Keto Diet May Prevent Weight Gain: A ketogenic diet may help prevent weight gain, but new research suggests the benefit could come with serious long-term metabolic risks. A study from University of Utah Health has found that while mice fed a ketogenic diet remained lean, they developed fatty liver disease, abnormal blood lipid levels, and impaired blood sugar control, particularly when carbohydrates were reintroduced.
The findings, published in Science Advances, raise important questions about the safety of long-term ketogenic dieting—especially beyond short-term weight loss.
A Diet With Medical Roots—and Mass Appeal
The ketogenic diet was originally developed nearly a century ago as a medical therapy for children with drug-resistant epilepsy. By drastically reducing carbohydrate intake and increasing fat consumption, the diet forces the body into a metabolic state known as ketosis, in which fats are broken down into ketone bodies that serve as an alternative energy source for the brain.
This shift mimics the metabolic effects of fasting and can stabilize abnormal brain activity, helping to reduce seizures. Over time, the diet migrated beyond neurology clinics and into the mainstream, promoted as a powerful tool for weight loss, obesity management, and type 2 diabetes control.
While numerous short-term studies have documented keto’s ability to reduce body weight and lower blood glucose, much less is known about what happens when the diet is followed long term.
“We’ve seen short-term studies and those just looking at weight,” said Dr Molly Gallop, lead author of the study and now an assistant professor of anatomy and physiology at Earlham College. “But there really hasn’t been much work examining long-term effects or broader aspects of metabolic health.”
Designing a Long-Term Metabolic Test
To fill that gap, Gallop and her colleagues designed a long-duration experiment using adult male and female mice. The animals were divided into four dietary groups: a high-fat Western-style diet, a low-fat high-carbohydrate diet, a traditional ketogenic diet in which nearly all calories came from fat, and a protein-matched low-fat diet.
Unlike many metabolic studies that last only weeks, this experiment ran for nine months or longer, equivalent to several decades of human life. The mice were allowed to eat freely, and researchers closely monitored changes in body weight, body composition, food intake, blood lipid levels, liver fat accumulation, insulin secretion, and blood sugar regulation.
The team also analyzed gene activity in insulin-producing pancreatic cells and used advanced imaging techniques to examine cellular changes linked to metabolic dysfunction.
Leaner Bodies—but More Body Fat
At first glance, the ketogenic diet appeared to deliver on one of its most popular promises. Compared with mice consuming a Western-style diet, keto-fed mice gained significantly less weight over time. This effect was observed in both males and females.
However, a deeper look revealed a more complex picture. Any weight gain that did occur on the ketogenic diet came primarily from increased fat mass rather than lean muscle tissue, suggesting that the diet altered body composition in ways that may not be metabolically beneficial.
In other words, staying lean did not necessarily mean staying healthy.
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Fatty Liver Disease Despite Weight Control
One of the most striking findings of the study was the development of fatty liver disease in mice fed the ketogenic diet. Excess fat accumulation in the liver is a hallmark of metabolic disease and is often associated with obesity and insulin resistance.
“The ketogenic diet was definitely not protective in terms of fatty liver disease,” said Dr Amandine Chaix, senior author of the study and assistant professor of nutrition and integrative physiology at University of Utah Health.
“When you have a really high-fat diet, the lipids have to go somewhere,” she explained. “They often end up in the blood and the liver.”
Alarmingly, signs of liver fat buildup appeared within days of starting the ketogenic diet, and in male mice the condition progressed to severe liver dysfunction, an important indicator of advanced metabolic illness.
Female mice, however, showed little to no liver fat accumulation—a sex difference the researchers plan to explore further.
A Dangerous Blood Sugar Rebound
The ketogenic diet also produced unexpected effects on glucose control. After two to three months on the diet, mice displayed low blood sugar and low insulin levels, changes often interpreted as signs of improved metabolic health.
But the benefit came with a catch.
When researchers reintroduced carbohydrates, the mice experienced extreme and prolonged spikes in blood glucose, indicating a dangerous inability to regulate blood sugar.
“Their carb response was completely skewed,” Chaix said. “Blood glucose went really high for a really long time, and that’s quite dangerous.”
Further analysis revealed that insulin-producing pancreatic cells were failing to release enough insulin. The team suspects that prolonged exposure to high fat levels stressed these cells, disrupting protein transport and impairing insulin secretion.
Encouragingly, blood sugar regulation improved after the mice were taken off the ketogenic diet, suggesting that some of the damage may be reversible.
What It Means for Humans
The researchers stress that findings from mice do not automatically translate to humans. Still, the results raise important concerns—especially given how widely the ketogenic diet is promoted for long-term metabolic health.
The study suggests that while keto may prevent weight gain, it may do so at the cost of liver health, lipid balance, and glucose control, particularly if carbohydrates are reintroduced after prolonged restriction.
“I would urge anyone considering a ketogenic diet to talk with a health care provider,” Gallop said. “Weight loss alone doesn’t tell the full story of metabolic health.”
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A Trade-Off Worth Rethinking?
As keto continues to dominate diet trends, the study highlights a critical question: Is long-term weight control worth potential metabolic damage?
The findings suggest that the benefits of ketosis may be highly context-dependent—useful in clinical settings like epilepsy treatment, but potentially risky when adopted as a long-term lifestyle diet without medical supervision.
For now, the researchers hope their work encourages more long-term human studies and a broader definition of “metabolic health” that goes beyond the number on the scale.
Sometimes, staying lean may come at a hidden cost.
