Scientists at the German Cancer Research Centre (DKFZ) and the University of Tübingen have demonstrated that intermittent fasting, specifically on a 5:2 schedule, can block the progression of fatty liver disease to liver cancer in mice. This research suggests that intermittent fasting could be a powerful strategy for preventing and treating chronic liver inflammation and its severe consequences.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder and can lead to liver inflammation, cirrhosis, and liver cancer if left unchecked. This condition is strongly linked to obesity, which is on the rise in countries like India, China, Europe, and the United States, leading to a surge in liver disease cases.
The researchers tested intermittent fasting in mice, feeding them a high-sugar and high-fat diet typical of Western diets. One group of mice had constant access to food, resulting in weight gain, body fat accumulation, and chronic liver inflammation. In contrast, the second group followed a 5:2 intermittent fasting regimen, where they fasted for two days each week but could eat freely on other days. Despite the high-calorie diet, these fasting mice did not gain weight, exhibited fewer signs of liver disease, and had lower levels of liver damage biomarkers.
Interestingly, the protection against fatty liver and inflammation was independent of the total calorie intake, as the fasting mice compensated for missed meals on non-fasting days.
The protective effects of fasting were linked to two proteins in liver cells: the transcription factor PPARa and the enzyme PCK1. These proteins work together to increase the breakdown of fatty acids and gluconeogenesis while inhibiting fat build-up. When these proteins were genetically deactivated in mice, intermittent fasting failed to prevent chronic inflammation or fibrosis, highlighting their critical role.
The drug pemafibrate, which mimics the effects of PPARa, was tested to see if it could replicate the benefits of fasting. While it induced some favorable metabolic changes, it could only partially mimic the protective effects, likely because it only influenced one of the two key proteins.
The promising results in mice suggest that intermittent fasting could be effective in preventing and treating chronic liver inflammation and liver cancer in humans. The researchers call for clinical studies to determine if intermittent fasting offers the same benefits for patients.
Intermittent fasting, particularly the 5:2 regimen, is popular due to its flexibility and ease of integration into daily life. However, for those unable to adhere to strict diets, ongoing research aims to develop drug combinations that can fully replicate the protective effects of fasting.
Intermittent fasting on a 5:2 schedule shows great potential in both the prevention and treatment of fatty liver disease and liver cancer. The findings justify further research in humans to confirm these benefits and explore additional therapeutic options.
