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Numerous scientific studies have shown that fasting can be beneficial to health. In recent years, intermittent fasting has become the focus of research. In a new study, researchers have now found that intermittent fasting can protect the liver and reduce the risk of cancer.
Fatty liver disease often results in chronic liver inflammation and can even lead to liver cancer. A study by scientists from the German Cancer Research Center (DKFZ) and the University of Tübingen has now shown that intermittent fasting according to the 5:2 schedule can stop this development. The study results were published in the journal “Cell Metabolism”.
Dietary changes for fatty liver disease
As reported in a communication from the DKFZ, non-alcoholic fatty liver disease is the most common chronic liver disease. It can have serious consequences: If left untreated, the disease can lead to liver inflammation (metabolic dysfunction-associated steatohepatitis, MASH), liver cirrhosis and even liver cancer.
Fatty liver disease is largely considered to be a direct result of morbid overweight, adiposity.
“The vicious circle of unhealthy diet, obesity, liver inflammation and liver cancer is associated with great restrictions and suffering for those affected and also represents a considerable burden on the health systems,” explains Mathias Heikenwälder, DKFZ and University of Tübingen.
“We therefore investigated whether simple dietary changes can specifically interrupt this disastrous development.”
Intermittent fasting as an effective remedy
Intermittent fasting has already been proven in various studies to be an effective means of losing weight and alleviating certain metabolic disorders. Heikenwälder's team now used mice to test whether this approach can also protect the liver from fatty deposits and chronic inflammation.
The mice received food whose composition was high in sugar and fat and corresponded to the Western diet. One group of animals had constant access to food. As expected, these mice gained weight and body fat and developed chronic liver inflammation.
The animals in the other group were not given anything to eat on two days per week (5:2 intermittent fasting, or 5:2 IF for short), but were able to help themselves as they wished on the other days.
These mice did not gain weight despite the high-calorie diet, showed fewer signs of liver disease, and had lower levels of biomarkers that indicate liver damage. In short: they were resistant to the development of MASH.
Interestingly, the resistance to the development of a fatty liver was independent of the total calorie intake, because after the end of the fasting periods, the mice immediately made up for the missed rations.
Protection against liver inflammation
When experimenting with different variants of intermittent fasting, it turned out that several parameters determine protection against liver inflammation: the number and duration of fasting cycles play a role, as does the start of the fasting phase.
A 5:2 diet regimen works better than 6:1 and 24-hour fasting phases work better than 12-hour ones. A particularly unhealthy diet requires more frequent diet cycles.
The researchers then wanted to uncover the molecular background of the reaction to fasting. They compared protein composition, metabolic pathways and gene activities in the liver of fasting and non-fasting mice.
Two main factors responsible for the protective fasting reaction emerged: the transcription factor PPARα and the enzyme PCK1. These two molecular players work in cooperation to increase the breakdown of fatty acids and gluconeogenesis and inhibit the buildup of fats.
“The fasting cycles lead to profound metabolic changes, which together act as beneficial detoxification mechanisms and help combat MASH,” says Heikenwälder.
The fact that these connections do not represent a purely mouse phenomenon was shown when examining tissue samples from MASH patients: here, too, the researchers found the same molecular pattern with reduced PPAR α and PCK1.
Are PPAR α and PCK1 actually causally responsible for the beneficial fasting effects? If both proteins were genetically switched off at the same time in the mice's liver cells, intermittent fasting was unable to prevent chronic inflammation or fibrosis.
Active ingredient mimics effects
The active ingredient pemafibrate mimics the effects of PPARα in the cell. Can the substance also mimic the protective fasting effect? The scientists also examined this question in mice.
Pemafibrate produced some of the same favorable metabolic changes as those observed with 5:2 fasting. But he could only partially mimic the protective effects of fasting.
“This is not surprising, since with pemafibrate we can only influence one of the two key players. Unfortunately, an active ingredient that imitates the effects of PCK1 is not yet available,” explains Mathias Heikenwälder.
Intermittent fasting for prevention and as therapy
While the researchers initially focused on the effects of intermittent fasting on the prevention of MASH, they then examined whether existing chronic liver inflammation could also be alleviated by the 5:2 diet.
To do this, they examined mice that had developed MASH after months of feeding with food high in sugar and fat. After another four months of 5:2 intermittent fasting (with the same diet), these animals were compared with the non-fasting control group.
The fasting mice had better blood values, less fatty liver disease and liver inflammation and, above all, they were less likely to develop liver cancer and, if they did, they had fewer cancer foci in the liver.
“This shows us that 5:2 intermittent fasting has high potential – both in the prevention of MASH and liver cancer, as well as in the treatment of already established chronic liver inflammation,” says study leader Heikenwälder.
“The promising results justify studies on patients to find out whether intermittent fasting protects against chronic liver inflammation as well as in the mouse model.”
The 5:2 fasting schedule is popular. It is considered to be relatively easy to integrate into everyday life because the fasting days can be tailored to personal needs and no specific foods are forbidden.
“Nevertheless, there will always be people who cannot stick to a strict diet long-term,” says Heikenwälder. “In the future, we therefore want to continue to investigate which combinations of active ingredients we can use to fully imitate the protective effects of fasting.” (ad)