Human Milk: Composition, Clinical Benefits and Future Opportunities. Группа авторов

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^aDepartment of Clinical Sciences, Umeå University, Umeå, Sweden; ^bDepartment of Nutrition, University of California, Davis, CA, USA

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      Abstract

      Dietary supplementation with bovine milk fat globule membrane (MFGM) concentrates has recently emerged as a possible means to improve the health of infants and young children. Formula-fed infants are of special interest since infant formulas traditionally have lower concentrations of biologically active MFGM components than human milk. We identified 6 double-blind randomized controlled trials (DBRCT) exploring the effects of supplementing the diet of infants and children with bovine MFGM concentrates. Two studies found a positive effect on cognitive development in formula-fed infants. Three studies found a protective effect against infections at different ages during infancy and early childhood. We conclude that supplementation with MFGM during infancy and childhood appears safe, and the studies indicate positive effects on both neurodevelopment and defense against infections, especially in formula-fed infants. However, due to the small number of studies and the heterogeneity of interventions and outcomes, more high-quality DBRCTs are needed before firm conclusions can be drawn on the likely health benefits of MFGM supplementation to infants and children.

      © 2019 Nestlé Nutrition Institute, Switzerland/S. Karger AG, Basel

      Introduction

An increasing number of studies have reported various health benefits from oral supplementation with bovine milk fat globule membrane (MFGM) to humans of different ages, including infants and children [1, 2]. The MFGM is formed during the release of milk fat from the endothelial cell of the lactating mammary gland and is composed of a phospholipid and cholesterol triple layer which contains proteins and glycoproteins [3] (Fig. 1). Milk phospholipids, sphingomyelins, and gangliosides are largely located on the MFGM, although phospholipids are also secreted as smaller vesicles devoid of a triglyceride core, which typically separate from the whey fraction [3, 4]. The proteome of the human MFGM is very complex with several hundred proteins identified, including mucins, butyrophilin, lactoferrin, and lactadherin [5, 6]. Bovine MFGM-rich fractions contain approximately the same number of proteins [7]. MFGM is also rich in sialic acid as part of gangliosides [4] and glycosylated proteins. The genes regulating MFGM synthesis are conserved across species suggesting a functional benefit of this fraction in milk [8], even if the detailed MFGM composition varies among species [6].

      Breastfed infants have a higher intake of MFGM components than formula-fed infants because, traditionally, the MFGM fraction is discarded with the milk fat which is replaced by blends of vegetable oils as the source of fat in infant formulas. Resulting from advances in dairy technology, bovine MFGM concentrates are now commercially available and possible to use as a supplement to foods, including infant formulas.

      Physiological Effects of Single Components of the Milk Fat Globule Membrane

Dietary gangliosides [9], sialic acid [10], and sphingomyelin [11] have been shown to be important for optimal brain development and function in different animal models. However, it should be noted that some of these models are disease models or models with inhibited de novo synthesis, which is far from supplementing a healthy infant or child. In a small study on premature infants with a birth weight <1,500 g, infants receiving formula with high sphingomyelin content (20 vs. 13% of all phospholipids in milk) to cover shortages of breast milk performed better than those fed the lower content at neurobehavioral follow-up between 6 and 18 months corrected age [12]. Further, oral sphingomyelin [13], as well as a bovine MFGM concentrate [14], increased maturation of the intestine in rats. Gangliosides have also been suggested to play an important role in the development of intestinal microbiota composition, gut immunity, and, consequently, in the defense against infections [15]. Other components of MFGM are also involved in the defense against infections, e.g., the glycoproteins butyrophilin, lactadherin, and mucins [16], which all have antimicrobial effects, and the lipid fraction of bovine MFGM has antiviral effects in vitro [17]. Both lipid and protein components of MFGM have anticancer effects in vitro [18], and intake of MFGM in early life has also been suggested to protect against obesity later in life [19].

Fig. 1. Schematic drawing of the release of the milk fat globule and composition of the milk fat globule membrane (MFGM). Illustration by Erik Domellöf. Reproduced from Hernell et al. [1] with permission.

      Clinical Studies on Milk Fat Globule Membrane Concentrates Fed to Infants and Children

In a literature search (August 31, 2017), we identified 6 double-blind randomized controlled trials (DBRCT) exploring the effects of supplementing the diet of infants or children with MFGM (Table 1):

Table 1. Double-blind randomized controlled trials exploring the effects of milk fat globule membrane (MFGM) supplementation to the diet of infants or children

In a Peruvian DBRCT, 550 healthy, primarily breastfed 6- to 11-month-old infants consumed 40 g/day of an instant complementary food fortified with 1 recommended dietary allowance of multiple micronutrients and a protein source for 6 months. They were randomized to the protein source being either an MFGM-enriched protein fraction (Lacprodan® MFGM-10; Arla Foods Ingredients, Viby, Denmark) or skim milk powder (control group) [20]. There was no difference between the groups in the incidence of diarrhea, but longitudinal prevalence of diarrhea СКАЧАТЬ