Both calorie restriction and intermittent fasting can extend life in short-lived species such as mice, the former producing a larger benefit. Both appear to produce benefits to health in humans, though nowhere near the same effects on life span. Mice in past calorie restriction studies tended to be fed at intervals, such as daily, that were in practice imposing periods of fasting as well as a lowered calorie intake. How much of the observed benefits are due to the metabolic changes imposed by reduced calorie intake versus the metabolic changes imposed by time spent fasting? A growing interest in intermittent fasting in the research community has led to the discovery that both reduced calorie intake during a fast and then the restoration of a higher calorie intake at the end of a fast appear to produce distinct benefits. Researchers here report on their efforts to split apart the effects of reduced calorie intake from duration of fasting in mice. The results are interesting.
Researchers began to realize that previous studies had unintentionally combined calorie restrictions with long fasts by providing animals with food just once a day. It was difficult, then, to distinguish the effects of one from the other. "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."
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 - this gave them a long daily fast without reducing calories. The other two groups were given about 30% fewer calories either once a day or dispersed over the entire day. That meant that 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.
It turned out that many of the benefits originally ascribed to calorie restriction alone - better blood sugar control, healthier use of fat for energy, protection from frailty in old age and longer lifespans - all required fasting as well. Mice who ate fewer calories without fasting didn't see these positive changes. Fasting on its own, without reducing the amount of food eaten, was just as powerful as calorie restriction with fasting. Fasting alone was enough to improve insulin sensitivity and to reprogram metabolism to focus more on using fats as a source of energy. The livers of fasting mice also showed the hallmarks of healthier metabolism.
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 8 months earlier on average. "That was quite surprising. 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."