The high-fat, low-carbohydrate ketogenic diet has surged in popularity in recent years, largely driven by promises of fast weight loss. New evidence from a long-running mouse study, however, points to potentially serious downsides alongside the slimming effect.
“I would urge anyone to talk to a healthcare provider if they’re thinking about going on a ketogenic diet,” says physiologist Molly Gallop, the study’s lead author.
What the University of Utah study tested (ketogenic diet and metabolic health)
In research led by a team at the University of Utah, scientists tracked mice on four different eating patterns for at least nine months:
- a high-fat (Western-style) diet
- a very-high-fat, low-carbohydrate (keto-style) diet
- a low-fat, high-carbohydrate diet
- a low-fat diet with protein levels matched to the keto-style diet
The investigators were interested not only in body weight, but also broader markers of metabolic health over a longer timeframe than many earlier experiments.
“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,” Gallop says.
Why the keto diet causes ketosis
The keto diet takes its name from ketosis, the metabolic state it is designed to induce. In ketosis, the body shifts towards burning more fat for fuel rather than glucose. To trigger and maintain this state, the diet typically involves increasing dietary fat and substantially reducing carbohydrates.
Weight loss came with fatty liver disease in male mice
When compared with the standard high-fat diet, mice given the keto-style diet put on markedly less weight. That benefit came with a significant warning sign: male mice on the keto diet developed fatty liver disease and showed evidence of reduced liver function-features consistent with metabolic disease.
“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,” says University of Utah physiologist Amandine Chaix, the study’s senior author.
Blood glucose and insulin fell-then regulation looked impaired
In both male and female mice, the keto-style diet quickly produced low blood glucose and insulin levels, within roughly two to three months. Closer examination suggested this was not simply “better numbers”, but a regulatory problem: cells in the pancreas were not making enough insulin.
Although more work is needed to pin down the biology-and to clarify why the liver outcomes appeared to depend on sex-the team proposes that excess fats (lipids) circulating in the blood may place stress on pancreatic cells, undermining insulin production.
A reversible effect when the keto diet stopped
There was one encouraging observation. When mice were switched off the keto diet, blood sugar control returned to normal, suggesting the disruption to regulation can be reversible-at least in this animal model.
What this means for people considering a ketogenic diet
These findings have not yet been reproduced in humans, so they should not be treated as direct proof of harm in people. Even so, the results raise a cautionary possibility: the biological changes the ketogenic diet is intended to trigger may not all support healthy metabolism over time, particularly when dietary fat is extremely high.
If you are considering a ketogenic diet for weight loss, it is sensible to weigh potential benefits against possible risks, especially if you have existing concerns around liver health, cholesterol, diabetes risk, or are taking glucose-lowering medication. Discussing the plan with a qualified healthcare professional can also help you choose an approach that is safer and more sustainable for your circumstances.
Ketogenic diet origins: epilepsy, not weight loss
The ketogenic diet was first developed as a treatment for epilepsy, and it remains in clinical use for that purpose today. Ketosis imitates some metabolic features of starvation, pushing the body to rely on fat instead of sugar for energy. Researchers suspect that reduced sugar availability may also help to decrease seizures.
Bottom line
For uses beyond epilepsy, this study-together with earlier research-suggests the potential increase in other health risks may not be worth the possible upside of losing weight, particularly if the diet is followed for long periods.
The research has been published in Science Advances.
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