic diseases.

Abstract: Bovine colostrum contains high concentrations of cytokines, and colostral cytokines are considered to be an important factor in stimulation of maturation of the immune system in newborns. In this study, 5 proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha, IFN-gamma and IL-1 receptor antagonist, IL-1ra) present in colostrum were tested for their potential to enhance mitogenic response and to elicit expression of IL-2 mRNA and CD25 in peripheral blood mononuclear cells (PBMC) from newborn calves before being fed colostrum. PBMC were pretreated with each recombinant bovine cytokine for 2 hr before stimulation with concanavalin A (ConA). Pretreatment of PBMC from newborn calves with IL-1beta, TNF-alpha or IFN-gamma significantly enhanced the ConA response, whereas IL-1ra inhibited the response. The degree of enhancement or inhibition of mitogenic response by these cytokines was more pronounced in PBMC from newborn calves than in those from adult cows. Although IL-2 mRNA expression in ConA-stimulated PBMC from newborn calves was weaker than that in those from adult cows of ConA-stimulated controls, the expression levels became comparable after pretreatment with IL-1beta, TNF-alpha or IFN-gamma. The CD25 expression in PBMC from newborn calves was also enhanced by pretreatment with IL-1beta, TNF-beta and IFN-gamma. These results suggest that pretreatment of neonatal PBMC with IL-1beta, TNF-alpha or IFN-gamma promotes mitogenic response to ConA through up-regulating the production of IL-2 and the expression of the mature IL-2 receptor.

The coexistence of interleukin (IL)-1beta with IL-1 receptor antagonist (ra) in bovine colostrum and the possibility of simultaneous transfer of these cytokines to neonates via colostrum have been demonstrated. In the present study, we investigated the effect of IL-1ra on the mitogenic response of calf peripheral blood mononuclear cells (PBMC) stimulated by concanavalin A (ConA), which was mediated by IL-1. Pretreatment of PBMC with recombinant bovine (rb) IL-1ra alone significantly suppressed the proliferation of ConA-stimulated cells. However, in the presence of rbIL-1beta, the suppressive activity of rbIL-1ra was counteracted. These results suggest that coexistence of IL-1ra with IL-1 in colostrum may have no effect on the activation of the neonatal immune system by IL-1beta.

The anion binding properties of human lactoferrin (Lf), with Fe3+ or Cu2+ as the associated metal ion, highlight differences between the two sites, and in the anion binding behaviour when different metals are bound. Carbonate, oxalate and hybrid carbonate-oxalate complexes have been prepared and their characteristic electronic and EPR spectra recorded. Oxalate can displace carbonate from either one or both anion sites of Cu2(CO3)2Lf, depending on the oxalate concentration, but no such displacement occurs for Fe2(CO3)2Lf although it does for the bovine analogue. Addition of oxalate and the appropriate metal ion to apoLf under carbonate-free conditions gives dioxalate complexes with both Fe3+ and Cu2+. The anion sites as determined from the crystal structures of Fe2(CO3)2Lf, Fe2(C2O4)2Lf, Cu2(CO3)2Lf, and Cu2(CO3)(C2O4)Lf have been compared. Both the carbonate and oxalate ions bind in bidentate fashion to the metal, except that the carbonate ion in the N-lobe site of dicupric lactoferrin is monodentate. The hybrid copper lactoferrin complex shows that the oxalate ion binds preferentially in the C-lobe site in a bidentate mode. A series of complexes containing the synergistic anion O,N-chelates with increasing substitution on the N atom (glycinate, iminodiacetate and nitrilotriacetate) have been prepared with iron bovine lactoferrin for comparison with the O,O-chelate oxalate. Overall these observations lead to a generalised model for synergistic anion binding by transferrins and allow comparisons to be made with nonsynergistic anions such as citrate and succinate.

152. Biokhimiia. 1975 Jan-Feb;40(1):145-9. [Interaction of trypsin with a trypsin inhibitor from bovine colostrum]. [Article in Russian] Cechová D, Kazanskaia NF, Larionova NI, Berezin IV. Kinetics of trypsin association with trypsin inhibitor from colostrum (IC) was studied. The association rate constant is 3-10-5 M- minus 1 sec- minus 1 at pH 7,8, 25 degrees C. The rate constant for the complex dissociation was determined from the kinetics of the IC displacement from the complex with trypsin by a specific substrate and was found to be 5-10- minus 6 sec- minus 1 (pH 7,8; 25 degrees C). The equilibrium constant (Ki) was measured in a special experiment and was equal to 4-10- minus 12 M (p H 7,8; 25 degrees C). The similarity of this reaction and the association of trypsin with other protein inhibitors was discussed.

153. J Dairy Sci. 1971 Dec;54(12):1886-94. doi: 10.3168/jds.S0022-0302(71)86130-1. Selective transport of IgGl into the mammary gland: role of estrogen and progesterone. Smith KL, Muir LA, Ferguson LC, Conrad HR.

154. Berl Munch Tierarztl Wochenschr. 1968 Dec 15;81(24):483-5. [Research with a gamma globulin preparation. 3. Tests on white mice to prove a synergistic protective effect of the combination of colostral bovine gamma globulin with penicillin-streptomycin]. [Article in German] Walzl HL.

BACKGROUND: Maternal milk-borne transforming growth factor (TGF-β plays a potential role in the development of the mucosal immune system in infants. However, it remains unclear what factors determine TGF-β levels in breast milk. We hypothesized that microbial pressures during pregnancy might affect the expression levels of TGF-β in colostrum. OBJECTIVE: This study compared TGF-β2 levels in colostrum of lactating women living in Japan and Nepal with contrasting hygiene statuses. Additionally, we identified environmental and intrinsic factors influencing TGF-β levels in colostrum. METHODS: Breast milk samples and structured questionnaires were collected from 80 women living in Japan and 208 women living in Nepal. A robust regression model was used to identify factors associated with colostral TGF-β levels. RESULTS: Analysis using the Mann-Whitney U test showed that TGF-β levels were significantly higher in Japanese women than in Nepalese women. Japanese women who consumed animal milk daily during pregnancy and had atopic dermatitis expressed lower levels of TGF-β in colostrum, as compared to Japanese women who did not. Among Nepalese women, large family size and higher birth order were associated with lower TGF-β levels and women who gave birth to infants with low birth weight had higher expression of TGF-β levels in milk than women who gave birth to infants with normal birth weight. CONCLUSION: The results suggest that induction of TGF-β levels in colostrum depends on differences in the ethnicity of lactating women. Consumption of animal protein and parturition characteristics may affect TGF-β levels in breast milk, and may explain differences in these levels in breast milk between countries.

Background/Objectives: Dietary treatment may play a complimentary part alongside established medical treatment pathways for children with Crohn's disease. The aim of this review was to explore the impact of a range of dietary treatments, including the capability of preserving the mucosal barrier, during the maintenance phase of Crohn's disease. Methods: Randomised controlled trials and cohort studies were retrieved from five databases (Cochrane library, MEDLINE, EMBASE, ScienceDirect, and Web of Science) and through hand searching (last search: June 2025). In the inclusion criteria, this review only included studies that directly assessed children with Crohn's disease who achieved clinical remission after the induced phase but simultaneously appeared to have signs of inflammation. Results: Six studies were identified, three of which reported outcomes directly associated with the mucosal barrier, while the other studies reported intestinal inflammation and nutritional status. A range of dietary approaches were investigated, with mixed outcomes. A carbohydrate-based diet had a mixed-effect influence on the mucosal barrier, whereas an exclusion diet significantly reduced intestinal inflammation (p = 0.01). One study reported that bovine colostrum (BC) milk (a novel approach) demonstrated mucosal integrity improvement, while the timing of partial enteral nutrition (PEN) also improved nutritional status. Importantly, compliance with all these strict regimes is complex and difficult to implement, even with the support of a dietitian. Conclusions: Consideration of the most appropriate dietary approach within CD management including remission has reported mixed effects to date. Further research is needed, especially to establish the benefits and any negative consequences of dietary intervention more clearly, and especially regarding mucosal integrity.

Background: Oral mucositis (OM) is a frequent complication of anticancer therapy which arises from cytotoxic injury, having significant clinical implications. Nutritional and supplement-based interventions have been proposed as adjunctive strategies to improve outcomes. Objectives: This systematic review aimed to identify and synthesize evidence from randomized controlled trials (RCTs) evaluating nutritional or natural supplement interventions for prevention or management of OM in pediatric oncology. Methods: We conducted a systematic search (17 August 2025) of Scopus, PubMed/MEDLINE, and Google Scholar (1 January 2000-1 June 2025) following PRISMA guidelines and registered in PROSPERO (CRD420251134454). The review included randomized controlled trials in pediatric cancer patients (≤18 years; up to 25 years for follow-up) receiving chemo-/radiotherapy, assessing nutritional, dietary, or natural product interventions for oral mucositis prevention or treatment. Non-randomized, adult, non-English, non-peer-reviewed, or inaccessible studies were excluded. Outcomes included incidence, severity, duration of OM, and mucositis-associated pain. Risk of bias was assessed using the NIH Study Quality Assessment Tools and the Cochrane RoB 2 tool. Results were qualitatively summarized. Results: Of 5870 records identified, 20 RCTs met inclusion criteria resulting in 1430 total included patients. Interventions tested included systemic supplements (e.g., glutamine, zinc, and bovine colostrum), topically applied agents (e.g., honey, vitamin E, Aloe vera, and olive oil), and nutrient-containing rinses (e.g., chamomile, Caphosol, and Traumeel S). Honey-based interventions showed promising outcomes. Discussion: Study designs and sample sizes varied considerably, and outcome measures were heterogeneous. Challenges with blinding, variable compliance, and inconsistent reporting reduce confidence and precision in the findings. Conclusions: Evidence from pediatric RCTs remains limited but highlights nutritional and natural products as promising supportive care options for OM. Findings suggest potential for practical, low-cost adjuncts to established oral care protocols, warranting furthe