Researchers conducting scientific trials with mice have discovered that a long-term, high-fat, low-carbohydrate ketogenic diet—which is popular for weight loss—could trigger significant health issues, according to multiple scientific reports, including findings published in Science Advances.
What the Mouse Study Found
Researchers at the University of Utah Health ran a trial with female and male mice for around nine months or more. The mice were separated and put onto one of four different diets, and allowed to eat freely:
A traditional ketogenic diet: In this regimen, most of the calories come from fat. It’s designed to induce ketosis, which is a metabolic state that shifts the body into fat burning.A high-fat Western diet: This style of diet is often used in metabolic and obesity research. It has a very high fat content—including saturated fats and calorie-dense items—and is designed to mimic a typical Western-style of eating. A protein-matched low-fat diet: This diet keeps the protein content high (similar to the ketogenic diet), but significantly reduces the fat content, and includes higher levels of carbohydrates. A low-fat, high-carbohydrate diet: This diet contains very little fat, but substantially higher levels of carbohydrates, often with moderate levels of protein.
The study found that although the mice that were fed the strict, traditional ketogenic diet gained less weight than their peers on the other diets did, they also developed fatty liver disease, unhealthy levels of fats in the blood, and impaired blood sugar regulation.
According to the research, the mice on the ketogenic diet had low blood sugar and low insulin after a few months, but when they were given carbohydrates again, their blood sugar spiked and stayed high—showing that their bodies weren’t releasing enough insulin, rather than becoming insulin‑resistant.
Senior author Amandine Chaix, an assistant professor of nutrition and integrative physiology at the University of Utah Health, said: “The problem is that when you then give these mice a little bit of carbs, their carb response is completely skewed…Their blood glucose goes really high for really long, and that’s quite dangerous.”
Sex-specific effects emerged too: Male mice on the ketogenic diet showed more fatty liver and impaired liver function, while females didn’t develop the same liver fat buildup under the same conditions.
What the Study Means for People
While mouse findings do not always translate directly to humans, the study does potentially begin to address gaps in long-term safety data for ketogenic diets—which have been widely adopted for weight loss and diabetes management—despite limited evidence on what happens if a strict ketogenic diet is followed for long periods of time.
Molly Gallop, the study’s lead author and a physiologist, told Science Alert that she “would urge anyone to talk to a health care provider if they’re thinking about going on a ketogenic diet.”
“We’ve seen short-term studies and those just looking at weight, but not really any studies looking at what happens over the longer term or with other facets of metabolic health.”
Chaix also said: “One thing that’s very clear is that if you have a really high-fat diet, the lipids have to go somewhere, and they usually end up in the blood and the liver.”