While previous studies have linked intermittent fasting to benefits such as reductions in weight and dementia risk, new research in mice points to a potential downside of periodic food abstinences: an increase in the risk of cancer.
The discovery follows a previous study that found fasting in mice led to a boost in the regenerative capabilities of their intestinal stem cells, protecting against injury and inflammation.
Now an international team of researchers have determined this increase in stem cell production accelerates as mice refeed after fasting. What's more, eating can introduce mutagens – compounds like the heterocyclic amines in burned meats, which can cause genetic mutations – that increase the risk of triggering cancerous tumors.
"Having more stem cell activity is good for regeneration, but too much of a good thing over time can have less favorable consequences," says biologist Omer Yilmaz from the Massachusetts Institute of Technology (MIT).
"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."
Intestinal stem cells are amongst the busiest in the body, constantly dividing and growing to reline the intestine every 5 to 10 days. This high level of activity also means cancer-causing aberrations are more likely – and that likelihood increases even further during the supercharged post-fasting period, the study shows.
The team identified a biological pathway, called mTOR, which the stem cells operate through. This pathway is involved in cell growth and metabolism, and after fasting it increases the production of small molecules called polyamines, which drive cell proliferation.
These molecules are key to helping the body recover and regenerate after being deprived of the nutrients and energy supplied by a regular diet. However, the study demonstrates the probability of tumors rises as well, especially in conditions more favorable to cancer growth.
"We think that fasting and refeeding represent two distinct states," says MIT molecular biologist Shinya Imada.
"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."
Previous studies have implied fasting and fasting-mimicking diets could actually be beneficial for reducing the risk of cancer, and potentially even boost the efficacy of anti-cancer therapies. Yet these studies have focussed largely on abstaining from food, without considering the potential consequences of breaking the fast.
Further investigation could help identify ways to promote the benefits while limiting the risks.
As is often the case in studies like these, animal models can only tell us so much. The pros and cons might be completely different in our own species, requiring even more studies to deepen our understanding.
"I want to emphasize that this was all done in mice, using very well-defined cancer mutations," says Yilmaz. "In humans it's going to be a much more complex state."