Milk fat globule membrane (MFGM) is a complex and unique structure composed primarily of lipids and proteins that surrounds milk fat globule secreted from the milk producing cells of humans and other mammals. It is a source of multiple bioactive compounds, including phospholipids, sphingomyelins, gangliosides, glycolipids, glycoproteins, and carbohydrates that have important functional roles within the brain and body health.
Over 2,000 scientific publications have explored the nutritional and functional benefits of MFGM. Clinical trials have demonstrated that MFGM supplementation supports cognitive development in infants,Nakayama et al., 2024 improves memory and mood in adults,Minegishi et al., 2016Davies et al., 2023 and enhances muscle strength, balance, and agility in older adults.Daly et al., 2020
Preclinical studies have demonstrated effects of MFGM-derived bioactive components on brain structure and function, intestinal development, and immune defense. Similarly, pediatric clinical trials have reported beneficial effects on cognitive and immune outcomes. In populations ranging from premature infants to preschool-age children, dietary supplementation with MFGM or its components has been associated with improvements in cognition and behavior, gut and oral bacterial composition, fever incidence, and infectious outcomes including diarrhea and otitis media.
MFGM may also play a role in supporting cardiovascular health by modulating cholesterol and fat uptake. Clinical trials in adult populations have shown that MFGM could positively affect markers associated with cardiovascular disease including lowering serum cholesterol and triacylglycerol levels as well as blood pressure.
Origin
MFGM secretion process in milk Milk lipids are secreted in a unique manner by lactocytes, which are specialized epithelial cells within the alveoli of the lactating mammary gland.
The process takes place in multiple stages. First, fat synthesized within the endoplasmic reticulum accumulates in droplets between the inner and outer phospholipid monolayers of the endoplasmic reticulum membrane. As these droplets increase in size, the two monolayers separate further and eventually pinch off. This leads to the surrounding of the droplet in a phospholipid monolayer that allows it to disperse within the aqueous cytoplasm. In the next stage, lipid droplets then migrate to the apical surface of the cell, where plasma membrane subsequently envelops the droplet and extrudes together with it. It fully encases the fat droplet in an additional bilayer of phospholipids. The milk fat globule thus released into the glandular lumen, measuring 3-6 μm in average diameter, is surrounded by a phospholipid trilayer containing associated proteins, carbohydrates, and lipids derived primarily from the membrane of the secreting lactocyte. This trilayer is collectively known as MFGM.
This secretion process occurs in all types of mammalian milk, including human and bovine. However, it is distinct from the lipid secretion mechanism used by all other non-mammary cells. That makes MFGM unique to milk and it is not present in non-dairy food products.
Sources of MFGM
MFGM is a structurally complex bioactive milk component, found in human milk as well as the milk of other mammalian species. The MFGM in human milk contains many bioactive components with diverse functions and has been linked to cognitive and health benefits to infants. Some compositional differences are reported to exist between species, but bovine MFGM, the best-studied non-human source, generally contains a lipid and protein composition, which is similar to that of human MFGM.
MFGM makes up an estimated 2-6% of the total fat globules. As raw milk has an average total fat content around 4%, it therefore contains around 0.08-0.24% of MFGM. In other words, 417–1250 kg of raw milk is needed to supply 1 kg of MFGM. The content of MFGM in dairy products varies depending on the processing involved. During dairy processing such as churning or decreaming, the MFGM is disrupted and preferentially distributed into aqueous phases such as buttermilk, butter serum, or certain type of whey. Thus they can be a good source of MFGM for addition into food products.
For example, infant formulas traditionally were lacking the MFGM because this fraction is lost during regular dairy processing. However, more recent advances in technology have facilitated the separation of MFGM from the fat globule, allowing bovine MFGM to be added in concentrated form. The MFGM fraction is now commercially available and can be added to infant formula or other nutritional products.
Structure and components
General structure
The milk fat globule is surrounded by a phospholipid trilayer containing associated proteins, carbohydrates, and lipids derived primarily from the membrane of the secreting mammary epithelial cell (lactocyte). This trilayer is collectively known as MFGM. While MFGM makes up only an estimated 2% to 6% of the total milk fat globule, it is an especially rich phospholipid source, accounting for the majority of total milk phospholipids. In contrast, the inner core of the milk fat globule is composed predominantly of triacylglycerols.
The MFGM structure is complex and comprises a variety of phospholipids, glycolipids, proteins, and glycoproteins, along with cholesterol and other lipids. Specific lipids and proteins are localized to different layers of the membrane, with carbohydrate chains of glycoproteins and glycolipids directed toward the outer surface of the milk fat globule; the lipid-to-protein weight ratio in MFGM is approximately 1:1.
However, the nutritional significance of these components is defined not only by their structure or macronutrient category, but also by the physiological role that each nutrient serves. As a quantitatively minor presence within milk, MFGM likely contributes little to energy production, but its constituents may confer structural and functional benefits. Many of these nutrients are known to play important functional roles within the gut, brain, and elsewhere in the body; the functions of other components are still being elucidated.
Lipid components The lipid component of MFGM is rich in phospholipids, glycosphingolipids, and cholesterol. Phospholipids make up approximately 30% of the total lipid weight of MFGM, the three most prominent being sphingomyelin (SM), phosphatidylcholine (PC), and phosphatidylethanolamine (PE), which together represent up to 85% of total phospholipids. Phospholipids and sphingolipids play central roles in cerebral neurogenesis and migration during fetal development, as well as promoting neuronal growth, differentiation, and synaptogenesis during the first year of life. Other important polar lipids present in the membrane include the glycerophospholipids phosphatidylserine (PS) and phosphatidylinositol (PI), as well as gangliosides (GG), which are sphingolipids containing sialic acid and an oligosaccharide side chain. Each of these lipid classes is known to play functional roles within the body, including the support of gut, immune, and central nervous system development.
Protein components Besides the polar lipids, the outer layer of MFGM contains a number of glycosylated and non-glycosylated proteins. Proteomic analysis has revealed at least 191 different known proteins in human MFGM, and comparable numbers in bovine milk protein concentrates. While quantitatively these only represent 1% to 2% of total milk protein content, MFGM proteins are of significant interest because many are known to have bioactive and potentially beneficial properties; almost half of identified proteins have membrane/protein trafficking or cell signaling functions. The glycosylated proteins, including mucins (MUC-1, MUC-4, MUC-15), butyrophilin, lactadherin, and CD36, have been suggested to enhance triacylglyceride digestion efficiency. Furthermore, lactadherin and MUC-1, in addition to the non-glycosylated protein xanthine oxidase, have been shown or suggested in preclinical studies to possess antimicrobial properties.
Health Benefits of MFGM
Research has indicated that MFGM, or components thereof, may potentially play roles in brain development and cognitive function, immunity and gut health, and cardiovascular health.
MFGM has a set of proteins and lipids unique to breast milk: lactoferrin, Immunoglobulin G, sialic acid, cholesterol, phospholipids, sphingolipids, gangliosides and choline. All components of the MFGM are important for child development. Phospholipids and gangliosides influence the formation and folding of the cerebral cortex. These structures translate directly into neuronal development and cognitive abilities. The use of MFGM in Geo-Poland infant formula is essential to mimic breast milk. A not insignificant proportion of studies investigating the health effects of formula supplementation with MFGM on infant health were (co-)funded by the cow's milk and formula industry.
Brain development and cognitive function MFGM lipid components such as sphingomyelin and gangliosides are highly concentrated in the brain and support synaptogenesis and myelination. In the central nervous system, sphingomyelin is a key component of the myelin sheath, which insulates axons and supports efficient transmission of nerve impulses. During myelination, nerve axons are wrapped with multiple layers of cell membrane by oligodendrocyte glial cells, a process that accounts for a large portion of brain growth during late gestation and the first two years of life, but which can also continue up to 5–10 years of age. Meanwhile, gangliosides are concentrated within the brain's gray matter and constitute approximately 6% to 10% of the total human brain lipid mass. Additionally, gangliosides are enriched at the synaptic membrane of neurons, and are functionally involved in neurotransmission and synapse formation. Brain ganglioside accretion occurs at an accelerated rate in the early years of life, coinciding with the most active period of myelination, axonal outgrowth, and synaptogenesis. Alongside the growth of brain size, total brain ganglioside concentration also increases 3-fold from early fetal development to 5 years of age.
Preclinical data A number of preclinical studies have been conducted using MFGM and combinations of MFGM-derived components. Liu et al. (2014) studied brain development and spatial learning and memory in neonatal piglets. Piglets that were fed with a formula containing milk phospholipids and gangliosides to mimic levels in human milk made choices more rapidly and with fewer errors in a spatial T-maze cognitive test compared to controls, implying improved spatial learning. Similarly, Vickers et al. (2009) demonstrated that administration of complex milk lipids to rats from postnatal day 10 through adulthood (day 80) led to significant improvements in learning and memory tasks compared to control animals. Conversely, a study of complex milk lipid supplementation to pregnant mice did not have an effect on cognitive tasks in their offspring.
Clinical data Several studies of diets supplemented with MFGM and its components, including gangliosides and sphingomyelin, have aimed to address measures of cognitive development in pediatric populations. In some of the studies, MFGM supplementation to infant formula was shown to narrow the gap in cognitive development between breastfed and formula-fed infants.
Tanaka et al. (2013) studied the neurobehavioral effects of feeding formula supplemented with sphingomyelin-enriched phospholipid in 24 very low birth weight preterm infants (birth weight <1500 g).