Study identifies multi-organ response to seven days without food

New findings reveal that the body undergoes significant, systematic changes across multiple organs during prolonged periods of fasting. The results demonstrate evidence of health benefits beyond weight loss, but also show that any potentially health-altering changes appear to occur only after three days without food. 

The study, published today in Nature Metabolism, advances our understanding of what’s happening across the body after prolonged periods without food.  

By identifying the potential health benefits from fasting and their underlying molecular basis, researchers from Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) and the Norwegian School of Sports Sciences provide a road map for future research that could lead to therapeutic interventions – including for people that may benefit from fasting but cannot undergo prolonged fasting or fasting-mimicking, such as ketogenic, diets. 

Over millennia, humans have developed the ability to survive without food for prolonged periods of time. Fasting is practiced by millions of people throughout the world for different medical and cultural purposes, including health benefits and weight loss. Since ancient times, it has been used to treat diseases such as epilepsy and rheumatoid arthritis.  

During fasting, the body changes its source and type of energy, switching from consumed calories to using its own fat stores. However, beyond this change in fuel sources, little is known about how the body responds to prolonged periods without food and any health impacts – beneficial or adverse – this may have. New techniques allowing researchers to measure thousands of proteins circulating in our blood provide the opportunity to systematically study molecular adaptions to fasting in humans in great detail. 

Researchers followed 12 healthy volunteers taking part in a seven-day water-only fast. The volunteers were monitored closely on a daily basis to record changes in the levels of around 3,000 proteins in their blood before, during, and after the fast. By identifying which proteins are involved in the body’s response, the researchers could then predict potential health outcomes of prolonged fasting by integrating genetic information from large-scale studies. 

As expected, the researchers observed the body switching energy sources – from glucose to fat stored in the body – within the first two or three days of fasting. The volunteers lost an average of 5.7 kg of both fat mass and lean mass. After three days of eating after fasting, the weight stayed off – the loss of lean was almost completely reversed, but the fat mass stayed off.  

For the first time, the researchers observed the body undergoing distinct changes in protein levels after about three days of fasting – indicating a whole-body response to complete calorie restriction. Overall, one in three of the proteins measured changed significantly during fasting across all major organs. These changes were consistent across the volunteers, but there were signatures distinctive to fasting that went beyond weight loss, such as changes in proteins that make up the supportive structure for neurons in the brain. 

Claudia Langenberg, Director of Queen Mary’s Precision Health University Research Institute (PHURI), said: 

“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.” 

Maik Pietzner, Health Data Chair of PHURI and co-lead of the Computational Medicine Group at Berlin Institute of Health at Charité, said: 

“Our findings have provided a basis for some age-old knowledge as to why fasting is used for certain conditions. 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.” 

NOTES TO EDITORS 

For more information, please contact:  

Honey Lucas 

Faculty Communications Officer – Medicine and Dentistry  

Queen Mary University of London  

Email: h.lucas@qmul.ac.uk  

Paper details: ‘Systemic proteome adaptions to 7-day complete caloric restriction in humans’ will be published in Nature Metabolism on 10.00 am GMT 1 March 2024. 

DOI: 10.1038/s42255-024-01008-9 

Paper available upon request. 

Available after publication at the following URL: https://www.nature.com/articles/s42255-024-01008-9.  

About the Precision Healthcare University Research Institute (PHURI)  

Through world-class multidisciplinary research and innovation, the Precision Healthcare University Research Institute (PHURI) is driving a new era of personalised healthcare in East London to address unmet health needs, tackle health inequalities and improve lives in our local community and across the world.  

About Queen Mary University of London 

At Queen Mary University of London, we believe that a diversity of ideas helps us achieve the previously unthinkable.  

Throughout our history, we’ve fostered social justice and improved lives through academic excellence. And we continue to live and breathe this spirit today, not because it’s simply ‘the right thing to do’ but for what it helps us achieve and the intellectual brilliance it delivers.  

Our reformer heritage informs our conviction that great ideas can and should come from anywhere. It’s an approach that has brought results across the globe, from the communities of east London to the favelas of Rio de Janeiro.  

We continue to embrace diversity of thought and opinion in everything we do, in the belief that when views collide, disciplines interact, and perspectives intersect, truly original thought takes form.  

About the Berlin Institute of Health at Charité (BIH) 

The mission of the Berlin Institute of Health at Charité (BIH) is medical translation: transferring biomedical research findings into novel approaches to personalized prediction, prevention, diagnostics and therapies and, conversely, using clinical observations to develop new research ideas. The aim is to deliver relevant medical benefits to patients and the population at large. As the translational research unit within Charité, the BIH is also committed to establishing a comprehensive translational ecosystem – one that places emphasis on a system-wide understanding of health and disease and that promotes change in the biomedical translational research culture. The BIH was founded in 2013 and is funded 90 percent by the Federal Ministry of Education and Research (BMBF) and 10 percent by the State of Berlin. The founding institutions, Charité – Universitätsmedizin Berlin and Max Delbrück Center, were independent member entities within the BIH until 2020. Since 2021 the BIH has been integrated into Charité as its so-called third pillar. The Max Delbrück Center is now the Privileged Partner of the BIH.