Some infant formula fats may contribute to early liver disease, study finds

Certain fats used in some infant formulas may strain the developing liver and contribute to early signs of steatotic liver disease, according to a new study led by researchers in Virginia Tech’s College of Agriculture and Life Sciences.

In the study, published in the American Journal of Physiology-Endocrinology and Metabolism, newborn pigs fed formulas with specific medium-chain fats accumulated liver fat faster than pigs fed formulas with long-chain fats, despite receiving the same calories and protein.

The researchers also found that steatotic liver disease develops differently in early life than it does in adults. In adults, fat builds up when the liver slows down its fat burning. In the developing liver, however, they observed that fat accumulated even as fat burning increased.

Steatotic liver disease, formerly known as non-alcoholic fatty liver disease, happens when excess fat builds up in the liver. Once considered a condition affecting adults with obesity, it is increasingly being diagnosed in children and also has been identified in some infants, raising questions about how early nutrition may influence liver health.

To explore that connection, the research team, led by Associate Professor Samer El-Kadi of the School of Animal Sciences, used a neonatal pig model to study how different fats commonly used in infant formulas affect liver metabolism during early development.

Two fats with surprisingly different effects

Infant formulas are designed to provide complete nutrition and typically use blends of plant-based oils to approximate the fat composition of breast milk. Newborn pigs are widely used in nutrition research because their digestion and fat metabolism are similar to those of human infants.

To understand how individual fats affect the developing liver, the researchers tested two simplified formulas that differed only in fat type. One was rich in medium-chain fatty acids derived primarily from coconut oil, a common fat source used in some infant formulas. The other was rich in long-chain fatty acids derived from animal fat, which more closely resembles the natural fat composition of whole sow milk.

Pigs fed the medium-chain fat formula accumulated liver fat more rapidly than pigs fed the long-chain fat formula, despite receiving the same amount of calories and protein.

“Even within seven days, we could see fat starting to build up in the liver,” El-Kadi said. “By about two weeks, it had progressed from simple steatosis to a more severe inflammatory form of the disease.”

Under normal circumstances, increased fat burning would be expected to protect the liver from fat buildup. In this study, however, the opposite occurred.

“We saw the liver activate both fat-making and fat-burning pathways at the same time,” El-Kadi said. “Even with those adaptive responses, the developing liver became overwhelmed. That was surprising to us. Based on what we know from adult disease, increased fat burning should have been protective.”

Samer El-Kadi (in back) and Ph.D. student Anthony Shafron examine research data related to their study on how certain medium-chain fatty acids may contribute to early signs of steatotic liver disease in newborn models. Photo by Marya Barlow for Virginia Tech.

Designing better infant formulas

El-Kadi emphasized that the study does not suggest parents should avoid infant formula. He said breast milk remains “the gold standard” for infant nutrition, and formula is a critical and often lifesaving alternative when breastfeeding is not possible or sufficient.

“When our own child needed supplemental nutrition, we used formula — no questions asked,” El-Kadi said. “The immediate benefits of feeding far outweigh any potential long-term risks. Our goal is not to discourage formula use. It’s to understand how different components of formula affect the developing body, so they can be improved over time.”

That goal reflects the broader focus of El-Kadi’s research, which examines how early-life nutrition shapes metabolic health during critical periods of development.

The research comes as the U.S. Department of Health and Human Services and the Food and Drug Administration re-evaluate infant formula composition through the Operation Stork Speed initiative, which encourages research to improve formula safety and nutritional quality.

El-Kadi’s team is continuing to study how specific fatty acids influence liver metabolism during early life, including whether different types of medium-chain fatty acids have distinct effects and in what quantities.

“If we understand how early nutrition shapes liver metabolism, that knowledge can eventually help guide better nutritional strategies,” El-Kadi said.

Reference:

Ravi Yadav, Marta R. M. Lima, Ryan P. McMillan, Nishanth E. Sunny, Concurrent increase in fatty acid oxidation and fatty acid synthesis: a unique metabolic state in a pig model of pediatric steatotic liver disease, American Journal of Physiology-Endocrinology and Metabolism, https://doi.org/10.1152/ajpendo.00299.2025