For years, doctors noticed that when patients with certain diseases went without eating for a day or so, their condition sometimes improved. Patients with rheumatoid arthritis would say they felt better while fasting during Ramadan and, more recently, studies have shown that fasting improves multiple sclerosis symptoms in mice.
“They have less pain," says Dr. Vassiliki Boussiotis, a professor of medicine at Beth Israel Deaconess Medical Center. "The symptoms of the disease are more controlled.”
Why that happens has eluded researchers, but three new studies on mice and humans published in the journal Cell on Thursday offer a few explanations for how fasting might temporarily confer certain health benefits.
“It’s very exciting,” says Boussiotis, who did not work on the studies. The papers are able to bring together "fragmented information" on different immune cell types to show the body's orchestrated effort to protect them during fasting, she says.
In all the studies, researchers had mice either eat less food or go on a water-only fast for roughly a day.
For some mice, “we reduced calories by 20%. It’s like skipping a meal,” says Dr. Yasmine Belkaid, the author of one study and an immunologist at the National Institutes of Health.
Each study looked at a different type of immune cell and found that each type had a unique response to fasting.
Two of the studies looked at T cells and B cells, which are involved in creating immunity against past infections and identifying and destroying pathogens. When the mice in these studies began fasting, Belkaid says, T and B cells vanished from the bloodstream and organ tissues.
“All those memory cells seem to disappear from the body when you decrease calories,” she says.
When the researchers looked in the mice, they found these immune cells hiding inside the bone marrow. “They were able to take shelter there and be protected,” Belkaid says.
With fewer nutrients available in the bloodstream and a greater concentration of toxic stress hormones, Belkaid says, these immune cells migrated to food-rich bone marrow compartments where they can survive during a fast.
In Belkaid’s study, she found that memory T cells, which produce molecular weapons to kill pathogens and cancers, suddenly became supercharged when they retreated to the bone marrow. “Not only were they able to survive, they were also optimized, and these T cells were able to protect [the body] better,” Belkaid says.
When the mice in her study were injected with a pathogen that they’d already fought off once before, well-fed mice took around a week to destroy the pathogen. Mice that were fasting cleared the infection in two days.
“It’s a striking enhancement,” Belkaid says. “The goal is to [eventually] understand this magic soup in the bone marrow and extract what’s making that response. If we can train our cells to do these things, we can have an extraordinary impact on human health.”
The third study focused on monocytes, white blood cells that directly attack pathogens.
“This cell in particular is really good at inducing inflammation,” says Dr. Miriam Merad, the study's author and an immunologist at the Icahn School of Medicine at Mount Sinai. “When you feel under the weather, achy and feverish, this is the work of these inflammatory cells.”
In her study, the monocytes circulating in the bloodstreams of both humans and mice went down when they fasted. When Merad looked inside the bodies of fasting mice to see what was happening, she found that their bone marrow was still producing monocytes, but fewer of them were being released into the bloodstream.
Fasting had somehow created a roadblock between the bone marrow and the blood for these cells. “They were also in a quiet state. They were less inflammatory,” Merad says.
That had important consequences for mice that had multiple sclerosis-like symptoms in Merad’s experiment. With fewer monocytes circulating through the body, she says, overall inflammation went down in these mice, and they started looking healthier.
This drop in inflammation might help explain findings in some human trials where fasting improved symptoms in multiple sclerosis, she says.
These three studies suggest that we can manipulate the immune system simply by changing how much we eat, says Boussiotis of Beth Israel Deaconess. Fasting could be leveraged more effectively to help patients with certain diseases, she says.
“Now we know a mechanism through which this can be beneficial for patients with these diseases,” she says. “Perhaps patients with immune diseases can go under starvation for some days or change their diet so that they have less nutrients and reduce their inflammation.”
The work also suggests that intermittent fasting might provide certain benefits to healthy people as well, Merad says, like lower inflammation throughout the body.
Humans likely evolved in an environment where short-term fasting was inevitable, and these immune responses to fasting may be part of a natural, beneficial cycle, she says.
“Our ancestors probably only ate once every few days when they found food,” she says. “So, why do we eat three times a day? Is this the best thing for us? Maybe we don’t have to eat that much. Maybe we should learn to fast.”