In a new study published in Frontiers in Cardiovascular Medicine, our research team at the University of California, Davis reveals how a single 36-hour water-only fast can lead to major changes in fat molecules in the blood. In an earlier study, we showed that going without food for 36 hours causes big changes to the thousands of small molecules circulating in blood plasma. We found that certain chemicals produced by the body during a 36-hour fast helped strengthen immune cells called macrophages. These fasting chemicals also increased the typical lifespan of a worm species by as much as 96%. In the new paper, we analyzed the blood samples of the same 20 healthy, young people after an overnight fast, after eating, after a 36-hour water-only fast, and after eating again after the 36-hour fast. As expected, we found that 36 hours of fasting markedly increased free fatty acids, molecules that can be used for energy, while decreasing triglycerides, a type of fat found in blood that when elevated can increase the risk of cardiovascular disease. Fasting for 36 hours also decreased two types of fat molecules called lysophospholipids, which are linked to inflammation, cardiovascular disease, Alzheimer’s disease, and other health conditions when elevated. According to our findings, even a short fast of a day and a half can “vastly remodel” fats in the bloodstream, which may have benefits for cardiometabolic health and healthy aging. Bouts of 36 hours of fasting may be useful to “reset” plasma lipids toward a more beneficial profile in individuals whose blood lipids put them at risk for cardiovascular disease, neurodegenerative disease and other metabolic conditions. However, researchers do not know yet how many bouts of prolonged fasting would be beneficial in different individuals, how frequently these fasts should be performed for maximal benefit, and how best to manage the potential downsides of prolonged fasting, for example, making sure to minimize the loss of muscle mass and micronutrient deficiency.