Beyond a diet fad: Fasting alters your genetic expression, experts say

The surprising health benefits of fasting go far beyond mere weight loss, and can even make your organs healthier

By Troy Farah

Science & Health Editor

Published January 25, 2023 5:30AM (EST)

Vegetables on round chopping board (Getty Images/Westend61)
Vegetables on round chopping board (Getty Images/Westend61)

One of the fastest growing diet trends has less to do with what you eat or how much, but when you eat. Restricting meal times, a practice sometimes called intermittent fasting or time restricted eating, comes in many forms, but it generally involves limiting when you eat to certain windows.

Intriguingly, fasting isn't merely about weight loss. A great deal of research suggests that this behavior can spur a whole host of health benefits, from improved mental state to more restful sleep. Weight loss, of course, is the benefit often most hyped. The Reddit forum for intermittent fasting, for example, has over 860,000 members, many of which share before and after photos of massive weight loss.

Simply restricting eating to an 8 to 10 hour window can change the way our genes express themselves, which has broad implications for human health.

But while intermittent fasting has been linked to a myriad of health benefits, researchers still have many questions about it — such as how it compares to counting calories, how different populations respond, even some fundamental questions about safety and side effects. One of the biggest questions is how it works. On a molecular level, why does changing the times we eat seem to have such a dramatic effect on our bodies?

Dr. Satchidananda Panda, a biology professor at the Salk Institute for Biological Studies, has spent considerable time researching the underlying mechanisms of intermittent fasting. He says simply restricting eating to an 8 to 10 hour window can change the way our genes express themselves, which has broad implications for human health.

In a recent study in the journal Cell Metabolism, Panda and his colleagues gave two groups of young, male mice the same obesogenic diet, meaning it was high in sugar and fat. One group was permitted ad libitum feeding, which is eating whenever they wanted. The other group could only eat during restricted hours, a form of intermittent fasting called time restricted feeding.

The difference between time restricted feeding and intermittent fasting is that people who do intermittent fasting are also counting calories. With time restricted feeding, you can generally eat whatever and as much as you want, just sticking between those 8 to 10 hours. In the experiment, the mice on the ad libitum schedule gained weight and experienced metabolic dysfunction, whereas the mice on time restricted feeding did not. This is remarkable given they were both on the same diet.

Next, Panda and his colleagues analyzed the organs of the mice, looking for genetic changes in 22 different organ and brain regions, screening for more than 21,000 genes from over 1,000 samples. Importantly, they took samples at different periods throughout the day and night. Gene expression can change throughout the day, depending on their function.

"Our genes are not static. So you just can't look at one time one morning or evening and figure out what's going on," Panda told Salon. "To our surprise, we found that almost every organ that we looked at experienced a huge impact from time restricted eating."

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More than 80 percent of the organs looked at had some level of change in the genes that code for proteins, which means time restricted feeding could alter metabolic efficiency. In simpler terms, constraining the time when you eat could make the entire way your body processes energy more flexible, which translates into other health benefits.

On the surface, this isn't an entirely surprising result. Intermittent fasting has previously been linked to improved liver function, insulin sensitivity and even hormone regulation. It seems to have a broad effect across many different systems in the body, but some of these organs, especially the brain, have been looked at a lot less than others.

"We are seeing a signature of gene expression changes that are indicating that people who have chronic kidney disease may benefit from this."

Of course, this research was in mice, and only male mice to boot. This may not translate directly to humans. But the research provides a "transcriptome map" which gives researchers a good idea of where to start looking next when researching intermittent fasting. Potential targets include metabolic disorders, neurodegenerative diseases and cancer.

"I think this is a good blueprint for what diseases can be treated," Panda said. "This study is giving us clues, for example, in the kidney. We are seeing a signature of gene expression changes that are indicating that people who have chronic kidney disease may benefit from this."

Panda has studied the effects of intermittent fasting in humans as well, such as an experiment with 15 Australian men with obesity who were kept on a time restricted diet for eight weeks.

"We took their biopsy. A little bit of belly fat was taken out, almost like a mini liposuction," Panda explained. "What we found were good changes in gene expression in these individuals which now gives us some idea what to expect when people with obesity do time restricted eating."

"Our adipose tissue or fat is almost like a hormone-producing organ. It produces a lot of different hormones good and bad," Panda added. "Time restricting actually improves the production of good hormones."

Studying intermittent fasting could also open the door to new therapies, such as drugs designed to target these gene expressions, maybe no time restricting required. Already, drugs that target certain metabolic pathways and can reduce weight in some individuals are becoming all the rage on social media. Semaglutide, also known by the brand names Wegovy or Ozempic, is a diabetes drug sometimes used for weight loss. It's become so popular that it's caused shortages in some areas, encouraging some patients to seek out risky alternatives or attempt brewing it up at home using raw chemicals. It should go without saying you shouldn't try to make your own weight loss drug.

However, the long-term effects of semaglutide for weight aren't well known. Many folks seem to gain back lost weight once they stop taking the drug, which can come with its own set of side effects like indigestion and nausea.

New, more effective medications to meet the demand for treating obesity and diabetes are necessary and studying intermittent fasting could help produce them. This is somewhat how metformin, a commonly prescribed drug for diabetes, was discovered. Although initially synthesized in the 1920s, it wasn't until 1957 that metformin was first used to treat diabetes. The reason for this multi-decade gap is because scientists didn't fully understand the mechanisms it uses to lower blood sugar levels. Unfortunately, despite metformin's widespread usage today, it still comes with some side effects that can be serious, even life-threatening. Alternative drugs would certainly be useful for some people.

But there will be no silver bullet for any of this. Medications or intermittent fasting alone can't form the foundation of a healthy lifestyle, Panda said.

"We have to keep in mind that medication is not going to give us long-term benefits. It will help us to reverse our disease," Panda said. "But to stay healthy for very long term, we have to adopt at least two out of the three foundations of health: that's sleep, exercise and nutrition."

The full extent to which intermittent fasting can help people, or even backfire, is not entirely known. Few things are as complex as how human bodies turn food into energy. More detailed research into how time restricted eating works will help us better understand the ways to make it useful for promoting good health.

By Troy Farah

Troy Farah is a science and public health journalist whose reporting has appeared in Scientific American, STAT News, Undark, VICE, and others. He co-hosts the drug policy and science podcast Narcotica. His website is and can be found on Twitter at @filth_filler

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