Study finds multi-organ reaction to a week without food

The findings published in the Journal Nature Metabolism demonstrated the health benefits of fasting beyond weight loss but also showed that any potentially health-altering changes appear to occur only after three days without food.

Over millennia, humans have developed the ability to survive without food for prolonged periods. Fasting is practised by millions of people throughout the world for different medical and cultural purposes, including health benefits and weight loss. During fasting, the body shifts from consuming calories to utilising its fat stores for energy. However, the broader effects of prolonged fasting on health remain largely unknown. Advanced techniques for analysing circulating proteins in the blood help analyze how the body molecularly adapts to fasting in humans.

For the study, researchers recruited 12 healthy volunteers for a seven-day water-only fast. They closely monitored the volunteers daily to track changes in approximately 3,000 proteins in their blood before, during, and after the fast. By pinpointing the proteins involved in the body's response, researchers could forecast the potential health effects of prolonged fasting by integrating genetic data from extensive studies.

Researchers discovered that during fasting, the body shifted its energy source from glucose to stored fat within the first few days. Volunteers lost an average of 5.7 kg of fat and lean mass. After three days of refeeding, weight remained stable, with lean mass mostly restored but fat loss maintained. Protein levels underwent notable changes after three days of fasting, indicating a systemic response to calorie restriction. Approximately one-third of measured proteins changed significantly across major organs during fasting, with distinctive signatures beyond weight loss, including alterations in brain neuron-supporting proteins.

“For the first time, we’re able to see what’s happening on a molecular level across the body when we fast. 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.” said Claudia Langenberg, Director of Queen Mary’s Precision Health University Research Institute (PHURI).

Reference: Journal: Nature Metabolism; Maik Pietzner, Burulça Uluvar, Kristoffer J. Kolnes, Per B. Jeppesen, S. Victoria Frivold, Øyvind Skattebo, Egil I. Johansen, Bjørn S. Skålhegg, Jørgen F. P. Wojtaszewski, Anders J. Kolnes, Giles S. H. Yeo, Stephen O’Rahilly, Jørgen Jensen & Claudia Langenberg; DOI: 10.1038/s42255-024-01008-9