Going without food for several days does far more than force the body to burn fat. Research published in Nature Metabolism revealed that extended fasting sets off widespread biological changes throughout the body, including shifts linked to the brain, metabolism, and immune system.
Scientists found that many of the most significant effects did not appear right away. Instead, the body seemed to enter a very different biological state after about three days without food.
The findings offer one of the clearest pictures yet of what prolonged fasting does inside the human body at a molecular level. Researchers say the work could eventually help scientists develop treatments that mimic some of fasting’s effects without requiring people to stop eating for days.
What Happens to the Body During Prolonged Fasting?
Humans evolved to survive periods of food scarcity. When food is unavailable, the body switches from using glucose from meals to relying on stored fat for energy.
Fasting has been practiced for thousands of years for religious, cultural, and medical reasons. It has also attracted growing attention in recent years because of studies linking fasting and intermittent fasting to weight loss, improved metabolic health, and cellular repair processes.
Still, scientists have had only a limited understanding of exactly how the body responds during longer fasts.
To investigate, researchers from Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) and the Norwegian School of Sports Sciences monitored 12 healthy volunteers during a seven day water-only fast. Blood samples were collected daily before, during, and after fasting.
Using advanced proteomics technology, the team tracked roughly 3,000 proteins circulating in the bloodstream. These proteins can provide clues about what is happening across organs and tissues throughout the body.
The Biggest Changes Started After Day Three
As expected, the body quickly shifted from burning glucose to burning fat within the first two to three days of fasting.
Participants lost an average of 5.7 kilograms (about 12.5 pounds), including both fat and lean tissue. After participants resumed eating for three days, most of the lean tissue loss returned while much of the fat loss remained.
But researchers discovered something more surprising.
Large scale changes in protein activity throughout the body did not begin immediately. Instead, major molecular changes became much more noticeable after around three days without calories.
More than one third of the proteins measured changed significantly during fasting. Some of the strongest shifts involved proteins linked to the extracellular matrix, which helps provide structural support for tissues and organs, including neurons in the brain.
The protein changes were remarkably consistent among volunteers, suggesting the body may follow a highly coordinated response to prolonged fasting.
“For the first time, we’re able to see what’s happening on a molecular level across the body when we fast,” said Claudia Langenberg, Director of Queen Mary’s Precision Health University Research Institute (PHURI).
“Fasting, when done safely, is an effective weight loss intervention. Popular diets that incorporate fasting, such as intermittent fasting, claim to have health benefits beyond weight loss. Our results provide evidence for the health benefits of fasting beyond weight loss, but these were only visible after three days of total caloric restriction — later than we previously thought.”
Potential Benefits Beyond Weight Loss
Researchers used genetic data from large human studies to examine how the protein changes observed during fasting might influence long term health.
The results suggested possible links to improvements in several biological pathways associated with disease risk and inflammation. Scientists also identified changes connected to proteins involved in brain support structures.
The findings have fueled interest in whether fasting could someday help researchers develop therapies for conditions involving metabolism, aging, inflammation, or neurological health.
Interest in fasting research has continued growing since the 2024 study was published. More recent reviews have linked intermittent fasting to improved insulin sensitivity, healthier lipid levels, and possible benefits for brain function and cardiovascular health.
Other recent studies on prolonged fasting have also found that the body enters a deep ketogenic state during multi day fasts, dramatically changing how cells use fuel.
Scientists Also Found Possible Risks
While fasting may produce beneficial biological effects, researchers caution that prolonged fasting is not risk free.
A later proteomics study involving prolonged water-only fasting found evidence of increased inflammation, platelet activation, and changes in blood clotting related pathways during extended fasting periods. The researchers said these effects may represent temporary stress responses, but they also highlighted the need for more research into the long term health consequences of extreme fasting.
Experts also warn that prolonged fasting can increase the risk of dehydration, electrolyte imbalances, dizziness, muscle loss, and complications for people with underlying health conditions.
Because of these risks, extended fasting should not be attempted without medical guidance, especially for people with diabetes, eating disorders, cardiovascular disease, or other chronic illnesses.
Why Scientists Are Excited About the Findings
Researchers say one of the most important discoveries was the timing of the body’s response.
Many popular fasting approaches focus on shorter fasting windows, but this study suggests some of the body’s more dramatic molecular changes may require several days of complete calorie restriction.
“Our findings have provided a basis for some age-old knowledge as to why fasting is used for certain conditions,” said Maik Pietzner, Health Data Chair of PHURI and co-lead of the Computational Medicine Group at Berlin Institute of Health at Charité.
“While fasting may be beneficial for treating some conditions, often times, fasting won’t be an option to patients suffering from ill health. We hope that these findings can provide information about why fasting is beneficial in certain cases, which can then be used to develop treatments that patients are able to do.”