Bovine lactoferrin and lactoferricin derived from milk: production and applications

Abstract

Bovine lactoferrin is produced on an industrial scale from cheese whey or skim milk. The safety of purified lactoferrin has been confirmed from the results of a reverse mutation test using bacteria, a 13-week oral repeated-dose toxicity study in rats, and clinical studies. In order to apply active lactoferrin to various products, a process for its pasteurization was developed. Subsequently, lactoferrin has been used in a wide variety of products since it was first added to infant formula in 1986. A pepsin hydrolysate of lactoferrin is also used in infant formula. This hydrolysate contains a potent antimicrobial peptide named lactoferricin that is derived from the lactoferrin molecule by pepsin digestion. Semilarge-scale purification of lactoferricin can be performed by hydrophobic interaction chromatography. Lactoferricin also exhibits several biological actions and appears to be the functional domain of lactoferrin. Recent studies have demonstrated that oral administration of lactoferrin or lactoferricin exerts a host-protective effect in various animals and in humans. The results of these studies strongly suggest that the effects of oral lactoferrin are mediated by modulation of the immune system. Further elucidation of the clinical efficacy and mechanism of action of lactoferrin will increase the value of lactoferrin-containing products.

Antimicrobial peptides in animals and their role in host defences

“…Bovine lactoferrin, a byproduct from cheese whey or skim milk, is commercially available as a health food in Japan [114] and has been used in a wide variety of products since it was first added to infant formula in 1986 [115]. Similarly, recombinant human lactoferrin (rhLF), was found in transgenic cow's milk at gram per litre concentrations [116].…”

“…Lactoferrins have little toxicity and are very safe, especially when administered orally. The oral toxicity of purified lactoferrin is extremely low and 2000 mg/kg/day did not cause any adverse effects in rats of both sexes [115,117]. Similarly, 434 mg/kg lactoferrin was not toxic for mice [118].…”

“…Similarly, 434 mg/kg lactoferrin was not toxic for mice [118]. Based on these results, lactoferrin was considered to be a highly safe food additive in supplemented infant formula, milk, skim milk, yoghurt, chewing gum, nutritional supplements, skin care cosmetics, therapeutic diet for relief of inflammation in dogs and cats and in aquaculture feed [115].…”

Effect of orally administered bovine lactoferrin on the immune response in the oral candidiasis murine model

“…LF has a number of biological functions, including antimicrobial and immunomodulatory effects in vitro and in vivo (Brock, 1995;Tomita et al, 2002;Vorland, 1999). It has been reported that orally administered bovine LF reduces the number of pathogenic organisms not only in the gastrointestinal tract (Teraguchi et al, 1995;Wada et al, 1999) but also in tissues distant from the gastrointestinal tract in several animal models of infection (Abe et al, 2000;Bhimani et al, 1999;Haversen et al, 2000) and in humans with chronic hepatitis C and tinea pedis (Ishii et al, 2003;Iwasa et al, 2002;Yamauchi et al, 2000).…”

Milk Derived Peptides with Immune Stimulating Antiviral Properties

“…Bovine and human lactoferricin, from N-terminal end of bovine and human lactoferrin, respectively, are known for their ability to improve and modulate the function of host immune system [145][146][147]. Additional, deletion fragments of lactoferrin like the peptide sequence FKCRRWQWRW, corresponding to N-terminal fragment 17-26 of bovine lactoferrin, has demonstrated potent activation of polymorphonuclear leukocytes [21].…”