- Fasting, or restricting your intake of solid foods, is often promoted as a means of losing weight.
- Studies have suggested that intermittent fasting — alternating restricted food intake with usual eating patterns — may have several health benefits.
- Now, a study in mice suggests that fasting and then refeeding boosts cell regeneration in the intestines.
- However, the research found that this also increased the risk of intestinal tumors in the mice.
Fasting has long been part of many traditions and religions, but it is only in recent years that the health benefits of restricting food intake have been investigated. Most recently, many studies have researched the effects of intermittent fasting — short periods of no or limited food intake interspersed with periods of normal eating — on health.
Health benefits of intermittent fasting may include:
- weight loss
- lower risk of type 2 diabetes
- improved heart and brain health
- lower risk of cancer
- reduced oxidative stress and inflammation
- improved longevity
To date, intermittent fasting has only shown benefits for weight loss and type diabetes in humans with regards to weight loss. As a result, more research is needed to investigate whether the same effects might be seen in people.
Now, a study led by researchers from MIT has found out how fasting and then refeeding stimulates cell regeneration in the intestines but has also shown that it carries the risk of stimulating the formation of intestinal tumors.
The study, which was carried out in mice, is published in Nature.
Previous studies from the same research group have shown that mice that are fasted for 24 hours, then fed their normal diet have enhanced intestinal stem cell function, which may promote intestinal regeneration and aid recovery from injuries or inflammation.
In this study, researchers divided the mice into three groups: group one fasted for 24 hours; group 2 fasted for 24 hours and then was allowed to eat whatever they wanted during a 24-hour refeeding period; and a control group ate whatever they wanted throughout the experiment. All groups had unlimited access to water at all times.
At different time points during the experiment, the researchers analyzed the mice’s intestinal stem cells.
They found that the stem cells’ ability to multiply was highest during the 24-hour refeeding period in mice that had previously fasted for 24 hours. These cells also replicated more rapidly than intestinal stem cells from mice that had not fasted at all.
The cells also activated a cellular signaling pathway, called mTOR, that is involved in cell metabolism, growth, and regulating protein synthesis. When it is activated, cells produce more protein, which is vital for proliferation of stem cells.
The researchers demonstrated that when mTOR is activated in these stem cells, they produce higher levels of polyamines — small molecules needed for cell growth and division.
Study authors Ömer Yılmaz, Shinya Imada, and Saleh Khawaled told Medical News Today:
“Intestinal stem cells are the cells responsible for replenishing the intestinal epithelium in normal physiology and after damage. As refeeding enhanced the regeneration capacity of these cells, this is highly beneficial for the renewal of the intestinal tissue especially in damaged tissue as we found with the irradiation models that we used in our current manuscript.”
Eamon Laird, visiting adjunct assistant professor at TCD Dublin, and assistant lecturer ATU Sligo, Ireland, agreed that this rapid regeneration could be beneficial:
“Evolutionarily this would make sense – after a difficult time or a period without resources, the body would prioritize cell regeneration as soon as it got food or resources again. It does not know when the next hardship is going to come, so it needs to repair and prepare the cells for the next difficult period.”
However, he added: “The downside is what is the metabolic or cellular cost of these constant swings from resource rich to resource poor?”
According to the National Cancer Institute: “Cancer is a disease in which some of the body’s cells grow uncontrollably and spread to other parts of the body.” So could cells that are prompted to proliferate lead to cancers?
This study suggests that this might be the case — the intestinal stem cells in this highly regenerative state were much more likely to become cancerous.
“During fasting the body switches to a different type of fuel generating process and then during re-feeding this seems to stimulate some of the cells to undergo rapid metabolism which may have unintended consequences.”
— Eamon Laird
When the researchers turned on a cancer-causing gene in the mice during refeeding, the cells were much more likely to develop into precancerous polyps than if the gene was turned on during fasting.
In addition, cancer-linked mutations that happened during refeeding were more likely to cause the development precancerous polyps when compared to mutations during fasting.
“Post-fast refeeding leads to a burst in stem-cell-driven regeneration and these refed stem cells when exposed to genetic alterations have an elevated risk of developing cancers. It is the sudden exposure to a resource-rich environment leading to sudden and expansive regeneration which could leave the cells highly vulnerable.”
— Eamon Laird
The authors cautioned that, although these results were in mice, it is possible that if you were to eat a mutagenic food—a food at risk of causing mutations—such as a piece of charred meat soon after fasting, you might increase the chance of developing a cancerous lesion.
“As biological pathways are highly complex and interconnected, the main take home message of our current study is that careful studies should be done to test the effects of any dietary intervention on the human body. While intermittent fasting is a very popular diet used by millions of humans around the world and has been shown to have immense benefits in multiple diseases, careful dissection of the contribution of each of the fasting phases (fasting vs post-fast refeeding) will give us a greater understanding of how to plan such dietary interventions to maximize regeneration while avoiding increased risk of other diseases such as cancer.”
— Ömer Yılmaz, Shinya Imada and Saleh Khawaled
Kelsey Costa, MS, RDN, a registered dietitian nutritionist and founder of Dietitian Insights, told MNT.
“Fasting regimens, especially those lasting 24 hours or more, have been shown to enhance metabolic health and promote tissue regeneration across various species, including some research in humans. This practice may reverse age-related declines in stem cell function, rejuvenating both blood-forming and intestinal stem cells.”
“In people,” she added, “fasting regimens may decrease calorie intake, body weight, body fat, blood pressure, triglycerides, blood glucose, glucose intolerance, and inflammatory markers, supporting a healthy metabolism and helping to prevent or treat chronic conditions like obesity and type 2 diabetes.”
However, she cautioned:
“This study also suggests that while fasting and calorie restriction may prevent or slow tumor growth, the period of eating after fasting, known as refeeding, might increase the risk of developing tumors if exposed to carcinogens or genetic changes (mutations) occur during this time.”
“More research is needed to understand how different fasting schedules and meal contents affect cancer risk. Overall, the study suggests being cautious about fasting and refeeding cycles in diet planning to promote regeneration without increasing cancer risk,” she advised.