While long-term calorie restriction can provide health benefits, fasting may provide a boost to the effects, new research suggests.
Studies have suggested restricting calories could result in lower weight, better blood sugar control and even longer lifespans.
But new research in mice indicates that reduced calorie intake alone is not enough, and fasting was essential for the animals to get the full benefit.
The new findings lend support to preliminary evidence that fasting can boost health in people, scientists say.
They add that the studies contribute to the growing picture of how health is controlled by when and what is eaten, and not just how much.
Combined with eating less, fasting reduces frailty in old age and extends the lifespan of mice, the study found.
It also discovered that fasting alone can improve blood sugar and liver metabolism.
Researchers found that mice that ate fewer calories but never fasted died younger than mice that ate as much as they wanted, suggesting that calorie restriction alone may be harmful.
The research was led by University of Wisconsin–Madison School of Medicine and Public Health metabolism researcher Dudley Lamming, his graduate student Heidi Pak, colleagues at the university and other institutions.
Professor Lamming said: “This overlap of treatment – both reducing calories and imposing a fast – was something that everybody saw, but it wasn’t always obvious that it had biological significance.
“It’s only been in the past few years that people started getting interested in this issue.”
The researchers designed four different diets for mice to follow.
One group ate as much as they wanted whenever they wanted. Another group ate a full amount but in a short period of time – giving them a long daily fast without reducing calories.
The other two groups were given around 30% fewer calories either once a day or spread over the entire day.
That meant some mice had a long daily fast while others ate the same reduced-calorie diet but never fasted, which differed from most previous studies of calorie restriction.
The results suggest that many of the benefits originally linked to calorie restriction alone all required fasting as well.
Mice who ate fewer calories without fasting did not see these positive changes, according to the study published in Nature Metabolism.
Fasting on its own, without reducing the amount of food eaten, was just as powerful as calorie restriction with fasting, the research suggests.
Fasting alone was also enough to improve insulin sensitivity and to reprogramme metabolism to focus more on using fats as a source of energy.
The livers of fasting mice also showed the hallmarks of healthier metabolism.
However, the researchers did not study the effect of fasting alone on lifespan or frailty as mice aged, but other studies have suggested that fasting can provide these benefits as well.
While the mice that ate fewer calories without ever fasting did show some improved blood sugar control, they also died younger.
Compared with mice who both ate less and fasted, these mice that only ate less died about eight months earlier on average.
The team also measured frailty through metrics like grip strength and coat condition.
Prof Lamming said: “In addition to their shorter lifespans, these mice were worse in certain aspects of frailty, but better in others.
“So, on balance their frailty didn’t change much, but they didn’t look as healthy.”
The primary studies were done in male mice but Prof Lamming’s lab also found similar metabolic effects of fasting in female mice.
He added: “If fasting is the main driver of health, we should be studying drugs or diet interventions that mimic fasting rather than those that mimic fewer calories.”