Giving your gut a break now and then can deliver huge health benefits.
Calorie restriction, a practice adopted by people from Silicon Valley biohackers to Buddhist monks, has been found to have a long list of positive effects. Periodic fasting can help people ward off diseases like diabetes, high cholesterol, and obesity; it can boost the production of a protein that strengthens connections in the brain and can serve as an antidepressant. And scientists even think fasting can lengthen our lifespan by keeping cells healthy and youthful longer.
New research from biologists at Massachusetts Institute of Technology, published in the journal Cell Stem Cell, is starting to reveal why fasting is so beneficial at the cellular level — and how future drugs might be able to trigger that process without any restrictions on food intake.
Fasting switches off the body's simplest energy source: the muscle-feeding glycogen that we typically get from eating carbohydrates. Take away carbs, and the body kicks into a kind of a starvation mode, tapping into fat stores and releasing ketone bodies produced by the liver.
The MIT researchers haven't studied the cellular effects of fasting in people yet, but in mice, they observed big improvements in stem-cell performance even after a single 24-hour fast. When a mouse switched to burning fat for fuel, its intestinal stem cells kicked into high gear and acted more youthful and spry, doubling their capacity to regenerate and renew.
Adult stem cells are builder cells — they can essentially repair and replace every kind of cell inside a tissue like an intestine.
"When a tissue becomes injured, this tissue needs to repair itself," study author Omer Yilmaz told Business Insider. "Stem cells can generate all of the cell types."
Having healthy, highly productive stem cells that can regenerate tissue quickly is therefore vitally important to our health. Nowhere is that more true than the intestine, which is the most highly regenerative organ in the body. The intestine's inner lining gets completely replaced every five days or so. It does so by regenerating stem cells and turning them into new intestine parts. That's what allows the organ to continue efficiently breaking down food, absorbing nutrients, and producing waste.
More efficient stem cells, then, can more quickly repair intestinal damage and spur recovery from infections.
The new MIT research suggests stem cells perform much better when fuelled by fat instead of carbs — the fasting mice doubled their capacity to regenerate stem cells.
"We found that a 24-hour fast enhanced intestinal stem cell function by changing their energy metabolism," Yilmaz said.
In people, the researchers suggest, that enhanced function could help with processes of repairing damaged tissue, recovering from infections, and even bouncing back from chemotherapy treatments. These functions are typically easier for young cells to do, but get more difficult with age and wear and tear.
But when stem cells run on fat, age seems to be nothing but a number.
The researchers think mice — and people — may not have to stop eating to get the cell-boosting benefits they observed, though. That's because the scientists zeroed in on some specific genes in the mice that got turned on by fasting. When they turned off those genes, the beneficial effects of fasting for stem cells disappeared.
Yilmaz's team hopes that by better understanding the molecules and proteins that turn those genes on and off during a fast, they’ll one day be able to create drugs that can mimic some of the cell-boosting effects of temporary starvation. Patients may not even need to be deprived of food to see the benefits.
"If we can identify the mechanism by which fasting enhances the function of these intestinal stem cells, we might be able to identify new treatment modalities that mimic the effects of fasting," Yilmaz said.
The MIT scientists think such a drug could be especially helpful for cancer patients and people recovering from gastrointestinal infections.
"We think that any type of intervention that improves stem-cell function — irrespective of age — will have a lot of uses for patients that undergo chemotherapy," Yilmaz said.
The FDA has not yet approved any trials of fasting-mimicking drugs in people, so it will likely be years before the scientists can try such an approach out on human cancer patients.
Meanwhile, the practice of intermittent fasting has taken off as a way to gain the health benefits of fasting in daily life. A plan known as the 5:2 diet suggests that people severely limit what they eat on two days each week. Another regimen, called the fasting-mimicking diet, instructs people to eat normally 25 days of the month, then cut their daily calorie load down to just 800 per day (with a specific blend of nutrients) for the other five days.
The popular keto diet doesn't involve fasting, but instead pushes people to fuel up on fats and severely limit carbs to trigger the same fat-burning ketosis effect that happens when we’re fasting.
If scientists can understand more about the biological mechanisms at work in various fasting states, new cancer treatments may only be the beginning.
"It's been well known for probably more than 100 years that low-calorie states such as fasting, or caloric restriction often have beneficial effects on health, and in some cases on lifespan," Yilmaz said.
"Understanding the similarities and differences of these different types of low-calorie states we think is going to uncover some important biology that may ultimately promote human health."