Researchers at the Icahn School of Medicine at Mount Sinai, using sophisticated, single-cell technology,have isolated the molecular underpinning that explains why short-term fasting and a low-calorie diet are beneficial to people with inflammatory and autoimmune diseases, such as atherosclerosis and rheumatoid arthritis. Until now, the connection between reduced caloric intake and improved health has been a widely held but poorly understood hypothesis that has captured the public’s attention as high-profile celebrities attest to the success of frequent fasting.
In the new study, published in the August 22, 2019, issue of Cell, the researchers, led by Miriam Merad, MD, PhD, Director of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai, were able to describe how dietary intake actually controls the quality and quantity of monocytes—a particular group of white blood cells.
The scientists found a direct link between the amount of glucose and protein in the body and the number of circulating monocytes. These white blood cells, likened to military “reserve forces,” respond to inflammatory stimuli and also play a major role in metabolic equilibrium, growth, and other processes. When digestible carbohydrates, protein, and fat were removed from the diet, the investigators found the pool of circulating monocytes decreased. Importantly, the size of the monocyte pool that was circulating in the blood depended upon the amount of carbohydrates ingested.
The study profiled 12 healthy, normal-weight volunteers 3 hours after eating and 19 hours after fasting, as well as mice that had fasted for 4 hours.
“Monocytes are highly inflammatory immune cells that can cause serious tissue damage,” says Dr. Merad. “We have seen more of these monocytes in blood circulation as Western-style eating habits have been adopted by increasing numbers of people around the world. Now that we have a better understanding of what is driving this incidence, we can work to treat it more effectively.”
Stefan Jordan, PhD, the study’s first author and a postdoctoral fellow in the Department of Oncological Sciences at the Icahn School of Medicine at Mount Sinai, says, “There is enormous potential in investigating the anti-inflammatory effects of fasting, considering the broad spectrum of diseases that are caused by chronic inflammation. Our discoveries could lay the groundwork for novel treatments in the future.”
Indeed, chronic diseases such as type 2 diabetes, metabolic syndrome, and cardiovascular disease are believed to be mostly caused by chronic inflammation. According to a study by the RAND Corp., 60 percent of Americans had at least one chronic condition and 42 percent had multiple chronic conditions as of 2014, the last year for which this data was available. In 2018, the Milken Institute released a report that stated the most common chronic diseases cost the U.S. economy more than $1 trillion annually.
One of the study’s important findings was that short-term fasting did not compromise the body’s ability to protect itself from acute infections or repair tissue, whereas starvation for 48 hours prior to infection did compromise the body’s antimicrobial immunity and ability to repair tissue.
Another finding by Dr. Merad and her team was that by activating a key cellular pathway in the liver, AMPK, they were able to regulate the number of monocytes regardless of caloric intake.
“Targeting liver energy sensors could be an innovative strategy for the prevention and treatment of chronic inflammatory and autoimmune diseases,” says Dr. Merad.