Cancer treatments can attack healthy tissues while attacking tumors. This review asks whether colostrum proteins, especially lactoferrin, could reduce those injuries while preserving or even improving treatment effects. This review examines colostrum and colostrum-derived proteins in animal models and clinical trials involving chemotherapy with antimetabolic drugs, radiotherapy and surgical interventions.

Most investigations used bovine colostrum, or native bovine or recombinant human lactoferrin, either alone, in nutraceutics or with probiotics. The review reports that bovine colostrum and lactoferrin reduced side effects, augmented therapeutic efficacy and improved patient wellness.

Its conclusion is that colostrum proteins, preferably administered with probiotic bacteria, are highly recommended for cancer treatment protocols involving chemotherapy, radiotherapy and surgery. Anticancer therapy can be highly effective, but its mechanism of action also makes it toxic to the patient’s tissues.

The immune system, nervous system, gastrointestinal tract and physiological microbiota of the gut and reproductive tract are commonly damaged. That tissue toxicity produces adverse side effects in patients undergoing therapy.

Because treatment toxicity creates adverse side effects, supportive care is desirable during primary therapy. During radiochemotherapy, supportive care aims to prevent and treat complications caused both by the cancer and by anticancer therapy. These complications can occur during and after treatment and range from somatic to psychological and social symptoms.

They can reduce treatment effectiveness, make treatment impossible to complete and impair well-being and quality of life, making intensive protective care often as important as primary therapy. Existing agents used to alleviate cancer-treatment side effects are only moderately effective and can have undesirable effects.

That creates demand for new agents that assist basic therapeutic protocols and lower their side effects. The most desirable products would be natural, multidirectional, bioavailable, non-toxic, safe, easy to self-apply, acceptable to patients and relatively inexpensive.

Bovine colostrum and preparations containing mainly lactoferrin meet these requirements, according to numerous in vitro, animal and clinical trials. The review covers bovine colostrum and mainly lactoferrin as adjuncts to chemotherapy, radiotherapy, anti-hormone therapy and surgical cancer treatment in animal and clinical studies.

It also discusses a possible protective mechanism shown in vitro and practical clinical use of these colostrum-derived products. The authors state that, to their knowledge, a literature review on this topic was not previously available. Colostrum contains nutrients and bioactive components including proteins, peptides, fatty acids, oligosaccharides, vitamins, minerals, cytokines, growth factors, hormones, enzymes, immunoglobulins and maternal immune cells.

Important bioactive constituents with microbiostatic and immune-enhancing properties include caseins, alpha-lactoalbumin, beta-lactoglobulin, lactoferrin, lysozyme, lactoperoxidase, colostrinin and immunoglobulins. Colostrum is valuable as a nutraceutic and is essential for mammalian newborn growth and development, especially resistance to infections and development of immune, gastrointestinal and neural systems.

Bovine colostrum and its ingredients are used as functional foods and dietary supplements for pathological conditions in humans, pets and livestock. Bovine colostrum and its constituents have beneficial effects on the gastrointestinal tract in infections, inflammatory bowel disease, short bowel syndrome, necrotizing enterocolitis and drug-induced lesions.

Lactoferrin and other colostrum components act on tumor cells by controlling proliferation, survival and metastasis, and anti-tumor effects were confirmed in preclinical and clinical trials. Lactoferrin, proline-rich polypeptide and other colostrum proteins also support central nervous system function and provide neuroprotection during early brain development.

The biological functions of bovine colostrum components may support prevention and treatment of diseases such as cancer, infections and inflammation. They can also protect against therapy side effects and complications and act as regenerative agents for patients weakened by drugs, radiotherapy or surgery.

Using bovine colostrum or its proteins with classical drugs may enhance therapeutic effects, while lower therapeutic doses may further reduce toxicity. The review therefore focuses on their use as supportive care in cancer models, animals and humans, summarized in Table 2.

Table two summarizes protective and therapeutic effects of bovine lactoferrin in chemotherapy-related models, focusing here on in vitro and animal studies. In mice exposed to cyclophosphamide, methotrexate, or combined treatment with busulfan and bone-marrow transplantation, lactoferrin was associated with reported restoration of immune responses, blood-cell composition, and hematopoiesis.

The table also describes low-dose recombinant human lactoferrin in a silk-sericin hydrogel, which protected splenic follicles and helped normalize intestinal flora after chemotherapy-induced gastrointestinal damage. Cyclophosphamide is among the most frequently used immunosuppressants in clinical practice and animal models of immunosuppression.

In mouse studies, lactoferrin proved effective in reconstituting or normalizing impaired immune responses. A sublethal intraperitoneal cyclophosphamide dose of four hundred milligrams per kilogram strongly suppressed delayed-type hypersensitivity to ovalbumin in mice.

Bovine lactoferrin restored delayed-type hypersensitivity and partially recovered splenocyte proliferation, blood leukocytosis, spleen T-cell content and peritoneal macrophage numbers. Bovine lactoferrin also increased the humoral immune response tenfold and normalized peripheral blood cell composition after cyclophosphamide treatment.

Weaned piglets receiving doxorubicin provide a relevant large-animal model for studying chemotherapy-induced mucositis and possible interventions. The animals were fed bovine colostrum to reduce chemotherapy side effects.

In one study, pigs received doxorubicin at three point seven five milligrams per kilogram and bovine colostrum at five milliliters per kilogram three times daily, beginning one day before doxorubicin and continuing through day five. Doxorubicin caused reduced food intake and weight gain, diarrhea, vomiting, small-intestinal mucosal damage, increased tumor-necrosis-factor alpha concentration and chlorine secretion, and reduced glucose uptake.

Administration of colostrum partially prevented these toxic side effects. Bovine lactoferrin protected against intestinal methotrexate-induced toxicity in a rat model. After methotrexate at twenty milligrams per kilogram, rats showed histopathological changes, reduced small-intestinal absorptive surface and increased intestinal-barrier permeability.

Lactoferrin supplementation reversed these adverse changes. The proposed mechanism may involve inhibition of endogenous glucagon-like peptide two activity in the gut. Lactoferrin inhibited intestinal epithelial proliferation in rats and glucagon-like-peptide-two-mediated proliferation of Caco-2 epithelial cells in vitro.

Active bovine-colostrum components have multidirectional anticancer activity, with lactoferrin being the best studied. Lactoferrin regulates the cell cycle, inhibits proliferation, induces maturation and apoptosis of neoplastic-transformed cells and induces antitumor proteins such as p53, p21 and Rb.

It also binds iron needed for tumor growth, inhibits tumor angiogenesis and metastasis, inhibits inflammation and oxidative stress, and activates immune cells. These activities may support elimination of cancer, protect against recurrence and enhance classical chemotherapy.

Lactoferrin-loaded liposomes and polymersomes were shown to work as anticancer drug carriers. Polyethylene-glycol-modified liposomes containing lactoferrin and doxorubicin delivered doxorubicin more effectively and inhibited tumor growth in mice more strongly than liposomes containing doxorubicin alone.

For glioma in rats, biodegradable polymersomes containing doxorubicin, tetrandrine and lactoferrin were designed to facilitate crossing the blood-brain barrier. These polymersomes showed the highest cytotoxicity against glioma C6 cells and the highest uptake index compared with polymersomes containing only doxorubicin, tetrandrine or lactoferrin.

Rats receiving these polymersomes had significantly smaller tumors and significantly longer survival than rats in other therapeutic groups. In an open-label, prospective, randomized trial, one hundred forty-eight anemic advanced-cancer patients undergoing chemotherapy received either oral bovine lactoferrin or intravenous ferric gluconate.

Both treatments were combined with subcutaneous recombinant human erythropoietin. Both groups showed a significant increase in hemoglobin, with no differences in hematopoiesis, serum iron, C-reactive protein or erythrocyte sedimentation rate.

Ferritin decreased in lactoferrin-treated patients but increased in the ferric-gluconate group, a pattern that may benefit anemia associated with cancer and chronic inflammatory disease. In a multicenter, blinded, placebo-controlled randomized trial, bovine lactoferrin delivered in an ice-cream medical food protected one hundred ninety-seven cancer patients from diarrhea and neutropenia during chemotherapy.

The mean number of days with diary-recorded chemotherapy-induced diarrhea was lower in the experimental group than in the placebo group. Diarrhea reported during doctor’s rounds and neutropenia were also diagnosed in a lower proportion of patients.

Chemotherapy-induced diarrhea results from therapy-related mucosal toxicity and bowel mucositis, is common with many chemotherapy regimens and strongly affects quality of life. Alimentary-tract mucositis is reported in thirty to eighty percent of patients receiving cytotoxic drugs and increases mortality, morbidity and patient-care cost.

A two-center, randomized, double-blind, placebo-controlled trial gave daily oral bovine colostrum or placebo for four weeks to sixty-two children with acute lymphoblastic leukemia and gastrointestinal toxicity during induction chemotherapy. The children were monitored for fever, bacteremia, antibiotic need and mucosal toxicity.

The groups did not differ in fever, need for antibiotics or incidence of bacteremia. However, bovine-colostrum supplementation significantly lowered the peak severity of oral mucositis and the weekly peak of self-reported oral mucositis.

The review describes this as a possible mitigating effect on mucositis, without an effect on inflammation or infectious morbidity. Colostrum, lactoferrin and lactoferrin-derived peptides were evaluated for protective and reconstituting properties in humans, animals, organs and cells exposed to gamma and X irradiation.

The review also describes protective effects on ultraviolet-damaged cells. In one study, mice were lethally irradiated with eight gray of X-rays, and bovine lactoferrin was administered intraperitoneally four hours before irradiation and for three days afterward.

The study observed improved survival time and small-intestinal epithelial histology, including increased villus length and its ratio to crypt depth. It also observed decreased serum interleukin six and tumor-necrosis-factor alpha, together with reduced radiation-induced IKK alpha, IKK beta and NF-kappa B activity in intestinal tissues.

The reported beneficial effects were prolonged survival, regeneration of intestinal damage and inhibition of inflammation. Across animal models and clinical trials, orally administered colostrum, lactoferrin and lactoferrin-derived peptides alleviated side effects from anticancer interventions and enhanced their efficacy.

Effects were reported when colostrum or lactoferrin was used alone and when combined with other nutraceutics or probiotics. The review links these benefits to promotion of T- and B-cell maturation, myelopoiesis, hypothalamus-pituitary-adrenal-axis function, iron regulation, beneficial intestinal microbiota and intestinal-mucosal stabilization.

The review recommends including colostrum proteins in cancer-therapy protocols to enhance effectiveness and mitigate adverse effects. Across animal models and clinical trials, colostrum and lactoferrin were associated with fewer treatment side effects and, in some studies, stronger therapeutic effects.

The review therefore supports considering them as supportive care, preferably with probiotics.