Exploring how fasting blunts inflammation



Prolonged periods without consuming calories from food or drinks, known as intermittent fasting, has recently been touted for its potential health benefits. Recent research supports use of this strategy to protect against diseases linked to inflammation, including cardiovascular disease and asthma. However, it remains unclear how exactly intermittent fasting combats inflammation. Most earlier research on that question has been conducted in mouse models, but the human and mouse immune systems have numerous differences, so it is important to explore the effects of intermittent fasting specifically within the human immune system.


In this study, IRP researchers led by Michael Sack, M.D., Ph.D., studied how fasting affects immune cells in healthy human volunteers. The study examined the effects of multiple different fasting regimens, as well as changes in the cells that occurred after the volunteers had a meal following a prolonged fast. The results indicated that a longer fasting period, such as fasting for 24 hours rather than just overnight, had stronger effects on multiple types of circulating immune cells. In addition, the researchers discovered that during periods of fasting, a protein called FOXO4 turned off inflammation in specific types of immune cells that have been linked to inflammatory conditions such as autoimmune diseases and diabetes.


The IRP team submitted the data from the study to a public database so that other researchers can further explore the mechanisms behind fasting’s anti-inflammatory effects. In this way, the study will permit additional research to be conducted that aims to identify regulatory pathways in immune cells that could be directly targeted by therapeutic strategies in order to mimic the health benefits produced by intermittent fasting, including pathways that utilize proteins similar to FOXO4. These ‘fasting mimetics’ can then be tested as treatments for a variety of ailments.


Han K, Singh K, Rodman MJ, Hassanzadeh S, Wu K, Nguyen A, Huffstutler RD, Seifuddin F, Dagur PK, Saxena A, McCoy JP, Chen J, Biancotto A, Stagliano KER, Teague HL, Mehta NN, Pirooznia M, Sack MN. (2021). Fasting-induced FOXO4 bluntshuman CD4+ T helper cell responsiveness. Nat Metab. Mar 15;3(3):318-326. doi: 10.1038/s42255-021-00356-0.

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This page was last updated on Thursday, June 8, 2023