Fasting may be detrimental to fighting off infection, and could lead to an increased risk of heart disease, according to a new study by the Icahn School of Medicine at Mount Sinai. The research, which focused on mouse models, is among the first to show that skipping meals triggers a response in the brain that negatively affects immune cells. The results that focus on breakfast were published in the February 23 issue of Immunity, and could lead to a better understanding of how chronic fasting may affect the body long term.
"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."
Researchers aimed to better understand how fasting — from a relatively short fast of only a few hours to a more severe fast of 24 hours — affects the immune system. They analyzed two groups of mice. One group ate breakfast right after waking up (breakfast is their largest meal of the day), and the other group had no breakfast. Researchers collected blood samples in both groups when mice woke up (baseline), then four hours later, and eight hours later.
When examining the blood work, researchers noticed a distinct difference in the fasting group. 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 heart disease, to cancer.
At baseline, all mice had the same amount of monocytes. But after four hours, monocytes in mice from the fasting group were dramatically affected. Researchers found 90 percent of these cells disappeared from the bloodstream, and the number further declined at eight hours. Meanwhile monocytes in the non-fasting group were unaffected.
In fasting mice, researchers discovered the monocytes traveled back to the bone marrow to hibernate. Concurrently, production of new cells in the bone marrow diminished. The monocytes in the bone marrow—which typically have a short lifespan—significantly changed. They survived longer as a consequence of staying in the bone marrow, and aged differently than the monocytes that stayed in the blood.
The researchers continued to fast mice for up to 24 hours, and then reintroduced food. The cells hiding in the bone marrow surged back into the bloodstream within a few hours. This surge led to heightened level of inflammation. Instead of protecting against infection, these altered monocytes were more inflammatory, making the body less resistant to fighting infection.
This study is among the first to make the connection between the brain and 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—that's what makes people "hangry" (feeling hungry and angry) —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."
This study was funded by grants from the National Institutes of Health and the Cure Alzheimer"s Fund,
About the Icahn School of Medicine at Mount Sinai
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the eight member hospitals of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to a large and diverse patient population.
Ranked No. 14 nationwide in National Institutes of Health funding and in the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges, Icahn Mount Sinai has a talented, productive, and successful faculty. More than 3,000 full-time scientists, educators, and clinicians work within and across 34 academic departments and 44 multidisciplinary institutes, a structure that facilitates tremendous collaboration and synergy. Our emphasis on translational research and therapeutics is evident in such diverse areas as genomics/big data, virology, neuroscience, cardiology, geriatrics, and gastrointestinal and liver diseases.
Icahn Mount Sinai offers highly competitive MD, PhD, and master's degree programs, with current enrollment of approximately 1,300 students. It has the largest graduate medical education program in the country, with more than 2,600 clinical residents and fellows training throughout the Health System. In addition, more than 535 postdoctoral research fellows are in training within the Health System.
A culture of innovation and discovery permeates every Icahn Mount Sinai program. Mount Sinai's technology transfer office, one of the largest in the country, partners with faculty and trainees to pursue optimal commercialization of intellectual property to ensure that Mount Sinai discoveries and innovations translate into health care products and services that benefit the public.
Icahn Mount Sinai's commitment to breakthrough science and clinical care is enhanced by academic affiliations that supplement and complement the School's programs. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai. Additionally, MSIP develops research partnerships with industry leaders such as Merck & Co., AstraZeneca, Novo Nordisk, and others.
The Icahn School of Medicine at Mount Sinai is located in New York City on the border between the Upper East Side and East Harlem, and classroom teaching takes place on a campus facing Central Park. Icahn Mount Sinai's location offers many opportunities to interact with and care for diverse communities. Learning extends well beyond the borders of our physical campus, to the eight hospitals of the Mount Sinai Health System, our academic affiliates, and globally.
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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Beth Israel; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai.
