Is keto diet safe? Research reveals serious side effects of long-term keto eating

A new study by researchers at University of Utah Health, published in Science Advances, has raised fresh concerns about the long-term safety of the ketogenic diet, one of the world’s most popular approaches for weight loss and metabolic control. While the diet is known for preventing weight gain and improving short-term metabolic markers, the research shows that long-term keto eating may trigger hidden biological changes that disrupt how the body processes fats and sugars. Conducted over many months in mice, the study challenges the widely held belief that extended keto dieting is harmless, revealing metabolic side effects that could carry significant health implications.

The hidden trade-offs of long-term keto diet

The ketogenic diet forces the body into ketosis by drastically cutting carbohydrates and increasing fat intake. In this state, the liver produces ketone bodies to fuel the brain and stabilise energy levels. Originally used as a medical therapy for epilepsy, the diet has since grown into a mainstream weight-loss strategy celebrated for quick results and improved blood sugar control.


However, the new University of Utah Health study suggests that the long-term metabolic consequences of the ketogenic diet may be far more complex than previously understood. The researchers analysed how prolonged adherence to a high-fat, very low-carbohydrate eating pattern affects the body over extended periods.

Their findings indicate that, even when the diet helps prevent excessive weight gain and maintains a leaner body profile, it may simultaneously place significant strain on key metabolic systems. Over time, this heavy reliance on dietary fat appears to alter the body’s ability to manage lipids and regulate blood sugar, revealing hidden vulnerabilities that could undermine long-term health.

The body struggled to manage the constant influx of dietary fat, leading to elevated fat levels in the blood and changes in liver function. These shifts hinted at an underlying biological cost that is not immediately apparent during short-term dieting.

Keto linked to fatty liver disease

One of the most concerning discoveries was the rapid development of fatty liver disease in male mice consuming the ketogenic diet. Fatty liver is a major warning sign of broader metabolic dysfunction and a risk factor for diabetes and heart disease. Interestingly, female mice did not show the same degree of liver fat accumulation, highlighting sex-specific differences that researchers plan to explore in future studies.

According to senior author Amandine Chaix, PhD, the liver becomes overwhelmed by the high-fat load, forcing excess fat to build up within liver cells. Over time, this compromises liver function and sets the stage for metabolic disease, despite the mice not gaining significant body weight.

Weight loss that hides deeper issues

Although the ketogenic diet prevented weight gain in both male and female mice, it did not eliminate deeper metabolic problems. The appearance of lower body weight masked underlying disruptions in glucose regulation and insulin production.

After two to three months on the diet, keto-fed mice had unusually low levels of both glucose and insulin when fasting. But when they were given even a small amount of carbohydrates, their blood sugar spiked dramatically and remained elevated for an extended period.

Lead author Molly Gallop, PhD, explained that this indicates an impaired ability to regulate blood sugar. Despite appearing metabolically stable at rest, the mice struggled to handle carbohydrates — a dangerous sign of metabolic inflexibility.

Stress inside the pancreas

Further investigation revealed that pancreatic beta cells, which produce insulin, were under severe stress. High-fat exposure disrupted how these cells transported and processed proteins, leaving them unable to respond properly when glucose levels rose.

This cellular stress likely caused the impaired insulin secretion and unstable blood glucose seen in the mice. Notably, some of these issues reversed once the animals were removed from the ketogenic diet, suggesting that not all effects are permanent — but they are still cause for caution.

Implications for human keto dieters

Although mice are not humans, the study raises red flags about the long-term metabolic safety of ketogenic diets. Most human studies focus on short-term outcomes such as weight loss or improved glucose control, while long-term biological effects remain largely understudied.

The new findings highlight that a diet high in fat and extremely low in carbohydrates may strain key organs such as the liver and pancreas if followed for extended periods. They also raise questions about how sex, genetics and lifestyle may influence individual responses to keto.

The bottom line

The University of Utah Health study offers an important reminder: while keto can produce impressive short-term results, it is not without risks. Long-term keto eating may trigger hidden metabolic side effects, including fatty liver, impaired blood sugar regulation and cellular stress in key organs.

As scientists work to better understand the full spectrum of ketogenic diet effects, one message is clear — the diet’s benefits come with trade-offs, and long-term safety is far from guaranteed.