Intermittent fasting has gained popularity of late and has been associated in the press with various health benefits including weight reduction, reduced risk of cardiovascular disease, extended longevity and improved cognitive function. However, the vast majority of fasting research has been conducted with animals, and evidence of health improvements from fasting in humans is preliminary at best.
A new study from scientists at the Icahn School of Medicine at Mount Sinai Hospital introduces a note of caution to those wishing to use fasting as a route to improved health. Their study on mice found that skipping meals triggers a response in the brain that negatively affects immune cells and may make the mice less able to fight off infections.
“There is a growing awareness that fasting is healthy, and there is indeed abundant evidence for the benefits of fasting. Our study provides a word of caution as it suggests that there may also be a cost to fasting that carries a health risk,” says lead author Filip Swirski, PhD, Director of the Cardiovascular Research Institute at Icahn Mount Sinai. “This is a mechanistic study delving into some of the fundamental biology relevant to fasting. The study shows that there is a conversation between the nervous and immune systems.”
Not much is understood about the mechanisms by which fasting brings about the beneficial changes observed, but studies of humans fasting between dawn and dusk during Ramadan have indicated that inflammatory cytokines are suppressed in fasting individuals. Cytokines are crucial in the immune system for controlling the growth and activity of other immune cells.
In the current study, researchers aimed to better understand how fasting affects the immune system in mice. They analyzed two groups of mice, one that ate breakfast immediately after waking and the other that had no breakfast. Fasting mice were kept from eating for a few hours, or up to 24 hours, before being given food. Their blood was sampled after waking up and then four hours and eight hours later.
The results, published in the journal Immunity, show distinct differences in blood characteristics between the fed and the fasting mice. Specifically, the researchers saw a difference in the number of monocytes, which are white blood cells that are made in the bone marrow and travel through the body, where they play many critical roles, from fighting infections, to repairing tissues and preventing heart disease and cancer.
After waking, all mice had the same levels of monocytes in their blood. But after four hours, 90 percent of these important immune system cells had disappeared from the bloodstream of the fasting mice. Monocyte levels in mice that didn’t skip breakfast were unchanged from the initial values. The researchers discovered that monocytes in fasting mice had travelled back to the bone marrow, where they remained inactive.
While hibernating in the bone marrow, the monocytes underwent significant changes. They aged differently and survived for longer than they would have in the bloodstream. In addition, the production of new monocytes in the bone marrow declined while the hibernating cells were present.
Once food was again given to the fasting mice, the monocytes hiding in the bone marrow flooded back into the bloodstream within a few hours. This surge of altered monocytes resulted in increased levels of inflammation that would have made their bodies less able to fight infections.
This study is among the first to find a connection between the brain and the behavior of these immune cells during fasting. Researchers found that specific regions in the brain controlled the monocyte response during fasting. This study demonstrated that fasting elicits a stress response in the brain and this instantly triggers a large-scale migration of these white blood cells from the blood to the bone marrow, and then back to the bloodstream, shortly after food is reintroduced.
Dr. Swirski emphasized that while there is also evidence of the metabolic benefits of fasting, this new study is a useful advance in the full understanding of the body’s mechanisms.
“The study shows that, on the one hand, fasting reduces the number of circulating monocytes, which one might think is a good thing, as these cells are important components of inflammation. On the other hand, reintroduction of food creates a surge of monocytes flooding back to the blood, which can be problematic. Fasting, therefore regulates this pool in ways that are not always beneficial to the body’s capacity to respond to a challenge such as an infection,” explains Dr. Swirski. “Because these cells are so important to other diseases like heart disease or cancer, understanding how their function is controlled is critical.”
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