Long-Term Keto Diet May Damage Your Metabolic Health—Even If You Lose Weight

While the ketogenic diet can help prevent weight gain, new research shows it may quietly damage your metabolic health over time, causing fatty liver disease and impairing your body's ability to control blood sugar. Scientists from University of Utah Health conducted a long-term study published in Science Advances that challenges the safety of extended keto use, revealing metabolic problems that weren't visible in short-term studies.

What Happens to Your Body on a Long-Term Ketogenic Diet?

Researchers tracked adult mice on four different diets for nine months or longer, measuring body weight, blood lipid levels, liver fat accumulation, and blood sugar control. The ketogenic diet—which derives nearly all calories from fat while severely restricting carbohydrates—did prevent weight gain compared to a high-fat Western diet in both male and female mice. However, the weight that did accumulate came primarily from fat mass rather than lean tissue, and more troubling metabolic problems emerged.

"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," explains Dr. Amandine Chaix, assistant professor of nutrition and integrative physiology at University of Utah Health and senior author of the study. The research revealed striking differences between sexes: male mice developed severe fatty liver disease with impaired liver function—a key marker of metabolic illness—while female mice showed no significant fat buildup in the liver.

How Does Keto Disrupt Blood Sugar Control?

The study uncovered a dangerous paradox in how the ketogenic diet affects blood sugar regulation. After two to three months on the diet, mice showed low blood sugar and insulin levels, which might seem beneficial at first. But when researchers reintroduced even small amounts of carbohydrates, the mice's blood glucose spiked dramatically and remained elevated for extended periods—a response that researchers describe as "quite dangerous".

The problem stems from pancreatic cell dysfunction. Prolonged exposure to the high-fat ketogenic diet appeared to stress the pancreatic cells responsible for releasing insulin, impairing their ability to move proteins properly. This cellular stress prevented the pancreas from responding appropriately when carbohydrates returned to the diet. The good news: blood sugar regulation improved once mice were removed from the ketogenic diet, suggesting some metabolic damage may be reversible.

Tips for Recognizing Metabolic Issues from Long-Term Keto Use

• Fatty Liver Disease: Excess fat accumulation in the liver emerged within days of starting the ketogenic diet, with male mice developing severe liver dysfunction and impaired metabolic health.
• Abnormal Blood Fats: The high-fat diet caused lipids to accumulate in both the bloodstream and liver tissue, disrupting normal lipid metabolism and cardiovascular health markers.
• Impaired Glucose Response: Mice developed an exaggerated blood sugar spike when reintroduced to carbohydrates, indicating their pancreatic cells could no longer regulate insulin secretion properly.
• Sex-Based Differences: Male mice experienced significantly more severe metabolic damage than females, though researchers are still investigating why females appeared resistant to fatty liver disease.

These findings raise important questions about whether the ketogenic diet's short-term weight loss benefits justify the potential long-term metabolic costs. Most previous research has focused on short-term effects and weight loss alone, without examining broader metabolic health over extended periods.

What Should People Considering Keto Know?

Although results from animal studies don't always translate directly to humans, the research highlights potential long-term metabolic risks that haven't been thoroughly explored in human populations. The study was funded by the National Institutes of Health, including grants from the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and the National Cancer Institute, underscoring the significance of these findings for cardiovascular and metabolic health.

Dr. Molly Gallop, who led the study as a postdoctoral fellow at University of Utah Health and is now an assistant professor at Earlham College, offered clear guidance: "I would urge anyone to talk to a health care provider if they're thinking about going on a ketogenic diet". This recommendation is especially important for people with existing metabolic concerns, liver disease, or diabetes.

If you're interested in sustainable dietary approaches backed by decades of research, the Mediterranean diet offers a well-studied alternative. This eating pattern emphasizes whole, minimally processed foods including fruits, vegetables, whole grains, fish rich in omega-3 fatty acids, and healthy oils like olive oil—and research consistently shows it reduces major risk factors for cardiovascular disease, type 2 diabetes, and obesity without the metabolic complications observed with long-term keto use.

Before making any major dietary changes, consult with your primary care physician or a registered dietitian who can assess your individual health status and help you choose an eating pattern that supports both short-term and long-term metabolic wellness.