The ketogenic diet has gained global popularity for its rapid weight-loss effects and its ability to shift the body’s metabolism from glucose to fat utilization. However, emerging scientific evidence suggests that its long-term health impacts—particularly on liver health—may be more complex than widely assumed. Two recent studies published between 2025 and 2026 have drawn attention to unexpected risks related to fatty liver disease. One large population study involving more than 180,000 individuals found that people with lean fatty liver may experience worse long-term outcomes, including higher risks of severe liver disease and mortality, compared with those with obesity-associated fatty liver. Another experimental study investigating diets with different carbohydrate-to-fat ratios reported that mice fed a ketogenic diet developed liver injury, dyslipidemia, and early signs of liver fibrosis, although supplementation with dietary fiber partially improved metabolic markers. Together, these findings highlight that body weight alone is not a reliable indicator of metabolic health and that extreme dietary patterns may have unintended consequences. Maintaining balanced nutrition, regular health monitoring, and evidence-based lifestyle habits remains essential for protecting liver health.
A Global Diet Trend Under Debate
“Ketogenic” diets have become one of the most popular dietary trends in recent years. The core logic behind the diet is straightforward: since the body primarily relies on glucose for energy, drastically reducing carbohydrate intake forces the body to switch to burning fat for fuel.
As a result, eating large amounts of meat while avoiding staple foods quickly became a “golden rule” for many people trying to lose weight. However, as the saying goes, popularity often attracts controversy. Increasing numbers of studies have begun to reveal another side of ketogenic dieting.
Previous research has suggested that long-term adherence to a ketogenic diet may lead to impaired glucose tolerance, rising rather than falling fasting blood glucose levels, and even slower metabolism. Some studies have also suggested that such metabolic changes may promote cellular aging.
While debates about the benefits and risks of ketogenic diets continue, the medical community has recently published two important studies related to liver health—one released in 2025 and another newly published in 2026. The findings have surprised many observers.
Although these two studies focused on different aspects—one examining human populations and the other examining dietary patterns in experimental models—they both pointed toward the same organ: the liver. Together, they highlight a striking possibility that some widely accepted assumptions about health may need to be reconsidered.
The 2025 study first turned attention toward individuals who appear thin and healthy. People who are naturally slim may assume they are safe from metabolic diseases. However, the research suggests that if a person appears lean but is diagnosed with fatty liver during a health examination, the condition may actually be more dangerous than fatty liver associated with obesity.
The data indicate that individuals with “lean fatty liver” may face higher risks of developing cirrhosis, liver cancer, or even premature death compared with people who develop fatty liver in the context of obesity. This conclusion challenges the long-standing perception that fatty liver disease primarily affects overweight individuals and serves as a reminder that even people with normal body weight should pay close attention to regular health screenings.
If the 2025 study raised concerns among slim individuals, the newly released 2026 study may worry those who are actively following ketogenic diets for weight loss. Many people choose ketogenic diets because they promise rapid weight reduction without severe hunger, allowing individuals to eat satisfying foods while still losing weight. However, this new experimental study suggests that the long-term effects may not always align with expectations.
The findings indicated that such a diet did not help the experimental mice lose weight in a healthy way. Instead, the animals developed fatty liver and even signs of liver fibrosis.
One study described a condition in which individuals who are not overweight still develop metabolic disease, while the other explored how a popular dietary strategy intended to improve health might potentially cause harm. When viewed together, the studies form a compelling narrative about liver health.
Today, we take a closer look at these two studies published between 2025 and 2026 to understand what they reveal about the complex relationship between body weight, diet, and liver health. The findings may remind us that the liver—although often silent—can be deeply affected by our long-term lifestyle habits.
Lean Fatty Liver May Carry Higher Risks
For many people, fatty liver disease is often associated with obesity. However, a 2025 study published in a leading hepatology journal challenged this perception.
Researchers combined data from three major databases: the UK Biobank, China’s Kailuan cohort, and the China Kadoorie Biobank. In total, the study included more than 180,000 individuals diagnosed with fatty liver disease, making it one of the largest studies conducted in this field.
Participants were categorized into two groups:
lean fatty liver (body mass index below 23 or 25, depending on ethnic criteria) and non-lean fatty liver. The researchers followed these individuals for up to 14 years to monitor the occurrence of severe liver disease, mortality, cardiovascular events, and other outcomes.
Figure: Flowcharts of study populations in three independent cohorts
The results showed that individuals with lean fatty liver had worse long-term prognoses compared with those with obesity-associated fatty liver.
Specifically:
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Risk of severe liver disease increased by 114%
Lean fatty liver patients had a 2.14-fold higher risk of developing severe liver disease events such as liver failure or cirrhosis. -
Overall mortality increased
Their overall risk of death was 26% higher, while the risk of death directly caused by liver disease was 131% higher.
Figure: Comparison of adverse outcome risks between lean and non-lean patients with metabolic dysfunction-related fatty liver disease in three independent cohorts
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Mixed cardiovascular findings
The good news was that their risk of developing cardiovascular disease was 11% lower. However, the concerning finding was that once cardiovascular disease occurred, their risk of death was 22% higher compared with individuals with obesity-related fatty liver.
Why might this occur?
Researchers suggest that lean fatty liver may have distinct pathophysiological characteristics. Although these individuals appear thin, they may have higher levels of visceral fat, more pronounced low-grade inflammation, and differences in gut microbiota composition.
Another important factor may be awareness. Because these individuals do not appear overweight, they may underestimate their health risks and fail to monitor liver health regularly. As a result, when the disease is eventually detected, it may already be at a more advanced stage.
The study also found that lean fatty liver patients with higher liver fibrosis scores (FIB-4 ≥ 2.67) faced particularly elevated risks.
Can a Ketogenic Diet Promote Fatty Liver in Experimental Models?
If the previous findings raised concerns among people who rely on body weight as an indicator of health, the second study may raise questions for those following strict low-carbohydrate diets.
To investigate how diets with different carbohydrate-to-fat ratios affect metabolic health, researchers from Pennsylvania State University conducted a 16-week longitudinal experiment using healthy young mice.
The animals were randomly assigned to several dietary groups:
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High-carbohydrate diet:
70% of energy from carbohydrates and 11% from fat, representing traditional grain-based diets. -
High-fat diet:
42% carbohydrates and 40% fat, representing a milder version of a Western-style diet. -
Ketogenic diet:
Only 1% carbohydrates and 81% fat, representing an extreme ketogenic dietary pattern. -
Fiber-supplemented ketogenic diet:
A ketogenic diet combined with the prebiotic fiber inulin. -
Standard chow diet:
A balanced whole-grain diet used as the control group.
All diets contained approximately 18% protein.
During weeks 2, 4, 8, and 16, researchers measured body weight, blood glucose, blood lipids, and liver function markers. At the end of the experiment, the mice underwent liver tissue analysis and gene-expression profiling.
Figure: Mice fed a high-fat, low-carbohydrate diet exhibited obesity, impaired glucose utilization, dyslipidemia, systemic inflammation, and liver dysfunction
The findings revealed that the ketogenic diet did not lead to weight loss in the experimental animals. Although the mice entered a state of nutritional ketosis and produced ketone bodies, their body weight increased in a pattern similar to that observed in the high-fat diet group.
More importantly, significant changes were observed in liver health.
First, liver function markers increased. After only two weeks, mice fed the ketogenic diet showed elevated levels of ALT and AST in the blood, and these markers continued to rise throughout the 16-week period, suggesting ongoing liver injury.
Second, lipid metabolism was disrupted. Blood cholesterol levels increased significantly by week 2, and triglyceride levels rose beginning at week 8 and remained elevated until the end of the study.
Third, fat accumulation occurred in the liver. Further examination revealed increased levels of total fatty acids, saturated fatty acids, and monounsaturated fatty acids in liver tissue. Histological analysis also showed visible fat deposition and inflammatory changes.
Fourth, early signs of liver fibrosis appeared. Genes associated with fibrosis, including Mmp9 and Timp1, were significantly upregulated, and collagen deposition increased, indicating early fibrotic changes in the liver.
Researchers proposed that these effects may occur because extremely low carbohydrate intake forces the liver into a metabolic state characterized by enhanced fatty-acid oxidation. In this process, genes involved in fat metabolism, such as PPARα, become highly active.
However, genes responsible for de novo lipogenesis, including Scd1, Scd2, and Fas, were also activated. This creates a metabolic situation in which the liver simultaneously increases fat breakdown and fat synthesis, potentially leading to excessive lipid accumulation.
Interestingly, the study also identified a potential mitigating factor. When researchers added inulin, a type of dietary fiber, to the ketogenic diet, several metabolic parameters improved.
In the fiber-supplemented ketogenic group:
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Blood glucose levels decreased
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Glucose tolerance improved
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Serum triglyceride levels declined
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Liver enzyme levels decreased at weeks 8 and 16
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Systemic inflammation markers were reduced
Importantly, the addition of inulin did not reduce ketone production, meaning that ketosis was maintained.
Figure: Experimental diets (HCD, HFD, KD, and KD-F) reduced gut microbiota diversity compared to standard diets.
This finding suggests that incorporating dietary fiber into ketogenic dietary patterns may help reduce some of the metabolic disturbances observed in the experiment.
Overall, these two studies highlight an important reminder: health rarely has shortcuts. Being thin does not necessarily protect someone from fatty liver disease, and popular dieting strategies may not always produce the expected health benefits.
Maintaining a balanced diet, undergoing regular medical examinations, and engaging in consistent physical activity remain among the most reliable strategies for protecting liver health.
Although the liver is often described as a silent organ, these studies suggest that it carefully reflects long-term lifestyle choices. Paying closer attention to our daily habits may ultimately provide the best protection for long-term health.
References
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Invited: Longitudinal Assessment of Diets with Varying Carbohydrate-to-Fat Ratios and Fiber Supplementation on Immunometabolic Markers, Liver Function, and Gut Microbiome
DOI: 10.1016/j.tjnut.2025.101285 -
Long-term Prognosis of Lean MASLD: Evidence from Three Population-Based Prospective Cohorts
DOI: 10.1136/gutjnl-2025-336127