WAPM Working Group on Nutrition: Potential chronobiotic role of human milk in sleep regulation

Sertac Arslanoglu 1 , Enrico Bertino 2 , Margherita Nicocia 2  and Guido E. Moro 1
  • 1 WAPM Working Group on Nutrition, Milan, Italy
  • 2 Neonatal Care Unit, Department of Pediatrics, University of Turin, Turin, Italy


Background: Organization of the sleep states and a normal sleep pattern in the neonatal period and early infancy is essential for brain development and plasticity. The establishment of a consolidated circadian sleep-wake cycle occurs between 1 and 4 months of life in term infants. This period may be even longer for preterm infants who are exposed to relentless interventions in neonatal intensive care units. The sleep should be respected and protected.

Objective and methods: Human milk (HM) contains bioactive sleep-promoting components, and recent evidence shows that some of these components show circadian oscillations. This article reviews the existing evidence regarding the role of these HM components on sleep. This topic is prefaced with a brief information about the basic concepts concerning sleep. Consecutively, chronobiotic and chrononutrition concepts are introduced.

Results: Melatonin, tryptophan, nucleosides/nucleotides, and vitamin B12 are components of HM that have sleep-promoting characteristics. The sleep-inducing effects of these components are well-established in animal and adult human studies. Interestingly, melatonin, tryptophan, and 5′-adenosine monophosphate and 5′-guanosine monophosphate nucleotides in HM have been shown to exhibit also circadian oscillations. Although 5′-uridine monophosphate does not have a circadian rhythm, its levels increase during the night.

Conclusion: HM has a potential to function as a “synchronizer,” helping the infant to consolidate a circadian sleep-wake cycle, thanks to its several bioactive components with chronobiotic characteristics. Research is warranted to address gaps in this field, such as the association between the circadian oscillations of the sleep-promoting factors in HM and the quantity/quality of infant sleep.

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