Human milk fats: the lipidome

What is the human milk lipidome?

Lipids are a broad group of naturally occurring molecules which include fats, fatty acids, cholesterol, waxes, fat-soluble vitamins, and phospholipids. The subgroup of lipids known as fats are comprised of triglycerides.

• The human milk lipidome contributes about 50% of the infant’s daily caloric requirement.

• Yet the human milk lipidome makes up only 5% of milk. This is why human milk looks bluer or thinner than cow’s milk, which contains more lipids.

• 98-99% of the lipidome is comprised of lipids strategically packaged as milk fat globules.

• Fat is the most highly variable human milk macronutrient ranging from an average of 21.6 g/L to 53.5 g/L.35. The greatest variations occur with the degree of fullness of the breast; it can change from 3.5 g/L pre-feed to 106 g/L post-feed making it difficult to estimate infant intake unless measured over a 24-hour period.

What is a milk fat globules?

A milk fat globule in milk is composed of

1. A triacylglyceride-rich core

2. The milk fat globule membrane (MFGM), a tri-layer biological membrane wrapped around the core.

1. How is the triacylglyceride core of the fat globule synthesised?

Fatty acids enter lactocytes from capillaries or are synthesised within lactocytes. The lactocyte synthesises the triglycerides found inside the milk fat globules from fatty acids. Maternal diet influences fatty acid composition but does not change total lipid content of human milk.

The fatty acids used to synthesise the triglyceride core are of two types.

1. Medium chain fatty acids containing 4-14 carbons are made by de novo synthesis in the lactocytes of the mammary gland.

2. Long chain fatty acids, which have 16 carbons, are derived from body stores or diet and are transported by the blood stream into the lactocytes. Long chain fatty acids which can’t be synthesised are referred to as essential fatty acids.

Smaller milk fat globules then coalesce into larger droplets or milk fat globules inside the lactocyte. The fat globules inside the lactocyte are heterogeneous in size and composition.

Fat globule composition

• Varies between individuals

• Is dynamic over the course of lactation but also over a single breastfeed.

• Is affected not only by diet, but by maternal genetics, body composition, and the changing needs of infant over lactation.

Colostrum has more total phospholipids and long chain polyunsaturated fatty acids relative to transitional and mature milk. Otherwise, long chain fatty acid content remains similar throughout lactation.

However, as milk matures, the average fatty acid chain length decreases because the mammary gland increases its capacity to produce medium chain (12-14 carbon) fatty acids.

2. How is the fat globule transferred into milk and then transported?

Lipids and any lipid digestive derivatives must be transported in globular form within the cell, blood, and tissue spaces due to the insolubility of lipids.

Milk is an emulsion, with tiny fat globules dispersed in milk's aqueous environment. Milk fat globules vary in size. Their mean diameter is largest in colostrum, then mature milk, and smallest in transitional milk. The fat globules don’t coalesce and form a separate layer (like oil) because they are protected by a membrane layer, which keeps the fat globules separate from the water phase.

Docking at the apical membrane

The membrane tri-layer is created when the fat globules inside the lactocytes ‘lean into’ (or create a docking complex) at the apical membrane of the lactocyte. The fat globule is then wrapped in a portion of the lactocyte cell membrane and pinched off into the alveolar lumen, in a process known as parturition. Because the milk fat globule membrane originates in the lactocyte’s cell wall, it is composed of phospholipids, cholesterol, glycoproteins, and proteins.

Dynamic shape of lactocytes limits lipid secretion

When the alveolus is rather empty, the apical (or lumen-facing) aspect of the lactocyte is rounded and the lactocyte has a triangular shape. As the mechanical or hydrostatic pressure of increasing milk volume in the lumen acts upon the lactocytes, they stretch, become elongated and rectangular. When the apical surface of the lactocyte is stretched flat and long, it no longer pinches off fat globules.

The milk fat globule membrane

Here are other useful things to know about milk fat globule membranes.

• The proteins in the membrane of the milk fat globule account for one to four percent of the total protein fraction in milk. Smaller fat globules have more phospholipids.

• The milk fat globule membrane in human milk is of special interest to researchers due to its potential functional and health benefits.

• The bovine milk fat globule membrane is altered in many processed dairy products and is absent from standard infant milk formulas. In formula, the processed lipid droplets are coated by milk proteins.

The infant gut emulsifies and hydrolyses milk fat globules

The core triacylglycerols are not active until hydrolysis by lipase releases their free fatty acids and monacylglycerol products. This hydrolysis occurs through action of the infant’s lingual and gastric lipases, which penetrate the membrane of the milk fat globules.

Globules of fat are also emulsified in the stomach into smaller droplets by bile salts during digestion, speeding up the rate of digestion by the enzyme lipase when they pass further down the gut.

The rate at which milk fat globules are digested is related to their diameter and the proteins found in their membrane. Some milk fat globule membranes resist pepsin hydrolysis better than others, and survive digestion, enabling passage of some milk fat globules to the colon.

Human milk fat content is highly variable

Lipids are the most variable macronutrient of human milk, with sample concentrations ranging between 2 – 100 gm/L. Other researchers have estimated that the total amount of fat that an exclusively breastfeeding mother-baby pair removes in a 24 hour period ranges from 15-50 gm. That is, one woman’s milk might contain more than three times the amount of fat compared to another’s, even though both babies are thriving.

Lipid concentration increases throughout a feed, decreases throughout the day, varies between breasts, and typically increases throughout lactation.

For example, the amount of fat in milk increases as the total volume removed in that same breastfeeding event increases. This is often framed as the breast ‘emptying’, which is misleading terminology. However, both frequent and infrequent breastfeeders remove roughly the same amount of fat in total in a 24 hour period.

What is the role of the milk lipidome in the complex adaptive system of the mother-infant pair?

The human milk lipidome is a vital participant in the complex and dynamic biological system of the mother-baby system, extending maternal physiological protection to the infant in multiple ways.

1. The lipidome is the infant’s main source of energy-dense nutrition.

2. The lipidome provides structural components for the infant’s developing neural and retinal systems.

3. The lipidome regulates mammary gland and infant immunological interactions and defence.

   • For example, proteins in the milk fat globule membrane are associated with immune defence. Antimicrobial peptides and surface carbohydrate moieties surrounding the milk fat globule shape gut microbial populations, promoting protection against immune and inflammatory diseases.

   • Once the milk fat globule is hydrolysed in the intestine, high amounts of medium chain fatty acids are released, which inhibit growth of certain bacteria with pathogenic potential. These fatty acids are incorporated into the lipid layer of a microbe to rupture the lipid envelope and cause death of the microorganism.

4. The lipidome assists in the postnatal development of the intestinal mucosa, vasculature, and motility. Milk fat globules and the bioactive components of the milk fat globule membrane improve intestinal integrity and maturation by

   • Serving as essential building blocks for cellular membrane structure

   • Acting as signalling messengers for cell growth, proliferation, and migration.

5. The lipidome helps establish the infant’s gut microbiota. Milk fat globule membrane fragments which are resistant to digestion appear to shift microbial populations in the lower gut. Here are two hypothesised mechanisms.

   • The milk fat globule membrane contains two forms of glycoconjugates (glycoproteins and glycolipids) which have antimicrobial, anti-inflammatory and prebiotic functions in the gut.

   • Probiotic bacteria (lactobacillus and bifidobacterium genera) adhere to components of the MFGM, and are transported this way from the mammary gland to the infant colon.

Whilst amounts of lipid vary over a feed, it's important to note, as Perrella et al write (2021): "The milk intake volume of the infant has been shown to be related to infant growth rather than energy content. Interestingly, the concentrations of milk components are not often associated with infant growth."

Recommended resources

You don't need to worry about 'emptying' your breasts when baby feeds because your milk is rich in healthy fats regardless

Selected references

Lai CT, Geddes DT, Trengove N, et al. Human milk lipid composition is associated with maternal and infant characteristics. Am J Clin Nutr. 2023;117(2):315-324.

Lee H, Padhi E, Hasegawa Y, Larke J. Compositional dynamics of the milk fat globule and its role in infant development. Frontiers in Pediatrics. 2018;6(313):doi:10.3389/fped.2018.00313.

Perrella SL, Gridneva Z, Tat Lai C. Human milk composition promotes optimal infant growth, development and health. Seminars in Perinatology. 2021;45(151380):https://doi.org/10.1016/j.semperi.2020.151380.