Skipping breakfast could result in an increased risk of heart disease, and trigger a response in the brain that negatively impacts immune cells, according to a study published February 23 in the journal Immunity. The study, conducted by the Icahn School of Medicine at Mount Sinai, is among the first to show how skipping meals compromises the immune system. 


The research, which was carried out on mouse models, is important because it could lead to a better understanding of how chronic fasting could be detrimental to fighting off infection, and may affect the body in the long run.


In a statement released by the Mount Sinai Hospital, Filip Swirski, the lead author on the paper, said there is a growing awareness that fasting is healthy, and there is indeed abundant evidence for the benefits of fasting. He also said that the study provides a word of caution as it suggests that there may also be a cost to fasting that carries a health risk. 


Swirski explained that this is a mechanistic study delving into some of the fundamental biology relevant to fasting. The research shows that there is a conversation between the nervous and immune systems. 


What was the objective of the study?


The aim of the study was 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. As part of the study, the researchers analysed two groups of mice. 


How the study was conducted


One group was given breakfast right after waking up, while the other group was given no breakfast. Breakfast was their largest meal of the day. 


When the mice woke up, the researchers collected their blood samples. After that, they collected blood samples four hours later and eight hours later. 


The researchers, upon examining the blood work, noticed a distinctive difference in the fasting group. They found a difference in the number of monocytes, which are white blood cells made in the bone marrow and travel throughout the body. Monocytes perform many critical roles including fighting infections, and preventing heart disease and cancer. 


What happened to the mice after fasting?


All mice had the same amount of monocytes at the baseline, or immediately after waking up. However, after four hours the monocytes in the mice from the fasting group were dramatically affected. According to the study, 90 per cent of the cells disappeared from the bloodstream, and after eight hours, the number further declined. Monocytes in the non-fasting group were not affected, the study said. 


The researchers discovered in the fasting mice that the monocytes travelled back to the bone marrow to hibernate. At the same time, the production of new cells in the bone marrow diminished. Monocytes in the bone marrow typically have a short lifespan. In the fasting mice, the monocytes 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. 


What happened after the reintroduction of food at the end of 24 hours?


As part of the research, the team continued to fast mice for up to 24 hours. At the end of 24 hours, they reintroduced food to the mice. 


Within a few hours of reintroducing food, the cells hiding in the bone marrow surged back into the bloodstream. The surge in monocytes resulted in an increased level of inflammation. 


The altered monocytes were more inflammatory, and instead of protecting the body against infection, they were making it less resistant to fight infection. 


According to Mount Sinai Hospital, the study is among the first to make the connection between the brain and these immune cells during fasting. 


How the brain controlled the monocyte response during fasting


Specific regions of the brain controlled the monocyte response during fasting, the study said. Fasting elicits a stress response in the brain, the study showed. This is what makes people "hangry", or feeling hungry and angry at the same time, and instantly triggers a large-scale migration of these white blood cells from the blood to the bone marrow. Then, the brain signals the white blood cells to be reintroduced back to the bloodstream shortly after food is introduced.


According to Swirski, while there is also evidence of the metabolic benefits of fasting, the new study is a useful advance in the full understanding of the body's mechanisms. 


Swirski said 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 white blood cells are important components of inflammation. On the other hand, reintroduction of food creates a surge of monocytes flooding back to the blood, Swirski said, which can be problematic. 


Therefore, fasting regulates the brain and immune system in ways that are not always beneficial to the body's capacity to respond to a challenge such as an infection. Swirski concluded that since monocytes are so important to other diseases like heart disease or cancer, understanding how their function is controlled during fasting is critical.