Human milk is a living tissue

Human milk is a dynamic and bioactive fluid which has developed over the past 310 million years of mammalian evolution to meet the nutritional, developmental, and immunological needs of human infants. Initially mammalian milk evolved to meet a newborn's anti-infection and hydration needs, as secretions from a modified sweat gland. The nutrient function of milk is a later evolutionary development.

• Human milk's composition varies across stages of lactation, throughout the day, and between mothers, reflecting both genetic and environmental influences. The milk a woman makes for a term infant is different to the milk her breasts generate for an infant born prematurely.

• Human milk provides a complex blend of living cells, nutrients, bioactive components, microorganisms, and immunological factors for the support of growth and development.

As Dr Sharon Perrella and her research team wrote:

"Human milk composition is species-specific and is vastly different to infant formula. This multi-faceted fluid has been shaped by evolution to contain essential nutrient and bioactive components that provide not only nutrition but developmental and appetite control factors as well as protection against infectious and non-communicable diseases. Human milk remains unmatched by any other diet, with a dose-response effect observed for health and cognitive outcomes across the lifespan. Longer durations of exclusive and any breastfeeding are associated with greater protection from gastrointestinal and respiratory disease, atopy, overweight and obesity in childhood, and improved performance in intelligence tests and educational attainment in adulthood ... The composition of human milk changes dramatically during the transition from colostrum, that is low in lactose and rich in proteins including immunomodulatory and growth factors, to mature milk that is relatively stable from two weeks postpartum until weaning ... Human milk consists of 87% water, 7% lactose, 3.8% fat and 1% protein." (2021)

Variability in composition

The composition of human milk is dynamic over time.

1. Composition varies with stages of lactation

• Colostrum (days 1–5) is rich in proteins, immune factors, and growth factors.

• Transitional milk (days 6–14) shows increasing fat and lactose.

• Mature milk stabilizes but adapts dynamically to infant needs.

2. Composition varies within a breastfeed

• The first portion of a breastfeed is lower in fat and higher in lactose, while the latter part of a breastfeed is richer in lipids.

• Maternal nutrition, health, genetics, and even circadian rhythm influence composition.

Macronutrients

The macronutrient composition of human milk breaks down to about 7% carbohydrates, 5% lipids, 0.9% protein, and 0.2% minerals. 87% of human milk is water.

Human milk contains three primary macronutrients: carbohydrates, proteins, and fats.

Carbohydrates

• Lactose is the predominant carbohydrate in human milk, comprising about 7 g/100 ml.

• Lactose is the main source of energy for the infant and facilitates calcium absorption.

• The relative stability of lactose as the primary carbohydrate contrasts with the dynamic variability in fat concentrations across feeds.

• Additionally, human milk contains oligosaccharides—complex sugars (HMOs) that act as prebiotics, promoting the growth of beneficial gut bacteria and protecting against pathogens.

Proteins

The protein content of human milk is approximately 0.9-1.2 g/100 ml of mature milk, lower than that of cow’s milk but more digestible. The protein concentration of human milk reduces from 14-16 g/L in early lactation to 8-10g/L at three to four months of lactation to 7-8g/L at 6 months and beyond. Major proteins include casein and whey, with whey proteins more prevalent.

Whey proteins are easily digestible and play significant roles in immune defense and nutrient absorption. They include

• Lactoferrin (antimicrobial)

• α-lactalbumin (which aids lactose synthesis and provides essential amino acids and minerals), and

• Immunoglobulin A (or secretory IgA), which provides mucosal protection.

Casein proteins include

• Beta-casein, a highly phosphorylated protein which facilitates the absorption of calcium and other minerals

• Alpha-s1 caseine, the most abundant casein fraction

• Kappa-casein, a heavily glycosylated protein which inhibits the adhesion of bacteria to the gastric mucosa.

Early preterm milk may exhibit higher protein relative to term milk to support rapid growth. This pattern evolves over time, highlighting the need for individualized fortification strategies in very preterm infants.

"Human milk proteins predominantly consist of caseins and whey proteins, and also enzymes, endogenous peptides and mucins that are derived from the milk fat globule membrane. Indeed, more than 1700 human milk proteins are present in changing concentrations across the course of lactation to meet the needs of the developing breastfed infant." (Perrella 2021)

Fats

• Lipids provide about 50% of the energy in human milk, with concentrations ranging from 3.5-4.5 g/100 mls.

• Human milk fat globules contain triglycerides, phospholipids, cholesterol, and essential fatty acids such as linoleic and alpha-linolenic acid. Long-chain polyunsaturated fatty acids (LC-PUFAs) such as DHA and ARA are critical for brain and retinal development.

• The fatty acid profile reflects maternal diet and physiology, varying throughout breastfeeds and over the course of lactation. Fat content is the most variable of the macronutrients.

Micronutrients

Human milk provides essential vitamins and minerals, although concentrations vary. The bioavailability of these micronutrients in human milk is high, compensating for their relatively low concentrations in human milk compared to formula or cow’s milk.

Micronutrients include

• Fat-soluble vitamins such as Vitamins A, D, E, and K, though these depend heavily on maternal diet and sun exposure. Vitamin D may be insufficient, necessitating maternal supplementation.

• Water-soluble vitamins such as Vitamin C, B vitamins, and folate are generally adequate, though maternal deficiencies can reduce their levels in milk.

• Minerals including calcium, phosphorus, magnesium, sodium, potassium, iron, and trace elements (zinc, copper, selenium) are supplied in bioavailable forms.

Bioactive components

A bioactive factor is a substance that has a biological effect on a living organism. Human milk is not only nutritive but also astonishingly biologically active. Many or possibly most components of milk have multiple roles.

• The milk microbiome is a complex community of microorganisms, including bacteria, viruses, fungi, and archaea, discussed elsewhere in this section.

• Somatic cells provide immune protection.

  • The role of lactocytes in human milk is still being elucidated.

  • Immune cells (leukocytes) and cytokines (signaling molecules) provide antimicrobial defense and modulate infant immune maturation.

• Hormones and growth factors such as insulin, leptin, and epidermal growth factor influence infant metabolism, appetite regulation, and tissue development.

• Extracellular vesicles, including exosomes, carry diverse biologically active cargo including proteins, lipids, enzymes, and messenger RNA and microRNA. They

  • Mediate cell-cell signaling between maternal and infant tissues

  • Play a role in the development of the infant microbiome, genetic expression and immune development.

• Human milk contains a diverse array of enzymes, including digestive enzymes like lipases, proteases, and amylase, and protective enzymes such as lysozyme. These enzymes contribute to infant nutrition, digestion, and immune defense. Their levels and activities are dynamic, influenced by factors like the stage of lactation and processing methods.

Selected references

Ballard O, Morrow AL. Human milk composition: nutrients and bioactive factors. Pediatr Clin North Am. 2013;60(1):49-74. https://doi.org/10.1016/j.pcl.2012.10.002

Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012;22(9):1147-1162. https://doi.org/10.1093/glycob/cws074

Chen S, Geddes DT, Kakulas F, et al. The human milk proteome and peptidome: insights into mammary physiology and pathology. Front Nutr. 2024;11:1398472.

Dombrowska-Pali A, Wiktorczyk-Kapischke N, Chrustek A. Human milk microbiome - a review of scientific reports. Nutrients. 2024;16:1420.

Geddes DT, Lee K, Brennan C, et al. The dynamic nature of human milk composition. Ann Nutr Metab. 2022;80(Suppl 1):1-10.

Geddes DT, Lee K, Brennan C, et al. The effect of maternal and infant characteristics on human milk composition. J Hum Lact. 2020;36(4):673-682.

Innis SM. Human milk: maternal dietary lipids and infant development. Proc Nutr Soc. 2007;66(3):397-404. https://doi.org/10.1017/S0029665107005632

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.

Perrella SL, Gridneva Z, Lai CT. Human milk composition promotes optimal infant growth, development and health. Semin Perinatol. 2021;45:151380. https://doi.org/10.1016/j.semperi.2020.151380

Victora CG, Bahl R, Barros AJD, et al. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet. 2016;387(10017):475-490. https://doi.org/10.1016/S0140-6736(15)01024-7