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Milk Fat Globule Membrane | Functional Benefits

Key Points

  • Breastfeeding provides infants with human MFGM and its functional benefits in the brain, immune system and gut

  • Supplementation of bovine-derived MFGM in infants and children has clinically demonstrated functional effects in brain development, immune health and gut health

  • Milk fat globule comprises a fat core surrounded by a milk fat globule membrane

  • MFGM lipid components support brain development and functions

  • MFGM protein components support immune and gut functions

Breastfeeding provides infants with human MFGM and its functional benefits in the brain, immune system and gut1,2

MFGM plays an important role in the neurodevelopmental processes, such as neurogenesis, neuron migration, neuron maturation, synapse formation and myelination.1


MFGM and its components are involved in the immune system to reduce the risk of infection in the newborn, through acting as decoy to mitigate pathogen adherence to the intestinal epithelium and though its direct bactericidal effect.2


MFGM and its components have been suggested to mediate the colonization of bacterial favourable to the developing infant, thus sensitizing the immune system. In addition, there is emerging evidence to suggest MFGM and its components play a role in modulating an infant’s behaviour, through the gut-brain axis.2


There is also emerging evidence that suggests the role MFGM plays in infant metabolism.2


Brain, Immunity & Gut Effects
women-daughter

For infants and children, bovine-derived MFGM supplementation has clinically demonstrated functional effects in brain development, immune health and gut health.3

A tabulated summary of the clinical evidence demonstrating the role of MFGM-supplementation on brain development, immune health and gut health in infants and children is found Here

Brain Development

In infants and children, the assessment of developmental milestones is broadly centred around 4 key domains, namely cognition, social-emotion, language/communication, and gross and fine motor functions.

MFGM supplementation has been clinically shown to support brain development in these 4 domains.



Brain Effects

BRAIN DEVELOPMENT

Cognitive development4,5,8

Infants fed milk formula with MFGM achieved higher cognitive score on Bayley scale.5

The Bayley Scales of Infant and Toddler Development is a standard series of measurements used primarily to assess the development of infants and toddlers, ages 1–42 months. Infants and toddlers are assessed in the five key developmental domains:

  • Cognition – includes items such as attention to familiar and unfamiliar objects, looking for a fallen object, and pretend play
  • Language – taps understanding and expression of language, for example, recognition of objects and people, following directions, and naming objects and pictures
  • Social-emotional – asks caregivers about such behaviors as ease of calming, social responsiveness, and imitation play
  • Motor – assesses gross and fine motor skills such as grasping, sitting, stacking blocks, and climbing stairs
  • Adaptive behavior – asks about adaptions to the demands of daily life, including communication, self-control, following rules, and getting along with others

Infants fed milk formula with MFGM + LF reached cognitive milestones faster based on higher cognitive score on Bayley scale.4 The tasks performed by the infants are illustrated in this video.

Infants fed milk formula with MFGM achieved higher scores for General IQ, Performance IQ, and Hand and Eye Coordination on Griffith’s Scale.8

Griffiths III Mental Development Scales is used to measure the rate of development of infants and young children from birth to eight years, as well as their individual profile of strengths and needs across five areas:

  • Foundations of learning – assesses critical aspects of learning during the early childhood years.
  • Language and communication – measures overall language development, including expressive language, receptive language, and (to a lesser extent) use of language to communicate socially with others.
  • Eye and hand coordination – considers fine motor skills, manual dexterity and visual perception skills.
  • Personal-social-emotional – measures constructs relating to the child’s developing sense of self and growing independence, interactions with others, plus many aspects of emotional development.
  • Gross motor – assesses postural control, balance and gross body coordination, among other abilities.

BRAIN DEVELOPMENT

Socio-emotional development4,6 and enhanced behavioural regulation7

Infants fed milk formula with MFGM achieved higher scores in the social emotional and general adaptive behaviour domains on Bayley scale.6

Infants fed milk formula with MFGM + LF achieved higher scores in the personal-social domain on the Ages & Stages Questionnaire.4

The Ages & Stages Questionnaires is a developmental screening tool that pinpoints developmental progress in children between the ages of one month to 5 ½ years. The areas covered include communication, gross motor, fine motor, problem solving, and personal-social.

Children fed milk formula with MFGM achieved higher scores on the personal-social domain in the Achenbach System of Empirically Based Assessment (ASEBA).7

The Achenbach System of Empirically Based Assessment (ASEBA) is a collection of questionnaires used to assess adaptive and maladaptive behavior and overall functioning in individuals. It is considered the “gold standard” for developmental research in mental health, emotional, and behavioral problems of children and adolescents. In the preschool-aged children ASEBA, the 100 items to grade behaviour separately by caregivers and teachers are grouped into

  • internal (emotional, anxious/depressed, somatic, and withdrawn) score
  • external (attention and aggressive) score
  • total T score

BRAIN DEVELOPMENT

Language development4

Infants fed milk formula with MFGM + LF reached language milestone faster based on higher language score on Bayley scale.4 The tasks performed by the infants are illustrated in this video.

Infants fed milk formula with MFGM + Lactoferrin(LF) achieved a higher score for sentence complexity in the MacArthur-Bates Communicative Development Inventories.4 The tasks performed by the infants are illustrated in this video.

The MacArthur-Bates Communicative Development Inventories (MB-CDIs) are parent report instruments which capture important information about children’s developing abilities in early language, including vocabulary comprehension, production, gestures, and grammar.

BRAIN DEVELOPMENT

Motor skill development4,8

Infants fed milk formula with MFGM + LF reached motor skills milestone faster based on higher motor score on Bayley scale.4 The tasks performed by the infants are illustrated in this video.

Immune Health

MFGM supplementation has been clinically demonstrated to support immune health in terms of reducing the following

Immunity Effects

IMMUNE HEALTH

Number of infective episodes7,9,10

Infants fed milk formula with MFGM had fewer otitis media.9

Fewer ear infection
Babies fed infant formula with added MFGM suffered fewer ear infections and were less likely to need treatment to reduce fever than babies given formula without MFGM
p=0.034
MFGM-10 vs. formula without MFGM
Adapted from Timby et al. 2015
MFGM, milk fat globule membrane
Timby N, Hernell O, Vaarala O et al. Infections in infants fed formula supplemented with bovine milk fat globule membranes, JPGN 2015: 60:384-389.
Incidence of Otitis Media

Infants fed milk formula with MFGM had fewer bloody diarrhoea.10

Less Diarrhea
Adding an MFGM- enriched protein fraction to complementary food had beneficial effects on diarrhea in babies
Adjusted by baseline anemia (105g/L) and potable water, OR 0.54 (0.31-0.93), p<0.025 in 40g of complementary food enriched with 8% MFGM vs complementary food without MFGM. Adapted from Zavelta et al. 2011
MFGM, milk fat globule membrane: OR, odds ratio
Zavelta N, Kvistgaard AS, Graverholt G et al. Efficacy of an MFGM-enriched complementary food in diarrhea, anemia, and micronutrient status in infants. JPGN 2011; 53:561-568

Children fed milk formula with MFGM had fewer febrile episodes.7

Less Fever
For Preschool children, regulary drinking formula enriched with MFGM was shown to be safe, well tolerated and associated with a significant decrease in the number of episodes of fever
p=0.0028 Chocolate milk supplemented with 500 mg phospholipids + 2.5% of MFGM vs. unsupplemented chocolate milk Adapted from Veereman-Wauters et al. 2012 1
MFGM, milk fat globule membrane
Veereeman-Wauters G, Staelens S, Rombaut R et al. Milk fat globule membrane enriched formula milk decreases febrile episodes and may improve behavioral regulation in young children. Nutrition 2012;28:749-752.

IMMUNE HEALTH

Duration of infection11

Children fed milk formula with MFGM recovered more quickly (i.e. shorter total duration) from rotavirus-associated diarrhoea.11

Recovered more quickly from rotavirus-associated diarrhea
In children up to two years of age, rotavirus-associated diarrhea lasted for a shorter time in those fed whole milk supplemented with MFGM than those fed unsupplemented milk
p=0.003
Fresh milk supplemented with 2g MFGM + 3g whole milk powder (n=225) or 5g whole milk powder (control supplement, n=225) Adapted from Poppitt et al. 2014
MFGM, milk fat globule membrane
Poppitt SD, McGregor RA, Wiessing KR et al. Bovine complex milk lipid containing gangliosides for prevention of rotavirus infection and diarrhea in Northern India infants. JPGN 2014:59:167-171

IMMUNE HEALTH

Medication use9

Infants fed milk formula with MFGM required less antipyretics medication.9

Less Treatment for fever
Babies fed infant formula with added MFGM suffered fewer ear infections and were less likely to need treatment to reduce fever than babies given formula without MFGM
p=0.034
MFGM-10 vs. formula without MFGM Adapted from Timby et al. 2015
MFGM, milk fat globule membrane
Timby N, Hernell O, Vaarala O et al. Infections in infants fed formula supplemented with bovine milk fat globule membranes, JPGN 2015: 60:384-389.

Gut health

MFGM supplementation milk formulas have been clinically demonstrated to influence the gut microbiome.

  • Shape gut microbial activity and function12
  • Promote growth of Bacteroides13
  • Promote growth of Bifidobacterium14
Gut Effects

For adults, bovine-derived MFGM supplementation – in milk formulas, snack bars and pills – has clinically demonstrated functional effects in cognition, gut health, cardiovascular health and mobility.15

Emerging clinical evidence on MFGM supplementation in adults suggests the potential functional effects may include the following

  • Improve cognition and memory functions by downregulating cortisol15
  • Promote gut and immune health through its antimicrobial and decoy activities15
  • Promote cardiometabolic health by reducing LDL-C and total cholesterol, and improving insulin sensitivity.15
  • Mitigate risk of frailty by improving neural and ambulatory functions15

MFGM supplementation has been clinically demonstrated to be safe and well tolerated in infants5,17-19 and in adults15,16.

References

  1. Cohen Kadosh K, Muhardi L, Parikh P, Basso M, Jan Mohamed HJ, Prawitasari T, Samuel F, Ma G, Geurts JM. Nutritional Support of Neurodevelopment and Cognitive Function in Infants and Young Children-An Update and Novel Insights. Nutrients. 2021 Jan 10;13(1):199.
  2. Brink LR, Gueniot JP, Lönnerdal B. Effects of milk fat globule membrane and its various components on neurologic development in a postnatal growth restriction rat model. J Nutr Biochem. 2019 Jul;69:163-171.
  3. Isabelle Le Huërou-Luron, Marion Lemaire, Sophie Blat. Health benefits of dairy lipids and MFGM in infant formula. OCL 25 (3) D306 (2018).
  4. Li F, Wu SS, Berseth CL, Harris CL, Richards JD, Wampler JL, Zhuang W, Cleghorn G, Rudolph CD, Liu B, Shaddy DJ, Colombo J. Improved Neurodevelopmental Outcomes Associated with Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula: A Randomized, Controlled Trial. J Pediatr. 2019 Dec;215:24-31.e8.
  5. Timby N, Domellöf E, Hernell O, Lönnerdal B, Domellöf M. 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. 2014 Apr;99(4):860-8.
  6. Xia Y, Jiang B, Zhou L, Ma J, Yang L, Wang F, Liu H, Zhang N, Li X, Petocz P, Wang B. Neurodevelopmental outcomes of healthy Chinese term infants fed infant formula enriched in bovine milk fat globule membrane for 12 months - A randomized controlled trial. Asia Pac J Clin Nutr. 2021 Sep;30(3):401-414.
  7. Veereman-Wauters G, Staelens S, Rombaut R, Dewettinck K, Deboutte D, Brummer RJ, Boone M, Le Ruyet P. Milk fat globule membrane (INPULSE) enriched formula milk decreases febrile episodes and may improve behavioral regulation in young children. Nutrition. 2012 Jul;28(7-8):749-52.
  8. Gurnida DA, Rowan AM, Idjradinata P, Muchtadi D, Sekarwana N. Association of complex lipids containing gangliosides with cognitive development of 6-month-old infants. Early Hum Dev. 2012 Aug;88(8):595-601.
  9. Timby N, Hernell O, Vaarala O, Melin M, Lönnerdal B, Domellöf M. Infections in infants fed formula supplemented with bovine milk fat globule membranes. J Pediatr Gastroenterol Nutr. 2015 Mar;60(3):384-9.
  10. Zavaleta N, Kvistgaard AS, Graverholt G, Respicio G, Guija H, Valencia N, Lönnerdal B. Efficacy of an MFGM-enriched complementary food in diarrhea, anemia, and micronutrient status in infants. J Pediatr Gastroenterol Nutr. 2011 Nov;53(5):561-8.
  1. Poppitt SD, McGregor RA, Wiessing KR, Goyal VK, Chitkara AJ, Gupta S, Palmano K, Kuhn-Sherlock B, McConnell MA. Bovine complex milk lipid containing gangliosides for prevention of rotavirus infection and diarrhoea in northern Indian infants. J Pediatr Gastroenterol Nutr. 2014 Aug;59(2):167-71.
  2. He X, Parenti M, Grip T, Lönnerdal B, Timby N, Domellöf M, Hernell O, Slupsky CM. Fecal microbiome and metabolome of infants fed bovine MFGM supplemented formula or standard formula with breast-fed infants as reference: a randomized controlled trial. Sci Rep. 2019 Aug 12;9(1):11589.
  3. Chichlowski M, Bokulich N, Harris CL, Wampler JL, Li F, Berseth CL, Rudolph C, Wu SS. Effect of Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula on Gut Microbiome and Metabolome at 4 Months of Age. Curr Dev Nutr. 2021 Apr 2;5(5):nzab027.
  4. Zhao J, Yi W, Liu B, Dai Y, Jiang T, Chen S, Wang J, Feng B, Qiao W, Liu Y, Zhou H, He J, Hou J, Chen L. MFGM components promote gut Bifidobacterium growth in infant and in vitro. Eur J Nutr. 2021 Jul 29.
  5. Raza GS, Herzig KH, Leppäluoto J. Invited review: Milk fat globule membrane-A possible panacea for neurodevelopment, infections, cardiometabolic diseases, and frailty. J Dairy Sci. 2021 Jul;104(7):7345-7363. doi: 10.3168/jds.2020-19649. Epub 2021 Apr 23. PMID: 33896625
  6. Hari S, Ochiai R, Shioya Y, Katsuragi Y. Safety evaluation of the consumption of high dose milk fat globule membrane in healthy adults: a double-blind, randomized controlled trial with parallel group design. Biosci Biotechnol Biochem. 2015;79(7):1172-7.
  7. Jiang B, Xia Y, Zhou L, Liang X, Chen X, Chen M, Li X, Lin S, Zhang N, Zheng L, Tao M, Petocz P, Gallier S, Rowan A, Wang B. Safety and tolerance assessment of milk fat globule membrane-enriched infant formulas in healthy term Chinese infants: a randomised multicenter controlled trial. BMC Pediatr. 2022 Aug 3;22(1):465. doi: 10.1186/s12887-022-03507-8. PMID: 35918695; PMCID: PMC9347101.
  8. Hedrick J, Yeiser M, Harris CL, Wampler JL, London HE, Patterson AC, Wu SS. Infant Formula with Added Bovine Milk Fat Globule Membrane and Modified Iron Supports Growth and Normal Iron Status at One Year of Age: A Randomized Controlled Trial. Nutrients. 2021 Dec 18;13(12):4541. doi: 10.3390/nu13124541. PMID: 34960093; PMCID: PMC8708584.
  9. Jaramillo-Ospina AM, Toro-Campos R, Murguía-Peniche T, Wampler JL, Wu SS, Berseth CL, Uauy R. Added bovine milk fat globule membrane in formula: Growth, body composition, and safety through age 2: An RCT. Nutrition. 2022 May;97:111599. doi: 10.1016/j.nut.2022.111599. Epub 2022 Jan 14. PMID: 35193081.

  1. Cohen Kadosh K, Muhardi L, Parikh P, Basso M, Jan Mohamed HJ, Prawitasari T, Samuel F, Ma G, Geurts JM. Nutritional Support of Neurodevelopment and Cognitive Function in Infants and Young Children-An Update and Novel Insights. Nutrients. 2021 Jan 10;13(1):199.
  2. Brink LR, Gueniot JP, Lönnerdal B. Effects of milk fat globule membrane and its various components on neurologic development in a postnatal growth restriction rat model. J Nutr Biochem. 2019 Jul;69:163-171.
  3. Isabelle Le Huërou-Luron, Marion Lemaire, Sophie Blat. Health benefits of dairy lipids and MFGM in infant formula. OCL 25 (3) D306 (2018).
  4. Li F, Wu SS, Berseth CL, Harris CL, Richards JD, Wampler JL, Zhuang W, Cleghorn G, Rudolph CD, Liu B, Shaddy DJ, Colombo J. Improved Neurodevelopmental Outcomes Associated with Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula: A Randomized, Controlled Trial. J Pediatr. 2019 Dec;215:24-31.e8.
  5. Timby N, Domellöf E, Hernell O, Lönnerdal B, Domellöf M. 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. 2014 Apr;99(4):860-8.
  6. Xia Y, Jiang B, Zhou L, Ma J, Yang L, Wang F, Liu H, Zhang N, Li X, Petocz P, Wang B. Neurodevelopmental outcomes of healthy Chinese term infants fed infant formula enriched in bovine milk fat globule membrane for 12 months - A randomized controlled trial. Asia Pac J Clin Nutr. 2021 Sep;30(3):401-414.
  7. Veereman-Wauters G, Staelens S, Rombaut R, Dewettinck K, Deboutte D, Brummer RJ, Boone M, Le Ruyet P. Milk fat globule membrane (INPULSE) enriched formula milk decreases febrile episodes and may improve behavioral regulation in young children. Nutrition. 2012 Jul;28(7-8):749-52.
  8. Gurnida DA, Rowan AM, Idjradinata P, Muchtadi D, Sekarwana N. Association of complex lipids containing gangliosides with cognitive development of 6-month-old infants. Early Hum Dev. 2012 Aug;88(8):595-601.
  9. Timby N, Hernell O, Vaarala O, Melin M, Lönnerdal B, Domellöf M. Infections in infants fed formula supplemented with bovine milk fat globule membranes. J Pediatr Gastroenterol Nutr. 2015 Mar;60(3):384-9.
  10. Zavaleta N, Kvistgaard AS, Graverholt G, Respicio G, Guija H, Valencia N, Lönnerdal B. Efficacy of an MFGM-enriched complementary food in diarrhea, anemia, and micronutrient status in infants. J Pediatr Gastroenterol Nutr. 2011 Nov;53(5):561-8.
  11. Poppitt SD, McGregor RA, Wiessing KR, Goyal VK, Chitkara AJ, Gupta S, Palmano K, Kuhn-Sherlock B, McConnell MA. Bovine complex milk lipid containing gangliosides for prevention of rotavirus infection and diarrhoea in northern Indian infants. J Pediatr Gastroenterol Nutr. 2014 Aug;59(2):167-71.
  12. He X, Parenti M, Grip T, Lönnerdal B, Timby N, Domellöf M, Hernell O, Slupsky CM. Fecal microbiome and metabolome of infants fed bovine MFGM supplemented formula or standard formula with breast-fed infants as reference: a randomized controlled trial. Sci Rep. 2019 Aug 12;9(1):11589.
  13. Chichlowski M, Bokulich N, Harris CL, Wampler JL, Li F, Berseth CL, Rudolph C, Wu SS. Effect of Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula on Gut Microbiome and Metabolome at 4 Months of Age. Curr Dev Nutr. 2021 Apr 2;5(5):nzab027.
  14. Zhao J, Yi W, Liu B, Dai Y, Jiang T, Chen S, Wang J, Feng B, Qiao W, Liu Y, Zhou H, He J, Hou J, Chen L. MFGM components promote gut Bifidobacterium growth in infant and in vitro. Eur J Nutr. 2021 Jul 29.
  15. Raza GS, Herzig KH, Leppäluoto J. Invited review: Milk fat globule membrane-A possible panacea for neurodevelopment, infections, cardiometabolic diseases, and frailty. J Dairy Sci. 2021 Jul;104(7):7345-7363. doi: 10.3168/jds.2020-19649. Epub 2021 Apr 23. PMID: 33896625
  16. Hari S, Ochiai R, Shioya Y, Katsuragi Y. Safety evaluation of the consumption of high dose milk fat globule membrane in healthy adults: a double-blind, randomized controlled trial with parallel group design. Biosci Biotechnol Biochem. 2015;79(7):1172-7.
  17. Jiang B, Xia Y, Zhou L, Liang X, Chen X, Chen M, Li X, Lin S, Zhang N, Zheng L, Tao M, Petocz P, Gallier S, Rowan A, Wang B. Safety and tolerance assessment of milk fat globule membrane-enriched infant formulas in healthy term Chinese infants: a randomised multicenter controlled trial. BMC Pediatr. 2022 Aug 3;22(1):465. doi: 10.1186/s12887-022-03507-8. PMID: 35918695; PMCID: PMC9347101.
  18. Hedrick J, Yeiser M, Harris CL, Wampler JL, London HE, Patterson AC, Wu SS. Infant Formula with Added Bovine Milk Fat Globule Membrane and Modified Iron Supports Growth and Normal Iron Status at One Year of Age: A Randomized Controlled Trial. Nutrients. 2021 Dec 18;13(12):4541. doi: 10.3390/nu13124541. PMID: 34960093; PMCID: PMC8708584.
  19. Jaramillo-Ospina AM, Toro-Campos R, Murguía-Peniche T, Wampler JL, Wu SS, Berseth CL, Uauy R. Added bovine milk fat globule membrane in formula: Growth, body composition, and safety through age 2: An RCT. Nutrition. 2022 May;97:111599. doi: 10.1016/j.nut.2022.111599. Epub 2022 Jan 14. PMID: 35193081.