The Benefits of MFGM

This summary is adapted from ‘Clinical Benefits of Milk Fat Globule Membranes for Infants and Children’ by Hernell et al. 2016 There has long been research attempting to make infant formula as similar to breast milk as possible. Aside from the major components, there is growing interest in some of the substances which are present in breast milk at low concentrations, but may still be having an important effect on infant health. One of these substances is milk fat globule membrane (MFGM). This substance surrounds the fat droplets which are released from the mammary glands. MFGM is made up of multiple fats and proteins, which are released when it is broken down. These proteins and fats have various functions in the developing infant that may confer health advantages. Choline is one such substance which makes up MFGM. Choline is processed similarly to folate in the body, and similar to folate it is essential for the development of the infant’s nervous system. There are high concentrations of choline circulating in the fetus and neonates. Women with low levels of choline have twice the risk of having a baby with a neural tube defect, a central nervous system malformation which can be very serious, compared to women with high levels of choline¹. Furthermore, low levels of choline in the first half of pregnancy were associated with poor cognitive development of the infant at 18 months². Therefore, MFGM may be an important additional source. Sphingomyelin is another substance which makes up MFGM, which is a fat that is important for nerve cell structure. In a small study, low birth weight infants received sphingomyelin-fortified formula in addition to breast milk, or standard formula. Infants which received the sphingomyelin-fortified milk group had better neurodevelopmental measures at 6 and 18 months³. This indicates potential beneficial effects; however larger studies are needed for confirmation. Gangliosides are another fat that are involved in nervous system development also comprising MFGM. There is evidence from animal models that dietary gangliosides are important for brain development during early life, but this has yet to be validated in humans. Cholesterol is present in MFGM and despite negative effects of dietary cholesterol which are widely known, this fat is essential for the development of the nervous system in infants. It has been well established that serum cholesterol in infancy is higher in breastfed infants compared to formula-fed infants, as cholesterol is higher in breast milk than in formula⁴. This may be in part due to the absence of MFGM in infant formula. In addition to fats, there are also important proteins making up MFGM. These proteins are only a small fraction of the total protein content in breast milk (1-4%), they have gained a lot of interest after multiple studies showed that they have beneficial health effects. These effects include anticancer effects and antimicrobial effects⁵. In addition, sialic acid is found in MFGM, yet another component of breast milk thought to support optimal nervous system function. There have been multiple trials investigating MFGM supplementation in infant formula. A large Peruvian study including nearly 500 infants randomised to receive complementary food enriched with MFGM or skim milk powder⁶. They were focusing on the effect of MFGM on diarrhea, where they found no difference to the control group aside from a possible reduction in bloody diarrhea. Another study including 70 infants in Indonesia investigated the impact of ganglioside supplementation on cognitive function up to 24 weeks of age⁷. Those with ganglioside supplementation had greater hand and eye coordination and IQ compared to those receiving standard formula. These values were comparable to those in a breast-fed reference group. A trial of 450 infants aged 8-24 months in India found that ganglioside supplementation also did not affect incidence of diarrhea⁸. A trial conducted in Sweden with 73 infants further supplemented infant formula with protein-rich MFGM to compare with standard formula⁹. The infants who received this supplementation had higher cognitive development scores than those who received standard formula, with these scores comparable to breast-fed infants. They also had a lower incidence of ear infections. Their serum cholesterol was higher and reached a similar level to that of breast-fed infants, which as previously mentioned is thought to be beneficial for infant health. Another study supplemented infant formula with lipid-rich MFGM or protein-rich MFGM compared with standard formula¹⁰. There were no differences in the groups at 4 months of age in weight gain and adverse events, apart from higher rates of eczema in the MFGM protein-rich group (13.9% vs 1.4%). The goal of infant formula supplementation is to narrow the gap in health benefits between breast-fed and formula fed infants. These studies provide an indication that MFGM supplementation is safe, as growth has been seen to be normal and no serious adverse events have been reported. Larger studies may further confirm or disprove the association with eczema seen in one of the current studies, as even though there was increased incidence, the incidence was still low. There has been some evidence of potential benefit associated with MFGM supplementation in infants, related to both neurodevelopment and defense against infections. These findings are also backed up by preclinical studies. Yet, the number of studies conducted is still small and there has been heterogeneity in the methods used, with different concentrations of MFGM trialed at different ages and for different lengths of times. More trials with consistent methodology will help us understand if MFGM is effective and should be used in standard infant formula.

Read more about the role of MFGM here

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References

1. Shaw GM, Carmichael SL, Yang W, Selvin S, Schaffer DM. Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. American journal of epidemiology. 2004 Jul 15;160(2):102-9.
2. Wu BT, Dyer RA, King DJ, Richardson KJ, Innis SM. Early second trimester maternal plasma choline and betaine are related to measures of early cognitive development in term infants.
3. Tanaka K, Hosozawa M, Kudo N, Yoshikawa N, Hisata K, Shoji H, Shinohara K, Shimizu T. 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 and Development. 2013 Jan 1;35(1):45-52.
4. FOMON SJ, BARTELS DJ. Concentrations of cholesterol in serum of infants in relation to diet. AMA Journal of Diseases of Children. 1960 Jan 1;99(1):27-30.
5. Spitsberg VL. Invited review: Bovine milk fat globule membrane as a potential nutraceutical. Journal of dairy science. 2005 Jul 1;88(7):2289-94.
6. 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. Journal of pediatric gastroenterology and nutrition. 2011 Nov 1;53(5):561-8.
7. 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 human development. 2012 Aug 1;88(8):595-601.
8. 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. Journal of pediatric gastroenterology and nutrition. 2014 Aug 1;59(2):167-71.
9. 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. The American journal of clinical nutrition. 2014 Apr 1;99(4):860-8.
10. Billeaud C, Puccio G, Saliba E, Guillois B, Vaysse C, Pecquet S, Steenhout P. Safety and tolerance evaluation of milk fat globule membrane-enriched infant formulas: a randomized controlled multicenter non-inferiority trial in healthy term infants. Clinical Medicine Insights: Pediatrics. 2014 Jan;8:CMPed-S16962.