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Going without food for several days triggers far more than a switch from burning glucose to stored fat, with prolonged fasting causing coordinated biological changes across multiple organs, according to research published in Nature Metabolism in 2024.
The study found that some of the most significant changes emerged only after about three days without calories, suggesting that extended fasting produces a broader biological response than the metabolic changes associated with short-term fasting.
Researchers from Queen Mary University of London’s Precision Healthcare University Research Institute and the Norwegian School of Sports Sciences studied 12 healthy volunteers who completed a seven-day water-only fast.
The participants were closely monitored throughout the fast and after they resumed eating. Researchers measured changes in about 3,000 proteins in their blood to track how different organs and biological systems responded.
As expected, the body began shifting from glucose toward stored fat as a major source of energy within the first two to three days. Participants lost an average of 5.7 kilogrammes during the seven-day fast, with the reduction coming from both fat and lean mass.
When they had resumed eating for three days, most of the lost lean mass had returned, while much of the reduction in fat mass remained.
But the researchers found a much broader biological response emerging around the third day.
About one-third of the proteins measured changed significantly during the fasting period, with alterations associated with all major organs. Many of these changes were consistent among participants and could not be explained simply by weight loss.
The findings included changes in proteins linked to the structural support of neurons in the brain. Neurons are specialised cells responsible for transmitting information through the nervous system, while surrounding proteins help maintain their structure and function.
The researchers said the results provide a detailed picture of how the human body adapts to prolonged calorie restriction.
Humans have evolved to tolerate periods without food, an ability that was important when food supplies were unpredictable. Today, fasting is practised for cultural and religious reasons as well as for weight management and medical purposes.
Fasting has also been explored in the treatment of conditions including epilepsy and rheumatoid arthritis.
However, the researchers stressed that the study does not establish that prolonged fasting is beneficial for health or that people should undertake extended fasts themselves.
Instead, identifying the molecular changes associated with fasting could help scientists understand which effects might eventually be harnessed for medical treatment.
The researchers hope their findings will provide a foundation for developing therapies that can reproduce some of the biological effects of fasting without requiring people to go without food for several days.
Such approaches could be particularly useful for people who may benefit from certain fasting-related biological changes but cannot safely undertake prolonged fasting or follow fasting-mimicking diets.