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At first glance, the practice of intermittent fasting may appear similar to other trends that have captured the attention of the diet science world. In recent years, many have advocated for the practice of intermittent fasting, claiming benefits such as increased lifespan, mitigation of chronic disease risk, and improvements in physical performance. However, the actual potential for intermittent fasting in disease management and its benefit for healthy individuals have been topics of debate.

According to a review published in The New England Journal of Medicine, evidence from preclinical studies and clinical trials on intermittent fasting reveals benefits for a number of health conditions, including obesity, diabetes mellitus, cardiovascular disease, cancers, and neurologic disorders. Several of the benefits of intermittent fasting were found to be unassociated with its effects on weight loss. Some of these identified benefits include improvements in glucose regulation, blood pressure, and heart rate, as well as in the efficacy of endurance training and abdominal fat loss. While the review authors noted that we do not fully understand the specific mechanisms of how intermittent fasting facilitates these benefits, it is thought to be due to a phenomenon known as metabolic switching.

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Underlying Mechanism

Intermittent fasting uses distinct periods of feeding and fasting. In the fasted state, cells increase glucose regulation and stress resistance and suppress inflammation. This occurs in concert with the catabolism of triglycerides stored in adipose tissue, which subsequently leads to the production of ketone bodies that can serve as an energy source for tissues including the brain. In the fed state, cells use a glucose-based metabolism to engage in tissue-specific growth and plasticity. One of the more notable effects of switching between these 2 metabolic states is that the respiratory-exchange ratio in fasted individuals is reduced, which may indicate greater metabolic flexibility and energy production.

Clinical Impact

Intermittent fasting brings about an adaptive and evolutionarily conserved cellular response across a number of organ systems, which in turn leads to improved glucose regulation, increased stress resistance, and suppression of inflammation. “We’re built to function mentally and physically well in a food-deprived state. Of course, in the wild it’s not voluntary fasting – there’s food scarcity and food deprivation,” noted Mark Mattson, PhD, a professor of neuroscience at Johns Hopkins University in Baltimore and co-author of this review. He added that, “During evolution, presumably, the brains and bodies that functioned well in a food-deprived state were those that were successful at getting food and surviving and passing their genes on.”

Although this eating pattern has shown potential for treating or managing chronic disorders including obesity, diabetes mellitus, cardiovascular disease, cancers, and neurodegenerative brain diseases, the review authors highlighted that further research is needed to generalize these findings to groups not involved in each study. Moreover, although preclinical animal studies have shown intermittent fasting to extend lifespan, clinical research in this area is limited due to the lack of longitudinal study data.

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Practical Considerations

While an intermittent fasting eating pattern may be appropriate for some individuals, it can be difficult to adhere to and may not be the ideal pattern for everyone. “I think it’s important that when we are looking at intermittent fasting or any diet, what works needs to be sustainable over a long period of time,” indicated Fatima Cody Stanford MD, MPH, MPA, an obesity medicine physician, scientist, and policy maker at Massachusetts General Hospital and Harvard Medical School in Boston.

Clinicians who consider prescribing this eating pattern should also determine its appropriateness for their respective patients. This may include consulting a dietitian and/or psychologist to determine whether a given patient is a good candidate for intermittent fasting. Furthermore, clinicians may want to discuss the willingness or ability to sustain such an eating pattern for an extended period of time with each patient. Because many individuals are accustomed to 3 meals with interspersed snacks as part of their daily routine, switching to this eating pattern may prove to be an early challenge in their treatment course.

It is also important to counsel patients on the initial adverse effects that may be associated with this eating pattern, such as irritability and reduced ability to concentrate during periods of food restriction. In order to ameliorate these adverse effects, it may be appropriate to consider a gradual transition into this eating pattern.

Intermittent fasting may have gained traction as a diet fad, but preliminary research has established a clear, if untested, scientific and medical benefit via its use as a prescribed and monitored eating pattern.


De Cabo R, Mattson MP. Effects of intermittent fasting on health, aging, and disease [published online December 26, 2019]. New Engl J Med. doi:10.1056/NEJMra1905136