Global Levels and Variations of Cholesterol and Polar Lipids of Human Milk: A Systematic Review and Meta-analysis

Polar lipids and cholesterol are vital structural components of the milk fat globule membrane, playing a crucial role in infant growth and development; however, systematic global reports on their content in human milk are currently lacking. This study conducted a systematic literature search in Chinese and English databases, including 69,392 human milk samples from 96 studies. A random-effects model based on global data was used to assess the content of total lipids, cholesterol, gangliosides, and phospholipids in human milk and their variations with the lactation stage, geographical region, and sample year. The mean contents of total lipids, cholesterol, and total phospholipids were 2774.15 mg/100 g (95% CI: 2614.88, 2933.42 mg/100 g), 21.15 mg/100 g (18.35, 23.95 mg/100 g), and 70.72 mg/100 g (68.84, 72.60 mg/100 g), respectively, with gangliosides GM3 and GD3 at 0.63 mg/100 g (0.54, 0.72 mg/100 g) and 0.34 mg/100 g (0.32, 0.36 mg/100 g). The major phospholipids SM, PC, PE, PS, and PI averaged 24.19 mg/100 g (23.17 and 25.21 mg/100 g), 21.27 mg/100 g (19.92 and 22.62 mg/100 g), 18.28 mg/100 g (17.46 and 19.10 mg/100 g), 2.86 mg/100 g (2.32 and 3.40 mg/100 g), and 2.12 mg/100 g (1.75 and 2.49 mg/100 g). With the progression of lactation, total lipids, gangliosides, and most phospholipids (SM, PC, PS, PI) increased, while cholesterol and PE decreased. Over the years, total lipids, gangliosides, and PE showed an upward trend, whereas cholesterol and most phospholipids declined. Human milk from Europe had lower total lipid and cholesterol levels compared with other regions. While the total phospholipid content did not show significant regional differences (P > 0.05), variations in phospholipid composition were observed. These findings emphasize the importance of understanding spatiotemporal changes in human milk lipids to develop personalized nutrition strategies that support optimal infant growth and development.