Going without food for several days does more than force the body to burn stored fat. Research published in 2024 found that prolonged fasting produces widespread and coordinated biological changes in multiple organs, with some of the most noticeable effects only appearing after about three calorie-free days.
The results, published in Natural metabolismoffer an unusually detailed look at how the human body responds during prolonged fasting. The researchers found evidence of biological effects beyond weight loss, although many potentially health-related changes only became apparent after participants had gone about three days without food.
Scientists from the Precision Healthcare University Research Institute (PHURI) at Queen Mary University of London and the Norwegian School of Sports Sciences carried out the work. By identifying molecular changes associated with fasting, researchers hope to provide a basis for future studies that could eventually lead to treatments that can replicate some of the effects of fasting.
This could be particularly important for people who might benefit from some biological effects of fasting but cannot safely follow prolonged fasting or follow fasting-mimicking approaches such as ketogenic diets.
How the body adapts to fasting
Humans evolved to tolerate prolonged periods without food, an essential ability when meals were unpredictable. Today, millions of people fast for cultural, religious, medical or weight loss purposes.
Fasting also has a long history in medicine. It has been used in various forms to help manage conditions such as epilepsy and rheumatoid arthritis.
One of the most obvious changes during fasting is in the body’s energy supply. Under normal conditions, much of the body’s readily available energy comes from glucose from food. Once this incoming energy disappears, the body gradually begins to draw more from stored fat.
Scientists have already understood this fundamental metabolic change. What is much less clear is the effect of prolonged fasting on the rest of the body, particularly whether it produces biological changes that could be beneficial, harmful, or both (beneficial or undesirable).
Modern protein analysis has made it possible to study these questions in much more detail. Proteins perform a wide range of tasks in the body, from building tissues to controlling chemical reactions and transmitting signals between cells. Measuring thousands of proteins in the blood can therefore provide an overall picture of how different organs and biological systems respond.
Followed by a seven-day water-only fast
For the study, researchers followed 12 healthy volunteers who completed a seven-day water-only fast.
Participants were closely monitored every day. The scientists measured changes in about 3,000 proteins in their blood before fasting, throughout the fasting period, and after they started eating again.
The researchers then combined these protein measurements with genetic information from studies of large populations. This allowed them to study which biological pathways changed during fasting and predict some of the possible health consequences associated with these changes.
As expected, the body began to shift away from glucose and toward stored fat as a major energy source during the first two or three days without food.
Participants lost an average of 5.7 kilograms during the fast, with this loss coming from both fat and lean mass. Lean mass includes tissues that are not body fat, such as muscle and other water-rich tissues.
Three days after the participants started eating again, their overall weight remained below its initial level. However, most of the lost lean mass had returned, while the reduction in fat mass persisted.
A major change appeared around the third day
The most striking finding was what happened after about three days of fasting.
At this point, researchers began to detect distinct changes in protein levels throughout the body. This pattern suggested that complete calorie restriction produced a coordinated whole-body response rather than simply changing how the body obtained energy.
About a third of all proteins measured changed significantly during the fasting period, with effects linked to all major organs.
Many of these changes appeared consistently across participants. The researchers also detected biological signatures that could not be explained by weight loss alone.
One example involved changes in proteins associated with the structural support of neurons in the brain. Neurons are the specialized cells that transmit information throughout the nervous system, and the proteins that surround and support them help maintain their structure and function.
The results suggest that prolonged fasting could influence a much wider range of biological processes than just fat metabolism.
Potential Benefits Go Beyond Weight Loss
Claudia Langenberg, Director of the Precision Health University Research Institute (PHURI) at Queen Mary, said:
“For the first time, we are able to see what happens at the molecular level throughout the body when we fast. Fasting, when practiced safely, is an effective intervention for weight loss. Popular diets that incorporate fasting – such as intermittent fasting – claim to have health benefits beyond weight loss. Our results provide evidence of the health benefits of fasting beyond weight loss, but these were only visible after three days of restriction total calories – later than we previously thought.
Timing is important. Intermittent fasting can involve much shorter periods without food, while this study looked at complete calorie restriction lasting several days. The results therefore do not mean that shorter fasting programs necessarily produce the same effects.
Instead, the study helps identify when some of the most important molecular responses to prolonged fasting begin to appear.
Could scientists reproduce the effects of fasting?
Understanding why fasting produces particular biological changes may eventually prove more important than fasting itself.
If researchers can determine which molecular pathways are responsible for potentially beneficial effects, it may become possible to develop treatments that activate these pathways without requiring patients to stop eating for several days.
This possibility could be particularly useful for people whose medical conditions make prolonged fasting impractical or dangerous.
Maik Pietzner, President of PHURI Health Data and Co-Head of the Computational Medicine Group at the Berlin Health Institute at Charité, said:
“Our results have provided a basis for some age-old knowledge about why fasting is used for certain conditions. Although fasting may be beneficial for treating certain conditions, fasting will often not be an option for patients with health conditions. We hope that these results 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.”
The study provides a detailed molecular map of how the human body adapts during prolonged fasting. This also highlights a notable threshold: while the shift to burning stored fat begins within the first few days, many of the broader biological changes associated with fasting only become detectable after about three calorie-free days.
This distinction could help researchers separate the effects of weight loss from the deeper biological responses triggered by prolonged fasting, while also providing new clues about how these responses might one day be replicated without forcing people to endure prolonged periods without food.
Gn Health
