The ketogenic diet continues to attract attention for its promise of fast weight loss and better blood sugar control. Yet new long-term research suggests that staying in ketosis for months may quietly strain the body’s metabolic system.
A detailed study from the University of Utah Health shows that while keto helped prevent weight gain, it also triggered serious issues tied to liver health, blood fats, and glucose control—especially once carbohydrates returned to the diet.
A Popular Diet With Medical Roots
The ketogenic diet began as a medical therapy for epilepsy, not a weight-loss plan. By sharply reducing carbohydrate intake and increasing fat intake, the body shifts into ketosis, a state in which fat-derived ketones fuel the brain. This metabolic switch helps stabilize brain activity, similar to fasting.
Over time, keto expanded far beyond clinical use. Many people now follow it to manage obesity or type 2 diabetes. Still, most existing research has focused on short-term results, leaving a gap in understanding what happens after months or years on the diet.
That gap prompted a new long-term investigation.
Inside the Long-Term Keto Study
Researchers led by Molly Gallop, PhD, now an assistant professor of anatomy and physiology at Earlham College, designed a prolonged experiment while she was a postdoctoral fellow in nutrition and integrative physiology at the University of Utah Health.
As Gallop explained:
“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.”
The team followed adult male and female mice for nine months or longer. The mice ate freely and were placed on one of four diets:
1. A high-fat Western-style diet
2. A low-fat, high-carbohydrate diet
3. A traditional ketogenic diet with nearly all calories from fat
4. A protein-matched low-fat diet
Researchers tracked body weight, food intake, blood lipid levels, liver fat buildup, blood sugar, and insulin. They also studied gene activity in insulin-producing pancreatic cells and examined cellular changes using advanced microscopy.
Weight Stayed Down, But Body Fat Did Not
Mice on the ketogenic diet gained much less weight than those eating a Western-style diet. This pattern appeared in both males and females.
However, the composition of that weight told a different story. Any weight gained on keto came largely from fat mass rather than lean tissue. So while the scale moved less, fat storage still increased.
Fatty Liver Disease Appeared Early
Despite limiting weight gain, the ketogenic diet led to rapid and serious metabolic changes.
Amandine Chaix, PhD, assistant professor of nutrition and integrative physiology at the University of Utah Health and senior author of the study, explained the underlying issue:
“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.”
Excess fat accumulation in the liver, known as fatty liver disease, is a strong marker of metabolic dysfunction. According to Chaix:
“The ketogenic diet was definitely not protective in the sense of fatty liver disease.”
Male Mice Faced Greater Liver Damage
The study uncovered a sharp difference between sexes. Male mice developed severe fatty liver disease along with impaired liver function, both signs of advanced metabolic stress.
Female mice, however, showed little to no liver fat buildup. The reason for this resistance remains unclear, and the research team plans to explore the biological factors behind it in future studies.
Blood Sugar Control Broke Down Over Time
At first glance, the ketogenic diet appeared to improve blood sugar markers. After two to three months, mice showed low blood glucose and insulin levels. Yet this benefit came with a major drawback.
When carbohydrates were reintroduced, blood sugar levels surged and stayed high for extended periods. Chaix described the reaction clearly:
“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.”
Further testing revealed that pancreatic cells failed to release enough insulin. Prolonged exposure to high fat levels appeared to stress these cells, disrupting protein movement inside them and weakening insulin secretion.
One notable finding offered a measure of reassurance. Once the mice stopped the ketogenic diet, their blood sugar regulation improved. This shift suggests that some metabolic damage may not be permanent, though the long-term implications still need study.
What This Means Beyond the Lab
Mouse studies do not always mirror human biology. Even so, these results raise important questions about long-term keto use, especially for people cycling on and off the diet.
Gallop offered a clear takeaway:
“I would urge anyone to talk to a health care provider if they’re thinking about going on a ketogenic diet.”
The ketogenic diet continues to show short-term benefits for weight control. Still, this long-term study highlights potential risks tied to liver health, blood fats, and glucose regulation that may surface over time.
The findings suggest that weight stability alone does not equate to metabolic health, and dietary choices can have effects that only appear after months of adherence.