In recent years, fasting has become a new favorite in the scientific research community, and people have proposed various intermittent fasting programs for the prevention and treatment of obesity. In fact, the benefits of fasting are more than that. In addition to basic weight loss, fasting can also help improve cardiometabolic diseases and neurodegenerative diseases, and even extend the life of animals. However, at this stage, there is still a lack of large-scale prospective clinical trials to reveal “the changes in the human system caused by long-term fasting” (after all, it is really too difficult for people not to eat for five, six or seven consecutive days).

In order to fill this gap, a research team from the University of Cambridge in the UK recently conducted a 7-day human fasting trial and found that: 7 days of fasting (only drinking water) reduced the average weight of the participants by 5.7kg. It is worth mentioning that only after 3 days of complete calorie restriction will obvious health benefits appear.

It seems that only after persisting in “bigu for three days” can you enjoy the benefits of fasting.

https://doi.org/10.1038/s42255-024-01008-9

The researchers collected 12 healthy volunteers, including 5 women (body fat above 15%) and 7 men (body fat above 12%), with an average weight of 77.5 kg and an average body mass index (BMI) of 25.4 kg/m2 (slightly overweight). During the 7 days of the experiment, the participants were required to fast completely (drink water when thirsty and smack their mouths when hungry).

The most intuitive data shows that after 7 days of fasting, the average weight of the 12 volunteers decreased by 5.7±0.8 kg, which is equivalent to a decrease of 1.9 units in BMI. Among them, the weight loss includes total, total lean body mass and fat mass; and from the composition point of view, the subcutaneous fat mass decreased significantly by 0.21 kg after 7 days of fasting, but the reduction of visceral fat was not significant.

In the first 2-3 days of the 7-day fasting process, the glucose concentration in plasma decreased, while the fatty acid content increased significantly and then stabilized. It can be seen that in the early stage of fasting, the body gradually switched from using glucose for energy to using fat. During the entire fasting period, the concentration of 3-hydroxybutyrate in plasma continued to rise, proving that the production of ketone bodies in the body continued to increase.

It is worth mentioning that no volunteers reported adverse reactions during the 7-day fasting process.

Even after resuming free eating 3 days after fasting, the weight of the participants was still lower than the initial level (still reduced by 3.1±0.6kg). However, the good news is that after resuming eating, the participants’ lost lean body weight was almost completely restored (-0.69±0.49 kg), but the lost fat was not completely restored (-1.85±0.34 kg).

Experimental process and basic information changes

During the entire 7-day fasting period, the researchers also closely monitored the health data of the participants-before, during and after fasting, the researchers recorded the changes in the levels of about 3,000 proteins in the plasma proteome to explore the possible effects of fasting on health.

In terms of quantity, 35.9% of the plasma proteome underwent significant changes, of which 22 protein targets increased and 122 decreased by more than 2 standard deviation units. However, from a temporal perspective, systemic proteomic changes need to be fasted for 3 days before they become apparent, while few proteins change after 24 and 48 hours.

Specifically, the protein targets of these changes include: plasma leptin levels decreased, reaching a minimum on the fourth day of fasting, a decrease of about 2.39 standard deviations, and the hypothalamus-pituitary-thyroid axis was also suppressed (i.e., thyroxine dropped to a minimum on the second day). However, other proteins related to eating/fasting did not change much, such as: ghrelin, adiponectin, and brain-derived neurotrophic factor only showed slight changes.

But interestingly, follistatin reached its highest value on the third day, increasing by 5.62 units; proprotein convertase subtilisin/kexin convertase 9 (PCSK9) increased by about 4.75 units throughout the fasting period; neuroblastoma suppressor protein 1 (NBL1) dropped to a minimum on the last day, decreasing by 5.20 standard deviation units. Perhaps these three data will become markers for long-term fasting (>3 days).

In addition, from the perspective of pathways, proteins related to insulin-like growth factor (IGF) signaling, cytokine signaling, lipoprotein metabolism, and protein metabolism all showed significant changes during fasting.

Changes in multiple proteins in the body during fasting

In fact, long-term fasting not only affects molecules in the circulatory system, but also affects changes in proteins in the extracellular matrix, especially the significant enrichment of the brain-specific ECM protein tenascin-R, which plays an important role in maintaining neurons and stabilizing synapses.

The researchers also further evaluated the effects of changes in 212 proteins during fasting on about 500 health outcomes, both positive and negative.

For example, the SWAP70 protein associated with rheumatoid arthritis continued to decrease with the increase in fasting time and reached its peak after 6 days of fasting, that is, long-term fasting may relieve rheumatoid arthritis; in addition, fasting for up to 7 days can also help reduce proteins related to childhood epilepsy and heart disease, thereby alleviating the disease.

Of course, during fasting, researchers also observed that pulmonary surfactant protein D (SFTPD) and interleukin-7 receptor (IL7R) decreased with weight loss, which is also closely related to reduced immunity. Therefore, when fasting for a long time, you should pay more attention to the body’s immune status.

Changes in the genome during fasting

As Claudia Langenberg, co-corresponding author of this article, said, this is the first time that changes in the body at the molecular level during fasting have been seen. However, it is worth noting that the benefits of complete fasting appear later than expected, and it will not be fully apparent until 3 days after fasting, but the effect is sustainable. In addition, this study also answers a question: Compared with dieting, long-term fasting is more conducive to weight loss.

In summary, fasting for up to 7 days can effectively reduce weight by 5.7kg, but it must be persisted for 3 days before the health benefits can be realized. However, fasting is a double-edged sword. Everything is better in moderation. Fasting for too long may also cause damage to the body, such as low immunity.

Of course, this article does not encourage everyone to fast for up to 7 days. You should still do what you can to lose weight, and never lose the big picture for the small.