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An animal study suggests fasting may negatively affect the immune system. Sergio Delle Vedove/EyeEm/Getty Images
  • Fasting has been linked to many health benefits, but a new study in mice suggests that there may be a cost in terms of reduced immunity.
  • The study found that immune cells migrated from the animals’ blood to their bone marrow during fasting and surged back when feeding re-started.
  • Hunger triggers a hormonal stress response in the brain, which may compel the immune system to conserve resources when food is scarce.
  • The research hints that regularly skipping breakfast could compromise immune defenses in humans, though this has yet to be established.

Breakfast is popularly known as “the most important meal of the day”, but scientific research into the health effects of skipping breakfast remains inconclusive.

Confusingly, a large number of studies have found that regular daytime fasting — such as limiting meals to a narrow window of time or “time-restricted feeding” — has several health benefits.

For example, studies show that fasting and calorie restriction are linked to reduced risk of age-related illnesses, such as hypertension, atherosclerosis, obesity, and diabetes.

But a new study in mice now suggests that fasting has a potential downside.

The research found that there was a rapid reduction in the number of circulating immune cells in animals that were not allowed to eat in the hours after they awoke.

“There is a growing awareness that fasting is healthy, and there is indeed abundant evidence for the benefits of fasting,” explains lead author Filip Swirski, Ph.D., director of the Cardiovascular Research Institute at the Icahn School of Medicine at Mount Sinai in New York, NY.

“Our study provides a word of caution as it suggests that there may also be a cost to fasting that carries a health risk,” he adds.

The study has been published in Immunity.

Mice are nocturnal, which means they are inactive during the day and forage for food at night.

The researchers compared mice that could eat whenever they wanted with mice that had no access to food in the hours after they became active.

After just four hours, the scientists recorded a 90% decrease in the numbers of monocytes — a type of immune cell — in the bloodstream of the mice that fasted.

Bone marrow generates monocytes, which normally patrol the body in search of pathogens. The cells also play a role in inflammation and tissue repair.

In further experiments, the scientists showed that during periods of fasting, the immune cells returned from the bloodstream to the bone marrow.

However, monocytes poured back into the bloodstream after feeding restarted, which resulted in unusually high concentrations of these immune cells, known as monocytosis.

“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,” says Dr. Swirski.

“On the other hand, reintroduction of food creates a surge of monocytes flooding back to the blood, which can be problematic,” he adds.

The scientists also gauged how fasting followed by feeding affects mice’s ability to fight off an infection.

After a 24-hour fast followed by 4 hours of feeding, they infected the mice with a bacterium called Pseudomonas aeruginosa, which is a common cause of pneumonia in hospitals.

Compared with mice that had free access to food throughout, the mice that fasted died sooner and in larger numbers, seemingly as a result of increased inflammation in their lungs.

Dr. Swirski explains that monocytes also play an important role in illnesses such as heart disease and cancer, so it will be important to understand exactly how fasting affects them.

In further experiments, the scientists showed that fasting led to changes in the brains of the mice, which in turn triggered the release of the stress hormone corticosterone.

The immune system responded to this stress signal by recalling the immune cells to the bone marrow. This may help the animals to conserve resources in times of scarcity.

“The study shows that there is a conversation between the nervous and immune systems,” says Dr. Swirski.

“We have plenty of evidence that there is a benefit to fasting,” Dr. Swirski told Medical News Today.

He said the new study demonstrates that there may also be a cost, however.

“It is the combination of cost and benefit that’s at stake here,” he said.

The key to balancing the costs and benefits may be more measured forms of fasting and controlled re-feeding, as opposed to feasting after fasting, he added.

It is too early to say whether studies like this one in mice have implications for people who skip breakfast, or who fast in order to lose weight.

However, Dr. Swirski pointed out that some research has found that fasting also reduces blood monocyte levels in humans.

“The broad implications of these studies to human health remain to be determined but it is worth saying that monocytes are critical cells involved in infections, cancer, cardiovascular disease, etc.,” he added.

In several of the experiments in the new study, mice fasted for 24 hours.

This may not reflect what happens in a human diet plan that involves fasting for much shorter periods, said Satchidananda Panda, Ph.D., who studies circadian rhythms at the Salk Institute for Biological Studies in La Jolla, CA.

A recent study co-authored by Dr. Panda — in which mice fasted for only 12–16 hours — found that the animals’ immunity actually improved.

The authors of the new research acknowledge that it may not apply very well to fasting in humans:

“Our study has limitations for translation into human physiology regarding the length of the fast and the related stress response. A [24-hour] fast in mice is different in humans, which makes our findings potentially more translatable to situations of severe food scarcity or eating disorders.”

“Human metabolism and immunity are not identical to that of mice,” pointed out Dr. Panda, who was not involved in the new study.

He added that research suggests that calorie reduction and fasting can help to control tumor growth in humans. “So, it will be important to test which form of immunity is improved and which ones are compromised in human fasting of various forms,” he told MNT.