Circadian Variation in Human Milk Composition, a Systematic Review

Abstract

Background: Breastfeeding is considered the most optimal mode of feeding for neonates and mothers. Human milk changes over the course of lactation in order to perfectly suit the infant’s nutritional and immunological needs. Its composition also varies throughout the day. Circadian fluctuations in some bioactive components are suggested to transfer chronobiological information from mother to child to assist the development of the biological clock. This review aims to give a complete overview of studies examining human milk components found to exhibit circadian variation in their concentration. Methods: We included studies assessing the concentration of a specific human milk component more than once in 24 h. Study characteristics, including gestational age, lactational stage, sampling strategy, analytical method, and outcome were extracted. Methodological quality was graded using a modified Newcastle-Ottawa Scale (NOS). Results: A total of 83 reports assessing the circadian variation in the concentration of 71 human milk components were included. Heterogeneity among studies was high. The methodological quality varied widely. Significant circadian variation is found in tryptophan, fats, triacylglycerol, cholesterol, iron, melatonin, cortisol, and cortisone. This may play a role in the child’s growth and development in terms of the biological clock.

Variability of Lipids in Human Milk

“…Consistent with prior studies of total fat [ 29 ], TAGs [ 39 , 49 ], and cholesterol [ 14 , 49 , 50 ] in human milk, we found that the concentrations of many species of glycerolipids, phospholipids, and sphingolipids were higher in the evening compared with the morning. By comparison, earlier studies have found that sterol lipids including cortisol and cortisone reach their peak in breastmilk in the morning [ 29 ], similar to the rhythm observed in blood plasma and saliva [ 19 , 51 ]. There is little evidence, however, that concentrations of free fatty acids exhibit diurnal variation in HM [ 29 ], which contrasts with results in blood plasma [ 52 ].…”

“…By comparison, earlier studies have found that sterol lipids including cortisol and cortisone reach their peak in breastmilk in the morning [29], similar to the rhythm observed in blood plasma and saliva [19,51]. There is little evidence, however, that concentrations of free fatty acids exhibit diurnal variation in HM [29], which contrasts with results in blood plasma [52].…”

“…Several studies have investigated diurnal variation of total fat content in HM using different methods of collection including pre-/post-feed expressed samples [ 21 , 22 , 23 ], total milk from a fully expressed breast [ 24 , 25 , 26 , 27 , 28 ], and demand feeding versus scheduled samples. Despite different sampling approaches, it has been consistently observed that total milk fat exhibits a 24-h rhythm, with most studies finding higher concentrations in the evening compared with other times of day [ 29 ]. Diurnal variation has also been observed for other milk components, including amino acids, minerals, and melatonin [ 30 , 31 , 32 , 33 ].…”

“…These studies suggest that the circadian system regulates the composition of milk and may serve as an important source of intra-individual variance. While prior studies have reported diurnal variation of total TAG levels, cholesterol, and cortisol in milk [ 29 ], there is almost no information on diurnal regulation of low abundant lipids, e.g., sphingolipids or phospholipids.…”

Variation of the human milk bacterial diversity during the time of the day.

“…Likewise, in the human milk there are beneficial bacteria that are transferred to the newborn by breastfeeding, colonizing the gastrointestinal tract [6]. In addition, other studies suggest that some components of the human milk such as proteins, nucleotides, vitamins among others undergo diurnal variations in the same way the gut microbiota does in both mice and humans [4,7]. We believe in the human milk; these oscillations enhance the well-being of the breast-fed infant.…”