Intermittent fasting has become a popular approach for people trying to lose weight, but new research suggests the body undergoes far more significant changes when food is withheld for longer periods.
Unlike standard dieting, intermittent fasting involves alternating between set windows of eating and longer stretches without food. While many people use it in a moderate way, some fasting regimens extend far beyond a typical daily schedule. Researchers say those longer fasts appear to trigger a different biological response rather than simply extending the early stages of hunger.
Researchers at Queen Mary University of London, working with colleagues at the Norwegian School of Sports Sciences, wanted to understand how the body responds during a much longer fast. Their study, published in Nature Metabolism on 1 March 2024, reported “major changes appearing only after about three days without food.”
In a separate seven-day water-only fasting trial, scientists monitored thousands of proteins in the blood and found “widespread shifts affecting organs throughout the body,” including the brain.
The research followed 12 healthy participants — five women and seven men — who consumed only water for seven days. Investigators tracked around 3,000 proteins circulating in their blood, taking samples before the fast, daily during it and again after refeeding. After roughly two to three days, the body had shifted away from using glucose and began relying more heavily on stored fat for energy, a transition that was accompanied by rising ketone use.
Although the volunteers did lose weight, the most notable result was not the drop on the scales but the biological changes taking place throughout the body.
Blood samples were collected before, during and after the fast. By the end of the week, about a third of the measured proteins had changed significantly. Some of these were linked to structural support for neurons in the brain, immune pathways and the extracellular matrix — the network that helps support tissues throughout the body. The findings raise further questions about whether fasting could one day play a role in tackling issues such as inflammation, though the study did not test fasting as a treatment for disease.
The researchers said the results indicate that longer fasting does more than simply prolong the body’s initial reaction to going without food. Instead, it may push the body into a separate physiological state. In the paper, the team described nine distinct protein response patterns over the course of the fast, with more than 1,000 proteins showing significant changes across participants.
Across the 12 participants, the average weight loss recorded during the fast was 5.7 kg. According to the researchers, that total included both fat mass and lean tissue, underlining why extended fasting should not be treated as a casual weight-loss shortcut.
“For the first time, we’re able to see what’s happening on a molecular level across the body when we fast,” Director of Queen Mary’s Precision Health University Research Institute said.
“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,”
The study’s authors also used genetic and proteogenomic data to estimate how some of the protein shifts seen during fasting might relate to longer-term health outcomes. They identified signals that could point to possible benefits in certain conditions, alongside potential adverse effects, but stressed that these were estimates rather than proof that fasting prevents or treats disease.
The team also stressed that the study was small, involving only 12 healthy people, so the results should not be taken to mean extended fasting is safe or suitable for everyone. The trial did not include people with chronic illness, pregnant women, children or older adults, and it was designed to examine short-term biological changes rather than long-term health effects.
Health experts generally warn that prolonged fasting can carry risks such as dehydration, dizziness, headaches, low blood pressure, electrolyte imbalances and loss of lean mass, especially without medical supervision. People taking medications, particularly for diabetes or blood pressure, can face additional dangers if they attempt an extended fast on their own.
“While fasting may be beneficial for treating some conditions, oftentimes, 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,” researchers added.