A new study from MIT has revealed the exact mechanism by which fasting causes intestinal stem cells to regenerate, which is one of the practice's benefits. However, the study also showed a downside that needs to be considered when breaking a fast.
Fasting, either for several days a week or several hours a day, is a popular approach used by thousands of people to help control their weight, rest their guts, and potentially deliver other health benefits. A study earlier this year, for example, showed that fasting for 24 hours twice a week boosted the cancer-fighting abilities of natural killer cells in the body. Another 2024 study showed that the same eating pattern also conferred protection against liver inflammation.
Omer Yilmaz, an associate professor of biology and a member of MIT’s Koch Institute for Integrative Cancer Research, has been studying the effects of fasting in rodents for years. In 2018 he and his team discovered that 24-hour fasts boosted the regeneration of intestinal stem cells, a process that tends to decline with age.
Now, Yilmaz is the senior author on a new study that identified the pathways through which fasting impacts these stem cells and found a potentially troubling complication.
The study authors discovered that it's not so much the fasting that causes the stem cell regeneration, but the period of "refeeding" that takes place after the fast.
To reach their conclusion, the researchers divided mice into three groups: one that fasted for 24 hours; another that fasted for 24 hours and then ate whatever they chose during a subsequent 24-hour refeeding period; and a control group that simply ate normally through the study period.
They found that the highest rate of intestinal stem cell regeneration took place at the end of the 24-hour refeeding period.
“We think that fasting and refeeding represent two distinct states,” says Shinya Imada, a MIT postdoc who is one of the study's lead authors. “In the fasted state, the ability of cells to use lipids and fatty acids as an energy source enables them to survive when nutrients are low. And then it’s the postfast refeeding state that really drives the regeneration. When nutrients become available, these stem cells and progenitor cells activate programs that enable them to build cellular mass and repopulate the intestinal lining.”
The wrong type of regeneration
But there was a catch. The researchers found that during this extensive regeneration period the intestinal stem cells were more prone to become cancerous. They reached this conclusion by testing the 24-hour fasting/refeeding regimen on mice that had a cancer-causing gene turned on. The cancerous mutations they saw during the regeneration phase were also more likely to lead to polyps than in the cancer-prone mice that did not fast.
While intestinal stem cells are always more prone to cancer-causing mutations because of their vigorous rate of division, the researchers believe their findings might be cause for concern. Importantly, they also point out that the findings from a rodent study don't always translate to humans.
“I want to emphasize that this was all done in mice, using very well-defined cancer mutations," says Ilmaz. "In humans it’s going to be a much more complex state. But it does lead us to the following notion: Fasting is very healthy, but if you’re unlucky and you’re refeeding after a fasting, and you get exposed to a mutagen, like a charred steak or something, you might actually be increasing your chances of developing a lesion that can go on to give rise to cancer.”
The research has been published in the journal Nature.
Source: MIT
