Origin & Historical Context

Bovine colostrum (BC) is the initial milk produced by cows after the birth of a calf, specifically during the first 24 to 72 hours. Historically, it is known as a "pre-milk" substance essential for the nutritional and immunological support, growth, and development of the newborn. While its biological purpose is to aid the transition of neonatal animals, the significant impact it has on developing animal immune systems led to its adaptation for human health products. In a clinical context, it has been formally identified as an Ayurveda proprietary drug from India.

Botanical Overview

(Information from outside the sources: Bovine colostrum is an animal-derived substance, not a botanical or plant-based product.) Biologically, BC is composed of highly concentrated bioactive components including immunoglobulins (IgA, IgG, IgM), growth factors, and antimicrobial factors. It is particularly rich in growth factors like Insulin-like Growth Factors (IGF-1 and 2) and Transforming Growth Factors (TGF-α and β), which are critical for cell proliferation and tissue repair. Its composition is often described as more closely resembling blood than regular milk.

Geographic Origin

The sources identify several geographic locations for the production and study of bovine colostrum:

• India: It is produced as a proprietary Ayurvedic medicine.

• South Korea: Colostrum used in tissue regeneration research was obtained from multiple specific farms, including Cheong-Sol, Sa-rang, Yeo-won, and Ha-yan.

• Global Dairy Industry: Commercial forms are produced by the dairy industries in Australia, New Zealand, Finland, the Netherlands, and the United Kingdom.

Cultural Origins

The cultural use of bovine colostrum in humans stems from its role in nature as the primary source of natural immunity for newborns, which helps reduce mortality rates. Its integration into human medicine is heavily linked to the Ayurvedic tradition in India, where it is used for its perceived regenerative properties.

Traditional Use Patterns

Traditionally, BC has been used as a nutraceutical—a food product providing health benefits as an alternative or adjuvant therapy. 

Common use patterns include:

• Immune Support: Boosting the natural defense system to prevent or mitigate infectious diseases like rotavirus and H. pylori.

• Tissue and Bone Repair: It is used as a cost-effective alternative to bone grafts during periodontal surgery to enhance bone regeneration.

• Gastrointestinal Health: Treating conditions such as immunodeficiency-related diarrhea and inflammation caused by nonsteroidal anti-inflammatory drugs.

• Oral Hygiene: Improving symptoms for individuals with oral lichen planus or Sjogren’s syndrome.

• Athletic Performance: Supplementation by athletes to reduce upper respiratory tract infections and aid in muscle injury recovery.

  Bovine colostrum acts as a biological "starter kit," providing the foundational tools and blueprints needed to build an immune system and repair bodily structures from the ground up.

The biological rationale for concentrated bovine colostrum (BC), particularly formulations with high immunoglobulin G (IgG) levels, centers on its role as a nutraceutical that provides a dense "cocktail" of bioactive components to support immunity and tissue repair.

Preclinical and Biological Rationale

• Immunological Support: BC is naturally rich in immunoglobulins (IgA, IgG, IgM), which are essential for building natural immunity. Specifically, serum IgG-2 concentrations have a direct correlation with the body’s ability to produce antibodies against bacterial polysaccharide antigens.

• Counteracting Exercise-Induced Stress: In athletes, intensive training can lead to "exercise-induced immunodepression," increasing susceptibility to upper respiratory tract infections (URTI). The rationale for BC supplementation in this group is to blunt this immune responsiveness decrease and stimulate factors like the neutrophil oxidative burst to maintain defense mechanisms.

• Tissue Regeneration: BC contains high concentrations of growth factors (IGF-1, IGF-2, TGF-α, and TGF-β) that are not found in regular milk. These factors are biologically programmed to promote cell proliferation, migration, and the maturation of the digestive tract.

Metabolism and Stability

The metabolism of BC components depends heavily on how they are "packaged":

• Digestive Stability: Many bioactive factors in milk are designed to pass through the digestive system to be properly absorbed by the body. However, free growth factors can be degraded by digestive enzymes when taken orally, which is why systemic or topical application is sometimes researched to increase effectiveness.

• Extracellular Vesicles (EVs): Much of the potency of colostrum is attributed to Extracellular Vesicles, which are membrane-encased containers that protect cargo like microRNAs (miRNA) and proteins. These EVs are highly resistant to the gastrointestinal environment and even survive industrial processes like freeze-drying (lyophilization), making them efficient delivery systems for bioactive molecules.

• Absorption of Powder: Using BC in powder form may facilitate faster resorption of the material compared to larger particle sizes.

Mechanistic Pathways

The bioactive agents in colostrum trigger several specific intracellular signaling cascades:

1. The TGF-β/Smad Signaling Pathway BC regulates wound healing and epithelialization through the Smad proteins.

• It decreases Smad7 (an inhibitory regulator that usually delays healing).

• This reduction leads to the increased phosphorylation of Smad2/3, which drives cell growth and the formation of the extracellular matrix (ECM).

2. Growth Factor Cascades (Ras/MAPK and PI3K/Akt) Growth factors in BC bind to specific receptors on cell surfaces (such as EGFR or IGF1R), initiating a cascade of events:

• Ras/MAPK Pathway: Directs gene expression to regulate cell proliferation and survival.

• PI3K/Akt/mTOR Pathway: Crucially involved in cell growth, metabolism, and angiogenesis (the formation of new blood vessels).

3. The miRNA-21 Pathway Colostrum-derived EVs are overexpressed with miRNA-21, a small RNA molecule that binds to mRNA to enable post-transcriptional gene regulation. miRNA-21 specifically promotes healing by acting through the Smad7-Smad2/3-elastin pathway, facilitating the transition from inflammation to tissue regeneration.

4. Macrophage Repolarization BC influences the "behavior" of immune cells in the gut and wound sites. It has been shown to help repolarize M1 macrophages (which are pro-inflammatory) into M2 macrophages (which are anti-inflammatory), thereby resolving excessive inflammation and promoting repair.

Analogy: If your body is a construction site under repair, Bovine Colostrum provides not just the raw materials (proteins and fats), but the specialized foremen (growth factors) and encrypted blueprints (miRNA) contained in armored trucks (extracellular vesicles) that ensure the work proceeds quickly and the security guards (IgG) stay alert.

Bovine Colostrum Human Clinical Trail Landscape

The human clinical investigation landscape for bovine colostrum (BC) is expanding into specialized fields such as sports medicine, regenerative dentistry, and intensive care, though large-scale consensus is still developing.

Human Clinical Investigation Landscape

Current human research is categorized by its focus on immune protection and tissue repair:

• Athletic and Physical Activity: Meta-analyses show that while BC supplementation has minimal impact on basal concentrations of serum immunoglobulins (IgA, IgG) or leukocytes in healthy athletes, it is effective in reducing the incidence and duration of upper respiratory tract infections (URTI). It specifically helps blunt the "open window" of immunodepression following high-intensity exercise.

• Regenerative Dentistry: Clinical case series demonstrate that BC, used in powder or dough form during flap surgery, significantly reduces probing depth and enhances bone regeneration in vertical osseous defects, serving as a cost-effective alternative to traditional bone grafts.

• Critical Care and GI Health: In randomized controlled trials (RCTs) involving mechanically ventilated patients, BC supplementation increased serum levels of IGF-1 and reduced the incidence of diarrhea. It has also been clinically used to treat immunodeficiency-related diarrhea and gastrointestinal inflammation caused by NSAIDs.

• Dermatology: Clinical trials have confirmed that Epidermal Growth Factor (EGF), a core component of BC, accelerates epidermal regeneration in skin burns and reduces healing time for lesions in conditions like pemphigus vulgaris.

Preclinical & Mechanistic Research Directions

Research is shifting toward the molecular "cargo" found in extracellular vesicles (EVs):

• The Smad Signaling Pathway: Preclinical models show that Colos-derived EVs decrease Smad7 (an inhibitor) while increasing the phosphorylation of Smad2, which promotes cell growth, re-epithelialization, and the maturation of the extracellular matrix (ECM).

• miRNA-21 Regulation: Colostrum is overexpressed with miRNA-21, which facilitates the transition from the inflammatory phase to the tissue regeneration phase via the Smad7-Smad2/3-elastin pathway.

• Macrophage Repolarization: BC components help repolarize M1 macrophages (pro-inflammatory) into M2 macrophages (anti-inflammatory), resolving chronic inflammation at wound sites.

• Growth Factor Synergies: The combination of IGF-1, PDGF, and TGF-β works synergistically to stimulate fibroblasts, increase collagen production, and activate angiogenesis (the formation of new blood vessels).

Emerging Applications & Knowledge Gaps

• Emerging Applications:

    ◦ Advanced Drug Delivery: Because BC-derived EVs are resistant to the gastrointestinal environment and lyophilization (freeze-drying), they are being investigated as stable oral delivery systems for small molecules and nucleic acids.

    ◦ Neurological and Eye Health: Preliminary research suggests IGF-2 plays a role in memory consolidation in the hippocampus, while TGF-β2 is critical for corneal morphogenesis and eye development.

• Knowledge Gaps:

    ◦ Supplementation Strategy: There is currently no consensus on the optimal dose, duration, or timing of BC supplementation for athletes.

    ◦ Long-term Safety: While BC is well-tolerated for short-term use, there is a scarcity of data regarding long-term safety in humans.

    ◦ Standardization: Raw colostrum is highly heterogeneous, requiring more refined industrial processes to remove potential pathogenic bacteria while preserving delicate bioactive factors.

Evidence Tier Summary

Analogy: If your immune system is a defense fleet, Bovine Colostrum doesn't necessarily build more ships (basal immunoglobulins), but it acts as a high-tech communication upgrade that helps the existing fleet respond faster to threats (URTI) and provides mobile repair docks (growth factors and EVs) to fix damage to the hull (tissue and bone) with unprecedented speed.

Patient Populations and Associated Benefits 

Human clinical research on bovine colostrum (BC) has identified specific populations that benefit from its high concentration of immunoglobulins and growth factors. While meta-analyses sometimes show limited impact on resting systemic biomarkers, clinical outcomes—particularly in infection prevention and tissue repair—are significant.

Primary Populations Studied

• Athletes and Physically Active Adults: This is one of the most researched groups. Supplementation is used to counter "exercise-induced immunodepression" and the "open window" of susceptibility to illness following intense training. Clinical trials demonstrate a reduction in the incidence and duration of upper respiratory tract infections (URTI), although resting levels of serum IgA and IgG often remain unchanged.

• Periodontitis Patients: BC is used as a bioactive material during periodontal flap surgery to treat vertical osseous defects. Clinical results show significant reduction in probing depth and enhanced bone regeneration, making it a cost-effective alternative to traditional bone grafts.

• Neonates (Newborns): Biologically, BC is the primary source of natural immunity for newborns. It provides essential support for the maturation of the digestive tract and the development of the immune system, which is critical for reducing neonatal mortality.

Secondary & Exploratory Populations

• Gastrointestinal (GI) Patients: Research highlights benefits for those suffering from immunodeficiency-related diarrhea, H. pylori infections, and GI inflammation caused by nonsteroidal anti-inflammatory drugs (NSAIDs). BC helps maintain the integrity of intestinal epithelial cells and protects against cytokine-induced damage.

• Critical Care/ICU Patients: In randomized controlled trials of mechanically ventilated patients, BC supplementation resulted in increased serum levels of IGF-1 and a lower incidence of diarrhea.

• Dermatology and Wound Care: BC is applied to patients with skin burns, chronic wounds, and acne scars. It accelerates epidermal regeneration and reduces the healing time for lesions in conditions like pemphigus vulgaris.

• Geriatric Populations (Sarcopenia): Early research explores BC's role in muscle regeneration for the elderly. Pro-IGF-2 found in BC may enhance muscle repair by promoting satellite cell proliferation and blood vessel creation.

• Patients with Oral Hygiene Disorders: Benefits have been observed in individuals with oral lichen planus and Sjogren’s syndrome, where BC-based oral care products improve hygiene and symptom management.

Contextual Use Considerations

• Nutraceutical Framing: BC is defined as a nutraceutical, a food-derived substance that provides health benefits as an adjuvant therapy.

• Structure/Function Support: Rather than acting as a targeted drug for a single pathology, BC is used to support the natural defense system and provide a biological "cocktail" of factors for tissue remodeling, angiogenesis, and bone repair.

• Safety Profile: BC is generally considered safe and well-tolerated, with only mild potential side effects such as nausea or flatulence.

• Synergistic Activity: The rationale for its use centers on the synergy between its components (growth factors, immunoglobulins, and extracellular vesicles), which are more effective together than as isolated supplements.

Analogy: For athletes, Bovine Colostrum acts like a security detail that steps in only when the main defense is exhausted; for surgical patients, it acts like biological mortar, filling in gaps in bone and tissue that the body would otherwise struggle to repair on its own.

The rationale for a Krafted formulation of a 30% IgG bovine colostrum supplement focuses on moving beyond basic nutrition to a precision bioactive delivery system that aligns with the latest clinical evidence and dietary safety standards.

Krafted Formulation Rationale Supplements Krafted Different

Sourcing Standard

The foundation of a Krafted formulation is the collection of colostrum within the first 24 to 72 hours after a calf is born. This "pre-milk" is distinct from regular milk because its composition more closely resembles blood and is uniquely high in biological "blueprints" for development. To ensure a high-quality phenotype, sourcing should target specific dairy regions like Australia, New Zealand, or certified farms like those in South Korea (e.g., Cheong-Sol or Ha-yan), which have been utilized in tissue regeneration studies.

Standardization Targets

A 30% IgG target provides a concentrated dose of natural immunity. The Krafted logic prioritizes several key bioactives:

• Immunoglobulins: Specifically IgG-2, which has a direct correlation with the body's ability to produce antibodies against bacterial polysaccharide antigens.

• Growth Factors: Targets include IGF-1 (870 ng/mL) and TGF-β (100.7 ng/mL) to support cellular growth and wound healing.

• Extracellular Vesicles (EVs): The formulation must preserve these membrane-encased containers, as they carry the miRNA-21 required for the transition from the inflammatory phase to the remodeling phase of repair.

Purity Thresholds + Third-Party Testing Plan

Because raw colostrum can be heterogeneous and potentially harbor pathogenic bacteria like S. aureus or E. coli, rigorous purification is essential.

• Industrial Contaminants: Per the latest clinical concerns, testing must ensure the absence of packaging-derived contaminants like bisphenols and phthalates, which are endocrine-disrupting chemicals.

• Processing Byproducts: The plan must test for neo-formed contaminants like acrylamide, which can be produced during high-temperature industrial processing.

• EV Integrity: Testing should confirm the presence of specific protein markers—TSG101 and CD9—which verify that the extracellular vesicles remain intact and functional.

Formulation Logic (Phenotype Ratios + Excipient Rationale)

The "Krafted" mindset views the supplement as a bioactive "cocktail" where the components work synergistically.

• Macrophage Repolarization: The formulation is designed to guide the body's immune response by helping repolarize M1 macrophages (pro-inflammatory) into M2 macrophages (anti-inflammatory).

• Excipient Rationale: Aligning with new American Medical Association (AMA) resolutions and federal guidelines to "eat real food," the formulation avoids added sugars, artificial flavors, and dyes. These additives are characteristic of ultra-processed foods (UPF), which have been linked to 32 damaging health outcomes. Instead, the logic uses minimally processed ingredients that maintain the food's natural structure.

Delivery Form Justification (Capsule vs. Powder/Liquid)

The choice of delivery is critical for the stability of delicate growth factors:

• Powder Form: Historically used in the dairy industry and clinical trials, powder allows for faster resorption. In dental applications, colostrum used in powder or dough form significantly enhanced bone regeneration.

• Lyophilization (Freeze-Drying): Krafted formulations should use lyophilized powder because it preserves the spherical shape and efficacy of Colos EVs. While free growth factors can be degraded by digestive enzymes, EVs are highly resistant to the gastrointestinal environment, ensuring the "cargo" reaches its destination.

Clinical Mindset + Future FDA Pathway Readiness

By defining bovine colostrum as a nutraceutical (a hybrid of nutrition and pharmaceuticals), the formulation is prepared for a more rigorous regulatory future.

• Structure/Function Framing: Current use focuses on supporting the natural defense system and tissue remodeling rather than making specific drug claims.

• Addressing Knowledge Gaps: To ready the product for an FDA pathway, the clinical mindset prioritizes Randomized Controlled Trials (RCTs) to establish the optimal dose and duration for specific populations, such as athletes suffering from exercise-induced immunodepression.

• Food as Medicine: This formulation aligns with the emerging paradigm that nutrient-dense, minimally processed foods are essential for lowering chronic disease and healthcare costs.

Analogy: A standard colostrum supplement is like sending loose building materials to a construction site; a Krafted 30% IgG formulation is like sending armored delivery trucks (Extracellular Vesicles) filled with specialized foremen (Growth Factors) and encrypted digital blueprints (miRNA) to ensure the repairs are made correctly and the site stays secure.

Safety, Interactions & Quality Considerations

When considering the use of bovine colostrum (BC), especially concentrated 30% IgG formulations, it is vital to evaluate the supplement’s biological stability, potential sensitivities, and the industrial standards used during its production.

Bioavailability & Dose Considerations

• Dosage Ranges: Clinical trials typically utilize daily dosages ranging from 10 to 25 grams of powder or 25 to 125 mL of liquid.

• Bioavailability Mechanisms: BC powder may facilitate faster resorption compared to larger particle sizes. Furthermore, the most potent bioactives are often delivered via extracellular vesicles (EVs), which are naturally resistant to the harsh gastrointestinal environment and digestive enzymes, ensuring the "cargo" (such as miRNA and growth factors) reaches systemic circulation intact.

• Timeframes: Evidence suggests that higher doses (above 20g) split throughout the day and taken for longer than 4 weeks may be necessary to observe significant changes in mucosal immunity markers like SIgA.

Known Safety Profile & Common Side Effects

• General Tolerance: Bovine colostrum is generally considered safe and well-tolerated for the human population.

• Reported Side Effects: Side effects are typically mild and include nausea, diarrhea, flatulence, unpleasant taste, and general abdominal discomfort, which often resolve over time.

• Long-term Data: There is currently a scarcity of data regarding the long-term safety of BC supplementation in humans.

Contraindications & Medication Interactions

• Dairy and Lactose Sensitivity: BC is an animal-derived product. Clinical studies frequently exclude individuals with dairy allergies or lactose intolerance. However, the side-effect profile regarding lactose intolerance is generally lower in colostrum proteins than in standard milk.

• Immunomodulating Supplements: Those already taking immunological-modulating medications or other concentrated growth factor supplements should exercise caution, as the synergistic effects of BC could theoretically lead to dysregulated cell signaling if used improperly.

• Alcohol: General dietary guidelines recommend avoiding the combination of supplements and alcohol for individuals with medical conditions that may interact with both.

Quality Risks

• Biological Contaminants: Raw colostrum is highly heterogeneous and can harbor pathogenic bacteria such as E. coli or S. aureus.

• Industrial Contaminants: High-temperature processing can create neo-formed contaminants like acrylamide. Additionally, complex packaging materials can leach endocrine-disrupting chemicals such as bisphenols and phthalates into the supplement.

• Ultra-Processing Risks: Formulations that include added sugars, artificial flavors, or dyes are classified as ultra-processed and are linked to 32 damaging health outcomes, including cardiovascular and metabolic disorders.

Quality Control Solutions

• Purification Standards: To ensure clinical safety, specific industrial processes must be used to remove pathogenic bacteria while preserving delicate bioactive microvesicles.

• Lyophilization (Freeze-Drying): Utilizing freeze-dried powder is the preferred solution for maintaining the structural integrity and efficacy of Colos EVs and growth factors during storage and transport.

• Biomarker Verification: Quality testing should verify the presence of specific protein markers—TSG101, Alix, and CD9—to confirm the presence of intact EVs, while testing for GM130 ensures the absence of apoptotic cellular debris.

• "Real Food" Alignment: Consistent with recent AMA resolutions and federal dietary guidelines, high-quality formulations should avoid added sugars and chemical additives, focusing instead on nutrient-dense, minimally processed protein sources.

Analogy: Taking a high-quality colostrum supplement is like downloading a security update for your body. If the software is unfiltered (unpurified), it might contain viruses (pathogens); if it’s packaged poorly (ultra-processed), the file might get corrupted by bugs (toxins). But when verified and encrypted (lyophilized and tested), it installs seamlessly and strengthens your system's firewalls.

Regulatory Status & Transparency

To ensure regulatory compliance and transparency for a 30% IgG bovine colostrum supplement, the formulation must align with specific "structure/function" language, rigorous manufacturing safety protocols, and the emerging federal emphasis on "real food" and minimal processing.

Dietary Supplement Positioning + Structure/Function Language

Bovine colostrum (BC) is defined as a nutraceutical—a food-derived product that provides health benefits as an adjuvant or alternative support. Positioning should focus on its role as a biological "cocktail" of immunoglobulins and growth factors.

• Permissible Language: Use claims such as "supports natural immunity," "promotes tissue growth and maturation of the digestive tract," and "supports bone and muscle development".

• Biological Rationale: Labeling can highlight that BC stimulates the neutrophil oxidative burst and helps maintain mucosal immunity (SIgA levels) during periods of intensive training or physical stress.

Labeling Guardrails (No Disease Claims)

While clinical studies investigate BC for conditions like diarrhea, H. pylori, and vertical osseous defects, the supplement label must not claim to "treat, cure, or prevent" these diseases.

• Avoiding "Ultra-Processed" Stigmas: New federal guidelines emphasize avoiding "ultra-processed foods" (UPFs), which are linked to 32 damaging health outcomes. Labels should reflect a "real food" mindset by being free from added sugars, artificial flavors, and synthetic dyes, as these additives are characteristic of harmful industrial formulations.

• Non-Therapeutic Framing: Frame the product as supporting the "integrity of intestinal epithelial cells" rather than treating gastrointestinal inflammation or IBD.

Manufacturing Standards (cGMP, COAs, Lot Traceability)

Because raw colostrum is highly heterogeneous, manufacturing transparency is critical for safety.

• Purification & Safety: Industrial processes must remove pathogenic bacteria such as E. coli and S. aureus while preserving delicate bioactives.

• Contaminant Monitoring: Documentation must ensure the absence of packaging-derived contaminants like bisphenols and phthalates (endocrine disruptors) and industrial byproducts like acrylamide.

• Bioactive Integrity (COAs): A Certificate of Analysis (COA) for a Krafted colostrum should go beyond protein counts to include specific biomarkers of quality, such as the presence of protein markers TSG101, CD9, and MFG-E8, which confirm that the potent extracellular vesicles remain intact.

Documentation Discipline (Internal QC/QA)

Transparency requires a "clinical mindset" regarding data and lot-specific verification.

• Verification of Stability: Internal QA should utilize Lyophilization (freeze-drying) to maintain the spherical shape and efficacy of the colostrum’s bioactives during storage.

• Adherence to Standards: Documentation should confirm the absence of GM130 (a Golgi marker), which verifies that the product is free from contaminating cellular debris arising from cell death (apoptosis).

• Transparency Policy: Manufacturers should adopt a policy where the data supporting the bioactive concentrations (like IGF-1 or miRNA-21) are available upon request, ensuring an "honest, accurate, and transparent account" of the product's composition.

Analogy: Proper regulatory and documentation discipline acts like a passport and background check for a supplement. While the bioactive components (the IgG and growth factors) are the "travelers" bringing benefits, the documentation (COAs and QC) ensures they are who they say they are and that they aren't carrying any dangerous "contraband" (pathogens or toxins) into your body.

References

Core Reviews and High-Value Overviews

(Authoritative syntheses, consensus statements, and field-defining reviews)

• Główka N, Durkalec-Michalski K, Woźniewicz M. Immunological outcomes of bovine colostrum supplementation in trained and physically active people: A systematic review and meta-analysis. Nutrients.2020;12(4):1023. doi:10.3390/nu12041023. PMID: 32276466; PMCID: PMC7231218.

• Rathe M, Müller K, Sangild PT, Husby S. Clinical applications of bovine colostrum therapy: a systematic review. Nutr Rev. 2014 Apr;72(4):237-54. doi: 10.1111/nure.12089. Epub 2014 Feb 26. PMID: 24571383.

• Bagwe S., Tharappel L.J.P., Kaur G., Buttar H.S. Bovine colostrum: An emerging nutraceutical. J. Complement. Integr. Med. 2015;12:175–185. doi: 10.1515/jcim-2014-0039. [DOI] [PubMed] [Google Scholar]

• Bermon S, Castell LM, Calder PC, et al. Consensus statement: Immunonutrition and exercise. Exerc Immunol Rev. 2017;23:8–50.

Clinical Trials

(Human intervention studies with defined outcomes)

• Brinkworth G.D., Buckley J.D. Concentrated bovine colostrum protein supplementation reduces the incidence of self-reported symptoms of upper respiratory tract infection in adult males. Eur. J. Nutr. 2003;42:228–232. doi: 10.1007/s00394-003-0410-x. [DOI] [PubMed] [Google Scholar]

• Ravishankar PL, Guruprasath P, Vangipuram P, Vaidya J, Visithiriyan G, Raj AT, Bhandi S, Patil S, Ghosh S. Bone Regeneration in Vertical Osseous Defect in Periodontitis Patients using Bovine Colostrum. Case Rep Dent. 2022 Jun 21;2022:4183552. doi: 10.1155/2022/4183552. PMID: 35774248; PMCID: PMC9239770.

Safety Signals, Interactions, and Adverse Events

(Tolerability, immune balance, and physiological context)

• Główka N, Durkalec-Michalski K, Woźniewicz M. Immunological Outcomes of Bovine Colostrum Supplementation in Trained and Physically Active People: A Systematic Review and Meta-Analysis. Nutrients. 2020 Apr 8;12(4):1023. doi: 10.3390/nu12041023. PMID: 32276466; PMCID: PMC7231218.

• Gleeson M, Walsh NP. BASES expert statement on exercise, immunity, and infection. J Sports Sci.2012;30:321–324. doi:10.1080/02640414.2011.627371.

Mechanism and Bioactive Constituents

(Growth factors, immunoglobulins, extracellular vesicles, and tissue repair)

• Yalçıntaş YM, Duman H, López JMM, et al. Revealing the potency of growth factors in bovine colostrum.Nutrients. 2024;16(14):2359. doi:10.3390/nu16142359. PMID: 39064802; PMCID: PMC11279796.

• Dos Santos PR, Kraus RB, da Silva Nascente P. Exploring the potential of bovine colostrum as a bioactive agent in human tissue regeneration: A comprehensive analysis of mechanisms of action and challenges to be overcome. Cell Biochem Funct. 2024 Jun;42(4):e4021. doi: 10.1002/cbf.4021. PMID: 38682573.

• Kim H, Kim DE, Han G, et al. Bovine colostrum-derived extracellular vesicles promote resolution of inflammation and tissue regeneration. Adv Healthc Mater. 2022;11(6):e2102027. doi:10.1002/adhm.202102027. PMID: 34865307; PMCID: PMC11468066.

• Siber G.R., Schur P.H., Aisenberg A.C., Weitzman S.A., Schiffman G. Correlation between serum IgG-2 concentrations and the antibody response to bacterial polysaccharide antigens. N. Engl. J. Med. 1980;303:178–182. doi: 10.1056/NEJM198007243030402. [DOI] [PubMed] [Google Scholar]

Phenotype / Processing / Identity / Metabolomics / Quality Control

(Bioactivity drivers, fractionation relevance, and standardization signals)

• Yalçıntaş YM, Duman H, López JMM, Portocarrero ACM, Lombardo M, Khallouki F, Koch W, Bordiga M, El-Seedi H, Raposo A, Alves JLB, Karav S. Revealing the Potency of Growth Factors in Bovine Colostrum. Nutrients. 2024 Jul 21;16(14):2359. doi: 10.3390/nu16142359. PMID: 39064802; PMCID: PMC11279796. (Growth-factor profiling and compositional relevance.)

• Kim H, Kim DE, Han G, et al. Adv Healthc Mater. 2022. (Extracellular vesicles as identity-defining bioactives.)

Supporting Context

(Exercise immunology, baseline immune variation, and physiological framing)

• Hejazi K., Hosseini S.-R.A. Influence of Selected Exercise on Serum Immunoglobulin, Testosterone and Cortisol in Semi-Endurance Elite Runners. Asian J. Sports Med. 2012;3:185. doi: 10.5812/asjsm.34689. [DOI] [PMC free article] [PubMed] [Google Scholar]

• Gleeson M., Walsh N.P. British Association of Sport and Exercise Sciences The BASES expert statement on exercise, immunity, and infection. J. Sports Sci. 2012;30:321–324. doi: 10.1080/02640414.2011.627371. [DOI] [PubMed] [Google Scholar]

• Bermon S., Castell L.M., Calder P.C., Bishop N.C., Blomstrand E., Mooren F.C., Krüger K., Kavazis A.N., Quindry J.C., Senchina D.S., et al. Consensus Statement Immunonutrition and Exercise. Exerc. Immunol Rev. 2017;23:8–50. [PubMed] [Google Scholar]