Could Too Little Choline Affect Blood Sugar?

Insulin resistance is one of the earliest signs that metabolic health is slipping. It happens when cells stop responding properly to insulin, the hormone that moves sugar out of the bloodstream and into cells for energy. The pancreas compensates by producing more insulin, and over time blood sugar begins to climb. It is a common step on the path to type 2 diabetes, and it is usually talked about as a consequence of carrying excess weight. But new research from the UNC Nutrition Research Institute suggests metabolic health may also be influenced by whether the body receives enough of a single essential nutrient: choline. 

In a new study, researchers examined how long-term choline restriction affected metabolism in mice. Male mice consuming low-choline diets developed higher blood sugar and insulin resistance—even though they did not become obese. Female mice did not experience the same effects, pointing to important differences in how the body may respond to the same nutrient intake. 

Because the study was conducted in mice, the findings do not establish that low choline intake causes insulin resistance in people. However, they offer researchers a clearer picture of the biological pathways that may connect nutrient intake, liver metabolism, and blood sugar regulation. 

"Choline is an essential nutrient, and most people in the United States consume less than the recommended amounts, so low intake is not a hypothetical exposure but something many people experience every day," said Evan Paules, PhD, the study's first author. "Our results suggest that choline plays a much larger role in metabolic health than we previously appreciated, and they add to existing evidence that inadequate intake may raise the risk of poor metabolic health." The researchers also discovered that low choline intake changed how the liver processed fats. What is remarkable is that they did not stop at documenting the change; they were able to identify the specific molecular players behind it. Their analysis identified a biological pathway involving CD36, which helps transport fatty acids, and ETNPPL, a gene that codes an enzyme involved in nutrient metabolism. Both stood out as the liver's most choline-responsive genes, rising as choline in the diet fell. This pathway may help explain how choline availability influences liver metabolism and the body’s response to insulin. 

Choline supports several essential functions in the body, including cell structure, brain and nervous system activity, and lipid metabolism. It is found in foods such as eggs, meat, fish, dairy products, beans, nuts, and cruciferous vegetables. According to the National Institutes of Health, the diets of most people in the United States provide less than the recommended amounts of choline.  

“This gives us a really good model for understanding what chronic low choline intake actually does to the body,” said Isis Trujillo-Gonzalez, PhD, the study’s senior author. “It also shows what precision nutrition looks like in practice. The males that did not get enough choline developed insulin resistance and liver damage, while the females eating exactly the same diet did not. Same nutrient, same amount, very different outcome, and that is the kind of difference our recommendations need to account for.” 

The study adds to a growing understanding that nutrition cannot always be reduced to calories or body weight alone. Instead, it points toward a more precision nutrition approach, where individual differences—such as sex, genetics, and metabolic pathways—may shape how the body responds to specific nutrients like choline. The nutrients in our food, and the ways our bodies uniquely process and utilize them, therefore play an important role in long-term metabolic health and could eventually inform more personalized dietary recommendations. 

Paules, EM, Rushing, B, Aguilar-Ordonez, I, Garduno-Hernandez, JL, Reid, A, Davis, BJ, Bottiglieri, T, Kalecky, K, Lopez-Gallardo, E, Hursting, SD and Trujillo-Gonzalez, I. "Chronic choline restriction remodels hepatic lipid metabolism and drives insulin resistance through a CD36-ETNPPL regulatory axis." Mol Metab. 2026 Jul 7:102411. DOI:10.1016/j.molmet.2026.102411.