Table 3.
Summary of the studies on circadian changes in human milk macronutrient content
| Reference | Site | Participants (number) | Lactation stage | Macronutrients investigated | Analytical methods | Results |
|---|---|---|---|---|---|---|
| Gunther M et al., 1949 [8] | Germany | 8 | 8–11 days of lactation | Fat | Gerber | The highest concentrations in the morning and at noon and the lowest between 8 PM and 4 AM |
| Prentice A et al., 1981 [17] | Gambia | 60 | 1–18 months after delivery | Fat | CMT | A marked diurnal variation (the highest values in the early morning, the lowest in the late afternoon) |
| Harzer G et al., 1983 [18] | Germany | 17 (13 German and 4 English) | First 5 weeks of lactation | Lipid | Thin-layer chromatography |
Milk samples from German mothers had their peak lipid content in the afternoon (noon to 6 PM), while the English samples had their respective peaks in the evening (6 PM to midnight) |
| Lavine ME et al., 1986 [19] | US | 6 (mothers of term infants) | 8th week of lactation | Nitrogen, lipid | Micro-Kjeldahl method (nitrogen), modified Folch procedure (lipid) | Total nitrogen remained fairly constant during the day; total lipid exhibited significant circadian variation, with peak concentration in the morning (10.00 h) and afternoon (14.00 h) samples |
| Clark RM, 1987 [20] | US | 7 (mothers of term infants) | 8th week of lactation | Protein, urea nitrogen, free amino acids (taurine, glutamine, glutamic acid) | Micro-Kjeldahl method (total nitrogen) Crocker method (urea nitrogen) | Concentrations of nitrogen substances in the milk differed significantly among women but were relatively constant during the day |
| Jackson DA et al., 1988 [21] | Thailand | 25 (mothers of term infants) | From the 1st to 9th months after delivery | Fat | CMT | Significant circadian variation, with maximum values between 16.00–20.00 h and minimum values between 04.00–08.00 h |
| Lammi-Keefe CJ et al., 1990 [22] | US | 6 (mothers of term infants) | 8 weeks after delivery | Lipid, carbohydrate, protein, calories | Modified Folch procedure (lipid), YSI model 27 Industrial Analyser (lipid), micro- Kjeldahl method (protein), Southgate-Durnin equation (calories) | Significant circadian variation of protein content, with maximum values at 6 AM and 6 PM. None of the other components varied significantly. |
| Stafford J, 1994 [23] | Mexico | 10 | Not specified | Lipid | Modified Folch method | Significant circadian variations of volume and lipid yield were noted, peaking at 8.00–12.00 and 16.00–20.00 h |
| Weber A et al., 2001 [24] | Germany | 20 (mothers of VLBW infants) | The first 4 weeks of lactation | Protein, fat | Bicinchoninic acid method (protein), CMT (fat) | Fat but not protein was lower in morning samples than in samples collected later in the day |
| Lubetzky R et al., 2006 [10] | Israel | 39 (mothers of preterm infants, 26–33 weeks) | 7–14 days after delivery | Fat | CMT | CMT was significantly higher in evening (between 21.00 h and 24.00) than in morning (between 6.00 h and 9.00 h) samples |
| Lubetzky R et al., 2007 [9] | Israel | 22 (mothers of preterm infants, 26–31 weeks) | 2–7 weeks after delivery | Fat | CMT | Mean CMT was significantly higher in evening (9 PM to midnight) than morning samples (6–9 AM) during the first 7 weeks of lactation |
| Sanchez Lopez CL et al., 2011 [25] | Spain | 69 (11 colostral group, 27 transitional group, 31 mature group) | < 2 months of lactation | Total nitrogen and protein content | Kjeldahl method | In the group of mature lactating women, protein content was significantly higher during the night-time (20.00 h – 8.00 h) than during the daytime (8.00–20.00 h) |
| Khan S et al., 2013 [26] | Australia | 15 (mothers of term infants) | From the 1st to 6th months after delivery | Fat, lactose, total protein, casein, whey protein content | CMT (fat), enzymatic spectrophoto-metric method (lactose), Bradford protein assay (protein) | Fat content significantly differed over 24 h (higher during the day and lower at night, with no difference between morning and evening); the concentration of lactose and protein remained the same |
| Moran-Lev H et al., 2015 [11] | Israel | 32 (mothers of preterm infants, 26–33 weeks) | 2–7 weeks after delivery | Fat, carbohydrate, protein, energy | Mid-infrared transmission spectroscopy | Fat and energy contents during the whole period were significantly higher in evening samples; no significant differences between morning and evening in carbohydrates and protein contents |
| Çetinkaya AK et al., 2017 [27] | Turkey | 52 (mothers of 30 preterm and 22 term infants) | 5–15 lactation days (n = 27) and > 15 lactation days (n = 25) | Protein, fat, carbohydrate | Mid-infrared transmission spectroscopy | No significant difference was found in the protein, fat, and carbohydrate content of milk samples throughout the day |
| Hollanders JJ et al., 2019 [28] | Netherlands | 10 (mothers of term infants) | 1 month after delivery (± 5 days) | Cortisol, cortisone levels and fat, carbohydrate and protein content | Mid-infrared transmission spectroscopy | While in all the mothers, a diurnal rhythm of cortisol and cortisone could be seen, no rhythm appeared to be present for fat, carbohydrates, and protein |
US United States, VLBW very low birthweight, CMT creamatocrit