Human milk fat globule membrane (MFGM) is a trilayer membrane enveloping milk fat secreted as lipid droplets in milk[1]. Milk fat is secreted as lipid droplets, of sizes ranging from 0.1 to 10 μm in humans, enabling fat to be conveyed in an aqueous environment[2],[3].

Protein components of MFGM, such as mucin, support gut health and development by inhibiting pathogenic viruses and bacteria.

MFGM mainly consists of polar lipids (0.2-1% of milk lipids), cholesterol (0.46% of milk lipids) and proteins (1-2% of the total protein fraction in milk)[4],[5]. Polar lipids are rich in phospholipids including glycerophospholipids and sphingomyelin, and glycosphingolipids[5],[6]. Glycosphingolipids are quantitatively minor constituents of the MFGM, and are comprised of cerebrosides and gangliosides.

Aspects of MFGM related to brain

Key components of dietary MFGM, sphingomyelin and gangliosides, are absorbable and utilizable as measured in infants by blood levels[7],[8], by their cognitive effects[7],[8],[9] and by the fact that higher protein- and ganglioside-bound sialic acid levels are found in brains from infants that were breastfed than formula fed[10]. Animal data also show that dietary sphingomyelin and gangliosides are absorbable, and can increase sphingomyelin and ganglioside levels in the brain[11],[12].

Sphingomyelin and gangliosides are enriched in the brain, and are important for myelination of axons[13],[14],[15]. The myelin insulates the neuronal axons for faster signaling along the axon compared to unmyelinated axons[16].

Gangliosides have been reported to play roles in synaptic transmission and long-term potentiation[17],[18],[19],[20],[21]. Long term potentiation increases the synapse strength, and is believed to be a cellular process underlying learning and memory[16].

A clinical study in infants in Sweden showed that infants fed an experimental infant formula supplemented with a bovine MFGM source (Lacprodan® MFGM-10) at 6 g/L for the first 6 months of life had significantly higher cognitive scores in the Bayley Scales of Infant and Toddler Development (BSID-III) at 12 months of age compared to infants fed a standard infant formula without MFGM-10, but not different than the breastfed reference group[9].

A clinical study in young children and children showed that young children and children given chocolate milk formula with MFGM, derived from bovine buttermilk, providing 500 mg/day of dairy-derived phospholipids had improved internal, external, and total behavioral problem scores as rated by parents compared to those fed a standard chocolate milk formula without supplemental MFGM[22].

Aspects of MFGM related to gastrointestinal health & immunity

MFGM and MFGM components have also been shown to play a role in the maintenance of gut health, mainly through their anti-pathogenic activities, and to support immunity.

A clinical study in infants in Sweden showed that infants fed an experimental infant formula supplemented with a bovine MFGM source (Lacprodan® MFGM-10) at 6 g/L for the first 6 months of life had cumulative incidence of acute otitis media, from inclusion until 6 months of age, significantly lower than those fed a standard formula, but did not differ from the breastfed reference group[23]. The incidence and longitudinal prevalence of antipyretic use were also significantly lower in the experimental group than the control group, during the intervention period.

A clinical study in infants and young children showed that infants and young children given MFGM-10 in a milk-based meal twice daily for 6 months (with an average daily intake of 5.9 g MFGM-10) had a significantly lower prevalence of diarrhea than the control group, in a double-blind randomized controlled-trial[24]. In this study, infants were enrolled at 6-11 months of age, and fed for 6 months up to 12-17 months of age.

A clinical study in infants showed that an adapted low birth weight infant formula supplemented with gangliosides (1.43 mg gangliosides per 100 kcal) significantly reduced the fecal counts of the pathogenic E. coli and increased the fecal counts of the probiotic bifidobacteria in preterm infants compared to a standard adapted low birth weight infant formula without supplemental gangliosides[25].

 


[1] Lopez, C. and O. Menard. 2011. Human milk fat globules: polar lipid composition and in situ structural investigations revealing the heterogeneous distribution of proteins and the lateral segregation of sphingomyelin in the biological membrane. Colloids Surf B Biointerfaces 83(1):29-41.
[2] Hamosh, M., J. A. Peterson, T. R. Henderson, C. D. Scallan, R. Kiwan, R. L. Ceriani, M. Armand, N. R. Mehta, and P. Hamosh. 1999. Protective function of human milk: the milk fat globule. Semin Perinatol 23(3):242-249.
[3] Mesilati-Stahy, R. and N. Argov-Argaman. 2014. The relationship between size and lipid composition of the bovine milk fat globule is modulated by lactation stage. Food Chem 145:562- 570.
[4] Riccio, P. 2004. The proteins of the milk fat globule membrane in the balance. . Trends in Food Science & Technology 15:458-461.
[5] Lopez, C. and O. Menard. 2011. Human milk fat globules: polar lipid composition and in situ structural investigations revealing the heterogeneous distribution of proteins and the lateral segregation of sphingomyelin in the biological membrane. Colloids Surf B Biointerfaces 83(1):29-41.
[6] Contarini, G. and M. Povolo. 2013. Phospholipids in milk fat: composition, biological and technological significance, and analytical strategies. Int J Mol Sci 14(2):2808-2831.
[7] Gurnida, D. A., A. M. Rowan, P. Idjradinata, D. Muchtadi, and N. Sekarwana. 2012. Association of complex lipids containing gangliosides with cognitive development of 6-month-old infants. Early Hum Dev 88(8):595-601.
[8] Tanaka, K., M. Hosozawa, N. Kudo, N. Yoshikawa, K. Hisata, H. Shoji, K. Shinohara, and T. Shimizu. 2013. The pilot study: sphingomyelin-fortified milk has a positive association with the neurobehavioural development of very low birth weight infants during infancy, randomized control trial. Brain Dev 35(1):45-52.
[9] Timby, N., E. Domellof, O. Hernell, B. Lonnerdal, and M. Domellof. 2014. Neurodevelopment, nutrition, and growth until 12 mo of age in infants fed a low-energy, low-protein formula supplemented with bovine milk fat globule membranes: a randomized controlled trial. Am J Clin Nutr 99(4):860-868.
[10] Wang, B., P. McVeagh, P. Petocz, and J. Brand-Miller. 2003. Brain ganglioside and glycoprotein sialic acid in breastfed compared with formula-fed infants. Am J Clin Nutr 78(5):1024-1029.
[11] Oshida, K., T. Shimizu, M. Takase, Y. Tamura, and Y. Yamashiro. 2003. Effects of dietary sphingomyelin on central nervous system myelination in developing rats. Pediatr Res 53(4):589- 593.
[12] Park, E. J., M. Suh, K. Ramanujam, K. Steiner, D. Begg, and M. T. Clandinin. 2005. Dietinduced changes in membrane gangliosides in rat intestinal mucosa, plasma and brain. J Pediatr Gastroenterol Nutr 40(4):487-495.
[13] Rueda, R., J. Maldonado, E. Narbona, and A. Gil. 1998a. Neonatal dietary gangliosides. Early Hum Dev 53 Suppl:S135-147.
[14] Oshida, K., T. Shimizu, M. Takase, Y. Tamura, and Y. Yamashiro. 2003. Effects of dietary sphingomyelin on central nervous system myelination in developing rats. Pediatr Res 53(4):589- 593.
[15] Jana, A. and K. Pahan. 2010. Sphingolipids in multiple sclerosis. Neuromolecular Med 12(4):351-361.
[16] Purves, D., G. J. Augustine, D. Fitzpatrick, W. C. Hall, A.-S. LaMantia, and L. E. White. 2012. Neuroscience, 5th edition. Sinauer Associates, Inc., Sunderland, MA, USA.
[17] Wieraszko, A. and W. Seifert. 1986. Evidence for the functional role of monosialoganglioside GM1 in synaptic transmission in the rat hippocampus. Brain Res 371(2):305-313.
[18] Frieder, B. and M. M. Rapport. 1987. The effect of antibodies to gangliosides on Ca2+ channellinked release of gamma-aminobutyric acid in rat brain slices. J Neurochem 48(4):1048-1052.
[19] Fujii, S., K. Igarashi, H. Sasaki, H. Furuse, K. Ito, K. Kaneko, H. Kato, J. Inokuchi, H. Waki, and S. Ando. 2002. Effects of the mono- and tetrasialogangliosides GM1 and GQ1b on ATP-induced long-term potentiation in hippocampal CA1 neurons. Glycobiology 12(5):339-344.
[20] Buchwald, B., G. Zhang, A. K. Vogt-Eisele, W. Zhang, R. Ahangari, J. W. Griffin, H. Hatt, K. V. Toyka, and K. A. Sheikh. 2007. Anti-ganglioside antibodies alter presynaptic release and calcium influx. Neurobiol Dis 28(1):113-121.
[21] Fujiwara, H., K. Ikarashi, Y. Yamazaki, J. Goto, K. Kaneko, M. Sugita, H. Kato, H. Sasaki, J. Inokuchi, K. Furukawa, and S. Fujii. 2012. Impairment of hippocampal long-term potentiation and failure of learning in mice treated with d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol. Biomed Res 33(5):265-271.
[22] Veereman-Wauters, G., S. Staelens, R. Rombaut, K. Dewettinck, D. Deboutte, R. J. Brummer,M. Boone, and P. Le Ruyet. 2012. Milk fat globule membrane (INPULSE) enriched formula milk decreases febrile episodes and may improve behavioral regulation in young children. Nutrition 28(7-8):749-752.
[23] Timby, N., E. Domellof, O. Hernell, B. Lonnerdal, and M. Domellof. 2014. Neurodevelopment, nutrition, and growth until 12 mo of age in infants fed a low-energy, low-protein formula supplemented with bovine milk fat globule membranes: a randomized controlled trial. Am J Clin Nutr 99(4):860-868.
[24] Zavaleta, N., A. S. Kvistgaard, G. Graverholt, G. Respicio, H. Guija, N. Valencia, and B. Lonnerdal. 2011. Efficacy of an MFGM-enriched complementary food in diarrhea, anemia, and micronutrient status in infants. J Pediatr Gastroenterol Nutr 53(5):561-568.
[25] Rueda, R., J. L. Sabatel, J. Maldonado, J. A. Molina-Font, and A. Gil. 1998b. Addition of gangliosides to an adapted milk formula modifies levels of fecal Escherichia coli in preterm newborn infants. J Pediatr 133(1):90-94.