Researchers studied what happens when mice eat a ketogenic (keto) diet for a long time. While the diet helped mice lose weight at first, the study found that after extended use, it caused problems like high cholesterol, fatty liver disease, and difficulty controlling blood sugar. Interestingly, the mice didn’t develop insulin resistance like those on other high-fat diets, but their bodies stopped making enough insulin. The findings suggest that while keto diets might help with short-term weight loss, people should be cautious about using them long-term without medical supervision, as they may cause serious health issues.

The Quick Take

  • What they studied: Whether eating a ketogenic diet (very low carbs, very high fat) for a long time causes health problems in the body
  • Who participated: Male and female laboratory mice that were fed a ketogenic diet over an extended period and compared to mice eating normal diets
  • Key finding: Keto diets helped mice lose weight initially, but after weeks of eating this way, the mice developed high cholesterol, fatty livers, and trouble controlling blood sugar because their pancreas stopped making enough insulin
  • What it means for you: If you’re considering a keto diet, especially for long-term use, talk to your doctor first. This research suggests keto may work for short-term weight loss but could cause serious health problems if followed for extended periods without medical monitoring

The Research Details

Scientists fed mice a ketogenic diet (which is very high in fat and very low in carbohydrates) and tracked what happened to their bodies over time. They compared these mice to other mice eating regular diets to see the differences. The researchers measured various health markers including weight, cholesterol levels, liver health, and how well the mice’s bodies controlled blood sugar. They also looked inside the mice’s pancreas cells (the organ that makes insulin) using advanced microscopes to see what was happening at a cellular level. Additionally, they analyzed the genes being used in these pancreas cells to understand what was going wrong.

This research is important because keto diets are very popular with people trying to lose weight and manage diabetes, but we don’t know much about what happens if people follow them for years. By studying mice over a long period, scientists can understand potential long-term risks before recommending these diets to humans. The detailed cellular analysis helps explain exactly how and why the diet causes problems, not just that it does.

This study was published in Science Advances, a respected scientific journal. The researchers used multiple methods to confirm their findings, including blood tests, imaging, cell studies, and genetic analysis. They studied both male and female mice to check if results were similar across sexes. However, because this was done in mice, results may not directly apply to humans, and the specific sample size wasn’t detailed in the abstract provided.

What the Results Show

The ketogenic diet initially worked as intended—mice lost weight and didn’t gain as much weight as mice on regular high-fat diets. However, after extended time on the keto diet, the mice developed three major problems: first, their blood cholesterol levels became dangerously high (hyperlipidemia); second, their livers accumulated too much fat (hepatic steatosis); and third, their bodies became very poor at controlling blood sugar (glucose intolerance). When researchers gave the mice sugar and measured their response, the mice couldn’t bring their blood sugar down to normal levels. This was different from mice on other high-fat diets, which developed insulin resistance (where the body ignores insulin signals). The keto-fed mice’s bodies were still listening to insulin, but the problem was that their pancreas wasn’t making enough of it.

When scientists examined the pancreas cells that make insulin, they found that these cells were stressed and damaged. The cells’ internal structures (called the endoplasmic reticulum and Golgi apparatus) were swollen and not working properly. These structures are like the cell’s packaging and shipping department—they prepare insulin and send it out into the bloodstream. When these structures don’t work right, insulin can’t be made or released properly. Electron microscopy (a super-powerful microscope) showed that the Golgi apparatus was abnormally enlarged, confirming that the insulin-packaging system was broken. Gene analysis revealed that the cells were experiencing stress signals, indicating they were struggling to function.

Previous research has shown that high-fat diets can cause insulin resistance, where the body stops responding to insulin signals. This new study found something different: keto-fed mice remained sensitive to insulin (their bodies still listened to it), but couldn’t make enough of it. This suggests that ketogenic diets damage the pancreas in a unique way compared to other high-fat diets. The weight loss benefits seen early in the study align with previous short-term keto diet research, but the long-term complications are concerning and suggest that previous studies looking only at short-term effects may have missed important dangers.

This research was conducted in mice, not humans, so we can’t be completely certain the same effects would happen in people. Mice have different body systems and lifespans than humans. The study doesn’t specify exactly how many mice were used or provide detailed information about the duration of the diet. The research doesn’t tell us whether these problems would reverse if mice stopped eating the keto diet. Additionally, this was an animal study in a controlled laboratory setting, which is very different from how people eat keto diets in real life with varying food choices and other lifestyle factors.

The Bottom Line

Based on this research, if you’re considering a ketogenic diet, consult with your doctor first, especially if you plan to follow it long-term. This study suggests that while keto may help with short-term weight loss, it may cause serious health problems like high cholesterol, fatty liver disease, and blood sugar control issues after extended use. Your doctor can monitor your cholesterol, liver function, and blood sugar if you do try a keto diet. Consider limiting keto diets to short-term use (weeks to a few months) rather than years. These recommendations have moderate confidence because they’re based on animal studies, but the findings are concerning enough to warrant caution.

People considering long-term ketogenic diets should pay special attention to this research, including those with obesity, type 2 diabetes, or family history of liver disease or high cholesterol. People with existing liver problems or high cholesterol should be especially cautious. This research is less relevant to people using keto diets for short periods (a few weeks) or under close medical supervision. Healthy individuals considering keto for weight loss should understand the potential long-term risks.

In this mouse study, the harmful effects developed over weeks of eating the keto diet. In humans, whose bodies work more slowly than mice, similar problems might take months to years to develop. You wouldn’t expect to see problems immediately, but extended use (months to years) appears to be when damage occurs based on this research.

Want to Apply This Research?

  • If using a keto diet, track weekly measurements of: energy levels (1-10 scale), digestive health, and any symptoms like unusual thirst or fatigue. Also note weight weekly and take monthly photos. Most importantly, schedule regular blood work (every 3 months) to monitor cholesterol levels, liver enzymes, and fasting blood sugar.
  • If you’re on or considering a keto diet, use the app to set reminders for: (1) scheduling doctor appointments every 3 months for blood work, (2) tracking daily carbohydrate intake to ensure you’re following the diet correctly, (3) logging any symptoms like unusual fatigue or digestive issues, and (4) setting a time limit for how long you’ll follow the diet before reassessing with your doctor.
  • Create a long-term tracking dashboard that monitors: monthly weight trends, quarterly blood work results (cholesterol, liver function, blood sugar), daily energy and symptom logs, and appointment reminders. Set alerts if any measurements go outside normal ranges. Share this data with your doctor at each visit to catch any problems early.

This research was conducted in mice and has not been proven in humans. Individual responses to ketogenic diets vary greatly based on genetics, overall health, and other lifestyle factors. Before starting or continuing a ketogenic diet, especially for extended periods, consult with your healthcare provider or registered dietitian. This is particularly important if you have existing conditions like liver disease, high cholesterol, diabetes, or heart disease. Regular blood work and medical monitoring are recommended if you choose to follow a ketogenic diet long-term. This summary is for educational purposes and should not replace professional medical advice.