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Modulating Sterol Concentrations in Infant Formula Influences Cholesterol Absorption and Synthesis in the Neonatal
Elizabeth A Babawale1, Peter Jh Jones2,3, Kelly E Mercer4,5
1Department of Food and Human Nutritional Science, University of Manitoba, Winnipeg, MB R3T 2N2, Canada. abosedee@myumanitoba.ca.
Insights
Phytosterols (PS) in infant formula may reduce cholesterol absorption and increase cholesterol synthesis rates. Further research is needed to understand long-term effects on infant development.
Area of Science:
- Nutritional Biochemistry
- Pediatric Nutrition
- Metabolic Research
Background:
- Formula-fed infants exhibit distinct cholesterol metabolism compared to breast-fed infants, with higher synthesis rates and lower circulating levels.
- Infant formulas contain vegetable oils rich in phytosterols (PS), which structurally resemble cholesterol and may impact its absorption.
- The precise mechanisms by which PS influence infant cholesterol metabolism remain incompletely understood.
Purpose of the Study:
- To investigate the inhibitory effects of phytosterols (PS) on cholesterol absorption in a piglet model during postnatal feeding.
- To determine how PS in infant formula affects cholesterol synthesis and absorption markers.
Main Methods:
- A 7-day-old piglet model was utilized, feeding them milk-based formulas with varying phytosterol (PS) and cholesterol levels for 21 days.
- Apparent cholesterol digestibility was assessed in ileal digesta.
- Cholesterol, PS, and cholesterol synthesis markers (including hepatic lathosterol-to-cholesterol ratio and SREBP2 expression) were analyzed in plasma and liver samples.
Main Results:
- Piglets fed low phytosterol (PS) formulas showed increased ileal cholesterol digestibility.
- Hepatic cholesterol synthesis rates, indicated by the lathosterol-to-cholesterol (L:C) ratio, were decreased in piglets fed low PS formulas.
- Reduced nuclear expression of SREBP2 was observed in piglets fed low PS formulas compared to high PS formulas, suggesting inhibited cholesterol synthesis.
Conclusions:
- Phytosterols (PS) present in infant formula appear to inhibit cholesterol absorption and stimulate cholesterol synthesis.
- These findings support the hypothesis that PS influences infant cholesterol metabolism.
- Further investigation is required to ascertain if early exposure to PS via formula leads to long-term programming of cholesterol synthesis.
Abstract:
Formula-fed infants present higher cholesterol synthesis rates and lower circulating cholesterol during the postnatal feeding period compared to breast-fed infants, though the mechanisms underlying this phenotype are not fully understood. Typical infant formulas contain vegetable-based fats, inherently including phytosterols (PS), which are structurally similar to cholesterol and may interfere with their absorption. A seven-day old piglets model was used to test the inhibitory effects of PS on cholesterol absorption during postnatal feeding. Following feeding for 21 days with milk-based formulas containing PS and cholesterol levels resembling those in formulas or human-milk, apparent cholesterol digestibility was analyzed in ileal digesta, and cholesterol, PS, and cholesterol synthesis markers were analyzed in plasma and liver samples. Ileal cholesterol digestibility content was increased in the piglets fed low PS formulas and the rate of the hepatic cholesterol synthesis, as determined by the lathosterol-to-cholesterol ratios (L:C), was decreased in the piglets fed LP-formulas and corresponded to reduced nuclear expression of SREBP2 relative to those fed HP-formulas. These results are consistent with the hypothesis that PS in formula can inhibit cholesterol absorption and enhance cholesterol synthesis. Whether or not this leads to entrainment of cholesterol synthesis later in life via early programming awaits further research.
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