Going without eating for a few days doesn’t just make your body burn fat. Research published in natural metabolism We have shown that long-term fasting causes a wide range of biological changes throughout the body, including changes related to the brain, metabolism, and immune system.
Scientists have found that many of the most significant effects are not immediate. Instead, after about three days without food, the body seemed to enter a very different biological state.
The findings provide one of the clearest pictures yet of how long-term fasting affects the human body at a molecular level. Researchers say this study could ultimately help scientists develop treatments that mimic some of the effects of fasting without having to stop eating for several days.
What happens to your body during long-term fasting?
Humans evolved to survive times of food scarcity. When food is unavailable, the body switches from using dietary glucose to relying on stored fat for energy.
Fasting has been practiced for thousands of years for religious, cultural, and medical reasons. It has also received increasing attention in recent years due to research linking fasting and intermittent fasting to weight loss, improved metabolic health, and cellular repair processes.
Still, scientists have limited understanding of exactly how the body responds during longer fasts.
For the study, researchers from Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) and the Norwegian School of Sport Science observed 12 healthy volunteers undergo a seven-day water-only fast. Blood samples were taken daily before, during, and after fasting.
Using advanced proteomics techniques, the team tracked approximately 3,000 proteins circulating in the bloodstream. These proteins provide clues about what is happening in organs and tissues throughout the body.
The biggest changes started after day 3
As expected, within the first few days after fasting, the body quickly transitioned from burning glucose to burning fat.
Participants lost an average of 5.7 kilograms (approximately 12.5 pounds), including both fat and lean tissue. After participants resumed the diet for three days, much of the fat loss remained, but most of the lean tissue loss returned.
But researchers discovered something even more surprising.
Large-scale changes in protein activity throughout the body did not begin immediately. Instead, the large molecular changes became more pronounced after about three days without calorie intake.
More than a third of the proteins measured changed significantly during fasting. Some of the most powerful changes involve proteins bound to the extracellular matrix, which help provide structural support for tissues and organs, including neurons in the brain.
The protein changes were surprisingly consistent across volunteers, suggesting that the body may follow a highly calibrated response to long-term fasting.
Claudia Langenberg, director of Queen Mary’s Precision Health University Research Institute (PHURI), said: “For the first time during fasting, we can now see at a molecular level what is happening throughout the body.”
“Fasting is an effective weight loss intervention when done safely. Common diets that incorporate fasting, such as intermittent fasting, claim health benefits beyond weight loss. Our results provide evidence of health benefits beyond weight loss through fasting, but these only appeared after three days of total calorie restriction, which was later than previously thought.”
Potential benefits beyond weight loss
Researchers used genetic data from large-scale human studies to investigate how protein changes observed during fasting affect long-term health.
This result suggested a possible association between disease risk and improvement of several biological pathways related to inflammation. The scientists also identified changes associated with proteins involved in the brain’s supporting structures.
The findings raise interest in whether fasting could one day help researchers develop treatments for conditions involving metabolism, aging, inflammation, or neurological health.
Interest in fasting research has continued to grow since the study was published in 2024. A recent review has linked intermittent fasting to improved insulin sensitivity, healthier lipid levels, and potential benefits for brain function and cardiovascular health.
Other recent studies on long-term fasting have also found that during several days of fasting, the body enters a deep ketogenic state, dramatically changing the way cells use fuel.
Scientists also discovered potential risks
Although fasting can have beneficial biological effects, researchers caution that long-term fasting is not without risks.
Subsequent proteomic studies involving prolonged water-only fasting found evidence of increased inflammation, platelet activation, and changes in blood coagulation-related pathways during prolonged fasting periods. The researchers said these effects may represent a temporary stress response, but also stressed the need for further research into the long-term health effects of extreme fasting.
Experts also warn that long-term fasting can increase the risk of dehydration, electrolyte imbalances, dizziness, muscle weakness and complications for people with underlying health conditions.
Because of these risks, people especially those with diabetes, eating disorders, cardiovascular disease, or other chronic conditions should not attempt long-term fasting without medical guidance.
Why scientists are excited about the findings
Researchers say one of the most important findings was the timing of the body’s response.
While many common fasting approaches focus on shorter fasting periods, this study suggests that some of the more dramatic molecular changes in the body may require several days of complete calorie restriction.
“Our findings provide a basis for long-standing knowledge about why fasting is used for certain conditions,” said Mike Pietzner, PHURI’s Health Data Chair and co-leader of the Computational Medicine Group at the Berlin Institute for Health Research Charité.
“While fasting may be beneficial in treating some symptoms, in many cases fasting is not an option for patients suffering from unwellness. We hope that these findings can be used to provide information about why fasting is beneficial in certain cases and to develop treatments that patients can implement.”
