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Bovine colostrum as therapy

Bovine colostrum has proved to be highly feasible as treatment for several diseases and disorders related to either gastrointestinal health or immune system. It is often used as diet supplement provided against specific diseases, generally immunological protection or as a treatment for adverse side effects.

Research evidence for positive effects from colostrum

Knowledge about the importance of bovine colostrum for the calf’s ability to resists infections and diseases has naturally lead to a marked interest in the potentials for bovine colostrum to exert similar effects on humans. The value of bovine colostrum as diet supplement and biologic medicine is now documented in multiple clinical trials and supported by relatively large databases on case reports and other anecdotal evidence (Struff & Sprotte, 2008).

Adverse effects from oral ingestion of bovine colostrum are absent in clinical research, even on repeated application of high doses. The only contradiction reported so far is lactose intolerance (Struff & Sprotte, 2008).

Health related effects from bovine colostrum

Evidence from numerous studies report that bovine colostrum has immune-modulating capabilities that may be beneficial for maintaining or improving patients’ own immune defense when they are experiencing detrimental conditions or diseases. Bovine colostrum is also feasible in the maintenance of the gastrointestinal mucosal integrity due to its antimicrobial, -viral, -bacterial and endotoxin-neutralizing effects, together with its ability to suppress gut inflammation and promote tissue repair. Additionally, contact with the gut mucosa, may trigger immunological events leading to systemic effects (Rathe et al., 2014).


Effect from bioactive components

The positive effects making bovine colostrum feasible as human diet supplementation come from the contents of bovine colostrum which includes extremely high amounts of bioactive factors, such as immunoglobulins, growth factors, antimicrobial factors, anti-inflammatory factors, immune-regulating factors (Larson et al., 1980; Weaver et al., 2000; Stelwagen et al., 2009). Besides them, colostrum contains a range of nutrients, vitamins, minerals, proteins, lipids, carbohydrates and amino acids (Thapa, 2005).

Immunoglobulins can neutralize enteric pathogens, growth factors promote wound healing and tissue growth, immune factors acting anti-inflammatory and antibacterial, -viral and -microbial, while essential vitamins and minerals are important for the whole system (Kelly, 2003; Haug et al., 2007; Struff & Sprotte, 2008; Stelwagen et al., 2009; Rathe et al., 2014; Bagwe et al., 2015).


The important milk matrix

The complex structure of the milk is believed to probably influence the release, transformation and bioactivity of nutrients in the gut. Retaining colostrum intact is therefore important in order to maintain the beneficial effects. Furthermore, many proteins and compounds found in colostrum survive digestion better when ingested incorporated in the milk matrix. Unprocessed whole colostrum with an unchanged milk matrix seems to be superior to processed colostrum products and milk products enriched with whey proteins or other bioactive components (Rathe et al., 2014; Pontoppidan et al., 2015).

Administration of multiple peptides, such as growth factors, is reported to result in additive or synergistic activity, and the multiple growth factors in colostrum appears in a formation in the matrix that provides protection of the peptides against proteolytic digestion in the gastrointestinal tract. Thus, the growth factors are not destroyed during digestion and arrive intact at the place of injury (Playford et al., 2001).

No species specification in colostrum

Due to the similar molecular structure of many bioactive compounds found in the colostrum from several mammalian species, many effects may also be shared across species. This indicates that colostrum from one mammal can benefit individuals from another mammal. The benefits of bovine colostrum on neonatal calves can thus benefit specific groups of humans. Recent studies certainly suggest so; bovine colostrum has been studied extensively as a clinical nutritional supplement for a variety of conditions, e.g. treatment of non-steroid anti-inflammatory drugs, abdominal surgery, human immunodeficiency patients, short bowel syndrome and sports nutrition (Rathe et al., 2014).

Several studies have specifically reported an absence of adverse effects, and bovine colostrum is considered safe and well tolerated (Rathe et al., 2014). Most healthy cows produce colostrum in vast excess of the calf’s requirement and this surplus is feasible to collect (Foley & Otterby, 1978).

Areas of interest

Several diseases, infections and detrimental states have been investigated in the search for beneficial utilization of bovine colostrum. The majority of studies are conducted in medical areas related to either gastrointestinal health or host immune system. This includes immunological responses, infections, tissue damage, enteric pathogens, adverse effects from chemotherapy, diarrhea, gut problems, respiratory tract infections, preterm birth and more. Bovine colostrum is often used as an orally ingested diet supplement provided against specific diseases, generally immunological protection or as a treatment for adverse side effects.

In the following, several examples of positive effects from bovine colostrum on different diseases and illnesses are presented. Some of the examples are discussed more detailed as cases.

Immune responses

Studies have reported positive effects from oral intake of bovine colostrum on immunological diseases. Some of reported results appear valid, while others suffer from weak methodological methods and non-significant results. A large number of anecdotal evidence is concerning the effect of bovine colostrum as generally improving the immunological state of the body, preventing common colds and enhancing daily life quality. Results from two studies investigating the effects of bovine colostrum on the immune response to immunization in healthy subject both suggested that colostrum could trigger immunological events that were followed by system events, after the colostrum had been in contact with the gut mucosa (Rathe et al., 2014).

Gut immunity

The gut is a major immunological defense barrier in the body, as it the first point of contact with microbes, bacteria, viruses and other pathogens from ingested food and the environment. Studies have shown that bovine colostrum improves gut structure and function during inflammation and damage of the intestinal mucosa (Støy et al., 2014). Such findings suggests bovine colostrum as a clinically relevant alternative to humans with compromised gut and immune function, such as short bowel syndrome or chronic pain syndrome (Rathe et al., 2014), preterm infants (Jensen et al., 2013; Shen et al., 2015) or children with chemotherapy-induced gut toxicity (Shen et al., 2016).


Leaky gut syndrome

The leaky gut syndrome is a condition that is associated with many autoimmune diseases, such as type 1 diabetes, inflammatory and irritable bowel disease, chronic fatigue syndrome and multiple sclerosis, and is characterized by a loss of the protective function of the mucosal barriers in the gastrointestinal tract that interact with the environment (Fasano, 2012). Colostrum supplements not only possess anti-inflammatory properties but also appear to enhance nutrient bioavailability and prevent subclinical leaky gut syndrome in patients who use colostrum as a dietary supplement (Thapa, 2005; Bagwe et al., 2015).


Sport-related immune responses

Elite athletes appear to be more susceptible to infections, particularly when training is intensified shortly before competition. This paradox of last-minute illness is caused by periods of very intense training weaken the immune system and lead to an increased risk of infections, but the exact mechanism behind in still unknown. Apparently, the mucous membranes in the mouth and in the intestine change when the body is exposed to an increased level of stress during very intensive exercise (Walsh et al., 2011). Recent studies indicate that colostrum can help the immune system to withstand the extra training load, and that a daily intake of colostrum over some weeks can reduce the incidence of respiratory tract infections in athletes (Davison & Diment, 2010).

Diabetes

Type 1 diabetes and insulin diabetes are likely based on an autoimmune disorder, and bovine colostrum contain various bioactive factors thought to potentially control and inhibit such autoimmune disorders and other similar allergies (Bagwe et al., 2015). Findings suggest that bovine colostrum also has a positive effect on metabolic control in type 2 diabetes patients, but the mechanisms and actual benefits remain unestablished (Rathe et al., 2014). One study found a continuous decrease in postprandial blood glucose levels throughout the study period together with a significant decrease in total cholesterol, triglyceride and ketone body levels (Kim et al., 2009).

The probable anabolic effect from bovine colostrum and the potential ability of it to improve nutrient absorption in the gut have started speculations about the feasibility of colostrum supplementation in managing failure to thrive, but no valid evidence is yet established (Rathe et al., 2014).

Infections

Colostrum is reported to be beneficial against infections from enteric pathogens, as it probably improve the mucosal integrity, tissue repair and perform direct antibacterial and antiviral actions. (Rathe et al., 2014). Inflammation caused by enteric pathogens such as Escherichia coli, Cryptosporidium and rotavirus and other is also known to be diminished as bovine colostrum seems to kill the pathogens (Bagwe et al., 2015). It has also been demonstrated that colostrum seems highly helpful in reversing infection-induced inflammation in the digestive tract of HIV patients (Rona, 1998).

Respiratory tract infections

Studies have reported an increase in salivary IgA content after ingestion of bovine colostrum, which is beneficial against upper respiratory tracts infections (URTI), as well as dental infection, chronic bronchitis and respiratory allergic disorders. It was reported that most of the patients remained free of symptoms during the time period they ingested bovine colostrum (Thapa, 2005).

Elite athletes are often developing URTI during periods of intense exercise. Bovine colostrum has proven a beneficial diet supplementation against such. Significantly fewer patients receiving colostrum reported URTI within 7 weeks after ended ingestion, compared to those receiving placebo. However, colostrum showed no effect on symptoms once they had developed (Brinkworth & Buckley, 2003).

These data suggest that bovine colostrum may have a prophylactic effect against URTI, and may correspond to the findings of increased salivary IgA levels in athletes receiving colostrum as diet supplementation. However, further studies are needed to fully elucidate and confirm the effects of bovine colostrum on URTI (Rathe et al., 2014).

Diarrhea

Diarrhea is generally defined as the condition of having three or more loose or liquid stools per day. It is usually a symptom of an infection in the gastrointestinal tract, and is related to malfunction in the gut mucosa and high permeability. It is commonly caused by bacteria, viruses, microbes or other enteric pathogens. Besides being a disease in itself, diarrhea is also a symptom of several diseases and disorders, where the mucosal integrity in the gut has been compromised (WHO, 2017).

Studies on the effect from bovine colostrum as diet supplement against diarrhea, all report markedly improvements (Playford et al., 2000; Kelly, 2003; Struff & Sprotte, 2008; Elfstrand & Flóren, 2010; Feasey et al., 2011; Marchbank et al., 2011; Rathe et al., 2014). The effects most likely come from the range of bioactive factors with immunological, antibacterial, -viral, and –microbial effects found in bovine colostrum (Pakkanen & Aalto, 1997). Since the 1980’s, an increasing number clinical studies on the efficiency of immune compounds from bovine colostrum on bacterial gastrointestinal infections, oral infections, viral infections, cryptosporidium infections have all provided positive results (Korhonen et al., 2000).

NSAIDs

Non Steroidal Anti-Inflammatory Drugs (NSAID) are widely and commonly used prescribed medicine. In Denmark, commonly types of NSAID includes Ibuprofen and Diclofenac. Chronic use is reported to result in gastric and intestinal damages in both the small and large intestine, causing increased permeability with blood and protein loss and stricture formation, the latter being a distinctive feature of Crohn’s disease (Bjarnason et al., 1987; Allison et al., 1992).

Bovine colostrum has been reported to reduce gut permeability in patients taking long-term and short-term NSAID treatment when co-administrated, indicating a huge potential for future treatment. The positive effects of colostrum is likely influenced by the presence of numerous growth factors, such as epidermal growth factors (EGF’s) and tissue growth factors (TGF-α and TGF-β) (Playford et al., 2000; Kelly, 2003).

Chemotherapy-induced toxicity

Toxic side effects from chemotherapy on the gastrointestinal tract can be a limiting factor on the dose or the duration of the treatment. Actions to protect gastrointestinal tissues and promote their recovery could benefit the use of higher doses of chemotherapy, with greater potential for cure (Playford et al., 2000).

Gastrointestinal toxicity, also known as mucositis, is a common chemotherapy-induced adverse effect complication and occur in 40-100% of all pediatric leukemia patients, depending on the disease, type of drug, dose, dosing schedule and individual factors (Sonis, 2010).

Recent studies have proven the efficiency of bovine colostrum in reducing chemotherapy induced toxicity in the gut (Pontoppidan et al., 2015; Shen et al., 2016; Shen et al., 2016). These results highlight the great potential in bovine colostrum as a diet supplement to minimize the adverse effects of chemotherapy in pediatric patients (Sangild et al., 2013).

Surgery

Besides providing immune support and protect against infections, bovine colostrum also has muscular-skeletal repair and growth capabilities and can promote growth in the intestinal tissue (Purup et al., 2007). Colostrum is the only natural source of transforming growth factors alpha and beta (TGF-α and TGF-β), and insulin like growth factors 1 and 2 (IGF-I and IGF-II). These major growth factors have significant muscle and cartilage repair characteristics and promote wound healing. Colostrum also contain additional growth factors, all with multiple regenerative effects on body cells. Such effects are highly beneficial and practical for trauma and surgical patients (Uruakpa et al., 2002).

Evidence points to bovine colostrum as diet supplement could reduce microbial translocation across the gut mucosa in patients undergoing abdominal surgery. When provided before the intervention, patients showed no increase in endotoxins (Kelly, 2003; Thapa, 2005). These results is likely attributable to the characteristic of bovine colostrum as antibacterial, endotoxin-neutralizing, gut-inflammation suppressing and promoting of mucosal integrity and tissue repair (Rathe et al., 2014).

Bovine colostrum has also been reported to promote growth of nerve cells and skin, and topical application of bovine colostrum constituents has been shown to promote open wound healing (Bagwe et al., 2007)

Short Bowel Syndrome

Short Bowel Syndrome is characterized by inefficient nutrient absorption in the gut and thus malnutrition in patients that lack parts of the small intestine as the result of massive surgical resection or congenital defects. The ability of the small intestine to adapt after surgery is crucial for sufficient uptake of fluid, electrolytes and nutrients in the patients, and may be influenced by several bioactive factors in colostrum, such as peptide growth factors, growth hormones and different nutrients (Uko et al., 2012). Some studies have suggested improvement of intestinal adaptation from colostrum, while others have failed to confirm this finding (Heemskerk et al., 2002).

The apparent absence of beneficial effects from colostrum in clinically stable patients with Short Bowel Syndrome is in line with other findings of colostrum being most beneficial against inflammation and mucosal damage in the gastrointestinal tract. It also lines up with previous finding of colostrum apparently not having effect on intestinal nutrient absorption in healthy adults (Rathe et al., 2014).


Necrotizing enterocolitis

Approximately 10 % of all infants are born prematurely (defined as before 37 weeks of gestation), and prematurity is the single most important direct cause of death in the critical first months of life (Blencowe et al., 2012). Some of the most obvious features about preterms are their low birth weight, immature gastrointestinal tract and impaired maturation of the immune system (Hawson et al., 2013). Necrotizing enterocolitis (NEC) is a life-threatening, but common, complication in preterm infants that causes severe ulceration of the small and large gut. The mortality rate range from 20-30%, with the highest rate among infants requiring surgery (Neu & Walker, 2011). Nutrition is considered important in the prevention and management of necrotizing enterocolitis (Fallon et al., 2012).

Mother’s milk is the optimal diet for the newborn and preterm babies, but as the supply of human colostrum and milk is often limited or even absent in preterm births, diet supplements are needed. Recent studies have established that several of the active substances in bovine colostrum are not species specific and therefore may be beneficial effects to other species (Rathe et al., 2014). Several studies have reported a significant positive effect of bovine colostrum on preterm piglets, leading to a strong hope, that bovine colostrum may be the needed agent against necrotizing enterocolitis in preterm infants (Jensen et al., 2013; Li et al., 2014; Støy et al., 2014; Shen et al., 2015). Bovine colostrum is now tested in a safety and feasibility study in preterm infants (ClinicalTrials.gov NCT02054091) and more studies are planned.



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